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https://www.readbyqxmd.com/read/28538141/cancer-cell-and-macrophage-cross-talk-in-the-tumor-microenvironment
#1
REVIEW
Nathalie Dehne, Javier Mora, Dmitry Namgaladze, Andreas Weigert, Bernhard Brüne
Tumors are composed of tumor cells, nonmalignant cells, and the vascular system. Among them is intense communication via cell-cell contact-dependent mechanisms and/or soluble messengers. In the tumor microenvironment cells often face a certain degree of oxygen and nutrient deprivation. Hypoxic stress alters the metabolism of tumor cells but also of macrophages, as one dominating immune cell population in most solid tumors, with subsequent changes in the microenvironment. This alters the phenotype and metabolism of macrophages, to induce a tumor-promoting reprogramming...
May 21, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28537912/braf-mek-inhibitors-promote-cd47-expression-that-is-reversible-by-erk-inhibition-in-melanoma
#2
Fen Liu, Chen Chen Jiang, Xu Guang Yan, Hsin-Yi Tseng, Chun Yan Wang, Yuan Yuan Zhang, Hamed Yari, Ting La, Margaret Farrelly, Su Tang Guo, Rick F Thorne, Lei Jin, Qi Wang, Xu Dong Zhang
The expression of CD47 on the cancer cell surface transmits "don't eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses. Here we report that oncogenic activation of ERK plays an important role in transcriptional activation of CD47 through nuclear respiratory factor 1 (NRF-1) in melanoma cells. Treatment with BRAF/MEK inhibitors upregulated CD47 in cultured melanoma cells and fresh melanoma isolates. Similarly, melanoma cells selected for resistance to the BRAF inhibitor vemurafenib expressed higher levels of CD47...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534943/bu-fei-decoction-attenuates-the-tumor-associated-macrophage-stimulated-proliferation-migration-invasion-and-immunosuppression-of-non-small-cell-lung-cancer-partially-via-il-10-and-pd-l1-regulation
#3
Lina Pang, Shuyan Han, Yanna Jiao, Shantong Jiang, Xiran He, Pingping Li
Macrophages play a pivotal role in tumor microenvironment. Bu-Fei Decoction (BFD) is a classical formula of traditional Chinese medicine (TCM) to alleviate lung cancer related symptoms, whether it has antitumor effect or could influence cancer microenvironment deserves further study. The aim of the present study was to examine the antitumor effect of BFD on non-small cell lung cancer (NSCLC), and to investigate the underlying mechanisms through tumor associated macrophages (TAMs). M2-polarized TAMs were induced by Phorbol 12-myristate 13-acetate (PMA) and interleukin 4 (IL-4)...
May 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534931/leucine-rich-glioma-inactivated-3-integrative-analyses-support-its-role-in-the-cytokine-network
#4
Hyun A Kim, Nyoun Soo Kwon, Kwang Jin Baek, Dong-Seok Kim, Hye-Young Yun
Leucine-rich glioma inactivated (LGI)3 is a secreted protein member of LGI family. We previously repo-rted that LGI3 was upregulated in adipose tissues from obese mice and suppressed adipogenesis through its receptor, a disintegrin and metalloproteinase domain-containing protein 23 (ADAM23). We demonstrated that LGI3 regulated tumor necrosis factor-α and adiponectin, and proposed that LGI3 may be a pro-inflammatory adipokine involved in adipose tissue inflammation. In this study, we analyzed adipokine and cytokine profiles in LGI3 knockout mice and demonstrated that multiple factors were increased or decreased in the adipose tissues and plasma of the LGI3 knockout mice...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534709/mdscs-are-involved-in-the-protumorigenic-potentials-of-gm-csf-in-colitis-associated-cancer
#5
Ning Ma, Qilin Liu, Lin Hou, Yalin Wang, Ziling Liu
Chronic inflammation is thought to be a major driving force for the development of colitis-associated colorectal cancer (CAC). As one member of proinflammatory cytokine family, granulocyte macrophage colony-stimulating factor (GM-CSF) has been identified to play a key role in CAC pathogenesis recently. The underlying mechanisms, however, remain largely unknown. In this study, we found that myeloid-derived suppressor cells (MDSCs) accumulated increasingly in the lesions during the progression from colitis to cancer, which was critical for CAC formation...
