Publications by authors named "Jyh-Cherng Yu"

217 Publications

MiR-139 Modulates Cancer Stem Cell Function of Human Breast Cancer through Targeting CXCR4.

Cancers (Basel) 2021 May 25;13(11). Epub 2021 May 25.

Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.

Elevated expression of C-X-C motif chemokine receptor 4 (CXCR4) correlates with chemotaxis, invasion, and cancer stem cell (CSC) properties within several solid-tumor malignancies. Recent studies reported that microRNA (miRNA) modulates the stemness of embryonic stem cells. We aimed to investigate the role of miRNA, via CXCR4-modulation, on CSC properties in breast cancer using cell lines and xenotransplantation mouse model and evaluated miR-193 levels in 191 patients with invasive ductal carcinoma. We validated miR-139 directly targets the 3'-untranslated region of CXCR4. Hoechst 33342 fluorescence-activated cell sorting (FACS) and sphere-forming assay were used to identify CSCs. MiR-139 suppressed breast CSCs with mesenchymal traits; led to decreased migration and invasion abilities through down-regulating CXCR4/p-Akt signaling. In lung cancer xenograft model of nude mice transplanted with human miR-139-carrying MDA-MB-231 cells, metastatic lung nodules were suppressed. Clinically, microdissected breast tumor tissues showed miR-139 reduction, compared to adjacent non-tumor tissues, that was significantly associated with worse clinicopathological features, including larger tumor size, advanced tumor stage and lymph node metastasis; moreover, reduced miR-139 level was predominately occurred in late-stage HER2-oreexpression tumors. Collectively, our findings highlight miR-139-mediated suppression of CXCR4/p-Akt signaling and thereby affected mesenchymal stem-cell genesis, indicating its potential as a therapeutic target for invasive breast cancer.
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http://dx.doi.org/10.3390/cancers13112582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198393PMC
May 2021

Long-term oncologic result of laparoscopic versus open gastrectomy for gastric cancer: a propensity score matching analysis.

World J Surg Oncol 2021 Apr 7;19(1):101. Epub 2021 Apr 7.

Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, 325 Chenggong Rd Sec 2, Nei-hu, 114, Taipei, Taiwan.

Background: Laparoscopic gastrectomy is an acceptable procedure for early-stage gastric cancer; however, most patients are diagnosed at an advanced stage and older age in Taiwan. The feasibility and safety of applying laparoscopic gastrectomy in daily practice remain unclear. This study aimed to examine the short- and long-term outcomes of laparoscopic gastrectomy versus open procedures.

Methods: From 2007 to 2015, 192 patients who underwent open gastrectomy and 189 patients who underwent laparoscopic gastrectomy for gastric cancer at a single center were included. Propensity score matching analysis was used to adjust selection biases associated with age, preoperative hemoglobin, the extent of resection, tumor size, and stage of the disease. The demographics, perioperative parameters, short-term postoperative results, and 5-year survival data were analyzed.

Results: Open gastrectomy was more frequently performed in the elderly, larger tumor size, advanced stage of the disease, and disease requiring total gastrectomy or combined organ resection. After propensity score matching, 108 patients with laparoscopic gastrectomy were compared to 108 patients with open gastrectomy. The morbidity rates were not different in both groups (25.9%), while hospital stay was shorter in the laparoscopic group (16.0 vs. 18.8 days, p = 0.04). The 5-year overall survival and disease-free survival were superior in the laparoscopic group (p = 0.03 and p = 0.01, respectively); however, the survival differences were not significant in the subgroup analysis by stage. Laparoscopic gastrectomy had fewer recurrences than open gastrectomy. The pattern of recurrence was not different between the groups.

Conclusions: Laparoscopic gastrectomy can be safely applied in both early and locally advanced gastric cancer without compromising oncologic outcomes.

Trial Registration: Retrospective registration.
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http://dx.doi.org/10.1186/s12957-021-02217-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028734PMC
April 2021

Genetic co-expression networks contribute to creating predictive model and exploring novel biomarkers for the prognosis of breast cancer.

Sci Rep 2021 Mar 31;11(1):7268. Epub 2021 Mar 31.

Division of Medical Informatics, Department of Epidemiology, School of Public Health, National Defense Medical Center, Taipei, Taiwan.

