Inhibition of colony formation in agarose of metastatic human breast carcinoma and melanoma cells by synthetic glycoamine analogs

We studied the influence of 10 synthetic glycoamine analogs on colony formation in 0.3 and 0.9% agarose by metastatic human breast carcinoma (MDA-MB-435) and melanoma (TXM-13) cells. Nine synthetic analogs significantly inhibited the colony formation in 0.9% agarose of MDA-MB-435 human breast carcinoma cells; five compounds caused a 73–83% reduction of colony formation. Seven synthetic glycoamines caused a significant inhibition of colony formation in 0.9% agarose by TXM-13 melanoma cells with the inhibitory effect ranging from 71 to 87%. The 50% inhibition (I₅₀) doses and relative activity rank of the compounds were similar for both breast carcinoma and melanoma cell lines. The murine B16 melanoma cell aggregation assay was employed to elucidate the potential mechanism(s) of the inhibitory activity of synthetic glycoamines. The relative activity ranks of the compounds based on the independently determined I₅₀ doses for both cell aggregation and clonogenic growth assays were very similar for the four most active synthetic analogs and clearly indicated the importance of hydrophobic amino acid in mediating the bioactivity of synthetic glycoamines. In both experimental systems (clonogenic growth in agarose and cell aggregation assay) the leading compound was N-(1-deoxy-d-fructos-1-y1)-d-leucine (Fru-d-Leu) and the least active analog was N-(1-deoxy-d-fructos-1-yl)-glycine (Fru-Gly). These results show that synthetic glycoamines may act by competing for specific carbohydrate-lectin interactions, particularly those involving -galactoside-specific lectins expressed on metastatic cells.     

Effect of natural allergen exposure during the grass pollen season on airways inflammatory cells and asthma symptoms.

BACKGROUND: Bronchial challenge with allergen causes a specific form of airways inflammation consisting of an influx of neutrophils, eosinophils, and T cells. Because the relevance of the challenge model to clinical asthma is uncertain, the cellular changes that occur in the lungs of asthmatic subjects during natural seasonal allergen exposure were investigated. METHODS: Seventeen grass pollen sensitive asthmatic subjects with previously reported seasonal exacerbations of asthma kept records of symptoms and underwent fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial biopsy before and during the peak of the grass pollen season. The BAL cells were analysed for differential cell counts and by flow cytometry for T cell subsets and surface activation markers. The biopsy samples were processed into glycol methacrylate resin and immunohistochemical analysis was performed for mast cells, activated eosinophils, T cells and interleukin 4 (IL-4), a cytokine with a pivotal role in allergen-induced inflammation. RESULTS: In the pollen season there was an increase in T lymphocyte activation in the BAL fluid as identified by increased expression of interleukin 2 receptor (IL-2R). In the submucosa these changes were paralleled by an increase in CD4+ T cells. By contrast, the numbers of metachromatic cells in BAL fluid staining with toluidine blue were reduced, possibly because of degranulation following allergen stimulation. In keeping with mast cell activation, the number of mucosal mast cells staining for secreted IL-4 increased during the season. In comparison with the period shortly before the onset of the season, all but two subjects experienced an asthma exacerbation which followed the rise in pollen counts but, compared with the period preceding the first bronchoscopic examination, asthma symptoms were not increased during the pollen season. CONCLUSIONS: The data suggest that natural allergen exposure, leading to a clinical exacerbation of asthma, may induce an inflammatory response involving T cells, mast cells and eosinophils. The relationship between allergen exposure, cellular infiltration and activation, and clinical symptoms appears to be complex, with factors other than allergen also contributing to asthmatic activity.     

Therapeutic ratio of photodynamic therapy in the treatment of superficial tumours of skin and subcutaneous tissues in man

Six patients with a total of 34 assessible subcutaneous or cutaneous lesions were treated with photodynamic therapy using 1.0, 1.5 or 2.0 mg kg-1 of photofrin II and 25-100 J cm-2 of red light (630 nm). The incidence of complete tumour response and skin necrosis were used to try to assess the therapeutic ratio of photodynamic therapy. The tumour response rate was 47%. The rate of tumour control and necrosis increased in parallel with dose of photosensitizer and light used, implying a low therapeutic ratio. However, the use of necrosis with eschar formation as an end-point for severe normal tissue damage is questioned as the skin healed completely in all cases and with minimal discomfort to the patients.     

