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S Sagae

Publications and source records attributed to S Sagae.

At least 55 records · Page 3Linked to original sources

Activation of phospholipase D by prostaglandin F2 alpha in rat luteal cells and effects of inhibitors of arachidonic acid metabolism.

In rat luteal cells labeled with [3H]oleic acid, PGF2 alpha-stimulated phospholipase D (PLD) activation was investigated. The PLD activity was detected by measuring the accumulation of [3H]phosphatidylethanol (PtdEt) in the presence of ethanol. PGF2 alpha stimulated PtdEt accumulation at concentrations of more than 100 nM in the presence of ethanol. However, PtdEt accumulation did not change in the absence of ethanol. PGF2 alpha (1 microM) increased PtdEt accumulation after 1 min, and the accumulation reached a plateau by 2-3 min. These results indicate that PGF2 alpha activates PLD in rat luteal cells. U-73122, a phospholipase C (PLC) inhibitor, and staurosporine, a protein kinase C (PKC) inhibitor, did not inhibit PGF2 alpha-stimulated [3H]PtdEt accumulation. These results suggest that PGF2 alpha-induced PLD activation is different from PLC-PKC systems. We reported previously that PGF2 alpha stimulated the release of arachidonic acid. The effects of indomethacin, nordihydroguaiaretic acid (NDGA), and 5,8,11,14-eicosatetraynoic acid (ETYA), inhibitors of arachidonic acid metabolism, on PGF2 alpha-stimulated PtdEt accumulation were examined. Pretreatment with indomethacin enhanced PGF2 alpha-induced PtdEt accumulation. In contrast, pretreatment with NDGA and ETYA inhibited PGF2 alpha-induced PtdEt accumulation. It is suggested that PGF2 alpha-stimulated PLD activation is mediated via lipoxygenase products.

5,8,11,14-Eicosatetraynoic Acid↗

Demonstration of selective protein complexes of p53 with 73 kDa heat shock cognate protein, but not with 72 kDa heat shock protein in human tumor cells.

It has been demonstrated that p53, especially, mutant p53 (mp53), makes protein complexes with major heat shock proteins hsp72/hsc73. However, there is no direct evidence showing whether hsp72 or hsc73 could bind preferentially to p53. In the present study, using TYKnu human ovarial carcinoma cells and monoclonal antibodies reacting specifically to hsp72/hsc73, we were able to find the selective protein complex formation with p53, presumably mp53, and hsc73, but not in the case of p53 and hsp72. The p53-hsc73 protein complexes dissociate with the addition of ATP, indicating that the dissociation is dependent upon the ATP-hydrolysis. These data suggest that hsc73 rather than hsp72 plays an important role in the yet undefined mechanism of disregulated cell growth control by mp53.

Adenosine Triphosphate↗

Detailed deletion mapping of chromosome 17q in ovarian and breast cancers: 2-cM region on 17q21.3 often and commonly deleted in tumors.

Using 11 restriction fragment length polymorphism markers, we examined loss of heterozygosity on the long arm of chromosome 17, where one or more genes responsible for hereditary breast and ovarian cancers may be present, in sporadic forms of 94 ovarian and 246 breast cancers. Loss of heterozygosity was observed in 33 of 84 (39.3%) ovarian and in 88 of 214 (41.1%) breast cancers that were informative with at least one marker. Detailed deletion mapping of chromosome 17q in these cancers identified two distinct, commonly deleted regions. One was located between 17q12 and 17q21.3 and the other between 17q25.1 and 17q25.3. In breast cancers, the proximal commonly deleted region was between two loci defined by markers CI17-701 and CI17-730 at 17q21.3, which are 2.4 cM apart. This segment overlaps the region that includes the putative gene for hereditary breast and ovarian carcinomas. The results suggest that at least two tumor suppressor genes associated with sporadic ovarian and breast cancers are present on chromosome 17q and that one of them may be the same gene that is responsible for the hereditary form.

Adenocarcinoma↗

Protein interaction of retinoblastoma gene product pRb110 with M(r) 73,000 heat shock cognate protein.

