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Pan Y, Lee YJ, Kim JH, Song MJ, Kwack K, Park SH, Sin SI, Chung JH, Park KY. Suppressor effects of carrots on azoxymethane/dextran sulfate sodium-induced colon cancer according to cultivation method. Front Immunol 2025; 16:1554801. [PMID: 40292300 PMCID: PMC12021845 DOI: 10.3389/fimmu.2025.1554801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 03/25/2025] [Indexed: 04/30/2025] Open
Abstract
Introduction This study investigated the suppressor effects of carrots depending on cultivation method on AOM/DSS-induced colon cancer in mice by examining cell apoptosis, inflammation response, and metabolites. Carrots grown using different fertilizers significantly suppressed tumor development by modulating cell apoptosis and inflammatory responses in our experimental settings. Methods and Results Naturaldream Fertilizer Carrot (NFC) cultivated with deep sea water minerals (DSWM) showed effectively increased the expression of apoptosis-related genes and proteins including p53, p21, Bim, Bad, Bax, Bak, Caspase 9, and Caspase 3 in colon tissue, while inhibiting the production of inflammatory factors and related genes and proteins such as TNF-a, IL-1b, IL-6, IFN-g, NF-kB, and iNOS in serum, spleen cells, and liver tissues. Intestinal microbiota analysis revealed a distinct composition in mice receiving carrots compared to the control group, with accumulation of intestinal microorganisms such as Lachnospiraceae, and Mucispirillum schaedleri closely associated with anti-tumor effects. Discussion and Conclusion Overall, our results indicate that carrots, especially carrots grown with DSWM fertilizers, play a crucial role in inhibiting AOM/DSS-induced colon cancer in mice by regulating cell apoptosis and inflammation responses. The present findings provide valuable insights for further exploration of carrots depending on the cultivation method, as a potential dietary source against colon cancer.
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Affiliation(s)
- Yanni Pan
- Collaborative Innovation Center for Child Nutrition and Health Development, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China
| | - Yeon-Jun Lee
- Department of Biotechnology, CHA University, Seongnam, Republic of Korea
| | - Jin Hyeop Kim
- Department of Biotechnology, CHA University, Seongnam, Republic of Korea
| | - Min Ji Song
- Department of Biotechnology, CHA University, Seongnam, Republic of Korea
| | - KyuBum Kwack
- Department of Biomedical Science, CHA University, Seongnam, Republic of Korea
| | - Seung-Hwan Park
- Organic Anti-Cancer Agriculture Institute, iCOOP Natural Dream Company, Goesan-gun, Chungcheongbuk-do, Republic of Korea
| | - Sin-Il Sin
- Organic Anti-Cancer Agriculture Institute, iCOOP Natural Dream Company, Goesan-gun, Chungcheongbuk-do, Republic of Korea
| | - Ji Hyung Chung
- Department of Biotechnology, CHA University, Seongnam, Republic of Korea
| | - Kun-Young Park
- Graduate School of Integrative Medicine, CHA University, Seongnam, Republic of Korea
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Taghizadeh-Teymorloei M, Jafarlou V, Matin S, Raeisi M, Roosta Y, Mansouri-Derakhshani S, Feizi AAH, Karimi A. Clinical implications of Alu-based cell-free DNA and serum onco-piRNA monitoring in colorectal cancer management. Clin Transl Oncol 2025:10.1007/s12094-025-03863-8. [PMID: 39969763 DOI: 10.1007/s12094-025-03863-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 01/28/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND Colorectal cancer (CRC) remains a significant global health challenge, characterized by high morbidity and mortality rates. This study explores the potential of Alu-based cell-free DNA (cfDNA) and specific PIWI-interacting RNAs (piRNAs) as innovative biomarkers for monitoring treatment responses in CRC patients. METHODS We analyzed plasma samples from 70 CRC patients, equally divided between those undergoing chemotherapy and surgical interventions. RESULTS Our findings reveal that certain piRNAs, particularly piRNA-823, piRNA-54265, and piRNA-1245, exhibit significant prognostic value, with notable expression changes observed in the chemotherapy group compared to the surgery group. Furthermore, the levels of ALU-based cfDNA fragments showed a marked decrease post-chemotherapy, suggesting their utility in assessing therapeutic efficacy. CONCLUSIONS This research underscores the importance of integrating these molecular tools particularly piRNA-823 and ALU-based cfDNA into clinical practice, potentially enhancing the management strategies for CRC patients and improving their outcomes.
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Affiliation(s)
- Mohammad Taghizadeh-Teymorloei
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golgasht St., Tabriz, 5166614756, East Azerbaijan, Iran
| | - Vahid Jafarlou
- Cancer Institute of Imam Khomeini Hospital, Tehran University of Medical Science, Tehran, Iran
| | - Somaieh Matin
- Lung Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mortaza Raeisi
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yousef Roosta
- Department of Internal Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Sima Mansouri-Derakhshani
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Genetics, Tabriz, Iran
| | - Abbas Ali Hosseinpour Feizi
- Hematology-Oncology Research Center, Tabriz University of Medical Sciences, Tabriz Children's Hospital, Tabriz, Iran
| | - Abbas Karimi
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golgasht St., Tabriz, 5166614756, East Azerbaijan, Iran.
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Mousavikia SN, Darvish L, Firouzjaei AA, Toossi MTB, Azimian H. PI3K/AKT/mTOR Targeting in Colorectal Cancer Radiotherapy: A Systematic Review. J Gastrointest Cancer 2025; 56:52. [PMID: 39849185 DOI: 10.1007/s12029-024-01160-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2024] [Indexed: 01/25/2025]
Abstract
BACKGROUND Radioresistance is a major challenge in the treatment of patients with colorectal cancer (CRC) and impairs the efficacy of radiotherapy. The PI3K/AKT/mTOR signaling pathway plays a critical role in CRC and contributes to the development of radioresistance. Accordingly, targeting this signaling pathway may be a promising strategy to improve oncotherapy. METHODS We performed a systematic search of Scopus, PubMed, Web of Science, Embase, and Medline databases. We included articles that investigated the effects of PI3K/AKT/mTOR pathway inhibitors on improving the efficacy of radiotherapy. RESULT Of the 32 articles included in our review, 27 were preclinical studies and 5 were clinical trials. We examined the effects of various signaling pathway inhibitors in combination with radiotherapy. While the efficacy of these therapies when used alone is limited, their combination is associated with reduced survival, induction of apoptosis, and cell cycle arrest, which may increase radiosensitivity. Despite the limited number of studies, this combination therapy has shown favorable treatment outcomes in patients with CRC. CONCLUSION PI3K/AKT/mTOR is a critical signaling pathway for cancer cell survival. By inhibiting this pathway, we can increase the efficacy of radiotherapy. These results provide valuable insights for the further development of research and clinical practice in the treatment of colorectal cancer.
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Affiliation(s)
- S N Mousavikia
- Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - L Darvish
- Department of Radiology, Faculty of Paramedicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
- Mother and Child Welfare Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - A A Firouzjaei
- Bioinformatics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - M T Bahreyni Toossi
- Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - H Azimian
- Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Kopec K, Quaranto D, DeSouza NR, Jarboe T, Islam HK, Moscatello A, Li XM, Geliebter J, Tiwari RK. The HOX Gene Family's Role as Prognostic and Diagnostic Biomarkers in Hematological and Solid Tumors. Cancers (Basel) 2025; 17:262. [PMID: 39858044 PMCID: PMC11763641 DOI: 10.3390/cancers17020262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 01/07/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
The HOX gene family encodes for regulatory transcription factors that play a crucial role in embryogenesis and differentiation of adult cells. This highly conserved family of genes consists of thirty-nine genes in humans that are located in four clusters, A-D, on different chromosomes. While early studies on the HOX gene family have been focused on embryonic development and its related disorders, research has shifted to examine aberrant expression of HOX genes and the subsequent implication in cancer prediction and progression. Due to their role of encoding master regulatory transcription factors, the abnormal expression of HOX genes has been shown to affect all stages of tumorigenesis and metastasis. This review highlights the novel role of the HOX family's clinical relevance as both prognostic and diagnostic biomarkers in hematological and solid tumors.
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Affiliation(s)
- Kaci Kopec
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
| | - Danielle Quaranto
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
| | - Nicole R. DeSouza
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
| | - Tara Jarboe
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
| | - Humayun K. Islam
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
- Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA
| | - Augustine Moscatello
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
- Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA
| | - Xiu-Min Li
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
- Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA
- Department of Dermatology, New York Medical College, Valhalla, NY 10595, USA
| | - Jan Geliebter
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
- Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA
| | - Raj K. Tiwari
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; (K.K.); (D.Q.); (N.R.D.); (T.J.); (H.K.I.); (A.M.); (X.-M.L.); (R.K.T.)
- Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA
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Kamal R, Awasthi A, Paul P, Mir MS, Singh SK, Dua K. Novel drug delivery systems in colorectal cancer: Advances and future prospects. Pathol Res Pract 2024; 262:155546. [PMID: 39191194 DOI: 10.1016/j.prp.2024.155546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 08/10/2024] [Accepted: 08/14/2024] [Indexed: 08/29/2024]
Abstract
Colorectal cancer (CRC) is an abnormal proliferation of cells within the colon and rectum, leading to the formation of polyps and disruption of mucosal functions. The disease development is influenced by a combination of factors, including inflammation, exposure to environmental mutagens, genetic alterations, and impairment in signaling pathways. Traditional treatments such as surgery, radiation, and chemotherapy are often used but have limitations, including poor solubility and permeability, treatment resistance, side effects, and post-surgery issues. Novel Drug Delivery Systems (NDDS) have emerged as a superior alternative, offering enhanced drug solubility, precision in targeting cancer cells, and regulated drug release. Thereby addressing the shortcomings of conventional therapies and showing promise for more effective CRC management. The present review sheds light on the pathogenesis, signaling pathways, biomarkers, conventional treatments, need for NDDS, and application of NDDS against CRC. Additionally, clinical trials, ongoing clinical trials, marketed formulations, and patents on CRC are also covered in the present review.
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Affiliation(s)
- Raj Kamal
- Department of Quality Assurance, ISF College of Pharmacy, Moga, Punjab 142001, India; School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab 147301, India
| | - Ankit Awasthi
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab 142001, India; Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.
| | - Priyanka Paul
- Department of Pharmaceutical Science, PCTE Group of Institute, Ludhiana, Punjab, India
| | - Mohammad Shabab Mir
- School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab 147301, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia
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Gatasheh MK. Identifying key genes against rutin on human colorectal cancer cells via ROS pathway by integrated bioinformatic analysis and experimental validation. Comput Biol Chem 2024; 112:108178. [PMID: 39191167 DOI: 10.1016/j.compbiolchem.2024.108178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 08/04/2024] [Accepted: 08/16/2024] [Indexed: 08/29/2024]
Abstract
Colorectal cancer (CRC) poses a significant global health challenge, characterized by substantial prevalence variations across regions. This study delves into the therapeutic potential of rutin, a polyphenol abundant in fruits, for treating CRC. The primary objectives encompass identifying molecular targets and pathways influenced by rutin through an integrated approach combining bioinformatic analysis and experimental validation. Employing Gene Set Enrichment Analysis (GSEA), the study focused on identifying potential differentially expressed genes (DEGs) associated with CRC, specifically those involved in regulating reactive oxygen species, metabolic reprogramming, cell cycle regulation, and apoptosis. Utilizing diverse databases such as GEO2R, CTD, and Gene Cards, the investigation revealed a set of 16 targets. A pharmacological network analysis was subsequently conducted using STITCH and Cytoscape, pinpointing six highly upregulated genes within the rutin network, including TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Gene Ontology (GO) analysis predicted functional categories, shedding light on rutin's potential impact on antioxidant properties. KEGG pathway analysis enriched crucial pathways like metabolic and ROS signaling pathways, HIF1a, and mTOR signaling. Diagnostic assessments were performed using UALCAN and GEPIA databases, evaluating mRNA expression levels and overall survival for the identified targets. Molecular docking studies confirmed robust binding associations between rutin and biomolecules such as TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Experimental validation included inhibiting colorectal cell HT-29 growth and promoting cell growth with NAC through MTT assay. Flow cytometric analysis also observed rutin-induced G1 phase arrest and cell death in HT-29 cells. RT-PCR demonstrated reduced expression levels of target biomolecules in HT-29 cells treated with rutin. This comprehensive study underscores rutin's potential as a promising therapeutic avenue for CRC, combining computational insights with robust experimental evidence to provide a holistic understanding of its efficacy.
