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Tumor microenvironent

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https://www.readbyqxmd.com/read/27922687/immature-myeloid-derived-suppressor-cells-a-bridge-between-inflammation-and-cancer-review
#1
Caterina Musolino, Alessandro Allegra, Govanni Pioggia, Sebastiano Gangemi
Chronic inflammation is considered to be one of the hallmarks of tumor initiation and progression. Changes occurring in the microenvironment of progressing tumors resemble the process of chronic inflammation, which begins with ischemia followed by interstitial and cellular edema, appearance of immune cells, growth of blood vessels and tissue repair, and development of inflammatory infiltrates. Moreover, long‑term production and accumulation of inflammatory factors lead to local and systemic immunosuppression associated with cancer progression...
December 5, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922590/neutrophils-are-essential-in-short-hairpin-rna-of-indoleamine-2-3-dioxygenase-mediated-antitumor-efficiency
#2
Kuan-Ting Liu, Yao-Hua Liu, Hsin-Liang Liu, Inn-Wen Chong, Meng-Chi Yen, Po-Lin Kuo
Indoleamine 2,3-dioxygenase (IDO) is a rate limiting enzyme in tryptophan-degrading pathways and IDO activity results in immune suppression. Targeting IDO is a strategy of cancer immunotherapies. Our previous studies demonstrate that delivery of short hairpin against IDO (IDO shRNA) suppresses tumor growth and increases neutrophils infiltration into tumor. Neutrophils reveal antitumorigenic "N1" or protumorigenic "N2" phenotype in tumor microenvironment. However, the function of IDO shRNA-induced neutrophils is not clear...
December 6, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27920705/heterotopic-ossification-in-rectal-carcinoma-report-of-a-case-and-review-of-the-literature
#3
Jiro Shimazaki, Akira Takemura, Kiyotaka Nishida, Hideki Kajiyama, Mitsugi Shimoda, Shuji Suzuki
Heterotopic ossification in colorectal carcinoma is extremely rare. This report presents the case of a 57-year-old male who had undergone a low anterior resection following a diagnosis of rectal carcinoma. Histological examination showed heterotopic ossification in the tumor. The patient was referred to Ibaraki Medical Center, Tokyo Medical University, with a diagnosis of rectal carcinoma by a local physician. Abdominal computed tomography revealed thickening of the rectal wall with calcified deposits, and virtual colonoscopy showed stenosis with a mass in the rectum...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920023/il4-from-t-follicular-helper-cells-downregulates-antitumor-immunity
#4
Hidekazu Shirota, Dennis M Klinman, Shuku-Ei Ito, Hiroyasu Ito, Masato Kubo, Chikashi Ishioka
Immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL4 in particular is upregulated. Here we demonstrate that T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the LNs...
December 5, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27919940/vitamin-d-and-myofibroblasts-in-fibrosis-and-cancer-at-cross-purposes-with-tgf-%C3%AE-smad-signaling
#5
REVIEW
Shraga Shany, Ina Sigal-Batikoff, Sergio Lamprecht
The multifaceted involvement of the active vitamin D metabolite 1,25-dihydroxyvitamin D3 (henceforth referred to by the synonyms 1,25(OH)2D3, calcitriol or vitamin D) in blunting the growth of cancer cells is amply recognized. In this review we focused our attention on the cross-talk between 1,25 (OH)2D3 and the tumor microenvironment (TME), signaling out stromal cancer-associated fibroblasts (CAFs), the most abundant TME population, as a target for calcitriol anticancer action. In view of the commonality of the phenotypic signature in myofibroblasts, resident in the cancer stroma and in non-neoplastic fibrotic loci, we examined modes of action of vitamin D in non-neoplastic chronic diseases and in cancer to assess mechanistic similarities and divergences...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919908/targeting-the-pd-1-pd-l1-axis-in-multiple-myeloma-a-dream-or-a-reality
#6
Jacalyn Rosenblatt, David Avigan
PD-1/PD-L1 pathway is a negative regulator of immune activation that is up-regulated in multiple myeloma and is a critical component of the immunosuppressive tumor microenvironment. Expression is increased in advanced disease and in the presence of bone marrow stromal cells. PD-1/PD-L1 blockade is associated with tumor regression in several malignancies but single agent activity is limited in myeloma patients. Combination therapy involving strategies to expand myeloma specific T cells and T cell activation via PD-1/PD-L1 blockade are currently being explored...
