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V600E
V600E is a mutation of the '' BRAF'' gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600. It is a driver mutation in a proportion of certain diagnoses, including melanoma, hairy cell leukemia, papillary thyroid carcinoma, colorectal cancer, non-small-cell lung cancer, Langerhans cell histiocytosis, Erdheim–Chester disease (a non-Langerhans-cell histiocytosis) and ameloblastoma. The mechanism of the mutation is that the negative charge of the acidic glutamic acid residue causes it to be phosphomimetic. This mimics the phosphorylation of the nearby T599 threonine and S602 serine residues in the activation segment of BRAF, which are used to activate the wild type form of the protein. The glutamate residue of the mutant therefore functions to activate BRAF by inhibiting the interaction of the BRAF's glycine rich loop and activation segment, which would ordinarily be inhibitory. The loss of inhibition of BRAF leads to an increase in its basal activity a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRAF (gene)
''BRAF'' is a human gene that encodes a protein called B-Raf. The gene is also referred to as proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B, while the protein is more formally known as serine/threonine-protein kinase B-Raf. The B-Raf protein is involved in sending signal transduction, signals inside cells which are involved in directing cell growth. In 2002, it was shown to be Mutation, mutated in some human cancers. Certain other inherited ''BRAF'' mutations cause birth defects. Drugs that treat cancers driven by ''BRAF'' mutations have been developed. Two of these drugs, vemurafenib and dabrafenib, are approved by FDA for treatment of late-stage melanoma. Vemurafenib was the first approved drug to come out of fragment-based drug discovery. Function B-Raf is a member of the Raf kinase family of growth signal transduction protein kinases. This protein plays a role in regulating the Mitogen-activated protein kinase, MAP kinase/extracellular signal-reg ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Encorafenib
Encorafenib, sold under the brand name Braftovi, is an anti-cancer medication used for the treatment of certain melanoma cancers. It is a small molecule BRAF inhibitor that targets key enzymes in the MAPK signaling pathway. This pathway occurs in many different cancers including melanoma and colorectal cancers. The most common (≥25%) adverse reactions include fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia. Encorafenib was developed by Novartis and Array BioPharma. In June 2018, it was approved by the FDA in combination with binimetinib for the treatment of people with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. Medical uses Encorafenib is indicated in combination with binimetinib, for the treatment of people with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test; in combination with cetuximab, for the treatment of adults with metastatic colorectal cancer w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vemurafenib
Vemurafenib ( INN), sold under the brand name Zelboraf, is a medication used for the treatment of late-stage melanoma.; It is an inhibitor of the B-Raf enzyme and was developed by Plexxikon. Mechanism of action Vemurafenib causes programmed cell death in melanoma cell lines. Vemurafenib interrupts the B-Raf/MEK step on the B-Raf/MEK/ERK pathway − if the B-Raf has the common V600E mutation. Vemurafenib only works in melanoma patients whose cancer has a V600E BRAF mutation (that is, at amino acid position number 600 on the B-Raf protein, the normal valine is replaced by glutamic acid). About 60% of melanomas have this mutation. It also has efficacy against the rarer V600K BRAF (the normal valine is replaced by lysine) mutation. Melanoma cells without these mutations are not inhibited by vemurafenib; the drug paradoxically stimulates normal BRAF and may promote tumor growth in such cases. Resistance Three mechanisms of resistance to vemurafenib (covering 40% of cases) h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ameloblastoma
Ameloblastoma is a rare, benign or cancerous tumor of odontogenic epithelium ( ameloblasts, or outside portion, of the teeth during development) much more commonly appearing in the lower jaw than the upper jaw. It was recognized in 1827 by Cusack. This type of odontogenic neoplasm was designated as an '' adamantinoma'' in 1885 by the French physician Louis-Charles Malassez. It was finally renamed to the modern name ''ameloblastoma'' in 1930 by Ivey and Churchill. While these tumors are rarely malignant or metastatic (that is, they rarely spread to other parts of the body), and progress slowly, the resulting lesions can cause severe abnormalities of the face and jaw leading to severe disfiguration. Additionally, as abnormal cell growth easily infiltrates and destroys surrounding bony tissues, wide surgical excision is required to treat this disorder. If an aggressive tumor is left untreated, it can obstruct the nasal and oral airways making it impossible to breathe without oro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dabrafenib
Dabrafenib, sold under the brand name Tafinlar among others, is an anti-cancer medication used for the treatment of cancers associated with a mutated version of the gene BRAF (gene), BRAF. Dabrafenib acts as an enzyme inhibitor, inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth. The most common side effects include papilloma (warts), headache, nausea, vomiting, hyperkeratosis (thickening and toughening of the skin), hair loss, rash, joint pain, fever and tiredness. When taken in combination with trametinib, the most common side effects include fever, tiredness, nausea, chills, headache, diarrhea, vomiting, joint pain and rash. Dabrafenib was approved for medical use in the United States in May 2013, and in the European Union in August 2013. Medical uses Dabrafenib is indicated as a single agent for the treatment of people with unresectable or metastatic melanoma with BRAF V600E mutation. Dabrafenib is indicated, in combination wit ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Erdheim–Chester Disease
