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Nahm WJ, Falanga V. The Adverse Impact of Tyrosine Kinase Inhibitors on Wound Healing and Repair. Int Wound J 2025; 22:e70513. [PMID: 40251464 PMCID: PMC12008022 DOI: 10.1111/iwj.70513] [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: 08/21/2024] [Revised: 02/20/2025] [Accepted: 04/02/2025] [Indexed: 04/20/2025] Open
Abstract
Tyrosine kinase inhibitors (TKIs) can treat various cancers, primarily through their antiangiogenic effects. However, as angiogenesis is crucial for successful wound healing, TKIs may adversely impact wound repair. This review analysed all 63 FDA-approved TKIs and identified evidence for wound healing and repair implications in 24 agents. The primary mechanism contributing to impaired wound healing appears to be the inhibition of vascular endothelial growth factor receptors, with secondary targets, such as epidermal growth factor receptors and platelet-derived growth factor receptors, potentially playing a role. Information from safety package inserts, preclinical studies, case reports and clinical trials suggests that these TKIs can cause delayed or impaired wound healing. The safety information generally recommends discontinuing treatment for at least one to 2 weeks before elective surgery and resuming treatment only after adequate wound healing has occurred. Neoadjuvant therapy with TKIs may be feasible if sufficient time is allowed between the cessation of the TKI and the onset of surgery. As the use of TKIs continues to increase, healthcare professionals should be aware of their potential impact on wound healing and take appropriate precautions to minimise the risk of wound-related complications.
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Affiliation(s)
- William J. Nahm
- New York University Grossman School of MedicineNew YorkNew YorkUSA
| | - Vincent Falanga
- Department of DermatologyBoston University Chobanian and Avedisian School of MedicineBostonMassachusettsUSA
- Department of Biochemistry & Cell BiologyBoston University Chobanian and Avedisian School of MedicineBostonMassachusettsUSA
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Tufail M, Jiang CH, Li N. Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence. Mil Med Res 2025; 12:7. [PMID: 39934876 PMCID: PMC11812268 DOI: 10.1186/s40779-025-00595-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 01/26/2025] [Indexed: 02/13/2025] Open
Abstract
Cancer recurrence, driven by the phenomenon of tumor dormancy, presents a formidable challenge in oncology. Dormant cancer cells have the ability to evade detection and treatment, leading to relapse. This review emphasizes the urgent need to comprehend tumor dormancy and its implications for cancer recurrence. Despite notable advancements, significant gaps remain in our understanding of the mechanisms underlying dormancy and the lack of reliable biomarkers for predicting relapse. This review provides a comprehensive analysis of the cellular, angiogenic, and immunological aspects of dormancy. It highlights the current therapeutic strategies targeting dormant cells, particularly combination therapies and immunotherapies, which hold promise in preventing relapse. By elucidating these mechanisms and proposing innovative research methodologies, this review aims to deepen our understanding of tumor dormancy, ultimately facilitating the development of more effective strategies for preventing cancer recurrence and improving patient outcomes.
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Affiliation(s)
- Muhammad Tufail
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Can-Hua Jiang
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, 410008, China
- Institute of Oral Precancerous Lesions, Central South University, Changsha, 410008, China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Ning Li
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, 410008, China.
- Institute of Oral Precancerous Lesions, Central South University, Changsha, 410008, China.
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
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Pawlak M, Rudnicki W, Popiela T, Brandt L, Dobrowolska M, Lipinska M, Łuczyńska E. Comparative analysis of diagnostic performance of automatic breast ultrasound and spectral mammography as complementary methods to mammography examination. Pol J Radiol 2025; 90:e55-e65. [PMID: 40196314 PMCID: PMC11973704 DOI: 10.5114/pjr/199755] [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: 10/14/2024] [Accepted: 12/26/2024] [Indexed: 04/09/2025] Open
Abstract
Purpose This single-centre study includes a comparative analysis of the diagnostic performance of contrast-enhanced mammography (CEM) and automatic breast ultrasound (ABUS). The study involved 81 patients with focal breast lesions, who underwent ABUS, full-field digital mammography (FFDM), and CEM. Material and methods A total of 169 focal lesions were found in 81 patients, of which 110 lesions were histopathologically verified, 92 were malignant, 5 were B3 lesions, and 13 were benign. On CEM 19 additional lesions not visible on other imaging examinations were found, and as many as 36 new lesions were detected on ABUS. The number of lesions detected in patients with multiple lesions were 106 from 169 on ABUS, 65 on FFDM, and 88 on CEM. The highest correlation between the lesion's margin and its histopathological character was found in FFDM (p < 0.00), then ABUS (p = 0.038), and the lowest in CEM (p = 0.043). Compliance in determining the lesions' size comparing to histopathology as a gold standard was the highest for ABUS (p = 0.258) and lower for CEM (p = 0.012). Results The sensitivity of ABUS, FFDM, and CEM was, respectively: 80.43, 90.22, and 93.48; specificity: 27.78, 11.11, and 11.11; positive predictive value (PPV): 85.06, 83.84, and 84.31; negative predictive value (NPV): 21.74, 18.18, and 25; and accuracy: 71.82, 77.27, and 80. The sensitivity and accuracy of the combination of FFDM and ABUS were, respectively, 100 (p = 0.02) and 84.55 (AUC = 0.947) and for the combination of FFDM + CEM 93.48 (p = 0.25) and 79.09 (AUC = 0.855). Conclusions The study confirms that both ABUS and CEM may serve as a valuable complementary method for FFDM.
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Affiliation(s)
- Marta Pawlak
- Department of Radiology, University Hospital in Cracow, Cracow, Poland
| | - Wojciech Rudnicki
- Department of Electroradiology, Jagiellonian University Medical College, Cracow, Poland
| | - Tadeusz Popiela
- Chair of Radiology, Jagiellonian University Medical College, Cracow, Poland
| | - Lukasz Brandt
- Department of Electroradiology, Jagiellonian University Medical College, Cracow, Poland
| | | | - Milena Lipinska
- Department of Radiology, University Hospital in Cracow, Cracow, Poland
| | - Elżbieta Łuczyńska
- Department of Electroradiology, Jagiellonian University Medical College, Cracow, Poland
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Zhang R, Lu J, Di W, Gui Z, Chan SW, Yang F, Shang Y. Diffuse correlation tomography: a technique to characterize tissue blood flow abnormalities in benign and malignant breast lesions. BIOMEDICAL OPTICS EXPRESS 2024; 15:6259-6276. [PMID: 39553863 PMCID: PMC11563337 DOI: 10.1364/boe.535330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/30/2024] [Accepted: 09/30/2024] [Indexed: 11/19/2024]
Abstract
Accurate assessment and quantification of neoangiogenesis associated with breast cancer could be potentially used to improve the sensitivity and specificity of non-invasive diagnosis, as well as predict outcomes and monitor treatment effects. In this study, we adapted an emerging technology, namely diffuse correlation tomography (DCT), to image microvascular blood flow in breast tissues and evaluate the potential for discriminating between benign and malignant lesions. A custom-made DCT system was designed for breast blood flow imaging, with both the source-detector array and reconstruction algorithm optimized to ensure precise imaging of breast blood flow. The global features and local features of three-dimensional blood flow images were extracted from the relative blood flow index (rBFI), which was obtained from most of the breasts targeted to the lesion. A total of 37 women with 19 benign and 18 malignant lesions were included in the study. Significant differences between malignant and benign groups were found in 12 image features. Moreover, when selecting the lesion mean relative blood flow index (MrBFI) as a single indicator, the malignant and benign tumors were discriminated with an accuracy of 89.2%. The blood flow features were found to successfully identify malignant and benign tumors, suggesting that DCT, as an alternate functional imaging modality, has the potential to be translated into clinical practice for diagnosis and assessment of breast cancers. There is potential to reduce the need for biopsy of benign lesions by improving the specificity of diagnostic imaging, as well as monitoring response to breast cancer treatment.
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Affiliation(s)
- Ruizhi Zhang
- State Key Laboratory of Dynamic Measurement Technology, North University of China, Taiyuan 030051, China
| | - Jianju Lu
- Department of Breast Surgery, The First Hospital of Jiaxing, Affiliated hospital of Jiaxing University, Jiaxing 314000, China
| | - Wenqi Di
- State Key Laboratory of Dynamic Measurement Technology, North University of China, Taiyuan 030051, China
| | - Zhiguo Gui
- State Key Laboratory of Dynamic Measurement Technology, North University of China, Taiyuan 030051, China
| | - Shun Wan Chan
- Department of Food and Health Sciences, Technological and Higher Education Institute of Hong Kong SAR, Hong Kong, China
| | - Fengbao Yang
- State Key Laboratory of Dynamic Measurement Technology, North University of China, Taiyuan 030051, China
| | - Yu Shang
- School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, China
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Singh A, Melendez-Moreno A, Krohn J, Zabor EC. Predictive model for iris melanoma. Br J Ophthalmol 2024; 108:1598-1604. [PMID: 38609162 DOI: 10.1136/bjo-2023-324558] [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: 09/13/2023] [Accepted: 03/17/2024] [Indexed: 04/14/2024]
Abstract
AimTo develop a predictive model for the diagnosis of iris melanoma. METHODS Retrospective consecutive case series that included 100 cases of pathologically confirmed iris melanoma and 112 cases of Iris naevus, either pathological confirmation or documented stability of >1 year. Patient demographic data, features of clinical presentation, tumour characteristics and follow-up were collected. Iris melanoma with ciliary body extension was excluded. Lasso logistic regression with 10-fold cross-validation was used to select the tuning parameter. Discrimination was assessed with the area under the curve (AUC) and calibration by a plot. RESULTS There was a significant asymmetry in the location of both nevi and melanoma with preference for inferior iris quadrants (83, 74%) and (79, 79%), respectively (p=0.50). Tumour seeding, glaucoma and hyphaema were present only in melanoma. The features that favoured the diagnosis of melanoma were size (increased height (OR 3.35); increased the largest basal diameter (OR 1.64)), pupillary distortion (ectropion uvea or corectopia (OR 2.55)), peripheral extension (angle or iris root involvement (OR 2.83)), secondary effects (pigment dispersion (OR 1.12)) and vascularity (OR 6.79). The optimism-corrected AUC was 0.865. The calibration plot indicated good calibration with most of the points falling near the identity line and the confidence band containing the identity line through most of the range of probabilities. CONCLUSIONS The predictive model provides direct diagnostic prediction of the lesion being iris melanoma expressed as probability (%). Use of a prediction calculator (app) can enhance decision-making and patient counselling. Further refinements can be undertaken with additional datasets, forming the basis for automated diagnosis.
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Affiliation(s)
- Arun Singh
- Department of Ophthalmic Oncology, Cleveland Clinic Main Campus Hospital, Cleveland, Ohio, USA
| | | | - Jørgen Krohn
- Department of Clinical Medicine, Bergen University College, Bergen, Norway
- Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway
| | - Emily C Zabor
- Department of Quantitative Health Sciences & Taussig Cancer Institute, Cleveland Clinic Main Campus Hospital, Cleveland, Ohio, USA
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Senevirathna K, Mahakapuge TAN, Jayawardana NU, Rajapakse J, Gamage CU, Seneviratne B, Perera U, Kanmodi KK, Jayasinghe R. Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR. BMC Oral Health 2024; 24:1062. [PMID: 39261828 PMCID: PMC11391664 DOI: 10.1186/s12903-024-04834-1] [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: 06/05/2024] [Accepted: 08/29/2024] [Indexed: 09/13/2024] Open
Abstract
BACKGROUND Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.
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Affiliation(s)
- Kalpani Senevirathna
- Department of Biochemistry, Uva Wellassa University of Sri Lanka, Badulla, Sri Lanka
- Centre for Research in Oral Cancer, University of Peradeniya, Peradeniya, Sri Lanka
| | | | | | - Jayanthe Rajapakse
- Department of Veterinary Pathobiology, University of Peradeniya, Peradeniya, Sri Lanka
| | | | - Bimalka Seneviratne
- Department of Pathology, Sri Jayewardenepura University, Gangodawila, Sri Lanka
| | - Unil Perera
- Department of Physics & Astronomy, Georgia State University, Atlanta, USA
| | - Kehinde Kazeem Kanmodi
- Applied BioSciences, Macquarie University, Sydney, Australia.
