Search

Background: Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation. Methods: OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation. Results: IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation. Conclusions: A2B5+OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.

Aims. This study sought to report the 10-year clinical outcomes of patients who underwent unprotected left main (LM) percutaneous coronary intervention (PCI) in a large centre. Methods and Results. A total of 913 consecutive patients who underwent unprotected LM PCI from January 2004 to December 2008 at Fu Wai Hospital were retrospectively analysed; the mean age was 60.0 ± 10.9 years, females accounted for 22% of patients, diabetes was present in 27.7% of patients, and an LM bifurcation lesion occurred in 82.9% of patients. During the median follow-up of 9.7 years, major adverse cardiac or cerebrovascular events (MACCEs) occurred in 25.6% (234) of patients, and the rates of all-cause death, myocardial infarction, and stroke were 14.9%, 11.0%, and 7.1%, respectively. Cardiac death occurred in only 7.9% of patients. The estimated event rate was 41.9% for death/myocardial infarction/any revascularization and 45.9% for death/MI/stroke/any revascularization. Definite/probable stent thrombosis occurred in 4.3% (39) of patients. According to the subgroup analysis, IVUS-guided PCI was associated with less long-term MACCEs. Further multivariate analysis identified that age and LVEF

Heterogeneity in breast cancer leads to diverse morphological features and different clinical outcomes. There are inherent differences in breast cancer between the populations in Asia and in western countries. The use of immune-based treatment in breast cancer is currently in the developmental stage. The VGH-TAYLOR study is designed to understand the genetic profiling of different subtypes of breast cancer in Taiwan and define the molecular risk factors for breast cancer recurrence. The T-cell receptor repertoire and the potential effects of immunotherapy in breast cancer subjects is evaluated. The favorable biomarkers for early detection of tumor recurrence, diagnosis and prognosis may provide clues for the selection of individualized treatment regimens and improvement in breast cancer therapy.Lay abstract We describe the rationale and design for the VGH-TAYLOR study, which includes Taiwanese patients with breast cancer and with a wide spectrum of clinical scenarios covering different breast cancer subtypes and clinical settings, such as the neoadjuvant, adjuvant and metastatic settings. The gene expression profile and genetic mutations of breast cancer subjects with the primary and recurrent tumors are compared. We also explore whether immune-related gene expression and diversity have any impact on response to treatment and survival. This study aims to discover biomarkers of detection of cancer relapse, diagnosis and prognosis that may enable personalized medicine and improvement in breast cancer treatment.

Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed to explore the clinical significance of GPNMB in TNBC. Among 759 specimens, immunohistochemistry (IHC) exhibited GPNMB expressions were variable in different subtypes and significantly higher in TNBC. Kaplan–Meier analysis revealed GPNMB overexpression in TNBC was associated with worse prognosis especially distant metastasis (P = 0.020, HR = 2.515, CI 1.154–5.480). Multivariate analysis showed GPNMB expression was an independent prognostic factor in terms of recurrence and distant metastasis (P = 0.008, HR = 3.22, CI 1.36–7.61; P = 0.017, HR = 3.08, CI 1.22–7.74). In silico analysis showed high mRNA expression of GPNMB was associated with distant metastasis and GPNMB was overexpressed in TNBC. Furthermore, GPNMB positively correlated with epithelial–mesenchymal transition (EMT) regulators, mesenchymal marker vimentin, MMP and integrins. The protein levels of Twist and MMP2 were upregulated by GPNMB overexpression in TNBC cells. GPNMB-enhanced cell invasion was attenuated by broad spectrum MMP inhibitor (GM 6001) and the selective inhibitor of MMP-2 (ARP100). In summary, GPNMB expression is prevalent in TNBC and may be implicated as a prognostic biomarker in patients with TNBC.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Because of the lack of reliable prognostic and predictive biomarkers for CRC, most patients are often diagnosed at a late stage. The tryptophan–kynurenine pathway plays a crucial role in promoting cancer progression. Kynurenine is considered an oncometabolite in colon cancer, and its downstream metabolites are also associated with CRC. Kynurenine 3-monooxygenase (KMO), a pivotal enzyme that catalyzes kynurenine metabolism, is essential for several cellular processes. In the current study, we explored the role of KMO in CRC. Immunohistochemical results showed that KMO was upregulated in CRC tissues relative to paired healthy tissue and polyps. Moreover, CRC patients with higher KMO expression were associated with higher metastasis and poorer survival rates. Knockdown of KMO decreased the expression of cancer stem cell markers, as well as the sphere-forming, migration, and invasion abilities of CRC cells. Additionally, blockade of the enzymatic activity of KMO using an inhibitor suppressed sphere formation and cell motility in CRC cells. These findings suggest the clinical relevance of KMO in CRC tumorigenesis and aggressiveness.

Objective The present study compared 10-year clinical outcomes between transradial access (TRA) and transfemoral access (TFA) for left main (LM) percutaneous coronary intervention (PCI). Background There are limited data regarding the long-term safety and efficacy of TRA for LM PCI. Methods This retrospective study evaluated consecutive patients who underwent unprotected LM PCI between January 2004 and December 2008 at Fu Wai Hospital. The exclusion criteria were age of less than 18 years and presentation with acute myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), which was defined as a composite of all-cause death, myocardial infarction, stroke, and any revascularization at the 10-year follow-up. Results Among 913 eligible patients, TRA was used for 417 patients (45.7%) and TFA was used for 496 patients (54.3%). The 30-day clinical outcomes were similar between the two groups. Results from the 10-year follow-up revealed that MACCE occurred in 180 patients (46.7%) from the TRA group and in 239 patients (51.2%) from the TFA group (log-rank p = .3). The TRA and TFA groups also had low and comparable cumulative rates of all-cause death (14.6% vs. 17.3%, log-rank p = .56) and cardiac death (7.9% vs. 9.1%, log-rank p = .7). Conclusion The present study revealed no significant differences in long-term clinical outcomes when TRA or TFA were used for LM PCI.

Objectives. To assess the impact of different guidewires on stent coating integrity in jailed wire technique (JWT) for bifurcation treatment. Background. JWT is commonly adopted to protect side branch in provisional one-stent strategy for coronary bifurcation lesions. However, this technique may cause defects in stent coatings. The degree of coating damage caused by different types of jailed wires remains unknown. Methods. A fluid model with a bifurcation was established to mimic the condition in vivo. One-stent strategy was performed with three types of guidewire (nonpolymer-jacketed wire, intermediate polymer-jacketed wire, and full polymer-jacketed wire) tested for JWT. Scanning electron microscopy (SEM) was used to evaluate stent coating integrity and wire structure. The degrees of coating defects were recorded as no, slight, moderate, and severe defects. Results. A total of 27 samples were tested. Analyses of SEM images showed a significant difference in the degree of coating damage among the three types of wire after the procedure of JWT ( P < 0.001 ). Nonpolymer-jacketed wire could inevitably cause a severe defect in stent coatings, while full polymer-jacketed wire caused the least coating damages. Besides, there were varying degrees of coil deformation in nonpolymer-jacketed wires, while no surface damage or jacket shearing was observed in full polymer-jacketed wires. Conclusions. Although nonpolymer-jacketed wire has long been recommended for JWT, our bench-side study suggests that full polymer-jacketed wire may be a better choice. Further clinical studies are needed to confirm our findings.

