Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study

Vergis, Roy; Corbishley, Catherine M.; Norman, A.; Bartlett, J. Blake; Jhavar, Sameer; Borre, Michael; Heebøll, Sara; Horwich, A.; Huddart, Robert; Khoo, Vincent; Eeles, Rosalind; Cooper, Christopher S.; Sydes, Matthew R.; Dearnaley, D.; Parker, Chris

doi:10.1016/s1470-2045(08)70076-7

Cited by 250 publications

(232 citation statements)

References 43 publications

Supporting

Mentioning

209

Contrasting

Order By: Relevance

“…Administration of DXR or DNR potently inhibited HIF-1 transcriptional activity in human prostate cancer xenografts and potently inhibited tumor growth. These results are consistent with clinical data correlating increased HIF-1␣ levels with prostate cancer progression (8).…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells

Lee¹,

Qian²,

Rey³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

272

206

View full text Add to dashboard Cite

Using a cell-based reporter gene assay, we screened a library of drugs in clinical use and identified the anthracycline chemotherapeutic agents doxorubicin and daunorubicin as potent inhibitors of hypoxia-inducible factor 1 (HIF-1)-mediated gene transcription. These drugs inhibited HIF-1 by blocking its binding to DNA. Daily administration of doxorubicin or daunorubicin potently inhibited the transcription of a HIF-1-dependent reporter gene as well as endogenous HIF-1 target genes encoding vascular endothelial growth factor, stromal-derived factor 1, and stem cell factor in tumor xenografts. CXCR4 ؉ /sca1 ؉ , VEGFR2 ؉ /CD34 ؉ , and VEGFR2 ؉ / CD117 ؉ bone-marrow derived cells were increased in the peripheral blood of SCID mice bearing prostate cancer xenografts but not in tumor-bearing mice treated for 5 days with doxorubicin or daunorubicin, which dramatically reduced tumor vascularization. These results provide a molecular basis for the antiangiogenic effect of anthracycline therapy and have important implications for refining the use of these drugs to treat human cancer more effectively.hypoxia ͉ xenograft ͉ adriamycin ͉ endothelial progenitor cells ͉ hepatocellular carcinoma

show abstract

Section: Discussionsupporting

confidence: 91%

“…In prostate cancer patients treated with radiotherapy or radical prostatectomy, increased HIF-1␣ levels are associated with reduced time to disease progression (8). In hepatocellular carcinoma, increased HIF-1␣ levels are associated with venous and lymph node invasion and patient mortality (9).…”

mentioning

confidence: 99%

Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells

Lee¹,

Qian²,

Rey³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

272

206

View full text Add to dashboard Cite

show abstract

“…HIF-1a, an oxygen-sensitive HIF-1 subunit, plays an important role in protecting solid tumours against radio-and chemotherapy by promoting angiogenesis, increasing glucose metabolism and modulating apoptosis. In fact, Koukourakis et al and Vergis et al (Vergis et al, 2008) demonstrated that the overexpression of HIF-1a in squamous cell head-and-neck cancer and prostate cancer was associated with incomplete responses to surgery, chemotherapy, radiotherapy and chemoradiotherapy and with poor overall survival in clinical studies (Koukourakis et al, 2002). HIF-1a generally inhibits the induction of apoptosis by anticancer agents (Semenza, 2003;Kilic et al, 2007).…”

mentioning

confidence: 99%

Inhibition of HIF-1α by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo

et al. 2008

View full text Add to dashboard Cite

In a previous study, we showed that a novel anticancer drug, 1-(3-C-ethynyl-b-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd) increased the antitumour efficacy of X-irradiation. However, its effects on hypoxic cells in tumours remain unclarified. Here, we show that TAS106 enhances the induction of apoptosis in X-irradiated human gastric adenocarcinoma MKN45 and MKN28 cells under hypoxia in vitro. At the same time, the accumulation of HIF-1a observed under hypoxia was shown to be decreased to the level of normoxia in the presence of 0.1 mM TAS106. To study the function of HIF-1a protein in apoptosis of hypoxic cells, we employed an HIF-1a reductive approach using its specific antisense oligodeoxynucleotide. The reduction of HIF-1a gene expression dramatically enhanced X-ray-induced apoptosis in hypoxic cells. In in vivo experiments in which MKN45 cells were transplanted into severe combined immunodeficient (SCID) mice, TAS106 (0.5 mg kg À1 ) suppressed HIF-1a expression and subsequently reduced the area of the hypoxic region in the tumour and enhanced the induction of apoptosis in the hypoxic region when combined with 2 Gy of X-irradiation. These results suggest the possibility that TAS106 acts as a potent radiosensitiser through the inhibition of HIF-1a expression and can be a useful agent against radiotherapy-resistant hypoxic cells in solid tumours.

show abstract

“…Increased OPN expression is responsible for shorter survival in breast, prostate and gastric cancers (Bramwell et al, 2006;Wu et al, 2007;Vergis et al, 2008). However, the number of clinical studies investigating the efficacy of OPN in SCHNC cases is limited (Lu et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Osteopontin in Patients Treated with Primary Radiotherapy for Head and Neck Cancer

Etiz¹,

Ataizi²,

Bayman³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: The prognostic value of tumor osteopontin (OPN) in patients with squamous-cell head and neck cancer (SCHNC) was investigated. Materials and Methods: OPN expression was assessed by immunohistochemical methods in 50 patients, who were treated with primary radiotherapy (RT) for locally advanced SCHNC. The effects of OPN on clinical parameters, local-regional control after RT and metastasis-free survival, was assessed. Results: The rate of OPN expression in tumor tissue was 76%. OPN positive cases had lower Hb levels (p=0.088). Mean time to local recurrence was 53.8 months (SE 3.9) in OPN-negative cases and 39.1 months (SE 4.7) in OPN-positive cases (p=0.047). OPN increased the risk of local recurrence 5.9 times (p=0.085). It had no effect on metastasis-free (p=0.116) or overall survival (p=0.123). OPN was positive in 12 of 19 cases that developed grade 3-4 acute radiation dermatitis (p=0.096). Conclusions: OPN expression is associated with an increase in local recurrence in patients who were treated with primary RT for locally advanced SCHNC.

show abstract

Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study

Cited by 250 publications

References 43 publications

Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells

Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells

Inhibition of HIF-1α by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo

Prognostic Value of Osteopontin in Patients Treated with Primary Radiotherapy for Head and Neck Cancer

Contact Info

Product

Resources

About