31 research outputs found
Vitamin D analogues exhibit antineoplastic activity in breast cancer patient-derived xenograft cells
Despite advances in breast cancer (BC) treatment, its mortality remains high due to intrinsic or acquired resistance to therapy. Several ongoing efforts are being made to develop novel drugs to treat this pathology with the aim to overcome resistance, prolong patient survival and improve their quality of life. We have previously shown that the non-hypercalcemic vitamin D analogues EM1 and UVB1 display antitumor effects in preclinical studies employing conventional cell lines and animal models developed from these cells. In this work, we explored the antitumor effects of EM1 and UVB1 employing BC cells derived from patient-derived xenografts (PDXs), which are a powerful preclinical tool for testing new drugs. We demonstrated that the analogues reduced the viability of HER2-positive and Triple Negative BC-PDXs. Moreover, using an in vitro model of acquired resistance to Trastuzumab-emtansine, UVB1 displayed anti-proliferative actions under 2D and 3D culture conditions. It inhibited both formation and growth of established organoids. In addition, a direct correlation between UVB1 antitumor effects and VDR expression in PDXs was found. In conclusion, all the results reinforce the potential use of these vitamin D analogues as antitumor agents to treat HER2-positive and Triple Negative BC.Fil: Ferronato, MarĂa Julia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Nadal, Serrano Mercedes. Universidad Autonoma de Barcelona. Hospital Vall D' Hebron. Instituto de InvestigaciĂłn Vall D'hebron; EspañaFil: Arenas Lahuerta, Enrique Javier. Universidad Autonoma de Barcelona. Hospital Vall D' Hebron. Instituto de InvestigaciĂłn Vall D'hebron; EspañaFil: Morales, Cristina BernadĂł. Universidad AutĂłnoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Paolillo, Giuliana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Martinez Sabadell, Aliguer Alex. Universidad AutĂłnoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: MascarĂł, Marilina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Vitale, Cristian Alejandro. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de QuĂmica del Sur. Universidad Nacional del Sur. Departamento de QuĂmica. Instituto de QuĂmica del Sur; ArgentinaFil: Fall, Yagamare. Universidad de Vigo; EspañaFil: Arribas, JoaquĂn. Universidad AutĂłnoma de Barcelona. Hospital Vall D' Hebron; España. Universitat AutĂČnoma de Barcelona; España. Centro de InvestigaciĂłn BiomĂ©dica en Red de CĂĄncer; España. InstituciĂł Catalana de Recerca i Estudis Avancats; EspañaFil: Facchinetti, MarĂa Marta. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; Argentin
The UVB1 Vitamin D Analogue Inhibits Colorectal Carcinoma Progression
Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear ÎČ-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease.Fil: Ferronato, MarĂa Julia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Fermento, MarĂa Eugenia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Villegas, MarĂa Emilia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Quevedo, Mario Alfredo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Unidad de InvestigaciĂłn y Desarrollo en TecnologĂa FarmacĂ©utica. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Unidad de InvestigaciĂłn y Desarrollo en TecnologĂa FarmacĂ©utica; ArgentinaFil: Arevalo, Julian. Hospital Municipal General de Agudos Doctor JosĂ© Penna; ArgentinaFil: LĂłpez Romero, Alejandro. Laboratorios IACA. Departamento de HematologĂa; ArgentinaFil: Rivadulla, Marcos Lois. Universidad de Vigo. Facultad de Ciencias; EspañaFil: GĂłmez, Generosa. Universidad de Vigo. Facultad de Ciencias; EspañaFil: Fall, Yagamare. Universidad de Vigo. Facultad de Ciencias; EspañaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentin
Application des reactions de Sila Hofmann et de Sila Cope a la synthese de pheromones
SIGLECNRS T 59349 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc
New Experimental and Computational Tools for Drug Discovery. From Old Way to New Series - Part-X
The series began with several special issues edited by many researchers worldwide and co-edited/supervised or invited by Prof. Gonzalez-Diaz H. (CTMC Enabling Tech Editor, Co-EIC, Europe Editor) [...]The authors acknowledge grants from MINECO (CTQ2016-74881-P) and Basque Government (No. IT1045-16, No. IT1066-16).Peer reviewe
From Hydrindane to Decalin: A Mild Transformation through a Dyotropic Ring Expansion
An
unexpected ring expansion converting hydrindane cores into decalins
has been observed. The process occurs under very mild conditions and
with exquisite transfer of chiral information. The ring expansion
provides access to decorated decalins with complete stereocontrol.
The reaction mechanism is studied in order to gain insight into the
underlying causes for the low thermal requirements in this reaction
and the nature of the chirality transfer process. Interestingly, both
result from an unprecedented dyotropic reaction involving a mesylate
group
From Hydrindane to Decalin: A Mild Transformation through a Dyotropic Ring Expansion
An
unexpected ring expansion converting hydrindane cores into decalins
has been observed. The process occurs under very mild conditions and
with exquisite transfer of chiral information. The ring expansion
provides access to decorated decalins with complete stereocontrol.
The reaction mechanism is studied in order to gain insight into the
underlying causes for the low thermal requirements in this reaction
and the nature of the chirality transfer process. Interestingly, both
result from an unprecedented dyotropic reaction involving a mesylate
group