Aim. Based on optical coherence tomography (OCT), we aimed to determine the diagnosis, clinical characteristics, and interventions of braid-like coronary arteries, which are rare and tend to be diagnosed as a woven coronary artery (WCA) anomaly. Methods and Results. We identified braid-like lesions on coronary angiography (CAG) in 7 patients (6 men; median age 47 years; age range 26 to 57 years). All patients were heavy smokers. Four patients were diagnosed with an old myocardial infarction and the other 3 with unstable angina. The braid-like lesions were located in the left anterior descending arteries in 2 patients and in the right coronary arteries in the other 5. TIMI grade 2 flow was observed in all involved vessels. OCT findings of all lesions were consistent with recanalization of organized thrombi, which consisted of septa that divided the lumen into multiple small cavities communicating with each other. No separate three-layered structure could be defined. Based on the significance of the stenosis and its related symptoms, drug-eluting stents were implanted in all of the lesions. All patients experienced symptomatic improvement after the intervention and were followed up event-free for 12 months. Conclusions. Braid-like coronary arteries are likely to undergo recanalization of organized thrombi rather than WCA according to our OCT findings. The majority of cases affect men who smoke heavily. Percutaneous stent implantation may be beneficial in selected patients when feasible.

Purpose: Stimulator of interferon genes (STING) is an upstream regulator of interferon and NF-κB, the key mediators of immune and inflammatory responses associated with cancer, triggered by cytosolic DNA. Downregulation of STING in breast tumor tissues has been reported. STING elicits caspase-8-dependent cell apoptosis via NF-κB in breast cancer cells. STING agonists are considered as potent anti-cancer agents. The current study aims to assess the biological functions of STING in breast cancer progression. Experimental design: Data of mRNA expression levels and recurrence-free survival in patients with breast cancer from The Cancer Genome Atlas and Kaplan Meier-plotter databases were analyzed. Transwell assays were used to evaluate cell migrated and invaded abilities. Sphere formation was performed in stem cell-selective medium and ultra-low attachment plates. Two STING agonists, ADU-S100 and diABZI STING agonist-1 trihydrochloride, were used for in vitro studies. The molecular events were examined by Western blot analysis. Results: Data from public database showed that lower transcripts levels of STING in Her2 and luminal B breast cancer tissues than normal breast tissues. Luminal-type breast cancer cell lines harbored low STING transcripts compared with other subtypes. Importantly, breast cancer patients with low expression levels of STING was associated with worse recurrence-free survival. Results of immunoblotting indicated that breast cancer cell lines have lower STING protein expressions than normal MCF10A cells. Knockdown of STING led to aggressive phenotypes of MCF10A and BT474 cells. In contrast, overexpression of STING suppressed the abilities of migration, invasion and sphere formation of MCF7 and BT474 cells. The markers of epithelial were increased while the markers of mesenchymal and stemness were decreased by STING overexpression. STING agonist slightly suppressed cell viability of breast cancer cells but not MCF10A cells. Treatment of STING agonists reduced cell migrated ability with upregulation of E-cadherin and γ-catenin. Conclusion: These findings suggest that STING serves tumor-suppressive effects in breast cancer. Citation Format: Chun-Yu Liu, Ji-Lin Chen, Chun-Teng Huang, Pei-Yi Chu, Mei-Fang Tseng, Yu-Hsuan Lee, Wan-Lun Wang, Ling-Ming Tseng. Pleiotropic anti-cancer effects of STING in estrogen receptor positive breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2486.

Triple-negative breast cancer (TNBC) is a complex disease associated with the aggressive phenotype and poor prognosis. TNBC harbors heterogeneous molecular subtypes with no approved specific targeted therapy. It has been reported that HER receptors are overexpressed in breast cancer including TNBC. In this study, we evaluated the efficacy of varlitinib, a reversible small molecule pan-HER inhibitor in TNBC. Our results showed that varlitinib reduced cell viability and induced cell apoptosis in most TNBC cell lines but not in MDA-MB-231 cells. MEK and ERK inhibition overcame resistance to varlitinib in MDA-MB-231 cells. Varlitinib inhibited HER signaling which led to inhibition of migration, invasion and mammosphere formation of TNBC cells as well as significant suppression of tumor growth of MDA-MB-468 xenograft mouse model. In summary, these results suggest that HER signaling plays an important role in TNBC progression and that pan-HER inhibition is potentially an effective treatment for TNBC patients.

Objectives The aim of this study was to assess the impact of operator experience on prognosis after left main coronary artery (LM) percutaneous coronary intervention (PCI). Background LM PCI can be technically challenging and potentially risky considering the amount of supplied myocardium. Methods Consecutive patients who underwent unprotected LM PCI at a single institution were included and compared according to whether the primary operator was an experienced, high-volume LM operator (defined as an operator who performed at least 15 LM PCIs per year for at least 3 consecutive years) or not. Kaplan-Meier estimates and Cox proportional hazards models are presented. Results From January 2004 to December 2011, a total of 1,948 patients underwent unprotected LM PCI by 25 operators. Of these, 7 operators (28%) were considered experienced, and 18 (72%) were considered less experienced, with an overall mean experience of 12.0 ± 11.5 LM PCIs per year. LM PCI was performed in 1,422 patients (73%) by experienced operators and in 526 patients (27%) by less experienced operators. Patients treated by experienced operators had more complex and extensive coronary artery disease. Unadjusted and adjusted risks for cardiac death were lower for patients who were treated by experienced operators, both at 30-day (unadjusted hazard ratio [HR]: 0.23; 95% confidence interval [CI]: 0.09 to 0.60; p = 0.003; adjusted HR: 0.22; 95% CI: 0.09 to 0.59; p = 0.003) and 3-year (unadjusted HR: 0.53; 95% CI: 0.32 to 0.89, p = 0.02; adjusted HR: 0.49; 95% CI: 0.29 to 0.84; p = 0.009) follow-up. Discrimination improved when operator experience was added to Cox proportional hazards models containing the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (integrated discriminatory index = 0.004, p = 0.03) or SYNTAX score II (integrated discriminatory index = 0.007, p = 0.02). No significant interaction was detected between operator experience and distal bifurcation LM lesion, 2-stent bifurcation stenting, and intravascular ultrasound use (p > 0.10 for all). Conclusions Patients who underwent LM PCI by high-volume and experienced operators had better short- and long-term prognoses. Operator experience is an important factor in a complex intervention such as LM PCI.

