Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies.

Long-standing scarcity of efficacious treatments and tumor heterogeneity have contributed to triple-negative breast cancer (TNBC), a subtype with a poor prognosis and aggressive behavior that accounts for 10-15% of all new cases of breast cancer. TNBC is characterized by the absence of progesterone and estrogen receptor expression and lacks gene amplification or overexpression of HER2. Genomic sequencing has detected that the unique mutational profile of both the somatic and germline modifications in TNBC is staggeringly dissimilar from other breast tumor subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. Nevertheless, reports regarding the penetrance and risk of other susceptibility genes are relatively scarce. Recurring mutations (e.g., TP53 and PI3KCA mutations) occur together with rare mutations in TNBC, and the shared effects of genomic modifications drive its progression. Given the heterogeneity and complexity of this disease, a clinical understanding of the genomic modifications in TNBC can pave an innovative way toward its therapy. In this review, we summarized the most recent discoveries associated with the underlying biology of developmental signaling pathways in TNBC. We also summarize the recent advancements in genetics and epidemiology and discuss state-of-the-art vaccine-based therapeutic strategies for TNBC that will enable tailored therapeutics.

Push-out bond strength and intratubular biomineralization of a hydraulic root-end filling material premixed with dimethyl sulfoxide as a vehicle.

Objectives: This study was designed to evaluate the parameters of bonding performance to root dentin, including push-out bond strength and dentinal tubular biomineralization, of a hydraulic bioceramic root-end filling material premixed with dimethyl sulfoxide (Endocem MTA Premixed) in comparison to a conventional powder-liquid-type cement (ProRoot MTA). Materials and Methods: The root canal of a single-rooted premolar was filled with either ProRoot MTA or Endocem MTA Premixed (n = 15). A slice of dentin was obtained from each root. Using the sliced specimen, the push-out bond strength was measured, and the failure pattern was observed under a stereomicroscope. The apical segment was divided into halves; the split surface was observed under a scanning electron microscope, and intratubular biomineralization was examined by observing the precipitates formed in the dentinal tubule. Then, the chemical characteristics of the precipitates were evaluated with energy-dispersive X-ray spectroscopic (EDS) analysis. The data were analyzed using the Student's t-test followed by the Mann-Whitney U test (p < 0.05). Results: No significant difference was found between the 2 tested groups in push-out bond strength, and cohesive failure was the predominant failure type. In both groups, flake-shaped precipitates were observed along dentinal tubules. The EDS analysis indicated that the mass percentage of calcium and phosphorus in the precipitate was similar to that found in hydroxyapatite. Conclusions: Regarding bonding to root dentin, Endocem MTA Premixed may have potential for use as an acceptable root-end filling material.

Non-Polar Myxococcus fulvus KYC4048 Metabolites Exert Anti-Proliferative Effects via Inhibition of Wnt/ß-Catenin Signaling in MCF-7 Breast Cancer Cells.

The Wnt/ß-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/ß-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, ß-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/ß-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/ß-catenin pathway.

Pregnancy, childbirth, and puerperium outcomes in female firefighters in Korea.

BACKGROUND: Female firefighters are exposed to hazardous environmental (chemical and physical) and working (shift work, psychological, and ergonomic factors) conditions that have reported or are suspected of adverse effects on reproductive health. However, no previous studies have reported on pregnancy, childbirth, and puerperium outcomes (PCPOs) in female firefighters. METHODS: The present study compared hospital admissions for PCPOs, based on 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes, among Korean female firefighters with those of the general Korean population. Standardized admission ratios (SARs) and their 95% confidence intervals (CIs) were calculated. RESULTS: The study population included 1,766 female firefighters. Total follow-up duration was 9,659 person-years. Compared to the general female population, the female firefighters' SARs were higher in all admissions for PCPOs (SAR, 1.92; 95% CI: 1.79-2.05); pregnancy and abortive outcomes (SAR, 1.56; 95% CI: 1.12-2.12); other maternal disorders predominantly related to pregnancy (SAR, 2.65; 95% CI: 1.99-3.46); maternal care related to the fetus, amniotic cavity, and possible delivery problems (SAR, 2.13; 95% CI: 1.74-2.57); labor and delivery complications (SAR, 1.55; 95% CI: 1.15-2.06); delivery (SAR, 1.94; 95% CI: 1.80-2.08); and complications predominantly related to puerperium (SAR, 4.68; 95% CI: 2.02-9.23). CONCLUSION: The results of this study showed high SARs in all and specific subcategories of PCPOs in female firefighters.

