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Biomedical subjects

K Hasumi

Publications and source records attributed to K Hasumi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enhancement of fibrinolytic activity of vascular endothelial cells by chaetoglobosin A, crinipellin B, geodin and triticone B.

Four fungal metabolites, chaetoglobosin A (CGA), crinipellin B (CPB), geodin (GE) and triticone B (TTB), were found to enhance fibrinolytic activity of bovine aortic endothelial cells. Plasmin generation on the cells was elevated 2- to 4-fold when treated with these agents at a concentration of 3 approximately 100 microM. These effects were dependent on plasminogen and inhibited by anti-urokinase antibody. The effect of CGA, but not of CPB, GE and TTB, was abolished by cycloheximide. In a cell-free system, plasmin and urokinase activities as well as urokinase-catalyzed plasminogen activation were not enhanced by these agents. CGA, but not others, induced the production of urokinase in endothelial cells. CPB and GE accelerated plasminogen activator inhibitor- 1 (PAI-1) inactivation, and TTB caused direct, reversible inhibition of PAI-1. Thus, induction of urokinase by CGA and inhibition of PAI-1 by CPB, GE and TTB may, at least partly, account for the elevation of fibrinolytic activity of endothelial cells.

Animals↗
PubMed1999

Assessment of the revised International Federation of Gynecology and obstetrics staging for early invasive squamous cervical cancer.

OBJECTIVE: The aim of this study was to investigate the value of the International Federation of Obstetrics and Gynecology (FIGO) classification (1995) for early invasive cervical cancer. Methods. Clinico-pathological analysis was performed in 402 patients with invasive squamous cervical cancer in whom the depth of stromal invasion was 5 mm or less. RESULTS: The incidence of lymph node metastasis was 1.2% (1/82) in patients with 3 mm or less depth of invasion; the node-positive patient was in stage IA1. The incidence of lymph node metastasis was 6.8% (5/73) in patients with 3-5 mm depth of invasion; this increased with increasing horizontal spread from 3.4% for 7 mm or less to 9.1% for more than 7 mm. None of the patients in this series had metastasis to the parametrial tissues. Of 4 patients with recurrence, 3 had horizontal spread of more than 7 mm and the remaining patient was in stage IA2. CONCLUSION: The FIGO definition of early squamous cervical cancer is generally acceptable in its present form.

Adult↗
PubMed1999

Low-grade endometrial stromal sarcoma with cardiovascular involvement--a report of three cases.

BACKGROUND: In low-grade endometrial stromal sarcoma, it has been reported that vascular space involvement in surgical specimens is found in over 50% of patients. However, in contrast to intravenous leiomyomatosis, it has been thought that further tumor extension to large vessels is rarely observed. CASES: We present three cases of low-grade endometrial stromal sarcoma with cardiovascular involvement by recurrent tumors observed on imaging studies. Two cases demonstrated tumor infiltration inside the inferior vena cava while the other case showed tumor growth in the left ventricle. CONCLUSION: This report suggests that attention should be paid to the possibility of cardiovascular invasion during the entire course of this disease.

Adult↗
PubMed1999

Utility of the monoclonal antibody HIK1083 in the diagnosis of adenoma malignum of the uterine cervix.

OBJECTIVES: The aim of this study was to qualify a staining technique for the diagnosis of adenoma malignum. METHODS: The gastric mucin expression of adenoma malignum, ordinary endocervical adenocarcinoma, and normal cervical glands was immunohistochemically compared using the monoclonal antibody HIK1083. RESULTS: The three categories were clearly distinguished, with 90% (9/10) of cases with positive adenoma malignum, 30% (3/10) of cases with weakly positive ordinary cervical adenocarcinoma, and no (0/10) cases of positive normal cervical glands. CONCLUSIONS: This preliminary report indicates that the use of HIK1083 is valuable in the diagnosis of adenoma malignum.

Adenoma↗
PubMed1999

Inhibition of plasminogen activator inhibitor-1 by 11-keto-9(E),12(E)-octadecadienoic acid, a novel fatty acid produced by Trichoderma sp.

