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https://www.readbyqxmd.com/read/29165815/development-and-validation-of-a-liquid-chromatography-tandem-mass-spectrometry-analytical-method-for-the-therapeutic-drug-monitoring-of-eight-novel-anticancer-drugs
#1
M Herbrink, N de Vries, H Rosing, A D R Huitema, B Nuijen, J H M Schellens, J H Beijnen
To support therapeutic drug monitoring (TDM) of patients with cancer, a fast and accurate method for simultaneous quantification of the registered anticancer drugs afatinib, axitinib, ceritinib, crizotinib, dabrafenib, enzalutamide, regorafenib and trametinib in human plasma using liquid chromatography tandem mass spectrometry was developed and validated. Human plasma samples were collected from treated patients and stored at -20 (o) C. Analytes and internal standards (stable isotopically labeled analytes) were extracted with acetonitrile...
November 22, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29165314/towards-natural-mimetics-of-metformin-and-rapamycin
#2
Alexander Aliper, Leslie Jellen, Franco Cortese, Artem Artemov, Darla Karpinsky-Semper, Alexey Moskalev, Andrew G Swick, Alex Zhavoronkov
Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals-safer, naturally-occurring compounds-that mimic the anti-aging effects of metformin and rapamycin without adverse effects...
November 15, 2017: Aging
https://www.readbyqxmd.com/read/29165087/nucleotide-reverse-transcriptase-inhibitors-a-thorough-review-present-status-and-future-perspective-as-hiv-therapeutics
#3
Ashley D Holec, Subhra Mandal, Pavan Kumar Prathipati, Christopher J Destache
Human immunodeficiency virus type-1 (HIV-1) infection leads to acquired immunodeficiency syndrome (AIDS), a severe fatal viral infection that has claimed approximately 658,507 lives in the US within the year 2010-2014. Antiretroviral (ARV) therapy has proven to inhibit HIV-1, but unlike other viral illness, not cure the infection. Among various Food and Drug Administration (FDA)-approved ARVs, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are most effective in limiting HIV-1 infection. This review focuses on NRTIs mechanism of action and metabolism...
November 19, 2017: Current HIV Research
https://www.readbyqxmd.com/read/29165075/preferential-formulation-of-second-generation-antipsychotic-asenapine-as-inclusion-complex-with-sulphobutylether-%C3%AE-cd-captisol-in-vitro-and-in-vivo-evaluation
#4
Amelia Makarand Avachat, Juilee A Kulkarni, Charul M Avachat, Rohan Pradhan, Tushar S Suryawanshi, E M Khan, Elvis A F Martis, Evans C Coutinho, Subhash Padhye
Asenapine is an anti-psychotic agent approved by the US-FDA for treatment of acute schizophrenia and manic or bipolar I disorder in adults. It is poorly absorbed when administered orally, hence exhibits poor oral bioavailability, which limits its use in clinical practice. Consequently, enhancement in its solubility through complexation with three different cyclodextrins, viz. βCD (β cyclodextrin), HPβCD (Hydroxypropyl β cyclodextrin) and sulphobutylether-βCD (Captisol®) was attempted and compared. Kneading method was used for preparation of inclusion complexes which were characterized by FTIR, DSC, and XRD methods...
November 20, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29164603/18f-pet-with-florbetapir-for-the-early-diagnosis-of-alzheimer-s-disease-dementia-and-other-dementias-in-people-with-mild-cognitive-impairment-mci
#5
REVIEW
Gabriel Martínez, Robin Wm Vernooij, Paulina Fuentes Padilla, Javier Zamora, Xavier Bonfill Cosp, Leon Flicker
BACKGROUND: (18)F-florbetapir uptake by brain tissue measured by positron emission tomography (PET) is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using amyloid biomarkers tests like (18)F-florbetapir...
November 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29164602/18f-pet-with-flutemetamol-for-the-early-diagnosis-of-alzheimer-s-disease-dementia-and-other-dementias-in-people-with-mild-cognitive-impairment-mci
#6
REVIEW
Gabriel Martínez, Robin Wm Vernooij, Paulina Fuentes Padilla, Javier Zamora, Leon Flicker, Xavier Bonfill Cosp
BACKGROUND: (18)F-flutemetamol uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and the confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like (18)F-flutemetamol...
November 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29164600/18f-pet-with-florbetaben-for-the-early-diagnosis-of-alzheimer-s-disease-dementia-and-other-dementias-in-people-with-mild-cognitive-impairment-mci
#7
REVIEW
Gabriel Martínez, Robin Wm Vernooij, Paulina Fuentes Padilla, Javier Zamora, Leon Flicker, Xavier Bonfill Cosp
BACKGROUND: (18)F-florbetaben uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like (18)F-florbetaben...
