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https://www.readbyqxmd.com/read/27913513/minimal-residual-disease-in-mantle-cell-lymphoma-insights-into-biology-and-impact-on-treatment
#1
Eva Hoster, Christiane Pott
Despite the recent substantial improvement of clinical outcome in mantle cell lymphoma (MCL), resistance to immunochemotherapy and common relapses are challenges for long-term tumor control. The assessment of minimal residual disease (MRD) by real-time quantitative polymerase chain reaction has emerged as a widely feasible and standardized tool for direct assessment of therapy-induced reduction of tumor burden and regrowth after cytotoxic treatment in MCL, with much improved sensitivity compared with conventional staging procedures...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913493/novel-agents-in-follicular-lymphoma-choosing-the-best-target
#2
Laurie H Sehn
Outcomes in patients with follicular lymphoma (FL) have improved dramatically over the last decade. However, novel agents are greatly needed for those who exhibit treatment resistance, in order to minimize lifelong toxicity and to enable combinations that may allow us to achieve the elusive goal of cure. Biological advances have led to the discovery of a large number of potential therapeutic targets and the development of a plethora of novel agents designed to exploit these processes. Possible targets include tumor cell surface markers, key components of intracellular pathways and epigenetic mechanisms, and reactive cells of the microenvironment...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910030/recurrent-cytogenetic-abnormalities-in-non-hodgkin-s-lymphoma-and-chronic-lymphocytic-leukemia
#3
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/27909217/the-small-foxp1-isoform-predominantly-expressed-in-activated-b-cell-like-diffuse-large-b-cell-lymphoma-and-full-length-foxp1-exert-similar-oncogenic-and-transcriptional-activity-in-human-b-cells
#4
Martine van Keimpema, Leonie J Grüneberg, Esther J M Schilder-Tol, Monique E C M Oud, Esther Beuling, Paul J Hensbergen, Johann de Jong, Steven T Pals, Marcel Spaargaren
The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 (FOXP1-iso), rather than full-length FOXP1 (FOXP1-FL), may possess this oncogenic activity. Corroborating those studies, we here show that activated B cell-like diffuse large B-cell lymphoma cell-lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express FOXP1-iso and that the 5-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukaemia virus- and transposon-mediated insertional mutagenesis screens...
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27899998/expression-level-of-crkl-and-axl-combined-with-exon-19-deletion-in-egfr-and-alk-status-confer-differential-prognosis-of-lung-adenocarcinoma-subtypes
#5
Yi-Ran Cai, Yu-Jie Dong, Hong-Bo Wu, Da-Ping Yu, Li-Juan Zhou, Dan Su, Li Zhang, Xue-Jing Chen
Non-small cell lung cancer (NSCLC) is a lethal cancer-related disease in population. Adenocarcinoma (AC) is subclassified into several subtypes based on the new classification by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society in 2011. Correlation between original expression of Crk-like (CRKL) and anaplastic lymphoma receptor tyrosine kinase in diverse histological components of AC and epidermal growth factor receptor (EGFR) or ALK status was evaluated by immunohistochemistry and sequencing in present study...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899193/genetic-predisposition-to-leukemia-and-other-hematologic-malignancies
#6
REVIEW
Simone Feurstein, Michael W Drazer, Lucy A Godley
In this review, we provide an overview of familial myelodysplastic syndromes (MDS)/acute leukemia (AL) and bone marrow failure syndromes, as well as insights into familial myeloproliferative neoplasms (MPNs), familial multiple myeloma (MM), familial Waldenström macroglobulinemia (WM), familial lymphoma, and cancer predisposition syndromes with increased risk of MDS/AL. This field will continue to accelerate as next-generation sequencing (NGS) techniques identify novel predisposition alleles in families with a genetic predisposition to hematologic malignancies...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27897376/photo-tethers-for-the-multi-cyclic-conformational-caging-of-long-oligonucleotides
#7
Patrick Seyfried, Laura Eiden, Nikolai Grebenovsky, Günter Mayer, Alexander Heckel
Intramolecular circularization of DNA oligonucleotides was accomplished by incorporation of alkyne-modified photolabile nucleosides into DNA sequences, followed by a Cu(I) -catalyzed alkyne-azide cycloaddition with bis-azido linker molecules. We determined a range of ring sizes, in which the caged circular oligonucleotides exhibit superior duplex destabilizing properties. Specific binding of a full-length 90 nt C10 aptamer recognizing human Burkitt's lymphoma cells was then temporarily inhibited by locking the aptamer in a bicircularized structure...
