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https://www.readbyqxmd.com/read/29239031/molecular-alterations-of-neuroendocrine-tumours-of-the-lung
#1
REVIEW
Giulio Rossi, Luca Bertero, Caterina Marchiò, Mauro Papotti
Neuroendocrine tumours of the lung comprise low [typical carcinoid (TC)], intermediate [atypical carcinoid (AC)] and high-grade [small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC)] malignancies, while a pre-invasive lesion [diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)] may generate a subset of peripheral carcinoid tumours. These neoplasms are differentiated conventionally based on mitotic rate, presence of necrosis and cytological details, according to the 2015 World Health Organisation (WHO) classification...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29222670/venetoclax-for-treating-chronic-lymphocytic-leukaemia-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#2
REVIEW
Hema Mistry, Chidozie Nduka, Martin Connock, Jill Colquitt, Theodoros Mantopoulos, Emma Loveman, Renata Walewska, James Mason
Venetoclax is licensed to treat relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL). As part of the Single Technology Appraisal (STA) ID944, the National Institute for Health and Care Excellence (NICE) invited AbbVie, the manufacturer, to submit evidence on the use of venetoclax, within its licensed indication. The Evidence Review Group (ERG), Warwick Evidence, was asked to provide an independent and critical review of the submitted evidence. Evidence came from three single-arm trials in CLL patients with or without 17p deletion [del(17p])/TP53 chromosomal abnormalities...
December 8, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/29222278/safety-profiles-of-novel-agent-therapies-in-cll
#3
REVIEW
Inhye E Ahn, Matthew S Davids
A 70-year-old man with relapsed/refractory chronic lymphocytic leukemia has multiple comorbidities including atrial fibrillation (on warfarin for anticoagulation), irritable bowel syndrome, and chronic renal insufficiency. Two years ago, he received bendamustine and rituximab as first-line therapy for chronic lymphocytic leukemia and achieved partial response, but now has relapsed. Fluorescence in situ hybridization cytogenetics reveals deletion 17p. Which novel agent would you recommend for this patient?
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29217907/synchronous-breast-cancer-and-gallbladder-diseases-a-chromosomal-analysis-a-pilot-study-at-a-tertiary-care-centre
#4
Devendra Chaudhary, Rahul Ahluwalia, Arvind Rai
Out of a total of 50 study-eligible patients, 15 patients were found to have synchronous breast cancer and gallbladder diseases. Fourteen such patients had breast cancer and cholelithiasis while 1 patient had breast cancer with gallbladder cancer. Amongst these 15 patients, 7 patients tested positive for chromosomal aberrations on karyotyping. Aberrations in these patients were seen on chromosomes 13 and 17 with 2 patients having deletion 13q, 2 having deletion 17q, and 2 having deletions on 17p while one patient had multiple deletions on chromosomes 13q and 17p...
December 2017: Indian Journal of Surgery
https://www.readbyqxmd.com/read/29209431/combining-cytogenetic-and-epigenetic-approaches-in-chronic-lymphocytic-leukemia-improves-prognosis-prediction-for-patients-with-isolated-13q-deletion
#5
Cristina Bagacean, Christelle Le Dantec, Christian Berthou, Adrian Tempescul, Hussam Saad, Anne Bordron, Mihnea Zdrenghea, Victor Cristea, Nathalie Douet-Guilbert, Yves Renaudineau
Background: Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods: CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints])...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29209123/prediction-of-early-stage-hepatocellular-carcinoma-using-oncoscan-chromosomal-copy-number-aberration-data
#6
Ming-Chin Yu, Chao-Wei Lee, Yun-Shien Lee, Jang-Hau Lian, Chia-Lung Tsai, Yi-Ping Liu, Chun-Hsing Wu, Chi-Neu Tsai
AIM: To identify chromosomal copy number aberrations (CNAs) in early-stage hepatocellular carcinoma (HCC) and analyze whether they are correlated with patient prognosis. METHODS: One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded (FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosin-stained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix OncoScan platform to assess CNAs and loss of heterozygosity (LOH)...
November 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29194741/-double-hit-chronic-lymphocytic-leukemia-an-aggressive-subgroup-with-17p-deletion-and-8q24-gain
#7
Elise Chapiro, Claude Lesty, Clémentine Gabillaud, Eric Durot, Simon Bouzy, Marine Armand, Magali Le Garff-Tavernier, Nadia Bougacha, Stéphanie Struski, Audrey Bidet, Elodie Laharanne, Carole Barin, Lauren Veronese, Nolwen Prié, Virginie Eclache, Baptiste Gaillard, Lucienne Michaux, Christine Lefebvre, Jean-Baptiste Gaillard, Christine Terré, Dominique Penther, Christian Bastard, Nathalie Nadal, Sandra Fert-Ferrer, Nathalie Auger, Catherine Godon, Laurent Sutton, Olivier Tournilhac, Santos A Susin, Florence Nguyen-Khac
Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL...
