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Shahpari M, Hashemi M, Younesirad T, Hasanzadeh A, Mosanne MM, Ahmadifard M. The functional roles of competitive endogenous RNA (ceRNA) networks in apoptosis in human cancers: The circRNA/miRNA/mRNA regulatory axis and cell signaling pathways. Heliyon 2024; 10:e37089. [PMID: 39524849 PMCID: PMC11546195 DOI: 10.1016/j.heliyon.2024.e37089] [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: 08/18/2024] [Accepted: 08/27/2024] [Indexed: 11/16/2024] Open
Abstract
Circular RNAs are noncoding RNAs with circular conformation mainly due to backsplicing event. CircRNAs can potentially impact cell biological processes by interacting with cell signaling pathways. Numerous circRNAs have been found to be aberrantly expressed in a variety of cancers. These RNAs can act as ceRNA (competitive endogenous RNA) by sponging certain miRNAs to form circRNA/miRNA/mRNA networks. Dysregulation of ceRNA networks may lead to dysfunctions in various cell pathways, which modulate apoptosis-associated genes and ultimately result in cancer progression. Since disruption of apoptosis is one of the leading causes of cancer development, one approach for cancer treatment is to drive cells toward apoptosis. In this review, we present a summary of studies on the role of ceRNA networks in cellular signaling pathways that regulate apoptosis; these networks are suggested to be potential biomarkers for cancer treatment.
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Affiliation(s)
| | | | - Tayebeh Younesirad
- Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Aida Hasanzadeh
- Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad mahdi Mosanne
- Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mohamadreza Ahmadifard
- Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
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2
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Lima WG, Brito JCM, Verly RM, de Lima ME. Jelleine, a Family of Peptides Isolated from the Royal Jelly of the Honey Bees ( Apis mellifera), as a Promising Prototype for New Medicines: A Narrative Review. Toxins (Basel) 2024; 16:24. [PMID: 38251241 PMCID: PMC10819630 DOI: 10.3390/toxins16010024] [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: 12/11/2023] [Revised: 12/27/2023] [Accepted: 12/30/2023] [Indexed: 01/23/2024] Open
Abstract
The jelleine family is a group of four peptides (jelleines I-IV) originally isolated from the royal jelly of honey bee (Apis mellifera), but later detected in some honey samples. These oligopeptides are composed of 8-9 amino acid residues, positively charged (+2 to +3 at pH 7.2), including 38-50% of hydrophobic residues and a carboxamide C-terminus. Jelleines, generated by processing of the C-terminal region of major royal jelly proteins 1 (MRJP-1), play an important biological role in royal jelly conservation as well as in protecting bee larvae from potential pathogens. Therefore, these molecules present numerous benefits for human health, including therapeutic purposes as shown in preclinical studies. In this review, we aimed to evaluate the biological effects of jelleines in addition to characterising their toxicities and stabilities. Jelleines I-III have promising antimicrobial activity and low toxicity (LD50 > 1000 mg/Kg). However, jelleine-IV has not shown relevant biological potential. Jelleine-I, but not the other analogues, also has antiparasitic, healing, and pro-coagulant activities in addition to indirectly modulating tumor cell growth and controlling the inflammatory process. Although it is sensitive to hydrolysis by proteases, the addition of halogens increases the chemical stability of these molecules. Thus, these results suggest that jelleines, especially jelleine-I, are a potential target for the development of new, effective and safe therapeutic molecules for clinical use.
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Affiliation(s)
- William Gustavo Lima
- Programa de Pós-Graduação Stricto Sensu em Medicina e Biomedicina, Faculdade de Saúde da Santa Casa de Belo Horizonte, Avenida dos Andradas, 2688, Santa Efigênia, Belo Horizonte 30110-005, MG, Brazil;
| | - Julio Cesar Moreira Brito
- Fundação Ezequiel Dias (FUNED), Rua Conde Pereira Carneiro, 8, Gameleira, Belo Horizonte 30510-010, MG, Brazil;
| | - Rodrigo Moreira Verly
- Departamento de Química, Faculdade de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Rodovia MGT 367, 5000, Auto da Jacuba, Diamantina 39100-000, MG, Brazil;
| | - Maria Elena de Lima
- Programa de Pós-Graduação Stricto Sensu em Medicina e Biomedicina, Faculdade de Saúde da Santa Casa de Belo Horizonte, Avenida dos Andradas, 2688, Santa Efigênia, Belo Horizonte 30110-005, MG, Brazil;
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3
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Ihlamur M, Akgul B, Zengin Y, Korkut ŞV, Kelleci K, Abamor EŞ. The mTOR Signaling Pathway and mTOR Inhibitors in Cancer: Next-generation Inhibitors and Approaches. Curr Mol Med 2024; 24:478-494. [PMID: 37165594 DOI: 10.2174/1566524023666230509161645] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 02/03/2023] [Accepted: 02/07/2023] [Indexed: 05/12/2023]
Abstract
mTOR is a serine/threonine kinase that plays various roles in cell growth, proliferation, and metabolism. mTOR signaling in cancer becomes irregular. Therefore, drugs targeting mTOR have been developed. Although mTOR inhibitors rapamycin and rapamycin rapalogs (everolimus, rapamycin, temsirolimus, deforolimus, etc.) and new generation mTOR inhibitors (Rapalink, Dual PI3K/mTOR inhibitors, etc.) are used in cancer treatments, mTOR resistance mechanisms may inhibit the efficacy of these drugs. Therefore, new inhibition approaches are developed. Although these new inhibition approaches have not been widely investigated in cancer treatment, the use of nanoparticles has been evaluated as a new treatment option in a few types of cancer. This review outlines the functions of mTOR in the cancer process, its resistance mechanisms, and the efficiency of mTOR inhibitors in cancer treatment. Furthermore, it discusses the next-generation mTOR inhibitors and inhibition strategies created using nanoparticles. Since mTOR resistance mechanisms prevent the effects of mTOR inhibitors used in cancer treatments, new inhibition strategies should be developed. Inhibition approaches are created using nanoparticles, and one of them offers a promising treatment option with evidence supporting its effectiveness.
