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Tumor microenvironent

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https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#1
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28805874/microfluidic-modeling-of-the-biophysical-microenvironment-in-tumor-cell-invasion
#2
Yu Ling Huang, Jeffrey E Segall, Mingming Wu
Tumor cell invasion, whether penetrating through the extracellular matrix (ECM) or crossing a vascular endothelium, is a critical step in the cancer metastatic cascade. Along the way from a primary tumor to a distant metastatic site, tumor cells interact actively with the microenvironment either via biomechanical (e. g. ECM stiffness) or biochemical (e.g. secreted cytokines) signals. Increasingly, it is recognized that the tumor microenvironment (TME) is a critical player in tumor cell invasion. A main challenge for the mechanistic understanding of tumor cell-TME interactions comes from the complexity of the TME, which consists of extracellular matrices, fluid flows, cytokine gradients and other cell types...
August 14, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28805788/nrf2-keap1-pathway-promotes-cell-proliferation-and-diminishes-ferroptosis
#3
Z Fan, A-K Wirth, D Chen, C J Wruck, M Rauh, M Buchfelder, N Savaskan
Cancer cells are hallmarked by high proliferation and imbalanced redox consumption and signaling. Various oncogenic pathways such as proliferation and evading cell death converge on redox-dependent signaling processes. Nrf2 is a key regulator in these redox-dependent events and operates in cytoprotection, drug metabolism and malignant progression in cancer cells. Here, we show that patients with primary malignant brain tumors (glioblastomas, WHO °IV gliomas, GBM) have a devastating outcome and overall reduced survival when Nrf2 levels are upregulated...
August 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28805551/bone-targeted-cabazitaxel-nanoparticles-for-metastatic-prostate-cancer-skeletal-lesions-and-pain
#4
Andrew S Gdowski, Amalendu Ranjan, Marjana R Sarker, Jamboor K Vishwanatha
AIM: The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. MATERIALS & METHODS: Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed...
August 14, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28805111/chemoresistance-in-cancer-cells-exosomes-as-potential-regulators-of-therapeutic-tumor-heterogeneity
#5
Aman Sharma
Drug resistance in cancer cells remains a fundamental challenge. Be it nontargeted or targeted drugs, the presence of intrinsic or acquired cancer cell resistance remains a great obstacle in chemotherapy. Conventionally, a spectrum of cellular mechanisms defines drug resistance including overexpression of antiapoptotic proteins and drug efflux pumps, mutations in target and synergistic activation of prosurvival pathways in tumor cells. In addition to these well-studied routes, exosome-induced chemoresistance is emerging as a novel mechanism...
August 14, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28804691/combination-of-celecoxib-celebrex-%C3%A2-and-cd19-car-redirected-ctl-immunotherapy-for-the-treatment-of-b-cell-non-hodgkin-s-lymphomas
#6
REVIEW
Tam Nm Dinh, Alexandra S Onea, Ali R Jazirehi
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28803939/bubble-generating-nano-lipid-carriers-for-ultrasound-ct-imaging-guided-efficient-tumor-therapy
#7
Nan Zhang, Jia Li, Ruirui Hou, Jiangnan Zhang, Pei Wang, Xinyang Liu, Zhenzhong Zhang
Ideal therapeutic effectiveness of chemotherapy is obtained only when tumor cells are exposed to a maximal drug concentration, which is often hindered by dose-limiting toxicity. We designed a bubble-generating liposomal delivery system by introducing ammonium bicarbonate and gold nanorods into folic acid-conjugated liposomes to allow both multimodal imaging and the local release of drug (doxorubicin) with hyperthermia. The key component, ammonium bicarbonate, allows a controlled, rapid release of doxorubicin to provide an effective drug concentration in the tumor microenvironment...
August 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#8
REVIEW
Zachary Benson, Saeed H Manjili, Mehran Habibi, Georgi Guruli, Amir A Toor, Kyle K Payne, Masoud H Manjili
Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy...
August 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28803352/breast-cancer-in-elderly-women-and-altered-clinico-pathological-characteristics-a-systematic-review
#9
REVIEW
M Lodi, L Scheer, N Reix, D Heitz, A-J Carin, N Thiébaut, K Neuberger, C Tomasetto, C Mathelin
PURPOSE: Breast cancer is the most common malignancy in women in terms of incidence and mortality. Age is undoubtedly the biggest breast cancer risk factor. In this study we examined clinical, histological, and biological characteristics and mortality of breast cancer in elderly women along with their changes with advancing age. METHODS: We reviewed 63 original articles published between 2006 and 2016 concerning women over 70 years with breast cancer. RESULTS: Compared to patients 70-79 years, patients aged 80 and over had larger tumor size with fewer T1 (42...
