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Modelling in Oncobiology

Group: Modelling in Cancer

Group leader: Maria Filomena Botelho

Core CVs: José Guilherme Tralhão, Arnaldo Figueiredo e Margarida Abrantes

Description:

The Modelling in Cancer Group, headed by Maria Filomena Botelho, is a multidisciplinary team, with dynamic scientific production, aiming at exploring cancer physiopathology to develop new diagnostic and treatment approaches. Specifically, the group goals are (1) to take advantage of ionizing and non-ionizing radiation biologic effects for the improvement of diagnostics, treatment and theranostics, (2) to develop innovative treatment strategies based in novel compounds, biomaterials and drug combinations, and (3) to understand physiopathology and response to treatment through translational man-lab-men models.

A combination of computerized applications, mathematical models of cellular survival, cell and molecular biology techniques, animal studies, nuclear medicine and translational studies are models implemented at the premises of the Faculty of Medicine, mainly at the Institute of Biophysics and at the iCBR, to answer such objectives.

The vast experience in nuclear medicine constitutes a pillar in the evaluation and development of radiotracers and in the innovation in cancer imaging. In this topic, the project EASYPET (PT2020-SII&DT–Copromoção) stands-out by providing a low-cost high-performance PET equipment. The response to ionizing irradiation has been characterized in various types of cancer particularly the implications at the immune system level. Moreover, our current studies in radium therapy provide evidence to the indication of such therapy to a larger group of patients.

The development of new therapeutics is a focus, where new cytotoxic entities and new moieties with potential applicability in photodynamic therapy are developed and characterized. The current NanoBullet-PDT project (PTDC/QEQ-MED/0262/2014) already materialized in several published contributions and a patent application disclosing a group of a stable near infrared luminescent photosensitizers useful in imaging, oxygen sensing and therapy, therefore, with great potential for theranostics.

Other breaking-new-ground strategies include the study of plasmas as an approach for cancer and other non-malignant diseases. Likewise, the use of amniotic membrane in the treatment of cancer is a prospect with proven cytotoxic effect, particularly in hepatocellular carcinoma, a type of cancer, which is the subject of fundamental and translational investigation. In this context, the Cost Action SPRINT (CA17116), a collaborative structure formed by 18 countries, aims to implement a global integrated scientific, medical and industrial network to investigate and comprehensively explore the therapeutic potential of Perinatal Derivatives.

The Group is also part of an European cooperation project in oncology, ONCONET SUDOE project (SOE1/P1/F0082), co-financed by INTERREG SUDOE Programme 2016-2019. It seeks to connect researchers, care providers, diagnostic platforms and companies to set long-term relationships that foster innovation in the oncology sector.

Complementarily, several mechanisms associated with the development, progression and metastasis of cancer and having an influence on response to therapy, such as cancer stem cells, differentiation and dedifferentiation, microenvironment, hypoxia and multidrug resistance are under study, under study, using in vitro, in vivo and ex vivo approaches.

Main achievements in the last 5 years:

The development of new therapeutic approaches was one of the topics in which the team contributed, particularly regarding the therapy to retinoblastoma (confidential data), innovative therapies for solid cancers (Cur Med Chem,2015;22:3025; Med Oncol,2015;32:257; Inorg Chim Acta,2015; 438:160; Appl Appl Organomet Chem,2015;29:425; Restor Dent Endod,2015;40:236; Nutr & Cancer,2016;68(2):250-66; Cell Tissue Bank,2016 17(4):653-663; ACS Med Chem Lett,2017,8(3):310-315; Eur J Med Chem 2018;146:395-408; Front Physiol 2018;9:9111; Cell Tissue Res, 2018;373(2):459-476) and also potential targeted therapies (Radiochim Acta, 2015;103:765; Leukemia Res,2015;39:355; Oncology Reviews,2016;Oct 10;10(2):302; Eur J Cell Biol, 2016 95(6-7):208-18; Sci Rep,2016;Feb 17;6:21648).

