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Biomedical subjects

K Hasumi

Publications and source records attributed to K Hasumi.

At least 91 records · Page 5Linked to original sources
PubMed1995

Isolation, characterization and biological activities of novel triprenyl phenols as pancreatic cholesterol esterase inhibitors produced by Stachybotrys sp. F-1839.

Ten triprenyl phenol metabolites were isolated as inhibitors of pancreatic cholesterol esterase from cultures of Stachybotrys sp. F-1839 by solvent extraction and column chromatographies. Combination of spectroscopic analyses revealed that two of these compounds are K-76 (1) and stachybotrydial (2), and that the remaining eight are new congeners (designated F1839-A (3), -B (4), -C (5), -D (6), -E (7), -F (8), -I (9) and -J (10). These compounds inhibited pancreatic cholesterol esterase by 50% at 6 x 10(-5) to 1.1 x 10(-1) M. Inhibition of the enzyme by compound 2, the most potent one among these compounds, was time-dependent and irreversible. When administered to normal rats, 2, at a single oral dose of 100 mg/kg, reduced [14C]cholesterol absorption by 50-60%. In cholesterol-fed mice, dietary supplementation of 2 (0.1%) for 14 days resulted in a 20% reduction in serum total cholesterol level without causing significant change in the high density lipoprotein cholesterol level.

Animals↗
PubMed1995

[Endometrial carcinoma without myometrial invasion].

Between 1974 and 1991, 621 patients with endometrial cancer were treated with hysterectomy without any preoperative treatment. Subsequent pathological examinations revealed that 92 cases had no myometrial invasion. Clinicopathological analysis was carried out in the 92 patients. The results are as follows: 1. Complete surgery was carried out in all cases except one case with intraperitoneal dissemination. The relapse rate in the 91 cases was 2.2% (2/91). The 2 cases with recurrence had grade 1 (G1) and grade 2 (G2) adenocarcinoma and both cases manifested local recurrence. 2. Of 70 cases treated with pelvic lymphadenectomy, two cases (2.9%) with G1 adenocarcinoma exhibited a single node metastasis. The metastatic site was an external iliac lymph node in both cases. Despite the lymph node metastasis, the 2 cases have exhibited no relapse. 3. None of the 92 cases showed any evidence of adnexal metastasis. The positive rate of peritoneal cytology was 13.4% (9/67). Except for one case with peritoneal dissemination who also had positive peritoneal cytology, 8 cases with positive peritoneal cytology have not developed recurrence. This study showed that some endometrial cancer patients without myometrial invasion manifest recurrence, peritoneal dissemination or lymph node metastasis. It is therefore considered that lymphadenectomy and careful follow-up are necessary in every case of endometrial cancer, even in G1 cases without myometrial invasion.

Adenocarcinoma↗
PubMed1995

[Post-operative peritoneal washing cytology in cases of stage IIIa endometrial carcinoma with positive peritoneal cytology].

According to the new FIGO staging of corpus cancer, the cases with positive peritoneal cytology alone belong in stage IIIa. The authors previously reported, however, good prognosis of IIIa cases with only positive peritoneal cytology. In order to assess the potential of malignant cells in the peritoneal cavity to metastasize, post-operative peritoneal washing cytology was undertaken. This study was conducted on a total of 115 consecutive patients with endometrial carcinoma who underwent primary surgical therapy at the Cancer Institute Hospital during the 25-month period from December, 1991 to December, 1993. Fifteen cases were included in stage IIIa with positive intraoperative peritoneal cytology alone. In 12 cases with endometrioid adenocarcinoma, a Silascon tube was indwelt in the abdominal cavity before closure of the abdomen. The peritoneal cavity was washed with 500 ml of physiological saline through the indwelt tube 14 days after the operation. The cytology of recovered washings was negative in all cases. Only two cases received postoperative chemotherapy owing to other prognostic factors. These 12 cases are alive with no evidence of disease after 12 to 36 months. The present study demonstrated that malignant cells in the peritoneal cavity appear to have a very low potential for implantation into the peritoneum.

Adult↗
PubMed1995

[Effects of long-term administration of tamoxifen on vaginal epithelium and complications of endometrial lesions in breast cancer patients].

