RESUMO
Biobanking is a costly activity that manages valuable and sometimes irreplaceable specimens. These specimens must be managed and protected carefully as the loss of specimens can destroy years of research efforts, and potentially result in reputational damage to the institution. Therefore, risk management, mitigation, and disaster recovery plans must be in place for unexpected man-made or natural disaster events that will affect biobanking operations. In this chapter, we discuss the various aspects of disaster prevention, and recovery efforts during and after of a disaster event.
Assuntos
Bancos de Espécimes Biológicos/tendências , Desastres Naturais , Humanos , Gestão de RiscosRESUMO
AIMS: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype. RESULTS: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression. In an attempt to develop a clinically relevant approach to down-regulate MnSOD expression in patients with basal breast carcinoma, we employed activation of the peroxisome proliferator-activated receptor gamma (PPARγ) to repress MnSOD expression; PPARγ activation significantly reduced MnSOD expression, increased chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for the clinical use of PPARγ agonists to decrease MnSOD expression, biopsies derived from breast cancer patients who had received synthetic PPARγ ligands as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we provide evidence to implicate peroxynitrite as the mechanism involved in the increased sensitivity to chemotherapy induced by MnSOD repression. INNOVATION AND CONCLUSION: These data provide evidence to link increased MnSOD expression with the aggressive basal breast cancer, and underscore the judicious use of PPARγ ligands for specifically down-regulating MnSOD to increase the chemosensitivity of this subtype of breast carcinoma.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasia de Células Basais/genética , Superóxido Dismutase/genética , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Claudinas/genética , Claudinas/metabolismo , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Ligantes , Camundongos , Mitocôndrias/metabolismo , Neoplasia de Células Basais/tratamento farmacológico , Neoplasia de Células Basais/metabolismo , Neoplasia de Células Basais/mortalidade , Óxido Nítrico/metabolismo , PPAR gama/metabolismo , Ácido Peroxinitroso/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Recent years have seen a great many natural disasters-superstorms, droughts, earthquakes, among others-as well as, in the biobanking world, the constant threat of man-made disaster with everything from freezer malfunctions to theft. To help inform the increasingly important issue of protection from, and recovery after, disasters, Biopreservation and Biobanking put forth the question to our community of experts: How is your biobank handling disaster recovery efforts? Following is a selection of responses. Additionally, please see the Supplementary Information for contingency planning recommendations for biobanks and a threats assessment checklist from Intelsius ( supplementary material can be accessed from the online article at www.liebertpub.com/bio ).