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https://www.readbyqxmd.com/read/28089569/prevention-of-dietary-fat-fueled-ketogenesis-attenuates-braf-v600e-tumor-growth
#1
Siyuan Xia, Ruiting Lin, Lingtao Jin, Liang Zhao, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Guoqing Qian, Zhiyu Qian, Evmorfia Konstantakou, Baotong Zhang, Jin-Tang Dong, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Lu Zhou, Ragini R Kudchadkar, David H Lawson, Hanna J Khoury, Fadlo R Khuri, Lawrence H Boise, Sagar Lonial, Benjamin H Lee, Brian P Pollack, Jack L Arbiser, Jun Fan, Qun-Ying Lei, Jing Chen
Lifestyle factors, including diet, play an important role in the survival of cancer patients. However, the molecular mechanisms underlying pathogenic links between diet and particular oncogenic mutations in human cancers remain unclear. We recently reported that the ketone body acetoacetate selectively enhances BRAF V600E mutant-dependent MEK1 activation in human cancers. Here we show that a high-fat ketogenic diet increased serum levels of acetoacetate, leading to enhanced tumor growth potential of BRAF V600E-expressing human melanoma cells in xenograft mice...
January 9, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28088520/palmitic-acid-increases-invasiveness-of-pancreatic-cancer-cells-aspc-1-through-tlr4-ros-nf-%C3%AE%C2%BAb-mmp-9-signaling-pathway
#2
Makena J Binker-Cosen, Daniel Richards, Brenda Oliver, Herbert Y Gaisano, Marcelo G Binker, Laura I Cosen-Binker
Pancreatic cancer (PC) is an aggressive malady with proclivity for early metastasis. Overexpression of toll-like receptor 4 (TLR4) in pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, correlates to tumor size, lymph node involvement, venous invasion and pathological stage. Lipopolysaccharides (LPS) are natural TLR4 ligands that have been shown to increase the invasive ability of PC cells. However, rapid inactivation of circulating LPS and low systemic absorption of inhaled LPS from the bronchoalveolar compartment make other agonists such as saturated fatty acids more suitable to be considered for TLR4-related cell invasiveness...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28087485/stepwise-targeted-drug-delivery-to-liver-cancer-cells-for-enhanced-therapeutic-efficacy-by-galactose-grafted-ultra-ph-sensitive-micelles
#3
Guoqing Yan, Jun Wang, Liefeng Hu, Xin Wang, Guanqing Yang, Shengxiang Fu, Xu Cheng, Panpan Zhang, Rupei Tang
: To promote drug accumulation and cell-killing ability at tumor tissue, we have prepared a stepwise targeted drug delivery system that can remain stealthy and long-circulating in the blood vessels, improve drug retention at extracellular stimuli, enhance cellular uptake through special targeting ligands, and then achieve rapid drug release to improve toxicity to tumor cells at intracellular stimuli. Herein, galactose-grafted, ultra-pH-sensitive drug carriers (POEAd-g-LA-DOX micelles), which could respond to both extracellular and intracellular pH, and combine with galactose-receptors in cell membrane, were constructed by a facile method, therefore achieving: (i) remaining stable at pH 7...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28086834/detection-of-circulating-tumor-cells-with-ck20-rt-pcr-is-an-independent-negative-prognostic-marker-in-colon-cancer-patients-a-prospective-study
#4
Sebastian Hinz, Alexander Hendricks, Amke Wittig, Clemens Schafmayer, Jürgen Tepel, Holger Kalthoff, Thomas Becker, Christian Röder
BACKGROUND: Detection of circulating (CTC) or disseminated tumor cells (DTC) has been associated with negative prognosis and outcome in patients with colorectal cancer, though testing for these cells is not yet part of clinical routine. There are several different methodological approaches to detect tumor cells but standardized detection assays are not implemented so far. METHODS: In this prospective monocentric study 299 patients with colon cancer were included...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28086824/d-dimer-is-an-essential-accompaniment-of-circulating-tumor-cells-in-gastric-cancer
#5
Dongmei Diao, Yao Cheng, Yongchun Song, Hao Zhang, Zhangjian Zhou, Chengxue Dang
BACKGROUND: Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it's stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients. METHODS: We first verified our hypothesis in different murine gastric cancer metastasis models in vivo, plasma D-dimer and fibrinogen as well as its degradation products were directly examined in three metastasis immune-deficient mouse models and in controls...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28081183/circulating-cell-free-dna-in-dogs-with-mammary-tumors-short-and-long-fragments-and-integrity-index
#6
Giorgia Beffagna, Alessandro Sammarco, Chiara Bedin, Chiara Romualdi, Marta Mainenti, Antonio Mollo, Laura Cavicchioli, Silvia Ferro, Davide Trez, Raffaella De Maria, Donato Nitti, Andrea Saccani, Michelangelo Campanella, Marco Agostini, Valentina Zappulli
Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs...
