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Biomedical subjects

K Hasumi

Publications and source records attributed to K Hasumi.

At least 73 records · Page 4Linked to original sources

[Characterization of spontaneous liver metastatic model of BALB/c retroperitoneal sarcoma (LMFS) injected in footpad and antitumor effects of HCFU].

A new spontaneous liver metastasis model from LMFS tumor, a retroperitoneal sarcoma of BALB/c mouse origin, was reported. After a subcutaneous injection of LMFS cells in the footpad, amputation of the leg was performed every 5 days from day 5 to day 20, and mice were killed at day 25 under anesthesia. The LMFS cells proliferated at the inoculation site (100% take), and all mice operated after day 15 had metastatic nodules spontaneously in the liver. Local recurrence was not observed in any cases. Liver weight was correlated with tumor growth in the liver. The combination therapy of operation and HCFU was examined in comparison with the footpad injection model. The foot on the injection side was amputated on day 12 with or without HCFU administration, and mice were sacrificed on day 33 under anesthesia. Histological liver metastases were as follows: 1. no treatments: 100%; 2. early phase chemotherapy without operation: 80%; 3. operation without chemotherapy: 80%; 4. postoperative chemotherapy: 20%; 5. preoperative chemotherapy: 40%; and 6. late phase chemotherapy without operation: 100%. These results indicate that operation with chemotherapy is the most useful treatment for liver metastases. Using this liver metastatic model, we are investigating a new combination therapy of operation and anti-cancer drugs for liver metastases.

Animals↗

Estimation of the malignancy of pleural effusions by electron spin resonance.

We conducted an electron spin resonance (ESR) study on human pleural effusions obtained from patients (n = 15) with and without cancer at 77 K. We detected two kinds of signals which are considered to be due to transition metal ions in metalloproteins such as Fe3+ in transferrin and Cu2+ in ceruloplasmin from their g values (g = 4.2 and 2.049) and line shapes. We found a significant difference in the signal intensity ratio, Cu2+/Fe3+, of the pleural effusions between cancer and noncancer patients by the Mann-Whitney U test (P < 0.01). The ESR study of pleural effusion enabled us to estimate its malignancy and may have future applications.

Electron Spin Resonance Spectroscopy↗

Serum N-terminal osteocalcin is a good indicator for estimating responders to hormone replacement therapy in postmenopausal women.

To estimate the response to hormone replacement therapy (HRT) by bone metabolic markers, 36 patients with postmenopausal osteoporosis or osteopenia were studied to assess the correlation between percent baseline changes in lumbar bone mineral density (BMD) after 12 months and those in various bone metabolic markers after 3, 6, and 12 months of HRT. All the patients were treated with 0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone per day and continued for 12 months. BMD was significantly increased up to 4.19 +/- 0.87% after 6 months and 4.93 +/- 1.27% after 12 months of HRT (p = 0.0001 by analysis of variance). In accordance with this, changes in the levels of osteocalcin (p = 0.041), alkaline phosphatase (p = 0.0001), N-terminal osteocalcin (p = 0.0001), urinary excretion of pyridinoline/Cr (p = 0.0001), and deoxypyridinoline/Cr (p = 0.0001) were significantly decreased, respectively. Among these bone metabolic markers, only the change in the serum N-terminal osteocalcin at 3 months (r = 0.557, p = 0.0022), at 6 months (r = 0.470, p = 0.0184), and at 12 months (r = 0.545, p = 0.0061) significantly correlated with the change in BMD 12 months after HRT. The elution profiles of immunoreactive osteocalcin-related molecules in serum fractionated by reverse-phase high performance liquid chromatography revealed that the N-terminal fragment as well as the intact osteocalcin molecule decreased after 3 months of HRT. These results demonstrate that N-terminal osteocalcin is a suitable predictor for estimating good responders to HRT in postmenopausal women.

Analysis of Variance↗

Ovarian hemangioma associated with concomitant stromal luteinization and ascites.

A 62-year-old female presented with a pelvic mass and ascites. The Papanicolaou vaginal smear showed an unusual maturation, maturation index being 0/80/20. The serum level of estradiol was 48.7 pg/ml. The preoperative checkup suggested a pelvic malignancy with a differential diagnosis of hormone-secreting ovarian tumor. On surgical exploration, she had a hemangioma of the ovary without malignant cytology in the ascitic fluid. Histologically, this tumor was associated with stromal luteinization. This is the first case, reported in the literature, possessing ovarian hemangioma with stromal luteinization accompanying massive ascites. It should be noted that an ovarian hemangioma can be associated with stromal luteinization and ascites, and that MR imaging is sometimes of value for making a preoperative diagnosis of ovarian hemangioma.

Ascites↗

Pelvic lymph node metastasis in endometrial cancer with no myometrial invasion.

