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https://www.readbyqxmd.com/read/28529898/preclinical-rationale-for-combining-radiation-therapy-and-immunotherapy-beyond-checkpoint-inhibitors-i-e-cart
#1
REVIEW
James P Flynn, Mark H O'Hara, Saumil J Gandhi
An increasing appreciation for the role of the immune system in targeting cancer cells over the last decade has led to the development of several immunomodulatory agents aimed at enhancing the systemic antitumor immune response. One such method is the use of T cells that are genetically engineered to express chimeric antigen receptors (CARs). The remarkable success of this approach in advanced hematologic malignancies has garnered much enthusiasm for using this novel tool in treating other cancers. However, multiple challenges have hampered the application of this therapy to a broader set of solid tumors, most notably lung cancer...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28528668/trpv1-channels-in-immune-cells-and-hematological-malignancies
#2
Sofia A Omari, Murray J Adams, Dominic P Geraghty
Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal, and mechanical sensations. Originally associated exclusively with sensory neurons, TRPV1 is now known to be present in almost all organs, including cells of the immune system, where TRPV1 has been shown to play a pivotal role in inflammation and immunity. Monocytes, macrophages, and dendritic cells express TRPV1, with both mouse and human studies suggesting that TRPV1 activation protects against endotoxin-induced inflammation...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28514768/driving-better-and-safer-her2-specific-cars-for-cancer-therapy
#3
REVIEW
Xianqiang Liu, Nan Zhang, Huan Shi
Given the clinical efficacy of chimeric antigen receptor (CAR)-based therapy in hematological malignancies, CAR T-cell therapy for a number of solid tumors has been actively investigated. Human epidermal growth factor receptor 2 (HER2) is a well-established therapeutic target in breast, as well as other types of cancer. However, HER2 CAR T cells pose a risk of lethal toxicity including cytokine release syndrome from "on-target, off-tumor" recognition of HER2. In this review, we summarize the development of conventional HER2 CAR technology, the alternative selection of CAR hosts, the novel HER2 CAR designs, clinical studies and toxicity...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507811/adoptive-natural-killer-cell-therapy-is-effective-in-reducing-pulmonary-metastasis-of-ewing-sarcoma
#4
Alexander A Tong, Hasan Hashem, Saada Eid, Frederick Allen, Daniel Kingsley, Alex Y Huang
The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains dismal despite intensification of combination chemotherapy and radiotherapy, precipitating the need for novel alternative therapies with minimal side effects. Natural killer (NK) cells are promising additions to the field of cellular immunotherapy. Adoptive NK cell therapy has shown encouraging results in hematological malignancies. Despite these initial promising successes, however, NK cell therapy for solid tumors remains to be investigated using in vivo tumor models...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506131/new-drugs-and-allogeneic-hematopoietic-cell-transplantation-for-hematological-malignancies-do-they-have-a-role-in-bridging-consolidating-or-conditioning-transplantation-treatment
#5
Francesca Patriarca, Luisa Giaccone, Francesco Onida, Luca Castagna, Barbara Sarina, Vittorio Montefusco, Alberto Mussetti, Nicola Mordini, Elena Maino, Raffaella Greco, Jacopo Peccatori, Moreno Festuccia, Francesco Zaja, Stefano Volpetti, Antonio Risitano, Renato Bassan, Paolo Corradini, Fabio Ciceri, Renato Fanin, Michele Baccarani, Alessandro Rambaldi, Francesca Bonifazi, Benedetto Bruno
Novel targeted therapies and monoclonal antibodies can be combined with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1) before the transplant to reduce tumour burden, 2) as part of the conditioning in place of or in addition to conventional agents 3) after the transplant to allow long-term disease control. Areas covered This review focuses on the current integration of new drugs with allo-SCT for the treatment of major hematological malignancies for which allo-SCT has been a widely-adopted therapy...
