Purpose: Double-strand break repair via homologous recombination is essential in maintaining genetic integrity. RAD51 and XRCC3 are involved in the repair of DNA by this pathway, and polymorphisms have been identified in both the RAD51 (RAD51-G135C) and XRCC3 (XRCC3-Thr241Met) genes. The object of this study was to examine whether these polymorphisms may modulate susceptibility to the development of acute myeloid leukemia (AML), a disease that is characterized by genetic instability.Experimental Design: We studied the distribution of polymorphisms in RAD51 and XRCC3 in 216 cases of de novo AML, 51 cases of therapy-related AML (t-AML), and 186 control subjects using PCR followed by restriction enzyme digestion. The polymorphic deletion of the detoxification gene glutathione S-transferase M1 (GSTM1) was also examined by PCR.Results: The risk of the development of AML was found to be significantly increased when both variant RAD51-135C and XRCC3-241Met alleles are present [odds ratio (OR), 3.77; 95% confidence interval (CI), 1.39 -10.24], whereas the risk of t-AML development is even higher (OR, 8.11; 95% CI, 2.22-29.68), presumably because of the large genotoxic insult these patients receive after their exposure to radiotherapy or chemotherapy. If we further divide the AML group into patients in which the burden of DNA damage is increased, because of the deletion of the GSTM1 gene, the risk of development of AML is further increased (OR, 15.26; 95% CI, 1.83-127.27). Conclusions:These results strongly suggest that DNA double-strand breaks and their repair are important in the pathogenesis of both de novo and t-AML.
Learning Objectives Summarize trends of adjuvant treatment in gastric cancer. Describe the potential role of adjuvant chemotherapy versus radiation in gastric cancer.
Orphaned bears have been captive-reared and released back to the wild for more than 3 decades, often without a clear understanding of their fates because post-release monitoring is not a common practice. As a result, management agencies lack efficacy data on post-release success rates and are often reluctant to encourage increased use of this technique. We evaluated the potential management and conservation implications of releasing captive-reared bears by documenting post-release survival, causespecific mortality, human conflict activity, movements, and reproduction for 550 American black, brown and Asiatic black bears reared in 12 captive-rearing programs around the world. Survival rates in these programs ranged from 0.50 to 1.00 and were similar among the 3 species. The primary causes of mortality were sport hunting and road kills for American black bears, intra-specific predation and illegal kills for brown bears, and natural mortalities and illegal kills for Asiatic black bears. Although American and Asiatic black bears were involved in conflicts post-release, the majority of released bears (94%) were not documented in conflict situations. Movement patterns of captive-reared American black and brown bears showed no homing tendencies toward their rearing facility. Twenty captive-reared bears produced 21 litters. Our analyses reduce many of the uncertainties surrounding the fate of bears released as yearlings and provide evidence that releasing captive-reared bears is a defensible management alternative. Ó 2015 The Wildlife Society.
Several chromosomal abnormalities detected by conventional cytogenetic analysis have an adverse impact on the outcome in myeloma patients. A wide spectrum of abnormalities involving chromosomes 1, 13, 14, and 17 has been described. We analyzed the outcome of 83 patients with clonal cytogenetic abnormalities, who underwent high-dose therapy and autologous stem cell transplantation for multiple myeloma at our institution. Clonal abnormalities were detected at diagnosis by conventional cytogenetic analysis in 83 patients. Patients underwent a single autologous transplant between April 2000 and May 2005. Preparative regimen was high-dose melphalan alone (73), or a combination of topotecan, melphalan, and cyclophosphamide (TMC=10). The most commonly observed chromosomal abnormalities were deletion of chromosome 13 (32%), hyperdiploidy (21%), deletion of chromosome 1p (18%), and t (11; 14) in 7% patients. Median follow-up among surviving patients was 25.5 months. Median interval from diagnosis to autotransplant was 7.7 months (range: 2.5-52). Median progression-free survival (PFS) for the entire group was 19 months and the median overall survival (OS) was 52 months. On univariate analysis, both PFS and OS were significantly shorter in patients with deletion 1p (P=.001 and <.0001, respectively). Thirty-two patients whose cytogenetic abnormalities returned to normal prior to autotransplant had longer PFS and OS than patients with persistent abnormalities (P=.02 and .08, respectively). Deletion 1p is associated with a significantly shorter remission and survival in patients undergoing high-dose therapy and a single autologous transplant for myeloma.
Background Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. Objectives The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Methods One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 μg/μl). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. Results The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. Conclusion Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.
The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/ kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy. Avaliação dos efeitos quimiopreventivo e quimioterápico do extrato deArtemisia vulgaris contra carcinogênese hepatocelular induzida por dietilnitrosamina em camundongos Balb C Resumo O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 μl/mg) com extrato vegetal (AV: 150 mg/ kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 m...
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