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https://www.readbyqxmd.com/read/29684820/increased-oxidative-stress-mediates-the-antitumor-effect-of-parp-inhibition-in-ovarian-cancer
#1
Dong Hou, Zhaojian Liu, Xiuhua Xu, Qiao Liu, Xiyu Zhang, Beihua Kong, Jian-Jun Wei, Yaoqin Gong, Changshun Shao
PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells...
March 30, 2018: Redox Biology
https://www.readbyqxmd.com/read/29684754/increases-in-helminth-induced-il-21-protein-levels-disappear-upon-sample-freezing
#2
Anupama Ariyaratne, Edina K Szabo, Joel Bowron, Constance A M Finney
IL-21 is a much studied cytokine that has been implicated in the regulation of TH1, TH2, TH17 and regulatory immune responses; its signalling is a promising therapeutic target for autoimmune, inflammatory and infectious diseases. Despite its biological importance, measuring IL-21 reliably has proved difficult. ELISAs are commonly used to measure cytokines in various biological samples. However, results obtained are only as good as the quality of the sample. Here, we show that when using fresh samples, a significant increase in IL-21 was measured in the intestinal homogenate of mice infected with the intestinal worm Heligmosomoides polygyrus...
April 20, 2018: Cytokine
https://www.readbyqxmd.com/read/29684684/targeted-data-independent-acquisition-for-mass-spectrometric-detection-of-ras-mutations-in-formalin-fixed-paraffin-embedded-tumor-biopsies
#3
Yeoun Jin Kim, Andrew G Chambers, Fabiola Cecchi, Todd Hembrough
Genomic testing for KRAS and NRAS mutations in clinical biopsies of various cancers is routinely performed to predict futility of anti-epidermal growth factor receptor (anti-EGFR) therapies. We hypothesized that RAS mutations could be detected and quantified at the protein level for diagnostic purposes using data-independent acquisition (DIA)-based mass spectrometry in formalin-fixed, paraffin-embedded (FFPE) tumor samples. We developed a targeted DIA assay that surveys the specific mass range of all possible peptides harboring activating mutations in KRAS exon 2...
April 20, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29684680/licochalcone-a-an-effective-and-low-toxicity-compound-against-toxoplasma-gondii-in-vitro-and-in-vivo
#4
Hongfei Si, Chunyan Xu, Jili Zhang, Xukun Zhang, Bing Li, Xuzheng Zhou, Jiyu Zhang
Toxoplasma gondii, an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti-T. gondii activity and potential mechanism of Licochalcone A (Lico A) in vitro and in vivo. The safe concentration of Lico A in HFF cells was determined by MTT cell viability assays. The presence of T. gondii was assessed by qPCR and Giemsa staining. Azithromycin and sulfadiazine, commonly used effective treatments, served as drug controls...
March 1, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29684585/nogo-b-reticulon-4b-functions-as-a-negative-regulator-of-the-apoptotic-pathway-through-the-interaction-with-c-flip-in-colorectal-cancer-cells
#5
Nao Kawaguchi, Keitaro Tashiro, Kohei Taniguchi, Masaru Kawai, Keitaro Tanaka, Junji Okuda, Michihiro Hayashi, Kazuhisa Uchiyama
Nogo-B is a member of the Nogo/Reticulon-4 family and has been reported to be an inducer of apoptosis in certain types of cancer cells. However, the role of Nogo-B in human cancer remains less understood. Here, we demonstrated the functions of Nogo-B in colorectal cancer cells. In clinical colorectal cancer specimens, Nogo-B was obviously overexpressed, as determined by immunohistochemistry; and Western blot analysis showed its expression level to be significantly up-regulated. Furthermore, knockdown of Nogo-B in two colorectal cancer cell lines, SW480 and DLD-1, by transfection with si-RNA (siR) resulted in significantly reduced cell viability and a dramatic increase in apoptosis with insistent overexpression of cleaved caspase-8 and cleaved PARP...
