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https://www.readbyqxmd.com/read/27913567/drug-repositioning-screens-identify-triamterene-as-a-selective-drug-for-the-treatment-of-dna-mismatch-repair-deficient-cells
#1
Delphine Guillotin, Philip Austin, Rumena Begum, Marta O Freitas, Ashirwad Merve, Tim Brend, Susan C Short, Silvia Marino, Sarah A Martin
PURPOSE: The DNA Mismatch repair (MMR) pathway is required for the maintenance of genome stability. Unsurprisingly, mutations in MMR genes occur in a wide range of different cancers. Studies thus far have largely focused on specific tumor types or MMR mutations, however it is becoming increasingly clear that a therapy targeting MMR-deficiency in general would be clinically very beneficial. EXPERIMENTAL DESIGN: Based on a drug-repositioning approach, we screened a large panel of cell lines with various MMR deficiencies from a range of different tumor types with a compound drug library of previously approved drugs...
December 2, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27913523/advances-and-practical-use-of-monoclonal-antibodies-in-multiple-myeloma-therapy
#2
Hans C Lee, Donna M Weber
The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913503/diffuse-large-b-cell-lymphoma-r-chop-failure-what-to-do
#3
Bertrand Coiffier, Clémentine Sarkozy
Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL), ∼30% to 50% of patients are not cured by this treatment, depending on disease stage or prognostic index. Among patients for whom R-CHOP therapy fails, 20% suffer from primary refractory disease (progress during or right after treatment) whereas 30% relapse after achieving complete remission (CR). Currently, there is no good definition enabling us to identify these 2 groups upon diagnosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913502/mrd-in-aml-does-it-already-guide-therapy-decision-making
#4
Gert Ossenkoppele, Gerrit Jan Schuurhuis
Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease [MRD]) far below the level of 5% blast cells is changing the landscape of risk classification...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913472/novel-agents-in-chronic-lymphocytic-leukemia
#5
Nicole Lamanna, Susan O'Brien
The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming increasingly used in patients with relapsed disease, patients with 17p deletion, and, as of recently, also in the frontline setting for previously untreated patients with CLL. Moreover, many of these are oral therapies that are significantly less myelosuppressive than chemoimmunotherapy. However, these agents have their own set of unique toxicities with which providers must gain familiarity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#6
Jacqueline C Barrientos
It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL proliferation and survival...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912884/synergism-of-coumarins-from-the-chinese-drug-zanthoxylum-nitidum-with-antibacterial-agents-against-methicillin-resistant-staphylococcus-aureus-mrsa
#7
Guo-Ying Zuo, Chun-Juan Wang, Jun Han, Yu-Qing Li, Gen-Chun Wang
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious therapeutic challenge in current clinic and new drug development. Natural coumarins have diverse bioactivities and the potential of resistance modifying effects. PURPOSE: This study is to present in-depth evaluations of in vitro antimicrobial activities of four natural coumarins 5-geranyloxy-7-methoxycoumarin (Gm, 1), (5,7-dimethoxy-8-prenyloxycoumarin (artanin, Ar, 2)), isopimpinellin (Is, 3) and phellopterin (Ph, 4) from Zanthoxylum nitidum (Roxb...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912880/combination-of-baicalein-and-10-hydroxy-camptothecin-exerts-remarkable-synergetic-anti-cancer-effects
#8
Qin Tang, Fangling Ji, Wenhui Sun, Jingyun Wang, Jianli Guo, Lianying Guo, Yachen Li, Yongming Bao
BACKGROUND: 10-Hydroxy camptothecin (HCPT), a naturally occurring alkaloid, is a clinical drug for cancer chemotherapy. Baicalein (BA) is a flavonoid extracted from the root of Scutellaria baicalensis. The synergistic anti-cancer effect of BA and HCPT has not been reported. PURPOSE: To explore whether and how BA enhances the anti-cancer effect of HCPT in BGC823 cells. METHODS: Cell viability was measured by MTT assay. Apoptosis and cell cycle were analyzed through flow cytometry and western blotting analysis...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912835/second-line-chemotherapy-and-beyond-for-non-small-cell-lung-cancer
#9
REVIEW
Greg Durm, Nasser Hanna
