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https://www.readbyqxmd.com/read/28088074/anti-angiogenic-treatment-in-breast-cancer-facts-successes-failures-and-future-perspectives
#1
REVIEW
Kim C Aalders, Konstantinos Tryfonidis, Elżbieta Senkus, Fatima Cardoso
Angiogenesis is one of the hallmarks of cancer and a crucial requisite in the development of tumors. Interrupting this process by blocking the vascular endothelial growth factor (VEGF) with the monoclonal antibody bevacizumab has been considered a possible breakthrough in the treatment of various types of cancer, especially for advanced disease. However in breast cancer, studies have shown ambivalent results causing debate about the value of this drug. In this article, we review the evidence for anti-angiogenic treatment options for breast cancer, as well as discuss the possible factors limiting the effectiveness of anti-angiogenic agents and offer a recommendation regarding the future research on these therapies for the treatment of breast cancer...
January 3, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28087506/a-randomised-phase-ii-study-evaluating-the-efficacy-and-safety-of-subcutaneously-administered-ustekinumab-and-guselkumab-in-patients-with-active-rheumatoid-arthritis-despite-treatment-with-methotrexate
#2
Josef S Smolen, Sandeep K Agarwal, Elena Ilivanova, Xie Lillian Xu, Ye Miao, Yanli Zhuang, Ivo Nnane, Waldemar Radziszewski, Andrew Greenspan, Anna Beutler, Daniel Baker
OBJECTIVE: Interleukin (IL)-12 and IL-23 have been implicated in the pathogenesis of rheumatoid arthritis (RA). The safety and efficacy of ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA despite methotrexate (MTX) therapy. METHODS: Patients were randomly assigned (1:1:1:1:1) to receive placebo at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 12 weeks (n=55), guselkumab 50 mg at weeks 0, 4 and every 8 weeks (n=55), or guselkumab 200 mg at weeks 0, 4 and every 8 weeks (n=54) through week 28; all patients continued a stable dose of MTX (10-25 mg/week)...
January 13, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28087261/dna-aptamer-probes-for-detection-of-estrogen-receptor-%C3%AE-positive-carcinomas
#3
Arghya Sett, Bibhuti Bhusan Borthakur, Jagannath Dev Sharma, Amal Chandra Kataki, Utpal Bora
Estrogen receptor alpha (ERα) which is a ligand-activated transcription factor also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1). It is an important biomarker for breast cancer metastasis. In the present study, we report a novel DNA aptamer candidate against estrogen receptor (ER) alpha structure. The enriched aptamer candidate was obtained after 14 iterative cycles of in vitro protein-SELEX process. Isothermal calorimetry study suggests the nanomolar sensitivity of the candidate ER_Apt1 to its target protein...
December 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28087107/establishment-of-the-2nd-korean-national-biological-reference-standard-for-blood-coagulation-factor-viii-c-concentrate
#4
Naery Lee, Ji Suk Seo, Jae Ok Kim, Sang Ja Ban
Since the 1st Korean national biological reference standard for factor (F)VIII concentrate, established in 2001, has shown declining potency, we conducted this study to replace this standard with a 2nd Korean national biological reference standard for blood coagulation FVIII concentrate. The candidate materials for the 2nd standard were prepared in 8000 vials with 10 IU/ml of target potency, according to the approved manufacturing process of blood coagulation Factor VIII:C Monoclonal Antibody-purified, Freeze-dried Human Blood Coagulation Factor VIII:C...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28087106/charge-variant-analysis-of-proposed-biosimilar-to-trastuzumab
#5
Pravinkumar Dakshinamurthy, Pavithra Mukunda, Bhargav Prasad Kodaganti, Bharath Ravindra Shenoy, Bairavabalakumar Natarajan, Amol Maliwalave, Vivek Halan, Sathyabalan Murugesan, Sunit Maity
Trastuzumab is a humanized monoclonal antibody (mAb) employed for the treatment of HER2 Positive Breast Cancer. A HER2 overexpressing tumor cell binds to Trastuzumab and attracts immune cells which lead to induction of Antibody Dependent Cellular Cytotoxicity (ADCC) by binding to Fc receptors (CD16a or FcγRIIIa) on an effector cell, such as natural killer (NK) cells. The most commonly expressed receptor on NK cell is CD16a which binds to the Fc portion of Trastuzumab. The ligand-independent HER2-HER3 dimerization is the most potent stimulator of downstream pathways for regulation of cell growth and survival...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28087006/new-insights-into-the-pathogenesis-and-treatment-of-heavy-chain-deposition-disease
#6
Jonathan J Hogan, Glen S Markowitz
Heavy chain deposition disease is defined by the presence of tissue deposits of truncated monoclonal Ig heavy chains, usually associated with an underlying plasma cell clone. In this issue of Kidney International, Bridoux et al. described the clinical, histologic, and molecular characterization of 15 patients with heavy chain deposition disease, which is the largest case series to date. Notable findings included the frequent presence of C3 deposits and hypocomplementemia, the uniform finding of truncated heavy chains with the deletion in the heavy chain constant region 1, and the common occurrence of an abnormal serum-free κ:λ ratio, despite the absence of light-chain tissue deposition...
