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https://www.readbyqxmd.com/read/29791237/the-future-of-chronic-lymphocytic-leukemia-potential-directions-from-ash-2017
#1
Stefano Molica
Novel targeted therapies - including ibrutinib, venetoclax and idelalisib - have revolutionized the treatment landscape of chronic lymphocytic leukemia (CLL). Therefore, studying combinations of novel agents (NAs) with distinct mechanism of action and non-overlapping toxicities is challenging. Area covered: The 2017 American Society Hematology (ASH) Annual Meeting, has represented a showcase for several trials combining NAs. These studies are currently evaluating the efficacy NA plus anti-CD20 monoclonal antibody, NA plus NA (with or without anti-CD20 monoclonal antibody) and NA plus chemo-immunotherapy...
May 23, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29790899/advances-in-the-systemic-treatment-of-melanoma-brain-metastases
#2
I C Glitza Oliva, G Schvartsman, H Tawbi
Of the solid tumor types that metastasize to the brain, melanoma has the highest propensity to form brain metastases. In addition, much remains unknown regarding the pathophysiology involved in melanoma cell extravasation through the blood-brain barrier, which enables interactions with the microenvironment, and melanoma cell transcriptomic responses to brain-specific cues. However, recent developments in targeted therapy and immunotherapy have generated considerable optimism regarding the treatment of metastatic melanoma...
May 22, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29789418/juxtacrine-signaling-inhibits-antitumor-immunity-by-upregulating-pd-l1-expression
#3
Wen-Hao Yang, Jong-Ho Cha, Weiya Xia, Heng-Huan Lee, Li-Chuan Chan, Ying-Nai Wang, Jennifer L Hsu, Guoxin Ren, Mien-Chie Hung
Programmed death-ligand 1 (PD-L1) is a well-known immune checkpoint protein that helps cancer cells evade immune response. Anti-PD-L1 immune therapy has been approved for the treatment of several advanced human cancers. Therefore, further understanding of the regulatory mechanisms of PD-L1 is critical to improve PD-L1-targeting immunotherapy. Recent studies indicated that contact-dependent pathways may regulate anticancer immunity, highlighting the importance of cell contact-induced signaling in cancer immunity...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29786170/immunopeptidomic-profiling-of-hla-a2-positive-triple-negative-breast-cancer-identifies-potential-immunotherapy-target-antigens
#4
Nicola Ternette, Marloes J M Olde Nordkamp, Julius Muller, Amanda P Anderson, Annalisa Nicastri, Adrian V S Hill, Benedikt M Kessler, Demin Li
The recent development in immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells in the treatment of cancer has not only demonstrated the potency of utilising T-cell reactivity for cancer therapy, but has also highlighted the need for developing new approaches to discover targets suitable for such novel therapeutics. Here we analysed the immunopeptidomes of 6 HLA-A2-positive triple negative breast cancer (TNBC) samples by nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS2 )...
May 22, 2018: Proteomics
https://www.readbyqxmd.com/read/29785785/metabolism-within-the-tumor-microenvironment-and-its-implication-on-cancer-progression-an-ongoing-therapeutic-target
#5
REVIEW
Ma Carmen Ocaña, Beatriz Martínez-Poveda, Ana R Quesada, Miguel Ángel Medina
Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME)...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29784926/clinical-utility-of-circulating-non-coding-rnas-an-update
#6
REVIEW
Simone Anfossi, Anna Babayan, Klaus Pantel, George A Calin
Over the past decade, the amount of research and the number of publications on associations between circulating small and long non-coding RNAs (ncRNAs) and cancer have grown exponentially. Particular focus has been placed on the development of diagnostic and prognostic biomarkers to enable efficient patient management - from early detection of cancer to monitoring for disease recurrence or progression after treatment. Owing to their high abundance and stability, circulating ncRNAs have potential utility as non-invasive, blood-based biomarkers that can provide information on tumour biology and the effects of treatments, such as targeted therapies and immunotherapies...
May 21, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29784748/emerging-treatment-options-for-acute-lymphoblastic-leukemia-focus-on-car-t-cell-therapy
#7
Patrick A Brown, Bijal Shah
Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of diseases with different morphologic, cytogenetic, and molecular subgroups, some of which have significant therapeutic implications. It typically presents with an aggressive clinical course, and among adults, responds poorly to standard chemotherapy, and carries a high risk for relapse. Despite the significant progress made in inducing remission, frequent relapses remain a challenge. Novel drugs, such as potent later-generation tyrosine kinase inhibitors, antibody-drug conjugates, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies, are being investigated in patients with ALL...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784005/cd8-t-cells-mediate-the-antitumor-activity-of-frankincense-and-myrrh-in-hepatocellular-carcinoma
#8
Chun Xu, Xian Lu, Wei Liu, Anxian Chen, Gang Meng, Hailin Zhang, Binghua Li, Yonghui Zhang, Junhua Wu, Jiwu Wei
BACKGROUND: Tumor-promoting inflammation is an emerging hallmark of cancer, which participates in both cancer progression and immune escape. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer with an extremely poor prognosis. Frankincense and myrrh are anti-inflammation agents commonly used in clinic. The purpose of this study is to investigate whether extract of frankincense and myrrh (FM) downregulates inflammatory microenvironment of HCC and thereby restores antitumor immune responses...
May 21, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29782188/an-evaluation-of-nivolumab-for-the-treatment-of-metastatic-renal-cell-carcinoma
#9
Kevin Zarrabi, Shenhong Wu
The treatment paradigm for metastatic renal cell carcinoma (mRCC) has undergone a revolution with the rapid market approval of multiple agents over a three-year period. The immunogenicity of RCC provided the biological rationale to assess the clinical efficacy of nivolumab, an immune checkpoint inhibitor. Nivolumab is approved for second-line treatment after failure of angiogenesis targeted therapy and in combination therapy with ipilimumab for previously untreated intermediate or poor-risk advanced renal cell carcinoma...