Purpose: Luminal type breast cancers account for the most common subtypes of breast cancers, among which luminal B subtype is relatively faster tumor growing and confers substantial risk of recurrence after primary treatment despite adjuvant endocrine therapy. Understanding the molecular alterations underlying the poorer survival outcome for luminal B tumors represents an unmet medical need. Experimental design: The archival samples of 16 recurrences within 5 years, 3 recurrences between 5-10 years and 24 non-recurrence tumor tissues from luminal B breast cancer patients were retrieved. Genomic alterations of these 43 breast cancer samples were detected using deep next-generation sequencing of a 440-gene panel. The mRNA levels of candidate genes in breast cancer patients were analyzed from The Cancer Genome Atlas (TCGA) database. Results: Overall, genomic alterations were found in 340 genes, including single nucleotide variants and copy number variation. Comparing to the non-recurrence tumors, NUP98 (31.3%), MAPK4 (18.8%), PTEN (18.8%), PER1 (18.8%) and TRIP11 (18.8%) showed higher population frequency in the recurrence tumors, and IGF2R (50.0%), PIM1 (45.8%) and ROS1 (37.5%) were dominate in the non-recurrence tumors. After a validation with the public clinical dataset, we identified three potential prognostic biomarkers, including NUP98, PER1, and TRIP11. We observed missense mutation or copy number deletion of NUP98, PER1 and TRIP11 in early recurrence tumors. Data from TCGA database exhibited patients with breast cancer harbored lower NUP98, PER1 and TRIP11 transcripts levels. Notably, lower NUP98, PER1 and TRIP11 expression levels correlated with worse recurrence-free survival in luminal B breast cancer. Interestingly, based on algorithm for visualization of protein interaction network, we found these 3 genes were all involved in androgen receptor signaling network. Conclusion: Our study identified NUP98, PER1, and TRIP11 which potentially served as biomarkers to predict recurrence in luminal B breast cancer. Further research is required to understand the association between genomic alterations and androgen receptor signaling as well as its clinical impact. Citation Format: Chun-Yu Liu, Ji-Lin Chen, Yi-Ting Yang, Yi-Fang Tsai, Ta-Chung Chao, Kien Thiam Tan, Wan-Lun Wang, Pei-Ju Lien, Shu-Jen Chen, Ling-Ming Tseng. Prognostic genomic alterations associated with recurrence after primary therapy for patients with luminal B breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6468.

The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.

Adjuvant tamoxifen reduces the recurrence rate of estrogen receptor (ER)-positive breast cancer. Previous in vitro studies have suggested that tamoxifen can affect the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/phosphorylation Akt (pAkt) signaling in ER-negative breast cancer cells. In addition to CIP2A, SET nuclear proto-oncogene (SET) oncoprotein is another intrinsic inhibitor of PP2A, participating in cancer progression. In the current study, we explored the clinical significance of SET, CIP2A, PP2A, and Akt in patients with ER-positive breast cancer receiving adjuvant tamoxifen. A total of 218 primary breast cancer patients receiving adjuvant tamoxifen with a median follow-up of 106 months were analyzed, of which 17 (7.8%) experienced recurrence or metastasis. In an immunohistochemical (IHC) stain, SET overexpression was independently associated with worse recurrence-free survival (RFS) (hazard ratio = 3.72, 95% confidence interval 1.26–10.94, p = 0.017). In silico analysis revealed mRNA expressions of SET, PPP2CA, and AKT1 significantly correlated with worse RFS. In vitro, SET overexpression reduced tamoxifen-induced antitumor effects and drove luciferase activity in an Estrogen receptor element (ERE)-dependent manner. In conclusion, SET is a prognostic biomarker in patients with primary ER-positive breast cancer receiving adjuvant tamoxifen and may contribute to the failure of the tamoxifen treatment by modulating the ER signaling. Our study warrants further investigation into the potential role of SET in ER-positive breast cancer.

Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress-related ATF signaling and CIP2A. We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA). In addition, we demonstrated that tunicamycin-induced ER stress in vitro upregulated ATF6 and CIP2A. Mechanistically, we found that ATF6 directly bound to the CIP2A promoter and induced CIP2A gene expression, which contributed to colon cancer cell survival. Furthermore, knockdown of CIP2A reduced the viability of cells under ER stress. Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis. Taken together, our results show that ER stress-related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer. Targeting CIP2A may disrupt ER stress-mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer.

Background: Several platelet function tests are currently used to measure responsiveness to antiplatelet therapy. This study was to compare two tests, light transmittance aggregometry (LTA) and modified thrombelastography (mTEG), for predicting clinical outcomes in Chinese patients after percutaneous coronary intervention (PCI). Methods: Prospective, observational, single-center study of 789 Chinese patients undergoing PCI was enrolled. This study was investigated the correlations between the two tests and performed receiver operating characteristic curve (ROC) analysis for major adverse cardiovascular events (MACEs) at 1-year follow-up. Results: MACEs occurred in 32 patients (4.1%). Correlations were well between the two tests in the adenosine diphosphate induced platelet reactivity (Spearman r = 0.733, P < 0.001). ROC-curve analysis demonstrated that LTA (area under the curve [AUC]: 0.677; 95% confidence interval [CI]: 0.643-0.710; P = 0.0009), and mTEG (AUC: 0.684; 95% CI: 0.650-0.716; P = 0.0001) had moderate ability to discriminate between patients with and without MACE. MACE occurred more frequently in patients with high on-treatment platelet reactivity (HPR) when assessed by LTA (7.4% vs. 2.7%; P < 0.001), and by TEG (6.7% vs. 2.6%; P < 0.001). Kaplan-Meier analysis demonstrated that HPR based on the LTA and mTEG was associated with almost 3-fold increased risk of MACE at 1-year follow-up. Conclusions: The correlation between LTA and mTEG is relatively high in Chinese patients. HPR measured by LTA and mTEG were significantly associated with MACE in Chinese patients undergoing PCI.

Background: Whether final kissing balloon (FKB) dilatation after one-stent implantation at left-main (LM) bifurcation site remains unclear. Therefore, this large sample and long-term follow-up study comparatively assessed the impact of FKB in patients with unprotected LM disease treated with one-stent strategy. Methods: Total 1528 consecutive patients underwent LM percutaneous coronary intervention in one center from January 2004 to December 2010 were enrolled; among them, 790 patients treated with one drug-eluting stent crossover LM to left anterior descending (LAD) with FKB ( n = 230) or no FKB ( n = 560) were comparatively analyzed. Primary outcome was the rate of major adverse cardiovascular events, defined as a composite of death, myocardial infarction (MI) and target vessel revascularization (TVR). Results: Overall, The prevalence of true bifurcation lesions, which included Medina classification (1,1,1), (1,0,1), or (0,1,1), was similar between-groups (non-FKB: 37.0% vs. FKB: 39.6%, P = 0.49). At mean 4 years follow-up, rates of major adverse cardiovascular events (non-FKB: 10.0% vs. FKB: 7.8%, P = 0.33), death, MI and TVR were not significantly different between-groups. In multivariate propensity-matched regression analysis, FKB was not an independent predictor of adverse outcomes. Conclusions: For patients treated with one-stent crossover LM to LAD, clinical outcomes appear similar between FKB and non-FKB strategy.

