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https://www.readbyqxmd.com/read/28743125/surfactant-protein-b-suppresses-lung-cancer-progression-by-inhibiting-secretory-phospholipase-a2-activity-and-arachidonic-acid-production
#1
Sungmin Lee, Daehoon Kim, JiHoon Kang, EunGi Kim, Wanyeon Kim, HyeSook Youn, BuHyun Youn
BACKGROUND/AIMS: Radiotherapy is applied to patients with inoperable cancer types including advanced stage non-small cell lung cancer (NSCLC) and radioresistance functions as a critical obstacle in radiotherapy. This study was aimed to investigate the mechanism of radioresistance regulated by surfactant protein B (SP-B). METHODS: To investigate the role of SP-B in radioresistance, ΔSFTPB A549 cell line was established and SP-B expression was analyzed. In response to ionizing radiation (IR), the change of SP-B expression was analyzed in A549 and NCI-H441 cell lines...
July 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28741052/applying-near-infrared-photoimmunotherapy-to-b-cell-lymphoma-comparative-evaluation-with-radioimmunotherapy-in-tumor-xenografts
#2
Yusri-Dwi Heryanto, Hirofumi Hanaoka, Takahito Nakajima, Aiko Yamaguchi, Yoshito Tsushima
OBJECTIVE: Radioimmunotherapy (RIT) has proven effective for patients with relapsed and refractory lymphoma. However, new types of therapy are strongly desired as B-cell lymphoma remains incurable for many patients. Photoimmunotherapy (PIT) is an emerging targeted cancer therapy that uses photosensitizer (IR700)-conjugated monoclonal antibodies (mAbs) to specifically kill cancer cells. To evaluate the usefulness and potential role of PIT for treating B-cell lymphoma in a comparison with RIT, we performed in vivo PIT and RIT studies with an IR700 or (90)Y-conjugated anti-CD20 mAb, NuB2...
July 24, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28740549/targeted-delivery-to-tumor-associated-pericytes-via-an-affibody-with-high-affinity-for-pdgfr%C3%AE-enhances-the-in-vivo-antitumor-effects-of-human-trail
#3
Ze Tao, Hao Yang, Qiuxiao Shi, Qing Fan, Lin Wan, Xiaofeng Lu
Human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) has exhibited superior in vitro cytotoxicity in a variety of tumor cells. However, hTRAIL showed a disappointing anticancer effect in clinical trials, although hTRAIL-based regimens were well tolerated. One important reason might be that hTRAIL was largely trapped by its decoy receptors, which are ubiquitously expressed on normal cells. Tumor-targeted delivery might improve the tumor uptake and thus enhance the antitumor effect of hTRAIL...
2017: Theranostics
https://www.readbyqxmd.com/read/28738876/enterolactone-has-stronger-effects-than-enterodiol-on-ovarian-cancer
#4
Huidi Liu, Jianrui Liu, Siwen Wang, Zheng Zeng, Ting Li, Yongfang Liu, Emilio Mastriani, Qing-Hai Li, Hong-Xia Bao, Yu-Jie Zhou, Xiaoyu Wang, Sijing Hu, Shan Gao, Yingying Qi, Zhihang Shen, Hongyue Wang, Miao Yu, Tingting Gao, Randal N Johnston, Shu-Lin Liu
BACKGROUND: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases...
July 24, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28738498/microrna-299-3p-suppresses-proliferation-and-invasion-by-targeting-vegfa-in-human-colon-carcinoma
#5
Jia-Yong Wang, Jin-Bo Jiang, Yuan Li, Yan-Lei Wang, Yong Dai
Accumulating evidences have shown that microRNAs (miRNAs) are vital regulators and possess huge capabilities in post-transcriptional control. Although a large number of miRNAs have been identified to be dysregulated in human cancers especially in colon cancer, our understandings of the function of most miRNAs are still largely limited. In this study, we have demonstrated that miR-299-3p plays a critical role in suppressing colon carcinoma progression by targeting Vascular Endothelial Growth Factor A (VEGFA)...
