Cancer Research and Treatment

Original Articles

Genetic Alterations among Korean Melanoma Patients Showing Tumor Heterogeneity: A Comparison between Primary Tumors and Corresponding Metastatic Lesions: Si-Hyung Lee, Jee Eun Kim, Hong Sun Jang, Kyu Hyun Park, Byung Ho Oh, Sang Joon Shin, Kee Yang Chung, Mi Ryung Roh, Sun Young Rha; Cancer Res Treat. 2018;50(4):1378-1387. Published online January 22, 2018; DOI: https://doi.org/10.4143/crt.2017.535

Abstract PDF Supplementary Material PubReader ePub

Purpose
Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected.
Materials and Methods
In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions.
Results
Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. Conclusion
Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.

Citations

Citations to this article as recorded by

Elucidation of anti-human melanoma and anti-aging mechanisms of compounds from green seaweed Caulerpa racemosa
Danar Wicaksono, Nurpudji Astuti Taslim, Vincent Lau, Rony Abdi Syahputra, Aiman Idrus Alatas, Purnawan Pontana Putra, Trina Ekawati Tallei, Raymond Rubianto Tjandrawinata, Apollinaire Tsopmo, Bonglee Kim, Fahrul Nurkolis
Scientific Reports.2024;[Epub] CrossRef
Évolution du statut braf dans le melanome : mythe ou Réalité ?
Elicia Molines, Aurélie Haffner, Frédéric Fina, Nausicaa Malissen, L’Houcine Ouafik, Jean-Jacques Grob, Nicolas Macagno
Annales de Pathologie.2022; 42(2): 113. CrossRef
Metastatic uveal melanoma: The final frontier
Elina S. Rantala, Micaela M. Hernberg, Sophie Piperno-Neumann, Hans E. Grossniklaus, Tero T. Kivelä
Progress in Retinal and Eye Research.2022; 90: 101041. CrossRef
Variations in genetics, biology, and phenotype of cutaneous disorders in skin of color – Part I: Genetic, biologic, and structural differences in skin of color
Jessica B. Brown-Korsah, Shanice McKenzie, Deega Omar, Nicole C. Syder, Nada Elbuluk, Susan C. Taylor
Journal of the American Academy of Dermatology.2022; 87(6): 1239. CrossRef
PTEN Promoter Hypermethylation Is Associated with Breslow Thickness in Acral Melanoma on the Heel, Forefoot, and Hallux
Hae Seok Park, Jong Hoon Kim, Mi Yeon Cho, Kee Yang Chung, Mi Ryung Roh
Annals of Dermatology.2021; 33(1): 18. CrossRef
Heterogeneity of GNAQ/11 mutation inversely correlates with the metastatic rate in uveal melanoma
Chen Liang, Lan ya Peng, Ming Zou, Xuemei Chen, Yingying Chen, Hou Chen, Lirong Xiao, Naihong Yan, Junjun Zhang, Qing Zhao, Xi Huang
British Journal of Ophthalmology.2021; 105(4): 587. CrossRef
Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition
Jian-Ching Wu, Han-En Tsai, Yi-Hsiang Hsiao, Ji-Syuan Wu, Chieh-Shan Wu, Ming-Hong Tai
International Journal of Molecular Sciences.2020; 21(2): 681. CrossRef
Male sex and Breslow thickness are important risk factors for recurrence of localized melanoma in Korean populations
Yeongjoo Oh, Sooyie Choi, Mi Yeon Cho, Kyoung Ae Nam, Sang Joon Shin, Jee Suk Chang, Byung Ho Oh, Mi Ryung Roh, Kee Yang Chung
Journal of the American Academy of Dermatology.2020; 83(4): 1071. CrossRef
Tumor Heterogeneity on FDG PET/CT and Immunotherapy: An Imaging Biomarker for Predicting Treatment Response in Patients With Metastatic Melanoma
Y. Sanli, J. Leake, A. Odu, Y. Xi, R. M. Subramaniam
American Journal of Roentgenology.2019; 212(6): 1318. CrossRef
BRAF and NRAS mutations and antitumor immunity in Korean malignant melanomas and their prognostic relevance: Gene set enrichment analysis and CIBERSORT analysis
Kyueng-Whan Min, Ji-Young Choe, Mi Jung Kwon, Hye Kyung Lee, Ho Suk Kang, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Yun Joong Kim, Nan Young Kim, Ho Young Kim
Pathology - Research and Practice.2019; 215(12): 152671. CrossRef
Molecular and genetic diversity in melanoma of eye
N. N. Mazurenko, I. V. Tsyganova, V. V. Nazarova, I. A. Utyashev, K. V. Orlova, D. A. Ponkratova, D. V. Martinkov, L. V. Demidov
Advances in molecular oncology.2018; 5(3): 51. CrossRef