- School of Dentistry, University of Rwanda, Kigali, Rwanda.
- Faculty of Dentistry, University of Puthisastra, Phnom Penh, Cambodia.
| | - Ruwan Jayasinghe
- Faculty of Dentistry, University of Puthisastra, Phnom Penh, Cambodia
- Department of Oral Medicine and Periodontology, University of Peradeniya, Peradeniya, Sri Lanka
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Douglas KA, Drakonaki EE, Douglas VP, Detorakis ET. Shear-wave elastographic imaging in choroidal melanomas: clinical and hemodynamic correlations. Jpn J Ophthalmol 2024; 68:523-530. [PMID: 39088115 DOI: 10.1007/s10384-024-01086-y] [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: 09/18/2023] [Accepted: 05/29/2024] [Indexed: 08/02/2024]
Abstract
PURPOSE This study evaluated the role of shear wave elastography imaging (SWEΙ) in uveal melanomas and the associations between SWEI and clinical and hemodynamic findings. STUDY DESIGN Prospective, clinical study METHODS: Twelve patients with uveal melanomas, scheduled to undergo Ru-106 brachytherapy, were prospectively recruited from the Department of Ophthalmology of the University Hospital of Heraklion (September-December 2022). B-mode, hemodynamic and SWEI ultrasonography examinations were performed with the HiScan (OPTIKON 2000) and the LOGIQ E9 (GE Healthcare) sonographic systems, respectively. Differences in SWEI scores (kPa) between tumor (TS) and adjacent non-affected choroid (CS), as well as between TS and orbital fat (FS) were examined. Correlations between SWEI and intra-tumoral hemodynamic parameters, including peak systolic and end diastolic velocities and resistivity index (RI) were also examined. RESULTS TS was significantly correlated with intra-tumoral RI (Pearson's bivariate correlation coefficient 0.681, p=0.015) and with maximal tumor height (Pearson's bivariate correlation coefficient 0.620, p=0.031). TS was significantly higher than both FS and CS scores (paired-samples t-test, p=0.003 and p=0.006, respectively). CONCLUSIONS SWEI score is applicable as a quantitative biomechanical marker in the assessment of choroidal melanoma. Choroidal melanomas are stiffer than both adjacent choroid and orbital fat. Moreover, choroidal melanomas with higher RI as well as those with higher apical elevations display higher SWEI scores.
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Affiliation(s)
| | - Eleni E Drakonaki
- Department of Anatomy, Medical School, University of Crete, Heraklion, Greece
| | | | - Efstathios T Detorakis
- Medical School, University of Crete, Heraklion, Greece.
- Department of Ophthalmology, University Hospital of Heraklion, Stavrakia, Crete, 71111, Heraklion, Greece.
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Ratti M, Orlandi E, Toscani I, Vecchia S, Anselmi E, Hahne JC, Ghidini M, Citterio C. Emerging Therapeutic Targets and Future Directions in Advanced Gastric Cancer: A Comprehensive Review. Cancers (Basel) 2024; 16:2692. [PMID: 39123420 PMCID: PMC11311890 DOI: 10.3390/cancers16152692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/19/2024] [Accepted: 07/21/2024] [Indexed: 08/12/2024] Open
Abstract
Metastatic gastric cancer (GC) still represents a critical clinical challenge, with limited treatment options and a poor prognosis. Most patients are diagnosed at advanced stages, limiting the chances of surgery and cure. The identification of molecular targets and the possibility of combining immune checkpoint inhibitors with chemotherapy have recently reshaped the therapeutic landscape of metastatic gastric cancer. The new classification of gastric cancer, mainly based on immunologic and molecular criteria such as programmed cell death 1 (PD-1), microsatellite instability (MSI), and human epidermal growth factor receptor 2 (HER2), has made it possible to identify and differentiate patients who may benefit from immunotherapy, targeted therapy, or chemotherapy alone. All relevant and available molecular and immunological targets in clinical practice for the systemic treatment of this disease are presented. Particular attention is given to possible future approaches, including circulating tumor DNA (ctDNA) for therapeutic monitoring, new targeting agents against molecular pathways such as fibroblast growth factor receptor (FGFR) and MET, chimeric antigen receptor (CAR)-T cells, and cancer vaccines. This review aims to provide a comprehensive understanding of current targets in advanced gastric cancer and to offer valuable insights into future directions of research and clinical practice in this challenging disease.
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Affiliation(s)
- Margherita Ratti
- Oncology and Hematology Department, Piacenza General Hospital, Via Taverna 49, 29121 Piacenza, Italy; (E.O.); (I.T.); (S.V.); (E.A.); (C.C.)
| | - Elena Orlandi
- Oncology and Hematology Department, Piacenza General Hospital, Via Taverna 49, 29121 Piacenza, Italy; (E.O.); (I.T.); (S.V.); (E.A.); (C.C.)
| | - Ilaria Toscani
- Oncology and Hematology Department, Piacenza General Hospital, Via Taverna 49, 29121 Piacenza, Italy; (E.O.); (I.T.); (S.V.); (E.A.); (C.C.)
| | - Stefano Vecchia
- Oncology and Hematology Department, Piacenza General Hospital, Via Taverna 49, 29121 Piacenza, Italy; (E.O.); (I.T.); (S.V.); (E.A.); (C.C.)
| | - Elisa Anselmi
- Oncology and Hematology Department, Piacenza General Hospital, Via Taverna 49, 29121 Piacenza, Italy; (E.O.); (I.T.); (S.V.); (E.A.); (C.C.)
| | - Jens Claus Hahne
- Division of Molecular Pathology, The Institute of Cancer Research, Sutton, London SM2 5NG, UK;
| | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
| | - Chiara Citterio
- Oncology and Hematology Department, Piacenza General Hospital, Via Taverna 49, 29121 Piacenza, Italy; (E.O.); (I.T.); (S.V.); (E.A.); (C.C.)
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Xie W, Wang Z, Wang J, Wang X, Guan H. Investigating the molecular mechanisms of microRNA‑409‑3p in tumor progression: Towards targeted therapeutics (Review). Int J Oncol 2024; 65:67. [PMID: 38757364 PMCID: PMC11155714 DOI: 10.3892/ijo.2024.5655] [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: 12/14/2023] [Accepted: 05/02/2024] [Indexed: 05/18/2024] Open
Abstract
MicroRNAs (miRNAs) are a group of non‑coding RNAs that exert master regulatory functions in post‑-transcriptional gene expression. Accumulating evidence shows that miRNAs can either promote or suppress tumorigenesis by regulating different target genes or pathways and may be involved in the occurrence of carcinoma. miR‑409‑3p is dysregulated in a variety of malignant cancers. It plays a fundamental role in numerous cellular biological processes, such as cell proliferation, apoptosis, migration, invasion, autophagy, angiogenesis and glycolysis. In addition, studies have shown that miR‑409‑3p is expected to become a non‑invasive biomarker. Identifying the molecular mechanisms underlying miR‑409‑3p‑mediated tumor progression will help investigate miR‑409‑3p‑based targeted therapy for human cancers. The present review comprehensively summarized the recently published literature on miR‑409‑3p, with a focus on the regulation and function of miR‑409‑3p in various types of cancer, and discussed the clinical implications of miR‑409‑3p, providing new insight for the diagnosis and treatment of cancers.
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Affiliation(s)
- Wenjie Xie
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Zhichao Wang
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Junke Wang
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
| | - Xiu Wang
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Hongzai Guan
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
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Rodrigues LDS, Felix TF, Minutentag IW, Reis PP, Bertanha M. Deciphering Key microRNA Regulated Pathways in Tissue-Engineered Blood Vessels: Implications for Vascular Scaffold Production. Int J Mol Sci 2024; 25:6762. [PMID: 38928467 PMCID: PMC11203763 DOI: 10.3390/ijms25126762] [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: 05/07/2024] [Revised: 06/10/2024] [Accepted: 06/16/2024] [Indexed: 06/28/2024] Open
Abstract
MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important biological functions such as inflammation. miRNAs play roles associated with the pathogenesis of chronic degenerative disorders including cardiovascular diseases. Understanding the influence of miRNAs and their target genes can effectively streamline the identification of key biologically active pathways that are important in the development of vascular grafts through the tissue engineering of blood vessels. To determine miRNA expression levels and identify miRNA target genes and pathways with biological roles in scaffolds that have been repopulated with adipose-derived stem cells (ASCs) generated through tissue engineering for the construction of blood vessels. miRNA quantification assays were performed in triplicate to determine miRNA expression in a total of 20 samples: five controls (natural inferior vena cava), five scaffolds recellularized with ASCs and differentiated into the endothelium (luminal layer), five samples of complete scaffolds seeded with ASCs differentiated into the endothelium (luminal layer) and smooth muscle (extraluminal layer), and five samples of ASC without cell differentiation. Several differentially expressed miRNAs were identified and predicted to modulate target genes with roles in key pathways associated with angiogenesis, vascular system control, and endothelial and smooth muscle regulation, including migration, proliferation, and growth. These findings underscore the involvement of these pathways in the regulatory mechanisms that are essential for vascular scaffold production through tissue engineering. Our research contributes to the knowledge of miRNA-regulated mechanisms, which may impact the design of vascular substitutes, and provide valuable insights for enhancing clinical practice. The molecular pathways regulated by miRNAs in tissue engineering of blood vessels (TEBV) allowed us to elucidate the main phenomena involved in cellular differentiation to constitute a blood vessel, with the main pathways being essential for angiogenesis, cellular differentiation, and differentiation into vascular smooth muscle.
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Affiliation(s)
- Lenize da Silva Rodrigues
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil;
- Applied Biotechnology Laboratory, Clinical Hospital of Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
- Experimental Research Unit, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (T.F.F.); (I.W.M.); (P.P.R.)
| | - Tainara Francini Felix
- Experimental Research Unit, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (T.F.F.); (I.W.M.); (P.P.R.)
| | - Iael Weissberg Minutentag
- Experimental Research Unit, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (T.F.F.); (I.W.M.); (P.P.R.)
| | - Patricia Pintor Reis
- Experimental Research Unit, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (T.F.F.); (I.W.M.); (P.P.R.)
| | - Matheus Bertanha
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil;
- Applied Biotechnology Laboratory, Clinical Hospital of Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
- Experimental Research Unit, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (T.F.F.); (I.W.M.); (P.P.R.)
