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C Wilson, R Bell, S Hinsley, H Marshall, J Brown, D Cameron, D Dodwell, R Coleman
The fracture impact of adjuvant bisphosphonates in breast cancer is not defined with most trials reporting changes in bone mineral density as a surrogate. The AZURE trial (ISRCTN79831382) evaluated the impact of adjuvant zoledronic acid (ZOL) on fractures. The AZURE trial is an academic, multi-centre, randomised phase III study evaluating the addition of ZOL 4 mg to standard therapy (neo/adjuvant chemotherapy and/or endocrine therapy) for 5 years (administered by intravenous (iv) infusion every 3-4 weeks for 6 doses, then 3 monthly × 8 and 6 monthly × 5) in patients with stage II/III early breast cancer...
March 12, 2018: European Journal of Cancer
Leslee Sprague, Joel M Lee, Brian J Hutzen, Pin-Yi Wang, Chun-Yu Chen, Joe Conner, Lynne Braidwood, Kevin A Cassady, Timothy P Cripe
High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, other groups including previous reports from our laboratory highlight the synergistic effects of OVs with chemotherapy drugs. Here, we show that virus-free supernatants have varying cytotoxic potential, and HMGB1 is actively secreted by two established fibroblast cell lines (NIH 3T3 and 3T6-Swiss albino) following HSV1716 infection in vitro...
March 15, 2018: Viruses
Christine Juergens, James Trammel, Yasuko Shoji, Scott Patterson, Wendy Watson, Chris Webber, William C Gruber, Daniel A Scott, Beate Schmoele-Thoma
Injection site reactions (ISRs; redness, swelling and pain) commonly occur within 1-2 days after vaccination. After administration of toxoid vaccines including diphtheria toxoid, a later onset of ISRs has also been observed. As the serotype capsular polysaccharides in the 13-valent pneumococcal conjugate vaccine (PCV13) are conjugated to cross-reactive material 197 (CRM197 ), a nontoxic variant of diphtheria toxin, the onset of ISRs over 14 days was explored in 8 adult studies with 19 cohorts. Subjects received PCV13 with aluminum phosphate (AlPO4 , n = 5667) or without AlPO4 (n = 304); 109 subjects received 23-valent pneumococcal polysaccharide vaccine (PPSV23)...
March 15, 2018: Human Vaccines & Immunotherapeutics
Michael Untch, Gunter von Minckwitz, Bernd Gerber, Christian Schem, Mahdi Rezai, Peter A Fasching, Hans Tesch, Holm Eggemann, Claus Hanusch, Jens Huober, Christine Solbach, Christian Jackisch, Georg Kunz, Jens-Uwe Blohmer, Maik Hauschild, Tanja Fehm, Valentina Nekljudova, Sibylle Loibl
Purpose The GeparQuinto phase III trial demonstrated a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline-taxane chemotherapy compared with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Here, we report the long-term outcomes. Methods Patients with HER2-positive tumors (n = 615) received neoadjuvant treatment with epirubicin (E) plus cyclophosphamide (C), followed by docetaxel (T) in combination with either lapatinib (L) or trastuzumab (H; ECH-TH arm: n = 307; ECL-TL arm: n = 308)...
March 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Martina Gobec, Tihomir Tomašič, Adela Štimac, Ruža Frkanec, Jurij Trontelj, Marko Anderluh, Irena Mlinaric-Rascan, Žiga Jakopin
Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date...
March 15, 2018: Journal of Medicinal Chemistry
A V Petrayevsky, K S Trishkin
Pterygium is one of the modern problems of ophthalmology. The exact etiology and pathogenesis of this disease has not been reliably established and, as a result, there is no universal method for its recurrence-free treatment. The literature data on various methods of pterygium surgical treatment such as 'bare sclera', conjunctival autograft, limbal stem cells transplantation techniques, amniotic membrane plasty and other methods was analyzed. The advantages and disadvantages of those surgery methods were identified...
2018: Vestnik Oftalmologii
Narges Sadeghi, Farnoush Paknezhad, Mohamadreza Rashidi Nooshabadi, Maria Kavianpour, Sima Jafari Rad, Hossein Khadem Haghighian
Primary dysmenorrhea is one of the most common complaints of women. The aim of this study was to investigate the adjuvant effect of vitamin E and omega-3 fatty acids, separately or in combination, supplements on pain in the treatment of primary dysmenorrhea. This clinical trial conducted on students of university. Qualified girls completed the VAS before randomization. Arrangement was determined according to the severity of the pain (mild 0-3; moderate 3.1-6; severe 6.1-10). One hundred patients were randomly assigned to four groups receiving omega-3 (n = 25), vitamin E (n = 25), vitamin E- omega-3 (n = 25), or placebo (n = 25)...
