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https://www.readbyqxmd.com/read/29352732/long-term-effects-of-crizotinib-in-alk-positive-tumors-excluding-nsclc-a-phase-1b-open-label-study
#1
Carlo Gambacorti-Passerini, Sergey Orlov, Li Zhang, Fadi Braiteh, Huiqiang Huang, Taito Esaki, Keizo Horibe, Jin-Seok Ahn, Joseph T Beck, William Jeffrey Edenfield, Yuankai Shi, Matthew Taylor, Kenji Tamura, Brian A Van Tine, Shang-Ju Wu, Jolanda Paolini, Paulina Selaru, Tae Min Kim
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single-arm, open-label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK-positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily...
January 20, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29352717/should-we-use-cell-of-origin-and-dual-protein-expression-in-treating-dlbcl
#2
REVIEW
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352387/current-perspectives-on-erythema-multiforme
#3
REVIEW
Marianne Lerch, Carlo Mainetti, Benedetta Terziroli Beretta-Piccoli, Thomas Harr
Recognition and timely adequate treatment of erythema multiforme remain a major challenge. In this review, current diagnostic guidelines, potential pitfalls, and modern/novel treatment options are summarized with the aim to help clinicians with diagnostic and therapeutic decision-making. The diagnosis of erythema multiforme, that has an acute, self-limiting course, is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histological findings...
January 19, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29352235/systems-modeling-accurately-predicts-responses-to-genotoxic-agents-and-their-synergism-with-bcl-2-inhibitors-in-triple-negative-breast-cancer-cells
#4
Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen H M Prehn
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#5
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352124/hbv-infection-potentiates-resistance-to-s-phase-arrest-inducing-chemotherapeutics-by-inhibiting-chk2-pathway-in-diffuse-large-b-cell-lymphoma
#6
Xinying Zhao, Xudong Guo, Libo Xing, Wenqin Yue, Haisen Yin, Miaoxia He, Jianmin Wang, Jianmin Yang, Jie Chen
A considerable number of diffuse large B-cell lymphoma (DLBCL) patients are infected with hepatitis B virus (HBV), which is correlated with their poor outcomes. However, the role of HBV infection in DLBCL treatment failure remains poorly understood. Here, our data demonstrated that HBV infection was closely associated with poorer clinical prognosis independent of its hepatic dysfunction in germinal center B-cell type (GCB type) DLBCL patients. Interestingly, we found that DLBCL cells expressing hepatitis B virus X protein (HBX) did not exhibit enhanced cell growth but did show reduced sensitivity to methotrexate (MTX) and cytarabine (Ara-C), which induced S-phase arrest...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351987/cd83-is-a-new-potential-biomarker-and-therapeutic-target-for-hodgkin-lymphoma
#7
Ziduo Li, Xinsheng Ju, Kenneth Lee, Candice Clarke, Jennifer L Hsu, Edward Abadir, Christian E Bryant, Suzanne Pears, Neroli Sunderland, Scott Heffernan, Annemarie Hennessy, Tsun-Ho Lo, Geoffrey A Pietersz, Fiona Kupresanin, Phillip D Fromm, Pablo A Silveira, Con Tsonis, Wendy A Cooper, Ilona Cunningham, Christina Brown, Georgina J Clark, Derek N J Hart
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and interestingly, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351986/phase-ii-study-of-oral-jak1-jak2-inhibitor-ruxolitinib-in-advanced-relapsed-refractory-hodgkin-lymphoma
#8
Eric Van den Neste, Marc André, Thomas Gastinne, Aspasia Stamatoullas, Corinne Haioun, Amine Belhabri, Oumedaly Reman, Olivier Casasnovas, Hervé Guesquieres, Gregor Verhoef, Marie-José Claessen, Hélène A Poirel, Marie-Christine Copin, Romain Dubois, Peter Vandenberghe, Ioanna-Andrea Stoian, Anne S Cottereau, Sarah Bailly, Laurent Knoops, Franck Morschhauser
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29348865/targeting-t-cell-malignancies-using-anti-cd4-car-nk-92-cells
#9
Kevin G Pinz, Elizabeth Yakaboski, Alexander Jares, Hua Liu, Amelia E Firor, Kevin H Chen, Masayuki Wada, Huda Salman, William Tse, Nabil Hagag, Fengshuo Lan, Elaine Lai-Han Leung, Xun Jiang, Yupo Ma
Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and uniformly expressed...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348517/ndrg2-contributes-to-cisplatin-sensitivity-through-modulation-of-bak-to-mcl-1-ratio
#10
Soojong Park, Sang-Seok Oh, Ki Won Lee, Yeon-Kyeong Lee, Nae Yu Kim, Joo Heon Kim, Jiyun Yoo, Kwang Dong Kim
