Author:
Christine Pasero, Gwenaëlle Gravis, Mathilde Guerin, Samuel Granjeaud, Jeanne Thomassin-Piana, Palma Rocchi, Maria Paciencia-Gros, Flora Poizat, Mélanie Bentobji, Francine Azario-Cheillan, Jochen Walz, Naji Salem, Serge Brunelle, Alessandro Moretta, Daniel Olive
Publication Date:
15 Apr 2016
Description:
The field of immunotherapy for solid tumors, such as prostate cancer, has been recently focusing on therapies that can counter tumor-mediated immunosuppression. Precise quantification and characterization of the immune infiltrates in tumors is crucial to improve treatment efficacy. Natural killer (NK) cells, major components of the antitumor immune system, have never been isolated from prostate tumors, despite their suspected role in disease progression. Here, we examined the frequency, phenotype, and functions of NK cells infiltrating control and tumor prostate tissues. NK cell infiltrates in prostate tissues were mainly CD56 (NCAM1)-positive and displayed an unexpected immature, but activated, phenotype with low or no cytotoxic potential. Furthermore, we show that TGFβ1 (TGFB1) is highly secreted into the prostate environment and partly mediates the immunosuppressive effects on NK cells. In addition …
Author:
P Garrigue, A Moyon, X Liu, C Liu, P Rocchi, L Peng, D Taieb, B Guillet
Publication Date:
01 Oct 2015
Author:
Maria Katsogiannou, Hajer Ziouziou, Sara Karaki, Claudia Andrieu, Marie Henry de Villeneuve, Palma Rocchi
Publication Date:
01 Jul 2015
Source:
Cancer Treatment Reviews
Description:
Prostate cancer has become a real public health issue in industrialized countries, mainly due to patients’ relapse by castration-refractory disease after androgen ablation. Castration-resistant prostate cancer is an incurable and highly aggressive terminal stage of prostate cancer, seriously jeopardizing the patient’s quality of life and lifespan. The management of castration-resistant prostate cancer is complex and has opened new fields of research during the last decade leading to an improved understanding of the biology of the disease and the development of new therapies. Most advanced tumors resistant to therapy still maintain the androgen receptor-pathway, which plays a central role for survival and growth of most castration-resistant prostate cancers. Many mechanisms induce the emergence of the castration resistant phenotype through this pathway. However some non-related AR pathways like …
Author:
Marc-Antoine Moris, Claudia Andrieu, Palma Rocchi, Claire Seillan, Julie Acunzo, Frédéric Brunel, Frédéric Garzino, Olivier Siri, Michel Camplo
Publication Date:
20 May 2015
Source:
Tetrahedron Letters
Description:
A series of 2,3,7-trisubstituted phenazines were synthesized using an easy, efficient, and straightforward condensation method. These compounds were tested in vitro on human pancreatic (MiaPaCa-2) cell lines and dose response curves proved that these compounds appeared to be more cytotoxic than standard gemcitabine. Standard ethidium bromide assay showed that these phenazine derivatives were not intercalating agents suggesting a new mode of action. Finally, in vivo test on mice subcutaneously implanted with MiaPaca-2 cells with phenazine 11 showed an activity similar to that of gemcitabine (Gemzar®) standard drug at a 10 times lower concentration (1 mg/kg vs 10 mg/kg for gemcitabine); this result confirms the potential of this new class of phenazines.
