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Biomedical subjects

L E Gerlowski

Publications and source records attributed to L E Gerlowski.

4 recordsLinked to original sources
PubMed1986

Microvascular permeability of normal and neoplastic tissues.

A novel, noninvasive method was developed for microvascular permeability measurements in non-malignant (mature granulation) and neoplastic (VX2 carcinoma) tissues grown in the rabbit ear chamber. Dextran of 150,000 molecular weight, tagged with fluorescein isothiocyanate (FITC), was used as a representative tracer molecule. In vivo plasma concentration of dextran was measured by photometric analysis of the plasma layer of microvessels in the ear chamber. The plasma concentration in both normal and tumor preparations rose rapidly to a steady state with a time constant of 4.06 +/- 0.2 sec, and remained relatively constant at that level for the next 2 hr (elimination time constant = 1.77 +/- 0.9 X 10(5) sec). Extravasation of macromolecules from individual microvessels into the extravascular space was measured with the same photometric technique. Interstitial diffusion coefficients and microvascular permeability coefficients were determined by fitting a one-dimensional permeability-diffusion model to the extravasation data. The diffusivity of dextran in tumor interstitium was 2.2 +/- 1.4 X 10(-8) cm2/sec (n = 6) and in granulation tissue interstitium was 6.7 +/- 4.4 X 10(-10) cm2/sec (n = 6). Microvascular permeability in tumors was 7.26 +/- 3.29 X 10(-8) cm/sec (n = 11) and in granulation tissue was 57.24 +/- 39.24 X 10(-8) cm/sec (n = 10). These results on increased permeability (8-fold; P less than 0.002) and increased diffusivity (33-fold; P less than 0.001) in tumors provide a rational basis for the use of large-molecular-weight agents in the detection and treatment of solid tumors.

Animals↗
PubMed1986

Extravascular transport in normal and tumor tissues.

The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

Animals↗
PubMed1985

Effect of hyperthermia on microvascular permeability to macromolecules in normal and tumor tissues.

Microvascular permeability of macromolecules in normal and tumor tissues was measured under hyperthermic conditions. Fluorescein-isothiocyanate tagged dextran (150,000 molecular weight) was chosen as a tracer substance. The modified Sandison type rabbit ear chamber was used to study transport in normal (mature granulation) tissue and tumor (VX2 carcinoma) tissue. Hyperthermia (43 degrees C and 50 degrees C for one hour) was induced with a precision thermal water bath attached to the chamber. When heated to 43 degrees C, the normal tissue microvascular permeability increased to 9.4 +/- 7.3 X 10(-8) cm/s, but not statistically different from the control value of 7.3 +/- 3.3 X 10(-8) cm/s. When heated to 50 degrees C, the normal tissue microvascular permeability rose about six-fold to 44.4 +/- 35.3 X 10(-8) cm/s (p less than 0.01). When heated to 43 degrees C, the tumor microvascular permeability increased to 89.4 +/- 29.7 X 10(-8) cm/s, but not statistically different from the control value of 57.3 +/- 39.2 X 10(-8) cm/s. However, when the tumor tissue was heated to 50 degrees C, its permeability nearly doubled to 112.2 +/- 20.8 X 10(-8) cm/s (p less than 0.025).

Animals↗