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Affiliation(s)
- Murat Ihlamur
- Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, Istanbul, Turkey
- Department of Electronics and Automation, Biruni University, Istanbul, Turkey
| | - Busra Akgul
- Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, Istanbul, Turkey
| | - Yağmur Zengin
- Biomedical Engineering Institute, Department of Biomedical Engineering, Bogazici University, Istanbul, Turkey
| | - Şenay Vural Korkut
- Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Yildiz Technical University, Istanbul, Turkey
| | - Kübra Kelleci
- Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, Istanbul, Turkey
- Department of Medical Services and Techniques, Beykoz University, Istanbul, Turkey
| | - Emrah Şefik Abamor
- Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, Istanbul, Turkey
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Xu Y, Jin Y, Gao S, Wang Y, Qu C, Wu Y, Ding N, Dai Y, Jiang L, Liu S. Prognostic Signature and Therapeutic Value Based on Membrane Lipid Biosynthesis-Related Genes in Breast Cancer. JOURNAL OF ONCOLOGY 2022; 2022:7204415. [PMID: 36059802 PMCID: PMC9436593 DOI: 10.1155/2022/7204415] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/12/2022] [Accepted: 07/13/2022] [Indexed: 11/30/2022]
Abstract
There is a need to improve diagnostic and therapeutic approaches to enhance the prognosis of breast cancer, the most common malignancy worldwide. Membrane lipid biosynthesis is a hot biological pathway in current cancer research. It is unclear whether membrane lipid biosynthesis is involved in the prognosis of BRCA. With LASSO regression, a 14-gene prediction model was constructed using data from the TCGA-BRCA cohort. The prediction model includes GPAA1, PIGF, ST3GAL1, ST6GALNAC4, PLPP2, ELOVL1, HACD1, SGPP1, PRKD2, VAPB, CERS2, SGMS2, ALDH3B2, and HACD3. BRCA patients from the TCGA-BRCA cohort were divided into two risk subgroups based on the model. Kaplan-Meier survival curves showed that patients with lower risk scores had significantly improved overall survival (P=2.49e - 09). In addition, risk score, age, stage, and TNM classification were used to predict mortality in BRCA patients. In addition, the 14 genes in the risk model were analyzed for gene variation, methylation level, drug sensitivity, and immune cell infiltration, and the miRNA-mRNA network was constructed. Afterward, the THPA website then analyzed the protein expression of 14 of these risk model genes in normal and pathological BRCA tissues. In conclusion, the membrane lipid biosynthesis-related risk model and nomogram can be used to predict BRCA clinical prognosis.
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Affiliation(s)
- Yingkun Xu
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Yudi Jin
- Department of Pathology, Chongqing University Cancer Hospital, Chongqing 400045, China
| | - Shun Gao
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Yuan Wang
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Chi Qu
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Yinan Wu
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Nan Ding
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Yuran Dai
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Linshan Jiang
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Shengchun Liu
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
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Alhamadh MS, Alanazi RB, Algarni ST, Alhuntushi AAR, Alshehri MQ, Chachar YS, Alkaiyat M, Sabatin F. A Descriptive Study of the Types and Survival Patterns of Saudi Patients with Multiple Primary Solid Malignancies: A 30-Year Tertiary Care Center Experience. Curr Oncol 2022; 29:4941-4955. [PMID: 35877253 PMCID: PMC9315520 DOI: 10.3390/curroncol29070393] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/30/2022] [Accepted: 07/07/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Objective: Cancer survival has improved significantly, which reflects the achievements in screening, diagnosis, and treatment. As a consequence, multiple primary malignancies are diagnosed more frequently, with an incidence ranging from 0.52–11.7%. The types of malignancy that coexist and survival patterns vary notably in different countries and geographical areas. Due to the limited literature in Saudi Arabia, a baseline of prevalent malignancy combinations and their survival patterns would support early detection and disease management. Method: This was a retrospective descriptive study conducted from 1993–2022 at King Abdulaziz Medical City, Department of Medical Oncology, Riyadh, Saudi Arabia. Patients with at least two biopsy-proven solid malignancies were included. Patients with hematological malignancies, missing data, or an uncertain or indecisive pathology report were excluded. Result: In total, 321 patients were analyzed. More than half (57.3%) of the patients were female. A third (33%) of the cases were synchronous, and 67% were metachronous. The most frequent site of the first primary malignancy was breast cancer, followed by colorectal, skin, and thyroid cancers. The most frequent site of the second primary malignancy was colorectal cancer, followed by thyroid, breast, and liver cancers. Only 4% of the cases had a third primary malignancy, with colorectal and appendiceal cancers being the most frequent. The most frequently observed histopathology in the synchronous and metachronous malignancies was adenocarcinoma. Breast–colorectal, breast–thyroid, and kidney–colorectal were the most frequently observed malignancy combinations. Conclusion: The current study offers a baseline of multiple primary malignancies in Saudi Arabia and provides supporting evidence that the pattern of multiple primary malignancies varies among different countries and ethnicities. The possibility of developing another primary malignancy should be considered when treating and monitoring cancer patients.
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Affiliation(s)
- Moustafa S. Alhamadh
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of the National Guard—Health Affairs, Riyadh 14611, Saudi Arabia; (R.B.A.); (S.T.A.); (A.A.R.A.); (M.Q.A.)
- King Abdullah International Medical Research Center, Ministry of the National Guard—Health Affairs, Riyadh 11481, Saudi Arabia; (Y.S.C.); (M.A.); (F.S.)
