4982 Objective: 14-3-3 sigma, one isoform of the 14-3-3 family, plays a crucial role in the G2 checkpoint by sequestering Cdc2-cyclin B1 in the cytoplasm and the expression is frequently lost in human cancers. In this study, we examined the promoter methylation status and expression of 14-3-3 sigma, and evaluated its clinical significance in epithelial ovarian cancer. Materials and Methods: Twelve ovarian cancer cell lines, 2 ovarian surface epithelial cell lines, 8 normal, 8 benign, 12 borderline, and 102 ovarian cancer tissues were examined. Methylation specific PCR (MSP), quantitative RT-PCR, immunoblotting, and immunohistochemistry were employed to evaluate methylation status and expression of 14-3-3 sigma gene and protein. Results: Among the 12 ovarian cancer cell lines, the presence of methylated band was detected in 7 cell lines, 2 of which were together with unmethylated bands. Both of OSE cells were negative for methylated bands. By quantitative RT-PCR analysis, median values of relative 14-3-3 sigma gene expression in cancers with methylation (3.27) were significantly lower than those without methylation (16.4)(p 2cm, high serum CA125, high Ki-67 LI, and positive p53 immunoreactivity. In univariate analysis, 14-3-3 sigma immunoreactivity, age, performance status, grade, stage, residual tumor, and Ki-67 were significantly associated with overall survival. Negative 14-3-3 sigma cases were significantly worse overall survival and disease free survival (p=0.0058 and 0.002, respectively). In multivariate analysis, stage and residual tumor turned out to be independent prognostic factors. Conclusion: Our findings suggest that 14-3-3 sigma is inactivated mainly by aberrant DNA methylation and it may play an important role in the pathogenesis of epithelial ovarian cancer.
Abstract Obesity is a well-known risk factor for gynecological malignant tumors such as breast and endometrial cancers. In the cancer microenvironment, the interaction between cancer cells and adipocytes reportedly contributes to the malignant behavior of cancer. In breast cancer, the fatty acid transporter CD36, also known as fatty acid translocase, has been shown to mediate fatty acid uptake into cancer cells and activate signaling pathways that promote tumor progression. Fatty acids are speculated to play important roles in breast and endometrial cancer; however, detailed mechanisms remain unclear. In the present study, we first examined the expression of CD36 and acyl-CoA dehydrogenase long chain (ACADL) in breast (30 cases) and endometrial (35 cases) cancer tissues using immunohistochemistry. CD36 is a membrane protein that transports long-chain fatty acids, and ACADL catalyzes the initial β-oxidation reaction. We detected no correlation between the CD36 status and clinicopathological factors, including the estrogen receptor status in breast cancer tissues. CD36 status revealed a significant positive correlation with lymph node metastasis in endometrial cancer. There was no immunoreactivity for CD36 in morphologically normal mammary glands. Otherwise, CD36 immunoreactivity was detected in the endometrial glandular cells. In both cancers, ACADL expression did not correlate with any clinicopathological factor. Both CD36 and ACADL showed higher positivity rates in endometrial cancer than in breast cancer. In addition, the effect of lipid addition on cell proliferation was examined using breast (T-47D) and endometrial (AN3CA) cancer cell lines exhibiting equivalent CD36 levels. Lipid (Refeed JNS) was obtained from Remembrane, Italy. Lipid addition promoted cell proliferation in both T-47D and AN3CA cells. Intracellular fatty acid β-oxidation (FAO) was visualized using FAOBlue (Funakoshi, Tokyo, Japan), a nonanoic acid (C9) derivative of coumarin, a blue fluorescence dye. Following FAOBlue decomposition in the fourth FAO cycle, coumarin is released from propionic acid, and released coumarin shows strong blue fluorescence excited at 405 nm. T-47D cells showed blue fluorescence in the lipid-supplemented medium, indicating β-oxidative activity. Conversely, AN3CA cells exhibited weak fluorescence under the same conditions. It can be postulated that intracellular lipid uptake and subsequent β-oxidation are mediated via a specific pathway in breast and endometrial cancers. Lipid-mediated effects differ between breast and endometrial cancers, and further investigations are needed to elucidate intracellular signals mediating these effects. Presentation: No date and time listed
Enzymes trapped in fungal cell wall and free enzymes produced by koji molds were measured separately. Little differences in a tendency for trapping were recognized between Aspergillus oryzae and A. kawachii. More enzymes were trapped in liquid cultures, while the ratios of the trapped enzymes decreased in solid cultures. More than 80% of α-glucosidase and more than 50% of glucoamylase were trapped in liquid cultures; moreover, 10%-20% of the enzyme was trapped even in α-amylase. In solid culture, more than 20% of glucoamylase and more than 20% of a-glucosidase were still trapped, but the trapped a-amylase was negligible. The tendency of trapping was, α-amylase
Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2). CRH, CRHR1, and CRHR2 have recently been reported in several types of carcinoma, but the significance of these proteins has remained largely unknown in human endometrial carcinoma.
Materials and Methods
A total of 87 endometrial carcinoma specimens were obtained from Japanese female patients who underwent surgical treatment, fixed in 10% formalin, and embedded in paraffin wax. Immunohistochemistry for CRH, CRHR1, and CRHR2 was performed, and clinical data were obtained from the medical records.
Results
Immunopositivity of CRH, CRHR1, and CRHR2 in the specimens was 26%, 15%, and 10%, respectively. Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival. Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival.
Conclusions
These results suggest that intratumoral CRH-CRHR1 signaling plays an important role in the progression of endometrial carcinoma and that CRHR1 is a potent prognostic factor in patients with this disease.
Objectives: The purpose of this study was to evaluate the association of ABCF2 (adenosine triphosphate-binding cassette superfamily F2) protein expression with response to chemotherapy and prognosis in patients with clear cell adenocarcinoma (CCC) of the ovary. Methods: One hundred sixty-five patients with CCC were studied, and cytoplasmic ABCF2 expression was detected by immunohistochemical staining. All patients underwent platinum-based primary chemotherapy followed by primary surgery. Results: Adenosine triphosphate-binding cassette superfamily F2 expression was detected in 118 (71.5%) of 165 patients and was not related to age or clinical stage. The response rate to chemotherapy in 38 patients with measurable disease was 47.3% (18/38). The response rate tended to be higher in patients without ABCF2 expression than in those with ABCF2 expression; however, this difference was not significant (66.7% vs 34.8%, P = 0.096). There was no significant difference in overall survival between ABCF2-positive and ABCF2-negative cases (median survival time, 1175 vs 1257 days; P = 0.24). Conclusions: Adenosine triphosphate-binding cassette superfamily F2 protein was highly expressed in CCC of the ovary, but expression was not related to age, clinical stage, chemoresponse, or prognosis.