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Affiliation(s)
- Mansour K Gatasheh
- Department of Biochemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
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Jeo WS, Lalisang TJM, Siregar NC, Sudoyo AW, Pakasi T, Jusman SW, Asmarinah A. Semiquantitative assessment of phosphatase and tensin homolog value with immunohistochemistry in colorectal cancer. Int J Biol Markers 2024; 39:248-254. [PMID: 39118563 DOI: 10.1177/03936155241265346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
INTRODUCTION Colorectal cancer has emerged as a concerning health problem, ranking the third most common form of cancer in both men and women. The phosphatase and tensin homologue (PTEN) protein is widely known for its role as an inhibitor of the phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway, playing a major role inhibiting tumor development. Previous studies investigated the role of this protein in the PI3K pathway and how it affected colorectal cancer. However, a standardized cut-off value for PTEN expression has not been established. METHODS Immunohistochemistry was used in examining PTEN. The staining grade ranging from 0 to 3 was then multiplied by the number of 100 cancer cells counted, with total score between 0 and 300. In this study, receiver operating characteristic (ROC) curve was employed to determine the expression cut-off value for PTEN in colorectal cancer. RESULTS This study showed statistically significant results (P < 0.001) in either tumor or non-tumor tissues by using the ROC curve with a cut-off value of 199.0. This study also revealed significant correlation between nodal status with PTEN (P = 0.008) and stage with PTEN (P = 0.019) with sensitivity 0.753 and specificity 0.728. CONCLUSION Semiquantitative assessment with cell counting multiplied by color intensity is a good method in determining PTEN expression. The use of immunohistochemical staining intensity and cell scoring with ROC cut-off is effective to elaborate the effects of PTEN in colorectal cancer (PTEN value > 199.0 was classified as strong and ≤ 199.0 as weak).
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Affiliation(s)
- Wifanto S Jeo
- Department of Surgery, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Toar J M Lalisang
- Department of Surgery, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Nurjati C Siregar
- Department of Pathology Anatomy, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Aru W Sudoyo
- Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Trevino Pakasi
- Department of Primary Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Sri W Jusman
- Department of Biochemistry, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Asmarinah Asmarinah
- Department of Biology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
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Aleissa M, Drelichman ER, Mittal VK, Bhullar JS. Barriers in early detection of colorectal cancer and exploring potential solutions. World J Clin Oncol 2024; 15:811-817. [PMID: 39071472 PMCID: PMC11271734 DOI: 10.5306/wjco.v15.i7.811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 06/21/2024] [Accepted: 07/04/2024] [Indexed: 07/16/2024] Open
Abstract
This editorial discusses the literature review article by Tonini and Zanni, the paper was published in January 2024, and the authors provided very interesting conclusions regarding existing barriers to the early diagnosis of colon cancer. Many cancers do not have identifiable precursors, or there are currently no screening tests to find them. Therefore, these cancers do not have preventive screening options. Early detection is crucial for reducing mortality rates by identifying cancer at an earlier stage through screening, as opposed to no screening. Colorectal cancer develops from precancerous lesions, which can be detected early and potentially prevented and cured. Early detection leads to improved survival rates, decreased complications, and reduced healthcare expenses. This editorial provides a brief description of the biology of colon cancer, emphasizing the contrast in outcomes between early detection and late detection. We also describe screening programs around the globe and examine the barriers in each program. Finally, we explore potential future solutions to enhance inclusion in screening programs and improve patient compliance.
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Affiliation(s)
- Maryam Aleissa
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
- College of Medicine, Princess Norah University Hospital, Riyadh 11564, Saudi Arabia
| | - Ernesto Raul Drelichman
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Vijay K Mittal
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Jasneet Singh Bhullar
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
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Dezfuli AAZ, Abu-Elghait M, Salem SS. Recent Insights into Nanotechnology in Colorectal Cancer. Appl Biochem Biotechnol 2024; 196:4457-4471. [PMID: 37751009 DOI: 10.1007/s12010-023-04696-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2023] [Indexed: 09/27/2023]
Abstract
Colorectal cancer (CRC) is the third cancer among the known causes of cancer that impact people. Although CRC drug options are imperfect, primary detection of CRC can play a key role in treating the disease and reducing mortality. Cancer tissues show many molecular markers that can be used as a new way to advance therapeutic methods. Nanotechnology includes a wide range of nanomaterials with high diagnostic and therapeutic power. Several nanomaterials and nanoformulations can be used to treat cancer, especially CRC. In this review, we discuss recent insights into nanotechnology in colorectal cancer.
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Affiliation(s)
- Aram Asareh Zadegan Dezfuli
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Mohammed Abu-Elghait
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Salem S Salem
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Cairo, Egypt.
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Zheng E, Włodarczyk M, Węgiel A, Osielczak A, Możdżan M, Biskup L, Grochowska A, Wołyniak M, Gajewski D, Porc M, Maryńczak K, Dziki Ł. Navigating through novelties concerning mCRC treatment-the role of immunotherapy, chemotherapy, and targeted therapy in mCRC. Front Surg 2024; 11:1398289. [PMID: 38948479 PMCID: PMC11211389 DOI: 10.3389/fsurg.2024.1398289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 05/29/2024] [Indexed: 07/02/2024] Open
Abstract
Over the course of nearly six decades since the inception of initial trials involving 5-FU in the treatment of mCRC (metastatic colorectal cancer), our progressive comprehension of the pathophysiology, genetics, and surgical techniques related to mCRC has paved the way for the introduction of novel therapeutic modalities. These advancements not only have augmented the overall survival but have also positively impacted the quality of life (QoL) for affected individuals. Despite the remarkable progress made in the last two decades in the development of chemotherapy, immunotherapy, and target therapies, mCRC remains an incurable disease, with a 5-year survival rate of 14%. In this comprehensive review, our primary goal is to present an overview of mCRC treatment methods following the latest guidelines provided by the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the American Society of Colon and Rectal Surgeons (ASCRS). Emphasis has been placed on outlining treatment approaches encompassing chemotherapy, immunotherapy, targeted therapy, and surgery's role in managing mCRC. Furthermore, our review delves into prospective avenues for developing new therapies, offering a glimpse into the future of alternative pathways that hold potential for advancing the field.
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Affiliation(s)
- Edward Zheng
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Marcin Włodarczyk
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Andrzej Węgiel
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Aleksandra Osielczak
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Maria Możdżan
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Laura Biskup
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Agata Grochowska
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Maria Wołyniak
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
- Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
| | - Dominik Gajewski
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Mateusz Porc
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Kasper Maryńczak
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Łukasz Dziki
- Department of General and Oncological Surgery, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
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Bakhsh T, Alhazmi S, Farsi A, Yusuf AS, Alharthi A, Qahl SH, Alghamdi MA, Alzahrani FA, Elgaddar OH, Ibrahim MA, Bahieldin A. Molecular detection of exosomal miRNAs of blood serum for prognosis of colorectal cancer. Sci Rep 2024; 14:8902. [PMID: 38632250 PMCID: PMC11024162 DOI: 10.1038/s41598-024-58536-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 04/01/2024] [Indexed: 04/19/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening. In the present study, a number of 660 mature miRNAs were detected in patients diagnosed with CRC at different stages. Of which, 29 miRNAs were differentially expressed in CRC patients compared with healthy controls. Twenty-nine miRNAs with high abundance levels were further selected for subsequent analysis. These miRNAs were either highly up-regulated (e.g., let-7a-5p, let-7c-5p, let-7f-5p, let-7d-3p, miR-423-5p, miR-3184-5p, and miR-584) or down-regulated (e.g., miR-30a-5p, miR-99-5p, miR-150-5p, miR-26-5p and miR-204-5p). These miRNAs influence critical genes in CRC, leading to either tumor growth or suppression. Most of the reported diagnostic exosomal miRNAs were shown to be circulating in blood serum. The latter is a novel miRNA that was found in exosomal profile of blood serum. Some of the predicted target genes of highly expressed miRNAs participate in several cancer pathways, including CRC pathway. These target genes include tumor suppressor genes, oncogenes and DNA repair genes. Main focus was given to multiple critical signaling cross-talking pathways including transforming growth factor β (TGFβ) signaling pathways that are directly linked to CRC. In conclusion, we recommend further analysis in order to experimentally confirm exact relationships between selected differentially expressed miRNAs and their predicted target genes and downstream functional consequences.
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Affiliation(s)
- Tahani Bakhsh
- Department of Biology, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
| | - Safiah Alhazmi
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
- Immunology Unit, King Fahad Medical Research Centre, King Abdulaziz University, 80200, Jedaah, Saudi Arabia
- Neuroscience and Geroscience Research Unit, King Fahad Medical Research Centre, King Abdulaziz University, 80200, Jeddah, Saudi Arabia
- Central lab of biological Sciences, Faculty of Sciences, King Abdulaziz University, 80200, Jeddah, Saudi Arabia
| | - Ali Farsi
- Department of Surgery, Faculty of Medicine, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Abdulaziz S Yusuf
- Department of Biochemistry, Faculty of science, Stem Cell Unit, King Fahad Center for Medical Research, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
- Medical Laboratory Sciences Department, Fakeeh College for Medical Sciences, 21461, Jeddah, Saudi Arabia
| | - Amani Alharthi
- Department of Biology, College of Science Al-Zulfi, Majmaah University, 11952, Majmaah, Saudi Arabia
| | - Safa H Qahl
- Department of Biology, College of Science, University of Jeddah, Jeddah, Saudi Arabia
| | - Maha Ali Alghamdi
- Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia
| | - Faisal A Alzahrani
- Department of Biochemistry, Faculty of science, Stem Cell Unit, King Fahad Center for Medical Research, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Ola H Elgaddar
- Department of Chemical Pathology, Alexandria University, Alexandria, Egypt
| | - Mohanad A Ibrahim
- Data Science Program, King Abdullah International Medical Research Center, 11481, Riyadh, Saudi Arabia
| | - Ahmed Bahieldin
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
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12
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Ray SK, Mukherjee S. Molecular perspectives on systemic priming and concomitant immunity in colorectal carcinoma. J Egypt Natl Canc Inst 2024; 36:7. [PMID: 38462581 DOI: 10.1186/s43046-024-00211-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 02/15/2024] [Indexed: 03/12/2024] Open
Abstract
The progression of metastasis, a complex systemic disease, is facilitated by interactions between tumor cells and their isolated microenvironments. Over the past few decades, researchers have investigated the metastatic spread of cancer extensively, identifying multiple stages in the process, such as intravasation, extravasation, tumor latency, and the development of micrometastasis and macrometastasis. The premetastatic niche is established in target organs by the accumulation of aberrant immune cells and extracellular matrix proteins. The "seed and soil" idea, which has become widely known and accepted, is being used to this day to guide cancer studies. Changes in the local and systemic immune systems have a major impact on whether an infection spreads or not. The belief that the immune response may play a role in slowing tumor growth and may be beneficial against the metastatic disease underpins the responsiveness shown in the immunological landscape of metastasis. Various hypotheses on the phylogenesis of metastases have been proposed in the past. The primary tumor's secreting factors shape the intratumoral microenvironment and the immune landscape, allowing this progress to be made. Therefore, it is evident that among disseminated tumor cells, there are distinct phenotypes that either carry budding for metastasis or have the ability to obtain this potential or in systemic priming through contact with substantial metastatic niches that have implications for medicinal chemistry. Concurrent immunity signals that the main tumor induces an immune response that may not be strong enough to eradicate the tumor. Immunotherapy's success with some cancer patients shows that it is possible to effectively destroy even advanced-stage tumors by modifying the microenvironment and tumor-immune cell interactions. This review focuses on the metastasome in colorectal carcinoma and the therapeutic implications of site-specific metastasis, systemic priming, tumor spread, and the relationship between the immune system and metastasis.
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Affiliation(s)
- Suman Kumar Ray
- Independent Researcher, Bhopal, Madhya Pradesh, 462020, India
| | - Sukhes Mukherjee
- Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, 462020, India.
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13
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Zhong Q, Reyes-Jurado F, Calumba KF. Structured soft particulate matters for delivery of bioactive compounds in foods and functioning in the colon. SOFT MATTER 2024; 20:277-293. [PMID: 38090993 DOI: 10.1039/d3sm00866e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
The present review discusses challenges, perspectives, and current needs of delivering bioactive compounds (BCs) using soft particulate matters (SPMs) for gut health. SPMs can entrap BCs for incorporation in foods, preserve their bioactivities during processing, storage, and gastrointestinal digestion, and deliver BCs to functioning sites in the colon. To enable these functions, physical, chemical, and biological properties of BCs are integrated in designing various types of SPMs to overcome environmental factors reducing the bioavailability and bioactivity of BCs. The design principles are applied using food grade molecules with the desired properties to produce SPMs by additionally considering the cost, sustainability, and scalability of manufacturing processes. Lastly, to make delivery systems practical, impacts of SPMs on food quality are to be evaluated case by case, and health benefits of functional foods incorporated with delivery systems are to be confirmed and must outweigh the cost of preparing SPMs.