- Correspondence: ; Tel.: +96-656-333-4984
| | - Rakan B. Alanazi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of the National Guard—Health Affairs, Riyadh 14611, Saudi Arabia; (R.B.A.); (S.T.A.); (A.A.R.A.); (M.Q.A.)
- King Abdullah International Medical Research Center, Ministry of the National Guard—Health Affairs, Riyadh 11481, Saudi Arabia; (Y.S.C.); (M.A.); (F.S.)
| | - Sultan T. Algarni
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of the National Guard—Health Affairs, Riyadh 14611, Saudi Arabia; (R.B.A.); (S.T.A.); (A.A.R.A.); (M.Q.A.)
- King Abdullah International Medical Research Center, Ministry of the National Guard—Health Affairs, Riyadh 11481, Saudi Arabia; (Y.S.C.); (M.A.); (F.S.)
| | - Ahmed Abdullah R. Alhuntushi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of the National Guard—Health Affairs, Riyadh 14611, Saudi Arabia; (R.B.A.); (S.T.A.); (A.A.R.A.); (M.Q.A.)
- King Abdullah International Medical Research Center, Ministry of the National Guard—Health Affairs, Riyadh 11481, Saudi Arabia; (Y.S.C.); (M.A.); (F.S.)
| | - Mohammed Qasim Alshehri
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of the National Guard—Health Affairs, Riyadh 14611, Saudi Arabia; (R.B.A.); (S.T.A.); (A.A.R.A.); (M.Q.A.)
- King Abdullah International Medical Research Center, Ministry of the National Guard—Health Affairs, Riyadh 11481, Saudi Arabia; (Y.S.C.); (M.A.); (F.S.)
| | - Yusra Sajid Chachar
- King Abdullah International Medical Research Center, Ministry of the National Guard—Health Affairs, Riyadh 11481, Saudi Arabia; (Y.S.C.); (M.A.); (F.S.)
- College of Sciences and Health Professions, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of the National Guard—Health Affairs, Riyadh 14611, Saudi Arabia
| | - Mohammad Alkaiyat
- King Abdullah International Medical Research Center, Ministry of the National Guard—Health Affairs, Riyadh 11481, Saudi Arabia; (Y.S.C.); (M.A.); (F.S.)
- Department of Medical Oncology, King Abdulaziz Medical City, Ministry of the National Guard—Health Affairs, Riyadh 12713, Saudi Arabia
| | - Fouad Sabatin
- King Abdullah International Medical Research Center, Ministry of the National Guard—Health Affairs, Riyadh 11481, Saudi Arabia; (Y.S.C.); (M.A.); (F.S.)
- Department of Medical Oncology, King Abdulaziz Medical City, Ministry of the National Guard—Health Affairs, Riyadh 12713, Saudi Arabia
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Ling R, Chen G, Tang X, Liu N, Zhou Y, Chen D. Acetyl-CoA synthetase 2(ACSS2): a review with a focus on metabolism and tumor development. Discov Oncol 2022; 13:58. [PMID: 35798917 PMCID: PMC9263018 DOI: 10.1007/s12672-022-00521-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 07/01/2022] [Indexed: 02/08/2023] Open
Abstract
Acetyl-CoA synthetase 2 (ACSS2), an important member of the acetyl-CoA synthetase (ACSS) family, can catalyze the conversion of acetate to acetyl coenzyme A (acetyl-CoA). Currently, acetyl-CoA is considered an important intermediate metabolite in the metabolism of energy substrates. In addition, nutrients converge through acetyl-CoA into a common metabolic pathway, the tricarboxylic acid cycle and oxidative phosphorylation. Not only does ACSS2 play a crucial role in material energy metabolism, it is also involved in the regulation of various acetylation processes, such as regulation of histone and transcription factor acetylation. ACSS2-mediated regulation of acetylation is related to substance metabolism and tumorigenesis. In mammalian cells, ACSS2 utilizes intracellular acetate to synthesize acetyl-CoA, a step in the process of DNA and histone acetylation. In addition, studies in tumors have shown that cancer cells adapt to the growth conditions in the tumor microenvironment (TME) by activating or increasing the expression level of ACSS2 under metabolic stress. Therefore, this review mainly outlines the role of ACSS2 in substance metabolism and tumors and provides insights useful for investigating ACSS2 as a therapeutic target.
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Affiliation(s)
- Rui Ling
- Institute of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
| | - Gong Chen
- Department of Thoracic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Xiang Tang
- Institute of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Na Liu
- Institute of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Yuepeng Zhou
- Institute of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Deyu Chen
- Institute of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
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Huang Y, Li R, Yang Y. Role of Pyroptosis in Gynecological Oncology and Its Therapeutic Regulation. Biomolecules 2022; 12:biom12070924. [PMID: 35883480 PMCID: PMC9313147 DOI: 10.3390/biom12070924] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 02/04/2023] Open
Abstract
With the continuous advances in molecular biotechnology, many new cell death methods have been discovered. Pyroptosis is a programmed cell death process that differs from apoptosis and autophagy in cell morphology and function. Compared with apoptosis and autophagy, pyroptosis is primarily mediated by intracellular inflammasome and gasdermin D of the gasdermin protein family and involves the release of numerous inflammatory factors. Pyroptosis has been found to be involved in the occurrence and development of infectious diseases and other diseases involving the nervous system and the cardiovascular system. Recent studies have also reported the occurrence of pyroptosis in tumor cells. Accordingly, exploring its effect on tumors has become one of the research hotspots. Herein, recent research progress on pyroptosis is reviewed, especially its role in the development of gynecological tumors. As the pathogenesis of gynecological tumor is better understood, new targets have been introduced for the prevention and clinical treatment of gynecological tumors.
