Souei Sekiya

Serum vascular endothelial growth factor (VEGF) and VEGF-C levels as tumor markers in patients with cervical carcinoma

Vascular endothelial growth factor (VEGF) and VEGF‐C play a crucial role in the regulation of tumor growth and metastasis. The current study examined the significance of serum VEGF and VEGF‐C levels in relation to conventional clinicopathologic parameters, response to treatment, and survival in patients with cervical carcinoma.

Oncolytic Viral Therapy for Cervical and Ovarian Cancer Cells by Sindbis Virus AR339 Strain

Purpose: Recently, the application of replication-competent viruses has been studied as anticancer agents. Sindbis virus (SIN) is an RNA virus that belongs to the Alphavirus genus in the Togaviridae virus family. The AR339 strain of SIN has not been reported to induce any serious disease to humans. Experimental Design: In this study, we evaluated the feasibility of the replication-competent SIN AR339 strain as an agent for cervical and ovarian cancer therapy. Results: SIN infection was able to induce cytopathic effects and apoptosis in two cervical cancer cells (HeLaS3 and C33A) and three ovarian cancer cells (HOC-1, HAC-2, and OMC-3) but not in normal human keratinocytes in vitro. The analysis of cell viability, virus protein synthesis, and viral growth showed the cancer-specific cytotoxicity and virus growth of SIN. In nude mice, i.t. and i.v. inoculation of SIN resulted in significant regression of established cervical tumors implanted at their backs. Histologic studies revealed that systemic treatment with the single injection of SIN induces necrosis within tumors at a remote site. In the metastasis model of ovarian cancer, suppression of ascites formation was observed in nude mice with i.p. SIN treatment. By using an in vivo green fluorescent protein imaging system, we also showed that systemic treatment with SIN targeted tumors specifically. Conclusions: Our study suggested that SIN AR339 strain has a possibility as a novel agent for human cervical and ovarian cancer therapy.

Increased expression of GRP94 protein is associated with decreased sensitivity to X-rays in cervical cancer cell lines

Purpose: Radiation therapy is one of the standard treatments for cervical cancer. Glucose regulated protein 94 (GRP94) is a molecular chaperone, which increases in amount after X-ray irradiation. This study examined the involvement of GRP94 in radio-resistance in human cervical cancer cells. Materials and methods: Seven human cervical carcinoma cell lines (HeLa, SKG-I, SKG-IIIb, QG-U, Caski, SiHa and C33A) were examined for basal levels of GRP94 protein by western blotting analysis. Sensitivity to X-ray irradiation of these cell lines was determined with a colony survival assay. The suppression of GRP94 expression was performed using specific small-interfering RNA (siRNA) in HeLa and Caski cells. Results: HeLa cells and QG-U cells, with higher basal levels of GRP94, exhibited a low sensitivity to X-ray cell killing. In HeLa cells, the sensitivity increased when protein GRP94 levels were reduced by specific siRNA transfection. However, a reduction in GRP94 protein had little effect on the X-ray sensitivity of Caski cells, which expressed low basal GRP94 protein levels but showed a low sensitivity to X-rays. Conclusions: High basal protein levels of GRP94 were correlated with a modest decrease in sensitivity to X-ray cell death in some cervical cancer cell lines. These results suggest that higher GRP94 protein expression is one of the molecular mechanisms causing resistance to radiation, and therefore GRP94 siRNA might be useful in tumor-specific gene therapy by reversing radio-resistance prior to radiation in cervical cancer.

Successful Pregnancy and Delivery after Removal of Gonadotrope Adenoma Secreting Follicle-Stimulating Hormone in a 29-Year-Old Amenorrheic Woman

We report a case of ovarian hyperstimulation related to a gonadotroph adenoma in a 29-year-old woman. The patient presented with amenorrhea and large cystic ovaries. Her serum estradiol was markedly elevated (up to 31,100 pmol/l). Serum LH was low, but serum FSH and PRL were normal. Cranial magnetic resonance imaging study revealed a pituitary macroadenoma. After successful removal of the pituitary tumor, FSH, LH and estradiol normalized and fluctuated within normal ranges thereafter. The patient resumed regular cycles of menstruation and conceived spontaneously. During pregnancy, estradiol increased and FSH and LH decreased. The finding confirms restoration of negative feedback of estradiol on FSH and LH secretion. The pregnancy course was uneventful and enlargement of ovaries did not occur.

Discordance between serum level and tissue immunohistochemical staining of CA125 in endometrioid adenocarcinoma of the uterine corpus.