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Cheung KS. Big data approach in the field of gastric and colorectal cancer research. J Gastroenterol Hepatol 2024; 39:1027-1032. [PMID: 38413187 DOI: 10.1111/jgh.16527] [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: 01/28/2024] [Accepted: 02/07/2024] [Indexed: 02/29/2024]
Abstract
Big data is characterized by three attributes: volume, variety,, and velocity. In healthcare setting, big data refers to vast dataset that is electronically stored and managed in an automated manner and has the potential to enhance human health and healthcare system. In this review, gastric cancer (GC) and postcolonoscopy colorectal cancer (PCCRC) will be used to illustrate application of big data approach in the field of gastrointestinal cancer research. Helicobacter pylori (HP) eradication only reduces GC risk by 46% due to preexisting precancerous lesions. Apart from endoscopy surveillance, identifying medications that modify GC risk is another strategy. Population-based cohort studies showed that long-term use of proton pump inhibitors (PPIs) associated with higher GC risk after HP eradication, while aspirin and statins associated with lower risk. While diabetes mellitus conferred 73% higher GC risk, metformin use associated with 51% lower risk, effect of which was independent of glycemic control. Nonetheless, nonsteroidal anti-inflammatory drugs (NA-NSAIDs) are not associated with lower GC risk. CRC can still occur after initial colonoscopy in which no cancer was detected (i.e. PCCRC). Between 2005 and 2013, the rate of interval-type PCCRC-3y (defined as CRC diagnosed between 6 and 36 months of index colonoscopy which was negative for CRC) was 7.9% in Hong Kong, with >80% being distal cancers and higher cancer-specific mortality compared with detected CRC. Certain clinical and endoscopy-related factors were associated with PCCRC-3 risk. Medications shown to have chemopreventive effects on PCCRC include statins, NA-NSAIDs, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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12
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Li R, Zhang R, Shi X, Jiao X, Li Y, Zhao Y, Liu T, Zhang C. Expression of FAP in Oral Leukoplakia and Oral Squamous Cell Carcinoma. Int Dent J 2024; 74:581-588. [PMID: 38278714 PMCID: PMC11123527 DOI: 10.1016/j.identj.2023.12.011] [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: 08/16/2023] [Revised: 12/20/2023] [Accepted: 12/29/2023] [Indexed: 01/28/2024] Open
Abstract
OBJECTIVE This study aimed to investigate the potential of fibroblast activation protein (FAP) as a biomarker in the progression of oral leukoplakia (OLK) carcinogenesis. This was achieved by evaluating FAP expression at different levels of the organisation, namely oral normal mucosa (NM), OLK, and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS Altogether, 88 paraffin-embedded tissue samples were examined, including 55 cases of OLK, 13 cases of OSCC, and 20 cases of NM (control group). An exhaustive investigation was performed to examine FAP expression in NM, OLK, and OSCC tissues via immunohistochemistry (IHC). The relationship between FAP expression and clinical pathologic characteristics was analysed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) also proved the expression of FAP in NM, OLK, and OSCC cells. Aberrant FAP expression in OLK and OSCC was explored using in vitro experiments. RESULTS Immunohistochemical results showed that high FAP expression was significantly correlated with histopathologic grade (P = .038) but not correlated with age, sex, or region (P = .953, .622, and .108, respectively). The expression level of FAP in NM tissues (0.15 ± 0.01) was minimal, whereas it was observed in OLK (0.28 ± 0.04) and OSCC (0.39 ± 0.02) tissues with a noticeable increase in expression levels (P < .001). The expression level of FAP in OLK with severe abnormal hyperplasia (S-OLK) tissues (0.33 ± 0.04) was significantly higher than in OLK with mild abnormal hyperplasia (MI-OLK, 0.26 ± 0.02) and OLK with moderate abnormal hyperplasia (MO-OLK, 0.28 ± 0.03) tissues (P < .001 and P = .039, respectively). The results of RT-PCR illustrated that the relative expression of FAP mRNA in OLK cells (2.63 ± 0.62) was higher than in NM cells (0.87 ± 0.14), but lower than in OSCC cells (5.63 ± 1.06; P = .027 and .012, respectively). FAP expression was minimal in NM cells (0.78 ± 0.06), modest in OLK cells (1.04 ± 0.06), and significantly elevated in OSCC cells (1.61 ± 0.09) based on the results of WB (P < .001). CONCLUSIONS Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.
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Affiliation(s)
- Ran Li
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China.
| | - Rongrong Zhang
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China
| | - Xiaotong Shi
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China
| | - Xiaofeng Jiao
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China
| | - Yanwei Li
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China
| | - Yingjiao Zhao
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China
| | - Tiantian Liu
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China; Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China
| | - Chunye Zhang
- Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology.
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13
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De Palma M, Hanahan D. Milestones in tumor vascularization and its therapeutic targeting. NATURE CANCER 2024; 5:827-843. [PMID: 38918437 DOI: 10.1038/s43018-024-00780-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 04/22/2024] [Indexed: 06/27/2024]
Abstract
Research into the mechanisms and manifestations of solid tumor vascularization was launched more than 50 years ago with the proposition and experimental demonstrations that angiogenesis is instrumental for tumor growth and was, therefore, a promising therapeutic target. The biological knowledge and therapeutic insights forthcoming have been remarkable, punctuated by new concepts, many of which were not foreseen in the early decades. This article presents a perspective on tumor vascularization and its therapeutic targeting but does not portray a historical timeline. Rather, we highlight eight conceptual milestones, integrating initial discoveries and recent progress and posing open questions for the future.
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Affiliation(s)
- Michele De Palma
- Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
- Agora Cancer Research Center, Lausanne, Switzerland.
- Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.
| | - Douglas Hanahan
- Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
- Agora Cancer Research Center, Lausanne, Switzerland.
- Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.
- Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland.
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Zhang H, Yang Y, Cao Y, Guan J. Effects of chronic stress on cancer development and the therapeutic prospects of adrenergic signaling regulation. Biomed Pharmacother 2024; 175:116609. [PMID: 38678960 DOI: 10.1016/j.biopha.2024.116609] [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: 01/19/2024] [Revised: 04/14/2024] [Accepted: 04/17/2024] [Indexed: 05/01/2024] Open
Abstract
Long-term chronic stress is an important factor in the poor prognosis of cancer patients. Chronic stress reduces the tissue infiltration of immune cells in the tumor microenvironment (TME) by continuously activating the adrenergic signaling, inhibits antitumor immune response and tumor cell apoptosis while also inducing epithelial-mesenchymal transition (EMT) and tumor angiogenesis, promoting tumor invasion and metastasis. This review first summarizes how adrenergic signaling activates intracellular signaling by binding different adrenergic receptor (AR) heterodimers. Then, we focused on reviewing adrenergic signaling to regulate multiple functions of immune cells, including cell differentiation, migration, and cytokine secretion. In addition, the article discusses the mechanisms by which adrenergic signaling exerts pro-tumorigenic effects by acting directly on the tumor itself. It also highlights the use of adrenergic receptor modulators in cancer therapy, with particular emphasis on their potential role in immunotherapy. Finally, the article reviews the beneficial effects of stress intervention measures on cancer treatment. We think that enhancing the body's antitumor response by adjusting adrenergic signaling can enhance the efficacy of cancer treatment.
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Affiliation(s)
- Hao Zhang
- Department of Oncology, The Eighth Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing 100091, China; Department of Oncology, The Fifth Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing 100071, China.
| | - Yuwei Yang
- College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing Key Laboratory of OTIR, Beijing, 100091, China.
| | - Yan Cao
- College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing Key Laboratory of OTIR, Beijing, 100091, China.
| | - Jingzhi Guan
- Department of Oncology, The Fifth Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing 100071, China.
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Tang MY, Shen X, Yuan RS, Li HY, Li XW, Jing YM, Zhang Y, Shen HH, Wang ZS, Zhou L, Yang YC, Wen HX, Su F. Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients, may mediate immune evasion. World J Gastrointest Oncol 2024; 16:2091-2112. [PMID: 38764846 PMCID: PMC11099457 DOI: 10.4251/wjgo.v16.i5.2091] [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: 12/10/2023] [Revised: 01/17/2024] [Accepted: 02/22/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND For the first time, we investigated the oncological role of plexin domain-containing 1 (PLXDC1), also known as tumor endothelial marker 7 (TEM7), in hepatocellular carcinoma (HCC). AIM To investigate the oncological profile of PLXDC1 in HCC. METHODS Based on The Cancer Genome Atlas database, we analyzed the expression of PLXDC1 in HCC. Using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting, we validated our results. The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features, such as patient survival, methylation level, tumor immune microenvironment features, and immune cell surface checkpoint expression. Finally, to assess the immune evasion potential of PLXDC1 in HCC, we used the tumor immune dysfunction and exclusion (TIDE) website and immunohistochemical staining assays. RESULTS Based on immunohistochemistry, qRT-PCR, and Western blot assays, overexpression of PLXDC1 in HCC was associated with poor prognosis. Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor. In HCC patients with high methylation levels, the prognosis was worse than in patients with low methylation levels. Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling, and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup. The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis, and PLXDC1-related risk scores were also associated with a poor prognosis. CONCLUSION As a result of this study analyzing PLXDC1 from multiple biological perspectives, it was revealed that it is a biomarker of poor prognosis for HCC patients, and that it plays a role in determining immune evasion status.
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Affiliation(s)
- Ming-Yue Tang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Xue Shen
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Run-Sheng Yuan
- Otolaryngology and Head and Neck Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Hui-Yuan Li
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Xin-Wei Li
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Yi-Ming Jing
- Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Yue Zhang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Hong-Hong Shen
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Zi-Shu Wang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Lei Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Yun-Chuan Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - He-Xin Wen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Fang Su
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
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Scalia P, Marino IR, Asero S, Pandini G, Grimberg A, El-Deiry WS, Williams SJ. Autocrine IGF-II-Associated Cancers: From a Rare Paraneoplastic Event to a Hallmark in Malignancy. Biomedicines 2023; 12:40. [PMID: 38255147 PMCID: PMC10813354 DOI: 10.3390/biomedicines12010040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 12/18/2023] [Accepted: 12/20/2023] [Indexed: 01/24/2024] Open
Abstract
The paraneoplastic syndrome referred in the literature as non-islet-cell tumor hypoglycemia (NICTH) and extra-pancreatic tumor hypoglycemia (EPTH) was first reported almost a century ago, and the role of cancer-secreted IGF-II in causing this blood glucose-lowering condition has been widely established. The landscape emerging in the last few decades, based on molecular and cellular findings, supports a broader role for IGF-II in cancer biology beyond its involvement in the paraneoplastic syndrome. In particular, a few key findings are constantly observed during tumorigenesis, (a) a relative and absolute increase in fetal insulin receptor isoform (IRA) content, with (b) an increase in IGF-II high-molecular weight cancer-variants (big-IGF-II), and (c) a stage-progressive increase in the IGF-II autocrine signal in the cancer cell, mostly during the transition from benign to malignant growth. An increasing and still under-exploited combinatorial pattern of the IGF-II signal in cancer is shaping up in the literature with respect to its transducing receptorial system and effector intracellular network. Interestingly, while surgical and clinical reports have traditionally restricted IGF-II secretion to a small number of solid malignancies displaying paraneoplastic hypoglycemia, a retrospective literature analysis, along with publicly available expression data from patient-derived cancer cell lines conveyed in the present perspective, clearly suggests that IGF-II expression in cancer is a much more common event, especially in overt malignancy. These findings strengthen the view that (1) IGF-II expression/secretion in solid tumor-derived cancer cell lines and tissues is a broader and more common event compared to the reported IGF-II association to paraneoplastic hypoglycemia, and (2) IGF-II associates to the commonly observed autocrine loops in cancer cells while IGF-I cancer-promoting effects may be linked to its paracrine effects in the tumor microenvironment. Based on these evidence-centered considerations, making the autocrine IGF-II loop a hallmark for malignant cancer growth, we here propose the functional name of IGF-II secreting tumors (IGF-IIsT) to overcome the view that IGF-II secretion and pro-tumorigenic actions affect only a clinical sub-group of rare tumors with associated hypoglycemic symptoms. The proposed scenario provides an updated logical frame towards biologically sound therapeutic strategies and personalized therapeutic interventions for currently unaccounted IGF-II-producing cancers.
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Affiliation(s)
- Pierluigi Scalia
- The ISOPROG-Somatolink EPFP Research Network, Philadelphia, PA 19102, USA; 93100 Caltanissetta, Italy
| | - Ignazio R. Marino
- Department of Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Salvatore Asero
- The ISOPROG-Somatolink EPFP Research Network, Philadelphia, PA 19102, USA; 93100 Caltanissetta, Italy
- ARNAS Garibaldi, UOC Chirurgia Oncologica, Nesima, 95122 Catania, Italy
| | - Giuseppe Pandini
- The ISOPROG-Somatolink EPFP Research Network, Philadelphia, PA 19102, USA; 93100 Caltanissetta, Italy
| | - Adda Grimberg
- Perelman School of Medicine, University of Pennsylvania, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Wafik S. El-Deiry
- Legorreta Cancer Center, Brown University, Providence, RI 02903, USA
| | - Stephen J. Williams
- The ISOPROG-Somatolink EPFP Research Network, Philadelphia, PA 19102, USA; 93100 Caltanissetta, Italy
- Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
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Zhang J, Huang Q, Bian W, Wang J, Guan H, Niu J. Imaging Techniques and Clinical Application of the Marrow-Blood Barrier in Hematological Malignancies. Diagnostics (Basel) 2023; 14:18. [PMID: 38201327 PMCID: PMC10795601 DOI: 10.3390/diagnostics14010018] [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: 11/07/2023] [Revised: 12/15/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024] Open
Abstract
The pathways through which mature blood cells in the bone marrow (BM) enter the blood stream and exit the BM, hematopoietic stem cells in the peripheral blood return to the BM, and other substances exit the BM are referred to as the marrow-blood barrier (MBB). This barrier plays an important role in the restrictive sequestration of blood cells, the release of mature blood cells, and the entry and exit of particulate matter. In some blood diseases and tumors, the presence of immature cells in the blood suggests that the MBB is damaged, mainly manifesting as increased permeability, especially in angiogenesis. Some imaging methods have been used to monitor the integrity and permeability of the MBB, such as DCE-MRI, IVIM, ASL, BOLD-MRI, and microfluidic devices, which contribute to understanding the process of related diseases and developing appropriate treatment options. In this review, we briefly introduce the theory of MBB imaging modalities along with their clinical applications.