March 15, 2018: Gynecological Endocrinology
Weiping Cao, Margarita Mishina, Samuel Amoah, Wadzanai P Mboko, Caitlin Bohannon, James McCoy, Suresh K Mittal, Shivaprakash Gangappa, Suryaprakash Sambhara
Avian influenza virus infection is a serious public health threat and preventive vaccination is the most cost-effective public health intervention strategy. Unfortunately, currently available unadjuvanted avian influenza vaccines are poorly immunogenic and alternative vaccine formulations and delivery strategies are in urgent need to reduce the high risk of avian influenza pandemics. Cationic polymers have been widely used as vectors for gene delivery in vitro and in vivo. In this study, we formulated H5N1 influenza vaccines with GenJet™ or in vivo-jetPEI® , and showed that these formulations significantly enhanced the immunogenicity of H5N1 vaccines and conferred protective immunity in a mouse model...
November 2018: Drug Delivery
Dafina Ilijazi, Mohammad Abufaraj, Melanie R Hassler, Iris E Ertl, David D'Andrea, Shahrokh F Shariat
Bladder cancer (BCa) is the fifth most frequently diagnosed cancer worldwide and is, in fact, the most expensive cancer on a per-patient to treat basis. There is a critical need to implement new tests into clinical practice to improve the quality of clinical care, decrease unnecessary invasive therapies and ultimately save costs. Currently, no molecular or genetic biomarker has been widely integrated into daily clinical practice. However, major milestones have been achieved in our understanding of the molecular alterations in BCa that will provide the basis for integrating molecular and genetic biomarkers into clinical decision making to guide management...
March 15, 2018: Expert Review of Molecular Diagnostics
Shulian Wu, Yudian Huang, Qinggong Tang, Zhifang Li, Hannah Horng, Jiatian Li, Zaihua Wu, Yu Chen, Hui Li
Preoperative neoadjuvant treatment in locally advanced breast cancer is recognized as an effective adjuvant therapy, as it improves treatment outcomes. However, the potential complications remain a threat, so there is an urgent clinical need to assess both the tumor response and changes in its microenvironment using non-invasive and precise identification techniques. Here, two-photon microscopy was employed to detect morphological alterations in breast cancer progression and recession throughout chemotherapy...
March 1, 2018: Biomedical Optics Express
Ken Sasaki, Yasuto Uchikado, Itaru Omoto, Masahiko Amatatsu, Koichi Megumi, Hiroshi Okumura, Kosei Maemura, Shoji Natsugoe
Standard treatment strategies have not yet been established for primary malignant melanoma of the esophagus (PMME), and far much less for recurrent disease. There are no reports of anti-programmed death-1 antibody treatment of recurrent PMME. A 60-year-old Japanese man was diagnosed with a primary malignant melanoma in the lower esophagus. The patient underwent mediastinoscope-assisted subtotal esophagectomy, and two nodal involvements were detected in the lymph nodes (LN)s along the left gastric artery. Paclitaxel and oral fluoropyrimidine were administered for 2 months as adjuvant treatment based on results of a histoculture drug response assay...
April 2018: Molecular and Clinical Oncology
Xiao Sun, Tanxiao Huang, Fangsheng Cheng, Kaibing Huang, Ming Liu, Wan He, Mingwei Li, Xiaoni Zhang, Mingyan Xu, Shifu Chen, Ligang Xia
Postoperative monitoring for patients with colorectal cancer (CRC) requires sensitive biomarkers that are associated with medical response and adjuvant therapy following surgery. Conventional tumor biomarkers [including carcinoembryonic antigen (CEA), CA19-9 and CA125] are widely used, but none of the markers provide high sensitivity or specificity. Previous studies indicated that circulating tumor DNA (ctDNA) is useful for postoperative monitoring of patients with cancer. However, the majority of previous studies involved patients with lung cancer, and therefore further studies are required which investigate patients with CRC...
April 2018: Oncology Letters
Junichiro Kawamura, Fumiaki Sugiura, Yasushi Sukegawa, Yasumasa Yoshioka, Jin-Ichi Hida, Shoichi Hazama, Kiyotaka Okuno
The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34-kDa translocase of the outer mitochondrial membrane combined with uracil-tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)-A status was double-blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy...
