Biomedical subjects

K Hasumi

Publications and source records attributed to K Hasumi.

At least 19 recordsLinked to original sources

PubMed2003

Adenocarcinoma and multiple adenomas of the large intestine, associated with Cronkhite-Canada syndrome.

The Cronkhite-Canada syndrome is a rare non-hereditary disorder with generalised gastrointestinal polyposis, associated with ectodermal changes. We report here a case of adenocarcinoma and multiple adenomas of the large intestine associated with Cronkhite-Canada syndrome in a 61-year-old Japanese man. Histologically, the rectal tumour was composed of well-differentiated tubular adenocarcinoma, admixed with foci of adenomatous components, and associated with hyperplastic mucosa of Cronkhite-Canada syndrome. Multiple polyps, >20 polyps < or = 2.0 cm in diameter, were found near the carcinoma of the resected rectum. Histologically, superficial parts of the polyps were composed of tubular adenomas, and basal parts of the polyps were hyperplastic dilated glands. It was speculated that, in the present case, the rectal adenocarcinoma arose from mucosal hyperplasia (Cronkhite-Canada polyp)-adenoma-carcinoma pathway. This suggested that Cronkhite-Canada syndrome has definite malignant potential, although the frequency of malignant transformation is thought to be low in Cronkhite-Canada syndrome.

Adenocarcinoma↗

PubMed2002

Analysis of Helicobacter pylori and nonsteroidal anti-inflammatory drug-induced gastric epithelial injury.

BACKGROUND: Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are important factors in gastric mucosal injury. However, the relationship between H. pylori and NSAID-related gastroduodenal mucosal injury has not been clarified. AIM: To determine the role of H. pylori in NSAID-induced gastric mucosal injury and to examine the effects of H. pylori, indomethacin and sofalcone on gastric epithelial cells in culture, as a useful model to study gastric mucosal injury. In addition, we studied the effect of sofalcone, a gastric mucosal protection agent, on H. pylori and NSAID-induced gastric mucosal injury. METHODS: Cytotoxic and noncytotoxic strains of H. pylori were used, each with an inoculum of 10(7) cfu/mL. The effect on the growth of RGM-1 cells (a rat gastric epithelial cell line) was studied by MTT assay, and levels of prostaglandin E2 in culture supernatants were measured by EIA. RESULTS: Both cytotoxic and noncytotoxic strains of H. pylori tended to induce cell injury in RGM-1 cells at 48 h after inoculation. Indomethacin alone induced gastric epithelial injury in a dose-dependent manner, but did not augment cell injury induced by H. pylori. In addition, sofalcone (10(-5) mol/L) showed a suppressive effect on indomethacin-induced gastric epithelial injury. CONCLUSION: These findings indicate that indomethacin induces gastric mucosal injury regardless of H. pylori infection, and suggests that sofalcone may be a useful drug in the treatment of NSAID-induced mucosal injury.

Animals↗

PubMed2001

Biosynthesis of acaterin: coupling of C(5) unit with octanoate.

Acaterin (1), produced by Pseudomonas sp. A 92, is a secondary metabolite having a 2-penten-4-olide structure. Feeding experiments with (2)H- and (13)C-labeled decanoic acid, their 3-oxygenated congeners, and octanoic acid have suggested that 1 is biosynthesized via coupling of a C(5) unit with octanoate, rather than via introduction of a C(3) unit at the alpha position of a decanoate derivative. Further feeding study of [2,3-(13)C(2)]decanoic acid concluded that the former route is operating in the biosynthesis of 1.

Caprylates↗

PubMed2001

Prognostic value of the colposcopic tumor size in stage IB squamous cervical cancer.

BACKGROUND AND OBJECTIVES: To determine the prognostic significance of the colposcopic tumor size in the management of cervical cancer. METHODS: Clinicopathological analysis was performed in 751 consecutive patients with stage IB squamous cervical cancer who were surgically treated in a single institute. The colposcopic tumor size was measured postoperatively on surgical specimens. Univariate and multivariate analyses were performed to determine the prognostic significance of various pathological factors. RESULTS: Among the pathological factors examined, lymph node metastasis, parametrial extension, deep stromal invasion, vessel permeation, endometrial extension, and colposcopic tumor size were found to be prognostic factors in univariate analysis, whereas multivariate analysis has confirmed that only three factors, i.e., lymph node metastasis, parametrial involvement, and colposcopic tumor size were independently associated with the disease-free interval. CONCLUSIONS: These results indicate that the colposcopic tumor size is an independent prognostic factor in squamous cervical cancer and can be used as an indicator of treatment options.

