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Thalidomide

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https://www.readbyqxmd.com/read/28099781/old-drug-scaffold-new-activity-thalidomide-correlated-compounds-exerting-different-effects-on-breast-cancer-cell-growth-and-progression
#1
Alessia Carocci, Alessia Catalano, Domenico Iacopetta, Maria Stefania Sinicropi
Thalidomide was firstly used as morning sickness relief in pregnant women and then withdrawn from market because of its dramatic effects on fetal normal development. Over the last decades, it has been successfully used for the care of several pathologies, including cancer. Many analogues with improved activity were synthesized and tested. Herein, we report some effects on MCF-7 and MDA-MB-231 breast cancer cells growth and progression of a small series of thalidomide correlated compounds, very effective in inducing cancer cells death by triggering TNFα-mediated apoptosis...
January 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28094456/waldenstr%C3%A3-m-macroglobulinemia-2017-update-on-diagnosis-risk-stratification-and-management
#2
Morie A Gertz
: Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. DIAGNOSIS: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Risk Stratification: Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis...
February 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28093007/thalidomide-analog-cc-122-induces-a-refractory-state-in-monocytes-from-patients-with-diffuse-large-b-cell-lymphoma
#3
Carolina Cubillos-Zapata, Raúl Córdoba, Jose Avendaño-Ortiz, Eduardo Lopez-Collazo
No abstract text is available yet for this article.
January 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28092996/chromosome-1-amplification-has-similar-prognostic-value-to-del-17p13-and-t-4-14-p16-q32-in-multiple-myeloma-patients-analysis-of-real-life-data-from-the-polish-myeloma-study-group
#4
Norbert Grzasko, Roman Hajek, Marek Hus, Sylwia Chocholska, Marta Morawska, Krzysztof Giannopoulos, Krzysztof Czarnocki, Agnieszka Druzd-Sitek, Barbara Pienkowska-Grela, Jolanta Rygier, Lidia Usnarska-Zubkiewicz, Dominik Dytfeld, Tadeusz Kubicki, Artur Jurczyszyn, Maciej Korpysz, Anna Dmoszynska
The study aimed to assess prognostic significance of del(13q14), del(17p13), t(4;14)(p16;q32), and amp(1q21) in newly diagnosed myeloma patients treated mostly with thalidomide-based therapies. All genetic abnormalities except del(13q14) were independent prognostic factors associated with shortened progression-free survival (PFS) and overall survival (OS). Patients with no abnormalities, one abnormality, and ≥2 abnormalities had a median PFS of 41.8, 17.0, and 10.0 months, respectively; a median OS was not reached, 48...
January 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28088968/-para-neoplastic-autoimmune-multi-organ-syndrome-associated-with-follicular-lymphoma-a-case-report-and-literature-review
#5
D Chen, C Y Lin, X Han, B Chen, Z H Lu, X Y Chang, M H Duan
Objective: To broaden our knowledge of para-neoplastic autoimmune multi-organ syndrome (PAMS). Methods: A patient with PAMS associated with follicular lymphoma and bronchiolitis obliterans treated in our hospital was retrospectively analyzed and the clinical features of PAMS were reviewed. Results: A 49-year-old female patient suffered from painful ulcers in the oral cavity and vagina, dry cough and dyspnea. Imaging examinations suggested multiple lymph node enlargements. Inguinal lymph node biopsy revealed follicular lymphoma...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#6
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087699/activation-of-c-abl-kinase-potentiates-the-anti-myeloma-drug-lenalidomide-by-promoting-dda1-recruitment-to-the-crl4-ubiquitin-ligase
#7
Shaobing Gao, Chenlu Geng, Tianyu Song, Xuanru Lin, Jiye Liu, Zhen Cai, Yong Cang
Cullin Ring Ligase 4 (CRL4), a complex of Cul4 and DDB1, regulates cell cycle, DNA damage repair, and chromatin replication by targeting a variety of substrates for ubiquitination. CRL4 is also hijacked by viral proteins or thalidomide-derived compounds to degrade host restriction factors. Here we report that the c-Abl non-receptor kinase phosphorylates DDB1 at residue Y316 to recruit a small regulatory protein DDA1, leading to increased substrate ubiquitination. Pharmacological inhibition or genetic ablation of the Abl-DDB1-DDA1 axis decreases the ubiquitination of CRL4 substrates, including IKZF1 and IKZF3 in lenalidomide-treated multiple myeloma cells...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28074423/effectiveness-of-risk-evaluation-and-mitigation-strategies-rems-for-lenalidomide-and-thalidomide-patient-comprehension-and-knowledge-retention
