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https://www.readbyqxmd.com/read/29145602/genotype-based-selection-of-treatment-for-patients-with-advanced-colorectal-cancer-seticc-a-pharmacogenetic-based-randomized-phase-ii-trial
#1
A Abad, E Martínez-Balibrea, J M Viéitez, V A Orduña, P García Alfonso, J L Manzano, B Massutí, M Benavides, A Carrato, M Zanui, J Gallego, C Grávalos, V Conde, M Provencio, M Valladares, R Salazar, J Sastre, C Montagut, F Rivera, E Aranda
Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms...
November 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29145473/suppression-and-resolution-of-autoimmune-arthritis-by-rhesus-%C3%AE-defensin-1-an-immunomodulatory-macrocyclic-peptide
#2
Justin B Schaal, Dat Q Tran, Akshay Subramanian, Reshma Patel, Teresina Laragione, Kevin D Roberts, Katie Trinh, Prasad Tongaonkar, Patti A Tran, Dmitriy Minond, Gregg B Fields, Paul Beringer, André J Ouellette, Percio S Gulko, Michael E Selsted
θ-defensins constitute a family of macrocyclic peptides expressed exclusively in Old World monkeys. The peptides are pleiotropic effectors of innate immunity, possessing broad spectrum antimicrobial activities and immunoregulatory properties. Here we report that rhesus θ-defensin 1 (RTD-1) is highly effective in arresting and reversing joint disease in a rodent model of rheumatoid arthritis (RA). Parenteral RTD-1 treatment of DA/OlaHsd rats with established pristane-induced arthritis (PIA) rapidly suppressed joint disease progression, restored limb mobility, and preserved normal joint architecture...
2017: PloS One
https://www.readbyqxmd.com/read/29138774/exploring-the-effect-of-substituent-in-the-hydrazone-ligand-of-a-family-of-%C3%AE-oxidodivanadium-v-hydrazone-complexes-on-structure-dna-binding-and-anticancer-activity
#3
Debashis Patra, Subhabrata Paul, Indira Majumder, Nayim Sepay, Sachinath Bera, Rita Kundu, Michael G B Drew, Tapas Ghosh
The reaction of 2-hydroxybenzoylhydrazine (H2bh) separately with equimolar amounts of [V(IV)O(aa)2] and [V(IV)O(ba)2] in CHCl3 afforded the complexes [VO3(HL(1))2] (1) and [VO3(HL(2))2] (2) respectively in good to excellent yield ((HL(1))(2-) and (HL(2))(2-) represent respectively the dianionic form of 2-hydroxybenzoylhydrazones of acetylacetone (H3L(1)) and benzoylacetone (H3L(2)) (general abbreviation H3L)). From X-ray structure analysis, the V(V)-O-V(V) angle was found to be ∼115° and 180° in 1 and 2 respectively...
November 15, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29136066/unsuspected-lymphomatoid-granulomatosis-in-a-patient-with-antisynthetase-syndrome
#4
Stephanie L Skala, Alexandra C Hristov, Johann E Gudjonsson, May P Chan
Clinical diagnosis of lymphomatoid granulomatosis (LYG) often is difficult, especially in patients with multiple comorbidities. We present a 60-year-old woman with worsening fatigue, night sweats, unintentional weight loss, and dyspnea of 2 weeks' duration. Her medical history was remarkable for recent radiation therapy for recurrent breast cancer and antisynthetase syndrome complicated by interstitial lung disease and controlled with azathioprine. Computed tomography showed ground-glass opacities and nodular infiltrates in all lung lobes, raising concern for radiation pneumonitis and drug toxicity...
October 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/29133594/competitive-kinase-enrichment-proteomics-reveals-that-abemaciclib-inhibits-gsk3%C3%AE-and-activates-wnt-signaling
#5
Emily M Cousins, Dennis Goldfarb, Feng Yan, Jose Roques, David B Darr, Gary L Johnson, Michael B Major
The cellular and organismal phenotypic response to a small-molecule kinase inhibitor is defined collectively by the inhibitor's targets and their functions. The selectivity of small-molecule kinase inhibitors is commonly determined in vitro, using purified kinases and substrates. Recently, competitive chemical proteomics has emerged as a complementary, unbiased, cell-based methodology to define the target landscape of kinase inhibitors. Here, we evaluated and optimized a competitive multiplexed inhibitor bead mass spectrometry (MIB/MS) platform using cell lysates, live cells, and treated mice...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133048/structural-optimization-and-structure-activity-relationship-studies-of-n-phenyl-7-8-dihydro-6h-pyrimido-5-4-b-1-4-oxazin-4-amine-derivatives-as-a-new-class-of-inhibitors-of-ret-and-its-drug-resistance-mutants
#6
Jiao Yang, Kai Chen, Guo Zhang, Qiu-Yuan Yang, Yue-Shan Li, Shen-Zhen Huang, Yan-Lin Wang, Wei Yang, Xiao-Juan Jiang, Heng-Xiu Yan, Jing-Qiang Zhu, Rong Xiang, You-Fu Luo, Wei-Min Li, Yu-Quan Wei, Lin-Li Li, Sheng-Yong Yang
The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors. In this investigation, we report the structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of RET inhibitors. Among all the obtained kinase inhibitors, 1-(5-(tert-butyl)isoxazol-3-yl)-3-(4-((6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-yl)amino)phenyl)urea (17d) is a multi-kinase inhibitor and potently inhibits RET and its drug resistance mutants...