2017: PloS One
https://www.readbyqxmd.com/read/28079367/robust-responsive-and-targeted-plga-anticancer-nanomedicines-by-combining-reductively-cleavable-surfactant-and-covalent-hyaluronic-acid-coating
#7
Jintian Wu, Jian Zhang, Chao Deng, Fenghua Meng, Ru Cheng, Zhiyuan Zhong
PLGA-based nanomedicines have enormous potential for targeted cancer therapy. To boost their stability, targetability and intracellular drug release, here we developed novel multifunctional PLGA anticancer nanomedicines by combining a reductively cleavable surfactant (RCS), vitamin E-SS-oligo(methyl diglycol L-glutamate), with covalent hyaluronic acid (HA) coating. Reduction-sensitive HA-coated PLGA nanoparticles (rHPNPs) were obtained with small sizes of 55 - 61 nm and zeta potentials of -26.7 - -28.8 mV at 18...
January 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#8
Ainhoa Arina, Theodore G Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
January 11, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28076321/secretion-modification-region-derived-peptide-blocks-exosome-release-and-mediates-cell-cycle-arrest-in-breast-cancer-cells
#9
Ming-Bo Huang, Ruben R Gonzalez, James Lillard, Vincent C Bond
PURPOSE: Discovery and development of a novel anticancer PEG-SMR-Clu peptide to prevent breast cancer metastasis. How breast cancer cells and primary mammary epithelial cells interact and communicate with each other to promote tumorigenesis and how to prevent tumor metastasis has long been a concern of researchers. Cancer cells secrete exosomes containing proteins and RNA. These factors can influence tumor development by directly targeting cancer cells and tumor stroma. In this study, we determined the effects of a peptide as an inhibitor of exosome secretion on breast tumors...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075552/nanoparticles-coated-with-neutrophil-membranes-can-effectively-treat-cancer-metastasis
#10
Ting Kang, Qianqian Zhu, Dan Wei, Jingxian Feng, Jianhui Yao, Tianze Jiang, Qingxiang Song, Xunbin Wei, Hong-Zhuan Chen, Xiaoling Gao, Jun Chen
The dissemination, seeding and colonization of circulating tumor cells (CTC) serves as the root of distant metastasis. As a key step in the early stage of metastasis formation, colonization of CTC in the (pre-) metastatic niche appears to be a valuable target. Evidence showed that inflammatory neutrophils possess both CTC- and niche-targeting property by the intrinsic cell adhesion molecules on neutrophils. Inspired by this mechanism, we developed a nanosize neutrophil-mimicking drug delivery system (NM-NP) by coating neutrophils membranes on the surface of poly (latic-co-glycolic acid) nanoparticles (NP)...
