An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker.

We reported previously that an angiogenesis inhibitor, E7820, inhibits in vitro tube formation of human umbilical vein endothelial cell through the suppression of integrin alpha2 expression. Here we describe the antiangiogenic and antitumor effects of E7820 in mice and discuss the feasibility of using platelet integrin alpha2 expression on platelets as a biological marker of the efficacy of E7820. Oral administration of E7820 significantly inhibited basic fibroblast growth factor-induced angiogenesis in Matrigel implants and human colon WiDr tumor-induced angiogenesis in a dorsal air sac model. Twice-daily treatment with E7820 clearly inhibited the s.c. tumor growth of seven tumor cell lines derived from human colon, breast, pancreas, and kidney, and completely suppressed the growth of human pancreatic KP-1 and human colon LoVo cell lines. Moreover, E7820 significantly inhibited the growth of KP-1 and human colon tumor Colo320DM cells orthotopically implanted in the pancreas and cecum, respectively. The efficacy of E7820 was comparable in the s.c. and orthotopic transplantation models. Immunohistochemical analyses using anti-CD31 antibody showed that E7820 significantly reduced microvessel density in orthotopically implanted KP-1 tumor. E7820 reduced integrin alpha2 expression on a megakaryocytic cell line, Dami cells, induced by phorbol 12-myristate 13-acetate treatment. It also decreased the expression level of integrin alpha2 on platelets withdrawn from mice bearing s.c. KP-1 tumor at a dosage close to that affording antitumor activity. These data demonstrate that E7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E7820.     

Point mutations of ornithine decarboxylase gene are an infrequent event in colorectal cancer but a missense mutation was found in a replication error positive patient with hMSH2 germline mutation

BACKGROUND: Ornithine decarboxylase (ODC; EC 4.1.1.17) is the first rate-limiting enzyme in the biosynthesis of polyamines. ODC protein has a characteristic amino acid sequence, the PEST sequence, which is related to the enzyme's rapid degradation. ODC cDNA prepared from human hepatoma tissues has been reported to show nonsense or missense mutations. METHODS: We examined somatic mutations of ODC cDNA by RT-PCR-SSCP analysis and mRNA expressions by RT-PCR in 50 colorectal cancer tissues to investigate the involvement of ODC gene alterations in colorectal cancers. RESULTS: Increased expression of the ODC gene was observed in 36 cases (86%) out of the 42 examined by RT-PCR. In one case, a missense mutation was found in the cancer tissue but not in normal mucosa. The missense mutation from Asp to Asn at codon 424, in the PEST region, possibly stabilizes the ODC protein. In colorectal cancer, replication error and a germline mutation in hMSH2 gene were observed. CONCLUSIONS: The missense mutation at codon 424 is speculated to be a cause of stabilization and a passenger mutation owing to the mutator phenotype. Since only one of 50 colorectal cancers exhibited a missense mutation of the ODC gene, mutations in ODC gene are not frequent in colorectal cancer. The increased expression of the ODC gene was noted in 86% of colorectal cancer tissues by RT-PCR, however, it was not due to point mutations in ODC coding exons.      

Entire septal patch technique for postinfarction ventricular septal rupture

Postinfarction ventricular septal rupture is still a surgically challenging situation with high operative mortality. We report a case of ventricular septal rupture in a 75-year-old woman successfully treated with our newly devised technique, in which a pliable large septal path is fixed with transmural sutures placed in posterior left ventricular free wall and anterior ventriculotomy closing sutures, thus covering the septal wall almost entirely. Our method may simplify the operation and reduce the risk of residual leakage.     

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.     

Effect of plaunotol on bacterial translocation in the rat small intestine

BACKGROUND AND AIMS: Bacterial translocation is precipitated by an increase in bacteria or endotoxin, depression of the membrane barrier, and an increase in mucosal permeability. Plaunotol is a mucosal protective agent, and observed to have a strong suppressive effect on superoxide production. In this study, the effect of plaunotol on bacterial translocation was examined using the model of ischemia and reperfusion. METHOD: Male Sprague Dawley rats were used to create the following model for evaluation of bacterial translocation: (i) the control group; (ii) the preventive dose group (plaunotol 30 mg/kg/day one week before surgery); (iii) the therapeutic dose group (plaunotol 30 mg/kg/day one week after surgery); and (iv) the full dose group (plaunotol 30 mg/kg/day one week before surgery and one week after surgery). Bacterial translocation was assessed as the blood concentration of the endotoxin. RESULTS: In the control group, the endotoxin increased significantly 3 days postsurgery (13.7+/-5.6 pg/ml) compared with before surgery (1.1+/-0.1 pg/ml). In the preventive and full-dose groups, the erndotoxin decreased significantly 3 days postsurgery (4.4+/-2.8 pg/ml, 5.7+/-2.7 pg/ml, respectively) compared with that of the control group. CONCLUSION: Plaunotol in the preventive and full-dose groups decreased the endotoxin. This suggests that plaunotol is one of the protectors for bacterial translocation.     

