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Biomedical subjects

T Jobo

Publications and source records attributed to T Jobo.

At least 19 recordsLinked to original sources

Medroxyprogesterone acetate stimulates cdk inhibitors, p21 and p27, in endometrial carcinoma cells transfected with progesterone receptor-B cDNA.

PURPOSE OF INVESTIGATION: Progestin is reported to suppress the growth of endometrial carcinomas, although its precise mechanism of action is not clear. This study aimed to transfect progesterone receptor-B (PRB) cDNA into endometrial carcinoma cells and investigate the effect of medroxyprogesterone acetate (MPA) on cell growth, and p21 and p27 expression in the transfectant. METHODS: Immunoblotting for p21 and p27 was performed at predetermined times after the administration of MPA. RESULTS: PR expression was maximally induced in Ishikawa cells at 24 hrs after the transfection. At 1 x 10(-6) M, MPA suppressed the growth of the transfectant by 34% on day 6 and stimulated p21 accumulation at 48 to 72 hrs and p27 accumulation at 48 to 96 hrs after its administration. PRB cDNA was effectively transfected and in the transfectant MPA at 1 x 10(-6) M, the dosage suppressing growth, induced p21 and p27expression. CONCLUSION: p21 and p27 may be related to progesterone-induced growth suppression in human endometrial adenocarcinoma.

Blotting, Western↗

Optimal dose for stage IIIB adenocarcinoma of the uterine cervix on the basis of biological effective dose.

PURPOSE: Prognosis of uterine cervical adenocarcinoma in locally advanced stage treated with radiation therapy has been considered to be much worse than that of squamous cell carcinoma because the optimal dose for the former one has not been determined. Thus, the current study was performed to investigate the optimal dose for Stage IIIB, locally advanced stage, adenocarcinoma of the uterine cervix on the basis of the biological effective dose (BED). METHODS: One-hundred and seventy-nine patients with Stage IIIB carcinoma of the uterine cervix were treated with curative intended therapy at Kitasato University Hospital between 1976 and 2000. Out of them, 13 patients had an adenocarcinoma component in pathological findings. Nine patients were diagnosed with adenocarcinoma and four patients were diagnosed with adenosquamous cell carcinoma. All patients were treated with external radiation therapy combined with intracavitary radiation therapy. The total BED10 (T-BED10) was caluculated from the BED of the external beam radiation therapy (E-BED10) plus the BED of the intra-cavitary radiation therapy (A-BED). RESULTS: Overall survival rate was 51%. Stratified by T-BED10 overall survival rate of the T-BED10 > or = 100 Gy group was 57% and that of the T-BED10 < 100 Gy group was 30%. There was a trend toward a better survival rate of the T-BED10 > or = 100 Gy group than the T-BED10 < 100 Gy group. CONCLUSION: The current study suggested that the optimal dose for Stage IIIB adenocarcinoma of the uterine cervix might be T-BED10 > or = 100 Gy.

Adenocarcinoma↗

C-kit overexpression in neuroendocrine small cell carcinoma of the uterine cervix.

PURPOSE OF INVESTIGATION: Neuroendocrine small cell carcinoma of the uterine cervix (NESCC) grows aggressively, and is resistant to anticancer agents and radiation, having an extremely poor prognosis. The incidence of c-kit proto-oncogene overexpression is high in gastrointestinal stromal tumors (GISTs) and small cell lung cancer, and tyrosine kinase inhibitors have been used effectively to treat GISTs. Few studies have investigated whether c-kit is overexpressed in NESCC. To investigate whether NESCC can be a target for molecular targeted therapy with tyrosine kinase inhibitors, we examined the expression of c-kit in this tumor. METHODS: Twenty-one NESCCs were examined for c-kit expression by immunohistochemical staining using the labeled streptavidin-biotin complex (LSAB) method. The expression of c-kit was regarded as positive (overexpression) and negative when the membrane and cytoplasm of more or less than 25%, respectively, of tumor cells were stained. RESULTS: Nine NESCCs (43%) were c-kit-positive (overexpression). No difference in age or clinical stage was noted. No difference in prognosis was observed between the c-kit-positive and -negative patients. CONCLUSION: The incidence of c-kit overexpression was high in NESCC; therefore, the patients with this tumor may become a future target for molecular-targeted therapy with tyrosine kinase inhibitors.

