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https://www.readbyqxmd.com/read/29653206/late-effects-screening-guidelines-after-hematopoietic-cell-transplantation-hct-for-hemoglobinopathy-consensus-statement-from-the-second-pediatric-blood-and-marrow-transplant-consortium-international-conference-on-late-effects-after-pediatric-hct
#1
Shalini Shenoy, Javid Gaziev, Emanuele Angelucci, Allison King, Monica Bhatia, Angela Smith, Dorine Bresters, Anne E Haight, Christine N Duncan, Josu de la Fuente, Andrew C Dietz, K Scott Baker, Michael A Pulsipher, Mark C Walters
Allogeneic hematopoietic cell transplantation (HCT) can halt organ damage and eliminate symptoms in hemoglobin disorders, including sickle cell disease (SCD) and thalassemia major (TM). Managing the residual manifestations of pre-HCT disease complications and the long-term effects of HCT requires systematic monitoring, follow-up, and intervention when indicated. Late complications vary with age and disease status at HCT, and with transplant variables such as preparative regimen, donor source and compatibility, and immune reconstitution...
April 10, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29651744/prospects-of-chimeric-antigen-receptor-t-cell-therapy-in-ovarian-cancer
#2
REVIEW
Vishal Jindal, Ena Arora, Sorab Gupta, Amos Lal, Muhammad Masab, Rashmika Potdar
Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Immunotherapy provides a promising and novel treatment option for ovarian cancer. Recently, chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematological tumors and current research is going on in various solid tumors like ovarian cancer. CAR T cells are genetically engineered T cells with major histocompatibility complex-independent, tumor-specific, immune-mediated cytolytic actions against cancer cells...
April 12, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29643855/targeting-sphingosine-kinase-isoforms-effectively-reduces-growth-and-survival-of-neoplastic-mast-cells-with-d816v-kit
#3
Geethani Bandara, Rosa Muñoz-Cano, Araceli Tobío, Yuzhi Yin, Hirsh D Komarow, Avanti Desai, Dean D Metcalfe, Ana Olivera
Mastocytosis is a disorder resulting from an abnormal mast cell (MC) accumulation in tissues that is often associated with the D816V mutation in KIT, the tyrosine kinase receptor for stem cell factor. Therapies available to treat aggressive presentations of mastocytosis are limited, thus exploration of novel pharmacological targets that reduce MC burden is desirable. Since increased generation of the lipid mediator sphingosine-1-phosphate (S1P) by sphingosine kinase (SPHK) has been linked to oncogenesis, we studied the involvement of the two SPHK isoforms (SPHK1 and SPHK2) in the regulation of neoplastic human MC growth...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29643425/a-novel-two-score-system-for-interferon-status-segregates-autoimmune-diseases-and-correlates-with-clinical-features
#4
Y M El-Sherbiny, A Psarras, M Y Md Yusof, E M A Hensor, R Tooze, G Doody, A A A Mohamed, D McGonagle, M Wittmann, P Emery, E M Vital
Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity of the ISG transcriptome, cell-specific expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29625833/celyad-s-novel-car-t-cell-therapy-for-solid-malignancies
#5
Caroline Lonez, Alain Hendlisz, Leila Shaza, Philippe Aftimos, Michaël Vouche, Vincent Donckier, Jean-Pascal H Machiels, Marc Van Den Eynde, Jean-Luc Canon, Javier Carrasco, Kunle Odunsi, Solmaz Sahebjam, Sylvie Rottey, Nathalie Braun, Bikash Verma, David E Gilham, Frédéric F Lehmann
Celyad recently initiated several clinical trials with the CYAD-01 product, a natural killer group 2D (NKG2D)-based chimeric antigen receptor (CAR), in both solid and hematologic tumor types. This review discusses the unique properties of CYAD-01, expecting to provide a new paradigm to fight against solid tumors.
April 3, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29601858/-applications-of-gene-editing-technologies-to-cellular-therapies
#6
REVIEW
Lindsay A M Rein, Haeyoon Yang, Nelson J Chao
Hematologic malignancies are characterized by genetic heterogeneity making classic gene therapy with a goal of correcting one genetic defect ineffective in many of these diseases. Despite initial tribulations, gene therapy, as a field, has grown by leaps and bounds with the recent development of gene editing techniques including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR) sequences and CRISPR-associated protein-9 (Cas9) nuclease or CRISPR/Cas9...
March 27, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29600238/efficacy-and-tolerability-of-bortezomib-and-dexamethasone-in-newly-diagnosed-multiple-myeloma
#7
Mir Sadaqat Hassan Zafar, Afaq Ahmed Khan, Shyam Aggarwal, Manorama Bhargava
Background: Outcome in multiple myeloma (MM) has improved substantially over recent years as a result of the availability of multiple novel agents with acceptable safety profile. Study Design: Prospective observational study at a tertiary care institute. Methods: Twenty-five newly diagnosed patients of MM were treated with bortezomib and dexamethasone induction with monitoring for response and safety, followed by peripheral blood autologous stem cell transplant (PBASCT) in eligible patients or maintenance...
