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https://www.readbyqxmd.com/read/29149104/cumulative-incidence-rates-for-cns-and-non-cns-progression-in-two-phase-ii-studies-of-alectinib-in-alk-positive-nsclc
#1
Shirish Gadgeel, Alice T Shaw, Fabrice Barlesi, Lucio Crinò, James Chih-Hsin Yang, Anne-Marie C Dingemans, Dong-Wan Kim, Filippo de Marinis, Mathias Schulz, Shiyao Liu, Ravindra Gupta, Ahmed Kotb, Sai-Hong Ignatius Ou
BACKGROUND: We evaluated the cumulative incidence rate (CIR) of central nervous system (CNS) and non-CNS progression in alectinib-treated patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to determine the extent to which alectinib may treat or control CNS disease. METHODS: Patients with crizotinib-pretreated locally advanced or metastatic disease received alectinib 600 mg orally twice daily in two phase II trials. All patients underwent baseline imaging and regular centrally reviewed scans...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29134510/drug-design-for-alk-positive-nsclc-an-integrated-pharmacophore-based-3d-qsar-and-virtual-screening-strategy
#2
Nivya James, V Shanthi, K Ramanathan
The increasing death rates related to anaplastic lymphoma kinase (ALK)-positive lung cancer culminated in a significant interest in the discovery of novel inhibitors for ALK. In the present research work, pharmacophore-based 3D QSAR modeling and virtual screening strategy have been carried out to address these issues. Initially, a five-point pharmacophore model was developed using the biological data of 50 compounds which includes an FDA-approved ALK inhibitor, crizotinib. Using the generated pharmacophore, a 3D QSAR model was developed and used as a query to screen the DrugBank database...
November 13, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29110994/spinal-cord-involvement-in-primary-cns-lymphoma
#3
Arunmozhi Maran Elavarasi, Deepa Dash, Anand R Warrier, Rohit Bhatia, Lalit Kumar, Deepali Jain, Manjari Tripathi
LETM is a common syndrome and the diagnosis of CNS lymphoma is not usually considered in the list of differentials. Primary CNS lymphoma can present as longitudinally extensive transverse myelopathy. Failure to suspect and evaluate leads to delay in diagnosis and treatment. PCNSL may be non contrast enhancing on gadolinium enhanced MRI. CSF analysis should be done preferably before starting corticosteroids as it is usual practice in treatment of transverse myelitis, as steroids may lead to transient improvement and mask the correct diagnosis...
October 27, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29110485/discovery-of-aromatic-carbamates-that-confer-neuroprotective-activity-by-enhancing-autophagy-and-inducing-the-anti-apoptotic-protein-b-cell-lymphoma-2-bcl-2
#4
Nihar Kinarivala, Ronak Patel, Rose-Mary Boustany, Abraham J Al-Ahmad, Paul C Trippier
Neurodegenerative diseases share certain pathophysiological hallmarks that represent common targets for drug discovery. In particular, dysfunction of proteostasis and the resultant apoptotic death of neurons, represent common pathways for pharmacological intervention. A library of aromatic carbamate derivatives based on the clinically available drug flupirtine was synthesized to determine a structure-activity relationship for neuroprotective activity. Several derivatives were identified that possess greater protective effect in human induced pluripotent stem cell-derived neurons, protecting up to 80% of neurons against etoposide-induced apoptosis at concentrations as low as 100 nM...
November 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29103980/extranodal-marginal-zone-lymphoma-of-the-central-nervous-system
#5
REVIEW
Adanma Ayanambakkam, Sami Ibrahimi, Khalid Bilal, Mohamad A Cherry
Extranodal marginal zone lymphoma of the central nervous system (CNS EMZBL) is a rare disease. We present a review of the literature and describe its presentation, differential diagnosis, treatment options, and outcomes. Systematic search of PubMed, Medline, and Embase databases via the Ovid engine for primary articles and case reports yielded 37 unduplicated peer-reviewed articles of CNS EMZBL. We identified 69 cases in these articles and 1 unreported case at our institution, which were included for this review's analysis...
