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https://www.readbyqxmd.com/read/28109167/cell-cycle-tailored-targeting-of-metastatic-melanoma-challenges-opportunities
#1
Nikolas K Haass, Brian Gabrielli
The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the 'bad guy' to the 'poster child' in oncology. Current targeted therapies are effective; although here is a clear need to develop combination therapies to delay the onset of resistance. Many anti-melanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28109139/-imiquimod-combined-with-dendritic-cell-vaccine-decreases-treg-proportion-and-enhances-anti-tumor-responses-in-mice-bearing-melanoma
#2
Shurong Ren, Qiubo Wang, Yanli Zhang, Cuixiu Lu, Ping Li, Yumei Li
Objective To investigate the therapeutic effect of Toll-like receptor 7 (TLR7) agonist imiquimod combined with dendritic cell (DC)-based tumor vaccine on melanoma in mice and the potential mechanism. Methods Melanoma-bearing mouse models were established by subcutanous injection of B16-OVA cells into C57BL/6 mice. DCs were isolated from mouse bone marrow and propagated in culture medium with recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant mouse interleukin-4 (rmIL-4)...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109087/cd103-cell-growth-factor-flt3l-enhances-the-efficacy-of-immune-checkpoint-blockades-in-murine-glioblastoma-model
#3
Xiaolin Miao, Yiqi Chen, Ke Hao, Meiqin Zheng, Bingyu Chen, Kaiqiang Li, Ying Wang, Wei Zhang, Yu Zhang, Xiaozhou Mou, Shanshan Jiang, Zhen Wang
Glioblastoma is a lethal disease featured with a high proliferation of tumor cells, excessive angiogenesis, and heavydrug resistance. The overall survival of glioblastoma patients was dismal even with intensive standard care. Recent advantages in immune checkpoint blockades are changing the treatment of cancers. However, the efficacy of immune checkpoint blockades in glioblastoma were unclear. Here, we investigated the roles of CD103<sup>+</sup> cells in regulating the effects of immune checkpoint blockades in glioblastoma mouse models...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#4
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28108813/relationship-between-il-27-and-coronary-arterial-lesions-in-children-with-kawasaki-disease
#5
Feifei Si, Yao Wu, Fang Gao, Siqi Feng, Ruixi Liu, Qijian Yi
Kawasaki disease (KD) arises due to the disorder of the inflammation response and faulty immune regulation. Interleukin-27 (IL-27) is a novel cytokine with both pro-inflammatory and anti-inflammatory effects. This study investigated the relationship between serum levels of IL-27, Interleukin-17A (IL-17A), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and coronary artery lesions (CALs) in patients with KD. We obtained blood samples from 81 children with KD before intravenous immunoglobulin (IVIG) therapy...
January 20, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28108544/the-interplay-between-neutrophils-and-cd8-t-cells-improves-survival-in-human-colorectal-cancer
#6
Valeria Governa, Emanuele Trella, Valentina Mele, Luigi Tornillo, Francesca Amicarella, Eleonora Cremonesi, Maunele Giuseppe Muraro, Hui Xu, Raoul Droeser, Silvio Raffael Däster, Martin Bolli, Raffaele Rosso, Daniel Oertli, Serenella Eppenberger-Castori, Luigi Terracciano, Giandomenica Iezzi, Giulio C Spagnoli
PURPOSE: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer (CRC). Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes and functional features of CRC infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells. EXPERIMENTAL DESIGN: CD66b+ and CD8+ cell infiltration was analyzed by immunohistochemistry on a tissue microarray including >650 evaluable CRC samples...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108313/the-hsp70-inhibiting-peptide-aptamer-a17-potentiates-radiosensitization-of-tumor-cells-by-hsp90-inhibition
#7
Daniela Schilling, Carmen Garrido, Stephanie Combs, Gabriele Multhoff
The inhibition of heat shock protein 90 (Hsp90) is a promising strategy to increase the radiosensitivity of tumor cells. However, Hsp90 inhibition induces the expression of Hsp70 which is a prominent cytoprotective protein. Therefore, dual targeting of Hsp70 and Hsp90 might be beneficial to increase the radiosensitivity of tumor cells. Hsp70 inhibiting peptide aptamers have been shown to increase the sensitivity of tumor cells to apoptosis induced by different anticancer drugs. Herein, we studied the radiosensitizing activity of the Hsp70 inhibiting peptide aptamer A17 in combination with the Hsp90 inhibitor NVP-AUY922...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28108005/in-vitro-allogeneic-immune-cell-response-to-mesenchymal-stromal-cells-derived-from-human-adipose-in-patients-with-rheumatoid-arthritis
#8
P Usha Shalini, J V S Vidyasagar, Lakshmi Kumari Kona, Meenakshi Ponnana, Lakshmi Kiran Chelluri
We investigated the regulatory activity of human adipose-derived mesenchymal stromal cells (MSCs) (n=10) towards immune cells in a cohort of 84 rheumatoid arthritis (RA) patients, 36 apparently healthy controls. We co-cultured MSCs with lymphocyte subsets of T, B, and T regulatory cells (Tregs). Levels of the pro- and anti-inflammatory markers (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin-10 (IL-10)) were estimated in serum and co-culture supernatants. The study revealed a two-fold increase in the proportion of Tregs and an increased level of CD4(+)CD25(+)FoxP3...
