Distribution and haplotype analysis of all the non-synonymous and autoimmunity-related single nucleotide polymorphisms in the human deoxyribonuclease II gene using worldwide populations.

We have focused on the 14 SNPs including all the non-synonymous and autoimmunity-related ones in the DNase II gene (DNASE2). The distribution of each allele and haplotype in these SNPs was examined in eight Asian, three African, three Mexican and two Caucasian populations using the newly developed PCR-RFLP methods. Eight SNPs among nine non-synonymous ones were monomorphic, indicating that a specific allele generating the intact activity-harboring DNase II in these SNPs is well conserved in worldwide populations.

Genetic and expression analysis of SNPs in the human deoxyribonuclease II: SNPs in the promoter region reduce its in vivo activity through decreased promoter activity.

Five SNPs in the human DNase II gene have been reported to be associated with rheumatoid arthritis (RA). Genotype and haplotype analysis of 14 SNPs, nine SNPs of which reported in the NCBI dbSNP database in addition to these five SNPs, was performed in healthy subjects. The enzymatic activities of the amino acid substituted DNase II corresponding to each SNP and serum DNase II in healthy Japanese, and promoter activities derived from each haplotype of the RA-related SNPs were measured.

Determination of ABO genotypes by real-time PCR using allele-specific primers.

ABO grouping of biological specimens is informative for identifying victims and narrowing down suspects. In Japan and elsewhere, ABO grouping as well as DNA profiling plays an essential role in crime investigations. In the present study, we developed a new method for ABO genotyping using allele-specific primers and real-time PCR.

Simultaneous determination of seven informative Y chromosome SNPs to differentiate East Asian, European, and African populations.

Identification of the population origin of an individual is very useful for crime investigators who need to narrow down a suspect based on specimens left at a crime scene. Single nucleotide polymorphisms of the Y chromosome (Y-SNPs) are a class of markers of interest to forensic investigators because many of the markers indicate regional specificity, thus providing useful information about the geographic origin of a subject. We selected seven informative Y-SNPs (M168, M130, JST021355, M96, P126, P196, and P234) to differentiate the three major population groups (East Asian, European, and African) and used them to develop forensic application.

High incidence of synchronous or metachronous breast cancer in patients with malignant and benign thyroid tumor or tumor-like disorders.

Background: Although many reports indicated an association between thyroid diseases and breast cancer, such an association still remains controversial. The present study was aimed to clarify the association of thyroid diseases with the breast cancer incidence. In the patients with benign and malignant thyroid tumor or tumor-like disorders, the incidence of other malignancies was surveyed, and the frequency of thyroid cancer in patients with breast cancer was also surveyed.

Hyperbilirubinemia-related behavioral and neuropathological changes in rats: a possible schizophrenia animal model.

Background: Patients with schizophrenia show a significantly higher frequency of hyperbilirubinemia than patients suffering from other psychiatric disorders and the general healthy population. We examined the hyperbilirubinemia on behavioral and neuropathological changes in rats as a possible animal model of schizophrenia.

Methods: Gunn rats with severe hyperbilirubinemia (j/j), Gunn rats without severe hyperbilirubinemia (+/j), and Wistar rats were examined by open-field, social interaction, and prepulse inhibition tests.

Expression of orotate phosphoribosyl transferase in human pancreatic cancer: implication for the efficacy of uracil and tegafur-based adjuvant chemotherapy.

The enzyme orotate phosphoribosyl transferase (OPRT) is involved in the metabolism of the anticancer drug 5-fluorouracil (5-FU), and is a key enzyme for conversion of 5-FU to its active form in tumor tissue. Little is known regarding the significance of OPRT in human pancreatic cancer. The present study was designed to assess the association between the activity of OPRT in the tumor, and the clinicopathological status and prognosis of human resectable pancreatic cancer, especially regarding its relevance to the efficacy of adjuvant chemotherapy with uracil and tegafur (UFT), cyclophosphamide (CPA) and/or gemcitabine (GEM).

Cyclophosphamide augments the anti-tumor efficacy of uracil and tegafur by inhibiting dihydropyrimidine dehydrogenase.

The present study assesses the effects of neo-adjuvant chemotherapy (NAC) with uracil and tegafur (UFT) alone vs UFT plus cyclophosphamide (CPA), on the activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in breast cancer tissues. Breast cancer patients were randomly assigned to 3 groups; the control (no-treatment) group (n=13), the UFT (5-8 mg/kg/day) alone group (n=10) and the UFT plus CPA (1 mg/kg/one day interval) (UC) group (n=9), and they received NAC for 2-4 weeks. A total of 32 invasive ductal breast carcinomas were used to assay for TS and DPD activity.

