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Tumor microenvironment

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https://www.readbyqxmd.com/read/28339582/hypoxia-in-the-glioblastoma-microenvironment-shaping-the-phenotype-of-cancer-stem-like-cells
#1
Nicole Colwell, Mioara Larion, Amber J Giles, Ashlee N Seldomridge, Saman Sizdahkhani, Mark R Gilbert, Deric M Park
Glioblastoma is the most common and aggressive malignant primary brain tumor. Cellular heterogeneity is a characteristic feature of the disease and contributes to the difficulty in formulating effective therapies. Glioma stem-like cells (GSCs) have been identified as a subpopulation of tumor cells that are thought to be largely responsible for resistance to treatment. Intratumoral hypoxia contributes to maintenance of the GSCs by supporting the critical stem cell traits of multipotency, self-renewal, and tumorigenicity...
January 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28334399/association-of-hiv-status-with-local-immune-response-to-anal-squamous-cell-carcinoma-implications-for-immunotherapy
#2
Elizabeth L Yanik, Genevieve J Kaunitz, Tricia R Cottrell, Farah Succaria, Tracee L McMiller, Maria L Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J Lipson, Suzanne L Topalian, Eric A Engels, Janis M Taube
Importance: The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#3
Federico Carbone, Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Matteo Casula, Michele Cea, Fiammetta Monacelli, Irene Caffa, Santina Bruzzone, Fabrizio Montecucco, Alessio Nencioni
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333145/the-cryo-thermal-therapy-eradicated-melanoma-in-mice-by-eliciting-cd4-t-cell-mediated-antitumor-memory-immune-response
#4
Kun He, Ping Liu, Lisa X Xu
Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332353/port-site-metastases-and-chimney-effect-of-b-ultrasound-guided-and-laparoscopically-assisted-hyperthermic-intraperitoneal-perfusion-chemotherapy
#5
Ming Chen Ba, Hui Long, Xiang Liang Zhang, Yuan Feng Gong, Zhao Fei Yan, Shuai Wang, Yun Qiang Tang, Shu Zhong Cui
PURPOSE: CO₂ leakage along the trocar (chimney effect) has been proposed to be an important factor underlying port-site metastasis after laparoscopic surgery. This study aimed to test this hypothesis by comparing the incidence of port-site metastasis between B-ultrasound-guided and laparoscopically-assisted hyperthermic intraperitoneal perfusion chemotherapy (HIPPC). MATERIALS AND METHODS: Sixty-two patients with malignant ascites induced by gastrointestinal or ovarian cancer were divided into two groups to receive either B-ultrasound-guided or laparoscopically-assisted HIPPC...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28332219/targeting-immunotherapy-to-the-tumor-microenvironment
#6
Michael Dougan, Stephanie K Dougan
Targeting drugs to the tumor microenvironment has long been appreciated as a means of increasing local concentrations and decreasing systemic toxicities. How drug targeting might apply to immune-based therapies is less clear. In this review, we explain the immunology of cancer, with a focus on the principles of in situ vaccination. Certain types of therapies are more amenable to local versus systemic delivery; these include cytokines, adjuvants, radiation, and agents targeting tumor-resident cell populations...
March 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28332049/molecular-and-pharmacological-mechanisms-of-drug-resistance-an-evolving-paradigm
#7
Benedetta Colmegna, Lavinia Morosi, Maurizio D'Incalci
The high heterogeneity and genomic instability of malignant tumors explains why even responsive tumors contain cell clones that are resistant for many possible mechanisms involving intracellular drug inactivation, low uptake or high efflux of anticancer drugs from cancer cells, qualitative or quantitative changes in the drug target. Many tumors, however, are resistant because of insufficient exposure to anticancer drugs, due to pharmacokinetic reasons and inefficient and heterogeneous tumor drug distribution, related to a deficient vascularization and high interstitial pressure...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28331999/the-acidic-microenvironment-as-a-possible-niche-of-dormant-tumor-cells
#8
REVIEW
Silvia Peppicelli, Elena Andreucci, Jessica Ruzzolini, Anna Laurenzana, Francesca Margheri, Gabriella Fibbi, Mario Del Rosso, Francesca Bianchini, Lido Calorini
Although surgical excision, chemo-, and radio-therapy are clearly advanced, tumors may relapse due to cells of the so-called "minimal residual disease". Indeed, small clusters of tumor cells persist in host tissues after treatment of the primary tumor elaborating strategies to survive and escape from immunological attacks before their relapse: this variable period of remission is known as "cancer dormancy". Therefore, it is crucial to understand and consider the major concepts addressing dormancy, to identify new targets and disclose potential clinical strategies...