Genetic co-expression network (GCN) analysis augments the understanding of breast cancer (BC). We aimed to propose GCN-based modeling for BC relapse-free survival (RFS) prediction and to discover novel biomarkers. We used GCN and Cox proportional hazard regression to create various prediction models using mRNA microarray of 920 tumors and conduct external validation using independent data of 1056 tumors. GCNs of 34 identified candidate genes were plotted in various sizes. Compared to the reference model, the genetic predictors selected from bigger GCNs composed better prediction models. The prediction accuracy and AUC of 3 ~ 15-year RFS are 71.0-81.4% and 74.6-78% respectively (rfm, ACC 63.2-65.5%, AUC 61.9-74.9%). The hazard ratios of risk scores of developing relapse ranged from 1.89 ~ 3.32 (p < 10) over all models under the control of the node status. External validation showed the consistent finding. We found top 12 co-expressed genes are relative new or novel biomarkers that have not been explored in BC prognosis or other cancers until this decade. GCN-based modeling creates better prediction models and facilitates novel genes exploration on BC prognosis.
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http://dx.doi.org/10.1038/s41598-021-84995-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012617PMC
March 2021

Transmembrane and coiled-coil domain family 3 (TMCC3) regulates breast cancer stem cell and AKT activation.

Oncogene 2021 Apr 19;40(16):2858-2871. Epub 2021 Mar 19.

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.

Cancer stem cells (CSC) play a pivotal role in cancer metastasis and resistance to therapy. Previously, we compared the phosphoproteomes of breast cancer stem cells (BCSCs) enriched subpopulation and non-BCSCs sorted from breast cancer patient-derived xenograft (PDX), and identified a function unknown protein, transmembrane and coiled-coil domain family 3 (TMCC3) to be a potential enrichment marker for BCSCs. We demonstrated greater expression of TMCC3 in BCSCs than non-BCSCs and higher expression of TMCC3 in metastatic lymph nodes and lungs than in primary tumor of breast cancer PDXs. TMCC3 silencing suppressed mammosphere formation, ALDH activity and cell migration in vitro, along with reduced tumorigenicity and metastasis in vivo. Mechanistically, we found that AKT activation was reduced by TMCC3 silencing, but enhanced by TMCC3 overexpression. We further demonstrated that TMCC3 interacted directly with AKT through its 1-153 a.a. domain by cell-free biochemical assay in vitro and co-immunoprecipitation and interaction domain mapping assays in vivo. Based on domain truncation studies, we showed that the AKT-interacting domain of TMCC3 was essential for TMCC3-induced AKT activation, self-renewal, and metastasis. Clinically, TMCC3 mRNA expression in 202 breast cancer specimens as determined by qRT-PCR assay showed that higher TMCC3 expression correlated with poorer clinical outcome of breast cancer, including early-stage breast cancer. Multivariable analysis identified TMCC3 expression as an independent risk factor for survival. These findings suggest that TMCC3 is crucial for maintenance of BCSCs features through AKT regulation, and TMCC3 expression has independent prognostic significance in breast cancer. Thus, TMCC3 may serve as a new target for therapy directed against CSCs.
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http://dx.doi.org/10.1038/s41388-021-01729-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062265PMC
April 2021

Amongst Women Stratified to Receive Endocrine Therapy on the Basis of Their Tumor Estrogen and Progesterone Receptor Levels, Those with Higher Tumor Progesterone Receptor Levels Had a Better Outcome Than Those with Lower Levels of Tumor Progesterone Receptor.

Cancers (Basel) 2021 Feb 21;13(4). Epub 2021 Feb 21.

Department of Pathology and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, No. 161, Section 6, Minquan E. Road, Neihu District, Taipei 114, Taiwan.

Background: To realize the association between stratified expression levels of ER and PgR and long-term prognosis of breast cancer patients who received adjuvant hormone therapy, this study aimed to propose better prognostic cut-off levels for estrogen receptor (ER) and progesterone receptor (PgR).

Methods: Patients who received adjuvant hormone therapy after surgical intervention were selected. The ER and PgR status and their effects on breast cancer-specific survival (BCSS) and disease-free survival (DFS) over 5 and 10 years were evaluated. Next, subgroups were generated based on ER and PgR expression percentage and Allred scores. Survival curves were constructed using the Kaplan-Meier method.

Results: ER and PgR expression were significantly associated with better prognosis in 5 years, whereas only PgR expression was significantly associated during the 10-year follow-up. The optimal cut-off values for better 5-year BCSS were ER > 50%; ER Allred score > 7; PgR ≥ 1%; or PgR Allred score ≥ 3; the corresponding values for DFS were ER > 40%; ER Allred score > 6; PgR > 10%; or PgR Allred score ≥ 3. In the long-term follow-up, PgR of > 50% or Allred score of > 5 carriers revealed a better prognosis of both BCSS and DFS.

Conclusion: Patients with a PgR expression > 50% or an Allred score > 5 exhibited better 10-year BCSS and DFS.
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http://dx.doi.org/10.3390/cancers13040905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926358PMC
February 2021

Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium.