April 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29684530/supratherapeutic-concentrations-of-cilostazol-inhibits-%C3%AE-amyloid-oligomerization-in-vitro
#6
Hidenobu Shozawa, Tatsunori Oguchi, Mayumi Tsuji, Satoshi Yano, Yuji Kiuchi, Kenjiro Ono
Alzheimer disease (AD) is the most common type of dementia, and is currently incurable. The efficacy of existing treatments for AD such as acetylcholinesterase inhibitors is limited to symptom improvement. Research on disease-modifying therapies (DMTs) has conventionally focused on amelioration of CNS pathogenesis. Two neuropathological changes correlate strongly with AD, the appearance of neurofibrillary tangles containing the microtubule-associated protein tau and extracellular amyloid deposits containing amyloid β-protein (Aβ)...
April 20, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29684526/targeted-gene-silencing-of-braf-to-interrupt-braf-mek-erk-pathway-synergized-photothermal-therapeutics-for-melanoma-using-a-novel-fa-gnr-sibraf-nanosystem
#7
Yujuan Zhang, Xuelin Zhan, Shanshan Peng, Ying Cai, Yu Shrike Zhang, Yanling Liu, Zhigang Wang, Yanrong Yu, Yifan Wang, Qiaofa Shi, Xiaoping Zeng, Keng Yuan, Nanjin Zhou, Rakesh Joshi, Meng Zhang, Zhuxu Zhang, Weiping Min
Melanoma is significantly associated with mutant BRAF gene, a suitable target for siRNA-based anti-melanoma therapy. However, a tumor-specific delivery system is a major hurdle for clinical applications. Here, we developed a novel nano-carrier, FA-GNR-siBRAF for safe topical application, which consists of folic acid (FA) as the tumor-targeting moiety, golden nanorods (GNR) providing photothermal capability to kill tumor cells under laser irradiation, and siRNA specifically silencing BRAF (siBRAF). The in vitro and in vivo results revealed that FA-GNR-siBRAF displayed high transfection rates, and subsequently induced remarkable gene knockdown of BRAF, resulting in suppression of melanoma growth due to the interruption of the MEK/ERK pathway...
April 20, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29684419/recruited-t-cells-promote-the-bladder-cancer-metastasis-via-up-regulation-of-the-estrogen-receptor-%C3%AE-il-1-c-met-signals
#8
Le Tao, Jianxin Qiu, Spencer Slavin, Zhenyu Ou, Zhihong Liu, Jifu Ge, Elizabeth A Guancial, Edward M Messing, Chawnshang Chang, Shuyuan Yeh
Clinical data indicates that T cells can be recruited to bladder cancer (BCa) tumors, yet the impact of T cells on BCa progression remains unclear. In the present study, we found that T cells were recruited more to BCa tissues than to the surrounding normal bladder tissues. Results from an in vitro co-culture system also found that BCa recruited more CD4+ T cells than did normal bladder cells. The recruiting of T cells to BCa tissues may increase the proliferation and invasion of BCa cells. Mechanistic studies revealed that infiltrating T cells stimulate BCa estrogen receptor beta (ERβ) signaling and consequently increase the expression of MET proto-oncogene, receptor tyrosine kinase (c-MET), through either direct binding to its promoter or via modulation of IL-1 expression...
April 20, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29684396/jsh-23-prevents-depressive-like-behaviors-in-mice-subjected-to-chronic-mild-stress-effects-on-inflammation-and-antioxidant-defense-in-the-hippocampus
#9
Qi Wang, Xiaomei Dong, Nannan Li, Yan Wang, Xiaofeng Guan, Yiwei Lin, Jiguang Kang, Xia Zhang, Yuchen Zhang, Xiaobai Li, Tianchao Xu
Nuclear factor-kappa B (NF-κB), which is reported to play an important role in the pathogenesis of depression, also has a central role in the genesis and progression of inflammation. Here, we have targeted the nuclear translocation of NF-κB using 4-methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine (JSH-23) to elucidate its role in depression. We investigated the antidepressant-like effects of JSH-23 in the chronic mild stress (CMS) mouse model, which is a valid, reasonably reliable, and useful model of depression...
