35 research outputs found

    Targeting HOX transcription factors in prostate cancer

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    YesBackground: The HOX genes are a family of transcription factors that help to determine cell and tissue identity during early development, and which are also over-expressed in a number of malignancies where they have been shown to promote cell proliferation and survival. The purpose of this study was to evaluate the expression of HOX genes in prostate cancer and to establish whether prostate cancer cells are sensitive to killing by HXR9, an inhibitor of HOX function. Methods: HOX function was inhibited using the HXR9 peptide. HOX gene expression was assessed by RNA extraction from cells or tissues followed by quantitative PCR, and siRNA was used to block the expression of the HOX target gene, cFos. In vivo modelling involved a mouse flank tumour induced by inoculation with LNCaP cells. Results: In this study we show that the expression of HOX genes in prostate tumours is greatly increased with respect to normal prostate tissue. Targeting the interaction between HOX proteins and their PBX cofactor induces apoptosis in the prostate cancer derived cell lines PC3, DU145 and LNCaP, through a mechanism that involves a rapid increase in the expression of cFos, an oncogenic transcription factor. Furthermore, disrupting HOX/PBX binding using the HXR9 antagonist blocks the growth of LNCaP tumours in a xenograft model over an extended period. Conclusion: Many HOX genes are highly over-expressed in prostate cancer, and prostate cancer cells are sensitive to killing by HXR9 both in vitro and in vivo. The HOX genes are therefore a potential therapeutic target in prostate cancer.The authors gratefully acknowledge the support of the Prostate Project charity (UK)

    Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

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    <p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

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    Patient survival and risk of death after prostate cancer treatment in the Brazilian Unified Health System

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    OBJECTIVE Analyze the probability of specific survival and factors associated with the risk of death of patients with prostate cancer who received outpatient cancer treatment in the Brazilian Unified Health System, Brazil. METHODS Retrospective cohort study using the National Database of Oncology, developed through the deterministic-probabilistic pairing of health information systems: outpatient (SIA), hospital (SIH) and mortality (SIM). The probability of overall and specific survival was estimated by the time elapsed between the date of the first ambulatory treatment, from 2002 to 2003, until the patient’s death or the end of the study. Fine and Gray’s model of competing-risks regression was adjusted according to the variables: age of diagnostic, region of residence, tumor clinical staging, type of outpatient cancer treatment and hospitalization in the assessment of factors associated with risk of patient death. RESULTS Of 16,280 patients studied, the average age was 70 years, approximately 25% died due to prostate cancer and 20% for other causes. The probability of overall survival was 0.50 (95%CI 0.49–0.52) and the specific was 0.70 (95%CI 0.69–0.71). The factors associated with the risk of patient death were: stage III (HR = 1.66; 95%CI 1.39–1.99) and stage IV (HR = 3.49; 95%CI 2.91–4.18), chemotherapy (HR = 2.34; 95%CI 1.76–3.11) and hospitalization (HR = 1.6; 95%CI 1.55–1.79). CONCLUSIONS The late diagnosis of the tumor, palliative treatments, and worse medical condition were factors related to the worst survival and increased risk of death from prostate cancer patients in Brazil.OBJETIVO Analisar a probabilidade de sobrevida específica e os fatores associados ao risco de óbito dos pacientes com câncer de próstata, que receberam tratamento oncológico ambulatorial no SUS, Brasil. MÉTODOS Estudo de coorte retrospectivo utilizando a Base Nacional em Oncologia, desenvolvida por meio de pareamento determinístico-probabilístico dos sistemas de informação de saúde: ambulatorial (SIA), hospitalar (SIH) e de mortalidade (SIM). A probabilidade de sobrevida global e específica foi estimada pelo tempo decorrido entre a data do primeiro tratamento ambulatorial, entre 2002 e 2003, até o óbito dos pacientes ou fim do estudo. O modelo de regressão de riscos competitivos de Fine e Gray foi ajustado segundo as variáveis: idade ao diagnóstico, região de residência, estadiamento clínico do tumor, tipo de tratamento oncológico ambulatorial e internação na avaliação dos fatores associados ao risco de óbito dos pacientes. RESULTADOS Dos 16.280 pacientes estudados, a idade média foi de 70 anos, cerca de 25% foi a óbito devido ao câncer de próstata e 20% por outras causas. A probabilidade de sobrevida global foi de 0,50 (IC95% 0,49–0,52) e a específica 0,70 (IC95% 0,69–0,71) . Os fatores associados ao risco de óbito dos pacientes foram: estádio III (HR = 1,66; IC95% 1,39–1,99) e estágio IV (HR = 3,49; IC95% 2,91–4,18), tratamento quimioterápico (HR = 2,34; IC95% 1,76–3,11) e internação (HR = 1,6; IC95% 1,55–1,79). CONCLUSÕES O diagnóstico tardio do tumor, tratamentos não curativos e pior condição clínica foram fatores relacionados à pior sobrevida e ao maior risco de óbito dos pacientes com câncer próstata no Brasil
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