Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with familial adenomatous polyposis coli (FAP) carry heterozygous mutations of the APC gene. At a young age, these patients develop multiple colorectal adenomas that consistently display a second somatic mutation in the remaining APC wild-type allele. Inactivation of APC leads to impaired degradation of beta-catenin, thereby promoting continuous cell-cycle progression. The role of APC inactivation in rare extracolonic tumors of FAP patients has not been characterized sufficiently. Among tissue specimen from 174 patients with known APC germ-line mutations, we identified 8 tumors infrequently seen in FAP. To investigate the pathogenic role of APC pathway deregulation in these lesions, they were analyzed for second-hit somatic mutations in the mutational cluster region of the APC gene. Immunohistochemistry was performed to compare the expression pattern of beta-catenin to the mutational status of the APC gene. Exon 3 of the beta-catenin gene (CTNNB1) was analyzed for activating mutations to investigate alternative mechanisms of elevated beta-catenin concentration. Although CTNNB1 mutations were not observed, second somatic APC mutations were found in 4 of the 8 tumors: a uterine adenocarcinoma, a hepatocellular adenoma, an adrenocortical adenoma, and an epidermal cyst. These tumors showed an elevated concentration of beta-catenin. No APC mutations were seen in focal nodular hyperplasia of the liver, angiofibrolipoma, and seborrheic wart. This is the first study reporting second somatic APC mutations in FAP-associated uterine adenocarcinoma and epidermal cysts. Furthermore, our data strengthen a role for impaired APC function in the pathogenesis of adrenal and hepatic neoplasms in FAP patients.
 ...
PMID:Analysis of somatic APC mutations in rare extracolonic tumors of patients with familial adenomatous polyposis coli. 1528 21

To study the prevalence of oral lesions in HIV infected patients and its relationship with CD4+ cell count in Georgia 732 HIV positive adult patients who were admitted to the Infectious Diseases, AIDS and Clinical Immunology Research Center (IDACIRC) since January, 2006 till October, 2008 were evaluated. Each patient underwent full clinical and standard laboratory examination. CD4+ cell count was determined by the Becton-Dickinson FACSCalibur flow cytometer (MultiTEST CD3 FITC/CD8 PE/CD45 PerCP/CD4 APC Reagent). Socio-demographic data was obtained using a standard questionnaire at the epidemiology department of IDACIRC. Oral manifestations were diagnosed according to EEC clearinghouse classification (1993). Oral lesions were revealed in 546 patients (75%). 186 patients (25%) did not exhibit any oral complications. The prevalence of two or more simultaneously exhibited types of lesions was as follows: three types of lesions were detected in 45 patients (6%) and two types of lesions were detected in 245 patients (33%). The investigation revealed oral candidiasis constituted the most common form of oral lesions, representing a 64% (467 patients), followed by HIV associated periodontal diseases in 216 patients (30%), recurrent aphthous like ulcerations in 118 patients (16%), oral hairy leukoplakia in 58 patients (8%), orolabial herpes simplex infection in 50 patients (7%), human papillomavirus (wart like lesions) in 37 patients (5%) and Kaposi's sarcoma in 3 patients (0.4%). Most of oral lesions cases were found in patients with low CD4+ cell count. Results of this study provide evidence that mucous membrane disorders with HIV infection might serve as an indicator for advanced HIV infection, immunosuppression and decreased CD4 cell counts. The physicians who are taking care of HIV patients have to be familiar with HIV-associated mucocutaneous diseases, their diagnoses, and management.
 ...
PMID:Oral lesions in HIV-positive patients in Georgia. 1912 19

The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C)Cdh1 E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in Drosophila eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/CCdh1 represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.
 ...
PMID:Hippo signaling is intrinsically regulated during cell cycle progression by APC/CCdh1. 3100 Jun