February 2017: Kidney International
https://www.readbyqxmd.com/read/28086964/anti-%C3%AE-synuclein-immunotherapy-reduces-%C3%AE-synuclein-propagation-in-the-axon-and-degeneration-in-a-combined-viral-vector-and-transgenic-model-of-synucleinopathy
#7
Brian Spencer, Elvira Valera, Edward Rockenstein, Cassia Overk, Michael Mante, Anthony Adame, Wagner Zago, Peter Seubert, Robin Barbour, Dale Schenk, Dora Games, Robert A Rissman, Eliezer Masliah
Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models...
January 13, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28086930/mannose-binding-lectin-associated-serine-protease-2-masp-2-contributes-to-poor-disease-outcome-in-humans-and-mice-with-pneumococcal-meningitis
#8
E Soemirien Kasanmoentalib, Mercedes Valls Seron, Bart Ferwerda, Michael W Tanck, Aeilko H Zwinderman, Frank Baas, Arie van der Ende, Matthijs C Brouwer, Diederik van de Beek
BACKGROUND: Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the pro-inflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. METHODS: We investigated mannose-binding lectin-associated serine protease (MASP-2) levels in cerebrospinal fluid (CSF) samples derived from the diagnostic lumbar puncture, which was available for 307 of 792 pneumococcal meningitis episodes included in our prospective nationwide cohort study (39%), and the association between these levels and clinical outcome...
January 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28081547/diagnosis-of-pancreaticobiliary-malignancy-by-detection-of-minichromosome-maintenance-protein-5-in-biliary-brush-cytology
#9
Margaret G Keane, Matthew T Huggett, Michael H Chapman, Gavin J Johnson, George J Webster, Douglas Thorburn, James Mackay, Stephen P Pereira
BACKGROUND: Biliary brush cytology is the standard method of evaluating biliary strictures, but is insensitive at detecting malignancy. In pancreaticobiliary cancer minichromosome maintenance replication proteins (MCM 2-7) are dysregulated in the biliary epithelium and MCM5 levels are elevated in bile samples. This study aimed to validate an immunocolorimetric ELISA assay for MCM5 as a pancreaticobiliary cancer biomarker in biliary brush samples. METHODS: Biliary brush specimens were collected prospectively at ERCP from patients with a biliary stricture...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28081478/pulmonary-sarcomatoid-carcinoma-with-alk-rearrangement-frequency-clinical-pathologic-characteristics-and-response-to-alk-inhibitor
#10
Xinru Chen, Yu Zhang, Jiabin Lu, Chunwei Xu, Jianzhong Liang, Fang Wang, Wenyong Sun, Sangao Fang, Jingping Yuan, Huijuan Wang, Hui Wang, Xuewen Liu, Likun Chen
PURPOSE: The incidence of anaplastic lymphoma kinase (ALK) rearrangement in pulmonary sarcomatoid carcinoma (PSC) is controversial. In this study, we aimed to reveal the reliable frequency and the clinical-pathologic characteristics of pulmonary sarcomatoid carcinoma (PSC) with ALK rearrangement in Chinese population, and to provide insight into the translatability of anti-ALK treatment in this treatment-refractory disease. METHODS: Immunohistochemistry (IHC) using a Ventana anti-ALK (D5F3) rabbit monoclonal antibody was performed in 141 PSC specimens collected from multiple medical centers...