9,215 View
214 Download
13 Web of Science
11 Crossref

Overexpression of SOX2 Is Associated with Better Overall Survival in Squamous Cell Lung Cancer Patients Treated with Adjuvant Radiotherapy: Hong In Yoon, Kyu Hyun Park, Eun-Jung Lee, Ki Chang Keum, Chang Geol Lee, Chul Hoon Kim, Yong Bae Kim; Cancer Res Treat. 2016;48(2):473-482. Published online August 12, 2015; DOI: https://doi.org/10.4143/crt.2015.116

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate the prognostic significance of SOX2 gene amplification and expression in patients with American Joint Committee on Cancer stage III lung squamous cell carcinoma (SCC) who underwent surgery followed by adjuvant radiotherapy.
Materials and Methods
Pathological specimens were obtained from 33 patients with stage III lung SCC treated with surgery followed by adjuvant radiotherapy between 1996 and 2008. SOX2 gene amplification and protein expression were analyzed using fluorescent in situ hybridization and immunohistochemistry, respectively. Patients were divided into two groups according to their SOX2 gene amplification and protein expression status. Kaplan-Meier estimates and a Cox proportional hazards model were used to identify the prognostic factors affecting patient survival.
Results
The median follow-up period for surviving patientswas 58 months (range, 5 to 102 months). SOX2 gene amplification was observed in 22 patients and protein overexpression in 26 patients. SOX2 overexpression showed significant association with SOX2 gene amplification (p=0.002). In multivariate analysis, SOX2 overexpression was a significant prognostic factor for overall survival (OS) (hazard ratios [HR], 0.1; 95% confidence interval [CI], 0.002 to 0.5; p=0.005) and disease-free survival (DFS) (HR, 0.15; 95% CI, 0.04 to 0.65; p=0.01). Age (HR, 0.33; 95% CI, 0.11 to 0.98; p=0.046) and total radiation dose (HR, 0.13; 95% CI, 0.02 to 0.7; p=0.02) were the independent prognostic factors for OS and DFS. Patients with SOX2 amplification did not show a longer OS (p=0.95) and DFS (p=0.48).
Conclusion
Our data suggested that SOX2 overexpression could be used as a positive prognostic factor in patients with stage III lung SCC receiving adjuvant radiotherapy.

