Biomedical subjects

K Miyazaki

Publications and source records attributed to K Miyazaki.

889 records · Page 50Linked to original sources

PubMedDate not supplied

Cyclin D1 is a possible predictor of sensitivity to chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiotherapy is currently performed on patients with advanced esophageal squamous cell carcinoma (SCC). The preoperative administration revealed that the patients who responded well to chemoradiotherapy had favorable outcomes, whereas the poor responders conversely resulted in worse prognosis. The aim of this study was to identify molecular markers predicting sensitivity to chemoradiotherapy prior to this treatment. MATERIALS AND METHODS: Our clinical protocol for chemoradiotherapy for esophageal SCC were enrolled in 34 patients comprising 20 patients who underwent surgery after neoadjuvant chemoradiotherapy and 14 patients who were treated chemoradiotherapy without surgery. The expressions of cyclin D1, p53 and Ki-67 were investigated immunohistochemically in biopsy specimens obtained before the treatment from all 34 patients. The immunoreactivities were compared with responsiveness to chemoradiotherapy as evaluated by macroscopic or microscopic method. RESULTS: The mean rate of primary tumor reduction as estimated by esophagography was 75.3% in the cyclin D1 negative group whereas 42.7% reduction rate was observed in the cyclin D1 positive group. The difference in the reduction rate between cyclin D1 positive and negative groups was statistically significant (p = 0.0025). The immunoreactivities of p53 and Ki-67 did not show a significant correlation with responsiveness to chemoradiotherapy. In neoadjuvant group, patients with cyclin D1-positive tumors showed significantly worse overall survival than patients with cyclin D1-negative tumors (p = 0.0380). CONCLUSIONS: Among 34 patients with esophageal SCC, differences in the responsiveness to chemoradiotherapy were correlated with cyclin D1 immunoreactivity assessed in the biopsy specimens. Thus the cyclin D1 protein may be a useful predictor of sensitivity to concurrent chemoradiotherapy for esophageal SCC.

Adult↗

PubMedDate not supplied

Vascular endothelial growth factor expression in progression of cervical cancer: correlation with thymidine phosphorylase expression, angiogenesis, tumor cell proliferation, and apoptosis.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been linked not only to angiogenic activity but also to thymidine phosphorylase (TP), rapid tumor growth, and inhibition of apoptotic cell death. Our purpose was to examine how VEGF expression affect these factors in cervical cancer at varying stages of progression. METHODS: VEGF expression, TP expression, the microvessel count (reflected by factor VIII-related antigen), and proliferating cell nuclear antigen (PCNA) were assessed immunohistochemically in 19 specimens of normal cervical epithelium, 35 of carcinoma in situ (CIS), 34 of microinvasive carcinoma (MIC), and 34 of invasive cervical squamous cell carcinoma (SCC). Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. RESULTS: VEGF expression progressively increased along a continuum from normal epithelium to invasive SCC (P < 0.0001). VEGF expression significantly correlated with TP expression and PCNA index (P < 0.01 and P < 0.0001, respectively). In analyses within histological stages, VEGF expression significantly correlated with the PCNA index in CIS and MIC (P < 0.01 and P < 0.05, respectively), but not in invasive SCC. The PCNA index for combined analysis of VEGF and TP expression was similar to that for VEGF expression alone. VEGF expression tended to correlate with microvessel count, however, the difference was not significant (P = 0.09). No significant correlation was observed between VEGF expression and the apoptotic index. CONCLUSIONS: VEGF expression may stimulate tumor cell proliferation in the early stages of cervical cancer, and may be responsible for cervical tumorigenesis.

Apoptosis↗

PubMedDate not supplied

A case of a pregnant woman with luteal insufficiency and a mutation in the beta-subunit of luteinizing hormone.

We report a case of a pregnant woman with luteal insufficiency and infertility associated with a variant luteinizing hormone (LH) beta-subunit and normal follicle-stimulating hormone (FSH) concentration. A 29-year-old woman presented to our hospital with infertility. Given the presence of low mid-luteal serum progesterone concentration and out-of-phase endometrial biopsy, luteal insufficiency was suspected. Several forms of treatment (clomiphene citrate therapy and human menopausal gonadotrophin therapy) were administered, but did not improve the patient's luteal insufficiency. However, administration of hCG during the luteal phase could distinctly improve the luteal insufficiency. She became pregnant after luteal support with progesterone. Sequence analysis of the patient's LH beta-subunit gene indicated heterozygosity for the point mutations Trp8 to Arg8 and Ile15 to Thr15 in the coding sequence. LH hypersecretion resembling that seen in polycystic ovary syndrome was observed. Serum concentrations of variant LH showed a more rapid increase in response to gonadotrophin-releasing hormone and reached a higher apparent value than did those of normal LH. Therefore, abnormal bioactivity and mistimed secretion of variant LH at mid-cycle may have a deleterious effect on the completion of oocyte maturation, ovulation, and subsequent corpus luteum function.

Adult↗

PubMedDate not supplied

Expression of thymidine phosphorylase and vascular endothelial growth factor in epithelial ovarian cancer: correlation with angiogenesis and progression of the tumor.