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Affiliation(s)
- Jianling Zhang
- Department of Medical Imaging, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China; (J.Z.); (Q.H.); (W.B.)
| | - Qianqian Huang
- Department of Medical Imaging, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China; (J.Z.); (Q.H.); (W.B.)
| | - Wenjin Bian
- Department of Medical Imaging, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China; (J.Z.); (Q.H.); (W.B.)
| | - Jun Wang
- Department of Radiology, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan 030001, China;
| | - Haonan Guan
- MR Research China, GE Healthcare, Beijing 100176, China;
| | - Jinliang Niu
- Department of Radiology, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan 030001, China;
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Li Y, Hou H, Liu Z, Tang W, Wang J, Lu L, Fu J, Gao D, Zhao F, Gao X, Ling P, Wang F, Sun F, Tan H. CD44 targeting nanodrug based on chondroitin sulfate for melanoma therapy by inducing mitochondrial apoptosis pathways. Carbohydr Polym 2023; 320:121255. [PMID: 37659829 DOI: 10.1016/j.carbpol.2023.121255] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 07/27/2023] [Accepted: 08/01/2023] [Indexed: 09/04/2023]
Abstract
Neovascularization is crucial to the occurrence and progression of tumors, and the development of antiangiogenic drugs has essential theoretical value and clinical significance. However, antiangiogenesis therapy alone cannot meet the needs of tumor therapy. Meanwhile, polysaccharides are ideal drug carriers with promising applications in drug modification and delivery. In this research, we developed a novel redox and acid sensitive nanodrug (CDDP-CS-Cys-EA, CCEA) composed of chondroitin sulfate (CS), antiangiogenic peptide (endostatin2-alft1, EA) and chemotherapeutic drug (cisplatin, CDDP). CCEA exhibited redox and acid responsiveness, better blood hemocompatibility (hemolysis rate < 5 %), the ability to target tumors (CD44-mediated endocytosis), and strong antiangiogenesis and antitumor characteristics in vitro. Moreover, CCEA showed excellent antitumor activity and low toxicity in B16 xenograft mice. It also has been confirmed that CCEA induced tumor cell apoptosis through promoting the expression of Bax, suppressing the expression of Bcl-2, decreasing mitochondrial membrane potential, releasing cytochrome C (Cyto C), and enhancing the activities of Caspase 9 and Caspase 3. The results of this paper provided a theoretical basis and insight for the development of antitumor drugs.
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Affiliation(s)
- Yan Li
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Huiwen Hou
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Zengmei Liu
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Wen Tang
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Jie Wang
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Lu Lu
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Jiaai Fu
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Didi Gao
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Feiyan Zhao
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - XinQing Gao
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China
| | - Peixue Ling
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China; School of Pharmaceutical sciences, Shandong University, Jinan 250012, China
| | - Fengshan Wang
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; School of Pharmaceutical sciences, Shandong University, Jinan 250012, China
| | - Feng Sun
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China.
| | - Haining Tan
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, China; School of Pharmaceutical sciences, Shandong University, Jinan 250012, China.
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Chen Y, Yamamoto T, Takahashi Y, Moro T, Tajima T, Sakaguchi Y, Sakata N, Yokoyama A, Hijioka S, Sada A, Tabata Y, Ohki R. Metabolic intervention by low carbohydrate diet suppresses the onset and progression of neuroendocrine tumors. Cell Death Dis 2023; 14:597. [PMID: 37679316 PMCID: PMC10484927 DOI: 10.1038/s41419-023-06123-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 08/22/2023] [Accepted: 08/29/2023] [Indexed: 09/09/2023]
Abstract
Insulin signaling often plays a role in the regulation of cancer, including tumor initiation, progression, and response to treatment. In addition, the insulin-regulated PI3K-Akt-mTOR pathway plays an important role in the regulation of islet cell proliferation, and this pathway is hyperactivated in human non-functional pancreatic neuroendocrine tumors (PanNETs). We, therefore, investigated the effect of a very low carbohydrate diet (ketogenic diet) on a mouse model that develops non-functional PanNETs to ask how reduced PI3K-Akt-mTOR signaling might affect the development and progression of non-functional PanNET. We found that this dietary intervention resulted in lower PI3K-Akt-mTOR signaling in islet cells and a significant reduction in PanNET formation and progression. We also found that this treatment had a significant effect on the suppression of pituitary NET development. Furthermore, we found that non-functional PanNET patients with lower blood glucose levels tend to have a better prognosis than patients with higher blood glucose levels. This preclinical study shows that a dietary intervention that results in lower serum insulin levels leads to lower insulin signals within the neuroendocrine cells and has a striking suppressive effect on the development and progression of both pancreatic and pituitary NETs.
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Affiliation(s)
- Yu Chen
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Tatsuki Yamamoto
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
- Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Yura Takahashi
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
- Tokyo College of Biotechnology, 1-3-14 Kitakoujiya, Ohta-ku, Tokyo, 144-0032, Japan
| | - Tomoka Moro
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
- Tokyo College of Biotechnology, 1-3-14 Kitakoujiya, Ohta-ku, Tokyo, 144-0032, Japan
| | - Tomoko Tajima
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yukiko Sakaguchi
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Naoaki Sakata
- Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Nanakuma 7-45-1, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Akihiko Yokoyama
- Tsuruoka Metabolomics Laboratory, National Cancer Center, Yamagata, 997-0052, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Akane Sada
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yuko Tabata
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Rieko Ohki
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.
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20
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Dornelas EC, Kawassaki CS, Olandoski M, Bolzon CDL, de Oliveira RF, Urban LABD, Rabinovich I, Elifio-Esposito S. A three-sequence dynamic contrast enhanced abbreviated MRI protocol to evaluate response to breast cancer neoadjuvant chemotherapy. Magn Reson Imaging 2023; 102:49-54. [PMID: 37137344 DOI: 10.1016/j.mri.2023.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 04/20/2023] [Accepted: 04/26/2023] [Indexed: 05/05/2023]
Abstract
PURPOSE To develop an ABP-MRI to evaluate response to NAC for invasive breast carcinoma. STUDY TYPE A single-center, cross-sectional study. SUBJECTS A consecutive series of 210 women with invasive breast carcinoma who underwent breast MRI after NAC between 2016 and 2020. FIELD STRENGTH/SEQUENCE 1.5 T / Dynamic contrast-enhanced. ASSESSMENT MRI scans were independently reevaluated, with access to dynamic contrast-enhanced without contrast and to the first, second, and third post-contrast time (ABP-MRI 1-3). STATISTICAL TESTS The diagnostic performance of the ABP-MRIs and the Full protocol (FP-MRI) were analyzed. The Wilcoxon non-parametric test (p-value <0.050) was used to compare the capability in measuring the most extensive residual lesion. RESULTS The median age was 47 (24-80) years. ABP-MRI 1 showed higher specificity (84.6%; 77/91) but a higher probability of false-negatives (16.8%) and lower sensitivity (83.2%; 99/119) than ABP-MRI 2,3 and the FP-MRI, which were identical in specificity (81.3%; 74/91), probability of false-negatives (8.4%), and sensitivity (91.6%; 109/119). ABP-MRI 2 showed a mean underestimation of only 0.03 cm in the measurement of the longest axis of the residual lesion (p = 0.008) with an average reduction in the acquisition time of 75%, compared with the FP-MRI. CONCLUSION ABP-MRI 2 showed diagnostic performance equivalent to the FP-MRI with a 75% reduction in the acquisition time.
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Affiliation(s)
- Eduardo C Dornelas
- Medical School, Centro Universitário Católico Salesiano Auxilium (UNISALESIANO), Rod. Sen. Teotônio Vilela, 3821. Araçatuba, São Paulo 16016-500, Brazil; Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná, R. Imaculada Conceição, 1155. Curitiba, Paraná 80215-901, Brazil
| | - Christiane S Kawassaki
- Clínica de Diagnóstico Avançado por Imagem (DAPI), R. Brig. Franco, 122. Curitiba, Paraná 80430-810, Brazil
| | - Marcia Olandoski
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná, R. Imaculada Conceição, 1155. Curitiba, Paraná 80215-901, Brazil
| | - Carolina de L Bolzon
- Universidade Federal do Paraná (UFPR), Medical School, R. Gen. Carneiro, 181. Curitiba, Paraná 80060-900, Brazil
| | - Ronaldo F de Oliveira
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná, R. Imaculada Conceição, 1155. Curitiba, Paraná 80215-901, Brazil
| | - Linei A B D Urban
- Clínica de Diagnóstico Avançado por Imagem (DAPI), R. Brig. Franco, 122. Curitiba, Paraná 80430-810, Brazil
| | - Iris Rabinovich
- Universidade Federal do Paraná (UFPR), Medical School, R. Gen. Carneiro, 181. Curitiba, Paraná 80060-900, Brazil
| | - Selene Elifio-Esposito
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná, R. Imaculada Conceição, 1155. Curitiba, Paraná 80215-901, Brazil.
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21
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Amir S, Arathi A, Reshma S, Mohanan PV. Microfluidic devices for the detection of disease-specific proteins and other macromolecules, disease modelling and drug development: A review. Int J Biol Macromol 2023; 235:123784. [PMID: 36822284 DOI: 10.1016/j.ijbiomac.2023.123784] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/15/2023] [Accepted: 02/16/2023] [Indexed: 02/25/2023]
Abstract
Microfluidics is a revolutionary technology that has promising applications in the biomedical field.Integrating microfluidic technology with the traditional assays unravels the innumerable possibilities for translational biomedical research. Microfluidics has the potential to build up a novel platform for diagnosis and therapy through precise manipulation of fluids and enhanced throughput functions. The developments in microfluidics-based devices for diagnostics have evolved in the last decade and have been established for their rapid, effective, accurate and economic advantages. The efficiency and sensitivity of such devices to detect disease-specific macromolecules like proteins and nucleic acids have made crucial impacts in disease diagnosis. The disease modelling using microfluidic systems provides a more prominent replication of the in vivo microenvironment and can be a better alternative for the existing disease models. These models can replicate critical microphysiology like the dynamic microenvironment, cellular interactions, and biophysical and biochemical cues. Microfluidics also provides a promising system for high throughput drug screening and delivery applications. However, microfluidics-based diagnostics still encounter related challenges in the reliability, real-time monitoring and reproducibility that circumvents this technology from being impacted in the healthcare industry. This review highlights the recent microfluidics developments for modelling and diagnosing common diseases, including cancer, neurological, cardiovascular, respiratory and autoimmune disorders, and its applications in drug development.
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Affiliation(s)
- S Amir
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - A Arathi
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - S Reshma
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - P V Mohanan
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India.
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Abstract
Tumour progression is modulated by the local microenvironment. This environment is populated by many immune cells, of which macrophages are among the most abundant. Clinical correlative data and a plethora of preclinical studies in mouse models of cancers have shown that tumour-associated macrophages (TAMs) play a cancer-promoting role. Within the primary tumour, TAMs promote tumour cell invasion and intravasation and tumour stem cell viability and induce angiogenesis. At the metastatic site, metastasis-associated macrophages promote extravasation, tumour cell survival and persistent growth, as well as maintain tumour cell dormancy in some contexts. In both the primary and metastatic sites, TAMs are suppressive to the activities of cytotoxic T and natural killer cells that have the potential to eradicate tumours. Such activities suggest that TAMs will be a major target for therapeutic intervention. In this Perspective article, we chronologically explore the evolution of our understanding of TAM biology put into the context of major enabling advances in macrophage biology.