May 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28533483/high-il-1r8-expression-in-breast-tumors-promotes-tumor-growth-and-contributes-to-impaired-antitumor-immunity
#6
Luis Felipe Campesato, Ana Paula M Silva, Luna Cordeiro, Bruna R Correa, Fabio C P Navarro, Rafael F Zanin, Marina Marçola, Lilian T Inoue, Mariana L Duarte, Martina Molgora, Fabio Pasqualini, Matteo Massara, Pedro Galante, Romualdo Barroso-Sousa, Nadia Polentarutti, Federica Riva, Erico T Costa, Alberto Mantovani, Cecilia Garlanda, Anamaria A Camargo
Tumors develop numerous strategies to fine-tune inflammation and avoid detection and eradication by the immune system. The identification of mechanisms leading to local immune dysregulation is critical to improve cancer therapy. We here demonstrate that Interleukin-1 receptor 8 (IL-1R8 - previously known as SIGIRR/TIR8), a negative regulator of Toll-Like and Interleukin-1 Receptor family signaling, is up-regulated during breast epithelial cell transformation and in primary breast tumors. IL-1R8 expression in transformed breast epithelial cells reduced IL-1-dependent NF-κB activation and production of pro-inflammatory cytokines, inhibited NK cell activation and favored M2-like macrophage polarization...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533271/vhl-inactivation-in-precancerous-kidney-cells-induces-an-inflammatory-response-via-er-stress-activated-ire1%C3%AE-signaling
#7
Chan-Yen Kuo, Chih-Hung Lin, Tien Hsu
Mutations and epigenetic inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) are major causes of clear-cell renal cell carcinoma (ccRCC) that may originate from chronic inflammation. However, the role of VHL loss-of-function in the development of ccRCC via inflammation remains poorly understood. VHL mutant cells exhibit metabolic abnormalities that can cause chronic endoplasmic reticulum (ER) stress and unfolded protein response (UPR). We hypothesize that unresolved ER stress induces the inflammatory responses observed in ccRCC...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28530155/an-oncolytic-adenovirus-encoding-decorin-and-gm-csf-inhibits-tumor-growth-in-a-colorectal-tumor-model-by-targeting-pro-tumorigenic-signals-and-via-immune-activation
#8
Zhao Liu, Yuefeng Yang, Xiaoyan Zhang, Hao Wang, Weidong Xu, Hua Wang, FengJun Xiao, Zhigang Bai, Hongwei Yao, Xuemei Ma, Lan Jin, Chu-Tse Wu, Prem Seth, Zhongtao Zhang, Lisheng Wang
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while, there were increased Met and VEGFA levels...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28529645/tumor-penetrating-theranostic-nanoparticles-for-enhancement-of-targeted-and-image-guided-drug-delivery-into-peritoneal-tumors-following-intraperitoneal-delivery
#9
Ning Gao, Erica N Bozeman, Weiping Qian, Liya Wang, Hongyu Chen, Malgorzata Lipowska, Charles A Staley, Y Andrew Wang, Hui Mao, Lily Yang
The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery...
