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https://www.readbyqxmd.com/read/28647610/the-jak-stat3-axis-a-comprehensive-drug-target-for-solid-malignancies
#1
REVIEW
Jennifer Huynh, Nima Etemadi, Frédéric Hollande, Matthias Ernst, Michael Buchert
Intercellular communication between tumor cells, immune cells and the stroma characterises the tumor microenvironment, which is instrumental for establishing the ecological niche that fosters tumor growth and metastasis. While tumor cell intrinsic STAT3 signaling provides a crucial axis to support cell proliferation and survival, it also regulates many activities of the non-transformed cells that collectively make up the tumor microenvironment. Accordingly, excessive activation of STAT3 is a hallmark of many malignancies, and often occurs in response to cytokines of the IL-6 and IL-10 families...
June 21, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28646932/bcg-a-throwback-from-the-stone-age-of-vaccines-opened-the-path-for-bladder-cancer-immunotherapy
#2
Alvaro Morales
INTRODUCTION: It is 40 years since the initial documentation of the efficacy of bacille Calmette-Guérin (BCG) in the management of non-muscle invasive bladder cancer (NMIBC) and probably an opportune a time as any to retrace the origins of this development and to reflect on the progress that has occurred on the use of immune modifiers in the treatment of NMIBC. MATERIALS AND METHODS: A PubMed search for publications on the history of BCG was conducted, and those related to the development of the vaccine for protection against tuberculosis as well as those published in the last 40 years related to its use for treatment for NMIBC were selected for review...
June 2017: Canadian Journal of Urology
https://www.readbyqxmd.com/read/28646284/chd1l-expression-increases-tumor-progression-and-acts-as-a-predictive-biomarker-for-poor-prognosis-in-pancreatic-cancer
#3
Chuan Liu, Xiaowei Fu, Zhiwei Zhong, Jing Zhang, Haiyan Mou, Qiong Wu, Tianle Sheng, Bo Huang, Yeqing Zou
BACKGROUND: The chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) plays a key role in controlling various cellular phenomena, including immune-mediated inflammation, transformation, apoptosis, cell cycle progression, and proliferation. METHODS: This study investigated the function and clinical significance of CHD1L protein expression in pancreatic cancer (PC). We analyzed CHD1L expression in surgical specimens from 112 PC patients. The correlation between the clinical characteristics and prognosis was also determined...
June 23, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#4
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645564/immunotherapy-holds-the-key-to-cancer-treatment-and-prevention-in-constitutional-mismatch-repair-deficiency-cmmrd-syndrome
#5
Harm Westdorp, Sigrid Kolders, Nicoline Hoogerbrugge, I Jolanda M de Vries, Marjolijn C J Jongmans, Gerty Schreibelt
Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age. Less well known, is the constitutional mismatch repair deficiency (CMMRD) syndrome caused by biallelic germline mutations in MMR genes. This syndrome is characterized by the development of childhood cancer. Patients with CMMRD are at extremely high risk of developing multiple cancers including hematological, brain and intestinal tumors...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28645491/systematic-review-of-immune-checkpoint-inhibition-in-urological-cancers
#6
REVIEW
Maud Rijnders, Ronald de Wit, Joost L Boormans, Martijn P J Lolkema, Astrid A M van der Veldt
CONTEXT: In patients with advanced and metastatic urological cancers, clinical outcome may be improved by immune checkpoint inhibitors (ICIs). OBJECTIVE: To systematically review relevant literature on efficacy and safety of ICIs in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. EVIDENCE ACQUISITION: Relevant databases, including Medline, Embase, and the Cochrane Library, were searched up to March 16, 2017...
June 20, 2017: European Urology
https://www.readbyqxmd.com/read/28644837/real-world-first-line-treatment-and-overall-survival-in-non-small-cell-lung-cancer-without-known-egfr-mutations-or-alk-rearrangements-in-us-community-oncology-setting
#7
Amy P Abernethy, Ashwini Arunachalam, Thomas Burke, Caroline McKay, Xiting Cao, Rachael Sorg, David P Carbone
PURPOSE: To establish a baseline for care and overall survival (OS) based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC) without common actionable mutations. METHODS: Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old) newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015)...
