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Immuno therapy

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https://www.readbyqxmd.com/read/28215147/approaches-to-optimize-gene-therapy-for-the-treatment-of-hematologic-malignancies-overcoming-the-obstacles
#1
Yingzhe Jiang, Bing Xia, Yizhuo Zhang, Wen Xu
Gene transfer and oncolytic viruses provide new therapeutic approaches for the treatment of hematologic malignancies. However, it is still too early to introduce gene delivery or oncolytic viruses into standard clinical protocol. It is very important to discuss the obstacles that gene transfer and oncolytic virotherapy face for the further clinical application for treatment of hematologic malignancies, and updating the advances made to overcome them. The major concerns in this review include the approaches of the development of immuno-stimulatory gene transfer mediated-vaccination for leukemia therapy, RNAi-based therapy for leukemia and enhancement of sensitivity of target malignant cells to virotherapy and alteration of host immune response to favor oncolytic viruses...
February 15, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28213970/efficacy-and-safety-of-immuno-magnetically-sorted-smooth-muscle-progenitor-cells-derived-from-human-induced-pluripotent-stem-cells-for-restoring-urethral-sphincter-function
#2
Yanhui Li, Morgaine Green, Yan Wen, Yi Wei, Prachi Wani, Zhe Wang, Renee Reijo Pera, Bertha Chen
Human-induced pluripotent stem cells (hiPSCs)-based cell therapy holds promise for treating stress urinary incontinence (SUI). However, safety concerns, especially tumorgenic potential of residual undifferentiated cells in hiPSC derivatives, are major barriers for its clinical translation. An efficient, fast and clinical-scale strategy for purifying committed cells is also required. Our previous studies demonstrated the regenerative effects of hiPSC-derived smooth muscle progenitor cells (pSMCs) on the injured urethral sphincter in SUI, but the differentiation protocol required fluorescence-activated cell sorting (FACS) which is not practical for autologous clinical applications...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28212996/analysis-of-a-panel-of-druggable-gene-mutations-and-of-alk-and-pd-l1-expression-in-a-series-of-thymic-epithelial-tumors-tets
#3
Marcello Tiseo, Angela Damato, Lucia Longo, Fausto Barbieri, Federica Bertolini, Alessandro Stefani, Mario Migaldi, Letizia Gnetti, Roberta Camisa, Paola Bordi, Sebastiano Buti, Giulio Rossi
INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms with different prognosis lacking consistent molecular alterations possibly leading to targeted therapy. We collected a consecutive series of TETs aimed at investigating the mutational status of druggable genes (EGFR, c-KIT, KRAS, BRAF, PDGFR-alpha and -beta, HER2 and c-MET) and the expression of ALK and PD-L1. PATIENTS AND METHODS: One hundred twelve consecutive cases of TETs and relative clinico-pathologic features were collected...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28211579/impact-of-treatment-variability-on-survival-in-immuno-competent-and-immuno-compromised-patients-with-primary-central-nervous-lymphoma
#4
Reem Karmali, Chadi Nabhan, Adam M Petrich, Jeffrey Raizer, David Peace, Rimas Lukas, Leo I Gordon, Sanjib Basu, Vineela Chukkapalli, Parameswaran Venugopal
Patients with primary central nervous system lymphoma (PCNSL) treated in the 'real-world' setting do not represent those treated on clinical trials and might not be treated similarly. We studied characteristics and variability in care for 113 newly diagnosed PCNSL patients treated at 5 institutions in the Chicago area between 2000 and 2012. In 111 patients, single modality therapy with a high dose methotrexate (HD-MTX) regimen +/- rituximab, was most commonly employed (n = 65), and 34 underwent radiotherapy (+/- systemic therapy)...
