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Richter's transformation

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https://www.readbyqxmd.com/read/28203174/richter-s-syndrome-with-hypercalcemia-induced-by-tumor-associated-production-of-parathyroid-hormone-related-peptide
#1
Naoki Watanabe, Hajime Yasuda, Soji Morishita, Yasuo Aota, Junichi Tomomatsu, Masaru Tanaka, Akimichi Ohsaka, Norio Komatsu
Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter's syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter's syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28191372/richter-transformation-of-chronic-lymphocytic-leukemia-a-review-of-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-and-molecular-diagnostics
#2
REVIEW
Faiq Shaikh, Amna Janjua, Frederick Van Gestel, Adeel Ahmad
Chronic lymphocytic leukemia (CLL) is a low-grade B-cell proliferative disease with a generally indolent course. In a few cases, it undergoes transformation and becomes a more aggressive malignancy, such as diffuse large B-cell lymphoma (DLBCL). This process, which is called Richter transformation (RT), is often detected too late and is associated with a poor prognosis. There are multiple molecular diagnostic approaches to detect RT in preexisting CLL. Metabolic imaging using 18-fluorine fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) can be a very useful tool for early detection of RT and which can hence allow for timely intervention, thereby improving the patient's chances of survival...
January 9, 2017: Curēus
https://www.readbyqxmd.com/read/28171709/long-term-outcomes-for-patients-with-chronic-lymphocytic-leukemia-who-discontinue-ibrutinib
#3
Preetesh Jain, Philip A Thompson, Michael Keating, Zeev Estrov, Alessandra Ferrajoli, Nitin Jain, Hagop Kantarjian, Jan A Burger, Susan O'Brien, William G Wierda
BACKGROUND: Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported. METHODS: Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed...
February 7, 2017: Cancer
https://www.readbyqxmd.com/read/28095146/phase-i-first-in-human-study-of-venetoclax-in-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma
#4
Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A Humerickhouse, Gary B Gordon, John F Gerecitano
Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts...
January 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28067096/differential-response-of-normal-and-transformed-mammary-epithelial-cells-to-combined-treatment-of-anti-mir-21-and-radiation
#5
Vanja Radulovic, Theresa Heider, Sabine Richter, Simone Moertl, Michael J Atkinson, Nataša Anastasov
PURPOSE: MicroRNA miR-21 has emerged as a therapeutic target in the treatment of breast cancer. This study was designed to compare the responses of breast cancer cells and non-transformed breast epithelial cells to a combined regimen of miR-21 inhibition and radiation. MATERIALS AND METHODS: The MDA-MB-361 (breast cancer) and MCF-10A (non-transformed mammary epithelial) cell lines were used for the comparison in this in vitro study. The stable knockdown of miR-21 was performed by using lentiviral approach...
January 9, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27905140/herpes-simplex-infection-simulating-richter-transformation-a-series-of-four-cases-and-review-of-the-literature
#6
Alireza Salem, Sanam Loghavi, Joseph D Khoury, Rose Lou Marie C Agbay, Jeffrey L Jorgensen, Jeffrey L Medeiros
AIMS: Richter transformation (RT) occurs in 5-10% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and is associated with a poor outcome. Histologic manifestations of RT are variable and include an increase in the proportion of large cells including prolymphocytes, immunoblasts and other pleomorphic cells along with an increased proliferation rate and often necrosis. Rarely, superimposed Herpes simplex virus (HSV) infection involving lymph nodes in patients with CLL/SLL may mimic RT clinically and histologically...
December 1, 2016: Histopathology
https://www.readbyqxmd.com/read/27899414/sentinel-case-of-richter-transformation-from-chronic-lymphocytic-leukaemia-small-lymphocytic-lymphoma-to-cd3-diffuse-large-b-cell-lymphoma
#7
Ali Ismail, Jawed A Mallick, Dahui Qin, Mohammad O Hussaini
AIM: To report the first case of a Richter syndrome where small lymphocytic lymphoma (SLL) progressed to a CD3+ diffuse large B-cell lymphoma (DLBCL). METHODS: Macrodissection of small and large cell lymphomatous components was performed. This was followed by flow cytometric analysis along with molecular B-cell immunoglobulin (heavy and light chains) and T-cell receptor (γ and β chains) gene rearrangement studies to investigate a clonal relationship between the components...