January 2018: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/29576386/multiple-myeloma-clinical-updates-from-the-american-society-of-hematology-annual-meeting-2017
#8
REVIEW
Evangelos Terpos
The novel clinical data for myeloma that were presented in the 2017 Annual Meeting of the American Society of Hematology are summarized here. Studies with curative approach (CESAR) or prolonging progression-free survival (CENTAURUS) for patients with high-risk smoldering multiple myeloma (SMM) are described. Updated data from large phase III studies for patients with newly diagnosed MM (NDMM) who are eligible for autologous stem cell transplantation (ASCT) (EMN02, MRC XI) are described, along with the results of studies using novel anti-myeloma drug combinations for induction, consolidation, and maintenance as first-line therapy...
March 1, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29572239/identification-of-novel-mecom-gene-fusion-and-personalized-therapeutic-targets-through-integrative-clinical-sequencing-in-secondary-acute-myeloid-leukemia-in-a-patient-with-severe-congenital-neutropenia-a-case-report-and-literature-review
#9
James A Connelly, Rajen J Mody, Yi-Mi Wu, Dan R Robinson, Robert J Lonigro, Pankaj Vats, Erica Rabban, Bailey Anderson, Kelly Walkovich
Severe congenital neutropenia (SCN) is a rare hematologic disorder characterized by defective myelopoiesis and a high incidence of malignant transformation to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). SCN patients who develop MDS/AML have excessive toxicities to traditional chemotherapy and safer therapies are needed to improve overall survival in this population. In this report, we outline the use of a prospective integrative clinical sequencing trial (PEDS-MIONCOSEQ) in a patient with SCN and AML to help identify oncogenic targets for less toxic agents...
March 23, 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29569511/radioimmunotherapy-as-the-first-line-of-treatment-in-non-hodgkin-lymphoma
#10
Mahsa Eskian, MirHojjat Khorasanizadeh, Pier L Zinzani, Nima Rezaei
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy. The estimated deaths and new cases of NHL in the USA in 2018 have reached 19,910 and 74,680, respectively, with 5-year survival rate of 71%. Therapeutic interventions for NHL consist of chemotherapy, radiation therapy and immunotherapy. Radioimmunotherapy (RIT) is a potential alternative treatment for NHL that is currently used in different lines of treatment. Studies show that nuclear medicine physicians and radiation oncologists are not yet certain about the proper line for administration of RIT...
March 23, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29567781/a-novel-regimen-for-relapsed-refractory-adult-acute-myeloid-leukemia-using-a-kmt2a-partial-tandem-duplication-targeted-therapy-results-of-phase-1-study-nci-8485
#11
Alice S Mims, Anjali Mishra, Shelley Orwick, James Blachly, Rebecca B Klisovic, Ramiro Garzon, Alison R Walker, Steven M Devine, Katherine J Walsh, Sumithira Vasu, Susan Whitman, Guido Marcucci, Daniel Jones, Nyla A Heerema, Gerard Lozanski, Michael A Caligiuri, Clara D Bloomfield, John C Byrd, Richard Piekarz, Michael R Grever, William Blum
KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leukemia and is associated with adverse prognosis. KMT2A wild type is epigenetically silenced in KMT2A partial tandem duplication; re-expression can be induced with DNA methyltransferase and/or histone deacetylase inhibitors in vitro, sensitizing myeloid blasts to chemotherapy. We hypothesized that epigenetic silencing of KMT2A wildtype contributes to KMT2A partial tandem duplication-associated leukemogenesis and pharmacologic re-expression activates apoptotic mechanisms important for chemo-response...
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29561760/novel-indications-for-bruton-s-tyrosine-kinase-inhibitors-beyond-hematological-malignancies
#12
REVIEW
Robert Campbell, Geoffrey Chong, Eliza A Hawkes
Bruton's tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in proliferation of solid malignancies is expanding the indication of BTKi into non-hematological malignancies...
March 21, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29560124/cd30-targeted-oncolytic-viruses-as-novel-therapeutic-approach-against-classical-hodgkin-lymphoma
#13
Julia D S Hanauer, Benjamin Rengstl, Dina Kleinlützum, Johanna Reul, Anett Pfeiffer, Thorsten Friedel, Irene C Schneider, Sebastian Newrzela, Martin-Leo Hansmann, Christian J Buchholz, Alexander Muik
Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While most patients with early stage cHL can be cured by standard therapy, treatment options for relapsed or refractory cHL are still not sufficient, although immunotherapy-based approaches for the treatment of cHL patients have gained ground in the last decade...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29558277/stem-cell-transplantation-for-light-chain-amyloidosis-decreased-early-mortality-over-time
#14
M Hasib Sidiqi, Mohammed A Aljama, Francis K Buadi, Rahma M Warsame, Martha Q Lacy, Angela Dispenzieri, David Dingli, Wilson I Gonsalves, Shaji Kumar, Prashant Kapoor, Taxiarchis Kourelis, William J Hogan, Morie A Gertz
Purpose Autologous stem-cell transplantation (ASCT) has been used in patients with immunoglobulin light chain (AL) amyloidosis for more than two decades. Early experience raised concerns regarding safety with high early-mortality rates. Patients and Methods We report 20 years of experience with ASCT for AL amyloidosis at the Mayo Clinic Rochester. In all, 672 consecutive patients receiving ASCT for AL amyloidosis were divided into three cohorts on the basis of date of transplantation (cohort 1, 1996-2002 [n = 124]; cohort 2, 2003-2009 [n = 302]; and cohort 3, 2010-2016 [n = 246])...