April 20, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29684379/effect-of-a-long-term-treatment-with-metformin-in-dystrophic-mdx-mice-a-reconsideration-of-its-potential-clinical-interest-in-duchenne-muscular-dystrophy
#10
Paola Mantuano, Francesca Sanarica, Elena Conte, Maria Grazia Morgese, Roberta Francesca Capogrosso, Anna Cozzoli, Adriano Fonzino, Angelo Quaranta, Jean-Francois Rolland, Michela De Bellis, Giulia Maria Camerino, Luigia Trabace, Annamaria De Luca
The pharmacological stimulation of AMP-activated protein kinase (AMPK) via metabolic enhancers has been proposed as potential therapeutic strategy for Duchenne muscular dystrophy (DMD). Metformin, a widely-prescribed anti-hyperglycemic drug which activates AMPK via mitochondrial respiratory chain, has been recently tested in DMD patients in synergy with nitric oxide (NO)-precursors, with encouraging results. However, preclinical data supporting the use of metformin in DMD are still poor, and its actions on skeletal muscle appear controversial...
April 20, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29684335/emergence-of-breath-testing-as-a-new-non-invasive-diagnostic-modality-for-neurodegenerative-diseases
#11
REVIEW
N Siva Subramaniam, C S Bawden, H Waldvogel, R M L Faull, G S Howarth, R G Snell
Neurodegenerative diseases (NDDs) are incapacitating disorders that result in progressive motor and cognitive impairment. These disease include Alzheimer's disease the most common cause of dementia, frontotemporal dementia, amyotrophic lateral sclerosis, dementia with Lewy bodies, Parkinson's, Huntington's, Friedreich's ataxia, and prion disease. Dementia causing NDDs impose a high social and economic burden on communities around the world. Rapid growth in knowledge regarding the pathogenic mechanisms and disease-associated biomarkers of these diseases in the past few decades have accelerated the development of new diagnostic methods and therapeutic opportunities...
April 20, 2018: Brain Research
https://www.readbyqxmd.com/read/29684235/implications-of-mutation-profiling-in-myeloid-malignancies-part-1-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#12
REVIEW
Douglas Tremblay, Kelsey Sokol, Sheena Bhalla, Raajit Rampal, John O Mascarenhas
The advent of high-throughput gene sequencing has revolutionized our understanding of the genetic mutations that drive myeloid malignancies. While these mutations are of interest pathobiologically, they are increasingly being recognized as clinically meaningful in providing diagnostic, prognostic, and therapeutic information to guide patient care. In this first part of our two-part review, we introduce mutation profiling as a relevant clinical tool for hematologists treating patients with myeloid malignancies...
April 15, 2018: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/29684209/drug-review-pazopanib
#13
Shingo Miyamoto, Shigenori Kakutani, Yujiro Sato, Akira Hanashi, Yoshitaka Kinoshita, Akira Ishikawa
Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that primarily inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet endothelial growth factor receptor-α, and -β, and the stem-cell factor receptor c-kit. In preliminary experiments using angiogenesis models with mice and rabbits, pazopanib inhibited angiogenesis caused by combined vascular endothelial growth factor and basic fibroblast growth factor. Although pazopanib was developed as a therapeutic agent against various tumors, it is currently approved in many countries for advanced soft-tissue sarcoma and renal cell carcinoma...
April 19, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29684147/plasma-and-csf-pharmacokinetics-of-meropenem-in-neonates-and-young-infants-results-from-the-neomero-studies
#14
Eva Germovsek, Irja Lutsar, Karin Kipper, Mats O Karlsson, Tim Planche, Corine Chazallon, Laurence Meyer, Ursula M T Trafojer, Tuuli Metsvaht, Isabelle Fournier, Mike Sharland, Paul Heath, Joseph F Standing
Background: Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. Objectives: To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS)...
April 19, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29684015/cryosurgery-for-the-treatment-of-cutaneous-sporotrichosis-in-four-pregnant-women
#15
Vivian Fichman, Antonio Carlos Francesconi do Valle, Priscila Marques de Macedo, Dayvison Francis Saraiva Freitas, Manoel Marques Evangelista de Oliveira, Rodrigo Almeida-Paes, Maria Clara Gutierrez-Galhardo
BACKGROUND: Pregnant women with sporotrichosis should not receive systemic antifungal therapy except in severe cases when amphotericin B is recommended. Thermotherapy is the most reported treatment described in this group of patients. It entails weeks of daily self-application of heat to the lesions, requires that the patient faithfully apply it, and it could cause skin burns. Cryosurgery is a useful therapeutic tool for many cutaneous infectious diseases, safe for pregnant women, but not well evaluated for sporotrichosis treatment in this group...
