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Interferon melanoma

Cecilia Ferreira da Silva, Miriam Ventura da Silva, Claudia Garcia Serpa Osorio-de-Castro
Objective To analyze the pathway of clinical trials of monoclonal antibodies and biological medicines for cancer treatment involving Brazilian institutions from 2003 to 2012. Method This retrospective, descriptive study was based on review of two clinical trial registries, and the Brazilian registry ReBEC. Phase II or III studies with participation from Brazilian institutions listed in at least one of the registries were included. Following selection of the trials, the pathway of monoclonal antibodies and biological medicines was investigated from the research stage until licensing by the Brazilian Agency for Sanitary Surveillance (Anvisa), Food and Drug Administration (FDA), and European Medicines Agency (EMA)...
March 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
Joseph Markowitz, Zachary Abrams, Naduparambil K Jacob, Xiaoli Zhang, John N Hassani, Nicholas Latchana, Lai Wei, Kelly E Regan, Taylor R Brooks, Sarvani R Uppati, Kala M Levine, Tanios Bekaii-Saab, Kari L Kendra, Gregory B Lesinski, J Harrison Howard, Thomas Olencki, Philip R Payne, William E Carson
BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs that function to repress translation of mRNA transcripts and contribute to the development of cancer. We hypothesized that miRNA array-based technologies work best for miRNA profiling of patient-derived plasma samples when the techniques and patient populations are precisely defined. METHODS: Plasma samples were obtained from five sources: melanoma clinical trial of interferon and bortezomib (12), purchased normal donor plasma samples (four), gastrointestinal tumor bank (nine), melanoma tumor bank (ten), or aged-matched normal donors (eight) for the tumor bank samples...
2016: OncoTargets and Therapy
Thekkinghat Anantharaman Arvind, Pundi N Rangarajan
Mouse Apolipoprotein L9 (ApoL9) is an understudied cytoplasmic, interferon-inducible protein. The details of its intracellular localization and normal cellular functions are unclear. We report here that ApoL9 localizes to small puncta diffusely distributed in the cytoplasm, as well as to larger granules of varying size and number that are similar to aggresome-like induced structures (ALIS) and contain the autophagy receptor Sqstm1/p62, the autophagosome marker Lc3, and ubiquitin. Transfection of B16F10 mouse melanoma cells stably expressing ApoL9 (B16F10(L9)) with certain liposome-based transfection reagents causes dramatic disturbances in its subcellular distribution...
October 28, 2016: Biochemical and Biophysical Research Communications
Rak-Kyun Seong, Young-Ki Choi, Ok Sarah Shin
Melanoma differentiation associated gene-7 (mda-7)/interleukin- 24 (IL-24) is a secreted cytokine, which plays an essential role in tumor suppression. Although its role as a multifunctional protein affecting broad types of cancers is well described, functions of IL-24 in host defense against virus infection are yet to be determined. In this study, we explored the anti-viral effect of recombinant IL-24 treatment during influenza infection. Infection of human lung adenocarcinoma cells (A549) with the influenza A virus up-regulated IL-24 mRNA and protein expression in a time-dependent manner...
October 2016: Journal of Microbiology / the Microbiological Society of Korea
Tianli Xia, Hiroyasu Konno, Glen N Barber
The innate immune regulator STING stimulates cytokine production in response to the presence of cytosolic DNA, which can arise following DNA damage. Extrinsic STING signaling is also needed for antigen-presenting cells (APC) to stimulate antitumor T cell immunity. Here we show that STING signaling is recurrently suppressed in melanoma cells, where this event may enable immune escape after DNA damage. Mechanistically STING signaling was suppressed most frequently by epigenetic silencing of either STING or the cyclic GMP-AMP synthase (cGAS), which generates STING-activating cyclic dinucleotides (CDNs) after binding cytosolic DNA species...