January 12, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28107553/protective-effect-of-n-n-dimethylthiourea-against-stress-induced-gastric-mucosal-lesions-in-rats
#9
Yoshiji Ohta, Koji Yashiro, Takashi Kobayashi, Kazuo Inui, Junji Yoshino
In the present study, we examined the protective effect of N,N'-dimethylthiourea (DMTU), a scavenger of hydroxyl radical (•OH), against water-immersion restraint stress (WIRS)-induced gastric mucosal lesions in rats. When male Wistar rats fasted for 24 h were exposed to WIRS for 3 h, gastric mucosal lesions occurred with increases in the levels of gastric mucosal myeloperoxidase, an index of tissue neutrophil infiltration, pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin 1beta), lipid peroxide, and NOx (nitrite/nitrate), an index of nitric oxide synthesis, and decreases in the levels of gastric mucosal non-protein SH and vitamin C and gastric adherent mucus...
January 20, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28107450/systemic-t-cells-immunosuppression-of-glioma-stem-cell-derived-exosomes-is-mediated-by-monocytic-myeloid-derived-suppressor-cells
#10
Rossana Domenis, Daniela Cesselli, Barbara Toffoletto, Evgenia Bourkoula, Federica Caponnetto, Ivana Manini, Antonio Paolo Beltrami, Tamara Ius, Miran Skrap, Carla Di Loreto, Giorgia Gri
A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes...
2017: PloS One
https://www.readbyqxmd.com/read/28107341/complex-dynamics-of-virus-spread-from-low-infection-multiplicities-implications-for-the-spread-of-oncolytic-viruses
#11
Ignacio A Rodriguez-Brenes, Andrew Hofacre, Hung Fan, Dominik Wodarz
While virus growth dynamics have been well-characterized in several infections, data are typically collected once the virus population becomes easily detectable. Earlier dynamics, however, remain less understood. We recently reported unusual early dynamics in an experimental system using adenovirus infection of human embryonic kidney (293) cells. Under identical experimental conditions, inoculation at low infection multiplicities resulted in either robust spread, or in limited spread that eventually stalled, with both outcomes occurring with approximately equal frequencies...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28107190/radiosynthesis-and-validation-of-%C3%A2-18f-3-fluoro-2-hydroxypropionate-18f-flac-as-a-pet-tracer-of-lactate-to-monitor-mct1-dependent-lactate-uptake-in-tumors
#12
Vincent F Van Hée, Daniel Labar, Gwenaël Dehon, Debora Grasso, Vincent Grégoire, Giulio G Muccioli, Raphaël Frédérick, Pierre Sonveaux
Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107185/hyaluronan-synthase-3-mediated-oncogenic-action-through-forming-inter-regulation-loop-with-tumor-necrosis-factor-alpha-in-oral-cancer
#13
Yi-Zih Kuo, Wei-Yu Fang, Cheng-Chih Huang, Sen-Tien Tsai, Yi-Ching Wang, Chih-Li Yang, Li-Wha Wu
Hyaluronan (HA) is a major extracellular matrix component. However, its role and mediation in oral cancer remains elusive. Hyaluronan synthase 3 (HAS3), involved in pro-inflammatory short chain HA synthesis, was the predominant synthase in oral cancer cells and tissues. HAS3 overexpression significantly increased oral cancer cell migration, invasion and xenograft tumorigenesis accompanied with the increased expression of tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1). Conversely, HAS3 depletion abrogated HAS3-mediated stimulation...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106842/adenoviral-vectors-armed-with-cell-fusion-inducing-proteins-as-anti-cancer-agents
#14
REVIEW
Joshua Del Papa, Robin J Parks
Cancer is a devastating disease that affects millions of patients every year, and causes an enormous economic burden on the health care system and emotional burden on affected families. The first line of defense against solid tumors is usually extraction of the tumor, when possible, by surgical methods. In cases where solid tumors can not be safely removed, chemotherapy is often the first line of treatment. As metastatic cancers often become vigorously resistant to treatments, the development of novel, more potent and selective anti-cancer strategies is of great importance...