Both the tumor suppressor gene products, the retinoblastoma sensitivity gene product pRb110 and p53, are found in oligomer complexes with the oncogene products of the DNA tumor viruses. It has been demonstrated that p53 binds to the M(r) 70,000 heat shock protein family. However, the protein association of pRb110 with the M(r) 70,000 heat shock protein family is not yet known. We analyzed the immunoprecipitates made with TYK-nu human ovarial carcinoma cell lysate and anti-pRb110 or anti-heat shock protein monoclonal antibodies. In this paper, we demonstrate that pRb110 is associated with the M(r) 73,000 heat shock cognate protein, but not with the M(r) 72,000 heat shock protein. This selective protein association was also detected in HeLa cervical carcinoma cells. Furthermore, the protein complexes of the M(r) 73,000 heat shock cognate protein and pRb110 were dissociated with the presence of ATP, but not with ADP and the nonhydrolyzable ATP analogue, ATP gamma S. This indicates that the dissociation is dependent on the ATP hydrolysis. These data may suggest an as yet undefined important role of M(r) 73,000 heat shock cognate protein in the cell growth control in collaboration with pRb110.

Adenosine Triphosphate↗

Fine-scale deletion mapping of the distal long arm of chromosome 6 in 70 human ovarian cancers.

To define a small region on chromosome 6q containing a putative tumor suppressor gene for ovarian cancer, we examined loss of heterozygosity in 70 ovarian tumors of three histological types with nine restriction fragment length polymorphism markers located at 6q24-27. Among 33 cancers of serous type that were informative at one or more loci, 17 showed allelic loss at a few or all loci examined, whereas only 1 of 15 mucinous-type tumors and 2 of 12 clear-cell tumors revealed loss of heterozygosity. This result supported our earlier suggestion that alteration of a gene on chromosome 6q may play an important role during development of serous ovarian tumors (Sato et al., Cancer Res., 51: 5118-5122, 1991). Frequent losses were observed between loci defined by CI6-119 (D6S195) at 6q26 and CI6-49 (D6S161) at 6q27. A detailed deletion map indicated a commonly deleted region between loci defined by CI6-111 (D6S193) and CI6-24 (D6S149); these two markers are estimated to be 1.9 cM apart on the basis of linkage analysis. Our results further define a region containing a tumor suppressor gene involved in ovarian carcinoma within an approximately 2-megabase-long segment of chromosome 6q.

Blotting, Southern↗

[Treatment of recurrent ovarian cancer].

Significant prolongation of survival time among the patients with advanced ovarian cancer has been brought under the development of surgery and chemotherapy, but even those with clinical remission shows sometimes recurrence. For the recurrent ovarian cancer patients at present there are no definite strategy to treat the recurrent cases. Under these circumstance, we have reviewed the current treatment of cytoreductive surgery and chemotherapy for the recurrent cases. 1) surgical treatment Generally, in the cases of recurrent ovarian cancer, cytoreductive surgery is required to minimize the residual tumour in the abdomen. But sometimes we can find the distant metastasis including liver, lung, and lymph node. This means that surgery is not sufficient for control of recurrent tumor. Further adjuvant chemotherapy will be required to control metastatic tumors. 2) chemotherapy After the detail assessment of the initial treatment of cases, at first we should think about retreatment with CDDP-based regimen and secondly about dose-intensification of CDDP or CBDCA for the CDDP-resistant cases. And as combination regimens, topoisomerase inhibitors, etoposide or CPT-11 are also preferable to use, alkylating agents such as ifosfamide, 5-fluorouracil, and some current trials with new drug, taxol are effective for recurrent cases. In conclusion, further active chemotherapy using platinum compounds, topoisomerase inhibitors, taxol will be achieved for the control of the recurrent cases of ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Ras oncogene expression and progression in intraepithelial neoplasia of the uterine cervix.

