What causes patients with breast cancer to change employment?: evidence from the health insurance data in a medical facility.

This study aims to make clear the following aspects of breast cancer patients and their occupation. 1. What percentage of patients have changed their working status around surgery? 2. When did patients change their employment? 3. What is the cause of the employment change? We investigated 269 patients who underwent curative surgery for primary breast cancer at one university hospital in Tokyo. Patients who were under the age of 58 at the time of surgery and had the experience of being a company or government employee during a year prior to the surgery were used as sample for analysis. To determine factors related to the employment change, multiple logistic regression analysis was performed. Nineteen percent patients changed the employment status before and after surgery. Of those, 19% changed the employment by the end of surgery month while 42% did by the fourth month after surgery. Treatment-related factors such as mastectomy and the combination of chemotherapy and hormone therapy affected changes in employment. We believe that the validity of our study can be confirmed by comparing with the previous study results. We show the potential large effects of cancer treatment on patients' daily lives.

Activity of ERK regulates mucin 3 expression and is involved in undifferentiated Caco-2 cell death induced by 3-oxo-C12-homoserine lactone.

The signal molecule, 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), is similar to a mammalian hormone in bacteria. Although most studies have examined the effects of high 3-oxo-C12-HSL concentrations (>200 µM) on mammalian cellular functions because ~600 µM 3-oxo-C12-HSL can be secreted in biofilms of Pseudomonas aeruginosa grown in vitro, we previously showed that a low 3-oxo-C12-HSL concentration (30 µM) induces the apoptosis of undifferentiated Caco-2 cells through suppressing Akt activity. Here, we found that a low concentration of 3-oxo-C12-HSL-activated ERK1/2 in undifferentiated Caco-2 cells. Incubating cells with the ERK pathway inhibitor U0126 for 30 min alleviated the mucin 3 (MUC3) expression suppressed by 3-oxo-C12-HSL, and the upregulation of MUC3 expression induced by a 48-h incubation with U0126-reduced cell death. Thus, altered MUC3 expression caused by long-term attenuated ERK1/2 activity might correlate with the death of undifferentiated Caco-2 cells induced by 3-oxo-C12-HSL.

Mucin 3 is involved in intestinal epithelial cell apoptosis via N-(3-oxododecanoyl)-L-homoserine lactone-induced suppression of Akt phosphorylation.

N-acyl-homoserine lactones (AHL) are quorum-sensing molecules in bacteria that play important roles in regulating virulence gene expression in pathogens such as Pseudomonas aeruginosa. The present study compared responses between undifferentiated and differentiated Caco-2 cells to N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL). A low concentration of 3-oxo-C12-HSL (30 µM) is sufficient to reduce viability accompanied by apoptosis via the suppression of phosphorylation by Akt in undifferentiated Caco-2 cells. The suppression of Akt phosphorylation appears specific in 3-oxo-C12-HSL, because other AHLs did not influence the phosphorylation status of Akt. The reduced viability induced by 3-oxo-C12-HSL was partially recovered by constitutively active Akt overexpression in undifferentiated Caco-2 cells. Since mucin is considered a vital component of the gut barrier, we investigated whether mucin protects cellular functions induced by 3-oxo-C12-HSL in undifferentiated Caco-2 cells. The results showed that mucin protected undifferentiated Caco-2 cells from apoptosis induced by 3-oxo-C12-HSL. 3-Oxo-C12-HSL did not induce cell death in differentiated Caco-2 cells that expressed higher levels of mucin 3 (MUC3) than undifferentiated Caco-2 cells. In addition, 3-oxo-C12-HSL promoted cell death in undifferentiated Caco-2 cells transfected with MUC3 siRNA and reduced MUC3 expression in undifferentiated Caco-2 cells. Therefore, MUC3 might be responsible for the survival of undifferentiated intestinal epithelial cells in the presence of 3-oxo-C12-HSL through regulating Akt phosphorylation. In conclusion, 3-oxo-C12-HSL might influence the survival of undifferentiated intestinal epithelial cells as well as interactions between these cells and pathogens.

Unsaturated FAs prevent palmitate-induced LOX-1 induction via inhibition of ER stress in macrophages.

