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Biomedical subjects

T Kamura

Publications and source records attributed to T Kamura.

At least 73 records · Page 4Linked to original sources

Relationship between pelvic lymph node involvement and other disease sites in patients with ovarian cancer.

In 109 patients with epithelial ovarian cancer, 25 (23%) had pelvic lymph node (PLN) metastasis. Positive rates of PLN metastasis according to the clinical stage based on disease distribution except retroperitoneal lymph node were 2% for stage I, 6% for stage II, 44% for stage III, and 64% for stage IV. The nine disease sites, such as subdiaphragmatic surface, liver and spleen capsule, intestine and mesentery, omentum, pelvic peritoneum, sigmoid colon and rectum, uterus and tubes, peritoneal cytology, and paraaortic lymph node (PAN), were found to have a statistically significant relationship with PLN metastasis by univariate analysis. Multivariate analysis using a logistic regression model selected the omentum and PAN as independent factors with a statistical significance. The incidence of PLN metastasis in epithelial ovarian cancer with the above two parameters can be assumed to be greater than that without the two parameters by 42.6 times. The present data suggested that for the disease with PAN and/or omental metastasis, removal of the PLN may be mandatory from the standpoint of cytoreduction.

Adolescent↗

The prognostic value of semiquantitative nuclear grading in endometrial carcinomas.

The objective of this study was to evaluate the prognostic value of a convenient nuclear grading system based on only the proportion of nuclei measuring more than 10 microm in length at the shortest axis in endometrial carcinomas. Of the 235 cases reviewed, 9 serous and 5 clear cell adenocarcinomas and 2 small cell carcinomas were eliminated, resulting in a study population of 219 cases of endometrial adenocarcinoma. The architectural grade was determined by the FIGO system. The criteria for nuclear grade were as follows: grade 1, no nucleus measuring more than 10 microm in length at the shortest axis; grade 2, nuclei measuring more than 10 microm in length at the shortest axis seen in percentages ranging between 0 and 10% of tumor cells in active areas; and grade 3, more than 10% of tumor cells in active areas with nuclei measuring more than 10 microm in length at the shortest axis. The criteria for combined grades were as follows: the tumors were graded according to the architectural grade, but high-grade nuclear abnormalities increased the grade by one for architectural grade 1 and 2 tumors. The cumulative 10-year survival rates for architectural grades 1, 2, and 3 were 92.4, 82.6, and 65.2%, respectively (chi2 = 17.9, P = 0.001). The survival rates for nuclear grades 1, 2, and 3 were 96.2, 76.1, and 70.1%, respectively (chi2 = 21.6, P < 0.001), while for combined grades 1, 2, and 3 the survival rates were 98.3, 83.2, and 65.2%, respectively (chi2 = 26.9, P < 0.001). Even when the cases were limited to the 147 stage I endometrial carcinomas examined, the prognostic value of the combined grading system was still found to be superior to that of the architectural grading system. Our observations therefore supported the FIGO recommendation for nuclear grade not only in stage I endometrial carcinomas, but also in all stages of endometrial carcinomas.

Adenocarcinoma, Clear Cell↗

Early adenocarcinoma of the uterine cervix.

The purpose of this study was to evaluate the prognostic significance of the tumor depth, horizontal spread, and volume in early cervical adenocarcinoma while excluding adenocarcinoma in situ. Thirty cases who had been treated at our institution having cervical adenocarcinoma with a tumor depth of less than 5 mm were clinicopathologically reviewed. The volumes were estimated based on the portion with the largest tumor surface area by multiplying three dimensions: depth, horizontal spread, and a third dimension. The third dimension was calculated by the method of Burghardt to be 1.5 times the largest measured depth or spread. Two of the 30 patients recurred in the vagina at 18 and 163 months after the initial operation; the former patient died of disease 87 months postoperatively. The remaining 28 patients are all doing well without recurrence (range of follow-up from 24 to 232 months; median 79 months). No pelvic or paraaortic lymph node metastases were seen in 25 and 22 cases, respectively. None of the 21 cases with a lesion measuring less than 3 mm in depth had recurrence. On the other hand, 1 of 23 with a tumor volume up to 500 mm3 had recurrence. The estimated 5-year progression-free survival rates for patients with cervical adenocarcinoma with a depth of less than 3 mm and those with a depth of more than 3 mm were 100 and 88.89%, respectively (P = 0.116). The depth of stromal invasion may therefore be a good predictor of lymph node metastasis and recurrence in early cervical adenocarcinoma.

Adenocarcinoma↗

The significance of peritoneal cytology in uterine cervix and endometrial cancer.

OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to elucidate the prognostic value of peritoneal cytology in patients with uterine cervix and endometrial cancer. MATERIALS AND METHODS: The incidence of positive peritoneal cytology was investigated in 642 patients including 339 uterine cervix and 303 endometrial cancers. Survival was estimated by the Kaplan-Meier method in a subgroup of 116 stage II cervix and 199 stage I endometrial cancers, and multivariate analysis using Cox's proportional hazards model was used to identify an independent prognostic factor. RESULTS: The incidence of positive peritoneal cytology was found to be 9% in uterine cervix cancer and 15% in endometrial cancer. The incidence was higher in patients with some clinicopathologic status such as advanced stage, lymph node metastasis, ovarian metastasis, and deeper myometrial invasion. The 5-year survival rate for patients with positive or negative peritoneal cytology was 44 or 80% in stage II cervix cancers and 80 or 92% in clinical stage I endometrial cancers, respectively. Multivariate analysis revealed that independent prognostic determinants were pelvic and paraaortic lymph node metastasis and peritoneal cytology in stage II cervix cancer and peritoneal cytology in stage I endometrial cancer. Proper treatment protocol should be scheduled for patients with positive peritoneal cytology.

Endometrial Neoplasms↗

An attempt to generate an antitumor effect in the regional lymph nodes against endometrial cancer cells by inducing antitumor cytokines.

Phytohemagglutinin-stimulated regional lymph node cells obtained from gynecological cancer patients exerted a significant antiproliferative activity against an endometrial cancer cell line, RL95-2 on a human tumor clonogenic assay, and released a high amount of tumor necrosis factor alpha (TNF alpha), and interferons. The activity was thought to be partly due to released TNF alpha, because RL95-2 was highly sensitive to recombinant TNF alpha. However, anti-TNF alpha failed to inhibit the activity, which indicated the probability of some as yet unclarified participation of cytokines. Therefore, the regional lymph nodes might be used as sites of endogenous cytokine therapy in endometrial cancer patients.

Antibodies↗

A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas.

BACKGROUND: A large number of monoclonal antibodies (MoAbs) against human tumor cells have been generated and it has been shown that these MoAbs are useful tools in the diagnosis and treatment of cancer patients, as well as in the basic investigation of the oncogenesis and characterization of cancer cells. METHODS: The 22-1-1 MoAb was established by cell fusion between mouse myeloma cells and spleen cells derived from mice immunized with the human uterine cervical adenocarcinoma cell line, SiSo. The tissue distribution and biologic characteristics of the 22-1-1 antigen (Ag) were examined. RESULTS: The 22-1-1 Ag was distinct from the known tumor-associated antigens such as YH 206, GA 733, CA 125, carcinoembryonic antigen, and sialyl Le(x) molecules in an expression pattern in human tumor cell lines. An immunohistochemical study revealed that 22-1-1 Ag was expressed in 87.5% of uterine cervical adenocarcinomas, 66% of uterine endometrial adenocarcinomas, and 58.8% of ovarian carcinomas. Moreover, 22-1-1 Ag was detected in 87.7% of uterine cervical squamous cell carcinomas; however, it was not detected in 87.7% of uterine cervical or ovarian tissues, except in uterine endometrial glands, in which its expression was observed at low levels. The 22-1-1 Ag was secreted into cell culture supernatant fluids and was also detected in the vaginal discharges of uterine cervical carcinoma patients. The antigenic epitope of 22-1-1 Ag was shown to be a protein with a molecular weight of 78 kilodaltons using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. CONCLUSIONS: The 22-1-1 MoAb reactive to a novel tumor-associated antigen was generated. This Ag was expressed in cancer cells derived mainly from the uterus and ovary. Moreover, 22-1-1 Ag was associated in the vaginal discharges of uterine cervical carcinoma patients. 22-1-1 MoAb is a potential tool for the study of oncogenesis and the management of cancer patients.

Adenocarcinoma↗

Endometrial carcinoma associated with hyperplasia.

The aim of this study was to clarify the relationship of endometrial hyperplasia to endometrial carcinoma. From 1979 through 1990, 115 cases of stage I-IV endometrial carcinomas treated initially by hysterectomy were reviewed histologically. Forty-two of 115 (36.3%) patients had hyperplasia in the endometrium adjacent to the carcinoma. Women with both endometrial carcinoma and hyperplasia were significantly younger than those with carcinoma without hyperplasia (P < 0.05). In a comparison of patients with carcinoma without hyperplasia, those with hyperplasia were better differentiated (P = 0.0072), and lacked deep myometrial invasion (P < 0.0001), cervical involvement (P = 0.0192), lymph-vascular space invasion (P = 0.0102), and para-aortic lymph node metastases (P = 0.0434). The presence of endometrial metaplasia (P = 0.0001). The estimated 5-year survival rates for patients with carcinoma with hyperplasia and those with carcinoma without hyperplasia were 96.55 and 73.33%, respectively (P = 0.0016). In endometrial carcinomas, the presence of endometrial hyperplasia may demonstrate a more favorable prognosis.