To examine the correlations between ras oncogene expression and the development of cervical cancer, the authors studied the reactivity of cervical intraepithelial neoplasia (CIN) and microinvasive lesions of the human uterine cervix by using anti-ras p21 mouse monoclonal antibody rp35. The frequency of positive p21 staining increased with increased grades of malignancy from 17.9% in CIN 1 to 28.9% in CIN 2 and 53.9% in CIN 3, whereas in microinvasive carcinoma it was 50.0%. Furthermore, ten cases of lesions that regressed during a 1-year follow-up period were positive for ras p21 in 20% of cases, but 14 cases of lesions that progressed and developed into higher graded lesions during the 2- to 5-year follow-up period had a 50.0% rate of positive p21 staining. It was concluded that ras oncogene product p21 correlates with the early phase of carcinogenesis of squamous cells of the uterine cervix.

Epithelium↗

Vaginal hysterectomy without ligation of the ligaments of the cervix uteri.

An operative procedure for vaginal hysterectomy is reported. The procedure is performed without ligation of the paracervical ligaments to simplify and avoid ureteral injury. However, a portion of the cardinal ligament is ligated before peritoneal closure. In a study from 1955 to 1987, of 9,230 patients requiring vaginal hysterectomy, blood loss was less than 300 milliliters with this procedure in 83 per cent of the patients. Operative complications, such as bladder injury, occurred in 66 patients or 0.7 per cent. Ureteral injury occurred in only three patients or 0.03 per cent. From 1972 to 1987, only five of 2,460 patients (0.02 per cent) required postoperative hemostasis. These data indicate that vaginal hysterectomy without ligation of the paracervical ligaments is a safe and convenient operative method with fewer complications.

Female↗

ras oncogene expression and prognosis of invasive squamous cell carcinomas of the uterine cervix.

By using anti-ras p21 mouse monoclonal antibody rp35, the authors studied the reactivity of 170 squamous cell carcinomas of the uterine cervix of different histologic types. The overexpression of p21 was noted in 57.1% of keratinizing type (K type) and 54.2% of large cell nonkeratinizing type (LNK type), but only 38.7% of small cell type (S type). Upon statistical analysis of the correlations between p21 overexpression and patient prognosis with the Kaplan-Meier method and generalized Wilcoxon text, the p21-positive K and LNK types showed poorer prognosis, whereas the positive S type showed better prognosis in comparison with the negative cases. These findings suggest that the expression of ras p21 is one of the parameters related with prognosis of cervical cancers, but the mode of the correlation is dependent on their histologic types.

Antibodies, Monoclonal↗

Peritoneal cytology of ovarian cancer patients receiving intraperitoneal therapy: quantitation of malignant cells and response.

An analysis was performed of malignant and host cells found in peritoneal fluids obtained during intraperitoneal chemotherapy and immunotherapy in patients with ovarian cancer. The concentration of malignant cells and the surgically documented response to the intraperitoneal treatment were correlated. Twenty-three patients were treated with intraperitoneal cisplatin or alpha-2 interferon (rIFN-alpha 2) after persistent carcinoma was documented at second-look laparotomy. Six patients (26%) had a complete response to therapy, and all of these patients had a malignant cell concentration of less than 10(2)cells/cm2/dL. No responses were seen in patients whose initial malignant cell concentration was greater than 10(3)cells/cm2/dL. Among patients treated with intraperitoneal alpha-interferon, five of 11 whose initial concentration of malignant cells was less than 10(2) cells/cm2/dL responded to therapy, whereas none of the patients whose malignant cell concentration was 10(2) cells/cm2/dL or greater responded. In patients treated with intraperitoneal cisplatin, the initial concentration of malignant cells associated with any surgically documented response was less than 10(3)cells/cm2/dL. A host mesothelial reaction was prominent after intraperitoneal alpha-interferon, but not observed in women treated with intraperitoneal cis-platin. The fluctuating pattern of peritoneal white blood cells documented during therapy did not correlate with response. THe evaluation of peritoneal cytology specimens during intraperitoneal chemotherapy should include a quantitative assessment of malignant cells and reactive mesothelial cells in order to reflect more accurately the histologically documented findings. Initial quantitative cytology appears to correlate with the likelihood of a surgically documented response to intraperitoneal therapy.

Aged↗

Distant metastases in epithelial ovarian carcinoma.

