Over-expression of miR-106b promotes cell migration and metastasis in hepatocellular carcinoma by activating epithelial-mesenchymal transition process

Hepatocellular carcinoma (HCC) is one the the most fatal cancers worldwide. The poor prognosis of HCC is mainly due to the developement of distance metastasis. To investigate the mechanism of metastasis in HCC, an orthotopic HCC metastasis animal model was established. Two sets of primary liver tumor cell lines and corresponding lung metastasis cell lines were generated. In vitro functional analysis demonstrated that the metastatic cell line had higher invasion and migration ability when compared with the primary liver tumor cell line. These cell lines were subjected to microRNA (miRNAs) microarray analysis to identify differentially expressed miRNAs which were associated with the developement of metastasis in vivo. Fifteen human miRNAs, including miR-106b, were differentially expressed in 2 metastatic cell lines compared with the primary tumor cell lines. The clinical significance of miR-106b in 99 HCC clinical samples was studied. The results demonstrated that miR-106b was over-expressed in HCC tumor tissue compared with adjacent non-tumor tissue (p = 0.0005), and overexpression of miR-106b was signficantly correlated with higher tumor grade (p = 0.018). Further functional studies demonstrated that miR-106b could promote cell migration and stress fiber formation by over-expressing RhoGTPases, RhoA and RhoC. In vivo functional studies also showed that over-expression of miR-106b promoted HCC metastasis. These effects were related to the activation of the epithelial-mesenchymal transition (EMT) process. Our results suggested that miR-106b expression contributed to HCC metastasis by activating the EMT process promoting cell migration in vitro and metastasis in vivo. © 2013 Yau et al.published_or_final_versio

Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1

We previously demonstrated that the overexpression of homeoprotein Six1 in hepatocellular carcinoma (HCC) patients is associated with venous infiltration, advanced pathologic tumor metastasis (pTNM) stage and poor overall survival rate (Ng et al. Br J Cancer 2006;95:1050-5). In this study, short hairpin RNA (shRNA) interference approach was used to suppress the expression of Six1 in a metastatic HCC cell line MHCC97L. Stable transfectant MHCC97L-shSix1 carrying Six1-specific shRNA plasmid was established to downregulate Six1 expression to about 40% when compared with MHCC97L-Control. In vitro functional assays demonstrated that the growth rate and proliferation ability of MHCC97L-shSix1 cells were markedly decreased. Moreover, significant decrease of cell motility and invasiveness were observed in MHCC97L-shSix1 cells. Data from in vivo xenograft tumorigenesis model demonstrated that the size of tumor in MHCC97L-shSix1 group was dramatically reduced. Experimental and spontaneous metastasis models indicated that targeting Six1 suppression noticeably reduced the pulmonary metastasis in MHCC97L-shSix1 group. To identify Six1-regulated targets, cDNA microarray was employed to compare the expression profiles of MHCC97L-Control and MHCC97L-shSix1 cells. Twenty-eight downregulated and 24 upregulated genes with known functions were identified in MHCC97L-shSix1. The functions of these target genes are involved in diverse biological activities. Our data suggest that Six1 may be involved in regulation of proliferation and invasiveness of HCC; thus targeting suppression of Six1 is a viable option for treating HCC patients. © 2009 UICC.postprin

Giant synovial cell sarcoma of the thorax in a 46-year-old man: a case report

Background:Although synovial cell sarcoma is a common tumor of the extremities, its occurrence in the thorax has been less frequently documented. Case Presentation: A 46-year-old Pakistani man presented with a 2 month history of progressively increasing cough and left lower chest pain. Initial evaluation was done using a chest x-ray, the Patient was found to have a large mass involving the lower portion of the left chest. A computed tomography scan was performed next which showed a large mass involving the left chest wall with invasion into the pericardium and left hemidiaphragm. En bloc surgical resection of the tumor was undertaken. Final pathology showed synovial cell sarcoma of the thorax. At one-year follow-up, the Patient has shown no recurrence of the disease. Conclusions: We have described a rare case of a large synovial cell sarcoma of the thorax. Surgical resection appears an appropriate modus operandi for managing giant synovial cell sarcomas of the thorax. However, there is a need to clearly define post-operative strategies for cases with extensive involvement of surrounding structures

Seroprevalence of hepatitis C in type 2 diabetes: evidence for a positive association