2017: PloS One
https://www.readbyqxmd.com/read/28644756/immunological-effects-of-hypomethylating-agents
#8
Katherine E Lindblad, Meghali Goswami, Christopher S Hourigan, Karolyn A Oetjen
Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas Covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets...
June 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28644608/targeting-cpg-adjuvant-to-lymph-node-via-dextran-conjugate-enhances-anti-tumor-immunotherapy
#9
Weidong Zhang, Myunggi An, Jingchao Xi, Haipeng Liu
Nucleic acids based adjuvants recognized by Toll-like receptors (TLR) are potent immune system stimulants that can augment the anti-tumor immune responses in an antigen-specific manner. However, their clinical uses as vaccine adjuvants are limited primarily due to lack of accumulation in the lymph nodes, the anatomic sites where the immune responses are initiated. Here, we showed that chemical conjugation of type B CpG DNA, a TLR9 agonist to dextran polymer dramatically enhanced CpG's lymph node accumulation in mice...
June 23, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28644303/prostate-cancer-immunotherapy-the-path-forward
#10
Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer. RECENT FINDINGS: Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28644246/effects-of-exercise-on-the-immune-function-of-pediatric-patients-with-solid-tumors-insights-from-the-papec-randomized-trial
#11
Carmen Fiuza-Luces, Julio R Padilla, Jaime Valentín, Elena Santana-Sosa, Alejandro Santos-Lozano, Fabián Sanchis-Gomar, Helios Pareja-Galeano, Javier S Morales, Steven J Fleck, Margarita Pérez, Alvaro Lassaletta, Luisa Soares-Miranda, Antonio Pérez-Martínez, Alejandro Lucia
The purpose of this study was to assess the effects of an in-hospital exercise intervention during neoadjuvant chemotherapy on the inflammatory profile and immune cell subpopulation in 20 children with solid tumors (control [n = 11] and exercise group [n = 9]). Although no significant interaction (group × time) effect was found with an analysis of variance test, we found a trend toward an interaction effect for natural killer cells expressing the immunoglobulin-like receptor KIR2DS4, with their numbers remaining stable in the exercise group but increasing in controls...
June 21, 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28643865/characterization-and-biological-function-of-milk-derived-mirnas
#12
Regina Golan-Gerstl, Yaffa Elbaum Shiff, Vardit Lavi-Moshayoff, Daniel Schecter Dena Leshkowitz, Shimon Reif
SCOPE: Breastfeeding is associated with reduced risk of infection, immune mediated disorders, obesity and even cancer. Recently it was found that breast milk contains a variety of microRNAs (miRNAs) in the skim and fat layer that can be transferred to infants, and appear to play important roles in those biological functions. METHODS AND RESULTS: This study applied Next Generation Sequencing and quantitative real time PCR analysis to determine the miRNA expression profile of the skim and fat fraction of human, goat, and bovine milk as well as infant formulas...
June 23, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28643761/the-effects-of-gene-therapy-with-granulocyte-macrophage-colony-stimulating-factor-in-the-regression-of-tumor-masses-in-fibrosarcoma-mouse-model
#13
Saiedeh RaziSoofiyani, Tohid Kazemi, Farzaneh Lotfipour, Leila Mohammadnejad, Somayeh Hallaj-Nezhadi, Siamak Sandoghchian Shotorbani, Akbar Mohammad Hosseini, Behzad Baradaran
INTRODUCTION: Cytokine gene therapy is one of the cancer treatment strategies. Recently, granulocyte-monocyte colony-stimulating factor (GM-CSF), as an important cytokine in activating dendritic cells and boosting the anti-tumor immune responses, has been utilized as an immunotherapeutic agent in cancer gene therapy. The purpose of the present investigation was to study the GM-CSF gene therapy effects in regression of tumor masses in fibrosarcoma mouse model. MATERIALS AND METHODS: To investigate the therapeutic efficacy of GM-CSF, WEHI-164 tumor cells were transfected with murine GM-CSF plasmid...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28643743/dual-association-of-serum-interleukin-10-levels-with-colorectal-cancer
#14
Shabnam Abtahi, Forogh Davani, Zahra Mojtahedi, Seyed Vahid Hosseini, Alimohammad Bananzadeh, Abbas Ghaderi
