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PURPOSE To analyze the dose distribution achieved during 2D radiography-based brachytherapy (BRT) planning, by using a 3D MRI-based BRT replanning evaluation, in patients with advanced cervical carcinoma, treated with definitive concomitant chemoradiation (CCRT). METHODS The curative CCRT was applied to 30 patients with advanced cervical carcinoma. For each patient, 2D radiography-based planning and a 3D MRI-based BRT replanning were performed. Applying the same source positions and dwell times in both planning methods, it was possible to use the MRI replanning to evaluate the dose distribution, maximum organs at risk (OAR) doses and target volume coverage, that was obtained during 2D BRT planning. RESULTS A statistically significant difference for bladder and rectum maximum doses, between 2D planning (Bmax, Rmax) and 3D replanning (D0.1ccm, D1ccm, D2ccm) was found, except between Bmax and bladder D2ccm dose (p=0.07), and Rmax and rectal D2ccm dose in the group of patients with symmetrical rectum position regarding the applicator system (p=0.47). MRI evaluation of the HR-CTV volume, according to the 2D planning achieved dose distribution, revealed total EQD2 HR-CTV doses D90 (107.15±22.06 Gy) and D100 (80.66±14.58 Gy). CONCLUSION 2D radiography-based BRT planning can provide a good estimation for the bladder and rectum 3D D2ccm dose with a significant statistical difference for the doses in the smaller OAR volumes (D0.1ccm, D1ccm). Inability to visualize tumor tissue during 2D BRT planning provides no option in tailoring the dose distribution to the tumor volume and patient anatomy, leading to potential under/over-treatment in some patients.PURPOSE Our aim was to detect and evaluate potential alterations in the postoperative status of E6/E7 HPV mRNA in women treated for cervical intraepithelial lesions (CIN) and if so, to evaluate its potential use as a prognostic tool to identify patients with increased risk of treatment failure or recurrent disease. METHODS Our study retrospectively analyzed 101 women with an abnormal Pap smear, or in some cases with histological reports or molecular analysis requiring colposcopic evaluation. Thin-prep cytological samples were collected before colposcopy and histology (when necessary). After treatment, all women were scheduled for colposcopy in six months. The cytological material was analyzed with CLART-2 HPV-DNA test and HPV-PROOFER E6/E7 mRNA test. RESULTS Concerning demographics, no significant correlations were found for smoking, condom use or vaccination status. It seems that the only statistically significant correlation with actual severity came from the mRNA-test after treatment. This shows that clinical cases with more severe CIN may have higher chances of unsuccessful treatment. At the first post-op visit, 83.5% of HPV mRNA-positive women had a negative HPV mRNA-test while only 60.4% of HPV DNA-positive women became negative. There were 12 HPV-mRNA positive patients both before and after treatment, 3 of whom had a negative HPV DNA test, meaning that, if based only on HPV-DNA results, they would have been managed wrongly as successfully treated patients. Trastuzumab Emtansine mw Our study shows that E6/E7 mRNA detection has particularly high specificity and positive likelihood ratio for the prediction of treatment failure in comparison with HPV DNA-testing. CONCLUSIONS E6/E7 mRNA overexpression seems to be a promising candidate as an indicator-biomarker to determine the success of treatment.PURPOSE Bismahanine, a carbazole alkaloid, has been shown to exhibit tremendous pharmacological potential. In this study, the effect Bismahanine was examined against human cervical cancer cells. METHODS The HeLa human cervical cancer cells were treated with various concentrations of Bismahanine from 0-320 μM for 24 h. The anticancer effects of Bismahanine were measured by WST-1 cell viability assay. DAPI and annexin V/propidium iodide (PI) assays were employed to examine the induction of apoptosis. Transwell assays were performed to examine the cell migration and invasion. The expression of the proteins was examined by western blot analysis. RESULTS Bismahanine decreased the viability of HeLa cells and exhibited an IC50 of 20 µM due to induction of apoptosis as indicated by DAPI staining. Additionally, the annexin V/PI staining revealed that apoptotic cell percentage increased with increasing concentration of Bismahanine. The expression of Bcl-2 was decreased while that of Bax, Caspase 3 and 9 was increased. Bismahanine treatment also resulted in significant decrease of metalloproteinase (MMP) 2 , 3 and 9 expressions. Transwell assays showed that Bismahanine inhibited the migration and invasion of HeLa cells. CONCLUSION Bismahanine exhibits significant anti-proliferative effects on the cervical cancer cells and may prove essential in the development of chemotherapy for cervical cancer.PURPOSE Being the second most prevalent cancer in females, cervical cancer causes significant mortality across the globe. Owing to the adverse effects and inefficiency of the currently used anticancer drugs, there are increasing efforts for the identification of safer and effective anticancer agents from plants. This study was undertaken to investigate the anticancer effects of Ovatodiolide, a plant-derived macrocyclic diterpenoid, against the human cervical cancer. METHODS The anticancer effects were examined by WST-1 proliferation assay. DAPI and annexin V/propidium iodide (PI) staining were used for apoptosis detection. Flow cytometry was used for cell cycle analysis. Protein expression was used for cell cycle analysis. RESULTS The results revealed that Ovatodiolide caused inhibition of the viability of all the cervical cancer cells with IC50 ranging from to 14 to 56 µM. Ovatodiolide exerted more profound antiproliferative effects on the DoTc2 cells with and IC50 of 14 µM. However, minimal cytotoxicity was observed for the normal cervical cells as evidenced from the IC50 of 100 µM. Ovatodiolide triggered apoptotic cell death of the DoTc2 cells. The induction of apoptosis was accompanied with increase in Bax and decrease in Bcl-2 expression. Ovatodiolide also caused arrest of the DoTc2 cells at the G2/M phase of the cell cycle, which was also accompanied with suppression of cyclin B1 expression. Investigation of the effects of Ovatodiolide on NF-kB expression revealed that the molecule caused significant decrease in the expression of the NF-kB expression. CONCLUSION Taken together, Ovatodiolide may prove a lead molecule for the development of systemic therapy for cervical cancer.
Website: https://www.selleckchem.com/products/trastuzumab-emtansine-t-dm1-.html
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