Search PubMed⌕ Search

Biomedical subjects

K Nanbu

Publications and source records attributed to K Nanbu.

At least 37 records · Page 2Linked to original sources

Expression of vascular endothelial growth factor (VEGF) during folliculogenesis and corpus luteum formation in the human ovary.

Vascular endothelial growth factor (VEGF) has been suggested to be involved in angiogenesis and microvascular hyperpermeability. We examined immunohistochemically the expression of VEGF in the granulosa and theca cells, along with that of proliferating cell nuclear antigen (PCNA), in the vascular endothelium during the course of follicular development and corpora lutea formation in human ovaries. The immunolocalization of VEGF in these cells was compared with that of another putative angiogenic factor, basic fibroblast growth factor (bFGF). The granulosa cells in the primordial and primary follicles were VEGF negative, but at the preantral stage, the granulosa cells showed weakly positive immunostaining for VEGF. However, the VEGF immunostaining in the granulosa cells was weak throughout the folliculogenesis. In contrast, the theca interna cells of developing follicles showed strong staining for VEGF, which was well correlated with the PCNA positivity in the vascular endothelial cells in the thecal layer. In the atretic follicles, the granulosa and theca cells were VEGF negative. In the corpora lutea, VEGF was strongly expressed in both granulosa and theca lutein cells in the early luteal phase when the PCNA positivity in the endothelium increased, but the VEGF staining in these cells became weak in the mid- and late luteal phases. Accordingly, the PCNA positivity in the vascular endothelium was well correlated with the expression of VEGF in the theca cells during follicular development and atresia, and that in the granulosa and theca lutein cells in corpora lutea formation and regression. In addition, the immunolocalization of VEGF was different from that of bFGF.

Biopsy↗

Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Correlation with clinicopathology, sex steroid receptor status, and p53 protein expression.

BACKGROUND: It has been suggested that heat shock proteins HSP70 and HSP90 are involved in the functional modulation of sex steroid receptors and are expressed in normal endometrium. However, little is known about the expression of HSP70 and HSP90 in endometrial carcinomas. METHODS: The immunohistochemical reactivity of monoclonal antibodies against HSP70 and HSP90 was examined in 42 endometrial carcinomas, and the presence or absence of correlation with the clinicopathologic features, sex steroid receptor status, and p53 protein expression was analyzed. RESULTS: Expression of HSP70 was found in 52% of endometrial carcinomas and was correlated with nonendometrioid histology (P < 0.05), a poorly differentiated state (P < 0.01), p53 protein expression (P < 0.01), and absence of sex steroid receptors (P < 0.001) in the tumor. By contrast, strong expression of HSP90 was observed in 29% of endometrial carcinomas, and occurred more frequently in well-differentiated carcinomas that were positive for sex steroid receptors. CONCLUSIONS: Both HSP70 and HSP90 are significantly correlated with the histology and the sex steroid receptor status of endometrial carcinomas. Expression of HSP70 may be associated with a loss of sex steroid receptors in either nonendometrioid or poorly differentiated carcinoma of the endometrium, which frequently exhibits p53 protein expression. Conversely, strong expression of HSP90 may indicate high levels of sex steroid receptors in the tumor cells.

Adult↗

Rapid growth of an ovarian clear cell carcinoma expressing LH/hCG receptor arising from endometriosis during early pregnancy.

The complete clinical course of a case of ovarian clear cell carcinoma expressing luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor arising from endometriosis in a pregnant woman is presented. A 31-year-old woman visited a private clinic in May 1993 for screening tests for infertility. Transvaginal ultrasonography revealed no abnormal findings in the uterus or ovaries. Her menstrual cycle was regular; however, a slight luteal insufficiency was noted. She had been treated with clomiphene, and soon became pregnant. She was diagnosed to be at 5 weeks gestation in June, and at the same time, an ovarian tumor with the diameter of 5 cm was identified. Since the tumor had grown rapidly and was 9 cm in diameter 1 week later, she was referred to our hospital. When she was admitted to our hospital at 9 weeks gestation, the tumor diameter was 14 cm and we found the solid portion within the ovarian tumor. The levels of the tumor markers CA125 and CA19-9 were 106 and 51 U/ml, respectively. The crown-rump length of the fetus (24 mm) was compatible with the gestational age, and fetal heartbeat was confirmed. Under the diagnosis of ovarian carcinoma, right salpingo-oophorectomy was performed at 10 weeks of gestation. Postoperative histological examination revealed a clear cell carcinoma and endometriosis of the right ovary. Immunohistochemically, the clear cell carcinoma stained positively for LH/hCG receptors and estrogen receptors, but not progesterone receptor. No malignant cells were detected by ascitic cytology. Exploratory specimens obtained at the time of operation from the left ovary and pelvic lymph nodes exhibited no malignant cells. Based on these findings, the pregnancy was allowed to proceed, and she delivered a 3010-g male baby at 39 weeks of gestation. She had no signs of recurrence for 2 years after the operation.