November 29, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27893001/association-of-improved-locoregional-control-with-prolonged-survival-in-early-stage-extranodal-nasal-type-natural-killer-t-cell-lymphoma
#8
Yong Yang, Jian-Zhong Cao, Sheng-Min Lan, Jun-Xin Wu, Tao Wu, Su-Yu Zhu, Li-Ting Qian, Xiao-Rong Hou, Fu-Quan Zhang, Yu-Jing Zhang, Yuan Zhu, Li-Ming Xu, Zhi-Yong Yuan, Shu-Nan Qi, Ye-Xiong Li
Importance: The long-term survival benefit for radiotherapy (RT) in early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is not known, and it is unclear whether improved locoregional control (LRC) translates into a survival benefit. Objective: To investigate the dose-dependent effect and potential survival benefits of RT on the basis of LRC improvements. Design, Setting, and Participants: Review of clinical data of patients with early-stage NKTCL at 10 institutions in China between 2000 and 2014...
November 17, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27891503/tp53-gene-status-affects-survival-in-advanced-mycosis-fungoides
#9
Gitte Wooler, Linea Melchior, Elisabeth Ralfkiaer, Lise Mette Rahbek Gjerdrum, Robert Gniadecki
TP53 is frequently mutated in different types of neoplasms including leukemia and lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF), the most common type of cutaneous lymphoma. However, little is known about the frequency, spectrum of mutations, and their prognostic significance in MF. In this study, we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harbored mutations in TP53...
2016: Frontiers in Medicine
https://www.readbyqxmd.com/read/27889782/molecular-pathology-a-requirement-for-precision-medicine-in-cancer
#10
Manfred Dietel
The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27889452/an-rb-ezh2-complex-mediates-silencing-of-repetitive-dna-sequences
#11
Charles A Ishak, Aren E Marshall, Daniel T Passos, Carlee R White, Seung J Kim, Matthew J Cecchini, Sara Ferwati, William A MacDonald, Christopher J Howlett, Ian D Welch, Seth M Rubin, Mellissa R W Mann, Frederick A Dick
Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments...
November 12, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27888620/identification-of-different-alk-mutations-in-a-pair-of-neuroblastoma-cell-lines-established-at-diagnosis-and-relapse
#12
Lindi Chen, Angharad Humphreys, Lisa Turnbull, Angela Bellini, Gudrun Schleiermacher, Helen Salwen, Susan L Cohn, Nick Bown, Deborah A Tweddle
Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor kinase that belongs to the insulin receptor superfamily and has previously been shown to play a role in cell proliferation, migration and invasion in neuroblastoma. Activating ALK mutations are reported in both hereditary and sporadic neuroblastoma tumours, and several ALK inhibitors are currently under clinical evaluation as novel treatments for neuroblastoma. Overall, mutations at codons F1174, R1275 and F1245 together account for ~85% of reported ALK mutations in neuroblastoma...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27882350/plasma-vesicle-mirnas-for-therapy-response-monitoring-in-hodgkin-lymphoma-patients
#13
Monique A J van Eijndhoven, Josée M Zijlstra, Nils J Groenewegen, Esther E E Drees, Stuart van Niele, S Rubina Baglio, Danijela Koppers-Lalic, Hans van der Voorn, Sten F W M Libregts, Marca H M Wauben, Renee X de Menezes, Jan R T van Weering, Rienk Nieuwland, Lydia Visser, Anke van den Berg, Daphne de Jong, D Michiel Pegtel
BACKGROUND. Cell-free circulating nucleic acids, including 22-nt microRNAs (miRNAs), represent noninvasive biomarkers for treatment response monitoring of cancer patients. While the majority of plasma miRNA is bound to proteins, a smaller, less well-characterized pool is associated with extracellular vesicles (EVs). Here, we addressed whether EV-associated miRNAs reflect metabolic disease in classical Hodgkin lymphoma (cHL) patients. METHODS. With standardized size-exclusion chromatography (SEC), we isolated EV-associated extracellular RNA (exRNA) fractions and protein-bound miRNA from plasma of cHL patients and healthy subjects...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27879258/nucleophosmin-anaplastic-lymphoma-kinase-npm-alk-the-ultimate-oncogene-and-therapeutic-target
#14
Michael T Werner, Chen Zhao, Qian Zhang, Mariusz A Wasik
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase physiologically expressed by fetal neural cells. However, aberrantly expressed ALK is involved in the pathogenesis of diverse malignancies including distinct types of lymphoma, lung carcinoma, and neuroblastoma. The aberrant ALK expression in non-neural cells results from chromosomal translocations that create novel fusion proteins. These protein hybrids are comprised of the proximal part of a partner gene including its promoter region and the distal part of ALK including coding sequence for the entire kinase domain...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27865624/w-alk-into-the-next-stage
#15
REVIEW
Gouji Toyokawa, Takashi Seto, Mitsuhiro Takenoyama, Yukito Ichinose
In 2007, the rearrangement of anaplastic lymphoma kinase (ALK) was identified to be associated with the pathogenesis of a subset of patients with non-small-cell lung cancer (NSCLC). Surprisingly, approximately 4 years after the discovery of ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi), crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and Drug Administration. Subsequently, next-generation ALKis, such as alectinib and ceritinib, have been developed, and some of them have been applied in the clinical setting...
