Abstract:
:Oxygen is an essential regulator of cellular metabolism, survival, and proliferation. Cellular responses to oxygen levels are monitored, in part, by the transcriptional activity of the hypoxia inducible factors (HIFs). Under hypoxia, HIFs regulate a variety of pro-angiogenic and pro-glycolysis pathways. In solid cancers, regions of hypoxia are commonly present throughout the tissue because of the chaotic vascular architecture and regions of necrosis. In these regions, the hypoxic state fluctuates in a spatial and temporal manner. Transient hypoxic cycling causes an increase in the activity of the HIF proteins above what is typical for non-pathologic tissue. The extent of hypoxia strongly correlates to poor patient survival, therapeutic resistance and an aggressive tumour phenotype, but the full contribution of hypoxia and the HIFs to tumour biology is an area of active investigation. Recent reports link resistance to conventional therapies and the metastatic potential to a stem-like tumour population, termed cancer stem cells (CSCs). We and others have shown that within brain tumours CSCs reside in two niches, a perivascular location and the surrounding necrotic tissue. Restricted oxygen conditions increase the CSC fraction and promote acquisition of a stem-like state. Cancer stem cells are critically dependant on the HIFs for survival, self-renewal, and tumour growth. These observations and those from normal stem cell biology provide a new mechanistic explanation for the contribution of hypoxia to malignancy. Further, the presence of hypoxia in tumours may present challenges for therapy because of the promotion of CSC phenotypes even upon successful killing of CSCs. The current experimental evidence suggests that CSCs are plastic cell states governed by microenvironmental conditions, such as hypoxia, that may be critical for the development of new therapies targeted to disrupt the microenvironment.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Heddleston JM,Li Z,Lathia JD,Bao S,Hjelmeland AB,Rich JNdoi
10.1038/sj.bjc.6605551subject
Has Abstractpub_date
2010-03-02 00:00:00pages
789-95issue
5eissn
0007-0920issn
1532-1827pii
6605551journal_volume
102pub_type
杂志文章,评审abstract::The testis is the third common site of relapse after primary treatment of childhood acute lymphoblastic leukaemia, but in adults relatively few testicular relapses of acute lymphoblastic leukaemia have been reported. In the present investigation the differences in the behaviour of leukaemia in immature and mature rat ...
journal_title:British journal of cancer
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abstract::Tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/APO2L) is a recently identified member of the TNF family, which induces programmed cell death in a variety of neoplastic cell types, but not in most nonneoplastic cells. In this study, we report on the identification of two novel alternative splice ...
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journal_title:British journal of cancer
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.37
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abstract::This study was designed to evaluate new bone resorption and tumour markers as possible alternatives to serial plain radiographs for the assessment of response to treatment. Thirty-seven patients with newly diagnosed bone metastases from breast cancer, randomized to receive oral pamidronate or placebo tablets in additi...
journal_title:British journal of cancer
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doi:10.1038/sj.bjc.6690506
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pub_type: 杂志文章,随机对照试验
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abstract::Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the ...
journal_title:British journal of cancer
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doi:10.1038/sj.bjc.6604163
更新日期:2008-01-15 00:00:00
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doi:10.1038/sj.bjc.6602029
更新日期:2004-08-31 00:00:00
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doi:10.1038/sj.bjc.6605901
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.329
更新日期:1995-08-01 00:00:00
abstract::During the period from 1950 to 1952, three patients were studied by electrophoresis according to Tiselius on account of anticomplementary activity at WR; the presence of an M-component was demonstrated. On several later occasions it was observed that this component at first seemed to remain unchanged, later it was sli...
journal_title:British journal of cancer
pub_type: 杂志文章
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journal_title:British journal of cancer
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journal_title:British journal of cancer
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pub_type: 杂志文章,meta分析,评审
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abstract::Two-tumour-cell-aggregation factors derived from rat ascites hepatoma cells had different antigenicity; one, with a strong potency, was not absorbed by immunoadsorbent chromatography with anti-rat serum antibody and the other, with a weak potency, was. The unabsorbed factor possessed mitogenic activity on lymphocytes ...
journal_title:British journal of cancer
pub_type: 杂志文章
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