Immunohistochemical detection of a hypoxia marker in spontaneous canine tumours

Cline, J. Mark; Thrall, Donald E.; Page, R L; Franko, Allan J.; Raleigh, James A.

doi:10.1038/bjc.1990.411

Cited by 53 publications

(17 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunohistochemical studies of patterns of tumour hypoxia, using hypoxia marker drugs, in canine and human tumours have typically reported that most intense binding occurs near regions of necrosis, which are typically farthest removed from the nearest microvessel (Cline et al, 1990;Kennedy et al, 1997). Immunohistochemical localization of microvessels would help to clarify this issue further because it is frequently difficult to positively identify microvessels on the basis of H and E staining alone.…”

Section: Discussionmentioning

confidence: 99%

Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia

et al. 1999

View full text Add to dashboard Cite

We previously reported that the arteriolar input in window chamber tumours is limited in number and is constrained to enter the tumour from one surface, and that the p O 2 of tumour arterioles is lower than in comparable arterioles of normal tissues. On average, the vascular p O 2 in vessels of the upper surface of these tumours is lower than the p O 2 of vessels on the fascial side, suggesting that there may be steep vascular longitudinal gradients (defined as the decline in vascular p O 2 along the afferent path of blood flow) that contribute to vascular hypoxia on the upper surface of the tumours. However, we have not previously measured tissue p O 2 on both surfaces of these chambers in the same tumour. In this report, we investigated the hypothesis that the anatomical constraint of arteriolar supply from one side of the tumour results in longitudinal gradients in p O 2 sufficient in magnitude to create vascular hypoxia in tumours grown in dorsal flap window chambers. Fischer-344 rats had dorsal flap window chambers implanted in the skin fold with simultaneous transplantation of the R3230AC tumour. Tumours were studied at 9–11 days after transplantation, at a diameter of 3–4 mm; the tissue thickness was 200 μm. For magnetic resonance microscopic imaging, gadolinium DTPA bovine serum albumin (BSA-DTPA-Gd) complex was injected i.v., followed by fixation in 10% formalin and removal from the animal. The sample was imaged at 9.4 T, yielding voxel sizes of 40 μm. Intravital microscopy was used to visualize the position and number of arterioles entering window chamber tumour preparations. Phosphorescence life time imaging (PLI) was used to measure vascular p O 2 . Blue and green light excitations of the upper and lower surfaces of window chambers were made (penetration depth of light ~50 vs >200 μm respectively). Arteriolar input into window chamber tumours was limited to 1 or 2 vessels, and appeared to be constrained to the fascial surface upon which the tumour grows. PLI of the tumour surface indicated greater hypoxia with blue compared with green light excitation ( P < 0.03 for 10th and 25th percentiles and for per cent pixels < 10 mmHg). In contrast, illumination of the fascial surface with blue light indicated less hypoxia compared with illumination of the tumour surface ( P < 0.05 for 10th and 25th percentiles and for per cent pixels < 10 mmHg). There was no significant difference in p O 2 distributions for blue and green light excitation from the fascial surface nor for green light excitation when viewed from either surface. The PLI data demonstrates that the upper surface of the tumour is more hy...

show abstract

Section: Discussionmentioning

confidence: 99%

Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia

et al. 1999

View full text Add to dashboard Cite

show abstract

“…The rabbit polyclonal, anti-pimonidazole antisera used in the calibrated ELISA were prepared and characterised in a manner analogous to that for CCI-103F -a 2-nitroimidazole compound with six fluorine atoms on the sidechain (Raleigh et at., Cline et al, 1990 Immunohistochemical patterns ofpimonidazole binding in liver As expected, immunostaining in livers perfused at low flow rates in the anterograde direction was localised in oxygenpoor, centrilobular regions ( Figure 3a). The pattern of immunostaining was reversed in liver perfused in the retrograde direction; that is, the staining was now localised in the oxygen-poor, periportal region of the tissue (Figure 3b).…”

mentioning

confidence: 99%

Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver

Arteel

Thurman²,

Yates³

et al. 1995

Br J Cancer

Self Cite

267

200

View full text Add to dashboard Cite

“…Hydroxyprobe is an exogenous nitroaromatic compound [1-[(2-hydroxy-3-piperidinyl)propyl]-2-nitroimidazole hydrochloride] frequently used to study hypoxia in cancer (27)(28)(29).…”

