@article{AsciertoWorschechYuetal.2011,
  author    = {Ascierto, Maria Libera and Worschech, Andrea and Yu, Zhiya and Adams, Sharon and Reinboth, Jennifer and Chen, Nanhai G and Pos, Zoltan and Roychoudhuri, Rahul and Di Pasquale, Giovanni and Bedognetti, Davide and Uccellini, Lorenzo and Rossano, Fabio and Ascierto, Paolo A and Stroncek, David F and Restifo, Nicholas P and Wang, Ena and Szalay, Aladar A and Marincola, Francesco M},
  title     = {Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68},
  series = {BMC Cancer},
  volume    = {11},
  journal   = {BMC Cancer},
  number    = {451},
  doi       = {10.1186/1471-2407-11-451},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141503},
  pages     = {1-14},
  year      = {2011},
  abstract  = {Background: Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. We previously described GLV-1h68, a modified Vaccinia Virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo. Methods: In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines. Selected cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain. In order to identify correlates of permissity to viral infection, we measured transcriptional profiles of the cell lines prior infection. Results: We observed highly heterogeneous permissivity to VACV infection amongst the cell lines. The heterogeneity of permissivity was independent of tissue with the exception of B cell derivation. Cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain and a significant correlation was found suggesting a common permissive phenotype. While no clear transcriptional pattern could be identified as predictor of permissivity to infection, some associations were observed suggesting multifactorial basis permissivity to viral infection. Conclusions: Our findings have implications for the design of oncolytic therapies for cancer and offer insights into the nature of permissivity of tumor cells to viral infection.},
  language  = {en}
}
@article{SpiveyDeGiorgiZhaoetal.2012,
  author    = {Spivey, Tara L. and De Giorgi, Valeria and Zhao, Yingdong and Bedognetti, Davide and Pos, Zoltan and Liu, Qiuzhen and Tomei, Sara and Ascierto, Maria Libera and Uccellini, Lorenzo and Reinboth, Jennifer and Chouchane, Lotfi and Stroncek, David F. and Wang, Ena and Marincola, Francesco M.},
  title     = {The stable traits of melanoma genetics: an alternate approach to target discovery},
  series = {BMC Genomics},
  volume    = {13},
  journal   = {BMC Genomics},
  number    = {156},
  doi       = {10.1186/1471-2164-13-156},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131992},
  year      = {2012},
  abstract  = {Background: The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number. Results: Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis. Conclusions: This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy.},
  language  = {en}
}
@article{GowdaGodderKmieciaketal.2011,
  author    = {Gowda, Madhu and Godder, Kamar and Kmieciak, Maciej and Worschech, Andrea and Ascierto, Maria-Libera and Wang, Ena and Francesco M., Marincola and Manjili, Masoud H.},
  title     = {Distinct signatures of the immune responses in low risk versus high risk neuroblastoma},
  series = {Journal of Translational Medicine},
  volume    = {9},
  journal   = {Journal of Translational Medicine},
  number    = {170},
  doi       = {10.1186/1479-5876-9-170},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135147},
  pages     = {1-8},
  year      = {2011},
  abstract  = {Background: Over 90\% of low risk (LR) neuroblastoma patients survive whereas less than 30\% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response. Methods: We performed microarray analysis of RNA extracted from the tumor specimens of HR and LR patients. Flow cytometry was performed to determine the cellular constituents in the blood while multiplex cytokine array was used to detect the cytokine profile in patients' sera. A HR tumor cell line, SK-N-SH, was also used for detecting the response to IL-1 beta, a cytokines which is involved in the innate immune responses. Results: Distinct patterns of gene expression were detected in HR and LR patients indicating an active T-cell response and a diminished adaptive immune response, respectively. A diminished adaptive immune response in LR patients was evident by higher levels of IL-10 in the sera. In addition, HR patients had lower levels of circulating myeloid derived suppressor cells (MDSC) compared with a control LR patient. LR patients showed slightly higher levels of cytokines of the innate immune responses. Treatment of the HR tumor line with IL-1b induced expression of cytokines of the innate immune responses. Conclusions: This data suggests that adaptive immune responses may play an important role in the progression of HR disease whereas innate immune responses may be active in LR patients.},
  language  = {en}
}