Adult↗

PubMed2001

Is the invasion depth in millimeters valid to determine the prognosis of early invasive cervical adenocarcinoma? A case of recurrent FIGO stage IA1 cervical adenocarcinoma.

BACKGROUND: Recurrence of FIGO stage IA1 cervical adenocarcinoma is extremely rare. We herein report a patient with early invasive cervical adenocarcinoma who developed a recurrence in the vaginal stump. CASE: A 52-year-old female complained of contact bleeding. Biopsy of the uterine cervix verified cervical adenocarcinoma, and the patient underwent Okabayashi hysterectomy with pelvic lymphadnectomy and bilateral adnectomy. Histopathologic examination of the uterus revealed an invasive cancer 3 mm in depth. Neither lymph node metastasis nor lymph-vascular space invasion was observed. However, the depth of her normal cervical gland area was 2 mm only, and the cancer invasion involved an area which was deeper than the normal cervical gland area. The vaginal stump recurrence developed 4 years after surgery. CONCLUSION: The depth of invasion with reference to that of normal cervical glands may become a possible prognostic factor for early invasive cervical adenocarcinoma.

Adenocarcinoma↗

PubMed2001

Positive peritoneal cytology in endometrial cancer: enhancement of other prognostic indicators.

OBJECTIVE: The goal of this study was to investigate the prognostic significance of positive peritoneal cytology in endometrial cancer. METHODS: A clinicocytopathological study was performed in 534 patients with endometrial cancer to assess the prognostic value of positive peritoneal cytology. The study population was divided into three groups: a low-risk group (disease limited to the uterus, grade 1, and depth of invasion < or =1/2), a moderate-risk group (disease limited to the uterus, grade 2 or 3, and/or depth of invasion >1/2), and a high-risk group (extrauterine disease). In each group, disease-free survival was compared in the patients who were positive or negative for malignant cells. RESULTS: The overall incidence of positive peritoneal cytology was 22.3% (119/534). The 5-year disease-free survival of patients positive or negative for malignant cells was 98.1% versus 100% in the low-risk group (n = 250), 77.5% versus 91.3% in the moderate-risk group (n = 211), and 42.9% versus 72.1% in the high-risk group (n = 73). A significant difference was noted in the moderate-risk (P = 0.044) and high-risk (P = 0.015) groups, but not in the low-risk group (P = 0.56). CONCLUSIONS: Positive peritoneal cytology is not a negative prognostic indicator itself, but it potentiates other prognostic indicators for endometrial cancer. Our findings also suggest that patients with positive peritoneal cytology in the absence of other adverse prognostic factors do not need upstaging.

Adult↗

PubMed2001

Effects of ipriflavone on bone loss following a bilateral ovariectomy and menopause: a randomized placebo-controlled study.

A randomized placebo controlled study was undertaken to evaluate the effect of ipriflavone (IP) against the bone loss in premenopausal ovariectomized women and postmenopausal women. Thirty-seven Japanese women who underwent premenopausal bilateral ovariectomy within 3 months (early stage group) and 52 Japanese women who were ovariectomized or who had undergone menopause more than 3 years before the start of the study (late stage group) were enrolled. The patients were randomly allocated into two groups: those who received IP (600 mg/day) and those who received placebo. The bone mineral density (BMD) of the lumbar vertebrae was measured by dual energy X-ray absorptiometry, and the markers of bone metabolism were measured at the same time that BMD was measured. In the early stage group, the IP group showed a 6.7% decrease in BMD from baseline levels, whereas the placebo group showed a 10.7% decrease (P < 0.01) at 12 months of treatment, and 7.1% and 12.6% decrease at 24 months of treatment, respectively (P < 0.01). In the late stage group, there was a 0.3% increase in BMD in the IP group and a 2.3% decrease in the placebo group at 6 months of treatment (P < 0.01), and similar changes were seen at 18 months (1.4% increase and 3.9% decrease; P < 0.01). IP suppressed bone loss compared with placebo, however, did not prevent acute bone loss in the early stage following ovariectomy. The effect of IP alone on bone loss in the early stage is not sufficient to reduce the risk of osteoporosis in later life.

Bone Density↗

PubMed2001

Malignant potential of positive peritoneal cytology in endometrial cancer.

