tbuckley/cabot-search huggingface dataset:
Interlesion Dependence of the Risk for Restenosis in Patients With Coronary Stent Placement in Multiple Lesions
Authors: AdnanKastrati, AlbertSchömig, ShpendElezi, HelmutSchühlen, ManfredWilhelm, JosefDirschinger
Journal: Circulation (1998)

Background—Little is known about the behavior with regard to restenosis of multiple lesions within the same patient treated with intracoronary stenting. Our objective was to test the hypothesis that there is an intrapatient dependence of restenosis between lesions. Methods and Results—Quantitative analysis was carried out on angiograms obtained before, immediately after, and at 6 months after coronary stent placement in 1734 lesions in 1244 patients. We used a specialized logistic regression that not only accounts for intraclass correlation but also quantifies it in the form of odds ratio (OR) as the change in risk of a lesion to develop restenosis if another companion lesion had restenosis. The model was based on 23 patient- and lesion-related variables with binary restenosis (diameter stenosis ≥50%) as end point. The overall restenosis rate was 27.5%: 24.4% for single-lesion, 28.6% for double-lesion, and 33.8% for ≥3-lesion interventions. After adjustment for the influence of significant factors (hyperc...
Abstract 17584: Only 20 % Patients Under Cardiac Arrest Enjoy Benefit of AEDs in Public Places
Authors: Hiroshi Kaneko, Tetsuo Hatanaka, Seishiro Marukawa, Aki Nagase, Tetsuya Sakamoto
Journal: Circulation (2017)

Introduction: In Japan, the number of automated external defibrillators (AEDs) placed in public area has climbed up to the estimated 530,000. However, of ~120,000 out-of-hospital cardiac arrest (CA...
Abstract 513: Antitumor <i>miR-451a</i> regulatory network is associated with poor prognosis of renal cell carcinoma
Authors: Yasutaka Yamada, Sho Sugawara, Takayuki Arai, Atsushi Okato, Satoko Kojima, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
Journal: Cancer Research (2018)

Abstract Renal cell carcinoma (RCC) is the most common neoplasm of the kidney, and approximately 70-80% of RCCs are classified as clear cell-type (ccRCC). Approximately 350,000 new cases are diagnosed worldwide, with over 140,000 deaths, every year. Although surgical resection remains the only known curative treatment for localized RCC, a significant percentage of these patients develop relapses or metastatic disease, which are associated with a poor prognosis. Recently developed targeted molecular therapies and immunomodulatory agents are currently being widely used for patients with metastatic or recurrent RCC. However, those advanced treatments are restricted to RCC patients in advanced stages of disease and the 5-year survival rate of the patients is only 5-10%. MicroRNAs (miRNAs) belong to a class of noncoding RNA molecules that fine-tune the expression of protein coding/noncoding RNAs by repressing translation or cleaving RNA transcripts in a sequence-dependent manner. Aberrantly expressed miRNAs contribute to the initiation, development, and metastasis of several types of cancers, including RCC. Current advanced technologies can be used to identify dysregulated miRNAs in HNSCC clinical specimens. Identification of differentially expressed miRNAs is the first step to elucidating novel miRNA-mediated RNA networks in cancer cell. Analyses of miRNA expression signature by RNA sequencing revealed that miR-451a is significantly downregulated in RCC tissues. Here, we aimed to identify novel RNA networks for miR-451a regulation in RCC cells. Ectopic expression of miR-451a significantly inhibited cancer cell aggressiveness in RCC cells. The Cancer Genome Atlas (TCGA) showed that low expression of miR-451a was significantly associated with poor survival of patients with RCC (p=0.00305). Genome-wide gene expression analyses were applied to identify miR-451a target genes. A total of 16 genes were identified as putative targets of miR-451a in RCC cells. Among these targets, high expression of 8 genes (F2, CRELD2, MSC, LENG8, CLEC2D, SPC25, PMM2, BST2 and NSMAF) were significantly associated with poor prognosis of the patients with RCC by large numbers of cohort analyses. Downregulated miR-451a acted as an antitumor miRNA in RCC cells. Antitumor miR-451a regulatory network was contributed to RCC aggressiveness. The identification of antitumor-mediated oncogenic networks may lead to a better understanding of RCC pathogenesis. Citation Format: Yasutaka Yamada, Sho Sugawara, Takayuki Arai, Atsushi Okato, Satoko Kojima, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki. Antitumor miR-451a regulatory network is associated with poor prognosis of renal cell carcinoma [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 513.
Ultrathin Cu-TCPP MOF nanosheets: a new theragnostic nanoplatform with magnetic resonance/near-infrared thermal imaging for synergistic phototherapy of cancers
Authors: Bo Li, Xiaoya Wang, Lei Chen, Yanling Zhou, Wentao Dang, Jiang Chang, Chengtie Wu
Journal: Theranostics (2018)

