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Biomedical subjects

I Konishi

Publications and source records attributed to I Konishi.

At least 37 records · Page 2Linked to original sources

HCG promotes proliferation of uterine leiomyomal cells more strongly than that of myometrial smooth muscle cells in vitro.

Uterine myomas often enlarge rapidly during pregnancy. This rapid increase in size may imply that human chorionic gonadotrophin (HCG) influences cell proliferation in uterine leiomyomata. To assess the direct effect of HCG on normal uterine smooth muscle and uterine leiomyomata, we investigated cell proliferation and the expression of cell cycle-related proteins in these cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that HCG/LH receptor was present in both cultured myometrial and leiomyomal cells. Treatment with HCG significantly increased cell proliferation in both myometrial and leiomyomal cells (P < 0.03), especially at an early phase in the 9 day culture. The increase in the viable cell number induced by HCG treatment was significantly greater in leiomyoma cells than in myometrial cells on day 3 in culture (P < 0.03). In leiomyomal cells, the expression of proliferating cell nuclear antigen (PCNA), cyclin E and cdc2 was significantly increased by HCG treatment (P < 0.05) even at the lowest concentration used (3 nmol/l). In myometrial cells, the expression of cyclin E and cdc2 was significantly increased by HCG treatment (P < 0.05) only at the highest concentration used (30 nmol/l). These results suggest that HCG directly promotes the proliferation of myometrial and leiomyomal cells, with the latter showing the greater response of the two.

Adult↗

Anti-CD9 monoclonal antibody-stimulated invasion of endometrial cancer cell lines in vitro: possible inhibitory effect of CD9 in endometrial cancer invasion.

Cell surface marker CD9 has been reported to play a role in inhibiting trophoblastic cell invasion. Since the invasive properties of cancer cells may resemble those of trophoblasts, we decided to investigate the role of CD9 in the invasion of endometrial cancer cells. In normal human endometrium, CD9 was found to be constitutively expressed on epithelial cells, as reported previously. While epithelial cells of endometrial hyperplasia (n = 5) were also positive for the expression of CD9, endometrial adenocarcinomas (n = 15) showed reduced expression. In order to clarify the significance of this reduced CD9 expression in endometrial cancer, an in-vitro invasion assay system was used to assess the effect of anti-CD9 monoclonal antibody (mAb) on the invasive properties of endometrial cancer cell line. Anti-CD9 mAb significantly enhanced invasion of the RL95-2 and Ishikawa cell lines, without affecting cell proliferation. Since CD9 is associated with the integrin subunits beta(1), alpha(3) and alpha(6) in human endometrium, we investigated the functional relationship between CD9 and these integrins in the RL95-2 cell line. Monoclonal antibodies against the integrins beta(1), alpha(3) and alpha(6) inhibited RL95-2 cell invasion. However, anti-CD9 mAb continued to show a stimulatory effect on RL95-2 cell invasion after treatment with anti-integrin alpha(3) mAb. In contrast, the anti-CD9 mAb had no effect after treatment with the mAb for integrins alpha(6) and beta(1). These findings indicate that CD9 is involved in regulating the invasive properties of endometrial carcinoma cells and that this effect is partially mediated by integrin subunits alpha(6) and beta(1). Thus, CD9 appears to be involved in the prevention of endometrial cancer invasion.

Adult↗

Immunohistochemical detection of the Wilms' tumor gene (WT1) in epithelial ovarian tumors.

The Wilms' tumor gene WT1 plays multiple roles in the development of the genitourinary organs and Wilms' tumors. The aims of this study were to immunohistochemically evaluate WT1 expression in normal female genital tissues and in epithelial ovarian tumors and to look for correlations between WT1 expression and histologic subtypes and cell proliferation in epithelial ovarian tumors. In normal female genital organs, WT1 expression was recognized in ovarian surface epithelium, the lining of inclusion cysts, and tubal epithelium, but not in the cervical or endometrial epithelium. In epithelial ovarian tumors, serous tumors generally revealed a high WT1 expression. Among adenocarcinomas, serous carcinoma revealed a significantly higher WT1 expression than the other histologic subtypes. There were no significant correlations between the WT1 labeling index and the Ki-67 labeling index, and no significant difference in survival between those showing high and low WT1 expression among the malignant cases. These results suggest that WT1 expression may be related to cell differentiation, and that the histologic subtypes of epithelial ovarian carcinomas may differ considerably in their biological characteristics.

Adenocarcinoma↗

Epithelioid trophoblastic tumor metastatic to the vagina: an immunohistochemical and ultrastructural study.

