End-of-life care at a community cancer center.

PURPOSE: The evidence-based use of resources for cancer care at end of life (EOL) has the potential to relieve suffering, reduce health care costs, and extend life. Internal benchmarks need to be established within communities to achieve these goals. The purpose for this study was to evaluate data within our community to determine our EOL cancer practices. METHODS: A random sample of 390 patients was obtained from the 942 cancer deaths in Wicomico County, Maryland, for calendar years 2004 to 2008. General demographic, clinical event, and survival data were obtained from that sample using cancer registry and hospice databases as well as manual medical record reviews. In addition, the intensity of EOL cancer care was assessed using previously proposed indicator benchmarks. The significance of potential relationships between variables was explored using χ(2) analyses. RESULTS: Mean age at death was 70 years; 52% of patients were male; 34% died as a result of lung cancer. Median survival from diagnosis to death was 8.4 months with hospice admission and 5.8 months without hospice (P = .11). Four of eight intensity-of-care indicators (ie, intensive care unit [ICU] admission within last month of life, > one hospitalization within last month of life, hospital death, and hospice referral < 3 days before death) all significantly exceeded the referenced benchmarks. Hospice versus nonhospice admissions were associated (P < .001) with ICU admissions (2% v 13%) and hospital deaths (2% v 54%). CONCLUSION: These data suggest opportunities to improve community cancer center EOL care.

Induction of growth arrest and apoptosis in human breast cancer cells by 3,3-diindolylmethane is associated with induction and nuclear localization of p27kip.

3,3'-Diindolylmethane (DIM) is a stable condensation product of indole-3-carbanol, a potential breast cancer chemoprevention agent. Human breast cancer cell lines were studied to better understand its mechanisms. In vitro experiments were done in MCF-7, T47D, BT-20 and BT-474 cells using MTT, ELISA, immunoblotting assays, reverse transcription-PCR, protein half-life, confocal microscopy, cell fractionation, and immunoprecipitation assays. We found that DIM inhibited the growth of all four breast cancer cell lines (IC(50)s, 25-56 micromol/L). Because BT-20 and BT-474 overexpressed Her-2 and activated Akt, and BT-20 lacks estrogen receptor, these were studied further. In both cell lines, DIM appeared to induce expression of p27(kip) protein before the loss of cell viability and apoptosis. In BT-20 cells, DIM also inhibited expression of activated Akt, but this appeared after p27(kip) induction. In both cell lines, DIM induced p27(kip) transcript expression within 6 h. DIM prolonged the p27(kip) protein half-life in BT-20 but not BT-474 cells. We also showed, for the first time, that DIM induced nuclear localization of p27(kip) in both cell lines. Moreover, in BT-20 cells, DIM induced a decrease in p27(kip) phosphorylation at Thr(187), and its association with the 14-3-3 protein, which helped to explain the protein half-life increase and nuclear localization, respectively. DIM modulates p27(kip) through transcription, prolongation of protein half-life, and nuclear localization. These effects appear to be independent of Her-2, Akt, or estrogen receptor status and should support further study for its chemoprevention potential in breast cancer.

Novel perspective: focusing on the X chromosome in reproductive cancers.

In an XX female, one of the two X chromosomes has been inactivated during early embryonic life to achieve a compensation of X-linked gene products between males and females, leaving only one allele of X-linked genes functional. There are some X-linked genes escaping the X-inactivation, i.e., being expressed from both alleles. Escape from X-inactivation varies at different levels; some genes have both alleles active in some women but only one allele active in others, whereas some other genes have both alleles active in neoplastic tissue but only one allele active normally. The X-inactivation may be considered functionally equivalent to a loss of heterozygosity (LOH) for some genes, whereas escape from X-inactivation may be equivalent to functional gene amplification for others. The physiological LOH may make X-linked tumor suppressor genes lose their function more easily, compared with autosomal tumor suppressor genes, thus predisposing women to cancer formation more easily. Moreover, the human X chromosome contains many genes related to cancer or to sex and reproduction. All these properties of the X chromosome suggest that it may play more important roles than any autosomal chromosome in the development and progression of reproductive and urologic cancers.

Episomally mediated overexpression of wild-type erbB-2 transforms MCF-10A breast epithelial cells.

MCF-10A are human non-transformed, EGF and insulin dependent breast epithelial cells. The cells were transfected with an episomal pCEP4 vector library containing cDNA from SKBR3 breast carcinoma cells, and selected in media without EGF. After two cycles of expression cloning, morphologically transformed cells appeared. Extracted episomes contained a high proportion of erbB-2 cDNA with wild-type transmembrane domains. Transfection of MCF-10A with individual erbB-2 containing episomes induced significant foci formation in low serum (0.1%) without EGF. MCF-10A sublines expanded from these foci contained a high number of erbB-2 gene copies, highly expressed erbB-2, and lost E-cadherin expression. These results show that if wild-type erbB-2 is sufficiently overexpressed, erbB-2 alone can cause EGF independent transformation of these nonmalignant breast cells. This expression system may be useful for expression cloning in MCF-10A cells, and simulating the effects of high erbB-2 gene amplification in breast epithelial cells.