tbuckley/cabot-search huggingface dataset:
Abstract 5714: SPADE identification of novel MDSC subsets
Authors: Kathryn Cole, Holly Britton, Phyllis Warkentin, James E. Talmadge
Journal: Cancer Research (2018)

Abstract Myeloid derived suppressor cells (MDSC's) are a heterogeneous population of myeloid cells at varying stages of differentiation that occur in increased numbers in the blood of cancer patients. The phenotypes of MDSC's, are controversial but are generally subdivided into three phenotypes: macrophage (M-), granulocytic (G-) and immature (i-) MDSC's. Our studies used a single staining tube with antibodies to linage markers (CD3, CD19 and CD56), HLA-DR, CD11b, CD14, CD15, CD16, CD33, CD34, CD45, PD-L1 and lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1). Mobilized apharesis products from lymphoma patients provided a product with a high frequency of MDSCs compared to normal donor blood samples. A total MDSC population (Lin-HLA-DR-CD11b+CD14+ and Lin-HLA-DR-CD11b+CD14-CD33+) was exported from FlowJo to Spanning tree progression analysis of density normalized events (Spade) in Matlab. This analysis identified nine MDSC sub-populations as nodes. Impressively, cells from the non-MDSC populations, including monocytes and granulocytes did not occur within these nodes. The SPADE analysis identified four M-MDSC nodes, four G-MDSC nodes and one iMDSC node. LOX-1 expression was limited to two G-MDSC and one M-MDSC subset. The nodes were differentiated based on CD14, CD15, CD33, CD16, LOX-1, and CD34 expression. The total populations were SPADE analyzed by overlaying non-MDSCs populations onto MDSCs and monocytes and granulocytes subset to nodes independent of MDSC nodes. The assessment of MDSC function used intracellular arginase-1 and nitric oxide synthetase-2 expression with the expected differential expression consistent with the M and G-MDSC subsets. The proportions of the different MDSC nodes varied between cancer patients and were generally at least a log higher than in the blood of normal donors. In summary, a SPADE analysis can cleanly identify MDSCs from monocytes and granulocytes and provide insight into novel MDSC subsets. Citation Format: Kathryn Cole, Holly Britton, Phyllis Warkentin, James E. Talmadge. SPADE identification of novel MDSC subsets [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 5714.
Abstract 5274: Role of obesity and dietary chemopreventive nutrients on risk for breast cancer among ethnically diverse women
Authors: Padma P. Tadi Uppala, Sozina Katuli, Alfredo Mejia, Sherine Brown-Fraser, Brian Yuen Yau Wong, Ryan Hayes, Maheswari Senthil, Carlos Garberoglio
Journal: Cancer Research (2018)

Abstract Dietary factors have been inconsistently associated with breast cancer risk among various ethnicities. Diet however, may influence breast cancer through mechanisms of obesity. The purpose of this study was to compare intake of dietary chemopreventive nutrients and obesity across three racial/ethnic groups: Latina, African American and Asian women. Methods: Eighty subjects from Inland Empire, California were enrolled into the study from five different sites. Dietary intake was assessed using a validated food frequency questionnaire. The questionnaire includes 19 adjustment questions used to modify food-item responses in regard to fat, fiber, and sodium intake followed by 122 specific food item-lines that capture frequency and serving sizes for select foods. Women also completed a demographic and breast cancer survey. Chi-square tests were used for categorical variables, ANOVA, and Kruskal-Wallis one-way analysis of variance was used for nutrient variables. Results: The age of the study population ranged from 24 to 79. Subjects included 30 Latina, 35 African American and 15 Asian women. The mean body mass index for Latina, African American and Asian women was 26.8±4.2, 30.8±7.24, 24.41±3.85 respectively. Mean fat percent for the three races was 34.21±5.80 for Latina, 41.57±6.33 for African American and 35.5±8.74 for Asian. African American women were significantly (p=0.001) more obese compared to Latina and Asian women. Total breast cancer cases for Latina is 3, African American 6 and Asian 2. Family history of reported breast cancer among Latina, African American and Asian was 0, 11, 0 respectively. There was a significant difference among racially ethic groups in alcohol consumption (p=0.001), alpha carotene (p=0.005), beta-carotene (p=0.031), beta-Cryptoxanthin (p=0.022), Lycopene (p=0.000) MUFA (p=0.017), PUFA (p=0.000) animal protein (0.49) and total Vitamin A (0.044). Conclusion: Significant differences were found in obesity and dietary intake of chemopreventive nutrients among the three racial groups. African Americans had higher rates of obesity and lower consumption of total vegetable intake. This data is consistent with the general US population data in terms of obesity and risk for breast cancer. Further studies will include larger sample size to identify specific nutrients that may protect against breast cancer risk among diverse populations. Citation Format: Padma P. Tadi Uppala, Sozina Katuli, Alfredo Mejia, Sherine Brown-Fraser, Brian Yuen Yau Wong, Ryan Hayes, Maheswari Senthil, Carlos Garberoglio. Role of obesity and dietary chemopreventive nutrients on risk for breast cancer among ethnically diverse women [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 5274.
Effects of Quinidine and Verapamil on Human Cardiovascular α1-Adrenoceptors
Authors: KatsushiShibata, AkiraHirasawa, RudolfFoglar, SatoshiOgawa, GozohTsujimoto
Journal: Circulation (1998)