We describe an epithelioid trophoblastic tumor (ETT) metastatic to the vagina in a 30-year-old Japanese woman. A polypoid tumor in the vaginal orifice was composed of nests of intermediate trophoblastic cells that showed a striking epithelioid appearance. In the hysterectomy specimen, a tumor infiltrated through the myometrium and showed histologic findings similar to those of the vaginal tumor. The tumor cells were positive for cytokeratin, inhibin-alpha, and melanoma cell adhesion molecule (Mel-CAM, CD146) but were only focally positive for human placental lactogen. Electron microscopic examination revealed bundles of well-developed, intermediate-type filaments surrounding the nuclei.

Adult↗

A comparative analysis of cross sectional imaging techniques in minimal deviation adenocarcinoma of the uterine cervix.

A pre-operative diagnosis of minimal deviation adenocarcinoma of the cervix is often difficult. We assessed transvaginal sonography, computed tomography and magnetic resonance imaging in 16 women with histologically confirmed minimal deviation adenocarcinoma. Increased fluid accumulation was frequently observed within the endometrial cavity and/or vagina by all three techniques. A multicystic cervical lesion was occasionally detected by transvaginal sonography or by computed tomography. On T2-weighted magnetic resonance images, a noncystic fine villous or multicystic lesion was noted in most cases. Among the three imaging techniques used, T2-weighted magnetic resonance images showed the most detailed features and the best correlation with the histology.

Adenocarcinoma↗

[Spreading patterns of hilar bile duct cancer].

Spreading patterns of hilar bile duct cancer were investigated based on cases resected in our institution and reported cases in Japan. Forty-seven patients underwent resection in our institution during the past 20 years. Three patients(12%) survived for more than 5 years. The depth of tumor invasion was m or fm in 4 and se or si in 26 patients. Positive cancer invasion in the cut end was classified as hm2 or dm2 in 8 patients and em2 in 13. Twenty-four (60%) of 40 patients investigated histologically had positive lymph node metastases. Invasion of the ss layer or deeper perineural invasion occurred in 92.5%. In terms of direct invasion of the liver, hinf1 occurred in 20(42.6%). Fourteen(29.8%) han invasion of the portal vein(more than vs1). Patients with invasion of the hepatic artery were not resected. The 5-year survival rate by cancer stage was 38% in stage I, 20% in stage II, 16% in stage III, and 0% in stage IV. Surgery was assessed as Cur A in 19 patients (46.3%), Cur B in 7 (17.1%), and Cur C in 15 (36.6%). In Cur A patients the 5-year survival rate was 18%, while that for our Cur B and Cur C patients was 0%. Our patient series was more advanced in terms of cancer stage than the statistical Japanese series and both included a significant number of noncurative cases. Hepatic resection of the right or left lobe, medial segment, and S4a and S5, combined resection of the caudal lobe, and combined portal vein resection are important as radical surgery in the treatment of this cancer.

Bile Duct Neoplasms↗

Expression of thymidylate synthase in relation to survival and chemosensitivity in gastric cancer patients.

Expression of thymidylate synthase (TS) has been studied as a prognostic factor and mechanism of drug resistance in gastric cancers. The relationship between TS expression in surgically resected specimens and clinicopathological factors was examined in 216 gastric cancer patients. Immunohistochemical demonstration of the protein was achieved using an anti-TS polyclonal antibody. Positive TS staining was observed in 50 patients (23.1%). Lymph node metastasis was more frequent in patients with TS-positive tumors than in those with TS-negative tumors (P<0.01). Patients were followed for more than 5 years and survival was examined. In 163 patients who received fluorouracil (FU)-based chemotherapy, the overall 5-year survival rate was 41.8% for patients with TS-positive tumors and 57.0% for patients with TS-negative tumors (P<0.01). In the 53 patients who did not receive chemotherapy, these figures were 25.6% and 79.5%, respectively (P<0.05). In patients with T3 gastric cancer who were treated with curative gastrectomy, however, FU-based chemotherapy did not affect survival of either patients with TS-positive tumors or with TS-negative tumors. Multivariate analysis also revealed TS expression to be a significant variable for predicting postoperative survival (P<0.05). These results indicate that TS expression can be used as an independent prognostic factor for patients with gastric cancer. However, TS expression is not a major predictor of the efficacy of FU-based chemotherapy.

Adult↗

Clinical results of transcatheter arterial infusion for uterine cervical cancer.

