• Mechanisms of Resistance to Cancer Immunotherapy
    Efforts to harness the immune system for management of cancer were first undertaken in the last 1890s,1 but these therapies were initially disregarded in favor of more consistently effective treatments such as chemotherapy and radiotherapy. Since then, multiple pioneering experiments have advanced understanding of tumor immunobiology and spurred development of cancer immunotherapies,2 several of which have been approved by the US Food and Drug Administration. These immunotherapies shift the focus of cancer treatment away from the tumor itself, and rather toward the patient’s immune system. These therapies may induce the immune system to act directly against the tumor (i.e., checkpoint inhibitors, monoclonal antibodies, adoptive cell transfer, treatment vaccines), or may enhance the body’s anti-cancer immune response (i.e., cytokines).
  • Microtubule-Associated Proteins (MAPs): Life’s Mini Conveyor Belts
    As their name suggests, microtubule-associated proteins (MAPs) are a family of proteins that reversibly interact with microtubules, a critical component of the cellular cytoskeleton. Composed of the protein tubulin, microtubules provide structural support, contribute to cell motility and mitosis, and serve as "conveyor belts" that transport vesicles, organelles, and other cellular components throughout the cytoplasm1. MAPs are a heterogeneous group of proteins that were originally identified in brain extracts based on their ability to co-purify with tubulin2. The "classic" and best-characterized MAPs are the structural proteins that promote tubulin polymerization and stabilize microtubules, and are regulated by phosphorylation3. In addition, the term MAP is also often extended to include enzymatically-active proteins such as the microtubule motors kinesin and dynein that move along microtubules by hydrolyzing ATP.
  • Modern Antibody Applications: Standing on the Shoulders of Giants
    Applications for antibodies in research and medicine have evolved tremendously since antibodies were first described in the late 1800s. The very first Nobel Prize in Physiology or Medicine was awarded in 1901 for work related to antibodies. Since then, the prize has been awarded an additional six times for antibody-related discoveries.
  • Molecular Abnormalities in Breast Cancer
    Sex hormones – estrogen in particular – are strongly implicated in breast cancer. Mutations in a number of genes such as BRCA1/2 that confer risk for the disease are thought to lead to elevated levels of estrogen and progesterone1. Increased exposure to estrogen and progestierone through the use of hormonal birth control is also associated with a higher risk for the disease2. Breast cancers are primarily classified by the presence or absence of estrogen receptor, progesterone receptor, and the non-hormone-related molecule human epidermal growth factor receptor 2 (HER2). Therapies targeting these receptors are among the most common treatments for the disease.
  • Move Over MHC-II, There’s a New LAG-3 Ligand in Town
    Lymphocyte-activation gene 3 (LAG-3), also known as CD223, is a transmembrane protein primarily associated with activated T cells. Functioning as an immune checkpoint protein, LAG-3 effectively inhibits T cell growth and activity.1 As T cells play a key role in fighting infections and cancer, certain tumors may exploit LAG-3's immune checkpoint function for their own benefit. That is, through stimulation of LAG-3, tumors are capable of inhibiting T cell activation and thereby avoiding detection and destruction.1
  • PBRM1 Joins p53 To Impact Kidney Cancer
    p53 is a well-known tumor suppressor protein which suppresses cancer by regulating the cell cycle. It is encoded by the gene, TP53. A key component of p53’s suppressor activity is modulated through post-translational modifications, namely acetylation. Acetylation patterns of p53 help determine the protein’s function. These acetylation patterns can be "written," "erased," and "read." "Writing" refers to the addition of acetyl groups by enzymes like histone acetyltransferases, and "Erasing" refers to the removal of acetyl groups by enzymes like histone deacetylases. "Readers" recognize and bind to the acetyl groups on the p53 protein and can inhibit or enhance p53 transcription.
  • Pancreatic Cancer Treatments: The Promise of Signal Transduction Pathways
    Successfully treating pancreatic cancer represents one of the biggest challenges in oncology to date. Pancreatic cancer has the lowest five-year survival rate of all cancers1; equivalent incidence and mortality rates2; and an underwhelming response to all widely available treatments, including surgical resection3,4. The poor prognosis of pancreatic cancer highlights the need to identify additional therapeutic targets in order to produce more efficacious therapies. To this end, signal transduction cascades associated with pancreatic cancer cells are an area of intense research that has much promise5,6.