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Affiliation(s)
| | - Jeffrey W Pollard
- MRC-Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
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23
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Fonta CM, Loustau T, Li C, Poilil Surendran S, Hansen U, Murdamoothoo D, Benn MC, Velazquez-Quesada I, Carapito R, Orend G, Vogel V. Infiltrating CD8+ T cells and M2 macrophages are retained in tumor matrix tracks enriched in low tension fibronectin fibers. Matrix Biol 2023; 116:1-27. [PMID: 36669744 DOI: 10.1016/j.matbio.2023.01.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 12/31/2022] [Accepted: 01/12/2023] [Indexed: 01/19/2023]
Abstract
Tracks rich in matrix and cells, as described in several cancer types, have immunosuppressive functions and separate tumor nests and stroma, yet their origin is unknown. Immunostainings of cryosections from mouse breast tumors show that these tracks are bordered by an endothelial-like basement membrane, filled with fibers of collagen adjacent to tenascin-C (TNC) and low-tension fibronectin (Fn) fibers. While present in early-stage tumors and maturing with time, tracks still form under TNC KO conditions, however, host (not tumor cell)-derived TNC is important for track maturation. Tumor infiltrating leukocytes (mostly M2 macrophages and CD8+ T cells) are retained in tracks of early-stage tumors. Following track maturation, retained tumor infiltrating leukocyte (TIL) numbers get reduced and more CD8+ TIL enter the tumor nests in the absence of TNC. As these tracks are enriched with platelets and fibrinogen and have a demarcating endothelial-like basement membrane often adjacent to endothelial cells, this suggests a role of blood vessels in the formation of these tracks. The Fn fiber tension probe FnBPA5 colocalizes with TNC and immune cells in the tracks and shows decreased binding in tracks lacking TNC. Consequently, FnBPA5 can serve as probe for tumor matrix tracks that have immune suppressive properties.
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Affiliation(s)
- Charlotte M Fonta
- Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Vladimir Prelog Weg, Zurich CH-8093, Switzerland
| | - Thomas Loustau
- The Tumor Microenvironment Laboratory, INSERM U1109, Hôpital Civil, Institut d' Hématologie et d'Immunologie, 1 Place de l'Hôpital, Strasbourg 67091, France; Université Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France
| | - Chengbei Li
- The Tumor Microenvironment Laboratory, INSERM U1109, Hôpital Civil, Institut d' Hématologie et d'Immunologie, 1 Place de l'Hôpital, Strasbourg 67091, France; Université Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France
| | - Suchithra Poilil Surendran
- The Tumor Microenvironment Laboratory, INSERM U1109, Hôpital Civil, Institut d' Hématologie et d'Immunologie, 1 Place de l'Hôpital, Strasbourg 67091, France; Université Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France
| | - Uwe Hansen
- Institute for Musculoskeletal Medicine (IMM), University Hospital Muenster, Muenster, Federal Republic of Germany
| | - Devadarssen Murdamoothoo
- The Tumor Microenvironment Laboratory, INSERM U1109, Hôpital Civil, Institut d' Hématologie et d'Immunologie, 1 Place de l'Hôpital, Strasbourg 67091, France; MN3T (The Microenvironmental Niche in Tumorigenesis and Targeted Therapy), INSERM U1109, 3 avenue Molière, Strasbourg, Hautepierre, France; Université Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France
| | - Mario C Benn
- Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Vladimir Prelog Weg, Zurich CH-8093, Switzerland
| | - Ines Velazquez-Quesada
- The Tumor Microenvironment Laboratory, INSERM U1109, Hôpital Civil, Institut d' Hématologie et d'Immunologie, 1 Place de l'Hôpital, Strasbourg 67091, France; MN3T (The Microenvironmental Niche in Tumorigenesis and Targeted Therapy), INSERM U1109, 3 avenue Molière, Strasbourg, Hautepierre, France; Université Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France
| | - Raphael Carapito
- Université Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France; Platform GENOMAX, INSERM UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, LabEx TRANSPLANTEX, Strasbourg 67091, France
| | - Gertraud Orend
- The Tumor Microenvironment Laboratory, INSERM U1109, Hôpital Civil, Institut d' Hématologie et d'Immunologie, 1 Place de l'Hôpital, Strasbourg 67091, France; MN3T (The Microenvironmental Niche in Tumorigenesis and Targeted Therapy), INSERM U1109, 3 avenue Molière, Strasbourg, Hautepierre, France; Université Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France.
| | - Viola Vogel
- Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Vladimir Prelog Weg, Zurich CH-8093, Switzerland.
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Saitburkhanov R, Kubanov A, Plakhova X, Kondrakhina I. Use of 585 and 1064 nm laser for the treatment of basal cell skin cancer. VESTNIK DERMATOLOGII I VENEROLOGII 2023. [DOI: 10.25208/vdv1390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Basal cell skin cancer is the most common malignant epithelial skin neoplasm in fair-skinned people and accounts for two-thirds of all skin cancers in this population. Tumor lesions have a supporting vascular network that serves as a target for vascular selective lasers.
Aim. To assess the effects of laser radiation at a wavelength of 585 and 1064 nm on the vasculature of various forms of basal cell skin cancer using dermatoscopy and in vivo confocal microscopy.
Materials and methods. The study included 20 patients with 20 lesions of histologically confirmed basal cell skin cancer treated with a pulsed dye laser (wavelength 585 nm) and a long-pulse neodymium laser (wavelength 1064 nm) in the conditions of the consultative and diagnostic center of the Federal State Budgetary Institution "GNTSDK" of the Ministry of Health RF in the period from 2021 to 2022. The effectiveness of therapy was assessed using non-invasive methods for examining the skin.
According to the results of the two-year follow-up period, 100% effectiveness of therapy in both groups is noted, in 2 patients treated with a neodymium laser, the formation of hypertrophic scars in the treatment area is noted.
Treatment of patients with basal cell skin cancer with selective vascular lasers may be an effective treatment option. Additional studies with a larger sample of observations and a long monitoring period are needed to confirm the effectiveness of this treatment method.
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25
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Polverini PJ, Nör F, Nör JE. Crosstalk between cancer stem cells and the tumor microenvironment drives progression of premalignant oral epithelium. FRONTIERS IN ORAL HEALTH 2023; 3:1095842. [PMID: 36704239 PMCID: PMC9872128 DOI: 10.3389/froh.2022.1095842] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 12/19/2022] [Indexed: 01/11/2023] Open
Abstract
Cancer stem cells (CSC) are a subpopulation of cancer cells that exhibit properties of self-renewal and differentiation and have been implicated in metastasis and treatment failures. There is mounting evidence that carcinogen-initiated mucosal epithelial stem cells acquire the CSC phenotype following exposure to environmental or infectious mutagens and are responsible for promoting the malignant transformation of premalignant (dysplastic) epithelium. CSC further contribute to the progression of dysplasia by activating signaling pathways through crosstalk with various cell populations in the tumor microenvironment. Two cell types, tumor-associated macrophages (TAM) and vascular endothelial cells (EC) nurture CSC development, support CSC stemness, and contribute to tumor progression. Despite mounting evidence implicating CSC in the initiation and progression of dysplastic oral epithelium to squamous cell carcinoma (SCC), the molecular mechanisms underlying these synergistic biological processes remain unclear. This review will examine the mechanisms that underlie the transformation of normal epithelial stem cells into CSC and the mechanistic link between CSC, TAM, and EC in the growth and the malignant conversation of dysplastic oral epithelium.
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Affiliation(s)
- Peter J. Polverini
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States,Correspondence: Peter J. Polverini
| | - Felipe Nör
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States
| | - Jacques E. Nör
- Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, United States
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Tuli HS, Vashishth K, Sak K, Mohapatra RK, Dhama K, Kumar M, Abbas Z, Lata K, Yerer MB, Garg VK, Sharma AK, Kaur G. Anticancer Role of Natural Phenolic Acids by Targeting Angiotensin-Converting Enzyme (ACE). ADVANCES IN BIOCHEMISTRY IN HEALTH AND DISEASE 2023:465-481. [DOI: 10.1007/978-3-031-23621-1_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/26/2024]
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27
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Zhang Q, Wang C, Li R, Liu J, Wang J, Wang T, Wang B. The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation. Front Oncol 2023; 13:1056903. [PMID: 36895489 PMCID: PMC9989165 DOI: 10.3389/fonc.2023.1056903] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 02/03/2023] [Indexed: 02/25/2023] Open
Abstract
Background B-cell receptor-associated protein 31 (BAP31) has been recognized as a tumor-associated protein and has largely been shown to promote metastasis in a variety of cancers. Cancer metastasis arises through multistep pathways, and the induction of angiogenesis is shown to be a rate-limiting step in the process of tumor metastasis. Methods and results This study explored the effect of BAP31 on colorectal cancer (CRC) angiogenesis by regulating the tumor microenvironment. First, exosomes from BAP31-regulated CRCs affected the transition of normal fibroblasts to proangiogenic cancer-associated fibroblasts (CAFs) in vivo and in vitro. Next, microRNA sequencing was performed to analyze the microRNA expression profile of exosomes secreted from BAP31- overexpressing CRCs. The results indicated that the expression of BAP31 in CRCs significantly altered the levels of exosomal microRNAs, such as miR-181a- 5p. Meanwhile, an in vitro tube formation assay showed that fibroblasts with high levels of miR-181a-5p significantly promoted endothelial cell angiogenesis. Critically, we first identified that miR-181a-5p directly targeted the 3'-untranslated region (3'UTR) of reversion-inducing cysteine-rich protein with kazal motifs (RECK) using the dual-luciferase activity assay, which drove fibroblast transformation into proangiogenic CAFs by upregulating matrix metalloproteinase-9 (MMP-9) and phosphorylation of mothers against decapentaplegic homolog 2/Mothers against decapentaplegic homolog 3 (Smad2/3). Conclusion Exosomes from BAP31-overexpressing/BAP31-knockdown CRCs are found to manipulate the transition of fibroblasts into proangiogenic CAFs by the miR-181a-5p/RECK axis.
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Affiliation(s)
- Qi Zhang
- College of Life Science and Health, Northeastern University, Shenyang, Liaoning, China
| | - Changli Wang
- College of Life Science and Health, Northeastern University, Shenyang, Liaoning, China
| | - Ruijia Li
- College of Life Science and Health, Northeastern University, Shenyang, Liaoning, China
| | - Jingjing Liu
- College of Life Science and Health, Northeastern University, Shenyang, Liaoning, China
| | - Jiyu Wang
- College of Life Science and Health, Northeastern University, Shenyang, Liaoning, China
| | - Tianyi Wang
- College of Life Science and Health, Northeastern University, Shenyang, Liaoning, China
| | - Bing Wang
- College of Life Science and Health, Northeastern University, Shenyang, Liaoning, China
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Mason J, Öhlund D. Key aspects for conception and construction of co-culture models of tumor-stroma interactions. Front Bioeng Biotechnol 2023; 11:1150764. [PMID: 37091337 PMCID: PMC10119418 DOI: 10.3389/fbioe.2023.1150764] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 03/31/2023] [Indexed: 04/25/2023] Open
Abstract
The tumor microenvironment is crucial in the initiation and progression of cancers. The interplay between cancer cells and the surrounding stroma shapes the tumor biology and dictates the response to cancer therapies. Consequently, a better understanding of the interactions between cancer cells and different components of the tumor microenvironment will drive progress in developing novel, effective, treatment strategies. Co-cultures can be used to study various aspects of these interactions in detail. This includes studies of paracrine relationships between cancer cells and stromal cells such as fibroblasts, endothelial cells, and immune cells, as well as the influence of physical and mechanical interactions with the extracellular matrix of the tumor microenvironment. The development of novel co-culture models to study the tumor microenvironment has progressed rapidly over recent years. Many of these models have already been shown to be powerful tools for further understanding of the pathophysiological role of the stroma and provide mechanistic insights into tumor-stromal interactions. Here we give a structured overview of different co-culture models that have been established to study tumor-stromal interactions and what we have learnt from these models. We also introduce a set of guidelines for generating and reporting co-culture experiments to facilitate experimental robustness and reproducibility.