Adult↗

Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study.

The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naïve or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status </=2 entered the study. Docetaxel 70 mg m(-2) was administered intravenously on day 1 of a 3-week cycle up to a maximum of six cycles. If patients responded well to docetaxel, additional cycles were administered until progressive disease or unacceptable toxicity occurred. Of 33 patients with a median age of 59 years (range, 39-74 years) who entered the study, 14 patients (42%) had received one prior chemotherapy regimen. In all, 32 patients were evaluable for efficacy, yielding an overall response rate of 31% (95% confidence interval, 16.1-50.0%); complete response and partial response (PR) were 3 and 28%, respectively. Of 13 pretreated patients, three (23%) had a PR. The median duration of response was 1.8 months. The median time to progression was 3.9 months. The predominant toxicity was grade 3-4 neutropenia, occurring in 94% of the patients, although febrile neutropenia arose in 9% of the patients. Oedema was mild and infrequent. Docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma, including those previously treated with chemotherapy; however, the effect was transient and accompanied by pronounced neutropenia in most patients.

Adenocarcinoma↗

Lymph node pathway in the spread of endometrial carcinoma.

OBJECTIVE: To elucidate the sentinel nodes of endometrial carcinoma, the spread pathway was clarified. The correlation between lymph node spread and other clinicopathological variables was also analyzed. METHODS: Dissected lymph node samples in 342 patients who underwent pelvic and selective paraaortic lymphadenectomy were reviewed. Pelvic and paraaortic node (PLN and PAN) status was compared with clinicopathological parameters. RESULTS: Lymph node metastasis was demonstrated in 52 patients, including 46 cases with PLN metastasis and six patients with independent PAN metastasis. The metastatic sites were most frequent in the obturator and internal iliac nodes. Eleven of 49 patients who underwent PAN dissection were positive for metastasis. Sixteen of 23 cases with parametrial metastasis also metastasized in the retroperitoneal lymph node. CONCLUSION: The lymph node spread pathway in endometrial carcinoma consists of a major route via the obturator node or internal iliac node with or without parametrial involvement, and rarely a direct PAN pathway.

Adenocarcinoma↗

PTEN immunohistochemical expression is suppressed in G1 endometrioid adenocarcinoma of the uterine corpus.

PURPOSE: PTEN is a tumor suppressor gene that inhibits cell proliferation by regulating intracellular signaling pathways, and this activity can be abolished by mutations of the PTEN gene. This study was designed to examine the correlation of PTEN expression with the expression of cell cycle regulators and with clinicopathological parameters in endometrioid adenocarcinoma of the uterine corpus. METHODS: Tissue samples of 117 endometrioid adenocarcinomas in addition to those of 19 normal endometria and 20 endometrial hyperplasias were used for the study. Immunohistochemical staining for PTEN protein was performed with the labeled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue samples. PTEN expression was represented as the staining score. RESULTS: Immunohistochemistry showed that the nuclei of cells were positive for PTEN. The PTEN staining score of normal endometrium was significantly higher in the proliferative phase than in the secretory phase. The scores of various endometrial hyperplasias were not significantly different from each other, regardless of the type of hyperplasia. The PTEN staining scores of endometrioid adenocarcinomas were 7.6+/-5.2 in G1, 9.6+/-5.2 in G2, and 11.9+/-3.7 in G3, and increased significantly as the histological grade increased. PTEN staining score was not significantly correlated with clinicopathological parameters such as FIGO stage, myometrial invasion, lymph-vascular space invasion (LVSI), lymph node metastasis or group, but was significantly correlated with labeling indices (LIs) of cell cycle regulators such as Ki-67, cdk2, cyclin A, cyclin D1, cyclin E, p27, and p53. The PTEN staining score of p53-wild cases was significantly lower than that of p53-mutant ones, but there was no significant difference of the score in cases with different PTEN gene status. PTEN expression was significantly lower in cases with both high levels of estrogen receptor and progesterone receptor. CONCLUSION: PTEN protein expression was decreased in well-differentiated and less growth-aggressive endometrial carcinoma with wild-type p53 gene and high levels of ER and PR. This suggests that disturbed PTEN expression occurs in an early phase of the tumorigenesis of well-differentiated endometrial carcinoma.