Background—The antiarrhythmic drugs quinidine and verapamil are known to block α1-adrenoceptors (α1ARs). α1ARs are a heterogeneous family of three subtypes (α1A, α1B, and α1D), and little is known about the effects of quinidine and verapamil on the different human α1AR subtypes. Methods and Results—Reverse transcriptase–polymerase chain reaction showed that all α1AR subtypes are expressed in both human heart (atrium and ventricle) and the mesenteric artery. Pharmacological profiles of quinidine and verapamil actions on the α1AR subtypes were characterized with Chinese hamster ovary cells stably expressing cloned human α1AR subtypes. Radioligand binding studies showed that quinidine and verapamil had high affinities for all α1AR subtypes. Also, both drugs synergistically inhibited α1AR-mediated inositol 1,4,5-triphosphate production at the clinical effective concentration range (1 μmol/L quinidine and 0.1 μmol/L verapamil). Conclusions—The results show that all α1AR subtypes are expressed in the human card...
Genetic Polymorphism of 5,10-Methylenetetrahydrofolate Reductase (MTHFR) as a Risk Factor for Coronary Artery Disease
Authors: HiroyukiMorita, Jun-ichiTaguchi, HirokiKurihara, MasaoKitaoka, HideakiKaneda, YukikoKurihara, KojiMaemura, TohruMinamino, MinoruOhno, KazuhideYamaoki, KenOgasawara, TadanoriAizawa, ShinSuzuki, YoshioYazaki
Journal: Circulation (1997)

Background Epidemiological studies have identified hyperhomocyst(e)inemia as an independent risk factor for coronary artery disease (CAD). Recently, the alanine/valine (A/V) polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, has been reported. The VV genotype correlates with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the distribution of the MTHFR genotypes in Japanese men and the association between the VV genotype and CAD. Methods and Results The diagnoses of CAD of all the studied patients were confirmed by coronary angiography. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. In 778 healthy male subjects, the frequency of the V allele was 0.33, comparable to that in a French Canadian population. In 362 patients with CAD, the VV genotype was significantly more frequent than in control subjects (...
Abstract LB-363: Characterization of in vitro and in vivo models generated from disseminated tumor cells of patients without manifest metastasis
Authors: Christian Werno, Kathrin Weidele, Steffi Treitschke, Catherine Botteron, Sebastian Scheitler, Bernhard Polzer, Melanie Werner-Klein, Christoph Andreas Klein
Journal: Cancer Research (2018)

