The BRCA1/2 gene is the most well-known and studied gene associated with hereditary breast cancer. BRCA1/2 genetic testing is widely performed in high-risk patients of hereditary breast cancer in ...Korea. This study aimed to investigate the clinicopathological characteristics of BRCA1/2 mutation-positive breast cancer patients.
The clinical data of 188 Korean breast cancer patients who underwent genetic testing of BRCA1/2 mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of BRCA1 and BRCA2 mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors.
The factor associated with BRCA1/2 gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (p = 0.033; odds ratio OR, 0.169; 95% confidence interval CI, 0.033-0.867), and there was a tendency to increase in stage II (p = 0.780; OR, 1.150; 95% CI, 0.432-3.064). BRCA1 was significantly associated with triple-negative breast cancer (TNBC) (p = 0.004; OR, 5.887; 95% CI, 1.778-19.498). Gene expression of BRCA2 was significantly reduced under 40 years of age (p = 0.040; OR, 0.198; 95% CI, 0.042-0.930). There was no difference in disease-free survival (p = 0.900) and overall survival (p = 0.733) between the BRCA1/2 mutation-positive and -negative groups.
In this study, the clinicopathological characteristics of breast cancer patients with BRCA1/2 gene mutations were identified. BRCA1 gene expression was highly correlated with TNBC. BRCA1/2 mutation did not have a poor prognosis regarding recurrence and death.
Objectives
The aim of this study was to evaluate the systemic effect of water fluoridation on dental caries prevalence and experience in Cheongju, South Korea, where water fluoridation ceased 7 years ...previously.
Methods
A cross‐sectional survey was employed at two schools where water fluoridation had ceased (WF‐ceased area) and at two schools where the water had never been fluoridated (non‐WF area). The schools in the non‐WF area were of a similar population size to the schools in the WF‐ceased area. Children of three age groups were examined in both areas: aged 6 (n = 505), 8 (n = 513), and 11 years (n = 467). The differences in the mean number of decayed or filled primary teeth (dft) and the mean number of decayed, missing, or filled permanent teeth (DMFT) scores between areas after adjusting for oral health behaviors and socio‐demographic factors were analyzed by a Poisson regression model.
Results
The regression model showed that the DMFT ratio for children aged 11 years in the WF‐ceased area was 0.581 (95% CI 0.450–0.751). In contrast, the dft ratio for age 6 in the WF‐ceased area was 1.158 (95% CI 1.004–1.335). Only the DMFT ratio for age 8 (0.924, 95% CI 0.625–1.368) was not significant.
Conclusions
While 6‐year‐old children who had not ingested fluoridated water showed higher dft in the WF‐ceased area than in the non‐WF area, 11‐year‐old children in the WF‐ceased area who had ingested fluoridated water for approximately 4 years after birth showed significantly lower DMFT than those in the non‐WF area. This suggests that the systemic effect of fluoride intake through water fluoridation could be important for the prevention of dental caries.
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•Mt(acac)x was used to demonstrate radical generation of n-butyl acrylate as monomer.•Mt(acac)x was used to investigate as catalyst effect on the urethane reaction.•Dual-curing ...reaction, including radical polymerization and the urethane reaction, was realized using Mt(acac)x.
The goal of our research has been to realize dual-curing reaction which is accompanied with radical reaction and urethane reaction at low temperature using a metal acetylacetonate (Mt(acac)x) such as Mn(acac)3, Mn(acac)2, Co(acac)3, Co(acac)2 and Zn(acac)2. To understand radical reaction relationship depending on what kind of metals, Mt(acac)x as a radical initiator is defined by DSC analysis in n-butyl acrylate and EPR spectroscopy. The role of finding TPeak in DSC and g` factor in EPR exhibit Mt(acac)x can generate radical effectively. In order to verify effect of Mt(acac)x in urethane reaction on HFUMO 4039-0 without acryl group and PL-350, real-time storage modulus (G’) was measured by rheometer for curing at 140 °C and checked the initiation temperature (Tinit) and storage modulus (G’). Finally, to evaluate the catalyst the effect of Mt(acac)x as a radical and urethane reaction, rheometer and nanoindenation were constructed with HFUMO 4039-60 with acryl group and PL 350 based on films cured at 140 °C, 120 °C and 100 °C. Considering the initiation temperature (Tinit) and storage modulus (G’) on rheometer and HIT value on nanoindenation, Mn(acac)3 is the best catalyst among tested Mt(acac)x and surface property also maintained despite 100 °C even low curing temperature.
