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Tumor resistence

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https://www.readbyqxmd.com/read/28732383/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#1
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732245/interleukin-4-receptor-targeted-delivery-of-bcl-xl-sirna-sensitizes-tumors-to-chemotherapy-and-inhibits-tumor-growth
#2
Padmanaban Guruprasath, Jihoon Kim, Gowri Rangaswamy Gunassekaran, Lianhua Chi, Soyoun Kim, Rang-Woon Park, Sang-Hyun Kim, Moon-Chang Baek, Sang Mun Bae, Sang-Yeob Kim, Dong-Kyu Kim, In-Kyu Park, Won-Jong Kim, Byungheon Lee
IL-4 receptor (IL-4R) is commonly up-regulated on tumor cells, and interactions between the receptor and Interleukin-4 (IL-4) can induce the expression of anti-apoptotic proteins, including Bcl-xL. This contributes to tumor cell survival and their resistance to chemotherapy. In this study, we exploited IL-4R-targeted delivery of Bcl-xL siRNA to IL-4R-expressing tumor cells in order to sensitize them to chemotherapy. To target IL-4R, an IL-4R-binding peptide, IL4RPep-1, was attached to branched polyethyleneimine-superparamagnetic iron oxide nanoparticles (BPEI-SPION)...
July 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28732213/comparison-of-blood-collection-tubes-from-three-different-manufacturers-for-the-collection-of-cell-free-dna-for-liquid-biopsy-mutation-testing
#3
Christina Alidousty, Danielle Brandes, Carina Heydt, Svenja Wagener, Maike Wittersheim, Stephan Christian Schäfer, Barbara Holz, Sabine Merkelbach-Bruse, Reinhard Büttner, Jana Fassunke, Anne Maria Schultheis
The improvement in sensitive techniques has allowed the detection of tumor-specific aberrations in circulating tumor (ct) DNA. Amplification-refractory mutation system PCR has been used for the analysis of ctDNA to detect resistance-causing mutations in the epidermal growth factor receptor gene (eg, EGFR T790M) in lung cancer patients. So far, Streck tubes have been widely used as standard blood collection tubes. Here, we compared blood collection tubes manufactured by Streck with tubes from Roche and Qiagen regarding their utility in stabilizing ctDNA in plasma samples...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28731456/upregulation-of-tet-activity-with-ascorbic-acid-induces-epigenetic-modulation-of-lymphoma-cells
#4
N Shenoy, T Bhagat, E Nieves, M Stenson, J Lawson, G S Choudhary, T Habermann, G Nowakowski, R Singh, X Wu, A Verma, T E Witzig
The Ten Eleven Translocation (TET) enzymes have been found to be mutated in both diffuse large B-cell (DLBCL) and peripheral T-cell (PTCL) lymphomas resulting in DNA hypermethylation. Recent studies in embryonal stem cells showed that ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity. We hypothesized that AA could potentially enhance TET activity in lymphoma cells to cause DNA demethylation, reactivate expression of tumor suppressor genes and enhance chemosensitivity...
July 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28731184/bufalin-reverses-acquired-drug-resistance-by-inhibiting-stemness-in-colorectal-cancer-cells
#5
Jian Sun, Ke Xu, Yanyan Qiu, Hong Gao, Jianhua Xu, Qingfeng Tang, Peihao Yin
Drug resistance is an obstacle to chemotherapy in tumor patients. Recent studies have shown that the high stemness of cancer cells may be induced by chemotherapeutic drugs, which is correlated with drug resistance. In the present study, we investigated the effects of bufalin on the stemness of colorectal cancer. We found that cisplatin could induce high stemness through the tumorsphere formation assay in vitro and in vivo in the colorectal cancer cell lines HCT116 and LoVo. In addition, cisplatin-treated tumorsphere cells showed drug‑resistant properties...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#6
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28731137/phosphorylation-of-bcl-2-plays-an-important-role-in-glycochenodeoxycholate-induced-survival-and-chemoresistance-in-hcc
#7
Maojun Zhou, Qi Zhang, Jinfeng Zhao, Mingmei Liao, Sailan Wen, Manyi Yang
Hepatocellular carcinoma (HCC) is a highly malignant tumor and can evolve rapidly to resistance to chemotherapies. Glycochenodeoxycholate (GCDA), which is toxic and hydrophobic, is the main ingredient in the bile and associated with carcinogenesis of gastrointenstinal tumors. Bcl-2 is the most important anti-apoptotic protein and overexpressed in various human tumors. In the present study, we found that GCDA can induce the chemoresistance of human liver cancer cells and specific depletion of Bcl-2 by RNA interference blocks GCDA-stimulated chemoresistance, which indicate the pivotal role of Bcl-2 in such process...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731026/the-novel-gene-ha117-promotes-in-vitro-and-in-vivo-drug-resistance-in-mouse-colon-tumor-cells
#8
Y X Guo, Y H Xu, G H Zheng, X Q Jin
In this study, we characterized the role of HA117, a novel gene we previously identified, in drug resistance in vitro and in vivo. Briefly, CT26 cells expressing HA117 were obtained by infection with a recombinant adenovirus, and tested for drug sensitivity by methyl thiazolyl tetrazolium assay. In addition, the effect of HA117 on drug sensitivity was assessed in CT26 colon tumors transplanted into nude mice. In vitro, expression of HA117 increased the resistance of CT26 cells to 5-fluorouracil 2.75 times (P<0...