Abstract We recently showed that dissemination of few melanoma cells to the lymph nodes is a quantitative risk factor for death from melanoma. However, the analysis of disseminated tumor cells (DTC) is limited by their extremely low frequency, resulting in a lack of in vitro/in vivo models for mechanistic studies of early systemic disease. Therefore, the objective of this study was to develop protocols to expand single DTC from lymph nodes of melanoma patients to establish better preclinical models for adjuvant cancer therapies. Sentinel lymph nodes from melanoma patients were cut in halves, disaggregated and analyzed for the presence of gp100-positive DTC. The other half was used for diagnostic assessment by histopathology. Single DTC within the lymph node-derived single cell suspension were then propagated under specific sphere forming conditions and expanded by transplantation in immunodeficient mice. DTC based pre-clinical in vitro/in vivo models were then characterized on molecular level and were used for functional analyses. To test drugs on DTC in presence of a human immune system we additionally generated humanized xenograft models. We successfully established cell lines and xenografts from DTCs of 17 melanoma patients. We confirmed the origin of the cells by genomic fingerprint and analyzed the genomic profile of the expanded cells over various culture and animal passages. DTC cell lines were used for functional analysis and for testing the efficacy of targeted therapies. In addition, we set up a novel preclinical mouse model based on expanded melanoma DTC. For this, we established a human immune system in immunodeficient mice, which were then transplanted with melanoma DTC-derived cells. Interestingly, the presence of a human immune system significantly induced tumor formation, as well as dissemination of melanoma cells and improved the response to a targeted therapy compared to mice without a humanized immune system. The development of DTC based pre-clinical in vitro/in vivo models enables mechanistic studies on DTCs and drug tests against the target cells of adjuvant therapies in the presence of human immune cells. These models may help to identify candidate adjuvant therapies targeting DTCs and to understand mechanisms of drug resistance of currently applied targeted therapies. Citation Format: Christian Werno, Kathrin Weidele, Steffi Treitschke, Catherine Botteron, Sebastian Scheitler, Bernhard Polzer, Melanie Werner-Klein, Christoph Andreas Klein. Characterization of in vitro and in vivo models generated from disseminated tumor cells of patients without manifest metastasis [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 LB-363.
Abstract P321: Healthy Eating Predicts Lower Risk of Major Noncommunicable Diseases in Chinese Adults
Authors: DanxiaYu, Xiao-OuShu, Yong-BingXiang, GongYang, HonglanLi, Yu-TangGao, WeiZheng, XianglanZhang
Journal: Circulation (2015)

Background: Noncommunicable diseases (NCDs) have emerged as a top threat to public health and economic growth worldwide, particularly in developing countries. Adopting healthy dietary patterns is one of the most important modifiable factors for NCD prevention. Objective: To examine whether higher adherence to the Dietary Guidelines for Chinese is associated with lower risk of developing major NCDs, including coronary heart disease (CHD), stroke, and type 2 diabetes. Design: A longitudinal analysis of 52,511 men and 64,784 women (40-74 y), who were participants of 2 population-based prospective cohort studies in Shanghai and free of CVD, diabetes, and cancer at baseline (1997-2002). Method: Habitual diets were assessed at baseline using validated food-frequency questionnaires. Dietary adherence score was estimated according to the 2007 Chinese Food Pagoda. Incident cases of major NCDs were identified via biennial follow-up home visits. Results: During mean follow-ups of 5.6-10.0 years, we documented self-r...
Abstract 3497: Fibroblast growth factor receptor 3 (FGFR3) aberrations in muscle-invasive urothelial carcinoma
Authors: Young Saing Kim, Soon Il Lee, Se Hoon Park
Journal: Cancer Research (2018)

Abstract Purpose: Muscle-invasive urothelial carcinoma (UC) has a poor prognosis and novel approaches to systemic therapy are required. Recent studies show that FGFR3 activation is an important contributor to tumor development and angiogenesis in UC. Therefore, FGFR3 is a potential therapeutic target in UC. The purpose of this study was to evaluate the rates and types of FGFR3 aberrations in invasive UC. Methods: We analyzed primary tumor samples from 74 UC patients who had received radical cystectomy (n=40) or ureteronephrectomy (n=34). Ion AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay were used to detect FGFR3 aberrations. Results: Fifty-four patients (73%) had high-grade tumors, and 62% had lymph node involvement. Sixteen patients (22%) harbored FGFR3 alterations, the most common of which was FGFR3 mutations (n=13). These mutations included Y373C (n=3), N532D (n=3), R248C (n=2), S249C (n=2), G370C (n=1), A797P (n=1), and 746_747insG (n=1). In all three patients with FGFR3 rearrangement, the fusion partner was TACC3. The frequency of FGFR3 aberrations was higher in bladder UC (28%) than in UC of the renal pelvis and ureter (15%), but the difference was not statistically significant (P=0.183). Genes that were co-aberrant with FGFR3 included APC (88%), PDGFRA (81%), RET (69%), and TP53 (69%). Conclusions: FGFR3 abnormalities are less frequently seen in upper tract UC than bladder UC. Patient selection could be critical in designing new approaches for anti-FGFR3 therapy in the perioperative setting. Citation Format: Young Saing Kim, Soon Il Lee, Se Hoon Park. Fibroblast growth factor receptor 3 (FGFR3) aberrations in muscle-invasive urothelial 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 3497.
Abstract 19213: Epigenetically Reprogrammed Mesenchymal Stem Cells Improve Myocardial Remodeling and Cardiac Function After Myocardial Infarction by Modulating Post-infarct Inflammation and Neoangiogenesis
Authors: Jin Jin Kim, Eun-Hye Park, Hyo Eun Park, Eunmin Kim, Young Choi, Kwan Yong Lee, Young Soo Lee, Ha-Wook Park, Tae-Hoon Kim, Yoon Seok Koh, Ki-Bae Seung, Byung-Hee Hwang, Eun Ho Choo, Sang-Hyun Ihm, Kiyuk Chang
Journal: Circulation (2015)

