Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Venous malformations are a common form of vascular anomaly that cause pain and disfigurement and can be life threatening if they involve critical organs. They occur sporadically or in a familial form, where multiple lesions are usually present. We have identified a large kindred showing autosomal dominant inheritance of venous malformations. Using this family we confirm linkage of a familial form of venous malformations to chromosome 9p. We suggest that blue rubber bleb naevus syndrome can be considered a particular manifestation of this form of familial venous malformations. The candidate region for this gene encompasses the interferon gene cluster and the MTS1 (p16) tumour suppressor gene.
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PMID:A gene for familial venous malformations maps to chromosome 9p in a second large kindred. 778 68

Linoleic and alpha-linolenic acids, obtained from plant material in the diet are the precursors in tissues of two families with opposing effects which are referred to as "essential fatty acids" (EFA): arachidonic acid (AA) and pentaene (eicosapentaenoic acid: EPA) and hexaene (docosahexaenoic acid: DHA) acids. The role of EFA is crucial, without a source of AA or compounds which can be converted into AA, synthesis of prostaglandins (PGs) by a cyclooxygenase (COX) enzyme would be compromised, and this would seriously affect many normal metabolic processes. COX, also known as prostaglandin endoperoxide synthase (Pghs) or as prostaglandin G/H synthase, is a key membrane bound enzyme responsible for the oxidation of AA to PGs. Two COX isoforms have been identified, COX-1 and COX-2 that form PGH2, a common precursor for the biosynthesis of thromboxane A2 (TxA2), prostacyclin (PGI2) and PGs (PGD2, PGE2, PGF2alpha. COX-1 enzyme is expressed constitutively in most cells and tissues. Its expression remains constant under either physiological or pathological conditions controlling synthesis of those PGs primarily involved in the regulation of homeostatic functions. In contrast, COX-2 is an intermediate response gene that encodes a 71-kDa protein. COX-2 is normally absent from most cells but highly inducible in certain cells in response to inflammatory stimuli resulting in enhanced PG release. PGs formed by COX-2 primarily mediate pain and inflammation but have multiple effects that can favour tumorigenesis. They are more abundant in cancers than in normal tissues from which the cancers arise. COX-2 is a participant in the pathway of colon carcinogenesis, especially when mutation of the APC (Adenomatous Polyposis Coli) tumour suppressor gene is the initiating event. In addition, COX-2 up-regulation and elevated PGE2 levels are involved in breast carcinogenesis. It seems that there is a correlation between COX-2 level of expression and the size of the tumours and their propensity to invade underlying tissue. Inhibition by non-steroidal anti-inflammatory drugs (NSAIDs) of COX enzymes which significantly suppress PGE2 levels, reduced breast cancer incidence and protected against colorectal cancer. Therefore it is suggested that consumption of a diet enriched in n-3 PUFA (specifically EPA and DHA) and inhibition of COX-2 by NSAIDs may confer cardioprotective effects and provide a significant mechanism for the prevention and treatment of human cancers.
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PMID:Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. 1219 20

Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma. HISTORY AND CLINICAL FINDINGS: A 39-year-old woman was admitted to our department of gastroenterology with recurrent epigastrical pain. Ten years previously the diagnosis of von Hippel-Lindau (VHL)-syndrome has been established. Two years before a germ line mutation in exon 3 of the VHL-tumour suppressor gene has been detected. The patient has a healthy son with a normal VHL-gene and four healthy siblings who had refused a genetic blood test. INVESTIGATIONS: At abdominal ultrasound at the head of the pancreas three 4 2 cm large cysts and in the region of the left adrenal gland a 2,9 2,7 cm large tumor were visible. MRI of the abdomen revealed in addition a 2,2 1,5 cm large tumour of the right adrenal gland. An asymptomatic biadrenal phaeochromocytoma was detected by elevated urine catecholamines and 123I-MIBG-scintigraphy. TREATMENT AND COURSE: The cysts of the pancreas were punctured under endosonographical control and analysis of the cyst fluid was not suspicious of a malignant cystic tumour. The patient had no further abdominal complaints. After oral treatment with the alpha-blocker phentolamine the biadrenal phaeochromocytoma was treated by retroperitoneal laparoscopic surgery in an organ-sparing fashion. Postoperatively ACTH-stimulating test revealed a normal cortisol response. CONCLUSION: Adrenocortical function can be preserved by la-paroscopic adrenal-sparing surgery in bilateral phaeochromocytoma.
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PMID:[Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma] 1275 Oct 23

Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15-18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5-5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection of malignancy seems justified. For secondary peripheral chondrosarcoma, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed.
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PMID:Multiple osteochondromas. 1827 66

Hereditary multiple exostoses (HME) is an autosomal-dominant disorder characterized by the development of benign tumours, multiple osteochondromas (exostoses), growing outward from the metaphyses of long bones. Birth prevalence is estimated to be one in 50,000, and the severity of the disease is variable. Osteochondromas may cause complications including pain, deformities and shortening of the long bones, restricted motion of joints, nerve or blood vessel compression, and malignant transformation (5% of cases) in adulthood. HME is a genetically heterogeneous disorder and is associated with mutations in EXT1 or EXT2 genes, which are both tumour suppressor genes. EXT genes encode glycosyltransferases, termed 'exostosins', which are involved in the biosynthesis of heparan sulphate. Enchondromatosis (or Ollier disease) is characterized by the presence of intra-osseous benign cartilaginous tumours. The estimated prevalence of the disease is one in 100,000. An asymmetrical distribution of cartilage lesions is observed in the disease. The number, size and location of the enchondromas can be extremely variable between patients. Clinical problems caused by enchondromas include skeletal deformities, limb length discrepancy, pain and the potential risk for malignant change to chondrosarcoma (20-50% of cases). The condition in which multiple enchondromas is associated with haemangiomas is known as 'Maffucci syndrome'. Ollier disease and Maffucci syndrome are not usually inherited disorders.
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PMID:Hereditary multiple exostoses and enchondromatosis. 1832 80