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Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
Ken Takai, Annie Le, Valerie M Weaver, Zena Werb
Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist...
October 14, 2016: Oncotarget
Xunian Zhou, Grace Gar-Lee Yue, Minghua Liu, Zhili Zuo, Julia Kin-Ming Lee, Mingyue Li, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Handong Sun, Jianxin Pu, Clara Bik-San Lau
Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from the plant Isodon eriocalyx var. laxiflora, has emerged as a promising anticancer agent. The effects of EriB on angiogenesis were explored in the present study. Here we demonstrated that the subintestinal vein formation was significantly inhibited by EriB treatment (10, 15 μM) in zebrafish embryos, which was resulted from the alteration of various angiogenic genes as shown in transcriptome profiling. In human umbilical vein endothelial cells, EriB treatment (50, 100 nM) could significantly block vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation, cell migration and cell invasion...
October 14, 2016: Oncotarget
Hamid Reza Kheiri Manjili, Parisa Ghasemi, Hojjat Malvandi, Mir Sajjad Mousavi, Elahe Attari, Hossein Danafar
Curcumin(CUR) has been associated with anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability.To progress thebioavailabilityand water solubility ofCUR, we synthesized five series of mono methoxy poly(ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL)diblock copolymers. The structureof thecopolymerswas characterized by HNMR, FTIR, DSC and GPC techniques. In this study, CUR was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of CUR-loaded mPEG-PCL (CUR/mPEG-PCL) micelles...
October 15, 2016: European Journal of Pharmaceutics and Biopharmaceutics
C M Wong, L A Nash, J Del Papa, K L Poulin, T Falls, J C Bell, R J Parks
When injected directly into a tumor mass, adenovirus (Ad) vectors only transduce cells immediately along the injection tract. Expression of fusogenic proteins from the Ad vector can lead to syncytium formation, which efficiently spreads the therapeutic effect. Fusogenic proteins can also cause cancer cell death directly, and enhance the release of exosome-like particles containing tumor-associated antigens, which boosts the anti-tumor immune response. In this study, we have examined whether delivery of an early region 1 (E1)-deleted, replication-defective Ad vector encoding the reptilian reovirus p14 fusion-associated small transmembrane (FAST) protein can provide therapeutic efficacy in an immunocompetent mouse tumor model...
October 14, 2016: Cancer Gene Therapy
Hongyan Zhang, Zhen Zhang, Yanhong Wang, Chuanchen Wu, Qingling Li, Bo Tang
A strategy based on immune-graphene oxide (GO)-magnetic microbead complex for the sensitive, rapid, portable and low-cost detection of cancer cells was developed. The high efficiency cell capture and high sensitive thermal contrast detection could be simultaneously achieved using magnetic microbeads and the photothermal effect of GOs. The temperature variation caused by irradiating the GOs with a laser was used to establish the standard curve of temperature variation and cancer cell number. Under optimal conditions, the limit of detection could reach 100 cells...
October 14, 2016: ACS Applied Materials & Interfaces
Xianxian Yao, Xingxing Niu, Kexin Ma, Ping Huang, Julia Grothe, Stefan Kaskel, Yufang Zhu
A multifunctional platform is reported for synergistic therapy with controlled drug release, magnetic hyperthermia, and photothermal therapy, which is composed of graphene quantum dots (GQDs) as caps and local photothermal generators and magnetic mesoporous silica nanoparticles (MMSN) as drug carriers and magnetic thermoseeds. The structure, drug release behavior, magnetic hyperthermia capacity, photothermal effect, and synergistic therapeutic efficiency of the MMSN/GQDs nanoparticles are investigated. The results show that monodisperse MMSN/GQDs nanoparticles with the particle size of 100 nm can load doxorubicin (DOX) and trigger DOX release by low pH environment...
October 13, 2016: Small
Grace Gar-Lee Yue, Sida Xie, Julia Kin-Ming Lee, Hin-Fai Kwok, Si Gao, Yin Nian, Xiao-Xiao Wu, Chun-Kwok Wong, Ming-Hua Qiu, Clara Bik-San Lau
Actein is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida (Chinese herb "shengma") which could inhibit the growth of breast cancer cells. Nevertheless, the effect of actein on angiogenesis, which is an essential step for tumor growth and metastasis, has never been reported. Hence, this study aimed to investigate the in vitro and in vivo effects of actein on angiogenesis using human microvascular endothelial cells (HMEC-1), matrigel plug and tumor-bearing mouse models. Our results showed that actein significantly inhibited the proliferation, reduced the migration and motility of endothelial cells, and it could suppress the protein expressions of VEGFR1, pJNK and pERK, suggesting that JNK/ERK pathways were involved...