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Affiliation(s)
- Yi Huang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (Y.H.); (R.L.)
| | - Ruiyun Li
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (Y.H.); (R.L.)
| | - Yuan Yang
- The Reproductive Medicine Center, The 1st Hospital of Lanzhou University, Lanzhou 730000, China
- Correspondence:
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Liu J, Chen Y, Zhan X, Yu Y, Yao H. Effect of prior cancer history on survival of patients with esophageal carcinoma: a propensity score matching, population-based study. J Thorac Dis 2022; 14:979-994. [PMID: 35572868 PMCID: PMC9096290 DOI: 10.21037/jtd-21-1707] [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: 10/27/2021] [Accepted: 03/04/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND When conducting esophageal cancer clinical trials, prior cancer history is frequently considered an exclusion criterion due to the assumption that prior malignancy may exert significant interference with the prognosis in patients with esophageal carcinoma. This study aimed to evaluate the impact of prior cancer on survival of patients with esophageal cancer and provide valuable assistance for trial design. METHODS Data regarding patients diagnosed with esophageal cancer between 2011 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and divided into two groups depending on the presence or absence of prior cancer history. Propensity score matching (PSM) was performed to minimize the confounding bias caused by covariates. Subsequently, Kaplan-Meier analysis and multivariate Cox proportional hazards models were used to compare all-cause and esophageal cancer-specific survival between patients with and without prior cancer. RESULTS Among 17,123 patients with esophageal carcinoma included in this study, 2,224 (13%) patients had prior cancer history. Before PSM, Kaplan-Meier curves between the two groups classified by prior cancer history showed no significant differences in all-cause (HR =1.047, 95% CI: 0.995-1.102, P=0.077) and esophageal cancer-specific survival (HR =0.986, 95% CI: 0.928-1.048, P=0.65). Similar results were obtained after PSM. In multivariate Cox analysis, prior malignancy was not significantly associated with all-cause (HR =1.002, 95% CI: 0.936-1.072, P=0.965) and esophageal cancer-specific survival (HR =0.964, 95% CI: 0.890-1.045, P=0.374). Subgroup analysis stratified by timing of prior cancer demonstrated that prior cancer had no significant effect on prognosis in the recent latency period subgroups (P>0.05). Furthermore, patients with a prior cancer of lung and bronchus (P=0.013) or head and neck (P=0.012) displayed significantly worse survival than patients without prior cancer, while other types of prior cancer showed no significant effect. CONCLUSIONS The findings suggest that prior cancer is likely not a definite factor that has an impact on all-cause and esophageal cancer-specific survival. Therefore, exclusion criteria of prior cancer history in esophageal cancer clinical trials should be seriously reconsidered.
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Affiliation(s)
- Jingwen Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Phase I Clinical Trial Centre, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yongjian Chen
- Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiangyu Zhan
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yunfang Yu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Phase I Clinical Trial Centre, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Herui Yao
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Phase I Clinical Trial Centre, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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9
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Li R, Lu C, Li X, Chen X, Huang G, Wen Z, Li H, Tao L, Hu Y, Zhao Z, Chen Z, Lai Y. A Four-MicroRNA Panel in Serum as a Potential Biomarker for Screening Renal Cell Carcinoma. Front Genet 2022; 13:897827. [PMID: 35938021 PMCID: PMC9355293 DOI: 10.3389/fgene.2022.897827] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/23/2022] [Indexed: 02/05/2023] Open
Abstract
Background: Renal cell carcinoma (RCC) has been a major health problem and is one of the most malignant tumors around the world. Serum microRNA (miRNA) profiles previously have been reported as non-invasive biomarkers in cancer screening. The aim of this study was to explore serum miRNAs as potential biomarkers for screening RCC. Methods: A three-phase study was conducted to explore serum miRNAs as potential biomarkers for screening RCC. In the screening phase, 12 candidate miRNAs related to RCC were selected for further study by the ENCORI database with 517 RCC patients and 71 NCs. A total of 220 participants [108 RCC patients and 112 normal controls (NCs)] were enrolled for training and validation. The dysregulated candidate miRNAs were further confirmed with 30 RCC patients and 30 NCs in the training phase and with 78 RCC patients and 82 NCs in the validation phase. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used for assessing the diagnostic value of miRNAs. Bioinformatic analysis and survival analysis were also included in our study. Results: Compared to NCs, six miRNAs (miR-18a-5p, miR-138-5p, miR-141-3p, miR-181b-5p, miR-200a-3p, and miR-363-3p) in serum were significantly dysregulated in RCC patients. A four-miRNA panel was built by combining these candidate miRNAs to improve the diagnostic value with AUC = 0.908. ABCG1 and RNASET2, considered potential target genes of the four-miRNA panel, may play a significant role in the development of RCC. Conclusion: A four-miRNA panel in serum was identified for RCC screening in our study. The four--miRNA panel has a great potential to be a non-invasive biomarker for RCC screening.