OBJECTIVE: The aim was first, to determine whether the expression of thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF) by epithelial ovarian cancer cells is correlated with the density of microvessels within the tumor and with ultrasonographic findings (B-mode classification and pulsed Doppler blood flow) and second, to speculate how these two angiogenesis factors participate in the tumorigenesis and tumor progression of epithelial ovarian cancer. METHODS: B-mode ultrasonography and color Doppler imaging and pulsed Doppler spectral analysis were used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of TP and VEGF and the intratumoral density of microvessels by immunohistochemistry using antibodies to TP, VEGF and Factor VIII related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were TP and VEGF positive or negative, the microvessel count and B-mode classification and the peak systolic velocity (PSV). RESULTS: Forty-four epithelial ovarian cancers were studied (6 of low malignant potential, 15 serous cystadenocarcinoma, 9 mucinous cystadenocarcinoma, 8 endometrioid adenocarcinoma, 4 clear cell carcinoma and 2 malignant Brenner tumor); 19 were Stage I, 6 Stage II, 15 Stage III and 4 Stage IV. Fourteen tumors (32%) were classified as TP positive and 21 (48%) as VEGF positive. The proportion of Stage I tumors that were TP positive (16%) was significantly lower (p = 0.022) than the corresponding value for Stages II-IV (44%), but the proportion with VEGF positive, the values for microvessel count and PSV were similar. Microvessel count did not significantly related to TP nor VEGF expression. The PSV was significantly higher in TP-positive tumors (p = 0.02) and VEGF-positive tumors (p = 0.006), respectively. There was a significant correlation between the microvessel count and the PSV (r = 0.34, p = 0.024). Moreover, specific B-mode classification significantly associated with disease stage and with TP expression, but not with VEGF expression. CONCLUSIONS: Angiogenesis is an early, critical step in the tumorigenesis of epithelial ovarian cancer, however, it does not provide significant information about tumor aggressiveness. When TP expression is superimposed upon the VEGF expression, the tumor might acquire the aggressive tumor phenotype.

Adenocarcinoma, Clear Cell↗

PubMedDate not supplied

Correlation of CT patterns with histologic findings in parauterine masses.

CT findings were correlated with histologic and surgical findings in 162 parauterine masses. CT findings were classified into four types and 14 patterns. These classifications were useful in the diagnosis and differential diagnosis of parauterine masses. Malignant ovarian tumors, uterine myogenic tumors, metastatic tumors, endometrial cysts, and benign cystadenoma revealed characteristic CT findings, making differential diagnosis possible on CT. Contrast enhancement of the solid part, bilaterality, and the presence of ascites were useful for differential diagnosis. Although CT is one of the major modalities for the diagnosis of intrapelvic mass lesions, MR imaging will be another important method for the delineation and characterization of these lesions in the future.

Adult↗

PubMedDate not supplied

Etiologic significance of anatomic variations in the main intrahepatic bile ducts in hepatolithiasis.

Abnormal union of intrahepatic bile ducts has been suggested as a possible etiologic factor in the occurrence of intrahepatic stones. A series of 241 patients were examined by direct cholangiography, and anatomic variations in the intrahepatic bile ducts were classified into four types: Type A-1, normal union having a true right hepatic duct; Type A-2, absence of a right hepatic duct, with a trifurcation; Type B, posterior segmental duct draining into left hepatic duct; Type C, anterior segmental duct draining into left hepatic duct. The most dominant type was Type A-1, which occurred in 58.3 to 66.0 per cent of the cases, followed by Type A-2 with 12.5 to 19.8 per cent. Type B showed the lowest incidence, occurring in 4.5 to 10.4 per cent. No statistical difference existed in the distribution of the type of union of intrahepatic bile ducts on the one hand and the presence or absence of intrahepatic stones on the other. Thus, anatomic variations in the main intrahepatic bile ducts do not seem to be associated with hepatolithiasis, and their etiologic significance seems to be unlikely.

Adult↗

PubMedDate not supplied

Intra-arterial neoadjuvant chemotherapy followed by radical surgery and radiotherapy for stage IIb cervical carcinoma.

BACKGROUND: The role of intra-arterial neoadjuvant chemotherapy (NAC) in the management of cervical carcinoma has not been established. The aim of this study was to determine whether pre-operative intra-arterial NAC is effective or not in patients with stage IIb cervical carcinoma. PATIENTS AND METHODS: A total of 28 patients with stage IIb cervical carcinoma (diameter > 4 cm) were treated with one cycle of intra-arterial NAC (cisplatin 70 mg/m2, and peplomycin sulfate 30 mg/m2 or doxorubicin 30 mg/m2) followed by radical surgery and post-operative radiotherapy. Immediate response, toxicity, survival, and prognostic factors for survival were evaluated. RESULTS: The overall clinical response rate was 79% (22/28) with a complete response in 1 patient (4%). Radical hysterectomy with pelvic lymphadenectomy was feasible in 25 patients (89%) 4 weeks after chemotherapy. Toxicity were generally mild, and there were no intraoperative complications related to intra-arterial NAC. The estimated 2- and 5-year survival rates for the entire group were 93% and 80%, respectively, with a median followup time in survivors of 62 months. Univariate analysis showed the following to be significantly related to survival: histologic type, PCNA index, clinical response to intraarterial NAC, and lymph node metastasis. Survival was not significantly related to age, grade of differentiation, serum level of squamous cell carcinoma antigen, p53 protein expression, or residual parametrial involvement. Multivariate Cox's proportional hazard analysis showed that only the histologic type significantly influenced survival (p = 0.0007). The estimated 2- and 5-year survival rates were 100% and 94% for patients with squamous cell carcinoma, and 75% and 50% for those with adenocarcinoma. CONCLUSIONS: Intra-arterial NAC followed by surgery and radiotherapy appeared to be effective in treating patients with stage IIb cervical squamous cell carcinoma, but was not as effective in patients with stage IIb cervical adenocarcinoma.

Adult↗