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"Melanoma model"

Sisi Liu, Wenjie Song, Fusheng Liu, Junwen Zhang, Siquan Zhu
Uveal melanoma (UM) is the most common primary intraocular tumor in adults, which has high frequency of metastasis to the liver, typically causing a fatal outcome. Chemo-resistance remains a major obstacle in the therapeutic approach to UM, leaving limited choice for treating UM. Other possible treatments have been explored but the results are yet to be evident. To improve therapy for UM, transcriptional suicide genes were transfected into the OCM-1 cell line. In the current study, OCM-1 cells transfected with lentiviral-meditated EGFP, cytosine deaminase (CD)/EGFP, and VP22-CD/EGFP were established...
April 13, 2018: Experimental Eye Research
Masaki Nagane, Eiichi Kanai, Yuki Shibata, Takuto Shimizu, Chie Yoshioka, Takuya Maruo, Tadashi Yamashita
The sodium-independent cystine-glutamate antiporter plays an important role in extracellular cystine uptake. It comprises the transmembrane protein, xCT and its chaperone, CD98. Because glutathione is only weakly cell membrane permeable, cellular uptake of its precursor, cystine, is known to be a key step in glutathione synthesis. Moreover, it has been reported that xCT expression affects the progression of tumors and their resistance to therapy. Sulfasalazine is an inhibitor of xCT that is known to increase cellular oxidative stress, giving it anti-tumor potential...
2018: PloS One
Alastair Hotblack, Angelika Holler, Alice Piapi, Sophie Ward, Hans J Stauss, Clare L Bennett
Ongoing clinical trials explore T cell receptor (TCR) gene therapy as a treatment option for cancer, but responses in solid tumors are hampered by the immunosuppressive microenvironment. The production of TCR gene-engineered T cells requires full T cell activation in vitro, and it is currently unknown whether in vivo interactions with conventional dendritic cells (cDCs) regulate the accumulation and function of engineered T cells in tumors. Using the B16 melanoma model and the inducible depletion of CD11c+ cells in CD11c...
March 16, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
J D Nosanchuk, A Jeyakumar, A Ray, E Revskaya, Z Jiang, R A Bryan, K J H Allen, R Jiao, M E Malo, B L Gómez, A Morgenstern, F Bruchertseifer, D Rickles, G B Thornton, A Bowen, A Casadevall, E Dadachova
Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with188 Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3...
April 3, 2018: Scientific Reports
Helma Zecena, Daniel Tveit, Zi Wang, Ahmed Farhat, Parvita Panchal, Jing Liu, Simar J Singh, Amandeep Sanghera, Ajay Bainiwal, Shuan Y Teo, Frank L Meyskens, Feng Liu-Smith, Fabian V Filipp
BACKGROUND: Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, the anti-tumorigenic effect and clinical benefit are only transient, and tumors are prone to treatment resistance and relapse. To elucidate mechanistic insights into drug resistance, we have established an in vitro cellular model of MAPK inhibitor resistance in malignant melanoma. METHODS: The cellular model evolved in response to clinical dosage of the BRAF inhibitor, vemurafenib, PLX4032...
April 4, 2018: BMC Systems Biology
Leonardo Vinícius Monteiro de Assis, Maria Nathália Moraes, Keila Karoline Magalhães-Marques, Gabriela Sarti Kinker, Sanseray da Silveira Cruz-Machado, Ana Maria de Lauro Castrucci
The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h...
April 3, 2018: International Journal of Molecular Sciences
P Jack Hoopes, Robert J Wagner, Kayla Duval, Kevin Kang, David J Gladstone, Karen L Moodie, Margaret Crary-Burney, Hugo Ariaspulido, Frank A Veliz, Nicole F Steinmetz, Steven Fiering
The presence and benefit of a radiation therapy-associated immune reaction is of great interest as the overall interest in cancer immunotherapy expands. Radiation therapy (RT) pathology studies have rarely demonstrated a consistent immune or inflammatory response following conventional RT. More recent information, primarily associated with the "abscopal effect", suggests a subtle radiation-based systemic immune response may be more common and have more therapeutic potential than previously believed...
