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Tumor microenvironent

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https://www.readbyqxmd.com/read/28917532/effects-of-tumor-microenvironments-on-targeted-delivery-of-glycol-chitosan-nanoparticles
#1
Ji Young Yhee, Sangmin Jeon, Hong Yeol Yoon, Man Kyu Shim, Hyewon Ko, Jiwoong Min, Jin Hee Na, Hyeyoun Chang, Hyounkoo Han, Jong-Ho Kim, Minah Suh, Hyukjin Lee, Jae Hyung Park, Kwangmeyung Kim, Ick Chan Kwon
In cancer theranostics, the main strategy of nanoparticle-based targeted delivery system has been understood by enhanced permeability and retention (EPR) effect of macromolecules. Studies on diverse nanoparticles provide a better understanding of different EPR effects depending on their structure, physicochemical properties, and chemical modifications. Recently the tumor microenvironment has been considered as another important factor for determining tumor-targeted delivery of nanoparticles, but the correlation between EPR effects and tumor microenvironment has not yet been fully elucidated...
September 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28916201/targeting-heparanase-to-the-mammary-epithelium-enhances-mammary-gland-development-and-promotes-tumor-growth-and-metastasis
#2
Ilanit Boyango, Uri Barash, Liat Fux, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
Heparanase is an endoglucuronidase that uniquely cleaves the heparan sulfate side chains of heparan sulfate proteoglycans. This activity ultimately alters the structural integrity of the ECM and basement membrane that becomes more prone to cellular invasion by metastatic cancer cells and cells of the immune system. In addition, enzymatically inactive heparanase was found to facilitate the proliferation and survival of cancer cells by activation of signaling molecules such as Akt, Src, signal transducer and activation of transcription (Stat), and epidermal growth factor receptor...
September 12, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28916105/selective-imaging-of-cancer-cells-with-a-ph-activatable-lysosome-targeting-fluorescent-probe
#3
Rongguang Shi, Lu Huang, Xiaoxue Duan, Guohao Sun, Gui Yin, Ruiyong Wang, Jun-Jie Zhu
Fluorescence imaging with tumor-specific fluorescent probe has emerged as a tool to aid surgeons in the identification and removal of tumor tissue. We report here a new lysosome-targeting fluorescent probe (NBOH) with BODIPY fluorephore to distinguish tumor tissue out of normal tissue based on different pH environment. The probe exhibited remarkable pH-dependent fluorescence behavior in a wide pH range from 3.0 to 11.0, especially a sensitive pH-dependent fluorescence change at pH range between 3.5 and 5.5, corresponding well to the acidic microenvironment of tumor cells, in aqueous solution...
October 2, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28915706/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#4
REVIEW
Lian Liu, Jia-Zhi Liao, Xing-Xing He, Pei-Yuan Li
Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell's components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915700/the-fat-and-the-bad-mature-adipocytes-key-actors-in-tumor-progression-and-resistance
#5
REVIEW
Minh Ngoc Duong, Aline Geneste, Frederique Fallone, Xia Li, Charles Dumontet, Catherine Muller
Growing evidence has raised the important roles of adipocytes as an active player in the tumor microenvironment. In many tumors adipocytes are in close contact with cancer cells. They secrete various factors that can mediate local and systemic effects. The adipocyte-cancer cell crosstalk leads to phenotypical and functional changes of both cell types, which can further enhance tumor progression. Moreover, obesity, which is associated with an increase in adipose mass and an alteration of adipose tissue, has been established as a risk factor for cancer incidence and cancer-related mortality...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#6
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#7
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4(th) leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914667/metabolic-regulation-of-macrophages-in-tumor-microenvironment
#8
Jaehong Kim, Jong-Sup Bae
PURPOSE OF REVIEW: Insight into the metabolic changes in cancer has become so important that cancer is regarded as a disease entity full of metabolic implications. We summarize the recent findings pertaining to cancer cell-derived metabolic changes that regulate the function of macrophages to favor cancer cell survival, and the reported approaches to reverse these changes. RECENT FINDINGS: Since the observation and dramatic revitalization of the Warburg effect, metabolic changes were thought to be confined in cancer cells...
September 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28914317/a-bifunctional-nanomodulator-for-boosting-cpg-mediated-cancer-immunotherapy
#9
Zhenzhen Wang, Yan Zhang, Zhen Liu, Kai Dong, Chaoqun Liu, Xiang Ran, Fang Pu, Enguo Ju, Jinsong Ren, Xiaogang Qu
Unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides (ODNs) possess high immunostimulatory activity and represent attractive tools for cancer treatment. However, their success in eliminating large solid tumors was hampered by the immunosuppressive tumor microenvironment. Herein, we report that the design of a novel MnO2-CpG-silver nanoclusters (AgNCs)-doxorubicin (DOX) conjugate for enhanced cancer immunotherapy, in which MnO2 nanosheets function as unique supports to integrate the chemotherapy drug DOX and the immunotherapeutic agent CpG-AgNCs...
September 15, 2017: Nanoscale
https://www.readbyqxmd.com/read/28912898/inhibition-of-bone-marrow-derived-mesenchymal-stem-cells-homing-towards-triple-negative-breast-cancer-microenvironment-using-an-anti-pdgfr%C3%AE-aptamer
#10
Simona Camorani, Billy Samuel Hill, Raffaela Fontanella, Adelaide Greco, Matteo Gramanzini, Luigi Auletta, Sara Gargiulo, Sandra Albanese, Enrico Lucarelli, Laura Cerchia, Antonella Zannetti
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are shown to participate in tumor progression by establishing a favorable tumor microenvironment (TME) that promote metastasis through a cytokine networks. However, the mechanism of homing and recruitment of BM-MSCs into tumors and their potential role in malignant tissue progression is poorly understood and controversial. Here we show that BM-MSCs increase aggressiveness of triple-negative breast cancer (TNBC) cell lines evaluated as capability to migrate, invade and acquire stemness markers...
2017: Theranostics
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#11
Yu-Pei Chen, Yu Zhang, Jia-Wei Lv, Ying-Qin Li, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Yan-Ping Mao, Jing-Ping Yun, Na Liu, Jun Ma
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number...
2017: Theranostics
https://www.readbyqxmd.com/read/28912626/clinical-impact-of-sphingosine-1-phosphate-in-breast-cancer
#12
REVIEW
Junko Tsuchida, Masayuki Nagahashi, Kazuaki Takabe, Toshifumi Wakai
Breast cancer metastasizes to lymph nodes or other organs, which determine the prognosis of patients. It is difficult to cure the breast cancer patients with distant metastasis due to resistance to drug therapies. Elucidating the underlying mechanisms of breast cancer metastasis and drug resistance is expected to provide new therapeutic targets. Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive lipid mediator that regulates many cellular functions, including proliferation, migration, survival, angiogenesis/lymphangiogenesis, and immune responses...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28912398/-therapeutic-cancer-vaccine-and-immune-checkpoint-inhibitor
#13
Kousaku Mimura, Koji Kono
Therapeutic cancer vaccine enhances a specific immune response against tumor cells in vivo, resulting in exertion of antitumor effects. On the other hand, immune checkpoint inhibitors promote the induction of tumor-specific T cells and also enhance the cytotoxic abilityof these T cells in tumor microenvironment. There is a possibilitythat immune checkpoint inhibitors enhance tumor immune responses induced bytherapeutic cancer vaccine, and it is expected that additive or synergistic effects will be obtained bythe combination of them...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28912374/collagen-embedded-tumor-transplantations-in-xenopus-laevis-tadpoles
#14
Maureen Banach, Jacques Robert
The Xenopus laevis tadpole provides a valuable model for studying tumorigenesis and tumor immunity by intravital real-time microscopy. Using well-characterized thymic lymphoid tumor lines (15/0 and ff-2) that are transplantable into their compatible hosts (LG-15 isogenic clones and the F inbred strain, respectively), a system of semisolid tumor engraftment has been designed. Because these lymphoid tumor cell lines are not adherent and grow in suspension, they are first immobilized in a matrix of type I rat tail collagen before transplantation as a semisolid tumor graft under the transparent dorsal skin in the head region of a tadpole...
September 14, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#15
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28912267/antitumor-immunity-is-defective-in-t-cell-specific-microrna-155-deficient-mice-and-is-rescued-by-immune-checkpoint-blockade
#16
Thomas B Huffaker, Soh-Hyun Lee, William W Tang, Jared A Wallace, Margaret Alexander, Marah C Runtsch, Dane K Larsen, Jacob Thompson, Andrew G Ramstead, Warren P Voth, Ruozhen Hu, June L Round, Matthew A Williams, Ryan M O'Connell
MicroRNA-155 (miR-155) regulates antitumor immune responses. However, its specific functions within distinct immune cell types have not been delineated in conditional knockout (KO) mouse models. In this study, we investigated the role of miR-155 specifically within T cells during the immune response to syngeneic tumors. We found that miR-155 expression within T cells is required to limit syngeneic tumor growth and promote interferon gamma (IFNγ) production by T cells within the tumor microenvironment. Consequently, we found that miR-155 expression by T cells is necessary for proper tumor-associated macrophage (TAM) expression of IFNγ-inducible genes...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912137/enhanced-cancer-immunotherapy-by-chimeric-antigen-receptor-modified-t-cells-engineered-to-secrete-checkpoint-inhibitors
#17
Pin Wang, Si Li, Natnaree Siriwon, Xiaoyang Zhang, Shuai Yang, Tao Jin, Feng He, Yu Jeong Kim, John Mac, Zhengfei Lu, Sijie Wang, Xiaolu Han
PURPOSE: Despite favorable responses of CAR-engineered T cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR-T cells secreting checkpoint inhibitors (CPIs) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model. EXPERIMENTAL DESIGN: To evaluate the effector function and expansion capacity of CAR...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28911823/towards-antibody-drug-conjugates-and-prodrug-strategies-with-extracellular-stimuli-responsive-drug-delivery-in-the-tumor-microenvironment-for-cancer-therapy
#18
REVIEW
Nicolas Joubert, Caroline Denevault-Sabourin, Francesca Bryden, Marie-Claude Viaud-Massuard
The design of innovative anticancer chemotherapies with superior antitumor efficacy and reduced toxicity continues to be a challenging endeavor. Recently, the success of Adcetris(®) and Kadcyla(®) made antibody-drug conjugates (ADCs) serious contenders to reach the envied status of Paul Ehrlich's "magic bullet". However, ADCs classically target overexpressed and internalizing antigens at the surface of cancer cells, and in solid tumors are associated with poor tumor penetration, insufficient targeting in heterogeneous tumors, and appearance of several resistance mechanisms...
August 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28911301/editorial-targeting-drug-resistant-and-metastatic-tumors-by-interference-with-tumor-and-microenvironment-related-alterations
#19
EDITORIAL
Paola Perego
No abstract text is available yet for this article.
2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28911166/hormonal-and-growth-regulation-of-epithelial-and-stromal-cells-from-the-normal-and-malignant-endometrium-by-pigment-epithelium-derived-factor
#20
Julien Daubriac, Unnati M Pandya, Kuang-Tzu Huang, Savvas C Pavlides, Patricia Gama, Stephanie V Blank, Pratibha Shukla, Susan E Crawford, Leslie I Gold
We discovered that pigment epithelium-derived factor (PEDF)-null mice have endometrial hyperplasia, the precursor to human type I endometrial cancer (ECA), which is etiologically linked to unopposed estrogen (E2), suggesting that this potent antiangiogenic factor might contribute to dysregulated growth and the development of type I ECA. Treatment of both ECA cell lines and primary ECA cells with recombinant PEDF dose dependently decreased cellular proliferation via an autocrine mechanism by blocking cells in G1 and G2 phases of the cell cycle...
September 1, 2017: Endocrinology
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