May 16, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28500633/the-novel-role-of-pyrvinium-in-cancer-therapy
#6
REVIEW
Amir Abbas Momtazi-Borojeni, Elham Abdollahi, Faezeh Ghasemi, Michele Caraglia, Amirhossein Sahebkar
Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially approved by FDA for its anthelmintic properties and therapeutic function against animal-like protists such as Cryp-tosporidium parvum and Plasmodium falciparum in the 1950 s. In the last 10 years, several studies have shown the novel activity of pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium could delay or inhibit tumor cell proliferation in cancer models including colon, breast, lung and prostate cancer and some hematological malignancies...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28479419/novel-tumor-suppressor-function-of-klf4-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#7
REVIEW
Ye Shen, Taylor J Chen, H Daniel Lacorazza
Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in pediatric patients. Despite advances in the treatment of this disease, many children with T-cell ALL (T-ALL) die from disease relapse due to low responses to standard chemotherapy and the lack of a targeted therapy that selectively eradicates the chemoresistant leukemia-initiating cells (LICs) responsible for disease recurrence. We recently reported that the reprogramming factor KLF4 has tumor-suppressive function in children with T-ALL...
May 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28472843/targeting-multiple-myeloma-cancer-stem-cells-with-natural-products-lessons-from-other-hematological-malignancies
#8
Mark E Issa, Sylvian Cretton, Muriel Cuendet
Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow. Multiple myeloma is the second most frequently diagnosed hematological malignancy, predominantly affecting the elderly. Despite recent advances in the development of novel therapies, multiple myeloma remains an incurable malignancy where the majority of patients relapse, develop resistance, and eventually die from the disease. This has been attributed to the fact that conventional therapy currently in use targets mainly the bulk of tumor cells, but not the tumor-initiating cancer stem cells...
May 4, 2017: Planta Medica
https://www.readbyqxmd.com/read/28469926/primary-hypertrophic-osteoarthropathy-due-to-a-novel-slco2a1-mutation-masquerading-as-acromegaly
#9
Ruth Mangupli, Adrian F Daly, Elvia Cuauro, Paul Camperos, Jaime Krivoy, Albert Beckers
SUMMARY: A 20-year-old man with an 8-year history of progressive enlargement of his hands and feet, coarsening facial features, painful joints and thickened, oily skin was referred for investigation of acromegaly. On examination, the subject was of normal height and weight. He had markedly increased skin thickness around the forehead, eyelids and scalp with redundant skin folds. Bilateral painful knee swelling was accompanied by enlargement of the extremities, and his fingers were markedly clubbed...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28462890/multiple-myeloma-clinical-updates-from-the-american-society-of-hematology-annual-meeting-2016
#10
REVIEW
Evangelos Terpos
The novel clinical data for plasma cell neoplasms (smoldering myeloma, multiple myeloma (MM) and AL-amyloidosis) that were presented in the 2016 Annual Meeting of the American Society of Hematology are summarized here. Data from large phase 3 studies for newly diagnosed MM patients who are eligible for autologous transplantation (EMN02, MRC XI and StaMINA trials) are described along with the results of phase 2 studies using novel anti-myeloma drug combinations for induction, consolidation and maintenance as first line therapy...
March 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28448171/novel-investigational-drugs-active-as-single-agents-in-multiple-myeloma
#11
Mattia D'Agostino, Marco Salvini, Antonio Palumbo, Alessandra Larocca, Francesca Gay
Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies...