July 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28736425/cd133-regulates-il-1beta-signaling-and-neutrophil-recruitment-in-glioblastoma
#6
Seon Yong Lee, Jun-Kyum Kim, Hee-Young Jeon, Seok Won Ham, Hyunggee Kim
CD133, a pentaspan transmembrane glycoprotein, is generally used as a cancer stem cell marker in various human malignancies, but its biological function in cancer cells, especially in glioma cells, is largely unknown. Here, we demonstrated that forced expression of CD133 increases the expression of IL-1beta and its downstream chemokines, namely, CCL3, CXCL3 and CXCL5, in U87MG glioma cells. Although there were no apparent changes in cell growth and sphere formation in vitro and tumor growth in vivo, in vitro trans-well studies and in vivo tumor xenograft assays showed that neutrophil recruitment was markedly increased by the ectopic expression of CD133...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28735070/suppression-of-the-atp-binding-cassette-transporter-abcc4-impairs-neuroblastoma-tumour-growth-and-sensitises-to-irinotecan-in%C3%A2-vivo
#7
Jayne Murray, Emanuele Valli, Denise M T Yu, Alan M Truong, Andrew J Gifford, Georgina L Eden, Laura D Gamble, Kimberley M Hanssen, Claudia L Flemming, Alvin Tan, Amanda Tivnan, Sophie Allan, Federica Saletta, Leanna Cheung, Michelle Ruhle, John D Schuetz, Michelle J Henderson, Jennifer A Byrne, Murray D Norris, Michelle Haber, Jamie I Fletcher
The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts...
July 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28734227/continuous-delivery-of-neutralizing-antibodies-elevate-ccl2-levels-in-mice-bearing-mcf10ca1d-breast-tumor-xenografts
#8
Min Yao, Curtis Smart, Qingting Hu, Nikki Cheng
Chemokines are small soluble molecules that play critical roles in wound healing, infection, and cancer progression. In particular, overexpression of the C-C motif chemokine ligand 2 (CCL2) in multiple cancer types correlates with poor patient prognosis. Animal studies have shown that CCL2 signals to macrophages and breast cancer cells to promote tumor growth, invasion, and metastasis, indicating that CCL2 is a promising therapeutic target. However, the effectiveness of human-specific neutralizing antibodies has not been fully evaluated...
July 19, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28733520/the-ketogenic-diet-is-not-feasible-as-a-therapy-in-a-cd-1-nu-nu-mouse-model-of-renal-cell-carcinoma-with-features-of-stauffer-s-syndrome
#9
Silvia Vidali, Sepideh Aminzadeh-Gohari, René Günther Feichtinger, Renaud Vatrinet, Andreas Koller, Felix Locker, Tricia Rutherford, Maura O'Donnell, Andrea Stöger-Kleiber, Bridget Lambert, Thomas Klaus Felder, Wolfgang Sperl, Barbara Kofler
The ketogenic diet (KD), a high-fat low-carbohydrate diet, has shown some efficacy in the treatment of certain types of tumors such as brain tumors and neuroblastoma. These tumors are characterized by the Warburg effect. Because renal cell carcinoma (RCC) presents similar energetic features as neuroblastoma, KD might also be effective in the treatment of RCC. To test this, we established xenografts with RCC 786-O cells in CD-1 nu/nu mice and then randomized them to a control diet or to KDs with different triglyceride contents...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733443/direct-metabolic-interrogation-of-dihydrotestosterone-biosynthesis-from-adrenal-precursors-in-primary-prostatectomy-tissues
#10
Charles Dai, Yoon-Mi Chung, Evan Kovac, Ziqi Zhu, Jianneng Li, Cristina Magi-Galluzzi, Andrew J Stephenson, Eric A Klein, Nima Sharifi
Purpose: A major mechanism of castration-resistant prostate cancer (CRPC) involves intratumoral biosynthesis of dihydrotestosterone (DHT) from adrenal precursors. We have previously shown that adrenal-derived androstenedione (AD) is the preferred substrate over testosterone (T) for 5α-reductase expressed in metastatic CRPC, bypassing T as an obligate precursor to DHT. However, the metabolic pathway of adrenal-derived DHT biosynthesis has not been rigorously investigated in the setting of primary disease in the prostate...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#11
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/28732214/crispr-cas9-technology-based-xenograft-tumors-as-candidate-reference-materials-for-multiple-eml4-alk-rearrangements-testing
#12
Rongxue Peng, Rui Zhang, Guigao Lin, Xin Yang, Ziyang Li, Kuo Zhang, Jiawei Zhang, Jinming Li
The echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (EML4-ALK) rearrangement is an important biomarker that plays a pivotal role in therapeutic decision making for non-small-cell lung cancer (NSCLC) patients. Ensuring accuracy and reproducibility of EML4-ALK testing by fluorescence in situ hybridization, immunohistochemistry, RT-PCR, and next-generation sequencing requires reliable reference materials for monitoring assay sensitivity and specificity...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28732118/pd-1-checkpoint-blockade-in-combination-with-an-mtor-inhibitor-restrains-hepatocellular-carcinoma-growth-induced-by-hepatoma-cell-intrinsic-pd-1
#13
Hui Li, Xiaoqiang Li, Shuang Liu, Lei Guo, Bo Zhang, Jubo Zhang, Qinghai Ye
Inhibitors of PD-1 administered as single agents have resulted in durable tumor regression in advanced cancer patients. However, only a minority of cancer patients respond to anti PD-1 immunotherapy. Here, we show that PD-1 expression in hepatocellular carcinoma (HCC) promotes tumor growth independently of adaptive immunity. Knockdown of PD-1 suppress tumor growth, whereas PD-1 overexpression enhances tumorigenesis in immunodeficient xenografted mice. Mechanistically, PD-1 binds the downstream mTOR effectors eukaryotic initiation factor 4E (eIF4E) and ribosomal protein S6 (S6), thus promoting their phosphorylation...
