Effective targeting of magnetic radioactive 90Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary in vitro and in vivo results

Magnetic biodegradable poly(lactic acid) microspheres that incorporate both magnetite and the beta-emitter 90Y were prepared. By applying a directional external magnetic field gradient in excess of 0.02 Tesla/cm across a 96-well plate containing neuroblastoma cells incubated with the 90Y magnetite loaded microspheres, the radiation dose to the cells could be enhanced or reduced relative to the dose from a uniform loading of the well with 90Y-DTPA. Using the MTT assay, cell survival was measured for the magnetic field directed from above (cell sparing) and from below (cell targeting) the well plate, resulting in 65 +/- 8% or 18 +/- 5% survival respectively. This method was then applied to an in vivo murine tumor model. The biodistribution of intraperitoneally injected magnetic radioactive microspheres, after 24 h in mice, showed that 73 +/- 32% of the radioactivity was found on the subcutaneous tumor that had a rare earth magnet fixed above it. In contrast, the tumor radioactivity with no attached magnet was 6 +/- 4%. Magnetically targeted radiopolymers such as 90Y-microspheres show great promise for regional or intracavitary radiotherapy.     

Participants' perceptions of a phase I colon cancer chemoprevention trial

To assess participants' perceptions of a phase I colon cancer chemoprevention trial using a calcium intervention, questionnaires were mailed to trial participants at the conclusion of the study. Responses to questionnaire items reported here include (1) perceived benefits and barriers of participation, (2) interest in participating in future trials, (3) willingness to pay trial expenses out of pocket, and (4) posttrial continuation of the calcium regimen. The study found that the most highly rated trial benefit was the perception of potential colon cancer prevention; the trial barrier reported to be the most troublesome was inappropriate or mistaken billing for study visits. Three fourths of the subjects expressed an interest in future trials of the same duration. For trials of longer duration, this percentage decreased to 66%. Approximately half did not object to participation in future trials involving placebos, and just over one third indicated that they would either definitely (8%) or probably (27%) have joined the calcium trial even if they had to pay some study expenses out of pocket. Over 90% indicated they would continue taking the calcium pills if calcium is shown to be effective. The level of perceived benefits was positively associated with reported interest in participating in future trials of the same and longer durations, and the level of reported difficulty with trial pills and procedures was inversely related to interest in future placebo-controlled trials. The results of this study, in conjunction with results of prospective studies of trial participation, may be applied in future chemoprevention trials to facilitate recruitment, reduce attrition, and promote positive trial experiences for participants by emphasizing frequently reported benefits and minimizing frequently reported barriers.     

Partial characterisation of human melanoma cell-derived factors that stimulate fibroblast glycosaminoglycan synthesis

Glycosaminoglycans (GAGs), and in particular hyaluronan, are known to play a role in tumour cell migration, invasion and metastasis. Conditioned medium from two human metastatic melanoma cell lines (Hs294T and C8161) shows potent fibroblast GAG-synthesis-stimulating activities which are active in fibroblast cultures derived from different anatomical sites. This ability is not specific to melanoma cells and is observed in several carcinoma cell lines. Initial characterisation studies have demonstrated that the GAG-stimulating activities in the medium conditioned with melanoma cells show a degree of heat and trypsin resistance. Fractionation of the conditioned medium with Amicon ultrafiltration membranes of various molecular weight cut-offs, ranging from 1 to 30 kD, resulted in a total loss of activity. Activity could be regained by recombination of the concentrated fraction with the filtrate, suggesting more than one factor to be involved in GAG stimulation, with a degree of interdependence between the individual fractions. The fraction greater than 30 kD and that less than 1 kD appear to contain the majority of the GAG-stimulating activity.     

Cancer-related issues for women

Tobacco and diet account for almost two-thirds of all cancer-related deaths and are among the most correctable risk factors. Up to 35% of cancer-related deaths could be avoided if appropriate screening measures were used. Research on the use of vaccines to treat or prevent cancer has intensified. Pharmacists can play a major role in women's health by acting as patient advocates, serving as referral sources, and recommending supportive care.     

Applicability of a continuum solvation model to the octanol water transfer: CFF91 based model for amino acids

A continuum hydration model based upon the atomic charges provided with the CFF91 force field [A. B. Schmidt and R. M. Fine (1994) Molecular Simulation, 13, 347-365] has been extended to the octanol-water transfer. The electrostatic component of the transfer free energy is calculated using the finite-difference solution to the Poisson-Boltzmann equation while the nonpolar contributions are assumed to be proportional to the solute-excluded volume in water. All atomic charges and radii besides the aromatic carbon radius are equal in both solvents. The octanol dielectric constant and the probe radius are the main fitting parameters defining the octanol phase. The model has been tested for 38 organic molecules related to the amino acid residues and generally provides a high accuracy. In particular, the mean unsigned error for N-acetyl amino acid amides is 0.5 kcal/mol.