January 9, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28081259/frequency-of-propionibacterium-acnes-infection-in-prostate-glands-with-negative-biopsy-results-is-an-independent-risk-factor-for-prostate-cancer-in-patients-with-increased-serum-psa-titers
#11
Tomoya Kakegawa, Yuan Bae, Takashi Ito, Keisuke Uchida, Masaki Sekine, Yutaka Nakajima, Asuka Furukawa, Yoshimi Suzuki, Jiro Kumagai, Takumi Akashi, Yoshinobu Eishi
BACKGROUND: Propionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative...
2017: PloS One
https://www.readbyqxmd.com/read/28079685/asymmetric-deep-stromal-keratopathy-in-a-patient-with-multiple-myeloma
#12
Laurel T Tainsh, Patrick A Coady, John H Sinard, Natalia Neparidze, Seth W Meskin, Ron A Adelman, Jessica Chow
PURPOSE: To report a case of asymmetric deep stromal keratopathy in a patient with multiple myeloma. METHODS: Case report and literature review. RESULTS: An 85-year-old woman was found to have progressive visually significant left-sided deep stromal opacity in the setting of monoclonal gammopathy. Hematologic workup resulted in a diagnosis of IgG kappa multiple myeloma. Histopathology was significant for semicrystalline deposits in the posterior stroma...
January 11, 2017: Cornea
https://www.readbyqxmd.com/read/28079637/ln2-cd10-and-ezrin-do-not-distinguish-between-atypical-fibroxanthoma-and-undifferentiated-pleomorphic-sarcoma-or-predict-clinical-outcome
#13
Allison Hanlon, Thomas Stasko, Dan Christiansen, Nika Cyrus, Anjela Galan
BACKGROUND: Atypical fibroxanthoma (AFX) is a rare cutaneous spindled cell neoplasm. For both diagnostic and therapeutic purposes, it is important to distinguish AFX from other poorly differentiated tumors, including undifferentiated pleomorphic sarcoma (UPS). OBJECTIVE: The authors aimed to identify the clinical, histologic, and immunohistochemical expression of LN2, ezrin, and CD10 in AFX and UPS tumors. METHODS AND MATERIALS: The authors retrospectively examined the charts of patients with AFX and UPS treated with Mohs micrographic surgery (MMS) at 2 academic institutions...
January 10, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28078656/biosimilars-for-the-treatment-of-cancer-a-systematic-review-of-published-evidence
#14
REVIEW
Ira Jacobs, Reginald Ewesuedo, Sadiq Lula, Charles Zacharchuk
BACKGROUND: Biologic treatments for cancer continue to place a significant economic burden on healthcare stakeholders. Biosimilar therapies may help reduce this burden through cost savings, thereby increasing patient access. OBJECTIVES: The purpose of this study was to collate all published data to assess the weight of available evidence (quantity and quality) for proposed monoclonal antibody biosimilars and intended copies, for the treatment of cancer. METHODS: MEDLINE(®), Embase(®), and ISI Web of Science(®) databases were searched to September 2015...