Cancer Epidemiol Biomarkers Prev 2021 04 26;30(4):623-642. Epub 2021 Jan 26.

Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype ( > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.

Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026532PMC
April 2021

The effect of age and sex on outcomes following isolated moderate to severe traumatic brain injury.

Eur J Trauma Emerg Surg 2020 Sep 15. Epub 2020 Sep 15.

Comparative Effectiveness and Clinical Outcomes Research Center, Riverside University Health System Medical Center, 26520 Cactus Ave., CPC Building, Suite 102-5, Riverside, Moreno Valley, CA, 92555, USA.

Purpose: The impact of female sex on traumatic brain injury (TBI) outcomes remains controversial. The combined impact of age and sex on TBI outcomes must be clarified. We hypothesized that females have better outcomes than males in the premenopausal age group.

Methods: Data from the 2007-2016 National Trauma Data Bank of the Committee on Trauma-American College of Surgeons were used. Of a total of 686,549 patients with moderate to severe TBI (AIS ≥ 3), 251,491 were female. Comparison analyses of clinical characteristics and outcomes between females and males were conducted at different age groups: < 45 years, 45-55, and > 55 years. Logistic regressions were performed to assess the impact of age and female sex on mortality and complications.

Results: Mortality rate between females and males aged < 45 and 45-55 years was similar, but significantly reduced in the > 55 years group. After multivariate logistic regression analysis controlling for multiple confounding factors, we found that females aged > 55 years had markedly decreased risk of mortality (AOR: 0.857, 95% CI 0.835-0.879, p < 0.001) and complications.

Conclusion: Female patients in the postmenopausal stage have better outcomes following TBI than males, but pre- and perimenopausal females do not, suggesting that female sexual hormones may not provide a significant protective effect on clinical outcomes following isolated moderate to severe TBI.
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http://dx.doi.org/10.1007/s00068-020-01491-1DOI Listing
September 2020

European polygenic risk score for prediction of breast cancer shows similar performance in Asian women.

Nat Commun 2020 07 31;11(1):3833. Epub 2020 Jul 31.

Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore, Singapore.

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.
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http://dx.doi.org/10.1038/s41467-020-17680-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395776PMC
July 2020

A functional variant near XCL1 gene improves breast cancer survival via promoting cancer immunity.

Int J Cancer 2020 04 25;146(8):2182-2193. Epub 2020 Jan 25.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Most genome-wide association studies (GWASs) identify genetic variants for breast cancer occurrence. In contrast, few are for recurrence and mortality. We conducted a GWAS on breast cancer survival after diagnosis in estrogen receptor-positive patients, including 953 Taiwanese patients with 159 events. Through Cox proportional hazard models estimation, we identified 24 risk SNPs with p < 1 × 10 . Based on imputation and integrated analysis, one SNP, rs1024176 (located in 1q24.2, p = 2.43 × 10 ) was found to be a functional variant associated with breast cancer survival and XCL1 gene expression. A series of experimental approaches, including cell-based analyses and CRISPR/Cas9 genome-editing system, were then used and identified the transcription factor MYBL2 was able to discriminately bind to the A allele of rs1024176, the protective variant for breast cancer survival, which promoted XCL1 expression, but not to the G allele of rs1024176. The chemokine XCL1 attracts type 1 dendritic cells (DC1s) to the tumor microenvironment. In breast cancer tissues, we applied a two-step Mendelian randomization analysis, using expression quantitative trait loci as instrumental variables, to confirm higher XCL1 expression was correlated with higher DC1 signatures and favorable disease progression, through the causal effect of rs1024176-A allele. Our study supports the genetic effect on preventing breast cancer survival through XCL1-induced DC1 recruitment in tumor microenvironment.
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http://dx.doi.org/10.1002/ijc.32855DOI Listing
April 2020

Propofol-based total intravenous anesthesia did not improve survival compared to desflurane anesthesia in breast cancer surgery.

PLoS One 2019 7;14(11):e0224728. Epub 2019 Nov 7.

Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China.

Background: Breast cancer is the most common cancer in women and several perioperative factors may account for tumor recurrence and metastasis. The anesthetic agents employed during cancer surgery might play a crucial role in cancer cell survival and patient outcomes. We conducted a retrospective cohort study to investigate the relationship between the type of anesthesia and overall survival in patients who underwent breast cancer surgery performed by one experienced surgeon.

Methods: All patients who underwent breast cancer surgery by an experienced surgeon between January 2006 and December 2010 were included in this study. Patients were separated into two groups according to the use of desflurane or propofol anesthesia during surgery. Locoregional recurrence and overall survival rates were assessed for the two groups (desflurane or propofol anesthesia). Univariable and multivariable Cox regression models and propensity score matching analyses were used to compare the hazard ratios for death and adjust for potential confounders (age, body mass index, American Society of Anesthesiologists physical status classification, TNM stage, neoadjuvant chemotherapy, Charlson Comorbidity Index, anesthesiologists, and functional status).