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Affiliation(s)
- Rongkang Li
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
- The Fifth Clinical Medical College of Anhui Medical University, Hefei, China
| | - Chong Lu
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
- The Fifth Clinical Medical College of Anhui Medical University, Hefei, China
| | - Xinji Li
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
- Shantou University Medical College, Shantou, China
| | - Xuan Chen
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
- Shantou University Medical College, Shantou, China
| | - Guocheng Huang
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
- Shantou University Medical College, Shantou, China
| | - Zhenyu Wen
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
- Shantou University Medical College, Shantou, China
| | - Hang Li
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
| | - Lingzhi Tao
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
| | - Yimin Hu
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
| | - Zhengping Zhao
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
| | - Zebo Chen
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
- *Correspondence: Zebo Chen, ; Yongqing Lai,
| | - Yongqing Lai
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China
- The Fifth Clinical Medical College of Anhui Medical University, Hefei, China
- *Correspondence: Zebo Chen, ; Yongqing Lai,
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10
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Xie J, Zhu Z, Cao Y, Ruan S, Wang M, Shi J. Solute carrier transporter superfamily member SLC16A1 is a potential prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma. Channels (Austin) 2021; 15:483-495. [PMID: 34254872 PMCID: PMC8279094 DOI: 10.1080/19336950.2021.1953322] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/14/2021] [Accepted: 07/02/2021] [Indexed: 12/13/2022] Open
Abstract
Melanoma is a type of cancer with a relatively poor prognosis. The development of immunotherapy for the treatment of patients with melanoma has drawn considerable attention in recent years. It is of great clinical significance to identify novel promising prognostic biomarkers and to explore their roles in the immune microenvironment. The solute carrier (SLC) superfamily is a group of transporters predominantly expressed on the cell membrane and are involved in substance transport. SLC16A1 is a member of the SLC family, participating in the transport of lactate, pyruvate, amino acids, ketone bodies, etc. The role of SLC16A1 in tumor immunity has been recently elucidated, while its role in melanoma remains unclear. In this study, bioinformatics analysis was performed to explore the role of SLC16A1 in melanoma. The results showed that high SLC16A1 expression was correlated with decreased overall survival in patients with melanoma. The genes co-expressed with SLC16A1 were significantly enriched in metabolic regulation, protein ubiquitination, and substance localization. Moreover, SLC16A1 was correlated with the infiltration of immune cells. In conclusion, SLC16A1 is a robust prognostic biomarker for melanoma and may be used as a novel target in immunotherapy.
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Affiliation(s)
- Jiaheng Xie
- Department of Burn and Plastic Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Zhechen Zhu
- Department of Burn and Plastic Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Yuan Cao
- The Forth School of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Shujie Ruan
- Department of Burn and Plastic Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Ming Wang
- Department of Burn and Plastic Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Jingping Shi
- Department of Burn and Plastic Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, China
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11
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Wassie M, Aemro A, Fentie B. Prevalence and associated factors of baseline anemia among cervical cancer patients in Tikur Anbesa Specialized Hospital, Ethiopia. BMC WOMENS HEALTH 2021; 21:36. [PMID: 33494721 PMCID: PMC7831239 DOI: 10.1186/s12905-021-01185-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 01/12/2021] [Indexed: 12/20/2022]
Abstract
Background Almost one patient with cancer in two is anemic. About 40 to 64% of cervical cancer patients are anemic at time of presentation. The rate of anemia increases with the use of chemotherapy, radiotherapy, hormonal therapy and associated with poorer treatment outcome and quality of life. Therefore, the aim of this study was to assess prevalence and associated factors of baseline anemia among cervical cancer patients in Tikur Anbesa Specialized Hospital (TASH), Ethiopia. Methods Institutional based cross-sectional study was done from March to April 2019 at TASH cancer center. Data were collected from patient’s chart using structured checklist and analyzed using Stata14.2. Binary logistic regression model was used to identify covariates which affected the outcome variable. Result This is a 3-years retrospective study from 2014 to 2016. The prevalence of baseline anemia among cervical cancer patients was 50.95%. Being stage IV [AOR = 2.38, 95% CI (1.21–4.67)], having comorbidity [AOR = 3.32, 95% CI (2.25–4.90)] and using substances (patients who used one, two or all of the three substances (cigarate, chat and alcohol)) [AOR = 2.03, 95% CI (1.21–3.41)] significantly increased the occurrence of anemia while being divorced [AOR = 0.6, 95% CI (0.36–0.98)] decreased the occurrence of anemia in the current study. Conclusion The prevalence of baseline anemia was high in the current study compared to other literatures. Significant factors of baseline anemia of cervical cancer in the current study were advanced stage (stage IV), presence of comorbidity, substance usage and being divorced (protective). The authors recommend that it is better to give special attention to those patients with the stated factors that could interfere treatment outcome.
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Affiliation(s)
- Mulugeta Wassie
- School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
| | - Agazhe Aemro
- School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Beletech Fentie
- School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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12
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Pal A, Curtin JF, Kinsella GK. In silico and in vitro screening for potential anticancer candidates targeting GPR120. Bioorg Med Chem Lett 2020; 31:127672. [PMID: 33161126 DOI: 10.1016/j.bmcl.2020.127672] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 10/30/2020] [Accepted: 11/01/2020] [Indexed: 01/02/2023]
Abstract
The G-protein coupled receptor - GPR120 has recently been implicated as a novel target for colorectal cancer (CRC) and other cancer managements. In this study, a homology model of GPR120S (short isoform) was generated to identify potential anti-cancer compounds targeting the GPR120 receptor using a combined in silico docking-based virtual screening (DBVS), structure-activity relationships (SAR) and in vitro screening approach. SPECS database of synthetic chemical compounds (~350,000) was screened using the developed GPR120S model to identify molecules binding to the orthosteric binding pocket followed by an AutoDock SMINA rigid-flexible docking protocol. The best 13 hit molecules were then tested in vitro to evaluate their cytotoxic activity against SW480 - human CRC cell line expressing GPR120. The test compound 1 (3-(4-methylphenyl)-2-[(2-oxo-2-phenylethyl)sulfanyl]-5,6-dihydrospiro(benzo[h]quinazoline-5,1'-cyclopentane)-4(3H)-one) showed ~ 90% inhibitory effects on cell growth with micromolar affinities (IC50 = 23.21-26.69 µM). Finally, SAR analysis of compound 1 led to the identification of a more active compound from the SPECS database showing better efficacy during cell-based cytotoxicity assay -5 (IC50 = 5.89-6.715 µM), while a significant reduction in cytotoxic effects of 5 was observed in GPR120-siRNA pre-treated SW480 cells. The GPR120S homology model generated, and SAR analysis conducted by this work discovered a potential chemical scaffold, dihydrospiro(benzo[h]quinazoline-5,1'-cyclopentane)-4(3H)-one, which will aid future research on anti-cancer drug development for CRC management.
