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Abstract: Vanadium belongs among the microelements and plays a role in human nutrition. However, it is not regarded as an essential micronutrient. Vanadium affects various biochemical processes and when present in the body, it is capable of interacting with a notable number of enzymes e.g. protein kinases, phosphatases, ATPases, peroxidases, ribonucleases, oxidoreductases and others. It is documented in scientific literature that vanadium takes part in biochemical processes in mammals. Vanadium is not carcinogenic but its presence in cancer cells and its interactions with many key enzymatic processes results in modified expression of p53 and Bax and in down regulation of Bcl2 proteins and in antiproliferative activity. Anti-carcinogenic and anticancer effects of vanadium in various forms have been demonstrated using in vitro and in vivo experiments. Presently, epidemiologic and clinical studies are necessary for developing a clinically useful, vanadium-based anticancer agent/drug for chemoprevention of cancer. This review summarizes recent scientific information on the role and potential use of vanadium in cancer chemoprevention and cancer therapy. Keywords: Vanadium, vanadium-containing compounds, anti-cancer activity, chemoprevention, anti-carcinogenic effect, apoptosis, antiproliferative activity.Download Full Article |
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Abstract: Background: To date, only a few studies have explored the relationship between vascular disease and Prostate Cancer (PCa), with conflicting results. The Aim of the research was to investigate the association of carotid vascular disease (CVD) or Coronary Artery disease (CAD) with PCa hormone-naïve at initial diagnosis. Methods: Retrospective analysis of 266 patients undergoing prostate biopsy at our institution between 2006 and 2009 was conducted. We examined associations of CVD or CAD in 133 patients with PCa diagnosis versus 133 age-matched controls. Men with incomplete data available, history of hormone therapy or chemotherapy, prostate or bladder surgery were excluded. Results:CVD was significantly linked to PCa in all cases versus controls at initial diagnosis of PCa (OR 2.42, p < 0.05). Similarly CAD was significantly related to PCa at initial diagnosis (OR 1.88, p < 0.05). Conclusions: In our study a significant relation was found between vascular damage and PCa hormone-naïve at initial diagnosis. Further research should elucidate these associations in larger samples to confirm these relationships and to stabilize future prevention strategies. Keywords: Carotid vascular disease, Coronary artery disease, Vascular disease, Prostate Cancer..Download Full Article |
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Abstract: Background:Men diagnosed with locally advanced high-risk prostate cancer have up to a 40% risk of biochemical recurrence after prostatectomy. The authors performed a phase II trial of neoadjuvant weekly ixabepilone prior to radical prostatectomy. Methods:Enrollment criteria included patients with high-risk prostate cancer defined by D’Amico criteria or high-volume Gleason 4+3 with a palpable nodule. Patients received ixabepilone 20 mg/m2/week or 16 mg/m2/week for 3 weeks every 28 days for 4 cycles followed by surgery 2-8 weeks later. Results:Sixteen patients were enrolled with a mean age of 56.5 years (range 43-70). PSA values decreased by a mean of 47% in 14/16 men with patients receiving a mean of 8.25 weeks of treatment (range 2-12). Nine men experienced an adverse event requiring dose modification or premature cessation of chemotherapy. Pathologic staging in 9 patients showed T3a, 5 with T3b, and 1 with T2c disease; 8 had R1 disease and 2 demonstrated nodal involvement. Mean operative time, blood loss, and hospital stay were 189 minutes, 184 mL, and 1.5 days, respectively. At median follow-up of 32 months (range 15-45), 4 patients experienced biochemical recurrence. Conclusions: Neoadjuvant weekly ixabepilone had a good PSA response and no increased surgical morbidity; however, a higher dose is associated with significant persistent neuropathy. There were no complete pathologic responses, but biochemical recurrence rate is low. Further assessment of time to treatment failure will require continued, planned follow-up to evaluate the long-term potential clinical benefit of this study. Keywords: Ixabepilone, prostate cancer, neoadjuvant chemotherapy, taxanes, epothilone.Download Full Article |
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Abstract: In this study, we examined the in vitro effects of vemurafenib, a specific inhibitor of V600E mutated BRAF enzyme, on the response of cells overexpressing the ATP binding cassette (ABC) efflux transporters ABCG2, ABCB1, ABCC1 and ABCC10. Vemurafenib, at 5 µM and 20 µM, produced a significant concentration-dependent increase in the cytotoxicity of paclitaxel in cells overexpressing ABCB1 and ABCC10 and mitoxantrone in cells overexpressing ABCG2. Vemurafenib also significantly enhanced the accumulation of paclitaxel in cell lines overexpressing ABCB1 and ABCC10. Vemurafenib significantly increased the intracellular accumulation of mitoxantrone in cells overexpressing ABCG2. In contrast, vemurafenib did not significantly alter the sensitivity of ABCC1 overexpressing HEK/ABCC1 cells to vincristine. Finally, as determined by Western blotting, vemurafenib (20 µM) did not significantly alter the expression of the proteins for ABCG2, ABCC10 or ABCB1. Thus, vemurafenib most likely reverses multidrug resistance by altering the transport function of these aforementioned ABC transporters, as opposed to affecting the expression of ABC proteins. The docking analysis of vemurafenib with the ABCB1 homology model also suggested that vemurafenib binds to the ABCB1 and ABCG2 drug binding site. These findings suggest that combination of specific inhibitors like vemurafenib with chemotherapeutic drugs may be used to overcome multidrug resistance in cells that overexpress ABCB1, ABCC10 and/or ABCG2 transporters. Keywords: Vemurafenib, ABCC10, ABCG2, MDR.Download Full Article |