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https://www.readbyqxmd.com/read/29455667/role-of-non-receptor-tyrosine-kinases-in-hematological-malignances-and-its-targeting-by-natural-products
#1
REVIEW
Kodappully S Siveen, Kirti S Prabhu, Iman W Achkar, Shilpa Kuttikrishnan, Sunitha Shyam, Abdul Q Khan, Maysaloun Merhi, Said Dermime, Shahab Uddin
Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29434279/oncogenic-activation-of-jak3-stat-signaling-confers-clinical-sensitivity-to-prn371-a-novel-selective-and-potent-jak3-inhibitor-in-natural-killer-t-cell-lymphoma
#2
M -L Nairismägi, M E Gerritsen, Z M Li, G C Wijaya, B K H Chia, Y Laurensia, J Q Lim, K W Yeoh, X S Yao, W L Pang, A Bisconte, R J Hill, J M Bradshaw, D Huang, T L L Song, C C Y Ng, V Rajasegaran, T Tang, Q Q Tang, X J Xia, T B Kang, B T Teh, S T Lim, C K Ong, J Tan
Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29427461/thromboembolism-prophylaxis-in-patients-with-philadelphia-negative-myeloproliferative-neoplasms-clinical-practice-among-nordic-specialists
#3
O W Bjerrum, J Samuelsson, W Ghanima, M Kauppila, C L Andersen
BACKGROUND: Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting and access to therapy, however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs...
February 10, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29409139/withdrawn-chemoimmunotherapy-versus-chemotherapy-for-metastatic-malignant-melanoma
#4
REVIEW
Andre D Sasse, Emma C Sasse, Luciana Go Clark, Otavio Augusto Camara Clark
BACKGROUND: Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone...
February 6, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29409124/current-developments-in-immunotherapy-in-the-treatment-of-multiple-myeloma
#5
REVIEW
Martin Köhler, Christine Greil, Michael Hudecek, Sagar Lonial, Noopur Raje, Ralph Wäsch, Monika Engelhardt
Multiple myeloma (MM) is the second most common hematologic malignancy and represents approximately 10% of all hematological neoplasms. Standard therapy consists of induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) or, if ASCT cannot be performed, standard doublet, triplet, or quadruplet, novel agent-containing induction treatment until progression. Although MM is still regarded as mostly incurable by current standards, the development of several novel compounds, combination therapies, and immunotherapy approaches has raised great hopes about transforming MM into an indolent, chronic disease and possibly achieving a cure for individual patients...
February 6, 2018: Cancer
https://www.readbyqxmd.com/read/29402479/advances-in-diagnostics-and-treatments-in-horses-with-acute-colic-and-postoperative-ileus
#6
REVIEW
Megan Burke, Anthony Blikslager
Differentiating between medical and surgical causes of colic is one of the primary goals of the colic workup, because early surgical intervention improves prognosis in horses requiring surgery. Despite the increasing availability of advanced diagnostics (hematologic analyses, abdominal ultrasound imaging, etc), the most accurate indicators of the need for surgery remain the presence of moderate to severe signs of abdominal pain, recurrence of pain after appropriate analgesic therapy, and the absence of intestinal borborygmi...
February 2, 2018: Veterinary Clinics of North America. Equine Practice
https://www.readbyqxmd.com/read/29399396/serine-protease-inhibitor-6-protects-alloreactive-t-cells-from-granzyme-b-mediated-mitochondrial-damage-without-affecting-graft-versus-tumor-effect
#7
Wei Du, Hemn Mohammadpour, Rachel E O'Neill, Sandeep Kumar, Chuan Chen, Michelle Qiu, Lin Mei, Jingxin Qiu, Philip L McCarthy, Kelvin P Lee, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies. Donor T cells are able to eliminate residual tumor cells after allo-HCT, producing the beneficial graft-versus-tumor (GVT) effect, but can also cause graft-versus-host disease (GVHD) when attacking host normal tissues. We previously reported that granzyme B (GzmB) is involved in activation-induced cell death (AICD) of donor T cells and exerts differential impacts on GVHD and GVT effect. Serine protease inhibitor 6 (Spi6) is the sole endogenous inhibitor of GzmB that can protect immune and tissue cells against GzmB-mediated damage...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29391334/invasive-fungal-infections-in-patients-with-hematological-malignancies-emergence-of-resistant-pathogens-and-new-antifungal-therapies
#8
Maria N Gamaletsou, Thomas J Walsh, Nikolaos V Sipsas
Invasive fungal infections caused by drug-resistant organisms, are an emerging threat to heavily immunosuppressed patients with haematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis, empirical and pre-emptive therapy result in long term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the non-linear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors...