The landscape for the second- and third-line treatment of advanced non-small cell lung cancer has changed dramatically over the last two decades. Immunotherapeutic agents have become a preferred choice following progression on platinum-based first-line chemotherapy. However, there remains a role for cytotoxic chemotherapy and pemetrexed and docetaxel (with or without ramucirumab) are approved for single-agent use in the second-line setting. With the discovery of new genetic alterations and the development of novel targeted drugs, the treatment of advanced non-small cell lung cancer following progression on first-line therapy continues to become more complicated as new treatment algorithms evolve...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912828/lung-cancer-biomarkers
#10
REVIEW
Pamela Villalobos, Ignacio I Wistuba
The molecular characterization of lung cancer has changed the classification and treatment of these tumors, becoming an essential component of pathologic diagnosis and oncologic therapy decisions. Through the recognition of novel biomarkers, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, it is possible to identify subsets of patients who benefit from targeted molecular therapies. The success of targeted anticancer therapies and new immunotherapy approaches has created a new paradigm of personalized therapy and has led to accelerated development of new drugs for lung cancer treatment...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912145/chloroquine-cq-exerts-anti-breast-cancer-through-modulating-microenvironment-and-inducing-apoptosis
#11
Yanjun Zhang, Yu Cao, Xiaodan Sun, Yonghui Feng, Yunting Du, Fei Liu, Chunyun Yu, Feng Jin
CQ is an anti-malaria drug, which has been used for years. However, there are published articles about its activity in anti-cancers. The aim of this approach was to look at possibility and related mechanisms of anti-breast cancer (mouse breast cancer cell line 4T1) by CQ alone. The studies of anti 4T1 in vitro and in vivo by CQ were performed. The growth of 4T1 in vitro and in vivo, survival of mice post treatment with CQ, changes of immune parameters and microenvironment in mice were evaluated. Our results demonstrate that CQ could markedly inhibit growth of 4T1 in vitro through inducing apoptosis of cells, inhibiting secretion of TGF-β and prolong the mice survival in vivo through boosting immune system by upregulating CD8+ T cell, and through down-regulating tumor associated macrophages (TAM), myeloid derived suppressing cells (MDSC) and Tregs, in microenvironment of mice bearing tumor...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27911857/yap1-regulates-abcg2-and-cancer-cell-side-population-in-human-lung-cancer-cells
#12
Yuyuan Dai, Shu Liu, Wen-Qian Zhang, Yi-Lin Yang, Phillip Hang, Hui Wang, Li Cheng, Ping-Chih Hsu, Yu-Chen Wang, Zhidong Xu, David M Jablons, Liang You
A small population of cancer cells called cancer-initiating cells or cancer stem cells (CSCs) are involved in drug resistance, metastasis, and cancer relapse. Finding pathways that regulate CSC is very important for clinical therapy. ATP-binding cassette sub-family G member 2 (ABCG2) plays a role in side population (SP) cell formation and contributes to chemotherapy resistance in common forms of cancer. Yes-associated protein 1 (YAP1) is a major transcriptional effector of the Hippo pathway, which plays important roles in organ size control and tumorigenesis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910983/investigation-and-intervention-of-autophagy-to-guide-cancer-treatment-with-nanogels
#13
Xudong Zhang, Xin Liang, Jianjun Gu, Danfeng Chang, Jinxie Zhang, Zhaowei Chen, Yanqi Ye, Chao Wang, Wei Tao, Xiaowei Zeng, Gan Liu, Yongjun Zhang, Lin Mei, Zhen Gu
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27910962/baricitinib-jak-inhibition-for-rheumatoid-arthritis
#14
J Gras
Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease characterized by inflammation and joint destruction, is associated with pain, progressive disability, systemic comorbidities and early death. Conventional disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs (bDMARDs) have been able to achieve remission or a very low disease activity status for RA. Nevertheless, since many patients do not reach a sufficient response with DMARDs or present with unacceptable side effects, new therapies are needed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910765/gene-therapy-for-rheumatoid-arthritis
#15
Shuang Liu, Kazutaka Maeyama