The effects of transcatheter intraarterial infusion of anticancer drugs on the prognosis of cervical cancer were retrospectively studied. Two or three sessions of transcatheter arterial infusion therapy were performed for 68 patients with primary uterine cervical cancer. The number of patients with stage I, II, III, or IV disease were 13, 22, 24, and 9, respectively. Patients with squamous cell carcinoma comprised 3, 17, 17, and 5 of the respective groups, and the patients with stage I and II disease had either adenocarcinoma or adenosquamous carcinoma, or bulky tumor (>4 cm). The drugs infused were cisplatin (60-70 mg/m2), doxorubicin hydrochloride (30-40 mg/m2), mitomycin (15 mg/m2), and 5-fluorouracil (500 mg/body). They were infused via the bilateral internal iliac arteries. Fifty-eight of the 68 patients (85%) received a radical hysterectomy after transcatheter arterial infusion: 12 of 13 with stage I disease, 21 of 22 with stage II disease, 20 of 24 with stage III disease, and five of nine with stage IV disease. Two patients with stage III disease received radical radiotherapy. The other eight patients (one with stage I disease, one with stage II disease, two with stage III disease, and four with stage IV disease) did not receive an operation after transcatheter arterial infusion because they had distant metastases at the time of operation. Thirty-two of 58 patients (56%) received postoperative radiotherapy. The complete histologic response rates (no active cancer cells) after transcatheter arterial infusion were: 2 of 12 patients with stage I disease, 3 of 21 patients with stage II disease, 5 of 20 patients with stage III disease, and one of five patients with stage IV disease. Tumors with squamous cell carcinoma disappeared at a significantly better rate (10/36, 28%) than did tumors with adenocarcinoma or adenosquamous cell carcinoma (1/22, 5%; p < 0.05). The overall 5-year survival rates of the patients with stages I, II, and III disease were 92.3%, 62.2%, and 71%, respectively. The 5-year survival rates of the patients who underwent surgery with stage I, II, and III disease were 100%, 66.3%, and 71.5%, respectively. Leukocytopenia and thrombocytopenia occurred as an acute complication in 75% and 79% of the patients, respectively. As a late complication, ileus occurred in 7%. Transcatheter arterial infusion may improve the prognosis of patients with cervical cancer without increasing the incidence of late complications.

Antineoplastic Combined Chemotherapy Protocols↗

Expression of steroid receptors, Ki-67, and p53 in uterine leiomyosarcomas.

The expression of estrogen receptor (ER), progesterone receptor (PR), tumor suppressor oncogene p53, and Ki-67 was compared in uterine smooth muscle tumors, including leiomyosarcoma (LMS), tumor of uncertain malignant potential (UMP), cellular leiomyoma (CL), bizarre leiomyoma (BL), and usual leiomyoma (UL). ER and PR were expressed in all ULs. PR was expressed in UL irrespective of the phase of the menstrual cycle; this staining was also observed in CL, UMP, and BL, although BL showed variable staining for ER. Compared to these tumors, the expression of both ER and PR was markedly reduced in LMS. The results of ER and PR transcripts by reverse transcription-polymerase chain reaction were compatible with those of immunohistochemistry. The number of Ki-67 positive cells in LMS was significantly higher than in UMP, BL, CL, and UL. p53 immunoreactivity was seen in 10 of 14 LMSs, and missense mutation in the p53 gene was found in 4 of 10 LMSs. These results suggest that abnormal expression of ovarian steroid receptors, p53, and Ki-67 is frequently associated with LMS of the uterus.

Adult↗

Unusual appearances of uterine leiomyomas: MR imaging findings and their histopathologic backgrounds.

Typical appearances of uterine leiomyoma at magnetic resonance (MR) imaging are well established, and diagnosis is usually easy. However, cases that, are extremely difficult to differentiate from other conditions are occasionally encountered. To understand the wide spectrum of MR imaging findings, such unusual appearances can be classified into three categories: degeneration and other histopathologic findings, specific types of unusual leiomyomas, and unusual growth patterns. The common types of degeneration are hyaline (>60% of cases), cystic (approximately 4%), myxoid, and red. Edema is not a phenomenon of degeneration but is a common histopathologic finding (approximately 50% of cases). Hemorrhage, necrosis, and calcification (approximately 4% of cases) may also be observed. Specific types of unusual leiomyomas include lipoleiomyoma and myxoid leiomyoma, which may have MR imaging features characteristic enough to allow differentiation from other gynecologic and nongynecologic diseases. Intravenous leiomyomatosis, metastasizing leiomyoma, diffuse leiomyomatosis, and peritoneal disseminated leiomyomatosis represent unusual growth patterns; other unusual growth patterns are retroperitoneal growth, parasitic growth, and the pattern that may occur in cervical leiomyoma. Because leiomyomas are the most common gynecologic tumors and are exclusively benign, it is important to be familiar with the variety of MR imaging appearances of uterine leiomyomas to distinguish them from other significant diseases.

