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M E Cazzaniga, L Cortesi, A Ferzi, L Scaltriti, F Cicchiello, M Ciccarese, S Della Torre, F Villa, M Giordano, C Verusio, M Nicolini, A R Gambaro, L Zanlorenzi, E Biraghi, L Legramandi, E Rulli
PURPOSE: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. METHODS: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS)...
October 17, 2016: Breast Cancer Research and Treatment
Kun Zhang, Yanxi Chen, Minfei Qiang, Yini Hao
Single, double, and triple hindfoot arthrodeses are used to correct hindfoot deformities and relieve chronic pain. However, joint fusion may lead to dysfunction in adjacent articular surfaces. We compared range of motion in adjacent joints before and after arthrodesis to determine the effects of each procedure on joint motion. The theory of moment of couple, bending moment and balanced loading was applied to each of 16 fresh cadaver feet to induce dorsiflexion, plantarflexion, internal rotation, external rotation, inversion, and eversion...
October 18, 2016: Scientific Reports
John F Obrycki, Kirk G Scheckel, Nicholas T Basta
Lead (Pb) contaminated soils are a potential exposure hazard to the public. Amending soils with phosphorus (P) may reduce Pb soil hazards. Soil from Cleveland, OH containing 726 ± 14 mg Pb kg(-1) was amended in a laboratory study with bone meal and triple super phosphate (TSP) at 5:1 P:Pb molar ratios. Soil was acidified, neturalized and re-acidified to encourage Pb phosphate formation. PRSTM-probes were used to evaluate changes in soil solution chemistry. Soil acidification did not decrease in vitro bioaccessible (IVBA) Pb using either a pH 1...
October 14, 2016: Environmental Pollution
Artem D Rogachev, Olga I Yarovaya, Sergey V Ankov, Mikhail V Khvostov, Tatyana G Tolstikova, Andrey G Pokrovsky, Nariman F Salakhutdinov
A fast, selective and sensitive procedure for quantitation of the camphor-based anti-influenza agent camphecene in whole rat blood was developed and validated using dried blood spots and LC-MS/MS. The method was validated according to recommendations of the FDA and EMA in terms of selectivity, linearity, accuracy, precision, recovery, matrix factor, stability, and carry-over. Sample preparation included spotting 20μL of whole blood taken from the tail vein onto the paper, drying and extracting the analyte, followed by evaporation of the solvent and analysis of the residue...
October 11, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Xiawen Liu, Lijun Zhu, Biyun Huang, Junjun Huang, Yi Cai, Liu Zhu, Bo Wu, Xiaojing Fu, Xingfei Zhang, Yi Rong, Qing Xiao, Jiewen Guo, Arong Li, Yifei Guo, Mu Yuan
Racemic naftopidil (NAF) is used to treat benign prostatic hyperplasia (BPH) and prostatic cancer (PCa). It exhibits greater efficacy but requires higher dose than other ɑ1-adrenoceptor blockers because of its poor bioavailability. It was previously shown that bioavailability of S(-)-NAF (14.5%) was twice that of R(+)-NAF (6.8%). The present study aimed to elucidate the major factors contributing to the poor and enantioselective bioavailability of NAF. First, absorption of NAF enantiomers was examined using a perfusated intestinal model...
September 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
Marina Vafeiadi, Theano Roumeliotaki, Georgia Chalkiadaki, Panu Rantakokko, Hannu Kiviranta, Eleni Fthenou, Soterios A Kyrtopoulos, Manolis Kogevinas, Leda Chatzi
BACKGROUND: Persistent organic pollutants (POPs) are a group of diverse substances, including polychlorinated biphenyls (PCBs) and organochlorine pesticides that are resistant to biodegradation and ubiquitously present in our environment. Exposure to endocrine disrupting chemicals such as POPs has been linked to type 2 diabetes and metabolic disturbances in epidemiological and animal studies, but little is known about POPs exposure during pregnancy and the development of gestational diabetes mellitus (GDM)...
October 12, 2016: Environment International
Yihung Huang, Evan Farkash
As both T cell and antibody-mediated rejection can have a subclinical phase, protocol biopsies provide an early opportunity to intervene before the onset of clinical allograft dysfunction. Protocol biopsies are usually done after reperfusion to establish baseline, between 3 and 6 months to identify subclinical rejection, and at 6-12 months to assess chronicity and persistent inflammation that have prognostic implication. Treatment of both subclinical T cell and antibody-mediated rejection prevents progression of rejection and development of interstitial fibrosis/tubular atrophy or transplant glomerulopathy...