September 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29083044/relapse-in-stage-i-e-diffuse-large-b-cell-lymphoma
#6
Marcel Nijland, Karin Boslooper, Gustaaf van Imhoff, Robbie Kibbelaar, Peter Joosten, Huib Storm, Eric N van Roon, Arjan Diepstra, Hanneke C Kluin-Nelemans, Mels Hoogendoorn
Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics...
October 30, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/29074098/lorlatinib-in-non-small-cell-lung-cancer-with-alk-or-ros1-rearrangement-an-international-multicentre-open-label-single-arm-first-in-man-phase-1-trial
#7
Alice T Shaw, Enriqueta Felip, Todd M Bauer, Benjamin Besse, Alejandro Navarro, Sophie Postel-Vinay, Justin F Gainor, Melissa Johnson, Jorg Dietrich, Leonard P James, Jill S Clancy, Joseph Chen, Jean-François Martini, Antonello Abbattista, Benjamin J Solomon
BACKGROUND: Most patients with anaplastic lymphoma kinase (ALK)-rearranged or ROS proto-oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops, commonly within the CNS. This study aimed to analyse the safety, efficacy, and pharmacokinetic properties of lorlatinib, a novel, highly potent, selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity against most known resistance mutations, in patients with advanced ALK-positive or ROS1-positive NSCLC...
October 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29071274/bilateral-central-retinal-artery-occlusion-associated-with-bilateral-lymphoproliferative-infiltrative-optic-neuropathy
#8
Philip J DeSouza, Claudia G Hooten, Christopher M Lack, Vishak J John, Timothy J Martin
BACKGROUND: Leukemic infiltration of the optic nerve is relatively rare. While previously described in acute leukemia, the infiltration in our case represents central nervous system (CNS) metastasis of Burkitt-type lymphoma that developed as a complication of solid-organ transplantation, resulting in a bilateral infiltrative optic neuropathy with sequential, bilateral central retinal artery occlusion (CRAO) and devastating vision loss. METHODS: The medical record, serial ophthalmic examination findings, clinical course, and imaging including magnetic resonance imaging (MRI), fundus photographs, and fluorescein angiography of a single patient were retrospectively reviewed...
September 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/29070116/-effect-of-b-cell-differentiation-markers-on-the-prognosis-of-primary-central-nervous-system-lymphoma
#9
Xiang-Lei Chen, Xiao-Yun Li, Wei Wang
OBJECTIVE: To investigate the value of B-cell differentiation markers in prognosis evaluation of 119 patients with primary CNS lymphoma(PCNSL). METHODS: The expressions of BCL-2, BCL-6, CD10 and MUM1/IRF4 protein were determined by immunohistochemistry, and their relationship with the prognosis of primary central nervous system lymphoma was analyzed. RESULTS: Univariate analysis showed that BCL-6 positive means shorter PFS (P=0.047) and OS (P=0...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29070115/-curative-efficacy-of-high-dose-mtx-combined-with-rituxan-for-treatment-primary-cns-lymphoma
#10
Kun Mou, Wei-Wei Gu, Cui-Hua Gu, Jiu-De Qi
OBJECTIVE: To explore the curative efficacy of methotrexate(MTX) combined with rituxan for treating patients with primary central nervous system(CNS) lymphoma. METHODS: One hundred patients with primary CNS lymphoma in our hospital were randomly divided into targeted treatment group(50 cases) and traditional treatment group (50 cases). Targeted treatment group adopted the therapy of high-dose methotrexate combined with rituxan, the traditional treatment group adopted the high-dose methotrexate combined with whole brain radiotherapy...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29063643/primary-central-nervous-system-extranodal-nasal-type-natural-killer-t-cell-lymphoma-with-cd20-expression
#11
Dujuan Li, Fangfang Fu, Lifei Lian
We report a unique case of primary CNS extranodal natural killer/T-cell lymphoma (PCNS ENKTCL) with CD20 expression and the monoclonal rearrangement of Ig heavey chain (IgH) gene. Resection specimens were evaluated using HE-stained sections, immunohistochemistry, in situ hybridization and PCR. Histopathologic examination, immunohistochemistry and molecular studies showed the intermediate-sized lymphoma cells expressing CD2, CD3ε, granzyme B, TIA-1, CD20 and Epstein-Barr virus-encoded RNA, with germline T-cell receptor gene and the monoclonal rearrangement of IgH gene...
