TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of <it>tumor necrosis factor (TNF) -α </it>and its surface receptors, <it>TNFRSF1A </it>and <it>TNFRSF1B </it>have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of <it>TNFRSF1B </it>gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed.</p> <p>Methods</p> <p>Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor <it>TNFRSF1B </it>gene were determined by a TaqMan^®MGB probe-based polymerase chain reaction.</p> <p>Results</p> <p>The genotype of <it>TNFSR1B </it>A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but <it>TNFRSF1B </it>A1466G genotype was independent of these factors.</p> <p>Conclusions</p> <p>Genetic polymorphism of <it>TNFRSF1B </it>A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of <it>TNFRSF1B </it>A1466G genotype after chemoradiotherapy.</p

Effects of plasma concentrations of 5-fluorouracil on long-term survival after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>A substantial body of literature has accumulated during the past 20 years showing the plasma concentrations of 5-fluorouracil (5-FU) to correlate with clinical response and/or toxicity in colorectal cancer, and head and neck cancer, but little information is available concerning effects on long-term survival. Here, Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed up for 5 years after treatment with a definitive 5-FU/cisplatin (CDDP)-based chemoradiotherapy (CRT), and the association between prognosis and the plasma concentration of 5-FU was evaluated.</p> <p>Methods</p> <p>Forty-nine patients with ESCC, who were treated with a definitive 5-FU/CDDP-based CRT, were enrolled. A course consisted of the continuous infusion of 5-FU at 400 mg/m²/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m²/day on days 1 and 8, and the radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days 4, 11, 39 and 46.</p> <p>Results</p> <p>The overall 5-year survival rate was 42.9%. Age (P = 0.020), body weight (P = 0.019), and disease stage (P = 0.048) affected the survival, and the survival depended on the clinical response assessed at 1 month after the treatment (P = 0.001). Higher plasma concentrations of 5-FU resulted in a better clinical response (P = 0.043), and trended to prolong survival (P = 0.321).</p> <p>Conclusions</p> <p>The long-term survival after treatment with a definitive 5-FU/CDDP-based CRT possibly depends on the plasma concentrations of 5-FU, and further clinical studies with a larger number of cases are needed to clarify the relationship between them.</p

Replacement of cisplatin with nedaplatin in a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

Objective: The effects of replacing cisplatin (CDDP) with cis-diammineglycolatoplatinum (nedaplatin, NDP), a second-generation platinum complex, on the pharmacokinetics of 5-fluorouracil (5-FU) were investigated in Japanese patients with esophageal squamous cell carcinoma, who were treated with a definitive 5-FU/CDDP-based chemoradiotherapy

近畿圏内薬学部の2015, 2016年度における薬剤師国家試験合否状況に関する検討

A four-year course of pharmaceutical education that emphasized the importance of basic sciences was implemented in Japan through 2005; in 2006, the curriculum was reorganized and transformed into a six-year course to improve education in applied pharmaceutics and clinical practice. Information on the numbers of incoming students, promoted fifth-year students, straightly graduated students and students who straightly passed for the national examination for pharmacists in each 6-year course of university for pharmacists is now available from Ministry of Education, Culture, Science and Technology (MEXT) and each university\u27s individual website. This study collected data on 12 universities in the Kinki region. Based on these date, two indexes were calculated: the "postponed graduation index" and the "retention and dropout index". Statistical analysis of the two indexes, along with straight pass rate from the numbers of straightly graduated and incoming students, revealed that the retention and dropout index is inversely related to deviation value at university admission examinations and positivery correlated with straight pass rate, suggesting that students unfit for pharmaceutical education were admitted to universities with low deviation value at university admission examinations. Cluster analysis based on four factors (pass rate of new graduates, straight pass rate, retention and dropout index, and postponed graduation index) suggests five clusters, strongly dependent on deviation value at university admission examinations. These results indicate the significance of high marks at university admission

唾液中カフェイン薬物動態に薬物代謝酵素CYP1A2 遺伝子多型が及ぼす影響に関する研究

Though drugstore pharmacists can also be known as primary health care pharmacists, it cannot yet be said that they completely fill this role. We believe that it is crucial for pharmacists to consult reliably with patients. To develop this ability, it is necessary to select a familiar and relevant theme by considering various factors that are worth discussing in their own right through conducting simple verification experiments. Caffeine is found in many foods and drinks, as well as in over the counter cold remedies and analgesics. Moreover, it has been widely used around the world to probe the effectiveness of drug-metabolizing enzyme activity of medications for liver disease. We have built a simple and easy experiment system to evaluate the pharmacokinetics of caffeine in saliva, and we examined the relationship between the drug-metabolizing enzyme CYP1A2 genetic polymorphism and various related constitutional hereditary factors

In vitro and in vivo cytotoxicity of troglitazone in pancreatic cancer

Abstract Background Troglitazone (TGZ) is a peroxisome proliferator-activated receptor gamma (PPARγ) agonist that has been investigated as a potential chemopreventive and chemotherapeutic agent. However, the antitumor efficacy and mechanisms of TGZ in pancreatic cancer have not been extensively investigated. This study was performed to investigate the in vitro and in vivo effects of TGZ against pancreatic cancer cell lines, as well as its action mechanisms in terms of PPARγ dependency and the Akt and mitogen-activated protein kinase (MAPK) pathways. We also evaluated the effects of TGZ on cell invasion and migration. Methods MIA Paca2 and PANC-1 human pancreatic cancer cell lines were used. Cell viability and caspase-3 activity were detected using fluorescent reagents, and chromatin condensation was observed after staining the cells with Hoechst 33342. Protein expression levels were detected by western blot analysis. Invasion and migration assays were performed using 24-well chambers. The in vivo antitumor effects of TGZ were investigated in nude mice inoculated with MIA Paca2 cells. Mice were orally administered TGZ (200 mg/kg) every day for 5 weeks, and tumor volumes were measured bi-dimensionally. Results TGZ showed dose-dependent cytotoxicity against both cell lines, which was not attenuated by a PPARγ inhibitor. Further, TGZ induced chromatin condensation, elevated caspase-3 activity, and increased Bax/Bcl-2 relative expression in MIA Paca2 cells. TGZ also increased phosphorylation of Akt and MAPK (ERK/p38/JNK) in both cell lines, and a JNK inhibitor significantly increased the viability of MIA Paca2 cells. TGZ moderately inhibited cell migration. Tumor growth in the MIA Paca2 xenograft model was inhibited by TGZ administration, while mouse body weights in the treated group were not different from those of the vehicle administration group. Conclusion We demonstrated for the first time the in vivo antitumor effects of TGZ in pancreatic cancer without marked adverse effects. TGZ induced mitochondria-mediated apoptosis in MIA Paca2 cells, and its cytotoxic effects were PPARγ-independent and occurred via the JNK pathway. Our results indicate that TGZ is a potential approach for the treatment of pancreatic cancer and warrants further studies regarding its detailed mechanisms and clinical efficacy