December 5, 2016: Blood
https://www.readbyqxmd.com/read/27919264/acidic-tumor-microenvironment-abrogates-the-efficacy-of-mtorc1-inhibitors
#7
Seraina Faes, Adrian P Duval, Anne Planche, Emilie Uldry, Tania Santoro, Catherine Pythoud, Jean-Christophe Stehle, Janine Horlbeck, Igor Letovanec, Nicolo Riggi, Nicolas Demartines, Olivier Dormond
BACKGROUND: Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study. METHODS: Cancer cell lines were treated with rapamycin in acidic or physiological conditions and cell proliferation was investigated...
December 5, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27919217/drug-delivery-nanoparticles-in-treating-chemoresistant-tumor-cells
#8
Giuseppina Barrera, Martina Daga, Benedetta Ferrara, Chiara Dianzani, Stefania Pizzimenti, Monica Argenziano, Roberta Cavalli, Francesco Trotta
Intrinsic or acquired chemoresistance represents the main obstacle to the successful treatment of cancer patients. Several mechanisms are involved in multidrug resistance: decreased uptake of hydrophilic drugs, increase of energy dependent efflux, alteration of the redox state, alteration of apoptotic pathways, and modification of the tumor microenvironment. In recent years, several types of nanoparticles have been developed to overcome these obstacles and improve the accumulation and release of drugs at the pathological site...
December 5, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27917327/p53-mutation-critical-mediator-of-therapy-resistance-against-tumor-microenvironment
#9
Ali S Arbab, Meenu Jain, B R Achyut
No abstract text is available yet for this article.
October 2016: Biochemistry & Physiology
https://www.readbyqxmd.com/read/27916875/proteinase-activated-receptor-2-is-a-novel-regulator-of-tgf-%C3%AE-signaling-in-pancreatic-cancer
#10
REVIEW
David Witte, Franziska Zeeh, Thomas Gädeken, Frank Gieseler, Bernhard H Rauch, Utz Settmacher, Roland Kaufmann, Hendrik Lehnert, Hendrik Ungefroren
TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor in normal cells and in the early stages of tumor development while promoting carcinogenesis and metastasis in advanced tumor stages. The final outcome of the TGF-β response is determined by cell-autonomous mechanisms and genetic alterations such as genomic instability and somatic mutations, but also by a plethora of external signals derived from the tumor microenvironment, such as cell-to-cell interactions, growth factors and extracellular matrix proteins and proteolytic enzymes...
November 30, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27916739/bioengineered-tumoral-microtissues-recapitulate-desmoplastic-reaction-of-pancreatic-cancer
#11
Virginia Brancato, Valentina Comunanza, Giorgia Imparato, Davide Corà, Francesco Urciuolo, Alessio Noghero, Federico Bussolino, Paolo A Netti
: Many of the existing three-dimensional (3D) cancer models in vitro fail to represent the entire complex tumor microenvironment composed of cells and extra cellular matrix (ECM) and do not allow a reliable study of the tumoral features and progression. In this paper we reported a strategy to produce 3D in vitro microtissues of pancreatic ductal adenocarcinoma (PDAC) for studying the desmoplastic reaction activated by the stroma-cancer crosstalk. Human PDAC microtissues were obtained by co-culturing pancreatic cancer cells (PT45) and normal or cancer-associated fibroblasts within biodegradable microcarriers in a spinner flask bioreactor...