#8
Nancy A Brandenburg, Robert Bwire, John Freeman, Florence Houn, Paul Sheehan, Jerome B Zeldis
INTRODUCTION: The effectiveness of patient education activities conducted within the lenalidomide and thalidomide risk evaluation and mitigation strategies (REMS) programs was evaluated by measuring understanding of serious risk and safe-use messages. METHODS: Results from mandatory knowledge, attitude, and behavior surveys and voluntary patient surveys completed between June 2012 and June 2013 were analyzed, and responses to questions relating to compliance with birth control measures and understanding of safe-use messages are presented by patient risk category...
January 10, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28061994/recommend-maintenance-therapy-with-lenalidomide-in-multiple-myeloma
#9
REVIEW
Elisabet E Manasanch
Thalidomide was the first immunomodulatory drug used as maintenance after autologous stem cell transplant (ASCT) in multiple myeloma (MM). This showed improved progression-free survival (PFS) and in some cases, overall survival (OS). Despite this, use of thalidomide was limited due to toxicity and high rates of therapy discontinuation. Lenalidomide, an analog of thalidomide, had a more favorable toxicity profile making its use in maintenance a potential approach. The use of lenalidomide as a maintenance therapy after ASCT in newly diagnosed MM patients has been investigated in four phase III randomized control studies...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28058282/protein-degradation-by-in-cell-self-assembly-of-proteolysis-targeting-chimeras
#10
Honorine Lebraud, David J Wright, Christopher N Johnson, Tom D Heightman
Selective degradation of proteins by proteolysis targeting chimeras (PROTACs) offers a promising potential alternative to protein inhibition for therapeutic intervention. Current PROTAC molecules incorporate a ligand for the target protein, a linker, and an E3 ubiquitin ligase recruiting group, which bring together target protein and ubiquitinating machinery. Such hetero-bifunctional molecules require significant linker optimization and possess high molecular weight, which can limit cellular permeation, solubility, and other drug-like properties...
December 28, 2016: ACS Central Science
https://www.readbyqxmd.com/read/28053546/comparing-efficacy-and-survivals-of-initial-treatments-for-elderly-patients-with-newly-diagnosed-multiple-myeloma-a-network-meta-analysis-of-randomized-controlled-trials
#11
Xiaoping Liu, Jiarui Chen, Yuncen A He, Xiangyu Meng, Kaili Li, Colin K He, Shangqin Liu
OBJECTIVE: The aim of this study was to evaluate the efficacy and clinical outcome of initial therapies for elderly patients with multiple myeloma (MM). METHODS: Randomized controlled trials (RCTs) were obtained through a comprehensive search. Response rate, progression-free survival (PFS) and overall survival (OS) were the interested outcome measures. Network meta-analysis (NMA) using graph theory methodology to construct an NMA model, and sensitivity analysis were performed...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28050994/autologous-stem-cell-transplantation-for-multiple-myeloma-long-term-results
#12
Lalit Kumar, Rakesh Reddy Boya, Rohit Pai, P Harish, Anjali Mookerjee, B Sainath, Mukesh Bhimrao Patekar, Ranjit Kumar Sahoo, Prabhat Singh Malik, O D Sharma, Ritu Gupta
BACKGROUND: Survival of myeloma patients has improved considerably in the past decade. However, limited data are available on their long-term outcome. We analysed the data of 225 consecutive patients who underwent autologous stem cell transplantation (ASCT) at our centre. METHODS: Between April 1990 and December 2013, a total of 225 patients with multiple myeloma (median age 53 years, range 27-67 years, 69.3% men) underwent ASCT. High-dose melphalan 200 mg/m2 was used for conditioning...