October 26, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27859472/effect-of-ketoconazole-a-strong-cyp3a-inhibitor-on-the-pharmacokinetics-of-venetoclax-a-bcl-2-inhibitor-in-patients-with-non-hodgkin-lymphoma
#16
Suresh K Agarwal, Ahmed Hamed Salem, Alexey V Danilov, Beibei Hu, Soham Puvvada, Martin Gutierrez, David Chien, Lionel D Lewis, Shekman L Wong
AIM: To examine the effect of a strong CYP3A inhibitor, ketoconazole, on the pharmacokinetics, safety, and tolerability of venetoclax. METHODS: Twelve patients with Non-Hodgkin lymphoma (NHL) were enrolled in this Phase 1, open-label, fixed-sequence study. Patients received a single 50 mg dose of venetoclax orally on Day 1 and Day 8, and a 400 mg once daily dose of ketoconazole on Days 5 through 11. Blood samples were collected predose and up to 96 hours after each venetoclax dose on Day 1 and Day 8...
November 2, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27856253/discovery-of-high-affinity-bcl6-binding-peptide-and-its-structure-activity-relationship
#17
Kotaro Sakamoto, Satoshi Sogabe, Yusuke Kamada, Nozomu Sakai, Kouhei Asano, Mie Yoshimatsu, Kou Ida, Yasuhiro Imaeda, Jun-Ichi Sakamoto
B cell lymphoma 6 (BCL6) is a transcriptional repressor that interacts with its corepressors BcoR and SMRT. Since this protein-protein interaction (PPI) induces activation and differentiation of B lymphocytes, BCL6 has been an attractive drug target for potential autoimmune disease treatments. Here we report a novel BCL6 inhibitory peptide, F1324 (Ac-LWYTDIRMSWRVP-OH), which we discovered using phage display technology; we also discuss this peptide's structure-activity relationship (SAR). For BCL6(5-129) binding, KD and IC50 values of F1324 were 0...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27854034/efficient-preparation-of-s-n-boc-3-hydroxylpiperidine-through-bioreduction-by-a-thermostable-aldo-ketoreductase
#18
Mengyan He, Shuo Zhou, Maolin Cui, Xiaolu Jin, Dunyue Lai, Shuangling Zhang, Zhiguo Wang, Zhenming Chen
(S)-N-Boc-3-hydroxypiperidine ((S)-NBHP) is a key pharmaceutical intermediate and the chiral source in synthesizing Imbruvica, which is a newly approved drug in lymphoma therapy by targeting Bruton's tyrosine kinase (BTK). Current chemical synthesis of (S)-NBHP suffered from the need of noble metal catalyst and low yield. The single reported bioconversion of (S)-NBHP was achieved by using recombinant ketoreductase, but enzyme sequence was kept confidential and the catalytic process suffered from the thermodeactivation and substrate inhibition...
November 16, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27835906/whole-exome-and-transcriptome-sequencing-of-refractory-diffuse-large-b-cell-lymphoma
#19
Ha Young Park, Seung-Bok Lee, Hae-Yong Yoo, Seok-Jin Kim, Won-Seog Kim, Jong-Il Kim, Young-Hyeh Ko
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refractory DLBCL, we conducted whole-exome sequencing and transcriptome sequencing for six patients with refractory and seven with responsive DLBCL. The average numbers of pathogenic somatic single nucleotide variants and indels in coding regions were 71 in refractory patients (range 28-120) and 38 (range 19-66) in responsive patients...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833662/differences-in-amino-acid-frequency-in-caga-and-vaca-sequences-of-helicobacter-pylori-distinguish-gastric-cancer-from-gastric-malt-lymphoma
#20
Masahiko Hashinaga, Rumiko Suzuki, Junko Akada, Takashi Matsumoto, Yasutoshi Kido, Tadayoshi Okimoto, Masaaki Kodama, Kazunari Murakami, Yoshio Yamaoka
BACKGROUND: Helicobacter pylori is a pathogenic bacterium that causes various gastrointestinal diseases. The most common gastric malignancies associated with H. pylori are gastric cancer and lymphoma of mucosa associated lymphoid tissue (MALT). Helicobacter pylori virulence genes, namely cagA and vacA, are known to be associated with malignancy development. Conventionally, cagA and vacA were classified by looking at partial sequences of the genes. However, such genotyping has hardly proven useful predicting different risks for gastric cancer or MALT lymphoma...
2016: Gut Pathogens
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