RESUMO
In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was replicated in in vivo murine subcutaneous tumour models. These findings suggest that bacterial presence in the body due to systemic or local infection may influence tumour responses or off-target toxicity during chemotherapy.
Assuntos
Antineoplásicos/farmacocinética , Aziridinas/farmacocinética , Cladribina/farmacocinética , Neoplasias do Colo/tratamento farmacológico , Desoxicitidina/análogos & derivados , Vidarabina/análogos & derivados , Animais , Antineoplásicos/farmacologia , Aziridinas/farmacologia , Biotransformação , Cladribina/farmacologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/microbiologia , Neoplasias do Colo/patologia , Desoxicitidina/farmacocinética , Desoxicitidina/farmacologia , Escherichia coli/crescimento & desenvolvimento , Feminino , Injeções Intralesionais , Injeções Subcutâneas , Listeria/crescimento & desenvolvimento , Camundongos , Transplante de Neoplasias , Pele/efeitos dos fármacos , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Vidarabina/farmacocinética , Vidarabina/farmacologia , GencitabinaRESUMO
There is an undisputed need for employment and improvement of robust technology for real-time analyses of therapeutic delivery and responses in clinical translation of gene and cell therapies. Over the past decade, optical imaging has become the in vivo imaging modality of choice for many preclinical laboratories due to its efficiency, practicality and affordability, while more recently, the clinical potential for this technology is becoming apparent. This review provides an update on the current state of the art in in vivo optical imaging and discusses this rapidly improving technology in the context of it representing a translation enabler or indeed a future clinical imaging modality in its own right.
Assuntos
Imagem Óptica/métodos , Animais , Terapia Baseada em Transplante de Células e Tecidos/instrumentação , Terapia Baseada em Transplante de Células e Tecidos/métodos , Descoberta de Drogas/instrumentação , Descoberta de Drogas/métodos , Corantes Fluorescentes/análise , Terapia Genética/instrumentação , Terapia Genética/métodos , Humanos , Imagem Óptica/instrumentaçãoRESUMO
Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-κB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.