February 2, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/29389768/integrative-view-on-how-erythropoietin-signaling-controls-transcription-patterns-in-erythroid-cells
#9
Andrea A Perreault, Bryan J Venters
PURPOSE OF REVIEW: Erythropoietin (EPO) is necessary and sufficient to trigger dynamic transcriptional patterns that drive the differentiation of erythroid precursor cells into mature, enucleated red cells. Because the molecular cloning and Food and Drug Administration approval for the therapeutic use of EPO over 30 years ago, a detailed understanding of how EPO works has advanced substantially. Yet, the precise epigenetic and transcriptional mechanisms by which EPO signaling controls erythroid expression patterns remains poorly understood...
January 30, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29383623/nk-cell-therapy-for-hematologic-malignancies
#10
REVIEW
Rohtesh S Mehta, Brion Randolph, May Daher, Katayoun Rezvani
Natural killer (NK) cells are part of the innate immune system and represent the first line of defense against infections and tumors. In contrast to T cells, NK cells do not require prior antigen sensitization to induce cytotoxicity and do not cause graft-versus-host disease. These, along with other advantages, make NK cells an attractive candidate for adoptive cellular therapy. Herein, we describe the mechanisms of NK cell cytotoxicity, which is governed by an intricate balance between various activating and inhibitory receptors, including the killer cell immunoglobulin-like receptors (KIRs)...
January 27, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29379294/exploring-the-effect-of-chidamide-on-blastic-plasmacytoid-dendritic-cell-neoplasm-a-case-report-and-literature-review
#11
Shunan Wang, Wei Guo, Xin Wan, Yongliang Teng, Xiaoge Zhou, Ou Bai
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy mainly affecting elderly patients. It is highly responsive to chemotherapy, but the median event-free survival is very short and has a high rate of relapse even after performing allogeneic stem cell transplantation; thus, the discovery of novel agents for the treatment of BPDCN is urgent. Chidamide is a new oral isotype-selective histone deacetylase inhibitor (HDACi). It is proved to exert a well-characterized anticancer property in a wide range of hematological malignancies, especially lymphoma...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29374487/current-trials-for-frontline-therapy-of-mantle-cell-lymphoma
#12
REVIEW
Raphael E Steiner, Jorge Romaguera, Michael Wang
Mantle cell lymphoma (MCL) is a rare and incurable subtype of non-Hodgkin's lymphoma that generally affects older individuals. However, the use of high-dose therapy and autologous stem cell transplant has improved significantly the prognosis of this hematological malignancy, but at the cost of increased toxicities, such as acute toxic death and secondary malignancies. But thanks to a rising understanding of the biology of MCL, the explosion of specifically targeted new efficacious agents, immunotherapy agents, and cellular therapies in the frontline setting, the prognosis of MCL is expected to improve dramatically...
January 27, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29371911/tlr-signaling-inhibitor-phenylmethimazole-in-combination-with-tamoxifen-inhibits-human-breast-cancer-cell-viability-and-migration
#13
Anthony L Schwartz, Eric Dickerson, Nilesh Dagia, Ramiro Malgor, Kelly D McCall
Heightened co-expression and dysregulated signaling associated with Toll-like receptor 3 (TLR3) and Wnt5a is an integral component of solid tumors and hematological malignancies. Our previous findings in pancreatic cancer and melanoma suggest that inhibition of these pathways by a TLR3 signaling inhibitor, phenylmethimazole (C10), results in significantly decreased IL-6 levels, STAT3 phosphorylation, minimal cancer cell migration and reduced cancer cell growth in vitro and in vivo. In this study, we extended our earlier observations by performing studies in human breast cancer cells...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29360721/preclinical-data-supporting-antitumor-activity-of-pd-1-blockade
#14
Michael A Curran
Antibodies that block the PD-1 coinhibitory receptor on T cells or its primary ligand, PD-L1, have demonstrated unprecedented efficacy across a diverse array of both solid and hematologic malignancies in the clinic. These advances were built on a foundation of murine preclinical tumor model studies, which both demonstrated the therapeutic potential of PD-1/PD-L1 antibody blockade and also provided critical insights into the cellular and molecular processes underlying their capacity to elicit immune-mediated tumor regressions...
