Cell surface fucose ablation as a therapeutic strategy for malignant neoplasms.

The sugar alpha-L-fucose is overexpressed in many human malignancies, especially on specific glycoproteins, glycolipids, certain mucins, and putative cell adhesion ligands found on cancer cell surfaces. Many of these molecules are known or suspected mediators of cell-cell adhesion, cell signaling, motility, or invasion. As knowledge of fucose metabolism evolves and specific mechanisms of its distribution and incorporation are more exactly documented, modulation of fucose expression in cancer is becoming increasingly more feasible. The authors propose that cancer cell surface alpha-L-fucose is a logical target for selective therapeutic ablation. Reduction of fucose content on the surfaces of malignant cells should effectively cripple the cells' physiologic functions by altering or dysregulating cell-cell or cell-matrix interactions, critical for maintaining the malignant phenotype. Significant therapeutic benefits might include modulation of adhesion abnormalities in the cancer cells, reduction of cancer cell motility or invasiveness, reexposure to immune surveillance, or a combination of these events.

Alpha-L-fucose: a potentially critical molecule in pathologic processes including neoplasia.

Alpha-L-fucose is a 6-carbon deoxyhexose that is commonly incorporated into human glycoproteins and glycolipids. It is found at the terminal or preterminal positions of many cell-surface oligosaccharide ligands that mediate cell-recognition and adhesion-signaling pathways. These include such normal events as early embryologic development and blood group recognition and pathologic processes including inflammation, infectious disease recognition, and neoplastic progression. Fucosylated oligosaccharide ligands mediate cell-cell adhesion through binding to cell-surface selectins (calcium-dependent binding proteins) and calcium-dependent interactions with other cell-surface carbohydrate counterligands. A number of fucose-containing "natural ligands" are common to inflammatory and malignant cell processes. We review evidence that alpha-L-fucose is critically important for cell-cell and cell-matrix adhesion in a variety of normal and pathologic processes, particularly neoplasia. Current results suggest that alpha-L-fucose provides the essential structure that enables carbohydrate ligands to bind to selectins and to carbohydrate counterligands and thereby alter cellular homeostasis.

Gadolinium-enhanced MR imaging of renal masses.

Preliminary reports indicate that gadolinium-enhanced magnetic resonance (MR) imaging is highly accurate for diagnosis of renal masses. The authors demonstrate the clinical utility of MR imaging for evaluating renal masses in 26 patients for whom contrast material-enhanced computed tomography (CT) was contraindicated or inadequate for diagnosis or staging. Nine patients had complex cysts, one had a perinephric hematoma, and 16 had a solid mass (three of which were benign). All patients underwent MR imaging before and after administration of gadopentetate dimeglumine. Multiple imaging techniques and sequences were used. All tumors and no cysts enhanced with gadolinium. Even though the three benign tumors enhanced, two were differentiated from renal carcinoma on the basis of other imaging features. Unenhanced MR imaging was accurate in staging of renal carcinomas, and use of gadolinium did not improve staging accuracy. Gadolinium-enhanced MR imaging is indicated when results of CT and sonography are indeterminate for malignancy and when contrast-enhanced CT is contraindicated because of renal failure or adverse reaction to iodinated contrast material. In this latter instance, MR imaging is useful for both diagnosis and staging.

Magnetic resonance imaging using a ribbonator: hand and wrist.

A modified version of a single-turn solenoid with rectangular symmetry, which we call a ribbonator, provides excellent magnetic resonance images of the hand and wrist when used as both the transmitter and the receiver in a 1.5-T clinical imaging system. The very high RF efficiency provides excellent signal-to-noise and anatomical resolution. Design equations and RF properties of the resonator are discussed.

Gastrointestinal contrast agents: a diamagnetic approach.

The clay minerals kaolin and bentonite are demonstrated as gastrointestinal contrast agents for MRI. Weak field dependence of the relaxation efficiency assures effectiveness of these agents at all field strengths in clinical use. These agents eliminate signals from their immediate environment and are not toxic.

Consistent unmasking of dopamine-induced dilation of the canine femoral vascular bed.

Dopamine (DA) produced dose-related vasodilation in the canine femoral vascular bed after the administration of two alpha adrenergic blocking agents, WR-149,024 (1,18-diamino-6,13-diaza-9,10-dithiaoctadecane) or yohimbine. DA-induced vasodilation unmasked by yohimbine was not antagonized by propranolol, pyrilamine and metiamide, hexamethonium or atropine, but was attenuated selectively by the DA antagonist, sulpiride. The R-enantiomer of sulpiride was more effective than the S-enantiomer in attenuating DA-induced dilation. Phenoxybenzamine produced moderate (apparently nonspecific) attenuation of vasodilator responses to DA. The weaker vascular DA agonist, N,N-di-n-propyl dopamine, was approximately 1/25 as potent as DA in eliciting femoral vasodilation after yohimbine treatment. These findings suggest that DA produces femoral vasodilation after WR-149,024 or yohimbine by activation of vascular DA receptors similar to those proposed to exist in the renal vascular bed.