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Affiliation(s)
- Ajay Pal
- School of Food Science and Environmental Health, College of Sciences and Health, Technological University Dublin, Dublin D07 ADY7, Ireland; Environmental Sustainability and Health Institute (ESHI), Grangegorman, Technological University Dublin, Dublin D07 H6K8, Ireland
| | - James F Curtin
- School of Food Science and Environmental Health, College of Sciences and Health, Technological University Dublin, Dublin D07 ADY7, Ireland
| | - Gemma K Kinsella
- School of Food Science and Environmental Health, College of Sciences and Health, Technological University Dublin, Dublin D07 ADY7, Ireland.
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Wang Q, Lu Z, Ma J, Zhang Q, Wang N, Qian L, Zhang J, Chen C, Lu B. Six-mRNA risk score system and nomogram constructed for patients with ovarian cancer. Oncol Lett 2019; 18:1235-1245. [PMID: 31423184 PMCID: PMC6607424 DOI: 10.3892/ol.2019.10404] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 03/01/2019] [Indexed: 12/11/2022] Open
Abstract
Platinum is a commonly used drug for the treatment of ovarian cancer (OC). The aim of the current study was to design and construct a risk score system for predicting the prognosis of patients with OC receiving platinum chemotherapy. The mRNA sequencing data and copy number variation (CNV) information (training set) of patients with OC were downloaded from The Cancer Genome Atlas database. A validation set, GSE63885, was obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) and CNV genes (DECNs) between platinum-resistant and platinum-sensitive groups were identified using the limma package. The intersection between DEGs and DECNs were selected. Cox regression analysis was used to identify the genes and clinical factors associated with prognosis. Risk score system assessment and nomogram analysis were performed using the survival and rms packages in R. Gene Set Enrichment Analysis was used to identify the enriched pathways in high and low risk score groups. From 1,144 DEGs and 1,864 DECNs, 48 genes that occurred in the two datasets were selected. A total of six independent prognostic genes (T-box transcription factor T, synemin, tektin 5, growth differentiation factor 3, solute carrier family 22 member 3 and calcium voltage-gated channel subunit α1 C) and platinum response status were revealed to be associated with prognosis. Based on the six independent prognostic genes, a risk score system was constructed and assessed. Nomogram analysis revealed that the patients with the sensitive status and low risk scores had an improved prognosis. Furthermore, the current study revealed that the 574 DEGs identified were involved in eight pathways, including chemokine signaling pathway, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, RIG I like receptor signaling pathway, natural killer cell mediated cytotoxicity, apoptosis, T cell receptor signaling pathway and Fc ε receptor 1 signaling pathway. The six-mRNA risk score system designed in the present study may be used as prognosis predictor in patients with OC, whereas the nomogram may be valuable for identifying patients with OC who may benefit from platinum chemotherapy.
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Affiliation(s)
- Qianqian Wang
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
| | - Zhuwu Lu
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
| | - Jinqi Ma
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
| | - Qingsong Zhang
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
| | - Ni Wang
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
| | - Li Qian
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
| | - Jun Zhang
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
| | - Chen Chen
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
| | - Bei Lu
- Department of Obstetrics and Gynecology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
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Rasool M, Malik A, Abdul Basit Ashraf M, Arooj M, Kiran A, Waquar S, Ayyaz U, Zahid A, Zaheer A, Jabbar A, Zain M, Raza A, Mehmood A, Batool Qaisrani T, Mirza Z, Hussein Al-Qahtani M, Karim S, Haque A. Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders. Saudi J Biol Sci 2018; 25:1724-1728. [PMID: 30591791 PMCID: PMC6303172 DOI: 10.1016/j.sjbs.2018.08.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 08/11/2018] [Accepted: 08/12/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Cancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders. MATERIALS AND METHODS The concentration of oxidative stress markers such as MDA, NO and levels of different antioxidant molecules such as SOD, CAT, GSH, GPx, GPr, VIT A, VIT E and VIT C present in the serum of chemotherapy treated patients (n = 50) and in normal persons (n = 20) were estimated by the direct spectrophotometric method while the concentration of TNF-α and MMP-9 activity were determined using human TNF-α and MMP-9 ELISA kits. RESULTS The concentration of SOD and CAT (0.356 ± 0.05 μg/dl and 1.26 ± 0.01 μmol/mol of protein) was significantly lower as compared to that (1.09 ± 0.03 μg/dl and 3.99 ± 0.04 μmol/mol of protein) in controls. The levels of GPx (0.06 ± 0.01 mmol/dl) in the cancer patients were much lower than those in the controls (0.78 ± 0.06 mmol/dl). Lower level of GSH (0.96 ± 0.003 μg/dl) in serum of the diseased group was observed as compared to healthy group (7.26 ± 1.40 μg/dl). The level of Vit A, Vit C and Vit E was lower in systemic circulation of cancer patients (109.99 ± 6.35 μg/ml, 1.26 ± 0.36 μg/ml and 1.29 ± 0.191 μg/ml) as compared to control subjects (166.35 ± 14.26 μg/ml, 3.25 ± 0.099 μg/ml and 6.354 ± 2.26 μg/ml) respectively. The concentration of nitric oxide was significantly higher in the cancer patients (45.26 ± 6.35 ng/ml) than that in the normal subjects (16.35 ± 3.26 ng/ml). The higher concentration of MDA (8.65 ± 3.26 nmol/ml) was observed in the patients than normal ones (1.254 ± 0.065 nmol/ml). The quantity of TNF-α was significantly higher in chemotherapy treated patients (32.68 ± 4.33 pg/ml) as compared to the control group (20.979 ± 1.98 pg/ml). Significantly higher concentration of MMP-9 (40.26 ± 3.26 ng/ml) was observed in the cancer patients than the controls (7.256 ± 1.95 ng/ml). CONCLUSION Lower levels of antioxidant enzymes and non-enzymatic small molecules and higher levels of oxidative stress and inflammatory clinical parameters such as NO, MDA, TNF-α and MMP-9 may be involved in the pathogenesis of systemic chemotherapy related ocular complications such as cataract, glaucoma, blepharitis, retinitis pigmentosa, macular degeneration, pterygium and retinal degeneration.