The effects of tamoxifen (TAM) on 56 postoperative breast cancer patients who were orally administered TAM and followed up at Cancer Institute Hospital from 1989 to 1992 were studied retrospectively. The maturation index (MI) and karyopyknotic index (KPI) were employed to investigate the effects of TAM on vaginal epithelial cells cytologically, and the patients were also monitored for complications. The results were as follows. (1) The relationship between the duration of TAM therapy and the changes in MI and KPI were analyzed. It was found that, for the MI, intermediate cells (IMT) increased and superficial cells (ST) decreased during TAM administration for up to 4 years, but when the TAM therapy was continued for longer than 4 years, IMT showed a gradual decrease and ST increased gradually. The KPI values showed similar changes. (2) Studies of the endometrium (26 cases) revealed a tendency for few of the long-term administration cases to show a picture of atrophy. Of the total of 56 patients, endometrial lesions were observed in five cases (8.9%), consisting of endometrial cancer in three and cystic glandular hyperplasia in two. The mean duration of TAM administration to these five patients was 54 (+/- S.D.26.8) months. These data indicate that long-term oral administration of TAM involves the possibility of having an estrogenic effect on the vaginal epithelium and the uterine endometrium.

Administration, Oral↗
PubMed1995

[Pharmacokinetic analysis of platinum in the continuous CDDP-CBDCA treatment; its relation to the changes of blood biochemistry].

Seven patients with recurrent gynecological malignancies (2 cervical, 2 endometrial, 3 ovarian) treated with CDDP at the initial chemotherapy were studied for the pharmacokinetic analysis of platinum (Pt) and changes of blood biochemistry in the continuous CDDP-CBDCA infusion therapy. All the patients were indwelled of the total parenteral nutrition catheter. A balloon type infuser (Baxter Inc., multiday type) was connected with the catheter and the drugs were infused continuously through it. CBDCA was infused continuously from day 1 through day 5 at a daily dose of 60 mg/m2, followed by continuous CDDP infusion from day 6 through day 30 at a daily dose of 2.5 mg/m2. All the patients received 3 courses of the treatment. The area under the [Pt]-time curve (AUC) of filterable Pt was as high as 60.98 +/- 8.20 mg.hr/ml (mean +/- SE), and that of total Pt 691.48 +/- 93.61 mg.hr/ml. However, the Cmax of filterable Pt was as low as around 400 ng/ml during day 1 to 6, and around 20 ng/ml during day 7 to day 30. As to the toxicity, only slight myelosuppression but no renal and gastrointestinal toxicity were observed in this therapy. The quality of life of the patients received this treatment were maintained well throughout of the therapy. Responders were evaluated as 1 CR, 2 PR, 2 NC and 1 PD. These data indicated that high AUC but low Cmax of filterable Pt by continuous CDDP-CBDCA therapy resulted in less toxicity. Further investigation was warranted to evaluate the efficacy of continuous CDDP-CBDCA therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Clinical and pathological study of 24 patients with fallopian tube malignancy].

Clinical and pathological analyses were carried out in 24 patients with fallopian tube malignancy. The results are as follows: 1. Twenty-three patients had adenocarcinoma (well differentiated 11, moderately 6, poorly 6) and one patient had MMT (Müllerian mixed tumors). 2. There were 11 cases in stage I, 4 in stage II, 8 in stage III and 1 in stage IV according to Dodson's classification. 3. Atypical genital bleeding was the most common symptom, whereas 12.5% of patients had no symptoms. 4. Positive rates in cytology were 25.0% in cervico-vaginal smear and 55.0% in endometrial aspiration cytology. 5. The overall 5-year survival rate is 60.0%. The 5-year survival rates for stage I/II and stage III/IV were 88.9% and 16.7%, respectively. 6. The relapse rate of 16 patients treated with complete surgery was 25.0% (well differentiated 11.1%, moderately 0%, poorly 75.0%). Based on these observation, it is likely that patients with stage I/II have a good prognosis, however, patients with poorly differentiated adenocarcinoma have a high relapse rate, indicating that intensive adjuvant chemotherapy would be necessary in these cases. Cytologic examination, particularly endometrial aspiration cytology, is an effective method to use in detecting cases with fallopian tube malignancy early.

Adenocarcinoma↗
PubMed1995

[Time course changes in bone metabolic markers after menopause--a cross-sectional study].

To clarify the clinical significance of the measurement of bone metabolic markers in postmenopausal subjects, a cross-sectional study of 546 healthy women (215 premenopausal, 164 bilateral oophorectomized and 167 natural menopausal) was conducted. All the subjects had their lumbar bone (L2-4 mineral density measured by means of DEXA. Bone metabolic markers (bone formation markers: serum alkaline phosphatase, osteocalcin and intact osteocalcin; bone resorption markers: urine excretion of hydroxyproline, pyridinoline and deoxypyridinoline) were also evaluated. After dividing the subjects according to the length of time after menopause, the time course changes in the Z-score values for bone metabolic markers were calculated. A triphasic pattern of lumbar bone loss was seen: there was a rapid phase in the first 5 years after menopause, a plateau phase in the second 5 years and a slow phase beginning 10 years menopause. The changes in bone metabolic markers coincided closely with the rapid phase of bone loss. In the plateau and slow phases, there were no markers which significant changed greatly. One possible clinical application of bone metabolic markers is in assessing the results of treatment for postmenopausal osteoporosis.