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Affiliation(s)
- James Mason
- Department of Radiation Sciences, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Daniel Öhlund
- Department of Radiation Sciences, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
- *Correspondence: Daniel Öhlund,
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29
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Gaspar TB, Lopes JM, Soares P, Vinagre J. An update on genetically engineered mouse models of pancreatic neuroendocrine neoplasms. Endocr Relat Cancer 2022; 29:R191-R208. [PMID: 36197786 DOI: 10.1530/erc-22-0166] [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: 08/31/2022] [Accepted: 09/29/2022] [Indexed: 11/09/2022]
Abstract
Pancreatic neuroendocrine neoplasms (PanNENs) are rare and clinically challenging entities. At the molecular level, PanNENs' genetic profile is well characterized, but there is limited knowledge regarding the contribution of the newly identified genes to tumor initiation and progression. Genetically engineered mouse models (GEMMs) are the most versatile tool for studying the plethora of genetic variations influencing PanNENs' etiopathogenesis and behavior over time. In this review, we present the state of the art of the most relevant PanNEN GEMMs available and correlate their findings with the human neoplasms' counterparts. We discuss the historic GEMMs as the most used and with higher translational utility models. GEMMs with Men1 and glucagon receptor gene germline alterations stand out as the most faithful models in recapitulating human disease; RIP-Tag models are unique models of early-onset, highly vascularized, invasive carcinomas. We also include a section of the most recent GEMMs that evaluate pathways related to cell cycle and apoptosis, Pi3k/Akt/mTOR, and Atrx/Daxx. For the latter, their tumorigenic effect is heterogeneous. In particular, for Atrx/Daxx, we will require more in-depth studies to evaluate their contribution; even though they are prevalent genetic events in PanNENs, they have low/inexistent tumorigenic capacity per se in GEMMs. Researchers planning to use GEMMs can find a road map of the main clinical features in this review, presented as a guide that summarizes the chief milestones achieved. We identify pitfalls to overcome, concerning the novel designs and standardization of results, so that future models can replicate human disease more closely.
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Affiliation(s)
- Tiago Bordeira Gaspar
- i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal
- Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, Porto, Portugal
- FMUP - Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - José Manuel Lopes
- i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal
- Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
- FMUP - Faculdade de Medicina da Universidade do Porto, Porto, Portugal
- Department of Pathology, Centro Hospitalar e Universitário de São João, Porto, Portugal
| | - Paula Soares
- i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal
- Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
- FMUP - Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - João Vinagre
- i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal
- Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
- FMUP - Faculdade de Medicina da Universidade do Porto, Porto, Portugal
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The inhibition of protein translation promotes tumor angiogenic switch. MOLECULAR BIOMEDICINE 2022; 3:18. [PMID: 35695994 PMCID: PMC9192909 DOI: 10.1186/s43556-022-00081-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 05/13/2022] [Indexed: 11/10/2022] Open
Abstract
The ‘angiogenic switch’ is critical for tumor progression. However, the pathological details and molecular mechanisms remain incompletely characterized. In this study, we established mammal xenografts in zebrafish to visually investigate the first vessel growth (angiogenic switch) in real-time, by inoculating tumor cells into the perivitelline space of live optically transparent Transgenic (flk1:EGFP) zebrafish larvae. Using this model, we found that hypoxia and hypoxia-inducible factor (HIF) signaling were unnecessary for the angiogenic switch, whereas vascular endothelial growth factor A gene (Vegfa) played a crucial role. Mechanistically, transcriptome analysis showed that the angiogenic switch was characterized by inhibition of translation, but not hypoxia. Phosphorylation of eukaryotic translation initiation factor 2 alpha (Eif2α) and the expression of Vegfa were increased in the angiogenic switch microtumors, and 3D tumor spheroids, and puromycin-treated tumor cells. Vegfa overexpression promoted early onset of the angiogenic switch, whereas Vegfa knockout prevented the first tumor vessel from sprouting. Pretreatment of tumor cells with puromycin promoted the angiogenic switch in vivo similarly to Vegfa overexpression, whereas Vegfa knockdown suppressed the increase. This study provides direc and dynamic in vivo evidences that inhibition of translation, but not hypoxia or HIF signaling promotes the angiogenic switch in tumor by increasing Vegfa transcription.
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Guo Y, Jiang Y, Rose JB, Nagaraju GP, Jaskula-Sztul R, Hjelmeland AB, Beck AW, Chen H, Ren B. Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity. Cells 2022; 11:3885. [PMID: 36497140 PMCID: PMC9739736 DOI: 10.3390/cells11233885] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/10/2022] [Accepted: 11/20/2022] [Indexed: 12/05/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are extremely diverse and highly vascularized neoplasms that arise from endocrine cells in the pancreas. The pNETs harbor a subpopulation of stem cell-like malignant cells, known as cancer stem cells (CSCs), which contribute to intratumoral heterogeneity and promote tumor maintenance and recurrence. In this study, we demonstrate that CSCs in human pNETs co-express protein kinase PKD1 and CD44. We further identify PKD1 signaling as a critical pathway in the control of CSC maintenance in pNET cells. PKD1 signaling regulates the expression of a CSC- and EMT-related gene signature and promotes CSC self-renewal, likely leading to the preservation of a subpopulation of CSCs at an intermediate EMT state. This suggests that the PKD1 signaling pathway may be required for the development of a unique CSC phenotype with plasticity and partial EMT. Given that the signaling networks connected with CSC maintenance and EMT are complex, and extend through multiple levels of regulation, this study provides insight into signaling regulation of CSC plasticity and partial EMT in determining the fate of CSCs. Inhibition of the PKD1 pathway may facilitate the elimination of specific CSC subsets, thereby curbing tumor progression and metastasis.
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Affiliation(s)
- Yichen Guo
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Yinan Jiang
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - J. Bart Rose
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- O’Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Ganji Purnachandra Nagaraju
- Department of Medicine, Division of Hematology and Oncology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Renata Jaskula-Sztul
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- O’Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Anita B. Hjelmeland
- O’Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Department of Cell Developmental and Integrative Biology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Adam W. Beck
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Herbert Chen
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- O’Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Bin Ren
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- O’Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- GBS Biomedical Engineering Program, Graduate School, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Agarwal A, Jain S, Sharma N. Expression of Vascular Endothelial Growth Factor in Patients With Premalignant Lesions and Squamous Cell Carcinoma of Oral Cavity. Indian J Otolaryngol Head Neck Surg 2022; 74:2190-2197. [PMID: 36452814 PMCID: PMC9702222 DOI: 10.1007/s12070-020-02082-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 08/18/2020] [Indexed: 10/23/2022] Open
Abstract
To evaluate and compare expression of VEGF in patients of premalignant lesions and squamous cell carcinoma of oral cavity. The cross sectional observational study is undertaken at the department of otorhionolaryngology and pathology, PGIMER and Dr RML Hospital, New Delhi,from 1st Nov 2017 to 31st March 2019,with a sample size of 30 cases each of premalignant lesions and oral squamous cell carcinoma immunohistochemistry by polymer method. In the participants with oral SCC, VEGF expression of Score 1 was observed in verrucous and well differentiated tumor, Score 2 in moderately differentiated SCC & Score 3 in poorly differentiated SCC with a p value of 0.0001. The observed difference and value of proportion p, is statically significant. In this study we concluded that VEGF expression increases as the lesion progresses from premalignant lesions to oral squamous cell carcinoma and is strongly associated with lymph node status (N-staging). Thus, VEGF can be a target in chemotherapy and its therapeutic implications in the HNSCC needs further research. Levels of Evidence 1A: Systematic review of randomized control trials.
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Affiliation(s)
| | - Shalini Jain
- Department of Otorhinolargngology, Atal Bihari Vajpayee Institute of Medical Sciences, Dr. RML Hospital, Krishan Kunj Appartments, Dwarka Sector 1A, A-103, Nasirpur, India
| | - Nishi Sharma
- Department of Otorhinolargngology, Atal Bihari Vajpayee Institute of Medical Sciences, Dr. RML Hospital, Krishan Kunj Appartments, Dwarka Sector 1A, A-103, Nasirpur, India
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Rasel MSI, Mohona FA, Akter W, Kabir S, Chowdhury AA, Chowdhury JA, Hassan MA, Al Mamun A, Ghose DK, Ahmad Z, Khan FS, Bari MF, Rahman MS, Amran MS. Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment. JOURNAL OF ONCOLOGY 2022; 2022:9396760. [PMID: 36284633 PMCID: PMC9588330 DOI: 10.1155/2022/9396760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 07/21/2022] [Indexed: 11/17/2022]
Abstract
Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collected regarding cancer and drug-targeting approaches from well reputed databases including MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov, Science Direct, PubMed, Scopus, Wiley, and Springer. The articles published between January 2010 and December 2020 were considered. Due to the existence of various mechanisms, it is challenging to choose which one is appropriate for a specific case. Moreover, a combination of more than one approach is often utilized to achieve optimal drug effects. In this review, we have summarized and highlighted central mechanisms of how the targeted drug delivery system works in the specific diseased microenvironment, along with the strategies to make an approach more effective. We have also included some pictorial illustrations to have a precise idea about different types of drug targeting. The core contribution of this work includes providing a cancer drug development scientist with a broad preliminary idea to choose the appropriate approach among the various targeted drug delivery mechanisms. Also, the study will contribute to improving anticancer treatment approaches by providing a pathway for lesser side effects observed in conventional chemotherapeutic techniques.
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Affiliation(s)
- Md. Shamiul Islam Rasel
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Shahbag, Dhaka 1000, Bangladesh
| | - Farhana Afrin Mohona
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Shahbag, Dhaka 1000, Bangladesh
| | - Wahida Akter
- College of Pharmacy, University of Houston, Houston, USA
| | - Shaila Kabir
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Shahbag, Dhaka 1000, Bangladesh
| | - Abu Asad Chowdhury
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Shahbag, Dhaka 1000, Bangladesh
| | - Jakir Ahmed Chowdhury
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Shahbag, Dhaka 1000, Bangladesh
| | - Md. Abul Hassan
- Department of Science & Technology, Tokushima University Graduate School, Tokushima, Japan
| | - Abdullah Al Mamun
- Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035 Zhejiang, China
| | - Dipayon Krisna Ghose
- Department of Biochemistry and Molecular Biology, Jagannath University, Dhaka 1100, Bangladesh
| | - Zubair Ahmad
- Unit of Bee Research and Honey Production, King Khalid University, Abha 61413, Saudi Arabia
- Department of Biology, College of Arts and Sciences, King Khalid University, Abha 61413, Saudi Arabia
| | - Farhat S. Khan
- Department of Biology, College of Arts and Sciences, King Khalid University, Abha 61413, Saudi Arabia
| | - Md. Fazlul Bari
- Department of Biochemistry and Molecular Biology, Trust University, Barishal, Ruiya, Nobogram Road, Barishal 8200, Bangladesh
| | - Md. Sohanur Rahman
- Department of Biochemistry and Molecular Biology, Trust University, Barishal, Ruiya, Nobogram Road, Barishal 8200, Bangladesh
| | - Md. Shah Amran
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Shahbag, Dhaka 1000, Bangladesh
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Prostate Cancer Tumor Stroma: Responsibility in Tumor Biology, Diagnosis and Treatment. Cancers (Basel) 2022; 14:cancers14184412. [PMID: 36139572 PMCID: PMC9496870 DOI: 10.3390/cancers14184412] [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: 08/11/2022] [Revised: 09/05/2022] [Accepted: 09/06/2022] [Indexed: 12/24/2022] Open
Abstract
Simple Summary The crosstalk between prostate stroma and its epithelium is essential to tissue homeostasis. Likewise, reciprocal signaling between tumor cells and the stromal compartment is required in tumor progression to facilitate or stimulate key processes such as cell proliferation and invasion. The aim of the present work was to review the current state of knowledge on the significance of tumor stroma in the genesis, progression and therapeutic response of prostate carcinoma. Additionally, we addressed the future therapeutic opportunities. Abstract Prostate cancer (PCa) is a common cancer among males globally, and its occurrence is growing worldwide. Clinical decisions about the combination of therapies are becoming highly relevant. However, this is a heterogeneous disease, ranging widely in prognosis. Therefore, new approaches are needed based on tumor biology, from which further prognostic assessments can be established and complementary strategies can be identified. The knowledge of both the morphological structure and functional biology of the PCa stroma compartment can provide new diagnostic, prognostic or therapeutic possibilities. In the present review, we analyzed the aspects related to the tumor stromal component (both acellular and cellular) in PCa, their influence on tumor behavior and the therapeutic response and their consideration as a new therapeutic target.
