Biomedical subjects

M Fukumoto

Publications and source records attributed to M Fukumoto.

At least 145 records · Page 8Linked to original sources

PubMed1995

[Changes in blood flow and skin reaction following radiation therapy].

Skin blood flow (SBF) during radiation therapy was measured and compared with skin reaction to examine the relationship between skin reaction and blood flow. The SBF of 50 patients including 16 with head and neck (H&N) cancer, 13 with breast cancer and eight with lung cancer were analyzed. In the H&N patients, SBF was increased according to the treated dose, while in the breast cancer patients SBF was slightly increased at 10 Gy, and did not change up to 40 Gy. In the lung cancer patients SBF was not increased until 20 Gy, and thereafter increased moderately at 30 Gy. Among H&N, breast and lung cancer patients, the most severe skin reaction was observed at the earliest time in breast cancer patients, while blood flow was only slightly increased. This must have resulted in a relatively higher skin dose than the reference point dose in breast cancer patients. Therefore, differences in the relationship between SBF and skin reaction were observed among different types of cancer patients. However, in H&N cancer patients, SBF was increased as skin dose increased. Skin blood flow could be a good indicator by which to estimate skin reaction quantitatively when the daily skin dose is around 1.6 Gy.

Aged↗

PubMed1995

Comparison of multidrug resistance gene expression levels with malignant potentials and influence of chemotherapy in urothelial cancers.

BACKGROUND: We sought to determine how often P-glycoprotein is involved in the drug-resistance of urothelial cancer, and whether MDR1 gene expression is correlated with tumor grade, invasiveness, or metastasis. METHODS: Forty-two tumor specimens and two normal bladder mucosal samples obtained from 34 urothelial cancer patients were analyzed. Reverse-transcription and polymerase chain reaction were conducted. MDR1 mRNA levels were determined by measuring the relative ratio of the MDR1 to beta-2-microglobulin (b2 m) mRNA specific PCR products. RESULTS: The MDR1/b2 m in two normal urothelial samples were 0.044 and 0.045. For untreated primary tumors, levels of MDR1 gene expression in 46% tumor samples were less than that of normal urothelium, while 27% showed expression levels with a MDR1/b2 m ratio more than 0.1. There was no statistical correlation between MDR1 mRNA level and tumor grade, stage, or metastatic status. There was higher MDR1 gene expression in two lymph node metastasis specimens and almost equal expressions in two more. There was no significant difference in the mean MDR1/b2 m ratio between postchemotherapy and untreated tumors. A remarkable elevation of the MDR1 mRNA level (15 times greater than prechemotherapy) was found in one tumor; mRNA levels of the multidrug resistance-associated protein (MRP) gene, glutathione S-transferase pi (GST-pi) gene or DNA topoisomerase II (topo II) gene did not increase. CONCLUSIONS: It is still unclear whether the MDR1 gene expression in urothelial tumor cells is inducible by the current combination chemotherapy regimens. RT-PCR quantitation is useful for determining the expression level of MDR1 gene in urothelial cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

[Characteristics of smoking, drinking, dietary habits, and physical exercise in health behavioral models].

Various kinds of preventive health behaviors are promoted by health education. The extent of behavioral modification achieved, however, obviously differs from individual to individual according to habits, one of the reasons being the characteristics of various health habits are perceived differently. This cross-sectional study examined the association of indices representing health behavior models with smoking, drinking, dietary habits, and physical exercise. The indices and their meaning were as follows; health locus of control (HLC) and saliency of health are thought to cause the most active behavioral change, health norm relatively passive change, and vulnerability to illness the most passive change. The indices and lifestyle (health related practices) were surveyed by a self-administered questionnaire in a rural town in March 1994. The study sample consisted of 1,010 males and 1,055 females aged 20 years or older who responded to all questions related to the indices. Results are as follows: 1) Smoking and alcohol drinking were associated with vulnerability to illness, suggesting that people who quit smoking or alcohol drinking do so because of perception of their association with illness. Alcohol drinking seemed to have a higher magnitude of being associated with becoming ill or with fear of illness than smoking. 2) Consuming green-yellow vegetables and fresh fish, and physical fitness were associated with internal HLC, saliency of health, and health norm. These habits appeared to be easy to modify by active personal behavior choice. 3) Consuming milk, yogurt, boiled beans, tofu, oranges, and other fruits were associated with saliency of health. These habits seemed to relate to personal sense of being "healthy". 4) It seemed that younger people more likely changed their behavior by active self-management, while, older people changed due to their sense of value or norm. While it is important for health education to promote "self-management of health" by active behavioral change, certain habits are more resistant to change despite educational efforts possibly because of their characteristics in health behavioral models. For cases such as these, techniques promoting passive behavioral change should be considered.

