Presentation
The aim of our LPS is to offer services in functional characterization and preclinical validation of compounds, nanovehicles, nanodrugs and biomaterials with a potential therapeutic use in cancer.
In vitro studies include: cytotoxicity assays of the compounds in cancer cells and/or cancer stem cells, and evaluation of the effect of these compounds in cancer cell migration and invasion abilities.
Preclinical in vivo studies include: toxicology assays, pharmacokinetic and distribution assays and evaluation of the therapeutic efficacy of the compounds. Our LPS uses noninvasive imaging technology (bioluminescence and/or fluorescence) using xenograft models for solid tumors. Our models are highly metastatic so we can measure the effect both in primary tumor and metastatic foci.
Services
The available services are:
S1. In vitro studies for the functional characterization of antitumor compounds:
S1.1. Cytotoxicity assays (XTT) Effect on cellular viability.
S1.2. Tumorsphere assays. Cytotoxicity evaluation of the compound in cancer stem cells.
S1.3. Migration assays (“wound healing” & Transwells) Effect of the compound in the cancer cell migration ability.
S1.4. Invasion assays (Transwells) Effect of the compound in the cancer cell invasion ability.
S2. In vivo studies for the evaluation of toxicology, pharmacokinetics and therapeutic efficacy of antitumor compounds:
S2.1 Generation of metastatic xenografts for physiopathology and therapeutic studies.
Our LPS has a wide expertise in the development of animal models for experimental oncology. Generated xenografts include metastatic models of different solid tumors, mainly gastrointestinal and gynecologic cancers. They are used for the evaluation experimental therapies, against both primary tumor and metastasis. Our LPS could generate new cancer models previous protocol acceptance and approval by the animal experimental committee and Generalitat de Catalunya.
S2.2 Toxicity assays. Determination of the MTD (maximum tolerated dose) and MTMD (maximum tolerated multiple doses) of the antitumor compounds.
S2.3 Evaluation of the antitumor activity of the compound in a subcutaneous xenograft model.
The service includes the implantation of “nodrize” mice of the chosen tumor line for subcutaneous tumor generation, whose tumors will be used to further implant the experimental mice. It also includes the chosen administration of the compound and the monitoring of the mice weigh and tumor volume twice a week. The evaluation of the bioluminescent signal will be optional.
S2.4 Evaluation of the antitumor and antimetastatic activity of the compound on a metastatic orthotopic xenograft.
The service includes the direct inoculation of the chosen tumor line into the origin organ or the implantation of tumor tissue to generate the experimental orthotopic mice. It also includes the randomization of the mice and the administration of the compound at the dose and the administration schedule planned, and the monitoring of the mice body weight and tumor bioluminescent signal twice a week using IVIS spectrum.
S2.5 Pharmacokinetic and biodistribution assays of the compound marked with fluorescence in a subcutaneous model.
The service includes the implantation of nodrize mice of the chosen tumor line for the generation of subcutaneous tumors and the further implantation of the experimental animals. It is also included the randomization and administration of the compound using 2 different doses and ex vivo recording of the fluorescence at 30 min, 1, 3,7,24 and 48h using IVIS spectrum.
S2.6 Pharmacokinetic and biodistribution assays of the compound marked with fluorescence in an orthotopic model.
The service includes the implantation of nodrize mice of the chosen tumor line for the generation of subcutaneous tumors and the further implantation of the experimental animals. Randomization and administration of the compound using 2 different doses and ex vivo recording of the fluorescence at 30 min, 1, 3,7,24 and 48h using
S2.7 Evaluation of the therapeutic efficacy of a compound in PDXs (patient derived xenografts)
These models are similar to the ones previously described but using samples derived from patients. These models are more reliable because they reflect the genetic background of the patient, being more suitable for translational studies.
S2.8 Collection, conservation and histological and molecular analysis of the samples from in vivo experiments.
S2.9 “Customized” in vivo experiments.
S2.10 Consulting for the redaction of investigation projects regarding in vivo investigation and animal experimentation protocols.
Planning, design, support and consulting for the ethic committee presentation of investigation projects and animal experimentation protocols
S2.11 Consulting for in vivo experiments performance. Planning, design, support and consulting for the performance of in vivo experiments. Selection and use of the most suitable imaging system and evaluation and interpretation of the results. Support through all the experiment.