We have recently found a novel fatty acid, 11-keto-9(E),12(E)-octadecadienoic acid (KOD), that enhances fibrinolytic activity of endothelial cells. The mechanism of action of KOD has been investigated. KOD increased 2-fold the plasmin activity of bovine aortic endothelial cells at 250 microM. The stimulation was dependent on plasminogen and was inhibited by anti-urokinase, whereas KOD did not enhance the urokinase-catalyzed plasminogen activation and the resulting plasmin activity in a cell-free system. Neither the production of urokinase nor the conversion of pro-urokinase to the active, two-chain form was elevated by KOD, but it decreased plasminogen activator inhibitor-1 (PAI-1) activity of cells and inactivated PAI-1 irreversibly in a purified system. These results demonstrated that the KOD enhancement of endothelial fibrinolytic activity was mediated, at least in part, by inactivation of PAI-1.

Animals↗
PubMed1999

[Chemotherapy with consecutive low-dose CDDP combined with 5-FU for gynecologic malignancies].

CDDP is generally given in a bolus fashion because it has been considered to act in a dose-dependent manner. However, early studies demonstrated anti-tumor activity of CDDP was both dose- and time-dependent. This indicated that the anti-tumor effect of CDDP dependent on the area under the concentration of filterable platinum-time curve (AUC) obtained following an administration of the agent, but not on the maximum concentration (C max) of the agent. To increase the AUC and treatment compliance, we designed a consecutive low-dose CDDP dosing method (10 mg/m2, days 1-7). This method was found to be accompanied by a good treatment compliance and high dose intensity due to significantly reduced toxic effects when CDDP was combined with several other agents. 5-FU alone has been reported to be effective in approximately 20-25% of gynecologic malignancies. Moreover, CDDP can augment the cytotoxic activity of 5-FU through biochemical modulation. Accordingly, combination treatment with consecutive low-dose CDDP with 5-FU could be designed. The present report reviews the efficacy of this combination chemotherapy for cervical carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Effects of HCFU and TNP 470 on liver metastasis of BALB/c retroperitoneal sarcoma (LMFS)].

Combination therapy using HCFU and TNP 470, which inhibits angiogenesis, was examined for effectiveness against the footpad injection model of LMFS tumor. This LMFS, a retroperitoneal sarcoma of BALB/c mice, proliferated at the inoculation site (100% take) and all mice operated on after day 15 had spontaneous metastatic nodules in the liver. Mice with the LMFS tumor were given HCFU and 5-FU (5 days/week), and/or TNP 470 (3 days/week) from day 3 for 3 weeks and sacrified at day 28 under anesthesia. Seven of 10 mice receiving 5-FU and TNP 470 died from the side effects of the drugs. Mean tumor weight and liver metastatic nodules were determined and compared with a control group. The results were as follows: HCFU group: 94.6%, 11.8%, 5 FU group: 73.9%, 28.8%, TNP 470 group: 67.6%, 44%, HCFU and TNP 470 group: 33.3%, 6.4%. Mice with LMFS were given HCFU and/or TNP 470 from day 3 for 4 weeks. The foot on the injected side was amputated on day 15, and the animals were sacrified on day 35. Liver metastatic nodules compared with those of the operation (OP) group as follows: OP + HCFU group: 14.4%, OP + TNP group: 39.1%, and OP + HCFU + TNP 470 group: 5.4%. Histologically, 5 of 5 mice of the OP group, 3 of 5 of the OP + HCFU group, 4 of 5 of the OP + TNP 470 group and 1 of 5 of the OP + HCFU + TNP 470 group had liver metastases. These results show that while either HCFU or TNP 470 is effective by itself, a combination of these drugs is more effective against liver metastasis.

Angiogenesis Inhibitors↗
PubMed1998

Induction of low-density lipoprotein catabolism in Hep G2 cells by a fungal sesquiterpene ester, FR111142.

A search for agents that can enhance low density lipoprotein (LDL) catabolism in Hep G2 cells has led to the identification of a fungal sesquiterpene ester, FR111142, as an active compound. The treatment of Hep G2 cells with 40 microM FR111142 at 37 degrees C for 18 h caused a 1.9- to 2.2-fold elevation of binding, internalization and degradation of 125I-LDL in the cells. The Scatchard analysis of the specific 125I-LDL binding demonstrated that the agent caused an increase in the maximum LDL binding along with a slight decrease in the apparent dissociation constant value. The effect of FR111142 was not seen in cells treated by the agent for shorter periods or in cycloheximide-treated cells, suggesting that the effect involves an induction of LDL binding sites. Unlike 3-hydroxy-3-methyglutaryl CoA reductase inhibitors, FR111142 affected neither cholesterol synthesis nor the level of LDL receptor in Hep G2 cells. These results suggest that FR111142 enhances LDL catabolism in Hep G2 cells by a mechanism that involves a receptor other than LDL receptor.