January 19, 2017: Viruses
https://www.readbyqxmd.com/read/28106295/macrophage-polarization-anti-cancer-strategies-to-target-tumor-associated-macrophage-in-breast-cancer
#15
Muhammad Tariq, Jieqiong Zhang, Guikai Liang, Ling Ding, Qiaojun He, Bo Yang
Tumor-associated macrophages (TAMs) are the most abundant inflammatory cells and orchestrate different stages of breast cancer development. TAMs participate in the tumor angiogenesis, matrix remodeling, invasion, immunosuppression, metastasis, and chemoresistance in breast cancer. Several clinical studies indicate the association between the high influx of TAMs in tumor with poor prognosis in hepatocellular, ovarian, cervical, and breast cancer. Previously developed hypotheses have proposed that TAMs participate in antitumor responses of the body, while recently many clinical and experimental studies have revealed that TAMs in tumor microenvironment predominantly resemble with M2-like polarized macrophages and produce a high amount of anti-inflammatory factors which are directly responsible for the development of tumor...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28105854/t-705-favipiravir-suppresses-tumor-necrosis-factor-%C3%AE-production-in-response-to-influenza-virus-infection-a-beneficial-feature-of-t-705-as-an-anti-influenza-drug
#16
T Tanaka, T Kamiyama, T Daikoku, K Takahashi, N Nomura, M Kurokawa, K Shiraki
Influenza virus infection induces the production of various cytokines, which play important roles in the pathogenesis of infection. Among the cytokines induced by influenza, tumor necrosis factor (TNF)-α production has been correlated with the severity of lung lesions. We investigated the effects of T-705 (Favipiravir, 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) on cytokine production due to influenza virus infection in vitro and in vivo, compared with oseltamivir or GS 4071, an active form of oseltamivir. TNF-α production in mouse macrophage-derived P388D1 cells infected with the influenza virus was lower following treatment with T-705 at concentrations of 0...
January 19, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#17
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105368/clinical-and-immunologic-correlates-of-response-to-pd-1-blockade-in-a-patient-with-metastatic-renal-medullary-carcinoma
#18
Kathryn E Beckermann, Pradeep C Jolly, Ju Y Kim, Jennifer Bordeaux, Igor Puzanov, W Kimryn Rathmell, Douglas B Johnson
BACKGROUND: Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105238/immune-associated-proteins-with-potential-in-vivo-anti-tumor-activities-are-upregulated-in-lung-cancer-cells-treated-with-umbelliprenin-a-proteomic-approach
#19
Narges Khaghanzadeh, Kazuyuki Nakamura, Yasuhiro Kuramitsu, Abbas Ghaderi, Zahra Mojtahedi
Umbelliprenin (Umb), a natural coumarin, has demonstrated anti-tumor activities, both in vitro and particularly in vivo, in several types of cancer, including lung cancer. The present study aimed to identify molecular targets of Umb using a high-throughput approach. Lung cancer cell lines, QU-DB (large-cell lung carcinoma) and A549 (adenocarcinoma), were treated with Umb. Differentially-expressed proteins were identified using two-dimensional electrophoresis coupled to mass spectrometry. In the QU-DB cells, differential expression of proteins, including downregulation of the tumorigenic protein heat shock protein 90 kDa and upregulation of the potential anti-tumor proteins Nipsnap1 and glycine-tRNA ligase (GRS), suggested that Umb is a strong anti-tumor compound...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104436/capsaicin-synergizes-with-camptothecin-to-induce-increased-apoptosis-in-human-small-cell-lung-cancers-via-the-calpain-pathway
#20
Jamie R Friedman, Haley E Perry, Kathleen C Brown, Yin Gao, Ju Lin, Cathyrn D Stevenson, John D Hurley, Nicholas A Nolan, Austin T Akers, Yi Charlie Chen, Krista L Denning, Linda G Brown, Piyali Dasgupta
Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients. Conventionally, camptothecin is used for recurrent SCLC and has poor survival outcomes...
January 16, 2017: Biochemical Pharmacology
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