The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression of the IGF1R gene constitutes a typical feature of most human cancers. Consistent with these biological roles, cells expressing high levels of IGF1R are expected not to die, a quintessential feature of cancer cells. Tumor specific chromosomal translocations that disrupt the architecture of transcription factors are a common theme in carcinogenesis. Increasing evidence gathered over the past fifteen years demonstrate that this type of genomic rearrangements is common not only among pediatric and hematological malignancies, as classically thought, but may also provide a molecular and cytogenetic foundation for an ever-increasing portion of adult epithelial tumors. In this review article we provide evidence that the mechanism of action of oncogenic fusion proteins associated with both pediatric and adult malignancies involves transactivation of the IGF1R gene, with ensuing increases in IGF1R levels and ligand-mediated receptor phosphorylation. Disrupted transcription factors adopt the IGF1R signaling pathway and elicit their oncogenic activities via activation of this critical regulatory network. Combined targeting of oncogenic fusion proteins along with the IGF1R may constitute a promising therapeutic approach.

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Many risk factors can potentially influence sperm quality. Telomeres confer stability on the chromosome and their dysfunction has been implicated in conditions such as cancer, aging, and lifestyle. The impact of lifestyle on sperm cell telomeres is unclear. The objectives of this study were to evaluate the impact of lifestyle behaviors on telomere length in sperm and to follow the correlation with pregnancy outcomes in patients undergoing in vitro fertilization (IVF). In this prospective observational study, sperm was analyzed for telomere length (TL). Men were asked to report lifestyle behaviors including occupation (physical or sedentary), smoking duration and amount, physical activity, dietary habits, and where they keep their cellular phone (bag, pants, or shirt pocket). Correlations among semen analysis, TL, men’s habits, and embryo quality and pregnancy outcomes were evaluated. Among 34 patients recruited, 12 had longer TL and 13 shorter TL. Sperm motility was negatively correlated with TL (Pearson correlation = −.588, p = .002). Smoking adversely affected native sperm motility (53% motility in nonsmokers vs. 37% in smokers; p = .006). However, there was no significant impact on TL. The group with longer telomeres demonstrated significant association with healthy diet (10/12 vs. 6/13; p = .05) and a trend toward more sports activity, weekly (16/84 vs. 7/91; p = .04) compared with the shorter telomeres group. This study suggests that lifestyle, healthy diet, and sports activity are associated with long telomeres in sperm. Sperm quality is also influenced by patients’ habits. The study strongly recommends maintaining a healthy lifestyle to preserve general health and fertility.

The insulin-like growth factors (IGF) are important players in the development of gynecological malignancies, including epithelial ovarian cancer (EOC). The identification of biomarkers that can help in the diagnosis and scoring of EOC patients is of fundamental importance in clinical oncology. We have recently identified the ZYG11A gene as a new candidate target of IGF1 action. The aim of the present study was to evaluate the expression of ZYG11A in EOC patients and to correlate its pattern of expression with histological grade and pathological stage. Furthermore, and in view of previous analyses showing an interplay between ZYG11A, p53 and the IGF1 receptor (IGF1R), we assessed a potential coordinated expression of these proteins in EOC. In addition, zyg11a expression was assessed in ovaries and uteri of growth hormone receptor (GHR) knock-out mice. Tissue microarray analysis was conducted on 36 patients with EOC and expression of ZYG11A, IGF1R and p53 was assessed by immunohistochemistry. Expression levels were correlated with clinical parameters. qPCR was employed to assess zyg11a mRNA levels in mice tissues. Our analyses provide evidence of reduced ZYG11A expression in high grade tumors, consistent with a putative tumor suppressor role. In addition, an inverse correlation between ZYG11A and p53 levels in individual tumors was noticed. Taken together, our data justify further exploration of the role of ZYG11A as a novel biomarker in EOC.

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