Postmastectomy educational needs and social support

Due to shorter hospitalization periods and changes in surgical procedures, breast cancer patients have less inpatient contact with rehabilitation resources. A questionnaire related to educational needs and social support was mailed statewide to 2,000 postmastectomy women who had received a Reach to Recovery visit. The findings are based on quantitative data reported by 933 women and from 27 women in follow-up interviews. Respondents ranked their educational needs in six categories from greatest to least importance as follows: (1) information about breast cancer, (2/3) personal hygiene/exercise and nutrition/weight control (both ranked of equal importance), (4) prosthesis/clothing information, (5) social support, and (6) sexual issues. Performance on the knowledge assessment correlated directly with the amount of educational experience and inversely with age. Respondents who lived in communities of less than 2,500 were less informed than those from other locations. Participation in formalized support groups was infrequent (11%). The major source of information was the media, with 88% indicating they would watch television programs about breast cancer. Thirty-three percent of the respondents indicated they owned a video cassette recorder (VCR); about 93% said VCRs were available for rent in their community. Work associates were identified as a group that encouraged information seeking; health care professionals were the most successful in motivating women to participate in support groups.     

Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study

There is a growing body of evidence which suggests that macular pigment (MP), which is entirely of dietary origin, protects against age-related maculopathy. We evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free lutein) supplement in patients with early age-related maculopathy (ARM), in terms of macular pigment optical density (MPOD) and plasma concentrations of lutein. MPOD was measured using a flicker photometric technique in seven ARM sufferers and six age-matched controls over a period of supplementation which lasted 18-20 weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182 (127)ng ml(-1) to a peak of 1077 (165)ng ml(-1) in ARM patients, and from 152 (57) to 1110 (605)ng ml(-1) in control subjects. Mean MPOD had increased significantly from baseline of 0.24 to a peak of 0.31 in ARM sufferers. This mean increment of 0.07 was the same for the age-matched controls (baseline: 0.20; peak: 0.27). The augmentation of MP, and plasma concentrations of lutein, following supplementation in subjects with ARM provides the first evidence the disease is not associated with intestinal malabsorption of the relevant macular carotenoids, and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects of lutein supplementation, if any, may be extended to subjects with established ARM.     

Perceptions of postmastectomy patients. Part II. Social support and attitudes towards mastectomy

To measure the relationships among social support, attitudes toward mastectomy, and self-esteem in women postmastectomy, the Mastectomy Attitude Scale (MAS), the Norbeck Social Support Questionnaire (NSSQ), and Rosenberg's Self-Esteem Scale (RSE) were used. A factor analysis of the MAS yielded six factors that were used in regression analyses. Stepwise regression was used to identify variables that significantly contributed to women's self-esteem. Covariates in the analyses were age, years of education, marital status, and adjuvant chemotherapy. The women (n = 456) averaged 54 years in age, had slightly more than a high school education (mean = 13.0 years), and were predominately married (80%); almost half had adjuvant chemotherapy (45.6%). The overall regression model was significantly (df = 16,440; F = 15.12, p less than 0.0001) and accounted for 35.5% of the variance. Seven of the 16 variables were significant accounting for the following percentages of variance: sexuality, 21.1%; outlook, 5.8%, appearance satisfaction, 3.1%; emotions, 1.3%; college education, 1.2%; adjuvant chemotherapy, 0.6%; and age (60-69), 0.6%. Thus, women's attitudes toward mastectomy accounted for a greater proportion of the variance in their self-esteem than did social support and other demographic variables.     

Staff consultation. Quite unheard of

Therapists consulted over the national plan in one trust expressed the need for recognition that the NHS was more than nurses and doctors. They proposed the introduction of consultant therapist posts to allow them to take on some of the work of doctors. They thought therapists were underrepresented in the top jobs. Most felt they were working at maximum capacity and that increasing productivity would be difficult.