Citations

Citations to this article as recorded by

Identifying the key hub genes linked with lung squamous cell carcinoma by examining the differentially expressed and survival genes
Anushka Pravin Chawhan, Norine Dsouza
Molecular Genetics and Genomics.2024;[Epub] CrossRef
Gene‐level dissection of chromosome 3q locus amplification in squamous cell carcinoma of the lung using the nCounter assay
Taesung Jeon, Uk Jeen Oh, Jaeyoung Min, Chungyeul Kim
Thoracic Cancer.2023; 14(26): 2635. CrossRef
The role of SOX family members in solid tumours and metastasis
Daniela Grimm, Johann Bauer, Petra Wise, Marcus Krüger, Ulf Simonsen, Markus Wehland, Manfred Infanger, Thomas J. Corydon
Seminars in Cancer Biology.2020; 67: 122. CrossRef
Blood-Based SOX2-Promoter Methylation in Relation to Exercise and PM2.5 Exposure among Taiwanese Adults
Chun-Lang Su, Disline Manli Tantoh, Ying-Hsiang Chou, Lee Wang, Chien-Chang Ho, Pei-Hsin Chen, Kuan-Jung Lee, Oswald Ndi Nfor, Shu-Yi Hsu, Wen-Miin Liang, Yung-Po Liaw
Cancers.2020; 12(2): 504. CrossRef
Epithelial-Mesenchymal Transition in Skin Cancers: A Review
Anastasia Hodorogea, Andreea Calinescu, Mihaela Antohe, Mihaela Balaban, Roxana Ioana Nedelcu, Gabriela Turcu, Daniela Adriana Ion, Ioana Anca Badarau, Catalin Mihai Popescu, Raluca Popescu, Cristiana Popp, Mirela Cioplea, Luciana Nichita, Ionela Hulea, A
Analytical Cellular Pathology.2019; 2019: 1. CrossRef
Towards understanding the mechanisms of actions of carcinoembryonic antigen‐related cell adhesion molecule 6 in cancer progression
Balsam Rizeq, Zain Zakaria, Allal Ouhtit
Cancer Science.2018; 109(1): 33. CrossRef
Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells
Ugo Testa, Germana Castelli, Elvira Pelosi
Cancers.2018; 10(8): 248. CrossRef
SOX2 knockdown inhibits the migration and invasion of basal cell carcinoma cells by targeting the SRPK1‑mediated PI3K/AKT signaling pathway
Zhuo‑Ran Li, Yong Jiang, Jian‑Zhong Hu, Yang Chen, Quan‑Zhong Liu
Oncology Letters.2018;[Epub] CrossRef
Association of SOX2 and Nestin DNA amplification and protein expression with clinical features and overall survival in non-small cell lung cancer: A systematic review and meta-analysis
Qingbao Li, Fang Liu, Yuan Zhang, Lei Fu, Cong Wang, Xuan Chen, Shanghui Guan, Xiangjiao Meng
Oncotarget.2016; 7(23): 34520. CrossRef

12,029 View
111 Download
11 Web of Science
9 Crossref

p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer: Se Hyun Kim, Kyu Hyun Park, Sang Joon Shin, Kang Young Lee, Tae Il Kim, Nam Kyu Kim, Sun Young Rha, Jae Kyung Roh, Joong Bae Ahn; Cancer Res Treat. 2016;48(1):208-215. Published online April 24, 2015; DOI: https://doi.org/10.4143/crt.2014.314

Abstract PDF PubReader ePub

Purpose
Hypermethylation of the CpG island of p16INK4a occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab.
Materials and Methods
Pyrosequencing was used to identify KRASmutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome.
Results
Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRASmutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027).
Conclusion
Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.

