Activity

The immune system is a potent defense mechanism regulating tumor development and progression. However, immune cells are often functionally compromised in cancer patients, and tumor rejection does not follow successful induction of a CTL response. This is, in part, due to the existing conflict between the tumor system and an unfavorable tumor microenvironment (TME) that is able to neutralize or paralyze the immune system of the host. The recent advances in the field of immune checkpoint inhibitors have changed the focus from targeting the tumor to targeting T lymphocytes. It has been well established that the TME and associated multiple factors contribute to the failures in cancer therapies, including immunotherapy. In this regard, hypoxia, which is a hallmark of solid tumors, is strongly associated with advanced disease stages and poor clinical outcomes. Hypoxia plays a crucial role in tumor promotion and immune escape by conferring tumor resistance, immunosuppression, and tumor heterogeneity, which contributtoxicity. Exploiting hypoxia-associated tumor escape capacities may hold promise for attenuating tumor heterogeneity and plasticity, overcoming alteration of antitumor cytotoxic response and improving its effectiveness in cancer patients.T lymphocytes undergo carefully orchestrated programming during development in the thymus and subsequently during differentiation in the periphery. This intricate specification allows for cell-type and context-specific transcriptional programs that regulate immune responses to infection and malignancy. Epigenetic changes, including histone modifications and covalent modification of DNA itself through DNA methylation, are now recognized to play a critical role in these cell-fate decisions. DNA methylation is mediated primarily by the actions of the DNA methyltransferase (DNMT) and ten-eleven-translocation (TET) families of epigenetic enzymes. In this review, we discuss the role of DNA methylation and its enzymatic regulators in directing the development and differentiation of CD4+ and CD8+ T-cells.We have previously demonstrated that natural killer (NK) cells are the main immune effectors that can mediate selection and differentiation of different cancer stem cells and undifferentiated tumors via lysis and secreted or membrane-bound interferon-γ and tumor necrosis factor-α, respectively. This leads to growth inhibition and tumor metastasis curtailment. In this review, we present an overview of our findings on NK cell biology and its significance in selection and differentiation of stem-like tumors using in vitro and in vivo studies conducted in nonobese diabetic/severe combined immunodeficiency (scid)/interleukin-Rγ–, humanized-bone-marrow/liver/thymus (hu-BLT) mice, and those of human cancer patients. Moreover, we present recent advances in NK cell expansion and therapeutic delivery and discuss the superiority of allogeneic supercharged NK cells over their autologous counterparts for cancer treatment. We review potential loss of NK cell numbers and function at neoplastic and preneoplastic stages of tumorigenesis as a potential mechanism for pancreatic cancer induction and progression. We believe that NK cells should be placed highly in the armamentarium of tumor immunotherapy due to their indispensable role in targeting cancer stem-like/poorly differentiated tumors and a variety of other key NK cell functions that are discussed in this report, including their role in CD8+ T-cell expansion and targeting gene knockout or dedifferentiated tumors. The combination of allogeneic supercharged NK cells and other immunotherapeutic strategies such as oncolytic viruses, antibody-dependent cellular cytotoxicity-inducing antibodies, checkpoint inhibitors, chimeric antigen receptor (CAR)-T cells and CAR-NK cells, chemotherapeutics, and radiotherapeutic strategies can be used for optimal eradication of tumors.

The study of the effects of simulated microgravity on primary cultures of human satellite cells represents a reliable model for identifying the biomolecular processes involved in mechanic load-related muscle mass loss. Therefore, this study aims to investigate the role of myostatin and Bone Morphogenetic Protein-2 in human satellite cells response to simulated microgravity condition.

In order to identify the main molecules involved in the phenomena of degeneration/regeneration of muscle tissue related to the alteration of mechanic load, we performed a morphological and immunohistochemical study on 27 muscle biopsies taken from control, osteoporotic and osteoarthritic patients, underwent hip arthroplasty. For each patient, we set up primary satellite cell cultures subjected to normogravity and simulated microgravity (110h) regimens. Cellular functionality has been studied through a morphological evaluation performed by optical microscopy, and an ultrastructural evaluation carried out by transmission electrsimulated microgravity, confirming the importance of Bone Morphogenetic Protein-2 and myostatin in the physio-pathogenesis of muscle tissue. In addition, these data can lay the foundation for new therapeutic approached in the prevention/cure of osteoporosis and sarcopenia.

The results obtained allowed us to hypothesize a possible molecular mechanism of response to simulated microgravity, confirming the importance of Bone Morphogenetic Protein-2 and myostatin in the physio-pathogenesis of muscle tissue. In addition, these data can lay the foundation for new therapeutic approached in the prevention/cure of osteoporosis and sarcopenia.Home dialysis, and mainly peritoneal dialysis, is indicated as the optimal choice as far as the comfort and lifestyle of uremic patients is concerned. Despite this, home treatments show a lack of growth. The reasons are mainly linked to the patients’ cognitive, psychosocial, familiar and physical barriers due to aging and morbidity. To overcome these barriers, we analyzed all the available institutional aids civil disability, not-self-sufficiency funds, home, social and nursing assistance, expenses refunds. The assessment of the patients’ needs is performed through validated instruments such as multidimensional evaluation (VMD) and equivalent economic index (ISEE). Overall, economic relief is limited to low income patients, and those in serious distress. Some Italian regions have issued specific measures dedicated to home dialysis. Angiogenesis inhibitor Our review shows a great heterogeneity of measures, centered in some cases on economic aids and on home assistance in others. Moreover, some Italian dialysis centers directly provide caregivers for home dialysis.