Female↗

Review: gonadotropins and development of ovarian cancer.

An epidemiological correlation between infertility therapy and ovarian cancer development has been reported in 1992; consequently, the possible role of gonadotropins in ovarian carcinogenesis has received much attention. Here, we review the effect of gonadotropins on epithelial ovarian carcinoma and ovarian surface epithelium (OSE), which is the histogenetic origin of carcinomas. Recent studies have demonstrated that gonadotropin receptors are expressed in OSE and in approximately half of the ovarian carcinomas. Gonadotropins have also been reported to stimulate cell proliferation and to inhibit apoptosis in OSE and ovarian cancer cells. These data suggest that gonadotropins play an important role in the development, progression, and/or chemoresistance of ovarian carcinomas. Hormonal therapy against gonadotropins may be applicable for patients with ovarian carcinoma.

Animals↗

Dermoid cysts of the ovary with malignant transformation: MR appearance.

OBJECTIVE: This study presents the MR appearances of five women with a total of six proven dermoid cysts of the ovary with malignant transformation. To our knowledge, the MR findings of this entity have not been reported. CONCLUSION: The lesions appeared to be fat-containing tumors with a solid component (4/6) that extended transmurally (4/6) and extensively invaded neighboring pelvic organs (3/6). The supervening malignancy was squamous cell carcinoma in four tumors, melanoma in one, and transitional cell carcinoma in one. The mode of spread differed from that of common ovarian tumors in that it included transmural extension and local invasion, reflecting squamous cell carcinoma.

Carcinoma, Squamous Cell↗

MR imaging of endometrial stromal sarcoma: correlation with pathologic findings.

OBJECTIVE: This study describes MR imaging of eight patients with endometrial stromal sarcoma and correlates the imaging findings with histopathologic findings. To our knowledge, the radiologic findings of this entity have not been reported in the literature. CONCLUSION: Endometrial stromal sarcoma typically presents with extensive myometrial involvement, which is either sharply demarcated or diffusely infiltrative. Bands of low signal intensity are observed within the areas of myometrial involvement on T2-weighted images. These bands correspond to the preserved bundles of myometrium on pathologic examination. Tumor extension along the vessels or ligaments is another characteristic of MR imaging of endometrial stromal sarcoma.

Adult↗

Expression of MAGE genes and survival in patients with hepatocellular carcinoma.

The human melanoma antigen (MAGE) gene family encode tumor-specific antigens recognized by autologous cytotoxic T lymphocytes. Some of these antigens may be potentially useful for cancer-specific immunotherapy. The expression of MAGE genes has been reported not only in melanoma but also in various other malignant tumors. However, little is known about the expression of these genes in human hepatocellular carcinoma (HCC). We therefore analyzed, by means of a reverse transcription-polymerase chain reaction (RT-PCR), the expression of MAGE-1, MAGE-2, and MAGE-3 genes in 60 tissue samples resected from HCCs. The MAGE-1, MAGE-2, and MAGE-3 genes were expressed in 18 (30.0%), 9 (15.0%), and 15 (25.0%), respectively, of the 60 tumor-tissue samples. Nineteen (31.7%) samples expressed at least one of the three MAGE genes, and 8 (13.3%) expressed all three genes. In contrast, none of the MAGE genes was expressed in any of the 60 adjacent non-tumorous liver samples. The age of patients was significantly older in at least one MAGE-positive group (MAGE-positive groups) than in the MAGE-negative ones (p<0.05). The tumor size was significantly larger in MAGE-positive groups than in the negative ones (p<0.05). The serum alpha-fetoprotein level was significantly lower in MAGE-positive groups than in negative ones (p<0.05). Patients with tumors expressing at least one MAGE gene showed a better recurrence-free survival rate than those with tumors showing no MAGE gene expression (p<0.05). These results indicated that the MAGE genes were exclusively expressed in cancerous tissues of a considerable proportion of patients affected by HCC, and that some of these patients might be potential candidates for tumor-specific immunotherapy using the MAGE encoded antigens.

Adult↗

[Studies on recurrent breast cancer--clinicopathological factors and p53, p21Cip1/Waf1 and cyclin D1 protein expression].