A review of 255 patients with epithelial ovarian carcinoma revealed that metastases consistent with Stage IV disease developed in 97 patients (38.0%) at some time during the natural history of their disease. Malignant pleural effusions developed in 63 patients (24.7%), and their median survival (from the time of diagnosis of the effusion) was 6 months. Parenchymal liver metastases developed in 24 patients (9.4%; median survival, 5 months); parenchymal lung metastases in 18 patients (7.1%; median survival, 8 months); distant lymph node metastases in 18 patients (7.1%; median survival, 9 months); subcutaneous nodules in nine patients (3.5%; median survival, 12 months); a malignant pericardial effusion in six patients (2.4%; median survival, 2.3 months); central nervous system metastases in five patients (2%; median survival, 1.3 months); and bone metastases in four patients (1.6%; median survival, 4 months). Patients with Stage IV disease at the time of diagnosis had a median survival of 9.1 months, while patients with a delayed occurrence of distant metastases had a median survival of only 4 months from the time of diagnosis of the distant metastases. Significant risk factors for distant metastases were malignant ascites, peritoneal carcinomatosis, large metastatic disease within the abdomen, and retroperitoneal lymph node involvement at the time of the initial surgery. The significance of positive retroperitoneal nodes and bulky upper abdominal disease has important therapeutic implications.

Adolescent↗

The cytological features and DNA content of cervical adenocarcinoma.

The relationship among cytological features, DNA content, and degree of histological differentiation of cervical adenocarcinoma was investigated in an attempt to discover a more accurate means of screening for this cancer. In highly differentiated adenocarcinoma (so-called adenoma malignum), the nuclei were only somewhat more irregular in size and shape than those of normal columnar epithelial cells. The cells were arranged in slightly multilayered clusters. The cells of well-differentiated adenocarcinoma were usually columnar in shape, and they exfoliated side by side in clusters. In moderately differentiated adenocarcinoma, solitary cells with markedly atypical nuclei were combined with multilayered cell clusters. The cells from poorly differentiated adenocarcinoma were roundish, occurred as solitary cells or irregularly overlapping cell clusters, and showed markedly atypical nuclei. As the degree of histological differentiation decreased, as determined by measurement of the DNA content of the cells, the DNA distribution covered a wider range in terms of ploidy, and the number of cells exceeding tetraploid DNA content increased.

Adenocarcinoma↗

Yolk sac tumors of the ovary and the human yolk sac.

In the present study a comparison was made between human yolk sacs and yolk sac tumors. Tubules surrounded by several to as many as 10 endodermal cells and intracellular tubules in one endodermal cell were frequently observed. The tubules were seen abundantly in the yolk sac of a 4-week pregnancy, and they resembled the reticular pattern of the yolk sac tumor. It was also observed that the papillary endoderm, which contained blood cells in the center and protruded into the endodermal tubules, resembled the Schiller-Duval body of yolk sac tumor. Ultrastructurally the tumor cells were similar to the yolk sac endoderm. alpha-Fetoprotein was positive in the yolk sac endoderm until approximately the seventh week of pregnancy. Yolk sac tumor was also alpha-fetoprotein-positive. In other words, our study of human yolk sacs of 4- to 11-week pregnancies presumes that the yolk sac tumor resembles the endoderm of 4- to 7-week pregnancies.

Endoderm↗

[Studies on the appropriated interval of mass screening for cervical cancer].

In order to study the appropriate interval for cervical cancer screening, we investigated mainly the screening history of 1,086 cervical squamous cancer cases detected by mass screening. 1) The cancer detection rate (CDR) for the 2-year successively screened group who were class I in the first screening was 0.051% and all cases were carcinoma in situ (CIS). In the 2-year interval screened group, detection rates for CIS, microinvasive cancer and stage 1b cancer were 0.053%, 0.035% and 0.018%. But there is no significant difference in CDR between the 2-year successively screened group and 2-year interval screened group (p less than 0.05). 2) In the 2-year successively screened group who were class II in the first screening, the CIS and microinvasive cancer detection rates were 0.044% and 0.022%. There is no significant difference in CDR between class I group and class II group. In the group who were class I in the first screening, we detected most cases in the stage 0 and a few cases in the stage Ia and Ib by mass screening at 2-year intervals. If the detection of a few cases in stage Ib is permitted, we can enforce mass screening for cervical squamous cancer at 2-year interval and it is considered that class II group can be screened at same interval as class I group.