Results: Of the 976 breast cancer patients, 632 patients underwent breast cancer surgery with desflurane anesthesia, while 344 received propofol anesthesia. After propensity scoring, 592 patients remained in the desflurane group and 296 patients in the propofol group. The mortality rate was similar in the desflurane (38 deaths, 4%) and propofol (22 deaths, 4%; p = 0.812) groups in 5-year follow-up. The crude hazard ratio (HR) for all patients was 1.13 (95% confidence interval [CI] 0.67-1.92, p = 0.646). No significant difference in the locoregional recurrence or overall 5-year survival rates were found after breast surgery using desflurane or propofol anesthesia (p = 0.454). Propensity score-matched analyses demonstrated similar outcomes in both groups. Patients who received propofol anesthesia had a higher mortality rate than those who received desflurane anesthesia in the matched groups (7% vs 6%, respectively) without significant difference (p = 0.561). In the propensity score-matched analyses, univariable analysis showed an insignificant finding (HR = 1.23, 95% CI 0.72-2.11, p = 0.449). After adjustment for the time since the earliest included patient, the HR remained insignificant (HR = 1.23, 95% CI 0.70-2.16, p = 0.475).

Conclusion: In our non-randomized retrospective analysis, neither propofol nor desflurane anesthesia for breast cancer surgery by an experienced surgeon can affect patient prognosis and survival. The influence of propofol anesthesia on breast cancer outcome requires further investigation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224728PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837387PMC
March 2020

Two truncating variants in FANCC and breast cancer risk.

Sci Rep 2019 08 29;9(1):12524. Epub 2019 Aug 29.

Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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http://dx.doi.org/10.1038/s41598-019-48804-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715680PMC
August 2019

GPER-induced signaling is essential for the survival of breast cancer stem cells.

Int J Cancer 2020 03 7;146(6):1674-1685. Epub 2019 Aug 7.

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan.

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER /PR breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.
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http://dx.doi.org/10.1002/ijc.32588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003894PMC
March 2020

FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

EBioMedicine 2019 Jul 28;45:25-38. Epub 2019 Jun 28.

Institute of Stem Cell & Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, University of California in San Diego, San Diego, CA, USA. Electronic address:

Background: The transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.

Methods: Interaction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.

Findings: We have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.

Interpretation: These findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan).
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http://dx.doi.org/10.1016/j.ebiom.2019.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642435PMC
July 2019

Integrated omics-based pathway analyses uncover CYP epoxygenase-associated networks as theranostic targets for metastatic triple negative breast cancer.

J Exp Clin Cancer Res 2019 May 9;38(1):187. Epub 2019 May 9.

Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan and National Chung Hsing University, Taichung, 402, Taiwan.

Background: Current prognostic tools and targeted therapeutic approaches have limited value for metastatic triple negative breast cancer (TNBC). Building upon current knowledge, we hypothesized that epoxyeicosatrienoic acids (EETs) and related CYP450 epoxygenases may have differential roles in breast cancer signaling, and better understanding of which may uncover potential directions for molecular stratification and personalized therapy for TNBC patients.

Methods: We analyzed the oxylipin metabolome of paired tumors and adjacent normal mammary tissues from patients with pathologically confirmed breast cancer (N = 62). We used multivariate statistical analysis to identify important metabolite contributors and to determine the predictive power of tumor tissue metabolite clustering. In vitro functional assays using a panel of breast cancer cell lines were carried out to further confirm the crucial roles of endogenous and exogenous EETs in the metastasis transformation of TNBC cells. Deregulation of associated downstream signaling networks associated with EETs/CYPs was established using transcriptomics datasets from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Comparative TNBC proteomics using the same tissue specimens subjected to oxylipin metabolomics analysis was used as validation set.

Results: Metabolite-by-metabolite comparison, tumor immunoreactivity, and gene expression analyses showed that CYP epoxygenases and arachidonic acid-epoxygenation products, EET metabolites, are strongly associated with TNBC metastasis. Notably, all the 4 EET isomers (5,6-, 8,9-, 11,12-, and 14,15-EET) was observed to profoundly drive the metastasis transformation of mesenchymal-like TNBC cells among the TNBC (basal- and mesenchymal-like), HER2-overexpressing and luminal breast cancer cell lines examined. Our pathway analysis revealed that, in hormone-positive breast cancer subtype, CYP epoxygenase overexpression is more related to immune cell-associated signaling, while EET-mediated Myc, Ras, MAPK, EGFR, HIF-1α, and NOD1/2 signaling are the molecular vulnerabilities of metastatic CYP epoxygenase-overexpressing TNBC tumors.