Nanostructures based on metal-organic frameworks (MOFs) have promising potential as theragnostic nanoplatforms for phototherapy of cancer cells. However, the MOFs alone are seldom reported to be used as photothermal agents mainly due to their poor near-infrared (NIR) light absorption. Methods: Ultrathin copper-tetrakis (4-carboxyphenyl) porphyrin (Cu-TCPP) MOF nanosheets were prepared by a facile solvothermal route. The photothermal therapy (PTT), photodynamic therapy (PDT), and T1 -weighted magnetic resonance (MR) imaging capabilities and the high biocompatibility of these composite nanosheets were evaluated in vitro as well as in vivo in a mouse tumor model. Results: The ultrathin Cu-TCPP MOF nanosheets exhibited 1) strong NIR absorption because of the d-d energy band transition of Cu2+ and the ultrathin characteristic translating into excellent photothermal performance, 2) ability to produce singlet oxygen because of the inherent characteristic of TCPP, and 3) capability for MR imaging because of the unpaired 3d electrons of copper. Conclusion: Our study demonstrated that the Cu-TCPP MOF nanosheets are a promising phototherapy nanoplatform with the synergistic ability for PTT and PDT of cancer, guided by MR and infrared thermal imaging.
Abstract 19218: Complete Intimal Healing of the Renal Arteries After Radio-frequency Renal Denervation in Long-term Follow-up by Optical Coherence Tomography
Authors: Tomasz Roleder, Mariusz Skowerski, Andrzej Wiecek, Marcin Adamczak, Beata Czerwienska, Wojciech Wanha, Tomasz Jadczyk, Lukasz Partyka, Grzegorz Smolka, Andrzej Ochala, Dariusz Dudek, Michal Tendera, Zbigniew Gasior, Wojciech Wojakowski
Journal: Circulation (2015)

Intoduction: Although radiofrequency renal denervation (RF-RND) may cause acute spasm, intimal injury and thrombus formation, there are no data on long-term renal artery (RA) healing. Hypothesis: Aim of this study was to assess the RA healing after RF-RND by optical coherence tomography (OCT) imaging and quantitative contrast angiography (QCA) at long-term follow-up. Methods: A single center registry enrolled 12 patients (22 RA) with refractory hypertension previously treated with RF-RND (Symplicity, Medtronic). Imaging studies (QCA and OCT) were done at (mean±SD) 18.41±5.83 months after RF-RND. Results: No adverse events or complications were noted during the follow-up. Ten patients (83%) achieved significant reductions of blood pressure by ≥10 mmHg on 4.50 ± 1.08 medications per patient. OCT analysis involved 518 mm of pullbacks and 518 cross-sections. There were 26 spots of focal intimal thickening found in 10 (83%) patients in 14 (64%) arteries and calcifications in 2 (9%) of treated RA. The mean area of focal intimal thickening was 0.054±0.033 mm2 and it was limited to the intimal layer. No vessel dissection, thrombus, intimal tear or acute vasospasms were observed during the OCT analysis. The QCA revealed that minimal lumen and proximal lumen diameter were smaller after the RND and this difference was persistent at follow-up, as compared to measurements obtained before RND [6.21±1.01 vs. 5.61 ± 0.60, p=0.005 and 5.53±0.99 vs. 5.15±0.67, p=0.034, respectively]. Conclusions: There is a favorable long-term vessel healing after RF-RND without significant RA stenosis. Only focal intimal thickening and a modest reduction of the minimal lumen diameter may be observed in long-term and their relation to the RND procedure needs further studies.
Abstract 1737: Efficacy of immunotherapy is attenuated with age in triple-negative breast cancer
Authors: Sandra S. McAllister, Jaclyn Sceneay, Tyler Laszewski, Molly DeCristo, Jessalyn Ubellacker, Kristin Wilson, Yuanbo Qin, John Hutchinson
Journal: Cancer Research (2018)