July 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#14
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
#15
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/28729405/super-enhancer-analysis-defines-novel-epigenomic-subtypes-of-non-apl-aml-including-an-rar%C3%AE-dependency-targetable-by-sy-1425-a-potent-and-selective-rar%C3%AE-agonist
#16
Michael R McKeown, M Ryan Corces, Matthew L Eaton, Chris Fiore, Emily Lee, Jeremy T Lopez, Mei Wei Chen, Darren Smith, Steven M Chan, Julie L Koenig, Kathryn Austgen, Matt G Guenther, David A Orlando, Jakob Lovén, Christian C Fritz, Ravindra Majeti
We characterized the enhancer landscape of 66 AML patients, identifying 6 novel subgroups and their associated regulatory loci. These subgroups are defined by their super-enhancer (SE) maps, orthogonal to somatic mutations, and are associated with distinct leukemic cell states. Examination of transcriptional drivers for these epigenomic subtypes uncovers a subset of patients with a particularly strong super-enhancer at the retinoic acid receptor alpha (RARA) gene locus. Presence of a RARA SE and concomitant high levels of RARA mRNA predisposes cell lines and ex vivo models to exquisite sensitivity to a selective agonist of RARα, SY-1425 (tamibarotene)...
July 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28729399/decitabine-priming-enhances-mucin-1-inhibition-mediated-disruption-of-redox-homeostasis-in-cutaneous-t-cell-lymphoma
#17
Salvia Jain, Abigail Washington, Rebecca Karp Leaf, Parul Bhargava, Rachael A Clark, Thomas S Kupper, Dina Stroopinsky, Athalia Pyzer, Leandra Cole, Myrna Nahas, Arie Apel, Jacalyn Rosenblatt, Jon Arnason, Donald Kufe, David Avigan
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous neoplasm and patients with relapsed/refractory disease exhibit resistance to standard therapies. We have previously demonstrated that the MUC1-C oncoprotein plays a critical role in protection from oxidative stress in CTCL cells. Targeting of MUC1-C with a pharmacologic inhibitor, GO-203, was associated with apoptosis in CTCL. However, disease responses were incomplete underscoring the need for combinatorial strategies that could exploit the vulnerability of CTCL cells to oxidative signals...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28729397/the-igf1r-insr-inhibitor-bi-885578-selectively-inhibits-growth-of-igf2-overexpressing-colorectal-cancer-tumors-and-potentiates-the-efficacy-of-anti-vegf-therapy
#18
Michael P Sanderson, Marco H Hofmann, Pilar Garin-Chesa, Norbert Schweifer, Andreas Wernitznig, Stefan Fischer, Astrid Jeschko, Reiner Meyer, Jurgen Moll, Thomas Pecina, Heribert Arnhof, Ulrike Weyer-Czernilofsky, Stephan K Zahn, Günther R Adolf, Norbert Kraut
Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28728846/the-effects-of-type-i-interferon-on-glioblastoma-cancer-stem-cells
#19
Ziyun Du, Chun Cai, Michelle Sims, Frederick A Boop, Andrew M Davidoff, Lawrence M Pfeffer
Glioblastomas (GBMs) are highly invasive brain tumors that are extremely deadly. The highly aggressive nature of GBM as well as its heterogeneity at the molecular and cellular levels has been attributed to a rare subpopulation of GBM stem-like cells (GSCs). Interferons (IFNs) are a family of endogenous antiviral proteins that have anticancer activity in vitro, and have been used clinically to treat GBM. IFN inhibits the proliferation of various established GBM cell lines, but the effects of IFNs on GSCs remain relatively unknown...
July 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28726783/kmt2a-promotes-melanoma-cell-growth-by-targeting-htert-signaling-pathway
#20
Changlin Zhang, Chen Song, Tianze Liu, Ranran Tang, Miao Chen, Fan Gao, Binyi Xiao, Ge Qin, Fen Shi, Wenbin Li, Yixin Li, Xiaoyan Fu, Dingbo Shi, Xiangsheng Xiao, Lan Kang, Wenlin Huang, Xiaojun Wu, Bing Tang, Wuguo Deng
Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway...
July 20, 2017: Cell Death & Disease
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