Comparison of ramosetron and azasetron for prevention of acute and delayed cisplatin-induced emesis in lung cancer patients

We performed a retrospective study that compared the efficacy and safety of ramosetron with azasetron in a case of acute and delayed emesis induced by cisplatin (CDDP)-included chemotherapy in patients with lung cancer. The study subjects were 100 lung cancer patients treated with combination therapy of cisplatin, ifosfamide, irinotecan (CIC therapy). The ramosetron group and azasetron group received, respectively, ramosetron 0.3 mg or azasetron 10 mg intravenous injection, 30 minutes prior to CDDP. All patients received 32 mg of dexamethasone intravenously. Protection from emesis showed no significant difference between two treatment groups. However, the grade of nausea was significantly lower in the ramosetron group than in the azasetron group. Furthermore, chlorpromazine hydrochloride for use as a rescue medication was required by significantly fewer in the ramosetron group than in the azasetron group. Adverse effects were observed in 27 cases in the ramosetron group and 24 cases in the azasetron group. However, because the symptoms were all mild, we did not consider there was any safety problem. In conclusion, it was suggested that ramosetron is a clinically useful treatment for acute and delayed emesis induced by cisplatin-induced chemotherapy in patients with lung cancer.     

Primary extramedullary plasmacytoma of the small intestine. A case report and review of the literature

A case of primary extramedullary plasmacytoma of the small intestine in a 73-year-old Japanese woman was reported. The patient underwent local resection of the tumor, and showed no signs of local recurrence or dissemination of the disease after 28 months follow-up.The tumor cells had relatively large nuclei with distinct nucleoli and wide and slightly basophilic cytoplasm with a high N/C ratio which showed the morphology of atypical plasma cells. Immunohistochemical examination revealed that the tumor cells contained IgG gamma-type immunoglobulin in their cytoplasm but they did not contain IgA, IgM, IgD, and kappa-light chains. The tumor cells were also positive for CD79a and CD138 and negative for LCA, CD20 and CD45RO. These findings clearly indicated this case to be plasmacytoma.     

Reduced expression of p63 has prognostic implications for patients with esophageal squamous cell carcinoma

The p63 gene is a member of the p53 family that plays a role in cell differentiation, development and carcinogenesis. The relationship between p63 expression and the prognosis of esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examines the clinical impact of p63 in patients with ESCC. Resected specimens from 180 patients with ESCC were immunostained for p63 and p53. After establishing a cut-off value for p63 expression, we statistically examined its clinical impact and relationship to p53 expression. At a 50% cut-off value for p63 expression, the 5-year overall survival was significantly longer in p63-positive (46.4%) than -negative patients (11.1%, p=0.05). Among the 180 ESCC patients, 171 (95.0%) were p63 immunoreactive and only 9 (5.0%) were negative. The correlation between p63 status and clinicopathological parameters was not significant, although p63-negativity tended to correlate with distant metastasis (p=0.06) and clinical stage (p=0.08). Univariate analysis demonstrated significant correlations between patient survival and tumor diameter, depth of invasion, lymphatic invasion, vascular invasion, lymph node metastasis and distant metastasis. The survival of patients who did not express p63 and p53 was obviously unfavorable (p=0.03). Multivariate analysis revealed that only lymph node metastasis was a critical independent prognostic marker for overall survival (p=0.0015). Expression of p63 was not an independent prognostic factor for overall survival in this study (p=0.69). These data suggest that, although a reduced expression of p63 is infrequent, it has a prognostic impact upon patients with ESCC.     

Loss of imprinting in IGF2 in colorectal carcinoma assessed by microdissection

To ascertain the implications of loss of imprinting (LOI) of the insulin-like growth factor II gene (IGF2) for carcinogenesis, the precise frequency of LOI in colorectal carcinoma was examined using a laser capture microdissection method, and compared to the matched normal colorectal mucosa. LOI was examined by PCR-restriction fragment length polymorphism in combination with direct sequencing. The status was assigned as imprinting when PCR-RFLP showed only one band or sequence with a single peak, otherwise cases were classified as LOI. LOI was found in 13 of 24 informative cases of carcinoma (54%), which was higher than the ratios reported previously. LOI was also found in the normal colorectal mucosae in 14 cases (58%). The LOIs in carcinomas and in the normal mucosae were closely correlated: 10 of 13 LOI-positive carcinomas showed LOI in the matched normal mucosae. These results suggest that LOI of IGF2 in colorectal carcinoma and LOI in the background mucosa play important roles in carcinogenesis.     

Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet

We evaluated the effects of bezafibrate, a peroxisome proliferator-activated receptor (PPAR) pan-agonist, and GW501516, a PPARdelta agonist, on mice fed a methionine- and choline-deficient (MCD) diet, a model of non-alcholic steatohepatitis (NASH), to investigate (a) the efficacy of bezafibrate against non-alcholic steatohepatitis and (b) the relation between non-alcholic steatohepatitis and the functional role of PPARdelta. Bezafibrate (50 or 100 mg/kg/day) and GW501516 (10 mg/kg/day) were administered by gavage once a day for 5 weeks. Hepatic lipid contents, plasma triglyceride, high density lipoprotein (HDL)-cholesterol and alanine aminotransferase (ALT) concentrations were evaluated, as were histopathological changes in the liver and hepatic mRNA expression levels. Bezafibrate and GW501516 inhibited the MCD-diet-induced elevations of hepatic triglyceride and thiobarbituric acid-reactants contents and the histopathological increases in fatty droplets within hepatocytes, liver inflammation and number of activated hepatic stellate cells. In this model, bezafibrate and GW501516 increased the levels of hepatic mRNAs associated with fatty acid beta-oxidation [acyl-CoA oxidase (ACO), carnitine palmitoyltransferase-1 (CPT-1), liver-fatty acid binding protein (L-FABP) and peroxisomal ketothiolase], and reduced the levels of those associated with inflammatory cytokines or chemokine [transforming growth factor (TGF)-beta1, interleukin (IL)-6, IL-1beta, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF) alpha and nuclear factor (NF)-kappaB1]. In addition, bezafibrate characteristically reduced the elevation in the level of plasma ALT, but enhanced that in plasma adiponectin and increased the mRNA expression levels of its receptors (adiponectin receptors 1 and 2). These results suggest that (a) bezafibrate (especially) and GW501516 might improve hepatic steatosis via an improvement in fatty acid beta-oxidation and a direct prevention of inflammation, (b) treatment with a PPARdelta agonist might improve non-alcholic steatohepatitis, (c) bezafibrate may improve non-alcholic steatohepatitis via activation not only of PPARalpha but also of PPARdelta, because bezafibrate is a PPAR pan-agonist.     

Anti-inflammatory activity of non-nucleoside adenosine deaminase inhibitor FR234938

Adenosine has anti-inflammatory activity. Adenosine deaminase (EC 3.5.4.4) metabolizes extracellular adenosine, resulting in an exacerbation of inflammation. Consequently, it was hypothesized that adenosine deaminase inhibitors produce anti-inflammatory activity by increasing extracellular adenosine concentration. This group recently developed a non-nucleoside adenosine deaminase inhibitor, FR234938, by using rational structure-based drug design. FR234938 inhibits recombinant human adenosine deaminase enzyme competitively. FR234938 inhibits interleukin (IL)-6-dependent immunoglobulin (Ig) M production by SKW6.4 cells, in the presence of adenosine. Inhibitory effect of FR234938/adenosine combination is blocked by an A2a adenosine receptor antagonist. FR234938 also inhibits anti-type II collagen delayed type hypersensitivity (DTH) in a dose-dependent manner, both in the presence and absence of recombinant human adenosine deaminase. Moreover, FR234938 inhibits tumor necrosis factor (TNF)-alpha and IL-10 production in a lipopolysaccharide (LPS)-induced cytokine production model in mice. These results indicate that FR234938 has potential anti-inflammatory activity. Non-nucleoside adenosine deaminase inhibitor FR234938 has good potential as a new type of anti-rheumatic and anti-inflammatory drug, by modulating host-defense concentrations of adenosine.     

SPF-32629 A and B, novel human chymase inhibitors produced by Penicillium sp

Two new human chymase inhibitors, SPF-32629A and B, were isolated from the cultured broth of Penicillium sp. SPF-32629. These structures were determined by spectroscopic methods and identified as new pyridone compounds. SPF-32629B was the carboxylated derivative of SPF-32629A. SPF-32629A and B specifically inhibited human chymase among four serine proteases tested with the IC50 of 0.25 and 0.42 microg/ml, respectively.     

A new antifungal macrolide, eushearilide, isolated from Eupenicillium shearii

In screening for antifungal substances, a new macrolide, eushearilide (1), was isolated from Eupenicillium shearii IFM54447. The structure of 1 was established to be 24-membered macrolide having a non-conjugated diene and a choline phosphate ester moetiy on the basis of detailed investigation of NMR, UV, IR and MS spectral data. Compound 1 showed antifungal activity against various fungi and yeasts, including human pathogens Aspergillus fumigatus, Trichophyton spp. and Candida spp.