December 1, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27916607/current-status-of-biomarker-and-targeted-nanoparticle-development-the-precision-oncology-approach-for-pancreatic-cancer-therapy
#12
Lei Zhu, Charles Staley, David Kooby, Bassel El-Rays, Hui Mao, Lily Yang
Pancreatic cancer remains one of the major causes of cancer-related mortality. The majority of pancreatic cancer patients are diagnosed at the advanced stage with unresectable and drug resistant tumors. The new treatments with the combination of chemotherapy, molecular targeted therapy, and immunotherapy have shown modest effects on therapeutic efficacy and survival of the patients. Therefore, there is an urgent need to develop effective therapeutic approaches targeting highly heterogeneous pancreatic cancer cells and tumor microenvironments...
December 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27916538/myofibroblasts-derived-from-hepatic-progenitor-cells-create-the-tumor-microenvironment
#13
Sayaka Sekiya, Shizuka Miura, Kanae Matsuda-Ito, Atsushi Suzuki
Hepatic progenitor cells (HPCs) appear in response to several types of chronic injury in the human and rodent liver that often develop into liver fibrosis, cirrhosis, and primary liver cancers. However, the contribution of HPCs to the pathogenesis and progression of such liver diseases remains controversial. HPCs are generally defined as cells that can differentiate into hepatocytes and cholangiocytes. In this study, however, we found that HPCs isolated from the chronically injured liver can also give rise to myofibroblasts as a third type of descendant...
November 26, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27916281/intratumoral-heterogeneity-of-macrophages-and-fibroblasts-in-breast-cancer-is-associated-with-the-morphological-diversity-of-tumor-cells-and-contributes-to-lymph-node-metastasis
#14
Lubov A Tashireva, Evgeny V Denisov, Tatiana S Gerashchenko, Daria N Pautova, Mikhail A Buldakov, Marina V Zavyalova, Julia Kzhyshkowska, Nadezhda V Cherdyntseva, Vladimir M Perelmuter
Recent studies have highlighted the heterogeneity of the tumor microenvironment (ME) and the importance of its analysis to the understanding of its impact on clinical outcomes. In this study, we aimed to analyze the intratumoral distribution of macrophages and fibroblasts in breast cancer (BC) based on the morphological diversity of tumor cells (tubular, alveolar, solid, trabecular and discrete structures) and the clinicopathological parameters of the disease. Thirty-six patients with invasive breast carcinoma of no special type were included in the study...
November 27, 2016: Immunobiology
https://www.readbyqxmd.com/read/27915976/strategies-to-strike-survival-networks-in-cancer
#15
Marzia Pennati, Graziella Cimino-Reale, Laura Gatti, Giuliana Cassinelli
The machinery that maintains cellular and tissue homeostasis in a healthy individual is recruited and hijacked by cancer cells to support tumor growth and progression. Activation of often unpredictable alternative or complementary signaling pathways allows cancer cells to bypass the intrinsic self-destructive machinery and the limited replicative potential present in every cell for correct homeostasis maintenance. Therefore, evasion/resistance to apoptosis/cell death, self-sufficiency in growth/survival signals, and limitless replicative potential remain undoubted hallmarks of cancer, contributing to drug resistance...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27915975/cell-death-induction-in-cancer-therapy-past-present-and-future
#16
Lisa Nonnenmacher, Sebastian Hasslacher, Julia Zimmermann, Georg Karpel-Massler, Katia La Ferla-Brühl, Sara E Barry, Timo Burster, Markus D Siegelin, Oliver Brühl, Marc-Eric Halatsch, Klaus-Michael Debatin, Mike-Andrew Westhoff
The induction of apoptosis, a physiological type of cell death, is currently the primary therapeutic aim of most cancer therapies. As resistance to apoptosis is an early hallmark of developing cancer, the success of this treatment strategy is already potentially compromised at treatment initiation. In this review, we discuss the tumor in Darwinian terms and describe it as a complex, yet highly unstable, ecosystem. Current therapeutic strategies often focus on directly killing the dominant subclone within the population of mutated cancer cells while ignoring the subclonal complexity within the ecosystem tumor, the complexity of the direct tumor/ microenvironment interaction and the contribution of the ecosystem human - that is, the global environment which provides the tumor with both support and challenges...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27915969/anoikis-and-emt-lethal-liaisons-during-cancer-progression
