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621.
Nayak CS Carvalho AL Jeronimo C Henrique R Kim MM Hoque MO Chang S Jiang WW Koch W Westra W Sidransky D Califano J 《The Laryngoscope》2007,117(8):1376-1380
OBJECTIVES/HYPOTHESIS: Promoter hypermethylation of tumor suppressor genes is common in head and neck cancer as well as other primary cancers resulting in epigenetic gene silencing. Tissue inhibitor of metalloproteinase-3 (TIMP-3) has been shown to have promoter hypermethylation in several solid tumors, but has not been identified in head and neck squamous cell carcinoma (HNSCC). Our objective was to determine if TIMP-3 promoter was hypermethylated in HNSCC, if there was any correlation with death associated protein kinase (DAPK), a tumor suppressor whose promoter has been hypermethylated at high levels in HNSCC, and if any clinical factors influence hypermethylation of either of these genes. STUDY DESIGN: Prospective study. METHODS: Tumor samples from 124 patients with HNSCC were evaluated for promoter hypermethylation for TIMP-3 and DAPK using quantitative methylation specific polymerase chain reaction (qMSP). We compared both TIMP-3 and DAPK hypermethylation in HNSCC with each other as well as with other clinical variables. RESULTS: We found that TIMP-3 was hypermethylated in approximately 71.8% of the tumor samples and DAPK was hypermethylated in 74.2%. The presence of TIMP-3 and DAPK promoter hypermethylation was significantly higher than in control specimens. More importantly, TIMP-3 and DAPK hypermethylations in these samples were highly correlated with a concordance of 78% (P < .001). DAPK was also correlated with current alcohol consumption (P < .028), but neither TIMP-3 nor DAPK hypermethylation was significantly correlated with other clinical variables or with survival. CONCLUSION: TIMP-3 promoter hypermethylation is elevated in HNSCC and is highly correlated with DAPK hypermethylation, implying a functional relationship between these genes. 相似文献
622.
BACKGROUND: Yellow nail syndrome (YNS) is characterized by the triad of characteristic nail changes, chronic respiratory disorders and primary lymphoedema. Over 100 cases have been published, most of which have been sporadic. Despite this, YNS is classified as a dominantly inherited lymphoedema with variable expression. There have been only a few published reports where a positive family history (FH) has been documented in cases of YNS. OBJECTIVES: To conduct a retrospective survey investigating the genetic basis of YNS. METHODS: The notes of 11 patients diagnosed with YNS were examined for documentation of a positive FH, and in addition a postal questionnaire was sent to these patients. RESULTS: Only one of the 11 patients had a relevant FH. In addition, four patients had complete recovery of their nail changes. CONCLUSIONS: This is the first retrospective study of YNS to document clear remission of nail changes. The lack of a positive FH in the majority of patients in our study, the late onset of the disease and recovery of nail changes in our patients suggest that YNS may not be primarily a genetic disease as it is currently classified. 相似文献
623.
Khalequzzaman M Kamijima M Sakai K Hoque BA Nakajima T 《Environmental health and preventive medicine》2010,15(4):236-243
Objectives
Indoor air pollution levels are reported to be higher with biomass fuel, and a number of respiratory diseases in children are associated with pollution from burning such fuel. However, little is known about the situation in developing countries. The aim of the study was to compare indoor air pollution levels and prevalence of symptoms in children between biomass- and fossil-fuel-using households in different seasons in Bangladesh. 相似文献624.
Mitochondria-encoded Cytochrome B (CYTB) gene mutations were reported in different cancers, but the effect of these mutations on cellular metabolism and growth is unknown. In a murine xenograft and human model of bladder cancer, we show the functional effect of overexpression of a 21-bp deletion mutation (mt) of CYTB. Overexpression of mtCYTB generated increased reactive oxygen species (ROS) accompanied by increased oxygen consumption and lactate production. MtCYTB overexpression induced significant tumor growth in vitro and in vivo by triggering rapid cell cycle progression through up-regulation of the nuclear factor-kappa B2 signaling pathway. Tumor-generated ROS induced in vitro lysis of normal splenocytes. Thus, we present physiologic and functional evidence for the role of a bona fide mitochondrial gene mutation in cancer. 相似文献
625.
