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https://www.readbyqxmd.com/read/28343201/-ibrutinib-new-tool-in-hematologist-hand-new-challenges-for-internist
#1
Maciej Majcherek, Marzena Dworacka, Grzegorz Dworacki
Chronic lymphocytic leukemia is the most common cancer of the lymphatic tissue in adults. The peak incidence falls on the 65-70 year old. Therefore, the majority of patients with chronic lymphocytic leukemia (CLL) has at least one coexisting disease. Successful oncological and supportive treatment, that is common in recent years, significantly prolongs the survival. This paper presents ibrutinib - a new drug used to treat CLL. The aim of this paper is, to show an example of this drug, meaning and benefits of modern methods of pharmacotherapy in the treatment of oncology...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28336937/results-of-the-randomized-phase-iib-arctic-trial-of-low-dose-rituximab-in-previously-untreated-cll
#2
D R Howard, T Munir, L McParland, A C Rawstron, D Milligan, A Schuh, A Hockaday, D J Allsup, S Marshall, A S Duncombe, J L O'Dwyer, A F Smith, R Longo, A Varghese, P Hillmen
ARCTIC was a multi-center, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated Chronic Lymphocytic Leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. 200 patients were recruited to assess the primary endpoint of complete remission (CR) rates according to IWCLL criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness...
March 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28331288/development-of-venetoclax-for-therapy-of-lymphoid-malignancies
#3
REVIEW
Huayuan Zhu, Alexandru Almasan
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28329554/eosinophilic-dermatosis-of-hematologic-malignancy
#4
Kathryn Martires, Shields Callahan, Vitaly Terushkin, Nooshin Brinster, Marie Leger, Nicholas A Soter
We report a 68-year-old woman with chroniclymphocytic leukemia, who developed numerous,pruritic, edematous, and vesicobullous skin lesionsof the face and extremities over the course of severalmonths. The diagnosis of eosinophilic dermatosis ofhematologic malignancy (EDHM) was made basedon the clinical history and histopathologic features.Owing to the possible link between EDHM and amore aggressive underlying CLL, she was startedagain on chemotherapy. This case serves as areminder that, although the precise pathogenesis ofEDHM remains unclear, the paraneoplastic disorderis the result of immune dysregulation...
December 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#5
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28324286/prolymphocytic-leukemia-new-insights-in-diagnosis-and-in-treatment
#6
REVIEW
Aude Collignon, Anne Wanquet, Elsa Maitre, Edouard Cornet, Xavier Troussard, Thérèse Aurran-Schleinitz
PURPOSE OF REVIEW: We aimed to produce a comprehensive update on clinical and biological data regarding two rare lymphoid neoplasms, B and T prolymphocytic leukemias, and assess therapeutic management in the light of new molecular insights and the advent of targeted therapies. RECENT FINDINGS: B cell prolymphocytic leukemia (B-PLL) diagnosis remains challenging in the absence of clear immunophenotypic or cytogenetic signature and overlap with mantle cell lymphoma...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28321119/notch1-mutated-chronic-lymphocytic-leukemia-cells-are-characterized-by-a-myc-related-overexpression-of-nucleophosmin-1-and-ribosome-associated-components
#7
F Pozzo, T Bittolo, E Vendramini, R Bomben, P Bulian, F M Rossi, A Zucchetto, E Tissino, M Degan, G D'Arena, F Di Raimondo, F Zaja, G Pozzato, D Rossi, G Gaidano, G Del Poeta, V Gattei, M Dal Bo
In chronic lymphocytic leukemia (CLL), the mechanisms controlling cell growth and proliferation in presence of NOTCH1 mutations remain largely unexplored. By performing a gene expression profile of NOTCH1 mutated (NOTCH1-mut) versus NOTCH1 wild type CLL, we identified a gene signature of NOTCH1-mut CLL characterized by upregulation of genes related to ribosome biogenesis, such as nucleophosmin1 (NPM1) and ribosomal proteins (RNPs). Activation of NOTCH1 signaling by EDTA or by co-culture with JAGGED1-expressing stromal cells increased NPM1 expression, and inhibition of NOTCH1 signaling by either NOTCH1-specific small interfering RNA (siRNA) or γ-secretase inhibitor reduced NPM1 expression...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28320322/exploring-the-nature-of-prediagnostic-blood-transcriptome-markers-of-chronic-lymphocytic-leukemia-by-assessing-their-overlap-with-the-transcriptome-at-the-clinical-stage
#8
Jelle Vlaanderen, Max Leenders, Marc Chadeau-Hyam, Lützen Portengen, Soterios A Kyrtopoulos, Ingvar A Bergdahl, Ann-Sofie Johansson, Dennie D G A J Hebels, Theo M C M de Kok, Paolo Vineis, Roel C H Vermeulen
BACKGROUND: We recently identified 700 genes whose expression levels were predictive of chronic lymphocytic leukemia (CLL) in a genome-wide gene expression analysis of prediagnostic blood from future cases and matched controls. We hypothesized that a large fraction of these markers were likely related to early disease manifestations. Here we aim to gain a better understanding of the natural history of the identified markers by comparing results from our prediagnostic analysis, the only prediagnostic analysis to date, to results obtained from a meta-analysis of a series of publically available transcriptomics profiles obtained in incident CLL cases and controls...