September 28, 2016: Cancer Research
Haiyan S Li, Chengwen Liu, Yichuan Xiao, Fuliang Chu, Xiaoxuan Liang, Weiyi Peng, Jianhua Hu, Sattva S Neelapu, Shao-Cong Sun, Patrick Hwu, Stephanie S Watowich
Despite the potent ability of dendritic cells (DCs) to stimulate lymphocyte responses and host immunity, granulocyte-macrophage colony-stimulating factor-derived DCs (GM-DCs) used as antitumor vaccines have demonstrated relatively modest success in cancer immunotherapy. We found that injecting GM-DCs into melanoma tumors in mice, or culturing GM-DCs with melanoma-secreted cytokines or melanoma-conditioned medium, rapidly suppressed DC-intrinsic expression of the gene encoding inhibitor of differentiation 2 (ID2), a transcriptional regulator...
2016: Science Signaling
Úrsula Amaranta Rossi, Liliana María Elena Finocchiaro, Gerardo Claudio Glikin
We evaluated the cytotoxic effects of the combination of bortezomib (BTZ) and interferon-β (IFNβ) gene lipofection on cultured melanoma cells. Four canine mucosal (Ak, Br, Bk and Ol) and two human dermal (A375 and SB2) melanoma cell lines were assayed. BTZ sub-pharmacological concentrations (5 nM) enhanced the cytotoxic effects of IFNβ transgene expression on melanoma cells monolayers and spheroids. The combination was also more effective than the single treatments when assayed for clonogenic survival and cell migration...
September 23, 2016: Anti-cancer Agents in Medicinal Chemistry
Naomi I Maria, Eline C Steenwijk, Arne S IJpma, Cornelia G van Helden-Meeuwsen, Petra Vogelsang, Wouter Beumer, Zana Brkic, Paul L A van Daele, P Martin van Hagen, Peter J van der Spek, Hemmo A Drexhage, Marjan A Versnel
OBJECTIVE: The interferon (IFN) type I signature is present in over half of patients with primary Sjögren's syndrome (pSS) and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered as the main source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of patients with pSS. METHODS: Blood samples from 42 healthy controls (HC) and 115 patients with pSS were stratified according to their IFN type I signature...
September 26, 2016: Annals of the Rheumatic Diseases
Jun Chen, Yang Liu, Qilin Sun, Beiqing Wang, Ningli Li, Xiangdong Chen
Cysteine-rich protein 61 (CCN1/CYR61) is an important marker of proliferation and metastasis in malignant melanoma, making it a potential target for melanoma treatment. In this study, we compared the expression of CRY61 in Chinese patients with malignant melanoma with its expression in patients with other skin tumors or with no skin pathological conditions. We examined the effects of anti-human CYR61 monoclonal antibody on proliferation and evaluated the changes in CYR61 expression and cell proliferation in response to treatment with either epirubicin or interferon (IFN)-α...
September 23, 2016: Oncology Reports
Tadaatsu Imaizumi, Chikashi Yano, Akiko Numata, Koji Tsugawa, Ryo Hayakari, Tomoh Matsumiya, Hidemi Yoshida, Shojiro Watanabe, Kazushi Tsuruga, Shogo Kawaguchi, Manabu Murakami, Hiroshi Tanaka
BACKGROUND/AIMS: Activation of Toll-like receptor 3 (TLR3) signaling followed by type I interferon (IFN) expression is crucial in antiviral and "pseudoviral" immune reactions in renal mesangial cells (MCs). These reactions are probably involved in the pathogenesis of chronic kidney disease (CKD). However, the role of IFN-induced 35-kDa protein 35 (IFI35), a type I IFN-dependent transcript, in glomerular inflammation is unclear. Here, we aimed to investigate the expression and the role of IFI35 in IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 and IFN-β/melanoma differentiation-associated gene 5 (MDA5)/CXCL10 axes in MCs...