Objectives Triple negative breast cancer (TNBC) lacks specific drug targets and remains challenging. Palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor is approved for metastatic estrogen receptor (ER)-positive and human epithermal growth factor 2 (HER2)-negative breast cancer. The nature of cell cycle inhibition by palbociclib suggests its potential in TNBC cells. Retinoblastoma (RB, a known substrate of CDK4/6) pathway deregulation is a frequent occurrence in TNBC and studies have revealed that pharmacological CDK4/6 inhibition induces a cooperative cytostatic effect with doxorubicin in RB-proficient TNBC models. In addition, recent studies reported that anti-androgen therapy shows preclinical efficacy in androgen-receptor (AR)-positive TNBC cells. Here we examined the effect of palbociclib in combination with an anti-androgen enzalutamide in TNBC cells. Method MDA-MB-453, BT-549, MDA-MB-231 and MDA-MB-468 TNBC cell lines were used for in vitro studies. Protein expressions were assessed by Western blot analysis. Cytostatic effect was examined by MTT assay. Cell cycle and apoptosis were examined by flow cytometry. Results Palbociclib showed inhibitory effect in RB-proficient TNBC cells, and enzalutamide inhibited cell viability in AR-positive TNBC cells. Enzalutamide treatment could enhance the palbociclib-induced cytostatic effect in AR-positive/RB-proficient TNBC cells. In addition, palbociclib-mediated G1 arrest in AR-positive/RB-proficient TNBC cells was attenuated by RB knockdown. Conclusion Our study provided a preclinical rationale in selecting patients who might have therapeutic benefit from combining CDK4/6 inhibitors with AR antagonists.

ObjectivesThis study sought to evaluate the long-term prognostic capacity of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score II (SS-II) and compare it with other risk scores among patients undergoing left main percutaneous coronary intervention (LM-PCI).BackgroundRecently, the SS-II was developed in an attempt to individualize and help the decision-making process between PCI and coronary artery bypass graft (CABG) surgery in the management of complex coronary artery disease (CAD). However, there is a paucity of data regarding the utility of SS-II in patients undergoing LM-PCI.MethodsData from 1,528 consecutive patients from a single center undergoing unprotected LM-PCI were prospectively collected. The SS-II and other scores were then derived using patients’ baseline clinical characteristics. Patients were stratified according to tertiles of SS-II for PCI: SS-II ≤21 (n = 508), SS-II >21 and ≤28 (n = 480), and >28 (n = 540). Predictive capability for long-term mortality was compared between angiographic scores and scores combining both angiographic and clinical variables.ResultsAt a mean follow-up of 4.4 years, mortality in the first, second, and third SS-II tertiles was 1.8%, 3.5%, and 9.4%, respectively (p < 0.0001). Multivariate analysis showed SS-II to be a strong independent predictor of mortality (hazard ratio: 1.76, 95% confidence interval: 1.10 to 2.82; p = 0.02) after LM-PCI. When compared with the angiographic SS, scores combining both clinical and angiographic variables, such as the SS-II, were superior in terms of long-term prognostication.ConclusionsResults of this large series of consecutive patients who underwent unprotected LM-PCI suggested that the SS-II has better long-term prognostic power in terms of mortality compared with the original purely angiographic SS.

Objectives The aim of the present study was to evaluate the safety, feasibility, procedural, and long-term outcomes by the transradial (TR) approach as compared to transfemoral (TF) approach in patients with triple vessel coronary artery disease undergoing one-stage percutaneous coronary intervention. Background The feasibility, safety, and efficacy between the TR and TF approach for coronary interventional treatment have been compared in some complex situations including AMI and unprotected left main disease. However, in terms of triple vessel disease (3VD) intervention, there has been no comparison regarding procedural and long-term outcomes between the TR and TF approach. Methods A total of 4,974 consecutive patients (TR n = 3,856, TF n = 1,118), who were diagnosed with 3VD without LM disease and underwent one-stage percutaneous revascularization, were enrolled in the study. Procedural results and clinical outcomes were obtained through database and follow-up. We used the propensity score matching method and obtained 930 pairs of patients with comparable baseline data in order to compare the procedural and long-term outcome between TR and TF groups. In the study cohort, risk reduction of all the clinical outcomes were evaluated with Cox's proportional-hazards models. Cumulative incidences concerning safety and efficacy of the cohort were estimated by the Kaplan–Meier method and a comparison was made utilizing the log-rank test. Results After propensity score matching, the baseline clinical and angiographic characteristics were similar between the 2 groups. Regarding procedural results, no significant differences were observed between the 2 groups, with the exception of a decreased hospital stay (TR 7.49 ± 4.46 days vs. TF 8.63 ± 6.23 days, P

To investigate the relevant factors of coronary artery disease (CAD) in young people under 40 years of age.The study population was 292 young patients accepting coronary angiography in Fuwai Hospital from July to December 2006, including 272 men and 20 women, with the mean age being 36.7 ± 3.7 years. The diagnosis of CAD was made in the cases presenting ≥ 50% stenosis in coronary lumen in coronary angiography. Based on the diagnosis, 217 patients (204 men, 13 women) were assigned to CAD group, and 75 (68 men, 7 women) to non-CAD group. Clinical data and metabolic characteristics of the patients were collected and analyzed using t-test, χ² test, and multinomial logistic regression with SPSS 8.0 software.Most study subjects were current smokers (209/292, 71.6%), and more than half had body mass index (BMI)24 kg/m² (230/292, 78.8%) and usually took high-fat diet (162/292, 55.5%). The proportion of heavy smokers (smoking history ≥ 10 years and ≥ 20 cigarettes per day) were significantly higher in the CAD group than in the non-CAD group [20.7% (45/217) vs. 9.3% (7/75), P=0.015)]. Heavy smoking [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.74-2.05], hypertension (OR, 1.56; 95% CI, 1.48-1.65), alcohol (OR, 1.37; 95% CI, 1.30-1.46), type 2 diabetes mellitus (OR, 1.37; 95% CI, 1.25-1.50), high-fat diet (OR, 1.35; 95% CI, 1.28-1.43), and BMI24 kg/m² (OR, 1.09; 95% CI, 1.03-1.17) were factors related to CAD in the young patients (all P0.05). Total cholesterol (4.56 ± 1.46 mmol/L vs. 4.09 ± 1.00 mmol/L), low-density lipoprotein cholesterol (2.38 ± 1.11 mmol/L vs. 2.14 ± 0.63 mmol/L), lipoprotein a (134.97 ± 109.70 mg/L vs. 101.58 ± 58.39 mg/L), uric acid (359.89 ± 100.09 μmol/L vs. 336.75 ± 94.36 μmol/L), erythrocyte sedimentation rate (9.98 ± 12.19 mm/hour vs. 4.89 ± 4.92 mm/hour), high-sensitivity C-reactive protein (3.42 ± 4.39 mg/L vs. 2.80 ± 3.77 mg/L) and Big endothelin-1 (1.41 ± 1.50 fmol/mL vs. 0.77 ± 1.13 fmol/mL) in plasma were significantly increased in the CAD group compared with the non-CAD group (all P0.05).Heavy smoking, hypertension, alcohol consumption, type 2 diabetes mellitus, high-fat diet and BMI24 kg/m² were significantly related to CAD in patients aged ≤ 40, with heavy smoking presenting the highest OR. Metabolic syndrome and inflammation were also more common in young CAD patients than in non-CAD patients.