Adenocarcinoma, Clear Cell↗

Malignant plexiform tumor of the uterus: an unusual variant of epithelioid leiomyosarcoma.

A 46-year-old woman with the complaint of hypermenorrhea underwent hysterectomy for a presumed uterine myoma. The solid tumor in the myometrium was gray in color, was 4 cm in diameter, and showed hemorrhage and necrosis. Histologically, the tumor consisted of round or polygonal cells arranged in cords and nests, and its histological features closely resembled those of plexiform tumor which has been reported as a benign, epithelioid smooth muscle tumor of the uterus. In the tumor in our patient, however, mild nuclear atypia and two to three mitoses/10 high-power fields were present. Two months after the hysterectomy, the patient was found to have metastatic foci in the lumbar vertebrae and iliac bone, which contained tumor cells with the same histological features. Accordingly, the present tumor might be interpreted as a malignant plexiform tumor of the uterus, an unusual variant of epithelioid leiomyosarcoma.

Biomarkers, Tumor↗

Ascitic positive cytology and intraperitoneal metastasis in ovarian dysgerminoma.

OBJECTIVES: To verify the pattern of the spread of tumors in ovarian dysgerminoma, with special reference to intraperitoneal metastasis, and to assess clinicopathologic factors for predicting tumor extension. METHODS: Detailed data regarding ascitic cytology, macroscopical findings at surgery, and the histopathology of the surgical specimens were retrospectively reviewed in 12 patients with dysgerminoma who were treated at Kyoto University Hospital. The relationships between the tumor extension and the period of symptoms, the serum lactic dehydrogenase (LDH) level, and the operative findings also were analyzed. RESULTS: Ascitic cytology revealed a high incidence of positivity in 6 of the 10 (60%) cases examined. Extraovarian metastases were present in 4 of the 6 (67%) cases with positive cytology, and in 1 of the 4 (25%) cases with negative cytology. Intraperitoneal metastatic nodules were detected in 5 of the 12 (42%) patients either by inspection during surgery or by postsurgical histological examination. In addition, these metastatic lesions were 5 or fewer in number and 7 mm or less in diameter, except in 1 patient with widespread disease. The presence or absence of extraovarian spread of the tumor was not significantly correlated with the period of symptom, the serum LDH level, the size of the primary tumor, or the volume of the ascitic fluid. CONCLUSION: The incidence of intraperitoneal spillage and/or metastases of dysgerminoma cells might be higher than previously reported. These findings indicate the importance of ascitic cytology and careful inspection at the time of operation, as well as the rationale of postsurgical chemotherapy for dysgerminoma of an apparently early stage.

Adolescent↗

Altered expression of nm23-H1 and c-erbB-2 proteins have prognostic significance in adenocarcinoma but not in squamous cell carcinoma of the uterine cervix.

BACKGROUND: The reduced expression of nm23-H1 protein and/or overexpression of c-erbB-2 protein reportedly is associated with a high incidence of lymphatic metastasis or poor prognosis of the patient in a variety of human malignant tumors. METHODS: The expression patterns of nm23-H1 and c-erbB-2 proteins were analyzed by immunohistochemical staining using formalin fixed, paraffin embedded sections of 88 cases of invasive carcinoma (39 matched pairs of adenocarcinoma and squamous cell carcinoma, 8 cases of adenosquamous carcinoma, and 2 cases of undifferentiated carcinoma) and 31 cases of preinvasive lesions of the uterine cervix. RESULTS: Expression of nm23-H1 was detected in 46% of adenocarcinoma and in 36% of squamous cell carcinoma of the uterine cervix, whereas c-erbB-2 expression was evident in 49% and 38%, respectively. Negative expression of nm23-H1, positive expression of c-erbB-2, and a combined nm23-H1-negative and c-erbB-2-positive expression were associated with a high incidence of lymph node involvement (P = 0.36, P = 0.0015, P = 0.0055, respectively) and with poor prognosis of patients (P = 0.034, P = 0.014, P = 0.00008, respectively) with adenocarcinoma of the uterine cervix, but not in those with squamous cell carcinoma. Multivariate analysis using the Cox's proportional hazard model also revealed that these three factors significantly contributed to the prognosis of patients with cervical adenocarcinoma. CONCLUSIONS: Reduced expression of the nm23-H1 protein, increased expression of the c-erbB-2 protein, and a combined nm23-H1-negative and c-erbB-2-positive expression have prognostic significance in patients with adenocarcinoma, whereas they may not be associated with the prognosis of squamous cell carcinoma of the uterine cervix, nm23-H1 and c-erbB-2 proteins may have different functions according to the subtype of cervical carcinoma.