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Affiliation(s)
- Qixin Zhong
- Department of Food Science, University of Tennessee, Knoxville, TN, USA.
| | | | - Kriza Faye Calumba
- Department of Food Science, University of Tennessee, Knoxville, TN, USA.
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14
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Khorasani M. Role of cGAS-STING in colorectal cancer: A new window for treatment strategies. Cytokine 2024; 173:156422. [PMID: 37948979 DOI: 10.1016/j.cyto.2023.156422] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 10/29/2023] [Accepted: 11/01/2023] [Indexed: 11/12/2023]
Abstract
Colorectal cancer (CRC) is a common and deadly form of cancer, leading to the need for new therapeutic targets and strategies for treatment. Recent studies have shown the cGAS-STING pathway to be a promising target for cancer therapy. The cGAS-STING pathway is a part of the innate immune system and serves to identify DNA damage and viral infection, promoting an immune response. Activation of this pathway leads to the production of immune mediators, such as type I interferons, that activate immune cells to attack cancer cells. Research has identified the cGAS-STING pathway as a frequently dysregulated component in CRC, promoting tumor growth and metastasis, or leading to chronic inflammation and tissue damage. The modulation of this pathway presents a potential therapeutic approach, either activating or inhibiting the pathway to enhance the immune response and prevent inflammation, respectively. Developing drugs that can modulate the cGAS-STING pathway offers promise for improving treatment outcomes for CRC patients. The present review explores recent research on the role of cGAS-STING in CRC and highlights the potential therapeutic benefits of targeting this pathway.
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Affiliation(s)
- Milad Khorasani
- Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran; Department of Biochemistry and Nutrition, Neyshabur University of Medical Sciences, Neyshabur, Iran.
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15
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Mirabdolhosseini SM, Yaghoob Taleghani M, Rejali L, Sadeghi H, Fatemi N, Tavallaei M, Famil Meyari A, Saeidi N, Ketabi Moghadam P, Sadeghi A, Asadzadeh Aghdaei H, Zali MR, Nazemalhosseini Mojarad E. Rare single-nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome. Cancer Rep (Hoboken) 2024; 7:e1930. [PMID: 37919876 PMCID: PMC10809271 DOI: 10.1002/cnr2.1930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/27/2023] [Accepted: 10/16/2023] [Indexed: 11/04/2023] Open
Abstract
BACKGROUND Approximately 5% of colorectal cancers (CRCs) are hereditary. Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is the most common form of recognized hereditary CRC. Although Iran, as a developing country, has a high incidence of CRC, the spectrum of variants has yet to be thoroughly investigated. AIMS This study aimed to investigate pathogenic and non-pathogenic variants in MLH1 and MSH2 genes in Iranian patients with suspected Lynch syndrome (sLS). METHODS AND RESULTS In the present study, 25 peripheral blood samples were collected from patients with sLS and high microsatellite instability (MSI-H). After DNA extraction, all samples underwent polymerase chain reaction and Sanger sequencing to identify the variants in the exons of MLH1 and MSH2 genes. The identified variants were interpreted using prediction tools, and were finally reported under ACMG guidelines. In our study population, 13 variants were found in the MLH1 gene and 8 in the MSH2 gene. Interestingly, 7 of the 13 MLH1 variants and 3 of the 8 MSH2 variants were novel, whereas the remaining variants were previously reported or available in databases. In addition, some patients with sLS did not have variants in the exons of the MLH1 and MSH2 genes. The variants detected in the MLH1 and MSH2 genes had specific characteristics regarding the number, area of occurrence, and their relationship with demographic and clinicopathologic features. CONCLUSION Overall, our results suggest that analysis of MLH1 and MSH2 genes alone is insufficient in the Iranian population, and more comprehensive tests are recommended for detecting LS.
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Affiliation(s)
- Seyed Mohsen Mirabdolhosseini
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Mohammad Yaghoob Taleghani
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Leili Rejali
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Hossein Sadeghi
- Genomic Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Nayeralsadat Fatemi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Mehdi Tavallaei
- Department of Colorectal SurgeryMedical Science of Shahid Beheshti UniversityTehranIran
| | - Amin Famil Meyari
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Narges Saeidi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Pardis Ketabi Moghadam
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
| | - Ehsan Nazemalhosseini Mojarad
- Gastroenterology and Liver Diseases Research CenterResearch Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesTehranIran
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16
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Sardari A, Usefi H. Machine learning-based meta-analysis of colorectal cancer and inflammatory bowel disease. PLoS One 2023; 18:e0290192. [PMID: 38134011 PMCID: PMC10745176 DOI: 10.1371/journal.pone.0290192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 11/30/2023] [Indexed: 12/24/2023] Open
Abstract
Colorectal cancer (CRC) is a major global health concern, resulting in numerous cancer-related deaths. CRC detection, treatment, and prevention can be improved by identifying genes and biomarkers. Despite extensive research, the underlying mechanisms of CRC remain elusive, and previously identified biomarkers have not yielded satisfactory insights. This shortfall may be attributed to the predominance of univariate analysis methods, which overlook potential combinations of variants and genes contributing to disease development. Here, we address this knowledge gap by presenting a novel multivariate machine-learning strategy to pinpoint genes associated with CRC. Additionally, we applied our analysis pipeline to Inflammatory Bowel Disease (IBD), as IBD patients face substantial CRC risk. The importance of the identified genes was substantiated by rigorous validation across numerous independent datasets. Several of the discovered genes have been previously linked to CRC, while others represent novel findings warranting further investigation. A Python implementation of our pipeline can be accessed publicly at https://github.com/AriaSar/CRCIBD-ML.
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Affiliation(s)
- Aria Sardari
- Department of Computer Science, Memorial University of Newfoundland, St. John’s, NL, Canada
| | - Hamid Usefi
- Department of Computer Science, Memorial University of Newfoundland, St. John’s, NL, Canada
- Department of Mathematics & Statistics, Memorial University of Newfoundland, St. John’s, NL, Canada
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17
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Alipourgivi F, Motolani A, Qiu AY, Qiang W, Yang GY, Chen S, Lu T. Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment. Int J Mol Sci 2023; 25:154. [PMID: 38203325 PMCID: PMC10779007 DOI: 10.3390/ijms25010154] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/06/2023] [Accepted: 12/11/2023] [Indexed: 01/12/2024] Open
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States, with an estimated 52,000 deaths in 2023. Though significant progress has been made in both diagnosis and treatment of CRC in recent years, genetic heterogeneity of CRC-the culprit for possible CRC relapse and drug resistance, is still an insurmountable challenge. Thus, developing more effective therapeutics to overcome this challenge in new CRC treatment strategies is imperative. Genetic and epigenetic changes are well recognized to be responsible for the stepwise development of CRC malignancy. In this review, we focus on detailed genetic alteration information about the nuclear factor (NF)-κB signaling, including both NF-κB family members, and their regulators, such as protein arginine methyltransferase 5 (PRMT5), and outer dynein arm docking complex subunit 2 (ODAD2, also named armadillo repeat-containing 4, ARMC4), etc., in CRC patients. Moreover, we provide deep insight into different CRC research models, with a particular focus on patient-derived xenografts (PDX) and organoid models, and their potential applications in CRC research. Genetic alterations on NF-κB signaling components are estimated to be more than 50% of the overall genetic changes identified in CRC patients collected by cBioportal for Cancer Genomics; thus, emphasizing its paramount importance in CRC progression. Consequently, various genetic alterations on NF-κB signaling may hold great promise for novel therapeutic development in CRC. Future endeavors may focus on utilizing CRC models (e.g., PDX or organoids, or isogenic human embryonic stem cell (hESC)-derived colonic cells, or human pluripotent stem cells (hPSC)-derived colonic organoids, etc.) to further uncover the underpinning mechanism of these genetic alterations in NF-κB signaling in CRC progression. Moreover, establishing platforms for drug discovery in dishes, and developing Biobanks, etc., may further pave the way for the development of innovative personalized medicine to treat CRC in the future.
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Affiliation(s)
- Faranak Alipourgivi
- Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (F.A.); (A.M.)
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA
| | - Aishat Motolani
- Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (F.A.); (A.M.)
| | - Alice Y. Qiu
- Center for Developmental Therapeutics, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA; (A.Y.Q.); (W.Q.)
| | - Wenan Qiang
- Center for Developmental Therapeutics, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA; (A.Y.Q.); (W.Q.)
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA;
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Guang-Yu Yang
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA;
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Shuibing Chen
- Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA;
| | - Tao Lu
- Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (F.A.); (A.M.)
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA
- Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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18
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Saadi S, Aarab M, Tabyaoui I, Jouti NT. Circulating tumor cells in colorectal cancer - a review of detection methods and clinical relevance. Contemp Oncol (Pozn) 2023; 27:123-131. [PMID: 38239860 PMCID: PMC10793619 DOI: 10.5114/wo.2023.133740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 09/08/2023] [Indexed: 01/22/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer; it is one of the leading malignancies contributing to cancer mortality. Colorectal cancer is the third most diagnosed cancer in men and the second in women worldwide. Diagnosis of CRC depends on several clinical features such as age, primary site, tumor-node-metastasis stage, genetic parameters and the presence or absence of metastasis. The latter is a phenomenon that is induced by the shedding of tumor cells in the blood circulation by the primary tumor. Such cells are known as circulating tumor cells (CTCs). The detection of CTCs is quite challenging due to their scarceness; thus it requires their enrichment and characterization. Studying the utility of CTCs in the diagnosis of CRC has been the aim of several studies; they demonstrated that ≥ 3 CTCs in 7.5 ml of blood is correlated with a worse prognosis and short progression-free and overall survival. Circulating tumor cells have also been monitored to study treatment response and predict future relapses. The present review aims to bring to light the different techniques used to detect and characterize these malignant cells in the peripheral blood of cancer patients as well as the clinical relevance of CTCs in CRC patients.
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Affiliation(s)
- Salma Saadi
- Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology – Faculty of Medicine and Pharmacy of Casablanca Hassan II University, Casablanca, Morocco
| | - Meryem Aarab
- Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology – Faculty of Medicine and Pharmacy of Casablanca Hassan II University, Casablanca, Morocco
| | - Imane Tabyaoui
- Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology – Faculty of Medicine and Pharmacy of Casablanca Hassan II University, Casablanca, Morocco
| | - Nadia Tahiri Jouti
- Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology – Faculty of Medicine and Pharmacy of Casablanca Hassan II University, Casablanca, Morocco
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19
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Shen L, Lin C, Lu W, He J, Wang Q, Huang Y, Zheng X, Wang Z. Involvement of the oncogenic small nucleolar RNA SNORA24 in regulation of p53 stability in colorectal cancer. Cell Biol Toxicol 2023; 39:1377-1394. [PMID: 36087186 DOI: 10.1007/s10565-022-09765-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 08/26/2022] [Indexed: 11/02/2022]
Abstract
Colorectal cancer (CRC) is a common malignant cancer worldwide. Although the molecular mechanism of CRC carcinogenesis has been studied extensively, the details remain unclear. Small nucleolar RNAs (snoRNAs) have recently been reported to have essential functions in carcinogenesis, although their roles in CRC pathogenesis are largely unknown. In this study, we found that the H/ACA snoRNA SNORA24 was upregulated in various cancers, including CRC. SNORA24 expression was significantly associated with age and history of colon polyps in CRC patient cohorts, with high expression associated with a decreased 5-year overall survival. Our results indicated that the oncogenic function of SNORA24 is mediated by promoting G1/S phase transformation, cell proliferation, colony formation, and growth of xenograft tumors. Furthermore, SNORA24 knockdown induced massive apoptosis. RNA-sequencing and gene ontology (GO) enrichment analyses were performed to explore its downstream targets. Finally, we confirmed that SNORA24 regulates p53 protein stability in a proteasomal degradation pathway. Our study clarifies the oncogenic role of SNORA24 in CRC and advance the current model of the role of the p53 pathway in this process.
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Affiliation(s)
- Liping Shen
- Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Chuxian Lin
- Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Wenqing Lu
- Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China
- College of Life Sciences, Hebei University, Baoding, Hebei, 071002, China
| | - Junyan He
- The First Affiliated Hospital, Department of Radiation Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Qi Wang
- Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Yujv Huang
- Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Xiaofei Zheng
- Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
| | - Zhidong Wang
- Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
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20
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Tian J, Afebu KO, Bickerdike A, Liu Y, Prasad S, Nelson BJ. Fundamentals of Bowel Cancer for Biomedical Engineers. Ann Biomed Eng 2023; 51:679-701. [PMID: 36786901 PMCID: PMC9927048 DOI: 10.1007/s10439-023-03155-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 01/21/2023] [Indexed: 02/15/2023]
Abstract
Bowel cancer is a multifactorial disease arising from a combination of genetic predisposition and environmental factors. Detection of bowel cancer and its precursor lesions is predominantly performed by either visual inspection of the colonic mucosa during endoscopy or cross-sectional imaging. Most cases are diagnosed when the cancer is already at an advanced stage. These modalities are less reliable for detecting lesions at the earliest stages, when they are typically small or flat. Removal of lesions at the earliest possible stage reduces the risk of cancer death, which is largely due to a reduced risk of subsequent metastasis. In this review, we summarised the origin of bowel cancer and the mechanism of its metastasis. In particular, we reviewed a broad spectrum of literatures covering the biomechanics of bowel cancer and its measurement techniques that are pertinent to the successful development of a bowel cancer diagnostic device. We also reviewed existing bowel cancer diagnostic techniques that are available for clinical use. Finally, we outlined current clinical needs and highlighted the potential roles of medical robotics on early bowel cancer diagnosis.
