Integrating Systems Biology and an Ex Vivo Human Tumor Model Elucidates PD-1 Blockade Response Dynamics.

Ex vivo human tumor models have emerged as promising, yet complex tools to study cancer immunotherapy response dynamics. Here, we present a strategy that integrates empirical data from an ex vivo human system with computational models to interpret the response dynamics of a clinically prescribed PD-1 inhibitor, nivolumab, in head and neck squamous cell carcinoma (HNSCC) biopsies (N = 50). Using biological assays, we show that drug-induced variance stratifies samples by T helper type 1 (Th1)-related pathways.

Activation of Epithelial-Mesenchymal Transition and Altered β-Catenin Signaling in a Novel Indian Colorectal Carcinoma Cell Line.

Colorectal cancer is the third major cause of cancer-related mortality worldwide. The upward trend in incidence and mortality rates, poor sensitivity to conventional therapies and a dearth of early diagnostic parameters pose a huge challenge in the management of colorectal cancer in India. Due to the high level of genetic diversity present in the Indian population, unraveling the genetic contributions toward pathogenesis is key for understanding the etiology of colorectal cancer and in reversing this trend.

Inhibition of rapamycin-induced AKT activation elicits differential antitumor response in head and neck cancers.

The PI3K/AKT/mTOR pathway is an important signaling axis that is perturbed in majority of cancers. Biomarkers such as pS6RP, GLUT1, and tumor FDG uptake are being evaluated in patient stratification for mTOR pathway inhibitors. In the absence of a clear understanding of the underlying mechanisms in tumor signaling, the biomarker strategy for patient stratification is of limited use.

Cathepsins B and L in peripheral blood mononuclear cells of pediatric acute myeloid leukemia: potential poor prognostic markers.

The diagnostic and prognostic significance of cathepsin B (CTSB) and L (CTSL) is well documented for solid tumors. However, their significance in acute leukemias is lacking. This study was planned to investigate expression and significance of these proteases in peripheral blood mononuclear cells (PBMCs) of patients with pediatric acute myeloid leukemia (AML).

Ets-1/Elk-1 is a critical mediator of dipeptidyl-peptidase III transcription in human glioblastoma cells.

Dipetidyl-peptidase III is a metallopeptidase involved in a number of physiological processes and its expression has been reported to increase with the histological aggressiveness of human ovarian primary carcinomas. Because no information regarding the regulation of its expression was available, experiments were designed to clone, define and characterize the promoter region of the human dipeptidyl-peptidase III (DPP-III) gene. In this study, we cloned a 1038 bp 5'-flanking DNA fragment of the human DPP-III gene for the first time and demonstrated strong promoter activity in this region.