January 2018: Cancer Journal
https://www.readbyqxmd.com/read/29349620/fatal-talaromyces-marneffei-infection-in-a-patient-with-autoimmune-hepatitis
#15
Sally C Y Wong, Siddharth Sridhar, Antonio H Y Ngan, Jonathan H K Chen, Rosana W S Poon, Susanna K P Lau, Patrick C Y Woo
Talaromyces marneffei, previously known as Penicillium marneffei, is the most important pathogenic thermally dimorphic fungus causing systemic mycosis in Southeast Asia. Traditionally, T. marneffei infection in human was mainly associated with acquired immunodeficiency syndrome caused by HIV infection. In recent years, there has been an increasing number of T. marneffei infections reported in non-HIV-infected patients with other immunocompromised conditions, including autoantibodies against interferon-gamma, systemic lupus erythematosis, solid organ transplantation, Job's syndrome, hematological malignancies, and use of novel targeted therapies...
January 18, 2018: Mycopathologia
https://www.readbyqxmd.com/read/29344207/novel-homobarringtonie-containing-therapy-for-the-treatment-of-patients-with-primary-acute-myeloid-leukemia-that-are-resistant-to-conventional-therapy
#16
Jingsong He, Li Li, Jingjing Zhu, Weiyan Zheng, Wenjun Wu, Yanlong Zheng, Xiujin Ye
The current study investigated the efficacy and safety of a novel treatment regime consisting of homobarringtonie, cytosine arabinoside and etoposide (HCE) for the treatment of primary acute myeloid leukemia (AML). In the present study, 141 patients diagnosed with AML were divided into the HCE (n=47) and the conventional AML therapy, consisting of idamycin combined with cytarabine (IA; n=94), treatment groups. The measured patient outcome parameters were the emission and response rates, as well as medication-induced adverse events, with a median follow-up time of 28 months...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29334169/impact-of-baseline-clinical-and-laboratory-features-on-the-risk-of-thrombosis-in-children-with-acute-lymphoblastic-leukemia-a-prospective-evaluation
#17
Uma H Athale, T Mizrahi, C Laverdière, T Nayiager, Y-L Delva, G Foster, L Thabane, M David, J-M Leclerc, A K C Chan
BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the effects of clinical (age, gender, ALL risk group) and laboratory variables (hematological parameters, ABO blood group, inherited and acquired prothrombotic defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in children (aged 1 to ≤18) treated on the Dana-Farber Cancer Institute ALL 05-001 study...
January 15, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29323537/investigational-therapies-targeting-cd37-for-the-treatment-of-b-cell-lymphoid-malignancies
#18
Magdalena Witkowska, Piotr Smolewski, Tadeusz Robak
While chemotherapy still remains a cornerstone of oncologic therapy, immunotherapy with monoclonal antibodies has steadily improved the treatment strategy for several hematologic malignancies. New treatment options need to be developed for relapsed and refractory non-Hodgkin lymphoma (NHL) patients. Currently, novel agents targeting specific molecules on the surface of lymphoma cells, such as anti-CD37 antibodies, are under considerable investigation. Here we report on anti-CD37 targeting for the treatment of patients with B-cell NHL...
February 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29319167/antibody-drug-conjugates-promising-and-efficient-tools-for-targeted-cancer-therapy
#19
REVIEW
Hadi Nasiri, Zahra Valedkarimi, Leili Aghebati-Maleki, Jafar Majidi
Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29310835/april-gene-expression-in-a-cohort-of-egyptian-acute-myeloid-leukemia-patients-clinical-and-prognostic-significance
#20
Amira Ahmed Hammam, Shereen Mohamed Elhoseiny, Rania El-Sayed Sheir, Hisham Issa
APRIL (A Proliferation Inducing Ligand) is a member of the tumor necrosis factor (TNF) family. It is essential for the survival of normal and malignant B lymphocytes. Increased expression of APRIL is noted in most of hematological malignancies and auto immune diseases. We investigated the expression level of APRIL mRNA in 50 de novo acute myeloid leukemia (AML) patients, together with 20 healthy controls using a Real-Time Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RTQ-PCR) with a specific aim of determining its relation to clinical features and laboratory findings at diagnosis and its impact on the response to therapy...
January 2018: Cancer Genetics
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