Transient perfusion in human melanoma xenografts

Tufto, Ingunn; Rofstad, Einar K.

doi:10.1038/bjc.1995.153

Cited by 14 publications

(9 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, chronic hypoxia arises in regions distant from the blood vessels owing to the limited diffusion distance of oxygen through solid and massive tumor tissues. Although the compositional contribution of acute hypoxia to total hypoxia in tumor tissues has been considered to be low (10,11), recently, Cárdenas-Navia et al proved the pervasive presence of fluctuating pO 2 in rat tumors (12), indicating that acute hypoxia is a more common phenomenon in tumor tissues than previously presumed. In clinical practice, fractionated radiation therapy, which leads to tumor reoxygenation is considered to be an effective method for killing cancer cells under conditions of chronic hypoxia (8).…”

Section: Introductionmentioning

confidence: 93%

Suppression of HIF-1α expression and radiation resistance in acute hypoxic conditions

Oike

Suzuki

Al-Jahdari

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract.Recently, it has become clear that acute hypoxia affecting radioresistance exists widely in tumor tissues. Concurrently, hypoxia-inducible factor-1α (HIF-1α) is recognized as an essential transcriptional factor, enabling cells to survive through hypoxia. However, it is unclear as to whether HIF-1α plays a direct role in the radioresistance caused by acute hypoxia. Therefore, in this study, we investigated the in vitro response of the human lung adenocarcinoma cell line, A549, to ionizing radiation in an experimental model that imitates acute hypoxia in the presence and absence of HIF-1α expression, using the HIF-1α inhibitor 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (YC-1). Cells were treated with or without 10 µM YC-1 for 2 h. Cells were exposed to either 95% N 2 and 5% CO 2 (hypoxic condition of <0.1 mmHg) or atmospheric air (normoxic condition) for 1 h, and irradiated with 2, 5 and 10 Gy. Western blot analysis revealed that, without YC-1, cells exposed to hypoxic conditions expressed increased levels of HIF-1α compared with those exposed to normoxic conditions. Under hypoxic conditions, HIF-1α expression was suppressed by YC-1 to the same extent as that observed in cells exposed to normoxic conditions without YC-1. Clonogenic survival assay revealed that under hypoxic conditions there was no significant difference between the surviving fraction of cells treated with YC-1 and without YC-1 at any dose point examined. The oxygen enhancement ratio at 10% surviving fraction was calculated as 2.7 and 2.6 in the presence and the absence of YC-1, respectively. These results indicate that HIF-1α itself is not an immediate cause of acute hypoxia-induced radioresistance in A549 cells. IntroductionHypoxia in the microenvironment of tumors is well recognized as one of the major factors affecting resistance against radiation therapy (1-4). In the clinical setting, a number of investigators have proven the existence of hypoxic cells in human cancers by directly measuring intratumoral oxygen partial pressure (pO 2 ) using special electrodes (5-7). We have also previously reported that low pretreatment intratumoral pO 2 correlates with poor clinical outcome in cervical cancer treated with photon therapy (7).It is recognized that hypoxia in tumors may result from two quite different mechanisms, namely 'acute hypoxia' and 'chronic hypoxia' (8). Acute hypoxia is the result of the abrupt temporary closing of a tumor blood vessel owing to the malformed vasculature of the tumor, which lacks smooth muscle functionality and often has an incomplete endothelial lining and basement membrane (9). Meanwhile, chronic hypoxia arises in regions distant from the blood vessels owing to the limited diffusion distance of oxygen through solid and massive tumor tissues. Although the compositional contribution of acute hypoxia to total hypoxia in tumor tissues has been considered to be low (10,11), recently, Cárdenas-Navia et al proved the pervasive presence of fluctuating pO 2 in rat tumors (12), indicating that acute hypoxia i...

show abstract

Section: Introductionmentioning

confidence: 93%

Suppression of HIF-1α expression and radiation resistance in acute hypoxic conditions

Oike

Suzuki

Al-Jahdari

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…The fraction of these (mostly coexisting) subtypes of hypoxia in solid tumors at a given time has been discussed controversially so far. In a series of experimental tumors, acute hypoxia has been described as the dominating type of oxygen depletion [13,20,22], whereas in others, only low levels of acute hypoxia were detected [4,8,9,15,24].…”