September 17, 2016: Kidney & Blood Pressure Research
Shalin Shah, James E Ward, Riyue Bao, Curtis R Hall, Bruce E Brockstein, Jason J Luke
Anti-Programed Death 1 (PD-1) is standard immunotherapy for multiple cancers and the expression of one of its ligands, PD-L1, has been described in germ cell tumors (GCTs). Neither the clinical activity of anti-PD-1 nor the incidence of an immunoresponsive tumor microenvironment has been described for GCTs. A patient initially diagnosed with melanoma via fine needle aspiration was treated with one dose of antibody to PD-1. A core needle biopsy was subsequently performed to acquire sufficient tissue for molecular analysis, which led to a change in diagnosis to metastatic embryonal carcinoma...
September 16, 2016: Cancer Immunology Research
Jelena Vasilevska, Gustavo Antonio De Souza, Maria Stensland, Dace Skrastina, Dmitry Zhulenvovs, Raimonds Paplausks, Baiba Kurena, Tatjana Kozlovska, Anna Zajakina
Alphavirus vectors are promising tools for cancer treatment. However, relevant entry mechanisms and interactions with host cells are still not clearly understood. The first step toward a more effective therapy is the identification of novel intracellular alterations that could be associated with cancer aggressiveness and could affect the therapeutic potential of these vectors. In this study, we observed that alphaviruses efficiently infected B16 mouse melanoma tumors/tumor cells in vivo, whereas their transduction efficiency in B16 cells under in vitro conditions was blocked...
August 11, 2016: Cancer Biology & Therapy
Alina Basnet, Nibal Saad, Sam Benjamin
BACKGROUND: Melanoma is among the top three cancers to present with brain metastasis. The risk of brain metastases in advanced melanoma increases with disease duration. Cytotoxic chemotherapy does not have a significant role in the management of melanoma patients with brain metastases, neither alone nor in conjunction with radiation therapy. PATIENTS AND METHODS: We herein discuss a case of a 66-year-old male diagnosed initially with stage III-B melanoma and underwent a wide local excision with a split thickness graft and sentinel lymph node biopsy, followed by adjuvant treatment with high-dose interferon...
September 2016: Anticancer Research
Valeria Lucarini, Carla Buccione, Giovanna Ziccheddu, Francesca Peschiaroli, Paola Sestili, Rossella Puglisi, Gianfranco Mattia, Cristiana Zanetti, Isabella Parolini, Laura Bracci, Iole Macchia, Alessandra Rossi, Maria Teresa D'Urso, Daniele Macchia, Massimo Spada, Adele De Ninno, Annamaria Gerardino, Pamela Mozetic, Marcella Trombetta, Alberto Rainer, Luca Businaro, Giovanna Schiavoni, Fabrizio Mattei
Resistance to Type I IFN (IFN-I)-induced anti-neoplastic effects has been reported in many tumors and arise, in part, from epigenetic silencing of IFN-stimulated genes by DNA methylation. We hypothesized that restoration of IFN-stimulated genes by co-administration of the demethylating drug 5-Aza-2'-Deoxycitidine (Decitabine; DAC) may enhance the susceptibility to IFN-I-mediated anti-tumoral effects in melanoma. We show that combined administration of IFN-I and DAC significantly inhibits the growth of murine and human melanoma cells, both in vitro and in vivo...
September 10, 2016: Journal of Investigative Dermatology
Laetitia Douguet, Lloyd Bod, Renée Lengagne, Laura Labarthe, Masashi Kato, Marie-Françoise Avril, Armelle Prévost-Blondel
γδ T lymphocytes may exert either protective or tumor-promoting functions in cancer, mostly based on their polarization toward interferon (IFN)-γ or interleukin (IL)-17 productions, respectively. Here, we demonstrate that γδ T cells accelerate the spontaneous metastatic melanoma development in a model of transgenic mice for the human RET oncogene (Ret mice). We identify unanticipated roles of inducible nitric oxide synthase (NOS2) in favoring the recruitment of pro-tumor γδ T cells within the primary tumor...
