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Germinal Center B-cell Like Diffuse Large B-cell Lymphoma
Gene expression profiling has revealed that diffuse large B-cell lymphoma ( DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.Staudt, Louis M, "Center for Cancer Research, Dr. Stoudt Description of Research", Updated 2/20/2009, accessed 1/28/2011 Genetics A gene translocation between chromosome 14 (containing the antibody heavy chain locus) and chromosome 18 (containing the BCL-2 locus) is present in 45% of GCB DLBCLs but has nev ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene Expression Profiling
In the field of molecular biology, gene expression profiling is the measurement of the activity (the expression) of thousands of genes at once, to create a global picture of cellular function. These profiles can, for example, distinguish between cells that are actively dividing, or show how the cells react to a particular treatment. Many experiments of this sort measure an entire genome simultaneously, that is, every gene present in a particular cell. Several transcriptomics technologies can be used to generate the necessary data to analyse. DNA microarrays measure the relative activity of previously identified target genes. Sequence based techniques, like RNA-Seq, provide information on the sequences of genes in addition to their expression level. Background Expression profiling is a logical next step after sequencing a genome: the sequence tells us what the cell could possibly do, while the expression profile tells us what it is actually doing at a point in time. Genes conta ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epratuzumab
Epratuzumab (planned trade name LymphoCide) is a humanized monoclonal antibody. Potential uses may be found in oncology and in treatment of inflammatory autoimmune disorders, such as systemic lupus erythematosus (SLE). Clinical trials A clinical trial for relapsed adult acute lymphoblastic leukemia (ALL) has reported initial results. Results have been published for a phase II trial in untreated follicular lymphoma. Early results from a phase II trial for Diffuse large B-cell lymphoma (DLBCL) were encouraging. The manufacturers in August 2009 announced success in early trials against SLE, and started two Phase III clinical trials. July 2015 : Both phase III trials (EMBODY1/2) for SLE failed to meet their primary endpoint. Mechanism of action Epratuzumab binds to the glycoprotein CD22 of mature and malignant B-cells. Elevated CD22 and other B-cell receptor (BCR) proteins are associated with SLE. "Epratuzumab's mechanism of action transfers these BCR proteins to helper cells ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tamatinib
Fostamatinib, sold under the brand names Tavalisse and Tavlesse, is a tyrosine kinase inhibitor medication for the treatment of chronic immune thrombocytopenia (ITP). The drug is administered by mouth. Fostamatinib blocks the activity of the enzyme spleen tyrosine kinase (SYK). This enzyme is involved in stimulating parts of the immune system. By blocking SYK's activity, fostamatinib reduces the immune system's destruction of platelets, so allowing the platelet count to rise, which reduces the likelihood of excessive bleeding. The most commonly reported side effects are diarrhea, high blood pressure, nausea, respiratory infection, dizziness, increased liver enzymes, rash, abdominal pain, fatigue, chest pain and decreased white blood cell count. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Fostamatinib is a drug used to treat adults with low platelet count due to chronic immune thrombocytopenia (ITP) when a prior tr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fostamatinib
Fostamatinib, sold under the brand names Tavalisse and Tavlesse, is a tyrosine kinase inhibitor medication for the treatment of chronic immune thrombocytopenia (ITP). The drug is administered by mouth. Fostamatinib blocks the activity of the enzyme spleen tyrosine kinase (SYK). This enzyme is involved in stimulating parts of the immune system. By blocking SYK's activity, fostamatinib reduces the immune system's destruction of platelets, so allowing the platelet count to rise, which reduces the likelihood of excessive bleeding. The most commonly reported side effects are diarrhea, high blood pressure, nausea, respiratory infection, dizziness, increased liver enzymes, rash, abdominal pain, fatigue, chest pain and decreased white blood cell count. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Fostamatinib is a drug used to treat adults with low platelet count due to chronic immune thrombocytopenia (ITP) when a prior t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Syk Inhibitor
Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the ''SYK'' gene. Function SYK, along with ZAP70, is a member of the Syk family of tyrosine kinases. These cytoplasmic non-receptor tyrosine kinases share a characteristic dual SH2 domain separated by a linker domain. However, activation of SYK relies less on phosphorylation by Src family kinases than ZAP70. SYK and ZAP70 share a common evolutionary origin and split from a common ancestor in the jawed vertebrates. While Syk and ZAP70 are primarily expressed in hematopoietic tissues, a variety tissues express Syk. Within B and T cells, respectively, Syk and ZAP70 transmit signals from the B-cell receptor and T-cell receptor. Syk plays a similar role in transmitting signals from a variety of cell surface receptors including CD74, Fc receptor, and integrins. Function during development Mice that lack Syk completely (Syk−/−, Syk-knockout) die during embryonic devel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MTOR
