Oxytocin and oxytocin receptor alterations,decreased survival,and increased chemoresistance in patients with pancreatic cancer

Background:Oxytocin(OXT)and its receptor(OXTR)is associated with cancer.The present study was to investigate the correlation between the genetic expression alterations of OXT and OXTR and the outcomes in patients with pancreatic cancer(PC).Methods:Information regarding OXT and OXTR genetic alterations and changes in gene expression were retrieved from the Cancer Genome Atlas(TCGA)databases and analyzed using the cBioPortal online tool.We assessed the correlation of overall survival and disease/progression-free months to either OXT or OXTR genetic alterations and changes in gene expression using Kaplan-Meier and Cox regression anal-yses.Quantitative PCR(qPCR)was conducted to assess the mRNA expression levels of OXT and OXTR in human PC cell lines.Results:Five percent of PC cases showed mRNA upregulation in the OXT gene.These PC cases also showed genetic alterations and changes in gene expression of OXTR.The median months of survival and disease-free survival were lower for PC cases with genetic alterations and changes in gene expression in the OXT and OXTR genes as compared to those without such alterations.qPCR data showed that OXT and OXTR mRNA expression were 1-fold and 10-fold higher,respectively in PANC-1 cell lines as compared to L3.6pl cell lines in direct negative correlation with responsiveness to gemcitabine.Conclusions:These data suggest that OXT and OXTR may potentially be important in PC progression,chemoresistance,and patient survival,and potentially could have prognostic and therapeutic implications in a subset of PC patients.

Mechanisms of hepatocellular carcinoma progression

Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.

Emergence of neural regulatory mechanisms in carcinogenesis

Emerging data indicate that the nervous system plays an important role in carcinogenesis. However, more studies are required to help further elucidate the mechanisms involved in the neural regulation of carcinogenesis. Some recent findings describing the neural regulatory mechanisms of action in prostate cancer, pancreatic cancer and hepatocellular carcinoma are discussed, with a focus on the sympathetic, parasympathetic, and sensory neuronal elements of the nervous system. Norepinephrine, which is released by the sympathetic nervous system and binds to the beta-adrenergic receptor, regulates cellular responses in both normal and tumor cells. It has also been shown that the destruction of sensory neurons can prevent or at least slow pancreatic cancer. Cortisol, the main stress hormone, is also discussed and how it could potentially be involved in hepatocellular carcinoma development. The importance of studying other signaling molecules in the nervous system, such as oxytocin and its receptor, the oxytocin receptor, and how they might be involved in carcinogenesis when aberrantly expressed is highlighted. This is an area of study which clearly needs further investigation. A clearer understanding of the detailed mechanisms of how the nervous system is involved in carcinogenesis could potentially aid in the identification of novel biomarkers and development of novel preventative and therapeutic strategies in various cancers.