ABSTRACT
The presence of checkpoint markers in cancer cells aids in immune escape. The identification of checkpoint markers and early cancer markers is of utmost importance to gain clarity regarding the relationship between colitis and progressive inflammation leading to cancer. Herein, the gene expression levels of checkpoint makers, cancer-related pathways, and cancer genes in colon tissues of mouse models of chronic colitis (Winnie and Winnie-Prolapse mice) using next-generation sequencing are determined. Winnie mice are a result of a Muc2 missense mutation. The identification of such genes and their subsequent expression and role at the protein level would enable novel markers for the early diagnosis of cancer in IBD patients. The differentially expressed genes in the colonic transcriptome were analysed based on the Kyoto Encyclopedia of Genes and Genomes pathway. The expression of several oncogenes is associated with the severity of IBD, with Winnie-Prolapse mice expressing a large number of key genes associated with development of cancer. This research presents a number of new targets to evaluate for the development of biomarkers and therapeutics.
ABSTRACT
Immune checkpoints are unique components of the body's defense mechanism that safeguard the body from immune responses that are potent enough to harm healthy body cells. When proteins present on the surface of T cells recognize and bind to the proteins present on other tumor cells, immune checkpoints are triggered. These proteins are called immunological checkpoints. The T cells receive an on/off signal when the checkpoints interact with companion proteins. This might avert the host's immune system from eliminating cancer cells. The standard care plan for the treatment of non-small cell lung cancer (NSCLC) has been revolutionized with the use of drugs targeting immune checkpoints, in particular programmed cell death protein 1. These drugs are now extended for their potential to manage SCLC. However, it is acknowledged that these drugs have specific immune related adverse effects. Herein, we discuss the use of immune checkpoint inhibitors in patients with NSCLC and SCLC, their outcomes, and future perspectives.
ABSTRACT
Inflammatory Bowel Disease (IBD) is a group of diseases that cause intestinal inflammation and lesions because of an abnormal immune response to host gut microflora. Corticosteroids, anti-inflammatories, and antibiotics are often used to reduce non-specific inflammation and relapse rates; however, such treatments are ineffective over time. Patients with chronic colitis are more susceptible to developing colorectal cancer, especially those with a longer duration of colitis. There is often a limit in using chemotherapy due to side effects, leading to reduced efficacy, leaving an urgent need to improve treatments and identify new therapeutic targets. Cancer immunotherapy has made significant advances in recent years and is mainly categorized as cancer vaccines, adoptive cellular immunotherapy, or immune checkpoint blockade therapies. Checkpoint markers are expressed on cancer cells to evade the immune system, and as a result checkpoint inhibitors have transformed cancer treatment in the last 5-10 years. Immune checkpoint inhibitors have produced long-lasting clinical responses in both single and combination therapies. Winnie mice are a viable model of spontaneous chronic colitis with immune responses like human IBD. Determining the expression levels of checkpoint markers in tissues from these mice will provide insights into disease initiation, progression, and cancer. Such information will lead to identification of novel checkpoint markers and the development of treatments with or without immune checkpoint inhibitors or vaccines to slow or stop disease progression.
ABSTRACT
Alzheimer's disease (AD) is a chronic neurodegenerative disorder that falls under the umbrella of dementia and is characterised by the presence of highly neurotoxic amyloid-beta (Aß) plaques and neurofibrillary tangles (NFTs) of tau protein within the brain. Historically, treatments for AD have consisted of medications that can slow the progression of symptoms but not halt or reverse them. The shortcomings of conventional drugs have led to a growing need for novel, effective approaches to the treatment of AD. In recent years, immunotherapies have been at the forefront of these efforts. Briefly, immunotherapies utilise the immune system of the patient to treat a condition, with common immunotherapies for AD consisting of the use of monoclonal antibodies or vaccines. Most of these treatments target the production and deposition of Aß due to its neurotoxicity, but treatments specifically targeting tau protein are being researched as well. These treatments have had great variance in their efficacy and safety, leading to a constant need for the research and development of new safe and effective treatments.
ABSTRACT
The cancer microenvironment, or tumor microenvironment (TME), describes the non-cancerous cells present in the tumor, such as fibroblasts, immune cells, and cells that comprise the blood vessels and proteins produced by all of the cells present in the tumor that support the growth of the cancer cells [...].
