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https://www.readbyqxmd.com/read/29016926/activation-of-wee1-confers-resistance-to-pi3k-inhibition-in-glioblastoma
#1
Shaofang Wu, Shuzhen Wang, Feng Gao, Luyuan Li, Siyuan Zheng, W K Alfred Yung, Dimpy Koul
Background: Oncogenic activation of phosphatidylinositol-3 kinase (PI3K) signaling plays a pivotal role in the development of glioblastoma (GBM). However, pharmacological inhibition of PI3K has so far not been therapeutically successful due to adaptive resistance through a rapid rewiring of cancer cell signaling. Here we identified that WEE1 is activated after transient exposure to PI3K inhibition and confers resistance to PI3K inhibition in GBM. Methods: Patient-derived glioma-initiating cells and established GBM cells were treated with PI3K inhibitor or WEE1 inhibitor alone or in combination, and cell proliferation was evaluated by CellTiter-Blue assay...
July 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28938619/anti-cancer-efficacy-of-biotinylated-chitosan-nanoparticles-in-liver-cancer
#2
Mingrong Cheng, Weiping Zhu, Qing Li, Dejian Dai, Yiming Hou
The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen(-1) nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1:1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900514/microrna-647-targets-srf-myh9-axis-to-suppress-invasion-and-metastasis-of-gastric-cancer
#3
Gengtai Ye, Kunzhai Huang, Jiang Yu, Liying Zhao, Xianjun Zhu, Qingbin Yang, Wende Li, Yuming Jiang, Baoxiong Zhuang, Hao Liu, Zhiyong Shen, Da Wang, Li Yan, Lei Zhang, Haipeng Zhou, Yanfeng Hu, Haijun Deng, Hao Liu, Guoxin Li, Xiaolong Qi
MicroRNAs (miRNAs) play important roles in regulating tumour development and progression. Here we show that miR-647 is repressed in gastric cancer (GC), and associated with GC metastasis. Moreover, we identify that miR-647 can suppress GC cell migration and invasion in vitro. Mechanistically, we confirm miR-647 directly binds to the 3' untranslated regions of SRF mRNA, and SRF binds to the CArG box located at the MYH9 promoter. CCG-1423, an inhibitor of RhoA/SRF-mediated gene transcription, inhibits the expression of MYH9, especially in SRF downregulated cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28791352/establishment-of-a-murine-pancreatic-cancer-pain-model-and-microarray-analysis-of-pain%C3%A2-associated-genes-in-the-spinal-cord-dorsal-horn
#4
Liqin Wang, Huihong Xu, Yanhu Ge, Hai Zhu, Dawei Yu, Weifeng Yu, Zhijie Lu
There is emerging evidence on the mechanisms of pancreatic cancer pain. Following the establishment of an orthotropic transplantation model of pancreatic cancer, microarray analysis was performed to identify changes in the expression levels of pain‑associated genes in the spinal cord. A mouse model of pancreatic cancer‑induced pain was established by implanting SW 1990 cells into the pancreases of female BALB/c‑nu mice. The survival rate and body weight were measured following orthotropic transplantation...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28758198/mir-15a-16-deficiency-enhances-anti-tumor-immunity-of-glioma-infiltrating-cd8-t-cells-through-targeting-mtor
#5
Jiao Yang, Ronghua Liu, Yuting Deng, Jiawen Qian, Zhou Lu, Yuedi Wang, Dan Zhang, Feifei Luo, Yiwei Chu
MiR-15a/16, a miRNA cluster located at chromosome 13q14, has been reported to act as an immune regulator in inflammatory disorders besides its aberrant expression in cancers. However, little is known about its regulation in tumor-infiltrating immune cells. In our study, using an orthotropic GL261 mouse glioma model, we found that miR-15a/16 deficiency in host inhibited tumor growth and prolonged mice survival, which might be associated with the accumulation of tumor-infiltrating CD8+ T cells. More importantly, tumor-infiltrating CD8+ T cells without miR-15a/16 showed lower expression of PD-1, Tim-3 and LAG-3, and stronger secretion of IFN-γ, IL-2 and TNF-α than WT tumor-infiltrating CD8+ T cells...
