tbuckley/cabot-search huggingface dataset:
Abstract 12757: ECG Patterns in Early Pulseless Electrical Activity and the Etiologies of In-Hospital Cardiac Arrest
Authors: Daniel Bergum, Gunnar W Skjeflo, Jan P Loennechen, Ole C Mjølstad, Trond Nordseth, Bjørn O Haugen, Eirik Skogvoll
Journal: Circulation (2015)

Introduction: The defibrillator is a mandatory diagnostic and therapeutic tool for the treatment of cardiac arrest (CA). The diagnostic potential of the defibrillator may not be fully utilized. Pulseless electrical activity (PEA) is increasingly common as the first presenting rhythm for a range of etiologies, in particular the ‘reversible causes 4H4T’ (figure). We investigated the etiology and its relation to the QRS duration and heart rate during PEA. Method: We conducted a prospective observational study of all CA episodes treated by an in-hospital emergency team (ET) at St.Olav University Hospital in Trondheim/Norway during 4.5 years. Two cardiologists independently examined the ECG recorded during the first compression pause after attachment of the defibrillator, and measured the duration of three consecutive QRS complexes. The averaged QRS duration was defined as normal if shorter than 120ms and the heart rate (HR) was defined as normal if between 59 and 100/minute, leading to six simple ‘patterns’ of PEA: normal, wide, narrow-slow, wide-slow, narrow-fast and wide-fast. PEA episodes with reliable causes of arrest confirmed by objective diagnostic criteria were included. Results: We identified 69 triggering causes in 51 PEA episodes. The figure shows the bivariate distribution of QRS/HR according to etiology, showing no obvious relationship.. In 48 episodes (83%) the initial ECGs were outside the ‘normal’ range regarding QRS duration, HR, or both. Six patients survived to hospital discharge, none of their presenting ECGs were ‘normal’ Conclusion: Four fifths of all presenting PEA patterns were found to be abnormal with respect to HR and QRS duration. An abnormal initial ECG did not point towards etiology nore precluded survival in this modest study sample.
Cancer stem cell markers in locally advanced breast cancer.
Authors: Daniel G. Tiezzi, Renata D Sicchieri, Heriton MR Antonio, Larissa R Mouro, Joao Santana da Silva, Jurandyr Moreira de Andrade
Journal: Journal of Clinical Oncology (2012)

1075 Background: the expressions of CD44/CD24, CXCR4 and ABCG2 have been reported as potential breast cancer stem-like cell (CSLC) markers. The association between the quantity of CSLCs and the response to neoadjuvant chemotherapy (NACT) remains unclear. Methods: we prospectively analyzed the expression of CD44/CD24, CXCR4 and ABCG2 in 20 patients with locally advanced or metastatic (LAMBC) invasive ductal carcinomas of the breast subjected to NACT. The mammosphere assay (Mammocult) was studied in 10 samples. Patients’ mean age was 55.6 ± 8.2 yo. According to clinical stage (CS), 5 patients were IIb, 4 - IIIa, 8 - IIIb and 3 - IV. The mean clinical tumor diameter was 6.3 ± 2.8cm. The ER, PgR and HER2 positive expression rates were 50%, 45% and 50%, respectively. Ten patients were treated with EC-T, eight were treated with EC-TH (HER2+) and two were treated with FEC75 combination as NACT. The median percentage CD44 + /CD24 - , CXCR4 + , ABCG2 + and ESA + cells within Lin- cells were determined by flow cytometry in fresh sampled tumors after tissue digestion. The relationship between flow cytometry analyses and clinical and pathological response to therapy was analyzed. Results: complete clinical response (cCR) and complete pathological response (pCR) was observed in 9 (45%) and 5 (25%) patients. We did not observe a significant association between pCR and ER, PgR or HER2 expression. We observed and association between the pCR with percentage of ABCG2 + cells within the tumor and with the number of mammospheres. No correlation between pCR and CD44 + /CD24 - cell population within the tumor was observed. The median percentage of ESA + /Lin - /ABCG2 + cells within the tumor in pCR patients was 0.6% and 3.5% in patients with no pCR (p= 0.02). The median number of sphere formation was 5/100 cells and 0.9/1000 cells in pCR and non-pCR patients, respectively (p= 0.02). Interestingly, there was a positive correlation between ABCG2 expression and the number of mammosfere formation (r= 0.66; p= 0.03). This correlation was not significant comparing to CD44+/CD24- cells or CXCR4. Conclusions: the percentage of ABCG2 + cancer cells within the tumor and the number of mammosphere formation are predictive factors for pCR in LAMBC patients subjected to NACT. ABCG2 is a potential marker for CSLCs.
State-of-the-art of microbubble-assisted blood-brain barrier disruption
Authors: Kang-Ho Song, Brandon K. Harvey, Mark A. Borden
Journal: Theranostics (2018)