With the aim of controlling disease relapse and bone deformation of individual joints, the application of gene therapy in rheumatoid arthritis (RA) has slowly progressed on a trial-and-error basis. Several new therapeutic targets have been identified in preclinical studies in animal models, although a limited number of gene-based clinical trials have been conducted. In this article, we summarize the status of gene therapy for RA by addressing issues related to innovating drug development. More disease- and target-specific preclinical tests are required to overcome the insufficient information regarding pharmacokinetics and toxicokinetics, which are related to safety issues in the field of RA gene therapy...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910061/inhaled-gene-transfer-for-pulmonary-circulation
#16
Jaume Aguero, Lahouaria Hadri, Nadjib Hammoudi, Lauren Leonardson, Roger J Hajjar, Kiyotake Ishikawa
Chronic pulmonary hypertension (PH) is associated with right ventricular failure and high mortality regardless of the underlying disease. Currently, therapies can improve clinical outcomes in specific subsets of patients, but have little impact on the progression of pulmonary vascular remodeling. Upon new advances in vector development and delivery techniques, gene therapy is a novel strategy in this field with the potential of overcoming the main limitations of approved drug therapies: modulation of novel anti-remodeling targets and selective pulmonary vasculature targeting with minimal systemic effects...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910030/recurrent-cytogenetic-abnormalities-in-non-hodgkin-s-lymphoma-and-chronic-lymphocytic-leukemia
#17
Edmond S K Ma
Characteristic chromosomal translocations are found to be associated with subtypes of B-cell non-Hodgkin lymphoma (NHL), for example t(8;14)(q24;q32) and Burkitt lymphoma, t(14;18)(q32;q21) and follicular lymphoma, and t(11;14)(q13;q32) in mantle cell lymphoma. Only few recurrent cytogenetic aberrations have been identified in the T-cell NHL and the best known is the ALK gene translocation t(2;5)(p23;q35) in anaplastic large cell lymphoma. Since lymph node or other tissue is seldom submitted for conventional cytogenetics study, alternative approaches for translocation detection are polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909794/prescription-of-oral-antidiabetic-drugs-in-tyrol-data-from-the-tyrol-diabetes-registry-2012-2015
#18
Lukas Lunger, Andreas Melmer, Willi Oberaigner, Marco Leo, Martin Juchum, Karin Pölzl, Johannes Gänzer, Martha Innerebner, Egon Eisendle, Gertrud Beck, Hermann Kathrein, Bernhard Heindl, Hans Robert Schönherr, Monika Lechleitner, Herbert Tilg, Christoph Ebenbichler
Diabetes mellitus affects 9% of the adult population worldwide and the economic burden of the disease is growing exponentially. In type 2 diabetes mellitus (T2DM), when life style interventions fail to achieve treatment targets, oral antidiabetic drugs are prescribed to improve glycemic control. Several new oral antidiabetics have been launched in the last few years, which enlarged the spectrum of available treatment options in T2DM. The present study aimed to examine T2DM treatment patterns in a cohort of 7769 patients recruited from the Diabetes Registry Tyrol (DRT) with at least one visit from 2012-2015...
December 1, 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27909535/search-for-the-ideal-antithrombotic-drug-utopian-task-likely-is-implemented-already
#19
REVIEW
Petras Stirbys Md PhD
Atrial fibrillation is the most prevalent cardiac arrhythmia with a high risk of ischemic stroke. Thromboprophylaxis plays a key role in prevention of cardioembolic and non-cardioembolic events. Oral antithrombotic drugs are most often used to reduce hypercoagulable state. Patients may suffer from both under- and overtreatment compromising the outcomes. Medication peculiarities at large are well-known and widely debated. Non-adherence to antithrombotic drug regimen poses a significant risk of stroke. There is a pressing need for more detailed delineation of risk factors, namely by incorporation of the letter "N" (meaning "Non-adherence to drug therapy") into the well-known risk score alphanumeric display: CHA2DS2N-VASc...
August 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27909447/stem-cell-therapy-a-prospective-treatment-for-alzheimer-s-disease
#20
REVIEW
Ji Han Lee, Il-Hoan Oh, Hyun Kook Lim
Alzheimer's disease (AD) without cure remains as a serious health issue in the modern society. The major neuropathological alterations in AD are characterized by chronic neuroinflammation and neuronal loss due to neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau, plaques of β-amyloid (Aβ) and various metabolic dysfunctions. Due to the multifaceted nature of AD pathology and our limited understanding on its etiology, AD is difficult to be treated with currently available pharmaceuticals...
November 2016: Psychiatry Investigation
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