Adult↗

PubMed1994

Effects of prostaglandin E2 on the micronucleus formation in mouse bone marrow cells by various mutagens.

The effects of prostaglandin E2 (PGE2), as a trigger of erythroid progenitor cells into the cell cycle, were studied on the induction of micronuclei by various mutagens; with mitomicin C (MMC) the optimal protocol was established. PGE2 itself did not induce any micronuclei in this experiment. The highest frequency of micronuclei and dose-response relationship between PGE2 doses and micronucleus frequency were observed 30 h after injection of MMC to mice administered PGE2 24 h previously. Sensitization by PGE2 pretreatment was also found for other mutagens, such as vincristine, 5-fluorouracil, benzo[a]pyrene, 1,1-dimethylhydrazine and 2-naphthylamine. These results support the hypothesis that accelerating the erythropoiesis increases the frequency of micronuclei induced by mutagens.

2-Naphthylamine↗

PubMed1994

Enhancement of sensitivity of urinary bladder tumor cells to cisplatin by c-myc antisense oligonucleotide.

BACKGROUND: Tumor cells have different degrees of sensitivity and resistance to anticancer agents. The acquisition of drug resistance is a major concern in cancer treatment. Because the c-myc oncogene has been implicated in the poor prognosis of some human tumors including urinary bladder tumor (UBT), the resistance of such tumors to anticancer drugs may correlate with c-myc expression. The present study tested this hypothesis by examining the effect of c-myc antisense oligonucleotide treatment on the sensitivity of human UBT cells to anticancer chemotherapeutic agents. METHODS: Cytotoxicity determined by a 1-day microculture tetrazolium dye assay. C-myc mRNA was examined by Northern blot analysis. RESULTS: The T24 human UBT cell line constitutively expresses c-myc mRNA. Treatment of T24 cells with the c-myc antisense oligonucleotide resulted in a significant inhibition of the expression of c-myc mRNA. Treatment of T24 cells with the c-myc antisense oligonucleotide in combination with mitomycin C, Adriamycin, or 5-fluorouracil (5-FU) did not overcome their resistance to these anticancer chemotherapeutic agents. However, combination treatment with the c-myc antisense oligonucleotide and CDDP resulted in a synergistic cytotoxic effect on T24 cells and two freshly derived UBT cells. Further, treatment of CDDP-resistant T24 cells (T24/CDDP) with c-myc antisense oligonucleotide and CDDP reversed the resistance. Pretreatment of T24 cells with either agent and then treatment with the second agent resulted in the same cytotoxic activity as achieved in the presence of the two agents. The combination of c-myc antisense oligonucleotide and carboplatin also resulted in a synergistic cytotoxic effect on T24 cells, and the combination of c-myc antisense oligonucleotide and trans-diamminedichloro-platinum resulted in an additive cytotoxic effect. Incubation of T24 or T24/CDDP cells with the c-myc antisense oligonucleotide increased the intracellular accumulation of CDDP, but not the accumulation of 5-FU. CONCLUSIONS: This study demonstrates that combination treatment with c-myc antisense oligonucleotide and CDDP can overcome the CDDP-resistance of UBT cells and that the increased intracellular accumulation of CDDP by c-myc antisense oligonucleotide may play a role in the enhanced cytotoxicity obtained. The synergistic effect obtained with established UBT cells and freshly isolated UBT cells suggests that combination treatment with c-myc antisense oligonucleotide and CDDP may have clinical application in the therapy of CDDP-resistant UBT.

Antineoplastic Agents↗

PubMed1994

Analysis of gene amplification and overexpression in human esophageal-carcinoma cell lines.