Effect of night shift work on the control of hypertension and diabetes in workers taking medication.

BACKGROUND: Night shift work induces physiological and psychological stress by altering sleep and biological rhythms and is associated with hypertension, diabetes, obesity, and cardiovascular diseases. Few studies have been conducted on the control of hypertension and diabetes. This study aimed to examine the effect of night shift work on the control rate of hypertension and diabetes. METHODS: Subjects comprised workers aged 20-65 years who underwent specific health examination at a single facility in seven different affiliated examination centers from 1 January to 31 December 2016. Workers were categorised into day workers and night shift workers. Demographic and medical history were taken, and physical examination was done. Blood pressure (BP) and fasting glucose were measured. The control rate of each disease was evaluated based on treatment goals presented in the treatment guidelines of the Korean Society of Hypertension and the Korean Diabetes Association (systolic BP < 140 mmHg and diastolic BP < 90 mmHg; fasting glucose ≤ 130 mg/dL). RESULTS: Among 631,418 subjects, 11.2% (70,450) were night shift workers. Of whom 6.1% (4,319) were taking antihypertensive medication and 2.5% (1,775) were taking diabetes medication. Among patients taking antihypertensive medications, the proportion of those whose BP was controlled to suit treatment goals was 81.7% (26,635) of day workers and 77.4% (3,343) of night shift workers, which was significantly different (p < 0.001). Among patients taking diabetes medications, the proportion of those whose blood glucose was controlled to suit treatment goals was 37.4% (4,489) of day workers and 36.5% (647) of night shift workers, but the difference was not significant. The control rates for patients taking antihypertensive medications (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.68-0.80) were lower among night shift workers than day workers with adjustment for age, sex, smoking history, alcohol consumption, exercise, and obesity. However, there were no differences in control rates for patients taking diabetes medications (OR: 0.99, 95% CI: 0.87-1.10) between day workers and night shift workers. CONCLUSIONS: Night shift work can have an effect on the uncontrolled BP in workers taking antihypertensive medications. Therefore, additional efforts for disease control are necessary for night shift workers with hypertension.

Association between urinary phthalate metabolites and obesity in adult Korean population: Korean National Environmental Health Survey (KoNEHS), 2012-2014.

BACKGROUND: Phthalate is a chemical that is commonly used as a plasticizer in processing plastic products and as a solvent in personal care products. Although previous experimental studies have reported that phthalate metabolites are associated with obesity, epidemiological study results have been inconsistent and insufficient. The objective of the present study was to investigate the association between urinary phthalate metabolites and obesity in adult Korean population. METHODS: The present study selected 4,752 Korean adults aged 19 years or older from the 2012-2014 Korean National Environmental Health Survey data. The concentrations of urinary di-(2-ethyl-5-carboxypentyl) phthalate (DEHP) metabolites-i.e., mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-carboxypentyl) phthalate-mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP) were adjusted using the urinary creatinine. We used logistic regression analysis to investigate the association between urinary phthalate metabolite concentration and body mass index (BMI) with respect to sex and age. RESULTS: Among women, urinary MEHHP and DEHP concentrations were found to have statistically significantly positive associations with obesity (Q4 versus Q1; odds ratio (OR): 1.72, 95% confidence interval (CI): 1.19-2.49 for MEHHP and OR: 1.52, 95% CI: 1.04-2.21 for DEHP). Among men, urinary MnBP concentration was found to have statistically significantly negative association with obesity (Q4 versus Q1; OR: 0.71, 95% CI: 0.50-0.99). In the analysis stratified by sex and age, women aged ≥ 50 years showed statistically significantly positive associations between the concentrations of urinary DEHP metabolites, DEHP, MBzP, and obesity (Q4 versus Q1; OR: 1.94, 95% CI: 1.28-2.94 for MEHHP, OR: 1.88, 95% CI: 1.21-2.94 for MEOHP, OR: 2.04, 95% CI: 1.31-3.18 for DEHP, and Q3 versus Q1; OR: 1.45, 95% CI: 1.02-2.05 for MBzP). Meanwhile, men aged ≥ 50 years showed no significant associations between urinary phthalate concentrations and obesity. CONCLUSIONS: In the present study, we found differences in the associations between urinary phthalate metabolites and BMI according to sex and age. However, because the present study was cross-sectional in nature, additional support through prospective studies is needed to estimate the causal associations.