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monoclonal antibodies in therapy

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https://www.readbyqxmd.com/read/28738235/treatment-decisions-in-metastatic-colorectal-cancer-beyond-first-and-second-line-combination-therapies
#1
REVIEW
A Vogel, R D Hofheinz, S Kubicka, D Arnold
Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30months in recent clinical trials of first line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important...
May 4, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28737051/pharmacokinetic-pharmacodynamic-drug-evaluation-of-benralizumab-for-the-treatment-of-asthma
#2
Maria Gabriella Matera, Luigino Calzetta, Barbara Rinaldi, Mario Cazzola
In many severe asthmatics, eosinophils cause inflammation and airways hyperresponsiveness, resulting in frequent exacerbations, impaired lung function, and reduced quality of life. Interleukin-5 (IL-5) is a key cytokine for eosinophil growth, differentiation, recruitment, activation, and survival. Anti-IL-5-based therapies (mepolizumab and reslizumab are humanized monoclonal antibodies (hmAbs) that recognize free IL-5, benralizumab is a hmAb directed at the α subunit of the IL-5R) target the IL-5-signaling in eosinophilic asthma...
July 24, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28736830/pcsk9-in-context-a-contemporary-review-of-an-important-biological-target-for-the-prevention-and-treatment-of-atherosclerotic-cardiovascular-disease
#3
REVIEW
Michael M Page, Gerald F Watts
Proprotein convertase subtilisin/kexin type 9 (PCSK9) and the identification of its critical role in lipoprotein metabolism has rapidly led to the development of PCSK9 inhibition with monoclonal antibodies (mAbs). PCSK9 mAbs are already in limited clinical use and are the subject of major cardiovascular outcomes trials, which if universally positive could see much wider clinical application of these agents. Patients with familial hypercholesterolaemia are the most obvious candidates for these drugs, but other patients with elevated cardiovascular risk, statin intolerance or hyperlipoproteinaemia(a) may also benefit...
July 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28736637/primary-and-acquired-resistance-to-biologic-therapies-in-gastrointestinal-cancers
#4
REVIEW
Sam J Lubner, Nataliya V Uboha, Dustin A Deming
Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736636/biological-agents-in-gastrointestinal-cancers-adverse-effects-and-their-management
#5
REVIEW
Nivedita Arora, Arjun Gupta, Preet Paul Singh
Biological therapy comprises agents that by virtue of their unique mechanisms of action, are able to specifically incite a response against or target malignant cells. They differ from conventional chemotherapy with regard to mechanisms of action, indications and side effect profile. Biologic agents have revolutionized therapy for a number of malignancies. In the setting of gastrointestinal (GI) malignancies, agents targeting vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (Her2/Neu) and epidermal growth factor receptor (EGFR) have proven to be invaluable additions to chemotherapy...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736635/immunotherapy-in-gastrointestinal-cancers
#6
REVIEW
Patrick Grierson, Kian-Huat Lim, Manik Amin
Gastrointestinal (GI) cancers such as gastric, esophageal, pancreas, hepatobiliary, colorectal and anal cancers are a major cause of cancer related mortality worldwide. Traditional treatment options such as chemotherapy, surgery, radiation therapy, monoclonal antibodies and anti-angiogenic agents have been the backbone of treatment of GI cancers in various stages. Current cancer research is moving forward to incorporate immunotherapies in the treatment of GI cancers either as single agent or in combination with current available treatment modalities...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#7
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28736183/immunotherapy-targeting-immune-check-point-s-in-brain-metastases
#8
Anna Maria Di Giacomo, Monica Valente, Alessia Covre, Riccardo Danielli, Michele Maio
Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype...
July 13, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28736182/immune-checkpoint-therapy-of-mesothelioma-pre-clinical-bases-and-clinical-evidences
#9
Luana Calabrò, Giovanni Luca Ceresoli, Armida D'Incecco, Arnaud Scherpereel, Joachim Aerts, Michele Maio
Treatment with immune-checkpoint blocking monoclonal antibody (mAb) is demonstrating a significant efficacy in different tumor types. Here, we discuss the impact of this promising approach in malignant mesothelioma (MM), a still dreadful disease in which medical treatment has been set on platinum based chemotherapy for decades with unsatisfactory results.