Adult↗
PubMed1994

Allelotype of uterine cancer by analysis of RFLP and microsatellite polymorphisms: frequent loss of heterozygosity on chromosome arms 3p, 9q, 10q, and 17p.

Cancers in which mutations have been identified in putative tumor suppressor genes, such as the TP53 gene, the retinoblastoma (RBI) gene, the adenomatous polyposis coli (APC) gene, and the Wilms tumor (WTI) gene, frequently show loss of the corresponding allele on the homologous chromosome. To identify locations of tumor suppressor genes involved in uterine cancer, we examined loss of heterozygosity (LOH) by using genomic probes detecting RFLPs in 35 uterine cancers at 29 loci throughout the genome, and with highly informative microsatellite markers in 21 uterine cancers at nine putative or known tumor suppressor gene loci. High frequencies of allelic loss found at loci on 3p (71%), 9q (38%), 10q (35%), and 17p (35%) suggest that tumor suppressor genes involved in uterine carcinogenesis exist in these regions. There were no significant differences in frequencies of LOH between cancers of the uterine cervix and cancers of the uterine endometrium at any of the loci tested.

Adenocarcinoma↗
PubMed1994

Human papillomavirus DNA in adenocarcinoma and adenosquamous carcinoma of the uterine cervix detected by polymerase chain reaction (PCR).

Although human papillomaviruses (HPV) have been implicated strongly in the pathogenesis of squamous cell carcinomas of the uterine cervix, a few studies have suggested that HPV may be an etiological factor for adenocarcinoma of the cervix. To evaluate the association between HPV infection and cervical adenocarcinoma, we analyzed formalin-fixed, paraffin-embedded tissues from 64 patients with adenocarcinoma or adenosquamous carcinoma of the uterine cervix for the presence of HPV DNA using polymerase chain reaction (PCR) with primers specific for the 6, 11, 16, 18, 31, 33, and 35 types. HPV DNA was detected in 24 of 43 (56%) cases of adenocarcinoma, and in 19 of 21 (91%) cases of adenosquamous carcinoma. Fifteen of the 43 (35%) adenocarcinomas and 10 of the 21 (48%) adenosquamous carcinomas contained HPV 18 DNA, and 10 of the 43 (23%) adenocarcinomas and 11 of the 21 (52%) adenosquamous carcinomas contained HPV 16 DNA. One specimen was positive for HPV 31 and five contained HPV 35 DNA, all but one as double infections with HPV 18. No evidence of HPV 6, 11, or 33 DNA carriage was seen. These results suggest that human papillomaviruses, particularly HPV 16 and 18, play a role in the etiology of cervical adenocarcinoma and adenosquamous carcinoma.

Adenocarcinoma↗
PubMed1994

Establishment and characterization of human cell lines from a serous papillary adenocarcinoma of the endometrium.

Two cell lines, SPAC-1-L and SPAC-1-S, derived from a human serous papillary endometrial adenocarcinoma, have been established and repetitively subcultured as a monolayer culture for over 3 years through 144 passage generations. Each of the two cell lines is a subline derived from one original tumor. They have been independently subcultured from the primary culture dishes without any attempt to clone subpopulations and were further characterized with regard to morphology, growth kinetics, tumor marker production, karyotype, and tumorigenicity. These studies indicated that the SPAC-1-L and -S cell lines are different from each other in some cell properties such as morphological character, growth kinetics, and tumor marker productions. Compared with cell lines from a serous papillary endometrial carcinoma that has been previously reported in the literature, our two cell lines are more tumorigenic on nude mice (100%), which possibly correlates with the unusually aggressive biological behavior of the original tumor. In addition, implanted nude mouse tumors, especially the tumor derived from SPAC-1-S cells, retained many characteristics of the original tumor and histologically closely resembled the original serous papillary adenocarcinoma. Since serous papillary carcinoma is a clinically aggressive histological variant of endometrial adenocarcinoma with a significantly poor prognosis, these SPAC-1-L and -S cell lines should prove useful in future studies of the extremely aggressive biological behavior and unique morphology of this tumor.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Combined assay of serum levels of CA125 and CA19-9 in endometrial carcinoma.