Conclusions: This study suggests that categorizing breast tumors according to their EET metabolite ratio classifiers and CYP epoxygenase profiles may be useful for prognostic and therapeutic assessment. Modulation of CYP epoxygenase and EET-mediated signaling networks may offer an effective approach for personalized treatment of breast cancer, and may be an effective intervention option for metastatic TNBC patients.
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http://dx.doi.org/10.1186/s13046-019-1187-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507159PMC
May 2019

Six novel immunoglobulin genes as biomarkers for better prognosis in triple-negative breast cancer by gene co-expression network analysis.

Sci Rep 2019 03 14;9(1):4484. Epub 2019 Mar 14.

Graduate of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

Gene co-expression network analysis (GCNA) can detect alterations in regulatory activities in case/control comparisons. We propose a framework to detect novel genes and networks for predicting breast cancer recurrence. Thirty-four prognosis candidate genes were selected based on a literature review. Four Gene Expression Omnibus Series (GSE) microarray datasets (n = 920) were used to create gene co-expression networks based on these candidates. We applied the framework to four comparison groups according to node (+/-) and recurrence (+/-). We identified a sub-network containing two candidate genes (LST1 and IGHM) and six novel genes (IGHA1, IGHD, IGHG1, IGHG3, IGLC2, and IGLJ3) related to B cell-specific immunoglobulin. These novel genes were correlated with recurrence under the control of node status and were found to function as tumor suppressors; higher mRNA expression indicated a lower risk of recurrence (hazard ratio, HR = 0.87, p = 0.001). We created an immune index score by performing principle component analysis and divided the genes into low and high groups. This discrete index significantly predicted relapse-free survival (RFS) (high: HR = 0.77, p = 0.019; low: control). Public tool KM Plotter and TCGA-BRCA gene expression data were used to validate. We confirmed these genes are correlated with RFS and distal metastasis-free survival (DMFS) in triple-negative breast cancer (TNBC) and general breast cancer.
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http://dx.doi.org/10.1038/s41598-019-40826-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418134PMC
March 2019

Routine Intraoperative Neuromonitoring of the Recurrent Laryngeal Nerve to Facilitate Complete Resection and Ensure Safety in Thyroid Cancer Surgery.

Am Surg 2018 Dec;84(12):1882-1888

Routine use of intraoperative neuromonitoring (IONM) in thyroid cancer surgery is controversial. We aimed to investigate whether it improves the completeness of thyroidectomy and ensures safety. This retrospective study included 380 thyroid cancer patients who underwent thyroidectomy, by one surgeon, between July 2006 and November 2015. Patients were grouped according to the surgeon's adaptation of IONM, as follows: none (period 1; n = 92), early (period 2; n = 141), and late (period 3; n = 147). The operative time and rates of vocal cord palsy were determined. Surgical completeness was assessed by technetium-99m imaging of the thyroid remnant and serum thyroglobulin measurement before ablation. The rate of recurrent laryngeal nerve (RLN) palsy showed a decreasing trend over time. No permanent RLN palsies occurred in nerves not invaded by tumor after routine IONM was introduced. Technetium-99m uptake (periods 1-3, 0.62 vs 0.32 vs 0.20; < 0.01) and thyroglobulin levels (periods 1 and 2, 37.93 vs 8.98 ng/mL, respectively; = 0.034; period 3, 9.10 ng/mL) progressively decreased. The mean thyroglobulin level dropped significantly after introduction of routine IONM. We conclude that routine IONM during thyroid cancer surgery improves surgical completeness and might prevent permanent RLN palsy over time.
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December 2018

Colon perforation caused by swallowing a shrimp leg: A case report.

Int J Surg Case Rep 2018 4;52:114-116. Epub 2018 Oct 4.

Division of General Surgery, Department of Surgery, Tri-Services General Hospital, National Defense Medical Center, No.325, Sec.2, Chenggong Rd., Neihu District, Taipei City 114, Taiwan. Electronic address:

Introduction: Ingestion of a foreign body rarely results in perforation of the gastrointestinal tract. Foreign bodies such as dentures, fish bones, chicken bones, toothpicks and cocktail sticks have been known to cause bowel perforation; however, bowel perforation caused by shrimp leg has not been reported so far.

Presentation Of Case: We report a case of a 69-years-old man who presented with a 4-months epigastric pain. Laboratory data revealed inflammation at the first hospital visit. Computed tomography revealed a hypodense lesion containing a hyperdense foreign body in the abdomen. Intra-abdominal abscess caused by foreign body perforation was diagnosed.