Patient Initials or Identifier Number PSL ### Relevant Clinical History and Physical Exam A 60-year male for chest discomfort ongoing 50 meters, could be relieved by rest or sublingual nitroglycerin for 3-5 minutes. The coronary risk factor was hypertension, hyperlipidemia current smoking.PE

Purpose: Tryptophan-kynurenine pathway involves in inflammation, immune response and tumorigenesis, in which kynurenine 3-monooxygenase (KMO), an outer mitochondrial membrane protein, mediating kynurenine metabolism. Previous studies indicated KMO showed increased activity in breast cancer. Triple-negative breast cancer (TNBC) tumors exhibited elevated levels of tryptophan metabolites compared to estrogen receptor positive breast cancers. We aimed to study the role of KMO in human TNBC. Experimental design: The gene alterations and transcripts of enzymes in kynurenine metabolism were analyzed from The Cancer Genome Atlas (TCGA) database. Immunohistochemical staining for KMO was performed and a H-score was assigned to quantify protein expression. Epithelial-mesenchymal transition (EMT) phenotypes were examined by transwell assay and EMT markers expressions. Stemness properties were assessed by mammosphere assay and pluripotent genes expressions. The molecular events were analyzed by Western blot, quantitative real-time PCR and luciferase reporter assay. Tumor growth and metastasis were conducted in nude mice and NOD-SCID mice by subcutaneous and tail vein injection respectively. Results: TCGA databases showed KMO but not KYNU and KAT2 was amplified in breast cancer. Both the data from TCGA and our in-house IHC-based tissue-microarray exhibited increased KMO expression in TNBC compared to normal tissue. In vitro, overexpression of KMO in TNBC cells resulted in increased cell growth and colony formation. The abilities migration and invasion as well as EMT markers expressions of TNBC cells were elevated by KMO overexpression. In addition, KMO increased mammosphere formation, pluripotent genes expressions and promoter activities. However, inhibition of KMO enzymatic activity by KMO inhibitors did not affect cancer progression or mitochondrial respiration of TNBC cells. KMO upregulated β-catenin, the upstream regulator of pluripotent genes, CD44 and Nanog expressions. Mechanistically, data showed KMO expressed in both cytosol and nuclear fractions and was associated with β-catenin. KMO enhanced pluripotent genes expressions through β-catenin upregulation. Importantly, KMO knockdown suppressed tumor growth and expressions of β-catenin, CD44 and Nanog in TNBC tumors. Moreover, KMO knockout significantly decreased lung metastasis in vivo. Conclusion: Our data indicated KMO can play an oncogenic role in TNBC, acting as a novel regulator of pluripotent genes via β-catenin and promoted TNBC progression. Citation Format: Chun-Yu Liu, Tzu-Ting Huang, Ji-Lin Chen, Chia-Han Lee, Wan-Lun Wang, Ka-Yi Lau, Chun-Teng Huang, Pei-Yi Chu, Hsin-Chen Lee, Ling-Ming Tseng. Kynurenine 3-monooxygenase (KMO) acts as a novel oncoprotein in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1711.

Background Drug-eluting stents (DES) are currently the most popular treatment modality for restenosis in bare metal stents and DES. This study compares risks of adverse cardiovascular events between DES-treated in-stent restenosis (ISR) and de novo lesions, an area that has not been systematically studied thus far. Methods and Results One thousand three hundred consecutive ISR patients were compared with 27,211 patients with de novo lesions who underwent DES treatment during the same period at the Fu Wai Hospital in Beijing. Angiographic success rate was similar between the ISR and de novo groups (98.0% vs. 98.2%; P = 0.61). Using logistic regression to derive the propensity score model, 1,266 matched patient pairs were compared. In this adjusted model, the rate of target lesion revascularization (TLR) was significantly higher in the ISR group (19.19% vs. 2.37%; P

Background A limited number of studies on the impact of complete revascularization (CR) vs. incomplete revascularization (IR) on long-term outcomes in patients with multivessel coronary disease (MVD) in current percutaneous coronary intervention (PCI) practice have yielded inconsistent results. Methods Between April 2004 and November 2010, 7,376 consecutive patients with MVD underwent PCI at the Fuwai Hospital in Beijing, China. Patients who underwent prior CABG and those who had an acute myocardial infarction (MI) within 24 hr before revascularization or presented with cardiogenic shock were excluded. Angiographic CR was defined as successful angioplasty of all diseased lesions in the major epicardial coronary vessels and their first degree side branches (diameter ≥2.5 mm), and proximal CR was defined as successful angioplasty of all diseased proximal arteries. Results Among 7,065 patients with MVD undergoing PCI treatment, angiographic CR was performed in 1,188 patients (16.8%), and proximal CR in 2,053 patients (29.1%). The study found that either angiographic or proximal IR were associated with significantly higher estimated 3-year rate of cardiac death (2.55% vs. 1.13%, log-rank P = 0.016; and 2.70% vs. 1.43%, log-rank P = 0.024, respectively). After adjustment for differences in baseline characteristics between IR and CR patients, angiographic IR was associated with a significantly higher rate of cardiac death (adjusted hazards ratio [HR]: 2.56, 95% confidence interval [CI]: 1.03–6.41) while proximal IR was associated with a numerically higher rate of cardiac death (adjusted HR: 1.72, 95% CI: 0.93–3.17). For the subgroup of ≥2-vessel IR with total occlusion, either angiographic or proximal IR patients had significantly higher rate of cardiac death (adjusted HR: 4.25, 95% CI: 1.50–12.09; and adjusted HR: 3.02, 95% CI: 1.40–6.52, respectively). Conclusion Compared with IR, patients with CR had better clinical outcomes, supporting CR as first choice for patients with MVD. © 2013 Wiley Periodicals, Inc.

Objective To investigate the outcomes of overlapping drug-eluting stenting (DES) in small and diffuse lesions. Background Clinical outcomes of overlapping heterogeneous versus homogeneous DES of diffuse lesions (requiring ≥30 mm of length) in small coronary arteries (requiring ≤2.75 mm of diameter) are unknown. Methods From January 2005 to December 2009, there were 99 patients with diffuse lesions in small coronary arteries receiving overlapping heterogeneous DES, and 558 patients receiving overlapping homogeneous DES at our institution. The clinical end-point of the study included in-hospital and 12-month major adverse cardiac events (death, nonfatal myocardial infarction, and target vessel revascularization (TVR). Results There were no statistically significant differences between overlapping heterogeneous and homogeneous DES groups in-hospital (2.0% vs. 1.4%, respectively; P = 0.66) and 12-month (9.1% vs. 9.3%, respectively; P = 0.94) major adverse cardiac events. After adjustment, no significant differences for major adverse cardiac events were noted, but the rate of nonfatal myocardial infarction was lower in overlapping homogeneous DES group (odds ratio: 4.20, P = 0.03). Conclusion In this analysis, there were no significant differences in major adverse cardiac events between the 2 types of overlapping DES for diffuse lesions in small coronary arteries, except for higher nonfatal myocardial infarction in overlapping heterogeneous DES. (J Interven Cardiol 2013;26:264–270)

Introduction Both CYP2C19 genotyping and platelet function testing are used to predict major adverse cardiac events (MACEs) in Chinese patients treated with clopidogrel and undergoing stent implantation, but the most accurate prognostic technique is still debated. Here, we combine both techniques, to determine if a more accurate prognosis is possible. Methods Patients undergoing stent implantation (1104) were genotyped and assessed for platelet reactivity, with a 12-month follow-up. The CYP2C19*2 (rs4244285), and *3 (rs4986893) alleles were genotyped. High on treatment platelet reactivity was defined as adenosine diphosphate (ADP)-induced platelet inhibition ≤ 30%. MACEs included death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis. Results and conclusions Hazard ratios (HRs) for cardiovascular ischemic outcomes based on the two testing methods are as follows. CYP2C19 genotyping: carriers of CYP2C19 loss-of-function alleles, HR: 2.515, 95% confidence interval (CI), 1.150–5.501, P = 0.021; ADP-induced platelet inhibition ≤ 30%, HR: 1.992, 95% CI, 1.040–3.818, P = 0.038. An ischemic risk score between zero and two was calculated. Compared with the group with a score of zero, HRs for adverse cardiovascular outcomes were 4.078 for those with a score of two (95% CI: 1.525–10.905, P = 0.005). However, there was no significant difference between the group with the score of zero and the group with the score of one. CYP2C19 genotyping combined with platelet reactivity is an independent and additive predictor of 1-year MACE in Chinese patients undergoing stenting with clopidogrel treatment, which is better than either test alone.