August 2016: Oncoimmunology
Ken Takashima, Yohei Takeda, Hiroyuki Oshiumi, Hiroaki Shime, Masaru Okabe, Masahito Ikawa, Misako Matsumoto, Tsukasa Seya
An interferon-inducing DNA sensor STING participates in tumor rejection in mouse models. Here we examined what mechanisms contribute to STING-dependent growth retardation of B16 melanoma sublines by NK cells in vivo. The studies were designed using WT and STING KO black mice, and B16D8 (an NK-sensitive melanoma line having STING) and STING KO B16D8 sublines established for this study. The results from tumor-implant studies suggested that STING in host immune cells and tumor cells induced distinct profiles of chemokines including CXCL10, CCL5 and IL-33, and both participated in NK cell infiltration and activation in B16D8 tumor...
September 30, 2016: Biochemical and Biophysical Research Communications
Romi Gupta, Matteo Forloni, Malik Bisseier, Shaillay Kumar Dogra, Qiahong Yang, Narendra Wajapeyee
Mutations in the NRAS oncogene are present in up to 20% of melanoma. Here, we show that interferon alpha-inducible protein 6 (IFI6) is necessary for NRASQ61K-induced transformation and melanoma growth. IFI6 was transcriptionally upregulated by NRASQ61K, and knockdown of IFI6 resulted in DNA replication stress due to dysregulated DNA replication via E2F2. This stress consequentially inhibited cellular transformation and melanoma growth via senescence or apoptosis induction depending on the RB and p53 pathway status of the cells...
September 8, 2016: ELife
Arash Salmaninejad, Mohammad Reza Zamani, Mehrnaz Pourvahedi, Zahra Golchehre, Ali Hosseini Bereshneh, Nima Rezaei
UNLABELLED: Cancer/testis antigens (CTAs) are named based on their expression pattern that is restricted in a number of normal and abnormal tissues. Tumor cells frequently express antigens whose expression is typically restricted to germ cells. Their unique expression pattern is guaranteed by precise epigenetic regulatory mechanisms. Because of their tumor-limited, high immunogenicity, and biased expression, discovery of these molecules provides unprecedented opportunities for further research and clinical development in the field of cancer diagnosis and immunotherapy...
October 2016: Immunological Investigations
Blanca Homet Moreno, Jesse M Zaretsky, Angel Garcia-Diaz, Jennifer Tsoi, Giulia Parisi, Lidia Robert, Katrina Meeth, Abibatou Ndoye, Marcus Bosenberg, Ashani T Weeraratna, Thomas G Graeber, Begoña Comin-Anduix, Siwen Hu-Lieskovan, Antoni Ribas
The programmed cell death protein 1 (PD-1) limits effector T-cell functions in peripheral tissues, and its inhibition leads to clinical benefit in different cancers. To better understand how PD-1 blockade therapy modulates the tumor-host interactions, we evaluated three syngeneic murine tumor models, the BRAF(V600E)-driven YUMM1.1 and YUMM2.1 melanomas, and the carcinogen-induced murine colon adenocarcinoma MC38. The YUMM cell lines were established from mice with melanocyte-specific BRAF(V600E) mutation and PTEN loss (BRAF(V600E)/PTEN(-/-))...
October 2016: Cancer Immunology Research
G V Seledtsova, A A Shishkov, E A Kaschenko, V I Seledtsov
An accumulating body of evidence suggests that xenogeneic vaccines can be very effective in breaking the immune tolerance to human tumor-associated antigens (TAAs). We assessed adverse effects, as well as clinical and immune responses induced by a lyophilized xenogeneic polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC cells in 60 stage IV colorectal cancer patients. Neither grade III/IV toxicities, nor laboratory and clinical signs of systemic severe autoimmune disorders were documented in any XPV-treated patient...
August 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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