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Hypoxia in prostate cancer: observation to intervention
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文摘
We applied a new, needle biopsy tissue microarray (TMA) technique to study diagnostic samples from men with localised, previously untreated prostate cancer treated in two randomised controlled trials of radiotherapy-dose escalation. Multivariate analysis by Cox proportional hazards was done to assess the association between clinical outcome, in terms of biochemical control, and immunohistochemical staining of hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and osteopontin expression. The analysis was repeated on an independent series of men with localised, previously untreated prostate cancer treated by radical prostatectomy. The main outcome was time to biochemical (ie, prostate-specific antigen [PSA]) failure.

Findings

Between Oct 12, 1995, and Feb 5, 2002, 308 patients were identified from two prospective, randomised trials at the Royal Marsden Hospital, London and Sutton, UK, for the radiotherapy cohort and diagnostic biopsies were available for 201 of these patients. Between June 6, 1995, and Nov 4, 2005, 329 patients were identified from the Aarhus University Hospital, Skejby, Denmark, for the prostatectomy cohort; of these, 40 patients were excluded because the tumour was too small to sample (19 patients), because the paraffin block was too thin (19 patients), or because the blocks were missing (two patients), leaving 289 patients for analysis. For patients treated with radiotherapy, increased staining for VEGF (p=0·008) and HIF-1 alpha (p=0·02) expression, but not increased osteopontin expression (p=0·978), were significant predictors of a shorter time to biochemical failure on multivariate analysis, independent of clinical tumour stage, Gleason score, serum PSA concentration, and dose of radiotherapy. For patients treated with surgery, increased staining for VEGF (p<0·0001) and HIF-1 alpha (p<0·0001) expression, and increased osteopontin expression (p=0·0005) were each significantly associated with a shorter time to biochemical failure on multivariate analysis, independent of pathological tumour stage, Gleason score, serum PSA concentration, and margin status.

Interpretation

To our knowledge, this is the largest study of intrinsic markers of hypoxia and angiogenesis in relation to the outcome of radical treatment of localised prostate cancer. Increased expression of VEGF, HIF-1 alpha, and, for patients treated with surgery, osteopontin, identifies patients at high risk of biochemical failure who would be suitable for enrolment into trials of treatment intensification.

Funding

Prostate Cancer Research Foundation, London, UK; Danish Cancer Society, Copenhagen, Denmark; Cancer Research UK, London, UK; and National Cancer Research Institute South of England Prostate Cancer Collaborative, London, UK.


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Over-expression of hypoxia-inducible factor 1 alpha inc...
Journal of Nanjing Medical University

jrn_sub.gif"" alt=""You are entitled to access the full text of this document"" title=""You are entitled to access the full text of this document"" width=12 height=14""> 48a9a35e8b316473b3ddaf761"">Over-expression of hypoxia-inducible factor 1 alpha increases angiogenesis of LNCaP cells
Journal of Nanjing Medical UniversityVolume 21, Issue 4July 2007, Pages 253-256
Yili Han, Dalin He, Yong Luo, Hepeng Cheng, Guangfeng Zhu

Abstract

Objective

To evaluate the effect of HIF-1 ± over-expression on angiogenesis in human prostate cancer cells.

Methods

LNCaP cells(a human prostate cancer cell line) were transfected with the recombinant plasmid pcDNA3.1(-)-HIF-1 α with Lipofectamine 2000 system. The positive clones were selected by G418 being further confirmed by Western blot and immunofluorescence. The expression levels of VEGF, iNOS and Ang- II were determined.

Results

The expression of HIF-1 α in the LNCaP/HIF1 α cells was significantly increased in transfected cells, which induced the up-regulation of VEGF, iNOS, whereas Ang- II expression remained un-changed.

Conclusion

Overexpression of HIF-1 α can induce angiogenesis proteins and may improve the angiogenesis potency of prostate cancer.


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Angiogenesis and the tumour hypoxia response in prostat...
International Journal of Surgery

jrn_sub.gif"" alt=""You are entitled to access the full text of this document"" title=""You are entitled to access the full text of this document"" width=12 height=14""> Angiogenesis and the tumour hypoxia response in prostate cancer: A review
International Journal of SurgeryVolume 3, Issue 12005, Pages 61-67
P. Sooriakumaran, R. Kaba

Abstract
The formation of new blood vessels, angiogenesis, is a highly-regulated active process that is critical for the development of the normal and malignant prostate. The vascular endothelial growth factor (VEGF) system assumes a critical role in the angiogenic process. Angiogenesis is a prerequisite for the expansion of solid tumours beyond 1–3 mm3 and is stimulated in response to a hypoxic environment. This review discusses the process of angiogenesis and the key angiogenic mediator, VEGF, and their role in tumour progression and metastasis. A better understanding of the mechanisms behind angiogenesis will ultimately lead to the development of new anti-angiogenic agents in the management of prostate cancer.

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doi:10.1016/S1470-2045(08)70081-0
Copyright © 2008 Elsevier Ltd All rights reserved.

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Hypoxia in prostate cancer: observation to intervention

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