2017: Theranostics
https://www.readbyqxmd.com/read/28526770/therapeutic-ige-antibodies-harnessing-a-macrophage-mediated-immune-surveillance-mechanism-against-cancer
#10
REVIEW
Sophia N Karagiannis, Debra H Josephs, Heather J Bax, James F Spicer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526302/an-important-role-of-vegf-c-in-promoting-lymphedema-development
#11
Epameinondas Gousopoulos, Steven T Proulx, Samia B Bachmann, Lothar C Dieterich, Jeannette Scholl, Sinem Karaman, Roberta Bianchi, Michael Detmar
Secondary lymphedema is a common post-cancer treatment complication but the pathomechanisms underlying the disease remain unclear. Using a mouse-tail lymphedema model, we found an increase in local and systemic levels of the lymphangiogenic factor VEGF-C, and identified CD68+ macrophages as a cellular source. Surprisingly, overexpression of VEGF-C in a transgenic mouse model led to aggravation of lymphedema with increased immune cell infiltration and vascular leakage in comparison to wild-type littermates. Conversely, blockage of VEGF-C by overexpression of soluble VEGFR3 reduced edema development, diminishing inflammation and blood vascular leakage...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28522599/engineering-macrophages-to-eat-cancer-from-marker-of-self-cd47-and-phagocytosis-to-differentiation
#12
REVIEW
Cory Alvey, Dennis E Discher
The ability of a macrophage to engulf and break down invading cells and other targets provides a first line of immune defense in nearly all tissues. This defining ability to "phagos" or devour can subsequently activate the entire immune system against foreign and diseased cells, and progress is now being made on a decades-old idea of directing macrophages to phagocytose specific targets, such as cancer cells. Engineered T cells provide precedence with recent clinical successes against liquid tumors, but solid tumors remain a challenge, and a handful of clinical trials seek to exploit the abundance of tumor-associated macrophages instead...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28521292/tumor-infiltrating-immune-cells-and-prognosis-in-gastric-cancer-a-systematic-review-and-meta-analysis
#13
Wen Jiang, Ke Liu, Qing Guo, Ji Cheng, Liming Shen, Yinghao Cao, Jing Wu, Jianguo Shi, Heng Cao, Bo Liu, Kaixiong Tao, Guobin Wang, Kailin Cai
Tumor-infiltrating immune cells are a pivotal component of the tumor microenvironment (TME), but their indicative role remains poorly defined. A meta-analysis was performed to reveal the prognostic efficiency of tumor-infiltrating immune cells in gastric cancer (GC). By searching PubMed and Embase, we identified a total of 35 eligible articles that involved 4888 patients. Random or fixed effect models were employed to extract pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Our results indicated that high CD3+ lymphocyte infiltration in all the locations (AG), the tumor nest (TN), and the tumor stroma (TS) predicted better overall survival (OS) (HR=0...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28518147/survivin-a-key-player-in-cancer-progression-increases-in-obesity-and-protects-adipose-tissue-stem-cells-from-apoptosis
#14
Miriam Ejarque, Victòria Ceperuelo-Mallafré, Carolina Serena, Gisela Pachón, Yaiza Núñez-Álvarez, Margarida Terrón-Puig, Enrique Calvo, Catalina Núñez-Roa, Wilfredo Oliva-Olivera, Francisco J Tinahones, Miguel Angel Peinado, Joan Vendrell, Sonia Fernández-Veledo
Adipose tissue (AT) has a central role in obesity-related metabolic imbalance through the dysregulated production of cytokines and adipokines. In addition to its known risk for cardiovascular disease and diabetes, obesity is also a major risk for cancer. We investigated the impact of obesity for the expression of survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic biomarker of tumor onset and recurrence. In a cross-sectional study of 111 subjects classified by body mass index, circulating levels of survivin and gene expression in subcutaneous AT were significantly higher in obese patients and positively correlated with leptin...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28518138/betulin-exhibits-anti-inflammatory-activity-in-lps-stimulated-macrophages-and-endotoxin-shocked-mice-through-an-ampk-akt-nrf2-dependent-mechanism
#15
Xinxin Ci, Junfeng Zhou, Hongming Lv, Qinlei Yu, Liping Peng, Shucheng Hua
Continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer. Nuclear factor erythroid 2-related factor (Nrf2), a critical transcriptional activator for antioxidative responses, has envolved to be an attractive drug target for the treatment or prevention of human diseases. In the present study, we investigated the effects and mechanisms of betulin on Nrf2 activation and its involvement in the lipopolysaccharide (LPS)-triggered inflammatory system...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28516983/nanoparticle-design-strategies-for-enhanced-anticancer-therapy-by-exploiting-the-tumour-microenvironment
#16
REVIEW
Yunlu Dai, Can Xu, Xiaolian Sun, Xiaoyuan Chen
Nanovehicles can efficiently carry and deliver anticancer agents to tumour sites. Compared with normal tissue, the tumour microenvironment has some unique properties, such as vascular abnormalities, hypoxia and acidic pH. There are many types of cells, including tumour cells, macrophages, immune and fibroblast cells, fed by defective blood vessels in the solid tumour. Exploiting the tumour microenvironment can benefit the design of nanoparticles for enhanced therapeutic effectiveness. In this review article, we summarized the recent progress in various nanoformulations for cancer therapy, with a special emphasis on tumour microenvironment stimuli-responsive ones...
