Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desmoid tumours (DT) are slow-growing tumours that consist of proliferations of well-differentiated fibroblasts. Although the typical characteristics of malignant tumours, such as distant metastases, are absent, the tumours are locally aggressive and grow into neighbouring structures. The prevalence of desmoid tumours in patients with FAP is 7-12%. The lifetime risk of developing desmoid tumours is about 20%. In FAP, most tumours are intra-abdominal or located in the abdominal wall. Next to colorectal cancer, desmoid tumours are the most frequent cause of death in FAP. Possible risk factors for the development of desmoid tumours are previous surgical procedures, pregnancy, female sex, a family history of desmoid tumours, and specific mutations in the APC-gene. Both CT scanning and MRI can be used to detect the tumours. An excision biopsy is needed to establish the diagnosis. Medicinal treatment with NSAIDs is the treatment of first choice, followed by hormonal treatment (e.g., tamoxifen) in combination with NSAIDs. Both forms of treatment lead to a response in about 30-50% of the patients. Surgery is the preferred treatment for extra-abdominal tumours or tumours located in the abdominal wall. Surgical treatment of intra-abdominal tumours is only indicated in patients with obstruction of the bowel or ureter. Chemotherapy is indicated in patients with progressive desmoid tumours when non-cytotoxic treatment has failed. Radiotherapy may play a role in the treatment of irresectable extra-abdominal or abdominal wall tumours, or as adjuvant treatment of tumours with positive margins.
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PMID:[Desmoid tumors in patients with familial adenomatous polyposis]. 1216 72

1. The mechanisms and receptors involved in the vasoactive intestinal peptide (VIP)- and pituitary adenylate cyclase-activating polypeptide (PACAP)-induced relaxations of the pig intravesical ureter were investigated. 2. VIP, PACAP 38 and PACAP 27 concentration-dependently relaxed U46619-contracted ureteral strips with a similar potency. [Ala(11,22,28)]-VIP, a VPAC(1) agonist, showed inconsistent relaxations. 3. The neuronal voltage-gated Ca(2+) channel inhibitor, omega-conotoxin GVIA (omega-CgTX, 1 microm), reduced the VIP relaxations. Urothelium removal or blockade of capsaicin-sensitive primary afferents, nitric oxide (NO) synthase and guanylate cyclase with capsaicin (10 microm), N(G)-nitro-l-arginine (l-NOARG, 100 microm) and 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 microm), respectively, did not change the VIP relaxations. However, the PACAP 38 relaxations were reduced by omega-CgTX, capsaicin, l-NOARG and ODQ. 4. The VIP and VIP/PACAP receptor antagonists, [Lys(1), Pro(2,5), Arg(3,4), Tyr(6)]-VIP (1 microm) and PACAP (6-38) (0.4 microm), inhibited VIP and VIP and PACAP 38, respectively, relaxations. 5. The nonselective and large-conductance Ca(2)-activated K(+) channel blockers, tetraethylammonium (3 mm) and charybdotoxin (0.1 microm), respectively, and neuropeptide Y (0.1 microm) did not modify the VIP relaxations. The small-conductance Ca(2)-activated K(+) channel blocker apamin (1 microm) did not change the PACAP 27 relaxations. 6. The cAMP-dependent protein kinase A (PKA) blocker, 8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate (Rp-8-CPT-cAMPS, 100 microm), reduced VIP relaxations. The phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator forskolin relaxed ureteral preparations. The rolipram relaxations were reduced by Rp-8-CPT-cAMPS. Forskolin (30 nm) evoked a potentiation of VIP relaxations. 7. These results suggest that VIP and PACAP relax the pig ureter through smooth muscle receptors, probably of the VPAC(2) subtype, linked to a cAMP-PKA pathway. Neuronal VPAC receptors localized at motor nerves and PAC(1) receptors placed at sensory nerves and coupled to NO release, seem also to be involved in the VIP and PACAP 38 relaxations.
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PMID:Heterogeneity of neuronal and smooth muscle receptors involved in the VIP- and PACAP-induced relaxations of the pig intravesical ureter. 1466 37

