Hypoxia-inducible Factor-1α is Associated with Risk of Aggressive Behavior and Tumor Angiogenesis in Gastrointestinal Stromal Tumor

Chen, Wan‐Tzu; Huang, Chi‐Yu; Wu, Ming-Tsang; Yang, Sheau-Fang; Su, Yue‐Chiu; Chai, Chee‐Yin

doi:10.1093/jjco/hyi067

Cited by 66 publications

(63 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, 16 of 25 of patients had been treated with more than two prior TKIs before study entry. The nine patients in our study who were treated with pazopanib as third-line therapy received a median of two cycles [1][2][3][4][5][6][7][8][9] which is comparable with nilotinib, but inferior to regorafenib [1][2][3]. The fact that our patients were heavily pretreated with multiple TKIs may have affected the outcome of this trial possibly due to multiple secondary mutations.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

et al. 2014

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

“…It is shown that hypoxia-induced factor (HIF-1α) is overexpressed in SDH-deficient GIST and can subsequently lead to increased angiogenesis through regulation of VEGF [7,8]. HIF-1α is also associated with development of metastatic disease in GIST [9].…”

Section: Discussionmentioning

confidence: 99%

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

et al. 2014

View full text Add to dashboard Cite

“…Both groups reported that increased VEGF tumor expression correlated with inferior outcome, including an increased likelihood of developing liver metastases. 13,14 Another group used an enzyme-linked immunosorbent assay (ELISA)-based method to determine tumor VEGF levels more quantitatively in 115 patients with soft-tissue sarcoma. 5 Higher tumor VEGF levels correlated with higher tumor stage, higher tumor grade, and increased risk of local and distant tumor recurrence.…”

Section: Soft-tissue Sarcomamentioning

confidence: 99%

Markers of angiogenesis and clinical features in patients with sarcoma

DuBois

Demetri

2007

Cancer

129

View full text Add to dashboard Cite

Objective: Patient outcome after traumatic brain injury (TBI) is highly variable. The underlying pathophysiology of this is poorly understood, but inflammation is potentially an important factor. Microglia orchestrate many aspects of this response. Their activation can be studied in vivo using the positron emission tomography (PET) ligand [11C](R)PK11195 (PK). In this study, we investigate whether an inflammatory response to TBI persists, and whether this response relates to structural brain abnormalities and cognitive function. Methods: Ten patients, studied at least 11 months after moderate to severe TBI, underwent PK PET and structural magnetic resonance imaging (including diffusion tensor imaging). PK binding potentials were calculated in and around the site of focal brain damage, and in selected distant and subcortical brain regions. Standardized neuropsychological tests were administered. Results: PK binding was significantly raised in the thalami, putamen, occipital cortices, and posterior limb of the internal capsules after TBI. There was no increase in PK binding at the original site of focal brain injury. High PK binding in the thalamus was associated with more severe cognitive impairment, although binding was not correlated with either the time since the injury or the extent of structural brain damage. Interpretation: We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed. ANN NEUROL 2011;

show abstract

“…Besides, it was shown that genetic mutations promoting overstabilization of HiF-1α are a feature of various types of cancers [8]. Finally, it is suggested that the intracellular level of HiF-1α can be related to the aggressiveness of the tumors [53,24,4,10] However, up to now, mathematical models describing the G1/S transition under hypoxia, did not take into account the HiF-1α factor in the hypoxia pathway.Therefore, we propose a mathematical model of the G1/S transition under hypoxia, which explicitly integrates the HiF-1α pathway. The model reproduces the slowing down of G1 phase under moderate hypoxia, and the entry into quiescence of proliferating cells under severe hypoxia.…”

mentioning

confidence: 99%

A mathematical model of HiF-1-mediated response to hypoxia on the G1/S transition

Bedessem

Stéphanou

2014

Mathematical Biosciences

View full text Add to dashboard Cite

Hypoxia is known to influence the cell cycle by increasing the G1 phase duration or by inducing a quiescent state (arrest of cell proliferation). This entry into quiescence is a mean for the cell to escape from hypoxia-induced apoptosis. It is suggested that some cancer cells have gain the advantage over normal cells to easily enter into quiescence when environmental conditions, such as oxygen pressure, are unfavorable [43,1]. This ability contributes in the appearance of highly resistant and aggressive tumor phenotypes [2].The HiF-1α factor is the key actor of the intracellular hypoxia pathway.As tumor cells undergo chronic hypoxic conditions, HiF-1α is present in higher level in cancer than in normal cells. Besides, it was shown that genetic mutations promoting overstabilization of HiF-1α are a feature of various types of cancers [8]. Finally, it is suggested that the intracellular level of HiF-1α can be related to the aggressiveness of the tumors [53,24,4,10] However, up to now, mathematical models describing the G1/S transition under hypoxia, did not take into account the HiF-1α factor in the hypoxia pathway.Therefore, we propose a mathematical model of the G1/S transition under hypoxia, which explicitly integrates the HiF-1α pathway. The model reproduces the slowing down of G1 phase under moderate hypoxia, and the entry into quiescence of proliferating cells under severe hypoxia. We show how the inhibition of cyclin D by HiF-1α can induce quiescence; this result provides a theoretical explanation to the experimental observations of Wen et al. (2010). Thus, our model confirms that hypoxia-induced chemoresistance can be linked, for a part, to the negative regulation of cyclin D by HiF-1α.

show abstract

Hypoxia-inducible Factor-1α is Associated with Risk of Aggressive Behavior and Tumor Angiogenesis in Gastrointestinal Stromal Tumor

Cited by 66 publications

References 34 publications

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

Markers of angiogenesis and clinical features in patients with sarcoma

A mathematical model of HiF-1-mediated response to hypoxia on the G1/S transition

Contact Info

Product

Resources

About