Biomedical subjects

R Kanamaru

Publications and source records attributed to R Kanamaru.

At least 73 records · Page 4Linked to original sources

PubMed1994

[Genetic alterations of human colorectal cancer].

Genetic alterations of several oncogenes and tumor suppressor genes are associated with human colorectal carcinogenesis. Especially in mutations, the K-ras, p53, APC and DCC gene frequently occurred, and these gene alterations seem to have important roles in colorectal carcinogenesis. We investigated 28 human colon cancer specimens obtained from surgery and five human colon cancer cell lines by PCR-SSCP assay, PCR-OSH assay, RT-PCR or sequencing method. Forty percent of cancers from surgical specimens had Ki-ras 2 (codon 12/13), p53 (Exon 5-8), APC (MCR) gene mutations, and fifty-seven percent of them had lower expression of DCC gene that of normal matched colon mucosa of the same patient. G to A transition was the most frequent in K-ras mutational spectrum in this case; 25% of patients had both k-ras and p53 gene point mutations. Form the results, we concluded that it in colorectal carcinogenesis for both K-ras and p53 gene point mutations might not necessary occur.

Colonic Neoplasms↗

PubMed1994

[Experimental study on the effectiveness of PET tumor images for cancer diagnosis].

Positron emission tomography (PET) with 2-deoxy-2 [18F] fluoro-D-glucose (18FDG), a structural analog of glucose, allows tumor images to be obtained, based on increased glycolysis in cancer cells. In the present study, in order to confirm the effectiveness of 18FDG-PET tumor images for cancer diagnosis, 18FDG tumor uptake values were measured in human gastric cancer xenografts in nude mice. Firstly, comparison of 18FDG uptake and histological grade in four gastric cancers showed that 18FDG uptake increased with loss of differentiation. Secondly, reduction of 18FDG uptake values after administration of anticancer drug was found to correlate with chemosensitivity to anticancer agent, and the values were reduced prior to suppression of tumor growth. These data suggest that 18FDG-PET tumor images may provide reliable indications for assessment of the histological grade of the tumor and the efficacy of cancer chemotherapy.

Adenocarcinoma↗

PubMed1994

Accumulation of 2-deoxy-2[18F]fluoro-D-glucose in human cancers heterotransplanted in nude mice: comparison between histology and glycolytic status.

UNLABELLED: The success of tumor imaging with PET and 2-deoxy-2-fluoro[18F]-D-glucose (18FDG) is based on preferential accumulation of 18FDG in tumors. METHODS: Fluorine-18-FDG uptake was measured in nine human cancers heterotransplanted in nude mice and compared with histologic subclassification. RESULTS: Mean 18FDG uptake by the human cancers was considerably less than that by the host's heart, but values at 60 min after injection were about 2.5 times as high as the liver and kidney, about two times as that for the muscle and about six times that for the blood. Comparison of 18FDG uptake and histological grade in four gastric, two pancreatic and three colonic cancers showed that 18FDG uptake increased with loss of differentiation. CONCLUSION: This nude mice model system is useful for studying correlations between physiological and morphological parameters of heterotransplanted human cancers.

Animals↗

PubMed1992

Mutations of p53 gene in human colorectal tumor in Japan: molecular epidemiological aspects.

Effects of environmental carcinogens on DNA can be detected, because, while each carcinogenic agent is inherently different, its corresponding "fingerprint" is unique to a specific mutation pattern. The p53 tumor suppressor gene is of particular interest because the relationship between environmental factors and genetic alterations of carcinogenesis can be investigated. In this report, we compared the mutation patterns of the p53 gene in human colorectal tumors from Japanese patients with those from US patients. The results show different rates of transversion and transition among these two populations, which suggests a difference between Japan and the US in the etiological factors underlying colorectal tumorigenesis.

Colorectal Neoplasms↗

PubMed1992

Histopathological evaluation on the effect of induced hypertension chemotherapy presurgically performed in patients with advanced carcinoma of the stomach.

Stomachs resected from 13 patients with an advanced gastric carcinoma were examined histopathologically to evaluate the effect of induced hypertension chemotherapy (IHC) using angiotensin II. Eight of the 13 patients, randomly chosen, were treated presurgically by IHC with a regimen of 5-fluorouracil, adriamycin and mitomycin C; the same regimen was used in the remaining five patients but without inducing hypertension. Clinical evaluation of the effect gave rise to the confirmation, presurgically, of complete response in three and partial response (PR) in two patients in the IHC group, whereas in the non-IHC group, the highest rating was PR, which was attained in only one patient. Also in the histopathological assessment based on a five-step grading, the IHC group earned in average a higher score than the non-IHC group, with a difference proved significant by Wilcoxon's test. A histological rating of Grade 3, the highest effectiveness, was given to three patients in the IHC group, in one of whom the resected stomach disclosed no viable carcinoma cells but only fibrotic areas replacing carcinoma. There was also a correlation between the clinical and histological ratings as proved to be significant by Spearman's test. We conclude that in gastric carcinoma, the effect of chemotherapy is enhanced by angiotensin II-IHC.

