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      • Palliative Treatment of Advanced Cervical Cancer with Radiotherapy and Thai Herbal Medicine as Supportive Remedy - Analysis of Survival

        Pesee, Montien,Kirdpon, Wichit,Puapairoj, Anucha,Kirdpon, Sukachart,Prathnadi, Pongsiri Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

        Background: To evaluate outcomes using a Thai herbal medicine, Vilac Plus (G716/45) with standard radiotherapy in comparison with historic controls from literature reports of the results of treatment in stage IIIB cervical cancer. Materials and Methods: Between March 2003 and June 2005, thirty patients with advanced cervical cancer stage IIIB-IV who had a poor performance status were treated by palliative radiotherapy along with an adjuvant daily dose of 15-30 ml of Thai herbal tonic solution (Vilac Plus G716/45) administered orally three times after meals as an additional supportive therapy. The results were analyzed from the aspect of the overall survival rates with curves estimated by the Kaplan-Meier method. Results:.The median follow -up time for stage IIIB was 4.2 years with a range of 7.9 months - 6.1 years. The overall 1, 3, and 5 year survival rates for stage IIIB were 88%, 60% and 52%. Conclusions: The overall 5 year survival rate for stage IIIB with a poor performance status was 52% when compared with 34-54.8% for historic controls. The combined complementary palliative radiotherapy (CCPR) had low rates of radiation morbidity. It was a simple technique and feasible for developing countries. The pilot study was limited by the small number of patients and further research will be necessary to assess interrelated and confounding factors in treatment of cervical cancer patients.

      • Association of NRF2 Polymorphism with Cholangiocarcinoma Prognosis in Thai Patients

        Khunluck, Tueanjai,Kukongviriyapan, Veerapol,Puapairoj, Anucha,Khuntikeo, Narong,Senggunprai, Laddawan,Zeekpudsa, Ponsilp,Prawan, Auemduan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

        Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be $344{\pm}138$ (95%CI: 73-615) days and $172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients.

      • Opisthorchis viverrini Infection Activates the PI3K/AKT/PTEN and Wnt/β-catenin Signaling Pathways in a Cholangiocarcinogenesis Model

        Yothaisong, Supak,Thanee, Malinee,Namwat, Nisana,Yongvanit, Puangrat,Boonmars, Thidarut,Puapairoj, Anucha,Loilome, Watcharin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

        Opisthorchis viverrini (Ov) infection is the major etiological factor for cholangiocarcinoma (CCA), especially in northeast Thailand. We have previously reported significant involvement of PI3K/AKT/PTEN and $Wnt/{\beta}$-catenin in human CCA tissues. The present study, therefore, examined the expression and activation of PI3K/AKT/PTEN and $Wnt/{\beta}$-catenin signaling components during Ov-induced cholangiocarcinogenesis in a hamster animal model. Hamsters were divided into two groups; non-treated and Ov plus NDMA treated. The results of immunohistochemical staining showed an upregulation of PI3K/AKT signaling as determined by elevated expression of the $p85{\alpha}$-regulatory and $p110{\alpha}$-catalytic subunits of PI3K as well as increased expression and activation of AKT during cholangiocarcinogenesis. Interestingly, the staining intensity of activated AKT (p-AKT) increased in the apical regions of the bile ducts and strong staining was detected where the liver fluke resides. Moreover, PTEN, a negative regulator of PI3K/AKT, was suppressed by decreased expression and increased phosphorylation during cholangiocarcinogenesis. We also detected upregulation of $Wnt/{\beta}$-catenin signaling as determined by increased positive staining of Wnt3, Wnt3a, Wnt5a, Wnt7b and ${\beta}$-catenin, corresponded with the period of cholangiocarcinogenesis. Furthermore, nuclear staining of ${\beta}$-catenin was observed in CCA tissues. Our results suggest the liver fluke infection causes chronic inflammatory conditions which lead to upregulation of the PI3K/AKT and $Wnt/{\beta}$-catenin signaling pathways which may drive CCA carcinogenesis. These results provide useful information for drug development, prevention and treatment of CCA.

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