Section: Introductionmentioning

confidence: 99%

Quantitative assessment of hypoxia subtypes in microcirculatory supply units of malignant tumors Using (immuno-)fluorescence techniques

et al. 2011

View full text Add to dashboard Cite

show abstract

“…However, laser Doppler flow studies of red cell flux instability performed in a number of preclinical models as well as in human tumors show typical cycle times of 2-to-5-per-hour variation magnitudes of a factor of 1.5-to 3-fold. Thus, these data are in the range that we predicted would be sufficient to cause transient hypoxia using the Green's function models (1,3,(25)(26)(27).…”

Section: Partial Pressure Of Oxygen Fluctuationsmentioning

confidence: 99%

Tumor-dependent Kinetics of Partial Pressure of Oxygen Fluctuations during Air and Oxygen Breathing

Cárdenas-Navia

Braun

et al. 2004

Cancer Research

View full text Add to dashboard Cite

The primary purpose of this study was to examine the kinetics of partial pressure of oxygen (pO 2 ) fluctuations in fibrosarcoma (FSA) and 9L tumors under air and O 2 breathing conditions. The overall hypothesis was that key factors relating to oxygen tension fluctuations would vary between the two tumor types and as a function of the oxygen content of the breathing gas. To assist in the interpretation of the temporal data, spatial pO 2 distributions were measured in 10 FSA and 8 9L tumors transplanted into the subcutis of the hind leg of Nembutal-anesthetized (50 mg/kg) Fischer 344 rats. Recessed-tip oxygen microelectrodes were inserted into the tumor, and linear pO 2 measurements were recorded in 50-m steps along a 3-mm path, and blood pressure was simultaneously measured via femoral arterial access. Additionally, pO 2 was measured at a single location for 90 to 120 minutes in FSA (n ‫؍‬ 11) or 9L tumors (n ‫؍‬ 12). Rats were switched from air to 100% O 2 breathing after 45 minutes. Temporal pO 2 records were evaluated for their potential radiobiological significance by assessing the number of times they crossed a 10-mm-Hg threshold. In addition, the data were subjected to Fourier analysis for air and O 2 breathing.FSA and 9L tumors had spatial median pO 2 measurements of 4 and 1 mm Hg, respectively. 9L had more low pO 2 measurements <2.5 mm Hg than did FSA, whereas between 2.5 and 10 mm Hg this pattern was reversed. Pimonidazole staining patterns in FSA and 9L tumors supported these results. Temporal pO 2 instability was observed in all experiments during air and O 2 breathing. Threshold analyses indicated that the 10 mm Hg threshold was crossed 2 to 5 times per hour, independent of tumor type. However, the magnitude of 9L pO 2 fluctuations was approximately eight times greater than FSA fluctuations, as assessed with Fourier transform analysis (Wilcoxon, P < 0.005). O 2 breathing significantly increased median pO 2 in FSA from 3 to 8 mm Hg (P < 0.005) and caused a significant increase in frequency and magnitude of pO 2 fluctuations. One hundred percent O 2 breathing had no effect on 9L tumor pO 2 , and it decreased the magnitude of pO 2 fluctuations with borderline significance.These results show that these two tumors differ significantly with respect to spatial and temporal oxygenation conditions under air and O 2 breathing. Fluctuations of pO 2 of the type reported herein are predicted to significantly affect radiotherapy response and could be a source for genetic instability, increased angiogenesis, and metastases.

show abstract

Transient perfusion in human melanoma xenografts

Cited by 14 publications

References 26 publications

Suppression of HIF-1α expression and radiation resistance in acute hypoxic conditions

Suppression of HIF-1α expression and radiation resistance in acute hypoxic conditions

Quantitative assessment of hypoxia subtypes in microcirculatory supply units of malignant tumors Using (immuno-)fluorescence techniques

Tumor-dependent Kinetics of Partial Pressure of Oxygen Fluctuations during Air and Oxygen Breathing

Contact Info

Product

Resources

About