Adenocarcinoma↗

PubMed1992

Human cytochrome P450IIE1 gene: DraI polymorphism and susceptibility to cancer.

Human cytochrome P450IIE1 (CYP2E) is involved in the metabolic activation of procarcinogens such as N-nitrosodimethylamine, benzene and ethyl carbamate. We screened DNA from 28 individuals for restriction fragment length polymorphisms (RFLPs) is the human P450IIE1 gene and detected an RFLP for the restriction endonuclease DraI. The distribution of the genotypes of this polymorphisms among lung cancer patients (n = 74) differed from that among controls (n = 73) with statistical significance of p < 0.05. In addition, the distribution among patients with cancers of the digestive system (n = 38) was also different from that among controls. Our findings indicate an association between the DraI polymorphism of the IIE1 gene and susceptibility to cancers of the lung and the digestive system.

Cytochrome P-450 CYP2E1↗

PubMed1992

Mutations of the p53 gene and other genes involving in human colorectal carcinogenesis.

In this study, structural changes of the p53 gene in primary specimens of human colorectal carcinomas were analyzed by polymerase chain reaction mediated-DNA sequencing method. Point mutations of p53 gene, including an intronic mutation case, were detected in 8 of 14 carcinomas (57%). Point mutations of the gene were also observed in 2 of 2 adenomas, suggesting that mutations occur prior to the carcinoma stage. These results support that p53 gene plays an important role in the development of colorectal cancer. The frequency of Ki-ras oncogene mutations was also studied by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP). This resulted in the rate of 42% (10/24), a quite similar value obtained by other methods. As PCR-SSCP analysis is a convenient method to detect point mutation, we have now examined 24 colorectal cancers for the p53 gene by this method, and detected the mutations. Furthermore, expression of the DCC gene, a candidate of tumor suppressor gene involved in colorectal carcinogenesis, was examined by reverse transcriptase-mediated PCR (RT-PCR) assay, resulting in significant reduction on the DCC expression in 8 of 14 carcinoma cases (57%).

Adenoma↗

PubMed1992

Influence on metastasis of the reduction of major histocompatibility complex (MHC) class I gene with an antisense oligonucleotide.

Cell surface MHC H-2K antigens expressed on various types of B16 melanoma cells of C57BL/6 mouse origin were stained by the avidin-biotinylated enzyme complex (ABC) technique. The low metastatic B16F1 cell line, which demonstrates high levels of H-2K antigen, stained strongly, while the high metastatic B16F10 cell line with no H-2K antigen was not stained. Metastatic colonies which developed in lungs after intravenous (i.v.) injection proved to be negative in both cases. Therefore, in consideration of decreased expression of H-2K antigen in the metastatic process both in vivo and in vitro, antisense oligonucleotides against the class I H-2K gene were transfected into B16F1 cells with H-2K antigens. Subsequent immunohistochemical assessment revealed lack of H-2K antigen expression in the cells, but nevertheless they still could not metastasize to lungs when i.v. injected. This may suggest that any link between the two is not directly causal.

Amino Acid Sequence↗

PubMed1992

[Chemotherapy-associated hemolytic uremic syndrome--a case report].

A 63-year-old male had undergone combination chemotherapy including adriamycin, cisplatin, mitomycin C, 5-fluorouracil and vindesine for six months for double cancer of esophagus and stomach. He complained of lassitude during therapy, and laboratory examinations revealed microangiopathic hemolytic anemia, thrombocytopenia and hyperbilirubinemia. Despite administration of prednisolone, dipyridamole and fresh frozen plasma, the patient died six days later. Postmortem examination disclosed multiple microthrombi in the liver, kidney and pancreas. It was presumed that MMC had caused the illness.

Adenocarcinoma↗

PubMed1992

[Pharmacokinetic studies on fluorinated pyrimidine in cancer cell and tissue].