October 12, 2016: Scientific Reports
Ping Sun, Wei Huang, Mingji Jin, Qiming Wang, Bo Fan, Lin Kang, Zhonggao Gao
Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line...
2016: International Journal of Nanomedicine
Jin Young Kim, Garam Kim, Sung-Chul Lim, Hong Seok Choi
LPIN1 is a protein that exhibits dual functions as a phosphatidic acid phosphatase enzyme in regulation of triglyceride and glycerophospholipid metabolism and a transcriptional coregulator. Through unknown tumour-promoting mechanism, LPIN1 frequently observed in various human cancer cell lines controls main cellular processes involved in cancer progression. Here, we demonstrate that LPIN1 enhances the tumour-promoting function of insulin receptor substrate 1 (IRS1) by controlling IRS1 stability. LPIN1 interacts with IRS1 in an insulin growth factor-1-dependent signalling pathway and inhibits its serine phosphorylation, and thereby eliminating ubiquitin-dependent degradation of IRS1 via proteasomal and lysosomal pathways...
October 11, 2016: Carcinogenesis
Jonas Steenbrugge, Koen Breyne, Sofie Denies, Melissa Dekimpe, Kristel Demeyere, Olivier De Wever, Peter Vermeulen, Steven Van Laere, Niek N Sanders, Evelyne Meyer
Breast tumorigenesis is classically studied in mice by inoculating tumor cells in the fat pad, the adipose compartment of the mammary gland. Alternatively, the mammary ducts, which constitute the luminal mammary gland compartment, also provide a suitable inoculation site to induce breast cancer in murine models. The microenvironments in these compartments influence tumor cell progression, yet this effect has not been investigated in an immunocompetent context. Here, we compared both mammary gland compartments as distinct inoculation sites, taking into account the immunological aspect by inoculating 4T1 tumor cells in immunocompetent mice...
October 6, 2016: Journal of Mammary Gland Biology and Neoplasia
Anne Mobergslien, Qian Peng, Vlada Vasovic, Mouldy Sioud
Therapeutic strategies aiming at mobilizing immune effector cells to kill tumor cells independent of tumor mutational load and MHC expression status are expected to benefit cancer patients. Recently, we engineered various peptide-Fc fusion proteins for directing Fcg receptor-bearing immune cells toward tumor cells. Here, we investigated the immunostimulatory and anti-tumor effects of one of the engineered Fc fusion proteins (WN-Fc). In contrast to the Fc control, soluble WN-Fc-1 fusion protein activated innate immune cells (e...
October 4, 2016: Oncotarget
Katherine Hughes, Maximilian Blanck, Sara Pensa, Christine J Watson
Mammary gland regression at the cessation of lactation (involution) is an exquisitely orchestrated process of cell death and tissue remodelling in which Stat3 signalling has an essential role. The involution microenvironment of the mammary gland is considered to be pro-tumourigenic and a proportion of cases of pregnancy-associated breast cancer are suggested to originate in tandem with involution. However, the apparent paradox that STAT3 is required for cell death in normal mammary gland, but is associated with breast cancer cell survival, has not been resolved...
October 6, 2016: Cell Death & Disease
Jian-Li Gao, Yan-Mei Shui, Wei Jiang, En-Yi Huang, Qi-Yang Shou, Xin Ji, Bai-Cheng He, Gui-Yuan Lv, Tong-Chuan He
Hypoxic in the tumor mass is leading to the myeloproliferative-like disease (leukemoid reaction) and anemia of body, which characterized by strong extensive extramedullary hematopoiesis (EMH) in spleen. As the key transcription factor of hypoxia, hypoxia-inducible factor-1 (HIF-1) activates the expression of genes essential for EMH processes including enhanced blood cell production and angiogenesis. We found ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, inhibited growth of breast cancer both in vivo and in vitro...
