Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have revealed the presence of beta-catenin mutations in a small subset of human and rat lung carcinomas, suggesting the involvement of the Wnt pathway in pulmonary carcinogenesis. LOH on chromosome 5q (APC locus) is frequent in lung cancer, but previous studies have found no adenomatous polyposis coli (APC) mutations. In this study, we screened 114 human lung cancer specimens for alterations in the mutation cluster region of the APC gene and in exon 3 of the beta-catenin gene. SSCP followed by direct DNA sequencing revealed APC mutations in 2/44 (5%) squamous cell carcinomas, a 2-bp deletion in codon 1465 (AGT-->A), and a GAA-->CAA (Glu-->Gln) mutation at codon 1317. One of 32 (3%) small cell lung carcinomas contained a GAA-->AAA (Glu-->Lys) mutation at codon 1284. Two cases with an APC mutation showed focal nuclear beta-catenin staining. These results suggest that disruption of the Wnt pathway through APC mutations is infrequent, but may be involved in the pathogenesis of a small subset of human lung carcinomas.
Cancer Lett 2004 Apr 30
PMID:APC mutations are infrequent but present in human lung cancer. 1507 29

Aortic endograft limb occlusion is a serious complication after endovascular abdominal aortic aneurysm repair. We describe a yet unreported cause of endograft limb occlusion, the lithotomy position. Two patients with abdominal aortic aneurysm and colorectal cancer underwent an initial endovascular repair followed by cancer resection in the lithotomy position. Aortic endograft limb occlusion occurred in both patients immediately after the cancer operation. Percutaneous rheolytic thrombectomy was performed successfully in both patients. Pelvic surgery requiring the lithotomy position should be performed with caution in patients with aortic endografts, because it can result in endograft occlusion.
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PMID:Aortic endograft thrombosis after colorectal surgery in lithotomy position. 1511 69

5-Azacytidine- and 5-aza-deoxycytidine (5-aza-CdR)-mediated reactivation of tumor suppressor genes silenced by promoter methylation has provided an alternate approach in cancer therapy. Despite the importance of epigenetic therapy, the mechanism of action of DNA-hypomethylating agents in vivo has not been completely elucidated. Here we report that among three functional DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), the maintenance methyltransferase, DNMT1, was rapidly degraded by the proteasomal pathway upon treatment of cells with these drugs. The 5-aza-CdR-induced degradation, which occurs in the nucleus, could be blocked by proteasomal inhibitors and required a functional ubiquitin-activating enzyme. The drug-induced degradation occurred even in the absence of DNA replication. Treatment of cells with other nucleoside analogs modified at C-5, 5-fluorodeoxyuridine and 5-fluorocytidine, did not induce the degradation of DNMT1. Mutation of cysteine at the catalytic site of Dnmt1 (involved in the formation of a covalent intermediate with cytidine in DNA) to serine (CS) did not impede 5-aza-CdR-induced degradation. Neither the wild type nor the catalytic site mutant of Dnmt3a or Dnmt3b was sensitive to 5-aza-CdR-mediated degradation. These results indicate that covalent bond formation between the enzyme and 5-aza-CdR-incorporated DNA is not essential for enzyme degradation. Mutation of the conserved KEN box, a targeting signal for proteasomal degradation, to AAA increased the basal level of Dnmt1 and blocked its degradation by 5-aza-CdR. Deletion of the catalytic domain increased the expression of Dnmt1 but did not confer resistance to 5-aza-CdR-induced degradation. Both the nuclear localization signal and the bromo-adjacent homology domain were essential for nuclear localization and for the 5-aza-CdR-mediated degradation of Dnmt1. Polyubiquitination of Dnmt1 in vivo and its stabilization upon treatment of cells with a proteasomal inhibitor indicate that the level of Dnmt1 is controlled by ubiquitin-dependent proteasomal degradation. Overexpression of the substrate recognition component, Cdh1 but not Cdc20, of APC (anaphase-promoting complex)/cyclosome ubiquitin ligase reduced the level of Dnmt1 in both untreated and 5-aza-CdR-treated cells. In contrast, the depletion of Cdh1 with small interfering RNA increased the basal level of DNMT1 that blocked 5-aza-CdR-induced degradation. Dnmt1 interacted with Cdh1 and colocalized in the nucleus at discrete foci. Both Dnmt1 and Cdh1 were phosphorylated in vivo, but only Cdh1 was significantly dephosphorylated upon 5-aza-CdR treatment, suggesting its involvement in initiating the proteasomal degradation of DNMT1. These results demonstrate a unique mechanism for the selective degradation of DNMT1, the maintenance DNA methyltransferase, by well-known DNA-hypomethylating agents.
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PMID:5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. 2971 69