October 24, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29061682/pearls-oy-sters-cns-lymphoma-in-a-patient-with-relapsing-remitting-multiple-sclerosis-treated-with-interferon
#12
Sharon Chiang, Navin K Kesari, Anthony Bradshaw, Wendy Chen, Rohini Samudralwar, Ammar M Alobaidy, Joseph S Kass
No abstract text is available yet for this article.
October 24, 2017: Neurology
https://www.readbyqxmd.com/read/29054815/whole-brain-radiotherapy-or-autologous-stem-cell-transplantation-as-consolidation-strategies-after-high-dose-methotrexate-based-chemoimmunotherapy-in-patients-with-primary-cns-lymphoma-results-of-the-second-randomisation-of-the-international-extranodal-lymphoma
#13
Andrés J M Ferreri, Kate Cwynarski, Elisa Pulczynski, Christopher P Fox, Elisabeth Schorb, Paul La Rosée, Mascha Binder, Alberto Fabbri, Valter Torri, Eleonora Minacapelli, Monica Falautano, Fiorella Ilariucci, Achille Ambrosetti, Alexander Roth, Claire Hemmaway, Peter Johnson, Kim M Linton, Tobias Pukrop, Jette Sønderskov Gørløv, Monica Balzarotti, Georg Hess, Ulrich Keller, Stephan Stilgenbauer, Jens Panse, Alessandra Tucci, Lorella Orsucci, Francesco Pisani, Alessandro Levis, Stefan W Krause, Hans J Schmoll, Bernd Hertenstein, Mathias Rummel, Jeffery Smith, Michael Pfreundschuh, Giuseppina Cabras, Francesco Angrilli, Maurilio Ponzoni, Martina Deckert, Letterio S Politi, Jürgen Finke, Michele Reni, Franco Cavalli, Emanuele Zucca, Gerald Illerhaus
BACKGROUND: The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested...
October 17, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29050112/-clinical-pathologic-characteristics-and-treatment-outcomes-of-19-relapsed-pediatric-b-cell-lymphoma
#14
S Huang, L Jin, J Yang, Y L Duan, M Zhang, C J Zhou, X L Ma, Y H Zhang
Objective: To review the clinical-pathology characteristics of 19 relapsed pediatric mature B cell lymphoma and to find the risk factors for recurrence and the feasible treatment after relapse. Method: Data of 212 pediatric B cell lymphomas cases in Beijing Children's Hospital from January 2006 to June 2015 were collected retrospectively. All the patients were treated according to the B cell lymphoma regimen of Beijing Children's Hospital. During the study period, 19 of 212 cases were relapsed; the clinio-pathological characteristics of relapsed patients before treatment and after relapse were analyzed retrospectively, the treatment outcomes after relapse were summarized and the patients were followed-up...
October 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29044419/myc-bcl2-co-expression-is-a-stronger-prognostic-factor-compared-with-the-cell-of-origin-classification-in-primary-cns-dlbcl
#15
COMPARATIVE STUDY
Qian-Yun Shi, Xiao Feng, Wei Bao, Jie Ma, Jing-Huan Lv, Xuan Wang, Qiu Rao, Qun-Li Shi
Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) is a subtype of DLBCL with an unfavorable prognosis and a poor response to the treatment. As we know, DLBCL is stratified into germinal center B-cell (GCB)-like and activated B-cell (ABC)-like subtypes with different prognosis according to their gene-expression characteristics. In this study, we analyzed a case series of 77 patients with primary CNS DLBCL. A difference in prognosis of GCB-like and ABC-like subtypes was noticed, but no statistical significance was found...
November 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29042334/primary-diffuse-large-b-cell-lymphoma-in-a-patient-with-rubinstein-taybi-syndrome-case-report-and-review-of-literature
#16
Christopher Sy, James Henry, Bhavani Kura, Andrew Brenner, Ramesh Grandhi
BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare, congenital syndrome that is known to be associated with neoplasms of various organ systems. Evaluation and treatment of such patients is challenging given the cognitive delay and heterogeneity of pathological presentations that define this syndrome. CASE DESCRIPTION: Presented here is a case of a patient with RSTS, diagnosed at birth, who presented with subtle symptoms of lethargy and a change in behavior. He was found to have a large (7...