Background: The efficacy of transplantation of default mesenchymal stem cells (MSCs) is controversial because of their limited plasticity and decreased function in elderly patients with myocardial infarction (MI). We investigated whether epigenetically reprogrammed-MSCs ameliorate myocardial remodeling in a mouse model of MI. Methods: Bone marrow-derived MSCs were sequentially treated with 5 mM/L of valproic acid and 100 nM/L of 5-azacytidine for 48 hours. Quantitative RT-PCR was performed to evaluate the effect of epigenetic modifiers on the gene expression of MSCs. 2 x 105 default MSCs, 2 x 105 epigenetically reprogrammed-MSCs, or phosphate-buffered saline were injected into peri-infarct zone immediately after ligating proximal portion of left anterior descending artery. On days 28 after MI, in vivo cardiac magnetic resonance (CMR) and harvest of heart tissue was sequentially performed. Results: Epigenetic modification of MSCs induced gene expression of anti-inflammatory markers such as transforming growth factor-β, indoleamine 2,3-dioxygenase. Fibroblast growth factor-β increased 37.5% and myocyte-specific enhancer factor 2C increased 36.8% at the mRNA level. Transplantation of modified-MSCs showed improved ejection fraction on CMR. In histopathologic analysis, infarct size was significantly decreased in modified-MSCs transplanted mice (p=0.002). When assessing capillary density of peri-infarct zone, larger number of CD31+ staining vascular structures was observed in modified-MSCs transplanted mice. Immunofluorescence stain showed marked increase of CD4+CD25+Foxp3+ regulatory T cells as well as CD68+MR+ M2 macrophage and decrease of CD68+iNOs+ M1 macrophage in modified-MSCs transplanted mice. Conclusions: Transplantation of epigenetically reprogrammed-MSCs significantly improves cardiac function by modulating post-infarct inflammation and neoangiogenesis in a preclinical model of AMI.
Randomized Evaluation of Heart Failure With Preserved Ejection Fraction Patients With Acute Heart Failure and Dopamine
Authors: Kavita Sharma, Joban Vaishnav, Rohan Kalathiya, Jiun-Ruey Hu, John Miller, Nishant Shah, Terence Hill, Michelle Sharp, Allison Tsao, Kevin M. Alexander, Richa Gupta, Kristina Montemayor, Lara Kovell, Jessica E. Chasler, Yizhen J. Lee, Derek M. Fine, David A. Kass, Robert G. Weiss, David R. Thiemann, Chiadi E. Ndumele, Steven P. Schulman, Stuart D. Russell
Journal: JACC Heart Failure (2018)
Tissue ingrowth within lumen-apposing metal stents. How long is long term?
Authors: Monica Saumoy, Luai Madanat, David Carr-Locke, Reem Sharaiha
Journal: Endoscopy (2018)

A 31-year-old woman with a history of alcohol pancreatitis presented with abdominal pain. During her initial admission, she developed an 8.2-cm peripancreatic fluid collection. She underwent successful endoscopic ultrasound-guided drainage of the collection with a 15 mm lumen-apposing metal stent (LAMS). Though instructed to return, the patient was lost to follow-up. She returned to an outside hospital 7 months later with recurrent pancreatitis secondary to alcohol use. Imaging demonstrated resolution of the peripancreatic collection, with the cyst-gastrostomy stent still in situ. The initial attempt at stent removal was unsuccessful. She was then transferred to our institution.
Validation of Collateral Fractional Flow Reserve by Myocardial Perfusion Imaging
Authors: HitoshiMatsuo, SachiroWatanabe, TohruKadosaki, TakahikoYamaki, ShinichiroTanaka, ShuusakuMiyata, TomonoriSegawa, YukihikoMatsuno, MasaakiTomita, HisayoshiFujiwara
Journal: Circulation (2002)