November 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28754854/anti-cancer-efficacy-of-biotinylated-chitosan-nanoparticles-in-liver-cancer
#6
Mingrong Cheng, Weiping Zhu, Qing Li, Dejian Dai, Yiming Hou
The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1:1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28645267/a-rapid-and-quantitative-method-to-detect-human-circulating-tumor-cells-in-a-preclinical-animal-model
#7
Shih-Hsin Tu, Yi-Chen Hsieh, Li-Chi Huang, Chun-Yu Lin, Kai-Wen Hsu, Wen-Shyang Hsieh, Wei-Ming Chi, Chia-Hwa Lee
BACKGROUND: As cancer metastasis is the deadliest aspect of cancer, causing 90% of human deaths, evaluating the molecular mechanisms underlying this process is the major interest to those in the drug development field. Both therapeutic target identification and proof-of-concept experimentation in anti-cancer drug development require appropriate animal models, such as xenograft tumor transplantation in transgenic and knockout mice. In the progression of cancer metastasis, circulating tumor cells (CTCs) are the most critical factor in determining the prognosis of cancer patients...
June 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28576130/the-g%C3%AE-h-plc%C3%AE-1-signaling-axis-drives-metastatic-progression-in-triple-negative-breast-cancer
#8
Shang-Pen Huang, Pei-Yao Liu, Chih-Jung Kuo, Chi-Long Chen, Wei-Jiunn Lee, Yu-Hui Tsai, Yuan-Feng Lin
BACKGROUND: Distant metastasis of triple-negative breast cancer (TNBC) to other organs, e.g., the lungs, has been correlated with poor survival rates among breast cancer patients. Therefore, the identification of useful therapeutic targets to prevent metastasis or even inhibit tumor growth of TNBC is urgently needed. Gαh is a novel GTP-binding protein and known as an inactive form of calcium-dependent tissue transglutaminase. However, the functional consequences of transamidating and G-protein activities of tissue transglutaminase in promoting cancer metastasis are still controversial...
June 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28573141/c-kit-positive-adipose-tissue-derived-mesenchymal-stem-cells-promote-the-growth-and-angiogenesis-of-breast-cancer
#9
Wenjie Li, Haiqian Xu, Cheng Qian
BACKGROUND: Adipose tissue-derived mesenchymal stem cells (ASCs) improve the regenerative ability and retention of fat grafts for breast reconstruction in cancer patients following mastectomy. However, ASCs have also been shown to promote breast cancer cell growth and metastasis. For the safety of ASC application, we aimed to identify specific markers for the subpopulation of ASCs that enhance the growth of breast cancer. METHODS: ASCs and bone marrow-derived vascular endothelial progenitor cells (EPCs) were isolated from Balb/c mice...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28528452/tumor-suppressor-protein-p53-exerts-negative-transcriptional-regulation-on-human-sodium-iodide-symporter-gene-expression-in-breast-cancer
#10
Madhura G Kelkar, Bhushan Thakur, Abhishek Derle, Sushmita Chatterjee, Pritha Ray, Abhijit De
PURPOSE: Aberrant expression of human sodium iodide symporter (NIS) in breast cancer (BC) is well documented but the transcription factors (TF) regulating its aberrant expression is poorly known. We identify the presence of three p53 binding sites on the human NIS promoter sequence by conducting genome-wide TF analysis, and further investigate their regulatory role. METHODS: The differences in transcription and translation were measured by real-time PCR, luciferase reporter assay, site-directed mutagenesis, in vivo optical imaging, and chromatin immunoprecipitation...