Responsibles
Contact mail: mcespedes@
Scientific Responsible / Manager Responsible
Technical Responsible
Experience and Trajectory
Industry contracts:
- Preclinical trial to assess efficacy of CEB-01 membrane in combination with 5-FU and leucovorin treatment in mice with pancreatic cancer. IP and Study Director: MV. Céspedes Navarro. Contract with CEBIOTEX 2019.
- Preclinical trial to assess safety, tolerability, and efficacy of CEB-1 membrane in mice with orthotopic pancreatic cancer. IP and Study Director: MV. Céspedes. Contract with CEBIOTEX. 2018.
- Evaluation of the anti-tumor efficacy of the test item ENAX003 after repeated oral administration in combination with intravenous ENAX-18 in the NP9 subcutaneous pancreatic carcinoma xenografts model. IP: R. Mangues. Study director: MV. Cespedes. ARGON PHARMA. 2012.
- A total of 11 preclinical assays as Study Director to evaluate antitumor compounds. IP: R. Mangues. Contract with PharmaMar SA. From 2003 to 2018.
Competitive projects:
- EP PERMED. AC24/00157. “Validating diagnostic OMICS tools for target identification and recurrence monitoring in glioblastoma” Consortium: IP.: MV. Céspedes (IR Sant Pau, Spain)/ IP: O. Schilling (Freiburg University, Germany); IP.: S. Katsahian (Clinical Research Unit & CIC1418- EC, AP-HP, European Hospital Georges Pompidou Paris, France); IP.: F. Mircea Brehar (Neurosurgery Dept.,” BagdasarArseni” Clinical Hospital University of Medicine and Pharmacy” Carol Davila”, Romania)/ IP.: M. Santos (Coimbra University, Portugal). Coordinator & IP.: JW. Bartsch (Marburg University, Germany) Fundings: Co-funded by European Union/ Instituto de Salud Carlos III (ISCIII)/); 2025-2027
- La Marató TV3. 201911-30-31. “Genomic signatures for the prediction of recurrence and metàstasis in Endometrial Cancers”, coordinated project. IP and coordinator: MV. Céspedes (IR Sant Pau, Barcelona) ; IP. Maria Macias (IRB, Barcelona). Fundings: Fundació La Marató TV3; 2020-2024.
- PI20/00623. “Innovative nanotherapy for highly-metastatic peritoneal cancers: activating neuroreceptors to kill cancer stem cells” Instituto de Salud Carlos III. IP: MV Cespedes Navarro; 2020-2024.
- PI17/00150. ISCIII, Spanish Government Targeted nanotherapy and combined SBRT radiotherapy for selective elimination of cancer stem cells in pancreatic cancer IP: MV. Céspedes; 2018-2020
- CP15/00167. ISCIII, Nanoconjugates for targeted therapy against CXCR4+ cancer stem cells in pancreatic cancer. IP: MV. Céspedes; 2016-2018
- AP1666942017. Mutua Madrileña Fundation (FMMA) Targeted therapy for the elimination of CXCR4+ metastatic cancer stem cells in endometrial cancer IP: MV. Céspedes; 2017-2019
Publications:
- Revilla G et al., Lenvatinib-Loaded Poly (lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior. Biomolecules. 2023 Nov 13;13(11):1647.
- Medina-Gutiérrez E, et al., Novel Endometrial Cancer Models Using Sensitive Metastasis Tracing for CXCR4-Targeted Therapy in Advanced Disease. Biomedicines. 2022 Jul 12;10(7):1680.
- Céspedes MV, et al., Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci. Adv Mater. 2020 Feb;32(7):e1907348.
- Céspedes MV, et al., Selective depletion of metastatic stem cells as therapy for human colorectal cancer. EMBO Mol Med. 2018 Oct;10(10):e8772.
- Céspedes MV, et al., Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models. Dis Model Mech. 2016 Dec 1;9(12):1461-1471.
- Alamo P, et al., Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models. Dis Model Mech. 2014 Mar;7(3):387-96.
- Céspedes MV et al., Orthotopic microinjection of human colon cancer cells in nude mice induces tumor foci in all clinically relevant metastatic sites. Am J Pathol. 2007 Mar;170(3):1077-85.
Equipment
Equipment involved in the performance of the service:
- Basic surgical instruments
- Small equipment: 2 magnifying glasses, 1 cold light source, 1 automatic injector, 1 cauterizer, 1 stereotaxic
- Animal Facility infrastructure at IR Sant Pau
