Japanese Journal of Cancer Research : Gann

cDNA microarray-based gene expression analysis has been successfully employed to explore the action mechanism and to validate the targets of several drugs. In the present study, we evaluated anti-angiogenic activity of demethoxycurcumin (DC), a structural analog of curcumin, isolated from Curcuma aromatica, and investigated the effect of DC on genetic reprogramming in cultured human umbilical vein endothelial cells (HUVECs) using cDNA microarray analysis. Of 1024 human cancer-focused genes arrayed, 187 genes were up-regulated and 72 genes were down-regulated at least 2-fold by DC...

Human head and neck squamous cell carcinoma cells transfected with mutant p53 (SAS/mp53) or with neo vector as a control (SAS/neo) were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. Tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. After administration of sodium borocaptate-10B (BSH) or p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutron beams. The tumors not treated with 10B-compound were irradiated with neutron beams or gamma-rays...

Anaplastic thyroid carcinoma is one of the most aggressive human malignancies. Outcomes of intensive multimodal therapy have been far from satisfactory. Furthermore, p53 gene dysfunction, often found in this type of cancer, is known to impair the efficacy of the therapeutic agents. Specific ligands for peroxisome proliferator activated receptor gamma (PPAR-gamma) induce growth suppression in some tumor cells. In this study, we investigated the role of PPAR-gamma in anaplastic thyroid cancer cell lines (OCUT-1, ACT-1)...

Recent studies have shown that the antiestrogen tamoxifen (TAM) can be used in the treatment of malignant neoplasms other than breast cancer. In the present study, we investigated the expression of estrogen receptor (ER) in six malignant rhabdoid tumor (MRT) cell lines. Alterations in MRT cell growth in response to estrogen or antiestrogens (4-hydroxytamoxifen (4-OHT), TAM, and ICI 182 780) were also investigated. RT-PCR and western blotting showed that ER-alpha was expressed in three of the six MRT cell lines...

We used real-time reverse-transcription polymerase chain reaction (RT-PCR) to assay expression of the mRNA of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in gastric cancer tissue with the objective of establishing a system to measure TS and DPD in ultra-low-volume samples. Nude mouse xenografts of 5 human gastric cancer cell lines and 85 clinical samples were used as the specimens in this study. Sensitivity to 5-fluorouracil (5-FU) was determined on the basis of the relative tumor proliferation rate in mice and the results of ATP assay using serum-free cultures of the clinical samples...

We have sought to clarify the potential activity of the S-phase-specific antileukemic agent 1-beta-D-arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, in quiescent cells that are substantially non-sensitive to nucleoside analogues. It was hypothesized that the combination of ara-C with DNA damaging agents that initiate DNA repair will expand ara-C cytotoxicity to non-cycling cells. The repair kinetics, which included incision of damaged DNA, gap-filling by DNA synthesis and rejoining by ligation, were evaluated using the single cell gel electrophoresis (Comet) assay and the thymidine incorporation assay...

We have previously demonstrated that costunolide, a biologically active compound that was isolated from the stem bark of Magnolia sieboldii, induced apoptosis in human cancer cells. In the present study, we investigated the underlying mechanisms and suggest that costunolide induces apoptosis in human promonocytic leukemia U937 cells by depleting the intracellular thiols. Costunolide treatment rapidly depleted the intracellular reduced glutathione (GSH) and protein thiols, and this preceded the occurrence of apoptosis...

Activated Akt/protein kinase B transmits oncogenic signals leading to inhibition of apoptosis, cellular proliferation, and tolerance to hypoxia. Presently, mutational inactivation of PTEN and activation of Ras are considered to be the major causes of Akt activation. Here we report differential mechanisms of constitutive Akt activation in 4 human pancreatic cancer cell lines (KMP-3, KMP-4, PCI-66, and PCI-68). These 4 cell lines displayed phosphorylation and functional activation of Akt both in the presence and absence of serum, while three control cell lines (PCI-79, KMP-8, and PSN-1) did so only in the presence of serum in culture...

Using reverse transcription-polymerase chain reaction (RT-PCR), six primary brain lymphomas, pathologically diagnosed as diffuse large B-cell lymphoma, were examined for rearranged VH-D-JH sequences of the immunoglobulin heavy chain gene, focusing on somatic mutations and intraclonal heterogeneity. The reliability of the isolated PCR clones was confirmed by in situ hybridization (ISH) with complementarity-determining region (CDR) 3 oligonucleotide probes. Sequence analysis of the PCR clones revealed a high frequency of somatic mutation, ranging from 8...

The effect of antioxidant, 0.25% 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) or 0.25% ascorbic acid (AsA), on carcinogenesis induced by administration of 0.05% aminopyrine (AP) and 0.05% sodium nitrite (NaNO2), was examined using a rat multi-organ carcinogenesis model. Groups of twenty F344 male rats were treated sequentially with an initiation regimen of N-diethylnitrosamine, N-methyl-N-nitrosourea, N-butyl-N-(4-hydroxybutyl)nitrosamine, N,N'-dimethylhydrazine and 2,2'-dihydroxy-di-n-propylnitrosamine during the first 4 weeks, followed by AP+NaNO2, AP+NaNO2+HTHQ, AP+NaNO2+AsA, NaNO2+HTHQ, NaNO2+AsA, each of the individual chemicals alone or basal diet and tap water as a control...

