المؤلفون: Shifa, Javed, Swati, Sood, Bhavana, Rai, Shalmoli, Bhattacharyya, Rashmi, Bagga, Radhika, Srinivasan

المصدر: The Indian journal of medical research. 154(2)

مصطلحات موضوعية: Isoenzymes, Recurrence, Biomarkers, Tumor, Humans, Retinal Dehydrogenase, Uterine Cervical Neoplasms, Female, Chemoradiotherapy, Cadherins, Aldehyde Dehydrogenase 1 Family

الوصف: Chemoradiation is the standard therapy for locally advanced invasive cervical cancer and response to treatment determines the outcome. Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) play a role in response to treatment and hence the aim of this study was to evaluate if their levels in pre-treatment biopsies by immunohistochemistry (IHC) could predict response to treatment and outcome.The study comprised 60 patients with FIGO Stage IIB/III invasive cervical carcinoma treated by chemoradiation. They were divided into two groups based on their clinical outcome: group 1, 30 patients who had no evidence of disease at 48 month follow up and group 2, 30 patients who had disease relapse within 6-12 months of treatment completion. IHC was performed for CSC markers (ALDH1, CD133, Nanog and Oct-4), EMT markers (E-cadherin and vimentin) and squamocolumnar junction (KRT7) markers and H-scores determined. Intergroup comparison was performed. The expression of these markers was also evaluated in histological sections of cervical pre-cancer (CIN1 and CIN3) in comparison to normal cervix.Cervical Intraepithelial Neoplasia grade 3 (CIN3) showed high expression of ALDH1 and KRT7 as compared to normal cervical epithelium. Aldehyde dehydrogenase 1 (ALDH1) and CD133 were overexpressed in 70 and 24 per cent cervical carcinoma cases whereas E-cadherin showed reduced expression in invasive carcinoma as compared to normal controls. ALDH1 overexpression was significantly associated with disease relapse in invasive cervical carcinoma treated by chemoradiation (P0.01).Determination of ALDH1 levels in pre-treatment cervical biopsies of invasive cervical carcinoma may be useful for prediction of response to chemoradiation, with high levels predicting for a poor response.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::49d7f3192ce951f687fbc421300cda91Test
https://pubmed.ncbi.nlm.nih.gov/35295009Test

المؤلفون: Rashmi Bagga, Radhika Srinivasan, Shalmoli Bhattacharyya, Shifa Javed

المصدر: Molecular and Cellular Biochemistry. 473:51-62

مصطلحات موضوعية: 0301 basic medicine, Epithelial-Mesenchymal Transition, medicine.medical_treatment, Clinical Biochemistry, Cell, Uterine Cervical Neoplasms, Biology, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, Cell Line, Tumor, Gene expression, medicine, Humans, Insulin-Like Growth Factor I, Molecular Biology, Cisplatin, Cervical cancer, Growth factor, Cell Biology, General Medicine, medicine.disease, Neoplasm Proteins, 030104 developmental biology, medicine.anatomical_structure, Apoptosis, Cell culture, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Cancer research, Female, Signal Transduction, medicine.drug

الوصف: Cancer stem cells (CSC) drive tumour progression and are implicated in relapse and resistance to conventional cancer therapies. Identification of differentially expressed genes by gene expression (GEP) profiling may help identify the differentially activated signalling pathways in cancer stem cells as opposed to bulk tumour cells which will provide new insights into cancer stem cell biology and aid in identification of novel therapeutic targets. Our study focused on the inhibition of CSC from cervical cancer cell lines by targeting insulin-like growth factor (IGF), which was identified by differential GEP. Targeted inhibition of IGF-1 by JB-1 trifluoroacetate (inhibitor of IGF) was carried out in SiHa, RSBS-14 and RSBS-43 cervical cancer derived cell lines. Effect of cisplatin was also evaluated. Inhibition of IGF-1 signalling was confirmed by demonstration of reduction in p-Akt levels. The cell biological effects of IGF-1 inhibition included an increase in G2M/S fraction, increased apoptosis and decreased invasive ability. JB-1 and cisplatin showed synergism. However, transcript levels of stemness and EMT markers showed variable levels following IGF inhibition. Overall, this proof-of-concept study has shown that IGF-1 is an attractive target for inhibition of CSC in invasive cervical cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::619fe4a597bb20186cf48bf314ac728cTest
https://doi.org/10.1007/s11010-020-03807-6Test

المؤلفون: Shifa Javed, Radhika Srinivasan, Renaissa De, Shalmoli Bhattacharyya, Anuka Sharma, Arnab Pal

المصدر: Journal of cellular physiology.