  • Programmed Cell Death-1 (PD-1)
    Programmed cell death-1 (PD-1) is an immune checkpoint molecule that belongs to the CD28 family, which also includes CTLA-4. PD-1 is expressed on T cells and functions as a negative regulator of helper and effector T cell activity. Its ligands, PD-L1 and PD-L2, are members of the B7 family and are expressed by antigen presenting cells as well as tissue type-specific cells throughout the body and cancer cells. Binding of PD-1 to its ligands activates an intracellular signaling cascade that results in the dephosphorylation of the T cell receptor or of CD281, and the consequent reduction in T cell activity. In healthy individuals, this pathway tunes the immune system to protect against autoimmunity by suppressing effector T cells and promoting the activity of regulatory T cells (Tregs)2, 3.
  • Prostate Cancer Detection
    Prostate cancer is the most frequently diagnosed cancer in American and European men1-2, and with almost 30,000 deaths in 2010, it is also one of the leading cancer killers3. The current primary clinical tests for prostate cancer screening are the digital rectal exam and the prostate specific antigen (PSA) blood serum test. PSA, also known as kallikrein gene 3, is a serine protease produced exclusively by prostate cells that is elevated in response to cancer. However, PSA levels can also rise due to several other factors such as age and benign conditions that produce an enlarged prostate, and therefore the utility of PSA for the detection of prostate cancer is controversial4.
  • Protein–Nucleic Acid Interactions
    Protein and nucleic acid interactions are vital to cellular processes. Proteins associate with nucleic acids to mediate transcription and translation of DNA and RNA to decode the information carried by genetic material. In addition, protein–nucleic acid interactions are required to maintain the integrity of DNA and RNA throughout generations. To do so, proteins interact with nucleic acids in processes such as DNA replication, repair and processing, as well as RNA processing and translocation.
  • Ran Proteins in Health and Disease
    Ras-related nuclear protein (Ran), a member of the Ras superfamily of small GTPases, plays a critical role in the transport of macromolecules between the nucleus and the cytoplasm that occurs through nuclear pores. More recently, research has shown that Ran participates in the coordination of mitosis, with specific roles in mitotic spindle assembly, centrosome duplication, microtubule dynamics, and chromosome alignment.1
  • Role of Kinesin Molecular Motor Proteins in Cancer
    Kinesin superfamily proteins, or KIFs, are microtubule-dependent molecular motors whose movement is critical to a variety of cellular processes including mitosis, meiosis, and axonal transport. So far, 45 KIF genes grouped into 15 families have been identified, and at least twice as many proteins are thought to exist due to alternative splicing1. KIFs transport cargo along microtubules much like a train moves along a rail, using the energy generated from the hydrolysis of ATP to drive conformational changes that produce motility2.
  • Introducing the Bethyl Laboratories SARS-CoV-2 IgG and IgM ELISA Kits
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, first emerged in late 2019. As the public health and economic impacts of COVID-19 continue worldwide, the need for appropriate antibody tests is increasing. In contrast to diagnostic tests which detect the virus itself, antibody tests assess immune response to SARS-CoV-2 infection via detection of antibodies in blood or serum. Such tests are valuable for understanding the infection and true mortality rates and subsequently informing public health policies aimed at containing the virus.
  • TIM-3 for a Change

    The Resistance

    Immune-checkpoint inhibitors is a popular topic of current discussion within the realm of tumor therapeutics. Most notably cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1) have garnered the most attention. The first immune checkpoint inhibitor associated with overall survival within a phase 3 metastatic melanoma study, Ipilimumab, is a fully humanized antibody against cytotoxic T-lymphocyte–associate-d antigen 4 (CTLA-4) antibody.1,2 Blockade of PD-1 has achieved revolutionary clinical impact in many solid cancers; however, there has been certain roadblocks which have prevented full response to anti-PD-1 therapy.3-5 A significant percentage of cancer patients fail to respond to these therapies due to compensatory immune inhibitory pathways.6
  • Targeting Both T and NK Cells via TIGIT
    Immune checkpoints play a central role in regulating the magnitude and duration of an immune response. When functioning properly, immune checkpoints ensure appropriate response to insults such as infection or malignancy, while also preventing harm to the host from excessive immune reaction. Importantly, dysregulation of immune checkpoints by malignant cells can promote their growth and expansion.1