Discussion: An increased incidence of perforation has been reported in association with Meckel's diverticulum, the appendix, and diverticular disease. The abdominal abscess in this case was located beside the diverticulum of transverse colon, so the perforation most likely occurred in the diverticulum of transverse colon.

Conclusion: Perforation of colon by shrimp leg is very rare and not reported currently. Although some cases have been successfully treated chronic foreign-body perforation with abscess by using antibiotics alone, typical treatments remains surgical drainage of the abscess and removal of foreign body.
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http://dx.doi.org/10.1016/j.ijscr.2018.09.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197384PMC
October 2018

Experienced trauma team leaders save the lives of multiple-trauma patients with severe head injuries.

Surg Today 2019 Mar 9;49(3):261-267. Epub 2018 Oct 9.

Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

The trauma team leader is a professional who receives and treats trauma patients. We aimed to evaluate whether or not the seniority of a qualified trauma team leader was a prognostic factor for multiple-trauma patients managed by a trauma team. This was a retrospective cohort study conducted at a Level I Trauma Center in North Taiwan. From January 2009 to December 2013, 284 patients were randomly assigned to one of two trauma team leaders (junior and senior leaders) on duty, irrespective of the seniority of the qualified trauma team leader. All parameters were collected and compared between these two groups. In the subgroup of multiple-trauma patients with Glasgow Coma Scale (GCS) ≤ 8, there were significant differences in the injury severity score, revised trauma score, and seniority of the leader between the alive and dead groups. A multivariate logistic regression analysis showed that the seniority of the trauma team leader was an important mortality risk factor [odds ratio (OR): 14.529, 95% confidence interval (CI) 1.683-125.429, p = 0.015] in patients with GCS ≤ 8. However, in patients with GCS > 8, age was the only independent risk factor [OR: 1.055, 95% CI 1.023-1.087, p = 0.001]. The seniority of the qualified trauma leader is important for teamwork, organization, and efficiency, all of which play an important role in improving the survival outcome of patients with GCS ≤ 8.
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http://dx.doi.org/10.1007/s00595-018-1723-yDOI Listing
March 2019

A Novel Strategy of Laparoscopic Insufflation Rate Improving Shoulder Pain: Prospective Randomized Study.

J Gastrointest Surg 2019 10 8;23(10):2049-2053. Epub 2018 Oct 8.

Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kung Road, Neihu, 114, Taipei, Taiwan.

Background: Laparoscopic surgery is the main trend method in a variety of surgical fields. Post-operative shoulder pain remains a bothersome issue although many surgical techniques have been applied to minimize it. A simple novel approach to reduce shoulder pain without adverse effects during and after laparoscopic surgery is desired.

Methods: This prospective randomized controlled study was conducted to enroll a total of 140 patients to evaluate the efficacy of low flow rate (1 L/min) for induction followed by high flow rate (10 L/min) for maintaining 12 mmHg pneumoperitoneum (group A, n = 70) during laparoscopic cholecystectomy (LC), compared to the continuous high flow rate group (group B, n = 70) in postoperative shoulder pain and other clinical features. The 10-visual analog scale (VAS) was applied for the severity of shoulder pain and scores were obtained at 1, 6, 12, 24, and 48 h after LC.

Results: There was no obvious difference in baseline characteristics as well as operative time, occurrence of bradycardia, or hospital stay between groups. The incidence of shoulder pain was not significantly different (group A 45.7% vs group B 48.6%, p = 0.866). However, the patients in group A with shoulder pain reported significantly less pain scores (p < 0.001) at 12 and 24 h after surgery, compared with those in group B.

Conclusions: Applying the strategy of low flow rate to induce pneumoperitoneum followed by high flow rate to maintain the pressure provides advantages to reduce the severity of shoulder pain for patients who underwent LC and then experienced shoulder pain.
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http://dx.doi.org/10.1007/s11605-018-3896-5DOI Listing
October 2019

Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression.

Int J Cancer 2019 04 3;144(8):1996-2007. Epub 2019 Jan 3.

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan.

ST3Gal1 is a key sialyltransferase which adds α2,3-linked sialic acid to substrates and generates core 1 O-glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1-silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF-β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC-MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O-glycans are sialyl-3T and disialyl-T. ST3GAL1-silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF-β1 by 2- to 3-fold and thereby dampening TGF-β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse-free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence (p = 0.025, HR = 2.967, 95% CI = 1.14-7.67). Since TGF-β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF-β1 upregulates ST3Gal1 to circumvent the negative impact of VASN.
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http://dx.doi.org/10.1002/ijc.31891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590135PMC
April 2019

Long-term outcomes in elderly patients with resectable large hepatocellular carcinoma undergoing hepatectomy.

