Processes that Inform Multicultural Supervision: A Qualitative Meta-Analysis.

As the fields of counseling and psychotherapy have become more cognizant that individuals, couples, and families bring with them a myriad of diversity factors into therapy, multicultural competency has also become a crucial component in the development of clinicians during clinical supervision and training. We employed a qualitative meta-analysis to provide a detailed and comprehensive description of similar themes identified in primary qualitative studies that have investigated supervisory practices with an emphasis on diversity. Findings revealed six meta-categories, namely: (a) Supervisor's Multicultural Stances; (b) Supervisee's Multicultural Encounters; (c) Competency-Based Content in Supervision; (d) Processes Surrounding Multicultural Supervision; (e) Culturally Attuned Interventions; and (f) Multicultural Supervisory Alliance. Implications for practice are discussed.

Development and characteristics of a human cell assay for screening agents for melanoma prevention.

This paper describes the development and initial evaluation of a human cell assay to identify potentially efficacious agents for preventing melanoma. Four human cell lines were used: normal melanocytes, a radial growth-phase-like melanoma cell line (WM3211), a vertical growth-phase-like melanoma cell line (Lu1205), and 83-2c, a cell strain cloned from metastatic melanoma. Four endpoints were evaluated in ultraviolet B-treated cells: annexin V, human leukocyte antigen-DR; E-cadherin, and N-cadherin. Annexin V was induced by nimesulide, 4-hydroxyphenylretinamide, and difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. None of the agents inhibited human leukocyte antigen-DR expression in ultraviolet-B-treated radial growth-phase-like melanoma cells, the only cells that strongly expressed human leukocyte antigen-DR. E-cadherin was overexpressed only in radial growth-phase-like melanoma cells relative to melanocytes, and ultraviolet B exposure dramatically reduced this expression. E-cadherin was only induced by difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. N-cadherin was over- expressed in all melanoma cell lines relative to melanocytes. In this study, all candidate preventive agents inhibited N-cadherin in ultraviolet B-treated radial growth-phase-like melanoma cells. Four agents inhibited N-cadherin in ultraviolet B-treated vertical growth-phase-like melanoma cells. The mean ratios of N-cadherin to E-cadherin levels and specific endpoint responses for both the radial growth-phase-like melanoma and vertical growth-phase-like melanoma cells were used to rank the agents. Agents were evaluated at clinically relevant concentrations. The rankings were difluoromethylornithine>4-hydroxyphenylretinamide>nimesulide>9-cis-retinoic acid>polyphenon E. Diphenylhydramine, D-mannitol, and nordihydroguaiaretic acid were inactive. The results of these initial studies suggest that ultraviolet-B-treated radial growth-phase-like melanoma cells are the most responsive to chemopreventive agents, and may be the cell line of choice for screening melanoma prevention agents.

Melanin as a target for melanoma chemotherapy: pro-oxidant effect of oxygen and metals on melanoma viability.

Melanoma cells have a poor ability to mediate oxidative stress, which may be attributed to constitutive abnormalities in their melanosomes. We hypothesize that disorganization of the melanosomes will allow chemical targeting of the melanin within. Chemical studies show that under oxidative conditions, synthetic melanins demonstrate increased metal affinity and a susceptibility to redox cycling with oxygen to form reactive oxygen species. The electron paramagnetic resonance (EPR)-active 5,5'-dimethyl-pyrollidine N-oxide spin adduct was used to show that binding of divalent Zn or Cu to melanin induces a pro-oxidant response under oxygen, generating superoxide and hydroxyl radicals. A similar pro-oxidant behaviour is seen in melanoma cell lines under external peroxide stress. Melanoma cultures grown under 95% O2/5% CO2 atmospheres show markedly reduced viability as compared with normal melanocytes. Cu- and Zn-dithiocarbamate complexes, which induce passive uptake of the metal ions into cells, show significant antimelanoma activity. The antimelanoma effect of metal- and oxygen-induced stress appears additive rather than synergistic; both treatments are shown to be significantly less toxic to melanocytes.

Disulfiram induces apoptosis in human melanoma cells: a redox-related process.

Melanoma is highly resistant to conventional chemotherapy. We have demonstrated that redox regulation in melanoma cells is aberrant, and redox-modulating agents can induce cell apoptosis. We have currently explored the effect of disulfiram (DSF), a member of the dithiocarbamate family, on apoptosis of melanoma cells in vitro. Human metastatic melanoma cells c81-46A, c81-61, and c83-2C were treated with DSF and apoptosis measured. DSF, at a dose of 25-50 ng/ml, consistently caused a 4-6-fold increase in apoptosis. The same dose of DSF did not significantly affect apoptosis in melanocytes. Coincubation of N-acetyl-cysteine reversed the DSF-induced apoptosis. Buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl-cysteine synthetase, as a single agent caused a approximately 2-fold increase in apoptosis when incubated with melanoma cells for 4 days. BSO slightly enhanced the level of apoptosis induced by DSF (4-10% higher than DSF alone). Intracellular glutathione was remarkably depleted with BSO treatment. DSF did not cause glutathione depletion; however, the ratio of reduced and oxidized glutathione was significantly decreased (14% of control), and N-acetyl-cysteine partially restored the ratio to 30% of control. There was a transient (2-fold) elevation of intracellular superoxide level after 24 h of DSF treatment (before the overt apoptosis). The intracellular H2O2 level progressively decreased with time. DSF decreased the mitochondrial membrane polarization in a time-dependent manner, and there was a significant inverse correlation between apoptosis and mitochondrial membrane polarization. We propose that DSF-induced apoptosis is redox related but involves a different mechanism from BSO-induced apoptosis in tumor cells. Our findings have provided new data for additional understanding of drug-induced apoptosis in melanoma cells and suggests an alternative therapeutic approach to melanoma.