Citations

Citations to this article as recorded by

Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging
Giuseppe Corrias, Eleonora Lai, Pina Ziranu, Stefano Mariani, Clelia Donisi, Nicole Liscia, Giorgio Saba, Andrea Pretta, Mara Persano, Daniela Fanni, Dario Spanu, Francesca Balconi, Francesco Loi, Simona Deidda, Angelo Restivo, Valeria Pusceddu, Marco Puz
Cancers.2024; 16(7): 1364. CrossRef
Alteration in DNA methylation patterns: Epigenetic signatures in gastrointestinal cancers
Zahra Heydari, Farideh Moeinvaziri, Seyed Mohammad Ali Mirazimi, Fatemeh Dashti, Olga Smirnova, Anastasia Shpichka, Hamed Mirzaei, Peter Timashev, Massoud Vosough
European Journal of Pharmacology.2024; 973: 176563. CrossRef
Chromatin factors: Ready to roll as biomarkers in metastatic colorectal cancer?
Cristina Moreta-Moraleda, Cristina Queralt, Carla Vendrell-Ayats, Sonia Forcales, Eva Martínez-Balibrea
Pharmacological Research.2023; 196: 106924. CrossRef
A 10-gene-methylation-based signature for prognosis prediction of colorectal cancer
Dong-hai Li, Xiao-hui Du, Ming Liu, Rui Zhang
Cancer Genetics.2021; 252-253: 80. CrossRef
Value of methylation markers in colorectal cancer (Review)
Can Kong, Tao Fu
Oncology Reports.2021;[Epub] CrossRef
Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma
Maja T. Tomicic, Mona Dawood, Thomas Efferth
Cancers.2021; 13(16): 4072. CrossRef
Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan
Chih-Hsiung Hsu, Cheng-Wen Hsiao, Chien-An Sun, Wen-Chih Wu, Tsan Yang, Je-Ming Hu, Yu-Chan Liao, Chi-Hua Huang, Chao-Yang Chen, Fu-Huang Lin, Yu-Ching Chou
Scientific Reports.2020;[Epub] CrossRef
Methylation-Based Therapies for Colorectal Cancer
Klara Cervena, Anna Siskova, Tomas Buchler, Pavel Vodicka, Veronika Vymetalkova
Cells.2020; 9(6): 1540. CrossRef
CpG Island Methylator Phenotype and Methylation of Wnt Pathway Genes Together Predict Survival in Patients with Colorectal Cancer
Se Hyun Kim, Kyu Hyun Park, Sang Joon Shin, Kang Young Lee, Tae Il Kim, Nam Kyu Kim, Sun Young Rha, Joong Bae Ahn
Yonsei Medical Journal.2018; 59(5): 588. CrossRef
Recent advances in understanding colorectal cancer
Sebastian Stintzing
F1000Research.2018; 7: 1528. CrossRef
Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer
Amana Saadallah-Kallel, Rania Abdelmaksoud-Dammak, Mouna Triki, Slim Charfi, Abdelmajid Khabir, Tahia Sallemi-Boudawara, Raja Mokdad-Gargouri
Medical Oncology.2017;[Epub] CrossRef
DNA methylation of CMTM3 , SSTR2 , and MDFI genes in colorectal cancer
Jinyun Li, Cheng Chen, Xuer Bi, Chongchang Zhou, Tao Huang, Chao Ni, Ping Yang, Si Chen, Meng Ye, Shiwei Duan
Gene.2017; 630: 1. CrossRef

12,910 View
110 Download
12 Web of Science
12 Crossref

Case Report

PTEN Methylation Dependent Sinonasal Mucosal Melanoma: Sang Hee Lee, Mi Ryung Roh, Beodeul Kang, Kyu Hyun Park, Soo Hee Kim, Sang Eun Lee, Sun Young Rha; Cancer Res Treat. 2016;48(2):853-858. Published online March 18, 2015; DOI: https://doi.org/10.4143/crt.2014.356

Abstract PDF PubReader ePub

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase–AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.

Citations

Citations to this article as recorded by

Mucosal Melanoma: Epidemiology, Clinical Features, and Treatment
Maria Chiara Sergi, Elisabetta Filoni, Giacomo Triggiano, Gerardo Cazzato, Valeria Internò, Camillo Porta, Marco Tucci
Current Oncology Reports.2023; 25(11): 1247. CrossRef
Mucosal melanomas of different anatomic sites share a common global DNA methylation profile with cutaneous melanoma but show location‐dependent patterns of genetic and epigenetic alterations
Philipp Jurmeister, Niklas Wrede, Inga Hoffmann, Claudia Vollbrecht, Daniel Heim, Michael Hummel, Peggy Wolkenstein, Ines Koch, Verena Heynol, Wolfgang Daniel Schmitt, Anne Thieme, Daniel Teichmann, Christine Sers, Andreas von Deimling, Julia Cara Thierau
The Journal of Pathology.2022; 256(1): 61. CrossRef
Actionable Mutation Profile of Sun-Protected Melanomas in South America
Ricardo Hsieh, Marcello M. S. Nico, Cláudia M. C. Camillo, Kátia K. Oliveira, Dirce M. Carraro, Martin Sangueza, Silvia V. Lourenço
The American Journal of Dermatopathology.2022; 44(10): 741. CrossRef
Mucosal melanoma: current strategies and future directions
Shaheer Khan, Richard D. Carvajal
Expert Opinion on Orphan Drugs.2019; 7(10): 427. CrossRef

