Bromodomain-Containing Protein 4: A Dynamic Regulator of Breast Cancer Metastasis through Modulation of the Extracellular Matrix

Metastasis is an extremely complex process that accounts for most cancer-related deaths. Malignant primary tumors can be removed surgically, but the cells that migrate, invade, and proliferate at distant organs are often the cells that prove most difficult to target therapeutically. There is growing evidence that host factors outside of the primary tumors are of major importance in the development of metastasis. Recently, we have shown that the bromodomain-containing protein 4 or bromodomain 4 (Brd4) functions as an inherited susceptibility gene for breast cancer progression and metastasis. In this paper, we will discuss that host genetic background on which a tumor arises can significantly alter the biology of the subsequent metastatic disease, and we will focus on the role of Brd4 in regulating metastasis susceptibility

Designing and implementing a tool to transform source code to UML diagrams

Currently, reverse engineering is considered as a significant process to extract the design information and abstractions of a system from the present software. The extracted source codes have been converted into a certain structure to be easily analyzed in the following procedure. For facilitating the software process development, it might be optimum to have tools beingcertain which generate automatically or help UML generating models from the codes as a source. The current study focuses on the reverse engineering process regarding the python and java source codes to the behavior diagrams: the use case and the activity diagrams which might be of high importance in the process of software maintenance. This approach is carried out in the current study in the application referred to as the RCUML tool with the use of the python language which helped in understanding python and java source codes in the software application, and enabling visualization regarding the software behavior

VERIFICATION AND VALIDATION OF A SOFTWARE: A REVIEW OF THE LITERATURE

With the development of the Internet, making software is often essential, also it is complicated to succeed in the project’s development. There is a necessity in delivering software of top quality. It might be accomplished through using the procedures of Verification and Validation (V&V) via development processes. The main aim of the V&V has been checking if the created software is meeting the needs and specifications of clients. V&V has been considered as collections related to testing as well as analysis activities across the software’s full life cycle. Quick developments in software V&V were of high importance in developing approaches and tools for identifying possible concurrent bugs and therefore verifying the correctness of software. It has been reflecting the modern software V&V concerning efficiency. The main aim of this study has been retrospective review related to various researches in software V&V and conduct a comparison between them.               In the modern competitive world related to the software, the developers of software must be delivering on-time quality products, also the developers should be verifying that the software has been properly functioning and validating the product for each one of the client’s requirements. The significance of V&V in the development of software has been maintaining the quality of software. The approaches of V&V have been utilized in all stages of the System Development Life Cycle. Furthermore, the presented study also provides objectives of V&V and describes V&V tools that can be used in the process of software development, the way of improving the software’s quality

تعريض حياة الغير وسلامتهم الجسدية للخطر في قانون العقوبات

يُعَد كان حق الإنسان في الحياة والسلامة الجسديَّة من أهم الحقوق التي يسعى القانون الجزائي إلى حمايتها, لذا لم يقتصر تجريمه على الأفعال التي تلحق هذا الحق بضرر فعلي, إنما وسَّع من نطاق الحماية لمن خلال تجريم الأفعال التي تهدد هذا الحق بالضرر دون المساس فيه بشكلٍ فعلي.  ومن أجل تحقيق هذا الهدف تضمَّن قانون العقوبات السوري العديد من النصوص القانونيَّة التي تسعى إلى حماية هذا الحق من التعريض للخطر يمكن إجمالها بجرائم الخطر الشامل من جهة, وجرائم تعريض الطفل والعاجز للخطر من جهة ثانية, إلا أنَّ المشرع السوري لم يتَّبع نهج التشريعات الأخرى ( كالقانونين الفرنسي والإماراتي) القائم على تجريم كل فعل من شأنه تعريض حق الغير في الحياة والسلامة الجسديَّة للخطر. بناءً على ما تقدَّم, وفي ظل غياب هذا النص العام, يتم من خلال هذا البحث إلقاء الضوء على النصوص المتفرِّقة التي يتضمنها قانون العقوبات السوري والتي تهدف إلى حماية حق الغير في الحياة والسلامة الجسدية من التعريض للخطر, بهدف البحث في مدى فعَّاليتها والبحث في كيفية تفادي أوجه القصور فيها, ومن ثم بحث النهج المتبع لدى القانون المقارن الذي تبّنَى نهج التجريم العام لكل فعل من شأنه تعريض هذا الحق للخطر وذلك بهدف الاستفادة من هذه القوانين لتحقيق الحماية المنشودة