September 2016: Advances in Chronic Kidney Disease
Chun-Hui Zhang, Kai Chen, Yan Jiao, Lin-Li Li, Ya-Ping Li, Rong-Jie Zhang, Ming-Wu Zheng, Lei Zhong, Shen-Zhen Huang, Chun-Li Song, Wan-Ting Lin, Jiao Yang, Rong Xiang, Bing Peng, Jun-Hong Han, Guang-Wen Lu, Yu-Quan Wei, Sheng-Yong Yang
Herein we report the sophisticated process of structural optimization towards a previously disclosed Src inhibitor, compound 1, which showed high potency in the treatment of triple negative breast cancer (TNBC) both in vitro and in vivo, but had considerable toxicity. A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives were synthesized. In vitro cell-based phenotypic screening together with in vivo assays, and structure-activity relationship (SAR) studies finally led to the discovery of N-(3-((4-amino-1-(trans-4-hydroxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)ethynyl)-4-methylphenyl)-4-methyl-3-(trifluoromethyl)benzamide (13an)...
October 14, 2016: Journal of Medicinal Chemistry
Ernesto Solis, R Aaron Bola, Bradley J Fasulo, Eugene A Kiyatkin
Glucose enters the brain extracellular space from arterial blood and its proper delivery is essential for metabolic activity of brain cells. By using enzyme-based biosensors coupled with high-speed amperometry in freely moving rats, we previously showed that glucose levels in the nucleus accumbens (NAc) display high variability, increasing rapidly following exposure to various arousing stimuli. In this study, the same technology was used to assess NAc glucose fluctuations induced by intravenous heroin. Heroin passively injected at a low dose optimal for maintaining self-administration behavior (100 μg/kg) induces a rapid but moderate glucose rise (~150-200 μM or ~15-25% over resting baseline)...
October 13, 2016: ACS Chemical Neuroscience
Jong-Lyel Roh, Hye Jin Jang, Eun Hye Kim, Daiha Shin
AIMS: The glutathione (GSH), thioredoxin (Trx), and Nrf2 systems represent a major defense against reactive oxygen species (ROS), the cellular imbalance of which in cancer promotes growth and therapeutic resistance. This study investigated whether targeting the GSH, Trx, and Nrf2 antioxidant systems effectively eliminated head and neck cancer (HNC). RESULTS: At high concentrations, auranofin, but not buthionine sulfoximine (BSO) alone, decreased the viability of HNC, whereas even at low concentrations, auranofin plus BSO synergized to kill HNC cells...
October 12, 2016: Antioxidants & Redox Signaling
Sandra J Tanenbaum
The formulation of the triple aim responds to three problems facing the US health care system: high cost, low quality, and poor health status. The purpose of this article is to analyze the potential of the health care system to achieve the triple aim and, specifically, the attempt to improve population health by rewarding providers who contain costs. The first section of the article will consider the task of improving population health through the health care system. The second section of the article will discuss CMS's efforts to pay providers to achieve the triple aim, that is, to improve health care and population health while containing cost...
October 11, 2016: Journal of Health Politics, Policy and Law
Ting Zhang, Hongyang Liu, Xue Chen, Zhirong Wang, Shuo Wang, Chunfeng Qu, Jingzhi Zhang, Xuemei Xu
Numerous types of human papillomaviruses (HPVs) have been identified, and the global burden of diseases associated with HPV infection is remarkable, especially in developing regions. Thus a low-cost broad-spectrum prophylactic vaccine is urgently needed. The N-terminal amino acid 17-36 of HPV 16 L2 protein is confirmed to be a major cross-neutralizing epitope (RG-1 epitope). Monomeric proteins containing RG-1 epitopes and scaffold proteins, such as bacterial thioredoxin or modified IgG1 Fc fragment and L2 epitope fusion protein, induced cross-neutralizing antibodies, arousing the possibility of the development of low-cost monomeric vaccine in bacterial expression system...
October 8, 2016: Vaccine
Ling Schneider, Nikolaj A Feidenhans'l, Agnieszka Telecka, Rafael J Taboryski
We report a simple one-step maskless fabrication of inverted pyramids on silicon wafers by reactive ion etching. The fabricated surface structures exhibit excellent anti-reflective properties: The total reflectance of the nano inverted pyramids fabricated by our method can be as low as 12% without any anti-reflective layers, and down to only 0.33% with a silicon nitride coating. The results from angle resolved scattering measurements indicate that the existence of triple reflections is responsible for the reduced reflectance...