Adenocarcinoma↗

Immunohistochemical expression of cyclin E in endometrial adenocarcinoma (endometrioid type) and its clinicopathological significance.

PURPOSE: Cyclin E is known as a G1-S phase regulatory protein and its abnormal expression has been implicated in cellular proliferation. This study aimed to investigate the correlation of cyclin E expression with tumorigenesis of the endometrium, proliferative activity, and clinicopathological features of endometrial adenocarcinoma. METHODS: Immunohistochemical staining for cyclin E in addition to cyclin-dependent kinase 2 (cdk2), Ki67, p27, and p53 was performed by the labeled streptavidin-biotin method on formalin-fixed, paraffin-embedded tissues of normal endometria (20 cases), endometrial hyperplasias (20 cases), and endometrial adenocarcinomas (endometrioid type) (127 cases). Positive staining was expressed as a labeling index (LI) based on percentages of positive nuclei in tumor cells. RESULTS: Immunohistochemistry showed that the nuclei of the cells were positive for cyclin E. Both proliferative and secretory endometria, and endometrial hyperplasia regardless of type were negligible for cyclin E expression. The expression in normal endometrium and hyperplasia was significantly less than that in endometrial adenocarcinomas (P<0.0001). LIs of cyclin E in well-differentiated, moderately differentiated, and poorly differentiated endometrial adenocarcinomas were 31.5+/-33.3%, 37.8+/-31.9%, and 51.1+/-30.8%, respectively. Cyclin E expression increased significantly more in histological grades. The LI of cyclin E in carcinoma was positively correlated with that of cdk2, Ki67, and p53 but not with p27. The cyclin E expression was correlated with myometrial invasion and lymph-vascular space involvement, but not with FIGO stage, lymph node metastasis, coexisting endometrial hyperplasia, estrogen receptor, progesterone receptor, and menopause. CONCLUSION: Cyclin E as a complex with cdk2 is associated with carcinogenesis and disease progression in endometrial adenocarcinoma, and might be a prognostic indicator of endometrial adenocarcinoma.

Adenocarcinoma↗

Parametrial spread is a prognostic factor in endometrial carcinoma.

OBJECTIVE: Parametrial spread of endometrial carcinoma, including the histopathological pattern of the spread and its significance as a prognostic factor, as well as its correlation with other prognostic factors are not well understood. METHODS: We reviewed histopathologically the resected parametria from 269 patients with endometrial carcinoma who underwent radical or modified radical hysterectomy with pelvic lymphadenectomy. The relationship between parametrial spread and other histopathological features, including histological type, tumor grade, depth of myometrial invasion, lymph vascular space invasion (LVSI) of the myometrium, cervical invasion, adnexal metastasis, lymph node metastasis and peritoneal cytology was studied. Clinical outcomes of the patients with parametrial spread were also evaluated. RESULTS: Parametrial spread was demonstrated in 16 patients (5.9%). Direct invasion of cancer cells to connective tissue, LVSI and lymph-node metastasis in the parametrium were seen in 13, seven and three cases, respectively. Three patients had all three spread patterns. According to the FIGO surgical stage, parametrial spread was found in none of the 164 patients in Stage I, two (6.3%) of 32 in Stage II, 12 (16.9%) of 71 in Stage III, and two (100%) of two in Stage IV. The presence of parametrial involvement was significantly correlated with depth of myometrial invasion, cervical involvement, lymph-node metastasis, adnexal metastasis. LVSI in the myometrium and peritoneal cytology (each, p < 0.01). With a median follow-up of 68.3 months, six (37.5%) of 16 patients with parametrial involvement developed recurrence and died. CONCLUSION: Direct parametrial extension or lymphatic involvement within the parametrium can occur in endometrial carcinoma. Patients with parametrial spread have a poor prognosis.