Serum levels of CA125 and CA19-9 were examined in 225 cases with endometrial carcinoma before treatment and 32 cases with recurrent endometrial carcinoma. The positive rates in the 225 cases were 27.1% for CA125, 24.0% for CA19-9, and 38.7% for the combined assay. The serum levels of both CA125 and CA19-9 significantly increased with surgical staging. The presence of lymph node metastasis and extrauterine spread exhibited a marked influence on the serum levels of both CA125 and CA19-9. Myometrial invasion and vessel permeation also increased serum levels of CA125, whereas peritoneal cytology and adnexal metastasis exhibited no influence on CA125 levels or CA19-9 levels. Twenty-five of 33 cases who showed either more than 100 U/ml of CA125 level or more than 100 U/ml of CA19-9 level were classified as surgical stage III or IV. The combined assay demonstrated a 71.9% positive rate at the time of detection of the recurrence (65.6% for CA125, 43.7% for CA19-9). In 34.4% of the 32 recurrent cases, elevated levels of the tumor markers were the first sign of recurrence. These data indicate that the use of CA19-9 in combination with CA125 is noteworthy in the management of patients with endometrial carcinoma.

Adult↗
PubMed1994

Gypsetin, a new inhibitor of acyl-CoA:cholesterol acyltransferase produced by Nannizzia gypsea var. incurvata IFO 9228. I. Fermentation, isolation, physico-chemical properties and biological activity.

A novel inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), designated gypsetin, was isolated from the cultured broth of Nannizzia gypsea var. incurvata IFO 9228 by solvent extraction, silica gel chromatography and crystallization. Gypsetin inhibited rat liver microsomal ACAT activity competitively with respect to the substrate oleoyl-CoA with an apparent Ki value of 5.5 microM. In cultured macrophage J774 cells incubated with oxidized low density lipoprotein, gypsetin inhibited cholesteryl ester formation from [14C]oleate by 50% at a concentration of 0.65 microM without affecting cell surface binding, uptake and degradation of the lipoprotein.

Animals↗
PubMed1994

Gypsetin, a new inhibitor of acyl-CoA: cholesterol acyltransferase produced by Nannizzia gypsea var. incurvata IFO 9228. II. Structure determination.

The elucidation of the structure of gypsetin, a new inhibitor of acyl-CoA: cholesterol acyltransferase, is described in this paper. By spectroscopic and X-ray crystallographic analyses, the structure of gypsetin has been determined to be 8a,16a-dihydroxy-5a,13a-bis[1,1-dimethylallyl]-[1]benzazolidine [3''' 2''':4'',5'']azolidino[1'',2'':4',5'][1,4]perhydrodiazin[1', 2':1, 5]azolidino[2,3-b]-[1]benzazolidine-7,15-dione.

Crystallography, X-Ray↗
PubMed1994

[Calcitonin physiologically regulates the postmenopausal bone loss and possibly inhibits the bone loss in fast losers].

To study the correlation between the basal serum calcitonin level and L2-4 bone mineral density (BMD), a cross sectional study of 384 healthy subjects (106 premenopausal, 88 perimenopausal and 109 postmenopausal subjects) and a longitudinal study of 42 oophorectomized subjects were conducted. A positive correlation was found in perimenopause (r = 0.219, p = 0.040) but not in premenopause (r = 0.069, p = 0.4898) and postmenopause (r = 0.141, p = 0.0554) in a cross sectional study. The percent reduction in L2-4BMD compared to the baseline also correlated with preoperative calcitonin levels at 6 months after oophorectomy (r = 0.333, p = 0.0442), but not significantly at 12 months (r = 0.224, p = 0.27). These data suggest that the basal calcitonin level correlates to L2-4BMD only at perimenopause or in the early postoophorectomized period when bone turnover is accelerated and bone resorption seems to be faster than bone formation. In addition the premenopausal basal calcitonin level may be an indicator of the fast loser after menopause.

Bone Density↗
PubMed1994

[Characteristic of cystic glandular hyperplasia as a precursor of endometrial carcinoma].

The natural history and biological behavior of cystic glandular hyperplasia (CGH), which has been considered to be a precursor of endometrial carcinoma, still remain unclear. The present prospective study included 52 patients with CGH, who were followed up for 6 months to 5 years with occasional curettage, surgical procedures or hormonal therapy. The lesion disappeared in 35 cases (67.3%), persisted in 12 cases (23.1%) and became more serious in 5 cases (9.6%). Of these 5 cases, one case was found to have endometrial carcinoma during her follow-up. Nuclear DNA analysis was performed by Flow cytometry in 8 CGH cases. Eighty four point nine % of the cells from these 8 cases were in G0+1 phase, 8.3% in S phase and 7.4% in G2 + M phase. The proliferation index for CGH was 15.7%. Proliferative and mitotic activities of CGH were found to be similar to those of adenomatous hyperplasia, and the levels of these activities were between those of normal endometrium and atypical hyperplasia.G1.

Adult↗