Targeting angiogenesis in advanced non-small-cell lung cancer: are biomarkers needed?

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Parallel J-W Monte Carlo Simulations of Thermal Phase Changes in Finite-size Systems

The thermodynamic properties of 59 TeF6 clusters that undergo temperature-driven phase transitions have been calculated with a canonical J-walking Monte Carlo technique. A parallel code for simulations has been developed and optimized on SUN3500 and CRAY-T3E computers. The Lindemann criterion shows that the clusters transform from liquid to solid and then from one solid structure to another in the temperature region 60-130 K.Comment: 4 pages, 5 figures; presented at the conference on computational physics, Aachen (2001) accepted for publication in Comp.Phys.Com

ANALISIS SISTEM PERAWATAN PADA HIDROLIK MESIN PEMOTONG PADI

Pada dasarnya Sistem hidrolik sebetulnya sudah banyak dikenal oleh kalangan masyarakat luas. Salah satu yang berperan penting dalam sistem hidrolik adalah silinder hidrolik, dari beberapa data yang ada, kerusakan yang paling sering ditemukan dalam sistem hidrolik yaitu silinder hidrolik. Silinder hidrolik berperan penting dalam mempermudah dan mempercepat sistem kerja pemanen atau pemotong padi. Silinder hidrolik berguna untuk menaikkan Bucket (penuai), Reel (penggulung). Silinder hidrolik memiliki presentase kerusakan yang cukup besar. Berdasarkan latar belakang permasalahan diatas, maka rumusan masalah yang dibahas adalah bagaimana mengetahui nilai Availability, Performance, dan Rate Of Quality dengan metode Overal Equipment Effectivenes (OEE) serta meminimalisir kerusakan silinder hidrolik menggunakan metode TPM (Total Productive Maintenance), mengetahui penyebab kerusakan pada silinder hidrolik. Mengetahui usulan masalah pada silinder hidrolik, Mengetahui faktor penyebab dan kerusakan pada silinder hidrolik, Pemeliharaan (maintenance) merupakan suatu kegiatan untuk memelihara atau menjaga fasilitas atau suatu mesin dan mengadakan perbaikan atau pergantian yang diperlukan agar dapat menghasilkan tenaga yang maksimum dan umur mesin yang awet. Dari hasil perhitungan nilai avaibility tersebut maka rasio operation time unit terhadap loading time periode maret – juni sesuai dengan standart dunia 90%. Untuk perhitungan nilai persentase performa efficiency belum sesuai standar dunia 95% dan untuk perhitungan nilai rate of quality belum sesuai dengan standart dunia 99,9%, kemudian dari perhitungan nilai persentase Overal Equipment Effectiveness Dari perhitungan nilai persentase Overal Equipment Effectiveness belum sesuai dengan standart dunia 85%

Maintenance bevacizumab beyond first-line paclitaxel plus bevacizumab in patients with Her2-negative hormone receptor-positive metastatic breast cancer. Efficacy in combination with hormonal therapy

Background: Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT.Methods: Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not.Results: Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev.Conclusion: Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents

Inflammatory markers as prognostic factors of survival in patients affected by hepatocellular carcinoma undergoing transarterial chemoembolization

Transarterial chemoembolization (TACE) is a good choice for hepatocellular carcinoma (HCC) treatment when surgery and liver transplantation are not feasible. Few studies reported the value of prognostic factors influencing survival after chemoembolization. In this study, we evaluated whether preoperative inflammatory factors such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio affected our patient survival when affected by hepatocellular carcinoma. Methods. We retrospectively evaluated a total of 72 patients with hepatocellular carcinoma that underwent TACE. We enrolled patients with different etiopathogeneses of hepatitis and histologically proven HCC not suitable for surgery. The overall study population was dichotomized in two groups according to the median NLR value and was analyzed also according to other prognostic factors. Results. The global median overall survival (OS) was 28 months. The OS in patients with high NLR was statistically significantly shorter than that in patients with low NLR. The following pretreatment variables were significantly associated with the OS in univariate analyses: age, Child-Pugh score, BCLC stage, INR, and NLR. Pretreated high NLR was an independently unfavorable factor for OS. Conclusion. NLR could be considered a good prognostic factor of survival useful to stratify patients that could benefit from TACE treatment

COX-2 targeting in cancer: a new beginning?