April 23, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29683874/time-dependent-decline-in-serum-phenytoin-concentration-with-heightened-convulsive-seizure-risk-by-prolonged-administration-of-fosphenytoin-in-japanese-a-retrospective-study
#16
Yuta Ohno, Takashi Niwa, Keita Hirai, Keiko Suzuki, Yuto Yamada, Yuichi Hayashi, Hideki Hayashi, Akio Suzuki, Yoshinori Itoh
BACKGROUND: Because clinical data to confirm the safety and effectiveness of fosphenytoin, a prodrug of phenytoin, are insufficient, the length of administration of fosphenytoin is restricted. Nevertheless, some cases require fosphenytoin administration for more than a few days. The aim of this study was to retrospectively investigate the serum concentration of phenytoin in adult Japanese patients who received intravenous fosphenytoin therapy for more than 3 days. METHODS: Patients injected with intravenous fosphenytoin for more than 3 days at Gifu University Hospital between January 2012 and September 2014 were enrolled...
April 20, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29683873/eltrombopag-induced-acute-liver-failure-in-a-pediatric-patient-a-pharmacokinetic-and-pharmacogenetic-analysis
#17
M Marano, J Serafinelli, S Cairoli, D Martinelli, M Pisani, G Palumbo, M G Cefalo, C Cecchetti, M Di Nardo, F S Falvella, B M Goffredo
Eltrombopag is an oral thrombopoietin-receptor-agonist (TPO-RA) approved for the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP), who are more than one year old, and show poor response to first-line therapy. ITP is a hematological disorder characterized by isolated thrombocytopenia in the absence of secondary causes or disorders. Eltrombopag is generally well tolerated in the pediatric population, therefore therapeutic drug monitoring (TDM) is not usually performed in clinical practice...
April 20, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29683851/detection-of-numerous-hiv-1-mo-recombinants-in-france
#18
Fabienne De Oliveira, Pierre Cappy, Véronique Lemée, Alice Moisan, Charlotte Pronier, Laurence Bocket, Magali Bouvier-Alias, Marie-Laure Chaix, Elyanne Gault, Odile Morvan, Jean-Dominique Poveda, Véronique Schneider, Marc Wirden, Elodie Alessandri-Gradt, Thomas Mourez, Jean-Christophe Plantier
BACKGROUND: The broad genetic divergence of HIV-1/O relative to HIV-1/M has important implications for diagnosis, monitoring and treatment. Despite this divergence, some HIV-1/M+O dual infections and HIV-1/MO recombinant forms have been reported, mostly in Cameroon, where both groups are prevalent. Here, we describe the characteristics of such infections detected in France in 10 new patients, and discuss their implications for biological and clinical practice, owing to the presence of group O species...
April 19, 2018: AIDS
https://www.readbyqxmd.com/read/29683803/is-cemented-or-cementless-femoral-stem-fixation-more-durable-in-patients-older-than-75-years-of-age-a-comparison-of-the-best-performing-stems
#19
Michael Tanzer, Stephen E Graves, Andrea Peng, Andrew J Shimmin
BACKGROUND: There is ongoing debate concerning the best method of femoral fixation in older patients receiving primary THA. Clinical studies have shown high survivorship for cemented and cementless femoral stems. Arthroplasty registry studies, however, have universally shown that cementless stems are associated with a higher rate of revision in this patient population. It is unclear if the difference in revision rate is a reflection of the range of implants being used for these procedures rather than the mode of fixation...
April 9, 2018: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/29683658/enhanced-biosynthesis-performance-of-heterologous-proteins-in-cho-k1-cells-using-crispr-cas9
#20
Wenpeng Wang, Wenyun Zheng, Fengzhi Hu, Xiujuan He, Dong Wu, Wenliang Zhang, Haipeng Liu, Xingyuan Ma
Chinese hamster ovary (CHO) cells are the famous expression system for industrial production of recombinant proteins, such as therapeutic antibodies. However, there retained still bottlenecks in protein quality and weakness in expression efficiency because of the intrinsic genetic properties of the cell. Here we have enhanced biosynthesis performance of heterologous proteins in CHO-K1 cell using CRISPR-Cas9 by editing the genome precisely with two genes for improving ER microenvironment and reinforcing anti-apoptotic ability...
April 23, 2018: ACS Synthetic Biology
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