September 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29132803/high-dose-irradiation-after-pleurectomy-decortication-or-biopsy-for-pleural-mesothelioma-treatment
#7
E Parisi, A Romeo, A Sarnelli, G Ghigi, S R Bellia, E Neri, S Micheletti, B Dipalma, D Arpa, G Furini, M A Burgio, G Genestreti, C Gurioli, S Sanna, P Bovolato, F Rea, G Storme, E Scarpi, C Arienti, A Tesei, R Polico
PURPOSE: The role played by radiation therapy after pleurectomy/decortication or surgical biopsy in malignant pleural mesothelioma is uncertain. We treated patients with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy in an attempt to keep lung toxicity to a minimum. The present study reports the feasibility and toxicity of this approach. MATERIAL AND METHODS: Between 2008 and 2012, 36 patients with malignant pleural mesothelioma underwent accelerated hypofractionated radiotherapy to the hemithorax after pleurectomy/decortication (19 patients) or biopsy (17 patients)...
November 10, 2017: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/29132040/inclusion-complexes-between-cisplatin-and-oxidized-carbon-nanostructures-a-theoretical-approach
#8
Leonardo A De Souza, Hélio F Dos Santos, Luciano T Costa, Wagner B De Almeida
The toxicity of inclusion compounds formed by carbon nanostructures depends on its functionalized surface, use of solvents, dosage and other properties. Molecular modeling has potentially contributed to the understanding of the chemical nature of the formation of these systems and allows advancement in studies of the mechanism of transport, release of drugs and their biological implications. This work reports a quantum chemical investigation of the inclusion complexes formation between oxidized carbon nanotube (CNTox)/nanocone (CNCox) structure and cisplatin molecule, using the density functional theory (DFT) with the B3LYP functional and 6-31G(d,p)/LanL2DZ standard basis sets...
November 3, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29130336/antiproliferative-and-cytotoxic-secondary-metabolites-from-fruits-of-leplaea-mayombensis
#9
Sidjui Sidjui Lazare, Soh Désiré, Dameue Tegang Joel Ebenezer, Happi Tchakounté Brice, Toghueo Kouipou Rufin Marie, Wembe Ngouonpe Alain, Shaiq Ali Muhammad, Folefoc Ngosong Gabriel
Two new seco-lanostane-type triterpenes, named mayomlactones A (1) and B (2) were isolated from the fruits of Leplaea mayombensis together with 10 known compounds (3-12). Structures of the new compounds were elucidated by extensive spectroscopic studies. Except compounds 11 and 12, all the other chemical compounds are newly reported from Leplaea genus. From the results of this investigation, compounds 1-10 were examined for antiproliferative activity against HeLa cells as well as cytotoxicity against 3T3 cell line...
November 13, 2017: Natural Product Research
https://www.readbyqxmd.com/read/29129744/upregulation-of-aquaporin-3-expression-by-diterpenoids-in-euphorbia-pekinensis-is-associated-with-activation-of-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-the-co-culture-system-of-ht-29-and-raw-264-7%C3%A2-cells
#10
Hongli Yu, Lian Liu, Kuilong Wang, Hao Wu, Wei Wang, Xingde Zhang, Guojing Cui, Xiaobing Cui, Jianyu Huang
This study was designed to evaluate the toxic effects of diterpenoids separated from the roots of Euphorbia pekinensis, a type of widely used traditional Chinese medicine. This herb has intestinal toxicity associated with its complex diterpenoids. In this study, the diterpenoids (pekinenin A, pekinenin C, pekinenin F, pekinenin G, yuexiandajisu A, (-)-(1S)-15-hydroxy-18-carboxycembrene) elevated the expression of interleukin 1 beta and tumor necrosis factor alpha in a dose-dependent manner at doses of 6.25, 12...