Focused ultrasound with microbubbles promises unprecedented advantages for blood-brain barrier disruption over existing intracranial drug delivery methods, as well as a significant number of tunable parameters that affect its safety and efficacy.This review provides an engineering perspective on the state-of-the-art of the technology, considering the mechanism of action, effects of microbubble properties, ultrasound parameters and physiological variables, as well as safety and potential therapeutic applications.Emphasis is placed on the use of unified parameters, such as microbubble volume dose (MVD) and ultrasound mechanical index, to optimize the procedure and establish safety limits.It is concluded that, while efficacy has been demonstrated in several animal models with a wide range of payloads, acceptable measures of safety should be adopted to accelerate collaboration and improve understanding and clinical relevance.
Abstract B67: Antitumor effect of black tea pigments, theaflavin-3/3’-gallate, against cisplatin-resistant ovarian cancer cells
Authors: Yi Charlie Chen
Journal: Clinical Cancer Research (2018)

Abstract Ovarian cancer ranks fifth in cancer deaths among women in the United States, accounting for approximately 5% of all cancer deaths. Acquired resistance to conventional platinum-based chemotherapy drives the development of more selective anticancer drugs. Theaflavin-3-gallate (TF2a) and theaflavin-3’-gallate (TF2b) are the major bioactive components in black tea. In this study, we evaluated TF2a and TF2b as potential anticancer agents using human ovarian cancer cells. The cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum at 37˚C in a humidified incubator with 5% CO2. The [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, flow cytometry, and Western blot analysis were used to confirm that TF2a and TF2b exhibited a potent growth-inhibitory effect against cisplatin-resistant ovarian cancer A2780/CP70 cells. Treatment with TF2a and TF2b (10-40 μM) significantly decreased A2780/CP70 cell viability (p&amp;lt; 0.05). Treatment with TF2a and TF2b (5, 10 and 20 μM) increased the percentage of apoptotic cells in a concentration-dependent manner. Western blot analysis was used to evaluate the expression of proteins related to apoptosis in A2780/CP70 cells treated with designated concentrations (0, 5, 10, and 20 μM) of TF2a and TF2b for 24 h. The protein levels of procaspase-3/7 for TF2a-treated cells and procaspase 3 for TF2b-treated cells decreased significantly in A2780/CP70 cells (p&amp;lt; 0.05). Treatment with TF2a or TF2b significantly increased the protein levels of cleaved caspase-3/7, full-length PARP, and cleaved PARP in A2780/CP70 cells. Our study demonstrated that TF2a and TF2b are potential agents for treating platinum-resistant ovarian cancer by inducing apoptosis. Note: This abstract was not presented at the conference. Citation Format: Yi Charlie Chen. Antitumor effect of black tea pigments, theaflavin-3/3’-gallate, against cisplatin-resistant ovarian cancer cells. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B67.
Phosphatidylinositol 3-Kinase and Calcium-Activated Transcription Pathways Are Required for VLDL-Induced Smooth Muscle Cell Proliferation
Authors: LarissaLipskaia, Marie-LucePourci, ClaudineDeloménie, LaurentCombettes, DominiqueGoudounèche, Jean-LouisPaul, ThierryCapiod, Anne-MarieLompré
Journal: Circulation Research (2003)

Little is known regarding the molecular mechanisms of atherogenicity of triglyceride-rich lipoproteins such as very low-density lipoproteins (VLDLs). We examined the effect of VLDL on proliferation of rat aortic smooth muscle cells, intracellular Ca2+ handling, and activity of cAMP-responsive element binding protein (CREB) and nuclear factor of activated T cells (NFAT) transcription factors. VLDL, isolated from human serum, dose- and time-dependently promoted proliferation. After 4 hours of exposure to VLDL (0.15 g/L proteins), the caffeine-induced Ca2+ release was inhibited and the IP3-sensitive Ca2+ release induced by ATP (10 μmol/L) was markedly prolonged. In quiescent cells, CREB was phosphorylated (pCREB) and NFAT was present in the cytosol, whereas in cells exposed to VLDL for 4 to 24 hours, pCREB disappeared and NFAT was translocated to the nucleus. VLDL-induced NFAT translocation and proliferation were blocked by cyclosporin A and LY294002 involving calcineurin and phosphatidylinositol 3-kinase (P...
Inconsistent Reporting of Potential Conflicts of Interest
Authors: Vinay Prasad
Journal: JAMA Pediatrics (2018)

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Abstract 2473: Association of functional genetic variants of long noncoding RNA HOTAIR with oral cancer susceptibility
Authors: Shun-Fa Yang, Shih-Chi Su, Chiao-Wen Lin
Journal: Cancer Research (2018)

