Imatinib
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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 growth or result in p ...
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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 magi ...
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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 categori ...
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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% of leuke ...
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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) ...
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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 urti ...
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Chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms ( palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that block extracellular signals (signal transduction). The development of therapies with specific molecular or genetic targets, wh ...
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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 receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and 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 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). ''CSF1R'' is 60.002 kilobases (kbs) in length. Hematopoietic stem cells express ''CSF1R'' at low levels, but ''CSF1R'' is highly expressed in more diffe ...
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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 and 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 complementary list. Some medicatio ...
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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 Sandoz brand ...
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Kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder. The kidney participates in the control of the volume of various body fluids, fluid osmolality, acid–base balance, various electrolyte concentrations, and removal of toxins. Filtration occurs in the glomerulus: one-fifth of the blood volume that enters the kidneys is filtered. Examples of substances reabsorbed are solute-free water, sodium, bicarbonate, glucose, and amino acids. Examples of substances secreted are hydrogen, ammonium, potassium and uric acid. The nephron is the structural and functional unit of the kidney. Each adult human kidney contains around 1 million nephrons, while a mouse kidney contains on ...
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Malignancy
Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not self-limited in its growth, is capable of invading into adjacent tissues, and may be capable of spreading to distant tissues. A benign tumor has none of those properties. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis. Malignant tumors are also characterized by genome instability, so that cancers, as assessed by whole genome sequencing, frequently have between 10,000 and 100,000 mutations in their entire genomes. Cancers usually show tumour heterogeneity, containing multiple subclones. They also frequently have reduced expression of DNA repair enzymes due to epigenetic methylation of DNA repair genes or altered microRNAs that control DNA repair gene expression. Tumours can be detected through the visual ...
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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 include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ...
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