August 12, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28802102/pnipaam-co-jeffamine-%C3%A2-pnj-scaffolds-as-in%C3%A2-vitro-models-for-niche-enrichment-of-glioblastoma-stem-like-cells
#10
John M Heffernan, James B McNamara, Sabine Borwege, Brent L Vernon, Nader Sanai, Shwetal Mehta, Rachael W Sirianni
Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance. Therefore, identifying GSC-niche interactions that regulate stem phenotypes may present a unique target for disrupting the maintenance and persistence of this treatment resistant population...
May 6, 2017: Biomaterials
https://www.readbyqxmd.com/read/28801910/application-of-synthetic-tumor-specific-promoters-responsive-to-the-tumor-microenvironment
#11
Eduardo G Cafferata, Maria Veronica Lopez, Felipe J Nuñez, Maria A R Maenza, Osvaldo L Podhajcer
Activity of endogenous promoters can be altered by including additional responsive elements (REs). These elements can be responsive to features of the tumor environment or alternatively to signaling pathways specifically activated in cancer cells. These REs incorporated into tumor-specific promoters can improve cancer targeting, the replicative capacity, and lytic activity of conditionally replicative adenovirus. Here we outline an approach to incorporate hypoxia and inflammation REs into a specific fragment of the SPARC promoter and the steps to clone a nucleosome positioning sequence (NPS ) identified in the osteocalcin promoter that contains a Wnt RE upstream of a heterologous synthetic promoter...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28801702/paeonol-attenuates-aging-mrc-5-cells-and-inhibits-epithelial-mesenchymal-transition-of-premalignant-hacat-cells-induced-by-aging-mrc-5-cell-conditioned-medium
#12
Lihua Yang, Shangping Xing, Kun Wang, Hua Yi, Biaoyan Du
Senescence-associated secretory phenotype (SASP) factors, such as IL-6 and IL-8, are extremely critical in tissue microenvironment. Senescent human fibroblasts facilitate epithelial-mesenchymal transition (EMT) in premalignant epithelial cells mainly through the secretion of SASP factors. Meanwhile, premalignant human HaCaT Keratinocyte (HaCaT) cells as immortal epithelial cells are susceptible to malignant transformation. Paeonol, an herbal phenolic component found in peonies, exerts anti-aging and anti-tumor efficacies, while the molecular mechanisms of paeonol on EMT in premalignant HaCaT cells induced by SASP factors are unclear...
August 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28801587/temozolomide-arrests-glioma-growth-and-normalizes-intratumoral-extracellular-ph
#13
Jyotsna U Rao, Daniel Coman, John J Walsh, Meser M Ali, Yuegao Huang, Fahmeed Hyder
Gliomas maintain an acidic extracellular pH (pHe), which promotes tumor growth and builds resistance to therapy. Given evidence that acidic pHe beyond the tumor core indicates infiltration, we hypothesized that imaging the intratumoral pHe in relation to the peritumoral pHe can provide a novel readout of therapeutic influence on the tumor microenvironment. We used Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), which utilizes chemical shifts of non-exchangeable protons from macrocyclic chelates (e...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801561/inflammation-mediated-sod-2-upregulation-contributes-to-epithelial-mesenchymal-transition-and-migration-of-tumor-cells-in-aflatoxin-g1-induced-lung-adenocarcinoma
#14
Li Yi, Haitao Shen, Mei Zhao, Peilu Shao, Chunping Liu, Jinfeng Cui, Juan Wang, Can Wang, Ningfei Guo, Lifei Kang, Ping Lv, Lingxiao Xing, Xianghong Zhang
Tumor-associated inflammation plays a critical role in facilitating tumor growth, invasion and metastasis. Our previous study showed Aflatoxin G1 (AFG1) could induce lung adenocarcinoma in mice. Chronic lung inflammation associated with superoxide dismutase (SOD)-2 upregulation was found in the lung carcinogenesis. However, it is unclear whether tumor-associated inflammation mediates SOD-2 to contribute to cell invasion in AFG1-induced lung adenocarcinoma. Here, we found increased SOD-2 expression associated with vimentin, α-SMA, Twist1, and MMP upregulation in AFG1-induced lung adenocarcinoma...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800469/immunotherapy-in-ovarian-endometrial-and-cervical-cancer-state-of-the-art-and-future-perspectives
#15
REVIEW
Jole Ventriglia, Immacolata Paciolla, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Rosa Tambaro, Daniela Califano, Simona Losito, Giosuè Scognamiglio, Sergio Venanzio Setola, Laura Arenare, Sandro Pignata, Chiara Della Pepa
The tumors of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Substantial progresses have been made in ovarian cancer, with the increasing knowledge about BRCA mutated tumors and the recent development of PARP inhibitors, and in cervical cancer, thanks to extensive screening and widespread of vaccination against Human Papilloma Virus. Nevertheless many needs remain unmet, advanced stage diseases are still incurable and cervical and endometrial carcinoma, as well as platinum-resistant ovarian carcinoma, can certainly be classifiable among the cancers with poor sensitivity to conventional chemotherapy...