مصطلحات موضوعية: 0301 basic medicine, Cervical cancer, Cyclopamine, Physiology, business.industry, Clinical Biochemistry, Cancer, Cell Biology, medicine.disease, Hedgehog signaling pathway, Metastasis, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Cancer stem cell, 030220 oncology & carcinogenesis, Cancer research, Medicine, Epithelial–mesenchymal transition, Stem cell, business

الوصف: Resistance to therapy and metastasis remains one of the leading causes of mortality due to cervical cancer despite advances in detection and treatment. The mechanism of epithelial to mesenchymal transition (EMT) provides conceptual explanation to the invasiveness and metastatic spread of cancer but it has not been fully understood in cervical cancer. This study aims to investigate the mechanism by which silencing of E-cadherin gene regulates EMT leading to proliferation, invasion, and chemoresistance of cervical cancer cells through the Hedgehog (Hh) signaling pathway. We developed an in vitro EMT model by the knockdown of E-cadherin expression in cervical cancer cell lines. To understand the role of developmental pathway like Hh in the progression of cervical cancer, we investigated the expression of Hh pathway mediators by array in E-cadherin low cervical cancer cells and observed upregulation of Hh pathway. This was further validated on low passage patient-derived cell lines and cervical carcinoma tissue sections from cervical cancer patients. Further, we evaluated the role of two inhibitors (cyclopamine and GANT58) of the Hh pathway on invasiveness and apoptosis in E-cadherin low cervical cancer cells. In conclusion, we observed that inhibition of Hh pathway with GANT58 along with current therapeutic procedures could be more effective in targeting drug-resistant EMT cells and bulk tumor cells in cervical cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ebb85a025d4c0d6c451d32e6dc678816Test
https://pubmed.ncbi.nlm.nih.gov/30714153Test

المؤلفون: Shifa Javed, Sharma, Bal, Sood, Swati, Sharma, Sanjeev, Bagga, Rashmi, Shalmoli Bhattacharyya, Rayat, Charan, Dhaliwal, Lakhbir, Srinivasan, Radhika

الوصف: (DOCX 20Â kb)

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a7d2777b8a3887627e8ba177a9c6a298Test

المؤلفون: Rashmi Bagga, Sanjeev Sharma, Shifa Javed, Bal Krishan Sharma, Swati Sood, Shalmoli Bhattacharyya, Lakhbir Kaur Dhaliwal, Radhika Srinivasan, Charan Singh Rayat

المصدر: BMC Cancer
BMC Cancer, Vol 18, Iss 1, Pp 1-12 (2018)

مصطلحات موضوعية: 0301 basic medicine, HPV16, Cancer Research, Epithelial-Mesenchymal Transition, Biopsy, Population, Karyotype, Uterine Cervical Neoplasms, Antineoplastic Agents, Minisatellite Repeats, Biology, Low passage, lcsh:RC254-282, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, Cell Line, Tumor, Genetics, medicine, Humans, Epithelial–mesenchymal transition, AC133 Antigen, CD133, Cell Self Renewal, education, Cervical cancer, education.field_of_study, Human papillomavirus 16, medicine.diagnostic_test, Cancer stem cells, Cell Cycle, Papillomavirus Infections, Cell cycle, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Flow Cytometry, 030104 developmental biology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Cancer research, Neoplastic Stem Cells, Adenocarcinoma, Cell lines, Female, Cisplatin, Research Article

الوصف: Background Cervical cancer is a major cause of cancer-related mortality in women in the developing world. Cancer Stem cells (CSC) have been implicated in treatment resistance and metastases development; hence understanding their significance is important. Methods Primary culture from tissue biopsies of invasive cervical cancer and serial passaging was performed for establishing cell lines. Variable Number Tandem Repeat (VNTR) assay was performed for comparison of cell lines with their parental tissue. Tumorsphere and Aldefluor assays enabled isolation of cancer stem cells (CSC); immunofluorescence and flow cytometry were performed for their surface phenotypic expression in cell lines and in 28 tissue samples. Quantitative real-time PCR for stemness and epithelial-mesenchymal transition (EMT) markers, MTT cytotoxicity assay, cell cycle analysis and cell kinetic studies were performed. Results Four low-passage novel cell lines designated RSBS-9, − 14 and − 23 from squamous cell carcinoma and RSBS-43 from adenocarcinoma of the uterine cervix were established. All were HPV16+. VNTR assay confirmed their uniqueness and derivation from respective parental tissue. CSC isolated from these cell lines showed CD133+ phenotype. In tissue samples of untreated invasive cervical cancer, CD133+ CSCs ranged from 1.3–23% of the total population which increased 2.8-fold in radiation-resistant cases. Comparison of CD133+ with CD133− bulk population cells revealed increased tumorsphere formation and upregulation of stemness and epithelial-mesenchymal transition (EMT) markers with no significant difference in cisplatin sensitivity. Conclusion Low-passage cell lines developed would serve as models for studying tumor biology. Cancer Stem Cells in cervical cancer display CD133+ phenotype and are increased in relapsed cases and hence should be targeted for achieving remission. Electronic supplementary material The online version of this article (10.1186/s12885-018-4237-5) contains supplementary material, which is available to authorized users.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::881722c58dca4a1e2f1ff97c4464c018Test
https://pubmed.ncbi.nlm.nih.gov/29609538Test