Gene amplification/overexpression was analyzed in 23 cell lines derived from human esophageal squamous-cell-carcinoma tissues by Southern and Northern hybridizations to c-myc, c-erbB, hst-1 and cyclin-D1 probes. Amplification of the c-myc gene was observed in 5 cell lines derived from well-differentiated carcinomas and all of them were accompanied by co-amplification of other examined oncogenes. The c-erbB gene was amplified in 3 cell lines. Co-amplification of hst-1 and cyclin D1, both of which are located in chromosome 11q13, was found in 9 cell lines. Without exception their amplification was simultaneous and the magnitudes were similar. Their amplification, but not their overexpression, was significantly correlated with poor prognosis in patients from whom the cell lines were established. While hst-1-gene expression was not detected, at least 1 of the genes analyzed was overexpressed in 20 cell lines vs. its expression in normal esophageal mucosal tissues. However, gene amplification was not necessarily accompanied by overexpression of the corresponding genes. Expression of the cyclin D1 gene, which has been assumed to be a target gene for 11q13 amplification, was not detected in one particular cell line with amplification of 11q13. These results suggest that the amplification/overexpression of more than I oncogene is involved in the carcinogenic process of esophageal carcinoma and that c-myc-gene amplification is associated with a well-differentiated subtype. There remains a possibility that key oncogenes other than cyclin D1 are involved in 11q13 amplification.

Animals↗

PubMed1994

Immunohistochemical study for basic fibroblast growth factor and fibroblast growth factor receptor I in pituitary adenomas.

Immunohistochemistry and RT-PCR of basic fibroblast growth factor (bFGF) and one of its receptors (FGFR-I) were performed in pituitary adenomas. Sixty percent of pituitary adenomas showed strong or moderate immunoreactivity to bFGF. The immunoreactivity for FGFR-I in tumor tissues showed positive correlation to that for bFGF (X2 = 6.176, P = 0.0456). Basic FGF-positive cells consisted of pituitary adenoma cells as well as folliculostellate cells and, their distribution was heterogeneous. Expressions of bFGF and FGFR-I were not related to cell proliferation of pituitary adenomas or hormones produced, suggesting that bFGF plays some role other than progression of pituitary adenomas.

Adenoma↗

PubMed1994

Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression.

To verity the role of metastasis-related nm23 genes in carcinogenesis and progression of ovarian carcinoma, we analyzed the mRNA levels of the nm23 genes of both isoforms, -H1 and -H2, together with those of the epidermal growth factor receptor, the c-erbB-2, and the c-erbB-3 genes in 45 ovarian carcinomas and 5 benign cystadenomas. Expressions of nm23 gene products/nucleoside diphosphate kinases, epidermal growth factor receptor, erbB-2 protein, and sex steroid receptor status in ovarian carcinomas were also examined by immunohistochemistry. The mRNA levels of nm23-H1 and nm23-H2 were higher in carcinoma tissues compared with benign tumors (H1, P < 0.01). The mRNA levels of c-erbB-2 and c-erbB-3 were also elevated in carcinoma tissues, and there was a positive correlation between mRNA levels of the nm23-H1 and the c-erbB-2 genes (r = 0.58; P < 0.05). Correlation of immunohistochemical staining between nucleoside diphosphate kinases and erbB-2 protein was also observed in ovarian carcinoma tissues. Sex steroid receptor positivity was related to a higher expression of nucleoside diphosphate kinases. Expression levels of the nm23 genes in ovarian carcinomas were not related to either histological subtype or local extension and peritoneal dissemination. Among stage III ovarian carcinomas, however, tumors possessing lymph node metastasis showed significantly lower nm23-H1 mRNA levels than those without nodal involvement (P < 0.05). Stage IV carcinomas also exhibited lower nm23-H1 and nm23-H2 expression levels compared with other stages (P < 0.05). These results suggest that expression of the nm23 genes, especially nm23-H1, is activated, accompanied by c-erbB-2 and c-erbB-3 overexpressions, in early stages of the carcinogenic process of ovarian carcinoma and reduction of nm23-H1 expression occurs in association with lymph nodal and/or distant metastasis.

Adenocarcinoma↗

PubMed1994

Expression of multidrug resistance gene and localization of P-glycoprotein in human primary ovarian cancer.