A 68-year-old man with ischemic heart disease, abdominal aortic aneurysm, and rectal cancer was referred. Coronary angiography indicated triple-vessel disease with jeopardized collaterals, and dipyridamole myocardial scintigraphy disclosed no viability in the inferior, posterior, and lateral walls. Abdominal computed tomography scanning revealed an infrarenal abdominal aortic aneurysm, 65 mm in diameter, with an expanding rate of 8 mm/year. Barium enema revealed stenosis 4 cm in length 5 cm inward from the anal verge, and an endoscopic finding was ulcerated type tumor with a clear margin and circumferential stenosis. Histological examination of a biopsy specimen revealed adenocarcinoma, and the clinical stage in the Japanese classification of colorectal carcinoma was II according to other examinations. Simultaneous operations were scheduled because of the jeopardized collaterals of the coronary arteries, rapid expansion of the aneurysm, and subileus due to the cancer. The patient underwent simultaneous off-pump coronary artery bypass grafting to the left anterior descending artery with the in situ internal thoracic artery through a median sternotomy, abdominal aortic aneurysm repair with a tube graft through a median laparotomy, and the Miles' operation with total mesorectal excision. Although infection of the perineal wound was postoperatively recognized, it remained local and was healed with irrigation only. The patient is doing well 12 months after the operation, without myocardial ischemic symptoms or recurrence of the cancer.
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PMID:Simultaneous operation of ischemic heart disease, abdominal aortic aneurysm, and rectal cancer. 1602 67

After analysing gene-expression profiles of colon cancers on a cDNA microarray containing cDNAs corresponding to 23 040 human genes, we focused on a gene annotated as C10orf3 (chromosome 10 open reading frame 3), whose expression was elevated in colorectal cancers (CRC) as well as in tumors arising in the stomach, lung, pancreas, and breast. The gene encodes a putative 464-amino-acid protein containing a domain known as AAA (ATPases associated with a variety of cellular activities). Western blot analysis using an antibody to the gene product confirmed that the protein was overexpressed in nine of the 15 clinical cancer tissues examined, compared to corresponding noncancerous epithelial cells. A subsequent proteomics analysis revealed that C10orf3 product associated with the product of tumor susceptibility gene 101 (TSG101), and that C10orf3 downregulated TSG101 in a post-transcriptional manner. Expression of short interfering RNA in cells derived from CRC caused significant decreases in C10orf3 expression and inhibited growth of the transfected cells, which was associated with increased apoptotic cells. These data suggest that elevated C10orf3 expression might play an essential role in the growth of cancer cells, and that suppression of C10orf3-mediated signal transduction may be a novel therapeutic strategy to a wide range of human tumors.
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PMID:Elevated expression of C10orf3 (chromosome 10 open reading frame 3) is involved in the growth of human colon tumor. 1617 Mar 51

This report details the case of a patient presenting with a periampullary cancer and an abdominal aortic aneurysm who underwent endovascular repair of the aneurysm prior to pancreaticoduodenectomy. Use of the endovascular approach avoided the need for two major operative interventions.
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PMID:Sequential endovascular repair and pancreaticoduodenectomy for abdominal aortic aneurysm copresenting with periampullary cancer. 1637 40

Mitotic spindle poisons (e.g., Taxol and vinblastine), used as chemotherapy drugs, inhibit mitotic spindle function, activate the mitotic spindle checkpoint, arrest cells in mitosis, and then cause cell death by mechanisms that are poorly understood. By expression cloning, we identified a truncated version of human TRIP1 (also known as S8, hSug1), an AAA (ATPases associated with diverse cellular activities) family ATPase subunit of the 19S proteasome regulatory complex, as an enhancer of spindle poison-mediated apoptosis. Stable expression of the truncated TRIP1/S8/hSug1 in HeLa cells [OP-TRIP1(88-406)] resulted in a decrease of measurable cellular proteasome activity, indicating that OP-TRIP1(88-406) had a dominant-negative effect on proteasome function. OP-TRIP1(88-406) revealed an increased apoptotic response after treatment with spindle poisons or with proteasome inhibitors. The increased apoptosis coincided with a significant decrease in expression of BubR1, a kinase required for activation and maintenance of the mitotic spindle checkpoint in response to treatment with spindle poisons. Small interfering RNA (siRNA)-mediated knockdown of TRIP1/S8/hSug1 resulted in a reduction of general proteasome activity and an increase in mitotic index. The siRNA treatment also caused increased cell death after spindle poison treatment. These results indicate that inhibition of TRIP1/S8/hSug1 function by expression of a truncated version of the protein or by siRNA-mediated suppression enhances cell death in response to spindle poison treatment. Current proteasome inhibitor drugs in trial as anticancer agents target elements of the 20S catalytic subcomplex. Our results suggest that targeting the ATPase subunits in 19S regulatory complex in the proteasome may enhance the antitumor effects of spindle poisons.
Mol Cancer Ther 2006 Jan
PMID:Inhibition of TRIP1/S8/hSug1, a component of the human 19S proteasome, enhances mitotic apoptosis induced by spindle poisons. 1643 60

