Permeability of Different Experimental Brain Tumor Models to Horseradish Peroxidase

In vivo Measurement of Regional Brain and Tumor pH Using [14C]Dimethyloxazolidinedione and Quantitative Autoradiography. II: Characterization of the Extracellular Fluid Compartment Using pH-Sensitive Microelectrodes and [14C]Sucrose

“…In the absence of direct measurements of RG-2 glioma pHe' we as sumed that tumor extracellular space was in acid base equilibrium with arterial plasma and that tumor pHe was equal to pH p . This assumption was based on the work of Groothuis et al (1981Groothuis et al ( , 1983a, who demonstrated that RG-2 tumors are permeable to horseradish peroxidase and that they possess a blood-tissue transport constant for (X aminoisobutyric acid that is 25 times greater than that of normal brain, despite similar regional blood flow. Our direct micro electrode measurements, summarized in Ta ble 1, indicate that RG-2 pHe is consistently more alkaline than pH p , averaging 0.3 pH higher than arterial blood pH.…”

“…We previously estimated RG-2 extracellular space to be 0.17 g water/g tissue based on autoradiographic measurements of tissue [14C]sucrose concentration 2 h following an intrave nous bolus injection of the radiotracer. The use of intravenously injected [l4C]sucrose to estimate ex tracellular water volume in RG-2 tumor tissue as- Groothuis et al (1981) that RG-2 tumors were " 100% permeable" to horse radish peroxidase within 15 min after an intrave nous bolus injection. However, Levin et al (1972) reported that in mice with intracerebral ependy moblastomas, inulin (molecular weight 7,000 daltons), a much larger molecule than sucrose (mo lecular weight 342 daltons), requires 3-5 h to equil ibrate with a tumor extracellular water space of �30%.…”

Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin

“…For many chemotherapy drugs, only low concentrations are found in normal brain and cerebrospinal fluid (CSF), because of the BBB and blood-CSF barrier, but the barrier is often largely disrupted in patients with brain tumours (Blasberg and Groothuis, 1986). In animal models, the degree of BBB disruption varies from one type of tumour to another and between parts of the same tumour (Groothuis et al, 1981;Blasberg and Groothuis, 1986). Lower concentrations of chemotherapy drugs (Levin et al, 1972;Tator, 1976;Groothuis et al, 1981) and lower capillary permeability (Hasegawa et al, 1983) It has also been argued that resistance of IC tumours may be due in part to invasion of tumour cells into the brain adjacent to tumour (BAT), where the BBB is more intact, and where drug concentrations are lower than in the main body of the tumour (Levin et al, 1975).…”

“…In animal models, the degree of BBB disruption varies from one type of tumour to another and between parts of the same tumour (Groothuis et al, 1981;Blasberg and Groothuis, 1986). Lower concentrations of chemotherapy drugs (Levin et al, 1972;Tator, 1976;Groothuis et al, 1981) and lower capillary permeability (Hasegawa et al, 1983) It has also been argued that resistance of IC tumours may be due in part to invasion of tumour cells into the brain adjacent to tumour (BAT), where the BBB is more intact, and where drug concentrations are lower than in the main body of the tumour (Levin et al, 1975). However, the importance in brain tumour chemotherapy of resistance of tumour cells in the BAT remains controversial.…”

“…In animal models, the degree of BBB disruption varies from one type of tumour to another and between parts of the same tumour (Groothuis et al, 1981;Blasberg and Groothuis, 1986). Lower concentrations of chemotherapy drugs (Levin et al, 1972;Tator, 1976;Groothuis et al, 1981) and lower capillary permeability (Hasegawa et al, 1983) have been reported in animal IC tumours compared with subcutaneous tumours. Moreover, some studies have reported that drug distribution is far more uniform in extracranial (EC) tumours than in IC tumours (Tator, 1976;Groothuis et al, 1981), and it has been argued that this may result in reistance in the areas of IC tumours that achieve only low drug concentrations.…”