Abstract Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). Polymorphisms in the HOX transcript antisense intergenic RNA (HOTAIR) have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms (SNPs) of the HOTAIR gene, rs920778, rs1899663, rs4759314, and rs12427129 were tested in 1200 normal controls and 907 OSCC patients. We detected a significant association of rs1899663 with the risk of OSCC (AOR, 2.227; 95% CI, 1.197-4.146; p=0.012) after adjustment for three potential confounders, smoking, betel nut chewing, and alcohol consumption. In the further analyses where habitual exposure to each of three environmental factors was individually excluded, we found that, in addition to rs1899663, non-betel nut users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: OR, 1.472; 95% CI, 1.069-2.029; p=0.018; TC+CC: OR, 1.448; 95% CI, 1.060-1.977; p=0.020). This genetic association was not seen while comparing subjects who do not smoke or consume alcohol between the case and control cohort. Moreover, as exploring the relationship between HOTAIR gene polymorphisms and clinical status of only OSCC patients who were non-betel nut chewers, besides the association with the advanced clinical stage, rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027-3.484; p=0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785-9.602; p=0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel nut chewing on the development and progression of oral cancer. Citation Format: Shun-Fa Yang, Shih-Chi Su, Chiao-Wen Lin. Association of functional genetic variants of long noncoding RNA HOTAIR with oral cancer susceptibility [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 2473.
Abstract 18514: Macrophage CARD9 Contributes to Cardiac Injury Following Myocardial Infarction by Regulating Inflammation and Apoptosis of Myocardiocytes
Authors: Yan Liu, Xuerui Wang, Youcai Ma, Junmeng Zhang, Weihong Ren, Jie Du
Journal: Circulation (2016)

Introduction: With high mortality rate, myocardial infarction (MI) is a severe type of coronary heart diseases. Innate immunity is activated after MI and mediates further injury to the heart. Caspa...
Mixed metabolic response on PET/CT in patients with metastatic breast cancer as an early predictor of disease progression.
Authors: Urmi Sen, Huichung Tina Ling, Akansha Chhabra, Kent P Friedman, Amy Tiersten
Journal: Journal of Clinical Oncology (2012)

e11522 Background: It has been observed that patients undergoing systemic therapy for metastatic breast cancer (MBC) may demonstrate a mixed metabolic treatment response on FDG PET (MMTR) while maintaining stable disease on CT (SDCT). The purpose of this study is to determine (1) the clinical outcome of MBC patients demonstrating MMTR+SDCT who were maintained on the same treatment regimen and (2) the behavior of oncologists when faced with a report of MMTR+SDCT. Methods: All FDG PET/CT scan reports performed at one institution between 2006-2011 were searched and studies describing a MMTR also containing the term “breast cancer” were identified. MBC patients without other active malignancies were extracted from the search and scans were re-analyzed. MMTR was defined as a PET/CT scan demonstrating a minimum of 2 lesions with a SUVmax change of +25% or more combined with at least 2 lesions demonstrating a SUVmax change of -25% or more. The subset of patients with MMTR+SDCT (by anatomical RECIST criteria) who were maintained on their current treatment regimen was further examined to identify time to progression (TTP). Results: Thirty-two cases were identified that demonstrated MMTR+SDCT in metastatic breast cancer patients. No change in therapy occurred within 3 months of the scan in 9/32 patients. Of the 9 patients who were maintained on their current treatment regimen, 5 patients demonstrated subsequent disease progression at 3 (n=2), 5 (n=2), and 11 (n=1) months (mean TTP = 5.4 months, range 3-11 months). One patient remains stable at 16 months and 3 patients have insufficient follow-up. Therapy was changed immediately after the scan in the remaining 22 patients for various reasons including preference of the treating oncologists, treatment toxicities, increase in tumor markers, or clinical progression. Conclusions: MMTR+SDCT in patients with MBC predicted subsequent disease progression within 6 months in the majority of individuals. Oncologists commonly alter treatment regimen when faced with a report of MMTR+SDCT. Based on the observation of outcomes in patients who did not change therapy, this practice seems justified.
Abstract A63: Estrogen receptor signaling in fallopian tube epithelia of BRCA mutation carriers
Authors: Leah V. Dodds, Omar Nelson, Patricia Shaw, Anca Milea, Ramlogan Sowamber, Sophia HL George
Journal: Clinical Cancer Research (2018)

