Biochemical pharmacology of adenylyl cyclases in cancer.

Globally, despite extensive research and pharmacological advancement, cancer remains one of the most common causes of mortality. Understanding the signaling pathways involved in cancer progression is essential for the discovery of new drug targets. The adenylyl cyclase (AC) superfamily comprises glycoproteins that regulate intracellular signaling and convert ATP into cyclic AMP, an important second messenger.

A two-photon responsive hydroxyphenylquinazolinone (HPQ)-based fluorescent organic nanoprodrug for HS release against oxidative stress.

Light-activated HS donors have attracted considerable interest in understanding the physiological role and clinical potential of HS, as their release is highly localized and controlled. Herein, we have evolved a new HPQ chromophore-based fluorescent organic nanosystem localized in a target area that tolerates oxidative stress and precisely releases HS under one- and two-photon irradiation with real-time monitoring capability. The two-photon absorption cross-section of this new phototrigger was calculated to be 283 GM at 720 nm.

TGF-β1 induced autophagy in cancer associated fibroblasts during hypoxia contributes EMT and glycolysis via MCT4 upregulation.

The Transforming growth factor-β1 (TGF- β1) in the tumor microenvironment (TME) is the major cytokine that acts as a mediator of tumor-stroma crosstalk, which in fact has a dual role in either promoting or suppressing tumor development. The cancer-associated fibroblasts (CAFs) are the major cell types in the TME, and the interaction with most of the epithelial cancers is the prime reason for cancer survival. However, the molecular mechanisms, associated with the TGF- β1 induced tumor promotion through tumor-CAF crosstalk are not well understood.

Understanding the function and regulation of Sox2 for its therapeutic potential in breast cancer.

Sox family of transcriptional factors play essential functions in development and are implicated in multiple clinical disorders, including cancer. Sox2 being their most prominent member and performing a critical role in reprogramming differentiated adult cells to an embryonic phenotype is frequently upregulated in multiple cancers. High Sox2 levels are detected in breast tumor tissues and correlate with a worse prognosis.

Screening of the Prime bioactive compounds from Aloe vera as potential anti-proliferative agents targeting DNA.

Background: Aloe vera extract and its bioactive compounds possess anti-proliferative properties against cancer cells. However, no detailed molecular mechanism of action studies has been reported. We have now employed a computational approach to scrutinize the molecular mechanism of lead bioactive compounds from Aloe vera that potentially inhibit DNA synthesis.

The transformation of cancer-associated fibroblasts: Current perspectives on the role of TGF-β in CAF mediated tumor progression and therapeutic resistance.

Over the last few years, the Transforming growth factor- β (TGF-β) has been significantly considered as an effective and ubiquitous mediator of cell growth. The cytokine, TGF-β is being increasingly recognized as the most potent inducer of cancer cell initiation, differentiation, migration as well as progression through both the SMAD-dependent and independent pathways. There is growing evidence that supports the role of secretory cytokine TGF-β as a crucial mediator of tumor-stroma crosstalk.

Active autophagy in cancer-associated fibroblasts: Recent advances in understanding the novel mechanism of tumor progression and therapeutic response.

Autophagy is primarily a homeostatic and catabolic process that is increasingly being recognized to have a pivotal role in the initiation and maintenance of cancer cells, as well as in the emergence of therapeutic resistance. Moreover, in the tumor microenvironment (TME) autophagy plays a crucial and sometimes dichotomous role in tumor progression. Recent studies show that during the early stages of tumor initiation, autophagy suppresses tumorigenesis.

Paracrine TGF-β1 from breast cancer contributes to chemoresistance in cancer associated fibroblasts via upregulation of the p44/42 MAPK signaling pathway.

Conventionally, Cancer-associated fibroblasts (CAFs) are considered as an inducer of chemoresistance in cancer cells. However, the underlying mechanism by which carcinomas induce chemoresistance in CAFs through tumor-stroma cross-talk is largely unknown. Henceforth, we uncovered a network of paracrine signals between carcinoma and CAFs that drives chemoresistance in CAFs.

The emerging roles of exosomes in anti-cancer drug resistance and tumor progression: An insight towards tumor-microenvironment interaction.

The tumor microenvironment (TME) is a complex network of cellular organization consisting of fibroblasts, adipocytes, pericytes, immune cells endothelial cells, and extracellular matrix proteins. Besides communicating with each other, tumor cells are also involved in the tumor stroma interaction. Presently, most of the studies have focused on the contribution of TME in supporting tumor growth through intercellular communication by physical contact between the cells or through paracrine signaling cascades of growth factors and cytokines.

Cancer associated fibroblast mediated chemoresistance: A paradigm shift in understanding the mechanism of tumor progression.

One of the undeniable issues with cancer eradication is the evolution of chemoresistance in due course of treatment, and the mechanisms of chemoresistance have been the subject of extensive research for several years. The efficacy of chemotherapy is hindered by cancer epithelium, mostly in a cell-autonomous mechanism. However, recently the valid experimental evidence showed that the surrounding tumor microenvironment (TME) is equivalently responsible for the induction of chemoresistance.

Real-time monitoring of a photoactivated hydrogen persulfide donor for biological entities.

Hydrogen persulfide (H2S2) plays an important role in sulfur-based redox signaling mechanisms. Herein, we developed a visible light activated ESIPT based H2S2 donor using a p-hydroxyphenacyl phototrigger. The unique feature of the designed H2S2 donor system is the ability to monitor the H2S2 release in real time through a non-invasive fluorescence color change approach, with the color changing from green to blue.

Exosome as a Novel Shuttle for Delivery of Therapeutics across Biological Barriers.

The effective delivery of target-specific siRNA to the brain by exploiting the exosomes derived from dendritic cells renders the paradigm shift for the prospective use of nanosized exosomes as a delivery system. Although the in vivo targeting strategies by other nanovesicles like liposomes exist, still this novel exosome-based delivery approach holds an inclusive dominance of in vivo security and reduced immunogenicity. Achieving promising exosome-based delivery strategies warrants more desirable exploration of their biology.

Photoresponsive Block Copolymer Prodrug Nanoparticles as Delivery Vehicle for Single and Dual Anticancer Drugs.

In recent decades, drug delivery systems (DDSs) based on polymer nanoparticles have been explored due to their potential to deliver drugs with poor water solubility. Some of the limitations of nanoparticle-based DDSs can be overcome by developing an appropriate polymer prodrug. In this work, poly(NIPA)--poly(HMNPPA)--poly(PEGMA--BA) was synthesized using reversible addition fragmentation chain transfer polymerization and Chlorambucil (Cbl), an anticancer drug, was conjugated to the copolymer via 3-(3-(hydroxymethyl)-4-nitrophenoxy)propyl acrylate (HMNPPA) units to prepare the prodrug.

Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo.

Although there is a strong correlation between multinucleated cells (MNCs) and cancer chemo-resistance in variety of cancers, our understanding of how multinucleated cells modulate the tumor micro-environment is limited. We captured multinucleated cells from triple-negative chemo-resistant breast cancers cells in a time frame, where they do not proliferate but rather significantly regulate their micro-environment. We show that oxidatively stressed MNCs induce chemo-resistance in vitro and in vivo by secreting VEGF and MIF.