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https://www.readbyqxmd.com/read/28732386/a-phase-i-trial-of-nk-92-cells-for-refractory-hematological-malignancies-relapsing-after-autologous-hematopoietic-cell-transplantation-shows-safety-and-evidence-of-efficacy
#1
Brent A Williams, Arjun Datt Law, Bertrand Routy, Neal denHollander, Vikas Gupta, Xing-Hua Wang, Amélie Chaboureau, Sowmya Viswanathan, Armand Keating
BACKGROUND: Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. MATERIALS AND METHODS: We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT)...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730918/clinical-and-economic-implications-of-urinary-tract-infections
#2
Samantha N Steiger, Rachel R Comito, David P Nicolau
Urinary tract infections represent one of the most frequent reasons for hospitalization. As a result of their prevalence from community-based origins as well as those which develop in hospital setting, this constellation of infections represents a tremendous burden to the global healthcare system. Areas Covered: Over the last several decades the management of these infections has become more complicated due to the underlying comorbid conditions of the patients as well as escalating antimicrobial resistance to many of the most frequently used oral and parenteral agents...
July 21, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28729199/violent-firearm-related-conflicts-among-high-risk-youth-an-event-level-and-daily-calendar-analysis
#3
Patrick M Carter, Maureen A Walton, Jason Goldstick, Quyen M Epstein-Ngo, Marc A Zimmerman, Melissa C Mercado, Amanda Garcia Williams, Rebecca M Cunningham
Firearm homicide is the leading cause of violence-related youth mortality. To inform prevention efforts, we analyzed event-level data to identify unique precursors to firearm conflicts. Youth (ages:14-24) seeking Emergency Department (ED) treatment for assault or for other reasons and reporting past 6-month drug use were enrolled in a 2-year longitudinal study. Time-line follow-back substance use/aggression modules were administered at baseline and each 6-month follow-up. Violent non-partner conflicts were combined across time-points...
July 17, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28728645/elevated-behavioral-economic-demand-for-alcohol-in-a-community-sample-of-heavy-drinking-smokers
#4
Michael Amlung, James MacKillop, Peter M Monti, Robert Miranda
OBJECTIVE: Cigarette smokers are more likely to consume alcohol at higher levels and experience poorer response to treatment for alcohol problems than are nonsmokers. One previous study in university students suggests that a potential reason for the high overlap between alcohol and tobacco use is that concurrent smoking is associated with overvaluation of alcohol, as reflected in elevated behavioral economic demand. The present study sought to extend these initial findings in a community sample with heavier levels of alcohol and tobacco use...
May 2017: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/28728493/treating-breast-cancer-with-cell-based-approaches-an-overview
#5
Susanna Gallo, Dario Sangiolo, Fabrizio Carnevale Schianca, Massimo Aglietta, Filippo Montemurro
Breast cancer is the most common malignancy in women. Despite there being considerable progress in the treatment of this disease, metastatic dissemination is still considered an incurable condition at the present time, causing 500,000 deaths worldwide every year. Although most of the research efforts have been focused on pharmacological approaches, over the last three decades, the use of bone marrow and peripheral blood-derived cell therapy approaches have been attempted and developed. Areas covered: This review will briefly address cell therapy for breast cancer, including autologous stem cell transplantations for overcoming the myelosuppressive effects of high-dose chemotherapy, allogeneic stem cell transplants and adoptive immunotherapy using bone-marrow derived T-cells...
July 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28727410/exosomes-mediate-epithelium-mesenchyme-crosstalk-in-organ-development
#6
Nan Jiang, Lusai Xiang, Ling He, Guodong Yang, Jinxuan Zheng, Chenglin Wang, Yimei Zhang, Sainan Wang, Yue Zhou, Tzong-Jen Sheu, Jiaqian Wu, Kenian Chen, Paulo G Coelho, Nicky M Tovar, Shin Hye Kim, Mo Chen, Yan-Heng Zhou, Jeremy J Mao
Organ development requires complex signaling by cells in different tissues. Epithelium and mesenchyme interactions are crucial for the development of the skin, hair follicles, kidney, lungs, prostate, major glands and the teeth. Despite myriad literature on cell-cell interactions and ligand-receptor binding, the roles extracellular vesicles in epithelium-mesenchyme interactions during organogenesis are poorly understood. Here, we discovered that ~100 nm exosomes were secreted by the epithelium and mesenchyme of a developing tooth organ, and diffused through the basement membrane...
July 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28726183/escalated-dose-somatostatin-analogues-for-antiproliferative-effect-in-gepnets-a-systematic-review
#7
REVIEW
David L Chan, Diego Ferone, Manuela Albertelli, Nick Pavlakis, Eva Segelov, Simron Singh
BACKGROUND/PURPOSE: Somatostatin analogues are the cornerstone of systemic therapy for metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours for both hormonal control and antiproliferative effect. Dose escalation of somatostatin analogues is often utilized in clinical practice, but small studies have yielded mixed results. The aim of this study was to systematically determine the efficacy and safety of escalated-dose somatostatin analogues in the above setting. METHODS: Eligible trials (using more than 30 mg octreotide or 120 mg lanreotide/28 days) were identified from MEDLINE, EMBASE, other databases and conference proceedings...
