Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy.Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Because of difficulties in detection, diagnosis and treatment, the overall survival (OS) rate of ovarian cancer patients is still poor. It is therefore necessary to overcome these difficulties. A majority of cases (61%) of EOC are diagnosed at an advanced stage, with a corresponding 5-year survival rate of only 27%. 1 The fact that survival of patients with stages I-II disease ranges from 60 to 90%, depending on tumor grade, suggests the potential for a high cure rate with earlier disease detection. 2,3 As physical symptoms are absent in early stages of ovarian cancer, efforts are being made to develop assays for blood or tissue biomarkers. Although the serum CA125, an ovarian cell surface glycoprotein of unknown biological significance, is elevated in 80% of patients with advanced EOC, this marker has a positive predictive value (PPV) of only 10% in early-stage disease. 3 One of the limitations for CA125 is its relatively low specificity. Elevated CA125 is often associated with various nonmalignant conditions, such as pregnancy, endometriosis, adenomyosis, uterine fibroids, pelvic inflammatory disease, menstruation and benign ovarian cysts. Abnormal CA125 is also associated with other malignant conditions such as pancreatic, breast, lung, gastric and colorectal cancers especially when they are associated with peritoneal spreading. [4][5][6][7][8] Although CA125 is hel...

(243 words)Background: We compared survival outcomes and risk of venous thromboembolism

Serum mesothelin may be a useful noninvasive biomarker surrogate for tumor mesothelin expression in future clinical trials for mesothelin-targeted therapy.

Neural signals are processed in nervous systems of animals responding to variable environmental stimuli. This study shows that a novel and highly conserved protein, macoilin (MACO-1), plays an essential role in diverse neural functions in Caenorhabditis elegans. maco-1 mutants showed abnormal behaviors, including defective locomotion, thermotaxis, and chemotaxis. Expression of human macoilin in the C. elegans nervous system weakly rescued the abnormal thermotactic phenotype of the maco-1 mutants, suggesting that macoilin is functionally conserved across species. Abnormal thermotaxis may have been caused by impaired locomotion of maco-1 mutants. However, calcium imaging of AFD thermosensory neurons and AIY postsynaptic interneurons of maco-1 mutants suggest that macoilin is required for appropriate responses of AFD and AIY neurons to thermal stimuli. Studies on localization of MACO-1 showed that C. elegans and human macoilins are localized mainly to the rough endoplasmic reticulum. Our results suggest that macoilin is required for various neural events, such as the regulation of neuronal activity.

Background: This study aimed to determine the efficacy of the risk of ovarian malignancy algorithm (ROMA), calculated using the carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) levels and the menopausal status, as a predictor of peritoneal dissemination in ovarian cancer. Methods: The CA125 and HE4 levels and the ROMA were compared between ovarian cancer patients (n = 122) with or without peritoneal dissemination. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and the results were compared with those of computed tomography (CT). Results: The CA125, HE4, and ROMA values differed significantly depending on the presence of peritoneal dissemination (p < 0.0001). The cut-off values were 181 U/ml for CA125, 161 pmol/ml for HE4, 44% for the ROMA (premenopausal), and 86% for the ROMA (postmenopausal). Among these markers, the ROMA (premenopausal) was the strongest predictor of peritoneal dissemination, with a specificity of 85.0% and a positive predictive value of 81.3%. In addition, the detection rates of small disseminations with less than 2 cm in diameter for the ROMA (93%) and HE4 (60%) were superior to that of CT (53%). Conclusions: The ROMA was a significant predictor of peritoneal dissemination and may be superior to CT for the detection of patients with small disseminations.