MEK inhibitor enhances the inhibitory effect of imatinib on pancreatic cancer cell growth.

Imatinib mesylate (imatinib) inhibits the c-Kit-dependent tyrosine kinase activities and highly effective in the treatment of CML and GIST patients. Although pancreatic cancer is reported to express c-Kit, imatinib does not effectively inhibit pancreatic cancer cell growth at physiological concentrations. Therefore, we investigated the mechanism of resistance of pancreatic cancer to imatinib treatment.

Appearances and chronological changes of mummichog Fundulus heteroclitus FSH cells and LH cells during ontogeny, sexual differentiation, and gonadal development.

To examine relationships between gonadal stages and the initial appearance and subsequent development of gonadotrophs, hatched larvae of the mummichog Fundulus heteroclitus were reared until first maturity under suitable conditions for maturation (20 degrees C-16L). Evident FSH cells generally appeared 1-2 weeks after hatching (wah), around or slightly before the morphological sex differentiation which occurred at 2 wah. During this period, 3beta-hydroxysteroid dehydrogenase positive cells also appeared in the gonads.

Hematopoietic stem cell transplantation for acute promyelocytic leukemia in second or third complete remission: a retrospective analysis in the Nagoya Blood and Marrow Transplantation Group.

Acute promyelocytic leukemia (APL) is the most curable subtype of acute myeloid leukemia. Second complete remission (CR2) can be easily achieved with several therapeutic options even after relapse. However, the optimal strategy to treat APL in CR2 is still controversial.

Identification and characterization of the first large deletion of the MYH9 gene associated with MYH9 disorders.

MYH9 disorders are autosomal dominant macrothrombocytopenias with leukocyte inclusion bodies. Single point mutations in the protein-coding sequence of the MYH9 gene are the most common cause. So far no large gene deletion/insertion and splicing defects have been reported.

Genome-wide network of regulatory genes for construction of a chordate embryo.

Animal development is controlled by gene regulation networks that are composed of sequence-specific transcription factors (TF) and cell signaling molecules (ST). Although housekeeping genes have been reported to show clustering in the animal genomes, whether the genes comprising a given regulatory network are physically clustered on a chromosome is uncertain. We examined this question in the present study.

Trend of drug-resistant HIV type 1 emergence among therapy-naive patients in Nagoya, Japan: an 8-year surveillance from 1999 to 2006.

We studied the emergence of drug-resistant human immunodeficiency virus type 1 (HIV-1) with major amino acid mutations in 402 therapy-naive patients at Nagoya Medical Center, Japan, between 1999 and 2006. The mean prevalence of drug-resistant HIV-1 was 6.7% (range, 2.

Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Delta-Prostaglandin J(2).

15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-gamma ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ(2) can suppress interleukin (IL)-1beta-induced prostaglandin E(2) (PGE(2)) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE(2) synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis.

Differential expression of wild-type and mutant NMMHC-IIA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders.

MYH9 disorders such as May-Hegglin anomaly are characterized by macrothrombocytopenia and cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, the gene for nonmuscle myosin heavy chain-IIA (NMMHC-IIA). We examined the expression of mutant NMMHC-IIA polypeptide in peripheral blood cells from patients with MYH9 5770delG and 5818delG mutations. A specific antibody to mutant NMMHC-IIA (NT629) was raised against the abnormal carboxyl-terminal residues generated by 5818delG.

Comparison of standard and hand-assisted laparoscopic radical nephrectomy for renal cell carcinoma.

A laparoscopic radical nephrectomy (LRN) for renal cancer can be performed using two methods, hand-assisted laparoscopic surgery (HALS) and standard laparoscopic surgery (SLS). This institute initially used HALS to perform all radical nephrectomy, but gradually shifted to SLS. This study compared the two methods of radical nephrectomy: HALS vs.

The cysteine-cluster motif of c-Src: its role for the heavy metal-mediated activation of kinase.

We have previously reported that c-Src is activated by mercuric chloride (HgCl(2)). We investigated the mechanism of this activation and found that in vitro activation of c-Src by HgCl(2) did not require tyrosine residues at 416 and 527. Both SH2 and SH3 domains of c-Src were dispensable for the activation by HgCl(2).

Clinical characteristics of chronic graft-versus-host disease following umbilical cord blood transplantation for adults.

Chronic GVHD is a significant complication following allogeneic hematopoietic stem cell transplantation; however, the clinical characteristics of chronic GVHD following cord blood transplantation (CBT) in adults have not been well described. Between March 2001 and November 2005, a total of 77 patients underwent CBT at eight transplantation centers of the Nagoya Blood and Marrow Transplantation Group. Of 77 patients, 29 survived without graft failure or progression of underlying diseases for at least 100 days after transplantation.

A case of lupus nephritis improved after appropriately adjusting the dosage of mizoribine.

A 29-year-old male presenting nephrotic syndrome and facial skin erythema was admitted to our hospital in September of 2000. We diagnosed him as having systemic lupus erythematosus (SLE) accompanied by lupus nephritis (WHO class V). The disease activity had decreased after treatment with methylprednisolone (m-PSL) pulse therapy, which was followed by oral PSL.

Lifestyle risk factors for intrahepatic stone: findings from a case-control study in an endemic area, Taiwan.

Background And Aim: To examine associations between lifestyle risk factors and intrahepatic stone (IHS), we conducted a case-control study in Taiwan, which has the highest incidence of IHS in the world.