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28204968/a-5%C3%A2-year-update-of-patients-with-hpv-positive-versus-negative-oropharyngeal-cancer-after-radiochemotherapy-in-austria
#5
Claudia Lill, Barbara Bachtiary, Edgar Selzer, Martina Mittlboeck, Dietmar Thurnher
BACKGROUND: After publishing promising results for the treatment of patients with human papilloma virus (HPV) positive oropharyngeal cancer with radiochemotherapy regarding 2‑year survival, we present an update of the disease-specific and disease-free survival after 5 years. PATIENTS AND METHODS: A total of 29 patients of which 18 were HPV negative and 11 HPV positive with squamous cell carcinoma of the oropharynx received radiation therapy with or without chemotherapy (cisplatin) or immunotherapy (cetuximab) between 2007 and 2009...
February 15, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28193529/heterogeneity-in-immune-marker-expression-after-acquisition-of-resistance-to-egfr-kinase-inhibitors-analysis-of-a-case-with-small-cell-lung-cancer-transformation
#6
Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
INTRODUCTION: Expression of immune-markers is of scientific interest due to their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune-markers, there is little data regarding this context. METHODS: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib...
February 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28191810/gist-institutional-experience-at-srms-ims-india
#7
Shubhanshu Gupta, Keshri Amit, Ashish Gupta, Tanu Argawal
Gastro-Intestinal Stromal Tumors (GIST) is a malignant, non-epithelial, mesenchymal tumor of the digestive tract that is not uncommon in clinical practice nowadays; diagnosis being based upon immuno-histo-chemical analysis of the resected or biopsied (FNAC) specimen. Abdominal lump with or without intra-luminal bleed is a common mode of presentation. Early diagnosis and appropriate management with surgery and/or Imatinib therapy improves recurrence free survival and may impact overall survival. We present here our institutional experience of four patients, admitted in Onco-Surgery Dept...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28179157/the-influence-of-cell-and-nanoparticle-properties-on-heating-and-cell-death-in-a-radiofrequency-field
#8
Yuri Mackeyev, Colette Mark, Natasha Kumar, Rita E Serda
: The use of non-invasive radiofrequency (RF) energy to induce mild thermal and non-thermal effects in cancer tissue is under study as an adjuvant to chemo, radio or immuno therapy. This study examines cell specific sensitivities to RF exposure and the potential of nanoparticles to elevate heating rates or enhance biological effects. Increases in the heating rate of water in an RF field operating at 13.56MHz (0.004-0.028°C/s) were positively correlated with concentration of hybrid nanoparticles (1-10mg/ml) consisting of water soluble malonodiserinolamide [60]fullerene (C60-ser) conjugated to the surface of mesoporous silica nanoparticles (SiO2-C60)...
February 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28173864/macrophage-activation-and-polarization-in-post-infarction-cardiac-remodeling
#9
REVIEW
Aleksandra Gombozhapova, Yuliya Rogovskaya, Vladimir Shurupov, Mariya Rebenkova, Julia Kzhyshkowska, Sergey V Popov, Rostislav S Karpov, Vyacheslav Ryabov
Adverse cardiac remodeling leads to impaired ventricular function and heart failure, remaining a major cause of mortality and morbidity in patients with acute myocardial infarction. It have been shown that, even if all the recommended therapies for ST-segment elevation myocardial infarction are performed, one third of patients undergoes progressive cardiac remodeling that represents morphological basis for following heart failure. The need to extend our knowledge about factors leading to different clinical scenarios of myocardial infarction and following complications has resulted in a research of immuno-inflammatory pathways and molecular activities as the basis for post-infarction remodeling...
February 7, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28167217/experimental-animal-modeling-for-immuno-oncology
#10
REVIEW
Qi-Xiang Li, Gerold Feuer, Xuesong Ouyang, Xiaoyu An
Immuno-oncology (I/O) research has intensified significantly in recent years due to the breakthrough development and the regulatory approval of several immune checkpoint inhibitors, leading to the rapid expansion of the new discovery of novel I/O therapies, new checkpoint inhibitors and beyond. However, many I/O questions remain unanswered, including why only certain subsets of patients respond to these treatments, who the responders would be, and how to expand patient response (the conversion of non-responders or maximizing response in partial responders)...