The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. In particular, as a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. mTORC2 has also been implicated in the control and maintenance ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Temsirolimus
Temsirolimus, sold under the brand name Torisel, is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in May 2007, and was also approved by the European Medicines Agency (EMA) in November 2007. It is a derivative and prodrug of sirolimus. Mechanism of action Temsirolimus is a specific inhibitor of mTOR and interferes with the synthesis of proteins that regulate proliferation, growth, and survival of tumor cells. Though temsirolimus shows activity on its own, it is also known to be converted to sirolimus (rapamycin) in vivo; therefore, its activity may be more attributed to its metabolite rather than the prodrug itself (despite claims to the contrary by the manufacturer). Treatment with temsirolimus leads to cell cycle arrest in the G1 phase, and also inhibits tumor angiogenesis by reducing synthesis of VEGF. mTOR (mammalian target of rapamycin) is a kinase enzyme ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Everolimus
Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours. It is the 40-''O''-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an inhibitor of mammalian target of rapamycin (mTOR). It is marketed by Novartis under the trade names Zortress (US) and Certican (European Union and other countries) in transplantation medicine, and as Afinitor (general tumours) and Votubia (tumours as a result of Tuberous Sclerosis Complex (TSC)) in oncology. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. Medical uses Everolimus is approved for various conditions: * Advanced kidney cancer (US FDA approved in March 2009) * Prevention of organ rejection after renal transplant(US FDA April 2010) * Subependymal giant cell astrocytoma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MTOR Inhibitor
mTOR inhibitors are a class of drugs that inhibit the mechanistic target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs (rapamycin and its analogs), which have shown tumor responses in clinical trials against various tumor types. History The discovery of mTOR was made a few decades ago while investigating the mechanism of action of its inhibitor, rapamycin. Rapamycin was first discovered in 1975 in a soil sample from Easter Island of South Pacific, also known as Rapa Nui, from where its name is derived. Rapamycin is a macrolide, produced by the microorganism ''Streptomyces hygroscopicus'' and showed antifungal properties. Shortly after its discovery, immunosuppressive ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fenretinide
Fenretinide (''N''-(4-hydroxyphenyl)retinamide; 4-HPR) (INN) is a synthetic retinoid derivative. Retinoids are substances related to vitamin A. It has been investigated for potential use in the treatment of cancer, as well as in the treatment of cystic fibrosis, rheumatoid arthritis, acne, psoriasis, and has been found to also slow the production and accumulation of a toxin that leads to vision loss in Stargardt's patients. In cancer studies, Fenretinide treatment may cause ceramide (a wax-like substance) to build up in tumor cells and is associated with the accumulation of reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen ... (ROS), resulting in cell death through apoptosis and/or necrosis. Fenretinide accumulates preferentially in fatty tissue such as the brea ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Navitoclax
Navitoclax (previously ABT-263) is an experimental orally active anti- cancer drug, which is a Bcl-2 inhibitor similar in action to obatoclax. Mechanism of action Navitoclax inhibits not only Bcl-2, but also Bcl-XL and Bcl-w proteins. Because navitoclax inhibits Bcl-XL, it reduces platelet lifespan, causing thrombocytopenia, and this makes it dose-limiting. Effects against senescent cells In animal studies, navitoclax was found to be a senolytic agent, inducing apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ... in senescent, but not non-senescent cells. Oral administration of ABT263 to either sublethally irradiated or normally aged mice reduced senescent cells, including senescent bone marrow hematopoietic stem cells and senescent muscle stem cells. This depl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ABT-737
ABT-737 is a small molecule drug that inhibits Bcl-2 and Bcl-xL, two members of the Bcl-2 family of evolutionarily-conserved proteins that share Bcl-2 Homology (BH) domains. First developed as a potential cancer chemotherapy, it was subsequently identified as a senolytic (a drug that selectively induces cell death in senescent cells). The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion; Bcl-2 and Bcl-xL are anti-apoptotic proteins. Because many cancers have mutations in these genes that allow them to survive, scientists began working to develop drugs that would inhibit this pathway in the 1990s. ABT-737 was one of the earliest of a series of drugs developed by Abbott Laboratories (now Abbvie) to target this pathway, based on their resolution of the 3D structure of Bcl-xL and studies using high-field solution nuclear magnetic resonance (NMR) that revealed how the BH domains of these proteins interacted ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
