tbuckley/cabot-search huggingface dataset:
Abstract 5395: MicroRNA-196b-3p identified from serum microRNA expression profiling is a potential diagnostic biomarker for gastritis and early gastric cancer
Authors: Atsushi Fujii, Sho Nambara, Yosuke Kuroda, Shuhei Ito, Hidetoshi Eguchi, Takaaki Masuda, Takao Otsuka, Masafumi Nakamura, Koshi Mimori
Journal: Cancer Research (2018)

Abstract Background: Gastric cancer is one of the most common forms of cancer worldwide. The progression of chronic atrophic gastritis (CAG) is involved in gastric carcinogenesis. With the progression of chronic atrophic gastritis, the risk of gastric cancer increased in a stepwise fashion. Non-invasive tools for early gastric cancer are required to improve the prognosis. MicroRNAs (miRNAs), a class of small non-coding RNAs of 19-22 nucleotides in length, function as post-transcriptional regulators by directly cleaving target messenger RNA or translational repression. MiRNAs in serum have been shown to be potential biomarkers in various type of cancers and several miRNAs have been reported in gastric cancer. The purpose of present study was to identify a serum miRNA expression profile that can serve as a novel diagnostic biomarker for early gastric cancer. Materials and Method: We defined a normal gastric mucosa as grade0, CAG classified C-1, 2 in Kimura-Takemoto classification as grade1, CAG classified C-3, O-1 in Kimura-Takemoto classification as grade2, and CAG classified O-2, 3 in Kimura-Takemoto classification as grade3. We obtained 344 serum samples, which gathered from 19 health people (grade0), 125 patients with chronic atrophic gastritis (grade1: 54, grade2: 36, grade3: 35), and 200 patients with early gastric cancer. The miRNAs were extracted from serums and miRNA microarray analysis was performed. In the discovery phase, we analyzed 71 cases (grade0: 11, grade1: 20, grade2: 20, grade3: 20). Next, in the training phase, we analyzed 73 cases (grade0: 8, grade1: 34, grade2: 16, grade3: 15). Then, we analyzed 200 early gastric cancer serum samples. Result: The microarray analysis identified a profile of miRNA (miRNA-196b-3p) as a biomarker for early gastric cancer. The analysis results showed that the expression level of the serum miRNA was correlated to degree of CAG and carcinogenesis. When compared with grade0,1,2 and grade3, the area under the receiver operating characteristic (ROC) curve of this serum miRNA signature was 0.730 and 0.763 for the two sets of serum samples. There was significant difference in serum value of miRNA-196b-3p between grade1-3 and early gastric cancer (p=0.003). Conclusion: Serum miRNA-196b-3p is good biomarker for early gastric cancer. Citation Format: Atsushi Fujii, Sho Nambara, Yosuke Kuroda, Shuhei Ito, Hidetoshi Eguchi, Takaaki Masuda, Takao Otsuka, Masafumi Nakamura, Koshi Mimori. MicroRNA-196b-3p identified from serum microRNA expression profiling is a potential diagnostic biomarker for gastritis and early 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 5395.
Abstract 2232: A high-sucrose diet does not enhance spontaneous metastases of Lewis lung carcinoma in mice
Authors: Lin Yan, Sneha Sundaram
Journal: Cancer Research (2018)

Abstract Obesity is a risk factor for cancer, and high caloric intake contributes to obesity. We previously reported that a high-fat diet enhances metastasis in mice (Clin Exp Metastasis 2010). The purpose of this study was to determine the effects of a high-sucrose diet in comparison to a high-fat diet, on an isocaloric basis, on the spontaneous metastasis of Lewis lung carcinoma (LLC) in C57BL/6 mice. Mice (male) were fed a low-fat (AIN93G-based), a high-fat, or a high-sucrose diet for eight weeks before receiving a subcutaneous injection of 2.5x105 viable LLC cells. These diets contained 16% of energy from corn oil, 45% of energy from corn oil, or sucrose. The resulting primary tumor was resected 10 days later. The experiment was terminated 10 days after resection. There were no differences in caloric intake among the groups. The body fat mass of the high-sucrose group was lower than the high-fat group but higher than the low-fat group. The number and size of lung metastases were significantly higher in the high-fat group than in the low-fat group; however, they were similar between the high-sucrose and the low-fat groups. Compared to the low-fat diet, the high-fat diet, but not the high-sucrose diet, significantly increased plasma concentrations of insulin, inflammatory cytokines (leptin, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1) and angiogenic factors (vascular endothelial growth factor and tissue inhibitor of metalloproteinase-1). These findings showed that the high-sucrose diet does not enhance metastasis in this LLC model. This null effect suggests that the high-sucrose diet, compared to the high-fat diet, is less capable of promoting adipogenesis and production of related inflammatory cytokines and angiogenic factors. Citation Format: Lin Yan, Sneha Sundaram. A high-sucrose diet does not enhance spontaneous metastases of Lewis lung carcinoma in mice [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 2232.
Abstract 2102: UFH-001: A novel triple-negative, CAIX-positive cell line for small-molecule targeting of human breast cancer
Authors: Mam Y. Mboge, Zhijuan Chen, Lingbao Ai, Chingkuang Tu, Fabrizio Carta, Claudiu Supuran, Christopher J. Frost, Zaihui Zhang, Robert McKenna, Coy Heldermon, Susan C. Frost
Journal: Cancer Research (2018)

