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Many known chemotherapeutic drugs kill abnormal cells through a process called apoptosis. Bcl-2 proteins are negative regulators of apoptosis that control cell survival and death. Increased expression of anti-apoptotic Bcl-2 proteins commonly occurs in up to 30% of all cancers, providing cancer cells a pro-survival advantage to evade cell death, grow, and proliferate. Drugs targeting these specific anti-apoptotic proteins are potential anti-cancer therapeutics.

In medical diagnostic procedures for examining the cervix and the tissues of the vagina and vulva, long working-distance (-30 cm) lighted binocular microscopes (colposcope) that provide up to 25x optical magnification are used to create an illuminated magnified view. Speculum dilations can give rise to specular reflections from the tissue surface, causing physicians to overlook possible abnormalities – thus decreasing the quality of a colposcopy. 

The tumor protein p53 is a cell cycle regulator. It responds to DNA damage by triggering the DNA repair pathway and allowing cell division to occur or inducing cell growth arrest, cellular senescence, and/or apoptosis. p53 therefore acts as a tumor suppressor by preventing uncontrolled cell division. However, mutations in p53 that impair its cell cycle regulatory functions can induce uncontrolled cell division leading to cancer.

Chronic leg ulcers are a debilitating vasculopathic complication for some patients with sickle cell disease (SCD). Prevalence of leg ulcers varies based on age and geographic location; about 5-10% of all SCD patients may suffer leg ulcers. These leg ulcers are painful, result in infections, hospitalization, disability, and negatively impact the patient’s social and psychological wellbeing on an ongoing basis.

Vaccines against non-viral cancers target mainly differentiation antigens, cancer testis antigens, and overexpressed antigens.  One common feature to these antigens is their presence in central immunological tolerance. Using these vaccines, T cells underwent depletion of high avidity clones directed against such antigens. This depletion can cause the loss of T cells bearing high affinity T cell receptors (TCRs) for their cognate antigens which have superior cytotoxic capacity, longer persistence in the tumor microenvironment, and decreased susceptibility to immune suppression.

The development of an effective HIV vaccine has been an ongoing area of research. High variability in HIV-1 virus strains, however,  represents a major challenge.  Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV.  Two major hurdles to overcome are immunodominance and sequence diversity. Researchers at the National Cancer Institute (NCI) have developed a vaccine that overcomes these major hurdles by utilizing a strategy that identifies conserved regions of the virus and exploits them for use in a targeted therapy.

Inflammatory processes associated with the over-production of tumor necrosis-alpha (TNF-alpha), a potent activator of the immune system accompany numerous neurodegenerative diseases. TNF-alpha has been validated as a drug target with the development of the inhibitors Enbrel and Remicade (fusion antibodies) as prescription medications. Both, however, are large macromolecules that require direct injection and have limited brain access.

Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene are among the most common oncogenic drivers in human cancers, affecting nearly a third of all solid tumors. Point mutations in the KRAS gene most frequently affect amino acid position 12, resulting in the substitution of the native glycine (G) residue for other amino acids (e.g., aspartic acid (D), valine (V), cysteine (C) or arginine (R)).

Mantle cell lymphoma (MCL) is a group of aggressive B-cell lymphomas displaying heterogeneous outcomes after treatment.  Some patients have the slowly progressing disease that does not require immediate treatment, while others have a disease that rapidly progresses despite highly aggressive treatment. A number of prognostic tools have been described to determine whether patients have slow or rapidly progressing diseases, including the mantle cell lymphoma International Prognostic Index (MIPI) and biomarkers, such as KI-67.

Researchers at the National Cancer Institute’s Biopharmaceutical Development Program recently developed massively parallel sequencing methods for virus-derived therapeutics such as viral vaccines and oncolytic immunotherapies.