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https://www.readbyqxmd.com/read/28636142/clinical-development-of-immunotherapy-for-prostate-cancer
#1
REVIEW
Masanori Noguchi, Noriko Koga, Tsukasa Igawa, Kyogo Itoh
Prostate cancer is the most common cancer in men, and the second leading cause of cancer-related death in Western countries. Prostate cancer-related death occurs in patients with metastatic castration-resistant prostate cancer. Although several new drugs for castration-resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28635521/assessment-of-an-innovative-voluntary-substance-abuse-treatment-program-designed-to-replace-compulsory-drug-detention-centers-in-malaysia
#2
Farrah Khan, Archana Krishnan, Mansur A Ghani, Jeffrey A Wickersham, Jeannia J Fu, Sin How Lim, Sangeeth Kaur Dhaliwal, Adeeba Kamarulzaman, Frederick L Altice
BACKGROUND: As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services. OBJECTIVES:   We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan...
February 22, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28634515/transarterial-chemoembolization-using-40-%C3%A2%C2%B5m-drug-eluting-beads-for-hepatocellular-carcinoma
#3
Giorgio Greco, Tommaso Cascella, Antonio Facciorusso, Roberto Nani, Rodolfo Lanocita, Carlo Morosi, Marta Vaiani, Giuseppina Calareso, Francesca G Greco, Antonio Ragnanese, Marco A Bongini, Alfonso V Marchianò, Vincenzo Mazzaferro, Carlo Spreafico
AIM: To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment. METHODS: Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging...
May 28, 2017: World Journal of Radiology
https://www.readbyqxmd.com/read/28634084/drug-delivery-to-melanoma-brain-metastases-can-current-challenges-lead-to-new-opportunities
#4
Gautham Gampa, Shruthi Vaidhyanathan, Jann N Sarkaria, William F Elmquist
Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease...
June 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#5
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#6
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
June 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28633036/recent-advances-in-understanding-multiple-myeloma
#7
REVIEW
Parameswaran Hari
There have been major recent advancements in the understanding and management of multiple myeloma which in turn has led to unprecedented survival outcomes for patients. Diagnostic and response criteria have been recently revised. Our understanding of clonal progression, evolution, and clonal tides will inform therapeutic choices and appropriate treatment for patients. Response rates to initial induction with modern triplet therapies containing proteasome inhibitors and immunomodulators have made this approach the global standard for initial treatment...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28632924/metabolomics-as-a-driver-in-advancing-precision-medicine-in-sepsis
#8
Michelle Eckerle, Lilliam Ambroggio, Michael Puskarich, Brent Winston, Alan E Jones, Theodore J Standiford, Kathleen A Stringer
OBJECTIVE: The objective of this review is to explain the science of metabolomics-a science of systems biology that measures and studies endogenous small molecules (metabolites) that are present in a single biological sample-and its application to the diagnosis and treatment of sepsis. In addition, we discuss how discovery through metabolomics can contribute to the development of precision medicine targets for this complex disease state and the potential avenues for those new discoveries to be applied in the clinical environment...
June 20, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#9
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632788/high-throughput-identification-and-rational-design-of-synergistic-small-molecule-pairs-for-combating-and-bypassing-antibiotic-resistance
#10
Morgan A Wambaugh, Viplendra P S Shakya, Adam J Lewis, Matthew A Mulvey, Jessica C S Brown
Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28632758/safety-and-tolerability-of-elvitegravir-cobicistat-emtricitabine-tenofovir-disoproxil-fumarate-in-a-real-life-setting-data-from-surveillance-cohort-long-term-toxicity-antiretrovirals-antivirals-scolta-project
#11
Nicola Squillace, Elena Ricci, Tiziana Quirino, Andrea Gori, Alessandra Bandera, Laura Carenzi, Giuseppe Vittorio De Socio, Giancarlo Orofino, Canio Martinelli, Giordano Madeddu, Stefano Rusconi, Paolo Maggi, Benedetto Maurizio Celesia, Laura Cordier, Francesca Vichi, Leonardo Calza, Katia Falasca, Antonio Di Biagio, Giovanni Francesco Pellicanò, Paolo Bonfanti
OBJECTIVES: The study aim was to evaluate the impact on Liver and Kidney toxicity of the single tablet regimen Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (EVG/COBI/FTC/TDF) on Antiretroviral Therapy (ART) experienced or naïve patients. METHODS: Patients initiating EVG/COBI/FTC/TDF were enrolled in the SCOLTA project, a multicenter observational study reporting grade 3-4 Adverse Events in subjects beginning new antiretroviral drug regimens...
2017: PloS One
https://www.readbyqxmd.com/read/28632424/the-progress-in-the-research-of-antiplatelet-agents-1995-2017
#12
Oscar Benimana, Lulu Zhao, Yi Kong, Zhiyu Li, Zhouling Xie
Antiplatelet therapy displays a critical role in the treatment and prevention of antithrombotic disorders. Many new antiplatelet agents have been developed following the emergence of various clinical limitations of classical antiplatelet drugs. This review covers mainly the recent advances in the development of P2Y12 antagonists and GPIIb/IIIa antagonists. Meanwhile, it summarizes promising approaches to new platelet surface receptors such as prostanoid EP3 receptor, thromboxane A2 prostanoid receptor, protease-activated receptors, GPIb-IX-V receptor and P-selectin...