Abstract Specific treatment options for patients with metastatic breast cancers, especially of the triple negative subtype (TNBC), are limited and most patients develop resistance to radiation and/or chemotherapy. Because of this, the mortality rate in women with TNBC remains high. Carbonic anhydrases (CAs), most specifically membrane-bound CAIX, has been shown to play an important role in tumor progression and as a result is validated as a therapeutic target in several aggressive cancers. In breast cancer, CAIX expression has been shown to be ubiquitous in hypoxic TNBC tissues and is considered a prognostic marker and a potential therapeutic target. Therefore targeting CAIX activity, using small molecule inhibitors, in these highly aggressive and metastatic TNBCs may serve to improve overall disease free survival and therapeutic outcome in clinics. Our goal for this study was to 1) Identify and/or develop a cell line that expresses CAIX in a hypoxia independent manner and is representative of TNBCs and 2) To target CAIX activity in this cell line and observe the effects of CAIX inhibition on its growth and metastasis. Our hypothesis is that CAIX inhibition, in the context of a hypoxic and/or acidic microenvironment, will dysregulate its ability to maintain the acidic pH preferred by cancer cells which favors their growth and migration. To achieve our aims, we newly developed and characterized an endogenous CAIX-expressing cell line named UFH-001. Our results show that CAIX expression and activity in this cell line, although endogenous under normoxic conditions, is increased more than 2 fold under hypoxic conditions. This cell line is also representative of TNBCs (ER/PR and HER2 negative) with a more epithelial-like morphology and phenotype. UFH-001 cells grow aggressively and have the ability to migrate/invade and form tumors in vivo. In these studies we have also shown how inhibition of CAIX activity, using sulfonamide-based inhibitors, affects UFH-001 growth in an apoptosis independent manner and decrease the migratory/inhibitory capacity of these cells. Taken together, our observations indicate that CAIX is a viable small molecular drug target for the treatment of patients with TNBCs. Citation Format: Mam Y. Mboge, Zhijuan Chen, Lingbao Ai, Chingkuang Tu, Fabrizio Carta, Claudiu Supuran, Christopher J. Frost, Zaihui Zhang, Robert McKenna, Coy Heldermon, Susan C. Frost. UFH-001: A novel triple-negative, CAIX-positive cell line for small-molecule targeting of human 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 2102.
Do all node positive breast cancer patients require axillary clearance after neo-adjuvant chemotherapy (NAC)? A 4-year retrospective study
Authors: A. Fitchie, G. Shaaban, N. Redmayne, A. Nagarajakumar, M. Patel, A. Kasem, S. Doddi, P. Sinha
Journal: International Journal of Surgery (2018)
Upregulation of Cardiac Uptake1 Carrier in Ischemic and Nonischemic Rat Heart
Authors: MartinUngerer, AndreasChlistalla, GertRichardt
Journal: Circulation Research (1996)

Abstract Neuronal uptake1 constitutes the main elimination process of cardiac norepinephrine under normoxic conditions. Uptake1 may be subject to changes during myocardial ischemia. We therefore studied the regulation of the uptake1 carrier in isolated perfused rat hearts, comparing ischemic and nonischemic conditions. Radioligand binding with [3H]mazindol was used to determine carrier densities and affinities, whereas cardiac clearance of [3H]norepinephrine served as a measure of the transport capacity of the uptake1 carrier. When exocytotic norepinephrine release was induced in nonischemic rat hearts by electrical field stimulations, we observed an increase in the cardiac density of uptake1 carriers (Bmax) to 210±5 fmol/mg protein (versus 134±3 fmol/mg in control hearts). Simultaneously, the cardiac clearance of [3H]norepinephrine increased to 41±4% versus 30±4% in control hearts. Both carrier density and norepinephrine clearance returned to baseline values within a period of 40 minutes after stimulatio...
Bcl2-Like Protein 12 Is Required for the Aberrant T Helper-2 Polarization in the Heart by Enhancing Interleukin-4 Expression and Compromising Apoptotic Machinery in CD4+ T Cells
Authors: Xiao Chen, Xian-Hai Zeng, Mangyuan Wang, Liang Chen, Ningning Zhang, Man Rao, Ping-Chang Yang, Jiangping Song
Journal: Circulation (2018)

