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https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#1
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27911276/the-mtor-inhibitor-everolimus-in-combination-with-azacitidine-in-patients-with-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-ii-study
#2
Peter Tan, Ing Soo Tiong, Shaun Fleming, Giovanna Pomilio, Nik Cummings, Mark Droogleever, Julie McManus, Anthony Schwarer, John Catalano, Sushrut Patil, Sharon Avery, Andrew Spencer, Andrew Wei
Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5-21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1-5 and 8-9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21)...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#3
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27911132/a-new-acute-myeloid-leukemia-case-with-stat5b-rara-gene-fusion-due-to-17q21-2-interstitial-deletion
#4
Chiara Pessina, Claudia Basilico, Angelo Genoni, Emanuela Meroni, Lorenzo Elli, Paola Granata, Rossana Righi, Francesco Pallotti, Barbara Mora, Andrea Ferrario, Francesco Passamonti, Rosario Casalone
No abstract text is available yet for this article.
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27910887/energy-metabolism-regulated-by-hdac-inhibitor-attenuates-cardiac-injury-in-hemorrhagic-rat-model
#5
Qiyuan Kuai, Chunyan Wang, Yanbing Wang, Weijing Li, Gongqing Zhang, Zhixin Qiao, Min He, Xuanlin Wang, Yu Wang, Xingwei Jiang, Lihua Su, Yuezhong He, Suping Ren, Qun Yu
A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910741/topotecan-liposomes-a-visit-from-a-molecular-to-a-therapeutic-platform
#6
Shivani Saraf, Ankit Jain, Pooja Hurkat, Sanjay Kumar Jain
Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27910030/recurrent-cytogenetic-abnormalities-in-non-hodgkin-s-lymphoma-and-chronic-lymphocytic-leukemia
#7
Edmond S K Ma
Characteristic chromosomal translocations are found to be associated with subtypes of B-cell non-Hodgkin lymphoma (NHL), for example t(8;14)(q24;q32) and Burkitt lymphoma, t(14;18)(q32;q21) and follicular lymphoma, and t(11;14)(q13;q32) in mantle cell lymphoma. Only few recurrent cytogenetic aberrations have been identified in the T-cell NHL and the best known is the ALK gene translocation t(2;5)(p23;q35) in anaplastic large cell lymphoma. Since lymph node or other tissue is seldom submitted for conventional cytogenetics study, alternative approaches for translocation detection are polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910029/recurrent-cytogenetic-abnormalities-in-acute-lymphoblastic-leukemia
#8
Mary Shago
Both B-cell and T-cell acute lymphoblastic leukemia (ALL) exhibit recurrent cytogenetic alterations, many with prognostic implications. This chapter overviews the major recurrent categories of cytogenetic abnormalities associated with ALL, with an emphasis on the detection and characterization of these cases by G-band and FISH analyses.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910028/recurrent-cytogenetic-abnormalities-in-myeloproliferative-neoplasms-and-chronic-myeloid-leukemia
#9
John Swansbury
The commonest types of myeloproliferative neoplasm (MPN) have remarkably similar recurrent chromosome abnormalities, but with varying incidence and prognostic implications. After a clear decade of treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors, the differing prognostic implications of abnormalities additional to the Ph chromosome are being revealed. This chapter provides a description of the main chromosome abnormalities in MPN and CML and their clinical implications in a time of rapid changes in both the application of new diagnostic techniques and the introduction of targeted therapies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910027/recurrent-cytogenetic-abnormalities-in-acute-myeloid-leukemia
#10
John J Yang, Tae Sung Park, Thomas S K Wan
The spectrum of chromosomal abnormality associated with leukemogenesis of acute myeloid leukemia (AML) is broad and heterogeneous when compared to chronic myeloid leukemia and other myeloid neoplasms. Recurrent chromosomal translocations such as t(8;21), t(15;17), and inv(16) are frequently detected, but hundreds of other uncommon chromosomal aberrations from AML also exist. This chapter discusses 22 chromosomal abnormalities that are common structural, numerical aberrations, and other important but infrequent (less than 1 %) translocations emphasized in the WHO classification...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910026/recurrent-cytogenetic-abnormalities-in-myelodysplastic-syndromes
#11
Meaghan Wall
Cytogenetic analysis has an essential role in diagnosis, classification, and prognosis of myelodysplastic syndromes (MDS). Some cytogenetic abnormalities are sufficiently characteristic of MDS to be considered MDS defining in the appropriate clinical context. MDS with isolated del(5q) is the only molecularly defined MDS subtype. The genes responsible for many aspects of 5q- syndrome, the distinct clinical phenotype associated with this condition, have now been identified. Cytogenetics forms the cornerstone of the most widely adopted prognostic scoring systems in MDS, the international prognostic scoring system (IPSS) and the revised international prognostic scoring system (IPPS-R)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910012/chromosome-preparation-for-chronic-lymphoid-malignancies
#12
Dorota Koczkodaj, Agata A Filip
Conventional cytogenetics is invariably one of the most important methods used in diagnostics of chronic lymphoproliferations. It complements fluorescence in situ hybridization (FISH) and molecular analysis. Presence of particular chromosomal alterations in chronic lymphocytic leukemia enables patients' stratification into appropriate cytogenetic risk groups and influences treatment decisions. In other non-Hodgkin lymphomas cytogenetic analyses are employed also in minimal residual disease assessment.As lymphocytes in chronic lymphoid malignancies are characterized by low proliferation rate in vitro, it is critical to induce their division in the culture properly...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910011/chromosome-preparation-for-acute-lymphoblastic-leukemia
#13
Mary Shago
The chromosome abnormalities observed in acute lymphoblastic leukemia have been demonstrated to contribute to patient management and treatment stratification. This chapter provides a basic protocol for the procurement, culture, harvest, and slide preparation of bone marrow aspirate and unstimulated peripheral blood specimens.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910009/cancer-cytogenetics-an-introduction
#14
Thomas S K Wan
The Philadelphia chromosome was the first chromosomal abnormality discovered in cancer using the cytogenetics technique in 1960, and was consistently associated with chronic myeloid leukemia. Over the past five decades, innovative technical advances in the field of cancer cytogenetics have greatly enhanced the detection ability of chromosomal alterations, and have facilitated the research and diagnostic potential of chromosomal studies in neoplasms. These developments notwithstanding, chromosome analysis of a single cell is still the easiest way to delineate and understand the relationship between clonal evolution and disease progression of cancer cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910003/bone-marrow-t-cell-percentage-a-novel-prognostic-indicator-in-acute-myeloid-leukemia
#15
Manar M Ismail, Nahla A B Abdulateef
Acute myeloid leukemia (AML) is an aggressive malignancy for which overall disease-free survival is less than 50%. Manipulation of the immune system is an interesting and promising therapy for AML patients. We aimed to characterize the immune system of AML patients, highlighting the clinical relevance of total bone marrow (BM) lymphocytes and subpopulations. Sixty-six new AML cases diagnosed according to WHO criteria from King Abdullah Medical City, KSA, from October 2012 to February 2015. Analysis of BM lymphocytes and subpopulations was done by flowcytometry...