Immunohistochemical expression of HER-1 and HER-2 in extrahepatic biliary carcinoma.

The clinicopathological significance of HER-1- and HER-2-overexpressions (OE) (HercepTest score 2+ or 3+) in biliary cancer and their relationship to the efficacy of adjuvant chemotherapy (ACT) were assessed. In 72 biliary cancer (28 gallbladder and 44 bile duct cancer), HER-1 and HER-2 were stained immunohistochemically in formalin-fixed, paraffin-embedded specimens. The ACT included uracil and tegafur (UFT)-based chemotherapies.

Immunohistochemical expression of receptor-tyrosine kinase c-kit protein and TGF-beta1 in invasive ductal carcinoma of the pancreas.

Background: The receptor tyrosine kinase c-kit is known to play an important role in the progression of gastrointestinal stromal tumors, but its biological significance in other solid malignancies is unclear. Recent publications have suggested a regulatory role for TGF-beta1 in c-kit-mediated cell growth. The present study assessed the clinicopathological significance of c-kit protein (KIT) and TGF-beta1 expression in resectable invasive ductal carcinomas (IDCs) of the pancreas.

The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome.

Background: The loss of expression of Dpc4 protein (pDpc4) has been demonstrated in about half of invasive ductal carcinoma (IDC) of the pancreas, but the expression of DPC4-mRNA remains to be evaluated. The present study assessed the comparative expression of pDpc4 and DPC4-mRNA in pancreatic IDC and their implication for patient outcome.

Materials And Methods: In the freshly separated specimens of 21 IDCs and the paraffin-embedded specimens of 88 resectable IDCs, the expression of mRNA was assessed by in situ hybridization and the expression of pDpc4 was assessed by immunohistochemistry.

Implication of HER-2/neu overexpression for the efficacy of oral fluoropyrimidine-based adjuvant chemotherapy in the patients with estrogen receptor negative breast cancer after surgery.

Background: The implications of HER-2/neu overexpression for the efficacy of adjuvant chemotherapy (ACT) and endocrine therapy (AET) have been controversial. The present study retrospectively assessed the effects of HER-2/neu overexpression on the efficacy of oral fluoropyrimidine-based ACT and AET after breast cancer surgery.

Patients And Methods: The expression of HER-2/neu protein and estrogen receptor (ER) in 217 primary breast cancers was assessed immunohistochemically using the HercepTest and an anti-ER monoclonal antibody.

Immunohistochemical expression of receptor-tyrosine kinase c-kit protein in invasive ductal carcinoma of the pancreas.

The expression of receptor tyrosine kinase c-kit and its biologic significance in pancreatic cancer are unclear. We studied the expression of c-kit protein (c-KIT) in resectable invasive ductal carcinomas (IDCs) of the pancreas, in order to assess whether a selective c-kit inhibitor, STI571 (Glivec), may be applied for the treatment of pancreatic IDCs. This study included 72 pancreatic IDC patients who received a pancreatectomy between 1982 and 2002.

p53 alteration is not an independent prognostic indicator, but affects the efficacy of adjuvant chemotherapy in human pancreatic cancer.

Background And Objectives: Mutations in the p53 gene are found in more than 50% of human cancers and are observed in 60-80% of pancreatic cancers. The clinicopathologic implications of p53 abnormalities and their effects on the efficacy of the adjuvant chemotherapy for pancreatic cancer remain controversial.

Methods: We investigated the p53 status in core exon-4 to -9 (codon 33-331) by direct DNA sequencing in a series of 72 pancreatic cancers and analyzed the effects of p53 abnormalities on the patients' survival and the efficacy of adjuvant chemotherapy.

A fractal dimension analysis: a new method for evaluating the response of anticancer therapy.

Background: The therapeutic effects of various anticancer therapies on malignant tumors are evaluated as objective response (OR) by comparing the tumor size before and after the therapy However, it is difficult to evaluate the OR because malignant tumors frequently have very irregular or stellate shapes. In the present study we investigated a new method for evaluating the response of esophageal cancer to radio-chemotherapy using the fractal dimension (FD).

Patients And Methods: The changes in tumor size or shape during therapy were recorded in 6 patients with esophageal cancer by esophageal fluoroscopy.