Differences in clinicopathologic features and subtype distribution of invasive breast cancer between women older and younger than 40 years

OBJECTIVES: We investigated and compared clinicopathologic features and subtype distribution of invasive breast cancer among women <40 and ≥40 years of age. METHODS: We retrospectively compared clinicopathologic characteristics and subtype distribution of invasive breast cancer in women <40 and ≥40 years of age, in a cohort of 1,130 patients. Subtypes included luminal A (positive for hormone receptors [HR]—estrogen receptor [ER] and/or progesterone receptor [PR]—and negative for human epidermal growth factor receptor 2 [HER2] with low Ki67), luminal B (HER2(–)) (HR(+)/HER2(–)/Ki67(High)), luminal B (HER2(+)) (HR(+)/HER2(+)), HER2-overexpressing (HR(–)/HER2(+)), and triple negative (ER(–)/PR(–)/HER2(–)). RESULTS: Breast cancers in younger women had unfavorable clinicopathologic characteristics, including larger tumors and more frequent node involvement. Subtypes among the 1,130 tumors were luminal A: 36.4%, luminal B (HER2(–)): 35.0%, luminal B (HER2(+)): 7.5%, HER2-overexpressing: 7.1%, and triple negative: 14.0%. The age groups significantly differed in subtype distribution (P<0.001). Luminal A subtype was more common in the older group (38.5%) than the younger group (16.2%), and luminal B (HER2(–)) was more common in the younger group (52.2%) than in the older group (33.2%; P<0.001). CONCLUSIONS: Breast cancers in women younger than 40 years have unfavorable clinicopathologic characteristics and are more likely to be luminal B (HER2(–)) and less likely to be luminal A than breast cancers in older women

Association of exposure level to passive smoking with hypertension among lifetime nonsmokers in Japan : a cross-sectional study

Brief exposure to passive smoking immediately elevates blood pressure. However, little is known about the association between exposure to passive smoking and chronic hypertension. We aimed to examine this association in a cross-sectional study, after controlling multiple potential confounders. Participants included 32,098 lifetime nonsmokers (7,216 men and 24,882 women) enrolled in the Japan Multi-Institutional Collaborative Cohort Study. Passive smoking was assessed using a self-administered questionnaire. The single question about exposure to passive smoking had five response options: “sometimes or almost never,” “almost every day, 2 hours/day or less,” “almost every day, 2 to 4 hours/day,” “almost every day, 4 to 6 hours/day,” and “almost every day, 6 hours/day or longer.” Hypertension was defined as any of the following: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were estimated by exposure level to passive smoking using unconditional logistic regression models. The multivariate-adjusted OR for hypertension in those exposed almost every day was 1.11 (95% CI: 1.03–1.20) compared with those exposed sometimes or almost never. The OR for a 1-hour per day increase in exposure was 1.03 (95% CI: 1.01–1.06, P for trend = .006). This association was stronger in men than in women; the ORs were 1.08 (95% CI: 1.01–1.15, P for trend = .036) and 1.03 (95% CI: 1.00–1.05, P for trend = .055), respectively. Our findings suggest importance of tobacco smoke control for preventing hypertension

Seismicity controlled by resistivity structure : the 2016 Kumamoto earthquakes, Kyushu Island, Japan

The M JMA 7.3 Kumamoto earthquake that occurred at 1:25 JST on April 16, 2016, not only triggered aftershocks in the vicinity of the epicenter, but also triggered earthquakes that were 50–100 km away from the epicenter of the main shock. The active seismicity can be divided into three regions: (1) the vicinity of the main faults, (2) the northern region of Aso volcano (50 km northeast of the mainshock epicenter), and (3) the regions around three volcanoes, Yufu, Tsurumi, and Garan (100 km northeast of the mainshock epicenter). Notably, the zones between these regions are distinctively seismically inactive. The electric resistivity structure estimated from one-dimensional analysis of the 247 broadband (0.005–3000 s) magnetotelluric and telluric observation sites clearly shows that the earthquakes occurred in resistive regions adjacent to conductive zones or resistive-conductive transition zones. In contrast, seismicity is quite low in electrically conductive zones, which are interpreted as regions of connected fluids. We suggest that the series of the earthquakes was induced by a local accumulated stress and/or fluid supply from conductive zones. Because the relationship between the earthquakes and the resistivity structure is consistent with previous studies, seismic hazard assessment generally can be improved by taking into account the resistivity structure. Following on from the 2016 Kumamoto earthquake series, we suggest that there are two zones that have a relatively high potential of earthquake generation along the western extension of the MTL