Methods: Study subjects were 151 patients newly diagnosed with IHS at Chang Gung Memorial Hospital between January 1999 and December 2001. Two control subjects per case were selected randomly from patients who underwent minor surgery at the same hospital and from family members or neighbors of the hospital staff.

Nek2 as an effective target for inhibition of tumorigenic growth and peritoneal dissemination of cholangiocarcinoma.

We investigated the role of Nek2, a member of the serine/threonine kinase family, Nek, in the tumorigenic growth of cholangiocarcinoma cells. Expression of Nek2 is elevated in cholangiocarcinoma in a tumor-specific manner as compared with that of normal fibroblast cells. Expression of exogenous Nek2 did not perturb the growth of cholangiocarcinoma cells, whereas suppression of the Nek2 expression with siRNA resulted in the inhibition of cell proliferation and induced cell death.

Notable effect of an electron-withdrawing group at C3 on the selective formation of alkylidenecyclobutanes in the thermal denitrogenation of 4-spirocyclopropane-1-pyrazolines. Nonstatistical dynamics effects in the denitrogenation reactions.

A detailed study of the thermal denitrogenation of 3-carbomethoxy-substituted 4-spirocyclopropane-1-pyrazolines 6 was conducted. Alkylidenecyclobutane derivatives 7 were selectively formed in a stereospecific manner. Unrestricted density functional calculations for a 1-pyrazoline 10a indicated that the concerted cleavage of two C-N bonds is the energetically favored process for the denitrogenation reaction to give the 2-spirocyclopropyl 1,3-diyl, followed by a conrotatory ring-closure process, which was calculated to be the energy minimum pathway, to afford a spiropentane derivative.

Successful efavirenz dose reduction in HIV type 1-infected individuals with cytochrome P450 2B6 *6 and *26.

Background: Efavirenz (EFV) is metabolized primarily by cytochrome P450 2B6 (CYP2B6), and high plasma concentrations of the drug are associated with a G-->T polymorphism at position 516 (516G-->T) of CYP2B6 and frequent central nervous system (CNS)-related side effects. Here, we tested the feasibility of genotype-based dose reduction of EFV.

Methods: CYP2B6 genotypes were determined in 456 human immunodeficiency virus type 1 (HIV-1)-infected patients who were receiving EFV treatment or were scheduled to receive EFV-containing treatment.

The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation.

Background: Nonalcoholic fatty liver disease (NAFLD) is closely associated with the metabolic syndrome.

Aim: We evaluated the association among the metabolic syndrome, visceral fat accumulation, and the severity of fatty liver with a new scoring system of ultrasonographic findings in apparently healthy Japanese adults.

Methods: Subjects consisted of 94 patients who received liver biopsy and 4,826 participants who were selected from the general population.

No observable correlation between central nervous system side effects and EFV plasma concentrations in Japanese HIV type 1-infected patients treated with EFV containing HAART.

The present study assessed the relationship between central nervous system (CNS) side effects and plasma concentrations of efavirenz (EFV) in Japanese HIV-1-infected patients. Subjects consisted of 69 HIV-1-infected patients (57 therapy-naive and 12 therapy-experienced patients) being treated using EFV in combination with other antiretroviral agents at the outpatient HIV clinic. Successful virological treatment was achieved in 61 patients.

Prognostic significance of insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 expression in breast cancer.

Background: Expression of estrogen-regulated genes has been considered as potential predictive markers for endocrine therapy. We focused on two insulin-like growth factor binding proteins (IGFBPs): IGFBP-4, which is an early-responsive estrogen-induced gene, and IGFBP-5, which is an estrogen-repressed gene. Investigation of IGFBP-4 and IGFBP-5 expression would provide important information for predicting prognosis and endocrine responsiveness.

SIRPalpha1 and SIRPalpha2: their role as tumor suppressors in breast carcinoma cells.

We have previously reported that expression of SIRPalpha1/SHPS-1 was strongly suppressed in v-Src-transformed cells and its forced expression resulted in the suppression of anchorage-independent growth of the cells [K. Machida, S. Matsuda, K.

The mRNA expression of fatty acid amide hydrolase in human whole blood correlates with sepsis.

An excessive accumulation of anandamide (N-archidonoylethanolamine, AEA) is associated with septic shock. Results of previous studies have suggested that mRNA coding for the AEA degrading enzyme fatty acid amide hydrolase (FAAH), which converts AEA into arachidonic acid and ethanolamine, might be down-regulated in septic shock. We used real-time reverse transcription PCR assays to measure relative FAAH mRNA concentrations in the whole blood of 30 healthy donors and eight sepsis patients to ascertain whether such down-regulation takes place.

DBC2 resistance is achieved by enhancing 26S proteasome-mediated protein degradation.

Tumor suppressor gene DBC2 stops growth of tumor cells through regulation of CCND1. Interference of CCND1 down-regulation prevented growth arrest caused by DBC2 [T. Yoshihara, D.

Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients.

Introduction: Single-nucleotide polymorphisms (SNPs) in codon 72 of the TP53 (also known as p53) gene (rs1042522) and in the promoter region of the MDM2 gene (SNP309; rs2279744) have been suggested to play roles in many cancers. We investigated whether these SNPs were associated with patient outcome and the effect of adjuvant systemic therapy.

Methods: The genotypes of TP53 codon 72 and MDM2 SNP309 were defined among 557 primary Japanese breast cancer patients (median follow-up, 61.

Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function.

The expression of tumor suppressor gene DBC2 causes certain breast cancer cells to stop growing [M. Hamaguchi, J.L.