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https://www.readbyqxmd.com/read/27919267/targeted-drug-delivery-of-near-ir-fluorescent-doxorubicin-conjugated-poly-ethylene-glycol-bisphosphonate-nanoparticles-for-diagnosis-and-therapy-of-primary-and-metastatic-bone-cancer-in-a-mouse-model
#1
S Rudnick-Glick, E Corem-Salkmon, I Grinberg, S Margel
BACKGROUND: Most primary and metastatic bone tumors demonstrate increased osteoclast activity and bone resorption. Current treatment is based on a combination of surgery, radiotherapy and chemotherapy. Severe side effects are associated with chemotherapy due to use of high dosage and nonspecific uptake. Bisphosphonates have a strong affinity to Ca(2+) ions and are widely used in the treatment of bone disorders. RESULTS: We have engineered a unique biodegradable bisphosphonate nanoparticle (NPs) bearing two functional surface groups: (1) primary amine groups for covalent attachment of a dye/drug (e...
December 5, 2016: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/27915436/bone-marrow-produces-sufficient-alloreactive-natural-killer-nk-cells-in-vivo-to-cure-mice-from-subcutaneously-and-intravascularly-injected-4t1-breast-cancer
#2
Michel van Gelder, Ariane Vanclée, Catharina H M J van Elssen, Pierre Hupperets, Lotte Wieten, Gerard M Bos
PURPOSE: Administration of 5 million alloreactive natural killer (NK) cells after low-dose chemo-irradiation cured mice of 4T1 breast cancer, supposedly dose dependent. We now explored the efficacy of bone marrow as alternative in vivo source of NK cells for anti-breast cancer treatment, as methods for in vitro clinical scale NK cell expansion are still in developmental phases. METHODS: Progression-free survival (PFS) after treatment with different doses of spleen-derived alloreactive NK cells to 4T1-bearing Balb/c mice was measured to determine a dose-response relation...
December 3, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27915371/histone-deacetylase-inhibitors-deplete-myeloid-derived-suppressor-cells-induced-by-4t1-mammary-tumors-in-vivo-and-in-vitro
#3
Hai-Fang Wang, Fen Ning, Zong-Cai Liu, Long Wu, Zi-Qian Li, Yi-Fei Qi, Ge Zhang, Hong-Sheng Wang, Shao-Hui Cai, Jun Du
Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells that suppress anti-tumor immunity. MDSC are increased in tumor-bearing hosts; thus, depletion of MDSC may enhance anti-tumor immunity. Histone deacetylase inhibitors (HDACi) are chemical agents that are primarily used against hematologic malignancies. The ability of these agents to modulate anticancer immunity has recently been extensively studied. However, the effect of HDACi on MDSC has remained largely unexplored...
December 3, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27913127/co-assembly-of-doxorubicin-and-curcumin-targeted-micelles-for-synergistic-delivery-and-improving-anti-tumor-efficacy
#4
Wenzhuan Ma, Qiang Guo, Ying Li, Xiaohui Wang, Jinling Wang, Pengfei Tu
Chemotherapeutic drugs have a series of limitations in anti-tumor treatment, mainly including multidrug resistance (MDR) and serious adverse reactions. Co-delivery system with two or more synergistic therapeutic drugs is an effective strategy to settle these limitations. In this study, active tumor-targeted co-delivery micelles (DOX+Cur)-PMs, with two synergistic drugs of a therapeutic drug of doxorubicin (DOX) and a chemosensitizer of curcumin (Cur) co-encapsulated into hyaluronic acid-vitamin E succinate (HA-VES) graft copolymer, were prepared and delivered simultaneously into tumor cells for improving therapeutic effects of DOX...