OBJECTIVE: To investigate the malignant potential of positive peritoneal cytology in endometrial cancer. METHODS: Fifty patients with clinical stage I-II endometrial cancer in whom the disease was completely surgically resected and positive peritoneal smears were found at surgery formed the study population. In these patients, a tube for cytologic analyses was inserted into the peritoneal cavity when closing the abdomen. The peritoneal cavity was irrigated with physiologic saline, and washings were obtained through the tube 7 and 14 days after the operation. RESULTS: Persistence of positive peritoneal cytology was observed in four of seven patients with adnexal metastasis, zero of nine patients with nodal disease, and one of 34 patients with disease confined to the uterus, for a total of 10% (5 of 50). In the remaining 45 (90%) patients, no malignant cells were found in any of the washings. CONCLUSION: The current series suggests that endometrial cancer cells found in the peritoneal cavity usually disappear within a short time and seem to have a low malignant potential. It also seems that only malignant cells from special cases, such as adnexal metastasis, may be capable of independent growth, and are possibly associated with intraperitoneal recurrence.

Adenocarcinoma↗

PubMed2001

Biological characteristics and chemosensitivity profile of four human anaplastic thyroid carcinoma cell lines.

Anaplastic thyroid carcinoma is a rapidly growing, aggressive neoplasm affecting the elderly which does not respond to most of the therapies. We established cultured cell lines from four untreated tumors. The cultures grew in a monolayer of spindle-shaped cells in three cell lines and of small polygonal cells in one line, having relatively long doubling times and chromosomal abnormalities. The xenotransplantation of the lines in athymic nude mice produced tumors with a histology similar to the original tumors. The immunocytochemical staining showed the expression of PCNA, HLA-class 1, cytokeratin, vimentin and FAS (fatty acid synthase) but not CEA, desmin or P-glycoprotein. The lines secreted TPA, IL-6, IL-8 and few or no thyroid-related hormones in the culture supernatant. One cell line produced G-CSF. The chemosensitivity assay revealed intrinsic drug resistance to nine out of 11 antineoplastic agents. The reverse transcriptase-polymerase chain reaction (RT-PCR) detected MRP (multidrug resistance-associated protein) mRNA but not mdr (multidrug resistance protein)-1 and mdr-3 mRNAs. This finding indicates that the multidrug resistance of these lines is mediated by a P-glycoprotein-unrelated mechanism. The RT-PCR also presented FAS mRNA in all the lines, and IL-6 and IL-8 mRNAs in some of the lines.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by ikarugamycin.

One well-characterized in vitro function of Nef is its ability to remove CD4, the human immunodeficiency virus (HIV) receptor, from the cell surface. Nef accomplishes this by accelerating the internalization and degradation of CD4. Current models propose that Nef promotes CD4 internalization via an increased association of CD4 with clathrin-coated pits (CCP). Here, we investigated the effect of a naturally occurring antiprotozoan antibiotic, ikarugamycin (IKA), on CD4 cell surface expression in human monocytic cells stably expressing HIV type 1 SF2 Nef. IKA was able to efficiently restore CD4 cell surface expression in Nef-expressing cells without affecting either CD4 synthesis or Nef expression. In addition, we demonstrate that IKA is also capable of efficiently blocking CD4 down-modulation in response to phorbol myristate acetate. Our data suggest that IKA may be an efficient and useful inhibitor of CCP-dependent endocytosis.

Anti-Bacterial Agents↗

PubMed2001

Selective production of staplabin and SMTPs in cultures of Stachybotrys microspora fed with precursor amines.

Staplabin and SMTPs, a family of triprenyl phenol metabolites of Stachybotrys microspora, enhance fibrinolysis by modulating plasminogen conformation to increase its susceptibility to activation by plasminogen activators. We found that the production of these metabolites were markedly elevated by feeding the microbial culture with an amino acid or an amino alcohol that is a partial molecular constituent of the compound. Thus, the addition of 5-aminovaleric acid, 2-aminoethanol, Ser, Phe, Leu, Trp, Orn and Lys at 100 mg/ml resulted in 7- to 45-fold increases in the production of staplabin, SMTP-1, -3, -4, -5, -6, -7 and -8, respectively. Although the feeding at day 0 to 3 of culture supported the selective production, the supplementation after 5 days had little or no effect. When non-constituent amino acids were supplemented to cultures, production of hitherto uncharacterized congeners was observed.

Amino Acids↗

PubMed2000

Treatment of fallopian tube cancer. Review of the literature.