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Affiliation(s)
- Jiyuan Tian
- Engineering Department, University of Exeter, North Park Road, Exeter, EX4 4QF UK
| | | | - Andrew Bickerdike
- Engineering Department, University of Exeter, North Park Road, Exeter, EX4 4QF UK
| | - Yang Liu
- Engineering Department, University of Exeter, North Park Road, Exeter, EX4 4QF UK
| | - Shyam Prasad
- Royal Devon University Healthcare NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW UK
| | - Bradley J. Nelson
- Multi-Scale Robotics Lab, ETH Zürich, Tannenstrasse 3, 8092 Zurich, Switzerland
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21
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Kim J, Kim H, Lee MS, Lee H, Kim YJ, Lee WY, Yun SH, Kim HC, Hong HK, Hannenhalli S, Cho YB, Park D, Choi SS. Transcriptomes of the tumor-adjacent normal tissues are more informative than tumors in predicting recurrence in colorectal cancer patients. J Transl Med 2023; 21:209. [PMID: 36941605 PMCID: PMC10029176 DOI: 10.1186/s12967-023-04053-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 03/10/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND Previous investigations of transcriptomic signatures of cancer patient survival and post-therapy relapse have focused on tumor tissue. In contrast, here we show that in colorectal cancer (CRC) transcriptomes derived from normal tissues adjacent to tumors (NATs) are better predictors of relapse. RESULTS Using the transcriptomes of paired tumor and NAT specimens from 80 Korean CRC patients retrospectively determined to be in recurrence or nonrecurrence states, we found that, when comparing recurrent with nonrecurrent samples, NATs exhibit a greater number of differentially expressed genes (DEGs) than tumors. Training two prognostic elastic net-based machine learning models-NAT-based and tumor-based in our Samsung Medical Center (SMC) cohort, we found that NAT-based model performed better in predicting the survival when the model was applied to the tumor-derived transcriptomes of an independent cohort of 450 COAD patients in TCGA. Furthermore, compositions of tumor-infiltrating immune cells in NATs were found to have better prognostic capability than in tumors. We also confirmed through Cox regression analysis that in both SMC-CRC as well as in TCGA-COAD cohorts, a greater proportion of genes exhibited significant hazard ratio when NAT-derived transcriptome was used compared to when tumor-derived transcriptome was used. CONCLUSIONS Taken together, our results strongly suggest that NAT-derived transcriptomes and immune cell composition of CRC are better predictors of patient survival and tumor recurrence than the primary tumor.
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Affiliation(s)
- Jinho Kim
- Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, 24341, Korea
| | - Hyunjung Kim
- Precision Medicine Center, Future Innovation Research Division, Seoul National University Bundang Hospital, Seongnam, 13620, Korea
| | - Min-Seok Lee
- Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, 24341, Korea
| | - Heetak Lee
- Precision Medicine Center, Future Innovation Research Division, Seoul National University Bundang Hospital, Seongnam, 13620, Korea
- Center for Genome Engineering, Institute for Basic Science, 55, Expo-ro, Yuseng-gu, Daejeon, 34126, Korea
| | - Yeon Jeong Kim
- Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, Korea
| | - Woo Yong Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea
| | - Seong Hyeon Yun
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea
| | - Hee Cheol Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea
| | - Hye Kyung Hong
- Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, Korea
| | - Sridhar Hannenhalli
- Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, Bethesda, 20814, MD, USA
| | - Yong Beom Cho
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Korea.
| | | | - Sun Shim Choi
- Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, 24341, Korea.
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22
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Zuo BW, Yao WX, Fang MD, Ren J, Tu LL, Fan RJ, Zhang YM. Boris knockout eliminates AOM/DSS-induced in situ colorectal cancer by suppressing DNA damage repair and inflammation. Cancer Sci 2023; 114:1972-1985. [PMID: 36692143 PMCID: PMC10154901 DOI: 10.1111/cas.15732] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 01/10/2023] [Accepted: 01/18/2023] [Indexed: 01/25/2023] Open
Abstract
The Brother of Regulator of Imprinted Sites (BORIS, gene symbol CTCFL) has previously been shown to promote colorectal cancer cell proliferation, inhibit cancer cell apoptosis, and resist chemotherapy. However, it is unknown whether Boris plays a role in the progression of in situ colorectal cancer. Here Boris knockout (KO) mice were constructed. The function loss of the cloned Boris mutation that was retained in KO mice was verified by testing its activities in colorectal cell lines compared with the Boris wild-type gene. Boris knockout reduced the incidence and severity of azoxymethane/dextran sulfate-sodium (AOM/DSS)-induced colon cancer. The importance of Boris is emphasized in the progression of in situ colorectal cancer. Boris knockout significantly promoted the phosphorylation of γH2AX and the DNA damage in colorectal cancer tissues and suppressed Wnt and MAPK pathways that are responsible for the callback of DNA damage repair. This indicates the strong inhibition of colorectal cancer in Boris KO mice. By considering that the DSS-promoted inflammation contributes to tumorigenesis, Boris KO mice were also studied in DSS-induced colitis. Our data showed that Boris knockout alleviated DSS-induced colitis and that Boris knockdown inhibited the NF-κB signaling pathway in RAW264.7 cells. Therefore Boris knockout eliminates colorectal cancer generation by inhibiting DNA damage repair in cancer cells and relieving inflammation in macrophages. Our findings demonstrate the importance of Boris in the development of in situ colorectal cancer and provide evidence for the feasibility of colorectal cancer therapy on Boris.
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Affiliation(s)
- Bo-Wen Zuo
- School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Wan-Xin Yao
- School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Meng-Die Fang
- School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Juan Ren
- School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Ling-Lan Tu
- School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Run-Jie Fan
- School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Yan-Mei Zhang
- School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
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23
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Peixoto C, Lopes MB, Martins M, Casimiro S, Sobral D, Grosso AR, Abreu C, Macedo D, Costa AL, Pais H, Alvim C, Mansinho A, Filipe P, Costa PMD, Fernandes A, Borralho P, Ferreira C, Malaquias J, Quintela A, Kaplan S, Golkaram M, Salmans M, Khan N, Vijayaraghavan R, Zhang S, Pawlowski T, Godsey J, So A, Liu L, Costa L, Vinga S. Identification of biomarkers predictive of metastasis development in early-stage colorectal cancer using network-based regularization. BMC Bioinformatics 2023; 24:17. [PMID: 36647008 PMCID: PMC9841719 DOI: 10.1186/s12859-022-05104-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 12/07/2022] [Indexed: 01/18/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most deathly worldwide. It is a very heterogeneous disease that can develop via distinct pathways where metastasis is the primary cause of death. Therefore, it is crucial to understand the molecular mechanisms underlying metastasis. RNA-sequencing is an essential tool used for studying the transcriptional landscape. However, the high-dimensionality of gene expression data makes selecting novel metastatic biomarkers problematic. To distinguish early-stage CRC patients at risk of developing metastasis from those that are not, three types of binary classification approaches were used: (1) classification methods (decision trees, linear and radial kernel support vector machines, logistic regression, and random forest) using differentially expressed genes (DEGs) as input features; (2) regularized logistic regression based on the Elastic Net penalty and the proposed iTwiner-a network-based regularizer accounting for gene correlation information; and (3) classification methods based on the genes pre-selected using regularized logistic regression. Classifiers using the DEGs as features showed similar results, with random forest showing the highest accuracy. Using regularized logistic regression on the full dataset yielded no improvement in the methods' accuracy. Further classification using the pre-selected genes found by different penalty factors, instead of the DEGs, significantly improved the accuracy of the binary classifiers. Moreover, the use of network-based correlation information (iTwiner) for gene selection produced the best classification results and the identification of more stable and robust gene sets. Some are known to be tumor suppressor genes (OPCML-IT2), to be related to resistance to cancer therapies (RAC1P3), or to be involved in several cancer processes such as genome stability (XRCC6P2), tumor growth and metastasis (MIR602) and regulation of gene transcription (NME2P2). We show that the classification of CRC patients based on pre-selected features by regularized logistic regression is a valuable alternative to using DEGs, significantly increasing the models' predictive performance. Moreover, the use of correlation-based penalization for biomarker selection stands as a promising strategy for predicting patients' groups based on RNA-seq data.
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Affiliation(s)
- Carolina Peixoto
- grid.9983.b0000 0001 2181 4263INESC-ID, Instituto Superior Técnico, Universidade de Lisboa, Rua Alves Redol 9, 1000-029 Lisbon, Portugal
| | - Marta B. Lopes
- NOVA Laboratory for Computer Science and Informatics (NOVA LINCS), NOVA School of Science and Technology, 2829-516 Caparica, Portugal ,Center for Mathematics and Applications (NOVA MATH), NOVA School of Science and Technology (FCT NOVA), 2829-516 Caparica, Portugal
| | - Marta Martins
- grid.9983.b0000 0001 2181 4263Instituto de Medicina Molecular - João Lobo Antunes, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal
| | - Sandra Casimiro
- grid.9983.b0000 0001 2181 4263Instituto de Medicina Molecular - João Lobo Antunes, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal
| | - Daniel Sobral
- grid.10772.330000000121511713Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal ,grid.10772.330000000121511713UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal
| | - Ana Rita Grosso
- grid.10772.330000000121511713Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal ,grid.10772.330000000121511713UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal
| | - Catarina Abreu
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Daniela Macedo
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Ana Lúcia Costa
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Helena Pais
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Cecília Alvim
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - André Mansinho
- grid.9983.b0000 0001 2181 4263Instituto de Medicina Molecular - João Lobo Antunes, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal ,grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Pedro Filipe
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Pedro Marques da Costa
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Afonso Fernandes
- grid.9983.b0000 0001 2181 4263Instituto de Medicina Molecular - João Lobo Antunes, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal
| | - Paula Borralho
- grid.9983.b0000 0001 2181 4263Instituto de Medicina Molecular - João Lobo Antunes, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal
| | - Cristina Ferreira
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - João Malaquias
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - António Quintela
- grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Shannon Kaplan
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Mahdi Golkaram
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Michael Salmans
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Nafeesa Khan
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Raakhee Vijayaraghavan
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Shile Zhang
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Traci Pawlowski
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Jim Godsey
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Alex So
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Li Liu
- grid.185669.50000 0004 0507 3954Illumina Inc., 5200 Illumina Way, San Diego, CA 92122 USA
| | - Luís Costa
- grid.9983.b0000 0001 2181 4263Instituto de Medicina Molecular - João Lobo Antunes, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal ,grid.418341.b0000 0004 0474 1607Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Susana Vinga
- grid.9983.b0000 0001 2181 4263INESC-ID, Instituto Superior Técnico, Universidade de Lisboa, Rua Alves Redol 9, 1000-029 Lisbon, Portugal ,grid.9983.b0000 0001 2181 4263IDMEC, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001 Lisbon, Portugal
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24
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Ashique S, Garg A, Singh V, Rai G, Mishra N, Soni ML, Kumar S, Madamsetty VS. Role of Block Copolymers in Colon Cancer. BLOCK CO-POLYMERIC NANOCARRIERS: DESIGN, CONCEPT, AND THERAPEUTIC APPLICATIONS 2023:181-209. [DOI: 10.1007/978-981-99-6917-3_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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25
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Shi Y, Yasui M, Hara-Chikuma M. AQP9 transports lactate in tumor-associated macrophages to stimulate an M2-like polarization that promotes colon cancer progression. Biochem Biophys Rep 2022; 31:101317. [PMID: 35967760 PMCID: PMC9372591 DOI: 10.1016/j.bbrep.2022.101317] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 07/04/2022] [Accepted: 07/15/2022] [Indexed: 11/18/2022] Open
Abstract
Macrophages play a major role in the immune defense against pathogenic factors; however, they can lead to tumor exacerbation and metastasis, as the tumor microenvironment (TME) polarizes tumor-associated macrophages (TAMs) into the M2 subtype. Lactate, a metabolite produced by carcinoma cells at high concentrations in the TME, induces an M2-polarization in macrophages, which ultimately leads to the secretion of factors, such as vascular endothelial growth factor (VEGF), and promotes tumor progression. However, the effect of TAM lactate import on tumor progression has not been fully elucidated. Aquaporin 9 (AQP9) is a transporter of water and glycerol expressed in macrophages. Here, we used a tumor allograft mouse model to show that AQP9 knockout (AQP9−/−) mice were more resistant against tumor cell growth and exhibited a suppressive M2-like polarization in tumor tissue than wild-type mice. Moreover, we discovered that the primary bone marrow-derived macrophages from AQP9−/− mice were less sensitive to lactate stimulation and exhibited reduced M2-like polarization as well as decreased VEGF production. To further investigate the role of AQP9 in macrophage polarization, we overexpressed AQP9 in Chinese hamster ovary cells and found that AQP9 functioned in lactate import. In contrast, primary AQP9−/− macrophages and AQP9 knockdown RAW264.7 cells exhibited a reduced lactate transport rate, suggesting the involvement of AQP9 in lactate transport in macrophages. Together, our results reveal the mechanism by which the TME modifies the polarization and function of tumor-infiltrating macrophages via AQP9 transport function.
