Cancer Research and Treatment

Original Articles

Enhancement of Radiation Effects by Flavopiridol in Uterine Cervix Cancer Cells: Suzy Kim, Hong-Gyun Wu, Jin Hee Shin, Hye Jin Park, In Ah Kim, Il Han Kim; Cancer Res Treat. 2005;37(3):191-195. Published online June 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.3.191

Purpose

To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line.

Materials and Methods

Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone.

Results

The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation.

Conclusion

Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.

Citations

Citations to this article as recorded by

Flavopiridol: a promising cyclin-dependent kinase inhibitor in cancer treatment
Uttam Singh Baghel, Priyanka Kriplani, Neelam M. Patel, Manpreet Kaur, Kapil Sharma, Monika Meghani, Abhay Sharma, Deeksha Singh, Bhawani Singh, William N. Setzer, Javad Sharifi-Rad, Daniela Calina
Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(4): 3489. CrossRef
BAIRDA: a novel in vitro setup to quantify radiobiological parameters for cervical cancer brachytherapy dose estimations
Braden Chow, Brad Warkentin, Kareena Nanda, Sunita Ghosh, Fleur Huang, Armin M Gamper, Geetha Menon
Physics in Medicine & Biology.2022; 67(4): 045012. CrossRef
Nutraceutical Compounds as Sensitizers for Cancer Treatment in Radiation Therapy
Marco Calvaruso, Gaia Pucci, Rosa Musso, Valentina Bravatà, Francesco P. Cammarata, Giorgio Russo, Giusi I. Forte, Luigi Minafra
International Journal of Molecular Sciences.2019; 20(21): 5267. CrossRef
Repositioning disulfiram as a radiosensitizer against atypical teratoid/rhabdoid tumor
Young Eun Lee, Seung Ah Choi, Pil Ae Kwack, Hak Jae Kim, Il Han Kim, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Sung-Hye Park, Kyung Duk Park, Do Won Hwang, Kyeung Min Joo, Seung-Ki Kim
Neuro-Oncology.2017; 19(8): 1079. CrossRef
Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines
Fang Cai, Olivier Sorg, Virginie Granci, Elena Lecumberri, Raymond Miralbell, Yves M. Dupertuis, Claude Pichard
Clinical Nutrition.2014; 33(1): 164. CrossRef
Antitumor Effects of Flavopiridol on Human Uterine Leiomyoma In Vitro and in a Xenograft Model
Hyun-Gyo Lee, Jong-Woo Baek, So-Jin Shin, Sang-Hoon Kwon, Soon-Do Cha, Won-Jin Park, Rosa Chung, Eun-Som Choi, Gun-Ho Lee, Chi-Heum Cho
Reproductive Sciences.2014; 21(9): 1153. CrossRef
In VitroRadiosensitization of Flavopiridol Did Not Translated intoIn VivoRadiosensitization
Suzy Kim
The Journal of the Korean Society for Therapeutic Radiology and Oncology.2011; 29(2): 83. CrossRef
Gold Nanoparticles as Radiation Sensitizers in Cancer Therapy
Devika B. Chithrani, Salomeh Jelveh, Farid Jalali, Monique van Prooijen, Christine Allen, Robert G. Bristow, Richard P. Hill, David A. Jaffray
Radiation Research.2010; 173(6): 719. CrossRef

9,419 View
51 Download
8 Crossref

Cislatin , Vincristine , Bleomycin and Methotrexate ( PVBM ) Combination Chemotherapy for Advanced Uterine Cervix Cancer: Young Hyuk Im, Kee Hyung Lee, Young Suk Park, Chang In Suh, Won Ki Kang, Hyo Jin Kim, Heung Tae Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim, Soon Beom Kang, Hyo Pyo Lee, Jin Yong Lee, Seung Wook; J Korean Cancer Assoc. 1990;22(3):505-518.

Abstract PDF: Twenty-nine patient with advanced cervix cancer were treated with a combination chemotherapy of cisplatin, vincristine, bleomycin, and methotrexate between January, 1987 and December, 1988. 1) Among 19 evaluable patients, 4 patients (20.1%) achieved complete response and 6 patients (31. 6%) achieved partial response, giving an overall response rate of 51.7%. The median duration of remission was 23 weeks in the responders. 2) The median survival of overall patients was 50 7 weeks. The median survival of the responders did not reach the median value during the follow-up period of 15-81 weeks. In contrast, the median survival of the non-responders was 30.7 weeks, which was significantly shorter than that of the responders (p<0.05). 3) The only factor influencing remission rate was the pattem of failure, and the patients with distant metastasis showed higher remission rates (p<0.01). There were no prognostic factors influencing the remission duration. The factors improving survival rates were the early stage at diagnosis (p< 0. 005), the previous history of curative operation (p<0.005), and the presence of distant metastasis (p<0.01). 4) Considerable number of patients experienced toxicities. Among these, leukopenia (50%) and thrombocytopenia (4.7%) were the main hematologic toxicities. Most patients experienced nausea, vomiting, diarrhea (89.49o), stomatitis (26 3%), and alopecia (73.7%). Neurotoxicity due to vincristine or cispatin was found in 36.896 of patients, and 2 patients showed pulmonary fibrosis due to bleomycin toxicity. In conclusion, this regimen (PVBM) seems to be effective in terms of remission rates, but did not show any additional benifits in terms of remission duration or overall survival. In addition, the large number of patients experienced considerable side effects. Based on these findings, further studies are needed to find out the new regimen which is more effective and less toxic for the patients with advanced uterine cervix cancer.