A number of the studies on pharmacokinetics of fluorinated pyrimidines have been precisely reported. In mice bearing Ehrlich ascites carcinoma, 5-FU showed highest concentration in the lung and kidney immediately after i.v. administration of 5-FU, and in the liver, it showed rather lower concentration but for a longer period. 5-FU in blood was transferred into ascites fluid rapidly, and thus, the level of 5-FU in ascites fluid became higher than that in blood. FT is a masked compound of 5-FU, having a tetrahydrofuryl group. Drug metabolizing enzyme, natural degradation, and thymidine phosphorylase are considered to be responsible for the molecular conversion of FT into 5-FU. In order to increase the level of drug metabolizing enzyme, P450 in the liver of tumor bearers, of which P450 level was extremely lower as compared to normal individuals, phenobarbital was very effective from our previous experiment. Clinically, phenobarbital 200mg/day for 3 successive days was administered in prior to FT, and a better response was obtained than FT alone. Prevention from degradation of 5-FU in the liver by uracil kept higher level of 5-FU in blood. HCFU and 5'DFUR are also masked form of 5-FU and are converted to 5-FU in the liver.

Animals↗

PubMed1991

Mutations of the P53 gene, including an intronic point mutation, in colorectal tumors.

In this study, analysis of structural changes of the p53 gene in colorectal tumors revealed point mutations detected in 8 of 14 carcinomas and 2 of 2 adenomas. Of these 10 cases with point mutations, eight had one or more missense mutations, one had a nonsense mutation, and the remaining one had, interestingly, an intronic point mutation with subsequent activation of a cryptic splice donor site in the flanking exon. This report contains the first identification of an intronic point mutation of the p53 gene in a colorectal cancer case.

Amino Acid Sequence↗

PubMed1991

Expression of glutathione S-transferase-pi messenger RNA in human esophageal cancers.

The expression of human glutathione S-transferase-pi (GST-pi) in resected primary esophageal tumors and in matching normal esophageal mucosa from 25 patients undergoing radical surgery was measured by RNA blot hybridization. The RNA transcript levels of GST-pi in the tumor tissues were higher than those in normal tissues in 20 of 25 cases (80%). The mean GST-pi mRNA value in the tumor tissues (n = 25) was significantly (P less than 0.01) elevated as compared with that in background mucosa (n = 29), and in ten of 25 tumors (40%) the level of GST-pi mRNA exceeded the mean normal tissue value by two standard deviations (normal mean value + 2 X SD). The results obtained from the current experiment thus suggests that GST-pi might be a useful marker for human esophageal cancer. No correlation between GST-pi mRNA level and clinical stage or histologic characteristics was apparent.

Adult↗

PubMed1991

Association between restriction fragment length polymorphism of the human cytochrome P450IIE1 gene and susceptibility to lung cancer.

Cytochrome P450IIE1 (P450IIE1) is involved in metabolic activation of carcinogenic nitrosamines, aniline and benzene. We detected a restriction fragment length polymorphism of the human P450IIE1 gene with the restriction endonuclease DraI. The population was thus divided into three genotypes, namely, heterozygotes (CD) and two forms of homozygotes (CC and DD). The distribution of these genotypes among lung cancer patients differed from that among controls with statistical significance of P less than 0.05 (chi 2 = 7.01 with 2 degrees of freedom). This result strongly suggests that host susceptibility to lung cancer is associated with the DraI polymorphism of the P450IIE1 gene.

Adenocarcinoma↗

PubMed1991

Induction of natural killer (NK) activity in mice by injection of chromomycin A3.

Intravenously or intraperitoneally administered Chromomycin A3 (CHRM), an anticancer drug, augmented natural killer (NK) activity of both spleen cells and peritoneal exudate cells in BALB/c mice. When CHRM was administered intravenously, NK activity increased to about five fold that in nontreated mice on the 3rd to the 5th day, then rapidly decreased by the 7th day. On the other hand, when CHRM was administered by the intraperitoneal route, a peak of increased NK activity was observed on 5th to 7th day followed by a more gentle decrease. Augmentation of NK activity by CHRM was enhanced by additional administration of Interferon- gamma (IFN-gamma). Experimental evidence that NK activity could be augmented by CHRM in various strains of mice, independent of H-2 haplotype, suggested that involvement of genetic control within class I region of major histocompatibility complex could be excluded. When BALB/c mice inoculated subcutaneously with Meth A cells were treated with i.p. injection of CHRM, or CHRM in combination with IFN-gamma, the growth of the tumor cells was inhibited, indicating in vivo significance for the increased NK activity. Since this inhibitory effect was decreased by the injection of anti Asialo GM1 antibody (alpha-ASGM1), the effector cells presumably exerting killing activity against Meth A cells were concluded to be Asialo GM1 antigen positive.

Animals↗

PubMed1991

Undifferentiated sarcoma of the liver in a 21-year-old woman: case report.