November 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29164374/fixed-dose-4-factor-prothrombin-complex-concentrate-for-the-emergent-reversal-of-warfarin-a-retrospective-analysis
#8
Greta Astrup, Preeyaporn Sarangarm, Allison Burnett
Published literature suggests that a fixed-dose 4-factor prothrombin complex concentrate (4FPCC) may be efficacious in managing warfarin-associated hemorrhage, however the ideal dose is still unclear. The purpose of this evaluation was to determine the efficacy of fixed-dose 4FPCC in reducing the International Normalized Ratio (INR) to ≤ 1.5 among warfarin patients with need for urgent or emergent anticoagulation reversal. Starting October 2016, our institution changed from standard 4FPCC FDA-labeled dosing based on the patient's presenting INR and weight, to a fixed-dose of 1500 units for all patients requiring urgent or emergent warfarin reversal...
November 21, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29163822/structural-basis-of-the-therapeutic-anti-pd-l1-antibody-atezolizumab
#9
Fei Zhang, Xiaoqiang Qi, Xiaoxiao Wang, Diyang Wei, Jiawei Wu, Lingling Feng, Haiyan Cai, Yugang Wang, Naiyan Zeng, Ting Xu, Aiwu Zhou, Ying Zheng
Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163815/pd-l1-expression-heterogeneity-in-non-small-cell-lung-cancer-evaluation-of-small-biopsies-reliability
#10
Enrico Munari, Giuseppe Zamboni, Marcella Marconi, Marco Sommaggio, Matteo Brunelli, Guido Martignoni, George J Netto, Francesca Moretta, Maria Cristina Mingari, Matteo Salgarello, Alberto Terzi, Vincenzo Picece, Carlo Pomari, Gianluigi Lunardi, Alberto Cavazza, Giulio Rossi, Lorenzo Moretta, Giuseppe Bogina
Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163675/effects-of-different-concentrations-of-type-i-collagen-hydrogel-on-the-growth-and-differentiation-of-chondrocytes
#11
Deshan Hu, Xiuli Shan
The objective of this study was to analyze the effects of type-I collagen hydrogel of different concentrations on the growth and differentiation of rabbit chondrocytes. Articular cartilage from New Zealand white rabbits was harvested and cultured. Second-generation chondrocytes were collected for in vitro culture with 10, 7, and 5 mg/ml type-I collagen hydrogel, respectively (denoted as groups A, B, and C). After in vitro culture for 1 day, chondrocytes were stained with fluorescein diacetate (FDA)/propidium iodide (PI), and cell viability was observed by laser confocal microscopy...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29162825/outcomes-of-patients-with-sarcoma-enrolled-in-clinical-trials-of-pazopanib-combined-with-histone-deacetylase-mtor-her2-or-mek-inhibitors
#12
Vikas Dembla, Roman Groisberg, Ken Hess, Siqing Fu, Jennifer Wheler, David S Hong, Filip Janku, Ralph Zinner, Sarina Anne Piha-Paul, Vinod Ravi, Robert S Benjamin, Shreyaskumar Patel, Neeta Somaiah, Cynthia E Herzog, Daniel D Karp, Jason Roszik, Funda Meric-Bernstam, Vivek Subbiah
Pazopanib is US FDA approved for the treatment of advanced soft tissue sarcomas. All patients with this disease ultimately develop resistance to therapy. Mechanisms of resistance include activation of the mTOR, histone deacetylase (HDAC), MAPK, and ERBB4 pathways. We hypothesized that combining pazopanib with other targeted agents inhibiting these pathways would increase response rates. We retrospectively evaluated the safety and efficacy of pazopanib plus vorinostat, everolimus, lapatinib or trastuzumab, and MEK inhibitor in patients with advanced sarcoma...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162426/current-status-and-unanswered-questions-for-food-allergy-treatments
#13
Rima Rachid, Corinne A Keet
Although there is no FDA approved therapy for food allergy, over the past decades, several routes of immunotherapy have been investigated for food allergy. Thus far, these therapies have shown variable levels of efficacy at desensitizing to foods, with oral immunotherapy (OIT) far more successful than sublingual immunotherapy (SLIT) or epicutaneous immunotherapy (EPIT). However, desensitization tends to be temporary, and safety remains a major concern with OIT. Moreover, although it seems logical that desensitization will result in fewer reactions, it is not clear whether OIT or other immunotherapies are associated with an overall lower or higher risk of reactions over the long term...
November 18, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29162137/potentiating-angiogenesis-arrest-in-vivo-via-laser-irradiation-of-peptide-functionalised-gold-nanoparticles
#14
Pedro Pedrosa, Amelie Heuer-Jungemann, Antonios G Kanaras, Alexandra R Fernandes, Pedro V Baptista
BACKGROUND: Anti-angiogenic therapy has great potential for cancer therapy with several FDA approved formulations but there are considerable side effects upon the normal blood vessels that decrease the potential application of such therapeutics. Chicken chorioallantoic membrane (CAM) has been used as a model to study angiogenesis in vivo. Using a CAM model, it had been previously shown that spherical gold nanoparticles functionalised with an anti-angiogenic peptide can humper neo-angiogenesis...