OBJECTIVE: To analyze the incidence of pelvic lymph node metastasis in endometrial carcinoma with no myometrial invasion. METHODS: Between 1971 and 1995, 684 women with stage I endometrial carcinoma underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph-adenectomy. The incidence of pelvic lymph node metastases in 100 cases without myometrial invasion was examined. RESULTS: Histologic examination of the surgical specimens revealed a single pelvic lymph node metastasis in each of four cases. The incidence of pelvic lymph node metastasis was four of 83 in grade 1, zero of 13 in grade 2, and zero of four in grade 3 tumors. CONCLUSION: Pelvic lymph node metastasis in endometrial cancer with no myometrial invasion is not rare, even with grade 1 tumors. Lymphadenectomies may be necessary in all patients with endometrial cancer, except when clinical or operative factors increase the procedure's risk of morbidity.

Adenocarcinoma↗

Serum levels of squamous cell carcinoma antigen and carcinoembryonic antigen as tumor markers of vulvar cancer.

OBJECTIVE: To assess whether squamous cell carcinoma (SCC) antigen and carcinoembryonic antigen (CEA) are useful as tumor markers of vulvar cancer. METHODS: The serum levels of SCC antigen and CEA were determined for 30 patients with invasive vulvar carcinoma. RESULTS: There was a significant difference not only between tumor sizes of 2 cm or larger and those of less than 2 cm (p < 0.001), but also between patients with lymph node metastasis and patients free from it (p < 0.001). Tumor marker levels well reflected the response to neoadjuvant chemotherapy. The sensitivity to recurrence was 63%, and the specificity was 94%. In 2 of 8 recurrent cases, it was only the re-increase in tumor markers that indicated the recurrence. CONCLUSION: The measurement of serum levels of SCC antigen and CEA is useful not only for preoperative evaluation of the risk of lymph node metastasis, but also for the detection of recurrence.

Adenocarcinoma↗

Studies on agents with vasodilator and beta-blocking activities. IV.

A series of novel pyridazinone derivatives (II) having a phenoxypropanolamine moiety was synthesized. Their hypotensive and beta-blocking activities were evaluated after intravenous administration of the compounds to anesthetized rats. Among them, the 5-chloro-2-cyanophenoxy derivative (29) showed the promising dual activities and was selected for further studies.

Adrenergic beta-Antagonists↗

Isolation of plactins A, B, C and D, novel cyclic pentapeptides that stimulate cellular fibrinolytic activity.

Four novel cyclic pentapeptides, designated plactins A, B, C and D, were isolated by solvent extraction and reverse-phase HPLC from mycelium of a fungal strain F165 that belongs to the order of Agonomycetales. By a combination of chemical and spectroscopic analyses and chemical synthesis, the structures of plactins A, B, C and D were determined to be cyclo(-D-Val-L-Leu-D-alloIle-L-Try-D-Arg-), cyclo(-D-Val-L-Leu-D-Leu-L-Tyr-D-Arg-), cyclo(-D-Val-L-Leu-D-alloIle-L-Phe-D-Arg-) and cyclo(-D-Val-L-Leu-D-Leu-L-Phe-D-Arg-), respectively. Plactins stimulated U937 cell-mediated degradation of 125I-fibrin plates by 50% at a concentration of 7.5 approximately 32 microM.

Amino Acid Sequence↗

Staplabin, a novel fungal triprenyl phenol which stimulates the binding of plasminogen to fibrin and U937 cells.

A novel triprenyl phenol, designated staplabin, has been isolated from a culture of Stachybotrys microspora IFO 30018 by solvent extraction and successive chromatographic fractionation using silica gel, Sephadex LH-20 and silica ODS columns. By a combination of spectroscopic analyses, the structure of staplabin is proposed to be 5-(2-(5,7-dihydroxy-8-methyl-8-(4,8-dimethyl-3,7-nonadienyl)-3-oxo -7, 8-dihydro-6H-pyrano[2,3-e][1,3]dihydroisoindolyl)pentanoic acid. Staplabin stimulated the binding of plasminogen, the zymogen of the fibrinolytic serine protease plasmin, to both fibrin and U937 cells. Binding was elevated 2-fold at a concentration of 0.3 approximately 0.5 mM.

Benzopyrans↗

[Successful treatment of clear cell adenocarcinoma of the ovary (OCCA) with a combination of CPT-11 and mitomycin C].

