High thymidylate synthase gene expression predicts poor outcome after resection of hepatocellular carcinoma.

IntroductionPrognosis after resection of hepatocellular carcinoma (HCC) is highly variable. Compared to clinicopathologic factors, the use of molecular markers to predict outcome has not been well studied. We investigated the prognostic importance of thymidylate synthase (TS) gene expression and polymorphisms in patients after resection of HCC.MethodsPatients who underwent complete resection of HCC for whom tissue was available were identified. TS gene expression level and polymorphisms were determined in HCC specimens. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazard models.ResultsThe study included 67 patients. In univariate analysis, variables that negatively influenced survival included TNM stage, microvascular invasion, and high TS expression. For the high TS expression group, median survival was 54 months and 5-year actuarial survival was 47%. For the low TS expression group, median survival was not reached and the 5-year actuarial survival was 91%. In multivariate analysis, only high TS expression remained an independent predictor of poor survival (HR = 10.77, 95% CI 1.36-84.91; P = 0.02). TS gene polymorphisms were not associated with TS expression or overall survival.ConclusionsHigh TS expression predicts poor outcome after resection of HCC. Molecular markers might be robust predictors of patient outcome after resection of HCC

Roles of tumor suppressors in regulating tumor-associated inflammation.

Loss or silencing of tumor suppressors (TSs) promotes neoplastic transformation and malignant progression. To date, most work on TS has focused on their cell autonomous effects. Recent evidence, however, demonstrates an important noncell autonomous role for TS in the control of tumor-associated inflammation. We review evidence from clinical data sets and mouse model studies demonstrating enhanced inflammation and altered tumor microenvironment (TME) upon TS inactivation. We discuss clinical correlations between tumor-associated inflammation and inactivation of TS, and their therapeutic implications. This review sets forth the concept that TS can also suppress tumor-associated inflammation, a concept that provides new insights into tumor-host interactions. We also propose that in some cases the loss of TS function in cancer can be overcome through inhibition of the resulting inflammatory response, regardless whether it is a direct or an indirect consequence of TS loss

A Study of Thymidylate Synthase Expression as a Biomarker for Resectable Colon Cancer: Alliance (Cancer and Leukemia Group B) 9581 and 89803.

PurposeTumor levels of thymidylate synthase (TS), a target of 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer, have been studied as a predictive or prognostic biomarker with mixed results.Patients and methodsTumor TS levels were prospectively evaluated in two adjuvant therapy trials for patients with resected stage II or III colon cancer. TS expression was determined by standard immunohistochemistry and by automated quantitative analysis. Tumor mismatch repair deficiency (MMR-D) and BRAF c.1799T > A (p.V600E) mutation status were also examined. Relationships between tumor TS, MMR-D, and BRAF mutation status, overall survival (OS), and disease-free survival (DFS) were investigated in the subset of stage III patients.ResultsPatients whose tumors demonstrated high TS expression experienced better treatment outcomes, with DFS hazard ratio (HR) = 0.67, 95% confidence interval (CI) = 0.53, 0.84; and OS HR = 0.68, 95% CI = 0.53, 0.88, for high versus low TS expression, respectively. No significant interaction between TS expression and stage was observed (DFS: interaction HR = 0.94; OS: interaction HR = 0.94). Tumors with high TS expression were more likely to demonstrate MMR-D (22.2% vs. 12.8%; p =  .0003). Patients whose tumors demonstrated both high TS and MMR-D had a 7-year DFS of 77%, compared with 58% for those whose tumors had low TS and were non-MMR-D (log-rank p =  .0006). Tumor TS expression did not predict benefit of a particular therapeutic regimen.ConclusionThis large prospective analysis showed that high tumor TS levels were associated with improved DFS and OS following adjuvant therapy for colon cancer, although tumor TS expression did not predict benefit of 5-FU-based chemotherapy. The Oncologist 2017;22:107-114Implications for Practice: This study finds that measurement of tumor levels of thymidylate synthase is not helpful in assigning specific adjuvant treatment for colorectal cancer. It also highlights the importance of using prospective analyses within treatment clinical trials as the optimal method of determining biomarker utility

Impact and compression after impact experimental study of a composite laminate with a cork thermal shield

The aim of this paper is to present an experimental study of impact and compression after impact (CAI) tests performed on composite laminate covered with a cork thermal shield (TS) intended for launchers fairing. Drop weight impact tests have been performed on composite laminate sheets with and without TS in order to study its effect on the impact damage. The results show the TS is a good mechanical protection towards impact as well as a good impact revealing material. Nevertheless, totally different damage morphology is obtained during the impact test with or without TS, and in particular at high impact energy, the delaminated area is larger with TS. Afterwards, CAI tests have been performed in order to evaluate the TS effect on the residual strength. The TS appears to increase the residual strength for a same impact energy, but at the same time, it presents a decrease in residual strength before observing delamination. In fact, during the impact tests with TS, invisible fibres’ breakages appear before delamination damage contrary to the impacts on the unshielded sheets

Studi Pengaruh Metode L-AD dan SS-AD terhadap Produksi Biogas dari Limbah Sekam Padi

