CD44+ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma.

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Survival Analysis of Re-resection Versus Radiofrequency Ablation for Intrahepatic Recurrence After Hepatectomy for Hepatocellular Carcinoma

Ó The Author(s) 2011. This article is published with open access at Springerlink.com Background Tumor recurrence after resection of hepatocellular carcinoma is a common phenomenon. Re-resection and radiofrequency ablation (RFA) are good options for treating recurrent HCC. This study compared the efficacy of these two modalities in the treatment of intrahepatic HCC recurrence after hepatectomy. Methods From January 2001 to December 2008, a total of 179 patients developed intrahepatic HCC recurrence after hepatectomy. To treat the recurrence, 29 patients underwent re-resection and 45 patients had RFA. Patient characteristics, clinicopathologic data, and survival outcomes were reviewed. Results Child-Pugh status, time to develop first recurrence (12.2 vs. 8.7 months), and recurrent tumor size (2.1 vs. 2.1 cm) were comparable for the two groups. Time to develop a second intrahepatic recurrence after re-resection and RFA was 5.9 and 4.0 months respectively. The 1-, 3-, and 5-year disease-free survival rates were 41.4%, 24.2%, and 24.2 % after re-resection and 32.2%, 12.4%, and 9.3% after RFA (p = 0.14). The 1-, 3-, and 5-year overall survival rates were 89.7%, 56.5%, and 35.2 % after re-resection and 83.7%, 43.1%, and 29.1 % after RFA (p = 0.48). For the second recurrence, 33.3 % of patients underwent a second round of RFA and 10.0 % underwent a third resection

miR-31 is consistently inactivated in EBV-associated nasopharyngeal carcinoma and contributes to its tumorigenesis

BACKGROUND: As a distinctive type of head and neck cancers, nasopharyngeal carcinoma (NPC) is genesis from the clonal Epstein-Barr virus (EBV)-infected nasopharyngeal epithelial cells accumulated with multiple genetic lesions. Among the recurrent genetic alterations defined, loss of 9p21.3 is the most frequent early event in the tumorigenesis of EBV-associated NPC. In addition to the reported CDKN2A/p16, herein, we elucidated the role of a miRNA, miR-31 within this 9p21.3 region as NPC-associated tumor suppressor. METHODS: The expression and promoter methylation of miR-31 were assessed in a panel of NPC tumor lines and primary tumors. Its in vitro and in vivo tumor suppression function was investigated through the ectopic expression of miR-31 in NPC cells. We also determined the miR-31 targeted genes and its involvement in the growth in NPC. RESULTS: Downregulation of miR-31 expression was detected in almost all NPC cell line, patient-derived xenografts (PDXs) and primary tumors. Both homozygous deletion and promoter hypermethylation were shown to be major mechanisms for miR-31 silencing in this cancer. Strikingly, loss of miR-31 was also obviously observed in the dysplastic lesions of nasopharynx. Restoration of miR-31 in C666-1 cells inhibited the cell proliferation, colony-forming and migratory capacities. Dramatic reduction of in vitro anchorage-independent growth and in vivo tumorigenic potential were demonstrated in the stable clones expressing miR-31. Furthermore, we proved that miR-31 suppressed the NPC cell growth via targeting FIH1 and MCM2. CONCLUSIONS: The findings provide strong evidence to support miR-31 as a new NPC-associated tumor suppressor on 9p21.3 region. The inactivation of miR-31 may contribute to the early development of NPC.published_or_final_versio

Aberrant Cell Cycle and Apoptotic Changes Characterise Severe Influenza A Infection – A Meta-Analysis of Genomic Signatures in Circulating Leukocytes

Influenza A infection is a global disease that has been responsible for four pandemics over the last one hundred years. However, it remains poorly understood as to why some infected individuals succumb to life threatening complications whilst others recover and are relatively unaffected. Using gene-expression analysis of circulating leukocytes, here we show that the progression towards severe influenza A infection is characterised by an abnormal transcriptional reprogramming of cell cycle and apoptosis pathways. In severely infected humans, leukocyte gene-expression profiles display opposing cell cycle activities; an increased aberrant DNA replication in the G1/S phase yet delayed progression in the G2/M phase. In mild infection, cell cycle perturbations are fewer and are integrated with an efficient apoptotic program. Importantly, the loss of integration between cell cycle perturbations and apoptosis marks the transition from a mild viral illness to a severe, life threatening infection. Our findings suggest that circulating immune cells may play a significant role in the evolution of the host response. Further study may reveal alternative host response factors previously unrecognized in the current disease model of influenza

Temporal trends and patterns of infective endocarditis in a Chinese population:A territory-wide study in Hong Kong (2002-2019)

BACKGROUND: The characteristics of infective endocarditis (IE) in Asians are poorly understood. Therefore, we aim to describe the epidemiological trends and clinical features of IE in Hong Kong. METHODS: All patients with incident IE from 2002–2019 in a territory-wide clinical database in Hong Kong were identified. We studied the age- and sex-adjusted and one-year mortality of IE between 2002 and 2019 and identified significant contributors to 1-year all-cause death using the attributable fraction. We used propensity score and inverse propensity of treatment weighting to study the association of surgery with mortality. FINDINGS: A total of 5139 patients (60.4 ± 18.2years, 37% women) were included. The overall incidence of IE was 4.9 per 100,000 person-year, which did not change over time (P = 0.17). Patients in 2019 were older and more comorbid than those in 2002. The one-year crude mortality rate was 30% in 2002, which did not change significantly over time (P = 0.10). Between 2002 and 2019, the rate of surgery increased and was associated with a 51% risk reduction in 1-year all-cause mortality (Hazard Ratio 0.49 [0.28–0.87], P = 0.015). Advanced age (attributable fraction 19%) and comorbidities (attributable fraction 15%) were significant contributors to death. INTERPRETATION: The incidence of IE in Hong Kong did not change between 2002 and 2019. Patients with IE in 2019 were older and had more comorbidities than those in 2002. Mortality of IE remains persistently high in Hong Kong. Together, these data can guide public health strategies to improve the outcomes of patients with IE. FUNDING: This work was supported by Sanming Project of Medicine in Shenzhen, China [No. SZSM201911020] and HKU-SZH Fund for Shenzhen Key Medical Discipline [No. SZXK2020081]

Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium (T1DGC)

Background and Purpose The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide

Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer

Background: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis

A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE