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https://www.readbyqxmd.com/read/29149720/a-robust-strategy-for-preparation-of-sequential-stimuli-responsive-block-copolymer-prodrugs-via-thiolactone-chemistry-to-overcome-multiple-anticancer-drug-delivery-barriers
#1
Wendong Ke, Wei Yin, Zengshi Zha, Jean Felix Mukerabigwi, Weijian Chen, Yuheng Wang, Chuanxin He, Zhishen Ge
Block copolymer prodrugs (BCPs) have attracted considerable attentions in clinical translation of nanomedicine owing to their self-assembly into well-defined core-shell nanoparticles for improved pharmacokinetics, stability in blood circulation without drug leakage, and optimized biodistribution. However, a cascade of physiological barriers against specific delivery of drugs into tumor cells limit the final therapeutic efficacy. Herein, we report a robust and facile strategy based on thiolactone chemistry to fabricate well-defined BCPs with sequential tumor pH-promoted cellular internalization and intracellular stimuli-responsive drug release...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29148852/sildenafil-citrate-improves-the-delivery-and-anticancer-activity-of-doxorubicin-formulations-in-a-mouse-model-of-breast-cancer
#2
Khaled Greish, Maryam Fateel, Sara Abdelghany, Nanitha Rachel, Houman Alimoradi, Moiz Bakhiet, Ahmed Alsaie
Sildenafil is an approved drug for the treatment of erectile dysfunction. The drug exerts its action through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. In this work, we tested whether the aforementioned effects of Sildenafil on tumor vasculatures could result in an improvement of anticancer drug concentration in tumor tissues, and hence improve its anticancer effect. Sildenafil when added to doxorubicin showed synergistic anticancer activity against 4T1 breast cancer cells in vitro...
November 17, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29148694/ambient-aqueous-synthesis-of-ultrasmall-ni0-85se-nanoparticles-for-non-invasive-photoacoustic-imaging-and-combined-photothermal-chemo-therapy-of-cancer
#3
Xianwen Wang, Fei Li, Xu Yan, Yan Ma, Zhaohua Miao, Liang Dong, Huajian Chen, Yang Lu, Zhengbao Zha
Big size induced long-term retention in the body has hampered the translational applications of many reported nanomedicine. Herein, we reported a multifunctional theranostic agent composed of ultrasmall polyacrylic acid functionalized Ni0.85Se nanoparticles (PAA-Ni0.85Se NPs), which were successfully obtained through a facile ambient aqueous precipitation strategy. Without exhibiting any noticeable toxicity, the as-prepared PAA-Ni0.85Se NPs (average diameter of 6.40 ± 1.89 nm) showed a considerable absorption in near-infrared (NIR) region and high photothermal conversion efficiency (PTCE) of 54...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29147627/stat1-gene-deficient-mice-develop-accelerated-breast-cancer-growth-and-metastasis-which-is-reduced-by-il-17-blockade
#4
Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K Ahirwar, Pablo C Alarcon, Rachel H Sperling, Ellen Moretti, Marissa S Pioso, Jennifer Kimble, Mohd W Nasser, Ramesh K Ganju, Cesar Terrazas, Abhay R Satoskar
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1(-/-) mice orthotopically implanted with metastatic 4T1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146246/nanoparticle-formulation-improves-doxorubicin-efficacy-by-enhancing-host-antitumor-immunity
#5
Eric M Mastria, Leon Y Cai, Matthew J Kan, Xinghai Li, Jeffrey L Schaal, Steven Fiering, Michael D Gunn, Mark W Dewhirst, Smita K Nair, Ashutosh Chilkoti
Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it has become recognized that doxorubicin can contribute to re-establishing host antitumor immunity through the generation of immunogenic cell death. However, the potential for delivery strategies to further enhance the immunological effects of doxorubicin has not been adequately examined...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29139296/differential-content-of-proteins-mrnas-and-mirnas-suggests-that-mdsc-and-their-exosomes-may-mediate-distinct-immune-suppressive-functions
#6
Lucia Geis-Asteggiante, Ashton T Belew, Virginia K Clements, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Nagib M El-Sayed, Catherine Fenselau
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC...