This study was designed to correlate tissue expression of CA125 with the corresponding serum value in endometrial cancer. The records of 52 endometrioid adenocarcinomas diagnosed were reviewed. Serum CA125 levels were examined before definitive surgery, and 20 U/ml was used as the cutoff value. Immunohistochemical staining for CA125 was assessed according to the ImmunoReactive Score. Statistical analyzes were performed to identify independent factor for high serum CA125 levels, including CA125 staining and the conventional pathologic features. Elevated serum CA125 levels were found in 15 of 52 patients (29%) (range, 0.1-172.1; mean 22.6 U/ml). The frequency of positive CA125 tissue staining (35/52, 67%) tended to be higher than that of elevated serum levels (p = 0.046). Fifteen patients with elevated serum CA125 levels statistically differed from the remaining 37 patients with normal serum CA125 level with respect to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.027) and lymph node metastasis (p = 0.024), and tended to have positive washing cytology (p = 0.052). In multivariate analysis, elevated serum CA125 significantly correlated only with FIGO stage III, but not with tumor size or CA125 tissue staining. Intrauterine tumor may not be the main source of serum CA125 in endometrial cancer, and elevated serum level is closely related to the presence of disseminated cancer cells in the peritoneal cavity.

Accelerated Bone Turnover in Pregnant Women with McCune-Albright Syndrome

Bone turnover in pregnant women with McCune-Albright syndrome may be affected by both the syndrome and pregnancy. This study evaluated changes in biochemical bone turnover markers in pregnant women with the syndrome. Serum calcium, phosphorus, 1,25-dihydroxyvitamin D (1,25-(OH)2D), intact osteocalcin (I-OC) and alkaline phosphatase (ALP), and urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and hydroxyproline (HPR) were measured during pregnancy and postpartum in 2 women with McCune-Albright syndrome. Serum calcitonin (CT), and plasma intact parathyroid hormone (I-PTH) and parathyroid hormone-related protein (PTHrP) were also measured in 1 patient. Serum corrected Ca levels were normal or low-normal; phosphorus levels were normal, and 1,25-(OH)2D levels increased toward term and decreased thereafter, similar to normal pregnant women. Urinary Pyr, D-Pyr and HPR were elevated during pregnancy compared to normal pregnant women, peaked just after delivery, and decreased thereafter. Serum I-OC and ALP levels were high during pregnancy and postpartum. Intact PTH levels were increased during pregnancy and postpartum compared to normal pregnant women, whereas serum CT and PTHrP levels were not elevated. Both bone formation and absorption appear to be more enhanced during pregnancy and postpartum in women with McCune-Albright syndrome than in normal pregnant women. Additional or amplified cyclic AMP synthesis in bone cells through activation of the α subunit of G protein, independent of hormonal control, may explain the high local bone turnover.

Phase I study of daily cisplatin and concurrent radiotherapy in patients with cervical carcinoma

5103 Background: Chemoradiation based on cisplatin is the standard treatment of locally advanced cervical carcinoma; however, the optimal scheduling, dosing were not still decision, the purpose of this study was to determine the maximum-tolerated dose (MTD) of cisplatin when administrated daily during pelvic radiation (RT). METHODS Patients with locally advanced cervical carcinoma and patients who required postoperative RT were registered. Low dose cisplatin (starting dose 6.0mg/m2, 0.5mg/m2 escalation per level) was given with daily application concurrently with RT (2Gy/ day; total dose of 50Gy). Cohorts of three patients were enrolled at each level. If one of three patients at any level developed dose-limiting toxicity (DLT), three additional patients were then treated at the same dose level. DLT was defined as grade 3/4 nonhematologic toxicity except for alopecia, nausea and vomiting, grade 3/4 neutropenia or thrombocytopenia. Cisplatin was interrupted when hematological DLT were observed.The MTD was defined as the dose level below that which produced DLT in more than one-third of treated patients. RESULTS Twenty-five patients were eligible in this study. In 21/25 patients (84%), cisplatin was administrated continuously as planned with no interruption. As shown in the table, the MTD was 8mg/m2 and the DLT was neutropenia. Fourteen patients were analysis for response: 11 complete response and 2 partial responses were obtained with an overall response rate of 92.9%. CONCLUSIONS A dose of 8 mg/m2 daily was determined to be MTD and considered the recommended dose of daily cisplatin. Daily cisplatin is a well-tolerated and effective radiosensitizer in cervical carcinoma patients. [Figure: see text] No significant financial relationships to disclose.