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https://www.readbyqxmd.com/read/29341936/rheumatic-manifestations-among-cancer-patients-treated-with-immune-checkpoint-inhibitors
#1
REVIEW
Merav Lidar, Eitan Giat, Daniela Garelick, Yuval Horowitz, Howard Amital, Yael Steinberg-Silman, Jacob Shachter, Ronnie Shapira-Frommer, Gal Markel
BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. Aim To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts...
January 13, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29341908/induction-of-au-methotrexate-conjugates-by-sugar-molecules-production-assembly-mechanism-and-bioassay-studies
#2
Wei-Yuan Wang, Xiu-Fen Zhao, Xiao-Han Ju, Ping Liu, Jing Li, Ya-Wen Tang, Shu-Ping Li, Xiao-Dong Li, Fu-Gui Song
Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes were used as the precursors to form Au-MTX conjugates. Addition of different types of sugar molecules with abundant hydroxyl groups resulted in the formation of Au-MTX conjugates featuring distinct characteristics that could be explained by the diverse capping mechanisms of sugar molecules. That is, the instant-capping mechanism of glucose favored the generation of peanut-like Au-MTX conjugates with high colloidal stability while the post-capping mechanism of dextran and sucrose resulted in the production of Au-MTX conjugates featuring excellent near-infrared (NIR) optical properties with a long-wavelength plasmon resonance near 630-760 nm...
January 13, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29341500/investigation-of-the-free-heavy-chain-homodimers-of-a-monoclonal-antibody
#3
Hyo Helen Chung, Lynette Buck, Kristi Daris, Brent Welborn, Quanzhou Luo, Jette Wypych
Monoclonal antibodies (mAbs) are composed of two heavy chain (HC) and two light chain (LC) polypeptides. The proper folding and assembly of HC and LC is critical for antibody production. Current dogma indicates that the free HCs are retained in the endoplasmic reticulum (ER) unless assembled with LCs into antibodies, while the LCs on the other hand can be secreted as free monomer or dimer molecules. In this study, high levels of extracellular HC homodimers (7-45%) were observed in the cell culture media during cell line development for mAb1...
January 17, 2018: Biotechnology Progress
https://www.readbyqxmd.com/read/29340266/18f-fdg-pet-ct-in-a-patient-with-methotrexate-associated-lymphoproliferative-disorder
#4
Hayato Shimizu, Hiroaki Nishioka
18F-FDG PET-CT clearly demonstrated the disease activity of MTX-LPD.
January 2018: Journal of General and Family Medicine
https://www.readbyqxmd.com/read/29339102/spirulina-ameliorates-methotrexate-hepatotoxicity-via-antioxidant-immune-stimulation-and-proinflammatory-cytokines-and-apoptotic-proteins-modulation
#5
Asmaa F Khafaga, Yasser S El-Sayed
AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, MTX (20 mg/kg bwt, single ip injection), SP (500 mg/kg bwt, oral gavage daily for 21 days), and MTX+SP...
January 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29336711/circulating-serum-interleukin-6-serum-chitinase-3-like-protein-1-and-plasma-vascular-endothelial-growth-factor-are-not-predictive-for-remission-and-radiographic-progression-in-patients-with-early-rheumatoid-arthritis-post-hoc-explorative-and-validation-studies
#6
C H Brahe, C Dehlendorff, M Østergaard, J S Johansen, L M Ørnbjerg, K Hørslev-Petersen, K Stengaard-Pedersen, P Junker, T Ellingsen, H Lindegaard, I Hansen, T Lottenburger, S Jacobsen, A G Jurik, M L Hetland
OBJECTIVE: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized controlled trials (RCTs). METHOD: Treatment-naïve patients with early RA (< 6 months' duration) and active disease, participating in two investigator-initiated RCTs, were treated according to a predefined treat-to-target algorithm aiming at inflammatory control, using methotrexate (MTX) + cyclosporine versus MTX + placebo (CIMESTRA study, n = 150, 5 year follow-up) or MTX + adalimumab versus MTX + placebo (OPERA study, n = 180, 2 year follow-up)...
January 16, 2018: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/29335345/s100a12-is-associated-with-response-to-therapy-in-juvenile-idiopathic-arthritis
#7
Faekah Gohar, Janneke Anink, Halima Moncrieffe, Lisette W A Van Suijlekom-Smit, Femke H M Prince, Marion A J van Rossum, Koert M Dolman, Esther P A H Hoppenreijs, Rebecca Ten Cate, Simona Ursu, Lucy R Wedderburn, Gerd Horneff, Michael Frosch, Dirk Foell, Dirk Holzinger
OBJECTIVE: Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response...
January 15, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29334721/efficacy-and-safety-of-tocilizumab-in-korean-patients-with-active-rheumatoid-arthritis
#8
Han Joo Baek, Mie Jin Lim, Won Park, Sung Hwan Park, Seung-Cheol Shim, Dae-Hyun Yoo, Hyun Ah Kim, Soo Kon Lee, Yun Jong Lee, Young Eun Park, Hoon-Suk Cha, Yeong-Wook Song
Background/Aims: To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). Methods: The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks...