Female↗

Surgery for germ cell tumors.

We performed a review of the current modalities of surgical treatment of malignant ovarian germ cell tumors by clinical stages and histological types. Stage IA dysgerminoma is performed with a unilateral salpingo-oophorectomy (USO) without chemotherapy. However, for Stage IB or IC patients with dysgerminoma, USO plus chemotherapy as a primary treatment may or may not be followed with a second-look operation (SLO). For non-dysgerminomas, USO is indicated only for Stage IA immature teratoma grade 1. The treatment for Stage IA immature teratoma grade 2 or 3 and other histological types is USO plus chemotherapy. Patients with Stage IB, IC or higher with non-dysgerminoma are treated with USO plus chemotherapy or USO with contralateral partial ovariectomy plus chemotherapy. For patients who require non-conservative surgery, a total abdominal hysterectomy (TAH) and a bilateral salpingo-oophorectomy (BSO) plus chemotherapy are performed. For patients with Stage II of all histological types, conservative surgery consists of USO and a cytoreductive operation plus chemotherapy, followed by SLO or a second cytoreductive operation. For non-conservative surgery, TAH+BSO with or without a cytoreductive operation plus chemotherapy is followed by SLO. Conservative surgery for patients with Stage III and IV is USO and a cytoreductive operation plus chemotherapy followed by a second cytoreductive operation. Non-conservative surgery is TAH+BSO with a cytoreductive operation plus chemotherapy, followed by SLO or a second cytoreductive operation. However, primary or secondary cytoreductive surgery with or without lymphadenectomy and SLO are still controversial in terms of improving patient survival.

Adolescent↗

Minimal-deviation adenocarcinoma (adenoma malignum) of the uterine cervix; four case reports.

Four cases of minimal-deviation adenocarcinoma (adenoma malignum) of the uterine cervix are analysed in this clinicopathological study. Four patients, one Ib, two IIb and one IIIb stage, showed poor prognosis, which included three patients who died within 36 months, because of diagnostic delays of 5 years, 6 months and 1 year due to cytohistologically benign appearances. Cytologically, the nuclei were somewhat more irregular in size and shape than those of normal columnar epitherial cells. Slightly multilayered cell clusters were arranged as honeycombs, palisades or sheets with glandular openings. The characteristic histological features were the presence of sharp points projecting from the glands and marked variation in the size and shape of the glands. Ultrastructurally, intestinal metaplastic cells containing both microvilli with core filaments and rootlets, and secretary granules in the same cell were present in the specimens of two evaluable patients. These features indicate a disorder of differentiation. In order to diagnose this tumor accurately, comprehensive analysis should be required concerning the clinical features, cytohistological findings and ultrastructural findings.

Adenocarcinoma↗

Morphology of adenocarcinoma in situ and microinvasive adenocarcinoma of the uterine cervix. A cytologic and ultrastructural study.

Adenocarcinoma in situ (AIS) and microinvasive adenocarcinoma of the uterine cervix and normal endocervical columnar epithelium were studied by cytology, morphometry and electron microscopy to identify differentiating features and to ascertain the cellular origin of cervical adenocarcinoma. Smears from AIS showed the characteristic cytology, consisting of glandular rosettes, palisading and crowded sheets; most nuclei had a relatively uniform oval shape. Smears from microinvasive adenocarcinoma showed more crowded sheets, with enlarged, round and irregular-shaped nuclei and prominent oval nucleoli. These nuclear features were confirmed by the morphometric results. Ultrastructurally, reserve cells in the normal tissues contained tonofibers and secretory granules and showed squamous and adenomatous features. The ultrastructural features of microinvasive adenocarcinoma were similar to those of well-differentiated invasive adenocarcinoma. The cells from both contained tonofibers and secretory granules. These findings suggested that the reserve cell is the cell of origin for cervical adenocarcinoma.

Adenocarcinoma↗