There is growing awareness that a wide variety of synthetic and natural compounds that may be present in water sources, such as streams, wells, and ground water, may lead to adverse health effects, including increased cancer risk. Even low concentrations of these compounds are of concern, as they may have biological effects at concentrations of parts per billion or less.
Biofilms are complex microbial communities, surface attached and held together by self-produced polymer matrices. These matrices are mainly composed of polysaccharides, secreted proteins and nucleic acids. Poly-N-acetyl glucosamine (PNAG) is a highly conserved surface polysaccharide expressed by a range of bacterial, fungal and protozoan microorganisms.
Despite recent breakthroughs in cancer immunotherapy, T-cell based therapies achieve limited efficacy in solid tumors. Immunosuppression, antigen escape and physical barriers to entry into solid tumors are issues faced. Identifying regulators in T-cell dysfunction remains challenging due to limitations of current screening platforms.
Human leukocyte antigen (HLA) LOH (LOH) is a known resistance mechanism by which cancers evade T cell receptor-(TCR-)based immunotherapies. This class of therapies includes immune checkpoint inhibition (ICI, e.g., Pembrolizumab), engineered TCR (T cell receptor)-T cell adoptive transfer, tumor infiltrating lymphocytes (TIL), T-cell engagers, and other modalities. Dozens of therapies in this category were developed with many in clinical trials. The resistance mechanism noted here, HLA LOH, causes these therapies to fail.
Cell culture investigations using spheroids and organoid models have had a major impact on biomedical advancement as alternative sources for costly, in vivo animal testing. However, these 3-D cell constructs are limited in that they do not integrate extracellular components within the structure important for more reliable and accurate biological responses. Extracellular matrix (ECM) from decellularized tissues provide a physical scaffolding and offers crucial biochemical and biomechanical cues for cellular constituents.
Melanoma is an aggressive form of skin cancer that commonly becomes metastatic, spreading to nearby tissue or other parts of the body, including distant skin or subcutaneous sites such as the lungs, liver, brain, or bone. Metastatic melanoma is very drug resistant and difficult to treat, and therefore, the prognosis for these patients is poor. There is a need for effective therapies for aggressive melanoma and other drug-resistant solid cancers.
The Zbtb7b gene encodes the zinc finger transcription factor ThPOK (also known as cKrox) that promotes CD4 lineage differentiation in immature T cells. CD4+ T cells, also known as “helper” T cells, are critical for long-term immunity against pathogens as well as for promoting CD8+ “effector” T cell and effective B cell responses. ThPOK is needed for the development and functional fitness of CD4+ T cells as well as multiple aspects of the immune response to infection. As such, ThPOK offers a potential target for immune regulation.
Cyclin-dependent kinase inhibitor 2A gene, also known as CDKN2A, is a tumor suppressor gene and is commonly inactivated through somatic mutations in many human cancers. For example, inactivation of CDKN2A is highly prevalent in melanoma, gastrointestinal and pancreatic cancers. Through germline mutations, CDKN2A is associated with predisposition for a variety of cancers, including melanoma and pancreatic cancers. Despite the high frequency of CDKN2A mutations in cancer, there have been no successful therapies targeting these mutations to date.
Topoisomerase 1 (TOP1) is an essential enzyme that plays a critical role in DNA transcription and replication. TOP1 inhibitors are a known class of anti-cancer agents that work to interrupt DNA replication in cancer cells, causing cell death. Since the discovery of the TOP1 inhibitor camptothecin (CPT) from plant extracts more than 60 years ago, two CPT analogs (irinotecan and topotecan) were approved by the FDA for cancer treatment. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme involved in DNA repair created when TOP1 is inhibited.
Human immunodeficiency virus (HIV) remains a major global health challenge despite the advancement made in development of effective antiretrovirals (ARVs). ARVs are effective at limiting replication and spread of the virus, and progression to acquired immuno-deficiency syndrome (AIDS). However, ARVs often lead to emergence of drug-resistant virus strains insensitive to treatment and with toxic effects following long-term usage.