December 1, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29152232/recent-therapeutic-advances-in-chronic-lymphocytic-leukemia
#8
REVIEW
Prithviraj Bose, Varsha Gandhi
The last several years have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL). The course of this very heterogeneous disease, traditionally treated with chemotherapeutic agents usually in combination with rituximab, typically has been characterized by remissions and relapses, and survival times vary greatly, depending on intrinsic biological attributes of the leukemia. The developments of the last few years have been transformative, ushering in an era of novel, molecularly targeted therapies, made possible by extensive efforts to elucidate the biology of the disease that predated the new targeted drugs...
2017: F1000Research
https://www.readbyqxmd.com/read/29151530/successful-autologous-hematopoietic-stem-cell-transplantation-followed-by-bortezomib-maintenance-in-a-patient-with-relapsed-cd138-low-multiple-solitary-plasmacytomas-harboring-a-17p-deletion
#9
Hiroaki Kitamura, Yasushi Kubota, Kyosuke Yamaguchi, Kazuharu Kamachi, Atsujiro Nishioka, Masako Yokoo, Takero Shindo, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Solitary plasmacytoma of bone (SBP) tends to progress to multiple myeloma (MM); however, progression to multiple solitary plasmacytomas (MSP) is rare. We report a case of CD138-low MSP with 17p deletion in a patient with relapsed SBP. 17p deletion is associated with a poor outcome in patients with MM, and the low expression of CD138 in myeloma cells is associated with drug resistance and a poor prognosis. The patient was successfully treated with bortezomib plus dexamethasone induction therapy and autologous hematopoietic stem cell transplantation followed by bortezomib maintenance therapy...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29061914/therapeutics-targeting-bcl-2-in-hematological-malignancies
#10
REVIEW
Astrid Ruefli-Brasse, John C Reed
Members of the B-cell lymphoma 2 (BCL-2) gene family are attractive targets for cancer therapy as they play a key role in promoting cell survival, a long-since established hallmark of cancer. Clinical utility for selective inhibition of specific anti-apoptotic Bcl-2 family proteins has recently been realized with the Food and Drug Administration (FDA) approval of venetoclax (formerly ABT-199/GDC-0199) in relapsed chronic lymphocytic leukemia (CLL) with 17p deletion. Despite the impressive monotherapy activity in CLL, such responses have rarely been observed in other B-cell malignancies, and preclinical data suggest that combination therapies will be needed in other indications...
October 23, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29032274/assessment-of-impact-of-hla-type-on-outcomes-of-allogeneic-hematopoietic-stem-cell-transplantation-for-chronic-lymphocytic-leukemia
#11
Brian T Hill, Kwang Woo Ahn, Zhen-Huan Hu, Mahmoud Aljurf, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Mohamed A Kharfan-Dabaja, Siddhartha Ganguly, Nilanjan Ghosh, Michael R Grunwald, Yoshihiro Inamoto, Tamila Kindwall-Keller, Taiga Nishihori, Richard F Olsson, Ayman Saad, Matthew Seftel, Sachiko Seo, Jeffrey Szer, Martin Tallman, Celalettin Ustun, Peter H Wiernik, Richard T Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the sole known curative treatment for CLL...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29024486/development-of-locus-specific-sub-clone-separation-by-fluorescence-in-situ-hybridization-in-suspension-in-chronic-lymphocytic-leukemia
#12
Cuc H Do, Sheree Bailey, Cindy Macardle, Lauren A Thurgood, Karen M Lower, Bryone J Kuss
Intra-tumor genetic heterogeneity is a hallmark of cancer. The ability to monitor and analyze these sub-clonal cell populations can be considered key to successful treatment, particularly in the modern era of targeted therapies. Although advances in sequencing technologies have significantly improved our ability to analyze the mutational landscape of tumors, this utility is reduced when considering small, but clinically significant sub-clones, that is, those representing <10% of the tumor burden. We have developed a high-throughput method that utilizes a 17-probe labeled bacterial artificial chromosome contig to quantify sub-clonal populations of cells based on deletion of a single locus...
November 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28993409/malt1-inhibition-is-efficacious-in-both-na%C3%A3-ve-and-ibrutinib-resistant-chronic-lymphocytic-leukemia
#13
Nakhle S Saba, Deanna H Wong, Georges Tanios, Jessica R Iyer, Patricia Lobelle-Rich, Eman L Dadashian, Delong Liu, Lorena Fontan, Erik K Flemington, Cydney M Nichols, Chingiz Underbayev, Hana Safah, Ari Melnick, Adrian Wiestner, Sarah E M Herman
The clinical efficacy displayed by ibrutinib in chronic lymphocytic leukemia (CLL) has been challenged by the frequent emergence of resistant clones. The ibrutinib target, Bruton's tyrosine kinase (BTK), is essential for B cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK. Recent findings show that MI-2, a small molecule inhibitor of the para-caspase MALT1, is effective in preclinical models of another type of BCR pathway-dependent lymphoma...