Cyclo-oxygenase-2 (COX-2), the inducible enzyme catalyzing the rate-limiting step in the conversion of arachidonic acid into eicosanoids, is overexpressed in a wide variety of malignancies and associates with poor prognostic features [1]. Consequently, selective COX-2 inhibitors have been explored as therapeutic or chemopreventive agents in different settings; however, initial enthusiasm was tempered by reports of substantial gastrointestinal toxicity as well as of increased cardiovascular risk, mostly coming from postmarketing use as anti-inflammatory drugs and Cancer Research Campaign (UK) chemoprevention trials and eventually resulting in the withdrawal of rofecoxib from the market [2]

Do institutional arrangements make a difference to transport policy and implementation? Lessons for Britain

This paper describes local government decision-making in transport in three areas of the UK, London, West Yorkshire and Edinburgh, in which major changes in local government decision-making structures have taken place over the last decade, and between which arrangements are now very different. The research discusses whether institutional change has had a beneficial or adverse effect, and whether any of the current structures provides a more effective framework for policy development and implementation. The results show that although the sites share a broadly common set of objectives there are differences in devolved responsibilities and in the extent to which various policy options are within the control of the bodies charged with transport policy delivery. The existence of several tiers of government, coupled with the many interactions required between these public sector bodies and the predominantly private sector public transport operators appears to create extra transactional barriers and impedes the implementation of the most effective measures for cutting congestion. There is, however, a compelling argument for the presence of an overarching tier of government to organise travel over a spatial scale compatible with that of major commuter patterns. The extent to which such arrangements currently appear to work is a function of the range of powers and the funding levels afforded to the co-ordinating organisation

Osimertinib in patients with advanced epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: Rationale, evidence and place in therapy

The identification of epidermal growth factor receptor (EGFR) mutations represented a fundamental step forward in the treatment of advanced non-small cell lung cancer (NSCLC) as they define a subset of patients who benefit from the administration of specifically designed targeted therapies. The inhibition of mutant EGFR through EGFR-tyrosine kinase inhibitors (TKIs), either reversible, first-generation gefitinib and erlotinib, or irreversible, second-generation afatinib, has dramatically improved the prognosis of patients harboring this specific genetic alteration, leading to unexpected clinical benefit. Unfortunately, virtually all patients who initially respond to treatment develop acquired resistance to EGFR-TKIs within 9-14 months. The EGFR T790M secondary mutation has emerged as a cause of treatment failure in approximately 60% of resistant cases. To date, several compounds designed with the aim to overcome T790M-mediated resistance are under clinical investigation. The aim of this review is to discuss emerging data regarding the third-generation EGFR-TKI, osimertinib, for the treatment of EGFR T790M mutant advanced NSCLC

Clinical significance of PTEN and p-Akt co-expression in HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapies

Objective: The phosphatase and tensine homologue gene (PTEN) plays a crucial role in proliferation and survival of cancer cells by antagonizing the function of phosphatidylinositol 3'-kinase (PI3K), which, in turn, results in decreased Akt activity. We investigated the clinical impact of the expression of PTEN, p-Akt and PI3K in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab-based therapies. Methods: Seventy-three patients treated with trastuzumab-based therapies were included and followed prospectively. PTEN, p-Akt and PI3K expression was determined by immunohistochemistry. Results: PTEN, p-Akt and PI3K resulted positive in 48%, 71% and 46.5% of patients, respectively. A significant correlation between PTEN and p-Akt (kappa 0.22, p = 0.03) and p-Akt and PI3K (kappa 0.20, p = 0.05) was observed. PTEN-positive patients had a progression-free survival (PFS) longer than PTEN-negative ones (p = 0.06). When grouped together, patients co-expressing PTEN and p-Akt had a statistically significant longer PFS as compared to the rest of patients (p = 0.01). At the multivariate analysis, PTEN and p-Akt co-expression was an independent predictor of lower risk of progression (hazard ratio 0.53, p = 0.05). Conclusion: In HER2-positive MBC, basal co-expression of PTEN and p-Akt might identify those patients who are more likely to benefit from trastuzumab-based therapies