Anticholesteremic Agents↗
PubMed1998

The incidence of subsequent endometrial carcinoma with tamoxifen use in patients with primary breast carcinoma.

BACKGROUND: Tamoxifen commonly is used as adjuvant therapy for all stages of breast carcinoma. However, several studies have suggested an association between the use of tamoxifen in breast carcinoma patients and the subsequent development of endometrial carcinoma. The objective of this study was to determine the relation between long term tamoxifen usage and the risk of endometrial carcinoma in patients with breast carcinoma and to determine whether the increase in the cumulative incidence of endometrial carcinoma observed in previous studies is a true increase. METHODS: Eight hundred and twenty-five patients with primary breast carcinoma who underwent annual gynecologic examination and cancer screening were reviewed. None of the patients had undergone hysterectomy or received any prior estrogen replacement therapy. These patients underwent a pelvic examination and cytologic and/or histologic screening of the cervix and endometrium every year even if they had no gynecologic symptoms. The dose of tamoxifen, length of tamoxifen treatment, and potential confounding variables were recorded. The relative risk of subsequent endometrial carcinoma in patients with primary breast carcinoma was analyzed by the Cox proportional hazards model. RESULTS: Thirteen of the 825 patients developed a subsequent endometrial carcinoma. The cumulative incidence of endometrial carcinoma was 1.58%. Four of 13 patients who subsequently developed endometrial carcinoma received tamoxifen and 9 had not received tamoxifen. The relative risk of endometrial carcinoma by total dose of tamoxifen exposure was 1.0001 (P = 0.0145). There was no statistically significant correlation between the cumulative dose of tamoxifen or the length of tamoxifen treatment and the histologic type and grade of endometrial carcinoma. In addition, there was no statistical difference in the prognosis of endometrial carcinoma between the patients who received tamoxifen and patients who did not. CONCLUSIONS: The results of this study show that tamoxifen use does not appear to increase the incidence of subsequent endometrial carcinoma in patients with primary breast carcinoma who underwent annual screening for gynecologic carcinoma.

Adult↗
PubMed1998

The value of squamous cell carcinoma antigen as a predictor of nodal metastasis in cervical cancer.

Preoperative serum squamous cell carcinoma antigen (SCC) levels were examined in 148 cases of stage Ib squamous cervical cancer undergoing radical hysterectomy. The effect of the pelvic lymph node status on the marker level was examined by comparing 113 cases with cancer limited to the uterus and 23 cases with cancer confined to the uterus and pelvic lymph nodes using two different multivariate analyses. Ninety-five percent of patients with cancer limited to the uterus showed SCC levels of 4 ng/ml or below. Nearly two-thirds (65%) of patients with serum levels above 4 ng/ml exhibited pelvic lymph node metastasis. The marker values exceeding 4 ng/ml increased the risk of nodal metastasis by eight times, compared with serum levels of 4 ng/ml or below. Multivariate analyses confirmed that the pelvic lymph node metastasis had a larger impact on the marker level than did tumor size or depth of stromal infiltration. SCC levels greater than 4 ng/ml can be considered a high-risk zone for nodal metastasis.

Adolescent↗
PubMed1998

Toward the development of a universal grading system for ovarian epithelial carcinoma. I. Prognostic significance of histopathologic features--problems involved in the architectural grading system.

OBJECTIVE: Because there is no universally accepted grading system for ovarian epithelial carcinoma, we attempted to compare the prognostic utility of the individual components used in some systems--both architectural and cytologic features, as well as mitotic activity and histologic tumor type--to determine which of these components fit best with survival. METHODS: We studied 461 patients with invasive ovarian carcinoma who had uniform treatment, complete clinical data including staging and follow-up, and slides available for review. Each tumor was assigned a histologic subtype, architectural grade (based on whether the predominant pattern was glandular, papillary or solid), nuclear grade, mitotic count, and FIGO grade (based on the system for endometrial carcinoma). These features were compared with each other and with tumor stage and survival. RESULTS: The architectural grade, nuclear grade, and mitotic count were independent variables both in stage I/II and stage III/IV disease. Each of them correlated with survival for most combinations of histologic type and stage. By multivariate analysis, in stage I/II cancer, nuclear grade and architectural grade were significantly correlated with survival, mitotic count showed only a trend, and FIGO grade did not correlate. In stage III/IV disease, nuclear grade, architectural grade 3, and mitotic count were significant, and FIGO grade was not. CONCLUSION: The new architectural grading system proposed worked better than the FIGO system in this study. Furthermore, it could be applied to all histologic subtypes of carcinoma. The nuclear grade and mitotic count were also independent of each other, correlated with survival, and could be utilized for all histologic types. These data support the development of a grading system which combines these architectural, nuclear, and mitotic features and can be applied regardless of the histologic type of carcinoma, modeled after the Nottingham system for grading of breast carcinoma.

