Citations

AbstractThe underlying mechanisms by which tumor cells are resistant to CTL-mediated apoptosis are not clear. Using a human model of B-cell non-Hodgkin's lymphoma (B-cell NHL), we show that intratumoral Treg cells inhibit the proliferation and granule production of activated autologous infiltrating CD8+ T cells. Our results also show that degranulation and subsequent cytotoxic activity of infiltrating CD8+ T cells exposed to lymphoma B cells is completely attenuated by the presence of intratumoral Treg cells. Furthermore, we show that increased numbers of intratumoral Treg cells correlates with the number of CD8+ T cells in biopsy specimens from patients with B-cell NHL, supporting the in vitro findings that intratumoral Treg cells inhibit proliferation of infiltrating CD8+ T cells. Taken together, these data indicate that human lymphoma B cells are sensitive to autologous CTL-mediated cell death but are protected by the inhibitory function of intratumoral Treg cells. (Cancer Res 2006; 66(20): 10145-52)

AbstractThere is increasing evidence that vitamin D may protect against breast cancer. Some studies have suggested that dietary and supplemental vitamin D is associated with reduced mammographic density, which is highly associated with breast cancer risk, although this evidence is not entirely consistent. We investigated a possible association between circulating 25-hydroxyvitamin D (25OHD), the best indicator of vitamin D status, and quantitative mammographic density in the Minnesota Breast Cancer Family Study. Mean values of mammographic density (both percent and area densities) and circulating levels of 25OHD were compared across categories of covariates using ANOVA. Models were adjusted for age and body mass index, as well as other covariates, and also stratified by dietary calcium intake, menopause, and season. Serum, mammographic density, and questionnaire data were available from 487 women [133 premenopausal and 354 postmenopausal; mean age, 56.4 years (range, 27-85 years)] without breast cancer, and for 73%, the blood was drawn within 1 year of their mammogram. No evidence was found for an association between 25OHD and either percent density or total dense area. There was also no evidence for any association when the data were stratified by season of sample (winter and summer) or menopause. However, both percent density and dense area were lowest among those in the highest vitamin D quartile with calcium intake above the median. Unlike some previous reports, vitamin D does not seem to be related to mammographic density in this cohort. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1988–92)

In seven strains of cultured normal human osteoblast-like cells, a mean of 1615 molecules of tritium-labeled 17β-estradiol per cell nucleus could be bound to specific nuclear sites. The nuclear binding of the labeled steroid was temperature-dependent, steroid-specific, saturable, and cell type-specific. These are characteristics of biologically active estrogen receptors. Pretreatment with 10 nanomolar estradiol in vitro increased the specific nuclear binding of progesterone in four of six cell strains, indicating an induction of functional progesterone receptors. RNA blot analysis demonstrated the presence of messenger RNA for the human estrogen receptor. The data suggest that estrogen acts directly on human bone cells through a classical estrogen receptor-mediated mechanism.

A single intrathecal injection of capsaicin depletes substance P from primary sensory neurons and causes a prolonged increase in the thermal and chemical pain thresholds of the rat but no apparent change in responses to noxious mechanical stimuli.

Evidence from several model systems suggests that nonhistone chromosomal proteins may regulate gene expression in eukaryotic cells. The data indicate that the synthesis of new species of nonhistone chromosomal proteins as well as modifications of preexisting nonhistone chromosomal proteins are involved in the control of transcription. However, from the vast number of proteins included in this class, it is apparent that, in addition to regulating the transcription of defined genome loci, the nonhistone chromosomal proteins include enzymes that have a general function, proteins that are involved in determining the structure of chromatin, as well as proteins that serve as recognition sites for binding of regulatory macromolecules. The presence of a nucleoplasmic pool of nonhistone chromosomal proteins which may exchange with the chromatin has also been reported ( 89 ). While it is clear that the nonhistone chromosomal proteins play a key role in the regulation of gene expression, the exact manner in which they interact with the genome to initiate, modify, or augment the transcription of specific RNA molecules remains to be resolved.