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

المصدر: Indian Journal of Medical Research, Vol 154, Iss 2, Pp 367-374 (2021)

مصطلحات موضوعية: aldh1 - cancer stem cells - cd133 - cervical cancer - e-cadherin - epithelial–mesenchymal transition - keratin 7, Medicine

الوصف: Background & objectives: 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. Methods: 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. Results: 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 (P<0.01). Interpretation & conclusions: 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.

العلاقة: http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2021;volume=154;issue=2;spage=367;epage=374;aulastTest=Javed; https://doaj.org/toc/0971-5916Test; https://doaj.org/article/4da5e85523b3422a9d44b86d5434aee0Test

الإتاحة: https://doi.org/10.4103/ijmr.IJMR_709_20Test
https://doaj.org/article/4da5e85523b3422a9d44b86d5434aee0Test

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

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

مصطلحات موضوعية: CD133, Cancer stem cells, Cervical cancer, HPV16, Cell lines, Low passage, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract 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.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12885-018-4237-5Test; https://doaj.org/toc/1471-2407Test

الوصول الحر: https://doaj.org/article/4bccd81722884095b9955825b4909b51Test