Carcinoma↗
PubMed1998

Ovarian metastasis in endometrial carcinoma.

A retrospective study was conducted to investigate the clinical significance of ovarian metastasis in 439 patients with clinical stage I endometrial cancer surgically treated by performing total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Histologic examination revealed that 22 patients (5%) had ovarian metastasis. The maximum diameter of the ovarian metastases ranged from 1 to 100 mm. In 18.2% (4/22) of patients with ovarian metastasis, the maximum diameter was less than 2 mm. Patients with metastasis limited to the ovarian surface showed 100% positive peritoneal cytology, 0% lymph node metastases, and 50% recurrence, while patients with metastasis inside the ovary showed 10% positive peritoneal cytology, 36% lymph node metastases, and 53% recurrence. The prognosis of patients with ovarian metastasis alone was situated midway between that of patients with cancer limited to the uterus and that of patients with lymph node metastasis alone. The lymph node status was of importance to determine the prognosis of patients with ovarian metastasis. The series also suggests that there may be two routes for ovarian metastasis; one is a route via the fallopian tube to the ovarian surface and the other is a route via the lymphatics to the inside of the ovary.

Analysis of Variance↗
PubMed1998

A clinicocytopathologic study of adenoma malignum of the uterine cervix.

OBJECTIVES: To investigate the nature and the clinical course of adenoma malignum (the so-called minimal deviation adenocarcinoma) of the uterine cervix by conducting a retrospective study of 6 cases consecutively treated in a single institute. METHODS: The pathologic classification of adenoma malignum was performed according to the WHO classification (1994). RESULTS: These tumors accounted for only 1.32% (6/453) of invasive cervical adenocarcinomas. All the cases showed either a watery discharge or atypical genital bleeding, or both, at the time of diagnosis. The preoperative cytologic diagnosis of adenoma malignum was made in 83.3% (5/6) of cases. The preoperative punch biopsy, on the other hand, failed to confirm the diagnosis of adenoma malignum in all cases, although the presence of the disease was suspected in 2 cases (33%). The 5-year survival rate and 5-year disease-free survival rate were 100 and 83.3%, respectively. CONCLUSIONS: This series demonstrates that cytologic examination is a potent screening method to detect this rare disease. When the presence of this disease is suspected by the cytologic examination, a deep biopsy is necessary to make an accurate diagnosis. An ordinary cervical biopsy is usually insufficient to detect deeply positioned tumor glands. The prognosis of the disease may be better than that for ordinary cervical adenocarcinoma.

Adenocarcinoma, Mucinous↗
PubMed1998

Enhancement of low density lipoprotein binding to both low density lipoprotein receptor-positive and -negative cells by tetracycline antibiotics.

Some tetracycline (TC) antibiotics, including TC and anhydrotetracycline, have been found to enhance specific binding of low density lipoprotein (LDL) to both LDL receptor-positive and -negative cells at relatively higher concentrations. When incubated at 37 degrees C, the ability of LDL receptor-negative human fibroblasts to bind 125I-LDL was increased from < 2 to 45 ng/mg by 170 microM TC. In normal human fibroblasts and Hep G2 cells, 125I-LDL binding was elevated 1.4- to 2-fold by 113 microM TC. The 125I-LDL binding in the presence of TC was diminished by both heparin and EDTA. The enhancement by TC was not observed when 125I-LDL binding was assayed at 4 degrees C. TC enhanced LDL binding to paraformaldehyde-fixed Hep G2 cells, excluding LDL receptor induction in the mechanism. These results demonstrated that TC enhanced cellular LDL binding through a process not involving functional LDL receptors.