Tumor growth was suppressed in AQP9-deficient mice. M2-like TAMs were reduced in tumor tissues of AQP9-deficient mice. AQP9 deficiency attenuated lactate-induced M2 polarization in macrophages. AQP9 is a lactate transporter in macrophages.
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Affiliation(s)
- Yundi Shi
- Department of Pharmacology, Keio University School of Medicine, Japan
| | - Masato Yasui
- Department of Pharmacology, Keio University School of Medicine, Japan
- Center for Water Biology and Medicine, Keio University Global Research Institute, Japan
| | - Mariko Hara-Chikuma
- Department of Pharmacology, Keio University School of Medicine, Japan
- Corresponding author. Department of Pharmacology, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160, Japan.
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26
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Styk J, Buglyó G, Pös O, Csók Á, Soltész B, Lukasz P, Repiská V, Nagy B, Szemes T. Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer. Cancers (Basel) 2022; 14:3712. [PMID: 35954375 PMCID: PMC9367600 DOI: 10.3390/cancers14153712] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/21/2022] [Accepted: 07/26/2022] [Indexed: 12/02/2022] Open
Abstract
Colorectal cancer (CRC) is the 3rd most common malignant neoplasm worldwide, with more than two million new cases diagnosed yearly. Despite increasing efforts in screening, many cases are still diagnosed at a late stage, when mortality is high. This paper briefly reviews known genetic causes of CRC (distinguishing between sporadic and familial forms) and discusses potential and confirmed nucleic acid biomarkers obtainable from liquid biopsies, classified by their molecular features, focusing on clinical relevance. We comment on advantageous aspects such as better patient compliance due to blood sampling being minimally invasive, the possibility to monitor mutation characteristics of sporadic and hereditary CRC in a disease showing genetic heterogeneity, and using up- or down-regulated circulating RNA markers to reveal metastasis or disease recurrence. Current difficulties and thoughts on some possible future directions are also discussed. We explore current evidence in the field pointing towards the introduction of personalized CRC management.
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Affiliation(s)
- Jakub Styk
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia;
- Comenius University Science Park, Comenius University, 841 04 Bratislava, Slovakia; (O.P.); (B.N.); (T.S.)
- Geneton Ltd., 841 04 Bratislava, Slovakia
| | - Gergely Buglyó
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; (G.B.); (Á.C.); (B.S.)
| | - Ondrej Pös
- Comenius University Science Park, Comenius University, 841 04 Bratislava, Slovakia; (O.P.); (B.N.); (T.S.)
- Geneton Ltd., 841 04 Bratislava, Slovakia
| | - Ádám Csók
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; (G.B.); (Á.C.); (B.S.)
| | - Beáta Soltész
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; (G.B.); (Á.C.); (B.S.)
| | - Peter Lukasz
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1082 Budapest, Hungary;
| | - Vanda Repiská
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia;
- Medirex Group Academy, n.p.o., 949 05 Nitra, Slovakia
| | - Bálint Nagy
- Comenius University Science Park, Comenius University, 841 04 Bratislava, Slovakia; (O.P.); (B.N.); (T.S.)
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; (G.B.); (Á.C.); (B.S.)
| | - Tomáš Szemes
- Comenius University Science Park, Comenius University, 841 04 Bratislava, Slovakia; (O.P.); (B.N.); (T.S.)
- Geneton Ltd., 841 04 Bratislava, Slovakia
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, 842 05 Bratislava, Slovakia
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27
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Manzoor S, Muhammad JS, Maghazachi AA, Hamid Q. Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance. Front Oncol 2022; 12:924290. [PMID: 35912261 PMCID: PMC9329589 DOI: 10.3389/fonc.2022.924290] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/06/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal cancer (CRC) is among the topmost malignancies for both genders. Despite the high incidence rate and advances in diagnostic tools, treatment in many cases is still ineffective. Most cancerous lesions in CRC begin as benign, followed by the development of invasive forms and metastases. The development of CRC has been linked to defects in autophagy, which plays both a pro-and anti-tumor role and is mainly context-dependent. Autophagy suppression could enhance apoptosis via p53 activation, or autophagy also promotes tumor progression by maintaining tumor growth and increasing resistance to chemotherapy. Autophagy promotes the invasion and metastasis of CRC cells via increased epithelial-mesenchymal transition (EMT). Moreover, dysbiosis of gut microbiota upregulated autophagy and metastasis markers. Autophagy responses may also modulate the tumor microenvironment (TME) via regulating the differentiation process of several innate immune cells. Treatments that promote tumor cell death by stimulating or inhibiting autophagy could be beneficial if used as an adjunct treatment, but the precise role of various autophagy-modulating drugs in CRC patients is needed to be explored. In this article, we present an overview of the autophagy process and its role in the pathogenesis and therapeutic resistance of CRC. Also, we focused on the current understanding of the role of the EMT and TME, including its relation to gut microbiota and immune cells, in autophagic manipulation of CRC. We believe that there is a potential link between autophagy, TME, EMT, and drug resistance, suggesting that further studies are needed to explore this aspect.
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Affiliation(s)
- Shaista Manzoor
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Jibran Sualeh Muhammad
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Azzam A. Maghazachi
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Qutayba Hamid
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, QC, Canada
- *Correspondence: Qutayba Hamid,
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28
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Yan H, Ye Y, Zhao H, Zuo H, Li Y. Single-Cell RNA Sequencing for Analyzing the Intestinal Tract in Healthy and Diseased Individuals. Front Cell Dev Biol 2022; 10:915654. [PMID: 35874838 PMCID: PMC9300858 DOI: 10.3389/fcell.2022.915654] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/30/2022] [Indexed: 11/13/2022] Open
Abstract
The intestinal tract is composed of different cell lineages with distinct functions and gene expression profiles, providing uptake of nutrients and protection against insults to the gut lumen. Changes in or damage to the cellulosity or local environment of the intestinal tract can cause various diseases. Single-cell RNA sequencing (scRNA-seq) is a powerful tool for profiling and analyzing individual cell data, making it possible to resolve rare and intermediate cell states that are hardly observed at the bulk level. In this review, we discuss the application of intestinal tract scRNA-seq in identifying novel cell subtypes and states, targets, and explaining the molecular mechanisms involved in intestinal diseases. Finally, we provide future perspectives on using single-cell techniques to discover molecular and cellular targets and biomarkers as a new approach for developing novel therapeutics for intestinal diseases.
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Affiliation(s)
- Hua Yan
- Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China
- The Seventh Medical Center of PLA General Hospital, Beijing, China
| | - Yumeng Ye
- Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China
| | - HanZheng Zhao
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hongyan Zuo
- Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China
- Department of Pathology, Chengde Medical College, Chengde, China
- *Correspondence: Hongyan Zuo, ; Yang Li,
| | - Yang Li
- Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China
- Department of Pathology, Chengde Medical College, Chengde, China
- Academy of Life Sciences, Anhui Medical University, Hefei, China
- *Correspondence: Hongyan Zuo, ; Yang Li,
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29
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Song Y, Baxter SS, Dai L, Sanders C, Burkett S, Baugher RN, Mellott SD, Young TB, Lawhorn HE, Difilippantonio S, Karim B, Kadariya Y, Pinto LA, Testa JR, Shoemaker RH. Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability. Cancers (Basel) 2022; 14:3108. [PMID: 35804881 PMCID: PMC9264972 DOI: 10.3390/cancers14133108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 06/10/2022] [Accepted: 06/21/2022] [Indexed: 12/10/2022] Open
Abstract
Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. We characterized an orthotopic model using MMe cells derived from Cdkn2a+/-;Nf2+/- mice chronically injected with asbestos. These MMe cells were tumorigenic upon intraperitoneal injection. Moreover, MMe cells showed mixed chromosome and microsatellite instability, supporting the notion that genomic instability is relevant in MMe pathogenesis. In addition, microsatellite markers were detectable in the plasma of tumor-bearing mice, indicating a potential use for early cancer detection and monitoring the effects of interventions. This orthotopic model with rapid development of MMe without asbestos exposure represents genomic instability and specific molecular targets for therapeutic or preventive interventions to enable preclinical proof of concept for the intervention in an immunocompetent setting.
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Affiliation(s)
- Yurong Song
- Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (S.S.B.); (L.D.); (L.A.P.)
| | - Shaneen S. Baxter
- Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (S.S.B.); (L.D.); (L.A.P.)
| | - Lisheng Dai
- Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (S.S.B.); (L.D.); (L.A.P.)
| | - Chelsea Sanders
- Animal Research Technical Support of Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (C.S.); (S.D.)
| | - Sandra Burkett
- Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD 21702, USA;
| | - Ryan N. Baugher
- CLIA Molecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (R.N.B.); (S.D.M.); (T.B.Y.); (H.E.L.)
| | - Stephanie D. Mellott
- CLIA Molecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (R.N.B.); (S.D.M.); (T.B.Y.); (H.E.L.)
| | - Todd B. Young
- CLIA Molecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (R.N.B.); (S.D.M.); (T.B.Y.); (H.E.L.)
| | - Heidi E. Lawhorn
- CLIA Molecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (R.N.B.); (S.D.M.); (T.B.Y.); (H.E.L.)
| | - Simone Difilippantonio
- Animal Research Technical Support of Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (C.S.); (S.D.)
| | - Baktiar Karim
- Molecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA;
| | - Yuwaraj Kadariya
- Cancer Signaling and Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; (Y.K.); (J.R.T.)
| | - Ligia A. Pinto
- Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (S.S.B.); (L.D.); (L.A.P.)
| | - Joseph R. Testa
- Cancer Signaling and Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; (Y.K.); (J.R.T.)
| | - Robert H. Shoemaker
- Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA;
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Dawood M, Younus ZM, Alnori M, Mahmood S. The Biological Role of Advanced Glycation End Products in the Development and Progression of Colorectal Cancer. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
“Colorectal cancer” (CRC) is one of the most prevalent cancers, posing a scientific challenge and serving as a model for investigating the molecular pathways underlying its development. “Advanced glycation end products” (AGEs) have drawn interest in this context. The buildup of these diverse, chemically complex groups, which are formed by a “non-enzymatic interaction” between reducing sugar and a range of macromolecules, significantly increases “inflammation and oxidative stress” in the body, which has long been associated to cancer formation. The traditional pathways that promote AGE formation, as well as the significance of AGEs’ interaction with the receptor for “advanced glycation end products” (RAGE) and other means involved in CRC initiation and progression, are discussed in this review.
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Talebinasab F, Bandegi A, Naebi H, Hemmati H, Samidoust P, Delshad MSE, Norollahi SE, Vahidi S, Karimian P, Najafzadeh A, Samadani AA. Performance of KLF4 and Wnt1 genes expression fluctuations in tumoral and margin tissues of colorectal cancer in an Iranian population. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2021.101465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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32
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Alzahrani SM, Al Doghaither HA, Al-Ghafari AB. General insight into cancer: An overview of colorectal cancer (Review). Mol Clin Oncol 2021; 15:271. [PMID: 34790355 DOI: 10.3892/mco.2021.2433] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/28/2021] [Indexed: 12/13/2022] Open
Abstract
Cancer is currently among the leading causes of mortality globally. Colorectal cancer (CRC) ranks second among the most common types of cancer in terms of mortality worldwide. This type of cancer arises from mutations in the colonic and rectal epithelial tissues that target oncogenes, tumor suppressor genes and genes related to DNA repair mechanisms. The aim of the present review was to provide an explanation of CRC classification, which is carried out according to the histological subtype, location and molecular pathways implicated in its development. The pathogenic mechanisms implicated in CRC may involve one of three different molecular pathways: Chromosomal instability, microsatellite instability and cytosine preceding guanine island methylator phenotype. In addition, a variety of mutated genes associated with CRC, which affect certain signaling pathways, including DNA mismatch repair, cell cycle checkpoints and apoptotic pathways, were discussed. Moreover, a brief description of the risk factors and the symptoms associated with CRC was also provided. Finally, the treatment approaches to CRC were outlined.