March 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28331617/current-approaches-to-increase-car-t-cell-potency-in-solid-tumors-targeting-the-tumor-microenvironment
#9
REVIEW
Irene Scarfò, Marcela V Maus
Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary treatment for haematological malignancies (i.e. B-ALL). However, the success of this type of treatment has not yet been achieved in solid tumors. One hypothesis is that the immunosuppressive nature of the tumor microenvironment (TME) influences and affects the efficacy of adoptive immunotherapy. Understanding the role of the TME and its interaction with CAR T-cells is crucial to improve the potency of adoptive immunotherapy. In this review, we discuss the strategies and potential combinatorial approaches recently developed in mouse models to enhance the efficacy of CAR T-cells, with particular emphasis on the translational potential of these approaches...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331613/systematic-evaluation-of-immune-regulation-and-modulation
#10
REVIEW
David F Stroncek, Lisa H Butterfield, Michael A Cannarile, Madhav V Dhodapkar, Tim F Greten, Jean Charles Grivel, David R Kaufman, Heidi H Kong, Firouzeh Korangy, Peter P Lee, Francesco Marincola, Sergio Rutella, Janet C Siebert, Giorgio Trinchieri, Barbara Seliger
Cancer immunotherapies are showing promising clinical results in a variety of malignancies. Monitoring the immune as well as the tumor response following these therapies has led to significant advancements in the field. Moreover, the identification and assessment of both predictive and prognostic biomarkers has become a key component to advancing these therapies. Thus, it is critical to develop systematic approaches to monitor the immune response and to interpret the data obtained from these assays. In order to address these issues and make recommendations to the field, the Society for Immunotherapy of Cancer reconvened the Immune Biomarkers Task Force...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331288/development-of-venetoclax-for-therapy-of-lymphoid-malignancies
#11
REVIEW
Huayuan Zhu, Alexandru Almasan
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28330927/e3-ubiquitin-ligase-ubr5-drives-the-growth-and-metastasis-of-triple-negative-breast-cancer
#12
Liqiu Liao, Mei Song, Xin Li, Lili Tang, Tuo Zhang, Lixing Zhang, Yihang Pan, Lotfi Chouchane, Xiaojing Ma
Patients with triple negative breast cancers (TNBC) are at high risk for recurrence and metastasis at an early time despite standard treatment, underscoring the need for novel therapeutic modalities. Here we report for the first time a distinctive and profound role of the E3 ubiquitin ligase UBR5 in the growth and metastasis of TNBC. An analysis of primary TNBC specimen by whole exon sequencing revealed strong gene amplifications of UBR5 associated with the disease. UBR5 overexpression in TNBC tissues was confirmed at mRNA and protein levels...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28330383/progress-in-nonviral-gene-therapy-for-breast-cancer-and-what-comes-next
#13
Giulia Bottai, Marta Truffi, Fabio Corsi, Libero Santarpia
The possibility of correcting defective genes and modulating gene expression through gene therapy has emerged as a promising treatment strategy for breast cancer. Furthermore, the relevance of tumor immune microenvironment in supporting the oncogenic process has paved the way for novel immunomodulatory applications of gene therapy. Areas covered: In this review, the authors describe the most relevant delivery systems, focusing on nonviral vectors, along with the description of the major approaches used to modify target cells, including gene transfer, RNA interference (RNAi), and epigenetic regulation...
March 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#14
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28328502/spatial-statistics-for-segmenting-histological-structures-in-h-e-stained-tissue-images
#15
Luong Nguyen, A Burak Tosun, Jeffrey Fine, Adrian Lee, D Lansing Taylor, Chakra Chennubhotla
Segmenting a broad class of histological structures in transmitted light and/or fluorescence-based images is a prerequisite for determining the pathological basis of cancer, elucidating spatial interactions between histological structures in tumor microenvironments (e.g. tumor infiltrating lymphocytes), facilitating precision medicine studies with deep molecular profiling, and providing an exploratory tool for pathologists. Our paper focuses on segmenting histological structures in hematoxylin and eosin (H&E) stained images of breast tissues, e...
March 16, 2017: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28328191/enhancing-tumor-penetration-of-nanomedicines
#16
Qingxue Sun, Tarun Ojha, Fabian Kiessling, Twan Lammers, Yang Shi
Tumor-targeted nanomedicines have been extensively applied to alter the drawbacks and enhance the efficacy of chemotherapeutics. Despite the large number of preclinical nanomedicine studies showing initial success, their therapeutic benefit in the clinic has been rather modest, which is partially due to the inefficient tumor penetration caused by tumor microenvironment (high density of cells and extracellular matrix, increased interstitial fluid pressure). Furthermore, tumor penetration of nanomedicines is significantly influenced by physicochemical characteristics such as size, surface chemistry and shape...
March 22, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28327992/cyst-fluid-from-cystic-malignant-brain-tumors-a-reservoir-of-nutrients-including-growth-factor-like-nutrients-for-tumor-cells
#17
Daniel Dahlberg, Eduard A Struys, Erwin E Jansen, Lars Mørkrid, Øivind Midttun, Bjørnar Hassel
BACKGROUND: Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth. OBJECTIVE: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors. METHODS: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors. RESULTS: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3...
January 25, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#18
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325957/heat-shock-protein-hsp27-secretion-by-ovarian-cancer-cells-is-linked-to-intracellular-expression-levels-occurs-independently-of-the-endoplasmic-reticulum-pathway-and-hsp27-s-phosphorylation-status-and-is-mediated-by-exosome-liberation
#19
Matthias B Stope, Gerd Klinkmann, Karoline Diesing, Dominique Koensgen, Martin Burchardt, Alexander Mustea
The heat shock protein HSP27 has been correlated in ovarian cancer (OC) patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock...
2017: Disease Markers
https://www.readbyqxmd.com/read/28325212/chemokine-receptor-signaling-and-the-hallmarks-of-cancer
#20
R A Lacalle, R Blanco, L Carmona-Rodríguez, A Martín-Leal, E Mira, S Mañes
The chemokines are a family of chemotactic cytokines that mediate their activity by acting on seven-transmembrane-spanning G protein-coupled receptors. Both the ability of the chemokines and their receptors to form homo- and heterodimers and the promiscuity of the chemokine-chemokine receptor interaction endow this protein family with enormous signaling plasticity and complexity that are not fully understood at present. Chemokines were initially identified as essential regulators of homeostatic and inflammatory trafficking of innate and adaptive leucocytes from lymphoid organs to tissues...
2017: International Review of Cell and Molecular Biology
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