Among advanced ovarian cancer, OCCA has worse prognosis compared with serous cystadenocarcinoma because of its poor sensitivity to CDDP-based chemotherapy (CTX). Indeed, there has ever been no one patient with pure OCCA showing an appreciable response to CTX. OCCA has recently been increasing in prevalence and has occupied approximately 20-25% of all ovarian cancer. Thus, there is an urgent need to find effective regimens. Based on the results of chemosensitivity tests previously performed both in vitro and in vivo, we designed a combination of CPT (140 mg/m2, i.v.-infused over 4 hours on day 1, 15, and 29) and MMC (7 mg/m2, i.p. injection through a reservoir on day 1, 15, and 29). The course was repeated every 4 weeks. To date 10 pts were entered The median age was 53 (41-69). Among total 25 courses, grade 3 diarrhea was observed in 3 courses. Other toxic signs were acceptable. The responses by tumor size were 2 CR for disease < or = 2 cm in diameter, and 2 CR, 2 PR, 2 NC, and 2 PD for > 2 cm. Six responders showed a significantly longer survival compared with 4 non-responders (p < 0.0396 for Log-rank test). Thus, the present protocol is the first to demonstrate a significant activity for pure OCCA.

Adenocarcinoma, Clear Cell↗

[Feasibility of peritoneal washing cytology through the totally implanted reservoir for early detection of peritoneal recurrence of ovarian cancer].

UNLABELLED: There have been no reliable ways to follow up ovarian cancer patients receiving optimal debulking. In this study, we assessed the feasibility of cytological diagnosis on peritoneal washing cells collected through a totally implanted reservoir as a tool in following up these patients. Between 1988 and 1993, 31 patients underwent optimal debulking and were implanted with a reservoir. After the operation, the patients were followed up at 2-4 week intervals with peritoneal washing cytology. Six patients were diagnosed as having a recurrence by the peritoneal washing cytology alone. And at this point there had been no other positive findings by other conventional methods. There were no complications caused by reservoirs. Activated mesothelial cells, multinucleated histiocytes and hemosiderine-laden histiocytes were characteristic cytologic findings accompanying adenocarcinoma cells. Hemosiderin-laden histiocytes were found by peritoneal washing cytology even before the appearance of adenocarcinoma cells. The appearance of hemosiderin-laden histiocytes may therefore be a sign of intraperitoneal recurrence of ovarian cancer. CONCLUSION: 1) Peritoneal washing cytology through a reservoir is useful for early detection of intraperitoneal recurrence of optimally debulked ovarian cancer without any significant complications. 2) The appearance of intraperitoneal hemosiderin-laden histiocytes may be sign of intraperitoneal recurrence of ovarian cancer.

Adult↗

[A clinicopathological study in clear cell adenocarcinoma of the endometrium].

We clinicopathologically reviewed cases of clear cell adenocarcinoma (CCA) of the endometrium and adenocarcinoma of the endometrial type mixed with a clear cell component (AMC). 1. Among 1,152 cases of endometrial carcinoma, CCA and AMC were found in 16 (1.4%) and 21 (1.8%) cases, respectively. 2. As revealed by cumulative survival rates based on the Kaplan-Meier method, the prognosis was significantly poorer in CCA and AMC than in endometrial carcinoma (p < 0.001). 3. As for the subtype of CCA, 5 (31%), 9 (56%) and 2 (13%) cases were papillary, solid, and tubulocystic, respectively. 4. The frequency of epithelial hyaline body, bizarre nucleus, psammoma body, necrosis, lymphoplasmacytic infiltration, lymphatic invasion, vessel invasion, and atypical hyperplasia among cases of CCA was 8 (50%), 7 (44%), 5 (31%), 6 (38%), 8 (50%), 5 (36%), 4 (29%) and 1 (7%) cases, respectively. Histologically, lymphoplasmacytic response was the most closely correlated with the prognosis. 5. Among the cases of AMC, there were 6 cases of metastasis and recurrence. In 5 (83%) of these, the clear component increased markedly in metastatic and recurrent lesions although the component was very minor in the primary lesions.

Adenocarcinoma↗

Modulation of the plasma cholesteryl ester transfer by stachybotramide.

Plasma cholesteryl ester transfer protein (CETP), which mediates the transfer and exchange of neutral lipids (cholesteryl esters (CE) and triglycerides (TG) and phospholipids between plasma lipoproteins, plays an essential role in reverse cholesterol transport system. We have found that a fungal metabolite, stachybotramide, modulates the activity of CETP. Stachybotramide stimulated the [14C]CE transfer from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) and low density lipoprotein (LDL) by 1.3- to 1.5-fold at 0.2-0.5 mM. This stimulation was abolished in the presence of anti-CETP antibody. On the other hand, the transfer of [14C]CE from LDL and VLDL to HDL was slightly reduced by stachybotramide at 0.5 mM. Unlike the transfer of [14C]CE, the transfer of [3H]TG from HDL was not significantly affected by stachybotramide. These results suggest that stachybotramide preferentially stimulate the CETP-mediated transfer of CE from HDL to both VLDL and LDL.

Antibodies, Monoclonal↗

Alpha-fetoprotein-producing gastric carcinoma: biological properties of a cultured cell line.