October 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28972395/venetoclax-for-the-treatment-of-chronic-lymphocytic-leukemia
#14
REVIEW
Massimo Gentile, Annamaria Petrungaro, Giuseppina Uccello, Ernesto Vigna, Anna Grazia Recchia, Nadia Caruso, Sabrina Bossio, Laura De Stefano, Angela Palummo, Francesca Storino, Massimo Martino, Fortunato Morabito
Venetoclax, an orally bioavailable inhibitor of BCL-2, was approved in 2016 by the United States Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL) patients with 17p deletion [del(17p)], who have received at least one prior therapy. Areas covered: We focus on the mechanism of action of venetoclax and on the clinical trial data that led to the approval of venetoclax for CLL patients. We also review the studies in which this drug has being explored in combination with other anti-CLL drugs...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28938632/the-%C3%AE-secretase-inhibitors-enhance-the-anti-leukemic-activity-of-ibrutinib-in-b-cll-cells
#15
Paola Secchiero, Rebecca Voltan, Erika Rimondi, Elisabetta Melloni, Emmanouil Athanasakis, Veronica Tisato, Stefania Gallo, Gian Matteo Rigolin, Giorgio Zauli
Ibrutinib blocks B-cell receptor signaling and interferes with leukemic cell-to-microenvironment interactions. Ibrutinib plays a key role in the management of B-CLL and is recommended for first line treatment of high-risk CLL patients with 17p deletion. Therefore, elucidating the factors governing sensitivity/resistance to Ibrutinib represents a relevant issue. For this purpose, in 3 B-CLL patient samples harboring functional TP53 mutations, the frequency of the mutated clones was monitored during in vivo Ibrutinib therapy, revealing a progressive decline of the frequency of TP53(mut) clones during 12 months of treatment...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905994/microrna-324-5p-regulates-stemness-pathogenesis-and-sensitivity-to-bortezomib-in-multiple-myeloma-cells-by-targeting-hedgehog-signaling
#16
Bo Tang, Aoshuang Xu, Jian Xu, Haifan Huang, Lei Chen, Yan Su, Lannan Zhang, Junying Li, Fengjuan Fan, Jun Deng, Liang Tang, Chunyan Sun, Yu Hu
Chromosome 17p deletions are present in 10% of patients with newly diagnosed multiple myeloma (MM), and are associated with inferior prognosis. miR-324-5p is located on chromosome 17p, and shows diverse functions in different types of cancers. However, its role in MM is largely unknown. Here we found the expression of miR-324-5p was decreased in MM, especially in del(17p) MM. In contrast, the expression of hedgehog (Hh) signaling components was elevated, indicating a correlation between miR-324-5p and Hh signaling in MM...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28819574/sequential-kinase-inhibition-idelalisib-ibrutinib-induces-clinical-remission-in-b-cell-prolymphocytic-leukemia-harboring-a-17p-deletion
#17
H Coelho, M Badior, T Melo
B-cell prolymphocytic leukemia (B-PLL) is a rare lymphoid neoplasm with an aggressive clinical course. Treatment strategies for B-PLL remain to be established, and, until recently, alemtuzumab was the only effective therapeutic option in patients harboring 17p deletions. Herein, we describe, for the first time, a case of B-cell prolymphocytic leukemia harboring a 17p deletion in a 48-year-old man that was successfully treated sequentially with idelalisib-rituximab/ibrutinib followed by allogeneic hematopoietic stem cell transplant (allo-HSCT)...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28790111/amiloride-an-old-diuretic-drug-is-a-potential-therapeutic-agent-for-multiple-myeloma
#18
Elizabeta A Rojas, Luis Antonio Corchete, Laura San-Segundo, Juan F Martínez-Blanch, Francisco M Codoñer, Teresa Paíno, Noemí Puig, Ramón García-Sanz, María Victoria Mateos, Enrique M Ocio, Irena Misiewicz-Krzeminska, Norma C Gutiérrez
Purpose: The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent antimyeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.Experimental Design: Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq experiments, qRT-PCR, immunoblotting, and immunofluorescence assays...
November 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28782884/chronic-lymphocytic-leukemia-2017-update-on-diagnosis-risk-stratification-and-treatment
#19
REVIEW
Michael Hallek
DISEASE OVERVIEW: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells. DIAGNOSIS: The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen and B-cell markers...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28780145/what-is-the-role-of-chemotherapy-in-patients-with-chronic-lymphocytic-leukemia
#20
REVIEW
Bruce D Cheson
The current standard treatment for patients with chronic lymphocytic leukemia who require therapy is chemoimmunotherapy. However, the availability of an increasing number of targeted agents and combination warrants a reassessment of that approach. The high rate of durable responses with ibrutinib in relapsed refractory patients has established its role in this setting; however, because of its impressive efficacy as initial treatment, it should be considered as part of the algorithm in appropriate patients. There is virtually no role for chemotherapy in the relapsed or refractory setting, but, instead, consideration of active agents including idelalisib plus rituximab, or, particularly venetoclax...
November 2017: Clinical Lymphoma, Myeloma & Leukemia
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