January 17, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29333734/synthesis-cytotoxic-and-antibacterial-evaluation-of-quinazolinone-derivatives-with-substituted-amino-moiety
#9
Xiaoping Zhan, Yun Xu, Qi Qi, Yaolin Wang, Huiying Shi, Zhenmin Mao
A series of novel quinazolinone derivatives containing a substituted amino moiety were synthesized, evaluated for their cytotoxic and antibacterial activities. The results of MTT assay showed that all synthesized target compounds 5A~O showed potent cytotoxicity against SGC-7901 (IC50 , 0.72~1.41μM). Moreover, the compounds 5D, 5I and 5K showed better selectivity as compared with positive controls pemetrexed and MTX due to weak cytotoxicity against normal tissue cell line HUVSMC. Among synthesized compounds, the compounds 5E, 5J, 5L and 5N showed broad-spectrum cytotoxic activities against at least four cancer cell lines at a micromolar level...
January 14, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29333125/association-between-slc19a1-gene-polymorphism-and-high-dose-methotrexate-toxicity-in-childhood-acute-lymphoblastic-leukaemia-and-non-hodgkin-malignant-lymphoma-introducing-a-haplotype-based-approach
#10
Barbara Faganel Kotnik, Janez Jazbec, Petra Bohanec Grabar, Cristina Rodriguez-Antona, Vita Dolzan
Background: We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods: Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results: Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29331383/population-pharmacokinetics-of-high-dose-methotrexate-in-patients-with-primary-central-nervous-system-lymphoma
#11
Shenghui Mei, Xingang Li, Xueyun Jiang, Kefu Yu, Song Lin, Zhigang Zhao
The intra- and inter-individual variances of methotrexate (MTX) pharmacokinetics are extremely large, and the pharmacokinetic property of MTX in patients with primary central nervous system lymphoma (PCNSL) is unestablished. A total of 701 MTX plasma concentrations from 98 patients with PCNSL under High-dose methotrexate (HDMTX) therapy were used to develop the population pharmacokinetic (popPK) model of MTX by using the nonlinear mixed-effects modeling method. A two-compartment model was employed to describe the pharmacokinetic property of MTX...
January 10, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29329602/abatacept-used-in-combination-with-non-methotrexate-disease-modifying-antirheumatic-drugs-a-descriptive-analysis-of-data-from-interventional-trials-and-the-real-world-setting
#12
Rieke Alten, Harald Burkhardt, Eugen Feist, Klaus Krüger, Juergen Rech, Andrea Rubbert-Roth, Reinhard E Voll, Yedid Elbez, Christiane Rauch
BACKGROUND: Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly tolerated or contraindicated in some patients. There is a wealth of data supporting the use of abatacept in combination with MTX, but data on alternative conventional synthetic disease-modifying antirheumatic drug (csDMARD) combinations with abatacept are scarce. METHODS: In this post-hoc exploratory analysis, efficacy and safety data were extracted from abatacept RA studies in which combination with csDMARDs other than MTX was permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real-world study (ACTION)...
January 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29329419/a-single-mutation-unlocks-cascading-exaptations-in-the-origin-of-a-potent-pitviper-neurotoxin
#13
A Carl Whittington, Andrew J Mason, Darin R Rokyta
Evolutionary innovations and complex phenotypes seemingly require an improbable amount of genetic change to evolve. Rattlesnakes display two dramatically different venom phenotypes. Type I venoms are hemorrhagic with low systemic toxicity and high expression of tissue-destroying snake venom metalloproteinases (SVMP). Type II venoms are highly neurotoxic and lack SVMP expression and associated hemorrhagic activity. This dichotomy hinges on Mojave toxin (MTx), a phospholipase A2 (PLA2) based ᵝ-neurotoxin expressed in Type II venoms...
January 10, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29325248/-survival-of-patients-with-primary-central-nervous-system-diffuse-large-b-cell-lymphoma-impact-of-gene-aberrations-and-protein-overexpression-of-bcl-2-and-c-myc-and-selection-of-chemotherapy-regimens
#14
W J Yin, X Zhu, H Y Yang, W Y Sun, M J Wu
Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER)...
January 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29319136/the-use-of-99mtc-phytate-for-assessment-the-protective-effect-of-vitamin-e-against-hepatotoxicity-induced-by-methotrexat-in-rat
#15
Hossein Amirfakhrian, Seyed Mohammad Abedi, Hossein Sadeghi, Soheil Azizi, Seyed Jalal Hosseinimehr
In this study, we investigated the protective effect of vitamin E against methotrexate (MTX)-induced hepatotoxicity by quantitative liver 99mTc-phytate uptake and liver imaging and to compare its effect with histopathology in rat. Rats were divided into five groups as control, solvent, Vit E (100 mg/kg), MTX (20 mg/kg), Vit E + MTX and. Vit E was intraperitoneally administrated for 17 days before MTX injection and continued for 4 days. 99mTc-phytate was injected through the tail of rats after the drug administration...