Hoque MO Kim MS Ostrow KL Liu J Wisman GB Park HL Poeta ML Jeronimo C Henrique R Lendvai A Schuuring E Begum S Rosenbaum E Ongenaert M Yamashita K Califano J Westra W van der Zee AG Van Criekinge W Sidransky D 《Cancer research》2008,68(8):2661-2670
DNA methylation has a role in mediating epigenetic silencing of CpG island genes in cancer and other diseases. Identification of all gene promoters methylated in cancer cells "the cancer methylome" would greatly advance our understanding of gene regulatory networks in tumorigenesis. We previously described a new method of identifying methylated tumor suppressor genes based on pharmacologic unmasking of the promoter region and detection of re-expression on microarray analysis. In this study, we modified and greatly improved the selection of candidates based on new promoter structure algorithm and microarray data generated from 20 cancer cell lines of 5 major cancer types. We identified a set of 200 candidate genes that cluster throughout the genome of which 25 were previously reported as harboring cancer-specific promoter methylation. The remaining 175 genes were tested for promoter methylation by bisulfite sequencing or methylation-specific PCR (MSP). Eighty-two of 175 (47%) genes were found to be methylated in cell lines, and 53 of these 82 genes (65%) were methylated in primary tumor tissues. From these 53 genes, cancer-specific methylation was identified in 28 genes (28 of 53; 53%). Furthermore, we tested 8 of the 28 newly identified cancer-specific methylated genes with quantitative MSP in a panel of 300 primary tumors representing 13 types of cancer. We found cancer-specific methylation of at least one gene with high frequency in all cancer types. Identification of a large number of genes with cancer-specific methylation provides new targets for diagnostic and therapeutic intervention, and opens fertile avenues for basic research in tumor biology. 相似文献
626.
Cases of congenital double anus are very rare. The number of cases of hindgut duplication of all kinds is slightly higher, and some series include patients with genitourinary and genitalia duplications but with a single anus. However, double termination with tubular duplication is rarely heard of. We report on the case of a patient with 2 well-formed ani, total colon duplication, and 2 vaginas. 相似文献
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630.
Andrade-Souza YM Schwalb JM Hamani C Hoque T Saint-Cyr J Lozano AM 《Surgical neurology》2005,63(4):357-62; discussion 362-3
OBJECTIVE: The study aims to compare 2-dimensional (2D) and 3-planar (3P) reconstruction magnetic resonance imaging (MRI) methods of targeting the optimal region of the subthalamic nucleus (STN) for chronic stimulation in patients with Parkinson disease. METHODS: We studied 14 patients with Parkinson disease treated with bilateral STN deep brain stimulation (DBS) (28 STN targets). Electrode implantation was based on direct and indirect targeting based upon the position of the anterior and posterior commissures using 2D MRI, with selection of the final target based on microelectrode recording. Optimal settings, including the contacts used, were determined during the clinical follow-up. The position of the best contact was defined with postoperative MRI. Optimal contact position was compared to targets calculated by the direct method from the preoperative 2D MRI and 3P reconstruction. Optimal contact position was also compared to the indirect targets calculated from the preoperative 2D MRI and 3P reconstruction. The distance between the targets and the position of the best contact were calculated. RESULTS: The mean improvement in OFF-period Unified Parkinson Disease Rating Scale III subscores with STN DBS was 52%. The mean distance between the optimal contact position and the direct target was 4.66 mm (SD = 1.33) using the 2D MRI and 3.49 mm (SD = 1.29) using the 3P reconstruction (t test, P < .001). The mean distance between the optimal contact and the indirect target was 3.42 mm (SD = 1.34) using the 2D MRI and 2.61 mm (SD = 0.97; t test, P = .001) using the 3P reconstruction. The variance of the direct target was less using the 3P reconstruction than using the 2D MRI (F test, P = .002), indicating greater precision. Similarly, the variance of the indirect target using the 3P reconstruction was less than using the 2D MRI (F test, P = .012). CONCLUSION: Indirect and direct targets chosen using 3P reconstruction more closely approximate the position of the clinically optimal contact than targets chosen using 2D MRI. 相似文献