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Affiliation(s)
| | | | - Ayat Badr Al-Ghafari
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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33
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Tieng FYF, Abu N, Nasir SN, Lee LH, Ab Mutalib NS. Liquid Biopsy-Based Colorectal Cancer Screening via Surface Markers of Circulating Tumor Cells. Diagnostics (Basel) 2021; 11:2136. [PMID: 34829483 PMCID: PMC8618170 DOI: 10.3390/diagnostics11112136] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 11/15/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is ranked second for cancer-related deaths worldwide with approximately half of the patients being diagnosed at the late stages. The untimely detection of CRC results in advancement to the metastatic stage and nearly 90% of cancer-related deaths. The early detection of CRC is crucial to decrease its overall incidence and mortality rates. The recent introduction of circulating tumor cells (CTCs) has enabled a less invasive sampling method from liquid biopsies, besides revealing key information toward CRC metastasis. The current gold standard for CTC identification is the CellSearch® system (Veridex). This first-generation instrumentation relies on a single cell surface marker (CSM) to capture and count CTCs. Detection of CTCs allows the identification of patients at risk for metastasis, whereas CTC enumeration could improve risk assessment, monitoring of systemic therapy, and detection of therapy resistance in advanced metastatic CRC. In this review, we compared the pros and cons between single CSM-based CTC enrichment techniques and multi-marker-based systems. We also highlighted the challenges faced in the routine implementation of CSM-dependent CTC detection methods in CRC screening, prediction, prognosis, disease monitoring, and therapy selection toward precision medicine, as well as the dwelling on post-CTC analysis and characterization methods.
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Affiliation(s)
- Francis Yew Fu Tieng
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Nadiah Abu
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Siti Nurmi Nasir
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University of Malaysia, Subang Jaya 47500, Selangor, Malaysia
| | - Nurul-Syakima Ab Mutalib
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University of Malaysia, Subang Jaya 47500, Selangor, Malaysia
- Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
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34
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Brar B, Ranjan K, Palria A, Kumar R, Ghosh M, Sihag S, Minakshi P. Nanotechnology in Colorectal Cancer for Precision Diagnosis and Therapy. FRONTIERS IN NANOTECHNOLOGY 2021. [DOI: 10.3389/fnano.2021.699266] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is the third most frequently occurring tumor in the human population. CRCs are usually adenocarcinomatous and originate as a polyp on the inner wall of the colon or rectum which may become malignant in the due course of time. Although the therapeutic options of CRC are limited, the early diagnosis of CRC may play an important role in preventive and therapeutic interventions to decrease the mortality rate. The CRC-affected tissues exhibit several molecular markers that may be exploited as the novel strategy to develop newer approaches for the treatment of the disease. Nanotechnology consists of a wide array of innovative and astonishing nanomaterials with both diagnostics and therapeutic potential. Several nanomaterials and nano formulations such as Carbon nanotubes, Dendrimer, Liposomes, Silica Nanoparticles, Gold nanoparticles, Metal-organic frameworks, Core-shell polymeric nano-formulations, Nano-emulsion System, etc can be used to targeted anticancer drug delivery and diagnostic purposes in CRC. The light-sensitive photosensitizer drugs loaded gold and silica nanoparticles can be used to diagnose as well as the killing of CRC cells by the targeted delivery of anticancer drugs to cancer cells. This review is focused on the recent advancement of nanotechnology in the diagnosis and treatment of CRC.
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Ying K, Bai B, Gao X, Xu Y, Wang H, Xie B. Orally Administrable Therapeutic Nanoparticles for the Treatment of Colorectal Cancer. Front Bioeng Biotechnol 2021; 9:670124. [PMID: 34307319 PMCID: PMC8293278 DOI: 10.3389/fbioe.2021.670124] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/14/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common and lethal human malignancies worldwide; however, the therapeutic outcomes in the clinic still are unsatisfactory due to the lack of effective and safe therapeutic regimens. Orally administrable and CRC-targetable drug delivery is an attractive approach for CRC therapy as it improves the efficacy by local drug delivery and reduces systemic toxicity. Currently, chemotherapy remains the mainstay modality for CRC therapy; however, most of chemo drugs have low water solubility and are unstable in the gastrointestinal tract (GIT), poor intestinal permeability, and are susceptible to P-glycoprotein (P-gp) efflux, resulting in limited therapeutic outcomes. Orally administrable nanoformulations hold the great potential for improving the bioavailability of poorly permeable and poorly soluble therapeutics, but there are still limitations associated with these regimes. This review focuses on the barriers for oral drug delivery and various oral therapeutic nanoparticles for the management of CRC.
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Affiliation(s)
- Kangkang Ying
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Health Commission (NHC), Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
- Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Bingjun Bai
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xing Gao
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuzi Xu
- Department of Oral Implantology and Prosthodontics, The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, China
| | - Hangxiang Wang
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Health Commission (NHC), Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
| | - Binbin Xie
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Health Commission (NHC), Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
- Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
- Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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36
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Tomasini PP, Guecheva TN, Leguisamo NM, Péricart S, Brunac AC, Hoffmann JS, Saffi J. Analyzing the Opportunities to Target DNA Double-Strand Breaks Repair and Replicative Stress Responses to Improve Therapeutic Index of Colorectal Cancer. Cancers (Basel) 2021; 13:3130. [PMID: 34201502 PMCID: PMC8268241 DOI: 10.3390/cancers13133130] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/15/2021] [Accepted: 06/18/2021] [Indexed: 12/22/2022] Open
Abstract
Despite the ample improvements of CRC molecular landscape, the therapeutic options still rely on conventional chemotherapy-based regimens for early disease, and few targeted agents are recommended for clinical use in the metastatic setting. Moreover, the impact of cytotoxic, targeted agents, and immunotherapy combinations in the metastatic scenario is not fully satisfactory, especially the outcomes for patients who develop resistance to these treatments need to be improved. Here, we examine the opportunity to consider therapeutic agents targeting DNA repair and DNA replication stress response as strategies to exploit genetic or functional defects in the DNA damage response (DDR) pathways through synthetic lethal mechanisms, still not explored in CRC. These include the multiple actors involved in the repair of DNA double-strand breaks (DSBs) through homologous recombination (HR), classical non-homologous end joining (NHEJ), and microhomology-mediated end-joining (MMEJ), inhibitors of the base excision repair (BER) protein poly (ADP-ribose) polymerase (PARP), as well as inhibitors of the DNA damage kinases ataxia-telangiectasia and Rad3 related (ATR), CHK1, WEE1, and ataxia-telangiectasia mutated (ATM). We also review the biomarkers that guide the use of these agents, and current clinical trials with targeted DDR therapies.
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Affiliation(s)
- Paula Pellenz Tomasini
- Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre, Avenida Sarmento Leite, 245, Porto Alegre 90050-170, Brazil; (P.P.T.); (N.M.L.)
- Post-Graduation Program in Cell and Molecular Biology, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, Porto Alegre 91501-970, Brazil
| | - Temenouga Nikolova Guecheva
- Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology (IC-FUC), Porto Alegre 90620-000, Brazil;
| | - Natalia Motta Leguisamo
- Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre, Avenida Sarmento Leite, 245, Porto Alegre 90050-170, Brazil; (P.P.T.); (N.M.L.)
| | - Sarah Péricart
- Laboratoire D’Excellence Toulouse Cancer (TOUCAN), Laboratoire de Pathologie, Institut Universitaire du Cancer-Toulouse, Oncopole, 1 Avenue Irène-Joliot-Curie, 31059 Toulouse, France; (S.P.); (A.-C.B.); (J.S.H.)
| | - Anne-Cécile Brunac
- Laboratoire D’Excellence Toulouse Cancer (TOUCAN), Laboratoire de Pathologie, Institut Universitaire du Cancer-Toulouse, Oncopole, 1 Avenue Irène-Joliot-Curie, 31059 Toulouse, France; (S.P.); (A.-C.B.); (J.S.H.)
| | - Jean Sébastien Hoffmann
- Laboratoire D’Excellence Toulouse Cancer (TOUCAN), Laboratoire de Pathologie, Institut Universitaire du Cancer-Toulouse, Oncopole, 1 Avenue Irène-Joliot-Curie, 31059 Toulouse, France; (S.P.); (A.-C.B.); (J.S.H.)
| | - Jenifer Saffi
- Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre, Avenida Sarmento Leite, 245, Porto Alegre 90050-170, Brazil; (P.P.T.); (N.M.L.)
- Post-Graduation Program in Cell and Molecular Biology, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, Porto Alegre 91501-970, Brazil
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Hasan MK, Ara I, Mondal MSA, Kabir Y. Phytochemistry, pharmacological activity, and potential health benefits of Gly cyrrhiza glabra. Heliyon 2021; 7:e07240. [PMID: 34189299 PMCID: PMC8220166 DOI: 10.1016/j.heliyon.2021.e07240] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/26/2021] [Accepted: 06/03/2021] [Indexed: 12/16/2022] Open
Abstract
Nature has always been an excellent source for many therapeutic compounds providing us with many medicinal plants and microorganisms producing beneficial chemicals. Therefore, the demand for medicinal plants, cosmetics, and health products is always on the rise. One such plant from the Leguminosae family is licorice and the scientific name is Glycyrrhiza glabra Linn. It is an herb-type plant with medicinal value. In the following article, we shall elaborately look at the plants' phytochemical constituents and the pharmacological impact of those substances. Several compounds such as glycyrrhizin, glycyrrhizinic acid, isoliquiritin, and glycyrrhizic acid have been found in this plant, which can provide pharmacological benefit to us with its anti-cancer, anti-atherogenic, anti-diabetic, anti-asthmatic, anti-inflammatory, anti-microbial, and antispasmodic activity. Alongside, these products have a different role in hepatoprotective, immunologic, memory-enhancing activity. They can stimulate hair growth, control obesity, and have anti-depressants, sedatives, and anticoagulant activity. This review examines recent studies on the phytochemical and pharmacological data and describes some side effects and toxicity of licorice and its bioactive components.
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Affiliation(s)
- Md. Kamrul Hasan
- Department of Biochemistry and Molecular Biology, Tejgaon College, National University, Gazipur, 1704, Bangladesh
| | - Iffat Ara
- Department of Biochemistry and Molecular Biology, Tejgaon College, National University, Gazipur, 1704, Bangladesh
| | | | - Yearul Kabir
- Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, 1000, Bangladesh
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Tang M, Zeng L, Zeng Z, Liu J, Yuan J, Wu D, Lu Y, Zi J, Ye M. Proteomics study of colorectal cancer and adenomatous polyps identifies TFR1, SAHH, and HV307 as potential biomarkers for screening. J Proteomics 2021; 243:104246. [PMID: 33915303 DOI: 10.1016/j.jprot.2021.104246] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 01/05/2021] [Accepted: 04/21/2021] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions can promote early medical intervention and treatment, thereby reducing morbidity and mortality. Proteins are generally considered key biomarkers of cancer. Herein, we performed a quantitative, original-tissue proteomics study in a cohort of ninety patients from pre-cancerous to cancerous conditions via liquid chromatography-tandem mass spectrometry. In total, 134,812 peptides, 8697 proteins, 2355 union differentially expressed proteins (DEPs), and 409 shared DEPs (compared with adjacent tissues) were identified. The number of DEPs indicated a positive correlation with increasing severity of illness. The union and shared DEPs were both enriched in the KEGG pathway of focal adhesion, metabolism of xenobiotics by cytochrome P450, and drug metabolism by cytochrome P450. Among the 2355 union DEPs, 32 were selected for identification and validation by multiple reaction monitoring from twenty plasma specimens. Of these, three proteins, transferrin receptor protein 1 (TFR1), adenosylhomocysteinase (SAHH), and immunoglobulin heavy variable 3-7 (HV307), were significantly differentially expressed and displayed the same expression pattern in plasma as observed in the tissue data. In conclusion, TFR1, SAHH, and HV307 may be considered as potential biomarkers for CRC screening. SIGNIFICANCE: Although CRC is a malignant tumour with high morbidity and mortality worldwide, efficient screening strategies for CRC and pre-cancerous lesions can play an important role in addressing these issues. Screening of molecular biomarkers provide a non-invasive, cost-effective, and efficient approach. Proteins are generally considered key molecular biomarkers of cancer. Our study reports a quantitative proteomics analysis of protein biomarkers for colorectal cancer (CRC) and adenomatous polyps, and identifies TFR1, SAHH, and HV307 as potential biomarkers for screening. This research makes a significant contribution to the literature as although mass spectrometry-based proteomics research has been widely used for clinical research, its application to clinical translation as parallel specimens ranging from pre-cancerous to cancerous tissues-according to the degree of disease progression-has not been readily assessed.
