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https://www.readbyqxmd.com/read/28410299/antigen-discovery-and-therapeutic-targeting-in-hematologic-malignancies
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28356156/chimeric-antigen-receptor-t-cells-a-novel-therapy-for-solid-tumors
#6
REVIEW
Shengnan Yu, Anping Li, Qian Liu, Tengfei Li, Xun Yuan, Xinwei Han, Kongming Wu
The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types...
March 29, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28347250/chimeric-antigen-receptor-engineered-t-cells-for-liver-cancers-progress-and-obstacles
#7
REVIEW
Keyu Li, Yaliang Lan, Jiabei Wang, Lianxin Liu
Chimeric antigen receptor-engineered T cells therapy has become the hottest topic of immunotherapy, as its great successes achieved in treating refractory hematological malignancies. These successes also paved the road to novel strategies of treating various solid tumors including liver cancer. Many specific proteins can be expressed aberrantly in liver cancers; therefore, a series of experimental and clinical researches exploring chimeric antigen receptor-engineered T cells and liver cancer are in progress, acquiring obvious antitumor effect and revealing its feasibility in treating liver cancer...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28340877/adult-t-cell-leukemia-lymphoma-a-problem-abroad-and-at-home
#8
REVIEW
Christopher Dittus, J Mark Sloan
Adult T-cell leukemia/lymphoma (ATLL) is a rare T-cell disorder that is etiologically linked to chronic infection with human T-cell lymphotropic virus type 1. ATLL is divided into four subtypes: acute, lymphomatous, chronic, and smoldering. The acute and lymphomatous variants are often described clinically as the aggressive types of ATLL. Treatment strategies traditionally have focused on antiviral therapy with zidovudine and interferon-alpha and combination chemotherapy. Novel therapeutic approaches include the use of monoclonal antibodies, anti-CCR4 therapy, immunomodulatory therapy, and anti-TAX vaccines...
April 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28323922/fibrogenesis-imperfecta-ossium-and-response-to-human-growth-hormone-a-potential-novel-therapy
#9
Sanjay Kumar Bhadada, Vandana Dhiman, Soham Mukherjee, Sameer Aggarwal, Amanjit Bal, Suja P Sukumar, Ashwani Sood, Dinesh Chandra Sharma, Niranjan Khandelwal, Anil Bhansali, Wim Van Hul, Sudhaker D Rao
Context: Fibrogenesis imperfecta ossium (FIO) is a rare bone disease manifested by generalized bone pain, fragility fractures, progressive disability, and extensive mineralization defect on bone biopsy. The pathogenesis of the disease is unknown and currently there is no effective treatment. Objective: To report on the effect of recombinant human growth hormone (rhGH) therapy in FIO. Design: An observational study in two patients. Setting: Endocrinology Clinic in an Academic Institution Patients or Other Participants: Two siblings with FIO Intervention(s): rhGH was administered subcutaneously at a dose of 1U daily for one year...
February 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28316129/cognitive-compensatory-processes-of-older-clinically-fit-patients-with-hematologic-malignancies-undergoing-chemotherapy-a-longitudinal-cohort-study
#10
Yves Libert, Cindy Borghgraef, Yves Beguin, Nicole Delvaux, Martine Devos, Chantal Doyen, Stéphanie Dubruille, Anne-Marie Etienne, Aurore Liénard, Isabelle Merckaert, Christine Reynaert, Jean-Louis Slachmuylder, Nicole Straetmans, Eric Van Den Neste, Dominique Bron, Darius Razavi
OBJECTIVE: Despite the well-known negative impacts of cancer and anticancer therapies on cognitive performance, little is known about the cognitive compensatory processes of older patients with cancer. This study was designed to investigate the cognitive compensatory processes of older, clinically-fit patients with hematologic malignancies undergoing chemotherapy. METHODS: We assessed 89 consecutive patients (age ≥ 65 years) without severe cognitive impairment and 89 age-, sex-, and education level-matched healthy controls...
March 18, 2017: Psycho-oncology
https://www.readbyqxmd.com/read/28315358/isocitrate-dehydrogenase-idh-inhibition-as-treatment-of-myeloid-malignancies-progress-and-future-directions
#11
REVIEW
Vivek A Upadhyay, Andrew M Brunner, Amir T Fathi
Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme. Over the last two decades, there has been a growing focus on the metabolic derangements that occur with IDH1 and IDH2 mutations. The altered IDH protein leads to accumulation of 2-hydroxyglutarate (2-HG), a metabolite with oncogenic activity via epigenetic mechanisms. The advent of IDH inhibitors has engendered hope in novel and targeted therapies in IDH1/2 mutant myeloid malignancies. We here summarize the basic physiology of IDH, the metabolic and oncogenic consequences of mutant IDH1/2, and the clinical significance of IDH inhibition in hematologic malignancies...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315032/novel-indications-for-fecal-microbial-transplantation-update-and-review-of-the-literature
#12
REVIEW
Nathaniel Aviv Cohen, Nitsan Maharshak
BACKGROUND AND AIMS: Fecal microbial transplantation (FMT) is an established successful treatment modality for recurrent Clostridium difficile infection (CDI). The safety profile and potential therapeutic advantages of FMT for diseases associated with dysbiosis and immune dysfunction have led to many publications, mainly case series, and while many studies and reviews have been published on the use of FMT for inflammatory bowel disease (IBD), its potential use for other disease conditions has not been thoroughly reviewed...