January 10, 2018: Nuclear Medicine Review. Central & Eastern Europe
https://www.readbyqxmd.com/read/29316374/switched-memory-b-cells-are-increased-in-oligoarticular-and-polyarticular-juvenile-idiopathic-arthritis-and-their-change-over-time-is-related-to-response-to-tnf-inhibitors
#16
Emiliano Marasco, Angela Aquilani, Simona Cascioli, Gian Marco Moneta, Ivan Caiello, Chiara Farroni, Ezio Giorda, Valentina D'Oria, Denise Pires Marafon, Silvia Magni-Manzoni, Rita Carsetti, Fabrizio De Benedetti
OBJECTIVES: To investigate if abnormalities in B-cell subsets in JIA patients correlated with clinical features and response to treatment. METHODS: 109 patients diagnosed with oligo-JIA or poly-JIA were enrolled in the study. B-cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry. RESULTS: Switched memory B-cells (SwM B-cells) were significantly (p<0.0001) increased in patients compared to age- matched healthy controls (HC)...
January 5, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29315303/genome-wide-comparison-of-ethiopian-leishmania-donovani-strains-reveals-differences-potentially-related-to-parasite-survival
#17
Arie Zackay, James A Cotton, Mandy Sanders, Asrat Hailu, Abedelmajeed Nasereddin, Alon Warburg, Charles L Jaffe
Leishmania donovani is the main cause of visceral leishmaniasis (VL) in East Africa. Differences between northern Ethiopia/Sudan (NE) and southern Ethiopia (SE) in ecology, vectors, and patient sensitivity to drug treatment have been described, however the relationship between differences in parasite genotype between these two foci and phenotype is unknown. Whole genomic sequencing (WGS) was carried out for 41 L. donovani strains and clones from VL and VL/HIV co-infected patients in NE (n = 28) and SE (n = 13)...
January 9, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29314151/comparison-of-ebv-positive-mucocutaneous-ulcer-ebvmcu-associated-with-treated-lymphoma-or-methotrexate-in-japan
#18
Teerada Daroontum, Kei Kohno, Ahmed E Eladl, Akira Satou, Ayako Sakakibara, Shoichi Matsukage, Naoki Yakushiji, Charin Ya-In, Shigeo Nakamura, Naoko Asano, Seiichi Kato
AIMS: The present study compared treated lymphoma-associated EBV-positive mucocutaneous ulcer (EBVMCU) and methotrexate (MTX)-associated EBVMCU. METHODS AND RESULTS: Of a series of 15 Japanese patients (11 women, 4 men; median age 74 years, range 35-84 years). 7 received MTX for autoimmune disease and 8 developed EBVMCU after treatment of malignant lymphoma (diffuse large B-cell lymphoma [n=4] without EBV association, adult T-cell leukaemia/lymphoma [n=2], angioimmunoblastic T-cell lymphoma [n=1], and follicular lymphoma [n=1])...
January 4, 2018: Histopathology
https://www.readbyqxmd.com/read/29311456/-a-survey-of-the-adverse-effects-and-influence-of-concomitant-drugs-for-methotrexate-intrathecal-administration
#19
Masanobu Uchiyama, Miho Ueno, Yasushi Takamatsu, Koichi Matsuo, Osamu Imakyure, Hidetoshi Kamimura
 In general, the intraventricular administration of cytotoxic antitumor drugs provides a high drug concentration in the cerebrospinal fluid with a reduced risk of systemic adverse reactions. Methotrexate (MTX) high-dose therapy requires close monitoring when performed in combination with trimethoprim-sulfamethoxazole (ST) therapy and proton pump inhibitor (PPI) and nonsteroidal anti-inflammatory drug administration for excretion delay and toxicity enhancement. While the frequency of systemic side effects is thought to be low with intrathecal administration, such effects do rarely but occasionally occur...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29306656/association-between-a-microrna-binding-site-polymorphism-in-slco1a2-and-the-risk-of-delayed-methotrexate-elimination-in-chinese-children-with-acute-lymphoblastic-leukemia
#20
Shu-Mei Wang, Wei-Xin Zeng, Wan-Shui Wu, Lu-Lu Sun, Dan Yan
Organic anion-transporting polypeptide 1A2 (OATP1A2) is involved in the cellular uptake of methotrexate (MTX). Genetic variation in solute carrier organic anion transporter family member 1A2 (SLCO1A2, the coding gene of OATP1A2) has important implications for the elimination of MTX. We investigated the association between a microRNA (miRNA) binding site polymorphism (rs4149009 G > A) in the 3'-untranslated region (3'-UTR) of SLCO1A2 with the serum MTX concentrations in Chinese children with acute lymphoblastic leukemia (ALL)...
January 2, 2018: Leukemia Research
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