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Affiliation(s)
- Meifang Tang
- BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China; Clinical laboratory of BGI Health, BGI-Shenzhen, Shenzhen 518083, China
| | - Liuhong Zeng
- Clinical laboratory of BGI Health, BGI-Shenzhen, Shenzhen 518083, China
| | - Zhaolei Zeng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China
| | - Jie Liu
- BGI Genomics, BGI-Shenzhen, Shenzhen 518083, China
| | - Jie Yuan
- Department of General Surgery, the Fifth Affiliated Hospital, Southern Medical University, China
| | - Dongjie Wu
- BGI Genomics, BGI-Shenzhen, Shenzhen 518083, China
| | - Ying Lu
- Clinical laboratory of BGI Health, BGI-Shenzhen, Shenzhen 518083, China
| | - Jin Zi
- BGI Genomics, BGI-Shenzhen, Shenzhen 518083, China
| | - Mingzhi Ye
- BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China; BGI Genomics, BGI-Shenzhen, Shenzhen 518083, China; BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, Guangzhou 510006, China.
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Khan FA, Albalawi R, Pottoo FH. Trends in targeted delivery of nanomaterials in colon cancer diagnosis and treatment. Med Res Rev 2021; 42:227-258. [PMID: 33891325 DOI: 10.1002/med.21809] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 04/01/2021] [Accepted: 04/01/2021] [Indexed: 12/14/2022]
Abstract
Colon cancer is an adenocarcinoma, which subsequently develops into malignant tumors, if not treated properly. The current colon cancer therapy mainly revolves around chemotherapy, radiotherapy and surgery, but the search continues for more effective interventions. With the advancement of nanoparticles (NPs), it is now possible to diagnose and treat colon cancers with different types, shapes, and sizes of NPs. Nanoformulations such as quantum dots, iron oxide, polymeric NPs, dendrimers, polypeptides, gold NPs, silver NPs, platinum NPs, and cerium oxide have been either extensively used alone or in combination with other nanomaterials or drugs in colon cancer diagnosis, and treatments. These nanoformulations possess high biocompatibility and bioavailability, which makes them the most suitable candidates for cancer treatment. The size and shape of NPs are critical to achieving an effective drug delivery in cancer treatment and diagnosis. Most NPs currently are under different testing phases (in vitro, preclinical, and clinical), whereas some of them have been approved for therapeutic applications. We have comprehensively reviewed the recent advances in the applications of NPs-based formulations in colon cancer diagnosis and treatment.
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Affiliation(s)
- Firdos A Khan
- Department of Stem Cell Biology, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Reem Albalawi
- Department of Stem Cell Biology, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.,Student of the volunteer/training program at IRMC
| | - Faheem H Pottoo
- College of Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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40
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Fouad MA, Salem SE, Osman AS, Badr DM, Hussein MM, Zekri AN, Hafez HF, Kamel MM, Shouman SA. Fluoropyrimdine therapy induced alterations in interleukins expression in colorectal cancer patients. Int J Immunopathol Pharmacol 2021; 35:20587384211008332. [PMID: 33832346 PMCID: PMC8040557 DOI: 10.1177/20587384211008332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
This study monitored the changes in the expression of inflammatory IL-6 and IL-1β during the treatment period of Fluoropyrimidine (FP) based therapy. RNA was extracted from the peripheral blood of 102 CRC patients before treatment with FP therapy, and from 48 and 32 patients after 3 and 6 months of treatment, respectively. The genetic transcription of IL-6 and IL-1β was determined by real time PCR. Patients were stratified according to their levels of IL-6 and IL-1β genes expression for subgroup and survival analyses. Baseline CRC patients showed overexpression of IL-6 and IL-1β compared to healthy control. FP therapy significantly induced IL-6 and IL-1β expression. Subgroup analysis showed that patients with right colon tumors had significant elevation in both IL-6 and IL-1β with FP therapy. FP therapy significantly induced IL-1β expression in patients ⩽45 years, smokers, with high baseline level of CA19.9, right colon tumors, low grade pathology, T3 tumors and positive lymph nodes. Survival analysis showed that baseline levels of interleukins expression had insignificant effect on overall survival and event free survival. FP therapy has an impact on the level of interleukins expression declared in certain clinicopathological subgroups of CRC patients, but without a prognostic significance on patients' survival.
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Affiliation(s)
- Mariam A Fouad
- Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo, Egypt
| | - Salem E Salem
- Medical Oncology Department, National Cancer Institute, Cairo, Egypt
| | - Afaf S Osman
- Medical Pharmacology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Doaa M Badr
- Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo, Egypt
| | - Marwa M Hussein
- Medical Oncology Department, National Cancer Institute, Cairo, Egypt
| | - Abdelrahman N Zekri
- Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo, Egypt
| | - Hafez F Hafez
- Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo, Egypt
| | - Mahmoud M Kamel
- Clinical Pathology Department, National Cancer Institute, Cairo, Egypt
| | - Samia A Shouman
- Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo, Egypt
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41
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Tieng FYF, Abu N, Lee LH, Ab Mutalib NS. Microsatellite Instability in Colorectal Cancer Liquid Biopsy-Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker. Diagnostics (Basel) 2021; 11:544. [PMID: 33803882 PMCID: PMC8003257 DOI: 10.3390/diagnostics11030544] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/15/2021] [Accepted: 03/17/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the third most commonly-diagnosed cancer in the world and ranked second for cancer-related mortality in humans. Microsatellite instability (MSI) is an indicator for Lynch syndrome (LS), an inherited cancer predisposition, and a prognostic marker which predicts the response to immunotherapy. A recent trend in immunotherapy has transformed cancer treatment to provide medical alternatives that have not existed before. It is believed that MSI-high (MSI-H) CRC patients would benefit from immunotherapy due to their increased immune infiltration and higher neo-antigenic loads. MSI testing such as immunohistochemistry (IHC) and PCR MSI assay has historically been a tissue-based procedure that involves the testing of adequate tissue with a high concentration of cancer cells, in addition to the requirement for paired normal tissues. The invasive nature and specific prerequisite of such tests might hinder its application when surgery is not an option or when the tissues are insufficient. The application of next-generation sequencing, which is highly sensitive, in combination with liquid biopsy, therefore, presents an interesting possibility worth exploring. This review aimed to discuss the current body of evidence supporting the potential of liquid biopsy as a tool for MSI testing in CRC.
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Affiliation(s)
- Francis Yew Fu Tieng
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.)
| | - Nadiah Abu
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.)
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor 47500, Malaysia
| | - Nurul-Syakima Ab Mutalib
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.)
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor 47500, Malaysia
- Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
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Jo SJ, Kim SH, Park SJ, Lee Y, Son JH. Association between Texture Analysis Parameters and Molecular Biologic KRAS Mutation in Non-Mucinous Rectal Cancer. TAEHAN YONGSANG UIHAKHOE CHI 2021; 82:406-416. [PMID: 36238732 PMCID: PMC9431938 DOI: 10.3348/jksr.2020.0065] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 06/03/2020] [Accepted: 06/23/2020] [Indexed: 11/15/2022]
Abstract
Purpose To evaluate the association between magnetic resonance imaging (MRI)-based texture parameters and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in patients with non-mucinous rectal cancer. Materials and Methods Seventy-nine patients who had pathologically confirmed rectal non-mucinous adenocarcinoma with or without KRAS-mutation and had undergone rectal MRI were divided into a training (n = 46) and validation dataset (n = 33). A texture analysis was performed on the axial T2-weighted images. The association was statistically analyzed using the Mann-Whitney U test. To extract an optimal cut-off value for the prediction of KRAS mutation, a receiver operating characteristic curve analysis was performed. The cut-off value was verified using the validation dataset. Results In the training dataset, skewness in the mutant group (n = 22) was significantly higher than in the wild-type group (n = 24) (0.221 ± 0.283; -0.006 ± 0.178, respectively, p = 0.003). The area under the curve of the skewness was 0.757 (95% confidence interval, 0.606 to 0.872) with a maximum accuracy of 71%, a sensitivity of 64%, and a specificity of 78%. None of the other texture parameters were associated with KRAS mutation (p > 0.05). When a cut-off value of 0.078 was applied to the validation dataset, this had an accuracy of 76%, a sensitivity of 86%, and a specificity of 68%. Conclusion Skewness was associated with KRAS mutation in patients with non-mucinous rectal cancer.
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Yu JS, Huang T, Zhang Y, Mao XT, Huang LJ, Li YN, Wu TT, Zhong JY, Cao Q, Li YY, Jin J. Substrate-specific recognition of IKKs mediated by USP16 facilitates autoimmune inflammation. SCIENCE ADVANCES 2021; 7:7/3/eabc4009. [PMID: 33523871 PMCID: PMC7806237 DOI: 10.1126/sciadv.abc4009] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 10/22/2020] [Indexed: 05/11/2023]
Abstract
The classic NF-κB pathway plays crucial roles in various immune responses and inflammatory diseases. Its key kinase, IKKβ, participates in a variety of pathological and physiological processes by selectively recognizing its downstream substrates, including p105, p65, and IκBα, but the specific mechanisms of these substrates are unclear. Hyperactivation of one of the substrates, p105, is closely related to the onset of inflammatory bowel disease (IBD) in Nfkb1-deficient mice. In this study, we found that IKKβ ubiquitination on lysine-238 was substantially increased during inflammation. Using mass spectrometry, we identified USP16 as an essential regulator of the IKKβ ubiquitination level that selectively affected p105 phosphorylation without directly affecting p65 or IκBα phosphorylation. Furthermore, USP16 was highly expressed in colon macrophages in patients with IBD, and myeloid-conditional USP16-knockout mice exhibited reduced IBD severity. Our study provides a new theoretical basis for IBD pathogenesis and targeted precision intervention therapy.
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Affiliation(s)
- Jian-Shuai Yu
- MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
| | - Tao Huang
- MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
| | - Yu Zhang
- Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Xin-Tao Mao
- MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
| | - Ling-Jie Huang
- Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Yi-Ning Li
- MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
| | - Ting-Ting Wu
- Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Jiang-Yan Zhong
- MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
| | - Qian Cao
- Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Yi-Yuan Li
- Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China.
| | - Jin Jin
- MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
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Jiang L, Yang Y, Feng H, Zhou Q, Liu Y. Pinocembrin Inhibits the Proliferation, Migration, Invasiveness, and Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Regulating LACTB. Cancer Biother Radiopharm 2020; 37:527-536. [PMID: 33395536 DOI: 10.1089/cbr.2020.4052] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Background: Colorectal cancer (CRC) is a common malignancy of digestive tract. Pinocembrin (PINO) has been discovered to have proapoptotic effect on CRC. This study aimed to elucidate how other biological behaviors of CRC cells were affected under PINO treatment. Materials & Methods: The effect of PINO on HT29 and HCT116 cells were detected through treatment of different concentrations of PINO. The role of LACTB in PINO treatment was investigated by transfection of siRNA-LACTB. Cell counting kit-8 assay, wound healing assay, and Transwell assay were conducted to evaluate the proliferation, migration, and invasiveness of CRC cells, respectively. Western blot or quantitative reverse transcription-polymerase chain reaction was carried out to measure the expressions of LACTB, matrix metalloproteinase (MMP)-2, E-cadherin, and N-cadherin. Results: Gradient PINO inhibited the viability, migration, invasiveness, and expressions of MMP-2 and N-cadherin in CRC cells, while promoted E-cadherin and LACTB expressions. Silencing LACTB promoted the viability, migration, invasiveness, and expressions of MMP-2 and N-cadherin in CRC cells and inhibited E-cadherin expression. PINO counteracted the effect of silenced LACTB, and yet silencing LACTB partially abolished the effect of PINO on CRC cells. Conclusion: PINO inhibited the proliferation, migration, invasiveness, and epithelial-to-mesenchymal transition of CRC cells by regulating LACTB.