OBJECTIVE: To contribute toward the understanding of the therapeutic management of fallopian tube cancer. METHODS: Recent studies related to the treatment of fallopian tube cancer were reviewed. RESULTS: Current evidence indicates that even patients in early stages have nodal disease, and often experience relapses in distant sites. In advanced stages, survival prolongation by the use of platinum-based chemotherapy has been demonstrated. Aggressive cytoreductive surgery followed by chemotherapy and negative second-look laparotomy offer the possibility of long-term survival. However, a significant fraction of patients eventually relapses after negative second-look laparotomy, and a poor survival rate after positive second-look laparotomy has been observed. CONCLUSIONS: This series suggests the need for thorough evaluation of lymph nodes at the time of surgery. The use of platinum-based chemotherapy is probably the best adjuvant therapy for both early stages and advanced stages. The clinical value of second-look laparotomy will remain limited until effective salvage therapy is developed. The potential benefits of neoadjuvant chemotherapy and the use of paclitaxel will be increasingly important.

Fallopian Tube Neoplasms↗

PubMed2000

Dysfunctional regulation of the development of monocyte-derived dendritic cells in cancer patients.

Dendritic cells (DCs) are highly effective antigen (Ag)-presenting cells (APCs) that are required for the initiation of the immune response. DCs derived from cancer patients have been shown to be defective in several phenotypic and functional properties. However, little is known about the capacity of monocytes derived from cancer patients to differentiate into DCs. Herein, we examined the differentiation of monocyte-derived DCs in cancer patients. Flow cytometric analysis revealed that monocytes derived from cancer patients cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4) exhibited lower levels of CD11c, CD40, CD86, and HLA-DR expression as compared with those of monocyte-derived DCs from healthy volunteers. Furthermore, the capacities of DCs derived from cancer patients' monocytes to stimulate allogeneic T cell responses and to migrate in response to regulated-on-activation normal T cells expressed and secreted (RANTES) were impaired in comparison with those of monocyte-derived DCs from healthy volunteers. However, the two cell types had similar pinocytotic capacities for fluorescein isothiocyanate labeled-dextran (FITC-DX) and lucifer yellow (LY). These results suggest that monocytes from cancer patients may be defective in the capacity to develop into DCs.

Aged↗

PubMed2000

Inhibition of liver metastases and tumor cell invasion in spontaneous liver metastasis model (LMFS) by sodium D-glucaro-delta-lactam (ND2001).

We examined the inhibitory effect of sodium D-glucaro-delta-lactam (sodium 5-amino-5-deoxy-D-glucosaccharic acid-delta-lactam: ND2001) upon liver metastases of the LMFS tumor. A permanent cell line, LMFS, was established from a spontaneously occurring murine retroperitoneal tumor of BALB/c mouse origin, and after a subcutaneous injection, the LMFS cells proliferated at the inoculation site (100% take) with liver metastases. ND2001 had little effect on the cell growth, cell cycle and phagokinesis of the LMFS cells in vitro. However, when the invasive activity was measured by the Boydem chamber method, the number of LMFS cells was reduced, with inhibition rates of 98.0%. After the LMFS cells treated with ND2001 in vitro, the numbers of hepatic metastases of subcutaneous inoculation of treated cells were reduced dose-dependently, and those of intravenous inoculation were not found by microscopical study. When the LMFS tumor-bearing mice were treated with ND2001 (0, 30, 100 mg/kg/d) from day 1, ND2001 (30 mg/kg) inhibited the liver metastases with a rate of 56.4%, and when given from day 15, ND2001 (100 mg/kg) inhibited with a rate of 47.5%. But ND2001 showed neither cytocidal nor anti-tumor activity. Combination therapy of primary tumor resection and ND2001 administration revealed that preoperative use of ND2001 was more effective in preventing liver metastases. These results suggested that ND2001 might have a potential use as an anti-metastatic agent for operative patients without metastasis.

Animals↗

PubMed2000

Implication of ESR signals from ceruloplasmin (Cu(2+)) and transferrin (Fe(3+)) in pleural effusion of lung diseases.

Pleural effusions of seven lung cancer patients (mean age; 58) and seven non-cancer patients (mean age; 49) were examined and Cu(2+) was measured in ceruloplasmin and Fe(3+) in transferrin signals by electron spin resonance (ESR) method. The variations of total Fe and Cu ions, ceruloplasmin and transferrin, proteins, neutrophil cell counts, LDH and nitrite/nitrate were also examined. The Cu(2+) peak was decreased and the Fe(3+) peak was increased in the cancer group. The interrelationship among Cu(2+), total Cu and ceruloplasmin, and among Fe(3+), total Fe and transferrin clarified that Cu(2+) and Fe(3+) are not a representative of ceruloplasmin and transferrin, respectively. The ratio of Cu(2+)/Fe(3+) in pleural effusion distinguished lung cancer from benign inflammation as a cause. The ratio of total Cu/total Fe measured by the chemical analysis method also distinguished these, but the ratio of ceruloplasmin/transferrin was unable to distinguish the cancer. In conclusion, the simple and rapid measurement of Cu(2+)/Fe(3+) by ESR effectively abstracts the variation of total ion concentrations caused by malignant disease.

