Regulation of paclitaxel-induced programmed cell death by autophagic induction: A model for cervical cancer.

OBJECTIVE: Autophagy plays a vital role in homeostasis by combining organelles and cellular proteins with lysosome under starvation conditions. In addition, autophagy provides tumor cells with a source of energy. Continued autophagy will induce cells death. Here we aim to see if autophagic induction has an effect on conventional chemotherapeutic agents. METHODS: Rapamycin, or mammalian target of rapamycin and paclitaxel, apoptosis-inducing agents were used autophagy in HeLa cervical cancer cells. RESULTS: Growth inhibition of cells was not observed after the application of 0, 10, 20 nM of paclitaxel with or without rapamycin. Using a 5 nM concentration of paclitaxel, rapamycin administration inhibited cell growth significantly compared to no treatment. This implies the synergic antitumor effect of paclitaxel and rapamycin. Paclitaxel itself did not show any autophagic effect on cells but did show cell apoptosis by flow cytometry. Light chain 3, a microtubule-associated protein, which reflect autophagy, was increased with 5 nM of paclitaxel after pretreatment with 10 nM of rapamycin. CONCLUSION: These findings suggest that the autophagic inducer, rapamycin, can potentiate autophagic cell death when added as an apoptosis-inducing chemotherapeutic agent. In conclusion, the control of autophagy may be a future target for chemotherapy.

Outcomes and prognostic factors of cervical cancer after concurrent chemoradiation.

AIM: Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced cervical cancer. This study was undertaken to evaluate the outcomes and the prognostic factors for cervical cancer after CCRT. MATERIAL AND METHODS: The medical records of 174 patients with International Federation of Gynecology and Obstetrics stage IB1-IVA who were treated at three affiliated hospitals of the Catholic University of Korea between January 1999 and December 2008 were reviewed and analyzed. Patients received pelvic radiotherapy with one of three regimens of cisplatin-based chemotherapy concurrently and high-dose rate brachytherapy. The radiation field was extended to include para-aortic lymph nodes, if necessary. RESULTS: The median follow-up period was 29.5 months (range, 5-96 months). Using multivariate analysis, stage (P = 0.014), tumor size (P = 0.043), and clinical response (P = 0.001) had a significant effect on overall survival. Similarly, progression-free survival (PFS) was influenced by stage (P = 0.004), tumor size (P = 0.02), clinical response (P = 0.011), and normalized squamous cell carcinoma antigen level after CCRT (P = 0.007). The 5-year survival rates were 91.7% (standard error, 5.8%) for stages IB1-IIA, 71.5% (standard error, 7.8%) for stage IIB, 44.9% (standard error, 7.8%) for stage III, and 20.9% (standard error, 12.0%) for stage IVA. A total of 151 out of 174 patients (86.8%) completed the planned treatment. Toxicities were manageable with supportive therapy. CONCLUSIONS: Cisplatin-based CCRT is well-tolerated. Good clinical response revealed a favorable correlation to survival. A maximal effort to achieve this goal might prolong survival in patients with cervical cancer.

Specific human papillomavirus types and other factors on the risk of cervical intraepithelial neoplasia: a case-control study in Korea.

OBJECTIVE: Cervical neoplasia is attributed to a persistent human papillomavirus (HPV) infection. We performed a hospital-based, case-control study to evaluate the associations of HPV genotypes and other cofactors with cervical intraepithelial neoplasia (CIN). METHODS: A total of 158 women were enrolled after we received their informed consent, and the control group (the non-CIN group; n = 80) was selected from women at St Paul's Health Promotion Center. The CIN group (n = 78) was enrolled from the outpatient clinics at Kangnam St Mary's Hospital. Cervical intraepithelial neoplasia was confirmed with colposcopic-guided biopsy or loop electrosurgical excision procedure-conization. A structured questionnaire, Papanicolaou test, and HPV testing were completed. We compared each risk factor using chi2 tests and simple logistic regression analysis between the CIN and non-CIN groups. Finally, odds ratios (ORs) were calculated again by multiple logistic regression analysis. RESULTS: The most frequent HPV types in CIN were HPV-16, HPV-58, HPV-31/-33, and HPV-35/-56. The OR of the A9 group (HPV-16, HPV-31, HPV-33, HPV-35, HPV-52, HPV-58) was 22.7 (95% confidence interval [CI], 8.3-62.5), that of the A6 group (HPV-53, HPV-56, HPV-66) was 2.9 (95% CI, 1.1-7.5), and that of the A7 group (HPV-18, HPV-39, HPV-45, HPV-59, HPV-68) was 1.5. Sexual debut before 20 years old had significantly higher OR than did a sexual debut after 30 years (OR, 32.9; 95% CI, 2.8-364.7). The OR for CIN in single women versus married women was 6.2 (95% CI, 2.5-15.2). Compared with parous women (parity >3), nonparous women had a higher OR (95% CI, 1.4-16.7). On the multiple logistic regression analysis including the sexual debut age, the marital status, parity, cytology, and the HPV groups, the A9 group had a significant OR for CIN (6.1; 95% CI, 1.6-23.6). CONCLUSIONS: The risk of CIN was higher for women infected with the HPV-A9 group after multiple logistic regression analysis. The other clinical risk factors were not significant factors of CIN.