Abstract Age is associated with increasing immune dysfunction that includes significant changes to both the innate and adaptive immune responses. These age-related changes could present limitations to the application of immunotherapy in breast cancer, as over 50% of patients are over 60 years old at diagnosis. Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, but remains the only subtype that lacks any type of targeted therapy. Early results from clinical trials of anti-PD-1 therapy in metastatic TNBC patients have shown promise, with approximately 20% of patients demonstrating a partial or complete response. While TNBC incidence is similar in young and old patients, differences in disease progression and outcome with age suggest that treatment needs to be tailored to both age as well as breast cancer subtype. It is not known whether age impacts response to immunotherapy, particularly checkpoint blockade, in breast cancer. Using multiple preclinical models of age-dependent TNBC, we found that aged mice had significantly reduced ability to respond to either anti-PD-L1 or anti-CTLA4. Old mice showed decreased numbers of circulating CD4-positive and CD8-positive T cells, as well as NK cells. Furthermore, PD-1 expression was increased on these populations relative to young mice, suggesting increased immune cell exhaustion with age. The old mice also demonstrated increased central and effector memory T cells, but decreased naive T cells compared to young mice, consistent with reports from clinical studies of aged individuals. These findings suggest decreased ability to respond to neoantigens with age. Importantly, using high-content flow cytometric analyses and RNA-seq, we defined cellular and molecular mechanisms that correlate with response in young mice that are attenuated or lacking in old mice. Many of the differentially expressed genes that defined response to anti-CTLA4 in young mice and resistance to treatment in the old mice were also predictors of response to immunotherapy in cancer patients. Our data suggested novel combination therapies that, when combined with checkpoint blockade, improved responses and survival in old mice with TNBC. Our findings should suggest age-stratified treatments to ensure that TNBC patients see the most benefit possible and prevent overtreatment with futile and harsh chemotherapies. Citation Format: Sandra S. McAllister, Jaclyn Sceneay, Tyler Laszewski, Molly DeCristo, Jessalyn Ubellacker, Kristin Wilson, Yuanbo Qin, John Hutchinson. Efficacy of immunotherapy is attenuated with age in triple-negative breast cancer [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 1737.
Abstract 3555: TREM2 is upregulated and plays oncogenic role in gastric cancer
Authors: Yulong Zheng, Lihua Jiang, Cheng Xiao, Nong Xu, Qiqi Gao, Yinan Yao, Yongxian Hu, Yun Sun, Xin Xu
Journal: Cancer Research (2018)

Abstract Background Triggering receptor expressed on myeloid cells-2 (TREM2) is thought to be invovled in innate immunity and inflammation regulation. More recently, the importance of TREM2 has been highlighted by identification in several kinds of solid tumors. Nonetheless, the oncogenic roles and potential molecular mechanisms of TREM2 in gastric cancer (GC) remain unknown. Methods The expression levels of TREM2 were determined by quantitative PCR (qPCR) and immunohistochemistry (IHC). MTT, colony formation, 5-Ethynyl-2′-deoxyuridine (EdU) incorporation, and in vivo tumorigenicity assays were performed to determine the pro-proliferative role of TREM2 in GC cells. mRNA sequencing, qPCR, and Western blotting were used to explore the underlying molecular mechanism of pro-proliferative role of TREM2 in GC cells. Results The mRNA expression of TREM2 was markedly up-regulated in tumor tissues (n=16) in comparison with that in corresponding non-tumorous tissues. Immunohistochemical study were performed to determine the protein expression in 108 patients with surgically resected GC. Its expression was positively associated with TNM stage (P=0.023) and T classification (P=0.021), and was inversly correlated with the poor clinical outcome of the patients. The human GC cell lines MGC-803 and BGC-823 were used for proliferation analysis. The transfected GC cell lines with stable overexpression of TREM2 were established. Ectopic overexpression of TREM2 in GC cells promoted cell proliferation, whereas loss of TREM2 function inhibited proliferation. In vivo animal experiments further validated the pro-proliferative role of TREM2. Deep sequencing to profile global gene expression of MGC-803 cells with TREM2 overexpression. In the biological process analysis, these differentially expressed genes were mainly involved in the MAPK signaling. Molecular mechanistic investigations explored that TREM2 upregulated GREM1 expression, thereby activating ERK1/2 signaling via VEGFR2-PLC-γ-PKC axis and promoting GC cell proliferation. Conclusion High TREM2 expression predicts poor prognosis in GC and TREM2 promotes GC cells proliferation. Our findings suggest that GREM1-VEGFR2-PLC-γ-PKC-ERK1/2 signaling axis contributes to the oncogenic roles of TREM2 on GC cells. TREM2 could be an effective prognostic biomarker and a potential therapeutic target. Citation Format: Yulong Zheng, Lihua Jiang, Cheng Xiao, Nong Xu, Qiqi Gao, Yinan Yao, Yongxian Hu, Yun Sun, Xin Xu. TREM2 is upregulated and plays oncogenic role in gastric cancer [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 3555.
Abstract 2903: A novel compound induces synthetic lethality for p53 mutations in osteosarcoma cells
Authors: Tomoo Iwakuma, Alejandro Parrales, Peter McDonald, Anuradha Roy, Mitchell W. Braun, Frank J. Schoenen, Jenna Wang, Steve Rogers, Melinda Broward, Tyce Bruns, Shrikant Anant, Dan A. Dixon, Fred Meyer, Katherine M. Chastain, Douglas H. Thamm, Scott J. Weir, Kathleen Neville, Joy M. Fulbright
Journal: Cancer Research (2018)