November 29, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27912145/chloroquine-cq-exerts-anti-breast-cancer-through-modulating-microenvironment-and-inducing-apoptosis
#5
Yanjun Zhang, Yu Cao, Xiaodan Sun, Yonghui Feng, Yunting Du, Fei Liu, Chunyun Yu, Feng Jin
CQ is an anti-malaria drug, which has been used for years. However, there are published articles about its activity in anti-cancers. The aim of this approach was to look at possibility and related mechanisms of anti-breast cancer (mouse breast cancer cell line 4T1) by CQ alone. The studies of anti 4T1 in vitro and in vivo by CQ were performed. The growth of 4T1 in vitro and in vivo, survival of mice post treatment with CQ, changes of immune parameters and microenvironment in mice were evaluated. Our results demonstrate that CQ could markedly inhibit growth of 4T1 in vitro through inducing apoptosis of cells, inhibiting secretion of TGF-β and prolong the mice survival in vivo through boosting immune system by upregulating CD8+ T cell, and through down-regulating tumor associated macrophages (TAM), myeloid derived suppressing cells (MDSC) and Tregs, in microenvironment of mice bearing tumor...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27912060/the-hippo-pathway-kinases-lats1-2-suppress-cancer-immunity
#6
Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27895979/optical-redox-ratio-identifies-metastatic-potential-dependent-changes-in-breast-cancer-cell-metabolism
#7
Kinan Alhallak, Lisa G Rebello, Timothy J Muldoon, Kyle P Quinn, Narasimhan Rajaram
The development of prognostic indicators of breast cancer metastatic risk could reduce the number of patients receiving chemotherapy for tumors with low metastatic potential. Recent evidence points to a critical role for cell metabolism in driving breast cancer metastasis. Endogenous fluorescence intensity of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) can provide a label-free method for assessing cell metabolism. We report the optical redox ratio of FAD/(FAD + NADH) of four isogenic triple-negative breast cancer cell lines with varying metastatic potential...
November 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27895746/rnai-mediated-gene-silencing-of-vascular-endothelial-growth-factor-c-suppresses-growth-and-induces-apoptosis-in-mouse-breast-cancer-in-vitro-and-in-vivo
#8
Yong-Chao Liu, Wen-Hui Ma, Yin-Lin Ge, Mei-Lan Xue, Zheng Zhang, Jin-Yu Zhang, Lin Hou, Run-Hong Mu
Vascular endothelial cell growth factor (VEGF)-C promotes tumorigenesis by allowing lymph node metastasis and lymphangiogenesis, among other actions. RNA interference (RNAi) is a novel technique for suppressing target gene expression and may increase the effectiveness of cancer treatments. The present study assessed the influence of VEGF-C RNAi on the apoptosis and proliferation of mouse breast cancer cells in vitro and in vivo. A total of three pairs of small interfering RNA (siRNA) targeting mouse VEGF-C were designed and synthesized prior to transfection into 4T1 cells via a liposomal approach...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894589/discovery-and-preclinical-evaluation-of-7-benzyl-n-substituted-pyrrolo-3-2-d-pyrimidin-4-amines-as-single-agents-with-microtubule-targeting-effects-along-with-triple-acting-angiokinase-inhibition-as-antitumor-agents
#9
Roheeth Kumar Pavana, Shruti Choudhary, Anja Bastian, Michael A Ihnat, Ruoli Bai, Ernest Hamel, Aleem Gangjee
The utility of cytostatic antiangiogenic agents (AA) in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of AA with microtubule targeting agents (MTAs) have been particularly successful. The discovery, synthesis and biological evaluations of a series of 7-benzyl-N-substituted-pyrrolo[3,2-d]pyrimidin-4-amines are reported. Novel compounds which inhibit proangiogenic receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR), along with microtubule targeting in single molecules are described...
November 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27894093/new-use-of-an-old-drug-inhibition-of-breast-cancer-stem-cells-by-benztropine-mesylate
#10
Jihong Cui, Maija Hollmén, Lina Li, Yong Chen, Steven T Proulx, Daniel Reker, Gisbert Schneider, Michael Detmar
Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells)...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887890/non-additive-effects-of-repetitive-administration-of-lipoplexes-in-immunocompetent-mice
#11
Jamie L Betker, Thomas J Anchordoquy
Repetitive administration is routinely used to maintain therapeutic drug levels, but previous studies have documented an accelerated blood clearance of some lipid-based delivery systems under these conditions. To assess the effect of repetitive administration, non-PEGylated lipoplexes (+/- = 0.5) were administered four times via tail vein injection at 3-day intervals to immunocompetent Balb/c mice bearing 4T1 tumors. This study measured the effect of repeat administration of non-targeted lipoplexes on clearance, cytokine/chemokine response, plasmid distribution, reporter gene expression, and liver toxicity...
