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MEN1
Menin is a protein that in humans is encoded by the ''MEN1'' gene. Menin is a putative tumor suppressor associated with multiple endocrine neoplasia type 1 (MEN-1 syndrome) and has autosomal dominant inheritance. Variations in the MEN1 gene can cause pituitary adenomas, hyperparathyroidism, pancreatic neuroendocrine tumors, gastrinoma, and adrenocortical cancers. ''In vitro'' studies have shown that menin is localized to the nucleus, possesses two functional nuclear localization signals, and inhibits transcriptional activation by JunD. However, the function of this protein is not known. Two messages have been detected on northern blots but the larger message has not been characterized. Two variants of the shorter transcript have been identified where alternative splicing affects the coding sequence. Five variants where alternative splicing takes place in the 5' UTR have also been identified. History In 1988, researchers at Uppsala University Hospital and the Karolinska I ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Multiple Endocrine Neoplasia Type 1
Multiple endocrine neoplasia type 1 (MEN-1 aka Wermer Syndrome) is one of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas. Individuals suffering from this disorder are prone to developing multiple endocrine and nonendocrine tumors. It was first described by Paul Wermer in 1954. Signs and symptoms Parathyroid Hyperparathyroidism is present in ≥ 90% of patients. Asymptomatic hypercalcemia is the most common manifestation: about 25% of patients have evidence of nephrolithiasis or nephrocalcinosis. In contrast to sporadic cases of hyperparathyroidism, diffuse hyperplasia or multiple adenomas are more common than solitary adenomas. Pancreas Pancreatic islet cell tumors are today the major cause of death in persons with MEN-1. Tumors occur in 60-80% of persons with MEN-1 and they are usually multicentric. Multiple adenomas or diffuse islet cell hyperpla ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Revumenib
Revumenib, sold under the brand name Revuforj, is an anti-cancer medication used for the treatment of acute leukemias harboring lysine methyltransferase 2A gene (KMT2A) rearrangements. It is designed to disrupt the interaction between menin and KMT2A (also known as MLL), which plays a role in the pathogenesis of these leukemias. It is taken by mouth. The most common adverse reactions include hemorrhage, nausea, increased phosphate, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, increased alanine aminotransferase, increased intact parathyroid hormone, bacterial infection, diarrhea, differentiation syndrome, electrocardiogram QT prolonged, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, fatigue, and increased alkaline phosphatase. Revumenib was approved for medical use in the United States in November 2024. The US Food and Drug Administration (FDA) conside ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Knudson Hypothesis
The two-hit hypothesis, also known as the Knudson hypothesis, is the hypothesis that most tumor suppressor genes require both alleles to be inactivated, either through mutations or through epigenetic silencing, to cause a phenotypic change. It was first formulated by Alfred G. Knudson in 1971 and led indirectly to the identification of tumor suppressor genes. Knudson won the 1998 Albert Lasker Clinical Medical Research Award for this work. Knudson performed a statistical analysis on cases of retinoblastoma, a malignant tumor of the retina that occurs both as an inherited disease and sporadically. He noted that inherited retinoblastoma occurs at a younger age than the sporadic disease. In addition, the children with inherited retinoblastoma often developed the tumor in both eyes, suggesting an underlying predisposition. Knudson suggested that two "hits" to DNA were necessary to cause the cancer. In the children with inherited retinoblastoma, the first mutation in what later ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Zollinger–Ellison Syndrome
Zollinger–Ellison syndrome (Z-E syndrome) is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea. The syndrome is caused by the formation of a gastrinoma, a neuroendocrine tumor that secretes a hormone called gastrin. High levels of gastrin in the blood (hypergastrinemia) trigger the parietal cells of the stomach to release excess gastric acid. The excess gastric acid causes peptic ulcer disease and distal ulcers. Gastrinomas most commonly arise in the duodenum, pancreas or stomach. In 75% of cases, Zollinger–Ellison syndrome occurs sporadically, while the remaining 25% of cases are due to an autosomal dominant syndrome called multiple endocrine neoplasia type 1 (MEN 1). Signs and symptoms Patients with Zollinger–Ellison syndrome may experience abdominal pain and diarrhea. If left untreated, the condition could result in severe gastroesophageal reflux disease (GERD) and refractory pe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MEN2A