July 2016: National Medical Journal of India
https://www.readbyqxmd.com/read/28050001/light-chain-deposition-disease-diagnosed-with-laser-micro-dissection-liquid-chromatography-and-tandem-mass-spectrometry-of-nodular-glomerular-lesions
#13
Tomomichi Kasagi, Hironobu Nobata, Keisuke Suzuki, Naoto Miura, Shogo Banno, Akiyoshi Takami, Taro Yamashita, Yukio Ando, Hirokazu Imai
A 42-year-old man developed nephrotic syndrome and rapidly progressive renal failure. Kidney biopsy demonstrated nodular glomerulosclerosis, negative Congo red staining, and no deposition of light or heavy chains. Laser micro-dissection and liquid chromatography with tandem mass spectrometry of nodular lesions revealed the presence of a kappa chain constant region and kappa III variable region, which signified light chain deposition disease. Dexamethasone and thalidomide were effective in decreasing the serum levels of free kappa light chain from 147...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28043164/current-treatment-options-and-investigational-drugs-for-waldenstrom-s-macroglobulinemia
#14
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Waldenström's Macroglobulinemia (WM) is a rare, indolent, incurable, low-grade B-cell lymphoplasmacytic neoplasm. This review article provides a modern clinical perspective of the individualized management of patients with symptomatic WM, in the context of the updated treatment guidelines and the currently available trial data. Areas covered: Rituximab-based regimens (such as the dexamethasone, rituximab and cyclophosphamide combination, DRC) are the most widely used in the management of both newly diagnosed and relapsed/refractory patients with WM...
January 3, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28042431/vulvovaginal-gingival-lichen-planus-report-of-two-cases-and-review-of-literature
#15
REVIEW
A Lucchese, A Dolci, G Minervini, C Salerno, D DI Stasio, G Minervini, L Laino, F Silvestre, R Serpico
PURPOSE: Oral Lichen Planus (OLP) is a chronic inflammatory disease of skin and mucous membranes. Approximately 20% of women with oral lichen planus develops lesions in the genital mucosa. In 1982, Pelisse described a special form of lichen planus (LP), which consists of a triad of symptoms: vulval, vaginal and gingival (VVG)-LP lesions. Aim of the present report is to report two new cases and review the international literature. MATERIAL AND METHODS: Two cases of VVG-LP are reported and a review of recent literature is performed...
April 2016: Oral & Implantology
https://www.readbyqxmd.com/read/28009008/down-regulation-of-common-nf%C3%AE%C2%BAb-inos-pathway-by-chronic-thalidomide-treatment-improves-hepatopulmonary-syndrome-and-muscle-wasting-in-rats-with-biliary-cirrhosis
#16
Tzu-Hao Li, Pei-Chang Lee, Kuei-Chuan Lee, Yun-Cheng Hsieh, Chang-Youh Tsai, Ying-Ying Yang, Shiang-Fen Huang, Tung-Hu Tsai, Shie-Liang Hsieh, Ming-Chih Hou, Han-Chieh Lin, Shou-Dong Lee
Thalidomide can modulate the TNFα-NFκB and iNOS pathway, which involve in the pathogenesis of hepatopulmonary syndrome (HPS) and muscle wasting in cirrhosis. In bile duct ligated-cirrhotic rats, the increased circulating CD16(+) (inflammatory) monocytes and its intracellular TNFα, NFκB, monocyte chemotactic protein (MCP-1) and iNOS levels were associated with increased circulating MCP-1/soluable intercellular cell adehesion molecule-1 (sICAM-1), pulmonary TNFα/NOx, up-regulated M1 polarization, exacerbated angiogenesis and hypoxemia (increased AaPO2) in bronchoalveolar lavage (BAL) fluid and pulmonary homogenates...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28002971/new-and-developing-therapies-for-al-amyloidosis
#17
Giulia Zumbo, Omid Sadeghi-Alavijeh, Philip N Hawkins, Marianna Fontana
Systemic light-chain (AL) amyloidosis is an infiltrative disorder associated with an underlying plasma cells dyscrasia, in which monoclonal immunoglobulin light chains accumulate in an abnormal misfolded form as amyloid fibrils in the extracellular space. Symptoms and prognosis are governed by which organs are affected, and cardiac involvement is the major determinant of survival. Diagnosis requires demonstration of amyloid deposition and confirmation of the fibril protein type. Areas covered: This review will focus on the available treatments for systemic AL amyloidosis and on new drug targets and therapeutic approaches...
December 29, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28000010/two-cases-demonstrating-thalidomide-s-efficacy-in-refractory-lupus-nephritis
#18
REVIEW
Rita Raturi, Avani A Patel, John D Carter
Renal involvement in systemic lupus erythematosus (SLE) is common and has been associated with an increased risk of mortality [1]. Early diagnosis is imperative to control proteinuria and prevent the progression to end-stage renal disease. Standard induction therapies include cyclophosphamide (CYC) and mycophenolate mofetil (MMF); however, it has been estimated that approximately 30% of patients are refractory to these standard treatments after 1 year [2]. We present two cases of patients diagnosed with lupus nephritis (LN) who demonstrated persistent proteinuria while on standard treatments that markedly improved after addition of thalidomide (THD)...
December 20, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27999418/impact-of-time-varying-treatment-exposures-on-the-risk-of-venous-thromboembolism-in-multiple-myeloma
#19
Joshua D Brown, Val R Adams, Daniela C Moga
Multiple myeloma (MM) has one of the highest risks of venous thromboembolism (VTE) of all cancers due to pathologic changes and treatment-related exposures. This study assessed the one-year incidence of VTE in newly diagnosed MM and to determine the baseline and time-varying treatment-related factors associated with VTE risk in a U.S.-based cohort. MM patients were identified and age, gender, and baseline comorbidities were determined. Treatment-related exposures included thalidomide derivatives (IMIDs), proteasome inhibitors, cytotoxic chemotherapy, steroids, erythropoietin-stimulating agents (ESAs), stem cell transplants (SCT), hospitalizations, infection, and central venous catheters (CVC)...
December 20, 2016: Healthcare (Basel, Switzerland)
https://www.readbyqxmd.com/read/27991432/the-effect-of-proton-pump-inhibitors-on-the-cyp2c19-enzyme-activity-evaluated-by-the-pantoprazole-13-c-breath-test-in-gerd-patients-clinical-relevance-for-personalized-medicine
#20
Anil S Modak, Iryna Klyarytska, Valerij Kriviy, Tatjana Tsapyak, Yliya Rabotyagova
Patients with gastroesophageal reflux disease (GERD) are routinely prescribed one of the six FDA approved proton pump inhibitors (PPI). All of these PPI are inhibitors of CYP2C19 enzyme to varying degrees. The phenotype pantoprazole-(13)C breath test (Ptz-BT) was used to identify patients who are poor metabolizers (PM) and the extent of phenoconversion of CYP2C19 enzyme activity caused by four PPI (omeprazole, esomprazole pantoprazole and rabeprazole) in 54 newly diagnosed GERD patients prior to initiating randomly selected PPI therapy and 30 d after PPI therapy...
December 17, 2016: Journal of Breath Research
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