July 21, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28730960/protein-kinases-as-tumor-biomarkers-and-therapeutic-targets
#9
Chuntao Quan, Juanjuan Xiao, Lin Liu, Qiuhong Duan, Ping Yuan, Feng Zhu
Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied in clinical settings and have achieved very good treatment efficacy, many cancer patients died of tumor metastasis, drug toxicity or drug resistance due to tumor heterogeneity. Targeted molecular treatments based on the genes, receptors, and kinases expressed by a tumor make individualized treatment possible...
July 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28730758/platinum-derivatives-a-multidisciplinary-approach
#10
Sinziana Gheorghe-Cetean, Calin Cainap, Luminita Oprean, Adriana Hangan, Piroska Virag, Eva Fischer-Fodor, Alexandra Gherman, Simona Cainap, Anne-Marie Constantin, Istvan Laszlo, Catalin Vlad, Radu Oprean
Cancer is one of the most difficult diseases to be treated. The particularities regarding the tumors' occurrence mechanism, their evolution under chemotherapy, disease-free interval, but also the increasing number of patients make cancer an intensively studied health domain. Although introduced in therapy since the early 80s, platinum derivatives play an essential role in anticancer therapy. Their use in therapy resulted in improving the patient quality of life and prolonging disease-free interval, which makes them still a benchmark for other anticancer compounds...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#11
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730338/jagged1-promotes-aromatase-inhibitor-resistance-by-modulating-tumor-associated-macrophage-differentiation-in-breast-cancer-patients
#12
Hang Liu, Jingxuan Wang, Minghui Zhang, Qijia Xuan, Zhipeng Wang, Xin Lian, Qingyuan Zhang
PURPOSE: Endocrine resistance limits the efficacy of anti-estrogen therapies. Notch signaling is involved in modulating tumor-associated macrophage (TAM) differentiation and is upregulated in endocrine-resistant breast cancer cells. Here, we analyzed the role of Jagged1 in the regulation of TAM polarization to investigate whether the Jagged1-Notch pathway promotes the acquisition of aromatase inhibitor (AI) resistance by upregulating TAM infiltration. METHODS: The Jagged1 expression levels and M2 TAM infiltration density, in 203 tumor samples from ER-positive postmenopausal patients, who received AI treatment, were evaluated by immunohistochemical staining and the results were compared with clincopathological parameters and survival...
July 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28730293/clinical-predictors-of-survival-in-patients-with-castration-resistant-prostate-cancer-receiving-sipuleucel-t-cellular-immunotherapy
#13
Mehmet Asim Bilen, Kenneth R Hess, Sumit K Subudhi, Ana Aparicio, Jeri Kim, Amado J Zurita-Saavedra, John C Araujo, Paul G Corn, Jessica Stover, Sue-Hwa Lin, Christopher J Logothetis, Shi-Ming Tu
BACKGROUND: We evaluated the patterns of progression and determined clinical predictors of survival in patients with castration-resistant prostate cancer (CRPCa) who received sipuleucel-T. METHODS: We retrospectively analyzed 56 consecutive patients with asymptomatic or minimally symptomatic CRPCa treated with sipuleucel-T. Age, number of bone metastases, history of prior systemic treatment, and alkaline phosphatase level (ALP) were tested as predictors of survival in a multivariate Cox proportional hazards regression model...
