Nitric Oxide: The Missing Link in Omentum-Induced Metabolic reprogramming of ovarian cancers

A novel metabolic regulatory mechanism of ovarian cancer by omentum adipose-derived stroma cells (O-ASCs) has been discovered. O-ASCs induce survival, migration, and chemoresistance of ovarian cancer cells. However, the underpinning mechanism behind the metabolic modulation was not understood. Here, O-ASCs are shown to promote nitric oxide (NO) homeostasis in ovarian cancers by generating the pool of arginine. Ovarian cancer cells benefit from tumor microenvironment’s elements and expand their growth. In turn, cancer cells modify the elements’ fate to further take advantage of nutrients and resources. A unique combinatory drug treatment is proposed to target O-ASCs-induced chemoresistance of ovarian cancer cells

Modeling of Patient-Derived Xenografts in Colorectal Cancer.

Developing realistic preclinical models using clinical samples that mirror complex tumor biology and behavior are vital to advancing cancer research. While cell line cultures have been helpful in generating preclinical data, the genetic divergence between these and corresponding primary tumors has limited clinical translation. Conversely, patient-derived xenografts (PDX) in colorectal cancer are highly representative of the genetic and phenotypic heterogeneity in the original tumor. Coupled with high-throughput analyses and bioinformatics, these PDXs represent robust preclinical tools for biomarkers, therapeutic target, and drug discovery. Successful PDX engraftment is hypothesized to be related to a series of anecdotal variables namely, tissue source, cancer stage, tumor grade, acquisition strategy, time to implantation, exposure to prior systemic therapy, and genomic heterogeneity of tumors. Although these factors at large can influence practices and patterns related to xenotransplantation, their relative significance in determining the success of establishing PDXs is uncertain. Accordingly, we systematically examined the predictive ability of these factors in establishing PDXs using 90 colorectal cancer patient specimens that were subcutaneously implanted into immunodeficient mice. Fifty (56%) PDXs were successfully established. Multivariate analyses showed tissue acquisition strategy [surgery 72.0% (95% confidence interval (CI): 58.2-82.6) vs. biopsy 35% (95% CI: 22.1%-50.6%)] to be the key determinant for successful PDX engraftment. These findings contrast with current empiricism in generating PDXs and can serve to simplify or liberalize PDX modeling protocols. Better understanding the relative impact of these factors on efficiency of PDX formation will allow for pervasive integration of these models in care of colorectal cancer patients. Mol Cancer Ther; 16(7); 1435-42. ©2017 AACR