No TG mice developed HCC spontaneously after 14 months follow-up. However, TG mice were more resistant to DEN-induced hapatocarcinogenesis at 6, 10, and 12 months of age, showing delayed hepatocyte proliferation and apoptosis, lower tumor incidence, smaller size and fewer number, compared with age-matched WTs, partially through downregulation of MET and EGFR. In conclusion, continuous activation of PDGFRα signaling by expression of PDGFRα D842V does not promote, but inhibit hepatic regeneration and hepatocarcinogenesis, possibly through compensatory downregulation of MET and EGFR.Background To investigate the effects and safety profile of radiation dose escalation utilizing computerized tomography (CT) based radiotherapy techniques (including 3-Dimensional conformal radiotherapy, intensity-modulated radiotherapy and proton therapy) in the definitive treatment of patients with esophageal carcinoma (EC) with definitive concurrent chemoradiotherapy (dCCRT). Methods All relevant studies utilizing CT-based radiation planning, comparing high-dose (≥ 60 Gy) versus standard-dose (50.4 Gy) radiation for patients with EC were analyzed for this meta-analysis. Results Eleven studies including 4946 patients met the inclusion criteria, with 96.5% of patients diagnosed with esophageal squamous cell carcinoma (ESCC). The high-dose group demonstrated a significant improvement in local-regional failure (LRF) (OR 2.199, 95% CI 1.487-3.253; P less then 0.001), two-year local-regional control (LRC) (OR 0.478, 95% CI 0.309-0.740; P=0.001), two-year overall survival (OS) (HR 0.744, 95% CI 0.657-0.843; P less then 0.001) and five-year OS (HR 0.683, 95% CI 0.561-0.831; P less then 0.001) rates relative to the standard-dose group. In addition, there was no difference in grade ≥ 3 radiation-related toxicities and treatment-related deaths between the groups. Conclusion Under the premise of controlling the rate of toxicities, doses of ≥ 60 Gy in CT-based dCCRT of ESCC patients might improve locoregional control and ultimate survival compared to the standard-dose dCCRT. While our review supports a dose-escalation approach in these patients, multiple ongoing randomized trial initial and final reports are awaited to evaluate the effectiveness of this strategy.Background Non-alcoholic fatty liver disease (NAFLD) is a common disorder and a frequent side effect of endocrine therapy (ET) for breast cancer treatment. This was the first meta-analysis to investigate the impact of NAFLD on breast cancer survival. Material and Methods We searched Pubmed, Embase and Cochrane Central Register of Controlled Trials database for relevant studies that investigated the correlation between NAFLD and breast cancer survival. Fixed- and random-effect meta-analyses were conducted according to the heterogeneity of enrolled studies. Subgroup analyses were performed based on whether NAFLD was induced by ET administration Results Eight cohorts from six studies including 3684 breast cancer patients were enrolled. NAFLD was significantly associated with advanced age (p less then 0.001), obesity (p less then 0.001), lymph node metastases (p = 0.003) and hormone receptor positivity (p less then 0.001). NAFLD had no significant impact on disease free survival (DFS) [hazard ratio (HR) 1.07, 95% confidence interval (CI) = 0.64-1.77, p = 0.81] and overall survival (OS) (HR 1.29, 95% CI = 0.68-2.44, p = 0.44). In subgroup analyses, ET-associated NAFLD showed no significant impact on DFS and OS. Nonetheless, non-ET-associated NAFLD had a strong prognostic correlation with poor OS (HR 1.92, 95% CI = 1.09-3.41, p = 0.02). Conclusion NAFLD had no significant impact on breast cancer survival. However, non-ET-associated NAFLD implied increasing death risk. Future large-scale studies are warranted to further elucidate the correlation between NAFLD and breast cancer prognosis.Background and aim Refractoriness to transarterial chemoembolization is common during the therapeutic process of hepatocellular carcinoma, which is an intractable issue and may compromise the prognosis. We aim to establish a pre-treatment model to identify patients with high risks of refractoriness. Methods From 2010 to 2016, 824 treatment-naive patients who had initially underwent at least two sessions of transarterial chemoembolization in Zhongshan Hospital, Fudan University were retrospectively enrolled. These patients were randomly allocated into a training cohort and a validation cohort. The pre-treatment scoring model was established based on the clinical and radiological variables using logistic regression and nomogram. The discrimination and calibration of the model were also evaluated. Results Logistic regression identified vascularization pattern, ALBI grade, serum alpha-fetoprotein level, serum γ-glutamyl transpeptidase level and major tumor size as the key parameters related to refractoriness. The p-TACE model was established using these variables (risk score range 0-19.5). Patients were divided into six risk subgroups based on their scores ( less then 4, ≥4, ≥7, ≥10, ≥13, ≥16). The discriminative ability, as determined by the area under receiver operating characteristic curve was 0.784 (95% confidence interval 0.741-0.827) in the training cohort and 0.743 (95% confidence interval 0.696-0.789) in the validation cohort.  https://www.selleckchem.com/products/myk-461.html  Moreover, satisfactory calibration was confirmed by Hosmer-Lemeshow test with P values of 0.767 and 0.913 in the training cohort and validation cohort. Conclusions This study presents a pre-treatment model to identify patients with high risks of refractoriness after transarterial chemoembolization and shed light on clinical decision making.Acute myeloid leukemia (AML) is a clonal and heterogeneous disease characterized by proliferation of immature myeloid cells, with impaired differentiation and maturation. Spinster homolog (SPNS) is a widely distributed transmembrane transporter, which assists sphingolipids in playing their roles through the cell membrane. However, the expression and clinical implication of the SPNS family has not been investigated in AML. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and SPNS1-3 expression data were contained in our study. In patients who received chemotherapy only, high expressions of SPNS2 and SPNS3 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P less then 0.05). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in OS between the high and low SPNS3 expression groups (P=0.001), while other SPNS members showed no effect on survival. Multivariate analysis indicated that high SPNS2 expression was an independent risk factor for both EFS and OS in chemotherapy patients.