February 3, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28164088/effective-implementation-of-novel-met-pharmacodynamic-assays-in-translational-studies
#11
REVIEW
Apurva K Srivastava, Tony Navas, William G Herrick, Melinda G Hollingshead, Donald P Bottaro, James H Doroshow, Ralph E Parchment
MET tyrosine kinase (TK) dysregulation is significantly implicated in many types of cancer. Despite over 20 years of drug development to target MET in cancers, a pure anti-MET therapeutic has not yet received market approval. The failure of two recently concluded phase III trials point to a major weakness in biomarker strategies to identify patients who will benefit most from MET therapies. The capability to interrogate oncogenic mutations in MET via circulating tumor DNA (ctDNA) provides an important advancement in identification and stratification of patients for MET therapy...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28161113/-myocarditis
#12
G Hékimian, A Combes
Acute myocarditis must be considered in patients with recent onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackie virus and adenovirus being the most frequently viruses responsible for the disease. In this setting, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted...
February 1, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28156016/severe-pneumonia-associated-with-ibrutinib-monotherapy-for-cll-and-lymphoma
#13
Natalia Kreiniz, Jacob Bejar, Aaron Polliack, Tamar Tadmor
In recent years, there have been major advances in the treatment of chronic lymphocytic leukemia (CLL) particularly since the development of novel therapeutic agents, mostly "biological drugs." One of the obvious advantages of these agents is the decreased rate of infectious complications occurring during the course of therapy, compared to the use of standard immuno-chemotherapy regimens. Here, we describe 3 patients with CLL and 1 with mantle cell lymphoma who developed severe life-threatening pneumonias, during monotherapy with ibrutinib...
February 3, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28153100/systemic-delivery-of-tumor-targeted-bax-derived-membrane-active-peptides-for-the-treatment-of-melanoma-tumors-in-a-humanized-scid-mouse-model
#14
Anastassia Karageorgis, Michaël Claron, Romain Jugé, Caroline Aspord, Fabien Thoreau, Claire Leloup, Jérôme Kucharczak, Joël Plumas, Maxime Henry, Amandine Hurbin, Pascal Verdié, Jean Martinez, Gilles Subra, Pascal Dumy, Didier Boturyn, Abdel Aouacheria, Jean-Luc Coll
Melanoma is a highly metastatic and deadly form of cancer. Invasive melanoma cells overexpress integrin αvβ3, which is a well-known target for Arg-Gly-Asp-based (RGD) peptides. We developed a sophisticated method to synthetize milligram amounts of a targeted vector that allows the RGD-mediated targeting, internalization, and release of a mitochondria-disruptive peptide derived from the pro-apoptotic Bax protein. We found that 2.5 μM Bax[109-127] was sufficient to destabilize the mitochondria in ten different tumor cell lines, even in the presence of the anti-apoptotic Bcl2 protein, which is often involved in tumor resistance...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28127950/kartogenin-with-prp-promotes-the-formation-of-fibrocartilage-zone-in-the-tendon-bone-interface
#15
Yiqin Zhou, Jianying Zhang, Jinsong Yang, Manoj Narava, Guangyi Zhao, Ting Yuan, Haishan Wu, Nigel Zheng, MaCalus V Hogan, James H-C Wang
Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline...
January 27, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28122590/pd-1-pd-l1-b7-h1-and-tumor-site-immune-modulation-therapy-the-historical-perspective
#16
REVIEW
Jun Wang, Ruirong Yuan, Wenru Song, Jingwei Sun, Delong Liu, Zihai Li
The current success of targeted inhibition against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1/Programmed Death Ligand 1 (PD-1/PD-L1, herein collectively referred to as PD) pathways is hailed as a cancer immunotherapy breakthrough. PD-L1, known also as B7 homolog 1 (B7-H1), was initially discovered by Dr. Lieping Chen in 1999. To recognize the seminal contributions by Chen to the development of PD-directed therapy against cancer, the Chinese American Hematologist and Oncologist Network (CAHON) decided to honor him with its inaugural Lifetime Achievement Award in Hematology and Oncology at the CAHON's 2015 annual meeting...