Multiple endocrine neoplasia type 2 (also known as "Pheochromocytoma (codons 630 and 634) and amyloid producing medullary thyroid carcinoma", "PTC syndrome," and "Sipple syndrome") is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer). They generally occur in endocrine organs (e.g. thyroid, parathyroid, and Adrenal gland, adrenals), but may also occur in endocrine tissues of organs not classically thought of as endocrine. MEN2 is a sub-type of MEN (multiple endocrine neoplasia) and itself has sub-types, as discussed below. Variants in MEN2A have been associated with Hirschsprung disease. Screening for this condition can begin as young as eight years old for pheochromocytoma. Signs and symptoms MEN2 can present with a sign or symptom related to a tumor or, in the case of multiple endocrine neoplasia type 2b, with characteristic musculoskeletal and/or lip and/or gastrointestinal findings. Medullary thyroid car ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chromosome 11
Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the total DNA in cells. The shorter arm (p arm) is termed 11p while the longer arm (q arm) is 11q. At about 21.5 genes per megabase, chromosome 11 is one of the most gene-rich, and disease-rich, chromosomes in the human genome. More than 40% of the 856 olfactory receptor genes in the human genome are located in 28 single-gene and multi-gene clusters along the chromosome. Gene Number of genes The following are some of the gene count estimates of human chromosome 11. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies (for technical details, see gene prediction). Among various projects, the collaborative consensus coding sequence project ( CCDS) takes an extremely ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Icovamenib
Icovamenib is an investigational irreversible covalent inhibitor of menin. It is developed by Biomea Fusion for diabetes, lymphoma, leukemia, and multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone .... References {{reflist Covalent inhibitors 4-Morpholinyl compounds Pyrrolopyrimidines Disubstituted pyridines Piperidines Acrylamides Carboxamides ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzomenib
Enzomenib is an investigational new drug that is being evaluated for the treatment of acute leukemia. It is a small molecule inhibitor that targets the interaction between menin and mixed-lineage leukemia (MLL) proteins. Enzomenib particularly in patients with KMT2A (MLL) rearrangements or NPM1 mutations. The U.S. Food and Drug Administration (FDA) has granted both Fast Track and Orphan Drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ... designations to Enzomenib. References {{antineoplastic-drug-stub Alkenes Antineoplastic drugs Azetidines Benzamides Carboxamides Ethers Fluorobenzenes Isopropylamino compounds Piperidines Pyrimidines Spiro compounds ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nonsense Mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a ''nonsense codon'', or a premature stop codon in the transcribed mRNA, and leads to a truncated, incomplete, and possibly nonfunctional protein product. Nonsense mutations are not always harmful; the functional effect of a nonsense mutation depends on many aspects, such as the location of the stop codon within the coding DNA. For example, the effect of a nonsense mutation depends on the proximity of the nonsense mutation to the original stop codon, and the degree to which functional subdomains of the protein are affected. As nonsense mutations leads to premature termination of polypeptide chains; they are also called chain termination mutations. Missense mutations differ from nonsense mutations since they are point mutations that exhibit a single nucleotide change to cause substitution of a different amino acid. A nonsense mutation also differs from a nonstop mutation, which is a point muta ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tumor Suppressor Gene
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The Loss-of-function mutation, loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes. TSGs can be grouped into the following categories: caretaker genes, gatekeeper genes, and more recently landscaper genes. Caretaker genes ensure stability of the genome via DNA repair and subsequently when mutated allow mutations to accumulate. Meanwhile, gatekeeper genes directly regulate cell growth by either inhibiting cell cycle progression or inducing apoptosis. Lastly, landscaper genes regulate growth by contributing to the surrounding e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