July 19, 2017: Endocrine
https://www.readbyqxmd.com/read/28726170/prescribing-trends-in-a-glaucoma-clinic-and-adherence-to-egs-guidelines-a-retrospective-non-interventional-single-center-uk-study
#8
Mark Fajgenbaum, Ejaz Ansari
INTRODUCTION: The purpose of this study was to determine prescribing trends in a specialist glaucoma clinic in the UK. Specifically, the aims were to determine which drugs were prescribed as first-, second-, and third-line treatment, the persistence of first-, second-, and third-line treatment regimens, and the proportion of treatment decisions conforming to the European Glaucoma Society (EGS) guidelines. METHODS: A retrospective, non-interventional, single-center, case-note review was performed on a cohort of consecutive patients presenting to a specialist glaucoma clinic for follow-up...
July 19, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28726132/phase-i-dose-escalation-study-of-nms-1286937-an-orally-available-polo-like-kinase-1-inhibitor-in-patients-with-advanced-or-metastatic-solid-tumors
#9
Glen J Weiss, Gayle Jameson, Daniel D Von Hoff, Barbara Valsasina, Cristina Davite, Claudia Di Giulio, Francesco Fiorentini, Rachele Alzani, Patrizia Carpinelli, Alessandro Di Sanzo, Arturo Galvani, Antonella Isacchi, Ramesh K Ramanathan
Background Pharmacological inhibition of polo-like kinase 1 (PLK1) represents a new approach for the treatment of solid tumors. This study was aimed at determining the first cycle dose-limiting toxicities (DLTs) and related maximum tolerated dose (MTD) of NMS-1286937, a selective ATP-competitive PLK1-specific inhibitor. Secondary objectives included evaluation of its safety and pharmacokinetic (PK) profile in plasma, its antitumor activity, and its ability to modulate intracellular targets in biopsied tissue...
July 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28723274/identifying-voxels-at-risk-for-progression-in-glioblastoma-based-on-dosimetry-physiologic-and-metabolic-mri
#10
Mekhail Anwar, Annette M Molinaro, Olivier Morin, Susan M Chang, Daphne A Haas-Kogan, Sarah J Nelson, Janine M Lupo
Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease...
July 19, 2017: Radiation Research
https://www.readbyqxmd.com/read/28721887/external-beam-radiation-therapy-with-a-brachytherapy-boost-versus-radical-prostatectomy-in-gleason-pattern-5-prostate-cancer-a-population-based-cohort-study
#11
Chenyang Wang, Amar U Kishan, Mitchell Kamrava, Michael L Steinberg, Christopher R King
PURPOSE: Patients with prostate cancer (PCa) containing Gleason pattern (GP) 5 disease experience a greater and earlier incidence of prostate cancer-specific mortality (PCSM) than general PCa patients. This affords the statistical power to compare PCSM outcomes among different treatment modalities even when restricting the analysis to patients treated in the modern era. The purpose of the present study was to compare the survival outcomes among patients with GP 5 PCa on needle core biopsy or transurethral resection of the prostate who underwent extremely dose-escalated radiation therapy (RT; exemplified by external beam RT with a brachytherapy boost [EBRT + BT]) versus radical prostatectomy (RP) in the modern era...
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28721686/rationale-for-initiation-and-titration-of-the-basal-insulin-glp-1ra-fixed-ratio-combination-products-ideglira-and-iglarlixi-for-the-management-of-type-2-diabetes
#12
REVIEW
Virginia Valentine, Jennifer Goldman, Jay H Shubrook
Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response...
July 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28719715/long-term-recurrence-free-survival-after-an-unplanned-reduction-in-radiotherapy-for-hpv-positive-oropharyngeal-scc-two-cases-and-a-review-of-the-literature
#13
Jason Liu, David Goldenberg, Salah Almokadem, Henry Crist, Heath B Mackley
There is currently no clear distinction between the treatment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive OPSCC has been demonstrated to be more radiosensitive than its HPV-negative counterpart. Despite this, patients with HPV-positive OPSCC continue to receive a full dose of radiation (70 Gy) outside clinical trials. However, this high dose comes with considerable morbidities, including severe mucositis, dysphagia, and xerostomia. We describe the cases of 2 patients with HPV-positive OPSCC who received two cycles of high-dose cisplatin at 100 mg/m(2) on 3 separate days, along with concurrent radiotherapy at 50 Gy in 25 fractions for one and 46 Gy in 23 fractions for the other...