RDM1 (RAD52 Motif 1) is a vertebrate protein involved in the cellular response to the anti-cancer drug cisplatin. In addition to an RNA recognition motif, RDM1 contains a small amino acid motif, named RD motif, which it shares with the recombination and repair protein, RAD52. RDM1 binds to single- and double-stranded DNA, and recognizes DNA distortions induced by cisplatin adducts in vitro. Here, we have performed an in-depth analysis of the nucleic acid-binding properties of RDM1 using gel-shift assays and electron microscopy. We show that RDM1 possesses acidic pH-dependent DNA-binding activity and that it binds RNA as well as DNA, and we present evidence from competition gel-shift experiments that RDM1 may be capable of discrimination between the two nucleic acids. Based on reported studies of RAD52, we have generated an RDM1 variant mutated in its RD motif. We find that the L119GF --> AAA mutation affects the mode of RDM1 binding to single-stranded DNA.
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PMID:Nucleic acid-binding properties of the RRM-containing protein RDM1. 1663 May 39

Acute abdominal pain is a common presenting complaint in older patients. Presentation may differ from that of the younger patient and is often complicated by coexistent disease, delays in presentation, and physical and social barriers. The physical examination can be misleadingly benign, even with catastrophic conditions such as abdominal aortic aneurysm rupture and mesenteric ischemia. Changes that occur in the biliary system because of aging make older patients vulnerable to acute cholecystitis, the most common indication for surgery in this population. In older patients with appendicitis, the initial diagnosis is correct only one half of the time, and there are increased rates of perforation and mortality when compared with younger patients. Medication use, gallstones, and alcohol use increase the risk of pancreatitis, and advanced age is an indicator of poor prognosis for this disease. Diverticulitis is a common cause of abdominal pain in the older patient; in appropriately selected patients, it may be treated on an outpatient basis with oral antibiotics. Small and large bowel obstructions, usually caused by adhesive disease or malignancy, are more common in the aged and often require surgery. Morbidity and mortality among older patients presenting with acute abdominal pain are high, and these patients often require hospitalization with prompt surgical consultation.
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PMID:Diagnosis of acute abdominal pain in older patients. 1711 93

TIP48 and TIP49 are two related and highly conserved eukaryotic AAA(+) proteins with an essential biological function and a critical role in major pathways that are closely linked to cancer. They are found together as components of several highly conserved chromatin-modifying complexes. Both proteins show sequence homology to bacterial RuvB but the nature and mechanism of their biochemical role remain unknown. Recombinant human TIP48 and TIP49 were assembled into a stable high molecular mass equimolar complex and tested for activity in vitro. TIP48/TIP49 complex formation resulted in synergistic increase in ATPase activity but ATP hydrolysis was not stimulated in the presence of single-stranded, double-stranded or four-way junction DNA and no DNA helicase or branch migration activity could be detected. Complexes with catalytic defects in either TIP48 or TIP49 had no ATPase activity showing that both proteins within the TIP48/TIP49 complex are required for ATP hydrolysis. The structure of the TIP48/TIP49 complex was examined by negative stain electron microscopy. Three-dimensional reconstruction at 20 A resolution revealed that the TIP48/TIP49 complex consisted of two stacked hexameric rings with C6 symmetry. The top and bottom rings showed substantial structural differences. Interestingly, TIP48 formed oligomers in the presence of adenine nucleotides, whilst TIP49 did not. The results point to biochemical differences between TIP48 and TIP49, which may explain the structural differences between the two hexameric rings and could be significant for specialised functions that the proteins perform individually.
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PMID:Dodecameric structure and ATPase activity of the human TIP48/TIP49 complex. 1715 68


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