Adult↗

Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus - correlation with proliferation and clinicopathological parameters.

p27 is regarded as a cyclin-dependent kinase inhibitor of the G1-to-S cell cycle progression by suppressing the kinase activity of cyclin/cyclin-dependent kinase complex. This study aimed to investigate p27 expression in the normal endometrium and endometrioid adenocarcinoma of the uterine corpus and the correlation of its expression with cell proliferation and clinicopathological parameters. Tissue samples of 127 endometrioid adenocarcinomas and 15 normal endometria were used in the study. Immunohistochemical staining for detecting p27 and Ki-67 was performed by the labelled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue samples. The expression was given as the labelling index, which indicates the percentage of positive nuclei. p27 staining was observed in the nuclei of the glandular cells in the functional layer of the secretory phase endometrium, whereas it was negative in those of the proliferative phase. In endometrioid adenocarcinomas, the labelling index of p27 expression paradoxically increased more significantly in the higher histological grades and was correlated with that of Ki-67. The high level of p27 expression was associated with clinicopathological parameters such as FIGO stage, lymph node metastasis, lymphovascular space involvement and myometrial invasion. High p27 expression was linked to higher grades of endometrioid adenocarcinoma, cell proliferation and some clinical prognostic factors. These results indicate that p27 might be an indicator of poor prognosis.

Adenocarcinoma↗

Expression of cyclin A in endometrial adenocarcinoma and its correlation with proliferative activity and clinicopathological variables.

PURPOSE: Cyclin A is known as an S- and G2-M phase regulatory protein and its abnormal expression has been reportedly implicated in cellular proliferation. This study was designed to investigate the correlation of cyclin A expression with tumorigenesis of the endometrium and clinicopathological variables. METHODS: Immunohistochemical staining using labeled streptavidin-biotin complex was performed on formalin-fixed, paraffin-embedded tissue of normal endometrium (15 cases), endometrial hyperplasia (23 cases), and endometrial adenocarcinoma (endometrioid type) (112 cases). RESULTS: Immunohistochemistry showed that the nuclei of the cells were positive for cyclin A. In normal endometrium, only proliferative phase was focally positive for cyclin A. Cyclin A was also positive for endometrial hyperplasia. Its expression in hyperplasia was significantly more frequent than that of proliferative phase and less than that of endometrioid adenocarcinoma. The labeling index (LI) of cyclin A in endometrioid adenocarcinoma was 16.3+/-6.9 in well-differentiated, 18.3+/-8.8 in moderately differentiated, and 30.2+/-11.8 in poorly differentiated adenocarcinoma, respectively. Cyclin A expression increased significantly more in high histological grades. The area of squamous metaplasia in endometrioid adenocarcinoma was negative for cyclin A. The LI of cyclin A was positively correlated with that of Ki-67 and cyclin-dependent kinase 2. Cyclin A expression was significantly associated with carcinoma without coexisting endometrial hyperplasia and lymphovascular space involvement (LVSI), but not with FIGO stage, myometrial invasion, lymph node metastasis, estrogen receptor, progesterone receptor, and menopause as well as recurrence. CONCLUSIONS: Cyclin A expression was involved in the progression to malignancy of the endometrium and was correlated with proliferative activity and prognostic features including histological grade, without coexisting endometrial hyperplasia and LVSI.

Adenocarcinoma↗

Medroxyprogesterone acetate therapy for patients with adenocarcinoma of the endometrium who wish to preserve the uterus-usefulness and limitations.

BACKGROUND: To determine the effectiveness of medroxyprogesterone acetate therapy for women with endometrial adenocarcinoma who wish to preserve their uterus. STUDY DESIGN: Fifteen patients with endometrial carcinoma (12 with grade 1 endometrioid adenocarcinoma. 2 with grade 2 adenocarcinoma and 1 with adenoacanthoma) were treated with high-dose medroxyprogesterone acetate alone as primary therapy and their clinical responses evaluated. RESULTS: Seven of the 12 cases (58%) with grade I adenocarcinoma and one of the two (50%) with grade 2 carcinoma responded initially to medroxyprogesterone acetate. The median length of treatment required for regression was 29 weeks. Three patients who initially responded relapsed. Thirteen patients are alive without evidence of disease as of December 1999 (10 to 146 months, median; 4 years and 11 months) and one is continuing medroxyprogesterone acetate therapy as a final follow-up. One patient was lost to follow-up. Two patients have conceived having three healthy infants. CONCLUSION: Treatment of endometrial carcinoma with high-dose medroxyprogesterone acetate could be an alternative to hysterectomy, although the successful rate is limited.

Adenocarcinoma↗

Treatment for complex atypical hyperplasia of the endometrium.