Erdheim–Chester disease (ECD) is an extremely rare disease classified as a non- Langerhans-cell histiocytic neoplasm. In 2016, the World Health Organization (WHO) defined ECD as a slow-growing blood cancer that may originate in the bone marrow or precursor cells. Typical onset occurs in middle aged individuals, although pediatric cases have been documented. The exact cause of ECD remains unknown, though it is believed to be linked to an exaggerated TH1 immune response. The disease involves an infiltration of lipid-laden macrophages, multi-nucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones. Signs and symptoms Erdheim-Chester disease can range from having no symptoms to being fatal, depending on how severe the disease is. It can cause symptoms like bone pain, heart problems, neurological issues, exophthalmos, and constitutional changes in health. Bone pain is the most common symptom, u ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Melanoma
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare cases melanoma can also happen in the lung which is known as primary pulmonary melanoma and only happens in 0.01% of primary lung tumors. In women, melanomas most commonly occur on the legs; while in men, on the back. Melanoma is frequently referred to as malignant melanoma. However, the medical community stresses that there is no such thing as a 'benign melanoma' and recommends that the term 'malignant melanoma' should be avoided as redundant. About 25% of melanomas develop from nevus, moles. Changes in a mole that can indicate melanoma include increaseespecially rapid increasein size, irregular edges, change in color, itchiness, or nevus#Classification, skin breakdown. The primary cause of melanoma is ultraviolet light (UV) exposure in th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hairy Cell Leukemia
Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. The incidence of hairy cell leukemia (HCL) is 0.28-0.30 cases per 100,000 people in Europe and the United States and the prevalence is 3 cases per 100,000 in Europe with a lower prevalence in Asia, Africa and the Middle East. HCL has an indolent course but with frequent relapses, but with treatment life expectancy is usually the same as that for the general population. HCL was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis, and its characterization was significantly advanced by Bertha Bouroncle and colleagues at the Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the cytoplasmic projections from malignant B cells under a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Papillary Thyroid Carcinoma
Papillary thyroid cancer (papillary thyroid carcinoma, PTC) is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases.Chapter 20 in: 8th edition. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-cellular differentiation, differentiated, slow-growing, and localized, although it can metastasis, metastasize. Diagnosis Papillary thyroid carcinoma is usually discovered on routine examination as an asymptomatic thyroid nodule that appears as a neck mass. In some instances, the mass may have produced local symptoms. This mass is normally referred to a Needle aspiration biopsy, fine needle aspiration biopsy (FNA) for investigation. FNA accuracy is very high and it is a process widely used in these cases. Other investigation methods ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Langerhans Cell Histiocytosis
Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes. Symptoms range from isolated bone lesions to multisystem disease. LCH is part of a group of syndromes called histiocytoses, which are characterized by an abnormal proliferation of histiocytes (an archaic term for activated dendritic cells and macrophages). These diseases are related to other forms of abnormal proliferation of white blood cells, such as leukemias and lymphomas. The disease has gone by several names, including Hand–Schüller–Christian disease, Abt-Letterer-Siwe disease, Hashimoto-Pritzker disease (a very rare self-limiting variant seen at birth) and histiocytosis X, until it was renamed in 1985 by the Histiocyte Society. Classification The disease spectrum results from clonal accumulation and proliferation of cells resembling the epidermal dendritic cells called Lang ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication ( translesion synthesis). Mutations may also result from substitution, insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce detectable changes in the observable characteristics ( phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity. Mutati ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form under biological conditions), and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC. Occurrence This compound is one of the proteinogenic amino acids. Only the L- stereoisomer appears naturally in proteins. It is not essential to the human diet, since it is synthesized in the body from other metabolites, including glycine. Serine was first obtained from silk protein, a particularly rich source, in 1865 by Emil Cramer. Its name is derived from the Latin for silk, '' sericum''. Serine's structure was established in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