May 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28255357/stat3-nf-%C3%AE%C2%BAb-regulated-lentiviral-tk-gcv-suicide-gene-therapy-for-cisplatin-resistant-triple-negative-breast-cancer
#11
Wei-Ying Kuo, Luen Hwu, Chun-Yi Wu, Jhih-Shian Lee, Chi-Wei Chang, Ren-Shyan Liu
Triple-negative breast cancer (TNBC) represents approximately 20% of all breast cancers and appears resistance to conventional cytotoxic chemotherapy, demonstrating a particularly poor prognosis and a significantly worse clinical outcome than other types of cancer. Suicide gene therapy has been used for the in vivo treatment of various solid tumors in recent clinical trials. In tumor microenvironment, STAT3/NF-κB pathways are constitutively activated in stromal cells as well as in cancer stem cells (CSCs)...
2017: Theranostics
https://www.readbyqxmd.com/read/28182192/dabigatran-potentiates-gemcitabine-induced-growth-inhibition-of-pancreatic-cancer-in-mice
#12
Kun Shi, Helene Damhofer, Joost Daalhuisen, Marieke Ten Brink, Dick J Richel, C Arnold Spek
Pancreatic cancer is one of the most lethal solid malignancies with little treatment options. We have recently shown that expression of protease activated receptor (PAR)-1 in the tumor microenvironment drives progression and induces chemoresistance of pancreatic cancer. As thrombin is the prototypical PAR-1 agonist, here we addressed the effect of the direct thrombin inhibitor dabigatran on pancreatic cancer growth and drug resistance in an orthotropic pancreatic cancer model. We show that dabigatran treatment did not affect primary tumor growth whereas it significantly increased tumor dissemination throughout the peritoneal cavity...
February 6, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28115248/nanoparticle-mediated-radiopharmaceutical-excited-fluorescence-molecular-imaging-allows-precise-image-guided-tumor-removal-surgery
#13
Zhenhua Hu, Chongwei Chi, Muhan Liu, Hongbo Guo, Zeyu Zhang, Chaoting Zeng, Jinzuo Ye, Jing Wang, Jie Tian, Weidong Yang, Wanhai Xu
Fluorescent molecular imaging technique has been actively explored for optical image-guided cancer surgery in pre-clinical and clinical research and has attracted many attentions. However, the efficacy of the fluorescent image-guided cancer surgery can be compromised by the low signal-to-noise ratio caused by the external light excitation. This study presents a novel nanoparticle-mediated radiopharmaceutical-excited fluorescent (REF) image-guided cancer surgery strategy, which employs the internal dual-excitation of europium oxide nanoparticles through both gamma rays and Cerenkov luminescence emitted from radiopharmaceuticals...
May 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28089052/corrigendum-to-equivalency-challenge-evaluation-of-lipodox%C3%A2-as-the-generic-equivalent-for-doxil%C3%A2-in-a-human-ovarian-cancer-orthotropic-mouse-model-gynecol-oncol-141-2016-357-363
#14
Judith A Smith, Lata Mathew, Maryam Burney, Pranavanand Nyshadham, Robert L Coleman
No abstract text is available yet for this article.
February 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28035828/hepatic-carcinoma-selective-nucleic-acid-nanovector-assembled-by-endogenous-molecules-based-on-modular-strategy
#15
Fang Xie, Luchen Zhang, Jinliang Peng, Chong Li, Jun Pu, Yuhong Xu, Zixiu Du
We rationally formulated a nucleic acid nanovector platform utilizing endogenous molecules in the following steps: nucleic acids are initially packed by a multifunctional peptide and a cationic liposome to form positively charged ternary complexes through electrostatic interaction; then the ternary complexes were coated with hyaluronic acid (HA) to form negatively charged quaternary nanocomplexes (Q-complexes). Among the components of Q-complexes, the multifunctional peptide was composed of a poly-16-arginine (R16) and a hepatic tumor-targeted cell penetrating peptide (KRPTMRFRYTWNPMK); the cationic lipid component included DOTAP and fusogenic lipid DOPE; the HA component shielded the cationic ternary complexes and actively targeted the CD44 overexpressed on the surface of tumor cells...
