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1.
Br J Cancer ; 125(4): 534-546, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34155340

RESUMEN

BACKGROUND: There is a need to improve the treatment of prostate cancer (PCa) and reduce treatment side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy for low-risk low-volume localised PCa, which rapidly disrupts targeted tumour vessels. There is interest in expanding the use of VTP to higher-risk disease. Tumour vasculature is characterised by vessel immaturity, increased permeability, aberrant branching and inefficient flow. FRT alters the tumour microenvironment and promotes transient 'vascular normalisation'. We hypothesised that multimodality therapy combining fractionated radiotherapy (FRT) and VTP could improve PCa tumour control compared against monotherapy with FRT or VTP. METHODS: We investigated whether sequential delivery of FRT followed by VTP 7 days later improves flank TRAMP-C1 PCa tumour allograft control compared to monotherapy with FRT or VTP. RESULTS: FRT induced 'vascular normalisation' changes in PCa flank tumour allografts, improving vascular function as demonstrated using dynamic contrast-enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumour growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP, and improved overall survival. CONCLUSION: Combining FRT and VTP may be a promising multimodal approach in PCa therapy. This provides proof-of-concept for this multimodality treatment to inform early phase clinical trials.


Asunto(s)
Neovascularización Patológica/terapia , Fotoquimioterapia/métodos , Neoplasias de la Próstata/terapia , Animales , Línea Celular Tumoral , Terapia Combinada , Fraccionamiento de la Dosis de Radiación , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones , Neoplasias de la Próstata/irrigación sanguínea , Análisis de Supervivencia , Microambiente Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
2.
J Sep Sci ; 40(16): 3358-3367, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28605145

RESUMEN

A practical and relatively simple method to identify molecularly imprinted polymers capable of binding proteins via the molecular tagging (epitope-like) approach has been developed. In our two-step method, we first challenge a previously obtained anti-tag molecularly imprinted polymer with a small molecule including the said tag of choice (a biotin derivative as shown here or other) connected to a linker bound to a second biotin moiety. An avidin molecule partially decorated with fluorescent labels is then allowed to bind the available biotin derivative associated with the polymer matrix. At the end of this simple process, and after washing off all the low-affinity binding molecules from the polymer matrix, only suitable molecularly imprinted polymers binding avidin through its previously acquired small molecule tag (or epitope-like probe, in a general case) will remain fluorescent. For confirmation, we tested the selective performance of the anti-biotin molecularly imprinted polymer binding it to biotinylated alkaline phosphatase. Residual chemical activity of the enzyme on the molecularly imprinted polymer solid support was observed. In all cases, the corresponding nonimprinted polymer controls were inactive.


Asunto(s)
Impresión Molecular , Proteínas/química , Avidina , Biotina , Polímeros
3.
Lung Cancer ; 50(3): 319-28, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16159681

RESUMEN

Early, accurate detection of small-cell lung cancer (SCLC), before it becomes systemic, is essential for successful treatment. Fluorescence-based imaging provides safe, sensitive detection of malignancies. Targeted delivery of fluorophores increases sensitivity of endoscopic imaging. We synthesized novel somatostatin analogs, based on backbone cyclic peptides, and conjugated them with fluorescent agents. Nineteen conjugates differing in core peptide, length of alkyl linker and fluorescence moiety (rhodamine and fluorescein) were tested in vitro, using a receptor binding assay, and nine of the more promising conjugates were tested in vivo by fiber-optic spectrofluorimetry and quantitative spectral imaging, on an H69 human SCLC tumor mouse xenograft model. The lead compound showed exceptional tumor/normal tissue ratios, ranging from 9 to 90, and has potential for targeting SCLC overexpressing somatostatin receptors.


Asunto(s)
Carcinoma de Células Pequeñas/diagnóstico , Colorantes Fluorescentes , Neoplasias Pulmonares/diagnóstico , Somatostatina/análogos & derivados , Secuencia de Aminoácidos , Animales , Carcinoma de Células Pequeñas/química , Carcinoma de Células Pequeñas/metabolismo , Modelos Animales de Enfermedad , Femenino , Colorantes Fluorescentes/química , Colorantes Fluorescentes/metabolismo , Neoplasias Pulmonares/química , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Ensayo de Unión Radioligante , Receptores de Somatostatina/metabolismo , Somatostatina/química , Somatostatina/metabolismo , Espectrometría de Fluorescencia/métodos , Trasplante Heterólogo
4.
Biochemistry ; 46(16): 4716-24, 2007 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-17397140

RESUMEN

We describe a novel, potent peptide substrate mimetic inhibitor of protein kinase B (PKB/Akt). The compound selectively kills prostate cancer cells, in which PKB is highly activated, but not normal cells, or cancer cells in which PKB is not activated. The inhibitor induces apoptosis and inhibits the phosphorylation of PKB substrates in prostate cancer cell lines and significantly increases the efficacy of chemotherapy agents to induce prostate cancer cell death, when given in combination. In vivo, the inhibitor exhibits a strong antitumor effect in two prostate cancer mouse models. Moreover, treated animals develop significantly less lung metastases compared to untreated ones, and the effect is accompanied by a significant decrease in blood PSA [prostate-specific antigen] levels in treated animals. This compound and its potential analogues may be developed into novel, potent, and safe anticancer agents, both as stand-alone treatment and in combination with other chemotherapy agents.


Asunto(s)
Ésteres del Colesterol/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Oligopéptidos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Ratones , Mitoxantrona/farmacología , Modelos Moleculares , Antígeno Prostático Específico/sangre , Transducción de Señal/efectos de los fármacos
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