Resistance to chemotherapy is the major obstacle to controlling malignant tumors. To characterize multidrug resistance phenotype in human primary ovarian cancer without chemotherapy, expressions of the mdr1 gene in 52 cases of ovarian cancer (44 common epithelial, 5 nonepithelial, and 3 metastatic cancers) were analyzed by polymerase chain reaction of RNA after reverse transcription. Furthermore, localization of P-glycoprotein, which is encoded by the mdr1 gene, was studied immunohistochemically. Although overall expression of the mdr1 gene was relatively low, its expression level was the highest in well-differentiated cancer tissues. Serous and mucinous adenocarcinomas showed higher levels of expression compared with clear cell and endometrioid carcinomas. P-glycoprotein was positive on luminal surfaces of lining cells of ovarian cancer and on those of inclusion cysts from which epithelial ovarian cancer is considered to develop. Thus, some ovarian cancer cases before chemotherapy are intrinsically multidrug resistant, which can be determined by mdr1 gene expression, and this phenotype should be taken into account for effective chemotherapy of ovarian epithelial carcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Genetic predisposition to pre-B lymphomas in SL/Kh strain mice.

Genetic predisposition of SL/Kh mice to spontaneous pre-B lymphomas was investigated in crosses between SL/Kh and NFS/N, another inbred strain of mice lacking endogenous ecotropic provirus and spontaneous lymphoma. (SL/Kh x NFS/N) F1 hybrids developed lymphomas similar to those in SL/Kh but at a lower frequency and with a longer latent period. Of 83 backcross mice to NFS/N, 22 developed hemopoietic tumors: 8 were diffuse lymphoblastic lymphomas; 2 were myeloid leukemias arising by 12 months of age; and 12 were follicular center cell lymphomas found later in life. Of 6 endogenous ecotropic proviruses in SL/Kh, 2 were expressed in (SL/Kh x NFS) F1 backcrossed to NFS. One, encoded by a 27-kilobase EcoRI fragment, was closely linked to Gpi-1a on chromosome 7 and its expression seemed to be a prerequisite for the occurrence of all types of hemopoietic tumors. Microsatellite analysis of the backcross generation revealed multiple host genetic factors determining susceptibility to tumors. An allele derived from SL/Kh, mapped in the major histocompatibility locus on chromosome 17, was essential for development of early onset tumors. This locus was designated as Esl-1 (early lymphoma of SL-1). On the other hand, follicular center cell lymphomas developed mostly in the backcross mice homozygous for the NFS/N derived allele at the D4MIT17-linked locus, designated as foc-1 (follicular center cell lymphoma-1), on chromosome 4.

Animals↗

PubMed1994

Production of parathyroid hormone-related protein by cultured human myeloma cells.

We examined whether or not parathyroid hormone-related protein (PTH-rP) is produced in cultured human myeloma cells. PTH-rP protein was detected in the cell extract of one (U266) of 6 myeloma cell lines examined by radioimmunoassay. Also we demonstrated the expression of PTH-rP mRNA in all of the 6 lines. These findings indicate that PTH-rP may be one of the factors responsible for the bone destruction or hypercalcemia in multiple myeloma.

Base Sequence↗

PubMed1994

Colony-stimulating factor-producing tumours: production of granulocyte colony-stimulating factor and interleukin-6 is secondary to interleukin-1 production.

We have reported that tumours producing colony-stimulating factor (CSF) also secrete interleukin-1 (IL-1) and IL-6. In the present study, we characterised the role played by IL-1 in CSF production. IL-1 receptor antagonist inhibited the production of granulocyte (G)-CSF and IL-6 by approximately 90% in CSF-producing human lung carcinoma cell lines. Similar results were obtained with hydrocortisone, which suppresses IL-1 gene expression. In contrast, 15 non-CSF-producing human lung carcinoma cell lines did not show detectable IL-1 production, although seven of them were induced to produce G-CSF and IL-6 by exogenous IL-1 alpha. Cell lines that responded to IL-1 alpha, including the CSF-producing lines, expressed receptors for IL-1 alpha. These results indicate that CSF-producing tumours can be characterised by their constitutive IL-1 production, IL-1 receptor expression and IL-1-dependent excess production of G-CSF and IL-6. Furthermore, transcription factor(s) may be involved in the abnormal IL-1 alpha production.

