Lung cancer remains the most common cause of cancer-related death worldwide and it continues to lack effective treatment. The increasingly large and diverse public databases of lung cancer gene expression constitute a rich source of candidate oncogenic drivers and therapeutic targets. To define novel targets for lung adenocarcinoma (ADC), we conducted a large scale meta-analysis of genes specifically overexpressed in ADC. We identified an eleven-gene signature that was overexpressed consistently in ADC specimens relative to normal lung tissue. Six genes in this signature were specifically overexpressed in ADC relative to other subtypes of non-small cell lung cancer (NSCLC). Among these genes was the little studied protein tyrosine kinase PTK7. Immunohistochemical analysis confirmed that PTK7 is highly expressed in primary ADC patient samples. RNAi-mediated attenuation of PTK7 decreased cell viability and increased apoptosis in a subset of ADC cell lines. Further, loss of PTK7 activated the MKK7-JNK stress response pathway and impaired tumor growth in xenotransplantation assays. Our work defines PTK7 as a highly and specifically expressed gene in ADC and a potential therapeutic target in this subset of NSCLC.

Background Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival. Methods Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL – fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF – fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations. Results Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 μm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and β-myosin heavy chain did not differ between groups. Conclusion Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.

OBJECTIVE: To determine if Vitamin D prophylaxis decreases the incidence of hypertensive disorders of pregnancy. STUDY DESIGN: A single center, parallel, open label, randomized control trial was performed in which pregnant women received Vitamin D3 3000 IU daily or no supplement. The primary outcome was the incidence of hypertensive disorders of pregnancy. Based on a power analysis set at 80%, a sample size of 206 women in each group (n¼412) was planned for comparison. Maternal serum and cord blood were collected for 25-hydroxyvitamin D assessment. Patients were called to assess compliance with the study protocol. Maternal demographics and pregnancy outcomes were collected from the electronic medical record. Statistical analyses were performed using SPSS V24. Student's t tests and ANOVA analyses were performed for continuous variables that were normally distributed. Chi-Square or Fisher's exact tests were performed for categorical variables. Binary logistic regression for the primary outcome was performed adjusting for confounders. The analysis was conducted with an intent to treat model with omission of missing variables. A P value of <0.05 was statistically significant. RESULTS: Enrollment occurred between October 2016 and September 2019. Of the 412 women enrolled, 392 (95.1%) had completed pregnancies for analysis. Demographic characteristics including baseline maternal 25-hydroxyvitamin D (25(OH)D) levels were similar between groups. Compared to women who did not receive Vitamin D prophylaxis, those who did had a significantly higher 25(OH)D delivery serum level (29.18 +/-11.87 ng/mL vs. 23.79 +/-9.29 ng/mL; P<0.001) and cord blood level (33.73 +/-13.68 ng/mL vs. 26.06 +/-9.72 ng/mL; P<0.001). The incidence of hypertensive disorders of pregnancy was 10.5% (41/392). Vitamin D prophylaxis did not decrease the incidence of hypertensive disorders of pregnancy when compared to controls (13.1% vs. 7.7%; RR 1.7, 95% CI 0.9-2.9; P¼0.10). CONCLUSION: Vitamin D prophylaxis does not prevent hypertensive disorders of pregnancy, but does increase maternal and cord blood Vitamin D levels.