November 22, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27884084/losartan-loaded-liposomes-improve-the-antitumor-efficacy-of-liposomal-paclitaxel-modified-with-ph-sensitive-peptides-by-inhibition-of-collagen-in-breast-cancer
#12
Tai Xia, Qin He, Kairong Shi, Yang Wang, Qianwen Yu, Li Zhang, Qianyu Zhang, Huile Gao, Lifang Ma, Ji Liu
The dense collagen network in tumors restricts the penetration of drugs into tumors. Free losartan could inhibit collagen, but it would cause hypotension at the dosage of 10 mg/kg/d. In this study, losartan was encapsulated in liposomes (LST-Lip) and the collagen inhibition ability of LST-Lip was investigated. Our results showed the blood pressure was not affected by LST-Lip at the dosage of 2.5 mg/kg every other day. The amount of Evans Blue in tumor in LST-Lip group was 1.98 times of that in control group...
November 25, 2016: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/27878284/antitumor-effect-of-the-combination-of-manumycin%C3%A2-a-and-immodin-is-associated-with-antiplatelet-activity-and-increased-granulocyte-tumor-infiltration-in-a-4t1-breast-tumor-model
#13
Peter Solár, Veronika Sačková, Gabriela Hrčková, Vlasta Demečková, Monika Kassayová, Bianka Bojková, Dagmar Mudroňová, Soňa Gancarčíková, Rastislav Jendželovský, Peter Fedoročko
Manumycin A is a natural antibiotic isolated from Streptomyces parvulus with broad range of biological activities including antineoplastic activity in several in vitro and in vivo cancer models. Immodin [dialyzable leukocyte extract (DLE)] is a dialysate released from disintegrated blood leukocytes of healthy donors which exerts immunonormalizing effects on cell-mediated immune responses. The aim of the present study was to explore the antitumor potential of the combination of manumycin A and Immodin in an experimental breast cancer model...
November 22, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27877237/near-infrared-fluorescent-nanoparticles-derived-from-hyaluronic-acid-improve-tumor-contrast-for-image-guided-surgery
#14
Tanner K Hill, Sneha S Kelkar, Nicholas E Wojtynek, Joshua J Souchek, William M Payne, Kristina Stumpf, Frank C Marini, Aaron M Mohs
Tumor tissue that remains undetected at the primary surgical site can cause tumor recurrence, repeat surgery, and treatment strategy alterations that impose a significant patient and healthcare burden. Intraoperative near infrared fluorescence (NIRF) imaging is one potential method to identify remaining tumor by visualization of NIR fluorophores that are preferentially localized to the tumor. This requires development of fluorophores that consistently identify tumor tissue in different patients and tumor types...
2016: Theranostics
https://www.readbyqxmd.com/read/27863332/combined-effect-of-aerobic-interval-training-and-selenium-nanoparticles-on-expression-of-il-15-and-il-10-tnf-%C3%AE-ratio-in-skeletal-muscle-of-4t1-breast-cancer-mice-with-cachexia
#15
M Molanouri Shamsi, S Chekachak, S Soudi, L S Quinn, K Rangbar, J Chenari, M H Yazdi, M Mahdavi
Cancer cachexia is characterized by inflammation, loss of skeletal muscle and adipose tissue mass, and functional impairment. Oxidative stress and inflammation are believed to regulate pathways controlling skeletal muscle wasting. The aim of this study was to determine the effects of aerobic interval training and the purported antioxidant treatment, selenium nanoparticle supplementation, on expression of IL-15 and inflammatory cytokines in 4T1 breast cancer-bearing mice with cachexia. Selenium nanoparticle supplementation accelerated cachexia symptoms in tumor-bearing mice, while exercise training prevented muscle wasting in tumor-bearing mice...
