Bismuth-based drugs have long been used for the treatment of Helicobacter pylori infection. In this work, the metal content in H. pylori was monitored at the single-cell level by time-resolved ...inductively coupled plasma mass spectrometry, and ∼2.9 × 107 Mg atoms/cell was determined for the wild-type. Bacteria treated with a Bi antiulcer drug deposited nearly 1.0 × 106 Bi atoms/cell, whereas the uptake process took ∼3 h to reach the half-maximum. Interference of ferric ions on bismuth uptake was demonstrated, suggesting that the metallodrug can utilize certain iron-transport pathways in the pathogen. The approach provides a general strategy for monitoring metals in single cells, facilitating exploration of metal-relevant bioprocesses.
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IJS, KILJ, NUK, PNG, UL, UM
Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes ...based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes.
We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good modified Rankin Scale score 0-2, poor modified Rankin Scale score 4-6, and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes.
Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all
<0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all
<0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all
<0.001). All receiver operating characteristic models for location-specific cutoffs had good discriminant values (area under the curve >0.8), except in predicting good outcome for cerebellum.
ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.
Intra-operative frozen section (IFS) can provide an instinct guide for treatment of ovarian tumors intra-operatively, though limitations exist. This study intended to evaluate the diagnostic ...performance of IFS and possible clinicopathological factors influencing the diagnostic accuracy of IFS.
A retrospective review of IFS of ovarian lesions from 2006 to 2016 was done. The diagnostic performance of benign, borderline, and malignant IFS diagnosis was evaluated. Logistic regression analysis was used to assess the influence of clinicopathological parameters on the likelihood of underdiagnosis.
There were 1143 consecutive cases during the study period. The overall accuracy was 93.7%. For benign diagnoses, the IFS diagnostic accuracy, sensitivity, and specificity were 97.20%, 100%, and 92.51%, respectively. If borderline and malignant diagnoses were considered as a single group, the IFS diagnostic accuracy was 97.20%, with 92.51% sensitivity and 100% specificity. At univariate regression analysis, intact capsules at time of delivery (OR
= 1.9), stage I lesions (OR
= 3.76) and ultrasound (USG) score 0 (OR
= 2.52) were positively associated with underdiagnosis. Further multivariate analysis showed that only stage I lesions (OR = 3.62) and USG score 0 (OR = 2.32) were positively associated with underdiagnosis. For the cases with underdiagnosed IFS, 54% (34/63) received incomplete primary staging surgery.
The study demonstrated that IFS provided excellent specificity to differentiate borderline or malignant tumors from benign lesions. IFS in early-stage ovarian cancers needs to be interpreted with caution, though IFS is most important for this group of lesions. A reliable IFS diagnosis often requires efficient communication between surgeons and pathologists.
Coffee contains caffeine and diterpenes that were associated with decreased breast cancer risk, but results remained inconsistent. The study purpose was to investigate the associations between coffee ...products and breast cancer risk among Hong Kong Chinese women. We conducted a hospital-based case-control study in three public hospitals. 2169 Chinese women aged 24-84 years old were interviewed using a standardized questionnaire with questions asking types, cups and duration on coffee drinking. We used unconditional multivariate logistic regression to calculate the adjusted odds ratio (AOR) and 95% confidence interval (95% CI) for breast cancer risk with different coffee products. 238 (20.6%) cases and 179 (17.7%) controls are habitual coffee drinkers. No association was found between overall coffee drinking and breast cancer risk. Compared to the non-habitual coffee drinkers, women who consumed instant coffee (AOR = 1.50, 95% CI = 1.10-2.03) were significantly associated with an increased breast cancer risk. Women who drank brewed coffee (AOR = 0.48, 95% CI = 0.28-0.82) were negatively associated with breast cancer risk. A positive association between instant coffee and breast cancer risk was observed, contradicted to the outcomes of drinking brewed coffee. Larger studies are warranted to ascertain the role of different types of coffee products in breast cancer risk.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Heterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in ...non-European populations. Here, we aimed at characterizing the immune gene expression profile of luminal BC in an Asian population and associating it with patient characteristics and tumor genomic features.