September 30, 2016: Oncotarget
Mohsen Rashidi, Seyed Ali Ziai, Taraneh Moini Zanjani, Ahad Khalilnezhad, Hamidreza Jamshidi, Davar Amani
BACKGROUND: Resistance to chemotherapy is a growing concern, thus natural anticancer agents are drawing the attention of many scientists and clinicians. One natural anticancer agent, umbelliprenin, is a coumarin produced by many species of Ferula. OBJECTIVES: We aimed to examine the inhibitory effect of umbelliprenin on human and mouse bone marrow-derived stem cells (BMDSCs), peripheral blood mononuclear cells (PBMCs), and different cancer cell lines. MATERIALS AND METHODS: In this in vitro experimental study, the HT29, CT26, MCF-7, 4T1, A172, and GL26 cancer cells and human and mouse BMDSCs and PBMCs were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS), incubated at 37°C for 24 hours in a 5% CO2 atmosphere, and then were treated with different concentrations of umbelliprenin dissolved in dimethyl sulfoxide (DMSO) (3, 6, 12, 25, 50, 100, and 200 µg/mL) for 24, 48, and 72 hours at 37°C...
July 2016: Iranian Red Crescent Medical Journal
Ying Xu, Dongming Wu, Yuanchun Fan, Peigeng Li, Hongfei Du, Jiao Shi, Dan Wang, Xiaoping Zhou
The recombinant protein flagellin A (FlaA) N/C, derived from the flagellin protein of Legionella pneumophila, has been shown to increase the expression of cytoprotective cytokines, activate the nuclear factor-κB (NF-κB) signaling pathway, and increase the survival of mice following total body irradiation. Determi ning whether FlaA N/C has a sensitizing effect on tumor radiation or a direct tumoricidal effect is critical for its application as an effective radiation protection agent. The present study investigated the molecular mechanism underlying the tumor radiosensitivity of FlaA N/C...
October 2016: Oncology Letters
Mona Alibolandi, Marzieh Mohammadi, Seyed Mohammad Taghdisi, Mohammad Ramezani, Khalil Abnous
In the current study, dextran (DEX) was covalently conjugated to the surface of nano-GO sheets, making stable biocompatible dextran coated GO (GO-DEX). The prepared GO-DEX was nontoxic to 4T1 mammary carcinoma cell line at concentrations up to 300μg/mL. AS1411 aptamer, a ssDNA aptamer which can improve the intracellular uptake by nucleolin recognition, also has been introduced to hydroxyl groups of DEX in GO-DEX to produce GO-DEX-Apt. Moreover, curcumin (CUR), a natural polyphenol, found in the rhizomes of Curcuma longa (turmeric) which shows antineoplastic effects, was loaded onto the GO-DEX and GO-DEX-Apt via π-π stacking interactions with a high loading capacity (∼29wt%)...
January 2, 2017: Carbohydrate Polymers
Gabriel Ramirez, Ashley R Proctor, Ki Won Jung, Tong Tong Wu, Songfeng Han, Russell R Adams, Jingxuan Ren, Daniel K Byun, Kelley S Madden, Edward B Brown, Thomas H Foster, Parisa Farzam, Turgut Durduran, Regine Choe
The non-invasive, in vivo measurement of microvascular blood flow has the potential to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clinically relevant doses were investigated. Treatments with cyclophosphamide increased blood flow as early as 3 days after administration, whereas paclitaxel induced a transient blood flow decrease at 1 day after administration...
September 1, 2016: Biomedical Optics Express
Ladan Delphi, Houri Sepehri
PURPOSE: Increase in the number of cancer related deaths has made the study on developing new drugs and treatments essential. One of the main aims in developing new therapies is to use natural resources which have the ability to induce apoptosis. Pectin is one of these natural compounds, a complex polysaccharide found in apples with anti-cancer properties. The aim of this study was to examine anti-cancer properties of pectic acid both in vitro in 4T1 breast cancer cells and in vivo using an animal model of breast cancer...
September 30, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Alice Running, Mark Greenwood, Laura Hildreth, Jade Schmidt
As many as 80% of the 296,000 women and 2,240 men diagnosed with breast cancer in the United States will seek out complementary and alternative medicine (CAM) treatments. One such therapy is Healing Touch (HT), recognized by the National Center for Complementary and Integrative Health (NCCIH) as a treatment modality. Using a multiple experimental groups design, fifty-six six- to eight-week-old Balb/c mice were injected with 4T1 breast cancer tumor cells and randomly divided into intervention and positive control groups...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
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