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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 and ... [...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 signals inside cells which are involved in directing cell growth. In 2002, it was shown to be 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 Vemurafenib (INN, marketed as Zelboraf) is an inhibitor of the B-Raf enzyme developed by Plexxikon (now part of Daiichi-Sankyo) and Genentech for the treatment of late-stage melanoma.; The name "vemurafenib" comes from V600E mutated BRAF in ... 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. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vemurafenib
Vemurafenib (INN, marketed as Zelboraf) is an inhibitor of the B-Raf enzyme developed by Plexxikon (now part of Daiichi-Sankyo) and Genentech for the treatment of late-stage melanoma.; The name "vemurafenib" comes from V600E mutated BRAF inhibition. Approvals Vemurafenib received FDA approval for the treatment of late-stage melanoma on August 17, 2011, making it the first drug designed using fragment-based lead discovery to gain regulatory approval. Vemurafenib later received Health Canada approval on February 15, 2012. On February 20, 2012, the European Commission approved vemurafenib as a monotherapy for the treatment of adult patients with BRAF V600E mutation positive unresectable or metastatic melanoma, the most aggressive form of skin cancer. On November 6, 2017, the FDA approved Vemurafenib for the treatment of some patients with Erdheim–Chester disease (ECD), a rare type of histiocytic neoplasm. Mechanism of action Vemurafenib causes programmed cell death in m ... [...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 oropharyng ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In women, they most commonly occur on the legs, while in men, they most commonly occur on the back. About 25% of melanomas develop from moles. Changes in a mole that can indicate melanoma include an increase in size, irregular edges, change in color, itchiness, or skin breakdown. The primary cause of melanoma is ultraviolet light (UV) exposure in those with low levels of the skin pigment melanin. The UV light may be from the sun or other sources, such as tanning devices. Those with many moles, a history of affected family members, and poor immune function are at greater risk. A number of rare genetic conditions, such as xeroderma pigmentosum, also increase the risk. Diagnosis is by biopsy and analysis of any skin lesion ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dabrafenib
Dabrafenib, sold under the brand name Tafinlar & Rafinlar ( both by Novartis) among others, is a medication for the treatment of cancers associated with a mutated version of the gene BRAF. Dabrafenib acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth. Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF (V600)-mutated metastatic melanoma. Approvals and indications The US Food and Drug Administration initially approved dabrafenib as a single agent treatment for patients with BRAF V600E mutation-positive advanced melanoma on May 29, 2013. Dabrafenib was approved for use in the European Union in August 2013. Clinical trial data demonstrated that resistance to dabrafenib and other BRAF inhibitors occurs within six to seven months. To overcome this resistance, the BRAF inhibitor dabrafenib was combined with the MEK inhibitor trametinib. On January 8, 2014, the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Encorafenib
Encorafenib, sold under the brand name Braftovi, is a medication 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 substance was being developed by Novartis and then by Array BioPharma. In June 2018, it was approved by the FDA in combination with binimetinib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. The most common (≥25%) adverse reactions include fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia. Pharmacology Encorafenib acts as an ATP-competitive RAF kinase inhibitor, decreasing ERK phosphorylation and down-regulation of CyclinD1. This arrests the cell cycle in G1 phase, inducing senescence without apoptosis. Therefore, it is only effective in melanomas with a BRAF mutation, which make up 50% of all me ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Papillary Thyroid Carcinoma
Papillary thyroid cancer or papillary thyroid carcinoma 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 inclu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Erdheim–Chester Disease
Erdheim–Chester disease (ECD) is an extremely rare disease characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages (technically, this disease is termed a non- Langerhans-cell histiocytosis). It was declared a histiocytic neoplasm by the World Health Organization in 2016. Onset typically is in middle age, although younger patients have been documented. The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones. Signs and symptoms Long bone involvement is almost universal in ECD patients and is bilateral and symmetrical in nature. More than 50% of cases have some sort of extraskeletal involvement. This can include kidney, skin, brain and lung involvement, and less frequently retroorbital tissue, pituitary gland and heart involvement is observed. Bone pa ... [...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. It is usually classified as a subtype of chronic lymphocytic leukemia (CLL). Hairy cell leukemia makes up about 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined. Hairy cell leukemia (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 malignant B cells under a microscope. Signs and symptoms In HCL, the "hairy cells" (malignant B lymphocytes) accumulate in the bone marrow, interfering with the production of ... [...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 Langerhan ... [...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 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. Mutation is the ultimate source o ... [...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 naturally occurring 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 estab ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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