July 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28730141/extracellular-vesicles-as-modulators-of-tumor-microenvironment-and-disease-progression-in-glioma
#14
REVIEW
Abir Mondal, Divya Kumari Singh, Suchismita Panda, Anjali Shiras
Diffuse gliomas are lethal tumors of the central nervous system (CNS) characterized by infiltrative growth, aggressive nature, and therapeutic resistance. The recent 2016 WHO classification for CNS tumors categorizes diffuse glioma into two major types that include IDH wild-type glioblastoma, which is the predominant type and IDH-mutant glioblastoma, which is less common and displays better prognosis. Recent studies suggest presence of a distinct cell population with stem cell features termed as glioma stem cells (GSCs) to be causal in driving tumor growth in glioblastoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#15
Eliana Mc Tacconi, Xianning Lai, Cecilia Folio, Manuela Porru, Gijs Zonderland, Sophie Badie, Johanna Michl, Irene Sechi, Mélanie Rogier, Verónica Matía García, Ankita Sati Batra, Oscar M Rueda, Peter Bouwman, Jos Jonkers, Anderson Ryan, Bernardo Reina-San-Martin, Joannie Hui, Nelson Tang, Alejandra Bruna, Annamaria Biroccio, Madalena Tarsounas
Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. We demonstrate that inactivation of HR factors BRCA1, BRCA2, or RAD51 hypersensitizes cells to acetaldehyde treatment, in spite of the FA pathway being functional...
July 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28729428/fluorine-18-labeled-carboplatin-derivative-for-pet-imaging-of-platinum-drug-distribution
#16
Narottam Lamichhane, Gajanan K Dewkar, Sundaresan Gobalakrishnan, Li Wang, Purnima Jose, Muhammad Otabashi, Jean-Luc Morelle, Nicholas Farrell, Jamal Zweit
Increasing evidence indicates that reduced intracellular drug accumulation is the parameter most consistently associated with platinum drug resistance, and emphasizes the need to directly measure intra-tumor drug concentration. In the era of precision medicine and with the advent of powerful imaging and proteomics technologies, there is an opportunity to better understand drug resistance, by exploiting these techniques to provide new knowledge on drug-target interactions. Here, we are contributing to this endeavor by reporting on the development of a fluorine-18 labeled carboplatin derivative ((18)F-FCP) that can be used to potentially image drug uptake and retention, including intra-tumoral distribution, by positron emission tomography (PET)...
July 20, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28729417/mathematical-modeling-of-tumor-tumor-distant-interactions%C3%A2-supports-a-systemic-control-of-tumor-growth
#17
Sebastien Benzekry, Clare Lamont, Dominique Barbolosi, Lynn Hlatky, Philip Hahnfeldt
Interactions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, p<0...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28729403/autophagy-inhibition-improves-sunitinib-efficacy-in-pancreatic-neuroendocrine-tumors-via-a-lysosome-dependent-mechanism
#18
Tabea Wiedmer, Annika Blank, Sophia Pantasis, Lea Normand, Ruben Bill, Philippe Krebs, Mario P Tschan, Ilaria Marinoni, Aurel Perren
Increasing the efficacy of approved systemic treatments in metastasized pancreatic neuroendocrine tumors (PanNETs) is an unmet medical need. The anti-angiogenic tyrosine kinase inhibitor sunitinib is approved for PanNET treatment. Additionally, sunitinib is a lysosomotropic drug and such drugs can induce lysosomal membrane permeabilization as well as autophagy. We investigated sunitinib-induced autophagy as a possible mechanism of PanNET therapy resistance. Sunitinib accumulated in lysosomes and induced autophagy in PanNET cell lines...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28729402/wilms-tumor-ncam-expressing-cancer-stem-cells-as-potential-therapeutic-target-for-polymeric-nanomedicine
#19
Ela Markovsky, Einav Vax, Dikla Ben-Shushan, Anat Eldar-Boock, Rachel Shukrun, Eilam Yeini, Iris Barshack, Revital Caspi, Orit Harari-Steinberg, Naomi Pode-Shakked, Benjamin Dekel, Ronit Satchi-Fainaro
Cancer stem cells (CSC) form a specific population within the tumor that has been shown to have self-renewal and differentiation properties, increased ability to migrate and form metastases, and increased resistance to chemotherapy. Consequently, even a small number of cells remaining after therapy can repopulate the tumor and cause recurrence of the disease. CSCs in Wilms tumor, a pediatric renal cancer, were previously shown to be characterized by neural cell adhesion molecule (NCAM) expression. Therefore, NCAM provides a specific biomarker through which the CSC population in this tumor can be targeted...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28729142/nocardia-farcinica-brain-abscess-report-of-3-cases
#20
Ana Galacho-Harriero, Pedro D Delgado-López, Maria P Ortega-Lafont, Javier Martín-Alonso, José M Castilla-Díez, Belen Sánchez-Borge
BACKGROUND: Central nervous system nocardial infection is a rarely reported disease that usually affects patients with predisposing and debilitating conditions but also the immunocompetent population. The most common variant affecting the brain is Nocardia farcinica. Management of brain nocardiosis is troublesome and requires consideration of the severity of the underlying systemic disease, the difficulties in identifying the bacterium and the frequent delay in initiating adequate therapy...
July 17, 2017: World Neurosurgery
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