Abstract Osteosarcoma is the second-highest cause of cancer-related death in children and adolescents. Despite advances in chemotherapy and surgery, the survival rate for metastatic osteosarcoma remains below 30% for the last three decades. Discovery of new chemotherapy agents would be crucial for improving outcomes of osteosarcoma patients. Here, using high-throughput screening, we have found a new compound, called 2-{2-[(3,5-dimethoxybenzyl)sulfanyl]-1,3-thiazol-4-yl}-N-(2-thienylmethyl)acetamide (referred to as KU0171032), as an inducer of apoptosis in various canine and human osteosarcoma cells. This compound shows minimal effects on non-transformed osteoblast and fibroblast cells. Intriguingly, KU0171032-induced apoptosis is more robust in osteosarcoma cells having mutant p53 or null for p53, as compared to cells with wild-type p53. Knockdown of wild-type p53 in U2OS and SJSA-1 cells significantly enhances sensitivity to KU0171032 with increase in DNA damage and caspase-3 cleavage. Moreover, KU0171032 significantly reduces in vivo tumor growth of osteosarcoma cells with p53 knockdown or carrying mutant p53. Our results strongly suggest that KU0171032 shows synthetic lethality with p53 mutations in osteosarcoma cells. Given that loss of p53 activity is frequent event in many cancer types including osteosarcoma while normal cells usually retain wild-type p53, this compound could be used to develop novel therapeutic strategies that capitalize on vulnerabilities in osteosarcoma and other types of cancer. Citation Format: Tomoo Iwakuma, Alejandro Parrales, Peter McDonald, Anuradha Roy, Mitchell W. Braun, Frank J. Schoenen, Jenna Wang, Steve Rogers, Melinda Broward, Tyce Bruns, Shrikant Anant, Dan A. Dixon, Fred Meyer, Katherine M. Chastain, Douglas H. Thamm, Scott J. Weir, Kathleen Neville, Joy M. Fulbright. A novel compound induces synthetic lethality for p53 mutations in osteosarcoma cells [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 2903.
Abstract 2200: Intratumoral heterogeneity of copy number variation in lung cancer harboring L858R via immunohistochemical heterogeneous staining
Authors: Takafumi Hashimoto
Journal: Cancer Research (2018)