November 29, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27848974/differential-expression-of-tgf-%C3%AE-superfamily-members-and-role-of-smad1-5-9-signalling-in-chondral-versus-endochondral-chondrocyte-differentiation
#8
Verena Dexheimer, Jessica Gabler, Katharina Bomans, Tanja Sims, Georg Omlor, Wiltrud Richter
Proteins of the transforming-growth-factor-β (TGF-β)-superfamily have a remarkable ability to induce cartilage and bone and the crosstalk of TGF-β - and BMP-signalling pathways appears crucial during chondrocyte development. Aim was to assess the regulation of TGF-β-superfamily members and of Smad2/3- and Smad1/5/9-signalling during endochondral in vitro chondrogenesis of mesenchymal stromal cells (MSC) relative to chondral redifferentiation of articular chondrocytes (AC) to adjust chondrocyte development of MSC towards a less hypertrophic phenotype...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27752455/results-of-extended-plant-tests-using-more-realistic-exposure-scenarios-for-improving-environmental-risk-assessment-of-veterinary-pharmaceuticals
#9
Elisabeth Richter, Silvia Berkner, Ina Ebert, Bernhard Förster, Nadin Graf, Monika Herrchen, Ute Kühnen, Jörg Römbke, Markus Simon
BACKGROUND: Residues of veterinary medicinal products (VMPs) enter the environment via application of manure onto agricultural areas where in particular antibiotics can cause phytotoxicity. Terrestrial plant tests according to OECD guideline 208 are part of the environmental risk assessment of VMPs. However, this standard approach might not be appropriate for VMPs which form non-extractable residues or transformation products in manure and manure-amended soil. Therefore, a new test design with a more realistic exposure scenario via manure application is needed...
2016: Environmental Sciences Europe
https://www.readbyqxmd.com/read/27742070/richter-s-syndrome-novel-and-promising-therapeutic-alternatives
#10
Davide Rossi
Richter's syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate for RS is ∼0.5% per year of observation. In the presence of clinical suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of (18)FDG PET/CT. Molecular lesions of tumor suppression regulators (TP53), cell cycle (CDKN2A) and cell proliferation (NOTCH1, MYC) overall account for ∼90% of RS and may be responsible for its aggressive clinical phenotype...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27735950/increased-survival-and-cell-cycle-progression-pathways-are-required-for-ews-fli1-induced-malignant-transformation
#11
Tahereh Javaheri, Zahra Kazemi, Jan Pencik, Ha Tt Pham, Maximilian Kauer, Rahil Noorizadeh, Barbara Sax, Harini Nivarthi, Michaela Schlederer, Barbara Maurer, Maximillian Hofbauer, Dave Nt Aryee, Marc Wiedner, Eleni M Tomazou, Malcolm Logan, Christine Hartmann, Jan P Tuckermann, Lukas Kenner, Mario Mikula, Helmut Dolznig, Aykut Üren, Günther H Richter, Florian Grebien, Heinrich Kovar, Richard Moriggl
Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mesenchymal Prx1-directed conditional EF expression in mice to study bone development and to establish a reliable sarcoma model. EF expression arrested early chondrocyte and osteoblast differentiation due to changed signaling pathways such as hedgehog, WNT or growth factor signaling...
October 13, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27707629/richter-s-transformation-in-the-era-of-kinase-inhibitor-therapy-a-review
#12
REVIEW
Emily C Ayers, Anthony R Mato
Richter's transformation (RT) is the transformation of chronic lymphocytic leukemia (CLL) into rapidly progressive B-cell lymphoma. This disease has long been recognized as a difficult-to-treat illness with poor survival outcomes. Although the incidence of RT has been well documented in previous studies, less is understood in the era of novel therapeutics, such as kinase inhibitors (KIs). The present review discusses the current risk factors, incidence, and outcomes of patients with RT in the modern era of KI therapy...
September 8, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27688087/b-lymphoblastic-leukemia-in-a-patient-with-chronic-lymphocytic-leukemia-sequential-development-of-biclonal-b-cell-neoplasms-over-a-23-year-period-in-a-single-individual
#13
Bin Wu, Kimberly Ingersoll, Catherine Rehder, Endi Wang
Chronic lymphocytic leukemia (CLL) is an indolent mature B-cell neoplasm. During a prolonged disease course, a secondary B-cell neoplasm may arise in some patients, the most common example being the clonal evolution of CLL to diffuse large B-cell lymphoma, which is referred to as Richter transformation. Secondary de novo mature B-cell neoplasms arising in a patient with pre-existing CLL have been described; however, B-lymphoblastic leukemia (B-ALL) developing in untreated CLL is rare, and its clonal relationship to the primary neoplasm has been an interesting issue...
November 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27677095/pet-positive-lymphadenopathy-in-cll-not-always-richter-transformation
#14
Naveen Pemmaraju, Preetesh Jain, L Jeffrey Medeiros, Jeffrey L Jorgenson, Nitin Jain, Jason Willis, Dimitrios P Kontoyiannis, Zeev Estrov, William Wierda
No abstract text is available yet for this article.
September 27, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27660167/clinical-practice-recommendations-for-use-of-allogeneic-hematopoietic-cell-transplantation-in-chronic-lymphocytic-leukemia-on-behalf-of-the-guidelines-committee-of-the-american-society-for-blood-and-marrow-transplantation
#15
REVIEW
Mohamed A Kharfan-Dabaja, Ambuj Kumar, Mehdi Hamadani, Stephan Stilgenbauer, Paolo Ghia, Claudio Anasetti, Peter Dreger, Emili Montserrat, Miguel-Angel Perales, Edwin P Alyea, Farrukh T Awan, Ernesto Ayala, Jacqueline C Barrientos, Jennifer R Brown, Januario E Castro, Richard R Furman, John Gribben, Brian T Hill, Mohamad Mohty, Carol Moreno, Susan O'Brien, Steven Z Pavletic, Javier Pinilla-Ibarz, Nishitha M Reddy, Mohamed Sorror, Christopher Bredeson, Paul Carpenter, Bipin N Savani
We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations...