Background— Collateral fractional flow reserve (FFRcoll) is an index to quantify collateral blood flow, derived from coronary pressure measurements. Although well defined theoretically, its direct validation by myocardial perfusion imaging has not been established so far. Validating this index by myocardial perfusion imaging is the main aim of this study. Methods and Results— Twenty-four consecutive patients with stable angina and single left anterior descending artery stenosis underwent simultaneous measurement of aortic pressure (Pa), coronary wedge pressure (Pw), and central venous pressure (Pv) during balloon inflation. FFRcoll was calculated and compared with the extent and severity of the defect during coronary occlusion using 99mTc-sestamibi imaging at balloon inflation of the respective coronary artery. Although the pressure-derived collateral indexes (Pw, Pw/Pa, and FFRcoll) ranged widely, they were closely correlated with extent and severity scores of the nuclear occlusion images and superior to...
Short-Term Effects of Rapid Pacing on mRNA Level of Voltage-Dependent K+ Channels in Rat Atrium
Authors: TakeshiYamashita, YujiMurakawa, NoriyukiHayami, Ei-ichiFukui, YujiKasaoka, MasashiInoue, MasaoOmata
Journal: Circulation (2000)

Background—Atrial fibrillation causes electrophysiological changes of the atrium, thereby facilitating its maintenance. Although the expression of ion channels is modulated in chronic atrial fibrillation, it is yet unknown whether paroxysmal atrial fibrillation can also lead to electrical remodeling by affecting gene expression. Methods and Results—To examine the short-term effects of rapid pacing on the mRNA level of voltage-dependent K+ channels, high-rate atrial pacing was performed in Sprague-Dawley rat hearts. Total RNA was prepared from the atrial appendages from 0 to 8 hours after the onset of pacing, and mRNA levels of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2, Kv4.3, erg, KvLQT1, and minK were determined by RNase protection assay. Among these 9 genes, the mRNA level of the Kv1.5 channel immediately and transiently increased, with bimodal peaks at 0.5 and 2 hours after the onset of pacing. Conversely, the pacing gradually and progressively decreased the mRNA levels of the Kv4.2 and Kv4.3 channels. The inc...
Abstract 4739: Elucidation of immunosuppressive microenvironment in colorectal cancer
Authors: Tetsuro Sasada, Junya Ohtake, Tetsuta Satoyoshi, Keisuke Kazama, Satoshi Wada, Erika Yada, Manabu Shiozawa
Journal: Cancer Research (2018)

Abstract Colorectal cancer (CRC) is one of the most increasing cancers worldwide, and novel treatment modalities remain to be developed for advanced CRC patients. In recent years, immune checkpoint inhibitors have demonstrated impressive clinical efficacy in various types of cancers, but limited clinical responses were reported in CRC, except for MSI-high or MMR-deficient tumors. It has thus been suggested that immune suppressive mechanisms other than immune checkpoints might contribute to tumor progression in CRC. In the current study, various types of immune cells were isolated from peripheral blood or resected tumor/normal tissues and regional lymph nodes in 25 primary CRC patients, and their phenotypes and functions were comprehensively assessed. Flow cytometry analysis demonstrated a significant increase of CD4+FoxP3+ T cells, which might represent regulatory T cells, in proximal lymph nodes (N1 region), compared to distal (N2 or N3 region) or unrelated lymph nodes. In addition, the functional analysis of T cells assessed by cytokine production after non-specific stimulation (PMA and A23187) showed a significant decrease in the frequencies of IFN γ-producing CD8+ T cells in N1 region. Notably, reduction of IFN γ-producing CD8+ T cells seemed to be associated with advanced stages of disease. These results indicate that the immunosuppressive microenvironment, particularly in regional lymph nodes, may be related to tumor progression in CRC. The current study suggests that monitoring of immunosuppressive microenvironment would be useful as a predictive biomarker for cancer progression and patient prognosis in CRC. Further studies remain to be performed to more thoroughly elucidate immune suppressive mechanisms, and thereby to develop a novel immunotherapeutic strategy in CRC. Citation Format: Tetsuro Sasada, Junya Ohtake, Tetsuta Satoyoshi, Keisuke Kazama, Satoshi Wada, Erika Yada, Manabu Shiozawa. Elucidation of immunosuppressive microenvironment in colorectal 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 4739.