March 20, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28317752/facile-preparation-of-magnetic-carbon-nanotubes-immobilized-lipase-for-highly-efficient-synthesis-of-1-3-dioleoyl-2-palmitoylglycerol-rich-human-milk-fat-substitutes
#9
Mingming Zheng, Shi Wang, Xia Xiang, Jie Shi, Juan Huang, Qianchun Deng, Fenghong Huang, Junyong Xiao
In this study, Candida lipolytica lipase (CLL) was immobilized on magnetic multi-walled carbon nanotubes (mMWCNTs) via hydrophobic and cation-exchange interaction. The resultant immobilized CLL showed much better thermal stability, biocatalyst activity and easier recycling than the free form. A method for efficient enzymatic acidolysis of tripalmitin (PPP) with oleic acid (OA), to produce OPO-rich TAGs, was developed, using the immobilized CLL as the biocatalyst. Under optimized conditions (2% water, 20mg/ml enzyme, 1:6 PPP/OA, 50°C, 2h), the content of OPO in the final product reached 46...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28314854/common-nonmutational-notch1-activation-in-chronic-lymphocytic-leukemia
#10
Giulia Fabbri, Antony B Holmes, Mara Viganotti, Claudio Scuoppo, Laura Belver, Daniel Herranz, Xiao-Jie Yan, Yasmine Kieso, Davide Rossi, Gianluca Gaidano, Nicholas Chiorazzi, Adolfo A Ferrando, Riccardo Dalla-Favera
Activating mutations of NOTCH1 (a well-known oncogene in T-cell acute lymphoblastic leukemia) are present in ∼4-13% of chronic lymphocytic leukemia (CLL) cases, where they are associated with disease progression and chemorefractoriness. However, the specific role of NOTCH1 in leukemogenesis remains to be established. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ∼50% of peripheral blood CLL cases lacking gene mutations. We identify a "NOTCH1 gene-expression signature" in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation...
March 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28314441/erratum-to-higher-t-cell-imbalance-and-growth-factor-receptor-expression-in-b-cell-chronic-lymphocytic-leukemia-b-cll-as-compared-to-monoclonal-b-cell-lymphocytosis-of-undetermined-significance-b-mlus-leukemia-res-13-1-1989-31-37
#11
C Garcia, A Rosén, E Kimby, M Aguilar-Santelises, M Jondal, M Björkhilm, G Holm, H Mellstedt
No abstract text is available yet for this article.
March 14, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28306177/frequency-and-functional-characterization-of-exhausted-cd8-t-cells-in-chronic-lymphocytic-leukemia
#12
Saeid Taghiloo, Esmaeil Allahmoradi, Mohsen Tehrani, Hadi Hossein-Nataj, Ramin Shekarriz, Ghasem Janbabaei, Saeid Abediankenari, Hossein Asgarian-Omran
OBJECTIVES: The phenotypic and functional properties of Tim-3+/PD-1+/CD8+ cells as exhausted T-cells were investigated in chronic lymphocytic leukemia (CLL). METHODS: Frequency of CD8+/Tim-3+/PD-1+ exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads isolated CD8+ T-cells were stimulated with PHA and PMA/ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA, respectively. Cytotoxic activity of isolated CD8+ T-cells was determined using CD107a degranulation assay...
