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https://www.readbyqxmd.com/read/28432946/design-and-synthesis-of-sulfonamide-substituted-diphenylpyrimidines-sfa-dppys-as-potent-bruton-s-tyrosine-kinase-btk-inhibitors-with-improved-activity-toward-b-cell-lymphoblastic-leukemia
#1
He Liu, Menghua Qu, Lina Xu, Xu Han, Changyuan Wang, Xiaohong Shu, Jihong Yao, Kexin Liu, Jinyong Peng, Yanxia Li, Xiaodong Ma
A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine template, and then were biologically evaluated as potent Bruton's tyrosine kinase (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k displayed high potency against the BTK enzyme, with IC50 values of 1.18 nM, 0.92 nM, 0.42 nM and 1.05 nM, respectively. In particular, compound 10c could remarkably inhibit the proliferation of the B lymphoma cell lines at concentrations of 6...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28432815/immunoassays-for-the-quantification-of-alk-and-phosphorylated-alk-support-the-evaluation-of-on-target-alk-inhibitors-in-neuroblastoma
#2
Elizabeth R Tucker, Jennifer R Tall, Laura S Danielson, Sharon Gowan, Yann Jamin, Simon P Robinson, Udai Banerji, Louis Chesler
Targeted inhibition of Anaplastic Lymphoma Kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies, however the presence of resistant mutations necessitates both the development of more potent compounds and pharmacodynamic methods with which to determine their efficacy. We describe immunoassays designed to quantitate phosphorylation of ALK, and their use in preclinical models of neuroblastoma, a pediatric malignancy in which gain-of-function ALK mutations predict a poor overall outcome to conventional treatment...
April 22, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28432650/efficacy-and-tolerability-of-a-2-year-rituximab-maintenance-therapy-in-patients-with-advanced-follicular-lymphoma-after-induction-of-response-with-rituximab-containing-first-line-regimens-husom-study
#3
Tamás Schneider, András Rosta, Hajna Losonczy, Gáspár Radványi, György Ujj, Miklós Egyed, Árpád Illés, János Jakucs, László Szerafin, Zoltán Gasztonyi, Tamás Masszi, János Iványi, Judit Demeter, Péter Dombi, Antal Tóth, Zita Borbényi
Follicular lymphoma is a lymphoid malignancy commonly showing slow progression which makes the treatment of the disease challenging. Rituximab monotherapy and rituximab added to standard chemotherapy has been proven to increase survival among patients with advanced stage of the disease. However, the benefit of a rituximab maintenance therapy after induction was still unclear at the time of the initiation of this study. HUSOM was a phase III open-label, single-arm, multi-centre study aimed to assess the efficacy and the safety of the 12 cycles of rituximab (375 mg/m(2) every 8 weeks) maintenance therapy in patients had already presented partial or complete response to R-CVP or R-CHOP...
April 21, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28431340/first-macrocyclic-3-rd-generation-alk-inhibitor-for-treatment-of-alk-ros1-cancer-clinical-and-designing-strategy-update-of-lorlatinib
#4
REVIEW
Sulman Basit, Zaman Ashraf, Kwangho Lee, Muhammad Latif
Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to 2(nd)-generation ALK inhibitors. Lorlatinib (PF-06463922) (6) is a 3(rd)-generation macrocyclic ALK-TKI that demonstrates many advantages over 2(nd)-generation ALK inhibitors. Lorlatinib has demonstrated decent kinase selectivity, promising pharmacokinetic profile, selective brain-penetration and strong antiproliferative activity in several ALK/ROS1-driven tumor models. The current review describes the activity spectrum, key events from discovery to clinical applications and the evidences that lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430865/unmet-needs-in-the-first-line-treatment-of-follicular-lymphoma
#5
C Casulo, L Nastoupil, N H Fowler, J W Friedberg, C R Flowers
For the majority of patients with newly diagnosed follicular lymphoma (FL), current treatments, while not curative, allow for long remission durations. However, several important needs remain unaddressed. Studies have consistently shown that approximately 20% of patients with FL experience disease progression within 2 years of first-line treatment, and consequently have a 50% risk of death in 5 years. Better characterization of this group of patients at diagnosis may provide insight into those in need of alternate or intensive therapies, facilitate a precision approach to inform clinical trials, and allow for improved patient counseling...