11,181 View
101 Download
4 Web of Science
4 Crossref

Original Articles

Changes of Telomerase Activity and Proliferation by Inhibition of Reverse Transcriptase Activity in Human Cancer Cell: Hyun Jung Ji, Kyu Hyun Park, Tae Soo Kim, Sun Young Rha, Nae Choon Yoo, Jun Myung Kim, Jun Suk Kim, Jae Kyoung Roh, Woo Ick Jang, Hyun Cheol Chung; Cancer Res Treat. 2002;34(3):223-233. Published online June 30, 2002; DOI: https://doi.org/10.4143/crt.2002.34.3.223

Abstract PDF

PURPOSE
Activation of telomerase is proposed to be an essential step in cancer cell immortalization and cancer progression. 3'-azido-2',3'-dideoxythymidine (AZT), a reverse transcriptase inhibitor, was reported to be incorporated in telomeric sequences of immortalized cells in culture and to suppress the activity of telomerase and the cell proliferation. In this study, after induction of cancer cell senescence with long-term treatment of AZT, we investigated the dynamics of telomerase subunits (hTERT, hTR, TEP), transcription factors (c-Myc, Mad1), telomerase activity, and finally, telomere length in a human breast cancer cell line. MATERIALS AND METGODS: Human breast cancer cell (MDA-MB-231) was treated with AZT. Senescence was measured by senescence-associated beta-gal staining and apoptosis was counted by dTd enzyme assay. Telomerase activity (by TRAP assay), expression of telomerase subunit genes (by RT-PCR and real-time PCR) and telomere length (by Southern blot analysis) were measured after the AZT treatment.
RESULTS
We found evidences of senescence, apoptosis and growth delay after AZT treatment. In addition, AZT- treated cancer cells showed inhibition of telomerase activity and shortening of telomere length in a dose- and duration-dependent way. Among the telomerase subunits, hTERT and c-Myc were the first factors to change after AZT treatment, subsequently, followed by the changes of hTR, Mad1 and TEP.
CONCLUSION
The suppression of hTERT and c-Myc by AZT treatment was the initial genetic phenomenon, subsequently followed by the changes of hTR, Mad1 and TEP.

Citations

Citations to this article as recorded by

Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways
Bowei Liu, Zhigang Peng, Hao Zhang, Nan Zhang, Zaoqu Liu, Zhiwei Xia, Shaorong Huang, Peng Luo, Quan Cheng
Molecular Cancer.2025;[Epub] CrossRef

4,245 View
38 Download
1 Crossref

Restoration of Wild - type p53 Induces Chemo-sensitization in the Gastric Cancer Cell Line with Mutant p53: Ho Young Maeng, Sun Young Rha, Byung Soh Min, Yong Bae Kim, Hyun Joo Kwak, Tae Soo Kim, Kyu Hyun Park, Nae Choon Yoo, Ho Young Lim, Jin Hyuk Choi, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):497-507.

Abstract PDF: PURPOSE
It has been theorized that p53 may be involved in the sensitivity to chemotherapeutic agents. We evaluated the chemosensitivity of wild p53 after transduction into gastric cancer cell lines with mutant p53.
MATERIALS AND METHODS
YCC-3(parent cell line with mutant p53), YCC-3v(parent cell line transduced with vector alone) and YCC-3C3(clone with wild p53) cell lines were used in this study. p53 protein expression was measured by ELISA assay. Tumorigenicity and drug sensitivity were evaluated by soft agar and proliferation assay, respectively. Cell cycle analysis was performed by flowcytometry. Telomerase activity was measured by TRAP assay and terminal restriction fragment(TRF) length was measured after Southern blot analysis.
RESULTS
Even though p53 production from the YCC-3C3 cell line was three times higher than those of YCC-3 and YCC-3v cell lines, the cell cycle was the same in these three cell lines. In the YCC-3C3 cell line, drug sensitivity to etoposide and cisplatin was increased when we compared it to those of the YCC-3v cell line(etoposide, 50% versus 83%; cisplatin, 67% versus 83%). However, there was no chemo-sensitization effect with vincristine, vinblastine and carboplatin. After exposure to cisplatin, a G0/G1 check-point effect was found in the YCC-3C3 cell line, but not in the YCC-3v cell line. No differences were found in telomerase activity, TRFs length or DNA fragmentation between the YCC-3v and YCC-3C3 cell lines after cisplatin treatment.
CONCLUSION
Wild-type p53 gene transduction in the gastric cancer cell line induced sensitization to the cytotoxicity of etoposide and cisplatin. This suggests the possible application of combined chemo-gene therapy with an EP regimen and wild-type p53 in gastric cancer patients with p53 mutation.