Background Transradial percutaneous coronary intervention ( PCI ) has been increasingly adopted in clinical practice, given its potential advantages over transfemoral intervention; however, the impact of different access strategies on costs and clinical outcomes remains poorly defined, especially in the developing world. Methods and Results Using data from a consecutive cohort of 5306 patients undergoing PCI in China in 2010, we compared total hospital costs and in‐hospital outcomes for transradial intervention ( TRI) and transfemoral intervention. Patients receiving TRI (n=4696, 88.5%) were slightly younger (mean age 57.4 versus 59.5 years), less often women (21.6% versus 33.1%), more likely to undergo PCI for single‐vessel disease, and less likely to undergo PCI for triple‐vessel or left main diseases. The unadjusted total hospital costs were 57 900 Chinese yuan (¥57 900; equivalent to 9190 US dollars [$9190]) for TRI and ¥67 418 ($10,701) for transfemoral intervention. After adjusting for all observed patient and procedural characteristics using the propensity score inverse probability weighting method, TRI was associated with a lower total cost (adjusted difference ¥8081 [$1283]). More than 80% of the cost difference was related to lower PCI ‐related costs (adjusted difference −¥5162 [−$819]), which were likely driven by exclusive use of vascular closure devices in transfemoral intervention, and lower hospitalization costs (−¥1399 [−$222]). Patients receiving TRI had shorter length of stay and were less likely to experience major adverse cardiac events or post‐ PCI bleeding. These differences were consistent among clinically relevant subgroups with acute myocardial infarction, acute coronary syndrome, and stable angina. Conclusions Among patients undergoing PCI , TRI was associated with lower cost and favorable clinical outcomes compared with transfemoral intervention.

Objectives This study intended to compare outcomes between transradial (TR) and transfemoral (TF) percutaneous revascularization in high-risk coronary anatomy. Background The feasibility, efficacy and safety between TR and TF methods of percutaneous coronary revascularization for unprotected left main coronary artery (UPLM]) disease have not been compared. Methods Among 821 consecutive patients with UPLM disease treated with percutaneous revascularization by either TR (n = 353) or TF (n = 468) vascular access, procedural outcomes, resource use, in-hospital bleeding, and late clinical events were compared according to vascular access method. Results Clinical and angiographic characteristics were similar between groups, except that TR patients less commonly presented with unstable angina and had less UPLM bifurcation disease requiring treatment with 2 stents. No significant differences were observed between TR and TF methods for procedural success (97% TF vs. 96% TR, p = 0.57) or total procedural time. However, duration of hospital stay and in-hospital occurrence of Thrombosis In Myocardial Infarction (TIMI) major or minor bleeding (0.6% vs. 2.8%, p = 0.02) were significantly lower with TR access. Using propensity score modeling (254 matched pairs), over a mean follow-up period of 17 months, rates of cardiovascular death (1.2% vs. 2.0%, p = 0.48), nonfatal myocardial infarction (4.7% vs. 2.4%, p = 0.16), stent thrombosis (0.8% vs. 2.8%, p = 0.10) and any target vessel revascularization (6.0% vs. 6.7%, p = 0.72) did not statistically differ among TR and TF groups, respectively. Conclusions In contrast to TF vascular access, TR percutaneous coronary revascularization for UPLM disease is feasible and associated with similar procedural success, abbreviated hospitalization, reduced bleeding, and comparable late-term clinical safety and efficacy.

Background The introduction of drug-eluting stents (DES) dramatically changed the practice of percutaneous coronary intervention (PCI) in the 2000s. Little is known about trends in in-hospital outcome after PCI in the DES era. Hypothesis The in-hospital outcomes after PCI might be continuously improved over time. Methods We analyzed in-hospital outcomes of 21 667 patients who underwent PCI at Fu Wai Hospital in the past 5 years. The patients were divided into 5 groups according to the time of their intervention: group 1 (June 2004 to May 2005), group 2 (June 2005 to May 2006), group 3 (June 2006 to May 2007), group 4 (June 2007 to May 2008), and group 5 (June 2008 to May 2009). Results Procedural success rates for the 5 groups were 93.6%, 95%, 94.4%, 94.2%, and 94.3%, respectively (P = 0.39). Significant reduction in in-hospital major adverse cardiac events (3.1%, 3.4%, 2.8%, 1.6%, and 1.0%, P < 0.001) and need for target-vessel revascularization (2.0%, 2.2%, 1.5%, 0.4%, and 0.2%, P < 0.001) was noted over time, which was associated with a significant increase in use of DES (from 56.6% to 97.0%, P < 0.001). On multivariate analysis, use of DES, dissection during procedure, left main lesion, prior myocardial infarction, and age ≥ 65 years were independent predictors of major adverse cardiovascular events. Conclusions There were substantial reductions in in-hospital major adverse cardiac events and target-vessel revascularization over the past 5 years. This reduction was associated with the concurrent increased use of DES. Copyright © 2010 Wiley Periodicals, Inc. This work was performed at the Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Background: The incidence of stent thrombosis (ST) following 2 drug-eluting stent (DES) implantations for coronary bifurcation lesions needs to be identified. Methods: From April 2004 to April 2009, 705 consecutive patients with true bifurcation lesions who underwent a double stenting procedure with DES at the Fu Wai Hospital were analyzed. Results: Six (0.85%) patients had a definite ST, all of them had an early (4 acute and 2 subacute) definite ST. Probable ST occurred in 4 patients; in all of these cases, the event occurred early and was adjudicated because of the occurrence of sudden death within 30 days of the procedure. Therefore, a total of 10/705 (1.42%) patients had a definite or probable ST. Possible stent thrombosis was adjudicated only in 1 patient 371 days after the initial PCI in whom the cause of death was unexplained. Compared to the patients without definite and probable ST, patients with definite and probable ST were older, had more unstable angina, lower LVEF, and more left main bifurcation lesions (63.2 ± 8.9 vs. 56.8 ± 10.9 yrs; P = 0.049, 100% vs. 64.7%; P = 0.018, 50.6 ± 9.9 vs. 60.3 ± 12.4%; P = 0.019 and 70.0% vs. 36.1%; P = 0.043). Logistic analysis results indicated that only LVEF (OR 0.92, 95% CI 0.87–0.93; P = 0.017) was associated with definite and probable ST. Conclusions: The present study indicates that modern 2-DES technique for bifurcation lesions was comparatively safe with a low incidence of ST. (J Interven Cardiol 2010;23:346–351)

