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Combination Strategies

Section edited by Paolo A. Ascierto

This section aims to provide a focal point for research that highlights combination therapies, where two or more medications or therapies are strategically combined to improve the treatment of cancer, chronic infections, transplantation and potentially other complex and multi-factorial diseases.

Increasingly detailed understanding of the molecular basis driving complex disease has led to the identifications of new agents that target specific pathways. In some cases treatment of appropriately selected patients has led to striking clinical response, however both primary and secondary resistance mechanisms limited the success of many of these agents. It has become clear that combining or sequencing treatment modalities may enrich the communication between basic biological and immunological sciences and the clinical investigation arena.

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  1. To mimic clinical treatment situations in advanced human ovarian disease, we tested the efficacy of CpG-oligodeoxynucleotides (CpG-ODN), synthetic DNA sequences recognized by Toll-like receptor 9 and able to i...

    Authors: Michele Sommariva, Michelandrea de Cesare, Alessandra Meini, Alessandra Cataldo, Nadia Zaffaroni, Elda Tagliabue and Andrea Balsari
    Citation: Journal of Translational Medicine 2013 11:25
  2. Membrane-bound phospholipid scramblase 1 (PLSCR1) is involved in both lipid trafficking and cell signaling. Previously, we showed that PLSCR1 is overexpressed in many colorectal carcinomas (CRCs). In the prese...

    Authors: Chung-Wei Fan, Chun-Yu Chen, Kuei-Tien Chen, Chia-Rui Shen, Yung-Bin Kuo, Ya-Shan Chen, Yeh-Pin Chou, Wei-Shan Wei and Err-Cheng Chan
    Citation: Journal of Translational Medicine 2012 10:254
  3. Most DNA-damaging chemotherapeutic agents activate the transcription factor nuclear factor κB (NF-κB). However, NF-κB activation can either protect from or contribute to the growth suppressive effects of the a...

    Authors: Simona Caporali, Lauretta Levati, Grazia Graziani, Alessia Muzi, Maria Grazia Atzori, Enzo Bonmassar, Giuseppe Palmieri, Paolo A Ascierto and Stefania D’Atri
    Citation: Journal of Translational Medicine 2012 10:252
  4. The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our...

    Authors: Consolación Melguizo, Jose Prados, Beatriz González, Raul Ortiz, Angel Concha, Pablo Juan Alvarez, Roberto Madeddu, Gloria Perazzoli, Jaime Antonio Oliver, Rodrigo López, Fernando Rodríguez-Serrano and Antonia Aránega
    Citation: Journal of Translational Medicine 2012 10:250
  5. The vast majority of patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab eventually develop resistance to this agent. There is an unmet need therefore, for identifying biologica...

    Authors: George Fountzilas, Christos Christodoulou, Mattheos Bobos, Vassiliki Kotoula, Anastasia G Eleftheraki, Ioannis Xanthakis, Anna Batistatou, George Pentheroudakis, Nikolaos Xiros, Irene Papaspirou, Anna Koumarianou, Pavlos Papakostas, Dimitrios Bafaloukos, Dimosthenis V Skarlos and Konstantine T Kalogeras
    Citation: Journal of Translational Medicine 2012 10:212
  6. The concept of tissue banking as a “bio-repository” aimed to collection, storing and distribution of human biological material and clinical information, is emerging as a successful strategy to support clinical...

    Authors: Gerardo Botti, Renato Franco, Monica Cantile, Gennaro Ciliberto and Paolo Antonio Ascierto
    Citation: Journal of Translational Medicine 2012 10:204
  7. Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of su...

    Authors: Grazia Palomba, Maria Colombino, Antonio Contu, Bruno Massidda, Giovanni Baldino, Antonio Pazzola, MariaTeresa Ionta, Francesca Capelli, Vittorio Trova, Tito Sedda, Giovanni Sanna, Francesco Tanda, Mario Budroni, Giuseppe Palmieri and Antonio Cossu
    Citation: Journal of Translational Medicine 2012 10:178
  8. Sunitinib inhibits vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors, and stem cell factor receptor (KIT). The ability of soluble (s)KIT, VEGF-A, sVEGFR-2, and sVE...