Palmitic acid (PA) upregulates oxidized LDL receptor-1 (LOX-1), a scavenger receptor responsible for uptake of oxidized LDL (oxLDL), and enhances oxLDL uptake in macrophages. However, the precise underlying mechanism remains to be elucidated. PA is known to induce endoplasmic reticulum (ER) stress in various cell types. Therefore, we investigated whether ER stress is involved in PA-induced LOX-1 upregulation. PA induced ER stress, as determined by phosphorylation of PERK, eIF2α, and JNK, as well as induction of CHOP in macrophage-like THP-1 cells. Inhibitors [4-phenylbutyric acid (PBA), sodium tauroursodeoxycholate (TUDCA), and salubrinal] and small interfering RNA (siRNA) for the ER stress response decreased PA-induced LOX-1 upregulation. Thapsigargin, an ER stress inducer, upregulated LOX-1, which was decreased by PBA and TUDCA. We next examined whether unsaturated FAs could counteract the effect of PA. Both oleic acid (OA) and linoleic acid (LA) suppressed PA-induced LOX-1. Activation of the ER stress response observed in the PA-treated cells was markedly attenuated when the cells were cotreated with OA or LA. In addition, OA and LA suppressed thapsigargin-induced LOX-1 upregulation with reduced activation of ER stress markers. Our results indicate that activation of ER stress is involved in PA-induced LOX-1 upregulation in macrophages, and that OA and LA inhibit LOX-1 induction through suppression of ER stress.

[Eliciting preferences for mammography: using a discrete choice experiment approach].

OBJECTIVE: The consultation rate in Japan for mammography screening for breast cancer continues to drop. In order to examine this issue based on demand for mammography, the present study was conducted using Discrete Choice Experiments (DCEs), a type of Stated Preference (SP) method. The objectives of this study were as follows: (1) To consider what attributes of mammography screening are being potentially evaluated by general recipients in the target age group; (2) To verify the validity of the SP method by separating the sample group into sub-groups of previous mammography recipients and non-recipients, and to compare their findings; (3) To predict selection behavior by setting scenarios for screening options possibly in demand in the future. METHODS: 800 subjects aged between 40 to 59 years and with no history of breast cancer were randomly selected from the general population of Tokyo. A DCE was conducted using postal self-administered survey forms. A total of 301 survey responses were obtained. Subjects were presented with a pair of hypothetical screenings, including 5 attributes regarding mammography screening, and asked which screening they would prefer to receive. For the entire sample and sub-groups, estimations for parameters were made using the conditional logit model setting the screening attributes as independent variables and the selection of whether or not to receive each screening as a dependent variable. Based on these results, short-time/high-cost and long-time/low-cost screening options were set and selection behavior was predicted. RESULTS: The five attributes regarding mammography screening for all samples--total amount of time taken for the screening; degree of breast pain; possibility of breast cancer being missed during the screening; the effectiveness of reducing deaths caused by breast cancer; and the total cost required for the screening--were each estimated to be significant at the 5% level with coefficient signs consistent with expectations for the entire sample group. Next, comparing the estimated results of the sub-groups, a positive correlation was confirmed between behavior and preference. As for forecast of selection behavior, the percentage of respondents choosing the short-time option was predicted to be the same or higher than for those choosing long-time/low-cost option when the short-time option was offered for Yen 7500 or less. CONCLUSION: This study shows that subjects place significant value on attributes regarding the screening process as well as actual health outcomes. It also suggests the validity of using the SP methods in examining screening preferences. We found that short-time screening was able to compete against long-time/low-cost screening when it was offered for Yen 7500 or less. These results suggest that offering mammography screening with favorable settings could increase the demand.

Palmitic acid enhances lectin-like oxidized LDL receptor (LOX-1) expression and promotes uptake of oxidized LDL in macrophage cells.

OBJECTIVE: Elevated levels of nonesterified fatty acids (NEFA) in obesity and type 2 diabetes may contribute to the development of atherosclerosis. Therefore, we examined whether NEFA could regulate expression of scavenger receptors responsible for uptake of oxidized LDL (oxLDL) in macrophages, a critical step in atherogenesis. METHODS AND RESULTS: Expression level of scavenger receptors in NEFA-treated macrophage-like THP-1 and Raw264.7 cells were analyzed by real-time PCR. Palmitic acid showed the greatest enhancement of expression of lectin-like oxidized LDL receptor (LOX-1) among 7 NEFA examined (4 saturated and 3 unsaturated fatty acids). Upregulation of LOX-1 was selective as increases in expression level of other scavenger receptors (CD36, SR-AI, SR-BI, and CD68) were not observed. Western blotting analysis indicated that upregulation of LOX-1 also occurred at the protein level. Uptake of oxLDL by Raw264.7 cells was promoted by palmitic acid, and the enhanced uptake was abrogated when the cells were transfected with siRNA against LOX-1. Downregulation of Toll-like receptor (TLR) 2, TLR4, or IRAK4 with siRNA did not prevent LOX-1 upregulation, whereas inhibitors of p38 MAPK (p38) and reactive oxygen species (ROS) signal inhibited the upregulation of LOX-1 induced by palmitic acid. CONCLUSIONS: These results suggest that elevated level of palmitic acid may contribute to development of atherosclerosis through enhanced uptake of oxLDL via upregulation of LOX-1 in macrophages. The effects of palmitic acid may be mediated by ROS-p38 pathway rather than TLRs.