Besides therapy, the team also made efforts to contribute for prevention of human diseases (Cancer Metast Rev, 2015;34:465; Sci Rep,2016;Oct 11;6:34731; Acta Med Port;29(7-8):461-467; Eur J Pharm Biopharm,2016;Dec 19; J Surg Res,2017(216):87-98; J Nutr Biochem,2018;56:183-192; Ceram Int, 2018;44 (5):5025-503.) and to understand the underlying disease and therapeutics mechanisms (In Vivo, 2015;29:435; Clin Mol Hepatol,2015;21:257; Cancer Metast Rev,2015;34:401; J Clin Exp Hepatol,2015;5:183; Med Oncol, 2015;32:245; Liver Int, 2015;35:1116; Bioorganic Med Chem,2016; 15;24(16):3556-64; 1865(2):168-75; Life Sciences 164;1:31-4; Pathol Oncol Res,22(4):689-97; Rev Port Estomatol Med Dent Cir Maxilofac,2014;55(3):129-134; J Cancer Res and Treat,2016;4(1):9-16; The Breast 2018;38:22-29; Head & Neck,2018;40(10):2304-2313; Current cancer drug targets,2018;18:1; J Invest Surg,2018;31 (3):243-252, specifically understanding radiation effects on different types of tumors and its repercussions (Cancer Treat Rev 2018;68:47-54; Biochim Biophys Acta, 2016; Med Oncol,2015;32:266; Clin Mol Hepatol, 2015, 21(3)257-267; Cancer Metast Rev,2015;34:511; Brit J Biomed Sci,2015)

Selected Publications in the last 5 years:

1. Targeted Alpha Therapy using Radium-223: From physics to biological effects. IA Marques, AR Neves, AM Abrantes, AS Pires, E Tavares-da-Silva, A Figueiredo, MF Botelho. Cancer Treatment Reviews. 2018. 68:47-54. IF: 8.122. Q1. Oncology

2. Advances on photodynamic therapy of melanoma through novel ring-fused 5, 15-diphenylchlorins. NAM Pereira, M Laranjo, J Pina, ASR Oliveira, JD Ferreira, C Sánchez-Sánchez, J Casalta-Lopes, AC Gonçalves, AB Sarmento-Ribeiro, M Piñeiro, J Sérgio Seixas de Melo, MF Botelho, TMVD Pinho e Melo. European Journal of Medicinal Chemistry 2018. 146, 395-408. IF: 4.816. Q1. Chemistry, Medicinal

3. Butyrate, a dietary fiber derivative that improves irinotecan effect in colon cancer cells. JC Encarnação, AS Pires, RA Amaral, TJ Gonçalves, M Laranjo, J Eduardo Casalta-Lopes, AC Gonçalves, AB Sarmento-Ribeiro, AM Abrantes, MF Botelho. The Journal of Nutritional Biochemistry 2018. 56, 183-192. IF: 4.414. Q1. Biochemistry and Molecular Biology.

4. Ascorbic acid chemosensitizes colorectal cancer cells and synergistically inhibits tumor growth. AS Pires, CR Marques, JC Encarnação, AM Abrantes, IA Marques, Mafalda Laranjo, Rui Oliveira, João E Casalta-Lopes, Ana C Gonçalves, Ana B Sarmento-Ribeiro, Maria F Botelho. Frontiers in Physiology 2018;9: 9111. doi: 10.3389/fphys.2018.00911. IF: 3.394. Q1. Physiology

5. Can the regenerative potential of an alkali-free bioactive glass composition be enhanced when mixed with resorbable β-TCP? MM Ferreira, AF Brito, CF Marques, LF Freitas, E Carrilho, AM Abrantes, Ana S Pires, Maria J Aguiar, Lina Carvalho, Maria F Botelho, José MF Ferreira. Ceramics International 2018.44 (5), 5025-503. IF: 3.057. Q1. Materials Science, Ceramics