Journal Article↗

PubMed2000

The effect of Helicobacter pylori on cell proliferation and apoptosis in gastric epithelial cell lines.

BACKGROUND: Helicobacter pylori has been implicated in the pathogenesis of gastric cancer and malignant lymphoma. It is not known whether the bacterium stimulates cell proliferation directly or if apoptosis induced by H. pylori leads to a hyperproliferative response. AIM: To clarify the precise mechanism of H. pylori action on gastric epithelial cell growth, we compared the response of two cell lines, Kato III (p53 deletion) and MKN 45 (p53 wild type), to the organism. To determine the role of Helicobacter vacuolating cytotoxin in gastric mucosal injury, we examined the relation between vacuolating activity and apoptosis under several conditions. METHODS: Five cytotoxic and four noncytotoxic strains of H. pylori were used, each with an inoculum of 10(7) cfu/mL. The effect on the growth in MKN 45 and Kato III cells was studied by MTT assay. Vacuolating cytotoxin activity was determined using RK-13 cells. RESULTS: Neither cytotoxic nor noncytotoxic strains induced apoptosis, but death of MKN 45 cells was induced by pre-treatment with interferon-gamma and culture with TNF-alpha. In contrast, some strains of H. pylori increased proliferation of Kato III cells. Furthermore, cell death induced by cytotoxic strains, but not noncytotoxic strains, was significantly augmented by amoxycillin 5-50 g/mL (P=0.0016). On the other hand, acid-treated supernatant fluids from cultures of H. pylori showed enhanced vacuolating activity but did not induce cell death, suggesting that death is attributable to some factor other than the cytotoxin. CONCLUSION: These findings suggest that H. pylori induces apoptosis by a means independent of vacuolating cytotoxin.

Apoptosis↗

PubMed2000

Genetic aberrations detected by comparative genomic hybridization in ovarian clear cell adenocarcinomas.

Genetic abnormalities were detected by comparative genomic hybridization (CGH) in 12 ovarian clear cell adenocarcinomas. DNA sequence copy number abnormalities (CNAs) occurring in more than 20% of the cancers included increased copy numbers of 8q11-q13, 8q21-q22, 8q23, 8q24-qter, 17q25-qter, 20q13-qter and 21q22-qter and reduced copy numbers of 19p. Increases in copy numbers of 8q11-q13, 8q21-q22, 8q23 and 8q24-qter occurred more frequently in disease-free patients than in recurrent/non-surviving patients (p < 0.05). However, increases in copy numbers of 17q25-qter and 20q13-qter occurred more frequently in recurrent/non-surviving patients than in disease-free patients (p < 0.05). Furthermore, increases in copy numbers of 17q25-qter and 20q13-qter occurred together (p < 0.05). Additionally, there were negative correlations between increases in copy numbers of 8q21-q22 and 17q25-qter, and between 8q21-q22 and 20q13-qter (p < 0.05). It appears that ovarian clear cell adenocarcinomas can be classified into two subtypes, one being cancer with an increase in copy numbers of 8q and the other being cancer with increases in copy numbers of 17q25-qter and 20q13-qter.

Adenocarcinoma, Clear Cell↗

PubMed2000

Activation of fibrinolysis by SMTP-7 and -8, novel staplabin analogs with a pseudosymmetric structure.

Two novel staplabin analogs, SMTP-7 and -8, have been isolated from cultures of Stachybotrys microspora IFO 30018. Spectroscopic analyses showed that the SMTP-7 molecule consisted of two identical staplabin core structures and ornithine which bridges the two partial structures. In the SMTP-8 molecule, the bridging unit was lysine. At concentrations of 80 approximately 150 microM, the two compounds caused 2- to 12-fold increase in urokinase-catalyzed plasminogen activation, fibrin binding of plasminogen, and urokinase- and plasminogen-mediated fibrinolysis. These activities of SMTP-7 and -8 were two to ten times higher than those of staplabin and previously isolated SMTPs, which exerted such effects at concentrations ranging from 150 to 800 microM.

Benzopyrans↗