Treatment of Brain Tumors

Walker, Michael D.

doi:10.1016/s0025-7125(16)31280-9

Cited by 17 publications

(5 citation statements)

References 12 publications

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“…Furthermore, the increment in permeability due to the osmotic procedure was greater in intact brain than in tumour [63][64][65][66]. This may be critical for effective therapy (Figure 4), as the advancing growing edge of the tumour where the BBB is intact needs to be exposed to drug [62,[67][68][69]. Furthermore, if the capillary bed is tight in the tumour itself, as has been noted in 30% of patients with highly anaplastic astrocytomas and in 10% of patients with cerebral lymphomas [70,71], barrier opening within and around the tumour will maximise exposure to drug (Figure 4).…”

Section: Reversibility and Time Course Of Increased Bbb Permeability:mentioning

confidence: 99%

Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy

Rapoport¹

2001

Expert Opinion on Investigational Drugs

129

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The blood-brain barrier (BBB) to water-soluble drugs and macromolecules can be opened in vivo by infusing a hypertonic solution of arabinose or mannitol into the carotid artery for 30 sec. Opening involves widening of tight junctions between endothelial cells of the cerebrovasculature and is mediated by endothelial cell shrinkage, vascular dilatation associated with removal of water from brain, and modulation of the contractile state of the endothelial cytoskeleton and junctional proteins by increased intracellular calcium. A 10-fold increase in BBB permeability to intravascular substances, lasting about 10 min following osmotic exposure, reflects both increased diffusion and bulk fluid flow from blood into brain. Furthermore, recent evidence indicates that the duration of peak BBB opening can be extended beyond 30 min, by pre-treatment with a Na(+)/Ca(2+) channel blocker. In experimental animals, the osmotic method has been used to grant wide access to brain of water-soluble drugs, peptides, antibodies, boron compounds for neutron capture therapy, viral vectors for gene therapy and enzymes. Ongoing multi-centre clinical studies suggest that the method, when used with intra-arterially administered anticancer drugs, can prolong survival in patients with malignant brain tumours, with minimal morbidity. However, controlled clinical trials are critical to see if the osmotic procedure with intra-arterial drugs enhances survival in brain tumour patients compared with intra-arterial drug alone.

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Section: Reversibility and Time Course Of Increased Bbb Permeability:mentioning

confidence: 99%

Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy

Rapoport¹

2001

Expert Opinion on Investigational Drugs

129

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“…They number approximately 15000 annually in the USA, and occur predominantly 9 months [4,5], despite intensive therapy; whereas that for patients with metastatic brain tumours, particularly from lung primaries, often is only 6 months [6].…”

Section: Introductionmentioning

confidence: 99%

Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo: differential uptakes of palmitate, arachidonate and docosahexaenoate

et al. 1993

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This paper investigates the incorporation of intravenously (i.v.) administered radiolabelled fatty acids--[9,10(3)-H]palmitate (3H-PA), [1-14C]arachidonate (14C-AA) and [1-14C]docosahexaenoate (14C-DHA)--into intracerebrally implanted tumours in awake Fischer-344 rats. A suspension of Walker 256 carcinosarcoma tumour cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of 8- to 9-week-old rats. Seven days after implantation, the awake rat was infused i.v. for 5 min with 3H-PA (6.4 mCi/kg), 14C-AA (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty minutes after the start of infusion, the rat was killed and coronal brain sections were obtained for quantitative autoradiography and histology. Each fatty acid showed well-demarcated incorporation into tumour tissue. Areas of necrosis or haemorrhage showed no or small levels of incorporation. The ratios of incorporation into the tumour to incorporation into contralateral brain regions were 2.8-5.5 for 3H-PA, 2.1-3.3 for 14C-AA and 1.5-2.2 for 14C-DHA. The mean ratios differed significantly between the fatty acids (P < 0.01). 3H-PA was not incorporated into necrotic tumours despite the presence of an open blood-tumour barrier, indicated by extravasated horseradish peroxidase. The incorporation rate constant of 3H-PA was similar for small intracerebral and large extracerebral tumours. The results show that 3H-PA, 14C-AA and 14C-DHA are incorporated more readily into tumour tissue than into brain, and that the increase is primarily due to increased utilization of fatty acids by tumour cells and not due to a high blood-tumour permeability. The relative increases in rates of incorporation for the different fatty acids may be related to lipid composition of the tumour and to the requirement of and specific role of these fatty acids in tumour cell growth and division.

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“…It is probable that this ineffectiveness is due to the blood-brain barrier [14,28]. It is probable that this ineffectiveness is due to the blood-brain barrier [14,28].…”

Section: Introductionmentioning

confidence: 99%

“…However, at the tumour's infiltrative edge, where normal brain is encountered, it probably remains intact [15]. Due to the effective barrier at the infiltrative edge, and the diffusion sink created by the surrounding normal brain [20,28], drug levels at the leading edge are too low for tumour cell kill. Due to the effective barrier at the infiltrative edge, and the diffusion sink created by the surrounding normal brain [20,28], drug levels at the leading edge are too low for tumour cell kill.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced cerebrovascular permeability by Metrazol: significance for brain metastases

Greig¹,

Hellmann²

1983

Clin Exp Metast

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Metrazol enhanced the penetration of two proteins (125I human serum albumin and horseradish peroxidase), and the anticancer agent, razoxane, into the central nervous system of anaesthetized rats. Penetration was increased throughout the whole brain. With the exception of the bladder, no peripheral tissue was affected. The increase in brain permeability was temporary and reversed within 4 hours; brain levels of drug and protein were increased by up to three times.

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Treatment of Brain Tumors

Cited by 17 publications

References 12 publications

Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy

Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy

Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo: differential uptakes of palmitate, arachidonate and docosahexaenoate

Enhanced cerebrovascular permeability by Metrazol: significance for brain metastases

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