May 8, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28446716/targeted-alpha-therapy-using-a-novel-cd70-targeted-thorium-227-conjugate-in-in-vitro-and-in-vivo-models-of-renal-cell-carcinoma
#12
Urs B Hagemann, Dessislava Mihaylova, Steinar R Uran, Joergen Borrebaek, Derek Grant, Roger M Bjerke, Jenny Karlsson, Alan S Cuthbertson
The cell surface receptor CD70 has been previously reported as a promising target for B-cell lymphomas and several solid cancers including renal cell carcinoma. We describe herein the characterization and efficacy of a novel CD70 targeted thorium-227 conjugate (CD70-TTC) comprising the combination of the three components, a CD70 targeting antibody, a chelator moiety and the short-range, high-energy alpha-emitting radionuclide thorium-227 (227Th). In vitro analysis demonstrated that the CD70-TTC retained binding affinity to its target and displayed potent and specific cytotoxicity compared to an isotype control-TTC...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445872/successful-management-of-decitabine-prior-to-full-dose-idarubicin-and-cytarabine-in-the-treatment-of-refractory-recurrent-acute-myeloid-leukemia
#13
Hongyu Zhao, Li Xu, Yongjian Yang, Jianhua Shao, Ping Chen, Xuebin Dong, Linping Gu, Daqi Li
AIMS: To investigate the safety and efficacy of the triple therapy of decitabine, idarubicin, and cytarabine in the treatment of refractory or recurrent acute myeloid leukemia (R/R AML). METHODS: We conducted a single-center retrospective study in which decitabine treatment was administered prior to full-dose idarubicin and cytarabine (D-IA) for 21 R/R AML patients. RESULTS: After 1 cycle of D-IA, 10/21 (47.6%) patients experienced a complete remission (CR) and 2/21 (9...
April 27, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28441372/assessing-response-of-high-grade-gliomas-to-immune-checkpoint-inhibitors
#14
Solmaz Sahebjam, Dexter G Stallworth, Sepideh Mokhtari, Nam D Tran, John A Arrington
BACKGROUND: Immunotherapeutic agents, especially checkpoint inhibitors, have emerged as the mainstay of therapy for several solid and hematological malignancies. These therapies are under investigation for the treatment of high-grade gliomas and brain metastases. METHODS: This article reviews the unique challenges encountered when evaluating changes on magnetic resonance imaging (MRI) of glioblastomas seen in response to immunotherapy and checkpoint inhibitors and how to effectively incorporate MRI findings into the response assessment of high-grade gliomas to these emerging therapies...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28439081/long-lasting-neutralization-of-c5-by-sky59-a-novel-recycling-antibody-is-a-potential-therapy-for-complement-mediated-diseases
#15
Taku Fukuzawa, Zenjiro Sampei, Kenta Haraya, Yoshinao Ruike, Meiri Shida-Kawazoe, Yuichiro Shimizu, Siok Wan Gan, Machiko Irie, Yoshinori Tsuboi, Hitoshi Tai, Tetsushi Sakiyama, Akihisa Sakamoto, Shinya Ishii, Atsuhiko Maeda, Yuki Iwayanagi, Norihito Shibahara, Mitsuko Shibuya, Genki Nakamura, Takeru Nambu, Akira Hayasaka, Futa Mimoto, Yuu Okura, Yuji Hori, Kiyoshi Habu, Manabu Wada, Takaaki Miura, Tatsuhiko Tachibana, Kiyofumi Honda, Hiroyuki Tsunoda, Takehisa Kitazawa, Yoshiki Kawabe, Tomoyuki Igawa, Kunihiro Hattori, Junichi Nezu
Dysregulation of the complement system is linked to the pathogenesis of a variety of hematological disorders. Eculizumab, an anti-complement C5 monoclonal antibody, is the current standard of care for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). However, because of high levels of C5 in plasma, eculizumab has to be administered biweekly by intravenous infusion. By applying recycling technology through pH-dependent binding to C5, we generated a novel humanized antibody against C5, SKY59, which has long-lasting neutralization of C5...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28410299/antigen-discovery-and-therapeutic-targeting-in-hematologic-malignancies
#16
David A Braun, Catherine J Wu
Historically, immune-based therapies have played a leading role in the treatment of hematologic malignancies, with the efficacy of stem cell transplantation largely attributable to donor immunity against malignant cells. As new and more targeted immunotherapies have developed, their role in the treatment of hematologic malignancies is evolving and expanding. Herein, we discuss approaches for antigen discovery and review known and novel tumor antigens in hematologic malignancies. We further explore the role of established and investigational immunotherapies in hematologic malignancies, with a focus on personalization of treatment modalities such as cancer vaccines and adoptive cell therapy...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28404756/infusion-compatible-antibiotic-formulations-for-rapid-administration-to-improve-outcomes-in-cancer-outpatients-with-severe-sepsis-and-septic-shock-the-sepsis-stat-pack
#17
Jason D Goldman, Amelia Gallaher, Rupali Jain, Zach Stednick, Manoj Menon, Michael J Boeckh, Paul S Pottinger, Stephen M Schwartz, Corey Casper
Background: Patients with cancer are at high risk for severe sepsis and septic shock (SS/SSh), and a delay in receiving effective antibiotics is strongly associated with mortality. Delays are due to logistics of clinic flow and drug delivery. In an era of increasing antimicrobial resistance, combination therapy may be superior to monotherapy for patients with SS/SSh. Patients and Methods: At the Seattle Cancer Care Alliance, we implemented the Sepsis STAT Pack (SSP) program to simplify timely and effective provision of empiric antibiotics and other resuscitative care to outpatients with cancer with suspected SS/SSh before hospitalization...