October 11, 2016: Scientific Reports
Evan L Anderson, Nicole M Gingery, Paul Garrett Boswell, Xin V Chen, Jozsef Rabai, Philippe Buhlmann
Potentiometric selectivities show that in fluorous ion-selective electrode membranes the tetrabutylammonium ion binds to fluorophilic proton ionophores. For the ionophore bis 3-(perfluorooctyl)propyl](2,2,2-trifluoroethyl)amine, this type of interaction is confirmed by the effect of the ionophore on the ionic conductivity of perfluoro(perhydrophenanthrene) solutions of a fluorophilic NBu4(+) salt. In this system, ion pairs, triple ions, and higher ionic aggregates dominate over single ions, and the ionophore increases the conductivity by favoring the formation of ion aggregates with a net charge...
October 10, 2016: Journal of Physical Chemistry. B
Maneesh Gujrati, Amita M Vaidya, Margaret Mack, Dayton Snyder, Anthony Malamas, Zheng-Rong Lu
RNAi-mediated knockdown of oncogenes associated with drug resistance can potentially enhance the efficacy of chemotherapy. Here, we have designed and developed targeted dual pH-sensitive lipid-siRNA self-assembly nanoparticles, RGD-PEG(HZ)-ECO/siRNA, which can efficiently silence the oncogene, eukaryotic translation initiation factor 4E (eIF4E), and consequently resensitize triple-negative breast tumors to paclitaxel. The dual pH-sensitive function of these nanoparticles facilitates effective cytosolic siRNA delivery in cancer cells, both in vitro and in vivo...
October 10, 2016: Advanced Healthcare Materials
Juntuo Zhou, Yuxin Yin
Advances in liquid chromatography-mass spectrometry (LC-MS) instruments and analytical strategies have brought about great progress in targeted metabolomics analysis. This methodology is now capable of performing precise targeted measurement of dozens or hundreds of metabolites in complex biological samples. Classic targeted quantification assay using the multiple reaction monitoring (MRM) mode has been the foundation of high-quality metabolite quantitation. However, utilization of this strategy in biological studies has been limited by its relatively low metabolite coverage and throughput capacity...
October 10, 2016: Analyst
Yoon Yang Jung, Chang Lim Hyun, Min-Sun Jin, In Ae Park, Yul Ri Chung, Bobae Shim, Kyu Ho Lee, Han Suk Ryu
PURPOSE: There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy. METHODS: One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled...
September 2016: Journal of Breast Cancer
Yong Hwa Eom, Hyung Suk Kim, Ahwon Lee, Byung Joo Song, Byung Joo Chae
PURPOSE: B-cell lymphoma 2 (BCL2) is an antiapoptosis protein and an important clinical breast cancer prognostic marker. As the role of BCL2 is dependent on the estrogen receptor (ER) status, this effect might differ according to molecular subtypes. The aim of this study was to evaluate the relationship between the prognostic outcomes and BCL2 expression among the molecular subtypes. METHODS: We retrieved the data of 1,356 patients who were newly diagnosed with malignant breast cancer between November 2006 and November 2011...
September 2016: Journal of Breast Cancer
Valentina Damiano, Giulia Brisotto, Silvia Borgna, Alessandra di Gennaro, Michela Armellin, Tiziana Perin, Michela Guardascione, Roberta Maestro, Manuela Santarosa
Loss of expression of miR-200 family members has been implicated in cellular plasticity, a phenomenon that accounts for epithelial-to-mesenchymal transition (EMT) and stem-like features of many carcinomas and is considered a major cause of tumor aggressiveness and drug resistance. Nevertheless, the mechanisms of miR-200 downregulation in breast cancer are still largely unknown. Here we show that miR-200c expression inversely correlates with miR-200c/miR-141 locus methylation in triple-negative breast tumors (TNBC)...
September 22, 2016: Genes, Chromosomes & Cancer
Christoph Schliemann, Joachim Gerss, Stefanie Wiebe, Jan-Henrik Mikesch, Nicola Knoblauch, Tim Sauer, Linus Angenendt, Tobias Kewitz, Marc Urban, Trude Butterfass-Bahloul, Sabine Edemir, Kerstin Vehring, Carsten Müller-Tidow, Wolfgang E Berdel, Utz Krug
: Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles...
2016: PloS One
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