November 9, 2017: Biochimie
https://www.readbyqxmd.com/read/29129443/adjuvant-chemotherapy-with-or-without-bevacizumab-in-patients-with-resected-non-small-cell-lung-cancer-e1505-an-open-label-multicentre-randomised-phase-3-trial
#11
Heather A Wakelee, Suzanne E Dahlberg, Steven M Keller, William J Tester, David R Gandara, Stephen L Graziano, Alex A Adjei, Natasha B Leighl, Seena C Aisner, Jan M Rothman, Jyoti D Patel, Mark D Sborov, Sean R McDermott, Roman Perez-Soler, Anne M Traynor, Charles Butts, Tracey Evans, Atif Shafqat, Andrew E Chapman, Samer S Kasbari, Leora Horn, Suresh S Ramalingam, Joan H Schiller
BACKGROUND: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC. METHODS: We did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC...
November 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29129435/etirinotecan-pegol-nktr-102-in-third-line-treatment-of-patients-with-metastatic-or-recurrent-non-small-cell-lung-cancer-results-of-a-phase-ii-study
#12
Charu Aggarwal, Roger B Cohen, Eddy Yu, Wei-Ting Hwang, Joshua M Bauml, Evan Alley, Tracey L Evans, Corey J Langer
BACKGROUND: Third-line treatment options are limited for patients with metastatic non-small-cell lung cancer (NSCLC). Etirinotecan pegol (NKTR-102) is a long-acting topoisomerase-I inhibitor. We conducted a single-arm phase II trial to evaluate its efficacy in third-line treatment. PATIENTS AND METHODS: Patients aged ≥ 18 years with histologically proven NSCLC who had received 2 previous systemic therapy regimens, measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, and adequate end-organ function were eligible...
October 19, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29124649/angiotensin-receptor-blockade-a-novel-approach-for-symptomatic-radiation-necrosis-after-stereotactic-radiosurgery
#13
Mudit Chowdhary, Derick Okwan-Duodu, Jeffrey M Switchenko, Robert H Press, Jaymin Jhaveri, Zachary S Buchwald, Jim Zhong, Bhavana V Chapman, Ranjit S Bindra, Joseph N Contessa, Henry S Park, James B Yu, Roy H Decker, Jeffrey J Olson, Nelson M Oyesiku, Ross A Abrams, Hui-Kuo G Shu, Walter J Curran, Ian R Crocker, Kirtesh R Patel
Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes...
November 9, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29123537/association-mapping-of-ferrous-zinc-and-aluminum-tolerance-at-the-seedling-stage-in-indica-rice-using-magic-populations
#14
Lijun Meng, Baoxiang Wang, Xiangqian Zhao, Kimberly Ponce, Qian Qian, Guoyou Ye
Excessive amounts of metal are toxic and severely affect plant growth and development. Understanding the genetic control of metal tolerance is crucial to improve rice resistance to Fe, Zn, and Al toxicity. The multi-parent advanced generation inter-cross (MAGIC) populations were genotyped using a 55 K rice SNP array and screened at the seedling stage for Fe, Zn, and Al toxicity using a hydroponics system. Association analysis was conducted by implementing a mixed linear model (MLM) for each of the five MAGIC populations double cross DC1 (founders were SAGC-08, HHZ5-SAL9-Y3-Y1, BP1976B-2-3-7-TB-1-1, PR33282-B-8-1-1-1-1-1), double cross DC2 (founders of double cross were FFZ1, CT 16658-5-2-2SR-2-3-6MP, IR 68, IR 02A127), eight parents population 8way (founders were SAGC-08, HHZ5-SAL9-Y3-Y1, BP1976B-2-3-7-TB-1-1, PR33282-B-8-1-1-1-1-1, FFZ1, CT 16658-5-2-2SR-2-3-6MP, IR 68, IR 02A127), DC12 (DC1+DC2) and rice multi-parent recombinant inbred line population RMPRIL (DC1+DC2+8way)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29121563/benthic-invertebrate-exposure-and-chronic-toxicity-risk-analysis-for-cyclic-volatile-methylsiloxanes-comparison-of-hazard-quotient-and-probabilistic-risk-assessment-approaches
#15
Kent B Woodburn, Rita M Seston, Jaeshin Kim, David E Powell
This study utilized probabilistic risk assessment techniques to compare field sediment concentrations of the cyclic volatile methylsiloxane (cVMS) materials octamethylcyclotetrasiloxane (D4, CAS # 556-67-2), decamethylcyclopentasiloxane (D5, CAS # 541-02-6), and dodecamethylcyclohexasiloxane (D6, CAS # 540-97-6) to effect levels for these compounds determined in laboratory chronic toxicity tests with benthic organisms. The concentration data for D4/D5/D6 in sediment were individually sorted and the 95th centile concentrations determined in sediment on an organic carbon (OC) fugacity basis...