Abstrak – Proses biogas anaerobic digestion berdasarkan total padatannya terbagi menjadi 2 yaitu Liquid Anaerobic Digestion (L-AD) umumnya terjadi pada kondisi dengan konsentrasi solid antara 0,5% dan 15%. Sebaliknya, Solid State Anaerobic Digestion (SS-AD) terjadi pada konsentrasi padat lebih tinggi dari 15%. Penelitian ini bertujuan untuk mengetahui pengaruh produksi yield biogas dari limbah sekam padi dalam kondisi L-AD dan SS-AD. Variabel yang diamati dalam pengamatan yaitu yield biogas kumulatif. Skala laboratorium dari pencernaan anaerobik digunakan dalam penelitian ini dan dioperasikan dalam sistem batch pada suhu kamar. Rasio C/N yang ditetapkan sebesar 25oC. Jumlah total padatan (TS) bervariasi dari 5, 7, 9% untuk kondisi L-AD dan 19, 21, 23% untuk kondisi SS-AD. Karena kandungan lignin yang tinggi pada sekam padi maka dilakukan perlakuan pendahuluan kimia menggunakan natrium hidroksida (NaOH) untuk memecah struktur lignoselulosanya. Kemudian biogas yang dihasilkan diukur dengan menggunakan metode perpindahan air setiap dua hari selama 60 hari. Hasil penelitian menunjukkan pretreatment natrium hidroksida dapat meningkatkan produksi biogas baik pada kondisi L-AD maupun SS-AD. Didapatkan volume produktivitas tertinggi untuk sekam padi pada kondisi L-AD dengan rasio TS 7% dan pada kondisi SS-AD dengan rasio TS 19% masing-masing sebesar 793 dan 935,5 ml. Produksi biogas spesifik pada TS dari 5, 7, 9, 19, 21 dan 23% adalah 57; 56.64; 45.36; 24.62; 15.15; dan 12.45 ml/gr TS. Untuk hasil yield biogas kumulatif tertinggi didapatkan pada SS-AD dengan rasio TS 19% sedangkan kandungan TS lebih tinggi pada L-AD dengan rasio TS 7%. Hal tersebut karena kandungan TS yang lebih tinggi memilki efek minimal pada efisiensi TS dan penurunan dalam produksi biogas, sehingga kondisi L-AD lebih menguntungkan. Kata Kunci: Biogas, Sekam Padi, Konsentrasi Total Padatan (TS), Liquid Anaerobic Digestion (L-AD), Solid State Anaerobic Digestion (SS-AD) Abstract – The process of biogas anaerobic digestion based on its total solid is divided into 2 ie Liquid Anaerobic Digestion (L-AD) generally occurs in conditions with solid concentration between 0.5% and 15%. In contrast, Solid State Anaerobic Digestion (SS-AD) occurs at a solid concentration higher than 15%. This study aims to determine the effect of production of biogas yield from rice husk waste in the conditions of L-AD and SS-AD. The variables observed in the observation were cumulative biogas yield. The laboratory scale of anaerobic digestion was used in this study and operated in a batch system at room temperature. Estimated C / N ratio of 25oC. The total amount of solids (TS) varies from 5, 7, 9% for L-AD conditions and 19, 21, 23% for SS-AD conditions. Because of the high lignin content in rice husks, a chemical preliminary treatment using sodium hydroxide (NaOH) is used to break the lignocellulosic structure. Then the resulting biogas was measured using the method of water movement every two days for 60 days. The results showed that sodium hydroxide pretreatment can increase biogas production in both L-AD and SS-AD conditions. The highest productivity volume for rice husk was found in L-AD condition with TS ratio of 7% and SS-AD condition with TS 19% ratio of 793 and 935.5 ml, respectively. Specific biogas production on TS of 5, 7, 9, 19, 21 and 23% was 57; 56.64; 45.36; 24.62; 15.15; and 12.45 ml / g TS. The highest cumulative biogas yield was obtained in SS-AD with TS ratio of 19% while TS content was higher in L-AD with TS ratio of 7%. This is because the higher TS content has a minimal effect on TS efficiency and a decrease in biogas production, so the L-AD condition is more favorable. Keywords: Biogas, Rice husk, Concentration of Total Solids (TS), Liquid Anaerobic Digestion (L-AD), Solid State Anaerobic Digestion (SS-AD

Neurocognitive Predictors of Treatment Response to Randomized Treatment in Adults with Tic Disorders

Tourette\u27s disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics. However, the role of cognitive control in TS/CTD is not yet understood, particularly in adults. To examine the role of inhibitory control in TS/CTD, the present study investigated this association by assessing the relationship between inhibitory control and treatment response in a large sample of adults with TS/CTD. As part of a large randomized trial comparing behavior therapy versus supportive psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory control was administered to 122 adults with TS/CTD at baseline. We assessed the association between neuropsychological test performance and change in symptom severity, as well as compared the performance of treatment responders and non-responders as defined by the Clinical Global Impression Scale. Results indicated that change in symptoms, and treatment response were not associated with neuropsychological performance on tests of inhibitory control, intellectual ability, or motor function, regardless of type of treatment. The finding that significant change in symptom severity of TS/CTD patients is not associated with impairment or change in inhibitory control regardless of treatment type suggests that inhibitory control may not be a clinically relevant facet of these disorders in adults

Brain structure in pediatric Tourette syndrome

Previous studies of brain structure in Tourette syndrome (TS) have produced mixed results, and most had modest sample sizes. In the present multicenter study, we used structural magnetic resonance imaging (MRI) to compare 103 children and adolescents with TS to a well-matched group of 103 children without tics. We applied voxel-based morphometry methods to test gray matter (GM) and white matter (WM) volume differences between diagnostic groups, accounting for MRI scanner and sequence, age, sex and total GM+WM volume. The TS group demonstrated lower WM volume bilaterally in orbital and medial prefrontal cortex, and greater GM volume in posterior thalamus, hypothalamus and midbrain. These results demonstrate evidence for abnormal brain structure in children and youth with TS, consistent with and extending previous findings, and they point to new target regions and avenues of study in TS. For example, as orbital cortex is reciprocally connected with hypothalamus, structural abnormalities in these regions may relate to abnormal decision making, reinforcement learning or somatic processing in TS