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https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#1
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
August 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28819209/synergistic-immuno-photothermal-nanotherapy-symphony-for-the-treatment-of-unresectable-and-metastatic-cancers
#2
Yang Liu, Paolo Maccarini, Gregory M Palmer, Wiguins Etienne, Yulin Zhao, Chen-Ting Lee, Xiumei Ma, Brant A Inman, Tuan Vo-Dinh
Metastatic spread is the mechanism in more than 90 percent of cancer deaths and current therapeutic options, such as systemic chemotherapy, are often ineffective. Here we provide a proof of principle for a novel two-pronged modality referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) having the potential to safely eradicate both primary tumors and distant metastatic foci. Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)-mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817755/measuring-toxic-effects-and-time-to-treatment-failure-for-nivolumab-plus-ipilimumab-in-melanoma
#3
Alexander N Shoushtari, Claire F Friedman, Pedram Navid-Azarbaijani, Michael A Postow, Margaret K Callahan, Parisa Momtaz, Katherine S Panageas, Jedd D Wolchok, Paul B Chapman
Importance: Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs). Objective: To describe detailed toxic effects and time to treatment failure of patients with melanoma treated with nivo + ipi in a prospective cohort...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28815043/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#4
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#5
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
https://www.readbyqxmd.com/read/28807001/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#6
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28801576/disrupting-glutamine-metabolic-pathways-to-sensitize-gemcitabine-resistant-pancreatic-cancer
#7
Ru Chen, Lisa A Lai, Yumi Sullivan, Melissa Wong, Lei Wang, Jonah Riddell, Linda Jung, Venu G Pillarisetty, Teresa A Brentnall, Sheng Pan
Pancreatic cancer is a lethal disease with poor prognosis. Gemcitabine has been the first line systemic treatment for pancreatic cancer. However, the rapid development of drug resistance has been a major hurdle in gemcitabine therapy leading to unsatisfactory patient outcomes. With the recent renewed understanding of glutamine metabolism involvement in drug resistance and immuno-response, we investigated the anti-tumor effect of a glutamine analog (6-diazo-5-oxo-L-norleucine) as an adjuvant treatment to sensitize chemoresistant pancreatic cancer cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783251/safety-and-efficacy-of-allogeneic-lung-spheroid-cells-in-a-mismatched-rat-model-of-pulmonary-fibrosis
#8
Jhon Cores, M Taylor Hensley, Kathryn Kinlaw, S Michaela Rikard, Phuong-Uyen Dinh, Dipti Paudel, Junnan Tang, Adam C Vandergriff, Tyler A Allen, Yazhou Li, Jianhua Liu, Bo Niu, Yuepeng Chi, Thomas Caranasos, Leonard J Lobo, Ke Cheng
Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells...
August 7, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28780932/cancer-nanomedicine-lessons-for-immuno-oncology
#9
REVIEW
Shiladitya Sengupta
Cancer nanotechnology and cancer immunotherapy are two parallel themes that have emerged over the last few decades in the search for a cure for cancer. Exciting applications can emerge at the intersection of these two fields. However, it is important to learn from the past successes and failures of cancer nanomedicines for its future applications in cancer immunotherapy. This review discusses the two key parameters that defined clinical success in the case of cancer nanomedicines: (i) physicochemical design principles, and (ii) clinical trial design, which are frequently overlooked in most analyses of the state of the field...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28777342/immuno-stimulatory-peptides-as-a-potential-adjunct-therapy-against-intra-macrophagic-pathogens
#10
REVIEW
Tânia Silva, Maria Salomé Gomes
The treatment of infectious diseases is increasingly prone to failure due to the rapid spread of antibiotic-resistant pathogens. Antimicrobial peptides (AMPs) are natural components of the innate immune system of most living organisms. Their capacity to kill microbes through multiple mechanisms makes the development of bacterial resistance less likely. Additionally, AMPs have important immunomodulatory effects, which critically contribute to their role in host defense. In this paper, we review the most recent evidence for the importance of AMPs in host defense against intracellular pathogens, particularly intra-macrophagic pathogens, such as mycobacteria...