January 25, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28122343/targeted-breast-cancer-therapy-by-harnessing-the-inherent-blood-group-antigen-immune-system
#17
Wei Han, Wei Li, Xiaoying Zhang, Zhonghua Du, Xiaoliang Liu, Xin Zhao, Xue Wen, Guanjun Wang, Ji-Fan Hu, Jiuwei Cui
Cancer gene therapy has attracted increasing attention for its advantages over conventional therapy in specific killing of tumor cells. Here, we attempt to prove a novel therapeutic approach that targets tumors by harnessing the blood antigen immune response system, which is inherently present in patients with breast cancers. Breast cancer MDA-MB-231 cells expressed blood group H antigen precursor. After ectopic expression of blood group A glycosyltransferase, we found that the H precursor was converted into the group A antigen, appearing on the surface of tumor cells...
January 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28122336/distinct-patterns-of-infiltrating-cd8-t-cells-in-hpv-and-cd68-macrophages-in-hpv-oropharyngeal-squamous-cell-carcinomas-are-associated-with-better-clinical-outcome-but-pd-l1-expression-is-not-prognostic
#18
Kenneth Oguejiofor, Henry Galletta-Williams, Simon J Dovedi, Darren L Roberts, Peter L Stern, Catharine M L West
Immunotherapies are beginning to revolutionise treatment paradigms in oncology with monoclonal antibodies (mAb) targeting T-cell co-inhibitory (e.g. PD-1/PD-L1) and co-stimulatory pathways (e.g. CTLA-4/CD28) demonstrating clinical utility. Some clinical studies demonstrate that responsiveness to PD-1/PD-L1 mAb therapy is greater in patients with expression of PD-L1 in the tumour microenvironment. However, robust responses have also been observed in patients with low or absent expression of PD-L1. Using multiplex immuno-fluorescent labelling we sought to determine how infiltration of tumours by CD8+ T-cells, their expression of PD-1, and the expression of PD-L1 on both tumours and CD68 cells (macrophages) correlated with HPV status and outcome in a cohort of 124 oropharyngeal squamous cell carcinomas (OPSCC)...
January 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28112872/development-of-decellularised-conjunctiva-as-a-substrate-for-the-ex-vivo-expansion-of-conjunctival-epithelium
#19
Shivani Kasbekar, Stephen B Kaye, Rachel L Williams, Rosalind Mk Stewart, Sophie Leow-Dyke, Paul Rooney
PURPOSE: To develop a method to decellularise human conjunctiva. To characterise the tissue in terms of its DNA content, tensile strength, collagen denaturation, basement membrane, extracellular matrix components and its potential to support conjunctival epithelial growth. METHODS: Human conjunctival tissues were subjected to a decellularisation process involving hypotonic detergent and nuclease buffers. Variations in sodium dodecyl sulphate (SDS) concentration (0...
January 23, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28106467/follicular-lymphoma-a-b-cell-malignancy-addicted-to-epigenetic-mutations
#20
Koorosh Korfi, Sara Ali, James A Heward, Jude Fitzgibbon
While follicular lymphoma (FL) is exquisitely responsive to immuno-chemotherapy, many patients follow a relapsing remitting clinical course driven in part by a common precursor cell (CPC) population. Advances in next generation sequencing have provided valuable insights into the genetic landscape of FL and its clonal evolution in response to therapy, implicating perturbations of epigenetic regulators as a hallmark of the disease. Recurrent mutations of histone modifiers KMT2D, CREBBP, EP300, EZH2, ARIDIA, and linker histones are likely early events arising in the CPC pool, rendering epigenetic based therapies conceptually attractive for treatment of indolent and transformed FL...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
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