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Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases. Cancer Metastasis Rev 2022; 41:517-547. [PMID: 36074318 PMCID: PMC9470659 DOI: 10.1007/s10555-022-10058-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/29/2022] [Indexed: 12/24/2022]
Abstract
Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.
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Cytokine chemokine network in tumor microenvironment: Impact on CSC properties and therapeutic applications. Cytokine 2022; 156:155916. [DOI: 10.1016/j.cyto.2022.155916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 04/27/2022] [Accepted: 05/16/2022] [Indexed: 12/21/2022]
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Guleria K, Kaur S, Mahajan D, Sambyal V, Sudan M, Uppal MS. Impact of VEGFA promoter polymorphisms on esophageal cancer risk in North-West Indians: a case-control study. Genes Genomics 2022; 44:923-936. [PMID: 35767183 DOI: 10.1007/s13258-022-01269-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 05/05/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Angiogenesis play a critical role in the development and progression of tumors in solid tumors. Vascular endothelial growth factor (VEGF) is one of the most important endothelial cell mitogen which plays a critical role in normal physiological and tumor angiogenesis. OBJECTIVES The objective of this case-control study was to investigate the association of VEGF-2578C/A, -2549 I/D, and -460T/C promoter polymorphisms with esophageal cancer risk in North-West Indians. METHODS In this study, 200 sporadic esophageal cancer patients and 200 healthy, unrelated, age and gender matched controls were analyzed. The genomic DNA was extracted from blood samples using phenol chloroform method. Genotyping of VEGF- 2549I/D polymorphism was carried out by direct polymerase chain reaction (PCR) whereas VEGF -2578C/A and VEGF-460T/C) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS AA genotype (p = 0.005) and A allele (p = 0.005) VEGF -2578 C/A, II genotype (p = 0.011) and I allele (p = 0.012) of VEGF - 2549 I/D and CC genotype (p = 0.013) and C allele of VEGF-460T/C polymorphisms were significantly associated with increased risk of esophageal cancer. Stratification of data on the basis of gender showed that VEGF -2578 AA genotype (p = 0.001) and A allele (p = 0.001); VEGF -2549 II genotype (p = 0.002) and I allele (p = 0.002) and VEGF- 460CC genotype (p = 0.001) and C allele (p = 0.002) was significantly associated with increased risk of esophageal cancer in female group. Haplotype analysis revealed that A-2578 I- 2549 C- 460 haplotype was significantly associated with increased risk for esophageal cancer in total samples (p = 0.008) as well as in female group (p = 0.001). CONCLUSIONS The results of present study indicate that VEGF -2578C/A, - 2549I/D and -460T/C polymorphisms were significantly associated with increased risk of esophageal cancer in North-West Indians.
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Affiliation(s)
- Kamlesh Guleria
- Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
| | - Simranjot Kaur
- Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Deepanshi Mahajan
- Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Vasudha Sambyal
- Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Meena Sudan
- Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India
| | - Manjit Singh Uppal
- Department of Surgery, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India
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Xu Z, Wang Y, Liu G, Chen J, Wang W, Cheng Y, Ren Q, Cui Y, Yang W, Liu Z, Chen X, Xue J, Chang T, Qu X, Yu S, Zhou Y, Xu K, Su Z, Deng Q, Zhao Y, Yang H. A randomized, open-label, single-dose, two-cycle crossover study to evaluate the bioequivalence and safety of lenvatinib and Lenvima® in Chinese healthy subjects. Expert Opin Investig Drugs 2022; 31:737-746. [PMID: 35427205 DOI: 10.1080/13543784.2022.2067528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Zhongnan Xu
- Department of clinical research center, Chia Tai Tianqing Pharmaceutical Group Co.Ltd, Jiangsu, China
| | - Yanli Wang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Guangwen Liu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Jiahui Chen
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Wanhua Wang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Yang Cheng
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Qing Ren
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Yingzi Cui
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Wei Yang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Zhengzhi Liu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Xuesong Chen
- Ansiterui Medical Technology Consulting Co.,Ltd., Jilin, China
| | - Jinling Xue
- Department of clinical research center, Chia Tai Tianqing Pharmaceutical Group Co.Ltd, Jiangsu, China
| | - Tianying Chang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Xinyao Qu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Shuang Yu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Yannan Zhou
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Kaibo Xu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Zhengjie Su
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Qiaohuan Deng
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Yicheng Zhao
- Clinical Medical College, Changchun University of Chinese Medicine, Jilin, China
| | - Haimiao Yang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
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Clark J, Fotopoulou C, Cunnea P, Krell J. Novel Ex Vivo Models of Epithelial Ovarian Cancer: The Future of Biomarker and Therapeutic Research. Front Oncol 2022; 12:837233. [PMID: 35402223 PMCID: PMC8990887 DOI: 10.3389/fonc.2022.837233] [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: 12/16/2021] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Abstract
Epithelial ovarian cancer (EOC) is a heterogenous disease associated with variations in presentation, pathology and prognosis. Advanced EOC is typified by frequent relapse and a historical 5-year survival of less than 30% despite improvements in surgical and systemic treatment. The advent of next generation sequencing has led to notable advances in the field of personalised medicine for many cancer types. Success in achieving cure in advanced EOC has however been limited, although significant prolongation of survival has been demonstrated. Development of novel research platforms is therefore necessary to address the rapidly advancing field of early diagnostics and therapeutics, whilst also acknowledging the significant tumour heterogeneity associated with EOC. Within available tumour models, patient-derived organoids (PDO) and explant tumour slices have demonstrated particular promise as novel ex vivo systems to model different cancer types including ovarian cancer. PDOs are organ specific 3D tumour cultures that can accurately represent the histology and genomics of their native tumour, as well as offer the possibility as models for pharmaceutical drug testing platforms, offering timing advantages and potential use as prospective personalised models to guide clinical decision-making. Such applications could maximise the benefit of drug treatments to patients on an individual level whilst minimising use of less effective, yet toxic, therapies. PDOs are likely to play a greater role in both academic research and drug development in the future and have the potential to revolutionise future patient treatment and clinical trial pathways. Similarly, ex vivo tumour slices or explants have also shown recent renewed promise in their ability to provide a fast, specific, platform for drug testing that accurately represents in vivo tumour response. Tumour explants retain tissue architecture, and thus incorporate the majority of tumour microenvironment making them an attractive method to re-capitulate in vivo conditions, again with significant timing and personalisation of treatment advantages for patients. This review will discuss the current treatment landscape and research models for EOC, their development and new advances towards the discovery of novel biomarkers or combinational therapeutic strategies to increase treatment options for women with ovarian cancer.
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Affiliation(s)
- James Clark
- Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Christina Fotopoulou
- Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.,West London Gynaecological Cancer Centre, Imperial College NHS Trust, London, United Kingdom
| | - Paula Cunnea
- Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Jonathan Krell
- Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
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Venkatanarayana M, Nuchu R, Babu HS. Ultrasound assisted effective synthesis of benzopril based indole derivatives, docking studies: And there in vitro anti-proliferative effects on various cancer cell lines. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2021.132287] [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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41
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Current Nano-Strategies to Target Tumor Microenvironment to Improve Anti-Tumor efficiency. OPENNANO 2022. [DOI: 10.1016/j.onano.2022.100042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Li X, Peng X, Yang S, Wei S, Fan Q, Liu J, Yang L, Li H. Targeting tumor innervation: premises, promises, and challenges. Cell Death Dis 2022; 8:131. [PMID: 35338118 PMCID: PMC8956600 DOI: 10.1038/s41420-022-00930-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/17/2021] [Accepted: 02/28/2022] [Indexed: 01/03/2023]
Abstract
A high intratumoral nerve density is correlated with poor survival, high metastasis, and high recurrence across multiple solid tumor types. Recent research has revealed that cancer cells release diverse neurotrophic factors and exosomes to promote tumor innervation, in addition, infiltrating nerves can also mediate multiple tumor biological processes via exosomes and neurotransmitters. In this review, through seminal studies establishing tumor innervation, we discuss the communication between peripheral nerves and tumor cells in the tumor microenvironment (TME), and revealed the nerve-tumor regulation mechanisms on oncogenic process, angiogenesis, lymphangiogenesis, and immunity. Finally, we discussed the promising directions of ‘old drugs newly used’ to target TME communication and clarified a new line to prevent tumor malignant capacity.
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Affiliation(s)
- Xinyu Li
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Xueqiang Peng
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Shuo Yang
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Shibo Wei
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Qing Fan
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Jingang Liu
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Liang Yang
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
| | - Hangyu Li
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
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43
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Identification of dysregulated pathways and key genes in human retinal angiogenesis using microarray metadata. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2021.101434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Jazieh K, Khorrami M, Saad A, Gad M, Gupta A, Patil P, Viswanathan VS, Rajiah P, Nock CJ, Gilkey M, Fu P, Pennell NA, Madabhushi A. Novel imaging biomarkers predict outcomes in stage III unresectable non-small cell lung cancer treated with chemoradiation and durvalumab. J Immunother Cancer 2022; 10:e003778. [PMID: 35256515 PMCID: PMC8905876 DOI: 10.1136/jitc-2021-003778] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2022] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The landmark study of durvalumab as consolidation therapy in NSCLC patients (PACIFIC trial) demonstrated significantly longer progression-free survival (PFS) in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with durvalumab (immunotherapy, IO) therapy after chemoradiotherapy (CRT). In clinical practice in the USA, durvalumab continues to be used in patients across all levels of programmed cell death ligand-1 (PD-L1) expression. While immune therapies have shown promise in several cancers, some patients either do not respond to the therapy or have cancer recurrence after an initial response. It is not clear so far who will benefit of this therapy or what the mechanisms behind treatment failure are. METHODS A total of 133 patients with unresectable stage III NSCLC who underwent durvalumab after CRT or CRT alone were included. Patients treated with durvalumab IO after CRT were randomly split into training (D1=59) and test (D2=59) sets and the remaining 15 patients treated with CRT alone were grouped in D3. Radiomic textural patterns from within and around the target nodules were extracted. A radiomic risk score (RRS) was built and was used to predict PFS and overall survival (OS). Patients were divided into high-risk and low-risk groups based on median RRS. RESULTS RRS was found to be significantly associated with PFS in D1 (HR=2.67, 95% CI 1.85 to 4.13, p<0.05, C-index=0.78) and D2 (HR=2.56, 95% CI 1.63 to 4, p<0.05, C-index=0.73). Similarly, RRS was associated with OS in D1 (HR=1.89, 95% CI 1.3 to 2.75, p<0.05, C-index=0.67) and D2 (HR=2.14, 95% CI 1.28 to 3.6, p<0.05, C-index=0.69), respectively. RRS was found to be significantly associated with PFS in high PD-L1 (HR=3.01, 95% CI 1.41 to 6.45, p=0.0044) and low PD-L1 (HR=2.74, 95% CI 1.8 to 4.14, p=1.77e-06) groups. Moreover, RRS was not significantly associated with OS in the high PD-L1 group (HR=2.08, 95% CI 0.98 to 4.4, p=0.054) but was significantly associated with OS in the low PD-L1 group (HR=1.61, 95% CI 1.14 to 2.28, p=0.0062). In addition, RRS was significantly associated with PFS (HR=2.77, 95% CI 1.17 to 6.52, p=0.019, C-index=0.77) and OS (HR=2.62, 95% CI 1.25 to 5.51, p=0.01, C-index=0.77) in D3, respectively. CONCLUSIONS Tumor radiomics of pretreatment CT images from patients with stage III unresectable NSCLC were prognostic of PFS and OS to CRT followed by durvalumab IO and CRT alone.