June 20, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28632196/drug-hypersensitivity-and-desensitizations-mechanisms-and-new-approaches
#13
REVIEW
Leticia de Las Vecillas Sánchez, Leila A Alenazy, Marlene Garcia-Neuer, Mariana C Castells
Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS)...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28632134/targeting-hypoxic-cancer-stem-cells-cscs-with-doxycycline-implications-for-optimizing-anti-angiogenic-therapy
#14
Ernestina Marianna De Francesco, Marcello Maggiolini, Herbert B Tanowitz, Federica Sotgia, Michael P Lisanti
Here, we report new mechanistic insight into how chronic hypoxia increases 'stemness' in cancer cells. Using chemical inhibitors, we provide direct experimental evidence that ROS production and mitochondrial biogenesis are both required for the hypoxia-induced propagation of CSCs. More specifically, we show that hypoxic CSCs can be effectively targeted with i) simple mitochondrial anti-oxidants (Mito-TEMPO) and/or ii) inhibitors of mitochondrial biogenesis (Doxycycline). In this context, we discuss the idea that mitochondrial biogenesis itself may be a primary driver of "stemness" in hypoxic cancer cells, with metabolic links to fatty acid oxidation (FAO)...
June 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#15
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28630930/real-time-quantitative-analysis-of-metabolic-flux-in-live-cells-using-a-hyperpolarized-micromagnetic-resonance-spectrometer
#16
Sangmoo Jeong, Roozbeh Eskandari, Sun Mi Park, Julio Alvarez, Sui Seng Tee, Ralph Weissleder, Michael G Kharas, Hakho Lee, Kayvan R Keshari
Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or "fluxes" of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630494/structure-guided-design-of-c4-alkyl-1-4-dihydro-2h-pyrimido-4-5-d-1-3-oxazin-2-ones-as-potent-and-mutant-selective-epidermal-growth-factor-receptor-egfr-l858r-t790m-inhibitors
#17
Yongjia Hao, Jiankun Lyu, Rong Qu, Deheng Sun, Zhenjiang Zhao, Zhuo Chen, Jian Ding, Hua Xie, Yufang Xu, Honglin Li
Epidermal growth factor receptor (EGFR) T790M acquired drug-resistance mutation has become a major clinical challenge for the therapy of non-small cell lung cancer. Here, we applied a structure-guided approach on the basis of the previous reported EGFR inhibitor (compound 9), and designed a series of C4-alkyl-1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-one derivatives as novel mutant-selective EGFR inhibitors. Finally, the most representative compound 20a was identified, which showed high selectivity at both enzymatic and cellular levels against EGFR(L858R/T790M) (H1975 cell lines) over EGFR(WT) (A431 cell lines)...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630440/looking-to-nature-for-a-new-concept-in-antimicrobial-treatments-isoflavonoids-from-cytisus-striatus-as-antibiotic-adjuvants-against-mrsa
#18
Ana Cristina Abreu, Aline Coqueiro, Andi R Sultan, Nicole Lemmens, Hye Kyong Kim, Robert Verpoorte, Willem J B van Wamel, Manuel Simões, Young Hae Choi
The spread of multidrug-resistant Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA), has shortened the useful life of anti-staphylococcal drugs enormously. Two approaches can be followed to address this problem: screening various sources for new leads for antibiotics or finding ways to disable the resistance mechanisms to existing antibiotics. Plants are resistant to most microorganisms, but despite extensive efforts to identify metabolites that are responsible for this resistance, no substantial progress has been made...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630190/%C3%AE-lactam-antibiotics-with-a-high-affinity-for-pbp2-act-synergistically-with-the-ftsz-targeting-agent-txa707-against-methicillin-resistant-staphylococcus-aureus
#19
Edgar Ferrer-González, Malvika Kaul, Ajit K Parhi, Edmond J LaVoie, Daniel S Pilch
Methicillin-resistant Staphylococcus aureus (MRSA) is a multi-drug resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. Here we present results that demonstrate differing extents of synergy between TXA707 and a broad range of β-lactam antibiotics (including six cephalosporins, two penicillins, and two carbapenems) against MRSA. To explore whether there is a correlation between the extent of synergy and the preferential antibacterial target of each β-lactam, we determined the binding affinities of the β-lactam antibiotics for each of the four native penicillin binding proteins (PBPs) of S...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28629987/anti-herpes-simplex-virus-type-1-activity-of-houttuynoid-a-a-new-flavonoid-from-houttuynia-cordata-thunb
#20
Ting Li, Libao Liu, Hongling Wu, Shaodan Chen, Qinchang Zhu, Hao Gao, Xiongtao Yu, Yi Wang, Wenhan Su, Xinsheng Yao, Tao Peng
Early events in herpes simplex virus type 1 (HSV-1) infection reactivate latent human immunodeficiency virus, Epstein-Barr virus, and human papillomavirus in the presence of acyclovir (ACV). The common use of nucleoside analog medications, such as ACV and pencyclovir, has resulted in the emergence of drug-resistant HSV-1 strains in clinical therapy. Therefore, new antiherpetics that can inhibit early events in HSV-1 infection should be developed. An example of this treatment is Houttuynia cordata Thunb. water extract, which can inhibit HSV-1 infection through multiple mechanisms...
June 16, 2017: Antiviral Research
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