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Affiliation(s)
- Mahmood Rasool
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Arif Malik
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | | | - Mahwish Arooj
- University College of Medicine and Dentistry, the University of Lahore, Lahore, Pakistan
| | - Asia Kiran
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | - Sulayman Waquar
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | - Ujala Ayyaz
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | - Ayesha Zahid
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | - Ahmad Zaheer
- National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan
| | - Abdul Jabbar
- Department of Biotechnology, Mirpur University of Science and Technology (MUST), Mirpur (AJK), Pakistan
| | - Maryam Zain
- Microbiology and Molecular Genetics Department, The Women University, Multan, Pakistan
| | - Amir Raza
- National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan
| | - Asim Mehmood
- Department of Biosciences, COMSATS University, Sahiwal Campus, Sahiwal, Pakistan
| | | | - Zeenat Mirza
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | - Sajjad Karim
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Absarul Haque
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
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15
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Cheng L, Li L, Wang L, Li X, Xing H, Zhou J. A random forest classifier predicts recurrence risk in patients with ovarian cancer. Mol Med Rep 2018; 18:3289-3297. [PMID: 30066910 PMCID: PMC6102638 DOI: 10.3892/mmr.2018.9300] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 04/23/2018] [Indexed: 12/12/2022] Open
Abstract
Ovarian cancer (OC) is associated with a poor prognosis due to difficulties in early detection. The aims of the present study were to construct a recurrence risk prediction model and to reveal important OC genes or pathways. RNA sequencing data was obtained for 307 OC samples, and the corresponding clinical data were downloaded from The Cancer Genome Atlas database. Additionally, two validation datasets, GSE44104 (20 recurrent and 40 non-recurrent OC samples) and GSE49997 (204 OC samples), were obtained from the Gene Expression Omnibus database. Differentially expressed genes were screened using the differential expression via distance synthesis algorithm, followed by gene ontology enrichment analysis and weighted gene coexpression network analysis (WGCNA). Furthermore, subnetwork analysis was conducted for the protein-protein interaction (PPI) network using the BioNet package. Finally, a random forest classifier was constructed based on the subnetwork nodes, and its reliability was validated using the GSE44104 and GSE49997 validation datasets. A total of 44 upregulated and 117 downregulated genes were identified in the recurrent samples. Enrichment analysis indicated that cytochrome P450 family 17 subfamily A member 1 (CYP17A1) was associated with ‘positive regulation of steroid hormone biosynthetic processes’. WGCNA identified turquoise and grey modules that were significantly correlated with status and prognosis. A significant PPI subnetwork containing 16 nodes was also identified, including: Transcription factor GATA-4; fibroblast growth factor 9; aromatase; 3β-hydroxysteroid dehydrogenase/δ5-4-isomerase type 2; corticosteroid 11β-dehydrogenase isozyme 1; CYP17A1; pituitary homeobox 2; left-right determination factor 1; homeobox protein ARX; estrogen receptor β; steroidogenic factor 1; forkhead box protein L2; myocardin; steroidogenic acute regulatory protein mitochondrial; vesicular inhibitory amino acid transporter; and twist-related protein 1. A random forest classifier was constructed using the subnetwork nodes as feature genes, which exhibited a 92% true positive rate when classifying recurrent and non-recurrent OC samples. The classifying efficiency of the random forest classifier was validated using the two other independent datasets. Overall, 44 upregulated and 117 downregulated genes associated with OC recurrence were identified. Furthermore, the 16 subnetwork node genes that were identified may be important molecules in OC recurrence.
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Affiliation(s)
- Li Cheng
- Department of Obstetrics and Gynecology, Xiangyang Central Hospital (Affiliated Hospital of Hubei University of Arts and Science), Xiangyang, Hubei 441021, P.R. China
| | - Lin Li
- Department of Obstetrics and Gynecology, Xiangyang Central Hospital (Affiliated Hospital of Hubei University of Arts and Science), Xiangyang, Hubei 441021, P.R. China
| | - Liling Wang
- Department of Obstetrics and Gynecology, Xiangyang Central Hospital (Affiliated Hospital of Hubei University of Arts and Science), Xiangyang, Hubei 441021, P.R. China
| | - Xiaofang Li
- Department of Obstetrics and Gynecology, Xiangyang Central Hospital (Affiliated Hospital of Hubei University of Arts and Science), Xiangyang, Hubei 441021, P.R. China
| | - Hui Xing
- Department of Obstetrics and Gynecology, Xiangyang Central Hospital (Affiliated Hospital of Hubei University of Arts and Science), Xiangyang, Hubei 441021, P.R. China
| | - Jinting Zhou
- Department of Obstetrics and Gynecology, Xiangyang Central Hospital (Affiliated Hospital of Hubei University of Arts and Science), Xiangyang, Hubei 441021, P.R. China
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Bielecka AM, Obuchowicz E. Antidepressant drugs as a complementary therapeutic strategy in cancer. Exp Biol Med (Maywood) 2014; 238:849-58. [PMID: 23970405 DOI: 10.1177/1535370213493721] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
In the last decade, it has been increasingly recognized that antidepressant drugs may exert a range of effects, in addition to their well-documented ability to modulate neurotransmission. Although as a group they act on monoaminergic systems and receptors in different ways, a number of studies have demonstrated that at least some antidepressants might have other properties in common, including immunomodulatory, cyto/neuroprotective, analgesic and anti-inflammatory activities. These properties are partly related to the influence of antidepressants on glial cell function. Recently, emerging information about the possible anticancer properties of antidepressants has sparked increased interest within scientific community, and there is now evidence that these drugs affect the key cellular mechanisms of carcinogenesis. This review examines the putative cellular targets for the anticancer action of antidepressant drugs, and presents examples of the interaction between antidepressants and anticancer drugs. By reviewing the current state of research in this area, we hope to focus the attention of oncologists and researchers engaged in the study of cancer on the role that antidepressant drugs could play in the complementary therapy of cancer.