Adult↗

A sequence analysis of von Willebrand factor mRNA, gene, and pseudogene in two patients with von Willebrand disease type 2B, and an investigation of gene conversion in its gene.

We identified the point mutations in two unrelated patients with von Willebrand disease (vWD) type 2B using sequence analyses of the gene, pseudogene and messenger RNA of vWF. Both patients were determined to be heterozygotes with amino acid transitions of 1308 Arg-->Cys in Case 1 and 1316 Val-->Met in Case 2. Moreover, we also found single base transitions 7541 A-->G in intron 27 of the active gene, and 7642 A-->G, which thus destroyed the Kpn 1 site, in its pseudogene in both cases. Since these mutations represented changes in the base between the gene and its pseudogene, we studied the presence of gene conversion in exon 28 of vWF gene to clarify its pathological role. Using RT-PCR and an allele-specific restriction enzyme analysis, we identified no gene conversions in this region in four other patients with vWD, 25 normal subjects and one cell line, MEG01. Based on these findings, gene conversion in the vWF gene is not considered to be a frequent phenomenon in either vWD patients or normal subjects.

Adult↗

[Alteration of metastatic potential of ovarian cancer in clinical course].

Ovarian cancer is one of the significant and deadly disease. Since 1980 when cisplatin was introduced in the chemotherapy, about 30% of the patients with advanced disease have achieved 5-year survival. However, remaining patients have had progressive disease or recurrence after achieving NED. Forty-seven% of recurrent disease was discovered as distant metastasis, while at initial therapy. In the recurrent disease, distantly metastatic lesions were encountered more frequently than those in primary disease. In the recurrent tumor, expression of immunohistochemical markers of malignancy, such as p53 protein and CD44v6 antigen were increased. These clinical data suggest that recurrent ovarian cancer which are exposed to anticancer agents attain increased metastatic potential. In order to assure that anticancer agent contribute to this increment, an experimental system using two human ovarian cancer cell lines (HRA, KF) and nude mice in which cancer cells were exposed to cisplatin in vivo was introduced. Cancer cells exposed to cisplatin in vivo (treated cells) made spontaneously more metastatic nodules in the mouse lung than those exposed to PBS (untreated cells). This result suggest that cisplatin induce the increase of metastatic potential of cancer cells in vivo. Treated cells showed higher invasiveness compared with untreated cells when inoculated in the footpad. Three major factors which were generally proposed to be necessary for cancer cell to give rise to invasion, such as attachment to extracellular matrix, production of proteolytic enzyme, and cellular mobility. For all of these factors, treated cells were superior to untreated cells. These results obtained suggests that cisplatin could increase the metastatic potential of cancer by enhancing potential of invasion. To investigate the mechanism of this phenomenon from the standpoint of genetic mutation, clonal analysis of experimental cancer in vivo was performed using southern blot method. Cancer cells before inoculation to the mice consisted of multiple clones. In 5 week after inoculation, tumor was wholely occupied by only one clone which showed one band on the lane. At this point cisplatin were administered. In 6 week, new single clone appeared with different band pattern from that of the clone at the administration of cisplatin. Furthermore, the cisplatin-induced new clone metastasized to the lung, while no metastasis was observed in the mouse with PBS-treated tumor during the same period. These data suggest that increased metastatic potential after cisplatin treatment is due not to selection but to creation of highly metastatic clone caused by potential of genetic mutation of cisplatin. In conclusion, chemotherapeutic agent has a potential to create highly malignant cancer cells as well as a potential to kill cancer cells.

Animals↗

Endometrial carcinoma in women 65 years of age or older: a clinicopathologic study.

The purpose of this study is to clarify the clinical and pathologic features of endometrial carcinomas in women 65 years of age or older in Japan where the incidence of endometrial carcinoma is still low. Between 1979 and 1990, 24 of 164 patients with endometrial carcinoma were 65 years old or over. In addition, 41 patients 50 years of age or younger were also analyzed, comparing clinicopathologic features with those of older age group. Seventeen of 24 (71%) showed deep myometrial invasion (more than a half of the myometrium). Endometrial carcinomas in older age groups have deeper myometrial invasion, and higher histologic grade than those of younger age groups. The adjacent endometrium is usually atrophic and the presence of hyperplasia and/or metaplasia was significantly less frequent in the older group as compared with that in the younger group. Nine of these 24 patients died of disease in a relatively short follow-up period. The prognosis for the older group (expected 5-year survival 69.2%) is significantly worse than for the younger group (expected 5-year survival 94.3%) (P = 0.006). Endometrial carcinomas in patients over 65 years of age are usually of high histologic grade, and have deep myometrial invasion and an unfavorable prognosis.