Blotting, Northern↗

PubMed1994

Enhanced antitumor effect of Bacillus Calmette-Guérin in combination with fibrinogen on urinary bladder tumor.

Although intravesical instillation of Bacillus Calmette-Guérin (BCG) is an established and effective therapy for superficial urinary bladder tumor (UBT), the current major problems are BCG-resistant UBT and recurrence after BCG therapy. The injection of BCG and fibrinogen could be expected to induce the formation of a fibrin mesh, which would trap BCG and and prolong its antitumor action. The present study has been designed to investigate whether fibrinogen has the ability to augment antitumor activity of BCG against UBT. A single injection of BCG/fibrinogen solution into the subcutaneous tissue of C3H/He mice was performed. Histopathological examination revealed prolonged accumulation of BCG and marked infiltration of inflammatory cells at the injected site, as compared with the injection of BCG or fibrinogen alone. When BCG was used in combination with gelatin sponge, prolonged BCG accumulation was also observed, but not many inflammatory cells were induced, as compared with injection of BCG/fibrinogen combination. When BCG/fibrinogen solution was injected into MBT-2 murine UBT transplanted into C3H/He mice, the formation of fibrin fibers, which trap BCG, was induced, and many inflammatory cells around the tumor were seen. A pronounced inhibitory effect on tumor growth and prolonged survival of tumor-bearing mice were achieved, as compared with the injection of BCG alone. Dead BCG/fibrinogen solution had a modest inhibitory effect on the tumor growth. This study suggests that combination treatment with BCG and exogenous fibrinogen may prolong accumulation of BCG by BCG by trapping BCG in fibrin meshwork, and may induce marked infiltration of inflammatory cells into tumor stroma, causing marked regression of the tumor. The possible clinical implications of the combined use of BCG and fibrinogen are discussed.

Administration, Intravesical↗

PubMed1994

High incidence of uterine inversion in mast cell-deficient osteopetrotic mutant mice of mi/mi genotype.

Mutations at either W or mi (microphthalmia) loci in the mouse can lead to a deficiency in melanocytes and mast cells. In addition, W mutants can be anemic and sterile, whereas mi mice are osteopetrotic because of a monocyte/macrophage/osteoclast defect. Since c-kit receptor tyrosine kinase is the gene product of the W locus and mi mutation has been suggested to affect the transduction of signals from the c-kit and c-fms receptors, we here examined the effect of mi mutation on fertility. Testes and ovaries from mi/mi mice were histologically normal, and the pattern of c-kit protein expression was not different from that of +/+ mice. Homozygous mutant crosses (mi/mi x mi/mi) were fertile, but inversion of the uterus occurred in 86% of the deliveries. In some cases, the placenta was found still attached to the inverted uterus after delivery. Decidual cells were present and expressed c-kit protein normally in the placenta of mi/mi mice. The inversion was also observed in mi/mi females mated to +/+ males. No uterine inversion was noted when +/mi females were crossed with mi/mi or +/mi males, suggesting that the genotype of the mother but not of the father or fetus is important for the pathogenesis. The numbers and body weights of mi/mi newborns were less than those of +/mi littermates. Mast cells were absent, but c-kit-positive cells were present, in the uterine muscle layers of pregnant mi/mi mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

K-ras and p53 alterations in genomic DNA and transcripts of human pancreatic adenocarcinoma cell lines.

We analyzed 15 human pancreatic adenocarcinoma cell lines for alterations of the K-ras and the p53 genes and their transcripts. In 11 cell lines (73.3%), point mutations of the K-ras gene were found at codon 12 in exon 1. In 9 cell lines one allele was mutated and the other was wild type, and both the alleles were expressed into mRNA. In one cell line both alleles of codon 12 were mutated to TGT and GTT, respectively, but only TGT was transcribed into mRNA. Alterations in mRNA of the p53 gene were detected in 10 cell lines (66.7%). Analysis of the genomic sequence of the p53 gene revealed that the alterations consisted of 6 cases of base pair substitutions and 1 case of 1-bp deletion in evolutionarily conserved exons 5 to 8, 2 cases of splicing mutations in exon 4, and 1 case of novel deletion from exons 2 to 9. In 14 cell lines (93.3%), alterations were identified in the K-ras or p53 gene. Of these, 4 cell lines harbored K-ras mutations without p53 alteration, whereas 3 cell lines exhibited p53 alterations without K-ras mutation. Thus, it is suggested that activation of the K-ras gene and inactivation of the p53 gene are strongly and cooperatively associated with pancreatic carcinogenesis.