The downregulation of N-Myc downstream-regulated gene 2 (NDRG2) is known to be associated with the progression and poor prognosis of several cancers. Sensitivity to anti-cancer may be associated with a good prognosis in cancer patients, and NDRG2, which is induced by p53, sensitizes the cells to chemotherapy. However, the unique function of NDRG2 as an inducer of apoptosis under chemotreatment has not been sufficiently studied. In this study, we investigated the role of NDRG2 in chemo-sensitivity, focusing on cisplatin in U937 histiocytic lymphoma, which has the loss-of-functional mutation in p53...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348316/evaluation-of-next-generation-anti-cd20-antibodies-labeled-with-zirconium-89-in-human-lymphoma-xenografts
#11
Jason T Yoon, Mark S Longtine, Bernadette V Marquez-Nostra, Richard L Wahl
Radioimmunotherapies with monoclonal antibodies (mAbs) to the B-lymphocyte antigen 20 (CD20) are effective treatments for B-cell lymphomas, but United States Food and Drug Administration (FDA)-approved radioimmunotherapies exclusively use radiolabeled murine antibodies, potentially limiting re-dosing. The FDA recently approved two unlabeled anti-CD20 monoclonal antibodies, obinutizumab and ofatumumab, termed "next generation" as they are humanized (obinituzumab) or fully human (ofatumumab), thus potentially allowing a greater potential for re-dosing than with previous generation anti-CD20 antibodies, including rituximab (chimeric) and tositumumab (murine) which contain more murine peptide sequences...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29347836/strategies-to-overcome-resistance-mutations-of-bruton-s-tyrosine-kinase-inhibitor-ibrutinib
#12
Linyi Liu, Bingyu Shi, Xiangqian Wang, Hua Xiang
Ibrutinib, as the first Bruton's tyrosine kinase (Btk) inhibitor, has been shown to have clinically significant activity in leukemias and lymphomas. However, the initially responsive tumors will develop resistance during the process of treatment in few patients. Here, we summarized the mechanism of acquired resistance and suggested the next-generation Btk inhibitors that override the target resistance. Moreover, the development of combination of selective antagonists or inhibitors targeting to multiple protein kinases have increased therapeutic potency to reduce the risk of the emergence of kinases inhibitor resistance...
January 19, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29346498/association-of-treatment-for-hodgkin-lymphoma-with-estrogen-receptor-status-of-subsequent-breast-cancers
#13
Diana R Withrow, Lindsay M Morton, Rochelle E Curtis, Sara J Schonfeld, Amy Berrington de González
No abstract text is available yet for this article.
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29346274/irf4-mediates-the-oncogenic-effects-of-stat3-in-anaplastic-large-cell-lymphomas
#14
Cecilia Bandini, Aldi Pupuleku, Elisa Spaccarotella, Elisa Pellegrino, Rui Wang, Nicoletta Vitale, Carlotta Duval, Daniela Cantarella, Andrea Rinaldi, Paolo Provero, Ferdinando Di Cunto, Enzo Medico, Francesco Bertoni, Giorgio Inghirami, Roberto Piva
Systemic anaplastic large cell lymphomas (ALCL) are a category of T-cell non-Hodgkin's lymphomas which can be divided into anaplastic lymphoma kinase (ALK) positive and ALK negative subgroups, based on ALK gene rearrangements. Among several pathways aberrantly activated in ALCL, the constitutive activation of signal transducer and activator of transcription 3 (STAT3) is shared by all ALK positive ALCL and has been detected in a subgroup of ALK negative ALCL. To discover essential mediators of STAT3 oncogenic activity that may represent feasible targets for ALCL therapies, we combined gene expression profiling analysis and RNA interference functional approaches...
January 18, 2018: Cancers
https://www.readbyqxmd.com/read/29345696/antiemetic-efficacy-and-safety-of-granisetron-or-palonosetron-alone-and-in-combination-with-a-corticosteroid-for-abvd-therapy-induced-nausea-and-vomiting
#15
Mayako Uchida, Tsutomu Nakamura, Kojiro Hata, Hiroyuki Watanabe, Yasuo Mori, Koji Kato, Kenjiro Kamezaki, Katsuto Takenaka, Motoaki Shiratsuchi, Keiko Hosohata, Toshihiro Miyamoto, Koichi Akashi
Background: Antiemetic effects and safety of granisetron or palonosetron alone and in combination with a corticosteroid against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with Hodgkin lymphoma receiving adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy. Methods: A total of 39 patients were eligible for this study. Before ABVD therapy, granisetron or palonosetron was intravenously administered with or without a corticosteroid (dexamethasone or hydrocortisone) and aprepitant...
