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Imatinib
Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral chemotherapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple receptor tyrosine kinases such as CSF1R, ABL, c-KIT, FLT3, and PDGFR-β. Specifically, it is used for chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL) that are Philadelphia chromosome-positive (Ph+), certain types of gastrointestinal stromal tumors (GIST), hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), systemic mastocytosis, and myelodysplastic syndrome. Common side effects include vomiting, diarrhea, muscle pain, headache, and rash. Severe side effects may include fluid retention, gastrointestinal bleeding, bone marrow suppression, liver problems, and heart failure. Use during pregnancy may result in harm to the baby. Imatinib works by stopping the Bcr-Abl tyrosine-kinase. This can slow grow ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bcr-Abl Tyrosine-kinase Inhibitor
Bcr-Abl tyrosine-kinase inhibitors (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). More than 90% of CML cases are caused by a chromosomal abnormality that results in the formation of a so-called Philadelphia chromosome. This abnormality was discovered by Peter Nowell in 1960 and is a consequence of fusion between the Abelson ( Abl) tyrosine kinase gene at chromosome 9 and the break point cluster ( Bcr) gene at chromosome 22, resulting in a chimeric oncogene ( Bcr-Abl) and a constitutively active Bcr-Abl tyrosine kinase that has been implicated in the pathogenesis of CML. Compounds have been developed to selectively inhibit the tyrosine kinase. Before the 2001 U.S. Food and Drug Administration (FDA) approval of imatinib, no drugs were available to alter the natural progression of CML. Only cytotoxic drugs such as busulfan, hydroxyurea or interferon-alpha (rIFN-α) were utilized. Even though the first Bcr-Abl TK inhibitor was named ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gastrointestinal Stromal Tumor
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs stain positively for KIT (CD117). Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract. Classification GIST was introduced as a diagnostic term in 1983. Until the late 1990s, many non- epithelial tumors of the gastrointestinal tract were called "gastrointestinal stromal tumors". Histopathologists were unable to specifically distinguish among types we now know to be dissimilar molecularly. Subsequently, CD34, and later CD117 were identified as markers that could distinguish the various types. Additionally, in the absence of specific therapy, the diagnostic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chronic Myelogenous Leukemia
Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood. CML is a clonal bone marrow stem cell disorder in which a proliferation of mature granulocytes ( neutrophils, eosinophils and basophils) and their precursors is found. It is a type of myeloproliferative neoplasm associated with a characteristic chromosomal translocation called the Philadelphia chromosome. CML is largely treated with targeted drugs called tyrosine-kinase inhibitors (TKIs) which have led to dramatically improved long-term survival rates since 2001. These drugs have revolutionized treatment of this disease and allow most patients to have a good quality of life when compared to the former chemotherapy drugs. In Western countries, CML accounts for 15–25% of all adult leukemias and 14% o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-locations It is one of the largest pharmaceutical companies in the world. Novartis manufactures the drugs clozapine (Clozaril), diclofenac (Voltaren; sold to GlaxoSmithKline in 2015 deal), carbamazepine (Tegretol), valsartan (Diovan), imatinib mesylate (Gleevec/Glivec), cyclosporine (Neoral/Sandimmune), letrozole (Femara), methylphenidate (Ritalin; production ceased 2020), terbinafine (Lamisil), deferasirox (Exjade), and others. In March 1996, the companies Ciba-Geigy and Sandoz merged to form Novartis; the pharmaceutical and agrochemical divisions of both companies formed Novartis as an independent entity. Other Ciba-Geigy and Sandoz businesses were sold, or, like Ciba Specialty Chemicals, spun off as independent companies. The ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Philadelphia Chromosome
The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in Chromosome 22 (human), chromosome 22 of Leukemia, leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells). This chromosome is defective and unusually short because of Chromosomal translocation, reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 (human), chromosome 9 and chromosome 22, and contains a fusion gene called ''BCR-ABL1''. This gene is the ''ABL (gene), ABL1'' gene of chromosome 9 juxtaposed onto the breakpoint cluster region ''BCR (gene), BCR'' gene of chromosome 22, Gene expression, coding for a hybrid protein: a tyrosine kinase Cell signaling, signaling protein that is "always on", causing the cell to Cell division, divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle. The presence of this translocation is required for diagnosis of CML; in othe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive malignant cutaneous soft-tissue sarcoma. DFSP develops in the connective tissue cells in the middle layer of the skin (dermis). Estimates of the overall occurrence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year. In the United States, DFSP accounts for between 1 and 6 percent of all soft tissue sarcomas and 18 percent of all cutaneous soft tissue sarcomas. In the Surveillance, Epidemiology and End Results (SEER) tumor registry from 1992 through 2004, DFSP was second only to Kaposi sarcoma. Presentation Dermatofibrosarcoma protuberans begins as a minor firm area of skin most commonly about to 1 to 5 cm in diameter. It can resemble a bruise, birthmark, or pimple. It is a slow-growing tumor and is usually found on the torso but can occur anywhere on the body. About 90% of DFSPs are low-grade sarcomas. About 10% are mixed, containing a high-grade sarcomatous component (DFSP-FS ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ABL (gene)
Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ''ABL1'' gene (previous symbol ''ABL'') located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from the Abelson murine leukemia virus. Function The ''ABL1'' proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response such as DNA repair. Activity of ABL1 protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the '' BCR'' and ''ABL1'' genes, leading to a fusion gene present in many cases of chronic myelogenous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
KIT (gene)
Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding different isoforms have been found for this gene. KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit. Function KIT is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of cancer. KIT is a receptor tyrosine kinase type III, which binds to stem cell factor , also known as "steel factor" or "c-kit ligand". When this receptor binds to stem cell factor (SCF) it forms a dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. After ac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDGFR-β
Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the ''PDGFRB'' gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies. Gene The ''PDGFRB'' gene is located on human chromosome 5 at position q32 (designated as 5q32) and contains 25 exons. The gene is flanked by the genes for granulocyte-macrophage colony-stimulating factor and Colony stimulating factor 1 receptor (also termed macrophage-colony stimulating factor receptor), all three of which may be lost together by a single deletional mutation thereby causing development of the 5q-syndrome. Other genetic abnormalities in ''PDGFRB'' lead to various forms of potentially malignant bone marrow disorders: small deletions in and chromosome translocations causing fusions between ''PDGFRB'' and any one of at least 30 genes can cause Myeloproliferative neoplasms that commonly involve eosinophilia, eosinophil-induced organ injury, and possible progression ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acute Lymphocytic Leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li-Fraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme. While many drugs are deactivated by CYP3A4, there are also some drugs which are ''activated'' by the enzyme. Some substances, such as some drugs and furanocoumarins present in grapefruit juice, interfere with the action of CYP3A4. These substances will therefore either amplify or weaken the action of those drugs that are modified by CYP3A4. CYP3A4 is a member of the cytochrome P450 family of oxidizing enzymes. Several other members of this family are also involved in drug metabolism, but CYP3A4 is the most common and the most versatile one. Like all members of this family, it is a hemoprotein, i.e. a protein containing a heme group with an iron atom. In humans, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hypereosinophilic Syndrome
Hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow. HES is a diagnosis of exclusion, after clonal eosinophilia (such as ''FIP1L1-PDGFRA''-fusion induced hypereosinophelia and leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out. There are some associations with chronic eosinophilic leukemia as it shows similar characteristics and genetic defects. Last updated: Updated: Oct 4, 2009 by Venkata Samavedi and Emmanuel C Besa If left untreated, HES is progressive and fatal. It is treated with glucocorticoids such as prednisone. The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids. Signs and symptoms As HES affects many organs ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