<p>Abstract</p> <p>Background</p> <p>There is a growing body of literature on the relationship of Hepatitis C virus infection (HCV) and type 2 diabetes mellitus (T2DM). However, there are certain gaps in literature and the data is inconclusive. This study was, therefore, carried out to determine the prevalence of HCV infection in diabetic patients and to elucidate the presence of any possible relationship between HCV and T2DM in this region.</p> <p>Methods</p> <p>Serologic testing for anti-HCV antibody was done on a sample of 3000 individuals with T2DM visiting Diabetes Clinic of Nishtar Medical College Hospital, Multan and 10,000 volunteer blood donors visiting blood bank of the same hospital during the study period using Accurate rapid immunochromatographic kits which was later confirmed by using Chemelex S.A third generation ELISA kit for positive cases. Data about various variables was collected from diabetic patients using a structured questionnaire after taking informed consent.</p> <p>Results</p> <p>Prevalence rate of 13.7% for HCV infection was recorded among subjects having T2DM with seropositivity rate of 4.9% among the control group of volunteer blood donors without diabetes. The patients with T2DM were more likely to have HCV infection as compared to the control group (OR = 3.03, 95%CI = 2.64-3.48, p = 0.001). Diabetic patients with age above 55 years had higher prevalence rate as compared to younger individuals. Male patients had significantly high seropositivity as compared to female patients (15.3% vs. 12.4%, p = 0.02). Those with duration of diabetes 11 years and above and the ones with good glycemic control had higher seroprevalence rates of 18.2% and 18.7% respectively. There was no statistically significant difference among subjects when the distribution of HCV was studied on the basis of marital status, locality, or family history of diabetes.</p> <p>Conclusions</p> <p>The results show that there is a strong association between HCV and T2DM in the region as evident from significantly higher prevalence of HCV infection in diabetics as compared to the control group in the present study.</p

Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic

Reproduction numbers, defined as averages of the number of people infected by a typical case, play a central role in tracking infectious disease outbreaks. The aim of this paper is to develop methods for estimating reproduction numbers which are simple enough that they could be applied with limited data or in real time during an outbreak. I present a new estimator for the individual reproduction number, which describes the state of the epidemic at a point in time rather than tracking individuals over time, and discuss some potential benefits. Then, to capture more of the detail that micro-simulations have shown is important in outbreak dynamics, I analyse a model of transmission within and between households, and develop a method to estimate the household reproduction number, defined as the number of households infected by each infected household. This method is validated by numerical simulations of the spread of influenza and measles using historical data, and estimates are obtained for would-be emerging epidemics of these viruses. I argue that the household reproduction number is useful in assessing the impact of measures that target the household for isolation, quarantine, vaccination or prophylactic treatment, and measures such as social distancing and school or workplace closures which limit between-household transmission, all of which play a key role in current thinking on future infectious disease mitigation

Understanding the risk and protective factors associated with obesity amongst Libyan adults - a qualitative study

BACKGROUND: There are a range of multifaceted behavioural and societal factors that combine to contribute to the causes of obesity. However, it is not yet known how particularly countries' cultural norms are contributing to the global obesity epidemic. Despite obesity reaching epidemic proportions in Libya, since the discovery of oil in 1959, there is a lack of information about obesity in Libyan adults. This study sought to explore the views of key informants about the risk and protective factors associated with obesity among Libyan men and women. METHODS: A series of qualitative semi-structured interviews were conducted with Libyan healthcare professionals and community leaders. RESULTS: Eleven main themes (risk and protective factors) were identified, specifically: socio-demographic and biological factors, socioeconomic status, unhealthy eating behaviours, knowledge about obesity, social-cultural influences, Libya's healthcare facilities, physical activity and the effect of the neighbourhood environment, sedentary behaviour, Libyan food-subsidy policy, and suggestions for preventing and controlling obesity. CONCLUSIONS: Key recommendations are that an electronic health information system needs to be implemented and awareness about obesity and its causes and consequences needs to be raised among the public in order to dispel the many myths and misconceptions held by Libyans about obesity. The current political instability within Libya is contributing to a less-active lifestyle for the population due to security concerns and the impact of curfews. Our findings have implications for Libyan health policy and highlight the urgent need for action towards mitigating against the obesity epidemic in Libya

Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer

Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was found as a candidate TSG epigenetically downregulated in gastric cancer. FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation. Hypermethylation of the FBLN1 promoter was frequently (71%, 5 out of 7) detected in gastric cancer cell lines and primary gastric carcinoma tissues. Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis. In summary, FBLN1 was identified as a novel candidate TSG epigenetically downregulated in gastric cancer

Safety of Levetiracetam in paediatrics: a systematic review

Objective To identify adverse events (AEs) associated with Levetiracetam (LEV) in children. Methods Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis. Results Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems. Conclusion Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy

FluTE, a Publicly Available Stochastic Influenza Epidemic Simulation Model

Mathematical and computer models of epidemics have contributed to our understanding of the spread of infectious disease and the measures needed to contain or mitigate them. To help prepare for future influenza seasonal epidemics or pandemics, we developed a new stochastic model of the spread of influenza across a large population. Individuals in this model have realistic social contact networks, and transmission and infections are based on the current state of knowledge of the natural history of influenza. The model has been calibrated so that outcomes are consistent with the 1957/1958 Asian A(H2N2) and 2009 pandemic A(H1N1) influenza viruses. We present examples of how this model can be used to study the dynamics of influenza epidemics in the United States and simulate how to mitigate or delay them using pharmaceutical interventions and social distancing measures. Computer simulation models play an essential role in informing public policy and evaluating pandemic preparedness plans. We have made the source code of this model publicly available to encourage its use and further development