2018: Journal of Pharmaceutical Health Care and Sciences
https://www.readbyqxmd.com/read/29345517/pet-adapted-therapy-for-advanced-hodgkin-lymphoma-systematic-review
#16
Irina Amitai, Ronit Gurion, Liat Vidal, Eldad J Dann, Pia Raanani, Anat Gafter-Gvili
INTRODUCTION: Positron emission tomography-computed tomography (PET-CT) performed after two chemotherapy cycles (PET-2) has become an accepted prognostic tool in Hodgkin lymphoma (HL). We evaluated the effect of PET-adapted strategy on outcome in advanced stage HL. METHODS: In August 2017, we searched electronic databases, conference proceedings and ongoing trials. We included all studies in which treatment modification for advanced HL was performed based on the results of the interim PET scan...
January 18, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29345210/the-impact-of-time-from-diagnosis-to-treatment-in-diffuse-large-b-cell-lymphoma
#17
Colin Phipps, Yuh Shan Lee, Hao Ying, Chandramouli Nagarajan, Nicholas Grigoropoulos, Yunxin Chen, Tiffany Tang, Alan Z Goh, Aditi Ghosh, Heng Joo Ng, Sathish Gopalakrishnan, Yvonne Loh, Soon Thye Lim, William Hwang, Daryl Tan, Yeow Tee Goh
Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that requires treatment. We retrospectively analyzed the impact of time from diagnosis-to-treatment (TDT) on progression-free survival (PFS) and overall survival (OS) in 581 R-CHOP-treated patients. TDT was defined as the interval between diagnostic biopsy date and day 1 R-CHOP. Cox regression showed stage 3-4 disease (p = .01) and longer TDT (HR 1.13, p =.031) were associated with shorter OS. Eastern Cooperative Oncology Group ≥2 (p = ...
January 18, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29345103/incidence-of-common-cancers-in-users-of-antimuscarinic-medications-for-overactive-bladder-a-danish-nationwide-cohort-study
#18
Jesper Hallas, Andrea V Margulis, Anton Pottegård, Nina Sahlertz Kristiansen, Willem Jan Atsma, Kwame Appenteng, Stefan de Vogel, James A Kaye, Susana Perez-Gutthann, Alejandro Arana
The purpose of this study was to estimate the incidence rate (IR) of 10 common cancers in new users of antimuscarinic overactive bladder (OAB) medications. We conducted a cohort study using data recorded in Danish registers for patients newly exposed to the OAB drugs darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine or trospium in years 2004-2012, aged ≥18 years and without cancer before treatment initiation. We estimated IRs for each study cancer (bladder, breast, colorectal, lung, melanoma, non-Hodgkin lymphoma, pancreas, prostate, renal and uterine), standardised by age and sex and explored IR trends over time since treatment initiation...
January 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29345096/psychiatric-sequelae-of-corticosteroid-use-in-hematology-in-australia-a-qualitative-study
#19
Dianne Clifton, Margaret Ross, Clare O'Callaghan
Despite widespread steroid usage for treating hematological conditions, minimal attention focuses on associated psychiatric side-effects. In the present study, we examined hematology patients' experiences of high-dose steroid treatment. This was undertaken by the use of a qualitative, descriptive design, which included convenience sampling and the inductive, cyclic, and constant comparative thematic analysis of interview transcripts. Eighteen patients participated, who were diagnosed with lymphoma, myeloma, leukemia, or idiopathic thrombocytopenia purpura...
January 18, 2018: Nursing & Health Sciences
https://www.readbyqxmd.com/read/29344639/therapeutic-potential-of-a-dual-mtorc1-2-inhibitor-for-the-prevention-of-posterior-capsule-opacification-an-in-vitro-study
#20
Hao Feng, Zhibo Yang, Xue Bai, Meirong Yang, Yuan Fang, Xiaonan Zhang, Qiqiang Guo, Hong Ning
Mammalian target of rapamycin (mTOR) serves a central role in regulating cell growth and survival, and has been demonstrated to be involved in the pathological progression of posterior capsule opacification (PCO). In the present study, the potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the suppression of the growth of human lens epithelial cells (HLECs) was investigated. Using a Cell Counting Kit‑8 and a wound healing assay, it was demonstrated that PP242 inhibited the proliferation and migration of HLECs...
January 18, 2018: International Journal of Molecular Medicine
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