November 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29138867/effect-of-xanthohumol-on-th1-th2-balance-in-a-breast-cancer-mouse-model
#7
Wenchao Zhang, Yanlong Pan, Panhong Gou, Cheng Zhou, Lianqing Ma, Qiming Liu, Yuping Du, Jinbo Yang, Qin Wang
Xanthohumol (XN), a prenylflavonoid found in the hop plant, Humulus lupulus, exhibits a variety of biological activities. Numerous studies have reported that XN inhibits the growth of many types of cancer cells, but the effects of XN on tumor immunity have not yet been studied. We explored the effect of XN on Th1/Th2 balance and the underlying mechanism based on a BALB/c-4T1 breast cancer mouse model. The results showed that XN significantly slowed down tumor growth and inhibited expression of antitumor proliferation protein Ki-67 as well as breast cancer-specific marker cancer antigen 15-3 (CA15-3)...
November 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29134467/diterpenoid-natural-compound-c4-crassin-exerts-cytostatic-effects-on-triple-negative-breast-cancer-cells-via-a-pathway-involving-reactive-oxygen-species
#8
Cathy E Richards, Sri H Vellanki, Yvonne E Smith, Ann M Hopkins
PURPOSE: Triple-negative breast cancers (TNBC) lack expression of three common cell surface receptors, i.e., estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). Accordingly, TNBCs are associated with fewer treatment options and a relatively poor prognosis. Having screened a National Cancer Institute natural compound library, the purpose of this study was to investigate the bioactivity of compound C4 (Crassin) in TNBC cells. METHODS: Cell viability assays were performed in two TNBC cell lines, MDA-MB-231 and 4T1, following C4 treatment in the presence or absence of the antioxidant N-acetyl-L-cysteine (NAC)...
November 13, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29134085/gene-delivery-ability-of-polyethylenimine-and-polyethylene-glycol-dual-functionalized-nanographene-oxide-in-11-different-cell-lines
#9
Liping Wu, Jinshan Xie, Tan Li, Zihao Mai, Lu Wang, Xiaoping Wang, Tongsheng Chen
We recently developed a polyethylenimine (PEI) and polyethylene glycol (PEG) dual-functionalized reduced graphene oxide (GO) (PEG-nrGO-PEI, RGPP) for high-efficient gene delivery in HepG2 and Hela cell lines. To evaluate the feasibility and applicability of RGPP as a gene delivery carrier, we here assessed the transfection efficiency of RGPP on gene plasmids and siRNA in 11 different cell lines. Commercial polyalkyleneimine cation transfection reagent (TR) was used as comparison. In HepG2 cells, RGPP exhibited much stronger delivery ability for siRNA and large size plasmids than TR...
October 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/29131861/delivery-of-epirubicin-via-slow-infusion-as-a-strategy-to-mitigate-chemotherapy-induced-cardiotoxicity
#10
Fang Yang, Qiao Lei, Lu Li, Jian Chang He, Jiajia Zeng, Chunxiang Luo, Sai-Ching Jim Yeung, Runxiang Yang
BACKGROUND: Continuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. However, evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy. DESIGN AND METHODS: Healthy rats were randomized into groups: epirubicin (8 mg/kg) delivered intraperitoneally via micro osmotic pumps (MOP), epirubicin (8 mg/kg) by intraperitoneal (IP) bolus injection, and placebo control...
2017: PloS One
https://www.readbyqxmd.com/read/29129789/dual-ph-responsive-multifunctional-nanoparticles-for-targeted-treatment-of-breast-cancer-by-combining-immunotherapy-and-chemotherapy
#11
Yuanyuan Liu, Linan Qiao, Sipei Zhang, Guoyun Wan, Bowei Chen, Ping Zhou, Ning Zhang, Yinsong Wang
In the present study, a dual pH-responsive multifunctional nanoparticle system was designed for combining immunotherapy and chemotherapy to treat breast cancer through targeting immune cells and cancer cells. A proven anti-tumor immune regulator, R848, was encapsulated with poly(L-histidine) (PHIS) to form PHIS/R848 nanocores. Doxorubicin (DOX) was conjugated to hyaluronic acid (HA) through an acid-cleavable hydrazone bond linkage to synthesize polymeric prodrug HA-DOX, which was subsequently coated outside PHIS/R848 nanocores to form HA-DOX/PHIS/R848 nanoparticles...