August 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28771620/a-benign-helminth-alters-the-host-immune-system-and-the-gut-microbiota-in-a-rat-model-system
#11
Laura Wegener Parfrey, Milan Jirků, Radek Šíma, Marie Jalovecká, Bohumil Sak, Karina Grigore, Kateřina Jirků Pomajbíková
Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome...
2017: PloS One
https://www.readbyqxmd.com/read/28762681/-novel-antiviral-agents-for-the-treatment-of-hcv-among-renal-transplant-recipients
#12
REVIEW
Fabrizio Fabrizi, Francesca M Donato, Piergiorgio Messa
The frequency of hepatitis C virus infection remains high in renal transplant recipients and plays a detrimental role on survival in this population. According to the latest evidence, the adjusted relative risk of mortality and graft loss for anti-HCV seropositive versus anti-HCV negative renal transplant recipients was 1.85 with a 95% confidence interval (CI) of 1.49 ; 2.31 (P < 0.0001) and 1.76 (95% CI, 1.46 ; 2.11) (P < 0.0001), respectively. Interferon-based regimens have been recommended for the treatment of hepatitis C after renal transplantation only in selected circumstances because of an increased risk of acute rejection due to the immuno-stimulatory properties of interferon...
August 1, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28761752/cecog-educational-illustrations-the-blood-brain-barrier-and-its-relevance-for-targeted-cancer-therapies-and-immuno-oncology
#13
Matthias Preusser, Anna S Berghoff, Christiane Thallinger, Christoph Zielinski
The blood-brain barrier (BBB) protects the central nervous system (CNS) from potentially harmful substances and molecules by limiting their influx from the blood stream into the brain parenchyma. Understanding the structure and functioning of the BBB is of major importance for the development of effective medical treatments for primary and secondary brain tumours. Therefore, we provide here a concise and illustrated educational description of the anatomy and physiology of the BBB and current concepts on its role for targeted cancer therapies and immuno-oncology...
2017: ESMO Open
https://www.readbyqxmd.com/read/28757080/a-fusion-receptor-as-a-safety-switch-detection-and-purification-biomarker-for-adoptive-transferred-t-cells
#14
Xiuqi Wu, Bizhi Shi, Jiqin Zhang, Zhimin Shi, Shengmeng Di, Minliang Fan, Huiping Gao, Hai Wang, Jianren Gu, Hua Jiang, Zonghai Li
The incorporation of an endogenous safety switch represents a rational strategy for the control of toxicities following the administration of adoptive T cell therapies. An ideal safety switch should be capable of depleting the transferred T cells with minimal injury to normal tissues. We generated a fusion receptor by engineering a cryptic 806 epitope of human epidermal growth factor receptor (EGFR) into the N terminus of the full-length human folate receptor 1 (FOLR1), designated as FR806. The expression of FR806 allows transduced T cells to be targeted with CH12, a monoclonal antibody recognizing the 806 epitope, but not wild-type EGFR in healthy tissues...
July 3, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28748917/oesophageal-cancer
#15
REVIEW
Elizabeth C Smyth, Jesper Lagergren, Rebecca C Fitzgerald, Florian Lordick, Manish A Shah, Pernilla Lagergren, David Cunningham
Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and is therefore a major global health challenge. The two major subtypes of oesophageal cancer are oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), which are epidemiologically and biologically distinct. OSCC accounts for 90% of all cases of oesophageal cancer globally and is highly prevalent in the East, East Africa and South America. OAC is more common in developed countries than in developing countries...