Author:
Barbara Lelj-Garolla, Masafumi Kumano, Eliana Beraldi, Lucia Nappi, Palma Rocchi, Diana N Ionescu, Ladan Fazli, Amina Zoubeidi, Martin E Gleave
Publication Date:
01 May 2015
Source:
Molecular cancer therapeutics
Description:
Non–small cell lung cancer (NSCLC) is the most frequent cause of death from cancer worldwide. Despite the availability of active chemotherapy regimens and EGFR tyrosine kinase inhibitors, all advanced patients develop recurrent disease after first-line therapy. Although Hsp27 is a stress-induced chaperone that promotes acquired resistance in several cancers, its relationship to treatment resistance in NSCLC has not been defined. Understanding adaptive responses of acquired resistance will help guide new strategies to control NSCLC. Hsp27 levels were evaluated in an HCC827 erlotinib-resistant–derived cell line (HCC-827Resistant), and sensitivity to erlotinib was examined in Hsp27-overexpressing A549 cells. The role of Hsp27 in both erlotinib and cytotoxic treatment resistance was evaluated in HCC-827 and A549 NSCLC cells using the Hsp27 antisense drug OGX-427. The effect of OGX-427 in …
Author:
Christine Pasero, Gwenaëlle Gravis, Samuel Granjeaud, Mathilde Guerin, Jeanne Thomassin-Piana, Palma Rocchi, Naji Salem, Jochen Walz, Alessandro Moretta, Daniel Olive
Publication Date:
29 Apr 2015
Description:
Clinical outcome of patients with metastatic prostate cancer (mPC) at diagnosis is heterogeneous and unpredictable; thus alternative treatments such as immunotherapy are investigated. We retrospectively analyzed natural killer (NK) cells by flow cytometry in peripheral blood from 39 mPC patients, with 5 year-follow-up, and their correlation with time to castration resistance (TCR) and overall survival (OS). In parallel, NK functionality was carried out against prostate tumor cell lines, analyzed for the expression of NK cell ligands, to identify the receptors involved in PC recognition. NK cells from patients with longer TCR and OS displayed high expression of activating receptors and high cytotoxicity. The activating receptors NKp30 and NKp46 were the most obvious predictive markers of OS and TCR in a larger cohort of mPC patients (OS: p= 0.0018 and 0.0009; TCR: p= 0.007 and < 0.0001 respectively, log-rank test …
Author:
Tuo Wei, Chao Chen, Juan Liu, Cheng Liu, Paola Posocco, Xiaoxuan Liu, Qiang Cheng, Shuaidong Huo, Zicai Liang, Maurizio Fermeglia, Sabrina Pricl, Xing-Jie Liang, Palma Rocchi, Ling Peng
Publication Date:
10 Mar 2015
Source:
Proceedings of the National Academy of Sciences
Description:
Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug …
Author:
Xiaoxuan Liu, Cheng Liu, Jiehua Zhou, Chao Chen, Fanqi Qu, John J Rossi, Palma Rocchi, Ling Peng
Publication Date:
01 Jan 2015
Description:
RNA interference (RNAi) with small interfering RNA (siRNA) is expected to offer an attractive means to specifically and efficiently silence disease-associated genes for treating various diseases provided that safe and efficient delivery systems are available. In this study, we have established an arginine-decorated amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic PAMAM dendron bearing arginine terminals as nonviral vector for siRNA delivery. Indeed, this dendrimer proved to be very effective at delivering siRNAs in human prostate cancer PC-3 cells and in human hematopoietic CD34+ stem cells, leading to improved gene silencing compared to the corresponding nonarginine decorated dendrimer. Further investigation confirmed that this dendrimer was granted with the capacity to form stable nanoparticles with siRNA and significantly enhance cellular uptake of siRNA. In addition, this …
Author:
Mei Cong, Yi Xia, Jingjie Tang, Laurence Borge, Gilles Quéléver, Juan L Iovanna, Palma Rocchi, Ling Peng
Publication Date:
01 Jan 2015
Source:
New Journal of Chemistry
Description:
Synthetic nucleoside analogues with novel structural entities are of considerable importance in the search for new structural paradigms with biologically interesting activities. We report in this work that microwave promoted C–O coupling reaction is able to efficiently offer a large array of novel O-arylated triazole nucleosides with considerably improved yields and appreciably reduced reaction time. One of the synthesized compounds showed interesting anticancer activity against human prostate and pancreatic cancers. The synthetic method described in this work not only highlights the importance of microwave irradiation in organic synthesis but also provides a promising access towards synthesizing novel nucleoside analogues which can offer molecular diversity in the quest for new and potential drug candidates.
Author:
Sara Karaki, Claudia Andrieu, Hajer Ziouziou, Palma Rocchi
Publication Date:
01 Jan 2015
Source:
Advances in Protein Chemistry and Structural Biology
Description:
Cancer cells depend on cap-dependent translation more than normal tissue. This explains the emergence of proteins involved in the cap-dependent translation as targets for potential anticancer drugs. Cap-dependent translation starts when eIF4E binds to mRNA cap domain. This review will present eIF4E's structure and functions. It will also expose the use of eIF4E as a therapeutic target in cancer.