Purpose: Diffuse large B-cell lymphoma (DLBCL) is aggressive non-Hodgkin lymphoma. It is a heterogeneous disease and is classified as germinal center B-cell like (GCB) and activated B-cell like (ABC) subtypes according to gene-expression profiling. The oncogenic pathways in DLBCL are potential targets for new therapies. In present study, the role and regulation of SET/PP2A/SHP-1/Lyn axis in DLBCL were investigated. Experimental design: U2932, OCL-Ly3, OCI-Ly7, SU-DHL-6 and DB DLBCL cell lines were used for this study. TD-19, a novel SET/PP2A protein-protein interaction inhibitor, was used to address the molecular events of SET signaling. Cell viability was measured by MTT assay. The apoptotic cells were examined by PI/Annexin V staining and Western blotting. SHP-1, Lyn and pLyn were analyzed by immunohistochemistry on lymphoma tissue microarrays from DLBCL patients. Results: We first examined the effects of two different SET inhibitors, TD-19 that is a SET/PP2A protein protein interaction inhibitor, and FTY720 which is a sphingosine analogue that targets SET, on DLBCL cells. TD-19 and FTY720 significantly decreased cell viability and induced apoptosis. SET inhibition activated PP2A and SHP-1 by reducing pPP2AY307 and pSHP-1S591 and inactivated Lyn by decreasing pLynY396. Overexpression of SET rescued these molecular events, and promoted cell growth and migration. Interestingly, we observed the level of SET was declined by TD-19 and TFY720 treatment. We hypothesized Lyn might up-regulate SET expression. Overexpression of Lyn increased SET level, and was accompanied with phosphorylation of PP2A (pPP2AY307) and SHP-1 (pSHP-1S591). Lyn elevated cell growth and migration and suppressed PP2A and SHP-1 activities. Moreover, exogenous SET restored the FTY720- and TD-19-suppressed pSHP-1 and pLyn. Immunohistochemically, high SHP-1 level was linked to low pLyn level of patient with DLBCL and vice versa. Conclusion: This study established the existence of positive feedback of SET/PP2A/SHP-1/Lyn axis in DLBCL cells, and targeting SET could disrupt this regulation. Citation Format: Ji-Lin Chen, Wen-Chun Tsai, Tien-Yun Lan, Chun-Teng Huang, Pei-Yi Chu, Chia-Han Lee, Ka-Yi Lau, Wan-Lun Wang, Kuen-Feng Chen, Chung-Wai Shiau, Chun-Yu Liu. SET/PP2A/SHP-1/Lyn oncogenic signaling contributes to tumor aggressiveness in diffuse large B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4372.

Background: Estrogen receptor (ER) positive breast cancer accounts for 70% of breast cancer. Tamoxifen, a selective ER modulator, remains an important hormone therapeutic agent for patients with ER positive breast cancer. A number of patients receiving adjuvant tamoxifen still experience recurrence in the long term. In current study we explored the clinical significance of four biomarkers including SET, CIP2A, PP2A and Akt in ER positive breast cancer patients receiving adjuvant tamoxifen. Methods: Specimens were from ER positive breast cancer patients treated with adjuvant tamoxifen for a median of duration of 54.8 months with documented outcomes. The median follow-up was 106 months. Immunohistochemical staining for SET, CIP2A, p-PP2A (Tyr 307), p-Akt were performed and a H-score was assigned to quantify protein expression. In silico analysis of gene expression was evaluated from the public database KM plotter (available at: http://kmplot.com/analysis/). Human ER positive breast cancer cell line MCF7 cells were used for in vitro studies. MTT assay, flow cytometry and Western blot were used to assess the cells properties. Estrogen response element (ERE)-dependent luciferase activity was assessed by co-transfection of SET-expressing or control plasmids and 3⊆ERE bearing reporter plasmids into MCF7 cells and stimulated with estrogen. Results: In 218 primary ER positive breast cancer patients treated with adjuvant tamoxifen, 17 (7.8%) suffered from recurrence or metastasis. Higher expressions of SET and CIP2A by IHC analysis were associated with poor recurrence-free survival (RFS). Multivariate analysis revealed SET was independently correlated with worse RFS (Hazard ratio=3.72, 95% confidence interval 1.26-10.94, p=0.017). In silico, KM-plotter analysis revealed higher gene (mRNA) expressions of SET, PPP2CA and Akt1 significantly correlated with worse RFS in breast cancer patients receiving adjuvant tamoxifen therapy. Because SET appeared to be the most prognostic for RFS among the four markers, we next explored the biological role in vitro. Tamoxifen exerted anti-proliferation and apoptotic effects in a dose-dependent manner of MCF7 cells. SET overexpression reduced tamoxifen-induced anti-proliferation in MCF-7 cells, in association with upregulated p-ER, suggesting that SET may affect ER pathway via the serine/threonine kinase PP2A. SET drove luciferase activity in an ERE-dependent manner, and also enhanced estrogen-promoted luciferase activity. Conclusions: Protein SET is a prognostic biomarker in ER positive breast cancer patients treated with tamoxifen and may contribute to tamoxifen resistance by modulating ER signaling pathway. Citation Format: Yu-Hsiang Huang, Pei-Yi Chu, Ji-Lin Chen, Chun-Teng Huang, Chia-Han Lee, Ka-Yi Lau, Wan-Lun Wang, Yu-Ling Wang, Pei-Ju Lien, Ling-Ming Tseng, Chun-Yu Liu. SET overexpression is associated with recurrence-free survival in patients with primary breast cancer receiving adjuvant tamoxifen treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4612.

Background Although the efficacy and safety of Cypher and Taxus stents for particular patients and lesions had been proven by random clinical trials, their long-term comparative effect for unselected Chinese patients in daily practice is still unknown. Methods From April 2004 to April 2005, 682 consecutive patients who were implanted with a Cypher stent (C group: n = 456, 57.3 ± 10.8 years old) or a Taxus stent (T group: n = 226, 57.2 ± 10.2 years old) in our center were analyzed. A mean 3 year clinical and 7 month angiographic follow-up was performed. Results There was no difference in major adverse cardiac events (MACE) rates in the C and T groups (16.4% vs 21.7%; P = .113), and there was also no difference in cardiac death or myocardial infarction (MI) rates in both groups (2.6% vs 1.8%; P = .598, 3.3% vs 3.5%; P = .826 respectively), but target vessel revascularization (TVR) was higher in the T group (10.5% vs 16.4%; P = .036). There was no difference in total stent thrombosis or its components in both groups (total: 3.9% vs 3.5%; P = 1.000, early: 0.2% vs 0.9%; P = .256, late: 0.7% vs 1.3%; P = .404, and very late: 3.1% vs 1.3%; P = .201 respectively). A 7 month angiographic follow-up indicated that both in-stent and in-segment restenosis rate were significantly lower in the C group (11.1% vs 21.0%; P = .034 and 12.2% vs 24.0%; P = .018), and in-stent and in-segment late loss were significantly smaller in the C group (0.18 ± 0.08 mm vs 0.53 ± 0.38 mm; P = .000 and 0.17 ± 0.09 mm vs 0.38 ± 0.19 mm; P = .000). Conclusion Results from this 3 year follow-up, single-center study showed almost the same effective and safe profile for both Cypher and Taxus stents, except for a better reducing restenosis effect in the Cypher stent. Copyright © 2009 Wiley Periodicals, Inc.