November 21, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29161797/electromechanical-morcellators-black-box-warning-tribulations-expectations-and-solutions
#15
Papri Sarkar, Emad Mikhail, Lenox Hoyte, Shayne Plosker, Anthony Imudia
Laparoscopic minimally invasive gynecologic surgery (MIGS) for benign conditions results in decreased morbidity, and faster recovery, compared with laparotomy. Tissue fragmentation by electromechanical morcellation permits the removal of large specimens through small laparoscopic incisions. Since the US Food and Drug Administration (FDA) published its safety warning about the risk of power morcellators spreading cancer during fibroid surgery in 2014, power morcellation has become rare. MIGS for fibroids and other large tissue specimens has declined...
November 21, 2017: Minerva Ginecologica
https://www.readbyqxmd.com/read/29161781/in-silico-docking-studies-of-lupeol-with-mapk-pathway-proteins-raf-1-mek-erk
#16
Mital H Bhatt, Chirag K Prajapati, M N Reddy
Lupeol, A triterpenoid found in variety of plants is reported to have beneficial medicinal effects on several ailments. Lupeol is also found to show inhibitory effect on proliferation of breast cancer cells. Metastasis is considered to be a major cause for worldwide deaths related to cancer. Ras related MAPK Signaling Pathway is one of the crucial pathways leading to metastasis. Lupeols binding possibility with Ras is already reported. In present study, Interaction between with downstream proteins of Ras- MAPK pathway, Raf ,MEK ,ERK1/2 and their corresponding domains are studied using STRING Database and their structures are retrieved in PDB Format...
November 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29160059/deuterated-drug-molecules-focus-on-fda-approved-deutetrabenazinepublished-as-part-of-the-biochemistry-series-biochemistry-to-bedside
#17
Sheila H DeWitt, Bruce E Maryanoff
No abstract text is available yet for this article.
November 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/29158972/short-term-effects-of-co2-leakage-on-the-soil-bacterial-community-in-a-simulated-gas-leakage-scenario
#18
Jing Ma, Wangyuan Zhang, Shaoliang Zhang, Qianlin Zhu, Qiyan Feng, Fu Chen
The technology of carbon dioxide (CO2) capture and storage (CCS) has provided a new option for mitigating global anthropogenic emissions with unique advantages. However, the potential risk of gas leakage from CO2 sequestration and utilization processes has attracted considerable attention. Moreover, leakage might threaten soil ecosystems and thus cannot be ignored. In this study, a simulation experiment of leakage from CO2 geological storage was designed to investigate the short-term effects of different CO2 leakage concentration (from 400 g m(-2) day(-1) to 2,000 g m(-2) day(-1)) on soil bacterial communities...
2017: PeerJ
https://www.readbyqxmd.com/read/29158727/near-complete-response-in-a-patient-with-classical-hodgkin-lymphoma-treated-with-brentuximab-vedotin-concurrent-with-radiation-therapy
#19
Wilbur Montana, Dennis Andrew Buck, Tristan Smith
Brentuximab vedotin, an antibody drug conjugate that delivers monomethyl auristatin E into CD-30 expressing cells is FDA approved for the treatment of patients with Hodgkin lymphoma after the failure of autologous stem cell transplantation or at least 2 prior multi-agent chemotherapy regiments. This approval was based on a study that showed an overall response rate of 75% and complete remission in 34%. We present a case of a 24-year-old male with classical nodular sclerosing Hodgkin lymphoma who achieved near complete remission following 5 cycles of brentuximab concurrent with ISRT (involved site radiation therapy) following progression of first-line ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) and subsequent second-line ICE (ifosfamide, carboplatin, etoposide) chemotherapy...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29158469/molecular-basis-for-necitumumab-inhibition-of-egfr-variants-associated-with-acquired-cetuximab-resistance
#20
Atrish Bagchi, Jaafar N Haidar, Scott W Eastman, Michal Vieth, Michael Topper, Michelle D Iacolina, Jason M Walker, Amelie Forest, Yang Shen, Ruslan D Novosiadly, Kathryn M Ferguson
Acquired resistance to cetuximab, an antibody that targets the epidermal growth factor receptor (EGFR), impacts clinical benefit in head and neck, and colorectal cancers (CRC). One of the mechanisms of resistance to cetuximab is the acquisition of mutations that map to the cetuximab epitope on EGFR and prevent drug binding. We find that necitumumab, another FDA approved EGFR antibody, can bind to EGFR that harbors the most common cetuximab resistance substitution, S468R (or S492R, depending on the amino acid numbering system)...
November 20, 2017: Molecular Cancer Therapeutics
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