Abstract Background: Acquired resistance to EGFR-TKI is an inevitable event for advanced lung cancer patients harboring the EGFR-activating mutation. Although intratumoral heterogeneity is commonly observed in several cancers, such as renal cell carcinoma, few studies have shown its presence in EGFR-mutated lung cancer. We analyzed the intratumoral heterogeneity in EGFR-mutated (L858R) lung cancer through immunohistochemistry (IHC) for the primary site and targeted sequencing for specific cases in order to clarify the mechanism of acquired resistance. Methods: Twenty resected primary lung cancers known to harbor EGFR L858R were analyzed. IHC was performed using an L858R mutant-specific rabbit monoclonal antibody (clone43B2; Japan) and the samples were scored by staining intensity (0-3) and proportion. For cases with heterogeneous L858R protein expression, the nucleic acids were extracted from each differently stained lesion, and targeted sequencing (Oncomine Cancer Research Panel) was performed. Single-nucleotide variations (SNVs) and copy number variations (CNVs) from each site were then analyzed. The cell proliferation and apoptosis were also evaluated by the ki-67 labeling index and TUNEL staining. Results: Among 20 cases, 3 (15%) showed heterogeneous staining, defined as having both an L858R IHC-positive part and an IHC-negative one. Genetic analyses for cases with heterogeneous staining revealed an increase in the copy number of EGFR in the IHC-positive part (CNV 19.54) compared to the negative part (CNV 3.03), and an increase in the copy number of CCNE1 was observed in the IHC-positive part (CNV 18.59) compared to the negative part (CNV 2.59) in one case (case 1). In another case (case 2), an increase in the copy number of EGFR was observed in the IHC-positive part (CNV 8.21) compared to the negative part (CNV 2.90), and an increase in the copy number of MDM2 was observed in the IHC-positive part (CNV 6.65) compared to the negative part (CNV 1.37). Case 3 did not show any CNV. In three cases, no SNV changes were observed. An increase in the ki-67 labeling index in the L858R-positive part in case 1 and increased apoptosis in the L858R-positive part in case 2 were observed, suggesting the functional significance of CNV changes. Conclusion: These cases exhibiting L858R IHC intratumoral heterogeneity suggest a heterogeneous effect on the cell activity due to CNV heterogeneity. Citation Format: Takafumi Hashimoto. Intratumoral heterogeneity of copy number variation in lung cancer harboring L858R via immunohistochemical heterogeneous staining [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 2200.
Epidemiology and resistance phenotypes of carbapenemase-producing Klebsiella pneumoniae in Greece, 2014 to 2016
Authors: Irene Galani, Ilias Karaiskos, Irene Karantani, Vassiliki Papoutsaki, Sofia Maraki, Vassiliki Papaioannou, Polyzo Kazila, Helen Tsorlini, Nikoletta Charalampaki, Marina Toutouza, Helen Vagiakou, Konstantinos Pappas, Anna Kyratsa, Konstantina Kontopoulou, Olga Legga, Efthymia Petinaki, Helen Papadogeorgaki, Efrosini Chinou, Maria Souli, Helen Giamarellou
Journal: Eurosurveillance (2018)

Background and aim A multicentre nationwide surveillance study was conducted in Greek hospitals to evaluate epidemiology of carbapenemase-producing Klebsiella pneumoniae clinical isolates, and their susceptibilities to last-line antibiotics. Methods: Minimum inhibitory concentrations (MICs) were evaluated by Etest, colistin MICs were also evaluated by broth microdilution SensiTest (now known as ComASP) Colistin. Carbapenemase genes were detected by PCR. Clonal relatedness was assessed by PFGE. Isolates were prospectively collected between November 2014 and April 2016, from 15 hospitals. Results : Among 394 isolates, K. pneumoniae carbepenemase (KPC) remained the most prevalent carbapenemase (66.5%). NDM was the second most prevalent (13.7%), identified in 12 hospitals, followed by VIM (8.6%). OXA-48- and double carbapenemase-producers remained rare (3.6%, 6.3%, respectively). Carbapenemase-producing K. pneumoniae isolates showed high resistance to last-line antibiotics. Gentamicin and colistin were the most active in vitro with 61.9% and 59.6% of the isolates to be inhibited at ≤ 2mg/L, followed by fosfomycin (susceptibility (S): 58.4%) and tigecycline (S: 51.5%). Ceftazidime/avibactam inhibited 99.6% of KPC and 100% of OXA-48-like-producing isolates, while temocillin was active against 58% of KPC isolates at urinary breakpoint of ≤ 32mg/L* and only 2.7% at systemic breakpoint of ≤ 8mg/L. NDM-producing isolates belonged mainly to one clone, whereas KPC, VIM, OXA-48 and double carbapenemase-producers were mainly polyclonal. Conclusions : KPC remains the predominant carbapenemase among K. pneumoniae in Greece, followed by NDM, whereas changing trends of resistance rates to last-line antimicrobials against carbapenemase-producing K. pneumoniae with the exception of ceftazidime/avibactam mandates continuing surveillance to support clinical practice.