3,205 View
22 Download

Semi - quantitative Comparison of Terminal Restriction Fragment Length and Telomerase in Breast Cancer for Biotherapy: Sun Young Rha, Kyu Hyun Park, Tae Soo Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(2):231-241.

Abstract PDF: PURPOSE
We determined the clinical significance of telomerase activity and telomere length in breast cancer patients and also developed the measuring system of telomerase activity change with RNAse A pre-treatment.
MATERIALS AND METHODS
We measured the telomerase activity in 71 breast cancer tissues and paired normal tissues with TRAP (Telomeric Repeat Amplification Protocol) assay. Telomerase activity was calculated by computer-assisted densitometry compared to telomerase activity of the 293 control cell line. To develop the measuring system of telomerase activity modulation, we measured the telomerase activity after the treatment with RNAse A, 150microgram/ml, which inhibited 70% of telomerase activity compared to control in the 293 control cell line. In 59 paired tissues with telomerase activity, terminal restriction fragment (TRFs) length were measured using Southern blotting.
RESULTS
Sixty-three out of 71 cancer tissues showed telomerase activity (88.7%), while no telomerase activity was detected in their paired normal tissues. Telomerase activity was correlated to the node metastasis (p=0.02) and stage (p=0.005), but not to the tumor size or the hormonal receptor status. TRFs were neither specific to tumor tissues nor related to any of the clinical parameters. However, changes of TRFs of the tumor tissues from their paired normal tissues were correlated to the telomerase activities. Also the patients with different TRFs between cancer and normal tissues were in more advanced stage. After pre-treatment with the 150microgram/ml of RNAse A, telomerase activity in the tumor tissues showed variable inhibition. Relative inhibition, the ratio of inhibited telomerase activity in each tumor tissue compared to the inhibition of 293 control cell line, was proportional to the telomerase activity.
CONCLUSION
In breast cancer, telomerase activity was specific to the tumor tissues and correlated to tumor progression. A combination of telomerase activity and TRFs changes can be used as a guidline in detecting a better candidate for telomerase inhibition. Semi-quantitative assay with RI system can be used in evaluating the changes of telomerase activity after treatment with a new telomerase inhibitor with TRAP assay.

2,568 View
18 Download

Increment of Telomerase Activity with Breast Cancer Progression: Kyu Hyun Park, Sun Young Rha, Tae Soo Kim, Byung Chan Lee, Sei Ho Park, Hyun Cheol Chung, Won Young Lee, Joo Hang Kim, Jae Kyung Roh, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(6):1032-1040.

Abstract PDF: PURPOSE
We studied the telomerase activity in normal and cancer tissues of the breast and then compared it to the clinical parameters.
MATERIALS AND METHODS
36 paired normal and cancerous breast tissues were assayed for telomerase activity by PCR-based TRAP assay (telomeric repeat amplification protocol). In 17 cancer tissues, flow cytometric analysis for S-phase fraction was done.
RESULTS
None of the normal breast tissue expressed telomerase activity while 23 out of 26 breast cancer tissue expressed telomerase activity (92%). Clinical parameters such as T-factor, tumor grade, hormone receptor expression, mitosis, S-phase fraction did not correlate with telomerase expression. However, telomerase acitvity increased with cancer progression such as; in a state of lymph node metastasis and in an advanced pathological stage.
CONCLUSION
Telomerase activity was expressed only from cancer tissues. And this expression increased with cancer progression suggesting a possible therapeutic target in breast cancer.

2,933 View
25 Download

First
Prev
Page of 1
Next
Last

Search