The aim of the study was to evaluate the association between beta-fibrinogen gene -455G/A polymorphism and the plasma fibrinogen level in Chinese patients with different subtypes of coronary heart disease (CHD).We investigated beta-fibrinogen gene -455G/A polymorphism and plasma fibrinogen level in non-CHD control subjects (n = 466) and CHD patients (n = 1,019) including patients with stable angina pectoris (SAP) (n = 674), and acute coronary syndrome (ACS) (n = 345). Increased plasma fibrinogen levels were observed in the CHD groups compared with the control subjects (ACS: 380.92 +/- 92.35 mg/dl, SAP: 352.49 +/- 94.89 mg/dl, control: 311.72 +/- 87.09* mg/dl, *P0.001 vs. ACS and SAP). Individuals with the -455A/A genotype were associated with the highest plasma fibrinogen in the control subjects (P0.001) and patients with SAP (P0.001) but not in patients with ACS (P0.05). Allele frequency and genotype distribution were similar among the three groups (P = 0.314).This study demonstrated that elevated plasma fibrinogen level is related to increased CHD risk. The presence of -455A allele is significantly associated with higher fibrinogen in non-CHD control subjects and SAP patients but not in ACS patients while -455G/A polymorphism is not a risk factor for CHD in the Chinese population.

Objectives To assess the incidence, investigate the predictors and analyze the causes of ventricular fibrillation (VF) during coronary angiography (CA) on the condition of current techniques. Methods From April 2004 to January 2007, a total 22,254 patients (27,798 procedures) received CA procedures in our center; 27 patients developed VF during CA. This report was to retrospectively analyze the clinical basic characteristics, coronary angiographic characteristics and CA procedure records of these patients. Results The incidence of VF during CA was 0.097%. The incidence of VF in radial approaches and femoral approaches was 0.076% and 0.147% (p = 0.085). The VF patients had higher coronary artery bypass grafting (CABG) rates (11.1% vs 2.3%, p = 0.024) and were more likely to have a three-vessel disease (59.3% vs 31.2%, p = 0.002) and a total occlusion lesion (25.9% vs 11.1%, p = 0.014) than non-VF patients. On logistic regression analysis, three-vessel disease (OR: 2.582, 95% CI: 1.165-5.720, p = 0.019) and the history of CABG (OR: 3.959, 95% CI: 1.160-13.513, p = 0.028) were the two independent predictors of VF occurrences. Among 27 episodes of VF, 13 were ischemia-related; 11 were manipulation-related; two were contrast-related; one was hypokalemia-related; and the causes remain unclear in five episodes. Conclusions The incidence of VF during CA is low on the condition of current techniques. The severity of coronary artery disease (CAD) is an independent predictor of VF occurrence during CA. Acute ischemia and inappropriate manipulation may be the two main causes in VF development. Copyright © 2009 Wiley Periodicals, Inc.

An association between admission plasma glucose levels and an increased risk of no-reflow has been well documented. Although HMG-CoA reductase inhibitor (statin) therapy can reduce no-reflow, little is known about its effect on no-reflow in patients with hyperglycemia. In the present study, we investigated whether pretreatment with a statin could reduce no-reflow in patients with hyperglycemia, who underwent primary coronary intervention for acute myocardial infarction (AMI). A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. Blood glucose and creatinine kinase levels were measured on admission. All patients underwent 2-dimensional echocardiography and electrocardiographic analysis just after admission. No-reflow was defined as a Thrombolysis in Myocardial Infarction (TIMI) flow grade

BACKGROUND Multiple randomized clinical trials have demonstrated that drug eluting stents can significantly reduce the rates of restenosis and subsequent adverse events across lesion and patient. We investigated the medium term clinical efficacy and safety of Firebird sirolimus eluting stent (SES) in coronary artery disease. METHODS The sample was 509 consecutive patients with coronary artery disease (CAD) who were treated by Firebird SES and finished three-year clinical follow-up. The occurrences of major adverse cardiac events (MACE) and Academic Research Consortium defined stent thrombosis (ST) were evaluated in patients with and without diabetes mellitus. RESULTS Three hundred and thirty three patients (65.4%) were treated by Firebird SES by off label indications. Angiographic success was achieved in 98.3% of the lesions. MACE and target vessel revascularization rates at 6-month, 1 year's and 3 years' clinical follow-up were 2.4% and 1.4%, 4.1% and 2.8%, 7.9% and 5.1%, respectively. The cumulative 3-year MACE free survival rate was 92.1%. After 3 years, DM patients had significantly higher rates of MACE (13.7% vs 6.4%, P < 0.05) and TVR (9.8% vs 4.0%, P < 0.05) and the cumulative MACE free survival rate was very significantly lower in the DM group (86.4% vs 93.6%, P < 0.05). ST occurred in 7 patients (1.4%) at the end of 3 years' follow-up, 5 of them had definite ST with 4 cases presenting with myocardial reinfarction and 1 with unstable angina, the other 2 with probable ST had reinfarction in the stented coronary territory without angiographic follow-up. There was no difference in occurrence of ST between off label (1.5%) and on label groups (1.1%, P = 0.07). CONCLUSIONS In daily practice, about 2/3 of patients were treated by Firebird SES by off label indications. Medium term clinical follow-up of 3 years indicated CAD patients treated by Firebird SES had a low MACE and acceptable ST rate. DM patients had higher rates of adverse events and than non DM.

UNLABELLED It has been verified that adenosine can attenuate myocardial no-reflow. However, the effects of adenosine on adenosine triphosphate-sensitive K+ (KATP) channel and endothelin-1 (ET-1) are unknown. METHODS Forty mini-swines were randomized into 5 study groups: 8 in the control group, 8 in the adenosine pretreatment group, 8 in the glibenclamide (K(ATP) channel blocker)-treated group, 8 in the adenosine and glibenclamide-pretreated group and 8 in the sham-operated group. An acute myocardial infarction and reperfusion model was created with three-hour occlusion of the left anterior descending coronary artery followed by a one-hour reperfusion. RESULTS Compared with the control group, adenosine significantly decreased the area of no-reflow (myocardial contrast echocardiography: from 78.5 +/- 4.5% to 20.7 +/- 4.1%, pathological means: from 82.3 +/- 1.9% to 21.5 +/- 4.3% of ligation area, respectively; all P < 0.01), reduced necrosis size from 98.5 +/- 1.3% to 75 +/- 4.7% of ligation area, P < 0.05). It also decreased plasma ET-1 and myocardial tissue ET-1. However, glibenclamide abrogated the protective effect of adenosine. CONCLUSION The beneficial effect of adenosine on myocardial no-reflow could be due to its effect on ET-1 via the activation of K(ATP) channel.