Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer
Objectives: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurren...
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doaj-78add8ead53542b59823562ea1cf21a42020-11-25T00:50:03ZengOman Medical Specialty BoardOman Medical Journal1999-768X2070-52042019-05-0134322423010.5001/omj.2019.43Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical CancerLisnawati Rachmadi0Nurjati Chairani Siregar1Mpu Kanoko2Andrijono Andrijono3Saptawati Bardosono4Dwi Anita Suryandari5Sri Mutya Sekarutami6Bethy Suryawathy Hernowo7Department of Anatomical Pathology, Faculty of Medicine Universitas Indonesia–Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine Universitas Indonesia–Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine Universitas Indonesia–Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDepartment of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia–Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDepartment of Nutrition, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia4Department of Biology, Faculty of Medicine Universitas Indonesia, Jakarta, IndonesiaDepartment of Radiotherapy, Faculty of Medicine Universitas Indonesia–Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine Universitas Padjajaran–Hasan Sadikin Hospital, Jakarta, IndonesiaObjectives: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. Methods: We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. Results: Strong expression of SOX2 (p = 0.011, p = 0.001) and OCT4 (p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). Conclusions: Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer.http://www.omjournal.org/articleDetails.aspx?coType=1&aId=2469Cancer Stem CellsCervical CancerOct-4 Transcription FactorRadiation ToleranceSOXB1 Transcription Factors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lisnawati Rachmadi Nurjati Chairani Siregar Mpu Kanoko Andrijono Andrijono Saptawati Bardosono Dwi Anita Suryandari Sri Mutya Sekarutami Bethy Suryawathy Hernowo |
spellingShingle |
Lisnawati Rachmadi Nurjati Chairani Siregar Mpu Kanoko Andrijono Andrijono Saptawati Bardosono Dwi Anita Suryandari Sri Mutya Sekarutami Bethy Suryawathy Hernowo Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer Oman Medical Journal Cancer Stem Cells Cervical Cancer Oct-4 Transcription Factor Radiation Tolerance SOXB1 Transcription Factors |
author_facet |
Lisnawati Rachmadi Nurjati Chairani Siregar Mpu Kanoko Andrijono Andrijono Saptawati Bardosono Dwi Anita Suryandari Sri Mutya Sekarutami Bethy Suryawathy Hernowo |
author_sort |
Lisnawati Rachmadi |
title |
Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer |
title_short |
Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer |
title_full |
Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer |
title_fullStr |
Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer |
title_full_unstemmed |
Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer |
title_sort |
role of cancer stem cell, apoptotic factor, dna repair, and telomerase toward radiation therapy response in stage iiib cervical cancer |
publisher |
Oman Medical Specialty Board |
series |
Oman Medical Journal |
issn |
1999-768X 2070-5204 |
publishDate |
2019-05-01 |
description |
Objectives: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. Methods: We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. Results: Strong expression of SOX2 (p = 0.011, p = 0.001) and OCT4 (p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). Conclusions: Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer. |
topic |
Cancer Stem Cells Cervical Cancer Oct-4 Transcription Factor Radiation Tolerance SOXB1 Transcription Factors |
url |
http://www.omjournal.org/articleDetails.aspx?coType=1&aId=2469 |
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