December 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27646954/nitric-oxide-coupling-to-generate-n2o-promoted-by-a-single-heme-system-as-examined-by-density-functional-theory
#16
Jun Yi, Adam L O Campbell, George B Richter-Addo
Bacteria utilize a heme/non-heme enzyme system to detoxify nitric oxide (NO) to N2O. In order to probe the capacity of a single-heme system to mediate this NO-to-N2O transformation, various scenarios for addition of electrons, protons, and a second NO molecule to a heme nitrosyl to generate N2O were explored by density functional theory calculations. We describe, utilizing this single-heme system, several stepwise intermediates along pathways that enable the critical N-N bond formation step yielding the desired Fe-N2O product...
November 30, 2016: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/27631596/the-prognostic-value-of-glut-1-staining-in-the-detection-of-malignant-transformation-in-oral-mucosa
#17
Roman C Brands, Olga Köhler, Stephan Rauthe, Stefan Hartmann, Harald Ebhardt, Axel Seher, Christian Linz, Alexander C Kübler, Urs D A Müller-Richter
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most common tumor entity worldwide. Unfortunately, the multimodal treatment consisting of surgery, radiation, and chemotherapy does not show the desired efficacy. The intent of this study was to evaluate the sensitivity and specificity of an oral brush biopsy in combination with glucose transporter (GLUT)-1 staining in identifying premalignant and malignant lesions. METHODS: A total of 72 patients were included in the study, divided into four diagnostic subgroups (24 healthy, 15 carcinoma, 18 leukoplakia, 15 oral lichen planus)...
September 8, 2016: Clinical Oral Investigations
https://www.readbyqxmd.com/read/27626698/identification-of-a-structurally-novel-btk-mutation-that-drives-ibrutinib-resistance-in-cll
#18
Shruti Sharma, Natalie Galanina, Ailin Guo, Jimmy Lee, Sabah Kadri, Charles Van Slambrouck, Bradley Long, Weige Wang, Mei Ming, Larissa V Furtado, Jeremy P Segal, Wendy Stock, Girish Venkataraman, Wei-Jen Tang, Pin Lu, Yue Lynn Wang
Ibrutinib (ibr), a first-in-class Bruton tyrosine kinase (BTK) inhibitor, has demonstrated high response rates in both relapsed/refractory and treatment naïve chronic lymphocytic leukemia (CLL). However, about 25% of patients discontinue ibrutinib therapy at a median follow-up of 20 months and many patients discontinue the treatment due to leukemia progression or Richter transformation. Mutations affecting the C481 residue of BTK disrupt ibrutinib binding and have been characterized by us and others as the most common mechanism of ibrutinib resistance...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27601462/outcomes-of-cll-patients-treated-with-sequential-kinase-inhibitor-therapy-a-real-world-experience
#19
Anthony R Mato, Chadi Nabhan, Paul M Barr, Chaitra S Ujjani, Brian T Hill, Nicole Lamanna, Alan P Skarbnik, Christina Howlett, Jeffrey J Pu, Alison R Sehgal, Lauren E Strelec, Alexandra Vandegrift, Danielle M Fitzpatrick, Clive S Zent, Tatyana Feldman, Andre Goy, David F Claxton, Spencer Henick Bachow, Gurbakhash Kaur, Jakub Svoboda, Sunita Dwivedy Nasta, David Porter, Daniel J Landsburg, Stephen J Schuster, Bruce D Cheson, Pavel Kiselev, Andrew M Evens
B-cell receptor kinase inhibitor (KI) therapy represents a paradigm shift in chronic lymphocytic leukemia (CLL) management, but data on practice patterns after KI discontinuation and optimal sequencing are limited. We conducted a multicenter, retrospective, comprehensive analysis on 178 patients with CLL (ibrutinib = 143; idelalisib = 35) who discontinued KI therapy. We examined responses, toxicity, post-KI therapies, and overall survival (OS). Patients had a median of 3 prior therapies (range 0-11); del17p (34%), p53 mutation (27%), del11q (33%), and complex karyotype (29%)...
November 3, 2016: Blood
https://www.readbyqxmd.com/read/27495156/impact-of-disease-activity-and-treatment-of-comorbidities-on-the-risk-of-myocardial-infarction-in-rheumatoid-arthritis
#20
Yvette Meissner, Angela Zink, Jörn Kekow, Karin Rockwitz, Anke Liebhaber, Silke Zinke, Kerstin Gerhold, Adrian Richter, Joachim Listing, Anja Strangfeld
BACKGROUND: The aim was to estimate the impact of individual risk factors and treatment with various disease-modifying antirheumatic drugs (DMARDs) on the incidence of myocardial infarction (MI) in patients with rheumatoid arthritis (RA). METHODS: We analysed data from 11,285 patients with RA, enrolled in the prospective cohort study RABBIT, at the start of biologic (b) or conventional synthetic (cs) DMARDs. A nested case-control study was conducted, defining patients with MI during follow-up as cases...
August 5, 2016: Arthritis Research & Therapy
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