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Affiliation(s)
- Khalid Jazieh
- Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA
| | - Mohammadhadi Khorrami
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA
| | - Anas Saad
- Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Mohamed Gad
- Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA
| | - Amit Gupta
- Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Pradnya Patil
- Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | | | | | - Charles J Nock
- Louis Stokes Cleveland VA Medical Center Mental Health Services, Cleveland, Ohio, USA
| | - Michael Gilkey
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA
| | - Pingfu Fu
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA
| | - Nathan A Pennell
- Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Anant Madabhushi
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA
- Louis Stokes Cleveland VA Medical Center Mental Health Services, Cleveland, Ohio, USA
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Kasherman L, Liu S(L, Karakasis K, Lheureux S. Angiogenesis: A Pivotal Therapeutic Target in the Drug Development of Gynecologic Cancers. Cancers (Basel) 2022; 14:1122. [PMID: 35267430 PMCID: PMC8908988 DOI: 10.3390/cancers14051122] [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: 01/07/2022] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 01/27/2023] Open
Abstract
Since the discovery of angiogenesis and its relevance to the tumorigenesis of gynecologic malignancies, a number of therapeutic agents have been developed over the last decade, some of which have become standard treatments in combination with other therapies. Limited clinical activity has been demonstrated with anti-angiogenic monotherapies, and ongoing trials are focused on combination strategies with cytotoxic agents, immunotherapies and other targeted treatments. This article reviews the science behind angiogenesis within the context of gynecologic cancers, the evidence supporting the targeting of these pathways and future directions in clinical trials.
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Affiliation(s)
- Lawrence Kasherman
- Department of Medical Oncology, St. George Hospital, Kogarah, NSW 2217, Australia;
- St. George and Sutherland Clinical Schools, University of New South Wales, Sydney, NSW 2052, Australia
- Illawarra Cancer Care Centre, Department of Medical Oncology, Wollongong, NSW 2500, Australia
| | | | | | - Stephanie Lheureux
- Princess Margaret Cancer Centre, Division of Medical Oncology and Hematology, University Health Network, Toronto, ON M5G 2M9, Canada
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van Genugten EAJ, Weijers JAM, Heskamp S, Kneilling M, van den Heuvel MM, Piet B, Bussink J, Hendriks LEL, Aarntzen EHJG. Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy. Front Oncol 2022; 11:786089. [PMID: 35070990 PMCID: PMC8779734 DOI: 10.3389/fonc.2021.786089] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/10/2021] [Indexed: 12/14/2022] Open
Abstract
Metabolic reprogramming is recognized as one of the hallmarks of cancer. Alterations in the micro-environmental metabolic characteristics are recognized as important tools for cancer cells to interact with the resident and infiltrating T-cells within this tumor microenvironment. Cancer-induced metabolic changes in the micro-environment also affect treatment outcomes. In particular, immune therapy efficacy might be blunted because of somatic mutation-driven metabolic determinants of lung cancer such as acidity and oxygenation status. Based on these observations, new onco-immunological treatment strategies increasingly include drugs that interfere with metabolic pathways that consequently affect the composition of the lung cancer tumor microenvironment (TME). Positron emission tomography (PET) imaging has developed a wide array of tracers targeting metabolic pathways, originally intended to improve cancer detection and staging. Paralleling the developments in understanding metabolic reprogramming in cancer cells, as well as its effects on stromal, immune, and endothelial cells, a wave of studies with additional imaging tracers has been published. These tracers are yet underexploited in the perspective of immune therapy. In this review, we provide an overview of currently available PET tracers for clinical studies and discuss their potential roles in the development of effective immune therapeutic strategies, with a focus on lung cancer. We report on ongoing efforts that include PET/CT to understand the outcomes of interactions between cancer cells and T-cells in the lung cancer microenvironment, and we identify areas of research which are yet unchartered. Thereby, we aim to provide a starting point for molecular imaging driven studies to understand and exploit metabolic features of lung cancer to optimize immune therapy.
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Affiliation(s)
- Evelien A J van Genugten
- Department of Medical Imaging, Radboud University Medical Centre (Radboudumc), Nijmegen, Netherlands
| | - Jetty A M Weijers
- Department of Medical Imaging, Radboud University Medical Centre (Radboudumc), Nijmegen, Netherlands
| | - Sandra Heskamp
- Department of Medical Imaging, Radboud University Medical Centre (Radboudumc), Nijmegen, Netherlands
| | - Manfred Kneilling
- Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University, Tuebingen, Germany.,Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
| | | | - Berber Piet
- Department of Respiratory Diseases, Radboudumc, Nijmegen, Netherlands
| | - Johan Bussink
- Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboudumc, Netherlands
| | - Lizza E L Hendriks
- Department of Pulmonary Diseases, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre (UMC), Maastricht, Netherlands
| | - Erik H J G Aarntzen
- Department of Medical Imaging, Radboud University Medical Centre (Radboudumc), Nijmegen, Netherlands
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Inamasu E, Tsuchiya T, Yamauchi M, Nishi K, Matsuda K, Sugawara F, Sakaguchi K, Mori R, Matsumoto K, Miyazaki T, Hatachi G, Doi R, Watanabe H, Tomoshige K, Matsuda N, Higami Y, Shimokawa I, Nakashima M, Nagayasu T. Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models. JOURNAL OF RADIATION RESEARCH 2022; 63:19-29. [PMID: 34738103 PMCID: PMC8776698 DOI: 10.1093/jrr/rrab090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 08/22/2021] [Indexed: 06/13/2023]
Abstract
Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Takeshi Nagayasu
- Corresponding author. Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Tel: +81-95-819-7304; Fax: +81-95-819-7306;
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Arman T, Nelson PS. Endocrine and paracrine characteristics of neuroendocrine prostate cancer. Front Endocrinol (Lausanne) 2022; 13:1012005. [PMID: 36440195 PMCID: PMC9691667 DOI: 10.3389/fendo.2022.1012005] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/24/2022] [Indexed: 11/12/2022] Open
Abstract
Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a spectrum of uncommon tumor types occur including those with small cell and neuroendocrine cell features. Benign neuroendocrine cells exist in the normal prostate microenvironment, and these cells may give rise to primary neuroendocrine carcinomas. However, the more common development of neuroendocrine prostate cancer is observed after therapeutics designed to repress the signaling program regulated by the androgen receptor which is active in the majority of localized and metastatic adenocarcinomas. Neuroendocrine tumors are identified through immunohistochemical staining for common markers including chromogranin A/B, synaptophysin and neuron specific enolase (NSE). These markers are also common to neuroendocrine tumors that arise in other tissues and organs such as the gastrointestinal tract, pancreas, lung and skin. Notably, neuroendocrine prostate cancer shares biochemical features with nerve cells, particularly functions involving the secretion of a variety of peptides and proteins. These secreted factors have the potential to exert local paracrine effects, and distant endocrine effects that may modulate tumor progression, invasion, and resistance to therapy. This review discusses the spectrum of factors derived from neuroendocrine prostate cancers and their potential to influence the pathophysiology of localized and metastatic prostate cancer.
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Affiliation(s)
- Tarana Arman
- Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Peter S. Nelson
- Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA, United States
- *Correspondence: Peter S. Nelson,
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Chaudhary B, Kumar P, Arya P, Singla D, Kumar V, Kumar D, S R, Wadhwa S, Gulati M, Singh SK, Dua K, Gupta G, Gupta MM. Recent Developments in the Study of the Microenvironment of Cancer and Drug Delivery. Curr Drug Metab 2022; 23:1027-1053. [PMID: 36627789 DOI: 10.2174/1389200224666230110145513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 09/20/2022] [Accepted: 11/29/2022] [Indexed: 01/12/2023]
Abstract
Cancer is characterized by disrupted molecular variables caused by cells that deviate from regular signal transduction. The uncontrolled segment of such cancerous cells annihilates most of the tissues that contact them. Gene therapy, immunotherapy, and nanotechnology advancements have resulted in novel strategies for anticancer drug delivery. Furthermore, diverse dispersion of nanoparticles in normal stroma cells adversely affects the healthy cells and disrupts the crosstalk of tumour stroma. It can contribute to cancer cell progression inhibition and, conversely, to acquired resistance, enabling cancer cell metastasis and proliferation. The tumour's microenvironment is critical in controlling the dispersion and physiological activities of nano-chemotherapeutics which is one of the targeted drug therapy. As it is one of the methods of treating cancer that involves the use of medications or other substances to specifically target and kill off certain subsets of malignant cells. A targeted therapy may be administered alone or in addition to more conventional methods of care like surgery, chemotherapy, or radiation treatment. The tumour microenvironment, stromatogenesis, barriers and advancement in the drug delivery system across tumour tissue are summarised in this review.
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Affiliation(s)
- Benu Chaudhary
- Department of Pharmacology, Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana, India
| | - Parveen Kumar
- Department of Life Science, Shri Ram College of Pharmacy, Karnal, Haryana, India
| | - Preeti Arya
- Department of Pharmacology, Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana, India
| | - Deepak Singla
- Department of Pharmacology, Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana, India
| | - Virender Kumar
- Department of Pharmacology, Swami Dayanand Post Graduate Institute of Pharmaceutical Sciences, Rohtak, Haryana, India
| | - Davinder Kumar
- Department of Pharmacology, Swami Dayanand Post Graduate Institute of Pharmaceutical Sciences, Rohtak, Haryana, India
| | - Roshan S
- Department of Pharmacology, Deccan School of Pharmacy, Hyderabad, India
| | - Sheetu Wadhwa
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, 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, NSW 2007, Australia
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur, India
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Madan Mohan Gupta
- Faculty of Medical Sciences, School of Pharmacy, The University of the West Indies, St. Augustine, Trinidad & Tobago, West Indies
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Ismail AA, Shaker BT, Bajou K. The Plasminogen-Activator Plasmin System in Physiological and Pathophysiological Angiogenesis. Int J Mol Sci 2021; 23:ijms23010337. [PMID: 35008762 PMCID: PMC8745544 DOI: 10.3390/ijms23010337] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/20/2021] [Accepted: 12/23/2021] [Indexed: 12/20/2022] Open
Abstract
Angiogenesis is a process associated with the migration and proliferation of endothelial cells (EC) to form new blood vessels. It is involved in various physiological and pathophysiological conditions and is controlled by a wide range of proangiogenic and antiangiogenic molecules. The plasminogen activator–plasmin system plays a major role in the extracellular matrix remodeling process necessary for angiogenesis. Urokinase/tissue-type plasminogen activators (uPA/tPA) convert plasminogen into the active enzyme plasmin, which in turn activates matrix metalloproteinases and degrades the extracellular matrix releasing growth factors and proangiogenic molecules such as the vascular endothelial growth factor (VEGF-A). The plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of uPA and tPA, thereby an inhibitor of pericellular proteolysis and intravascular fibrinolysis, respectively. Paradoxically, PAI-1, which is expressed by EC during angiogenesis, is elevated in several cancers and is found to promote angiogenesis by regulating plasmin-mediated proteolysis and by promoting cellular migration through vitronectin. The urokinase-type plasminogen activator receptor (uPAR) also induces EC cellular migration during angiogenesis via interacting with signaling partners. Understanding the molecular functions of the plasminogen activator plasmin system and targeting angiogenesis via blocking serine proteases or their interactions with other molecules is one of the major therapeutic strategies scientists have been attracted to in controlling tumor growth and other pathological conditions characterized by neovascularization.
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Affiliation(s)
- Asmaa Anwar Ismail
- Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (A.A.I.); (B.T.S.)
- Human Genetics & Stem Cells Research Group, Research Institute of Sciences & Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Baraah Tariq Shaker
- Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (A.A.I.); (B.T.S.)
- Human Genetics & Stem Cells Research Group, Research Institute of Sciences & Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Khalid Bajou
- Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; (A.A.I.); (B.T.S.)
- Human Genetics & Stem Cells Research Group, Research Institute of Sciences & Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
- Correspondence:
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