Surg Oncol 2018 Sep 17;27(3):595-601. Epub 2018 Jul 17.

Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Division of Transplantation, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address:

Background: In contrast to the feasibility of hepatectomy for resectable large hepatocellular carcinoma (HCC, >5 cm) in the younger patients, the concerns of benefits for the elderly patients remain in practice. This study aimed to evaluate the long-term outcomes and safety after hepatectomy in elderly patients with resectable large HCC compared with younger patients.

Methods: Between 2003 and 2014, a total of 2211 HCC patients were reviewed using a prospective database and 257 patients with resectable large HCC undergoing hepatectomy were included: 79 elderly patients with age ≥70 years and 178 younger patients with age <70 years. The last follow-up was assessed in December 2017. The complications, long-term outcomes and risk factors of disease-free and overall survival were analysed.

Results: The 1-, 3-, 5- and 7-year overall survival rates in the elderly and younger groups were 76%, 55%, 48%, and 42% and 79%, 57%, 51%, and 49%, respectively (P = 0.319). The 1-, 3-, 5-, and 7-year disease-free survival rates in the elderly and younger groups were 60%, 40%, 38%, and 27% and 54%, 36%, 32%, and 32%, respectively (P = 0.633). The analysis of post-operative outcomes of interest, including hospital stay and hospital death and hepatectomy-related complications in both groups revealed no significant difference. Serum albumin and AJCC TNM stage were independent risk factors for survival. Serum alpha-fetoprotein, tumour number and AJCC TNM stage predicted HCC recurrence.

Conclusions: Our results suggested that hepatectomy can achieve comparable long-term outcomes in the selected younger and elderly patients with resectable large HCC.
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http://dx.doi.org/10.1016/j.suronc.2018.07.009DOI Listing
September 2018

Increased Cellular Levels of MicroRNA-9 and MicroRNA-221 Correlate with Cancer Stemness and Predict Poor Outcome in Human Breast Cancer.

Cell Physiol Biochem 2018 15;48(5):2205-2218. Epub 2018 Aug 15.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Background /Aims: Recent studies of microRNA (miRNA) involvement in tumorigenesis have indicated the critical role of these non-coding small RNAs in malignant transformation, but the prognostic role, if any, of miRNAs in breast cancer remains undetermined. Therefore, we assessed the prognostic significance of microRNA-9 (miR-9) and miR-221 in breast cancer toward the goal of understanding the contribution(s) of these miRNAs to cancer cell stemness.

Methods: The level of each of miR-9 and miR-221 in 206 paired laser capture microdissected tumor cells and non-tumor cells was determined by quantitative reverse transcription-PCR (qRT-PCR). The relationship between the miRNA signature and clinicopathological data and prognosis of breast cancer was assessed. Identification of a stem cell-enriched side population was achieved with fluorescence-activated cell sorting and a sphere-forming assay. Wound healing, Boyden chamber assays, and western blotting were used to study the contribution of each miRNA to tumor cell migration and invasion.

Results: We found that induction of miR-9 and miR-221 mimics conferred side-population cells to form spheroidal tumor colonies in suspension culture that maintained the mesenchymal stem-cell potential in non-invasive MCF-7 breast cancer cells. In contrast, knockdown of both miR-9 and miR-221 in invasive MDA-MB-231 breast cancer cells dramatically decreased the number of side-population colonies with stem cell-like potency, which reduced the capacity for tumor-cell renewal, invasion, and migration. Clinically, the mean proportion of miR-9- or miR-221-overexpressing cells was significantly greater in tumor cells compared with non-tumor cells (P < 0.05). Increased levels of miR-9 and miR-221 in breast tissue portended a significantly elevated risk of progression to malignancy with respect to larger tumor size, poor differentiation, late-stage evolution, lymph-node metastasis (P < 0.05), and lower overall survival (Ptrend = 0.017; eight-year follow-up).

Conclusion: Our findings provide strong evidence that miR-9 and miR-221 can enhance the generation of cancer stem cells to yield an invasive phenotype and that overexpression of these miRNAs predicts a poor outcome for breast cancer patients.
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http://dx.doi.org/10.1159/000492561DOI Listing
September 2018

Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.

Cancer Lett 2018 10 21;434:184-195. Epub 2018 Jul 21.