6. Mammospheres of hormonal receptor positive breast cancer diverge to triple-negative phenotype. M Laranjo, MJ Carvalho, T Costa, A Alves, RC Oliveira, J Casalta-Lopes, P Cordeiro, F Botas, AM Abrantes, A Paiva, C Oliveira, MF Botelho. The Breast 2018. 38, 22-29. IF: 2.951. Q1. Obstetrics & Gynecology. Q3 Oncology

7. Platinum(II) Ring-Fused Chlorins as Near-Infrared Emitting Oxygen Sensors and Photodynamic Agents. Pereira NAM, Laranjo M, Casalta-Lopes J, Serra AC, Piñeiro M, Pina J, Seixas de Melo JS, Senge MO, Botelho MF, Martelo L, Burrows HD, Pinho e Melo TMVD. ACS Medicinal Chemistry Letters, 2017, 8 (3):310-315. IF: 3.746. Q1: Chemistry, Medicinal.

8. The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Mendes F, Domingues C, Rodrigues-Santos P, Abrantes AM, Gonçalves AC, Estrela J, Encarnação J, Pires AS, Laranjo M, Alves V, Teixo R, Sarmento AB, Botelho MF, Rosa MS. Biochim. Biophys. Acta, 2016; 1865(2):168-75. DOI: 10.1016/j.bbcan.2016.02.002.2016. 2016. IF: 7.841. Q1: Biochemistry & Molecular Biology; Q1: Biophysics; Q1: Oncology.

9. MIA PaCa-2 and PANC-1 - pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors. R Gradiz, HC Silva, L Carvalho, M Filomena Botelho, A Mota-Pinto. Scientific Reports. 2016 Feb 17;6:21648. doi: 10.1038/srep21648. IF: 5.228; Q1. Multidisciplinary.

10. Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viability. J Carrapita, AM Abrantes, S Campelos, AC Gonçalves, D Cardoso, AB Sarmento-Ribeiro, C Rocha, JN Santos, M Filomena Botelho, JG Tralhão, O Farges, JM Barbosa. Scientific Reports. 2016 Oct 11;6:34731. doi: 10.1038/srep34731. IF: 5.228; Q1. Multidisciplinary.

People:

Integrated Members

Ana Cristina Santos, DMD, PhD

Ana Filipa Brito, PhD

Ana Margarida Abrantes, PhD

Ana Salomé Pires, PhD

Ana Sofia Coelho, DMD, PhD

Anabela Paula, DMD, PhD

António Bernardes, MD, PhD

Arnaldo Figueiredo, MD, PhD

Bárbara Oliveiros, PhD

Beatriz Costa, MD, PhD

Eunice Carrilho, DMD, PhD

Henrique Alexandrino, MD, PhD

João Carlos Ribeiro, MD, PhD

José Guilherme Tralhão, MD, PhD

Mafalda Laranjo, PhD

Manuel Marques Ferreira, DMD, PhD

Maria Alcide Marques, MD, PhD

Maria Filomena Botelho, MD, PhD

Maria João Carvalho, MD, PhD

Nuno Chichorro Ferreira, PhD

Paula Alves. MD, PhD

Rui Martins, MD, PhD

Siri Paulo, DMD, PhD

Collaborators

Ana Catarina Mamede, PhD

Denise Priolli, MD, PhD

Francisco Branquinho, MD

Maria Augusta Cipriano, MD

PhD Students

Ana Esmeralda Costa, MD

Ana Sofia Pais, MD

Carlos Miguel Marto, DMD

Catarina Guilherme, MSc

Daniela Madama, MD

David Castelo, MD

Edgar Tavares da Silva, MD

Fabiana Ribeiro, MSc

Hugo Antunes, MD

Inês Marques, MSc

João Casalta Lopes, MD

Karla Cardoso, MVD

Ricardo Martins, MD

Ricardo Teixo, MSc

Rui Pedro Caetano Oliveira, MD

Tarcísio Guimarães, MVD