#17
Zheng Cao, Theodore Livas, Natasha Kyprianou
Anoikis is a unique mode of apoptotic cell death that occurs consequentially to insufficient cell-matrix interactions. Resistance to anoikis is a critical contributor to tumor invasion and metastasis. The phenomenon is regulated by integrins, which upon engagement with components of the extracellular matrix (ECM) form adhesion complexes and the actin cytoskeleton drives the formation of cell protrusions used to adhere to ECM, directing cell migration. The epithelial-mesenchymal transition (EMT) confers stem cell properties and leads to acquisition of a migratory and invasive phenotype by causing adherens junction breakdown and circumventing anoikis in the tumor microenvironment...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27915154/lipopolysaccharides-stimulated-macrophage-products-enhance-withaferin-a-induced-apoptosis-via-activation-of-caspases-and-inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-human-cancer-cells
#18
Liang Piao, Zhao Canguo, Lu Wenjie, Cheng Xiaoli, Shi Wenli, Lu Li
Macrophages, as a major cellular component in tumor microenvironment, play an important role in tumor progression. However, their roles in modulation of cytotoxic chemotherapy are still not fully understood. Here, we investigated the influence of Lipoplysaccharides (LPS)-stimulated macrophage products (LSMP) on Withaferin A (WA), a natural compound that derived from the medicinal plant Withania somnifera, as an antitumor agent in human breast cancer cells MDA-MB-231 and prostate cancer cells PC-3. Our results revealed that LSMP may enhance WA-induced apoptosis in both cell lines, the underlying mechanisms of which are closely associated with activation of caspase-8, -9 and -3, cleavage of poly ADP-ribose polymerase (PARP), as well as specifically inhibiting the translocation of nuclear factor-κB (NF-κB) and down-regulation of anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and inhibitor of apoptosis protein (cIAP1/2)...
December 1, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27914984/recapitulating-the-human-tumor-microenvironment-colon-tumor-derived-extracellular-matrix-promotes-angiogenesis-and-tumor-cell-growth
#19
Mónica Romero-López, Andrew L Trinh, Agua Sobrino, Michaela M S Hatch, Mark T Keating, Cristhian Fimbres, David E Lewis, Paul D Gershon, Elliot L Botvinick, Michelle Digman, John S Lowengrub, Christopher C W Hughes
Extracellular matrix (ECM) is an essential and dynamic component of all tissues and directly affects cellular behavior by providing both mechanical and biochemical signaling cues. Changes in ECM can alter tissue homeostasis, potentially leading to promotion of cellular transformation and the generation of tumors. Therefore, understanding ECM compositional changes during cancer progression is vital to the development of targeted treatments. Previous efforts to reproduce the native 3D cellular microenvironment have utilized protein gels and scaffolds that incompletely recapitulate the complexity of native tissues...
November 24, 2016: Biomaterials
https://www.readbyqxmd.com/read/27914453/myeloid-derived-suppressor-cells-and-proinflammatory-cytokines-as-targets-for-cancer-therapy
#20
REVIEW
K-S N Atretkhany, M S Drutskaya
Myeloid-derived suppressor cells represent a heterogeneous population of immature myeloid cells. Under normal conditions, these cells differentiate into macrophages, dendritic cells, and granulocytes. However, in pathological states such as inflammation, infection, or tumor growth, there is an arrest of their differentiation that results in the accumulation of immature myeloid cells in the organism. In addition, these cells acquire a suppressor phenotype, expressing anti-inflammatory cytokines and reactive oxygen and nitrogen species, and suppress T-cell immune response...
November 2016: Biochemistry. Biokhimii︠a︡
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