May 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28314790/selinexor-kpt-330-induces-tumor-suppression-through-nuclear-sequestration-of-ikappab-and-down-regulation-of-survivin
#13
Jayasree S Nair, Elgilda Musi, Gary K Schwartz
PURPOSE: Selinexor, a small molecule that inhibits nuclear export protein XPO1 has demonstrated efficacy in solid tumors and hematologic malignancies with the evidence of clinical activity in sarcoma as a single agent. Treatment options available are very few and hence the need to identify novel targets and strategic therapies is of utmost importance. EXPERIMENTAL DESIGN: The mechanistic effects of selinexor in sarcomas as a monotherapy and in combination with proteasome inhibitor, carfilzomib, across a panel of cell lines in vitro and few in xenograft mouse models were investigated...
March 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28297624/genomics-of-acute-myeloid-leukemia-diagnosis-and-pathways
#14
Lars Bullinger, Konstanze Döhner, Hartmut Döhner
In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28290981/case-report-of-clinical-vignette-osteopetrosis
#15
John B Moore, Thanh D Hoang, Alfred F Shwayhat
INTRODUCTION: Osteopetrosis is a connective tissue disorder resulting from abnormally dense bone predisposing patients to fracture. The clinical pattern of fractures across time and space as well as suggestive radiographic findings usually raises diagnostic suspicion. Multiple genetic mutations resulting in dysfunctional osteoclasts have been implicated in the pathogenesis of osteopetrosis with variable inheritance patterns. In severe cases, usually inherited in an autosomal recessive pattern, the medullary cavity important in the production of normal blood cell progenitors is replaced by defective endochondral bone, leading to pancytopenia and consequential extramedullary hematopoiesis...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28280276/regulation-of-pi3k-signaling-in-t-cell-acute-lymphoblastic-leukemia-a-novel-pten-ikaros-mir-26b-mechanism-reveals-a-critical-targetable-role-for-pik3cd
#16
T Yuan, Y Yang, J Chen, W Li, W Li, Q Zhang, Y Mi, R S Goswami, J Q You, D Lin, M D Qian, S Calin, Y Liang, R N Miranda, G A Calin, X Zhou, L Ma, P A Zweidler-McKay, B Liu, A P Weng, L J Medeiros, Y Zhang, M J You
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, and T-ALL patients are prone to early disease relapse and suffer from poor outcomes. The PTEN, PI3K/AKT and Notch pathways are frequently altered in T-ALL. PTEN is a tumor suppressor that inactivates the PI3K pathway. We profiled miRNAs in Pten-deficient mouse T-ALL and identified miR-26b as a potentially dysregulated gene. We validated decreased expression levels of miR-26b in mouse and human T-ALL cells. In addition, expression of exogenous miR-26b reduced proliferation and promoted apoptosis of T-ALL cells in vitro, and hindered progression of T-ALL in vivo...
March 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28273184/-how-can-we-treat-waldenstr%C3%A3-m-s-macroglobulinemia
#17
Anna Orsolya Mucsi, Zsolt Nagy
Waldenström's macroglobulinemia is a rare, low-grade non-Hodgkin lymphoma of B cell origin, most common in elderly male patients with a median age of 64 years at diagnosis. It accounts for approximately 2% of hematologic malignancies. The disease is incurable now with a median overall survival of 6.2 years. In the past decade growing evidence suggests the role of the complex signaling pathways and microenvironment as a potential target of the therapy in the lymphoproliferative disorders as well as Waldenström's macroglobulinemia...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28270368/clinical-outcomes-related-to-the-use-of-bendamustine-therapy-for-multiple-myeloma-patients-relapsed-refractory-to-imids-and-proteasome-inhibitors
#18
Fevzi Fırat Yalnız, Nihan Akkoç, Ayşe Salihoğlu, M Cem Ar, Seniz Aydın, A Emre Eşkazan, Teoman Soysal, Yıldız Aydın
Multiple myeloma (MM) patients who are relapsed or refractory to both proteasome inhibitory (PIs) and immunomodulatory drugs (IMiDs) have been reported to have poor outcome. Bendamustine has been reported to have an antitumor effect in newly diagnosed as well as relapsed refractory multiple myeloma (RRMM). The aim of this retrospective study was to evaluate the efficacy of bendamustine therapy in heavily pretreated MM patients, who were refractory to PIs and IMiDs. Nineteen RRMM patients treated either with bendamustine and steroid (n=13) or a combination of bendamustine in with novel drugs (n=6) were included...
March 8, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28263217/peptide-receptor-radionuclide-therapy-with-177-lu-octreotate-in-patients-with-somatostatin-receptor-expressing-neuroendocrine-tumors-six-years-assessment
#19
Mohammadali Hamiditabar, Muzammil Ali, Joseph Roys, Edward M Wolin, Thomas M OʼDorisio, David Ranganathan, Izabela Tworowska, Jonathan R Strosberg, Ebrahim S Delpassand
OBJECTIVES: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a promising treatment for patients with inoperable, well to moderately differentiated metastatic neuroendocrine tumors (NETs). In continuation of our novel study with the radionuclide lutetium Lu, we now present further results of Lu DOTATATE therapy in managing NETs and other somatostatin receptor-expressing tumors in a larger and more diverse patient group. PATIENTS AND METHODS: One hundred forty-four consecutive patients (85 men and 59 women; age range, 11-87 years; mean age, 58...
March 3, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28259887/hiv-associated-lung-cancer
#20
Til R Kiderlen, Jan Siehl, Marcus Hentrich
Lung cancer (LC) is one of the most common non-AIDS (acquired immune deficiency syndrome)-defining malignancies. It occurs more frequently in persons living with human immunodeficiency virus (PLWHIV) than in the HIV-negative population. Compared to their HIV-negative counterparts, patients are usually younger and diagnosed at more advanced stages. The pathogenesis of LC in PLWHIV is not fully understood, but immunosuppression in combination with chronic infection and the oncogenic effects of smoking and HIV itself all seem to play a role...
2017: Oncology Research and Treatment
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