November 9, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29129754/cd44-targeting-hyaluronic-acid-coated-lapatinib-nanocrystals-foster-the-efficacy-against-triple-negative-breast-cancer
#12
Satish Agrawal, Monika Dwivedi, Hafsa Ahmad, Sangappa Basanna Chadchan, Abhishek Arya, Roshan Sikandar, Shweta Kaushik, Kalyan Mitra, Rajesh Kumar Jha, Anil Kumar Dwivedi
Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than its counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs not only increased the residence time of LPT, but also targeted the tumor, reduced the tumor burden, and increased overall survival...
November 9, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29128855/selective-inhibition-of-ido1-d-1-methyl-tryptophan-d-1mt-effectively-increased-epcam-cd3-bispecific-bite-antibody-mt110-efficacy-against-ido1-hi-breast-cancer-via-enhancing-immune-cells-activity
#13
Ri Hong, Yuhai Zhou, Xiujuan Tian, Lijuan Wang, Xiaoyun Wu
MuS110 and MT110 are BiTE antibodies bispecific for CD3 and EpCAM, which is the most frequently and highly expressed tumor-associated antigen on breast cancer. And pronounced expression of IDO1 has also been reported in breast cancer. Our study aimed to investigate whether IDO1 inhibitor D-1MT combing with MuS110/MT110 had synergistic antitumor effects on IDO expressing EpCAM-positive breast cancer cells in vitro and in vivo. Data suggested that the expression of IDO1 on Epcam-positive breast cancer 4T1 and MCF-7 decreased MuS110/MT110 antitumor efficacy by the suppression of T cells activation in vitro...
November 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29123422/neutrophil-derived-interleukin-16-in-premetastatic-lungs-promotes-breast-tumor-cell-seeding
#14
Kim Donati, Christelle Sépult, Natacha Rocks, Silvia Blacher, Catherine Gérard, Agnès Noel, Didier Cataldo
The premetastatic niche in distant organs prior to metastatic cell arrival emerged as an important step in the metastatic cascade. However, molecular mechanisms underlying this process are still poorly understood. In particular, whether neutrophil recruitment at a premetastatic stage promotes or inhibits metastatic cell seeding has to be clarified. We aimed at unraveling how neutrophil infiltration in lung parenchyma induced by the distant primary tumor influences the establishment of lung metastasis. Elevated neutrophil counts and IL-16 levels were found in premetastatic lungs in a syngenic mouse model using 4T1 tumor cells...
2017: Cancer Growth and Metastasis
https://www.readbyqxmd.com/read/29116108/precision-targeting-of-tumor-macrophages-with-a-cd206-binding-peptide
#15
Pablo Scodeller, Lorena Simón-Gracia, Sergei Kopanchuk, Allan Tobi, Kalle Kilk, Pille Säälik, Kaarel Kurm, Mario Leonardo Squadrito, Venkata Ramana Kotamraju, Ago Rinken, Michele De Palma, Erkki Ruoslahti, Tambet Teesalu
Tumor-associated macrophages (TAMs) expressing the multi-ligand endocytic receptor mannose receptor (CD206/MRC1) contribute to tumor immunosuppression, angiogenesis, metastasis, and relapse. Here, we describe a peptide that selectively targets MRC1-expressing TAMs (MEMs). We performed in vivo peptide phage display screens in mice bearing 4T1 metastatic breast tumors to identify peptides that target peritoneal macrophages. Deep sequencing of the peptide-encoding inserts in the selected phage pool revealed enrichment of the peptide CSPGAKVRC (codenamed "UNO")...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115583/unfavorable-effect-of-calcitriol-and-its-low-calcemic-analogs-on-metastasis-of-4t1-mouse-mammary-gland-cancer
#16
Artur Anisiewicz, Agata Pawlik, Beata Filip-Psurska, Eliza Turlej, Stanisław Dzimira, Magdalena Milczarek, Katarzyna Gdesz, Diana Papiernik, Joanna Jarosz, Dagmara Kłopotowska, Andrzej Kutner, Andrzej Mazur, Joanna Wietrzyk
Low vitamin D status is considered as a risk factor for breast cancer and has prognostic significance. Furthermore, vitamin D deficiency increases after adjuvant cancer therapy, which alters bone metabolism increasing the risk of osteoporosis. It is now postulated that vitamin D supplementation in breast cancer treatment delays the recurrence of cancer thereby extending survival. We evaluated the impact of calcitriol and its low-calcemic analogs, PRI‑2191 and PRI‑2205, on the tumor growth, angiogenesis, and metastasis of 4T1 mouse mammary gland cancer...