April 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28402953/mechanisms-of-pd-1-pd-l1-expression-and-prognostic-relevance-in-non-hodgkin-lymphoma-a-summary-of-immunohistochemical-studies
#18
REVIEW
Pauline Gravelle, Barbara Burroni, Sarah Péricart, Cédric Rossi, Christine Bezombes, Marie Tosolini, Diane Damotte, Pierre Brousset, Jean-Jacques Fournié, Camille Laurent
Immune checkpoint blockade therapeutics, notably antibodies targeting the programmed death 1 (PD-1) receptor and its PD-L1 and PD-L2 ligands, are currently revolutionizing the treatment of cancer. For a sizeable fraction of patients with melanoma, lung, kidney and several other solid cancers, monoclonal antibodies that neutralize the interactions of the PD-1/PD-L1 complex allow the reconstitution of long-lasting antitumor immunity. In hematological malignancies this novel therapeutic strategy is far less documented, although promising clinical responses have been seen in refractory and relapsed Hodgkin lymphoma patients...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402197/minimal-residual-disease-or-cure-in-mpns-rationales-and-perspectives-on-combination-therapy-with-interferon-alpha2-and-ruxolitinib
#19
Mads Emil Bjørn, Hans Carl Hasselbalch
The therapeutic landscape of the Philadelphia-negative myeloproliferative neoplasms (MPNs) is markedly changing consequent to the development of JAK-inhibitors and the use of ruxolitinib (RUX) in patients with myelofibrosis (MF) and patients with polycythemia vera (PV) who develop refractoriness or intolerance to hydroxyurea. The use of Interferon-alpha2 (IFN) is rapidly expanding in several countries, based upon favourable safety and efficacy profiles in several single-arm studies during the last 30 years, displaying complete hematological remissions in a large proportion of patients, a reduction in the JAK2V617 F and CALR mutational burden and in a subset of patients with PV with normalisation of the bone marrow after long-term treatment - even being sustained for several years after discontinuation of IFN...
April 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28369204/prediction-of-bloodstream-infection-due-to-vancomycin-resistant-enterococci-in-patients-undergoing-leukemia-induction-or-hematopoietic-stem-cell-transplantation
#20
Brandon J Webb, Regan Healy, Jacob Majers, Zachary Burr, Michaela Gazdik, Bert Lopansri, Daanish Hoda, Finn Bo Petersen, Clyde Ford
Background.: Bloodstream infection (BSI) due vancomycin-resistant Enterococcus (VRE) is an important complication of hematologic malignancy. Determining when to use empiric anti-VRE antibiotic therapy in this population remains a clinical challenge. Methods.: A single-center cohort representing 664 admissions for induction or hematopoietic stem cell transplant (HSCT) from 2006-2014 was selected. We derived a prediction score using risk factors for VRE BSI and evaluated the model's predictive performance by calculating it for each of 16,232 BSI at-risk inpatient days...
March 20, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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