May 18, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28516508/near-infrared-photodynamic-inactivation-of-s-pneumoniae-and-its-interaction-with-raw-264-7-macrophages
#17
Ilaiáli S Leite, Mariana C Geralde, Ana C G Salina, Alexandra I Medeiros, Lívia N Dovigo, Vanderlei S Bagnato, Natalia M Inada
Pneumonia is the main cause of children mortality worldwide, and its major treatment obstacle stems from the microorganisms increasing development of resistance to several antibiotics. Photodynamic therapy has been presenting, for the last decades, promising results for some subtypes of cancer and infections. In this work we aimed to develop a safe and efficient in vitro protocol for photodynamic inactivation of Streptococcus pneumoniae, one of the most commonly found bacteria in pneumonia cases, using two near-infrared light sources and indocyanine green, a FDA approved dye...
May 18, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28515351/local-immune-response-depends-on-p16ink4a-status-of-primary-tumor-in-vulvar-squamous-cell-carcinoma
#18
Jacek J Sznurkowski, Anton Żawrocki, Wojciech Biernat
BACKGROUND: The p16Ink4a is not a surrogate marker for high-risk human papilloma virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell carcinoma patients. Our recent study confirmed substantial mismatch between p16Ink4a and high-risk HPV-status as well as revealed that p16Ink4a-overexpression itself is an independent prognostic factor for vulvar cancer. AIM: To determine significance of the tumor infiltrating immune cells and p16Ink4a-status for better outcome of patients with vulvar cancer...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515123/all-trans-retinoic-acid-prevents-osteosarcoma-metastasis-by-inhibiting-m2-polarization-of-tumor-associated-macrophages
#19
Qian Zhou, Miao Xian, Senfeng Xiang, Danyan Xiang, Xuejing Shao, Jincheng Wang, Ji Cao, Xiaochun Yang, Bo Yang, Meidan Ying, Qiaojun He
M2-polarized tumor associated macrophages (TAM) play a critical role in cancer invasion and metastasis. Here, we report that M2 macrophages enhanced metastasis of K7M2 WT osteosarcoma cells to the lung in mice, thus establishing M2 TAMs as a therapeutic target for blocking osteosarcoma metastasis. We found that all-trans retinoic acid (ATRA) inhibited osteosarcoma metastasis via inhibiting the M2 polarization of TAMs. ATRA suppressed IL13 or IL4 induced M2-type macrophages, and then inhibited migration of osteosarcoma cells as promoted by M2-type macrophages in vitro ATRA reduced the number of pulmonary metastatic nodes of osteosarcoma and decreased expression of M2-type macrophages in metastatic nodes both in intravenous injection and orthotopic transplantation models...
May 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28514755/a-novel-serum-based-biomarker-panel-has-complementary-ability-to-preclude-presence-of-early-lung-cancer-for-low-dose-ct-ldct
#20
Xiaobing Wang, Xiuyi Zhi, Zhaogang Yang, Haimei Tian, Yanfen Li, Mo Li, Wenya Zhao, Chao Zhang, Teng Wang, Jing Liu, Di Shen, Cuining Zheng, Dan Zhao, Sheng Yang, Jun Qi, Hongwu Xin, Alexander Stojadinovic, Itzhak Avital, L James Lee, Jianyu Rao, Wei Zhang
Low Dosage Computerized Tomography (LDCT) has been shown to improve early detection of lung cancer and mortality rates in high-risk individuals, which was, however, limited by specifically coverage for heavy smokers and high rates of false positivity. Here, we aim to investigate a novel biomarker for early detection of lung cancer, and further extend to concentrate high-risk subjects for increasing specificity and coverage of LDCT. We performed retrospective blinded evaluation of lung cancer and healthy controls in training and validation cohorts...
April 27, 2017: Oncotarget
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