November 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29107385/ccl2-conditionally-determines-ccl22-dependent-th2-accumulation-during-tgf-%C3%AE-induced-breast-cancer-progression
#17
Palash Kumar Mandal, Subir Biswas, Gunjan Mandal, Suman Purohit, Arnab Gupta, Amita Majumdar Giri, Sougata Roy Chowdhury, Arindam Bhattacharyya
We investigated expressions of -CC chemokine ligand 2 (CCL2) and CCL5 in tumor samples from 147 breast cancer (BCa) patients and correlated with transforming growth factor-β (TGF-β) expression. We observed an inverse correlation of TGF-β expression with CCL2, CCL5 expression in early stages of BCa. On contrary, in late stages, CCL2, not CCL5, expression was found to be directly proportional with TGF-β expression. TGF-β stimulated MDA-MB-231 cells to express CCL2, however, downregulated both CCL2 and CCL5 in MCF-7...
October 16, 2017: Immunobiology
https://www.readbyqxmd.com/read/29094642/shell-crosslinked-zein-nanocapsules-for-oral-codelivery-of-exemestane-and-resveratrol-in-breast-cancer-therapy
#18
Ahmed O Elzoghby, Sarah A El-Lakany, Maged W Helmy, Marwa M Abu-Serie, Nazik A Elgindy
AIM: Oral administration of exemestane (EXM) and resveratrol (RES) for breast cancer therapy has been limited by their poor solubility and low permeability. METHODS: In this study, these issues were tackled using zein nanocapsules (ZNCs) for oral EXM/RES codelivery combining drug solubilization within oily core and resistance to digestion via hydrophobic protein shell. Furthermore, higher oral stability and sustained release could be enabled by glutaraldehyde crosslinking of zein shell...
November 2, 2017: Nanomedicine
https://www.readbyqxmd.com/read/29083862/tethering-of-chemotherapeutic-drug-imaging-agent-to-bile-acid-phospholipid-increases-the-efficacy-and-bioavailability-with-reduced-hepatotoxicity
#19
Vedagopuram Sreekanth, Nihal Medatwal, Sandeep Kumar, Sanjay Pal, Malyla Vamshikrishna, Animesh Kar, Priyanshu Bhargava, Aaliya Naaz, Nitin Kumar, Sagar Sengupta, Avinash Bajaj
Weakly basic drugs display poor solubility and tend to precipitate in the stomach's acidic environment causing reduced oral bioavailability. Tracing of these orally delivered therapeutic agents using molecular probes is challenged due to their poor absorption in the gastrointestinal tract (GIT). Therefore, we designed a gastric pH stable bile acid derived amphiphile where Tamoxifen (as a model anticancer drug) is conjugated to lithocholic acid derived phospholipid (LCA-Tam-PC). In vitro studies suggested the selective nature of LCA-Tam-PC for cancer cells over normal cells as compared to the parent drug...
November 9, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29082597/magnetic-resonance-molecular-imaging-of-metastatic-breast-cancer-by-targeting-extradomain-b-fibronectin-in-the-tumor-microenvironment
#20
Zheng Han, Han Cheng, Jenny G Parvani, Zhuxian Zhou, Zheng-Rong Lu
PURPOSE: Non-invasive early accurate detection of malignant breast cancer is paramount to the clinical management of the life-threatening disease. Here, we aim to test a small peptide targeted MRI contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein, extradomain-B fibronectin (EDB-FN), in the tumor microenvironment for MR molecular imaging of breast cancer. METHOD: EDB-FN expression in 4T1 and MDA-MB-231 cancers was analyzed with quantitative real-time PCR and western blot...
October 29, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
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