May 21, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29781871/early-onset-of-diffuse-melanosis-cutis-under-pembrolizumab-therapy-illustrates-the-limitations-of-anti-pd-1-checkpoint-inhibitors
#10
Alexander Thiem, Patrick Schummer, Simon Ueberschaar, Andreas Kerstan, Hermann Kneitz, David Schrama, Silke Appenzeller, Svenja Meierjohann, Bastian Schilling, Matthias Goebeler, Anja Gesierich
Anti-PD-1 targeted immunotherapies have revolutionized the treatment of advanced melanoma and other tumor entities, and long disease-free intervals have been reported in responding patients. However, a considerable number of patients still progress rapidly after the start of anti-PD-1 antibodies. Here, we document two patients, 78 and 85-year old, who suffered from advanced BRAF-V600 wild-type melanoma and received pembrolizumab 2 mg/kg every 3 weeks as the first systemic treatment. After only one, respectively, two infusions of pembrolizumab, both patients developed melanuria and diffuse melanosis cutis (DMC) on sun-exposed areas of their skin...
May 17, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29781548/multi-omics-in-high-grade-serous-ovarian-cancer-biomarkers-from-genome-to-the-immunome
#11
Cole Clifford, Natasha Vitkin, Sarah Nersesian, Gillian Reid-Schachter, Julie-Ann Francis, Madhuri Koti
Epithelial ovarian cancer (EOC) is a lethal gynaecological disease that imposes significant burden on health care and patient quality of life. High-grade serous carcinoma of the ovary (HGSC) is the most prevalent histological type of EOC. A vast majority of HGSC cases are diagnosed at late stages of the disease, limiting the opportunity for clinical intervention and resulting in a 10-year survival rate of <20%. Recent innovations in high-throughput molecular analysis of patient-derived specimens may address these clinical challenges by providing an enhanced understanding of the molecular aetiology of ovarian cancer, in addition to offering several opportunities for rational biomarker and targeted therapy discovery...
May 21, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29780254/are-ovarian-cancer-stem-cells-the-target-for-innovative-immunotherapy
#12
REVIEW
Liang Wang, Tianmin Xu, Manhua Cui
Cancer stem cells (CSCs), a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs) can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29776373/metabolic-therapy-with-peg-arginase-induces-a-sustained-complete-remission-in-immunotherapy-resistant-melanoma
#13
Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo, Francis Mussai
BACKGROUND: Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#14
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29774202/loss-of-the-cyclin-dependent-kinase-inhibitor-1-in-the-context-of-brachyury-mediated-phenotypic-plasticity-drives-tumor-resistance-to-immune-attack
#15
Duane H Hamilton, Kristen K McCampbell, Claudia Palena
The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#16
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29774055/immunotherapy-of-experimental-and-human-stroke-with-agents-approved-for-multiple-sclerosis-a-systematic-review
#17
REVIEW
Mirjam Dreikorn, Zeljko Milacic, Vladimir Pavlovic, Sven G Meuth, Christoph Kleinschnitz, Peter Kraft
Background: 'Thromboinflammation' describes a novel concept in stroke pathophysiology that has opened up the possibility of immunotherapeutic approaches which could become promising strategies for targeted stroke therapies in the future. Methods: We reviewed current evidence for agents approved for multiple sclerosis in preclinical and clinical stroke studies. A systematic review was performed in accordance with the PRISMA statement, searching MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 16 October 2017...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29773328/molecular-and-immune-biomarker-testing-in-squamous-cell-lung-cancer-effect-of-current-and-future-therapies-and-technologies
#18
REVIEW
Fred R Hirsch, Keith M Kerr, Paul A Bunn, Edward S Kim, Coleman Obasaju, Maurice Pérol, Philip Bonomi, Jeffrey D Bradley, David Gandara, James R Jett, Corey J Langer, Ronald B Natale, Silvia Novello, Luis Paz-Ares, Suresh S Ramalingam, Martin Reck, Craig H Reynolds, Egbert F Smit, Mark A Socinski, David R Spigel, Thomas E Stinchcombe, Johan F Vansteenkiste, Heather Wakelee, Nick Thatcher
Patients with non-small-cell lung cancer, including squamous-cell lung cancer (SqCLC), typically present at an advanced stage. The current treatment landscape, which includes chemotherapy, radiotherapy, surgery, immunotherapy, and targeted agents, is rapidly evolving, including for patients with SqCLC. Prompt molecular and immune biomarker testing can serve to guide optimal treatment choices, and immune biomarker testing is becoming more important for this patient population. In this review we provide an overview of current and emerging practices and technologies for molecular and immune biomarker testing in advanced non-small-cell lung cancer, with a focus on SqCLC...
March 21, 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#19
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29772353/cardiac-profile-of-chimeric-antigen-receptor-car-t-cell-therapy-in-children-a-single-institution-experience
#20
Danielle Burstein, Shannon Maude, Stephen Grupp, Heather Griffis, Joseph Rossano, Kimberly Lin
BACKGROUND: Immunotherapy with chimeric antigen receptor (CAR)-modified T-cells targeting CD19 for pediatric acute lymphoblastic leukemia (ALL) has demonstrated significant efficacy. The principle toxicity is cytokine release syndrome with resultant hypotension. However, the spectrum of cardiovascular effects associated with CAR T-cell therapy has not been systematically evaluated. METHODS: We reviewed all patients who received CD19-directed CAR T-cells at the Children's Hospital of Philadelphia between April 2012 and September 2016...
May 14, 2018: Biology of Blood and Marrow Transplantation
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