October 14, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29038675/secondary-central-nerve-system-lymphoma-with-intratumoral-hemorrhage-suggested-as-intravascular-lymphoma-by-autopsy-a-case-report
#17
Yutaro Suzuki, Hiroaki Tanaka, Kennichiro Suyama, Hidetoshi Mochida, Yoshio Suzuki
Intravascular large B-cell lymphoma (IVL) is a rare type of extranodal diffuse large B-cell lymphoma (DLBCL), which often infiltrates the central nervous system (CNS) during the clinical course. Cerebral hemorrhage in patients with CNS lymphoma at presentation is rare. Herein, we describe a case of secondary CNS lymphoma with intratumoral hemorrhage, which was suggested as IVL from autopsy findings. A 76-year-old Japanese man with a history of treatment for B-cell non-Hodgkin's lymphoma was transferred to our hospital in an ambulance for generalized convulsions...
November 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29025286/-thalidomide-therapy-in-relapsed-diffuse-large-b-cell-lymphoma-in-elderly-patients-three-cases
#18
Nikolett Wohner, Gergely Varga, Péter Szloboda, Péter Farkas, András Masszi, Laura Horváth, Gergely Szombath, Judit Várkonyi, Szabolcs Benedek, Tamás Masszi
Diffuse large B-cell lymphoma (DLBCL), a high-grade lymphoproliferative disease, is the most common lymphoma in adults, representing 31% of non-Hodgkin lymphomas (NHL). In elderly patients treatment is problematic because of the high toxicity of standard chemotherapy protocols, especially in relapsed cases, where high-dose chemotherapy and haematopoietic stem cell transplantation would be the best choice. More and more data is becoming available on alternative treatment of refractory/relapsed NHL, including studies on the positive effect of thalidomide and second generation IMiDs in DLBCL, which are already part of the standard treatment protocol in myeloma multiplex and myelodysplasia...
October 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/29016820/selective-bcl-xl-inhibition-promotes-apoptosis-in-combination-with-mln8237-in-medulloblastoma-and-pediatric-glioblastoma-cells
#19
Jane Levesley, Lynette Steele, Anke Brüning-Richardson, Adam Davison, Jia Zhou, Chunyong Ding, Sean Lawler, Susan C Short
Background: CNS tumors, including medulloblastoma and pediatric glioblastoma (pGBM) account for the majority of solid pediatric malignancies. There remains an unmet need to identify novel treatment approaches in poor prognosis and relapsed pediatric brain tumors, where therapeutic options are limited. Small-molecule B-cell lymphoma 2 (BCL-2) family inhibitors may enhance tumor cell killing when combined with conventional and targeted chemotherapeutic agents. We investigated the effect of disrupting BCL-2 and B cell lymphoma-extra large (BCL-XL) protein function using ABT-263, ABT-199 and WEHI-539 in medulloblastoma and pGBM cells following treatment with MLN8237, an Aurora kinase inhibitor under investigation as a novel agent for the treatment of malignant brain tumors...
July 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28984175/primary-central-nervous-system-lymphoma-retrospective-analysis-of-34-cases-in-a-single-centre
#20
Huafeng Wang, Ming Wang, Juying Wei, Lei Wang, Liping Mao, Jie Jin
Objective To retrospectively analyse outcomes in patients with primary central nervous system lymphoma (PCNSL), which is a malignant CNS non-Hodgkin's lymphoma with a poor prognosis. Methods This study retrospectively analysed the treatment and outcomes of patients with PCNSL, which were divided into two groups: surgery (S) group and surgery/biopsy+chemotherapy (SC) group. The latter group was further subdivided into four cohorts based on the treatment regimen: cyclophosphamide, epidoxorubicin, vincristine and prednisone (CHOP), high-dose methotrexate (HDM)+dexamethasone+rituximab (HDM+D+R), HDM+D+temozolomide (HDM+D+T), and HDM+D+R+T...
January 1, 2017: Journal of International Medical Research
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