April 24, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27813185/new-orally-active-dna-minor-groove-binding-small-molecule-ct-1-acts-against-breast-cancer-by-targeting-tumor-dna-damage-leading-to-p53-dependent-apoptosis
#16
Karan Singh Saini, Hamidullah, Raghib Ashraf, Dhanaraju Mandalapu, Sharmistha Das, Mohd Quadir Siddiqui, Sonam Dwivedi, Jayanta Sarkar, Vishnu Lal Sharma, Rituraj Konwar
Targeting tumor DNA damage and p53 pathway is a clinically established strategy in the development of cancer chemotherapeutics. Majority of anti-cancer drugs are delivered through parenteral route for reasons like severe toxicity, lack of stability, and poor enteral absorption. Current DNA targeting drugs in clinical like anthracycline suffers from major drawbacks like cardiotoxicity. Here, we report identification of a new orally active small molecule curcumin-triazole conjugate (CT-1) with significant anti-breast cancer activity in vitro and in vivo...
April 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27794222/neovasculature-and-circulating-tumor-cells-dual-targeting-nanoparticles-for-the-treatment-of-the-highly-invasive-breast-cancer
#17
Jianhui Yao, Jingxian Feng, Xiaoling Gao, Dan Wei, Ting Kang, Qianqian Zhu, Tianze Jiang, Xunbin Wei, Jun Chen
Antiangiogenesis therapy has been served as a potent cancer treatment strategy for decades, yet disrupting neovasculature would provoke tumor cells into invasive growth and result in distal metastasis. The basic cause of cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) which detach from primary tumor site and act as 'seeds'. Epithelial cell adhesion molecule (EpCAM) is a potential biomarker for selective capture of epithelium-derived CTCs. Here, we integrated tumor neovessles-targetable ligands K237 peptide with Ep23 aptamer against EpCAM into a single drug-loaded nanoplatform using paclitaxel (PTX) as the model drug, aiming at damaging the primary tumor and neutralizing CTCs simultaneously to achieve a synergistic anti-tumor therapeutic effect...
October 22, 2016: Biomaterials
https://www.readbyqxmd.com/read/27769887/a-drug-delivery-strategy-for-overcoming-drug-resistance-in-breast-cancer-through-targeting-of-oncofetal-fibronectin
#18
Phei Er Saw, Jinho Park, Sangyong Jon, Omid C Farokhzad
A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers...
February 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27705939/the-andean-anticancer-herbal-product-birm-causes-destabilization-of-androgen-receptor-and-induces-caspase-8-mediated-apoptosis-in-prostate-cancer
#19
Nagarajarao Shamaladevi, Shinako Araki, Dominic A Lyn, Rajnikanth Ayyathurai, Jie Gao, Vinata B Lokeshwar, Hugo Navarrete, Bal L Lokeshwar
BIRM is an anticancer herbal formulation from Ecuador. Previous study established its antitumor and antimetastatic activity against prostate cancer models. The activity of BIRM against human prostate cancer (PCa) cells was investigated to uncover its mechanism of antitumor activity. In androgen receptor (AR)-expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27223828/effective-rat-lung-tumor-model-for-stereotactic-body-radiation-therapy
#20
Zhang Zhang, Michelle Wodzak, Olivier Belzile, Heling Zhou, Brock Sishc, Hao Yan, Strahinja Stojadinovic, Ralph P Mason, Rolf A Brekken, Rajiv Chopra, Michael D Story, Robert Timmerman, Debabrata Saha
Stereotactic body radiation therapy (SBRT) has found an important role in the treatment of patients with non-small cell lung cancer, demonstrating improvements in dose distribution and even tumor cure rates, particularly for early-stage disease. Despite its emerging clinical efficacy, SBRT has primarily evolved due to advances in medical imaging and more accurate dose delivery, leaving a void in knowledge of the fundamental biological mechanisms underlying its activity. Thus, there is a critical need for the development of orthotropic animal models to further probe the biology associated with high-dose-per-fraction treatment typical of SBRT...
June 2016: Radiation Research
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