July 12, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28735814/tyrosine-kinase-inhibitors-as-modulators-of-trastuzumab-mediated-antibody-dependent-cell-mediated-cytotoxicity-in-breast-cancer-cell-lines
#10
Denis M Collins, Kathy Gately, Clare Hughes, Connla Edwards, Anthony Davies, Stephen F Madden, Kenneth J O'Byrne, Norma O'Donovan, John Crown
BACKGROUND: Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab...
July 15, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28735727/investigation-of-the-role-of-dna-methylation-in-the-expression-of-erbb2-in-human-myocardium
#11
Adolfo Quiñones-Lombraña, Rachael Hageman Blair, Javier G Blanco
The ERBB2 gene encodes a transmembrane tyrosine kinase receptor that belongs to the epidermal growth factor receptor (EGFR) family. ERBB2 plays a pivotal role during heart development and is essential for normal cardiac function, particularly during episodes of cardiac stress. The monoclonal antibody drug trastuzumab is used for the therapy of breast cancers that overexpress ERBB2. The clinical use of trastuzumab is limited by the development of cardiotoxicity in some patients. Inter-individual differences in the expression of ERBB2 in cardiac tissue may impact the risk of cardiotoxicity...
July 20, 2017: Gene
https://www.readbyqxmd.com/read/28735520/gemst-a-taylor-made-combination-that-reverts-neuroanatomical-changes-in-stroke
#12
Arturo Mangas, Javier Yajeya, Noelia González, Isabel Ruiz, Marianny Pernìa, Michel Geffard, Rafael Coveñas
In a single transient middle cerebral artery occlusion model of stroke and using immunohistochemical techniques, the effects of a new therapeutic approach named Gemst (a member of the Poly-L-Lysine innovative therapies) have been studied in the rat brain. The expression of inflammatory (CD45, CD11b), oxidative (NO-tryptophan, NO2-tyrosine) and indoleamine 2, 3-dioxygenase pathway (kynurenic acid, 3-hydroxy anthranilic acid) markers has been evaluated in early and late phases of stroke. For this purpose, we have developed eight highly specific monoclonal antibodies directed against some of these markers...
May 25, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28735439/surgical-management-of-periocular-cancers-high-and-low-risk-features-drive-treatment
#13
REVIEW
Richard C Allen
PURPOSE OF REVIEW: Recent advances in the treatment of eyelid tumors have centered on the excision, evaluation of margins, role of sentinel lymph node biopsy, and adjunctive/adjuvant systemic and radiation therapy. The purpose of this review is to elaborate on these advances. RECENT FINDINGS: Mohs excision of basal cell carcinoma and squamous cell carcinoma continues to provide the greatest success in complete excision of the cancer, especially in those cases of high-risk disease including medial canthal location and recurrent disease...
September 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28733263/consolidation-therapy-for-newly-diagnosed-pediatric-high-risk-neuroblastoma-patients-using-busulfan-melphalan-autologous-hematopoietic-cell-transplant-anti-gd2-antibody-gm-csf-il-2-and-haploidentical-nk-cells
#14
Aimee C Talleur, Brandon M Triplett, Sara Federico, Ewelina Mamcarz, William Janssen, Jianrong Wu, David Shook, Wing Leung, Wayne L Furman
The treatment of pediatric high-risk neuroblastoma is intensive and multimodal. Despite the introduction of immunotherapy for minimal residual disease, survival rates remain suboptimal and new therapies are needed. As part of a phase 2 trial, we are using a consolidation therapy regimen which combines a busulfan/melphalan conditioning schema, autologous hematopoietic cell transplant (AHCT), and experimental immunotherapy with hu14.18K322A (a humanized anti-GD2 monoclonal antibody), GM-CSF, and IL-2, with or without the adoptive transfer of haploidentical natural killer cells (NKs)...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28731207/polyclonal-and-monoclonal-antibodies-for-treating-acute-rejection-episodes-in-kidney-transplant-recipients
#15
REVIEW
Angela C Webster, Sunny Wu, Krishna Tallapragada, Min Young Park, Jeremy R Chapman, Sue J Carr
BACKGROUND: Registry data shows that the incidence of acute rejection has been steadily falling. Approximately 10% to 35% of kidney recipients will undergo treatment for at least one episode of acute rejection within the first post-transplant year. Treatment options include pulsed steroid therapy, the use of an antibody preparation, the alteration of background immunosuppression, or combinations of these options. Over recent years, new treatment strategies have evolved, and in many parts of the world there has been an increase in use of tacrolimus and mycophenolate and a reduction in the use of cyclosporin and azathioprine use as baseline immunosuppression to prevent acute rejection...