Adenocarcinoma↗

Peritoneal papillary serous carcinoma arising in an infertile woman during ovulation-induction therapy: immunohistochemical expression of LH/hCG receptors.

A case of peritoneal papillary serous carcinoma arising in an infertile patient during ovulation-induction therapy is presented. A 34-year-old woman with past history of ovulation-induction therapy for infertility again received fertility drugs. During the use of gonadotropic hormones, massive ascites developed and an exploratory laparotomy revealed serous papillary carcinoma on the surface of bilateral ovaries, pelvic peritoneum, and omentum. Immunohistochemical analysis showed the tumor cells to be positive for luteinizing hormone/human chorionic gonadotropin receptors and negative for sex steroid receptors. A possible relationship between the use of gonadotropic hormones and cancer development is discussed.

Adult↗

Minimal deviation adenocarcinoma of endometrioid type may arise in the isthmus: clinicopathological and immunohistochemical study of two cases.

Clinicopathological and immunohistochemical features of minimal deviation adenocarcinoma (MDA) of endometrioid type which may have arisen in the isthmus are presented. Hysterectomy specimens from two women, one 39 years of age and the other 64 years of age, showed the presence of endometrioid-type adenocarcinoma with minimal atypia and without back-to-back arrangement of the glands, which was consistent with a histological diagnosis of endometrioid MDA. However, the tumorous glands were most abundant in the isthmus, and extensively infiltrated into the cervical stroma, vagina, parametrium, and corpus in one case, and the tumor was confined to the isthmus in the other. Immunohistochemically, the tumorous glands were CEA-positive and vimentin-negative in both cases. p53 protein expression was found in one case. Histogenetic origin of MDA of endometrioid type is discussed.

Adult↗

Immunohistochemical analysis of p53 protein and 72 kDa heat shock protein (HSP72) expression in ovarian carcinomas. Correlation with clinicopathology and sex steroid receptor status.

Mutations of the tumour suppressor p53 gene have been reported in a variety of human malignant tumours, and are frequently associated with overexpression of p53 protein. To examine the significance of p53 gene alteration in malignant epithelial tumours of the ovary, we studied the immunohistochemical reactivity with a monoclonal antibody against p53 (PAb 1801) in 6 ovarian tumours of low malignant potential (LMP) and 32 ovarian carcinomas. The existence of any correlation of p53 overexpression with the clinicopathological features and with the immunohistochemical expression of 72 kDa heat shock protein (HSP72) and sex steroid receptors (oestrogen receptors; ER, progesterone receptors; PR) was also analysed. Expression of p53 was found in 2 of the 6 (33.3%) LMP tumours and in 15 of the 32 (46.9%) carcinomas. Strong expression of HSP72 was observed in 11 of the 17 (64.7%) p53-positive tumours, but only in 2 of the 21 (9.5%) p53-negative ones. Histologically, p53-positivity was observed in 7 of the 10 (70%) serous carcinomas, 4 of the 6 (66.7%) mucinous, 4 of the 10 (40%) endometrioid, and none of the 4 clear cell and 2 transitional cell carcinomas. Distribution of p53-positive cells in the tumour sections was homogenous in serous tumours, but heterogenous in mucinous lesions. All of the 4 carcinomas arising in endometriotic cysts were p53-negative. These differences support the thesis of heterogeneity in ovarian carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunohistochemical localization of heat shock proteins HSP70 and HSP90 in the human endometrium: correlation with sex steroid receptors and Ki-67 antigen expression.