Age Distribution↗

Expression of MAGE-1, MAGE-2, MAGE-3/-6 and MAGE-4a/-4b genes in ovarian tumors.

MAGE genes encoding tumor-rejection antigens recognized by cytotoxic T lymphocytes are expressed at the mRNA level in various malignant tumors. We have investigated the expression of genes MAGE-1, -2, -3/-6 and -4a/-4b at the mRNA level in malignant and non-malignant ovarian tumors as well as in normal ovaries by reverse transcription-polymerase chain reaction. MAGE-1, -2, -3/-6 and -4a/-4b were expressed in 12, 5, 11 and 4 of 58 malignant tumors, respectively. The majority of these MAGE-mRNA-positive tumors were histologically surface-epithelial-stromal tumors, in particular serous adenocarcinomas. They mostly consisted of either advanced-stage or recurrent tumors. In contrast, neither benign tumors nor normal ovaries expressed any of the MAGE genes investigated. A 46-kDa MAGE-1 protein was identified in MAGE-1-mRNA-positive serous adenocarcinomas by immunoblot analysis with polyclonal anti-MAGE-1 antibody. These results provide important information for specific immunotherapy of ovarian serous adenocarcinomas with MAGE gene products.

Amino Acid Sequence↗

An abnormal fibrinogen Fukuoka II (Gly-B beta 15-->Cys) characterized by defective fibrin lateral association and mixed disulfide formation.

A dysfibrinogenemia was attributable to a single amino acid substitution from glycine to cysteine at residue 15 of the B beta chain in a fibrinogen molecule designated as fibrinogen Fukuoka II. The fibrinogen Fukuoka II showed prolonged thrombin and reptilase times and impaired fibrinopeptide B release by thrombin, resulting in abolition of fibrin monomer repolymerization under physiological conditions. Repolymerization of the des-(B beta 1-42)-fibrin monomers, however, was not distinguished from the normal pattern of des-(B beta 1-42)-fibrin monomers, suggesting that no other abnormality existed in fibrinogen Fukuoka II. Although an additional cysteine was substituted at residue 15 of the B beta chain, fibrinogen Fukuoka II had no free sulfhydryl group within the molecule. Instead, fibrinogen Fukuoka II formed a disulfide bond with cysteine, albumin, another mutated B beta chain within the same molecule, or intermolecular dimeric fibrinogen Fukuoka II. The mutation in fibrinogen Fukuoka II was the same as that in fibrinogen Ise published previously (Yoshida, N., Wada, H., Morita, K., Hirata, H., Matsuda, M., Yamazumi, K., Asakura, S., and Shirakawa, S. (1991) Blood 77, 1958-1963). Fibrinogen Ise, however, has been described as having prolonged thrombin time but normal reptilase time. Reasons for the discrepancy were not clear. Analysis of the B beta 1-42 fragment showed that fibrinogen was heterogeneous at position 31 of the B beta chain with respect to proline or hydroxyproline.

Amino Acid Sequence↗

The prognostic significance of lymphovascular space invasion in endometrial cancer when conventional hemotoxylin and eosin staining is compared to immunohistochemical staining.

The current study was undertaken to compare the usefulness of hemotoxylin and eosin (H&E) staining and immunohistochemical staining to identify lymphovascular space invasion (LVSI) in endometrial cancer and to evaluate the presence of LVSI detected by either technique as an independent prognostic factor. Histologic sections from 92 patients with clinical stage I-II endometrial cancer were reviewed, and representative sections were stained immunohistochemically with antibodies for von Willebrand factor and blood group isoantigens. To compare the prognostic significance of LVSI detected by H&E staining with that detected by immunohistochemical staining, univariate and multivariate analyses were performed. Thirty (32.6%) of the 92 cases showed LVSI in H&E staining. In 8 of the 30 cases, LVSI was negative by immunohistochemical staining, while LVSI was positive by immunohistochemical stainings in 2 of 62 cases showing negative LVSI in H&E staining. In univariate analysis, LVSI detected by H&E and immunohistochemical staining was proved to be significant as a prognostic factor. In multivariate analysis by Cox's proportional hazards model, LVSI identified by H&E staining was selected as one of significant prognostic factors, but LVSI identified by immunohistochemical staining not selected. The results of this study indicate that LVSI is one of the independent prognostic factors in endometrial cancer, and that LVSI as detected by H&E is more prognostic of survival than immunohistochemical detection.

