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Biomedical subjects

R Kudo

Publications and source records attributed to R Kudo.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Management of the uterine endometrial cancer cases whose cytological and histologic specimens cannot be obtained from the uterine cavity--assessment by CA125 or vaginal ultrasonography].

An examination for endometrial cancer has been done by cytology. However, cytology is sometimes not possible because of closed or narrow cervix of postmenopausal woman. We did a retrospective study regarding the usefulness of CA125 or transvaginal ultrasonography in postmenopausal cases. The mean +/- S.D. of CA125 in normal menopausal women was 10.3 +/- 3.0 U/ml. The value of mean +/- 2S.D., the finding of Relative Operating Characteristic curve and the purpose that false positive was 0%, so we set 17 U/ml as the cut off value for CA125. In 46 cases with postmenopausal endometrial carcinoma, 23 cases were screened; and in 30 cases with surgical stage I, 10 cases were screened with this cut off value. The echoic patterns for uterine cavities which were observed by transvaginal ultrasonography were divided into 4 patterns (type I: anechoic pattern, type II: linear pattern, type III: clear mass pattern, type IV: unclear mass pattern). In 20 cases with postmenopausal endometrial cancer, 19 cases had type III or IV. In 41 normal postmenopausal women, 26 cases showed an anechoic pattern and 14 cases showed a linear pattern. It was found that 97.5% of cases with anechoic or linear patterns were normal endometrium. The screening by transvaginal ultrasonography was more useful than CA125. However CA125 was more useful than transvaginal ultrasonography in detecting lymph node metastasis.

Aged↗
PubMed1994

[Usefulness of CA125 determination in the diagnosis of lymph node metastasis in post menopausal uterine endometrial carcinoma].

It has been difficult to diagnose all but advanced cases of lymph node metastases with CT or MRI. It has been reported that the serum value of CA125 rises with the stage of endometrial cancer. This level is lower in the postmenopausal period than before menopause. In this study, we have examined the usefulness of CA125 for the assessment of lymph node metastasis in 43 postmenopausal endometrial cancer cases. There were significant differences in the CA125 level between lymph node metastasis positive cases and negative cases, between cancers occupying > or = 1/2 and < 1/2 of the uterine cavity, between lesions of > or = 1/3 and < 1/3 depth, and between surgical stages I, and III and IV. There was no significant correlation between serum CA125 levels and histological type. The serum CA125 value (mean +/- S.D., U/ml) was 179.0 +/- 291.0 (N = 6) in cases with lymph node metastasis and 15.8 +/- 8.5 (N = 37) in cases without metastasis (p < 0.001). We concluded that 32U/ml, which equals the mean + 2S.D., is a useful cut off value for suspicion of lymph node metastasis. The sensitivity and specificity of this cut off value were 100 (6/6) and 91.9% (34/37), respectively. This standard seems likely to considerably increase the accuracy of diagnosis of lymph node metastasis when taken in combination with the several factors already known to predict this. It may also be useful to diagnose lymph node metastasis in the preoperative period. Although the number of cases in this study was small, the data seem very promising for planning therapy for individual cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Phospholipase D activity of human amnion cells stimulated with phorbol ester and bradykinin.

We investigated the activity of phospholipase D (PLD) in human amnion cells labeled with [3H]oleate. The PLD activity was detected as signal-induced synthesis of phosphatidic acid (PA) and in the presence of ethanol, phosphatidylethanol (PEt). The PLD was shown to be activated by phorbol, 12-myristate, 13-acetate (PMA), calcium ionophore A23187, oxytocin, bombesin and bradykinin, but not by platelet-activating factor (PAF) and epidermal growth factor (EGF). The amniotic PLD thus appeared to be activated by a variety of agonists but with a certain specificity to stimulators. We examined the mode of the PLD activation using PMA (20 nM) and bradykinin (1 microM) as model stimulators. PMA and bradykinin elicited a rapid and sustained response with the peaks of PA-labeling attained at 5 and < 1 min after stimulation, respectively. In both cases, there was a concomitant rise of diacylglycerol (DG), and the PA accumulation was suppressed by ethanol at the expense of labeling of PEt. The PA synthesis caused by the two stimulators was similarly inhibited by staurosporine and by a chronic treatment with PMA (100 nM for 24 h), suggesting that the activation of PLD is linked to the action of protein kinase C. With the cells labeled with radioactive choline and ethanolamine, we found that the amniotic PLD hydrolyzed almost equally phosphatidylcholine and phosphatidylethanolamine. Although bradykinin and PMA stimulated cellular PLD to a comparable extent, prostaglandin (PG)E2 release was not stimulated by bradykinin in contrast to the marked effect by PMA. Further work is thus needed to clarify the significance of the novel PLD signaling pathway in the function of amnion cells.

Amnion↗
PubMed1993

Activities of antioxidant enzymes and lipid peroxidation in endometrial cancer.