Metal halide perovskite solar cells (PSCs) have been considered to be one of the most promising next‐generation energy harvesters over the past decades due to remarkably rapid improvement of power ...conversion efficiency in photovoltaics. However, energy harvesters based on the solar energy source have an intrinsic environment limitation for indoor applications. A feasible solution to the limitation is to add non‐solar energy harvesting functions to the solar energy harvesters. Here, the piezoelectric properties of two types of metal halide PSCs are investigated, the 3D only and the 3D/2D structure, showing PCEs of 21.3% and 23.2%, respectively. Piezo‐response force microscopy and synchrotron‐based X‐ray diffraction demonstrate that both types of PSC sample have piezoelectricity. Remarkably, the 3D/2D structure has considerably higher piezoelectric amplitude than the 3D‐only. The deep level transient spectroscopy results reveal that the enhancement in the piezoelectricity of the 3D/2D structure originates from PbBr defects. This study unravels the role of defects in the piezoelectricity of metal halide PSCs and provides a direction to develop the multi‐function energy harvesters based on the PSCs.
The piezoelectric properties of two types of metal halide perovskite solar cells (PSCs), the 3D and the 3D/2D structure are investigated. It is found that the 3D/2D structure has a considerably more intense piezoelectric features than the 3D‐only one. The deep level transient spectroscopy measurement unveils that the PbBr defects play a crucial role in enhancing piezoelectric properties for the PSCs of the 3D/2D heterostructure, which unravels the correlation between the deep level defects and piezoelectric properties in PSCs.
Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcriptional factor O1 (FoxO1) in the ...hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homoeostatic role of FoxO1 in DA system has not been investigated. Here we report that FoxO1 is highly expressed in DA neurons and mice lacking FoxO1 specifically in the DA neurons (FoxO1 KO
) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homoeostasis. Moreover, FoxO1 KO
mice exhibit an increased sucrose preference in concomitance with higher dopamine and norepinephrine levels. Finally, we found that FoxO1 directly targets and negatively regulates tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of the catecholamine synthesis, delineating a mechanism for the KO phenotypes. Collectively, these results suggest that FoxO1 in DA neurons is an important transcriptional factor that directs the coordinated control of energy balance, thermogenesis and glucose homoeostasis.
Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical ...studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer.
Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively.
This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.
ClinicalTrials.gov Identifier NCT01589367.
The prognostic significance of tumor size in thymic epithelial tumors (TETs) has not been fully evaluated. We aimed to clarify the prognostic value of tumor size in limited-stage and advanced-stage ...TETs.
Clinical records of patients with completely resected TETs were retrospectively collected from 4 tertiary centers between January 2000 and February 2013. Information on the Masaoka–Koga stage was available for 1215 patients (M-K group), and 433 patients were classified according to the eighth edition of the Tumor-Node-Metastasis staging system (TNM group). Limited-stage and advanced-stage TETs were defined according to whether they were confined within the surrounding fatty tissues without invasion. The optimal cutoff value was selected using a maximally selected log-rank statistic.
The median tumor size was 6.0 ± 2.8 cm in the M-K group and 6.5 ± 3.0 cm in the TNM group. In the multivariable analysis, tumor size had a significant effect on both overall survival (P = .003) and recurrence-free survival (P < .001) for limited-stage tumors (M-K stage I or II or TNM stage I), but not for advanced-stage tumors (M-K stage III or IV or TNM stage II-IV; P = .349 for overall survival and P = .439 for recurrence-free survival). The optimal cutoff value for tumor size was >5.5 cm for both overall survival and recurrence-free survival in limited-stage TETs.
Tumor size is an independent prognostic factor in patients with completely resected limited-stage TETs and a cutoff value >5.5 cm might help clinicians enact proper treatment strategies and surveillance.
An increasing number of studies show that genetic markers can aid in refining prognostic information and predicting the benefit from systemic therapy. Our goal was to develop a high throughput, ...cost-effective and simple methodology for the detection of clinically relevant hot spot mutations in colon cancer.
The Maldi-Tof mass spectrometry platform and OncoCarta panel from Sequenom were used to profile 239 colon cancers and 39 metastatic lymph nodes from NSABP clinical trial C-07 utilizing routinely processed FFPET (formalin-fixed paraffin-embedded tissue).