Heat shock proteins of 72 kDa and 90 kDa (HSP70, HSP90) have been suggested to be involved in the functional modulation of sex steroid receptors. We examined the immunohistochemical localization of HSP70 and HSP90 in both the functionalis and basalis layers of normal human endometrium during various phases of the menstrual cycle. Topological correlation with localization of estrogen receptors (ER), progesterone receptors (PR), and proliferation-related Ki-67 antigen was also analyzed. HSP70 was expressed in glandular cells of the basalis but not in the cells of the functionalis during the proliferative phase. In the secretory phase, however, glandular cells of both the basalis and functionalis markedly expressed HSP70. Endometrial stromal cells at the basal layer were positive for HSP70, whereas those cells in the functional layer were negative for HSP70 throughout the menstrual cycle. The topological expression of HSP70 in glandular and stromal cells of the basalis was inversely related to Ki-67 localization. Overexpression of HSP70 in the secretory glands was associated with down-regulation of ER and PR. These findings suggest that HSP70 expression is related to either hormonal regulation of cell proliferation and/or down-regulation of sex steroid receptors. HSP90 was strongly expressed in both glandular and stromal cells during the proliferative phase of the menstrual cycle; in the secretory phase, HSP90 expression was weak in both types of the cells. However, no topological difference in HSP90 expression between the basalis and the functionalis was observed.

Adult↗

Immunohistochemical analysis of p53 protein over-expression in endometrial carcinomas: inverse correlation with sex steroid receptor status.

Mutations of the tumour suppressor p53 gene have been reported in a variety of human malignant tumours, and are frequently associated with over-expression of p53 protein. To examine the significance of p53 gene alteration in endometrial carcinomas, we studied the immunohistochemical reactivity with a monoclonal antibody against p53 (PAb 1801) in 30 endometrial carcinomas as well as in 64 normal endometria. The presence or absence of correlation of p53 over-expression with the clinicopathological features and with the immunohistochemical expression of sex steroid receptors (oestrogen receptors; ER, progesterone receptors; PR) was also analysed. Expression of p53 was found in none of 64 normal endometria, but was identified in 5 of the 30 (16.7%) endometrial carcinomas. All 5 of the p53-positive tumours developed in women more than 3 years post-menopause, whereas the carcinomas in 5 pre-menopausal women and 3 women less than 3 years post-menopause were p53-negative. None of the 5 p53-positive carcinomas was associated with adjacent endometrial hyperplasia. Two of the 5 p53-positive tumours showed non-endometrioid histology: serous papillary and clear cell carcinomas. In contrast, 6 carcinomas accompanied by adjacent hyperplasia were p53-negative. In addition, ER and/or PR expression was found in none of the 5 p53-positive tumours, but was present in 21 of the 25 p53-negative tumours (p < 0.01). These clinicopathological features of p53-positive carcinomas and the inverse correlation of p53 immunoreactivity with sex steroid receptor status suggest that p53 over-expression is frequent in a specific category of endometrial carcinoma, presumably oestrogen-unrelated tumours.

Adult↗

The internal anal sphincter in anorectal malformation.

Recently it has been morphologically clarified that a layer of thick smooth muscle, mimicking the internal anal sphincter, exists at the rectal and even in high and intermediate anorectal malformations. This paper will describe two studies focussed on the internal anal sphincter in anorectal malformation. I. Experimental study: Utilisation of the rectal end for reconstructive surgery would necessitate the mobilisation of the rectum. We performed a chronic animal experiment in order to investigate the influence of rectal mobilisation on anal function and the role of the internal anal sphincter in anal continence. Fifteen dogs were operated on; rectal separation was performed in 5 dogs, resection of the internal anal sphincter in 5 dogs and both procedures in 5 dogs. Anorectal manometric studies for 24 weeks revealed that rectal separation caused only a transient mild disturbance in anal functions with the exception of long-standing high rectal compliance, while resection of the internal anal sphincter caused a persistent severe disturbance. II. Clinical study: The function of the smooth muscle thickening at the rectal end was investigated and operations to preserve the rectal end were evaluated in cases of high and intermediate anorectal malformations. In 5 infants with anorectal malformations (high type 2, intermediate type 3), for whom colostomies had been performed as newborn, a preoperative manometric study at the rectal end was performed with a probe introduced from the distal colostomy. Thereafter, they all underwent a rectal end preserving operation. They were followed up manometrically and clinically after the operation. A preoperative manometric study of the rectal end showed the presence of rhythmic activity in all and positive reflexive pressure fall by rectal distension in 4. The rectal end preserving operation maintained rhythmic activity in all of them, rectoanal reflex in 3 and good results are expected clinically. These two studies suggest that the functional internal anal sphincter, which exists at the rectal end also in high and intermediate anorectal malformations, should be utilised for reconstruction because of the essential role it plays in anal continence.

Anal Canal↗