April 2018: Oncology Letters
Jie Zhu, Hao Chen, Zhixiu Song, Xudong Wang, Zhenshuang Sun
Objective: This article aims to assess the effects of ginger (Zingiber officinale Roscoe) on type 2 diabetes mellitus (T2DM) and/or components of the metabolic syndrome (MetS). Methods: Electronic literature was searched in PubMed, Embase, the Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, and Wanfang Database from inception of the database to May 19, 2017, and supplemented by browsing reference lists of potentially eligible articles...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Maria Vono, Christiane Sigrid Eberhardt, Elodie Mohr, Floriane Auderset, Dennis Christensen, Mirco Schmolke, Rhea Coler, Andreas Meinke, Peter Andersen, Paul-Henri Lambert, Beatris Mastelic-Gavillet, Claire-Anne Siegrist
Neonates and infants are more vulnerable to infections and show reduced responses to vaccination. Consequently, repeated immunizations are required to induce protection and early life vaccines against major pathogens such as influenza are yet unavailable. Formulating antigens with potent adjuvants, including immunostimulators and delivery systems, is a demonstrated approach to enhance vaccine efficacy. Yet, adjuvants effective in adults may not meet the specific requirements for activating the early life immune system...
2018: Frontiers in Immunology
Mohammad Idrees Adhi, Sumbul Kashif, Kashif Muhammed, Nisar Siyal
OBJECTIVE: To document clinical pattern of retinoblastoma in Pakistani population. METHODS: This retrospective study, which was conducted at Department of Ophthalmology, Dow University of Health Sciences, Karachi, reviewed clinical records of patients with retinoblastoma from 1997 to 2012. Staging of disease was done by referring to retinal diagrams, RetCam images, and first magnetic resonance imaging. Ophthalmic notes, imaging reports and histopathology reports of enucleated eyes established optic nerve involvement...
March 2018: JPMA. the Journal of the Pakistan Medical Association
Yu-Chen Lu, Yu-Jun Wang, Bin Lu, Ming Chen, Ping Zheng, Jing-Gen Liu
Itch is an unpleasant sensation that initiates scratching behavior. Itch-scratch reaction is a complex phenomenon whose occurrence implicates supraspinal structures required for regulation of sensory, emotional, cognitive, and motivational aspects. However, the central mechanisms underlying the processing of itch and the interplay of the supraspinal regions and spinal cord in regulating itch-scratch processes are poorly understood. Here, we have identified that the neural projections from anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) constitute a critical circuit element for regulating itch-related behaviors in the brain of male C57BL/6J mice...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ronald Domalaon, Temilolu Idowu, George G Zhanel, Frank Schweizer
The global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies to overcome this problem. Intrinsic resistance in Gram-negative bacteria, such as their protective outer membrane and constitutively overexpressed efflux pumps, is a major survival weapon that renders them refractory to current antibiotics. Several potential avenues to overcome this problem have been at the heart of antibiotic drug discovery in the past few decades...
April 2018: Clinical Microbiology Reviews
Margareta Heby, Sebastian Lundgren, Björn Nodin, Jacob Elebro, Jakob Eberhard, Karin Jirström
BACKGROUND: Periampullary adenocarcinomas, including pancreatic cancer, are a heterogeneous group of tumors with poor prognosis, where classification into intestinal type (I-type) or pancreatobiliary type (PB-type) is a relevant prognostic factor. The clinical significance of deficient mismatch repair (dMMR) in periampullary adenocarcinoma is comparatively unexplored. Herein, we examined the associations of MMR immunophenotype with long-term survival in patients with resected periampullary adenocarcinoma, with particular reference to morphology and adjuvant treatment response...
March 14, 2018: Journal of Translational Medicine
Charline Kambrun, Olivier Roca-Lapirot, Chiara Salio, Marc Landry, Aziz Moqrich, Yves Le Feuvre
C-low-threshold mechanoreceptors (C-LTMRs) are sensory neurons that, beyond conveying pleasant touch, modulate nociceptive transmission within the spinal cord. However, pain alleviation by C-LTMRs remains poorly understood. Here, we show that the C-LTMR-derived TAFA4 chemokine induces a reinforcement of inhibitory synaptic transmission within spinal networks, which consequently depresses local excitatory synapses and impairs synaptic transmission from high-threshold C-fibers. In animals with inflammation induced by Freund's complete adjuvant, TAFA4 decreases the noxious stimulus-induced neuronal responses recorded in vivo and alleviates mechanical pain...
March 13, 2018: Cell Reports
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