BACKGROUND: Interleukin 10 (IL-10) is considered an immune modulator cytokine, showing both antitumor and pro-tumor characteristics. Its role in the pathogenesis and progression of colorectal cancer depends on microenvironmental milieu. MATERIALS AND METHODS: A case-control study with 58 newly diagnosed colorectal cancer (CRC) patients, and 30 healthy individuals was conducted to compare the serum IL-10 levels between patients and controls. Furthermore, the correlation of the cytokine levels with the pathological features and prognosis of the CRC was investigated...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#15
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28642817/cerebral-vasculitis-mimicking-intracranial-metastatic-progression-of-lung-cancer-during-pd-1-blockade
#16
Heinz Läubli, Jürgen Hench, Michal Stanczak, Ingmar Heijnen, Alexandros Papachristofilou, Stephan Frank, Alfred Zippelius, Frank Stenner-Liewen
BACKGROUND: Stimulation of the immune system by targeting the PD-1/PD-L1 pathway can result in activation of anti-tumor immunity. Besides its clinical benefit immune checkpoint therapy leads to significant immune-related adverse events (irAEs). Some rare irAEs are not well described yet but are critical in patient management. CASE PRESENTATION: Here, we describe a case of autoimmune cerebral vasculitis/encephalitis after PD-1 inhibitor treatment for metastatic adenocarcinoma of the lung...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28641531/application-of-alphaviral-vectors-for-immunomodulation-in-cancer-therapy
#17
Anna Zajakina, Karina Spunde, Kenneth Lundstrom
BACKGROUND: The lack of specific and efficient cancer therapies has influenced the development of novel approaches, such as immunotherapy, which from its original application of immunogenic protein delivery has developed into the use of more sophisticated recombinant gene delivery methods to achieve better safety and efficacy profiles. This approach involves viral and non-viral delivery systems. METHODS: Expression vectors have been engineered for alphaviruses, including Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28640929/modulation-of-tumor-microenvironment-by-chemopreventive-natural-products
#18
REVIEW
Sin-Aye Park, Young-Joon Surh
The tumor microenvironment provides a niche in which cancer cells and their surrounding stromal cells reside and in which their interactions occur. The cross talk between cancer and stromal cells in the tumor microenvironment promotes many biological processes to support cancer cell growth, invasion, angiogenesis, and metastasis. Recently, not only cancer cells but also multiple types of surrounding stromal cells, including endothelial cells, immune cells, and fibroblasts in the tumor microenvironment, have been recognized to be attractive targets for reducing resistance to anticancer therapy and tumor recurrence...
June 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28639898/targeting-interlukin-6-to-relieve-immunosuppression-in-tumor-microenvironment
#19
Qian Liu, Shengnan Yu, Anping Li, Hanxiao Xu, Xinwei Han, Kongming Wu
Immunotolerance is one of the hallmarks of malignant tumors. Tumor cells escape from host immune surveillance through various mechanisms resulting in tumor progression and therapeutic resistance. Interlukin-6 is a proinflammatory cytokine involved in many physiological and pathological processes by integrating with multiple intracellular signaling pathways. Aberrant expression of interlukin-6 is associated with the growth, metastasis, and chemotherapeutic resistance in a wide range of cancers. Interlukin-6 exerts immunosuppressive capacity mostly by stimulating the infiltrations of myeloid-derived suppressor cells, tumor-associated neutrophils, and cancer stem-like cells via Janus-activated kinase/signal transducer and activator of transcription 3 pathway in tumor microenvironment...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639409/anti-pd-1-antibodies-in-metastatic-uveal-melanoma-a-treatment-option
#20
Carolin Bender, Alexander Enk, Ralf Gutzmer, Jessica C Hassel
Uveal melanomas (UMs) are a rare form of cancer with clinical and pathological characteristics distinct from cutaneous melanomas. Ipilimumab has shown efficacy and safety in the treatment of metastatic UM. This provides a rationale for treatment with other immune checkpoint inhibitors. This is a retrospective review of 15 patients with metastatic UM treated between June 2014 and February 2016, who received treatment with the anti-PD-1 Abs pembrolizumab or nivolumab. Patients were treated at two German university hospitals...
June 21, 2017: Cancer Medicine
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