Serum Biomarker Signature Is Predictive of the Risk of Hepatocellular Cancer in Patients With Cirrhosis

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor β1, adipsin, fetuin-A, interleukin-1 β, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors

Allelic Variation and Differential Expression of the mSIN3A Histone Deacetylase Complex Gene Arid4b Promote Mammary Tumor Growth and Metastasis

Accumulating evidence suggests that breast cancer metastatic progression is modified by germline polymorphism, although specific modifier genes have remained largely undefined. In the current study, we employ the MMTV-PyMT transgenic mouse model and the AKXD panel of recombinant inbred mice to identify AT–rich interactive domain 4B (Arid4b; NM_194262) as a breast cancer progression modifier gene. Ectopic expression of Arid4b promoted primary tumor growth in vivo as well as increased migration and invasion in vitro, and the phenotype was associated with polymorphisms identified between the AKR/J and DBA/2J alleles as predicted by our genetic analyses. Stable shRNA–mediated knockdown of Arid4b caused a significant reduction in pulmonary metastases, validating a role for Arid4b as a metastasis modifier gene. ARID4B physically interacts with the breast cancer metastasis suppressor BRMS1, and we detected differential binding of the Arid4b alleles to histone deacetylase complex members mSIN3A and mSDS3, suggesting that the mechanism of Arid4b action likely involves interactions with chromatin modifying complexes. Downregulation of the conserved Tpx2 gene network, which is comprised of many factors regulating cell cycle and mitotic spindle biology, was observed concomitant with loss of metastatic efficiency in Arid4b knockdown cells. Consistent with our genetic analysis and in vivo experiments in our mouse model system, ARID4B expression was also an independent predictor of distant metastasis-free survival in breast cancer patients with ER+ tumors. These studies support a causative role of ARID4B in metastatic progression of breast cancer

Mechanisms of metastasis

Metastasis is an enormously complex process that remains to be a major problem in the management of cancer. The fact that cancer patients might develop metastasis after years or even decades from diagnosis of the primary tumor makes the metastatic process even more complex. Over the years many hypotheses were developed to try to explain the inefficiency of the metastatic process, but none of these theories completely explains the current biological and clinical observations. In this review we summarize some of the proposed models that were developed in attempt to understand the mechanisms of tumor dissemination and colonization as well as metastatic progression

Prevalence and determinants of colonic polyps in children undergoing colonoscopy: A large hospital-based cross-sectional study

Background. Colorectal polyps are abnormal growths in the wall of the colon including the rectum. The study aims to estimate the prevalence and type of colonic polyps in children undergoing colonoscopic examination at Texas Children\u27s Hospital (TCH) in Houston, Texas during 2000-2007. Also, to examine the factors associated with colonic polyps and the potential determinants of colonic polyps in children undergoing colonoscopy and compare those who had colonic polyps with those who did not on colonoscopy, and determine the significant risk factors of colonic polyps in these children. Methods. We conducted a cross sectional study to analyze data collected at TCH. We obtained demographic, clinical, and histopathology information on consecutive patients who underwent colonoscopy during 2000-2007 from endoscopic records contained in the PEDS-CORI registry (Pediatric Endoscopy Database System-Clinical Outcomes Research Initiative), and abstracted data from the accompanying histopathology reports. Results. We identified 2,693-unique patients, under 18 years of age, who underwent colonoscopy. Approximately 65.5% were white non-Hispanic, and 10.8% African-American. The mean age was 8.7 years and 51.8% were female patients. Polyps were present in 174 patients (6.5%). The most common two histological types were juvenile (60.6%), inflammatory (17.4%). We found that the prevalence of polyps was higher in younger aged children (12.9% in 0-5 years) than in older aged children (4% in 15-17 years), and slightly higher in males than in females (7.9% and 5.4% respectively). For males only, the odds of polyps were statistically significantly higher in Blacks and Hispanics compared to white non Hispanics (OR of 2.2 and 2.1, respectively, and 95% CI of 1.3, 3.9 and 1.3, 3.5 respectively). The indications for colonoscopy were different for children with polyps compared to those without polyps, i.e., 47.0% vs. 19.8% respectively for lower GI bleeding, 2.7% vs. 21.4% respectively for abdominal pain/bloating, and, or 0.9% vs. 9.6% respectively for diarrhea. Conclusion. Colorectal polyps occur in about 1 in 15 children and adolescents undergoing first colonoscopy. The demographic variable of younger age is strongly associated with having polyps irrespective of ethnicity. Lower GI bleeding is strongly related to the presence of colorectal polyps in children and adolescents undergoing colonoscopy