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orthotropic cancer model

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
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
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...
January 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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
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
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
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
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...
October 19, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
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
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
Cheng S Jin, Marta Overchuk, Liyang Cui, Brian C Wilson, Robert G Bristow, Juan Chen, Gang Zheng
BACKGROUND: The Magnetic Resonance Imaging (MRI)-guided focal laser therapy has shown early promise in Phase 1 trial treating low/intermediate-risk localized prostate cancer (PCa), but the lack of tumor selectivity and low efficiency of heat generation remain as drawbacks of agent-free laser therapy. Intrinsic multifunctional porphyrin-nanoparticles (porphysomes) have been exploited to treat localized PCa by MRI-guided focal photothermal therapy (PTT) with significantly improved efficiency and tumor selectivity over prior methods of PTT, providing an effective and safe alternative to active surveillance or radical therapy...
September 2016: Prostate
Qiuli Liu, Wenqiang Yuan, Dali Tong, Gaolei Liu, Weihua Lan, Dianzheng Zhang, Hualiang Xiao, Yao Zhang, Zaoming Huang, Junjie Yang, Jun Zhang, Jun Jiang
Cancer stem cells (CSCs) are a sub-population of tumor cells playing essential roles in initiation, differentiation, recurrence, metastasis and development of drug resistance of various cancers, including bladder cancer. Although multiple lines of evidence suggest that metformin is capable of repressing CSC repopulation in different cancers, the effect of metformin on bladder cancer CSCs remains largely unknown. Using the N-methyl-N-nitrosourea (MNU)-induced rat orthotropic bladder cancer model, we demonstrated that metformin is capable of repressing bladder cancer progression from both mild to moderate/severe dysplasia lesions and from carcinoma in situ (CIS) to invasive lesions...
May 10, 2016: Oncotarget
Run Xiao, Stephen M Bergin, Wei Huang, Andrew M Slater, Xianglan Liu, Ryan T Judd, En-Ju D Lin, Kyle J Widstrom, Steven D Scoville, Jianhua Yu, Michael A Caligiuri, Lei Cao
Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated, in part by a specific neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key brain mediator. Here, we investigated how an EE modulated T-cell immunity and its role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells were required to mediate the anticancer effects of an EE in an orthotropic model of melanoma...
2016: Cancer Immunology Research
Judith A Smith, Lata Mathew, Maryam Burney, Pranavanand Nyshadham, Robert L Coleman
BACKGROUND: The objective of this study was to evaluate the in vivo growth inhibition activity and tumor distribution of Doxil® compared to Lipodox® as its generic (GLD) in human ovarian cancer orthotopic mouse model. METHODS: In the efficacy study 50 mice were randomized to: vehicle, Doxil® 5mg/kg or 10mg/kg, or GLD 5mg/kg or 10mg/kg for a total of three cycles with monitoring for response and toxicity with 10 mice in each arm. In the microdialysis(MD) study, 60 mice were randomized to: Doxil® 5mg/kg or 10mg/kg, or GLD 5mg/kg or 10mg/kg single dose (n=15 mice/arm)...
May 2016: Gynecologic Oncology
Ashraf Bakkar, Mohammed Alshalalfa, Lars F Petersen, Hatem Abou-Ouf, Amal Al-Mami, Samar A Hegazy, Felix Feng, Reda Alhajj, Krikor Bijian, Moulay A Alaoui-Jamali, Tarek A Bismar
MicroRNAs (miRNAs) are small non-coding RNAs that function in transcriptional and post-transcriptional regulation of gene expression. Several miRNAs have been implicated in regulating prostate cancer (PCa) progression. Deregulations of miRNA regulatory networks have been reported in ERG positive PCa, which accounts for ~50 % of PCa and have been suggested to affect tumor aggressiveness. The function of miR338-3p, its prognostic significance, and its association with ERG positive PCa has not been fully investigated...