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Affiliation(s)
- Lai Jiang
- Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Yongbo Yang
- Department of Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Haiyang Feng
- Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Qinfei Zhou
- Department of Medical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Yong Liu
- Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
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Cid-Gallegos MS, Sánchez-Chino XM, Juárez Chairez MF, Álvarez González I, Madrigal-Bujaidar E, Jiménez-Martínez C. Anticarcinogenic Activity of Phenolic Compounds from Sprouted Legumes. FOOD REVIEWS INTERNATIONAL 2020. [DOI: 10.1080/87559129.2020.1840581] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- María Stephanie Cid-Gallegos
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Unidad Profesional Adolfo López Mateos, Mexico City, Mexico
| | - Xariss M. Sánchez-Chino
- Cátedra-CONACyT, Departamento de Salud, El Colegio de la Frontera Sur-Villahermosa, Villahermosa, Mexico
| | - Milagros Faridy Juárez Chairez
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Unidad Profesional Adolfo López Mateos, Mexico City, Mexico
| | - Isela Álvarez González
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Unidad Profesional Adolfo López Mateos, Mexico City, Mexico
| | - Eduardo Madrigal-Bujaidar
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Unidad Profesional Adolfo López Mateos, Mexico City, Mexico
| | - Cristian Jiménez-Martínez
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Unidad Profesional Adolfo López Mateos, Mexico City, Mexico
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Mishra RK, Ahmad A, Vyawahare A, Kumar A, Khan R. Understanding the Monoclonal Antibody Involvement in Targeting the Activation of Tumor Suppressor Genes. Curr Top Med Chem 2020; 20:1810-1823. [PMID: 32543361 DOI: 10.2174/1568026620666200616133814] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 04/28/2020] [Accepted: 05/08/2020] [Indexed: 12/14/2022]
Abstract
Monoclonal antibodies (mAbs) have always provided outstanding therapeutic arsenal in the
treatment of cancer, be it hematological malignancies or solid tumors. Monoclonal antibodies mediated
targeting of cancer genes in general and tumor-suppressor genes, in particular, have appreciably allowed
the possibilities of trafficking these antibodies to specific tumor mechanisms and aim for the pin-point
maneuvered tumor treatment strategies. The conventional cancer treatment options are associated with
enormous limitations like drug resistance, acute and pan-toxic side effects and collateral damage to other
unrelated cells and organs. Therefore, monoclonal antibody-mediated treatments have some special advantages
of specific targeting of cancer-related genes and minimizing the off-target side effects. A large
number of monoclonal antibody-mediated treatment regimen viz. use of immunoconjugates, clinically
targeting TGFβ with pan-TGFβ monoclonal antibodies, p53 by its monoclonal antibodies and EGFRtargeted
monoclonal antibodies, etc. have been observed in the recent past. In this review, the authors
have discussed some of the significant advances in the context of targeting tumor suppressor genes with
monoclonal antibodies. Approximately 250 articles were scanned from research databases like PubMed
central, Europe PubMed Central and google scholar up to the date of inception, and relevant reports on
monoclonal antibody-mediated targeting of cancer genes were selected. mAb mediated targeting of tumor
suppressor genes is a recent grey paradigm, which has not been explored up to its maximum potential.
Therefore, this review will be of appreciable significance that it will boost further in-depth understanding
of various aspects of mAb arbitrated cancer targeting and will warrant and promote further rigorous
research initiatives in this regard. The authors expect that this review will acquaint the readers
with the current status regarding the recent progress in the domain of mAbs and their employability and
targetability towards tumor suppressor genes in anti-cancer therapeutics.
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Affiliation(s)
- Rakesh Kumar Mishra
- Department of Nano-Therapeutics, Institute of Nano Science and Technology, Habitat Centre, Phase 10, Sector 64, Mohali, Punjab 160062, India
| | - Anas Ahmad
- Department of Nano-Therapeutics, Institute of Nano Science and Technology, Habitat Centre, Phase 10, Sector 64, Mohali, Punjab 160062, India
| | - Akshay Vyawahare
- Department of Nano-Therapeutics, Institute of Nano Science and Technology, Habitat Centre, Phase 10, Sector 64, Mohali, Punjab 160062, India
| | - Ajay Kumar
- Department of Nano-Therapeutics, Institute of Nano Science and Technology, Habitat Centre, Phase 10, Sector 64, Mohali, Punjab 160062, India
| | - Rehan Khan
- Department of Nano-Therapeutics, Institute of Nano Science and Technology, Habitat Centre, Phase 10, Sector 64, Mohali, Punjab 160062, India
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Ballout F, Monzer A, Fatfat M, Ouweini HE, Jaffa MA, Abdel-Samad R, Darwiche N, Abou-Kheir W, Gali-Muhtasib H. Thymoquinone induces apoptosis and DNA damage in 5-Fluorouracil-resistant colorectal cancer stem/progenitor cells. Oncotarget 2020; 11:2959-2972. [PMID: 32821342 PMCID: PMC7415406 DOI: 10.18632/oncotarget.27426] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 12/16/2019] [Indexed: 12/13/2022] Open
Abstract
The high recurrence rates of colorectal cancer have been associated with a small population of cancer stem cells (CSCs) that are resistant to the standard chemotherapeutic drug, 5-fluorouracil (5FU). Thymoquinone (TQ) has shown promising antitumor properties on numerous cancer systems both in vitro and in vivo; however, its effect on colorectal CSCs is poorly established. Here, we investigated TQ's potential to target CSCs in a three-dimensional (3D) sphere-formation assay enriched for a population of colorectal cancer stem/progenitor cells. Our results showed a significant decrease in self-renewal potential of CSC populations enriched from 5FU-sensitive and resistant HCT116 cells at 10-fold lower concentrations when compared to 2D monolayers. TQ decreased the expression levels of colorectal stem cell markers CD44 and Epithelial Cell Adhesion Molecule EpCAM and proliferation marker Ki67 in colonospheres derived from both cell lines and reduced cellular migration and invasion. Further investigation revealed that TQ treatment led to increased TUNEL positivity and a dramatic increase in the amount of the DNA damage marker gamma H2AX particularly in 5FU-resistant colonospheres, suggesting that the diminished sphere forming ability in TQ-treated colonospheres is due to induction of DNA damage and apoptotic cell death. The intraperitoneal injection of TQ in mice inhibited tumor growth of spheres derived from 5FU-sensitive and 5FU-resistant HCT116 cells. Furthermore, TQ induced apoptosis and inhibited NF-κB and MEK signaling in mouse tumors. Altogether, our findings document TQ's effect on colorectal cancer stem-like cells and provide insights into its underlying mechanism of action.
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Affiliation(s)
- Farah Ballout
- Department of Biology, American University of Beirut, Lebanon
| | - Alissar Monzer
- Department of Biology, American University of Beirut, Lebanon
| | - Maamoun Fatfat
- Department of Biology, American University of Beirut, Lebanon
| | - Hala El Ouweini
- Department of Biology, American University of Beirut, Lebanon
| | - Miran A. Jaffa
- Department of Epidemiology and Population Health, American University of Beirut, Lebanon
| | - Rana Abdel-Samad
- Department of Biochemistry and Molecular Genetics, American University of Beirut, Lebanon
| | - Nadine Darwiche
- Department of Biochemistry and Molecular Genetics, American University of Beirut, Lebanon
| | - Wassim Abou-Kheir
- Center for Drug Discovery and Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Lebanon
| | - Hala Gali-Muhtasib
- Department of Biology, American University of Beirut, Lebanon
- Center for Drug Discovery and Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Lebanon
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Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer. Nat Commun 2020; 11:3701. [PMID: 32709883 PMCID: PMC7381612 DOI: 10.1038/s41467-020-17549-y] [Citation(s) in RCA: 138] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 07/02/2020] [Indexed: 12/24/2022] Open
Abstract
Despite its importance in human cancers, including colorectal cancers (CRC), oncogenic KRAS has been extremely challenging to target therapeutically. To identify potential vulnerabilities in KRAS-mutated CRC, we characterize the impact of oncogenic KRAS on the cell surface of intestinal epithelial cells. Here we show that oncogenic KRAS alters the expression of a myriad of cell-surface proteins implicated in diverse biological functions, and identify many potential surface-accessible therapeutic targets. Cell surface-based loss-of-function screens reveal that ATP7A, a copper-exporter upregulated by mutant KRAS, is essential for neoplastic growth. ATP7A is upregulated at the surface of KRAS-mutated CRC, and protects cells from excess copper-ion toxicity. We find that KRAS-mutated cells acquire copper via a non-canonical mechanism involving macropinocytosis, which appears to be required to support their growth. Together, these results indicate that copper bioavailability is a KRAS-selective vulnerability that could be exploited for the treatment of KRAS-mutated neoplasms.
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Tieng FYF, Abu N, Sukor S, Mohd Azman ZA, Mahamad Nadzir N, Lee LH, Ab Mutalib NS. L1CAM, CA9, KLK6, HPN, and ALDH1A1 as Potential Serum Markers in Primary and Metastatic Colorectal Cancer Screening. Diagnostics (Basel) 2020; 10:E444. [PMID: 32630086 PMCID: PMC7400057 DOI: 10.3390/diagnostics10070444] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 05/28/2020] [Accepted: 05/29/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) screening at the earlier stages could effectively decrease CRC-related mortality and incidence; however, accurate screening strategies are still lacking. Considerable interest has been generated in the detection of less invasive tests requiring a small sample volume with the potential to detect several cancer biomarkers simultaneously. Due to this, the ELISA-based method was undertaken in this study. METHODS Concentrations of neural cell adhesion molecule L1 (L1CAM), carbonic anhydrase IX (CA9), mesothelin (MSLN), midkine (MDK), hepsin (HPN), kallikrein 6 (KLK6), transglutaminase 2 (TGM2) aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), epithelial cell adhesion molecule (EpCAM), and cluster of differentiation 44 (CD44) from blood serum of 36 primary CRC and 24 metastatic CRC (mCRC) were calculated via MAGPIX® System (Luminex Corporation, USA). RESULTS Significantly increased concentration (p < 0.05) of three serum biomarkers (L1CAM, CA9, and HPN) were shown in mCRC when compared with primary CRC. HPN and KLK6 showed significant differences (p < 0.05) in concentration among different stages of CRC. In contrast, levels of HPN and ALDH1A1 were significantly elevated (p < 0.05) in chemotherapy-treated CRC patients as compared with nontreated ones. Conclusion: Serum biomarkers could act as a potential early CRC diagnostics test, but further additional testings are needed.
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Affiliation(s)
- Francis Yew Fu Tieng
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (N.M.N.)
| | - Nadiah Abu
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (N.M.N.)
| | - Surani Sukor
- Prima Nexus Sdn. Bhd., Kuala Lumpur 50470, Malaysia;
| | - Zairul Azwan Mohd Azman
- Colorectal Unit, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia;
| | - Norshahidah Mahamad Nadzir
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (N.M.N.)
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya 47500, Malaysia
| | - Nurul Syakima Ab Mutalib
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (N.M.N.)
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50
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Nogués A, Gallardo-Vara E, Zafra MP, Mate P, Marijuan JL, Alonso A, Botella LM, Prieto MI. Endoglin (CD105) and VEGF as potential angiogenic and dissemination markers for colorectal cancer. World J Surg Oncol 2020; 18:99. [PMID: 32434528 PMCID: PMC7240983 DOI: 10.1186/s12957-020-01871-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 05/06/2020] [Indexed: 12/31/2022] Open
Abstract
Background Colorectal cancer (CRC) is an important current problem concerning public health due to its high incidence and mortality. Advances in molecular and cellular knowledge and the detection of new disease biomarkers are very important to improve prognosis, prediction, and early diagnosis. In this study, we aimed to analyze the gene and protein expression levels of two angiogenic markers, VEGF and soluble Endoglin, during different tumor stages as well as at different stages of cancer treatment, to predict the diagnosis and evolution of colon and rectal cancer. Material and methods This study includes 133 CRC patients (93 with colon cancer and 40 with rectal cancer) on which the gene and protein expression of Endoglin (membrane and soluble form) and VEGF were analyzed by molecular and immunohistochemical techniques on different tumor stage samples and plasma obtained preoperatively as well as 3, 6, and 9 months after resection of the tumor. Results VEGF and Endoglin gene expressions were higher in tumor tissue than in surrounding non-tumoral tissue for both types of cancer. The VEGF levels in plasma were found to decrease in less aggressive tumors, whereas soluble Endoglin was increased in preoperative samples of patients with metastasis. Membrane Endoglin expression was higher on the vascular endothelium of more aggressive tumors. In contrast, Endoglin expression was mainly in the colon epithelium in less aggressive stage tumors. Conclusion Endoglin and VEGF are proteins with a major role in the tumor angiogenesis process. This study performed with a wide cohort of human samples shows that both proteins seem to be valuable biomarkers in the diagnosis and prognosis of CRC.
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Affiliation(s)
- Ana Nogués
- Department of General Surgery, Hospital Universitario La Paz, 28046, Madrid, Spain.
| | - Eunate Gallardo-Vara
- Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain
| | - Mª Paz Zafra
- Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10021, USA
| | - Paloma Mate
- Department of General Surgery, Hospital Universitario La Paz, 28046, Madrid, Spain
| | - Jose Luis Marijuan
- Department of General Surgery, Hospital Universitario La Paz, 28046, Madrid, Spain
| | - Alfredo Alonso
- Department of General Surgery, Hospital Universitario del Sureste de Madrid, Arganda del Rey, Madrid, Spain
| | - Luisa Mª Botella
- Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain
| | - Mª Isabel Prieto
- Department of General Surgery, Hospital Universitario La Paz, 28046, Madrid, Spain
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