April 3, 2018: Molecular Pharmaceutics
Ursa Lampreht Tratar, Spela Kos, Urska Kamensek, Maja Ota, Natasa Tozon, Gregor Sersa, Maja Cemazar
The electrotransfer of interleukin-12 (IL-12) has been demonstrated as an efficient and safe treatment for tumors in veterinary oncology. However, the plasmids used encode human or feline IL-12 and harbor the gene for antibiotic resistance. Therefore, our aim was to construct plasmids encoding canine IL-12 without the antibiotic resistance genes driven by two different promoters: constitutive and fibroblast-specific. The results obtained in vitro in different cell lines showed that following gene electrotransfer, the newly constructed plasmids had cytotoxicity and expression profiles comparable to plasmids with antibiotic resistance genes...
March 29, 2018: Cancer Gene Therapy
Conglian Yang, Tingting Wu, Yuting Qin, Yan Qi, Yu Sun, Miao Kong, Xue Jiang, Xianya Qin, Yaqi Shen, Zhiping Zhang
Background: Doxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns. Methods: An amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor...
2018: International Journal of Nanomedicine
Catherine M Olsen, Nirmala Pandeya, Bridie S Thompson, Jean Claude Dusingize, Penelope M Webb, Adele C Green, Rachel E Neale, David C Whiteman
Background: Risk stratification can improve the efficacy and cost-efficiency of screening programs for early detection of cancer. We sought to derive a risk stratification tool for melanoma that was suitable for the general population using only self-reported information. Methods: We used melanoma risk factor information collected at baseline from QSKIN, a prospective cohort study of Queensland adults age 40 to 69 years at recruitment (n = 41 954). We examined two separate outcomes: 1) invasive melanomas and 2) all melanomas (invasive + in situ) obtained through data linkage to the cancer registry...
March 11, 2018: Journal of the National Cancer Institute
Y V Khramtsov, A V Ulasov, A A Rosenkranz, G P Georgiev, A S Sobolev
The distribution of modular nanotransporters (MNTs) that are used to deliver drugs into melanoma cell nuclei after their intravenous administration into mice with Cloudman S91 melanoma was studied. The modification of MNTs with polyethylene glycol (PEG) of different length and their administration during the treatment with docetaxel, nitroglycerin, and excess of nonspecific MNTs leads to an improved accumulation of MNTs in the tummor. Among the variants studied, the MNT with attached PEG with Mr 40 kDa exhibited the best properties...
January 2018: Doklady. Biochemistry and Biophysics
C Burkart, A Mukhopadhyay, S A Shirley, R J Connolly, J H Wright, A Bahrami, J S Campbell, R H Pierce, D A Canton
The use of immunomodulatory cytokines has been shown effective in regressing a wide range of tumors. However, systemic delivery of recombinant cytokines results in serious, potentially life-threatening, adverse effects. By contrast, nucleic acid transfer via electroporation (EP) is a safe and effective method of delivering plasmid-encoded cytokines to tumors. Intratumoral delivery of IL-12 plasmid DNA by electroporation (IT-pIL12-EP) produced objective response rates in Phase 2 clinical trials in metastatic melanoma...
March 9, 2018: Gene Therapy
Mustafa Aziz Hatiboglu, Abdurrahim Kocyigit, Eray Metin Guler, Kerime Akdur, Arife Nalli, Ersin Karatas, Saffet Tuzgen
BACKGROUND: Prognosis of patients with melanoma brain metastasis is poor despite various chemotherapeutic agents. Researchers focus on finding effective treatment with low risk of toxicity. Thymoquinone (TQ) has been found to be effective on different types of cancer. However, no data exists on the effect of TQ in intracerebral melanoma. The purpose of this study was to assess the effect of TQ in B16-F10 melanoma cell in vitro and intracerebral melanoma in vivo. METHODS: The mechanisms of efficacy were investigated by ATP assay for cytotoxicity, flow cytometry and Acridine-orange staining for apoptosis, Comet assay for genotoxicity, CM-H2 DCF-DA (2,7-dichlorodihydrofluorescein) for intracellular reactive oxygen species (ROS) generation and ELISA methods for inflammatory cytokines...