    Authors: Kiana Keyvanjah, Samuel E DePrimo, Charles S Harmon, Xin Huang, Kenneth A Kern and William Carley
    Citation: Journal of Translational Medicine 2012 10:165
  9. Procedural failure and untoward clinical outcomes after surgery remain problematic in critical limb ischemia (CLI) patients. This study tested a clopidogrel-cilostazol combination treatment compared with eithe...

    Authors: Jiunn-Jye Sheu, Kun-Chen Lin, Ching-Yen Tsai, Tzu-Hsien Tsai, Steve Leu, Chia-Hung Yen, Yung-Lung Chen, Hsueh-Wen Chang, Cheuk-Kwan Sun, Sarah Chua, Jenq-Lin Yang and Hon-Kan Yip
    Citation: Journal of Translational Medicine 2012 10:164
  10. Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that...

    Authors: Jan Belohlavek, Karel Kucera, Jiri Jarkovsky, Ondrej Franek, Milana Pokorna, Jiri Danda, Roman Skripsky, Vit Kandrnal, Martin Balik, Jan Kunstyr, Jan Horak, Ondrej Smid, Jaroslav Valasek, Vratislav Mrazek, Zdenek Schwarz and Ales Linhart
    Citation: Journal of Translational Medicine 2012 10:163
  11. P276-00 is a novel cyclin-dependent kinase inhibitor currently in Phase II clinical trials. Gemcitabine is a standard of care for the treatment of pancreatic cancer. The present study investigated the effect o...

    Authors: Maggie J Rathos, Kavita Joshi, Harshal Khanwalkar, Sonal M Manohar and Kalpana S Joshi
    Citation: Journal of Translational Medicine 2012 10:161
  12. Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i) counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal m...

    Authors: Judy SC Wang, Istvan Kovanecz, Dolores Vernet, Gaby Nolazco, George E Kopchok, Sheryl L Chow, Rodney A White and Nestor F Gonzalez-Cadavid
    Citation: Journal of Translational Medicine 2012 10:159
  13. Ipilimumab induces long-lasting clinical responses in a minority of patients with metastatic melanoma. To better understand the mechanism(s) of action and to identify novel biomarkers associated with the clini...

    Authors: Wenshi Wang, Daohai Yu, Amod A Sarnaik, Bin Yu, Maclean Hall, Dawn Morelli, Yonghong Zhang, Xiuhua Zhao and Jeffrey S Weber
    Citation: Journal of Translational Medicine 2012 10:146
  14. After more than 30 years, landmark progress has been made in the treatment of cancer, and melanoma in particular, with the success of new molecules such as ipilimumab, vemurafenib and active specific immunizat...

    Authors: Paolo A Ascierto, Antonio M Grimaldi, Brendan Curti, Mark B Faries, Soldano Ferrone, Keith Flaherty, Bernard A Fox, Thomas F Gajewski, Jeffrey E Gershenwald, Helen Gogas, Kenneth Grossmann, Axel Hauschild, F Stephen Hodi, Richard Kefford, John M Kirkwood, Sancy Leachmann…
    Citation: Journal of Translational Medicine 2012 10:83
  15. Exosome secretion is a notable feature of malignancy owing to the roles of these nanoparticles in cancer growth, immune suppression, tumor angiogenesis and therapeutic resistance. Exosomes are 30–100 nm membra...

    Authors: Annette M Marleau, Chien-Shing Chen, James A Joyce and Richard H Tullis
    Citation: Journal of Translational Medicine 2012 10:134
  16. Adeno-associated vectors (rAAV) have been used to attain long-term liver gene expression. In humans, the cellular immune response poses a serious obstacle for transgene persistence while neutralizing humoral i...

    Authors: Carmen Unzu, Sandra Hervás-Stubbs, Ana Sampedro, Itsaso Mauleón, Uxua Mancheño, Carlos Alfaro, Rafael Enríquez de Salamanca, Alberto Benito, Stuart G Beattie, Harald Petry, Jesús Prieto, Ignacio Melero and Antonio Fontanellas
    Citation: Journal of Translational Medicine 2012 10:122
  17. At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these...

    Authors: Alessandro Paccapelo, Ivan Lolli, Maria Grazia Fabrini, Giovanni Silvano, Beatrice Detti, Franco Perrone, Giuseppina Savio, Matteo Santoni, Erminio Bonizzoni, Tania Perrone and Silvia Scoccianti
    Citation: Journal of Translational Medicine 2012 10:90
  18. Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit from the use of anti-EGFR targeted antibodies even in the absence of a mutation o...