3,176 View
18 Download

Efficacy of Combined Modality , Multidisciplinary Treatment ( Neoadjuvant Chemotherapy , Difinite Local Treatment , and Adjuvant Chemotherapy ) in Locally Advanced Head and Neck Squamous Cell Carcinoma: Jae Kyung Roh, Wha Young Lee, Hyun Cheol Chung, Young Joon Park, Hyung Keun Roh, Chang Ok Suh, Gwi Eon Kim, Jun Kyu Loh, Won Pyo Hong, Cheong Soo Park, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(3):518-532.

Abstract PDF: Between January, 1986 and October, 1989, 40 patients with previously untreated, locally advanced head and neck squamous cell carcinoma enrolled for combined modality treatment (CMT) with neoadjuvant chemotherapy (2 cycles of infusional 5-FU and cis-platin), definite local treatment (DLT) (surgery and/or radiotheray) and adjuvant chemotherapy (3 cycles of infusional 5-FU and cis-platin) to enhance the therpeutic efficacy. Of the 40 enrolled, all the patients were evaluable for tumor responses and treatmen#t related toxicities after neoadjuvant chemotherapy, and 35 patients finished scheduled CMT. Male to female ratio were 33:7, median age 54 year old (34-69), and median ECOG performance grade 1 (0-2). Primary sites were nasopharynx 19, oral cavity 16, larynx 3, hypopharynx 1, and maxillary sinus l. After the 2 cycles of neoadjuvnt therpay, 8/40 (20%), 23/40 (72.5%) achieved compIete remission (CR) and partial remission (PR), respectively with 92.5% over all response rates. After the DLT, 23/ 35 (67.5%) 11/35 (31.4%) achieved CR, and PR respectively with 97.1% over all response rates. Of the 35 patients who finished the DLT, 15 received the 3 cycles of adjuvnat chemotherapy with infusional 5-FU and cis-platin. The median failure-free, and overal survival duration of 35 evaluable patients were 21.7 months and 31.0 months, respectively after the CMT. The median survival duration was significantly prolonged in patients with objective respanses after the neoadjuvant chemotherapy compared to those of non-responders (p<0.05). Of the 35 patients who finished the DLT, patients who received the adjuvant chemotherapy showed trend of prolongation of survival when compared to no adjuvant chemotherapy patients Imedian overall survival duration; adjuvant group 21.7 months, no adjuvant group 17.6 month (p>0.05). This study strongly suggests that CMT can increase the median response duration and survival especially in patients with locally advanced head and neck squamous cell carcinoma who showed responses after the neoadjuvant chemotherapy with infusional 5-FU and cis-platin, but phase III randomized controlled prospective studies are warranted for the verification of this study.

3,001 View
15 Download

Cyclophosphamide , Adriamycin and Cisplatin ( CAP ) Combination Chemotherapy for Invasive Thymoma: Young Suk Park, Young Hyuk Im, Won Ki Kang, Chang In Suh, Kee Hyung Lee, Kyung Hae Jung, Heung Tae Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1990;22(3):532-539.

Abstract PDF: Between October 1985 and January 1990, the combination chemotherapy with cyclophosphamide, adriamycin and cisplatin (CAP) has been administered in 16 patients with invasive, recurrent or metastatic thymoma. Among 14 evaluable patients, 1 patient(7%) achieved a complete response and 4 patients (29%) had a partial response. The 4 year overall survival rates were 56.7% with a median follow-up of 11.5 months. The mast frequent hematologic toxicity was leukopenia (15.9%) and nonhematologic toxicity (WHO criteria; grade II) were alopecia (80%) and nausea/vomiting (66.7%). The CAP regimen is effective and well tolerated for the treatment of invasive thymoma, and further study is needed to confirm the relative effectiveness of CAP regimen in comparison with other regimens and to find out the prognostic factors related to response rate and survival

3,381 View
39 Download

First
Prev
Page of 1
Next
Last

Search