March 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29554892/immune-thrombocytopenic-purpura-presenting-in-a-patient-after-renal-transplant-for-diabetic-nephropathy
#15
Raja Muhammad Rashid, Zahid Nabi, Ahmad Zaki Ansari, Quratul-Ain Qaiser
BACKGROUND: Immune thrombocytopenic purpura (ITP) is primarily characterized by immune-mediated destruction of platelets in circulation. Major treatment options range from careful observation, steroids, immunosuppressive medications, immunoglobulins to splenectomy. Interestingly and rarely, ITP has also been reported after solid organ transplantation in patients receiving immunosuppressive medications. While the incidence of new onset ITP after solid organ transplant is comparatively well documented, new onset ITP after renal transplant has only been reported in two patients...
March 20, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29554494/driving-cars-on-the-uneven-road-of-antigen-heterogeneity-in-solid-tumors
#16
REVIEW
Nan Chen, Xiaoyu Li, Navin K Chintala, Zachary E Tano, Prasad S Adusumilli
Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells...
March 16, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29553276/development-and-implementation-of-an-academic-cancer-therapy-stewardship-program
#17
Amir S Steinberg, Anish B Parikh, Sara Kim, Damaris Peralta-Hernandez, Talaat Aggour, Luis Isola
OBJECTIVES: Antibiotic stewardship is an integral aspect of hospital care, limiting the potential for resistance while working to minimize waste. A similar system is needed in oncology, given the rapid proliferation of new therapies and the challenges of navigating a complicated reimbursement environment. A "cancer therapy stewardship program" has never been described in the literature. Here, we detail our efforts to design and implement such a program and share lessons learned to inform future projects...
March 2018: American Journal of Managed Care
https://www.readbyqxmd.com/read/29527929/notch-signaling-as-a-therapeutic-target-for-acute-lymphoblastic-leukemia
#18
Diana Bellavia, Rocco Palermo, Maria Pia Felli, Isabella Screpanti, Saula Checquolo
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although the therapy of ALL has significantly improved, the heterogeneous genetic landscape of the disease often causes relapse, which is difficult to treat. Achieving a positive outcome for patients with relapsed or refractory ALL remains a challenging issue. The high prevalence of NOTCH-activating mutations in T-cell acute lymphoblastic leukemia (T-ALL) and the central role of NOTCH signaling in regulating cell survival and growth of ALL provide a rationale for the development of Notch signaling-targeted strategies in this disease...
March 12, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29510227/long-non-coding-rna-pvt1-as-a-novel-candidate-for-targeted-therapy-in-hematologic-malignancies
#19
Mohammad Houshmand, Narjes Yazdi, Alireza Kazemi, Amir Atashi, Amir Ali Hamidieh, Ali Anjam Najemdini, Mahshid Mohammadi Pour, Mahin Nikougoftar Zarif
Cancerous cells show resistance to various forms of therapy, so applying up to the minute targeted therapy is crucial. For this purpose, long non-coding RNA PVT1 as shown by recent studies is an important oncogene that interacts with vital cellular signaling pathways and different proteins such as c-Myc, NOP2 and LATS2. Due to the enormous role of long non-coding RNAs in development of leukemias, we aimed to show the role of PVT1 knock-down on fate of different hematologic cell lines. owing to this matter, various experiments such as Real-time PCR, cell cycle analysis and apoptosis assay were performed...
March 3, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29482842/the-pharmacology-of-cd38-nadase-an-emerging-target-in-cancer-and-diseases-of-aging
#20
REVIEW
Eduardo N Chini, Claudia C S Chini, Jair Machado Espindola Netto, Guilherme C de Oliveira, Wim van Schooten
Recent reports indicate that intracellular NAD levels decline in tissues during chronological aging, and that therapies aimed at increasing cellular NAD levels could have beneficial effects in many age-related diseases. The protein CD38 (cluster of differentiation 38) is a multifunctional enzyme that degrades NAD and modulates cellular NAD homeostasis. At the physiological level, CD38 has been implicated in the regulation of metabolism and in the pathogenesis of multiple conditions including aging, obesity, diabetes, heart disease, asthma, and inflammation...
February 23, 2018: Trends in Pharmacological Sciences
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