Adult↗

Malignant trophoblastic neoplasms with different modes of origin.

The genetic origin of 24 trophoblastic neoplasms was determined using PCR polymorphisms. Based on pregnancy history, these tumors included nine postmolar trophoblastic tumors, 12 tumors preceded by live birth or abortion, and three nongestational tumors. Androgenetic origin was defined in eight post-molar trophoblastic tumors, and the remaining one might have arisen from a normal fertilization. Six tumors retained genetic features carried by the homozygous complete mole. Two tumors showed PCR polymorphism compatible with that of the heterozygous complete mole. All 12 tumors in the second class had alleles of both paternal and maternal contribution. However, discordance of sex between the antecedent pregnancy product and the tumor was recognized in three choriocarcinomas. The absence of paternal contribution suggested a parthenogenetic origin of three nongestational choriocarcinomas. The findings that PCR polymorphisms were either homozygous in certain loci or heterozygous in others may mean that the tumor was derived from a germ cell after meiosis I. As a result, at least three subtypes with different modes of origin were demonstrated in the 24 trophoblastic tumors. These findings underscore the importance of precise genetic marker analyses in a large series to clearly identify clinical and biologic characteristics of each subset of tumors.

Base Sequence↗

The promotion of invasion through the basement membrane of cervical carcinoma cells by fibronectin as a chemoattractant.

An in vitro migration and invasion assay was used as the model system to study the effect of 3T3 fibroblast conditioned medium (FCM) and purified human fibronectin on the invasion of cervical carcinoma cells. The 3T3 FCM significantly enhanced both the migration and the invasion of a cervical carcinoma cell line, HeLa. This enhancement of migration and invasion was inhibited by anti-fibronectin antibody. Purified fibronectin alone enhanced the invasion in a dose-dependent manner for all cervical carcinoma cell lines, HeLa, CAC-1 and TMCC. The pretreatment of cells with cell binding aminosequences, GRGDSP and/or YIGSR blocked the enhancement of cell invasion. The implication of these findings for the invasion of cervical carcinoma is discussed.

3T3 Cells↗

Adenoma malignum of the uterine cervix detected by imaging methods in a patient with Peutz-Jeghers syndrome.

Adenoma malignum of the uterine cervix in a 25-year-old Japanese woman with Peutz-Jeghers syndrome (PJS) is described. A cervical multicystic mass was detected by CT scan, sonography, and MR imaging. These imaging findings strongly suggested the presence of adenoma malignum in spite of normal Pap smear, colposcopy, and cervical biopsy reports. Radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and para-aortic lymph node biopsy were performed after confirmation of adenoma malignum by conization. Both ovaries showed multicentric sex cord tumor with annular tubules. She is alive and well with no evidence of disease 23 months after surgery. Imaging methods including sonography, CT scan, and MR imaging may be useful aids in detecting the presence of adenoma malignum, especially in patients with PJS.

Adenoma↗

A comparative study of partial primary structures of the catalytic region of mammalian protein C.

Protein C (PROC) is a plasma vitamin K-dependent zymogen of a serine protease which regulates blood-clotting cascade through proteolytic inactivation of the non-enzymatic cofactors of blood coagulation, Va and VIIIa. We characterized the partial nucleotide and amino acid sequences for the catalytic domain of PROC in six mammalian species, rhesus monkey, dog, cat, goat, horse and mouse, and compared these sequences with known ones from humans, the bovine and rat. By using a pair of primers based on the nucleotide sequences from human and bovine PROC cDNA, the PROC gene fragments were enzymatically amplified from their genomic DNAs and were sequenced by the dideoxy-termination method. The cloned PROC gDNA encoded a part of the heavy chain of PROC including the lesions of active site residues corresponding to human PROC Asp-257 and Ser-360. Comparison of the sequences from these species revealed that there was a high degree of homology at the nucleotide and amino acid levels; from 69% to 96% of the amino acids in the catalytic region were identical among the nine species including humans, the bovine and rat. The locations of five Cys residues as well as the putative carbohydrate attachment sites were evolutionally conserved. All the amino acids recognized in the human abnormal PROC variants were conserved across species, suggesting their functional importance, and a comparison of the conserved residues among PROC from multiple species will provide considerable information in the investigations of PROC functions.

Amino Acid Sequence↗