April 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28430651/doxorubicin-loaded-platelets-conjugated-with-anti-cd22-mabs-a-novel-targeted-delivery-system-for-lymphoma-treatment-with-cardiopulmonary-avoidance
#6
Peipei Xu, Huaqin Zuo, Rongfu Zhou, Fan Wang, Xu Liu, Jian Ouyang, Bing Chen
B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429361/pathologic-character-and-diagnosis-of-female-primary-genital-system-diffuse-large-b-cell-lymphoma
#7
H Cheng, X Tang, J Cheng, B Zhang, Y-L Zhang, W-Q Wang, P Teng
OBJECTIVE: We investigated the clinicopathological characteristics and immunophenotype of female genital system diffuse large B-cell lymphoma (DLBCL) in order to improve diagnosis and therapy efficacy. PATIENTS AND METHODS: The clinicopathologic features of 13 cases with primary DLBCL of the female genital system were studied retrospectively. According to the immunophenotypes, 10 cases were classified as germinal center B-cell-like DLBCL and the other 3 as non-center B-cell-like DLBCL...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428969/targeted-lung-cancer-treatments-and-eye-metastasis
#8
REVIEW
Paul Zarogoulidis, Sofia Baka, Sofia Labaki, George Lazaridis, Georgia Trakada
Lung cancer remains the leading cause of death due to cancer. We do not have effective tools for the early detection of lung cancer, so patients are usually diagnosed at an advanced stage. However, novel therapies based on molecular pathways (such as those involving the epidermal growth factor receptor, anaplastic lymphoma kinase, serine/threonine-protein kinase B-Raf, proto-oncogene tyrosine-protein kinase ROS, c-Met proto-oncogene protein, and RET proto-oncogene protein) are now commonly used in the treatment of lung cancer...
2017: Medical Hypothesis, Discovery and Innovation in Ophthalmology
https://www.readbyqxmd.com/read/28428707/advanced-pancreatic-ductal-adenocarcinoma-complexities-of-treatment-and-emerging-therapeutic-options
#9
REVIEW
Chandra Diwakarla, Katherine Hannan, Nadine Hein, Desmond Yip
Pancreatic ductal adenocarcinoma is a devastating disease with a poor prognosis regardless of stage. To date the mainstay of therapy for advanced disease has been chemotherapy with little incremental improvements in outcome. Despite extensive research investigating new treatment options the current practices continue to utilise fluorouracil or gemcitabine containing combinations. The need for novel therapeutic approaches is mandated by the ongoing poor survival rates associated with this disease. One such approach may include manipulation of ribosome biogenesis and the nucleolar stress response, which has recently been applied to haematological malignancies such as lymphoma and prostate cancer with promising results...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428513/-comparison-of-preparation-efficiency-and-therapeutic-safety-between-generic-products-of-gemcitabine
#10
Yuhki Sato, Hiroyuki Ono, Kohei Amada, Ryosuke Nakahara, Hiroki Itoh
Because generic medicines reduce the financialburden on patients and medicalinsurance providers, they have become increasingly popular. However, there are only a few reports that have analyzed the efficacy and safety of generic medicines, especially in terms of their characteristics and side effects. Gemcitabine is an antineoplastic drug that is frequently used with good results in the treatment of lung cancer, pancreatic cancer, breast cancer, ovarian cancer, and malignant lymphoma. However, its fat solubility is high, and several adverse events, such as myelosuppression, are known to develop during its use...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28428442/combination-of-ibrutinib-and-abt-199-in-diffuse-large-b-cell-lymphoma-and-follicular-lymphoma
#11
Hsu-Ping Kuo, Scott A Ezell, Karl J Schweighofer, Leo Wk Cheung, Sidney Hsieh, Mutiah Apatira, Mint Sirisawad, Karl Eckert, Ssucheng J Hsu, Chun-Te Chen, Darrin M Beaupre, Matthias Versele, Betty Y Chang
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton's tyrosine kinase (BTK)-mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28428282/whither-radioimmunotherapy-to-be-or-not-to-be
#12
Damian J Green, Oliver W Press
Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B-cell lymphomas. Two "first-generation," directly radiolabeled anti-CD20 antibodies, (131)iodine-tositumomab and (90)yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but have been little utilized because of a variety of medical, financial, and logistic obstacles. Newer technologies employing multistep "pretargeting" methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy and diminished its toxicities...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427529/primary-central-nervous-system-lymphoma
#13
REVIEW
Giovanni Citterio, Michele Reni, Gemma Gatta, Andrés José Maria Ferreri
Primary CNS lymphomas (PCNSL) represent a subgroup of malignancies with specific characteristics, aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumour burden and/or histological type. Despite a high chemo- and radiosensitivity, remissions are frequently shortlasting, mainly because the blood brain-barrier limits the access of many drugs to the CNS. Moreover, survivor patients are at high risk of developing severe treatment-related toxicity, mainly disabling neurotoxicity, raising the question of how to balance therapy intensification with side-effects control...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427526/potential-application-and-prevalence-of-the-cd30-ki-1-antigen-among-solid-tumors-a-focus-review-of-the-literature