October 28, 2017: Chemosphere
https://www.readbyqxmd.com/read/29119293/asparaginase-erwinia-chrysanthemi-effectively-depletes-plasma-glutamine-in-adult-patients-with-relapsed-refractory-acute-myeloid-leukemia
#16
Ashkan Emadi, Jennie Y Law, Erin T Strovel, Rena G Lapidus, Linda J B Jeng, Myounghee Lee, Miriam G Blitzer, Brandon A Carter-Cooper, Danielle Sewell, Isabella Van Der Merwe, Sunita Philip, Mohammad Imran, Stephen L Yu, Hongxia Li, Philip C Amrein, Vu H Duong, Edward A Sausville, Maria R Baer, Amir T Fathi, Zeba Singh, Søren M Bentzen
Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of acute myeloid leukemia (AML), as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this Phase I study, we sought to determine the dose of Erwinaze that safely and effectively depletes plasma Gln levels to ≤ 120 μmol/L in patients with relapsed or refractory (R/R) AML...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29114607/the-impact-of-different-stereotactic-radiation-therapy-regimens-for-brain-metastases-on-local-control-and-toxicity
#17
Rachel B Jimenez, Brian M Alexander, Anand Mahadevan, Andrzej Niemierko, Selvan Rajakesari, Nils D Arvold, Scott R Floyd, Kevin S Oh, Jay S Loeffler, Helen A Shih
Purpose: Stereotactic radiation therapy (SRT) enables focused, short course, high dose per fraction radiation delivery to brain tumors that are less ideal for single fraction treatment because of size, shape, or close proximity to sensitive structures. We sought to identify optimal SRT treatment regimens for maximizing local control while minimizing morbidity. Methods and materials: We performed a retrospective review of patients treated with SRT for solid brain metastases using variable dose schedules between 2001 and 2011 at 3 academic hospitals...
July 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29114605/diffuse-large-b-cell-lymphoma-in-very-elderly-patients-over-80-years-old-incorporating-consolidative-radiation-therapy-into-management-decisions
#18
Chelsea C Pinnix, Therese Y Andraos, Bouthaina Dabaja, Sarah Milgrom, Grace Smith, Dai Chihara, Andrea Ng, Luis E Fayad, Yasuhiro Oki, Sattva Neelapu, Jason Westin, M Alma Rodriguez, Loretta J Nastoupil
Purpose: The population of patients aged 80 years or older who are diagnosed with diffuse large B-cell lymphoma (DLBCL) continues to increase, but an optimal treatment strategy has not been established. We sought to examine the influence of consolidative radiation therapy (RT) on outcome and toxicity among the very elderly diagnosed with stage I-IV DLBCL. Methods and materials: We evaluated 131 patients treated at a single institution between 2002 and 2014 who were eligible for RT after successful treatment with chemotherapy...
July 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29114597/neoadjuvant-twice-daily-chemoradiotherapy-for-esophageal-cancer-treatment-related-mortality-and-long-term-outcomes
#19
Stuart E Samuels, Matthew H Stenmark, Jae Y Lee, Jonathan B McHugh, James A Hayman, Mark B Orringer, Susan G Urba, Libin Sun, Congying Xie, Feng-Ming Kong, Kyle C Cuneo
Objective: Because of the short potential doubling time of esophageal cancer, there is a theoretical benefit to using an accelerated radiation treatment schedule. This study evaluates outcomes and treatment-related mortality and morbidity of patients treated with neoadjuvant hyperfractionated accelerated chemoradiation for resectable esophageal cancer. Methods and materials: Outcomes from 250 consecutive patients with resectable esophageal cancer treated with preoperative hyperfractionated accelerated chemoradiotherapy (45 Gy in 30 twice-daily fractions over 3 weeks) followed by planned transhiatal esophagectomy were analyzed...
July 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29109030/layer-by-layer-assembly-of-graphene-oxide-on-thermosensitive-liposomes-for-photo-chemotherapy
#20
Mohadeseh Hashemi, Meisam Omidi, Bharadwaj Muralidharan, Lobat Tayebi, Matthew J Herpin, Mohammad Ali Mohagheghi, Javad Mohammadi, Hugh D C Smyth, Thomas E Milner
Stimuli responsive polyelectrolyte nanoparticles have been developed for chemo-photothermal destruction of breast cancer cells. This novel system, called layer by layer Lipo-graph (LBL Lipo-graph), is composed of alternate layers of graphene oxide (GO) and graphene oxide conjugated poly (l-lysine) (GO-PLL) deposited on cationic liposomes encapsulating doxorubicin. Various concentrations of GO and GO-PLL were examined and the optimal LBL Lipo-graph was found to have a particle size of 267.9 ± 13 nm, zeta potential of +43...
November 8, 2017: Acta Biomaterialia
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