Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity.

Background: This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice.

Methods: The therapeutic EMF device generated a defined 120 Hz semi sine wave pulse signal of variable intensity. Murine 16/C mammary adenocarcinoma tumor fragments were implanted subcutaneously between the scapulae of syngeneic C3H mice.

Lack of appreciation of the role of osmotically unresponsive water in cell volume regulation.

The osmotic responsiveness of cell water has been re-evaluated of reports on the osmotic behaviour of cells. In seven animal cell types, the osmotically unresponsive water (OUR) fraction values ranged from 0.75 to 2.

Maintenance of low sodium and high potassium levels in cells and in tendon/collagen.

Mammalian cells have a higher concentration of potassium and a lower concentration of sodium than their extracellular environment. The mechanisms responsible for the unequal distribution of these ions are commonly ascribed to the presence of an energy requiring plasma membrane ATPase pump, and the presence of membrane channels that pass one ion selectively, while excluding others. This report deals with other mechanisms that might explain this heterogeneous distribution of ions.

The molecular stoichiometric hydration model (SHM) as applied to tendon/collagen, globular proteins and cells.

This report describes and documents the presence of multiple water-of-hydration fractions on proteins and in cells. Initial studies of hydration fractions in g of water/g of DM (dry mass) for tendon/collagen led to the development of the molecular SHM (stoichiometric hydration model) and the development of methods for calculating the size of hydration fractions on a number of different proteins of known amino acid composition. The water fractions have differences in molecular motion and other physical properties due to electrostatic interactions of polar water molecules with electric fields generated by covalently bound pairs of opposite partial charge on the protein backbone.

Micro-CT dilatometry measures of molecular collagen hydration using bovine extensor tendon.

Purpose: This article introduces a new method to study macromolecular hydration using micro-CT dilatometry. The complexity of hydration dependence on solvent temperature, pH, ionic charge, ionic activity, and ionic radii are barriers to comprehensive understanding of protein function. The crystalline character of collagen-tendon suggests that tendon dilatometry may give direct access to measures of molecular tropocollagen solvation response.

Ultrasound-guided intratumoral administration of collagenase-2 improved liposome drug accumulation in solid tumor xenografts.

Purpose: To investigate the effect of intratumoral administration of collagenase-2 on liposomal drug accumulation and diffusion in solid tumor xenografts.

Methods: Correlation between tumor interstitial fluid pressure (IFP) and tumor physiological properties (size and vessel fraction by B-mode and Doppler ultrasound, respectively) was determined. IFP response to intravenous or intratumoral collagenase-2 (0.

Characterization of water of hydration fractions in rabbit skeletal muscle with age and time of post-mortem by centrifugal dehydration force and rehydration methods.

Centrifugal dehydration force (CDF) and rehydration isotherm (RHI) methods were used to measure and characterize hydration fractions in rabbit psoas skeletal muscle. The CDF method assessed fluid flow rate from rabbit muscle and hydration capacity of the fractions. Bulk and multiple non-bulk water fractions were identified.

Water compartments in cells.

Human experience in the macrobiological world leads scientists to visualize water compartments in cells analogous to the bladder in the human pelvis or ventricles in the brain. While such water-filled cellular compartments likely exist, the volume contributions are insignificant relative to those of biomolecular hydration compartments. The purpose of this chapter is to identify and categorize the molecular water compartments caused by proteins, the primary macromolecular components of cells.

Verification of simple hydration/dehydration methods to characterize multiple water compartments on tendon type 1 collagen.

A molecular model of collagen hydration is used to validate centrifugal dehydration force (CDF) and re-hydration isotherm (RHI) methods to measure and characterize hydration compartments on bovine tendon. The CDF method assesses fluid flow rate from flexor and extensor tendons expressed in (g-water/g-dry mass-minute) and hydration capacity of compartments in (g-water/g-dry mass). Measured water compartment capacities agree with the molecular model of collagen hydration [Fullerton GD, Rahal A.

A simple centrifugal dehydration force method to characterize water compartments in fresh and post-mortem fish muscle.

A centrifugal dehydration force (CDF) method to quantify changes in tissue hydration in fresh and in post-mortem muscular fish tail tissue is presented. The data obtained were used to assess fluid flow rate from tissues and the size of hydration compartments expressed in g water/g dry mass (DM). Curve fit analysis demonstrated that muscle tissue has three detectable water compartments.

Numerical distribution of lymphoid nodules in the human sigmoid colon, rectosigmoidal junction, rectum, and anal canal.

There is little information on the numerical distribution of lymphoid nodules (LN) in distal segments of the human large bowel. A novel approach was therefore developed to assess the number of LN in the sigmoid colon, the rectosigmoid segment, the rectum, and the anal canal in humans. The distal large bowel from five cadavers was selected for quantitative study.