July 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#16
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28730960/protein-kinases-as-tumor-biomarkers-and-therapeutic-targets
#17
Chuntao Quan, Juanjuan Xiao, Lin Liu, Qiuhong Duan, Ping Yuan, Feng Zhu
Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied in clinical settings and have achieved very good treatment efficacy, many cancer patients died of tumor metastasis, drug toxicity or drug resistance due to tumor heterogeneity. Targeted molecular treatments based on the genes, receptors, and kinases expressed by a tumor make individualized treatment possible...
July 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28730660/bezlotoxumab-a-novel-agent-for-the-prevention-of-recurrent-clostridium-difficile-infection
#18
Wesley D Kufel, Aaron S Devanathan, Ashley H Marx, David J Weber, Lindsay M Daniels
Over the last decade, the incidence and severity of Clostridium difficile infection (CDI) have significantly increased, leading to a rise in CDI-associated hospitalizations, health care costs, and mortality. Although treatment options exist for CDI, recurrence is frequent following treatment. Furthermore, patients with at least one CDI recurrence are at an increased risk of developing additional recurrences. A novel approach to the prevention of recurrent CDI is the use of monoclonal antibodies directed against the toxins responsible for CDI as an adjunct to antibiotic treatment...
July 21, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28729154/tremelimumab-as-second-line-or-third-line-treatment-in-relapsed-malignant-mesothelioma-determine-a-multicentre-international-randomised-double-blind-placebo-controlled-phase-2b-trial
#19
Michele Maio, Arnaud Scherpereel, Luana Calabrò, Joachim Aerts, Susana Cedres Perez, Alessandra Bearz, Kristiaan Nackaerts, Dean A Fennell, Dariusz Kowalski, Anne S Tsao, Paul Taylor, Federica Grosso, Scott J Antonia, Anna K Nowak, Maria Taboada, Martina Puglisi, Paul K Stockman, Hedy L Kindler
BACKGROUND: New therapeutic strategies for malignant mesothelioma are urgently needed. In the DETERMINE study, we investigated the effects of the cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody tremelimumab in patients with previously treated advanced malignant mesothelioma. METHODS: DETERMINE was a double-blind, placebo-controlled, phase 2b trial done at 105 study centres across 19 countries in patients with unresectable pleural or peritoneal malignant mesothelioma who had progressed after one or two previous systemic treatments for advanced disease...
July 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28725493/interferon-alpha-based-immunotherapies-in-the-treatment-of-b-cell-derived-hematologic-neoplasms-in-today-s-treat-to-target-era
#20
REVIEW
Li Zhang, Yu-Tzu Tai, Matthew Zhi Guang Ho, Lugui Qiu, Kenneth C Anderson
B cell lymphoma and multiple myeloma (MM) are the most common hematological malignancies which benefit from therapeutic monoclonal antibodies (mAbs)-based immunotherapies. Despite significant improvement on patient outcome following the use of novel therapies for the past decades, curative treatment is unavailable for the majority of patients. For example, the 5-year survival of MM is currently less than 50%. In the 1980s, interferon-α was used as monotherapy in newly diagnosed or previously treated MM with an overall response rate of 15-20%...
2017: Experimental Hematology & Oncology
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