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan; Department of Pediatrics/Hematology Oncology, University of California in San Diego, San Diego, CA, USA. Electronic address:

GFRA1 and RET are overexpressed in estrogen receptor (ER)-positive breast cancers. Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes. Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported. We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells. Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation. Moreover, GDNF induced transcription of ST3GAL1, revealing a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers. Finally, we demonstrated ST3GAL1 knockdown augments anti-cancer efficacy of inhibitors of RET and/or ER. Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
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http://dx.doi.org/10.1016/j.canlet.2018.07.026DOI Listing
October 2018

T1-Weighted Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Distinguish Between Concurrent Cholesterol Granuloma and Invasive Ductal Carcinoma of the Breast: A Case Report.

Am J Case Rep 2018 May 23;19:593-598. Epub 2018 May 23.

Division of General Surgery, Department of Surgery, Tri-Services General Hospital, National Defense Medical Center, Taipei, Taiwan.

BACKGROUND Cholesterol granuloma is a benign condition that can be misdiagnosed as breast cancer on mammographic and ultrasound imaging. A case of concomitant cholesterol granuloma with invasive ductal carcinoma of the left breast was imaged with ultrasound elastography and magnetic resonance imaging (MRI) methods, including T1-weighted dynamic contrast-enhanced MRI (DCE-MRI), before biopsy and histopathology. CASE REPORT A 52-year-old woman, with a previous history of intraduct papillomas in both breasts, underwent six-monthly follow-up breast imaging. The most recent breast mammogram showed a progressively enlarging oval mass in the upper inner quadrant (UIQ) of the left breast, and an adjacent irregular mass with microcalcifications. Virtual Touch IQ (VTIQ) shear wave elastography was used with ultrasound of the breast lesions. T1-weighted fat saturation (T1WFS) MRI, T2-weighted short-tau inversion recovery (STIR) MRI, and T1-weighted DCE-MRI were used to image the left breast. T1-weighted DCE-MRI showed that the oval lesion had a high T1-weighted signal and mild progressive enhancement, with a Type I (benign) time-signal intensity curve; the second, irregular, mass showed rapid, intense enhancement with a washout pattern or Type III (malignant) time-signal intensity curve. Histopathology confirmed that the oval mass was a cholesterol granuloma, and the irregular mass was an invasive ductal carcinoma. CONCLUSIONS A case of concomitant cholesterol granuloma with invasive ductal carcinoma of the left breast, showed that ultrasound with shear wave elastography and T1-weighted DCE-MRI could distinguish between cholesterol granuloma and invasive ductal carcinoma.
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http://dx.doi.org/10.12659/AJCR.909161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994963PMC
May 2018

Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study.

Breast Cancer Res 2017 Nov 7;19(1):119. Epub 2017 Nov 7.

Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain.

Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis.

Methods: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years.

Results: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p < 0.0001), but this effect was not apparent at a later FFTP.

Conclusions: Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.
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http://dx.doi.org/10.1186/s13058-017-0909-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688822PMC
November 2017

Association analysis identifies 65 new breast cancer risk loci.

Nature 2017 11 23;551(7678):92-94. Epub 2017 Oct 23.

Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
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http://dx.doi.org/10.1038/nature24284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798588PMC
November 2017

Erratum to: Rescue strategy for advanced liver malignancy with retrohepatic inferior vena cava thrombi: experience to promote surgical oncological benefit.

World J Surg Oncol 2017 04 28;15(1):91. Epub 2017 Apr 28.

Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.

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http://dx.doi.org/10.1186/s12957-017-1156-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410073PMC
April 2017

Senior general surgery residents can be trained to perform focused assessment with sonography for trauma patients accurately.

Surg Today 2017 Dec 22;47(12):1443-1449. Epub 2017 Apr 22.

Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

Purposes: Researchers studying trauma have found that physicians are able to perform a focused assessment with sonography for trauma (FAST) with minimal training and achieve ideal accuracy. However, there are currently no consensus or standard guidelines regarding the performance of this assessment. The aim of our study was to clarify the value of FAST performed by well-qualified senior general surgery residents in cases of suspected blunt abdominal trauma, which presents an important diagnostic problem in emergency departments.

Methods: This was a retrospective study in the emergency department (ED) of our hospital performed from January 2011 to September 2013. Patients were included if they (1) had undergone a FAST examination performed by qualified residents and (2) had received subsequent formal radiographic or surgical evaluations. The results were compared against subsequent surgical findings or formal Department of Radiology reference standards.

Results: Among the 438 patients enrolled, false-negative results were obtained in 8 and false-positive results in 5. Only one patient was missed and required laparotomy to repair a small intestine perforation. The sensitivity and specificity were 87 and 99%, respectively; the accuracy was 97%.

Conclusions: Senior general surgery residents can be trained to perform accurate FAST examinations on trauma patients.
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http://dx.doi.org/10.1007/s00595-017-1535-5DOI Listing
December 2017
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