Project description:Neuroblastoma (NB) is the most common pediatric tumor malignancy that originates from the neural crest and accounts for more than 15% of all the childhood deaths from cancer. The neuroblastoma cancer research has long been focused on the role of MYCN oncogene amplification and the contribution of other genetic alterations in the progression of this malignancy. However, it is now widely accepted that, not only tumor cells, but the components of tumor microenvironment (TME), including extracellular matrix, stromal cells and immune cells, also contribute to tumor progression in neuroblastoma. The complexity of different components of tumor stroma and their resemblance with surrounding normal tissues pose huge challenges for therapies targeting tumor microenvironment in NB. Hence, the detailed understanding of the composition of the TME of NB is crucial to improve existing and future potential immunotherapeutic approaches against this childhood cancer. In this review article, I will discuss different components of the TME of NB and the recent advances in the strategies, which are used to target the tumor microenvironment in neuroblastoma.
Project description:Lynch syndrome is one of the most common hereditary cancer syndromes and is characterized by the development of many cancers, such as colorectal cancer (CRC), endometrial cancer, ovarian cancer, stomach cancer and many other cancers. Lynch syndrome is caused by pathogenic germline variants in one of four DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) or by an EPCAM deletion. The MLH1 variant is correlated with the highest risk of CRC, while the MSH2 variant is correlated with the highest risk of other cancers. CRC is the most common cancer type that develops in individuals with Lynch syndrome, followed by endometrial cancer. Recent advances have been made to help us further understand the molecular pathogenesis of this disease and help improve diagnostic testing efficiency and surveillance strategies. Moreover, recent advances in immunotherapy provided by clinical trials also provide clinicians with more chances to better treat Lynch syndrome. This study aims to review many advances in the molecular genetics, clinical features, diagnosis, surveillance and treatment of Lynch syndrome.
Project description:Lung transplantation can improve quality of life and prolong survival for individuals with end-stage lung disease, and many advances in the realms of both basic science and clinical research aspects of lung transplantation have emerged over the past few decades. However, many challenges must yet be overcome to increase post-transplant survival. These include successfully bridging patients to transplant, expanding the lung donor pool, inducing tolerance, and preventing a myriad of post-transplant complications that include primary graft dysfunction, forms of cellular and antibody-mediated rejection, chronic lung allograft dysfunction, and infections. The goal of this manuscript is to review salient recent and evolving advances in the field of lung transplantation.
Project description:The definition of cholangiocarcinoma (CCA) encompasses all tumors originating in the epithelium of the bile ducts, including the intrahepatic bile ducts (ICCA) and extrahepatic bile ducts (ECCA). The incidence of ICCA and ECCA has increased in the last few decades, and molecular advances in both entities have brought understanding of their differences and allowed treatment advances aimed at personalized therapy. In this review, we discuss recent progress in the molecular landscape of CCAs, emerging treatment biomarker-guided strategies, and future insights into the management of advanced disease.
Project description:Alcoholic hepatitis is the severest clinical presentation of alcoholic liver disease. Lacking an effective pharmacologic treatment, alcoholic hepatitis is associated with a poor prognosis and its recovery relies mostly on abstinence. With alcohol use disorder being universally on the rise, the impact of alcoholic hepatitis on society and health-care costs is expected to increase significantly. Prognostic factors and liver biopsy can help with timely diagnosis, to determine eligibility and response to corticosteroids, and for prognostication and transplant referral. Although recent discoveries in the pathophysiology of alcoholic hepatitis are encouraging and could pave the way for novel treatment modalities, a multidisciplinary approach considering timely identification and treatment of liver-related complications, infectious and metabolic disease, malnutrition, and addiction counseling should be emphasized. Apart from proper selection of candidates, transplant programs should provide adequate post-transplant addiction support in order to make of early liver transplantation for alcoholic hepatitis the ultimate sobering experience in the next decade.
Project description:Mercury (Hg) is a highly toxic, non-essential, naturally occurring metal with a variety of uses. Mercury is not required for any known biological process and its presence in the human body may be detrimental, especially to the nervous system. Both genetic and behavioral studies suggest that mercury levels, age (both of exposure and at testing), and genetic background determine disease processes and outcome. The metal receptors and genes responsible for mercury metabolism also appear to play a pivotal role in the etiology of mercury-induced pathology. This review presents information about the latest advances in mercury research, with particular focus on low-level exposures and the contribution of genetics to toxic outcome. Future studies should address the contribution of genetics and low-level mercury exposure to disease, namely gene x environment interactions, taking into consideration age of exposure as developing animals are exquisitely more sensitive to this metal. In addition to recent advances in understanding the pathology associated with mercury exposure, the review highlights transport mechanisms, cellular distribution and detoxification of mercury species in the body.