Abstract Background: The most common and aggressive type of epithelial ovarian cancers (EOC) is high-grade serous carcinoma (HGSC), which accounts for 90% of ovarian cancer deaths. HGSC is the predominant histotype associated with BRCA1 and BRCA2 mutations. Prophylactic surgery in BRCA mutation carriers has implicated the fallopian tube epithelium (FTE), a hormonal responsive tissue, as the etiologic site of origin for HGSC. Estrogen and its receptors are major regulators of growth and differentiation in normal ovaries and fallopian tubes, and its mutagenic properties have been linked to ovarian carcinogenesis. Estrogen receptors (ER) are rarely mutated, amplified, or deleted in HGSC, yet only 10% of patients respond to antiestrogen treatment. TP53 mutations in the form of the p53 signature have been found in serous tubal intraepithelial carcinomas (STIC) and are ubiquitously present in patients with HGSC. We hypothesized that in the presence of dysfunctional p53, subsequent promiscuous binding of ER will yield aberrant signaling, contributing to cellular transformation. Methods: We used our previously published gene expression profiles to generate a candidate gene list, which was chosen based on the presence of known estrogen-responsive elements. We analyzed expression of 6 ER responsive genes using data collected from laser capture microdissection in normal FTE tissues. Tissue microarray analysis (TMA) was also performed on a subset of HGSC tumor samples from this cohort, staining for PR, ER, and p53, and expression was analyzed alongside their respective outcome and overall survival Finally, to mimic the in vivo environment of early carcinogenesis, FTE-normal and FTE-p53 mutant cell lines were established and treated with 100nM estradiol, an estrogen analog, to observe changes in response. Results: Preliminary data showed that FTE-BRCA and FTE-nonBRCA seemingly look and express ER and PR proteins similarly. Underlying these morphologic similarities is a potential haploinsufficiency predisposing FTE-BRCA to cytotoxic stresses. Microarray gene expression of laser captured FTE-BRCA and FTE-nonBRCA showed varied levels of ER mRNA expression across samples (n=25) while PR transcript levels change dynamically. The data generated have facilitated the development of gene signatures and biomarkers that will predict response to antiestrogen therapy and identify patients who will benefit from hormonal therapies. Citation Format: Leah V. Dodds, Omar Nelson, Patricia Shaw, Anca Milea, Ramlogan Sowamber, Sophia HL George. Estrogen receptor signaling in fallopian tube epithelia of BRCA mutation carriers. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr A63.
Abstract 4186: Monensin is selectively cytotoxic to cancer cells in an EMT-like state
Authors: Marion Vanneste, Huang Qin, Devon Moose, Mengshi Li, Michael Schultz, Meng Wu, Michael Henry
Journal: Cancer Research (2018)

Abstract Metastatic, drug-resistant cancer is lethal. Epithelial-to-mesenchymal transition (EMT) is a type of phenotypic plasticity that has been implicated in cancer metastasis and drug resistance. One potential therapeutic approach is to specifically target cancer cells in an EMT-like state. In this study, we have developed a cell-based high-throughput screening (HTS) protocol using the high content Operetta imaging platform to identify EMT cytotoxic compounds. This screen was performed on epithelial (PC-3E) and mesenchymal-like (TEM 4-18) cell lines, both isolated from the parental PC-3 prostate cancer cell line based on their differential ability to invade an endothelial monolayer. A library of 2,640 compounds was screened on co-cultured PC-3E GFP cells and TEM 4-18 mCherry cells. After 72h exposure to compounds, relative numbers of GFP- and mCherry-positive cells were quantitated. Dose-response curves were established for each compound exhibiting a greater toxicity against EMT-like cells. The mechanisms of action of one of the most potent and selective compound against EMT-like cells, monensin, were further evaluated. Among the 2,640 compounds tested, salinomycin and monensin, both monovalent cation ionophores, displayed a potent and selective cytotoxic effect against EMT-like cells. A closely related compound absent from the compound library, nigericin, was also evaluated and appeared to be the most potent of the three compounds tested. Monensin (10nM) induced apoptosis, cell cycle arrest, and an increase in ROS production in TEM 4-18 cells. In addition, monensin rapidly induced swelling of Golgi apparatus, a previously known effect of monensin, in multiple cell lines most likely resulting in a blockage of intracellular protein trafficking and cell death. We then evaluated the toxicity of monensin in 24 human cancer cell lines and classified them as resistant or sensitive based on IC50 cutoff of 100nM. Supporting these findings, Gene Set Enrichment Analysis identified EMT as the top of the gene sets enriched in the sensitive group. Increased monensin sensitivity in EMT-like cells is associated with elevated uptake of H3-monensin compared to resistant cells. In conclusion, using a high-throughput screening approach, we identified monensin as a potent and specific inhibitor of cancer cells in an EMT-like state where it rapidly disrupts Golgi function. At least part of selectivity of monensin for EMT-like cells is due to increased uptake of this compound. Citation Format: Marion Vanneste, Huang Qin, Devon Moose, Mengshi Li, Michael Schultz, Meng Wu, Michael Henry. Monensin is selectively cytotoxic to cancer cells in an EMT-like state [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 4186.