We performed immune gene expression profiling of tumor and adjacent normal tissue in 92 luminal BC patients from Hong Kong using RNA-sequencing data and used unsupervised consensus clustering to stratify tumors. We then used luminal patients from The Cancer Genome Atlas (TCGA, N = 564) and a Korean breast cancer study (KBC, N = 112) as replication datasets.
Based on the expression of 130 immune-related genes, luminal tumors were stratified into three distinct immune subtypes. Tumors in one subtype showed higher level of tumor-infiltrating lymphocytes (TILs), characterized by T cell gene activation, higher expression of immune checkpoint genes, higher nonsynonymous mutation burden, and higher APOBEC-signature mutations, compared with other luminal tumors. The high-TIL subtype was also associated with lower ESR1/ESR2 expression ratio and increasing body mass index. The comparison of the immune profile in tumor and matched normal tissue suggested a tumor-derived activation of specific immune responses, which was only seen in high-TIL patients. Tumors in a second subtype were characterized by increased expression of interferon-stimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in TCGA and KBC, although the pattern was more similar in Asian populations. The germline APOBEC3B deletion polymorphism, which is prevalent in East Asian populations and was previously linked to immune activation, was not associated with immune subtypes in our study. This result does not support the hypothesis that the germline APOBEC3B deletion polymorphism is the driving force for immune activation in breast tumors in Asian populations.
Our findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification and a subset of luminal BC patients may benefit from checkpoint immunotherapy, at least in Asian populations.
Breast fibroepithelial lesions are biphasic tumors which comprise the common benign fibroadenomas (FAs) and the rarer phyllodes tumors (PTs). This study analyzed 262 (42%) conventional FAs, 45 (7%) ...cellular FAs, and 321 (51%) benign PTs contributed by the International Fibroepithelial Consortium, using a previously curated 16 gene panel. Benign PTs were found to possess a higher number of mutations, and higher rates of cancer driver gene alterations than both groups of FAs, in particular MED12, TERT promoter, RARA, FLNA, SETD2, RB1, and EGFR. Cases with MED12 mutations were also more likely to have TERT promoter, RARA, SETD2, and EGFR. There were no significant differences detected between conventional FAs and cellular FAs, except for PIK3CA and MAP3K1. TERT promoter alterations were most optimal in discriminating between FAs and benign PTs. Our study affirms the role of sequencing and key mutations that may assist in refining diagnoses of these lesions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A novel line of research suggests that eating at nighttime may have several metabolic consequences that are highly relevant to breast cancer. We investigated the association between nighttime eating ...habits after 10 p.m. and breast cancer in Hong Kong women.
A hospital-based case-control study was conducted during 2012-2015. A total of 922 patients with incident breast cancer (cases) and 913 hospital controls were recruited and interviewed using a standard questionnaire including information on eating behavior during both daytime and nighttime. We collected the timing, duration, types and frequencies of food intake of eating at nighttime. Odds ratios (ORs) for the risk of breast cancer in relation to nighttime eating-related variables were calculated by unconditional multivariable logistic regression.
Eating at night after 10 pm was significantly associated with breast cancer with an adjusted OR of 1.50 (95% confidence interval (CI) 1.06-2.12, P = 0.02), and the associations were stronger in women who had the longest duration of nighttime eating (≥20 years) (adjusted OR = 2.28 (95% CI 1.13-4.61, P = 0.02) and who ate late (midnight to 2 a.m.) (adjusted OR = 2.73, 95% CI 1.01-6.99, P = 0.04). Interestingly, nighttime eating was only associated with breast cancer among women who consumed staple foods (OR = 2.16, 95% CI 1.42-3.29, P < 0.001) but not those who ate vegetables or fruits as nighttime meals. The significant association between nighttime eating and breast cancer was observed among women with body mass index (BMI) <25 (OR = 2.29, 95% CI 1.48-3.52, P < 0.001) but not among women with BMI ≥25.
Results from this study suggest a possible association between nighttime eating behavior and breast cancer. These findings need to be confirmed by independent large studies.
