FBXW7 expression is associated with prognosis and chemotherapeutic outcome in Chinese patients with gastric adenocarcinoma.

BACKGROUND: FBXW7, a component of the Skp-Cullin1-F-box, mediates target protein recognition. It is a tumor suppressor gene that plays a role in the regulation of cell cycle exit and reentry via c-Myc, c-Jun and Notch degradation. There are few studies, particularly involving a large patient cohort, that have evaluated FBXW7 during gastric cancer progression. METHODS: Our study aimed to evaluate the value of FBXW7 as a clinical marker in gastric adenocarcinoma (GC) patients including a subset treated with postoperative chemotherapy. Quantitative reverse transcription PCR (qRT-PCR) assay was used to measure FBXW7 transcript levels in tumors paired with normal gastric tissue in 24 gastric adenocarcinoma patients. Subsequently, 546 additional GC samples were evaluated from patients that underwent radical gastrectomy, including 118 early stage cases(Stage I) and 428 advanced stage cases (Stages II or III). Amongst the advanced stage patient cases evaluated, 347 received postoperative adjuvant chemotherapy. All 546 gastric adenocarcinoma cases were then evaluated by tissue microarray and immunohistochemistry (IHC) for FBXW7 expression. Clinicopathological features and diagnoses were confirmed by histopathologic evaluation and review of clinical data. Overall survival (OS) was then evaluated in the 546 gastric cancer patients. RESULTS: By immunohistologic evaluation, low expression of FBXW7 in primary gastric cancer significantly correlated with poor differentiation of tumor cells. Moreover, low FBXW7 expression was associated with worse survival as well as worse adjuvant chemotherapy response. CONCLUSION: Our findings suggest that FBXW7 may serve as an important predictor in chemotherapeutic responses.

miRNA-218-loaded carboxymethyl chitosan - Tocopherol nanoparticle to suppress the proliferation of gastrointestinal stromal tumor growth.

Gastrointestinal stromal tumors (GIST) are one of the most common forms of mesenchymal cancers of the gastrointestinal tract. Although chemotherapeutic drugs inhibited the proliferation of GIST, however, sizable proportion of people developed resistance and therefore difficult to treat. In the present study, O-carboxymethyl chitosan (OCMC)-tocopherol polymer conjugate was synthesized and formulated into stable polymeric nanoparticles. The main aim of present study was to increase the therapeutic efficacy of miR-218 in GIST. The mean size of nanoparticles was ~110nm with a spherical shape. The miR-218 NP has been shown inhibit the cell proliferation and exhibited a superior cell apoptosis. The miR-218 NP inhibited the cell invasion and promoted the apoptosis of GIST cancer cells. In the present study, we have successfully showed that KIT1 is the target gene of miR-218 as shown by the luciferase reporter assay. These findings collectively suggest the miR-218 loaded nanoparticle by virtue of effective transfection could act as a tumor suppressor miRNA in the treatment of GIST.

Correlations of fascin-1 and cadherin-17 protein expression with clinicopathologic features and prognosis of patients with gastric cancer.

We aim to explore the associations of fascin-1 and cadherin-17 in gastric cancer (GC) to the clinicopathologic features and prognosis of GC. Case group included 204 GC tissues while control group comprised 204 paired adjacent cancer tissues. Expressions of fascin-1 and cadherin-17 were measured with immunohistochemistry and western blot and then analyzed statistically in relation to clinicopathologic features and survival time. Survival curve was drawn by Kaplan-Meier method, and independent prognostic factors were identified with Cox proportional hazards regression model. Fascin-1 was positively expressed in 45.1 % of GC tissues and in 27.5 % of adjacent cancer tissues, respectively (P < 0.05); cadherin-17 was positively expressed in 51.5 % of GC tissues and in 33.8 % of adjacent cancer tissues (P < 0.05). Fascin-1 expression in GC tissues was related to tumor size (P = 0.001) and Lauren classification (P = 0.001). Cadherin-17 expression in GC tissues was related to tumor size (P < 0.001), Lauren classification (P = 0.009), clinical staging (P = 0.001), and distant metastasis (P = 0.002). Fascin-1 expression was positively correlated with cadherin-17 expression in GC tissues (r = 0.828, P < 0.01). Patients with positive expression of both fascin-1 and cadherin-17 had lower survival rates than those with negative expression (all P < 0.01). Cox regression analysis showed that fascin-1 expression, cadherin-17 expression, tumor size, and differentiation were independent risk factors for GC (all P < 0.05). Fascin-1 and cadherin-17 are related to clinicopathologic features of GC and are independent adverse prognostic factors for GC.