E. coli Phagelysate: A Primer to Enhance Nanoparticles and Drug Deliveries in Tumor.

The tumor microenvironment (TME), where cancer cells reside, plays a crucial role in cancer progression and metastasis. It maintains an immunosuppressive state in many tumors and regulates the differentiation of precursor monocytes into M1 (anti-tumor)- and M2 (pro-tumor)-polarized macrophages, and greatly reduces anticancer drug and nanoparticle delivery. As a result, the effectiveness of recently developed chemo- and/or nanotechnology-mediated immune and magnetic nanoparticle hyperthermia (mNPH) therapies is inhibited significantly. One of the ways to overcome this limitation is to use E. coli phagelysate as a primer to modify the tumor microenvironment by switching tumor-associated M2 macrophages to anti-tumor M1 macrophages, and initiate the infiltration of tumor-associated macrophages (TAMs). Recently, bacteriophages and phage-induced lysed bacteria (bacterial phagelysates-BPLs) have been shown to be capable of modifying the tumor-associated environment. Phage/BPL-coated proteins tend to elicit strong anti-tumor responses from the innate immune system, prompting phagocytosis and cytokine release. It has also been reported that the microenvironments of bacteriophage- and BPL-treated tumors facilitate the conversion of M2-polarized TAMS to a more M1-polarized (tumoricidal) environment post-phage treatment. This paper demonstrates the feasibility and enhanced efficacy of combining E. coli phagelysate (EcPHL) and mNPH, a promising technology for treating cancers, in a rodent model. Specifically, we illustrate the EcPHL vaccination effect on the TME and mNP distribution in Ehrlich adenocarcinoma tumors by providing the tumor growth dynamics and histology (H&E and Prussian blue) distribution of mNP in tumor and normal tissue.

Urotensin-II As a Promising Key-Point of Cardiovascular Disturbances Sequel.

Arterial hypertension is a highly urgent problem of modern medicine since the crisis of blood pressure control remains open, due to the increasing number of uncontrolled arterial hypertension. Today, one of the most critical problems of cardiology is the study of the mechanisms of development and progression of arterial hypertension. Therefore, our international and multidisciplinary working group presents a vision of a new therapeutic target - urotensin II in the pathogenesis of arterial hypertension. Thus, this article reflects the concept of the Armenian, Georgian and Iranian medical schools.

Local drug delivery system for the treatment of tongue squamous cell carcinoma in rats.

The present study describes a local drug delivery system with two functions, which can suppress tumor growth and accelerate wound healing. Thе system consists of a two-layer multicomponent fibrin-based gel (MCPFTG). The internal layer of MCPFTG, which is in direct contact with the wound surface, contains cisplatin placed on a CultiSpher-S collagen microcarrier. The external layer of MCPFTG consists of a CultiSpher-S microcarrier with lyophilized bone marrow stem cells (BMSCs). The efficacy of MCPFTG was evaluated in a rat model of squamous cell carcinoma of the tongue created with 4-nitroquinoline 1-oxide. The results of the study showed that, within 20-25 days, a non-healing wound of the tongue was formed in animals that underwent only 85% resection of squamous cell carcinoma, while rapid progression of the residual tumor was concomitantly observed. Immunohistochemical methods revealed high expression of cyclin D1 and low expression of E-cadherin in these animals. Additionally, high expression of p63 and Ki-67 was noted. In 80% of animals with squamous cell carcinoma of the tongue that were treated with MCPFTG after 85% tumor resection, a noticeable suppression of tumor growth was evident throughout 150 days, and tumor recurrence was not detected. Immunohistochemistry revealed low or moderate expression of cyclin D1, and high expression of E-cadherin throughout the whole observation period. The MCPFTG-based local drug delivery system was shown to be effective in suppressing tumor growth and preventing recurrence. MCPFTG decreased the toxicity of cisplatin and enhanced its antitumor activity. In addition, lyophilized paracrine BMSC factors present in MCPFTG accelerated wound healing after tumor removal. Thus, the present study suggests novel opportunities for the development of a multifunctional drug delivery system for the treatment of squamous cell carcinoma.