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Affiliation(s)
- Anna M Bielecka
- Medical University of Silesia, Department of Pharmacology, Medyków 18, 40-752 Katowice, Poland.
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17
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Yang GY, Zhang CL, Liu XC, Qian G, Deng DQ. Effects of cigarette smoke extracts on the growth and senescence of skin fibroblasts in vitro. Int J Biol Sci 2013; 9:613-23. [PMID: 23847443 PMCID: PMC3708041 DOI: 10.7150/ijbs.6162] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2013] [Accepted: 05/27/2013] [Indexed: 12/24/2022] Open
Abstract
Epidemiological studies have shown that cigarette smoke (CS), a very common environmental factor, plays an important role in skin aging. Although some in vivo studies have suggested that CS affects skin aging, the detailed effects of CS on skin cells in vitro remain largely unknown. In this study, we investigated the effects of cigarette smoke extract (CSE) on the growth, proliferation, and senescene of skin fibroblasts and the possible mechanism underlying these effects. Primary cultured human fibroblasts were exposed to a range of concentrations of CSE. Cell viability and cell proliferation after CSE exposure were analyzed with the methyl thiazolyl tetrazolium (MTT) assay and bromodeoxyuridine incorporation assay, respectively. Growth curves of fibroblasts exposed to different concentrations of CSE were developed and prolonged CSE-exposed cells were observed. Morphological and ultrastructural changes in fibroblasts were assessed by inverted light microscopy and transmission electron microscopy (TEM). Dying cells were stained with senescence-associated β-galactosidase (SA β-gal). Intracellular reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were determined by a colorimetric method. We found that proliferative capacity and growth were inhibited by CSE exposure in a dose- and time-dependent manner. Fibroblasts exposed to even low concentrations of CSE for a long period of time (5 passages) showed significantly increased SA β-gal activity and typical features of aging cells. Meanwhile, CSE inhibited superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and augmented ROS levels. Our observations suggest that CSE exposure impairs fibroblast growth and proliferation and leads to features similar to those seen in senescent cells. Oxidative stress injury and inhibition of antioxidant defense activity may be involved in CSE-induced fibroblast senescence.
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Affiliation(s)
- Gao-yun Yang
- 1. Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chun-lei Zhang
- 2. Department of Dermatology, Peking University Third Hospital. Haidian District, Beijing, China
| | - Xiang-chen Liu
- 1. Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ge Qian
- 3. Department of Dermatology and Rheumatology, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Dan-qi Deng
- 3. Department of Dermatology and Rheumatology, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, China
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STAT5b as molecular target in pancreatic cancer--inhibition of tumor growth, angiogenesis, and metastases. Neoplasia 2013; 14:915-25. [PMID: 23097626 DOI: 10.1593/neo.12878] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2012] [Revised: 09/11/2012] [Accepted: 09/13/2012] [Indexed: 12/30/2022] Open
Abstract
The prognosis of patients suffering from pancreatic cancer is still poor and novel therapeutic options are urgently needed. Recently, the transcription factor signal transducer and activator of transcription 5b (STAT5b) was associated with tumor progression in human solid cancer. Hence, we assessed whether STAT5b might serve as an anticancer target in ductal pancreatic adenocarcinoma (DPAC). We found that nuclear expression of STAT5b can be detected in approximately 50% of DPAC. Blockade of STAT5b by stable shRNA-mediated knockdown showed no effects on tumor cell growth in vitro. However, inhibition of tumor cell motility was found even in response to stimulation with epidermal growth factor or interleukin-6. These findings were paralleled by a reduction of prometastatic and proangiogenic factors in vitro. Subsequent in vivo experiments revealed a strong growth inhibition on STAT5b blockade in subcutaneous and orthotopic models. These findings were paralleled by impaired tumor angiogenesis in vivo. In contrast to the subcutaneous model, the orthotopic model revealed a strong reduction of tumor cell proliferation that emphasizes the meaning of assessing targets in an appropriate microenvironment. Taken together, our results suggest that STAT5b might be a potential novel target for human DPAC.
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Perego S, Zabeo A, Marasco E, Giussani P, Fiorilli A, Tettamanti G, Ferraretto A. Casein phosphopeptides modulate calcium uptake and apoptosis in Caco2 cells through their interaction with the TRPV6 calcium channel. J Funct Foods 2013. [DOI: 10.1016/j.jff.2013.01.032] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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20
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Telomere length and its relationship with chronic diseases – New perspectives for periodontal research. Arch Oral Biol 2013. [DOI: 10.1016/j.archoralbio.2012.09.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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21
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Hachim D, Melendez J, Ebensperger R. Nanoencapsulation of Human Adipose Mesenchymal Stem Cells: Experimental Factors Role to Successfully Preserve Viability and Functionality of Cells. ACTA ACUST UNITED AC 2013. [DOI: 10.4236/jeas.2013.31001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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