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Imatinib
Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple 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 Water retention (medicine), 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 Bcr-Abl tyrosine-kinase inhibitor, stopp ... [...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 "the mag ... [...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 now known 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 catego ... [...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; characteristic increase in basophils is clinically relevant. 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger class of enzymes known as protein kinases which also attach phosphates to other amino acids such as serine and threonine. Phosphorylation of proteins by kinases is an important mechanism for communicating signals within a cell (signal transduction) and regulating cellular activity, such as cell division. Protein kinases can become mutated, stuck in the "on" position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Therefore, kinase inhibitors, such as imatinib and osimertinib, are often effective cancer treatments. Most tyrosine kinases have an associated protein tyrosine phosphatase, which removes the phosphate group. Reaction Protein kinases are a group of enzymes that possess a ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Philadelphia Chromosome
The Philadelphia chromosome or Philadelphia translocation (Ph) is an abnormal version of chromosome 22 where a part of the ''ABL (gene), Abelson murine leukemia'' 1 (''ABL1'') gene on chromosome 9 breaks off and attaches to the ''BCR (gene), breakpoint cluster region'' (''BCR'') gene in chromosome 22. The balanced reciprocal Translocation (genetics), translocation between the long arms of 9 and 22 chromosomes [t (9; 22) (q34; q11)] results in the fusion gene ''BCR::ABL1''. The Oncogene, oncogenic protein with persistently enhanced tyrosine kinase (TK) activity transcribed by the ''BCR''::''ABL1'' fusion gene can lead to rapid, uncontrolled growth of immature white blood cells that accumulates in the blood and bone marrow. The Philadelphia chromosome is present in the bone marrow cells of a vast majority ''chronic myelogenous leukemia'' (CML) patients. The expression patterns off different BCR-ABL1 transcripts vary during the progression of CML. Each variant is present in a distinct ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
WHO Model List Of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health system. The list is frequently used by countries to help develop their own local lists of essential medicines. , more than 155 countries have created national lists of essential medicines based on the World Health Organization's model list. This includes both Developed country, developed and Developing country, developing countries. The list is divided into core items and complementary items. The core items are deemed to be the most cost-effective options for key health problems and are usable with little additional health care resources. The complementary items either require additional infrastructure such as specially trained health care providers or diagnostic equipment or have a lower cost–benefit ratio. About 25% of items are in the ... [...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. Hypereosinophilic syndrome can manifest in many different ways from nonspecific symptoms and fatigue to neurological impairment and endomyocardial fibrosis, which may be fatal. There are three different variants of hypereosinophilic syndrome, myeloproliferative, lymphocytic, and idiopathic. 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: O ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Novartis
Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by revenue in 2024. 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; produced by Sandoz since 2023), terbinafine (Lamisil), deferasirox (Exjade), and others. Novartis was formed in 1996 by the merger of Ciba-Geigy and Sandoz. It was considered the largest corporate merger in history during that time. The pharmaceutical and agrochemical divisions of both companies formed Novartis as an independent entity. The name Novartis was based on the Latin terms, ''novae artes'' (new skills). After the merger, other Ciba-Geigy and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Targeted Therapy
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy (oncology), hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells (e.g. with traditional chemotherapy). Because most agents for targeted therapy are biopharmaceuticals, the term ''biologic therapy'' is sometimes synonymous with ''targeted therapy'' when used in the context of cancer therapy (and thus distinguished from chemotherapy, that is, cytotoxic therapy). However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy. Another form of targeted therapy involves the use of nanoengineered enzymes to bind to a tumor cell suc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Colony Stimulating Factor 1 Receptor
Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115 (Cluster of Differentiation 115), is a cell-surface protein encoded by the human ''CSF1R'' gene (known also as c-FMS). CSF1R is a Immune receptor, receptor that can be activated by two ligands: Macrophage colony-stimulating factor, colony stimulating factor 1 (CSF-1) and Interleukin 34, interleukin-34 (IL-34). CSF1R is highly expressed in Myeloid tissue, myeloid cells, and CSF1R signaling is necessary for the Cell survival, survival, Cell proliferation, proliferation, and Cell differentiation, differentiation of many myeloid cell types ''in vivo'' and ''in vitro.'' CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and Bone disease, inflammatory bone diseases. Gene In the human genome, the ''CSF1R'' gene is located on chromosome 5 (5q32), and in mice the ''Csf1r'' gene is located on chromosome 18 (18D). ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Systemic Mastocytosis
Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells (also called ''mastocytes'') and CD34+ mast cell precursors. People affected by mastocytosis are susceptible to a variety of symptoms, including itching, hives, and anaphylactic shock, caused by the release of histamine and other pro-inflammatory substances from mast cells. Signs and symptoms When mast cells undergo degranulation, the substances that are released can cause a number of symptoms that can vary over time and can range in intensity from mild to severe. Because mast cells play a role in allergic reactions, the symptoms of mastocytosis often are similar to the symptoms of an allergic reaction. They may include, but are not limited to * Fatigue * Skin lesions ('' urticaria pigmentosa''), itching, and dermatographic ''urticaria'' (skin writing) * "Darier's Sign", a reaction to stroking or scratching of urtic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Kinase Inhibitor
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are typically used as anticancer drugs. For example, they have substantially improved outcomes in chronic myelogenous leukemia. They have also been used to treat other diseases, such as idiopathic pulmonary fibrosis. They are also called tyrphostins, the short name for "tyrosine phosphorylation inhibitor", originally coined in a 1988 publication, which was the first description of compounds inhibiting the catalytic activity of the epidermal growth factor receptor (EGFR). The 1988 study was the first demonstration of a systematic search and discovery of small-molecular-weight inhibitors of tyrosine phosphorylation, which do not inhibit protein kinases that phosphor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