A case of hemorrhagic cyst of the pancreas resembling the cystic endometriosis

A 47-year-old Japanese woman with a history of epigastric pain and a recent episode of acute pancreatitis (back pain, nausea, and vomiting) and anemia was found to have a pancreatic cyst of the tail on CT-scan and ultrasonography. Especially, ultrasonography revealed the papillary solid lesion in the cyst. With the tentative diagnosis of a cystic neoplasm, distal pancreatectomy was performed. Histological examination of sections showed massive hemorrhage, surrounded fibrous connective tissue, and numerous macrophages with hemosiderin deposits; these histological findings resembled cystic endometriosis. The clinicopathological features and pathogenesis of the pancreatic endometrial cyst are discussed.     

Simultaneous removal of organic matter and nitrogen compounds by partitioned aeration in a 226 L-scale microbial fuel cell

Although microbial fuel cells (MFCs) have been widely studied as wastewater treatment technologies that convert organic matter to electricity, there are few reports of large-scale MFCs that treat both organic matter and nitrogen compounds. In this study, a 226 L reactor equipped with 27 MFC units was partially aerated at 10% of its total volume. The MFC unit consists of a cylindrical air core covered with a carbon-based air cathode, an anion exchange membrane, and a graphite non-woven fabric anode. The air-cathode MFC with 13 L min⁻¹ aeration rate produced a current density of 0.0012–0.15 A m⁻² with 40 to >93% biological oxygen demand (BOD) removal to have an effluent BOD of <5–36 mg L⁻¹ at a hydraulic retention time (HRT) of 12–47 h. Meanwhile, 55 ± 17% of the total nitrogen (TN) was removed, resulting in 9.7 ± 3.8 mg L⁻¹ TN in the effluent, although the TN removal was limited at ≥20 °C. The mono-exponential regression for BOD and TN (≥20 °C) estimated that an HRT of 21 h could meet the Japanese effluent quality standards of BOD and TN. Calculation of the total energy recovered via current generation and energy consumed by aeration suggested an energy consumption of 0.22 kW h m⁻³. Decreasing the aeration rate and HRT in the reactor would further reduce energy consumption and increase energy production.

Partial aeration simultaneously removed organic matters and nitrogen compounds in a 226 L reactor equipped with 27 microbial fuel cells.     

Medical visits of childhood cancer survivors in Japan: A cross‐sectional survey

Background: Although more children with cancer continue to be cured, these survivors experience various late effects. Details of the medical visit behaviors of childhood cancer survivors (CCS) in adulthood remain to be elucidated. Methods: In order to examine medical visits in the past and future of CCS, we performed a cross‐sectional survey with self‐rating questionnaires on medical visits of CCS compared with control groups (their siblings and the general population). Results: Questionnaires were completed by 185 CCS, 72 of their siblings and 1000 subjects from the general population and the results were analyzed. Mean ages at this survey and the duration after therapy completions of CCS were 23 and 12 years, respectively. We found that the previous treatment hospitals (where CCS were treated for their cancer) were the most commonly visited medical facilities for the CCS group (74% for female patients and 64% for male patients) and more than half of the CCS preferred to continue visiting the previous treatment hospital with enough satisfaction in Japan. The multivariate analysis showed that female sex and relapse were significantly associated with the past visits to the previous treatment hospital and that the CCS with brain tumors or bone/soft tissue sarcomas and CCS with any late effects tended to continue the relationships with the hospital. In addition female sex was also significantly associated with desired future visits to the previous treatment hospital. On the other hand, the married CCS tended to be disinclined to visit the hospital it in the future. Conclusions: In order to optimize risk‐based care and promote health for CCS after adulthood, we should discuss the medical transition with CCS and their parents.