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https://www.readbyqxmd.com/read/29759562/investigational-agents-to-enhance-the-efficacy-of-chemotherapy-or-radiation-in-pancreatic-cancer
#1
REVIEW
Myrna Hurtado, Umesh T Sankpal, Amalendu Ranjan, Rajasekhar Maram, Jamboor K Vishwanatha, Ganji Purnachandra Nagaraju, Bassel F El-Rayes, Riyaz Basha
Pancreatic cancer (PC) continues to be a fatal malignancy. With standard treatments having modest impact, alternative courses of actions are being investigated such as enhancing the efficacy of standard treatment through sensitization of PC cells to chemotherapy or radiation. This review emphasizes investigational agents that increase the responses to chemotherapy or radiation in PC models. Our group has extensively investigated on Curcumin (Cur), analogs (EF31, UBS109, and L49H37), nanoparticles and a small molecule Tolfenamic acid (TA) for enhancing therapeutic efficacy in both in vitro and in vivo assays...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29739364/pan-raf-and-mek-vertical-inhibition-enhances-therapeutic-response-in-non-v600-braf-mutant-cells
#2
Eszter Molnár, Dominika Rittler, Marcell Baranyi, Michael Grusch, Walter Berger, Balázs Döme, József Tóvári, Clemens Aigner, József Tímár, Tamás Garay, Balázs Hegedűs
BACKGROUND: Currently, there are no available targeted therapy options for non-V600 BRAF mutated tumors. The aim of this study was to investigate the effects of RAF and MEK concurrent inhibition on tumor growth, migration, signaling and apoptosis induction in preclinical models of non-V600 BRAF mutant tumor cell lines. METHODS: Six BRAF mutated human tumor cell lines CRL5885 (G466 V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464 V), CRL5922 (L597 V) and A375 (V600E as control) were investigated...
May 8, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29625858/m2-polarization-of-macrophages-by-oncostatin-m-in-hypoxic-tumor-microenvironment-is-mediated-by-mtorc2-and-promotes-tumor-growth-and-metastasis
#3
Richa Shrivastava, Mohammad Asif, Varsha Singh, Parul Dubey, Showkat Ahmad Malik, Mehraj-U-Din Lone, Brij Nath Tewari, Khemraj Singh Baghel, Subhashis Pal, Geet Kumar Nagar, Naibedya Chattopadhyay, Smrati Bhadauria
Oncostatin M (OSM), an inflammatory cytokine belonging to the interleukin-6 (IL-6) superfamily, plays a vital role in multitude of physiological and pathological processes. Its role in breast tumor progression and metastasis to distant organs is well documented. Recent reports implicate OSM in macrophage M2 polarization, a key pro-tumoral phenomenon. M2 polarization of macrophages is believed to promote tumor progression by potentiating metastasis and angiogenesis. In the current study, we delineated the mechanism underlying OSM induced macrophage M2 polarization...
April 3, 2018: Cytokine
https://www.readbyqxmd.com/read/29510387/suppression-of-non-small-cell-lung-cancer-growth-and-metastasis-by-a-novel-small-molecular-activator-of-reck
#4
Jia Shen, Banghua Wang, Tao Zhang, Ni Zhu, Zexia Wang, Jing Jin, Yi He, Meichun Hu
BACKGROUND/AIMS: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. METHODS: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine's efficacy on non-small cell lung cancer (NSCLC) cells in vitro...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29491256/establishment-of-a-patient-derived-tumor-xenograft-model-and-application-for-precision-cancer-medicine
#5
REVIEW
Seiji Okada, Kulthida Vaeteewoottacharn, Ryusho Kariya
Patient-derived xenograft (PDX) models can be created with the transplantation of cancerous cells or tissues from patients' primary tumors into immunodeficient mice. PDXs are now in the spotlight as more accurate human cancer models compared with mouse tumor and human cancer cell lines transplanted into mice. PDX technology leads to breakthroughs with the introduction of novel, highly immunodeficient mice such as NOG (NOD/Scid/IL2Rγnull ), NSG (NOD/Scid/IL2Rγnull ), and NOJ (NOD/Scid/Jak3null ) mice. Xenograft efficiency differs by type of tumor, site of implantation, and tumor aggressiveness...
2018: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29452146/the-hippo-yap1-pathway-interacts-with-fgfr1-signaling-to-maintain-stemness-in-lung-cancer
#6
Tingting Lu, Ziming Li, Ying Yang, Wenxiang Ji, Yongfeng Yu, Xiaomin Niu, Qingyu Zeng, Weiliang Xia, Shun Lu
The Hippo pathway plays a critical role in organ size control, tissue homeostasis and tumor genesis through its key transcription regulator Yes-associated protein1 (YAP1), but the mechanism underlying its role in lung cancer is unclear. We hypothesized that YAP1 influences FGFR1 signaling to maintain cancer stem-like cell (CSC) properties in FGFR1-amplified lung cancer. In support of this, our data confirms that expression levels of YAP1 are positively associated with those of FGFR1 in clinical lung carcinoma samples as measured by real-time PCR, western blot, and immunohistochemistry (IHC) staining...
June 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29391154/o-glcnacylation-affects-%C3%AE-catenin-and-e-cadherin-expression-cell-motility-and-tumorigenicity-of-colorectal-cancer
#7
Shani Ben Harosh-Davidovich, Isam Khalaila
O-GlcNAcylation, the addition of β-N-acetylglucosamine (O-GlcNAc) moiety to Ser/Thr residues, is a sensor of the cell metabolic state. Cancer diseases such as colon, lung and breast cancer, possess deregulated O-GlcNAcylation. Studies during the last decade revealed that O-GlcNAcylation is implicated in cancer tumorigenesis and proliferation. The Wnt/β-catenin signaling pathway and cadherin-mediated adhesion are also implicated in epithelial-mesenchymal transition (EMT), a key cellular process in invasion and cancer metastasis...
March 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29340047/inhibition-of-polo-like-kinase-4-plk4-a-new-therapeutic-option-for-rhabdoid-tumors-and-pediatric-medulloblastoma
#8
Simone Treiger Sredni, Anders W Bailey, Amreena Suri, Rintaro Hashizume, Xingyao He, Nundia Louis, Tufan Gokirmak, David R Piper, Daniel M Watterson, Tadanori Tomita
Rhabdoid tumors (RT) are highly aggressive and vastly unresponsive embryonal tumors. They are the most common malignant CNS tumors in infants below 6 months of age. Medulloblastomas (MB) are embryonal tumors that arise in the cerebellum and are the most frequent pediatric malignant brain tumors. Despite the advances in recent years, especially for the most favorable molecular subtypes of MB, the prognosis of patients with embryonal tumors remains modest with treatment related toxicity dreadfully high. Therefore, new targeted therapies are needed...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29016926/activation-of-wee1-confers-resistance-to-pi3k-inhibition-in-glioblastoma
#9
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...
January 10, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/28938619/anti-cancer-efficacy-of-biotinylated-chitosan-nanoparticles-in-liver-cancer
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
August 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
#19
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
#20
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
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