July 27, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28739693/correlation-between-nkg2dl-expression-and-antitumor-effect-of-protein-bound-polysaccharide-k-in-tumor-bearing-mouse-models
#16
Ayano Konagai, Kiyoshi Yoshimura, Shouichi Hazama, Noboru Yamamoto, Kazunori Aoki, Tomio Ueno, Masaki Fujioka, Hiroko Iijima, Mariko Kato, Motoyuki Uchida, Tsutomu Wada, Moeko Inoue, Tetsuhiko Asao, Masanori Fuse, Satoshi Wada, Atsuo Kuramasu, Ryoji Kamei, Shigeru Takeda, Shigeru Yamamoto, Shigefumi Yoshino, Masaaki Oka, Hiroaki Nagano
BACKGROUND/AIM: We investigated the relationship between the expression of natural killer group 2, member D ligands (NKG2DLs) and the antitumor effects of protein-bound polysaccharide-K (PSK). MATERIALS AND METHODS: PSK was administered to evaluate its effectiveness against tumor growth. The expression of Rae-1 and H60 were analyzed in multiple cell lines. RESULTS: PSK showed the highest antitumor effects in mice implanted with cells expressing neither Rae-1 nor H60...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28736230/pro-inflammatory-chemokines-and-cytokines-dominate-the-blister-fluid-molecular-signature-in-epidermolysis-bullosa-patients-and-affect-leukocyte-and-stem-cell-migration
#17
Vitali Alexeev, Julio Cesar Salas-Alanis, Francis Palisson, Lila Mukhtarzada, Giulio Fortuna, Jouni Uitto, Andy South, Olga Igoucheva
Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of chronic non-healing wounds. Although clinical studies have shown that cell-based therapies improve wound healing, recruitment of therapeutic cells to blistering skin and to more advanced skin lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids (BF) of patients affected by dystrophic, junctional and simplex EB. Our analysis revealed high levels of CXCR1, CXCR2, CCR2 and CCR4 ligands, particularly dominant in dystrophic and junctional EB...
July 20, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28726491/interview-with-thomas-powles-the-use-of-durvalumab-in-urothelial-cancer-the-latest-strides-in-immuno-oncology
#18
Thomas Powles
Thomas Powles speaks to Sebastian Dennis-Beron, Commissioning Editor: Dr. Thomas Powles is a clinical professor of genitourinary oncology and the lead for solid tumor research at Barts Cancer Institute in London. His main research interests are in genital and urinary cancers, in which he leads a spectrum of clinical studies from Phase I to randomized Phase III investigating novel targeted and immune therapies. His research also focuses on correlation of novel biomarkers and aims to define markers with prognostic value that may predict response or resistance to therapy...
July 20, 2017: Future Oncology
https://www.readbyqxmd.com/read/28723711/epidemiology-of-autoimmune-and-inflammatory-diseases-in-a-french-nationwide-hiv-cohort
#19
D Lebrun, M Hentzien, L Cuzin, D Rey, V Joly, L Cotte, C Allavena, P Dellamonica, A Servettaz, F Bani-Sadr
HIV infection and inflammatory and autoimmune diseases (IAD) are both related to immune dysfunction. Epidemiological data on IAD in patients living with HIV (PLHIV) are scarce. The aim of this study was thus to estimate the prevalence of 26 IAD among PLHIV followed in a large French multicenter cohort in the cART era (from January 2000 to July 2013), and to describe their occurrence according to cART onset, the immuno-virological status of patients and HCV and/or HBV co-infection.During the study period, 33 403 PLHIV were included in the Dat'AIDS cohort; 1381 patients with an IAD were identified...
July 18, 2017: AIDS
https://www.readbyqxmd.com/read/28721731/self-assembled-injectable-peptide-hydrogels-capable-of-triggering-antitumor-immune-response
#20
Ruirui Xing, Shukun Li, Ning Zhang, Guizhi Shen, Helmuth Möhwald, Xuehai Yan
Self-assembled peptide hydrogels are particularly appealing for drug delivery, tissue engineering, and antitumor therapy due to various advantageous features including excellent biocompatibility and biodegradability, defined molecular and higher organized structures, and easy availability. However, the poor mechanical and rheological properties of assembled peptide hydrogels cause difficulties in injection, thus limiting further applications. Herein, injectable peptide-based hydrogels with tunable mechanical and rheological properties were obtained by combination with a positively charged poly peptide (poly-l-lysine, PLL)...
August 2, 2017: Biomacromolecules
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