Disruption of RNA Splicing Increases Vulnerability of Cells to DNA-PK Inhibitors.

DNA-dependent protein kinase (DNA-PK) is a key effector of non-homologous end joining (NHEJ)-mediated double-strand break (DSB) repair. Since its identification, a substantial body of evidence has demonstrated that DNA-PK is frequently overexpressed in cancer, plays a critical role in tumor development and progression, and is associated with poor prognosis in cancer patients. Recent studies have also uncovered novel functions of DNA-PK, shifting the paradigm of the role of DNA-PK in oncogenesis and renewing interest in targeting DNA-PK for cancer therapy.

Tumor Cell Communications as Promising Supramolecular Targets for Cancer Chemotherapy: A Possible Strategy.

Fifty-two years have passed since President Nixon launched the "War on Cancer". Despite unparalleled efforts and funds allocated worldwide, the outlined goals were not achieved because cancer treatment approaches such as chemotherapy, radiation therapy, hormonal and targeted therapies have not fully met the expectations. Based on the recent literature, a new direction in cancer therapy can be proposed which targets connections between cancer cells and their microenvironment by chemical means.

Early transcriptomic response of innate immune cells to subcutaneous BCG vaccination of mice.

Objectives: Current data suggests that Bacille Calmette-Guerin (BCG) vaccination contributes to nonspecific enhancement of resistance to various infections. Thus, BCG vaccination induces both specific immunity against mycobacteria and non-specific "trained immunity" against various pathogens. To understand the fundamental mechanisms of "trained" immunity, studies of transcriptome changes occurring during BCG vaccination in innate immunity cells, as well as in their precursors, are necessary.

From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies.

The unprecedented non-reproducibility of the results published in the field of cancer research has recently come under the spotlight. In this short review, we try to highlight some general principles in the organization and evolution of cancerous tumors, which objectively lead to their enormous variability and, consequently, the irreproducibility of the results of their investigation. This heterogeneity is also extremely unfavorable for the effective use of molecularly targeted medicine.

Data Incompleteness May form a Hard-to-Overcome Barrier to Decoding Life's Mechanism.

In this brief review, we attempt to demonstrate that the incompleteness of data, as well as the intrinsic heterogeneity of biological systems, may form very strong and possibly insurmountable barriers for researchers trying to decipher the mechanisms of the functioning of live systems. We illustrate this challenge using the two most studied organisms: , with 34.6% genes lacking experimental evidence of function, and , with identified proteins for approximately 50% of its genes.

SOX9 Protein in Pancreatic Cancer Regulates Multiple Cellular Networks in a Cell-Specific Manner.

SOX9 is upregulated in the majority of pancreatic ductal adenocarcinoma cases. It is hypothesized that the increased expression of SOX9 is necessary for the formation and maintenance of tumor phenotypes in pancreatic cancer cells. In our research, we studied six pancreatic cancer cell lines, which displayed varying levels of differentiation and a range of oncogenic mutations.

The Origin of Genetic Code and Translation in the Framework of Current Concepts on the Origin of Life.

The origin of genetic code and translation system is probably the central and most difficult problem in the investigations on the origin of life and one of the most complex problems in the evolutionary biology in general. There are multiple hypotheses on the emergence and development of existing genetic systems that propose the mechanisms for the origin and early evolution of genetic code, as well as for the emergence of replication and translation. Here, we discuss the most well-known of these hypotheses, although none of them provides a description of the early evolution of genetic systems without gaps and assumptions.

Pancreatic Lineage Specifier PDX1 Increases Adhesion and Decreases Motility of Cancer Cells.

Intercellular interactions involving adhesion factors are key operators in cancer progression. In particular, these factors are responsible for facilitating cell migration and metastasis. Strengthening of adhesion between tumor cells and surrounding cells or extracellular matrix (ECM), may provide a way to inhibit tumor cell migration.

Possibility for Transcriptional Targeting of Cancer-Associated Fibroblasts-Limitations and Opportunities.

Cancer-associated fibroblasts (CAF) are attractive therapeutic targets in the tumor microenvironment. The possibility of using CAFs as a source of therapeutic molecules is a challenging approach in gene therapy. This requires transcriptional targeting of transgene expression by cis-regulatory elements (CRE).

PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma.

In cancer biology, metastasizing is one of the most poorly studied processes. Pancreatic ductal adenocarcinoma (PDAC) is characterized by early metastasis, which is the leading cause of death. The PDX1 protein is crucial for the development of cancer, and its low levels are characteristic of the most aggressive PDAC tumors.