July 31, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28800434/enhanced-photothermal-therapy-of-biomimetic-polypyrrole-nanoparticles-through-improving-blood-flow-perfusion
#16
Xuejun Wang, Haichun Li, Xianping Liu, Ye Tian, Huishu Guo, Ting Jiang, Zimiao Luo, Kai Jin, Xinping Kuai, Yao Liu, Zhiqing Pang, Wuli Yang, Shun Shen
In this study, we reported a strategy to improve delivery efficiency of a long-circulation biomimetic photothermal nanoagent for enhanced photothermal therapy through selectively dilating tumor vasculature. By using a simply nanocoating technology, a biomimetic layer of natural red blood cell (RBC) membranes was camouflaged on the surface of photothermal polypyrrole nanoparticles (PPy@RBC NPs). The erythrocyte-mimicking PPy NPs inherited the immune evasion ability from natural RBC resulting in superior prolonged blood retention time...
August 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28799818/the-expression-and-clinical-signification-of-pd-1-in-lymph-nodes-of-patients-with-non-small-cell-lung-cancer
#17
Haitao Ma, GuoCai Mao, GuangBo Zhang, HaiTao Huang
To screen anti-programmed cell death protein 1 (PD-1) antibody treatment of the dominant population, it is necessary to understand the expression of PD-1 in tumor metastasis microenvironment. The aim of the present study was to detect the expression of PD-1 in lymph nodes of 51 patients with non-small cell lung cancer (NSCLC) by using flow cytometry (FCM). The results showed that the PD-1 expression on CD3(+) T cells was significantly increased in NSCLC metastatic lymph nodes (50.08 ± 8.03%) compared with nonmetastatic lymph nodes (36...
August 11, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28799616/quantitative-investigation-of-mda-mb-231-breast-cancer-cell-motility-dependence-on-epidermal-growth-factor-concentration-and-its-gradient
#18
Tanzila Islam, Haluk Resat
Enhanced cell motility is one of the primary features of cancer. Accumulated evidence demonstrates that Epidermal Growth Factor Receptor (EGFR) mediated pathways play an important role in breast cancer cell proliferation and migration. We have quantified the MDA-MB-231 breast cancer cell migration in response to the stimulation of EGFR pathways with their ligand EGF to determine how the cell motility of MDA-MB-231 cells depends on the ligand concentration and gradient. Analysis at the single cell level combined with mathematical modeling and the ability to vary the ligand concentration and gradients locally using microfluidic devices allowed us to separate the unique contributions of ligand concentration and ligand gradient to cell motility...
August 11, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28798986/a-phase-ii-multicentre-open-label-proof-of-concept-study-of-tasquinimod-in-hepatocellular-ovarian-renal-cell-and-gastric-cancers
#19
Bernard Escudier, Sandrine Faivre, Eric Van Cutsem, Nathalie Germann, Jean-Christophe Pouget, Ruth Plummer, Ignace Vergote, Fiona Thistlethwaite, Georg A Bjarnason, Robert Jones, Helen Mackay, Julien Edeline, Laetitia Fartoux, Hal Hirte, Amit Oza
BACKGROUND: Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. PATIENTS AND METHODS: This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers...
August 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28798979/mucosa-associated-invariant-t-cells-infiltrate-hepatic-metastases-in-patients-with-colorectal-carcinoma-but-are-rendered-dysfunctional-within-and-adjacent-to-tumor-microenvironment
#20
Christopher R Shaler, Mauro E Tun-Abraham, Anton I Skaro, Khashayarsha Khazaie, Alexandra J Corbett, Tina Mele, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection...
August 10, 2017: Cancer Immunology, Immunotherapy: CII
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