January 11, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28078592/site-specific-detection-of-tyrosine-phosphorylated-cd95-following-protein-separation-by-conventional-and-phospho-protein-affinity-sds-page
#15
Krittalak Chakrabandhu, Sébastien Huault, Anne-Odile Hueber
Phosphorylation of two tyrosines in the death domain of CD95 is a critical mechanism in determining the receptor's choices between cell death and survival signals. Recently, site-specific monoclonal antibodies against phosphorylated tyrosines of CD95 have been generated and used to successfully detect each phosphorylated death domain tyrosine of CD95 directly and separately by immunoblotting. Here we provide detailed protocols and useful tips for a successful site-specific detection of phosphorylated death domain tyrosine of CD95 following a protein separation by sizes (conventional SDS-PAGE) and by degrees of phosphorylation (phospho-protein affinity, mobility shift SDS-PAGE)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078579/immunoprecipitation-of-death-inducing-signaling-complex-by-caspase-8
#16
Andrei Alexandru Constentinescu, Aymeric Morlé, Olivier Micheau
Analysis of CD95/Fas complexes by immunoprecipitation has long relied on the monoclonal antibody APO1 or tagged recombinant Fas ligand. Immunoprecipitation is an elegant and efficient procedure to investigate endogenous protein interactions or complexes. Provided that the targeted complex is soluble in mild detergent these complexes can be recovered using protein A/G-coupled Sepharose beads and further analyzed after denaturation and electrophoretic separation by western blotting or mass spectrometry. Herein, we describe in detail the method used in our laboratory to immunoprecipitate and analyze by immunoblot complexes containing caspase-8, using a commercial antibody directed against caspase-8...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078413/establishment-of-a-sandwich-enzyme-linked-immunosorbent-assay-for-specific-detection-of-bacillus-thuringiensis-bt-cry1ab-toxin-utilizing-a-monoclonal-antibody-produced-with-a-novel-hapten-designed-with-molecular-model
#17
Sa Dong, Xiao Zhang, Yuan Liu, Cunzheng Zhang, Yajing Xie, Jianfeng Zhong, Chongxin Xu, Xianjin Liu
Cry1Ab toxin is commonly expressed in genetically modified crops in order to control chewing pests. At present, the detection method with enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibody cannot specifically detect Cry1Ab toxin for Cry1Ab's amino acid sequence and spatial structure are highly similar to Cry1Ac toxin. In this study, based on molecular design, a novel hapten polypeptide was synthesized and conjugated to keyhole limpet hemocyanin (KLH). Then, through animal immunization with this antigen, a monoclonal antibody named 2C12, showing high affinity to Cry1Ab and having no cross reaction with Cry1Ac, was produced...
January 11, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28078198/multidisciplinary-approach-to-management-of-temporal-bone-giant-cell-tumor
#18
Taija K Nicoli, Riste Saat, Risto Kontio, Anna Piippo, Maija Tarkkanen, Jussi Tarkkanen, Jussi Jero
Background Giant cell tumors (GCTs) are rare osseous tumors that rarely appear in the skull. Methods We review the clinical course of a 28-year-old previously healthy woman with a complicated GCT. Results The reviewed patient presented with a middle cranial fossa tumor acutely complicated by reactive mastoiditis. Left tympanomastoidectomy was performed for drainage of the mastoiditis and for biopsies of the tumor. Due to the challenging tumor location, the patient was treated with denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor kappa-B ligand, for 7 months, which resulted in significant preoperative tumor shrinkage...
July 2016: Journal of Neurological Surgery Reports
https://www.readbyqxmd.com/read/28078108/egfr-family-and-cmet-expression-profiles-and-prognostic-significance-in-esophagogastric-adenocarcinoma
#19
Ellie Chan, Ahmad Alkhasawneh, Lizette Vila Duckworth, Tabish Aijaz, Tania Zuluaga Toro, Xiaomin Lu, Steven J Hughes, Amy Collinsworth, Thomas J George
BACKGROUND: Targeted therapy with anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody in patients with HER2 overexpressed esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Some studies suggest that cMet overexpression provides cross talk for epidermal growth factor receptor (EGFR) and HER2 inhibition. We sought to characterize the expression profile of the EGFR family and cMet receptors in untreated, resected EGA...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28077676/a-ptk7-targeted-antibody-drug-conjugate-reduces-tumor-initiating-cells-and-induces-sustained-tumor-regressions
#20
Marc Damelin, Alexander Bankovich, Jeffrey Bernstein, Justin Lucas, Liang Chen, Samuel Williams, Albert Park, Jorge Aguilar, Elana Ernstoff, Manoj Charati, Russell Dushin, Monette Aujay, Christina Lee, Hanna Ramoth, Milly Milton, Johannes Hampl, Sasha Lazetic, Virginia Pulito, Edward Rosfjord, Yongliang Sun, Lindsay King, Frank Barletta, Alison Betts, Magali Guffroy, Hadi Falahatpisheh, Christopher J O'Donnell, Robert Stull, Marybeth Pysz, Paul Escarpe, David Liu, Orit Foord, Hans Peter Gerber, Puja Sapra, Scott J Dylla
Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs)...
January 11, 2017: Science Translational Medicine
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