Section: Phenotypic Histological and Immunohistochemical Examinatiomentioning

confidence: 99%

Lung dysfunction causes systemic hypoxia in estrogen receptor β knockout (ERβ ^−/− ) mice

Morani¹,

Barros

Imamov³

et al. 2006

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

114

View full text Add to dashboard Cite

Estrogen receptor ␤ (ER␤) is highly expressed in both type I and II pneumocytes as well as bronchiolar epithelial cells. ER␣ is not detectable in the adult lung. Lungs of adult female ER␤ knockout (ER␤ ؊/؊ ) mice have already been reported to have fewer alveoli and reduced elastic recoil. In this article, we report that, by 5 months of age, there are large areas of unexpanded alveoli in lungs of both male and female ER␤ ؊/؊ mice. There is increased staining for collagen and, by EM, abnormal clusters of collagen fibers are seen in the alveolar septa of ER␤ ؊/؊ mice. Immunohistochemical analysis and Western blotting with lung membrane fractions of ER␤ ؊/؊ mice revealed down-regulation of caveolin-1, increased expression of membrane type-1 metalloproteinase, matrix metalloproteinase 2 (active form), and tissue inhibitors of metalloproteinases 2. Hypoxia, measured by immunohistochemical analysis for hypoxia-inducible factor 1␣ and chemical adducts (with Hypoxyprobe), was evident in the heart, ventral prostate, periovarian sac, kidney, liver, and brain of ER␤ ؊/؊ mice under resting conditions. Furthermore, both male and female adult ER␤ ؊/؊ mice were reluctant to run on a treadmill and tissue hypoxia became very pronounced after exercise. We conclude that ER␤ is necessary for the maintenance of the extracellular matrix composition in the lung and loss of ER␤ leads to abnormal lung structure and systemic hypoxia. Systemic hypoxia may be responsible for the reported left and right heart ventricular hypertrophy and systemic hypertension in ER␤ ؊/؊ mice. extracellular matrix ͉ caveolin ͉ metalloproteinase ͉ hypertension ͉ lung fibrosis T he importance of estrogens in development, physiology, and pathology of the lung has been known for some time. Estrogen hastens the onset of surfactant production and influences alveolar size and number. In fact, there is sexual dimorphism in late gestational and postnatal maturation of the lung in mammals (1, 2). The lack of detectable estrogen receptor ␣ (ER␣) in the lung led to the belief that effects of estrogen on the lung were indirect. It was not until the discovery of ER␤ in 1995 (3) that it became clear that estrogen, acting through ER␤, has direct actions on the lung. ER␤ knockout (ER␤ Ϫ/Ϫ ) mice (4) are characterized by right and left ventricle hypertrophy (5), systemic hypertension (6), ovarian dysfunction (7), and incompletely differentiated epithelium in ventral prostate (8), mammary gland (9), and colon (10). Compared with their WT littermates, female ER␤ Ϫ/Ϫ mice are reported to have fewer alveoli (11), reduced lung volume at a transpulmonary pressure of 20 cm of H 2 O and reduced elastic recoil (12). Massaro et al. (12) attributed the lung phenotype to some defect of the extracellular matrix (ECM) composition. ECM is essential for normal tissue development, homeostasis, and wound repair. Physiologically, there is a balance between matrix protein accumulation and degradation. The ECM is composed of collagenous and noncollagenous proteins in which turnover is predominantl...

show abstract

Immunohistochemical detection of a hypoxia marker in spontaneous canine tumours

Cited by 53 publications

References 35 publications

Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia

Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia

Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver

Lung dysfunction causes systemic hypoxia in estrogen receptor β knockout (ERβ ^−/− ) mice

Contact Info

Product

Resources

About

Immunohistochemical detection of a hypoxia marker in spontaneous canine tumours

Cited by 53 publications

References 35 publications

Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia

Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia

Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver

Lung dysfunction causes systemic hypoxia in estrogen receptor β knockout (ERβ −/− ) mice

Contact Info

Product

Resources

About

Lung dysfunction causes systemic hypoxia in estrogen receptor β knockout (ERβ ^−/− ) mice