The risk factors of prostate cancer: A multicentric case-control study in Iran

Prostate cancer (PC), in Iran, is the third most frequently diagnosed visceral cancer among men and the seventh most common underlying cause of cancer mortality. We evaluated the relation between speculated factors and PC risk using data from a multicentric case-control study conducted in Iran from 2005 to 2007 on 130 cases of incident, clinicopathologically confirmed PC, and 75 controls admitted to the same network of hospitals without any malignant disease. Odds ratios(OR) and corresponding 95 confidence intervals (CIs) were estimated using conditional logistic regression models. The risk of PC was increased with aging (OR: 5.35, 95 CI: 2.17-13.19; P<0.0001), and with the number of sexual intercourse �2 times/week (OR: 3.14, 95 CI: 1.2-8.2; P=0.02). One unit elevation in serum estradiol and testosterone concentration was related to increase (OR: 1.04, 95 CI: 1.01-1.06; P=0.006) and decrease (OR: 0.79; 95 CI: 0.64-0.96; P=0.02) of PC risk, respectively. Cases were less likely to have a history of diabetes (OR: 0.34, 95 CI: 0.12-0.98; P=0.04). Increasing in dietary consumption of lycopene and fat was associated with declined (OR: 0.45, 95 CI: 0.09-2.12) and increased (OR: 2.38, 95 CI: 0.29-19.4) PC development, respectively. Other factors including educational level, marriage status, dietary meat consumption, vasectomy and smoking have not been shown to affect PC risk in the Iranian population. Ourstudy adds further information on the potential risk factors of PC and is the first epidemiologic report from Iran. However, justification of these results requires more well-designed studies with a larger number of participants

Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a form of progressive interstitial lung disease with unknown etiology. Due to a lack of effective treatment, IPF is associated with a high mortality rate. The hallmark feature of this disease is the accumulation of activated myofibroblasts that excessively deposit extracellular matrix proteins, thus compromising lung architecture and function and hindering gas exchange. Here we investigated the origin of activated myofibroblasts and the molecular mechanisms governing fibrosis formation and resolution. Genetic engineering in mice enables the time-controlled labeling and monitoring of lipogenic or myogenic populations of lung fibroblasts during fibrosis formation and resolution. Our data demonstrate a lipogenic-to-myogenic switch in fibroblastic phenotype during fibrosis formation. Conversely, we observed a myogenic-to-lipogenic switch during fibrosis resolution. Analysis of human lung tissues and primary human lung fibroblasts indicates that this fate switching is involved in IPF pathogenesis, opening potential therapeutic avenues to treat patients

Fgf10 deficiency is causative for lethality in a mouse model of bronchopulmonary dysplasia

Inflammation-induced FGF10 protein deficiency is associated with bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely born infants characterized by arrested alveolar development. So far, experimental evidence for a direct role of FGF10 in lung disease is lacking. Using the hyperoxia-induced neonatal lung injury as a mouse model of BPD, the impact of Fgf10 deficiency in Fgf10(+/−) versus Fgf10(+/+) pups was investigated. In normoxia, no lethality of Fgf10(+/+) or Fgf10(+/−) pups was observed. By contrast, all Fgf10(+/−) pups died within 8 days of hyperoxic injury, with lethality starting at day 5, whereas Fgf10(+/+) pups were all alive. Lungs of pups from the two genotypes were collected on postnatal day 3 following normoxia or hyperoxia exposure for further analysis. In hyperoxia, Fgf10(+/−) lungs exhibited increased hypoalveolarization. Analysis by FACS of the Fgf10(+/−) versus control lungs in normoxia, revealed a decreased ratio of alveolar epithelial type II (AECII) cells over total Epcam-positive cells. In addition, gene array analysis indicated reduced AECII and increased AECI transcriptome signatures in isolated AECII cells from Fgf10(+/−) lungs. Such an imbalance in differentiation is also seen in hyperoxia and associated with reduced mature surfactant protein B and C expression. Attenuation of the activity of Fgfr2b ligands post-natally in the context of hyperoxia lead also to increased lethality with decreased surfactant expression. In summary, decreased Fgf10 mRNA levels leads to congenital lung defects, which are compatible with postnatal survival, but which compromise the ability of the lungs to cope with sub-lethal hyperoxic injury. Fgf10 deficiency affects quantitatively and qualitatively the formation of AECII cells. In addition, Fgfr2b ligands are also important for repair after hyperoxia exposure in neonates. Deficient AECII cells could be an additional complication for patients with BPD