Osmotically unresponsive water fraction on proteins: non-ideal osmotic pressure of bovine serum albumin as a function of pH and salt concentration.

How much does protein-associated water differ in colligative properties (freezing point, boiling point, vapor pressure and osmotic behavior) from pure bulk water? This question was approached by studying the globular protein bovine serum albumin (BSA), using changes in pH and salt concentration to alter its native structural conformation and state of aggregation. BSA osmotic pressure was investigated experimentally and analyzed using the molecular model of Fullerton et al. [Biochem Cell Biol 1992;70(12):1325].

On the osmotically unresponsive water compartment in cells.

Differences in colligative properties (freezing point, boiling point, vapor pressure and osmotic behavior) between water in living cells and pure bulk water were investigated by re-evaluating reports of the osmotic behavior of mammalian cells. In five different animal cells, osmotically unresponsive water (OUW) values ranged from 1.1 to 2.

Therapeutic Electromagnetic Field (TEMF) and gamma irradiation on human breast cancer xenograft growth, angiogenesis and metastasis.

Background: The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice.

Water in tendon: orientational analysis of the free induction decay.

The orientation dependence of the free induction decay (FID) of 1H NMR water signal in ex vivo bovine digital flexor tendon at the native level of hydration is reported. Residual dipolar coupling due to the overall tissue anisotropy produces a 6:1 change in the signal intensity as an angle between the long axis of a specimen and the external magnetic field is changed from the "magic angle" of 54.7 degrees to 0 degrees.

Endothelial cell pseudopods and angiogenesis of breast cancer tumors.

BACKGROUND: A neoplastic tumor cannot grow beyond a millimeter or so in diameter without recruitment of endothelial cells and new blood vessels to supply nutrition and oxygen for tumor cell survival. This study was designed to investigate formation of new blood vessels within a human growing breast cancer tumor model (MDA MB231 in mammary fat pad of nude female mouse). Once the tumor grew to 35 mm3, it developed a well-vascularized capsule.

Dietary omega-3 fatty acids and ionizing irradiation on human breast cancer xenograft growth and angiogenesis.

Background: The effects of an omega-3 (n-3) fatty acid enriched diet alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3 fatty acids.

High dietary level of synthetic vitamin E on lipid peroxidation, membrane fatty acid composition and cytotoxicity in breast cancer xenograft and in mouse host tissue.

BACKGROUND: d-alpha-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-alpha-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-alpha-tocopherol or sE).

Paracrine action of transforming growth factor-alpha in rectal crypt epithelium of humans.

Colon and rectal mucosal crypt epithelium is a rapidly renewing cell population, where cell proliferation is normally balanced by cell loss. This report concerns the putative paracrine action of transforming growth factor alpha(TGF-alpha) in this homeostatic process. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and TGF-alpha was performed on biopsy specimens of rectal mucosa taken from consenting patients.

Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice.

BACKGROUND: Supplementing mice with high levels of dietary n-3 polyunsaturated fatty acids (PUFAs) increases the n-3 PUFAs in cell membranes, increases the susceptibility of the cells for lipid peroxidation (LPO) and decreases the growth rate of mammary and other tumors. However, the results of an earlier study indicated that a factor in addition to LPO was involved in the reduction in tumor growth in n-3 PUFAs fed mice. Athymic mice bearing MDA-MB-231 human breast carcinoma xenografts, were fed fish oil concentrate (FOC) or control diets, with and without supplemental Vitamin E (2000 IU /kg diet) and were sacrificed both before and after doxorubicin (DOX) treatment to evaluate factors involved in tumor growth suppression.

Interactions of the DNA intercalator acridine orange, with itself, with caffeine, and with double stranded DNA.

Caffeine (CAF) inhibits the intercalation of acridine orange (AO) into cellular DNA. Optical absorption and fluorescence spectroscopy were employed to determine the molecular interactions of AO with itself, with CAF, and with double stranded herring sperm DNA (dsDNA). AO dimerization was observed at concentrations >2 micromol.

Caffeine and other xanthines as cytochemical blockers and removers of heterocyclic DNA intercalators from chromatin.

Caffeine (CAF) and other xanthines non-covalently bind with the cationic fluorescent dye acridine orange (AO) and with other heterocyclic mutagens and carcinogens that are known to intercalate into double-stranded DNA (dsDNA). Fluorescence microscopy and spectrofluorometry studies were employed to test the ability of caffeine and certain other methyl substituted xanthines, with different binding affinities for AO, to inhibit and to reverse the intercalation of AO and other heterocyclic agents from intercalation with the DNA of nuclear chromatin of air-dried cells. Results indicated that xanthines with binding affinity for AO greater than 150 m(-1) block the AO molecule in a concentration dependent manner and comply with mass action kinetics.