January 11, 2017: ACS Nano
https://www.readbyqxmd.com/read/28074906/antiproliferative-effects-of-1%C3%AE-oh-vitd3-in-malignant-melanoma-potential-therapeutic-implications
#11
Lucia Spath, Alessandra Ulivieri, Luca Lavra, Laura Fidanza, Marta Carlesimo, Maria Giubettini, Alessandra Narcisi, Emidio Luciani, Barbara Bucci, Daniela Pisani, Salvatore Sciacchitano, Armando Bartolazzi
Early detection and surgery represent the mainstay of treatment for superficial melanoma, but for high risk lesions (Breslow's thickness >0.75 mm) an effective adjuvant therapy is lacking. Vitamin D insufficiency plays a relevant role in cancer biology. The biological effects of 1α hydroxycholecalciferol on experimental melanoma models were investigated. 105 melanoma patients were checked for 25-hydroxycholecalciferol (circulating vitamin D) serum levels. Human derived melanoma cell lines and in vivo xenografts were used for studying 1α-hydroxycholecalciferol-mediated biological effects on cell proliferation and tumor growth...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073899/paper-based-microrna-expression-profiling-from-plasma-and-circulating-tumor-cells
#12
Sai Mun Leong, Karen Mei-Ling Tan, Hui Wen Chua, Mo-Chao Huang, Wai Chye Cheong, Mo-Huang Li, Steven Tucker, Evelyn Siew-Chuan Koay
BACKGROUND: Molecular characterization of circulating tumor cells (CTCs) holds great promise for monitoring metastatic progression and characterizing metastatic disease. However, leukocyte and red blood cell contamination of routinely isolated CTCs makes CTC-specific molecular characterization extremely challenging. METHODS: Here we report the use of a paper-based medium for efficient extraction of microRNAs (miRNAs) from limited amounts of biological samples such as rare CTCs harvested from cancer patient blood...
January 10, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28073294/circulating-tumor-cells-and-dna-for-real-time-egfr-detection-and-monitoring-of-non-small-cell-lung-cancer
#13
Jinfeng He, Wei Tan, Jingping Ma
AIM: We investigate the suitability of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in non-small-cell lung cancer management, which is challenging in conventional biopsies. MATERIALS & METHODS: We performed serial blood extraction from 120 patients of varying EGFR status. Molecular profiling was performed using droplet digital PCR and correlated to survival outcome. RESULTS: Overall, we observed 95% agreement using CTCs and ctDNA with conventional tissue biopsies, which indicated the disease's close correlation...
January 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28071891/dual-enzymatic-reaction-assisted-gemcitabine-delivery-systems-for-programmed-pancreatic-cancer-therapy
#14
Haijie Han, Daniel Valdeperez, Qiao Jin, Bin Yang, Zuhong Li, Yulian Wu, Beatriz Pelaz, Wolfgang J J Parak, Jian Ji
Dual enzymatic reactions were introduced to fabricate programmed gemcitabine (GEM) nanovectors for targeted pancreatic cancer therapy. Dual-enzyme sensitive GEM nanovectors were prepared by conjugation of matrix metalloproteinase-9 (MMP-9) detachable poly(ethylene glycol) (PEG), cathepsin B cleavable GEM, and targeting ligand CycloRGD to CdSe/ZnS quantum dots (QDs). The GEM nanovectors decorated with PEG corona could avoid nonspecific interactions and exhibit prolonged blood circulation time. After GEM nanovectors were accumulated in tumor tissue by the enhanced permeability and retention (EPR) effect, the PEG corona can be removed by overexpressed MMP-9 in tumor tissue and RGD would be exposed, which was capable of facilitating cellular internalization...
January 10, 2017: ACS Nano
https://www.readbyqxmd.com/read/28071889/enzyme-and-redox-dual-triggered-intracellular-release-from-actively-targeted-polymeric-micelles
#15
Lei Zhang, Yi Wang, Xiaobin Zhang, Xiao Wei, Xiang Xiong, Shaobing Zhou
Highly effective delivery of therapeutic agents into target cells using nanocarriers and subsequently rapid intracellular release are of great importance in cancer treatment. Here, we developed an enzyme and redox dual-responsive polymeric micelle with active targeting abilities to achieve rapid intracellular drug release. To overcome both its poor solubility in water and instability in the blood circulation, camptothecin (CPT) was chemically conjugated to monomethyl poly(ethylene glycol) (mPEG) via a redox-responsive linker to form polymeric prodrugs...
