ABSTRACT
Background: Gallstones are increasingly becoming a common diagnosis in hospitals across the continents, with predominance in women. Patients suspected of a gallstone disease require thorough evaluation including endoscopic ultrasound, magnetic resonance imaging, or magnetic resonance cholangiography. A delayed or missed diagnosis is associated with serious complications and poor prognosis. Case presentation: A 44-year-old female patient presented with fever, vomiting, hypochondria, and epigastric pain for 10 days. Clinical examination showed jaundice and tenderness at the right hypochondriac region. Blood analysis revealed elevated bilirubin, alkaline phosphatase, and white blood cells. The patient was sent for a computed tomography (CT) scan which showed a grossly enlarged liver about 17.2 cm in length and a hypo-attenuating mass in the gallbladder fossa that enhanced moderately and heterogeneously following intravenous contrast administration. Dilated intrahepatic biliary ducts were also appreciated. Explorative laparotomy was performed and revealed an enlarged, cirrhotic-appearing liver, a thickened gallbladder, and a whitish-yellow gallstone about 3 cm in the largest diameter situated at its neck. No isolated tumour was found. Clinical discussion: Although gallstone disease is very common, misdiagnosis still occurs especially in low and lower-middle-income countries. Inadequate evaluation and increased utilization of CT in emergency and surgical departments are the contributing factors for a missed diagnosis. Conclusions: A missed gallstone disease occurs due to various factors including inappropriate standard operating procedures, which set a CT scan as the first imaging test for all internal conditions. This case report presents the appropriate approach to achieving the diagnosis of a gallstone disease before surgical intervention.
ABSTRACT
Endometrioid endometrial carcinoma, commonly known as type 1 endometrial cancer, accounts for >80% of endometrial carcinomas and is dependent on estrogen. We recently reported on the prognostic significance of the BIRC5 survivin gene in endometrial cancer. Estradiol induces survivin expression in estrogen receptor-positive, but not in estrogen receptor-negative, cancer cells. Kaempferol, a bioflavonoid, reportedly inhibits estrogen receptor-α (ERα) in hormone receptor-positive breast cancer cells. However, whether kaempferol-mediated inhibition of ERα suppresses survivin and induces cell death in endometrial cancer remains unclarified. The present study evaluated the antitumor effects of kaempferol on endometrial cancer cells. Cell viability assays, flow cytometry analysis, western blotting and annexin V analyses were used to analyze the antitumor effects of kaempferol. The results demonstrated that kaempferol successfully suppressed the viability of two ER-positive endometrial cancer cell lines, with IC50 values of 83 and 65 µM. In addition, kaempferol induced sub-G1 cell accumulation and apoptotic cell death (P<0.01) in a dose-dependent manner. Treatment of cells with estradiol significantly induced co-expression of nuclear ERα and survivin proteins (P<0.001). Further evaluation revealed that kaempferol causes apoptotic cell death largely by suppressing ERα, survivin and Bcl-2 protein. Therefore, the results of the present study suggested that targeting ERα and survivin with kaempferol may be a novel therapeutic option against endometrial carcinoma.
ABSTRACT
INTRODUCTION: Survivin is an anti-apoptotic protein encoded by the baculoviral inhibitor of apoptosis repeat-containing (BIRC5) gene and is upregulated in 83% of endometrial cancers. We aimed to elucidate the prognostic importance of BIRC5 expression, and evaluate survivin as a therapeutic target for endometrial cancer, by knock-down of BIRC5 and using the survivin inhibitor-YM155. METHODS: RNA sequencing data in 234 patients with endometrial carcinoma was obtained from The Cancer Genome Atlas database, and analyzed using Kaplan-Meier method, log-rank test and Cox proportional hazard model. Expressions of survivin in 16 endometrial cancer cell lines were analyzed by western blotting. Knocking down effect on survivin expression was evaluated using a small interfering RNA (siRNA). The anti-proliferative and pro-apoptotic effects of YM155 were assessed with cell viability, flow cytometry, and annexin V/propidium iodide assays. RESULTS: High expression of BIRC5 was associated with poor progression free survival (P=0.006), and shown to be an independent prognostic factor (HR=1.97, 95% CI=1.29-4.5, P=0.045). Survivin was upregulated in 14 of 16 (87.5%) endometrial cancer cell lines, compared with endometrial immortalized cells. Apoptosis was induced by knockdown of BIRC5 in all 3 cell lines examined. YM155 showed increased population of sub-G1 cells (P<0.001) in all 16 cell lines, and IC50 values to YM155 were <50nm in 15 cell lines. YM155 dose-dependently and significantly increased the apoptotic cell population in all 16 cell lines (P<0.001). CONCLUSIONS: Present study indicated that survivin expression is a significant prognostic factor and that survivin is a promising therapeutic target for endometrial cancer.