Helicobacter pylori (H. pylori) is now well known to be associated with stomach cancer, with infection during childhood rather than as an adult considered to be more important for carcinogenesis. To evaluate the difference in susceptibility to stomach carcinogenesis in relation to age of acquisition of H. pylori infection, we designed an experiment involving inoculation of H. pylori ATCC43504 followed by N-methyl-N-nitrosourea (MNU) treatment at different ages. Four-week-old male Mongolian gerbils (MGs) were divided into twelve groups...

A case-control study was carried out to investigate the impact of factors including virus infection, aflatoxin B1, microcystins, smoking/drinking and dietary habits as well as genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P4502E1 (CYP2E1), on susceptibility to hepatocellular carcinoma (HCC) in Haimen, China. A total of 248 patients with HCC and 248 sex-, age- and residence-matched population-based controls were recruited into the study. Virus infection, and ALDH2 and CYP2E1 gene polymorphisms were assessed in 134 paired cases and controls...

To elucidate the roles of insulin-like growth factors (IGFs) in the development of lung cancer, we conducted a case-control study nested within the Japan Collaborative Cohort Study. Serum samples were collected at baseline from 39140 men and women between 1988 and 1990. We measured serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in 194 case subjects who subsequently died from lung cancer during an 8-year follow-up and in 9351 controls. The odds ratios (ORs), adjusted for smoking and other covariates, were smaller with higher levels of IGF-II and IGFBP-3...

Natural killer (NK) cell neoplasms are rare diseases. Frequent abnormalities of the tumor suppressor genes Rb, p53, p15INK4B, p16INK4A and p14ARF have been reported. However, no oncogenes associated with tumorigenesis of NK cell neoplasms have been reported so far. We analyzed the status of oncogenes including N-ras, K-ras, H-ras, c-myc, N-myc and mdm2 by Southern blot, PCR-SSCP, western blot analysis and immunohistochemical staining. We analyzed four cell lines derived from NK cell neoplasms and 31 clinical samples with five subclasses of NK cell neoplasms...

We previously found p16 promoter methylation in DNA in the sera of 13 colorectal cancer patients out of 44 (30%) whose tumor DNA exhibited the methylation, using methylation-specific PCR (MSP). To examine whether the cancer detection rate could be improved by using a different tumor marker, we examined the K-ras status in 90 colorectal cancer patients using a mismatch ligation assay. Among the 31 patients showing K-ras gene mutations in their tumors, the same mutations were observed in serum DNA of 11 patients (35%)...

We examined the expression level of several genes that regulate different steps in metastasis formation in formalin-fixed, paraffin-embedded biopsies of 189 primary human gastric carcinomas prior to surgical resection in patients in whom lymph node metastasis was not evident by endoscopic ultrasound or computed tomography (CT) scan. The expressions of epidermal growth factor receptor (EGF-R), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and E-cadherin were examined by a colorimetric in situ mRNA hybridization technique...

Ovarian clear cell adenocarcinoma (CCA) is generally chemo-resistant. Recently the poor prognosis and resistance to chemotherapeutic agents of HER2/neu over-expressing tumors have become clear. Thus, we investigated the expression level of HER2 in surgically resected CCA and ovarian serous adenocarcinoma, endometrioid adenocarcinoma, and mucinous adenocarcinoma specimens, as well as CCA cell lines, by an immunohistochemical method. HER2 was over-expressed in 42.9% of CCA (P=0.026, vs. ovarian serous adenocarcinoma), 20...

For effective administration of lipophilic trans(+/-)-1,2-diaminocyclohexaneplatinum(II) complexes of malonate derivatives [(dach)PtL, L=allylmalonate (AM), diallylmalonate (DAM), allylbenzylmalonate (ABM), or dibenzylmalonate (DBM)] in aqueous solution, we have applied three different liposome formulations and evaluated their physical and chemical properties, along with their in vitro cytotoxicity. The liposome formulations were composed of DMPC / DMPG [DMPC=1,2-dimyristoyl-sn-glycero-3-phosphocholine, DMPG=1,2-dimyristoyl-sn-glycero-3-(phospho-rac-1-glycerol) (sodium salt)] in different molar ratios (7/3 or 3/7) or an equimolar DOTAP/DOPE formulation (DOTAP=1,2-dioleoyl-3-trimethylammonium propane, DOPE=1,2-dioleoyl-sn-glycero-3-phosphoethanolamine)...

KRN5500 is a highly active new semi-synthetic water-insoluble anticancer agent. The only mechanism of anticancer activity of KRN5500 described so far is an inhibitory effect on protein synthesis. At the time of writing, a phase I clinical trial is under way at the National Cancer Center Hospital, Tokyo, and at the National Cancer Institute in the USA. Although preclinical data did not indicate lung toxicity, some cases of severe pulmonary disorder were reported in the phase I clinical trials. This study has been conducted to examine whether incorporation of KRN5500 into polymeric micelles (KRN/m) could reduce the toxic effects caused by the current formulation of KRN5500...

Progression of head and neck cancer is always associated with changes of gene expression profile. In this study, we characterized the expression of multidrug-resistance mdr1 gene, which may play a role in tumorigenesis and multidrug resistance in head and neck cancer. A TaqMan one-step RT-PCR with a linear range for quantification across at least a 5 log scale of concentration of mdr1 mRNA was designed to determine the level of mdr1 expression in 50 pairs of normal vs. malignant head and neck tissues. Both the absolute level of mdr1 mRNA in tumor (T) and the relative mdr1 expression between tumor and its normal counterpart (T/N) were measured and their associations with several clinical variables were analyzed...