Bacterial Proteins and Peptides as Potential Anticancer Agents: A Novel Search for Protein-based Therapeutics.

Tumor diseases remain among the world's primary causes of death despite substantial advances in cancer diagnosis and treatment. The adverse chemotherapy problems and sensitivity towards drugs for some cancer types are among the most promising challenges in modern treatment. Finding new anti-cancer agents and drugs is, therefore, essential. A significant class of biologically active substances and prospective medications against cancer is comprised of bacterial proteins and peptides. Among these bacterial peptides, some of them, such as anti-cancer antibiotics and many toxins like diphtheria are widely being used in the treatment of cancer. In contrast, the remaining bacterial peptides are either in clinical trials or under research in vitro studies. This study includes the most recent information on the characteristics and mechanism of action of the bacterial peptides that have anti-cancer activities, some of which are now being employed in cancer therapy while some are still undergoing research.

Deciphering the Nexus Between Oxidative Stress and Spermatogenesis: A Compendious Overview.

Oxidative stress (OS) and reactive oxygen species (ROS) are one of the main reasons for the multifactorial concern - male infertility. ROS are active components of cellular metabolism that are intrinsic to cellular functioning and are present at minimal and unreactive levels in normal cells. They are an integral component of the sperm developmental physiology, capacitation, and function. As said "anything in excess is poison," so is the case with ROS. These, when produced in excess to the antioxidants present in the seminal plasma, cause multiple malformations during the process of spermatogenesis such as lipid peroxidation, interfere with capacitation, sperm DNA fragmentation and damage to the membrane of the sperm which in turn reduces the motility of the sperm and its ability to fuse with the oocyte. Exposure of spermatozoa to oxidative stress is a major causative agent of male infertility. Thus, a delicate balance between the beneficial and detrimental effects of ROS for proper functions is of utter importance. In this chapter, the influence of ROS in OS which is a key player in male infertility along with the diagnosis, available treatment, and prevention of extensive ROS buildup within the spermatozoa are highlighted.

Antibody-based biosensor to detect oncogenic splicing factor Sam68 for the diagnosis of lung cancer.

OBJECTIVE: The present work aimed to investigate the potential utility of Sam68 protein as a prognostic marker in lung cancer. Then an electrochemical immunosensor is fabricated that is sufficiently sensitive to detect Sam68. RESULTS: Analysis of stage-specific Lung cancer microarray data shows that differential expression of Sam68 is associated with cancer stage and monotonically increases from early tumor stage to advanced metastatic stage. Moreover, the higher expression of Sam68 results in reduced survival of lung cancer patients. Based on these observations, an electrochemical immunosensor was developed for the quantification of Sam68 protein. The target protein was captured by the Anti-Sam68 antibody that was immobilized on the modified Glassy carbon electrode. The stepwise assembly process was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. This fabricated immunosensor displayed good analytical performance in comparison to commercial ELISA kit with good sensitivity, lower detection limit (LOD) of 10.5 pg mL-1, and wide linear detection range from 1 to 5 µg mL-1. This method was validated with satisfactory detection of Sam68 protein in lung adenocarcinoma cell line, NCI-H23. Besides, spike and recovery assay reconfirm that the sensor can precisely quantify Sam68 protein in a complex physiological sample. CONCLUSION: We conclude Sam68 as a valuable prognostic biomarker for early detection of lung cancer. Moreover, we report the first study on the development of an electrochemical immunosensor for the detection of Sam68. The fabricated immunosensor exhibit excellent analytical performance, which can accurately predict the lung cancer patient pathological state.

A comprehensive study on genome-wide coexpression network of KHDRBS1/Sam68 reveals its cancer and patient-specific association.

Human KHDRBS1/Sam68 is an oncogenic splicing factor involved in signal transduction and pre-mRNA splicing. We explored the molecular mechanism of KHDRBS1 to be a prognostic marker in four different cancers. Within specific cancer, including kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), acute myeloid leukemia (LAML), and ovarian cancer (OV), KHDRBS1 expression is heterogeneous and patient specific. In KIRP and LUAD, higher expression of KHDRBS1 affects the patient survival, but not in LAML and OV. Genome-wide coexpression analysis reveals genes and transcripts which are coexpressed with KHDRBS1 in KIRP and LUAD, form the functional modules which are majorly involved in cancer-specific events. However, in case of LAML and OV, such modules are absent. Irrespective of the higher expression of KHDRBS1, the significant divergence of its biological roles and prognostic value is due to its cancer-specific interaction partners and correlation networks. We conclude that rewiring of KHDRBS1 interactions in cancer is directly associated with patient prognosis.

Alternative splicing within the Wnt signaling pathway: role in cancer development.

BACKGROUND: The Wnt signaling cascade plays a fundamental role in embryonic development, adult tissue regeneration, homeostasis and stem cell maintenance. Abnormal Wnt signaling has been found to be prevalent in various human cancers. Also, a role of Wnt signaling in the regulation of alternative splicing of several cancer-related genes has been established. In addition, accumulating evidence suggests the existence of multiple splice isoforms of Wnt signaling cascade components, including Wnt ligands, receptors, components of the destruction complex and transcription activators/suppressors. The presence of multiple Wnt signaling-related isoforms may affect the functionality of the Wnt pathway, including its deregulation in cancer. As such, specific Wnt pathway isoform components may serve as therapeutic targets or as biomarkers for certain human cancers. Here, we review the role of alternative splicing of Wnt signaling components during the onset and progression of cancer. CONCLUSIONS: Splice isoforms of components of the Wnt signaling pathway play distinct roles in cancer development. Isoforms of the same component may function in a tissue- and/or cancer-specific manner. Splice isoform expression analyses along with deregulated Wnt signaling pathway analyses may be of help to design efficient diagnostic and therapeutic strategies.