July 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28719152/a-first-in-human-phase-i-multicenter-open-label-dose-escalation-study-of-the-oral-raf-vegfr-2-inhibitor-raf265-in-locally-advanced-or-metastatic-melanoma-independent-from-braf-mutation-status
#14
Benjamin Izar, William Sharfman, F Stephen Hodi, Donald Lawrence, Keith T Flaherty, Ravi Amaravadi, Kevin B Kim, Igor Puzanov, Jeffrey Sosman, Reinhard Dummer, Simone M Goldinger, Lyhping Lam, Shefali Kakar, Zhongwen Tang, Oliver Krieter, David F McDermott, Michael B Atkins
To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label, phase-I, dose-escalation trial of RAF265, an orally available RAF kinase/VEGFR-2 inhibitor, in patients with advanced or metastatic melanoma. Pharmacokinetic (PK) analysis, pharmacodynamics (PD) and tumor response assessment were conducted. We evaluated metabolic tumor response by 18[F]-fluorodeoxyglucose-positron-emission tomography (FDG-PET), tissue biomarkers using immunohistochemistry (IHC), and modulators of angiogenesis...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28717396/intraoperative-radiotherapy-review-of-techniques-and-results
#15
REVIEW
Avinash Pilar, Meetakshi Gupta, Sarbani Ghosh Laskar, Siddhartha Laskar
Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28712978/local-radiotherapy-intensification-for-locally-advanced-non-small-cell-lung-cancer-a-call-to-arms
#16
REVIEW
Noah S Kalman, Elisabeth Weiss, Paul R Walker, Julian G Rosenman
Chemoradiotherapy, the standard of care for locally advanced non-small-cell lung cancer (NSCLC), often fails to eradicate all known disease. Despite advances in chemotherapeutic regimens, locally advanced NSCLC remains a difficult disease to treat, and locoregional failure remains common. Improved radiographic detection can identify patients at significant risk of locoregional failure after definitive treatment, and newer methods of escalating locoregional treatment may allow for improvements in locoregional control with acceptable toxicity...
June 16, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28711582/a-novel-wnt-pathway-inhibitor-sm04690-for-the-treatment-of-moderate-to-severe-osteoarthritis-of-the-knee-results-of-a-24-week-randomized-controlled-phase-1-study
#17
Yusuf Yazici, Timothy E McAlindon, Roy Fleischmann, Allan Gibofsky, Nancy E Lane, Alan J Kivitz, Nebojsa Skrepnik, Eddie Armas, Christopher J Swearingen, Anita DiFrancesco, Jeyanesh R S Tambiah, John Hood, Marc C Hochberg
OBJECTIVE: To assess the safety, pharmacokinetics, and exploratory efficacy of SM04690, a novel Wnt pathway inhibitor, as a potential disease modifying treatment for knee OA. DESIGN: Subjects with Kellgren-Lawrence grade 2-3 knee OA were randomized in successive dose-escalation cohorts to receive a knee intra-articular injection with 0.03, 0.07, or 0.23 mg SM04690, or placebo (PBO) (4:1 ratio). Safety, pharmacokinetics, efficacy (WOMAC Total/Function/Pain, Pain VAS, Physician Global Assessment [MDGA], and OMERACT-OARSI Response), OA-related biomarker (P1NP, ß-CTX, and COMP), and radiographic/imaging data were collected at baseline and during 24-week follow-up...
July 12, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28709439/enhanced-antimicrobial-de-escalation-for-pneumonia-in-mechanically-ventilated-patients-a-cross-over-study
#18
Tracy Trupka, Kristen Fisher, Scott T Micek, Paul Juang, Marin H Kollef
BACKGROUND: Antibiotics are commonly administered to hospitalized patients with infiltrates for possible bacterial pneumonia, often leading to unnecessary treatment and increasing the risk for resistance emergence. Therefore, we performed a study to determine if an enhanced antibiotic de-escalation practice could improve antibiotic utilization in mechanically ventilated patients with suspected pneumonia cared for in an academic closed intensive care unit (ICU). METHODS: This was a prospective cross-over trial comparing routine antibiotic management (RAM) and enhanced antimicrobial de-escalation (EAD) performed within two medical ICUs (total 34 beds) at Barnes-Jewish Hospital, an academic referral center...
July 15, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28708802/characterization-and-expansion-of-autologous-gmp-ready-regulatory-t-cells-for-treg-based-cell-therapy-in-patients-with-ulcerative-colitis
#19
Caroline J Voskens, Anika Fischer, Susanne Roessner, Carmen Lorenz, Simon Hirschmann, Raja Atreya, Clemens Neufert, Imke Atreya, Markus F Neurath, Gerold Schuler
BACKGROUND: A local imbalance between regulatory (Treg) and effector T cells is believed to play a major role in gut-specific inflammation, including ulcerative colitis (UC). Restoration of this balance through an adoptive Treg transfer is an attractive new treatment approach in patients who are refractory to current standard therapies. It was our goal to develop a Good Manufacturing Practices (GMP)-conform protocol for expansion of UC Treg cells as a rational backbone for future studies on Treg therapy in UC...
August 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28707550/rising-cost-of-anticancer-medications-in-the-united-states
#20
Kristy Jackson, Milap C Nahata
With more than 1.6 million new cases of cancer occurring each year, anticancer medications are in high demand. Escalating prescription drug prices have become a significant concern. Anticancer medications are among the most expensive prescription medications, many of them exceeding $100 000 a year. The survival benefits of certain newer anticancer medications may be a few months more than that from the existing treatment but at a much higher price tag. Drug cost may play a substantial role in making treatment choices...
August 2017: Annals of Pharmacotherapy
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