We describe a gastric carcinoma cell line that has been maintained in vitro for more than 10 years and retains the capacity to produce a large amount of alpha-fetoprotein. This cell line was isolated from a metastatic lymph node of a 63-year-old male patient with advanced gastric carcinoma (T2N3P0H0M0) who showed high serum levels of alpha-fetoprotein. The primary tumor was moderately differentiated tubular adenocarcinoma and the lymph node was poorly differentiated adenocarcinoma without any particular pattern. The cultured cells grew as densely packed islet-like colonies with small polygonal cells. Electron microscopy revealed cells abundant in cytoplasmic organelles, with some cellular attachments being tight with junctional complexes and some being loose across intercellular spaces. The free cell surface had microvilli. The population doubling-time was 152 h at passage 58. Chromosomal analysis revealed the modal number to be 77, with numerous karyotype abnormalities. The tumorigenicity of the cultured cells in athymic nude mice was positive only when they were subcutaneously transplanted beneath a plastic plate, but when the cells were transplanted subcutaneously or administered by intrasplenic injection in intact or weakly irradiated nude mice, no tumorigenicity was shown. The cell line produced tumor-associated antigens, such as alpha-fetoprotein, carcinoembryonic antigen, and tissue polypeptide antigen. This cell line may be useful for comparative studies of different types of gastric carcinoma and alpha-fetoproteins of different origins.

Adenocarcinoma↗

Natural history of cervical human papillomavirus lesions.

A total of 87 HPV-positive patients with grade I and II cervical intraepithelial neoplasia (CIN I and II) were followed up by cytology and colposcopy every 3 months for more than 5 years following the first biopsy. These patients were classified into three groups (progressive, persistent, and regressive disease) according to the results. The human papillomavirus (HPV) genome and viral types were identified by Southern blot hybridization at Tm-40 degrees and Tm-20 degrees with DNA extracted from exfoliated cervical cells. The lesion progressed to CIN III in 4/87 patients (4.6%), persisted in 39 patients (44.8%), and regressed in 44 patients (50.6%). In the progressive disease group, HPV 16 was detected in 2 patients, HPV 33 in 1 patient, and HPV 52 in 1 patient. In the persistent disease group, HPV 58 was predominant (28%), whereas in the regressive disease group, there was no predominant HPV type. In 10/39 patients from the persistent disease group, cytological examination transiently revealed severe dysplasia and/or findings similar to carcinoma in situ. These patients showed severe cytological abnormalities only once or twice during the follow-up. These results suggest that the natural history of CIN possibly depends upon the type of HPV that infects the cervix, and the relative risk of progression was similar to that shown by previous cross-sectional studies.

Blotting, Southern↗

Inhibition of acyl-CoA: cholesterol acyltransferase by isohalobacillin, a complex of novel cyclic acylpeptides produced by Bacillus sp. A1238.

A complex of metabolites consisting of two isomeric cyclic acylpeptides was isolated from a culture of Bacillus sp. A1238 by successive chromatographies on Amberlite XAD-7, silica gel and silica ODS columns. By a combination of spectroscopic and chemical analyses, the two subcomponents were identified as isomers of halobacillin, and the complex was designated isohalobacillin. Each molecule of isohalobacillin subcomponents contains either a 3-hydroxy-1-oxo-13-methyltetradecyl or a 3-hydroxy-1-oxo-12 methyltetradecyl moiety in place of a 3-hydroxy-1-oxopentadecyl moiety that is found in the halobacillin molecule. In a cell-free assay, isohalobacillin inhibited acyl-CoA: cholesterol acyltransferase by 50% at a concentration of 50 microM. When added to a culture of macrophage J774, the agent inhibited oxidized low density lipoprotein-induced synthesis of cholesteryl ester from [14C]oleate without affecting surface binding, internalization and degradation of the lipoprotein in the cells.

Amino Acid Sequence↗

Inhibition of the binding of oxidized low density lipoprotein to the macrophages by iturin C-related compounds.

Binding of modified lipoproteins including oxidized low density lipoprotein (oxidized LDL) to cell surface receptors is an initial step of conversion of monocyte-derived macrophages into lipid-laden foam cells, a key cellular component in the early lesions of atherosclerosis. We have searched for microbial metabolites that inhibit oxidized LDL-induced lipid accumulation in macrophages and isolated three compounds from a strain of Bacillus sp. as inhibitors of oxidized LDL binding. By chemical and spectroscopic analyses, these metabolites were shown to be related to the cyclic lipopeptide iturin C. Two of these compounds were novel metabolites having long chain beta-amino acid moieties of different length. These agents, at concentrations ranging from 5 to 20 microM, inhibited cell surface binding of oxidized 125I-LDL, resulting in reduced intracellular accumulation and degradation of the lipoprotein as well as in reduced cholesteryl ester formation from [14C]oleate in macrophages J774.

Amino Acid Sequence↗