Author:
Yuting Fan, Yi Xia, Jingjie Tang, Palma Rocchi, Fanqi Qu, Juan Iovanna, Ling Peng
Publication Date:
17 Dec 2010
Description:
N-aryltriazole nucleosides are new chemical entities with potential biological activity. The two phosphor ligands, Synphos and Xantphos, had a selective and effective impact on Pd-catalyzed C−N coupling with the 5- and 3-bromotriazole acyclonucleoside isomers, affording the corresponding and otherwise difficult to achieve N-aryltriazole nucleosides with good to excellent yields. In addition, two of the synthesized nucleosides showed superior anticancer activity against drug-resistant pancreatic cancer, compared to the reference drug gemcitabine.
Author:
Menghua Wang, Yi Xia, Yuting Fan, Palma Rocchi, Fanqi Qu, Juan L Iovanna, Ling Peng
Publication Date:
15 Oct 2010
Source:
Bioorganic & medicinal chemistry letters
Description:
Novel arylethynyltriazole acyclonucleosides were synthesized and assessed for their anticancer activity on drug-resistant pancreatic cancer MiaPaCa-2 cells. One lead compound was found to have much more potent apoptosis-related antiproliferative effects than gemcitabine, the current first-line treatment for pancreatic cancer. Further investigations showed that this active compound did not inhibit DNA synthesis, which means that it does not resemble gemcitabine and may involve a different mechanism of action.
Author:
Yang Liu, Yi Xia, Yuting Fan, Alain Maggiani, Palma Rocchi, Fanqi Qu, Juan L Iovanna, Ling Peng
Publication Date:
15 Apr 2010
Source:
Bioorganic & medicinal chemistry letters
Description:
Novel N-aryltriazole nucleosides were synthesized via Cu-mediated C–N cross-coupling reaction starting with 3-aminotriazole ribonucleoside and various boronic acids. Two of them exhibited potent apoptosis-related antiproliferative activity against the drug-resistant pancreatic cancer cell line MiaPaCa-2, with an increased potency compared to gemcitabine, the reference treatment for pancreatic cancer. A preliminary SAR study suggests that the appended N-aryl moiety and the substituent at its para-position, as well as the ribose sugar component, contribute considerably to the observed antiproliferative activity.
Author:
C Andrieu, David Taieb, V Baylot, Susan Ettinger, Philippe Soubeyran, A De-Thonel, Colleen Nelson, Carmen Garrido, Alan So, Ladan Fazli, Franck Bladou, Martin Gleave, JL Iovanna, Palma Rocchi
Publication Date:
01 Apr 2010
Description:
One strategy to improve therapies in advanced prostate cancer (PC) involves targeting genes that are activated by androgen withdrawal to delay the emergence of the androgen-independent (AI) phenotype. Heat shock protein 27 (Hsp27) expression becomes highly upregulated in PC cells after androgen withdrawal or chemotherapy, in which it functions as a cytoprotective chaperone to confer broad-spectrum treatment resistance. The purpose of this study is to elucidate anti-apoptotic pathways regulated by Hsp27 that are activated during PC progression. Using two-hybrid experiment, we found that Hsp27 was having a major role in the protein translational initiation process. Furthermore, using complementary DNA (cDNA) microarray analysis, 4E binding protein 1 was identified as being proportionately and highly regulated by Hsp27. These data led us to analyze the protein synthesis initiation pathway, which is a …
Author:
Yi Xia, Yang Liu, Jinqiao Wan, Menghua Wang, Palma Rocchi, Fanqi Qu, Juan L Iovanna, Ling Peng
Publication Date:
08 Oct 2009
Source:
Journal of medicinal chemistry
Description:
A series of novel 3-arylethynyltriazolyl ribonucleosides were synthesized and assessed for their anticancer activity on the drug-resistant pancreatic cancer cell line MiaPaCa-2. Among them, one compound exhibited potent apoptosis-inducing properties and anticancer activity against the pancreatic cancer model MiaPaCa-2 both in vitro and in vivo with no adverse effects. This compound did not inhibit DNA synthesis and therefore does not resemble the clinical drug gemcitabine. It did, however, significantly down-regulate the expression of heat shock protein 27 (Hsp27), a small molecular chaperone playing an important role in drug resistance and highly expressed in drug-resistant cancer forms, and thus represents the first small molecular anticancer lead with such a mode of action.
