Unlike the tocopherols, the tocotrienols, also members of the vitamin E family, have an unsaturated isoprenoid side chain. In contrast to extensive studies on tocopherol, very little is known about tocotrienol. Because the nuclear factor-B (NF-B) pathway has a central role in tumorigenesis, we investigated the effect of ␥-tocotrienol on the NF-B pathway. Although ␥-tocotrienol completely abolished tumor necrosis factor ␣ (TNF)-induced NF-B activation, a similar dose of ␥-tocopherol had no effect. Besides TNF, ␥-tocotrienol also abolished NF-B activation induced by phorbol myristate acetate, okadaic acid, lipopolysaccharide, cigarette smoke, interleukin-1␤, and epidermal growth factor. Constitutive NF-B activation expressed by certain tumor cells was also abrogated by ␥-tocotrienol. Reducing agent had no effect on the ␥-tocotrienol-

Objective This study tested the effectiveness of a brief, learner-centered, breaking bad news (BBN) communication skills training module using objective evaluation measures. Methods This randomized control study (N=66) compared intervention and control groups of students (n=28) and residents' (n=38) objective structured clinical examination (OSCE) performance of communication skills using Common Ground Assessment and Breaking Bad News measures. Results Follow-up performance scores of intervention group students improved significantly regarding BBN (colon cancer (CC), p=.007, r=-.47; breast cancer (BC), p=.003, r=-.53), attention to patient responses after BBN (CC, p < .001, r=-.74; BC, p=.001, r=-.65), and addressing feelings (BC, p=.006, r=-.48). At CC follow-up assessment, performance scores of intervention group residents improved significantly regarding BBN (p=.004, r=-.43), communication related to emotions (p=.034, r=-.30), determining patient's readiness to proceed after BBN and communication preferences (p=.041, r=-.28), active listening (p=011, r=-.37), addressing feelings (p<.001, r=-.65), and global interview performance (p=.001, r=-.51). Conclusion This brief BBN training module is an effective method of improving BBN communication skills among medical students and residents. Practice Implications Implementation of this brief individualized training module within health education programs could lead to improved communication skills and patient care.

Background: Tocopherols are lipid soluble antioxidants that exist as eight structurally different isoforms. The intake of γ-tocopherol is higher than α-tocopherol in the average US diet. The clinical results of the effects of vitamin E as a cancer preventive agent have been inconsistent. All published clinical trials with vitamin E have used α-tocopherol. Recent epidemiological, experimental and molecular studies suggest that γ-tocopherol may be a more potent chemopreventive form of vitamin E compared to the more-studied α-tocopherol. γ-Tocopherol exhibits differences in its ability to detoxify nitrogen dioxide, growth inhibitory effects on selected cancer cell lines, inhibition of neoplastic transformation in embryonic fibroblasts, and inhibition of cyclooxygenase-2 (COX-2) activity in macrophages and epithelial cells. Peroxisome proliferator activator receptor γ (PPARγ) is a promising molecular target for colon cancer prevention. Upregulation of PPARγ activity is anticarcinogenic through its effects on downstream genes that affect cellular proliferation and apoptosis. The thiazolidine class of drugs are powerful PPARγ ligands. Vitamin E has structural similarity to the thiazolidine, troglitazone. In this investigation, we tested the effects of both α and γ tocopherol on the expression of PPARγ mRNA and protein in SW 480 colon cancer cell lines.

BackgroundMediterranean societies, with diets rich in vitamin E isoforms, have a lower risk for colon cancer than those of northern Europe and the Americas. Vitamin E rich diets may neutralize free radicals generated by fecal bacteria in the gut and prevent DNA damage, but signal transduction activities can occur independent of the antioxidant function. The term vitamin E represents eight structurally related compounds, each differing in their potency and mechanisms of chemoprevention. The RRR-γ-tocopherol isoform is found primarily in the US diet, while RRR-α-tocopherol is highest in the plasma.MethodsThe effectiveness of RRR-α- and RRR-γ-tocopherol at inhibiting cell growth and inducing apoptosis in colon cancer cell lines with varying molecular characteristics (SW480, HCT-15, HCT-116 and HT-29) and primary colon cells (CCD-112CoN, nontransformed normal phenotype) was studied. Colon cells were treated with and without RRR-α- or RRR-γ-tocopherol using varying tocopherol concentrations and time intervals. Cell proliferation and apoptosis were measured using the trypan blue assay, annexin V staining, DNA laddering and caspase activation.ResultsTreatment with RRR-γ-tocopherol resulted in significant cell death for all cancer cell lines tested, while RRR-α-tocopherol did not. Further, RRR-γ-tocopherol treatment showed no cytotoxicity to normal colon cells CCD-112CoN at the highest concentration and time point tested. RRR-γ-tocopherol treatment resulted in cleavage of PARP, caspase 3, 7, and 8, but not caspase 9. Differences in the percentage cell death and apoptosis were observed in different cell lines suggesting that molecular differences in these cell lines may influence the ability of RRR-γ-tocopherol to induce cell death.ConclusionThis is the first study to demonstrate that multiple colon cancer cell lines containing varying genetic alterations will under go growth reduction and apoptosis in the presence of RRR-γ-tocopherol without damage to normal colon cells. The amount growth reduction was dependent upon the molecular signatures of the cell lines. Since RRR-γ-tocopherol is effective at inhibition of cell proliferation at both physiological and pharmacological concentrations dietary RRR-γ-tocopherol may be chemopreventive, while pharmacological concentrations of RRR-γ-tocopherol may aid chemotherapy without toxic effects to normal cells demonstrated by most chemotherapeutic agents.