Among the 238 common hot-spot cancer mutations in 19 genes interrogated by the OncoCarta panel, mutations were detected in 7 different genes at 26 different nucleotide positions in our colon cancer samples. Twenty-four assays that detected mutations in more than 1% of the samples were reconfigured into a new multiplexed panel, termed here as ColoCarta. Mutation profiling was repeated on 32 mutant samples using ColoCarta and the results were identical to results with OncoCarta, demonstrating that this methodology was reproducible. Further evidence demonstrating the validity of the data was the fact that the mutation frequencies of the most common colon cancer mutations were similar to the COSMIC (Catalog of Somatic Mutations in Cancer) database. The frequencies were 43.5% for KRAS, 20.1% for PIK3CA, and 12.1% for BRAF. In addition, infrequent mutations in NRAS, AKT1, ABL1, and MET were detected. Mutation profiling of metastatic lymph nodes and their corresponding primary tumors showed that they were 89.7% concordant. All mutations found in the lymph nodes were also found in the corresponding primary tumors, but in 4 cases a mutation was present in the primary tumor only.
This study describes a high throughput technology that can be used to interrogate DNAs isolated from routinely processed FFPET and identifies the specific mutations that are common to colon cancer. The development of this technology and the ColoCarta panel may provide a mechanism for rapid screening of mutations in clinically relevant genes like KRAS, PIK3CA, and BRAF.
ClinicalTrials.gov: NSABP C-07: NCT00004931.
The purpose of this study was to examine the prognostic and oxaliplatin predictive value of mismatch repair (MMR) status and common hot spot mutations, which we previously identified in stage II and ...III colon cancer.
Mutations in BRAF, KRAS, NRAS, MET, and PIK3CA were profiled in 2,299 stage II and III colon tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials C-07 (n = 1,836) and C-08 (n = 463) with Type Plex chemistry and mass spectrometry. C-07 tested the worth of adding oxaliplatin to 5-fluorouracil plus leucovorin, and C-08 tested the worth of adding bevacizumab to FOLFOX. Cox proportional hazard models were used to assess prognostic or oxaliplatin predictive value of mutations for tumor recurrence, overall survival (OS), and survival after recurrence (SAR).
BRAF mutations were associated with MMR-deficient tumors (P < 0.0001), poor OS HR, 1.46; 95% confidence interval (CI), 1.20-1.79; P ≤ 0.0002, and poor SAR (HR, 2.31; 95% CI, 1.83-2.95; P < 0.0001). Mutations in KRAS, NRAS, MET, and PIK3CA were not associated with recurrence, OS, or SAR. MMR-deficient tumors were associated with an improved prognosis based on recurrence (HR, 0.48; 95% CI, 0.33-0.70; P < 0.0001). Mutations and MMR status were not predictive for oxaliplatin benefit.
This study shows that BRAF mutations profiled from stage II and III colon cancer tumors were associated with poor SAR and validates and explains, at least in part, previous observations associating it with poor OS. Profiling of all of these mutations is warranted for future clinical trials testing new targeted therapies that block relevant signaling pathways. Such clinical trials are under development at NSABP.
Core needle biopsy (CNB) is a widely used procedure for breast cancer diagnosis and analyzing results of immunohistochemistry (IHC). Several studies have shown concordance or discordance in IHC ...results between CNB and surgical specimens (SS). A double-check (CNB and SS) is inefficient and costly to perform a double-check on all patients. Therefore, it is important to determine which patients would benefit from a double-check.
We collected the medical records of patients who underwent breast cancer surgery at Pusan National University Yangsan Hospital between April 2009 and June 2018 (n = 620). Molecular subtypes were classified as follows by hormone receptors (HR) and human epidermal growth factor receptor-2 (HER2): HR+/HER2+, HR+/HER2-, HR-/HER2+, HR-/HER2-. Clinicopathological factors including age, obesity, histological grade, preoperative CEA, CA15-3, T stage, N stage, and menopausal status were assessed to determine whether they were associated with subtype change.
Increasing histological grade (P < 0.001; odds ratio OR, 3.693; 95% confidence interval CI, 1.941-7.025), preoperative CEA ≥ 5 ng/mL (P =0.042; OR, 2.399; 95% CI, 1.009-5.707) and higher T stage (P = 0.015; OR, 2.241; 95% CI, 1.152-4.357) were significantly associated with subtype change. On multivariable analyses, subtype changes were more common in high-grade breast cancer (P < 0.001; OR, 1.077; 95% CI, 1.031-1.113) and CEA ≥ 5 (P = 0.032; OR, 2.658; 95% CI, 1.088-6.490).
Patients with moderate- to high-grade tumors or CEA ≥ 5 ng/mL are required a double-check to determine the molecular subtype of breast cancer.
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