March 3, 2018: World Neurosurgery
Eva Sipos, Nikoletta Dobos, David Rozsa, Klara Fodor, Gabor Olah, Zsuzsanna Szabo, Lorant Szekvolgyi, Andrew V Schally, Gabor Halmos
Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy with very poor prognosis. Conventional chemotherapy only rarely prolongs the survival, therefore patients require novel treatment modalities. The discovery of specific receptors for hypothalamic hormones on cancer cells has led to the development of radiolabeled and cytotoxic hormone analogs. Materials and methods: In the present study, our aim was to investigate the expression of mRNA for receptors of luteinizing hormone-releasing hormone type I (LH-RH-I) and LH-RH ligand in OCM-1 and OCM-3 human uveal melanoma cell lines...
2018: OncoTargets and Therapy
Ting Kang, Yukun Huang, Qianqian Zhu, Hao Cheng, Yuanyuan Pei, Jingxian Feng, Minjun Xu, Gan Jiang, Qingxiang Song, Tianze Jiang, Hongzhuan Chen, Xiaoling Gao, Jun Chen
Recent breakthroughs in cancer immunotherapy offer new paradigm-shifting therapeutic options for combating cancer. Personalized therapeutic anti-cancer vaccines training T cells to directly fight against tumor cells endogenously offer tremendous benefits in working synergistically with immune checkpoint inhibitors. Biomimetic nanotechnology offers a versatile platform to boost anticancer immunity by efficiently co-delivering optimized immunogenic antigen materials and adjuvants to antigen presenting cells (APC)...
February 23, 2018: Biomaterials
Sharan Bobbala, Blake Gibson, Allan B Gamble, Arlene McDowell, Sarah Hook
Sustained release vaccine delivery systems may enhance the immunogenicity of subunit vaccines and reduce the need for multiple vaccinations. The aim of this study was to develop a thermoresponsive hydrogel using poloxamer 407-chitosan (CP) grafted copolymer as a delivery system for single-shot sustained release vaccines. The CP copolymer was synthesized using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The CP copolymer was a free flowing solution at ambient temperature and transformed rapidly into a gel at body temperature...
March 2, 2018: Immunology and Cell Biology
Urska Kamensek, Natasa Tesic, Gregor Sersa, Maja Cemazar
Plasmids, which are currently used in interleukin 12 (IL-12) gene electrotransfer (GET) clinical trials in the USA, contain antibiotic resistance genes and are thus, according to the safety recommendation of the European Medicines Agency (EMA), not suitable for clinical trials in the EU. In the current study, our aim was to prepare an IL-12 plasmid without an antibiotic resistance gene and test its functionality and toxicity after GET in a preclinical B16F10 mouse melanoma model. The antibiotic resistance-free plasmid encoding the human IL-12 fusion gene linked to the p21 promoter, i...
February 27, 2018: Cancers
Viviana Blank, Yanina Bellizzi, Elsa Zotta, Patricia G Cornier, Carina M L Delpiccolo, Dora B Boggián, Ernesto G Mata, Leonor P Roguin
In this study, we explored the in-vitro and in-vivo mechanism of antitumor action of a novel synthetic nonantibiotic triazolylpeptidyl penicillin derivative, named TAP7f, on B16-F0 murine melanoma cells. In-vitro assays showed that TAP7f caused an inhibition of S phase progression and a concomitant decrease of the percentage of cells in G0/G1 phase. We also found that TAP7f treatment induced an apoptotic response characterized by an increase of the sub-G1 fraction of B16-F0 hypodiploid cells, the occurrence of cells with picnotic nuclei, and the detection of phosphatidylserine exposure on the outer side of the plasma membrane...
February 28, 2018: Anti-cancer Drugs
Sandeep S Joshi, Shunlin Jiang, Emmanual Unni, Stephen R Goding, Tao Fan, Paul A Antony, Thomas J Hornyak
Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF...
2018: PloS One
Mark O Hardin, Timothy J Vreeland, Guy T Clifton, Diane F Hale, Garth S Herbert, Julia M Greene, Doreen O Jackson, John E Berry, Pauline Nichols, Sook Yin, Xianzhong Yu, Thomas E Wagner, George E Peoples
AIM:  We developed a novel approach to efficiently deliver autologous tumor antigens to the cytoplasm of dendritic cells (DC) using yeast cell wall particles (YCWP). MATERIALS AND METHODS:  Loading of YCWP, leakage of protein from loaded YCWP and cytoplasmic delivery of YCWP content was assessed using fluorescent-tagged experiments. Spectrophotometric analysis compared the epitope-specific T-cell responses following antigen presentation via YCWP versus exogenous loading...
April 2018: Immunotherapy
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