OBJECTIVE: To clarify the clinical outcome of women with complex atypical hyperplasia of the endometrium who were treated either by hysterectomy or a non-surgical treatment with medroxyprogesterone acetate (MPA). STUDY DESIGN: Thirty of the 53 patients with complex atypical hyperplasia of the endometrium were treated by undergoing hysterectomy and 20 were treated with MPA alone as the primary therapy. Their clinical features and outcomes were evaluated. RESULTS: The ages of the 53 patients ranged from 28 to 62 years (mean 46.2). Fifteen (75%) of the 20 patients (8 of 12 with low-dose MPA and 6 of 8 with high-dose MPA) responded initially to MPA therapy. Two of the 12 patients who were treated with low-dose MPA progressed to endometrial adenocarcinoma. Three patients treated with high-dose MPA conceived after treatment having three healthy infants. CONCLUSION: Primary treatment with high-dose MPA is a safe and effective therapy for women with complex atypical hyperplasia of the endometrium who wish to preserve their fertility.

Adult↗

Uterine leiomyoma causing massive ascites and left pleural effusion with elevated CA 125: a case report.

A 51-year-old patient presented with an abdominal mass and ascites as well as a left pleural effusion. Her serum CA125 was 820 U/ml. Surgical exploration revealed a benign leiomyoma of the uterus without malignant cytology in the ascites. Postoperatively, the pleural effusion was resolved dramatically and the CA125 decreased to the normal range after 4 months post-operatively. This is an extremely rare case of pseudo-Meigs' syndrome caused by uterine leiomyoma.

Ascites↗

Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases.

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.

Adenocarcinoma↗

Comparison of endometrial carcinoma coexisting with and without endometrial hyperplasia.

OBJECTIVE: It has been reported that endometrial carcinoma has two pathogenic types; one with and the other without endometrial hyperplasia. The present study was done to clarify whether this was true in our series of a large number of Japanese patients. METHODS: Three hundred and twenty-eight patients with endometrial carcinoma were classified into two groups, one coexisting endometrial hyperplasia (group 1; 182 cases) and the other having normal endometrium without endometrial hyperplasia (group 2; 107 cases). The clinical and pathological observations of the two groups were compared. RESULTS: The ages of the patients were significantly lower in group 1 (30-83; mean 50.7) than in group 2 (34-81; mean, 57.2). The incidence of the carcinoma with invasion limited to less than 1/3 of the myometrium, with surgical stage I, lower grade endometrioid type and higher levels of progesterone receptor, and without lymph node metastasis were significantly higher in group 1 than in group 2. The cumulative survival rate for stage I was also significantly higher in group 1 patients. CONCLUSION: A significant difference was found between groups 1 and 2 in age distribution, degree of progress and pathological observations. Stage I patients in the former group had a better prognostic than the latter.

Adult↗

Androgen-producing ovarian tumors: a clinicopathological study of 3 cases.

The clinical course and pathological findings of 3 rare cases of androgen-producing ovarian tumors are presented. The ages of the 3 patients (Cases 1, 2, and 3, respectively) were 43, 34, and 57 years, respectively. Their preoperative serum testosterone levels were 506, 491, and 231 ng/dl, respectively. The pathological diagnoses of Cases 1, 2, and 3 were a Sertoli-stromal cell tumor of intermediate differentiation, a stromal tumor containing Leydig cells, and a stromal tumor with minor sex cord elements, respectively. Patient 1 experienced a recurrence, of a lesion at the vaginal stump 1 year and 2 months after the initial surgery. The clinical courses of Cases 2 and 3 have been non-contributory.

Adult↗

[Hormone therapy of endometrial carcinoma].

Various hormone therapies for endometrial carcinoma have been reported in the literature using progestins, tamoxifen (anti-estrogen), danazol, Gn-RH etc. The response rates of these hormone therapies are reported to be approximately 30%, which is no longer superior to other types of treatment methods. On the other hand, endometrial carcinoma is considered to be one of hormone dependent tumors. Although sex steroid hormones play an important role in the mechanism of carcinogenesis and the progression of early and well-differentiated endometrial carcinoma, most of the advanced carcinomas treated by hormone therapy have transformed into hormone independent state. It is expected that endometrial hyperplasia and well-differentiated carcinoma especially in younger patients should be effective materials for hormone therapy.

Antineoplastic Agents, Hormonal↗