Author:
Xiao‐xuan Liu, Palma Rocchi, Fan‐qi Qu, Shu‐quan Zheng, Zi‐cai Liang, Martin Gleave, Juan Iovanna, Ling Peng
Publication Date:
03 Aug 2009
Description:
RNA interference (RNAi) holds great promise for the treatment of inherited and acquired diseases, provided that safe and efficient delivery systems are available. Herein we report that structurally flexible triethanolamine (TEA) core PAMAM dendrimers are able to deliver an Hsp27 siRNA effectively into prostate cancer (PC‐3) cells by forming stable nanoparticles with siRNA, protecting the siRNA nanoparticles from enzymatic degradation, and enhancing cellular uptake of siRNA. The Hsp27 siRNA resulted in potent and specific gene silencing of heat‐shock protein 27, an attractive therapeutic target in castrate‐resistant prostate cancer. Silencing of the hsp27 gene led to induction of caspase‐3/7‐dependent apoptosis and inhibition of PC‐3 cell growth in vitro. In addition, the siRNA–dendrimer complexes are non‐cytotoxic under the conditions used for siRNA delivery. Altogether, TEA core PAMAM dendrimer …
Author:
Gilles Karsenty, Joice Rocha, Simone Chevalier, Eleonora Scarlata, Claudia Andrieu, Fatima Z Zouanat, Palma Rocchi, Sophie Giusiano, Ehab A Elzayat, Jacques Corcos
Publication Date:
01 Aug 2009
Description:
INTRODUCTION AND OBJECTIVE Botulinum toxin type A (BTA) intraprostatic injection induces an improvement of urinary symptoms related to benign prostatic hypertrophy (BPH). Infra‐clinical prostate cancer (PCa) foci and pre‐neoplasic lesions occur concomitantly with BPH in a significant number of patients. The objective of this study was to address whether BTA influences the growth of prostate tumors. METHODS Proliferation of PC‐3 and LNCaP cell lines exposed or not to BTA (Botox) was assessed and compared. Presence of synaptic vesicle 2 (SV2) protein, the membrane receptor of BTA, was studied in both cell lines. After nude mice bearing LNCaP xenografts received intra‐tumoral BTA or saline injection, tumor volume, serum PSA, histopathology and detection of apoptosis were comparatively assessed. RESULTS BTA significantly reduced LNCaP cell proliferation and increased apoptosis in a dose …
Author:
Wei Li, Yuting Fan, Yi Xia, Palma Rocchi, Ruizhi Zhu, Fanqi Qu, Johan Neyts, Juan L Iovanna, Ling Peng
Publication Date:
01 Aug 2009
Source:
Helvetica Chimica Acta
Description:
Novel N‐aryltriazole nucleosides were synthesized via a Cu‐mediated CN cross‐coupling reaction, using 3‐aminotriazole acyclonucleosides and various boronic acid reagents. Interestingly, N‐arylation proceeded much more rapidly on the amide group than on the amine group, leading to selective N‐arylation of the amide functionality on nucleosides containing both groups on the triazole nucleobase.
Author:
Jinqiao Wan, Yi Xia, Yang Liu, Menghua Wang, Palma Rocchi, Jianhua Yao, Fanqi Qu, Johan Neyts, Juan L Iovanna, Ling Peng
Publication Date:
26 Feb 2009
Source:
Journal of medicinal chemistry
Description:
Novel ethynyltriazole ribonucleosides were synthesized using a simple and efficient two-step procedure involving Sonogashira coupling and subsequent ammonolysis. Compounds 2f and 3o inhibited hepatitis C virus (HCV) replication efficiently, whereas compound 3f demonstrated potent apoptosis-induced antiproliferative activity against pancreatic cancer MiaPaCa-2 cells both in vitro and in vivo. Most interestingly, the notable selective antiviral and antiproliferative activities were achieved respectively for 2f and 3f by modulating the ribose sugar moiety into deprotected and protected forms while retaining a similar trifluoromethylphenylethynyltriazole as the nucleobase. Preliminary structure−activity relationship study revealed that not only the ribose moiety but also the CF3 group at the p-position of the phenyl ring and the rigid triple bond functionality contributed critically to the observed antiviral activity of 2f …
Author:
J Cury, G Karsenty, C Andrieu, P Rocchi, F Bladou, S Chevallier, J Iovanna, J Corcos, V Cloutier, L Zini, P Perrotte, U Capitanio, C Jeldres, S Shariat, F Saad, A Duclos, P Arjane, H Widmer, F Montorsi, P Karakiewicz, F Yafi, M Duclos, J Correa, S Tanguay, A Aprikian, L Souhami, R Rajan, J Sturgeon, W Kassouf
Publication Date:
01 Oct 2008
Source:
Canadian Urological Association Journal= Journal de L'association des Urologues du Canada
Description:
Background: Even after stratification for stage, the cancer specific mortality of patients with penile squamous cell carcinoma (SCC) may be quite variable. Recently a nomogram was developed to provide standardized and individualized predictions of cancer specific survival (CSS) after removal of the primary tumour. Unfortunately, it relies on a large number (n= 8) of specific variables that are unavailable in routine clinical practice. This important limitation limits the usefulness of this nomogram.Objective: To develop a simple and accurate nomogram predicting cancer specific mortality after surgical removal of primary penile SCC. Design, setting and participants: The predictive model was developed on a cohort of 420 patients and externally validated using a cohort of 436 patients identified in the 1988–2004 Surveillance, Epidemiology and End Results (SEER) database. The predictors consisted of age, race, stage, grade, type of surgery and lymph node status. Measurements: A nomogram based on Cox regression model-derived coefficients was used for prediction of cancer-specific mortality (CSM) and it accuracy was tested using the area under the receiver operating characteristics (ROC) curve.Results and limitations: Of all candidate predictors, stage and histological grade variables qualified for inclusion in the final nomogram. In the external validation cohort, the nomogram achieved 77% accuracy for prediction of CSM at 5 years after resection of primary penile SCC.Conclusion: Our model is more accurate (77% v. 73%) and substantially less complex (2 v. 8 variables) than the previously published model. In
