Mutations of PIK3CA in gastric adenocarcinoma

BACKGROUND: Activation of the phosphatidylinositol 3-kinase (PI3K) through mutational inactivation of PTEN tumour suppressor gene is common in diverse cancer types, but rarely reported in gastric cancer. Recently, mutations in PIK3CA, which encodes the p110α catalytic subunit of PI3K, have been identified in various human cancers, including 3 of 12 gastric cancers. Eighty percent of these reported mutations clustered within 2 regions involving the helical and kinase domains. In vitro study on one of the "hot-spot" mutants has demonstrated it as an activating mutation. METHODS: Based on these data, we initiated PIK3CA mutation screening in 94 human gastric cancers by direct sequencing of the gene regions in which 80% of all the known PIK3CA mutations were found. We also examined PIK3CA expression level by extracting data from the previous large-scale gene expression profiling study. Using Significance Analysis of Microarrays (SAM), we further searched for genes that show correlating expression with PIK3CA. RESULTS: We have identified PIK3CA mutations in 4 cases (4.3%), all involving the previously reported hotspots. Among these 4 cases, 3 tumours demonstrated microsatellite instability and 2 tumours harboured concurrent KRAS mutation. Data extracted from microarray studies showed an increased expression of PIK3CA in gastric cancers when compared with the non-neoplastic gastric mucosae (p < 0.001). SAM further identified 2910 genes whose expression levels were positively associated with that of PIK3CA. CONCLUSION: Our data suggested that activation of the PI3K signalling pathway in gastric cancer may be achieved through up-regulation or mutation of PIK3CA, in which the latter may be a consequence of mismatch repair deficiency

Integration of DNA Copy Number Alterations and Transcriptional Expression Analysis in Human Gastric Cancer

Background: Genomic instability with frequent DNA copy number alterations is one of the key hallmarks of carcinogenesis. The chromosomal regions with frequent DNA copy number gain and loss in human gastric cancer are still poorly defined. It remains unknown how the DNA copy number variations contributes to the changes of gene expression profiles, especially on the global level. Principal Findings: We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC) arrays based comparative genomic hybridization (aCGH). Statistical analysis was applied to correlate previously published gene expression data obtained from cDNA microarrays with corresponding DNA copy number variation data to identify candidate oncogenes and tumor suppressor genes. We found that gastric cancer samples showed recurrent DNA copy number variations, including gains at 5p, 8q, 20p, 20q, and losses at 4q, 9p, 18q, 21q. The most frequent regions of amplification were 20q12 (7/72), 20q12-20q13.1 (12/72), 20q13.1-20q13.2 (11/72) and 20q13.2-20q13.3 (6/72). The most frequent deleted region was 9p21 (8/72). Correlating gene expression array data with aCGH identified 321 candidate oncogenes, which were overexpressed and showed frequent DNA copy number gains; and 12 candidate tumor suppressor genes which were down-regulated and showed frequent DNA copy number losses in human gastric cancers. Three networks of significantly expressed genes in gastric cancer samples were identified by ingenuity pathway analysis. Conclusions: This study provides insight into DNA copy number variations and their contribution to altered gene expression profiles during human gastric cancer development. It provides novel candidate driver oncogenes or tumor suppressor genes for human gastric cancer, useful pathway maps for the future understanding of the molecular pathogenesis of this malignancy, and the construction of new therapeutic targets. © 2012 Fan et al.published_or_final_versio

Dominância fiscal : uma investigação empírica sobre o caso brasileiro no período de 2003 a 2014