Adenocarcinoma↗

PubMed1994

S100-positive histiocytes in T-cell-dependent area in human lymph nodes express P-glycoprotein.

In the present study, we examined P-glycoprotein (P-gp)-expressing cells in human lymph nodes (LN) from patients with reactive lymph adenitis and various malignant lymphomas (ML). MDR1 mRNA was detected in all reactive LN and in 8 of 10 ML samples examined by reverse transcription polymerase chain reaction (RT-PCR). The signal intensity of the bands was stronger in samples from T-cell ML LN than in those from LN of reactive lymph adenitis and B-cell ML. Immunohistochemistry also showed positive reactivity with cellular components in the LN. The P-gp-positive cells, detected by UIC2, in reactive lymph adenitis and ML samples were large in size in the T-cell-dependent paracortical area in LN. Further, morphological characteristics were similar in UIC2-positive cells between reactive and ML LN. Double staining with UIC2 and a hematopoietic cell lineage-specific monoclonal antibody showed that UIC2-positive cell co-expressed S-100, but not other lymphocyte- and ML cell-specific antigens, indicating that these cells correspond to histiocytes in the T-cell-dependent paracortical area. Our results show that P-gp was expressed in histiocytes but not ML cells in LN, and suggest that this molecule may play an important role in the biological function of histiocytes and/or for maintenance of homeostatic levels in T-cell ML LN.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Coexpression of the collagen-binding stress protein HSP47 gene and the alpha 1(I) and alpha 1(III) collagen genes in carbon tetrachloride-induced rat liver fibrosis.

HSP47 is a collagen-binding stress protein and is assumed to act as a collagen-specific molecular chaperone during the biosynthesis and secretion of procollagen in the living cell. The synthesis of HSP47 has been reported to correlate with that of collagen in several cell lines. We examined the expression of HSP47 mRNA during the progression of carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Northern blot analysis revealed that the expression of HSP47 mRNA was markedly induced during the progression of fibrosis in parallel with alpha 1(I) and alpha 1(III) collagen mRNAs. By in situ hybridization, the distribution of HSP47 transcripts was similar to that of alpha 1(I) collagen and was observed only in cells lining collagen fibrils. These collagen-positive cells were confirmed to be Ito cells by immunohistochemistry for desmin. The absence of high levels of HSP47 mRNA in the liver of rats treated with only a single administration of CCl4 indicated that the induction of HSP47 mRNA was not due to the direct effect of CCl4 as a stressor, but was due to the progression of liver fibrosis. The function of HSP47 in liver fibrosis will also be discussed.

Animals↗

PubMed1994

Expression of fibroblast growth factor receptor-1 in human glioma and meningioma tissues.

We examined the expression of fibroblast growth factor receptor-1 (FGFR-1), namely FLG, in tissues of 18 human gliomas, 10 human meningiomas, 3 human metastatic brain tumors, and 2 normal human brains by means of immunohistochemistry. All tissues were positively stained for FGFR-1. Primary brain tumors were more abundantly immunoreactive than normal brain tissues (Mann-Whitney U test, P < 0.05). There was significant correlation between the expression level of basic fibroblast growth factor (basic FGF) and that of FGFR-1 in tissues of human glioma (Spearman's test, P < 0.05). The expression level of FGFR-1 of tumor cells increased in correlation with that of endothelial cells in glioma tissues (Spearman's test, P < 0.001). We previously reported that basic FGF is produced in more than 90% of human glioma and meningioma tissues. Together with these data, it is suggested that basic FGF is involved in autonomous cell growth and tumorigenesis of gliomas and meningiomas as an autocrine growth factor in vivo.

Adenocarcinoma↗