January 10, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28070168/circulating-tumor-microemboli-ctm-and-vimentin-circulating-tumor-cells-ctcs-detected-by-a-size-based-platform-predict-worse-prognosis-in-advanced-colorectal-cancer-patients-during-chemotherapy
#16
Dejun Zhang, Lei Zhao, Pengfei Zhou, Hong Ma, Fang Huang, Min Jin, Xiaomeng Dai, Xiumei Zheng, Shaoyi Huang, Tao Zhang
BACKGROUND: Circulating tumor cells (CTCs) detected in peripheral blood (PB) of cancer patients can be identified as isolated CTCs and circulating tumor microemboli (CTM). This study aimed to evaluate the prognostic value of CTM detection and CTC phenotype in advanced colorectal cancer (CRC) patients during chemotherapy. METHODS: A size-based platform for CTC isolation was applied. PB samples (5 ml) from 98 advanced CRC patients during 2-6 cycles chemotherapy were collected for CTC detection, and CTC count was correlated to patient's clinicopathological characteristics and clinical outcome...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28069554/encapsulation-of-two-different-tlr-ligands-into-liposomes-confer-protective-immunity-and-prevent-tumor-development
#17
Banu Bayyurt, Gizem Tincer, Kubra Almacioglu, Esin Alpdundar, Mayda Gursel, Ihsan Gursel
Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading...
January 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28068321/analysis-of-dna-methylation-in-single-circulating-tumor-cells
#18
C F Pixberg, K Raba, F Müller, B Behrens, E Honisch, D Niederacher, H Neubauer, T Fehm, W Goering, W A Schulz, P Flohr, G Boysen, M Lambros, J S De Bono, W T Knoefel, C Sproll, N H Stoecklein, R P L Neves
Direct analysis of circulating tumor cells (CTCs) can inform on molecular mechanisms underlying systemic spread. Here we investigated promoter methylation of three genes regulating epithelial-to-mesenchymal transition (EMT), a key mechanism enabling epithelial tumor cells to disseminate and metastasize. For this, we developed a single-cell protocol based on agarose-embedded bisulfite treatment, which allows investigating DNA methylation of multiple loci via a multiplex PCR (multiplexed-scAEBS). We established our assay for the simultaneous analysis of three EMT-associated genes miR-200c/141, miR-200b/a/429 and CDH1 in single cells...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28065871/targeted-glioma-chemotherapy-by-cyclic-rgd-peptide-functionalized-reversibly-core-crosslinked-multifunctional-poly-ethylene-glycol-b-poly-%C3%AE%C2%B5-caprolactone-micelles
#19
Ya Fang, Yu Jiang, Yan Zou, Fenghua Meng, Jian Zhang, Chao Deng, Huanli Sun, Zhiyuan Zhong
: Cyclic RGD peptide-functionalized reversibly core-crosslinked biodegradable poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) micelles (cRGD-RCCMs) were designed and developed for highly potent and targeted glioma chemotherapy. To achieve crosslinkable core, dithiolane-functionalized trimethylene carbonate (DTC) was incorporated into PCL block. Interestingly, cRGD-RCCMs displayed a high doxorubicin (DOX) loading content of ∼18 wt.%, small hydrodynamic size of ∼50 nm, and excellent colloidal stability with minimum drug leakage under physiological conditions whilst fast DOX release under cytoplasmic-mimicking reductive environments...
January 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28064546/targeting-protein-kinase-b3-akt3-signaling-in-melanoma
#20
SubbaRao V Madhunapantula, Gavin P Robertson
Deregulated Akt activity leading to apoptosis inhibition, enhanced proliferation and drug resistance has been shown to be responsible for 35-70% of advanced metastatic melanomas. Of the three isoforms, the majority of melanomas have elevated Akt3 expression and activity. Hence, potent inhibitors targeting Akt are urgently required, which is possible only if (a) the factors responsible for the failure of Akt inhibitors in clinical trials is known; and (b) the information pertaining to synergistically acting targeted therapeutics is available...
January 9, 2017: Expert Opinion on Therapeutic Targets
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