Anti-Bacterial Agents↗
PubMed1998

Prognostic validity of neoplastic cells with notable nuclear atypia in endometrial cancer.

OBJECTIVE: To investigate how the architectural grade of endometrial adenocarcinoma should be adjusted in the presence of neoplastic cells with notable nuclear atypia in order to assign the histologic grade. METHODS: Four hundred seventy-six patients with stage I endometrial cancer (endometrioid type) who were surgically treated in a single institute formed the study population. The architectural grade and the proportion of tumor cells with notable nuclear atypia were examined for each case. The effects of notable nuclear atypia on the disease-free survival of each architectural grade were analyzed. RESULTS: The disease-free survival of architectural grade 1 and grade 2 tumors was significantly affected and was worse than that of architectural grade 3 tumors when more than 25% of the tumor cells showed notable nuclear atypia. Tumors that had 26% to 50% of neoplastic cells with notable nuclear atypia showed a similar probability of recurrence as did tumors that had more than 50% of neoplastic cells with notable nuclear atypia. CONCLUSION: The series suggests that the upgrading of architectural grade 1 or 2 tumors, in which more than 25% of the neoplastic cells show notable nuclear atypia, into a grade 3 tumor may be more practical than upgrading by one architectural grade 1 or 2 tumors, in which the majority of neoplastic cells show notable nuclear atypia.

Adenocarcinoma↗
PubMed1998

Combination of consecutive low-dose cisplatin with bleomycin, vincristine, and mitomycin for recurrent cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of combination chemotherapy with bleomycin, vincristine, mitomycin, and consecutive low-dose (CLD) administration of cisplatin (CLD-BOMP) for patients with recurrent cervical carcinoma. PATIENTS AND METHODS: Ninety patients with recurrent cervical carcinoma and no prior chemotherapy were enrolled onto this study. The median age was 56 years. Eighty-seven of the 90 patients had received prior radiotherapy. The CLD-BOMP regimen was bleomycin 5 mg infused continuously days 1 through 7; vincristine 0.7 mg/m2 bolus day 7; mitomycin 7 mg/m2 bolus day 7; and cisplatin 10 mg/m2 infused over 4 hours days 1 through 7. The treatment was repeated at 3-week intervals. RESULTS: All 90 patients were assessable for response, toxicity, and survival. After a median of four cycles (range, two to 10 cycles), we observed objective responses in 68 patients (76%), with 25 (28%) complete responses (CRs) and 43 (48%) partial responses (PRs; 95% confidence interval (CI), 66 to 85; 18 to 38; 37 to 59, respectively). Median survival for all 90 patients was 24.3 months (range, 2.3 to 100 months). The median survival for patients who achieved CR, PR, no change (NC), and progressive disease (PD) were not reached (NR), 23.6, 8.2, and 6.4 months, respectively. The median progression-free survival for patients who achieved CR and PR were NR and 12.3 months, respectively. There was no significant nausea or vomiting, nephrotoxicity, or pulmonary toxicity, which was attributable to the CLD-cisplatin and the adequate dosing schedule of bleomycin. The reduced toxicities allowed this regimen to be administered at the projected dose-intensities. CONCLUSION: The CLD-BOMP regimen has significant antitumor activity with markedly reduced toxicity.

Adult↗
PubMed1998

Isolation of SMTP-3, 4, 5 and -6, novel analogs of staplabin, and their effects on plasminogen activation and fibrinolysis.

Four novel triprenyl phenol metabolites, designated SMTP-3, -4, -5, and -6, have been isolated from cultures of Stachybotrys microspora IFO 30018 by solvent extraction and successive chromatographic fractionation using silica gel and silica ODS columns. A combination of spectroscopic analyses showed that SMTP-3, -4, -5, and -6 are staplabin analogs, containing a serine, a phenylalanine, a leucine or a tryptophan moiety in respective molecules in place of the N-carboxybutyl portion of the staplabin molecule. SMTP-4, -5, and -6 were active at 0.15 to 0.3 mM in enhancing urokinase-catalyzed plasminogen activation and plasminogen binding to fibrin, as well as plasminogen- and urokinase-mediated fibrinolysis. On the other hand, the concentration of staplabin required to exert such effects was 0.4 to 0.6 mM, and SMTP-3 was inactive at concentrations up to 0.45 mM.

Benzopyrans↗