Of patients radically operated on for breast cancer in our department, 46 patients who had recurrent breast cancer were clinicopathologically evaluated to clarify the prognostic factors of recurrent breast cancer. Furthermore, p53, p21 and cyclin D1 protein expression were studied immunohistochemically and their prognostic value was evaluated. The relapse-free interval was highly related to the survival rate after the recurrence. p53 overexpression was correlated with the progression of clinical stage and lymph node metastasis and negatively correlated with the expression of estrogen receptor. The p21 positive and p53 negative cases had a significantly better prognosis than the p21 negative and p53 positive cases. The combination of p53 and p21 protein expression seemed to have prognostic value in recurrent breast cancer.

Breast Neoplasms↗

Measurement of the albumin content of urinary protein using dipsticks.

An albumin selective urine strip based on bis (3',3''-diiodo-4', 4''-dihydroxy-5',5''-dinitrophenyl)-3,4,5,6-tetrabromo sulfonphthalein dye (DIDNTB) dye was examined in populations with clinical proteinuria. The relationship of albumin to the sum concentration of all protein in urine was found to vary widely even though the albumin concentration generally increased with the total protein concentration. The albumin reagent strips correlated well with immuno-nephrometric assays for albumin on specimens from hypertensives, diabetics, and renal disease which tended to have albumin contents of >/= 50.0%. High proteinuria concentrations of > 250 mg/l, with low albumin contents of </= 30%, occurred more frequently in cases of cancer, infection, and myeloma. The albumin strip read higher than the immuno assay in samples with high proteinuria and low albuminuria. The albumin strip was also less affected by albumin fragmentation than by the immunological assay. Overall, the albumin strip gave a lower risk of false negatives than a protein strip based on tetrabromophenol blue (TBPB) dye and was more sensitive to disease condition. The protein strip was not sensitive to low levels of albumin and the agreement between TBPB dye strip and the quantitative analysis was not as affected by the albumin content.

Adult↗

[A case of rectal cancer with lymph node metastasis (N4) successfully treated with low-dose cisplatin and UFT].

A 65-year-old man was admitted to our hospital due to the swelling of bilateral inguinal lymph nodes and anal discomfort. Sigmoidoscopy revealed a type-1 tumor of the lower rectum which was histologically diagnosed as a poorly-differentiated adenocarcinoma, and inguinal lymph node biopsy showed metastatic adenocarcinoma. An abdominal CT scan revealed swelling of the paraaortic lymph nodes. After a full explanation of the treatment options, the patient chose chemotherapy. Treatment by intravenous infusion of 7.5 mg/body/day of cisplatin for 5 days a week and oral administration of 600 mg/day of UFT was carried out. After 4 weeks of treatment, the primary tumor and swelling of the paraaortic lymph nodes had disappeared, and there was a 61% reduction in the inguinal lymph nodes. Four months later, the primary lesion recurred but vanished again following the same treatment regimen for 6 weeks. The patient has been in good health for over 9 months with no adverse effects from the chemotherapy.

Adenocarcinoma↗

Expression of p21WAF1/CIP1 in adenocarcinoma of the uterine cervix: a possible immunohistochemical marker of a favorable prognosis.

BACKGROUND: The purpose of this study was to assess the prognostic significance of the expression of estrogen receptor and cell cycle regulatory gene products in cervical adenocarcinoma. METHODS: In 40 cases of adenocarcinoma of the uterine cervix and 10 normal cervices, expression of estrogen receptor and cell cycle regulatory gene products (cyclin E, p16, p21WAF1/CIP1, p27, p53, and Ki-67) was studied using immunohistochemical techniques. The survival of the patients was analyzed in terms of such variables as the expression of these molecules in the tumor and conventional clinicopathologic features, and the Cox proportional hazards model was used to predict the survival of patients with cervical adenocarcinoma. RESULTS: Expression of estrogen receptor was consistently observed in normal cervical glands, but in cervical adenocarcinoma it was lost (in 28 cases) or significantly diminished (in 12 cases). Normal cervical glandular cells were usually negative for the cell cycle regulatory gene products, whereas 47.5-85% of cervical adenocarcinomas were positive for these molecules. When the expression of these molecules was analyzed, significant positive correlations were found between p16 and p27, cyclin E and p27, and cyclin E and p21WAF1/CIP1. Univariate survival analysis revealed that the presence of parametrial invasion, the presence of lymph node metastasis, negative staining for p21WAF1/CIP1, and a moderately or poorly differentiated tumor all correlated significantly with a poor prognosis. In a stepwise regression analysis, the expression of p21WAF1/CIP1 and negative pelvic lymph nodes were the best predictors of a favorable prognosis. CONCLUSIONS: Expression of p21WAF1/CIP1 correlated with a favorable prognosis for patients with cervical adenocarcinoma and may serve as a useful marker of survival in cases of this disease.

Adenocarcinoma↗