The multistep development of malignant tumors with increasing accumulation of genetic alterations from preneoplastic lesions to invasive carcinoma is an accepted model of carcinogenesis. Urothelial carcinoma of the bladder and upper urinary tract is an interesting model system to study tumor development and progression. There is both clinical and molecular evidence that urothelial carcinoma can be divided in two groups with different characteristics: 1) well differentiated genetic stable and mostly superficial papillary tumors with frequent recurrence and low progression risk and 2) poorly differentiated mostly solid and invasive tumors with a high number of genetic alterations. The aim of the studies summarized in this manuscript were: 1) to identify genetic changes with importance for urothelial carcinogenesis by investigation of preneoplastic and early neoplastic urothelial lesions, 2) to define molecular markers for progression of papillary carcinoma, and 3) to investigate the importance of microsatellite instability and mismatch repair defects for development of tumors of the upper urinary tract which are frequently found within the HNPCC syndrome. The investigation of urothelial hyperplasias, dysplasias and carcinoma in situ by deletion mapping (LOH analysis), FISH, CGH and mutation detection revealed that urothelial hyperplasias are precursors of papillary bladder tumors and flat dysplasias can be regarded as precursors of solid bladder cancers. In bladder cancer patients, there are genetic alterations already detectable in histologically inconspicous urothelium. The investigation of papillary bladder cancers for progression-related genetic alterations showed that mutations in the wnt pathway genes APC and beta-Catenin do not play an important role in urothelial carcinogenesis. Instead, the expression of the antagonistic wnt-related genes WIF-1 and sFRPI is strongly reduced in bladder cancer and associated with poor prognosis in papillary tumors. Loss of sFRP1 expression is not due to gene mutation but to epigenetic inactivation by promoter hypermethylation and is related to deletions at chromosome 8p12. In contrast to bladder cancers, tumors of the ureter and renal pelvis develop through a different genetic pathway in 30% of cases. The loss of mismatch repair proteins (hMSH2, hMLH1 or hMSH6) leads to a mutator phenotype with accumulation of genetic alterations in multiple repetitive sequences (microsatellite instability, MSI). MSI-positive tumors were predominantly located in the ureter and showed a lower tumor stage and grade and papillary and frequently inverted growth pattern. They were more frequent in females and younger patients and had a higher incidence of colorectal carcinomas and other tumors in the family. Chromosome 9 deletions, a hallmark of urothelial carcinomas, and the number of chromosomal alterations as detected by CGH analysis were significantly less frequent in these tumors. These data strongly suggest a distinct molecular pathway in the development of upper urinary tract tumors with mutator phenotype.
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PMID:[Molecular changes in development and progression of urothelial carcinoma]. 1688 10

Hereditary colorectal cancer (CRC) is highly heterogeneous, both genotypically and phenotypically. The most frequently occurring hereditary colorectal cancer syndrome is Lynch syndrome, accounting for approximately 3% of the total colorectal cancer burden. Polyposis syndromes, such as familial adenomatous polyposis, account for a lesser percentage. Familial colorectal cancer, defined by family history, occurs in an estimated 20% of all colorectal cancer cases. With a worldwide annual colorectal cancer incidence of over one million, and annual mortality of over 600,000, hereditary and familial forms of colorectal cancer are a major public health problem. Lynch syndrome is attributable to DNA mismatch repair germline mutations, with the MSH2, MLH1, MSH6, and PMS2 genes being implicated. The characteristics of Lynch syndrome-associated colorectal tumors, including early age of onset and predilection to the proximal colon, mandate surveillance by colonoscopy beginning by age 20 to 25 and repeated every other year through age 40 and annually thereafter. Besides colorectal cancer, Lynch syndrome also predisposes to a litany of extracolonic cancers, foremost of which is endometrial cancer, followed by cancer of the ovary, stomach, renal pelvis and ureter, small bowel, hepatobiliary tract, pancreas, glioblastoma multiforme in the Turcot's variant, and sebaceous skin tumors in the Muir-Torre variant and, more recently identified, cancers of the breast and prostate. The most common polyposis syndrome is familial adenomatous polyposis, caused by mutations in the APC gene. Affected individuals have multiple colonic adenomas and, without treatment invariably develop colorectal cancer. Colonic surveillance with polypectomy may be pursued until the appearance of multiple colonic adenomas, at which time prophylactic colectomy should be considered. Extra-intestinal manifestations include desmoid tumor, hepatoblastoma, thyroid carcinoma, and medulloblastoma. Other polyposis syndromes include the hamartomatous polyp syndromes, including juvenile polyposis syndrome, Peutz-Jeghers syndrome, Cowden syndrome, and Bannayan-Ruvalcaba-Riley syndrome.
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PMID:Practical genetics of colorectal cancer. 2584 92