April 2016: Molecular Biology Reports
Victor Jeannot, Silvia Mazzaferro, Jonathan Lavaud, Laetitia Vanwonterghem, Maxime Henry, Mélanie Arboléas, Julien Vollaire, Véronique Josserand, Jean-Luc Coll, Sébastien Lecommandoux, Christophe Schatz, Amandine Hurbin
UNLABELLED: New approaches that are more efficient and able to specifically reach lung tumors are needed. We developed new hyaluronan-based nanoparticles targeting CD44 receptors of two different sizes and compared their lung cancer cells targeting efficacy in vitro and in vivo. The nanoparticles' cellular uptake was dose-dependent, and specific to hyaluronan receptors, particularly CD44. The binding and internalization differed according to nanoparticle size. In vivo biodistribution studies in two orthotopic lung tumor models showed that intrapulmonary nebulized nanoparticles accumulated in lungs, but not in the tumor nodules...
May 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Thi My Hien Nguyen, In-Whoan Shin, Tae Jin Lee, Junsoo Park, Jae Hyung Kim, Mi Sun Park, Eun-Ju Lee
OBJECTIVE: Integral membrane protein 2A (ITM2A) is a type 2 transmembrane protein of unknown function. The aim of this study was to investigate its expression pattern, clinical significance, and biological function in epithelial ovarian cancer. METHODS: ITM2A expression in 35 normal, 20 adenoma, 11 borderline and 90 cancerous ovarian tissues was measured by immunohistochemistry. Clinicopathological parameters were obtained from medical records. Survival data was analyzed using Kaplan-Meier estimates and multivariate analysis using the Cox-regression method...
March 2016: Gynecologic Oncology
Zhuoli Zhang, Linfeng Zheng, Weiguo Li, Andrew C Gordon, Yi Huan, Junjie Shangguan, Daniel Procissi, David J Bentrem, Andrew C Larson
OBJECTIVE: To demonstrate feasibility of performing quantitative MRI measurements in an immuno-competent rat model of pancreatic cancer by comparing in vivo anatomic and quantitative imaging measurements to tumor dissemination observations and histologic assays at necropsy. Meterials and methods: Rat ductal pancreatic adenocarcinoma DSL-6A/C1 cell line and Lewis rats were used for these studies. 10(8) DSL-6A/C1 cells were injected subcutaneously into the right flank of donor rats. Donor tumors reaching 10 mm were excised, and 1 mm(3) tumor fragments were implanted within recipient rat pancreas during mini-laparotomy...
2015: American Journal of Translational Research
Wenjuan Xu, Linlin Jing, Quanshi Wang, Chung-Chih Lin, Xiaoting Chen, Jianxin Diao, Yuanliang Liu, Xuegang Sun
Intrinsic apoptosis eliminates cells with damaged DNA and cells with dysregulated expression of oncogene. PGAM5, a member of the phosphoglycerate mutase family, has two splicing variants: PGAM5L (the long form) and PGAM5S (the short form). It has been well established that PGAM5 is at the convergent point of multiple necrosis pathways. However, the role of PGAM5 in intrinsic apoptosis is still controversial. Here we report that the PGAM5L, but not PGAM5S is a prerequisite for the activation of Bax and dephosphorylation of Drp1 in arenobufagin and staurosporine induced intrinsic apoptosis...
October 6, 2015: Oncotarget
Xiaochun Huang, Yinghua Chen, Yi Ma, Bing Liao, Xiaofeng Zhu, Xiaoshun He
OBJECTIVE: To explore the diagnosis, treatment and long-term outcome of late acute rejection (LAR) following adult orthotropic liver transplantation (OLT). METHODS: A total of 398 consecutive adult patients who underwent OLT in Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University between January 2007 and December 2012 were reviewed retrospectively. There were 48 patients (12. 1%) developed to LAR, including 43 male patients and 5 female patients, with an average age of (52 ± 13) years(18 - 70 years)...
March 2015: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
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