Detection of Progeny Immune Responses after Intravenous Administration of DNA Vaccine to Pregnant Mice

A number of factors influence the development of tolerance, including the nature, concentration and mode of antigen presentation to the immune system, as well as the age of the host. The studies were conducted to determine whether immunizing pregnant mice with liposome-encapsulated DNA vaccines had an effect on the immune status of their offspring. Two different plasmids (encoding antigens from HIV-1 and influenza virus) were administered intravenously to pregnant mice. At 9.5 days post conception with cationic liposomes, injected plasmid was present in the tissues of the fetus, consistent with trans-placental transfer. When the offspring of vaccinated dams were immunized with DNA vaccine, they mounted stronger antigen-specific immune responses than controls and were protected against challenge by homologous influenza virus after vaccination. Moreover, such immune responses were strong in the offspring of mothers injected with DNA plasmid 9.5 days after coitus. These results suggest that DNA vaccinated mothers confer the antigen-specific immunity to their progeny. Here we describe the methods in detail as they relate to our previously published work

Green Tea Polyphenol EGCG Sensing Motif on the 67-kDa Laminin Receptor

BACKGROUND: We previously identified the 67-kDa laminin receptor (67LR) as the cell-surface receptor conferring the major green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) responsiveness to cancer cells. However, the underlying mechanism for interaction between EGCG and 67LR remains unclear. In this study, we investigated the possible role of EGCG-67LR interaction responsible for its bioactivities. METHODOLOGY/PRINCIPAL FINDINGS: We synthesized various peptides deduced from the extracellular domain corresponding to the 102-295 region of human 67LR encoding a 295-amino acid. The neutralizing activity of these peptides toward EGCG cell-surface binding and inhibition of cancer cell growth were assayed. Both activities were inhibited by a peptide containing the 10-amino acid residues, IPCNNKGAHS, corresponding to residues 161-170. Furthermore, mass spectrometric analysis revealed the formation of a EGCG-LR161-170 peptide complex. A study of the amino acid deletion/replacement of the peptide LR161-170 indicated that the 10-amino acid length and two basic amino acids, K(166) and H(169), have a critical role in neutralizing EGCG's activities. Moreover, neutralizing activity against the anti-proliferation action of EGCG was observed in a recombinant protein of the extracellular domain of 67LR, and this effect was abrogated by a deletion of residues 161-170. These findings support that the 10 amino-acid sequence, IPCNNKGAHS, might be the functional domain responsible for the anti-cancer activity of EGCG. CONCLUSIONS/SIGNIFICANCE: Overall, our results highlight the nature of the EGCG-67LR interaction and provide novel structural insights into the understanding of 67LR-mediated functions of EGCG, and could aid in the development of potential anti-cancer compounds for chemopreventive or therapeutic uses that can mimic EGCG-67LR interactions

Inverse correlation between Ki67 expression as a continuous variable and outcomes in luminal HER2-negative breast cancer

OBJECTIVES: Few studies to date have investigated the prognostic significance of Ki67 expression as a continuous variable in breast cancer. This study aimed to evaluate the impact of Ki67 expression as a dichotomous or continuous variable on outcomes in estrogen receptor (ER)+ and human epidermal growth factor receptor 2 (HER2)– breast cancer. METHODS: Survival analysis was performed to estimate the likelihood of distant recurrence and death in retrospective data from 794 patients with ER+/HER2– breast cancer. We assessed the relationship between outcomes and two Ki67 cutoffs, 14% and 20%, and the Ki67 labeling index as a continuous variable. RESULTS: In univariate analysis, T stage, lymph node involvement, histological grade, progesterone receptor status, and Ki67 expression at the two cutoffs and as a continuous variable were identified as significant prognostic factors for distant disease-free survival (DDFS) and overall survival (OS). There were no statistical differences in DDFS and OS between women with Ki67 expression of <14% and 14–<20%. Multivariate analysis showed that Ki67 expression ≥20% was an independent prognostic indicator for DDFS. Regarding the risk of distant metastasis, the 20% cutoff was more reliable than 14%. We also found that Ki67 expression as a continuous variable was an independent prognostic factor for DDFS and OS in multivariate analyses. CONCLUSIONS: High Ki67 expression is associated with a survival disadvantage in patients with ER+/HER2– breast cancer, indicating that these patients might have a higher risk of recurrence after primary treatment and might therefore benefit from individualized treatment