    Authors: Mario Scartozzi, Riccardo Giampieri, Elena Maccaroni, Alessandra Mandolesi, Simona Biagetti, Simona Alfonsi, Lucio Giustini, Cristian Loretelli, Luca Faloppi, Alessandro Bittoni, Maristella Bianconi, Michela Del Prete, Italo Bearzi and Stefano Cascinu
    Citation: Journal of Translational Medicine 2012 10:71
  19. The RAS/MAP kinase pathway has attracted attention because activating mutations of the BRAF serine/threonine kinase was described in over 50% of melanomas. Very recently, selective and potent BRAF inhibitors h...

    Authors: Gabriele Madonna, Claudio Dansky Ullman, Giusy Gentilcore, Giuseppe Palmieri and Paolo Antonio Ascierto
    Citation: Journal of Translational Medicine 2012 10:53
  20. The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopatho...

    Authors: Hai-Yun Wang, Yang-Yang Li, Qiong Shao, Jing-Hui Hou, Fang Wang, Man-Bo Cai, Yi-Xin Zeng and Jian-Yong Shao
    Citation: Journal of Translational Medicine 2012 10:27
  21. Shuanglong formula (SLF), a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI) in clinical. Because of the complex natur...

    Authors: Qiong-Lin Liang, Xiao-Ping Liang, Yi-Ming Wang, Yuan-Yuan Xie, Rong-Li Zhang, Xi Chen, Rong Gao, Yi-Jun Cheng, Jun Wu, Qing-Bo Xu, Qing-Zhong Xiao, Xue Li, Shu-Feng Lv, Xue-Mei Fan, Hong-Yang Zhang, Qing-Li Zhang…
    Citation: Journal of Translational Medicine 2012 10:26
  22. Copper export protein ATP7A is important for maintaining copper homeostasis. Recent studies have shown that copper transporters are also involved in the transport of platinum. The goal of this study was to det...

    Authors: Zhuang-hua Li, Miao-zhen Qiu, Zhao-lei Zeng, Hui-yan Luo, Wen-jing Wu, Feng Wang, Zhi-qiang Wang, Dong-sheng Zhang, Yu-hong Li and Rui-hua Xu
    Citation: Journal of Translational Medicine 2012 10:21
  23. HER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively eva...

    Authors: George Fountzilas, Christos Valavanis, Vassiliki Kotoula, Anastasia G Eleftheraki, Konstantine T Kalogeras, Olympia Tzaida, Anna Batistatou, Ralf Kronenwett, Ralph M Wirtz, Mattheos Bobos, Eleni Timotheadou, Nikolaos Soupos, George Pentheroudakis, Helen Gogas, Dimitrios Vlachodimitropoulos, Genovefa Polychronidou…
    Citation: Journal of Translational Medicine 2012 10:10
  24. Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic.

    Authors: Julia B Sturm, Michael Hess, Stephanie Weibel, Nanhai G Chen, Yong A Yu, Qian Zhang, Ulrike Donat, Cora Reiss, Stepan Gambaryan, Georg Krohne, Jochen Stritzker and Aladar A Szalay
    Citation: Journal of Translational Medicine 2012 10:9
  25. Cancer patients receiving chemotherapy are at increased risk of thrombosis. Nadroparin has been demonstrated to reduce the incidence of venous and arterial thrombotic events (TEs) by about 50% in cancer outpat...

    Authors: Sandro Barni, Roberto Labianca, Giancarlo Agnelli, Erminio Bonizzoni, Melina Verso, Mario Mandalà, Matteo Brighenti, Fausto Petrelli, Carlo Bianchini, Tania Perrone and Giampietro Gasparini
    Citation: Journal of Translational Medicine 2011 9:179
  26. Platinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world. The aim of the present study was to compar...

    Authors: Chiara Arienti, Anna Tesei, Giorgio Maria Verdecchia, Massimo Framarini, Salvatore Virzì, Antonio Grassi, Emanuela Scarpi, Livia Turci, Rosella Silvestrini, Dino Amadori and Wainer Zoli
    Citation: Journal of Translational Medicine 2011 9:94

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