Optimal Breast Density Characterization Using a Three-Dimensional Automated Breast Densitometry System.

Dense breasts are a risk factor for breast cancer. Assessment of breast density is important and radiologist-dependent. We objectively measured mammographic density using the three-dimensional automatic mammographic density measurement device Volpara™ and examined the criteria for combined use of ultrasonography (US). Of 1227 patients who underwent primary breast cancer surgery between January 2019 and April 2021 at our hospital, 441 were included. A case series study was conducted based on patient age, diagnostic accuracy, effects of mammography (MMG) combined with US, size of invasion, and calcifications. The mean density of both breasts according to the Volpara Density Grade (VDG) was 0-3.4% in 2 patients, 3.5-7.4% in 55 patients, 7.5-15.4% in 173 patients, and ≥15.5% in 211 patients. Breast density tended to be higher in younger patients. Diagnostic accuracy of MMG tended to decrease with increasing breast density. US detection rates were not associated with VDG on MMG and were favorable at all densities. The risk of a non-detected result was high in patients without malignant suspicious calcifications. Supplementary use of US for patients without suspicious calcifications on MMG and high breast density, particularly ≥25.5%, could improve the breast cancer detection rate.

Quantification of bromide ion in biological samples using headspace gas chromatography-mass spectrometry.

OBJECTIVES: In this study, we aimed to establish a method for quantifying bromide ions (Br- ) in blood and urine using gas chromatograph-mass spectrometer (GC-MS) equipped with a headspace sampler, for biological monitoring of workers exposed to methyl bromide. METHODS: Samples were mixed with dimethyl sulfate, and Br- ions were detected using GC-MS with a headspace sampler. The validity of the proposed method was evaluated based on most of the US FDA guidance. The values obtained were compared with reference values by analysis using SeronormTM Trace Elements Whole Blood L-1 RUO. RESULTS: The calibration curve showed good linearity in the Br- concentration range of 0.1-20.0 mg/L, and the coefficient of determination R2 value was >.999. Intraday and interday accuracy values were 99.3%-103.1% and 97.4%-101.8%, respectively. The measured and reference values of Seronorm were concordant. Herein, eight urine and serum samples of workers were analyzed; the samples' Br- concentrations were known. The correlation coefficients of urine and serum samples were 0.97 and 0.96, respectively, and results were consistent. CONCLUSIONS: This study established a simple and rapid method for the determination of Br- concentration in biological samples using GC-MS with a headspace sampler. Moreover, it can be used for biological monitoring of occupational exposure to methyl bromide and for the determination of Br- concentration in a wide range of biological samples.

Zinc-containing Mohs' paste affects blood flow and angiogenesis suppression.

PURPOSE: Mohs' paste, which is composed of zinc chloride and zinc oxide starch, is used for hemostasis of superficial malignancy in the clinical setting. We investigated the concentration of intramuscular zinc in mice after Mohs' paste application and evaluated its relationship with angiogenesis from the perspective of blood flow levels within 24 h. METHODS: Male C57BL/6JJmsSlc mice were administered single dose of Mohs' paste at 25%, 50%, and 75% after unilateral hind limb surgery, and glycerin, a viscosity modifier, was administered to the control group (0%). Hind limb blood flow levels were measured with a laser Doppler perfusion imaging system (n = 6). The amounts of intramuscular zinc and vascular endothelial growth factor-A (VEGF-A) expression were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and western blotting, respectively (n = 5 or 3). RESULTS: Blood flow levels were significantly decreased in the 50% group after 8 h, and significantly decreased in the 25% and 50% groups after 24 h. Intramuscular zinc was significantly increased in the 50% and 75% groups after 8 h. Western blotting showed that VEGF-A levels were significantly increased in the 25% and 50% groups after 8 h. Based on analytical experiments and biological investigation, we predicated the pharmacological effect of Mohs' paste and found over 50% of it is critical in the blood flow and angiogenesis suppression after more than 8 h of its application. CONCLUSIONS: The results suggest that the mechanism of blood flow suppression is independent of VEGF-A levels and might suppress future angiogenesis. Our findings support that of previous studies, in which Mohs' paste was expected to induce hemostasis and suppress angiogenesis. It is an excellent ointment that facilitates hemostasis by suppressing blood flow regardless of angiogenesis, and may be apt for situations where hemostasis is required in the clinical setting.

The genotype of the transporter associated with antigen processing gene affects susceptibility to colorectal cancer in Japanese.

OBJECTIVE: Although colorectal cancer (CRC) is one of the most frequent malignancies in Japan, the associated genetic factors remain to be elucidated. Functional loss of the transporter associated with antigen processing (TAP) 1 gene induces carcinogenesis. We investigated whether single nucleotide polymorphisms (SNPs) in the TAP1 gene (rs735883) are associated with susceptibility to CRC in a Japanese population. METHODS: The study participants were 143 cases and 243 clinical controls. After extracting DNA from their peripheral blood cells, genotyping was conducted by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Participants with a mutated allele had an increased risk for CRC. The adjusted odds ratios for the C/T, T/T, and the mutation type (C/T + T/T) compared to that of wild type (C/C) were 2.27 [95 % confidence interval (CI), 1.43-3.67], 1.95 (95 % CI, 0.88-4.30), and 2.22 (95 % CI, 1.42-3.55), respectively. Furthermore, a significant trend in the rate of cases was observed with an increasing number of mutated alleles (P for trend = 0.0068). CONCLUSIONS: The genotype of the TAP1 gene is associated with susceptibility to CRC.

Increased plasma caveolin-1 levels are associated with progression of prostate cancer among Japanese men.

AIM: Up-regulation of caveolin-1 (CAV1) is associated with aggressive prostate cancer. Among Caucasian and African-American patients, plasma CAV1 levels are elevated in patients with castration-resistant prostate cancer (CRPC), but not in those with hormone-sensitive prostate cancer (non-CRPC), which implies that CAV1 could be a therapeutic target for CRPC. Here, we evaluated associations between plasma CAV1 levels and these types of cancer in Japanese men, and CAV1 expression in PC3 (CRPC) and LNCaP (non-CRPC) cell lines. MATERIALS AND METHODS: Plasma samples were obtained from 58 patients with prostate cancer: 36 with CRPC and 22 with non-CRPC. Enzyme-linked immuno sorbent assay (ELISA) kits were used to determine CAV1 plasma levels; qRT-PCR and western blots were used to evaluate the expression of CAV1 mRNA and protein in cell lines. RESULTS: Plasma CAV1 levels in patients with CRPC were greatly higher than in those with non-CRPC (1.46±1.37 ng/ml in CRPC; 0.56±0.32 ng/ml in non-CRPC, p<0.004). Western blot and real-time qRT-PCR showed CAV1 protein and mRNA in PC3 cells to be significantly overexpressed compared to its expression in LNCaP cells (p<0.0001). CONCLUSION: Our results showed a relationship between CAV1 expression and prostate cancer progression, and support the possibility of CAV1 as a therapeutic target for CRPC.

Functional polymorphism in the CAV1 T29107A gene and its association with prostate cancer risk among Japanese men.

AIM: To evaluate the relationship between the Caveolin-1 (CAV1) T29107A (rs7804372) polymorphism and the risk of prostate cancer among Japanese populations, and the associations between CAV1 polymorphisms and clinicopathological characteristics, including Gleason grade and prostate-specific antigen (PSA) grade. MATERIALS AND METHODS: We recruited 134 patients with prostate cancer and 86 healthy controls matched for age and smoking status. The CAV1 T29107A polymorphism status was determined by polymerase chain reaction and restriction fragment-length polymorphism analysis. RESULTS: Genotype distributions (p=0.0045) and allelic frequencies (p=0.0018) differed between prostate cancer and control groups in terms of the CAV1 T29107A polymorphism (Pearson's χ(2) test). Logistic regression analysis of case and control outcomes showed an odds ratio of 0.35 (95% Condifence interval=0.13-0.91, p=0.033) between the TT and AA polymorphisms, indicating a reduced risk of prostate cancer to be associated with the AA polymorphism. Subset analysis revealed no significant associations between this polymorphism and clinicopathological characteristics of prostate cancer. CONCLUSION: The results of this study demonstrated a relationship between the CAV1 T29107A variant and risk of prostate cancer. This polymorphism thus, merits further investigation as a potential genomic marker for the early detection of prostate cancer. Our results support the hypothesis that the CAV1 T29107A (rs7804372) polymorphism may influence susceptibility to prostate cancer; however, prostate cancer progression was not associated with this polymorphism in a Japanese population.

ADRB3 polymorphism associated with BMI gain in Japanese men.

OBJECTIVE: The aim of this study was to evaluate the association between the Trp64Arg polymorphism in the beta3-adrenergic receptor gene (ADRB3: rs4994) and BMI and serological and anthropometric data in healthy Japanese. METHODS: Healthy Japanese recruited in a large-scale integrated manufacturing facility in Japan (N = 1355; age: 37.25 ± 9.43; BMI: 22.86 ± 3.46) were eligible for analysis. The anthropometric data and serological data were measured during a comprehensive health check, and a self-reporting questionnaire was used to assess lifestyle habits (current exercise, smoking status, alcohol intake, and working style) and weight at age 20. Genotyping for the ADRB3 polymorphism was performed by PCR-RFLP method. RESULTS: Among 1355 participants, the genotype frequencies of the Trp/Trp, Trp/Arg, and Arg/Arg variants were 920 (67.9%), 394 (29.1%), and 41 (3.05%), respectively. In the multivariate analysis, a multiple linear regression model in men for the adjustment of age, drinking habits, smoking habits, exercise habits, working status and serological measurements statistically showed an overall weak significance between annual BMI gain from age 20 and age, LDL or ADRB3 polymorphism. CONCLUSIONS: The level of LDL, age, and ADRB3 polymorphism (Arg/Arg genotype) were statistically associated with annual BMI gain in Japanese men.