December 1, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27909895/invasive-cutaneous-infection-due-to-scopulariopsis-brevicaulis-unsuccessfully-treated-with-high-dose-micafungin-in-a-neutropenic-patient
#16
Daniela Gavril, Paul-Louis Woerther, Aicha Ben Lakhdar, Linda Mahjoubi, Emilie Routier, Elisabeth Chachaty, Bertrand Gachot, Stephane De Botton, Jean-Baptiste Micol, Christophe Willekens
Scopulariopsis brevicaulis onychomycosis with local cutaneous invasion was diagnosed in an acute leukemia patient and unsuccessfully treated with high-dose micafungin, based on antifungal susceptibility testing. This case should alert clinicians to the possible severe evolution of onychomycosis in neutropenic patients and suggests that surgery should be preferred in such a situation.
December 1, 2016: Infection
https://www.readbyqxmd.com/read/27909887/similar-outcome-after-allogeneic-stem-cell-transplantation-with-a-modified-flamsa-conditioning-protocol-substituting-4%C3%A2-gy-tbi-with-treosulfan-in-an-elderly-population-with-high-risk-aml
#17
Udo Holtick, Marco Herling, Natali Pflug, Geothy Chakupurakal, Silke Leitzke, Dominik Wolf, Michael Hallek, Christof Scheid, Jens M Chemnitz
The fludarabine, amsacrine, and cytarabine (FLAMSA)-reduced-intensity conditioning (RIC) protocol has been described to be effective in patients with high-risk and refractory acute myeloic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (aSCT). To increase safety and tolerability of the conditioning, we previously reported the feasibility to substitute the TBI component by treosulfan in elderly AML patients. We now present long-term follow-up data on patients treated with FLAMSA/treosulfan compared to the original FLAMSA/4Gy TBI protocol...
December 1, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27909636/imatinib-induced-ototoxicity-in-a-patient-with-gastrointestinal-stromal-tumor-gist
#18
Komal Wasif, Nawal Wasif, Muhammad W Saif
Imatinib (Gleevec) is a biological agent that is approved for the treatment of chronic myeloid leukemia (CML) as well as gastrointestinal stromal tumor (GIST). The most frequently seen adverse effects in patients treated with imatinib include superficial edema, muscle cramps, musculoskeletal pain, rash, fatigue, headache, abdominal pain, and joint pain. Ototoxicity has rarely been reported except in two cases. We report a case of bilateral irreversible sensorineural hearing loss (SNHL) caused by imatinib in a patient receiving this agent in the adjuvant setting...
October 26, 2016: Curēus
https://www.readbyqxmd.com/read/27909467/invasive-squamous-cell-carcinoma-of-the-scalp-and-calvarium-a-multidisciplinary-approach
#19
Jennifer Stark, Silvio Podda, Karen Szymanski
Objective: The correlation between immunosuppression-associated skin cancer and lymphoma has been well established. This includes squamous cell carcinoma and chronic lymphocytic leukemia. When a lesion requires excision, reconstruction can be challenging based on the depth and size of the tumor. We present a patient with chronic lymphocytic leukemia and invasive squamous cell carcinoma of the scalp that extended through the calvarium to the dura mater. His tumors were badly neglected for a long period of time and presented at an advanced stage...
2016: Eplasty
https://www.readbyqxmd.com/read/27909342/ristocetin-induced-platelet-aggregation-for-monitoring-of-bleeding-tendency-in-cll-treated-with-ibrutinib
#20
L Kazianka, C Drucker, C Skrabs, W Thomas, T Melchardt, S Struve, M Bergmann, P B Staber, E Porpaczy, C Einberger, M Heinz, A Hauswirth, M Raderer, I Pabinger, R Thalhammer, A Egle, C-M Wendtner, G Follows, G Hoermann, P Quehenberger, B Jilma, U Jaeger
Bleeding because of impaired platelet function is a major side effect of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib. We quantitatively assessed ristocetin-induced platelet aggregation (RIPA) in 64 patients with chronic lymphocytic leukemia (CLL) under ibrutinib at 287 time points. Eighty-seven bleeding episodes in 39 patients were registered (85 Common Toxicity Criteria (CTC) grade 1 or 2, 2 CTC grade 3) during a median observation period of 10.9 months. At times of bleeding, RIPA values were significantly lower (14 vs 28 U; P<0...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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