#14
REVIEW
Garrett K Berger, Kevin Gee, Cassandra Votruba, Ali McBride, Faiz Anwer
BACKGROUND: CD30 (Ki-1) is a cell membrane protein derived from the tumor necrosis factor (TNF) receptor family. The CD30 antigen has been associated primarily with Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Brentuximab vedotin (BV) is an antibody-drug conjugate targeting the CD30 antigen. FDA approval for BV includes relapsed and refractory HL and sALCL. The CD30 antigen also has been identified in many solid tumors, predominantly of germ cell origins and early clinical data is promising...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427522/the-role-of-anti-pd-1-and-anti-pd-l1-agents-in-the-treatment-of-diffuse-large-b-cell-lymphoma-the-future-is-now
#15
REVIEW
Luis Miguel Juárez-Salcedo, Jose Sandoval-Sus, Lubomir Sokol, Julio C Chavez, Samir Dalia
Immune checkpoints inhibitors have been incorporated into standard treatment protocols for advanced solid tumors. The aim of T-cell-based immune therapy in cancer has been to generate durable clinical benefits for patients, paired with enhanced side effect profiles. The beneficial antitumoral activity of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has been thoroughly demonstrated in certain metastatic malignancies (e.g. melanoma, non-small cell lung cancer, renal cell carcinoma); however, the therapeutic role in lymphoid cancers is complex...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427406/latent-membrane-protein-1-lmp1-expression-in-hodgkin-lymphoma-and-its-correlation-with-clinical-and-histologic-parameters
#16
Atif Ali Hashmi, Zubaida Fida Hussain, Kashif Ali Hashmi, Muhammad Irfan Zafar, Muhammad Muzzammil Edhi, Naveen Faridi, Mehmood Khan
BACKGROUND: Hodgkin lymphoma is one of the most prevalent lymphoproliferative disorders in Pakistan; however, no risk factors for this disease have yet to be established in our population. Epstein-Barr virus (EBV) is a well-known risk factor for Hodgkin lymphoma in endemic regions of the world; however, frequency of its association in our population has not been widely studied. Latent membrane protein 1 (LMP1) expression by immunohistochemistry (IHC) is a surrogate marker of EBV in Hodgkin lymphoma...
April 20, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28427281/the-servier-oncology-pipeline-in-2017
#17
Patrick Therasse, Beatrice Perron, Sarah A Novack, Jean-Pierre Abastado
Cancer is a complex, multifactorial disease that for years has been the focus of intensive research efforts to explore both the molecular and biological mechanisms involved and the development of novel agents to target these pathways. Servier is an independent French pharmaceutical company with a focus on oncology. Currently, Servier's commercial portfolio includes agents used to treat non-Hodgkin's lymphoma and metastatic colorectal cancer; Servier's oncology pipeline involves agents for the treatment of both solid and hematological tumors...
April 21, 2017: Future Oncology
https://www.readbyqxmd.com/read/28427247/molecular-testing-of-lung-cancers
#18
Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee
Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics...
April 21, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28427190/pygopus2-inhibits-the-efficacy-of-paclitaxel-induced-apoptosis-and-induces-multidrug-resistance-in-human-glioma-cells
#19
Cefan Zhou, Hongxia Cheng, Wenying Qin, Yi Zhang, Hui Xiong, Jing Yang, Huang Huang, Yefu Wang, Xing-Zhen Chen, Jingfeng Tang
Anti-microtubule drugs, such as paclitaxel (PTX), are extensively used for the treatment of numerous cancers. However, growing evidence has shown that PTX resistance, either intrinsic or acquired, frequently occurs in patients and results in the failure of treatment, contributing to the high cancer mortality rate. Therefore, it is necessary to identify the genes or pathways involved in anti-microtubule drug resistance for future successful treatment of cancers. Pygopus2 (Pygo2), which contains a Zn-coordinated plant homeodomain (PHD) finger domain, is critical for β-catenin-dependent transcriptional switches in normal and malignant tissues and is over-expressed in various cancers, including human brain glioma...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427156/the-effects-of-dleu1-gene-expression-in-burkitt-lymphoma-bl-potential-mechanism-of-chemoimmunotherapy-resistance-in-bl
#20
Sanghoon Lee, Wen Luo, Tishi Shah, Changhong Yin, Timmy O'Connell, Tae-Hoon Chung, Sherrie L Perkins, Rodney R Miles, Janet Ayello, Erin Morris, Lauren Harrison, Carmella van de Ven, Mitchell S Cairo
Following a multivariant analysis we demonstrated that children and adolescents with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in event free survival (EFS) despite identical short intensive multi-agent chemotherapy. However, how this deletion in the 13q14.3 region is associated with a significant decrease in EFS in children and adolescents with BL is largely unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the region of 13q14.3. Here, we report that DLEU1 expression is implicated in the regulation of BL programmed cell death, cell proliferation, and expression of apoptotic genes in transcription activator-like effector nuclease (TALEN)s-induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines...
February 24, 2017: Oncotarget
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