A successful surgical case of malignant undifferentiated (embryonal) sarcoma of the liver (USL), a rare tumor normally found in children, is reported. The patient was a 21-year-old woman, complaining of epigastric pain and abdominal fullness. Chemical analyses of the blood and urine and complete blood counts revealed no significant changes, and serum alpha-fetoprotein levels were within normal limits. A physical examination demonstrated a film, slightly tender lesion at the liver's edge palpable 10 cm below the xiphoid process. CT scan and ultrasonography showed an oval mass, confined to the left lobe of the liver, which proved to be hypovascular on angiography. At laparotomy, a large, 18 x 15 x 13 cm tumor, found in the left hepatic lobe was resected. The lesion was dark red in color, encapsulated, smooth surfaced and of an elastic firm consistency. No metastasis was apparent. Histological examination resulted in a diagnosis of undifferentiated sarcoma of the liver. Three courses of adjuvant chemotherapy, including adriamycin, cis-diaminodichloroplatinum, vincristine and dacarbazine were administered following the surgery with no serious adverse effects. The patient remains well with no evidence of recurrence 12 months after her operation.

Adult↗

PubMed1990

Characterization of glycyrrhizin-binding protein kinase from the crude membrane fraction of rat liver.

Using GL-affinity column chromatography, a casein phosphorylating protein kinase was purified selectively from the crude membrane fraction of rat liver. The biochemical characteristics of the purified kinase (approximately Mr 210 kDa) are very similar to those reported for polypeptide-dependent protein kinase (kinase P). Moreover, low doses of GL selectively inhibit phosphorylation of Mr 35-36 kDa polypeptides (which are cross-reacted with anti-lipocortins I and II) by the kinase in vitro. These results suggest that the anti-inflammatory activity of GL may involve the impairment of the physiological functions of lipocortins through their specific modification by the kinase at the cell membrane level.

Animals↗

PubMed1990

Comparative studies on the action of 7-N-[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]mitomycin C and of mitomycin C on cultured HL-60 cells and isolated phage and plasmid DNA.

The mechanism of action of a new mitomycin C (MMC) derivative, KT6149, was studied in human leukemia HL-60 cells and in isolated phage and plasmid DNA, and its effects were compared with those of MMC. Cell growth was markedly inhibited by KT6149, with an IC50 of 2 x 10(-9) M, that for MMC being 2 x 10(-8) M. DNA synthesis of HL-60 cells as determined by incorporation of [3H]-thymidine was also inhibited by KT6149, with an IC50 of 2 x 10(-7) M as compared with 2 x 10(-6) M for MMC. RNA and protein synthesis were less markedly inhibited at low concentrations. Alkaline sucrose density-gradient centrifugation revealed a significant decrease in sedimentation velocity for cellular DNA of the cells after 1 h treatment with KT6149 at concentrations higher than 10(-7) M. In contrast, no such change was observed for DNA of cells treated with MMC, even at a concentration of 10(-5) M. In a cell-free system, analysis by agarose gel electrophoresis patterns showed that the drug induced a decrease in the amount of covalently closed circular DNA of phage PM2 and an increase in that of open circular DNA in the presence of dithiothreitol (DTT), whereas MMC did not cause any change in DNA subfraction amounts. Furthermore, the electrophoretic mobility of linearized pBR322 DNA in alkaline agarose gel was significantly decreased by KT6149 in the presence of DTT and FeSO4, no such change being observed in the case of MMC. The results clearly indicate that the inhibitory effects of KT6149 on the growth and DNA synthesis of HL-60 cells are more potent than those of MMC and that KT6149-induced DNA damage is due to single-strand scission and to cross-linking of DNA, suggesting a mode of activation different from that of MMC.

Antineoplastic Agents↗

PubMed1990

Increase in the level of P-glycoprotein mRNA expression in multidrug-resistant K562 cell lines treated with sodium butyrate is not accompanied with erythroid differentiation.

We examined the effect of hemin, sodium butyrate and mitomycin C on levels of P-glycoprotein mRNA in human myelogenous K562 cells by northern blot analysis. After treatment with sodium butyrate a dose-dependent increase of P-glycoprotein mRNA expression was observed in the adriamycin-resistant K562 and vincristine-resistant K562 lines. With 10 mM sodium butyrate, the level of P-glycoprotein mRNA reached 20 times that of control adriamycin-resistant K562 and with 30 mM sodium butyrate, it exceeded 5 times that of control vincristine-resistant K562. In contrast, hemin and mitomycin C had almost no effect on P-glycoprotein mRNA. In this experiment, since expression of P-glycoprotein mRNA was not necessarily accompanied with induction of erythroid differentiation, the increased amount of P-glycoprotein mRNA is unlikely to be a result of differentiation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