November 15, 2016: Cytokine
https://www.readbyqxmd.com/read/27853369/the-effect-of-dual-functional-hyaluronic-acid-vitamin-e-succinate-micelles-on-targeting-delivery-of-doxorubicin
#16
Jinling Wang, Wenzhuan Ma, Qiang Guo, Ying Li, Zhongdong Hu, Zhixiang Zhu, Xiaohui Wang, Yunfang Zhao, Xingyun Chai, Pengfei Tu
Tumor-targeted delivery system has been developed as an attractive strategy for effective tumor therapy. In this study, in order to enhance the antitumor effects of doxorubicin (DOX), amphiphilic hyaluronic acid (HA)-conjugated vitamin E succinate (VES) copolymers (HA-VES) with different degrees of substitution (DS) were prepared with synergistic antitumor effects and active targeting activities, and utilized as nanocarriers for the efficient delivery of DOX. DOX-loaded HA-VES polymeric micelles (HA-VES/DOX) self-assembled from dual-functional HA-VES copolymer and exhibited excellent loading efficiency and superior colloidal stability...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27831902/local-and-transient-gene-expression-primes-the-liver-to-resist-cancer-metastasis
#17
Tyler J Goodwin, Yingqiu Zhou, Sara N Musetti, Rihe Liu, Leaf Huang
The liver is the primary site of metastasis for gastrointestinal cancers and is a location highly susceptible to the establishment of metastasis in numerous other primary cancers, including breast, lung, and pancreatic cancers. The current standard of care typically consists of primary tumor resection and systemic administration of potent but toxic chemotherapeutics, yielding a minimal improvement in the median survival rate. CXCL12, a chemokine, is a key factor for activating the migration/survival pathways of CXCR4(+) cancer cells and for recruiting immunosuppressive cells to areas of inflammation...
November 9, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27820870/inoculated-cell-density-as-a-determinant-factor-of-the-growth-dynamics-and-metastatic-efficiency-of-a-breast-cancer-murine-model
#18
Ana C Gregório, Nuno A Fonseca, Vera Moura, Manuela Lacerda, Paulo Figueiredo, Sérgio Simões, Sérgio Dias, João Nuno Moreira
4T1 metastatic breast cancer model have been widely used to study stage IV human breast cancer. However, the frequent inoculation of a large number of cells, gives rise to fast growing tumors, as well as to a surprisingly low metastatic take rate. The present work aimed at establishing the conditions enabling high metastatic take rate of the triple-negative murine 4T1 syngeneic breast cancer model. An 87% 4T1 tumor incidence was observed when as few as 500 cancer cells were implanted. 4T1 cancer cells colonized primarily the lungs with 100% efficiency, and distant lesions were also commonly identified in the mesentery and pancreas...
2016: PloS One
https://www.readbyqxmd.com/read/27812285/a-multifaceted-role-for-myd88-dependent-signaling-in-progression-of-murine-mammary-carcinoma
#19
Mary J Higgins, Antonio Serrano, Kofi Y Boateng, Victoria A Parsons, Tiffany Phuong, Alyssa Seifert, Jacob M Ricca, Kyle C Tucker, Alec S Eidelman, Maureen A Carey, Robert A Kurt
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal-regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C-C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth...
2016: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/27810342/interleukin-12-activated-cd8-t-cells-induces-apoptosis-in-breast-cancer-cells-and-reduces-tumor-growth
#20
Shi-Xin Yang, Wen-Song Wei, Qian-Wen Ouyan, Qi-Hua Jiang, Yu-Feng Zou, Wei Qu, Jian-Hong Tu, Zhi-Bing Zhou, Hao-Long Ding, Chun-Wei Xie, Qiu-Mo Lei, Cheng-Ren Zhong
During the past two decades, cytokines have emerged as key molecules to modulate innate and adaptive immunity and mediate anti-tumor activity. Although multiple cytokine types are implicated for such anti-tumor activity in several cancer types, it remains largely unknown in breast cancer. In this study, cytokines that are prior known for antitumor activity in different cancer types were examined against breast cancer using a 4T1 cells based xenograft-model. Our results showed Interleukin-12 (IL-12) (500ng/mouse) significantly suppressed the growth of tumors, while other cytokines showed minimal suppression...
October 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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