March 17, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28303898/circulating-tumour-dna-reflects-treatment-response-and-clonal-evolution-in-chronic-lymphocytic-leukaemia
#13
Paul Yeh, Tane Hunter, Devbarna Sinha, Sarah Ftouni, Elise Wallach, Damian Jiang, Yih-Chih Chan, Stephen Q Wong, Maria Joao Silva, Ravikiran Vedururu, Kenneth Doig, Enid Lam, Gisela Mir Arnau, Timothy Semple, Meaghan Wall, Andjelija Zivanovic, Rishu Agarwal, Pasquale Petrone, Kate Jones, David Westerman, Piers Blombery, John F Seymour, Anthony T Papenfuss, Mark A Dawson, Constantine S Tam, Sarah-Jane Dawson
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28302939/concurrent-with-t-zone-lymphoma-and-high-grade-gastrointestinal-cytotoxic-t-cell-lymphoma-in-a-dog
#14
Akihisa Suwa, Tetsuya Shimoda
A 9-year-old, spayed female Golden Retriever dog was referred to us for lymphocytosis and lymphadenopathy, secondary to suspected chronic lymphocytic leukemia (CLL). The dog had a clinical history of anorexia, vomiting and melena lasting two days. The popliteal lymph node contained small-to-intermediate lymphocytes, which led us to suspect low-grade lymphoma. Thickened lesions in the stomach and small intestine were detected by ultrasonography. Histopathology of the popliteal lymph node and small intestine revealed a simultaneous presence of T-zone lymphoma (TZL) and high-grade gastrointestinal (GI) cytotoxic T-cell lymphoma...
March 12, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28302688/ibrutinib-resistant-cll-unwanted-and-unwonted
#15
Daniel Mertens, Stephan Stilgenbauer
No abstract text is available yet for this article.
March 16, 2017: Blood
https://www.readbyqxmd.com/read/28302090/characterizing-and-prognosticating-chronic-lymphocytic-leukemia-in-the-elderly-prospective-evaluation-on-455-patients-treated-in-the-united-states
#16
Chadi Nabhan, Anthony Mato, Christopher R Flowers, David L Grinblatt, Nicole Lamanna, Mark A Weiss, Matthew S Davids, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Pavel Kiselev, Jeff P Sharman
BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is > 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28302063/epigenetic-and-genetic-alterations-and-their-influence-on-gene-regulation-in-chronic-lymphocytic-leukemia
#17
Di Huang, Ivan Ovcharenko
BACKGROUND: To understand the changes of gene regulation in carcinogenesis, we explored signals of DNA methylation - a stable epigenetic mark of gene regulatory elements - and designed a computational model to profile loss and gain of regulatory elements (REs) during carcinogenesis. We also utilized sequencing data to analyze the allele frequency of single nucleotide polymorphisms (SNPs) and detected the cancer-associated SNPs, i.e., the SNPs displaying the significant allele frequency difference between cancer and normal samples...
March 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28301251/chrysin-as-an-anti-cancer-agent-exerts-selective-toxicity-by-directly-inhibiting-mitochondrial-complex-ii-and-v-in-cll-b-lymphocytes
#18
Ahmad Salimi, Mehryar Habibi Roudkenar, Enayatollah Seydi, Leila Sadeghi, Alireza Mohseni, Nahal Pirahmadi, Jalal Pourahmad
We investigated the effect of chrysin on isolated normal and chronic lymphocytic leukemia (CLL) B-lymphocytes and their isolated mitochondria. We report that a selective and significant increase in cytotoxicity, intracellular reactive oxygen species, mitochondrial membrane potential collapse, ADP/ATP ratio, caspase 3 activation and finally apoptosis in chrysin-treated CLL B- lymphocytes. Also we determined that chrysin selectively inhibits complex II and ATPases in cancerous mitochondria. In this study we proved that the ability of chrysin to promote apoptosis in CLL B-lymphocytes performed by selectively targeting of mitochondria...
March 16, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28299881/the-regulation-of-tumor-suppressive-microrna-mir-126-in%C3%A2-chronic-lymphocytic-leukemia
#19
Daphne Guinn, Amy Lehman, Catherine Fabian, Lianbo Yu, Kami Maddocks, Leslie A Andritsos, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Jennifer A Woyach, John C Byrd, Amy J Johnson
The introduction of miR profiling of chronic lymphocytic leukemia (CLL) patients with different cytogenetic profiles and responses to therapy has allowed incorporation of important miR-mRNA interactions into the understanding of disease biology. In this study, we performed miR expression analysis using NanoString nCounter to discover differentially regulated miRs after therapy with the Bruton tyrosine kinase inhibitor ibrutinib. Of the differentially regulated miRs in the discovery set, miR-29c and miR-126 were confirmed using real-time PCR to be upregulated in CLL patient cells with ibrutinib therapy...
March 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28297623/clinical-implications-of-novel-genomic-discoveries-in-chronic-lymphocytic-leukemia
#20
Gregory Lazarian, Romain Guièze, Catherine J Wu
Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy with a remarkably heterogeneous course, ranging from indolent disease with no need for immediate therapy to rapidly progressive disease associated with therapeutic resistance. The recent US Food and Drug Administration approvals of novel targeted therapies such as inhibitors of B-cell receptor signaling and B-cell lymphoma 2 have opened up new opportunities in the clinical management of patients with CLL and heralded a new era in the clinical treatment of this disease...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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