Project description:Immunotherapy is revolutionizing tumor treatment by activating the immune response to tumors. Among them, immunotherapy represented by immune checkpoint inhibitors is considered to be a milestone in tumor treatment. It has revolutionized the management of advanced malignant tumors by activating T cells, promoting cytotoxic signaling pathways, and killing tumor cells, effectively improving the overall survival of patients. However, resistance to immunotherapy and immune-related adverse events remain challenges for immunotherapy. It has been demonstrated in previous studies that modulating intestinal microbiota can enhance immunotherapy response and reduce complications. Currently, the more mature method for microbiota regulation is fecal microbiota transplantation, which involves transfering a donor's microbiome to the recipient in the form of capsules or fecal microbiota suspension to restore the richness of the recipient's intestinal microbiota. In terms of cancer immunotherapy, fecal microbiota transplantation in patients who fail to respond to immune checkpoint inhibitors is expected to produce better prognosis for patients.
Project description:Immunotherapy represents the newest pillar in cancer care. Although there are increasing data showing the efficacy of immunotherapy there is a spectrum of response across unselected populations of cancer patients. In fact, response rates can be poor even among patients with immunogenic tumors for reasons that remain poorly understood. A promising clinical strategy to improve outcomes, which is supported by an abundance of preclinical data, is combining immunotherapy with radiation therapy. Here we review the existing evidence and future directions for combining immunotherapy and radiation therapy for patients with gastrointestinal cancers.
Project description:The incidence of cancer has shown a great increase during the past decades and poses tough challenges to cancer treatment. Anti-tumour immunotherapy, represented by immune checkpoint inhibitors (ICIs), possesses favorable remission in unrestricted spectrum of cancer types. However, its efficacy seems to be heterogeneous among accumulating studies. Emerging evidences suggest that gut microbiota can modulate anti-tumour immuno-response and predict clinical prognosis. Therefore, remodeling microbiota characteristics with fecal microbiota transplantation (FMT) may be capable of reinforcing host ICIs performance by regulating immune-tumour cell interactions and altering microbial metabolites, thereby imperceptibly shifting the tumour microenvironment. However, the long-term safety of FMT is under concern, which calls for more rigorous screening. In this review, we examine current experimental and clinical evidences supporting the FMT efficacy in boosting anti-tumour immuno-response and lessening tumour-related complications. Moreover, we discuss the challenges in FMT and propose feasible resolutions, which may offer crucial guidance for future clinical operations.
Project description:Desirable outcomes including rejection- and infection-free kidney transplantation are not guaranteed despite current strategies for immunosuppression and using prophylactic antimicrobial medications. Graft survival depends on factors beyond human leukocyte antigen matching such as the level of immunosuppression, infections, and management of other comorbidities. Risk stratification of transplant patients based on predisposing genetic modifiers and applying precision pharmacotherapy may help improving the transplant outcomes. Unlike certain fields such as oncology in which consistent attempts are being carried out to move away from the "error and trial approach," transplant medicine is lagging behind in implementing personalized immunosuppressive therapy. The need for maintaining a precarious balance between underimmunosuppression and overimmunosuppression coupled with adverse effects of medications calls for a gene-based guidance for precision pharmacotherapy in transplantation. Technologic advances in molecular genetics have led to increased accessibility of genetic tests at a reduced cost and have set the stage for widespread use of gene-based therapies in clinical care. Evidence-based guidelines available for precision pharmacotherapy have been proposed, including guidelines from Clinical Pharmacogenetics Implementation Consortium, the Pharmacogenomics Knowledge Base National Institute of General Medical Sciences of the National Institutes of Health, and the US Food and Drug Administration. In this review, we discuss the implications of pharmacogenetics and potential role for genetic variants-based risk stratification in kidney transplantation. A single score that provides overall genetic risk, a polygenic risk score, can be achieved by combining of allograft rejection/loss-associated variants carried by an individual and integrated into practice after clinical validation.
Project description:Despite significant therapeutic advances, heart failure remains the predominant cause of mortality worldwide. Currently, progenitor/stem cell biology holds great promise for a new era of cell-based therapy for salvaging the failing heart. However, the translational arm of progenitor/stem cell science is in a relatively primitive state. For the time being, the clinical trials have been both encouraging and disappointing. How to improve the engraftment, long-term survival and appropriate differentiation of transplanted progenitor/stem cell within the cardiovascular tissues may be the key issues to facilitate the transition of cardiogenic stem cell research from bench to bedside. In this review article we discuss the state-of-the-art in adult stem cell therapies for cardiovascular diseases and approaches to release cardiac regeneration potentials of progenitor/stem cells.
Project description:Probiotic bacteria have been associated with various health benefits and included in overwhelming number of foods. Today, probiotic supplements are consumed with increasing regularity and record a rapidly growing economic value. With billions of heterogeneous populations of probiotics per serving, probiotic supplements contain the largest quantity of probiotics across all functional foods. They often carry antibiotic-resistant determinants that can be transferred to and accumulate in resident bacteria of the gastrointestinal tract and risk their acquisitions by opportunistic pathogens. While the health benefits of probiotics have been widely publicized, this health risk, however, is underrepresented in both scientific studies and public awareness. On the other hand, the human gut presents conditions that are unfavorable for bacteria, including probiotics. It remains uncertain if probiotics from supplements can tolerate acids and bile salts that may undermine their effectiveness in conferring health benefits. Here, we put into perspective the perceived health benefits and the long-term safety of consuming probiotic supplements, specifically bringing intolerance to acids and bile salts, and the long-standing issue of antibiotic-resistant gene transfer into sharp focus. We report that probiotics from supplements examined in this study have poor tolerance to acids and bile salts while also displaying resistance to multiple antibiotics. They could also adapt and gain resistance to streptomycin in vitro. In an environment where consuming supplements is considered a norm, our results and that of others will put in perspective the persisting concerns surrounding probiotic supplements so that the current hype does not overpower the hope.
Project description:The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variable fragments (scFv) and "third generation" (3G), each representing a successive wave of antibody fragment technology. In parallel, drug developers have explored multi-specificity and conjugation with exogenous functional moieties in all three fragment types. Despite high hopes and an active pipeline, enthusiasm for differentiating performance of fragments should, perhaps, be tempered as there are yet few data that suggest these molecules have distinct clinical properties due only to their size.
Project description:The past 15 years have seen a boom in the use and integration of 'omic' approaches (limited here to genomic, transcriptomic, and epigenomic techniques) to study neurodegenerative disease in an unprecedented way. We first highlight advances in and the limitations of using such approaches in the neurodegenerative disease literature, with a focus on Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). We next discuss how these studies can advance human health in the form of generating leads for downstream mechanistic investigation or yielding polygenic risk scores (PRSs) for prognostication. However, we argue that these approaches constitute a new form of molecular description, analogous to clinical or pathological description, that alone does not hold the key to solving these complex diseases.