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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
#1
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...
November 4, 2016: 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
#2
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
#3
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 18, 2016: 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
#4
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...
October 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27223828/effective-rat-lung-tumor-model-for-stereotactic-body-radiation-therapy
#5
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
https://www.readbyqxmd.com/read/27198587/nanoparticle-enabled-selective-destruction-of-prostate-tumor-using-mri-guided-focal-photothermal-therapy
#6
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
https://www.readbyqxmd.com/read/27058422/metformin-represses-bladder-cancer-progression-by-inhibiting-stem-cell-repopulation-via-cox2-pge2-stat3-axis
#7
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
https://www.readbyqxmd.com/read/27045020/environmental-and-genetic-activation-of-hypothalamic-bdnf-modulates-t-cell-immunity-to-exert-an-anticancer-phenotype
#8
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...
June 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/26946092/equivalency-challenge-evaluation-of-lipodox%C3%A2-as-the-generic-equivalent-for-doxil%C3%A2-in-a-human-ovarian-cancer-orthotropic-mouse-model
#9
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
https://www.readbyqxmd.com/read/26907180/microrna-338-3p-exhibits-tumor-suppressor-role-and-its-down-regulation-is-associated-with-adverse-clinical-outcome-in-prostate-cancer-patients
#10
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
https://www.readbyqxmd.com/read/26724540/targeting-cd44-receptor-positive-lung-tumors-using-polysaccharide-based-nanocarriers-influence-of-nanoparticle-size-and-administration-route
#11
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
https://www.readbyqxmd.com/read/26691219/loss-of-itm2a-a-novel-tumor-suppressor-of-ovarian-cancer-through-g2-m-cell-cycle-arrest-is-a-poor-prognostic-factor-of-epithelial-ovarian-cancer
#12
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
https://www.readbyqxmd.com/read/26550449/quantitative-functional-mri-in-a-clinical-orthotopic-model-of-pancreatic-cancer-in-immunocompetent-lewis-rats
#13
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
https://www.readbyqxmd.com/read/26356820/bax-pgam5l-drp1-complex-is-required-for-intrinsic-apoptosis-execution
#14
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
https://www.readbyqxmd.com/read/26269011/-the-diagnosis-and-treatment-of-late-acute-rejection-after-adult-orthotopic-liver-transplantation
#15
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]
https://www.readbyqxmd.com/read/26225121/mechanistic-attributes-of-s100a7-psoriasin-in-resistance-of-anoikis-resulting-tumor-progression-in-squamous-cell-carcinoma-of-the-oral-cavity
#16
Kaushik Kumar Dey, Siddik Sarkar, Ipsita Pal, Subhasis Das, Goutam Dey, Rashmi Bharti, Payel Banik, Joygopal Roy, Sukumar Maity, Indranil Kulavi, Mahitosh Mandal
BACKGROUND: Squamous cell carcinoma of the oral cavity (SCCOC) is the dominant origin of cancer associated mortality. Previous findings by our study reported that acquisition of anoikis resistance has a significant role in tumor progression of oral cavity. Several genes were over-expressed in anoikis-resistant cells under detached conditions which we confirmed earlier by microarray. Normal oral squamous epithelia grow adherent to a basement membrane, and when detached from the extracellular matrix, undergoes programmed cell death...
2015: Cancer Cell International
https://www.readbyqxmd.com/read/26122018/photothermal-ablation-of-bone-metastasis-of-breast-cancer-using-pegylated-multi-walled-carbon-nanotubes
#17
Zhen Lin, Yi Liu, Xueming Ma, Shaoyu Hu, Jiawei Zhang, Qian Wu, Wenbin Ye, Siyuan Zhu, Dehong Yang, Dongbin Qu, Jianming Jiang
This study investigates therapeutic efficacy of photothermal therapy (PTT) in an orthotropic xenograft model of bone metastasis of breast cancer. The near-infrared (NIR) irradiation on Multi-Walled Carbon Nanotubes (MWNTs) resulted in a rapid heat generation which increased with the MWNTs concentration up to 100 μg/ml. MWNTs alone exhibited no toxicity, but inclusion of MWNTs dramatically decreased cell viability when combined with laser irradiation. Thermographic observation revealed that treatment with 10 μg MWNTs followed by NIR laser irradiation resulted in a rapid increase in temperature up to 73...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25873394/phosphatase-and-tensin-homolog-pten-represses-colon-cancer-progression-through-inhibiting-paxillin-transcription-via-pi3k-akt-nf-%C3%AE%C2%BAb-pathway
#18
Ling-Li Zhang, Gang-Gang Mu, Qian-Shan Ding, Yan-Xia Li, Yun-bo Shi, Jin-Fen Dai, Hong-Gang Yu
The tumor suppressor gene phosphatase and tensin homolog (PTEN) is frequently mutated in colon cancer. However, the potential contribution of loss of PTEN to colon cancer progression remains unclear. In this study, we demonstrated that PTEN overexpression or knockdown in Lovo colon cancer cells decreased or increased paxillin expression, respectively. Moreover, paxillin reversed PTEN-mediated inhibition of Lovo cell invasion and migration. Overexpression of PTEN in an orthotropic colon cancer nude mice model inhibited tumor formation and progression...
June 12, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25784049/suppressive-function-of-low-dose-deguelin-on-the-invasion-of-oral-cancer-cells-by-downregulating-tumor-necrosis-factor-alpha-induced-nuclear-factor-kappa-b-signaling
#19
Yu-Peng Liu, Jih-Jong Lee, Tsung-Ching Lai, Chien-Hsin Lee, Ya-Wen Hsiao, Po-Shen Chen, Wei-Ting Liu, Chi-Yuan Hong, Se-Kwan Lin, Mark-Yen Ping Kuo, Pei-Jung Lu, Michael Hsiao
BACKGROUND: Deguelin has both antiproliferation and antimetastasis activities. However, high-dose deguelin elicits many undesired side effects. The purpose of this study was to investigate whether the low-dose deguelin can prevent the metastasis of oral cancer. METHODS: The dose effects of deguelin on metastasis of oral cancer cells were analyzed by in vitro invasion assay and an orthotropic xenograft mouse model. The involvement of tumor necrosis factor alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) signaling was examined by Western blot and reporter assay...
April 2016: Head & Neck
https://www.readbyqxmd.com/read/25725361/poly-2-oxazoline-based-micelles-with-high-capacity-for-3rd-generation-taxoids-preparation-in-vitro-and-in-vivo-evaluation
#20
Zhijian He, Anita Schulz, Xiaomeng Wan, Joshua Seitz, Herdis Bludau, Daria Y Alakhova, David B Darr, Charles M Perou, Rainer Jordan, Iwao Ojima, Alexander V Kabanov, Robert Luxenhofer
The clinically and commercially successful taxanes, paclitaxel and docetaxel suffer from two major drawbacks, namely their very low aqueous solubility and the risk of developing resistance. Here, we present a method that overcomes both drawbacks in a very simple manner. We formulated 3rd generation taxoids, able to avoid common drug resistance mechanisms with doubly amphiphilic poly(2-oxazoline)s (POx), a safe and highly efficient polymer for the formulation of extremely hydrophobic drugs. We found excellent solubilization of different 3rd generation taxoids irrespective of the drug's chemical structures with essentially quantitative drug loading and final drug to polymer ratios around unity...
June 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
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