Age-related DNA methylation is a potential mechanism contributing to breast cancer development. Studies of primarily Caucasian women have identified many CpG sites of age-related methylation in ...non-diseased breast tissue possibly driving cancer development over time. There is a paucity of studies involving Asian women whose ages at breast cancer onset are usually younger than Caucasians. We identified the 181 most consistent age-related methylation events in non-diseased breast tissue across published studies. Age-related methylation events were measured in adjacent normal and breast tumour tissue in an exclusively Asian population at the previously identified age-related methylation sites. Age-related methylation was found in 118 probes in adjacent normal breast tissue. Methylation of 99% of these sites was increased with age and predominantly located on CpG islands in promoter regions. To ascertain biological relevance to breast cancer, we focused on the 37 sites with overall higher methylation in tumour compared to adjacent normal samples. Some sites positively related to age, including AQP5 and CORO6, inversely correlated with gene expression. Several others have known involvement in suppression of carcinogenesis including GPC5 and SST, suggesting that perturbation of epigenetic regulation at these sites due to ageing may contribute to the progression of carcinogenesis. This study highlights an age-related methylation landscape in non-tumour tissue, consistent not just across studies, but also across different populations. We present candidate age-related methylation sites warranting further investigation as potential epigenetic drivers of breast cancer. They may serve as potential targets of site-specific demethylation intervention strategies for the prevention of age-related breast cancer.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Preserved food such as cured foods may contain nitrate and nitrite that may contribute to the breast cancer development. Evidence on the associations between these preserved food intakes and risk of ...breast cancer is sparse. This study aimed to examine the associations between preserved foods (i.e. cured meat, pickled vegetables, canned meat, canned fruit/vegetables) and breast cancer risk in Hong Kong Chinese women. A total of 1307 breast cancer cases and 1050 age-matched controls were recruited from three hospitals during 11/2011-01/2018. We used a standardized questionnaire to collect information on dietary factors including preserved foods. Unconditional multiple logistic regression was performed to calculate the adjusted odds ratio(AOR) of breast cancer in relation to preserved food with adjustment of potential confounders. We further performed stratified analysis according to the breast cancer biology subtypes. We found that cured meat consumption was significantly associated with the risk of breast cancer AOR=1.32, 95% confidence interval 95%CI)=1.06-1.64. Compared to no cured meat consumption, cured meat intake {greater than or equal to} once per week was associated with an AOR of 2.66 (95%CI=1.38-5.35). Women with canned fruit/vegetable {greater than or equal to} consumption once per week had a higher risk of breast cancer (OR=1.19, 95%CI=1.00-1.41), particularly for the HER2-positive subtypes, but it became borderline after adjustment of confounders. Our study reveals a positive association between consumption of cured meat and breast cancer risk in Chinese population. Cured meat intake might be a potential novel risk factor for breast cancer but this would have to be confirmed by large prospective cohort studies.
Previous studies reported heterogeneous associations between obesity and reproductive-related breast cancer risk factors and breast cancer intrinsic subtypes; however, few studies have been conducted ...in Asian populations. Here, we aimed to examine whether risks associated with established breast cancer risk factors varied by breast cancer subtypes in Chinese women. We conducted a hospital-based case-control study in Hong Kong, including a total of 2169 Chinese women. Unconditional polytomous logistic regression models were used to calculate adjusted odds ratios (AORs) and 95% confidence intervals(95%CIs) to estimate relative risks associated with examined risk factors in case-control analyses and to test for heterogeneity across breast cancer subtypes in case-case analyses. In case-case analyses, compared with luminal A patients, luminal B (AOR = 1.76, 95% CI = 1.07–2.88), HER2 overexpressing (AOR = 3.40, 95% CI = 1.56–7.39), and triple negative (TNBC, AOR = 2.39, 95% CI = 1.18–4.82) patients were more likely to be postmenopausal. In case-control analyses, reduced risks associated with parity and younger age at first birth were only seen for luminal A and B cases especially among postmenopausal women, whereas having ≥ 3 children was associated with increased risk for HER2 overexpressing and TNBC among premenopausal women. Obesity was associated with increased risk for all subtypes. We found heterogeneous associations between parity-related risk factors by menopausal status and breast cancer subtypes among Chinese patients, which is similar to those observed in Western populations. Interestingly, obesity was associated with increased breast cancer risk regardless of menopausal status or subtypes, except for premenopausal luminal patients, which appears to be unique in Asian populations.
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