A estabilização econômica dos anos de 1990 e a adoção do tripé econômico, a partir de 1999, marcam o fim de um capítulo delicado da história brasileira; a partir de então, era necessária a existência de certa sintonia de políticas monetária e fiscal para a manutenção do controle dos diversos indicadores econômicos. Contudo, com essa reciprocidade na política econômica, são incitadas discussões sobre a orientação do governo na hora de definir suas prioridades nesse campo: as variáveis fiscais são priorizadas e, por conseguinte, determinadas, forçando as monetárias a se ajustarem – ou o contrário? A resposta para esse questionamento leva à discussão sobre a dominância fiscal. Assim, esse trabalho visa verificar empiricamente, usando das modelagens econométricas VAR e estudo de eventos, se há dominância fiscal ou monetária na economia brasileira e se a eficácia da política monetária mudou na transição do governo Lula para o governo Dilma. O resultado foi inconclusivo para o governo Lula e indicou dominância fiscal no governo Dilma. Ainda verificou-se não haver modificação na eficácia da política monetária.Economic stabilization, in the 1990s, and utilization of an economic tripod, after 1999, represents the end of a delicate chapter in Brazilian history. Ever since, it was necessary the existence of a certain agreement between monetary and fiscal politic, in order to maintain under control a variety of economic indicators. However, this reciprocity (in economic politic) starts discussions about the real government orientations when it comes to define its priority on this subject: are the fiscal variables priorized, and then, determined, forcing monetary variables to adjust themselves, or the opposite? The answer to these questions emerge from the fiscal dominance discussion. This paper intends to empiric verify, using econometric modeling VAR and event study, if there is fiscal dominance or monetary in Brazilian economy and whether the effectiveness of monetary politic has changed in the transition from Lula's government to the Dilma government. The result was inconclusive for the Lula government and indicated fiscal dominance in the Dilma government. There was still no change in the efficiency of the monetary politic.CAPE

Molecular genetics of colorectal cancer and its relevance to epidemiology in Chinese population

published_or_final_versiontocabstractMedicineMasterDoctor of Medicin

An autopsy study of pulmonary thromboembolism in Hong kong chinese

A retrospective study of autopsied material in the last 15 yrs is documented an increasing incidence of pulmonary thromboembolism (PTE) in Hong Kong Chinese. The incidence of significant PTE increased from 0.58% in the first 5 yr period to 2.08% in recent years. The topographic features and characteristics of these PTE patients are analysed and the factors contributing to the changes are discussed. © 1991 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.link_to_subscribed_fulltex

Fine-needle aspiration biopsy of pilomatrixoma: Still a diagnostic trap for the unwary

Of the 16 cases of fine-needle aspiration biopsy (FNAB) of pilomatrixomas reported since 1982, only 25% were correctly diagnosed prior to excision. The most common pitfall encountered was a false-positive or suspicious diagnosis of a carcinoma. All the reported cases had a polymorphous cellular and noncellular composition on low-power examination, including numerous basaloid cells, ghost cells, squamoid cells, foreign body giant cells, mixed inflammatory cells, keratin clumps, and granular debris which might be easily mistaken for a malignant necrotic background. Amongst these, ghost cells were the critical pathognomonic feature. This paper reported a further finding that had been under-emphasized in the literature: masses of refractile orangeophilic keratin clumps representing compact sheets and stacks of ghost cells. Their presence should alert the observer to search for the more diagnostic dispersed forms which otherwise might be inconspicuous and easily overlooked.link_to_subscribed_fulltex

Pattern of cerebral atherosclerosis in Hong Kong Chinese: Severity in intracranial and extracranial vessels

Background and Purpose: The clinical pattern of stroke and the angiographic distribution of cerebral atherosclerosis in Chinese are different from those in Caucasians. Pathological data from autopsy studies are lacking. Methods: The intracranial and extracranial arteries supplying the brains of 114 consecutive Chinese patients undergoing autopsy in a regional general hospital were examined by computer-assisted morphometric analysis under a microscope as well as by macroscopic grading for atherosclerotic narrowing. The severity was correlated with various atherosclerosis-related factors. Results: Atherosclerosis of the intracranial cerebral vessels was more severe than that of the extracranial vessels. The distal branches of the intracranial vessels were also commonly involved. Hypertension and diabetes mellitus were identified as factors associated only with intracranial atherosclerosis (p<0.001), whereas ischemic heart disease was associated with atherosclerosis in both the intracranial (p<0.001) and extracranial (p=0.012) vessels. Smoking was associated with narrowing of the extracranial vessels only (p=0.0054). Conclusions: Compared with figures from Caucasian and Japanese populations, the extent of intracranial atherosclerosis is much more severe in Hong Kong Chinese, whereas atherosclerotic narrowing of the extracranial carotid artery is less severe in Hong Kong Chinese than in Caucasians.link_to_subscribed_fulltex