Antioxidant enzyme activities and lipid peroxidation were analysed in normal endometrium and endometrial cancer tissues from Finnish and Japanese patients. The catalase and glutathione peroxidase activities of normal endometrium were significantly lower in Finns than in Japanese. Lipid peroxidation was slightly higher in endometrial cancer as compared with normal endometrium both in the Finns and in the Japanese. When cancer tissues were compared with normal endometrium both in Finns and Japanese the activity of superoxide dismutase was significantly lower in cancer tissue than in normal endometrium. In Finns glutathione S-transferase activity was also lower in endometrial cancer tissue than in normal endometrium, and a similar tendency was also found in Japanese. This study suggests that endometrial cancer tissue is associated with an impaired enzymic antioxidant defence system.

Catalase↗
PubMed1992

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↗
PubMed1992

Clinical implications of K-ras mutations in malignant epithelial tumors of the endometrium.

Tumorigenesis in humans and experimental animals appears to involve the activation of ras protooncogenes for a number of organ systems and seems to be important to the development of the metastatic phenotype in several model systems. Clinically, the presence of activated ras protooncogenes has been reported to be a negative prognostic factor in the myelodysplastic syndrome and in adenocarcinoma of the lung. In the present study we examined 49 cases of endometrial carcinoma for mutations in the first exon of K-ras using the polymerase chain reaction and direct sequencing. Mutations in codon 12 or 13 of K-ras were detected in 6 of 49 cases (12.2%). These six cases consisted of five endometrioid endometrial carcinomas, each of which had a mutation in codon 12, and one case of clear cell carcinoma, which had a mutation in codon 13. In our study the presence of mutations in K-ras appeared to be an unfavorable prognostic factor. Three of six patients with the mutation died during follow-up, while only 7% of the 43 patients without K-ras mutations expired during this same period. In multivariate analysis using the Cox proportional hazard model, K-ras activation appeared to be an independent risk factor when compared with clinical stage, depth of myometrial invasion, and patient age. Thus, our findings support the hypothesis that K-ras protooncogene activation plays an important role in determining the aggressiveness of endometrial carcinoma.

Base Sequence↗
PubMed1992

[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↗
PubMed1991

Lectin histochemistry in mucinous and serous ovarian neoplasms.

The lectin-binding properties of 44 cases of serous and mucinous ovarian cystadenoma, tumor of low malignant potential (LMP), and invasive carcinoma were examined histochemically. Wheat germ agglutinin (WGA), concanavalin A (con A), Ulex europaeus agglutinin I (UEA-I), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA-I), soybean agglutinin (SBA), and Robina pseudoaccacia (RPA) were employed. All the lectins examined were bound to neoplastic epithelial cells of benign and malignant tumors, but none bound exclusively to ovarian tumor cells. Different lectin-binding patterns between serous and mucinous neoplasms were observed, with the exception of RPA. UEA-I, con A, RPA, and PNA in serous neoplasms and UEA-I, RPA, and WGA in mucinous neoplasms demonstrated lectin-binding properties of LMP tumors intermediate between those of cystadenoma and invasive carcinoma. These findings indicate that serous and mucinous ovarian neoplasms contain different glycoconjugates, that malignant transformation of the neoplasms is associated with alteration of these glycoconjugates, and especially that LMP tumors have a different composition of cellular glycoconjugates from that of invasive ovarian carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1990

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↗
PubMed1990

Ultrastructural and immunohistochemical study of infiltration in microinvasive carcinoma of the uterine cervix.

Carcinoma in situ and microinvasive cancer of the cervix were compared by transmission electron microscopy to examine ultrastructural features of the locally infiltrating lesion of microinvasive cancer. Many pseudopod-like cytoplasmic protrusions of the cancer cells and abundant microfilaments parallel to the direction of the protrusion were seen. Concomitant with the disappearance of part of the basal lamina, many vesicles 70-90 nm in diameter were observed, suggesting a role for these vesicles in cancer infiltration. With the immunoperoxidase method, the distribution of fibronectin around the invasive lesion also was examined. Fibronectin is a component of extracellular matrices and presumably, in view of its action on cell adhesion, is a resistant factor against cancer cell infiltration. Fibronectin decreased in the transitional area between the cancer nest and the stroma during the stage of microinvasion.

Actin Cytoskeleton↗
PubMed1990

Immunohistochemical comparison of new monoclonal antibody 1C5 and carcinoembryonic antigen in the differential diagnosis of adenocarcinoma of the uterine cervix.

The reactivities of new monoclonal antibody 1C5 and anti-carcinoembryonic antigen (CEA) were determined immunohistochemically in 4 adenocarcinomas in situ, 20 invasive adenocarcinomas of various types, and 6 adenosquamous carcinomas of the uterine cervix, as well as in 10 endometrial adenocarcinomas and 10 normal cervices. Among the invasive adenocarcinomas, 90% were positively stained by 1C5 and 55% stained for CEA. Three of four in-situ adenocarcinomas were positively stained by 1C5 and two of four were positively stained by anti-CEA. All adenosquamous carcinomas were stained by 1C5 and four of six stained for CEA. Invasive adenocarcinomas always stained more intensely with 1C5 than did noninvasive lesions in the same specimen. Poorly differentiated adenocarcinomas were stained as strongly with 1C5 as were well-differentiated tumors, but CEA was less effective in identifying poorly differentiated lesions. 1C5 was also more useful than CEA was in distinguishing glandular from squamous neoplastic differentiation, and also appears to be useful in distinguishing endocervical from endometrial differentiation.

Adenocarcinoma↗