The biased T helper-2 (Th2) response plays a critical role in myocarditis. Bcl2-like protein 12 (Bcl2L12) is associated with the Th2 pattern of inflammation. This study aims to elucidate the role of Bcl2L12 in the pathogenesis of Th2-biased inflammation in the heart.Mice were treated with the myosin heavy-chain-α peptides to induce inflammation in the heart. Human hearts were collected from the surgically removed hearts of patients who had undergone heart transplantation.The expression of Bcl2L12 was detected in CD4+ T cells of the hearts, which was markedly higher in the hearts with myocarditis at the advanced stage of heart failure compared with the control (dilated cardiomyopathy) hearts without myocarditis. Mice with Bcl2L12-deficient CD4+ T cells failed to induce the Th2-biased inflammation in the heart. CD4+ T cells with a higher expression of Bcl2L12 were prone to differentiate into Th2 cells. Bcl2L12 formed a complex with GATA3 in CD4+ T cells to enhance the binding between GATA3 and the Il4 promoter, which promoted the Il4 gene transcription. Bcl2L12 compromised the apoptotic machinery by inhibiting the expression of p53 in CD4+ T cells to reduce the activation-induced CD4+ T cell death.CD4+ T cells isolated from hearts with myocarditis at the end stage of heart failure express high levels of Bcl2L12, and the latter is required for the development of aberrant Th2 polarization in the heart. The Bcl2L12 may be a novel target in the treatment of myocarditis as well as other Th2-biased inflammation.
Cholesterol Primes Vascular Smooth Muscle to Induce Ca2 Sensitization Mediated by a Sphingosylphosphorylcholine–Rho-Kinase Pathway
Authors: NoriyasuMorikage, HirokoKishi, MasafumiSato, FenglingGuo, SatoshiShirao, TakashiYano, MasaakiSoma, KimikazuHamano, KensukeEsato, SeiKobayashi
Journal: Circulation Research (2006)

Hypercholesterolemia is a major risk factor involved in abnormal cardiovascular events. Rho-kinase–mediated Ca2+ sensitization of vascular smooth muscle (VSM) plays a critical role in vasospasm and hypertension. We recently identified sphingosylphosphorylcholine (SPC) and Src family tyrosine kinase (Src-TK) as upstream mediators for the Rho-kinase–mediated Ca2+ sensitization. Here we report the strong linkage between cholesterol and the Ca2+ sensitization of VSM mediated by a novel SPC/Src-TK/Rho-kinase pathway in both humans and rabbits. The extent of the sensitization correlated well with the total cholesterol or low-density lipoprotein cholesterol levels in serum. However, an inverse correlation with the serum level of high-density lipoprotein cholesterol was observed, and a correlation with other cardiovascular risk factors was nil. When cholesterol-lowering therapy was given to patients and rabbits with hypercholesterolemia, the SPC-induced contractions diminished. Depletion of VSM cholesterol by β-c...
Abstract 2239: Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study
Authors: Huakang Tu, Colin P. Dinney, Yuanqing Ye, Barton H. Grossman, Seth P. Lerner, Xifeng Wu
Journal: Cancer Research (2018)

Abstract Background: Cancer patients are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification can lead to accumulation of unmetabolized folic acid in the systemic circulation and urine, and may promote cancer growth, especially among those with neoplastic alterations. Objective: We investigated the prospective association between synthetic versus natural folate intake and clinical outcomes in non-muscle-invasive bladder cancer (NMIBC), which is a highly recurrent disease. Design: In a cohort of 619 NMIBC patients, folate intake at diagnosis was assessed with a previously validated food frequency questionnaire and categorized according to tertiles. After a median follow-up of 5.2 years, 303 tumor recurrence and 108 progression events were documented from medical record review. Multivariable Cox proportional hazards and logistic models were used to estimate adjusted hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (95% CI). Results: Synthetic folic acid intake was positively associated with risk of recurrence among NMIBC patients (medium vs. low intake: HR=1.72; 95% CI=1.20, 2.48; P=0.003; high vs. low intake: HR=1.80; 95% CI=1.14, 2.84; P=0.01). Patients with higher folic acid intake were more likely to have multifocal tumors at diagnosis (medium/high vs. low: OR=2.08; 95% CI=1.08, 4.02; P=0.03). In contrast, natural folate intake tended to be inversely associated with risk of progression (medium/high vs. low: HR=0.68; 95% CI=0.44, 1.04; P=0.08). Conclusions: High intake of synthetic folic acid, in contrast to the natural forms, is associated with increased risk of recurrence in NMIBC and multifocal tumors at diagnosis, suggesting that folic acid may be unsafe for NMIBC patients. These findings provide some evidence for nutritional consultation regarding folate intake among NMIBC patients. Citation Format: Huakang Tu, Colin P. Dinney, Yuanqing Ye, Barton H. Grossman, Seth P. Lerner, Xifeng Wu. Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study [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 2239.
Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non–Small Cell Lung Cancer
Authors: Yi-Long Wu, Shun Lu, You Lu, Jianying Zhou, Yuan-kai Shi, Virote Sriuranpong, James C.M. Ho, Choo Khoon Ong, Chun-Ming Tsai, Chin-Hee Chung, Keith D. Wilner, Yiyun Tang, Elizabeth T. Masters, Paulina Selaru, Tony S. Mok
Journal: Journal of Thoracic Oncology (2018)

IntroductionThe phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population.MethodsIn this open-label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3-week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration–time curve of 5–6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point.ResultsCrizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286–0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6–93.2%) with crizotinib versus 45.6% (95% CI: 35.8–55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient-reported outcomes were seen in crizotinib-treated versus chemotherapy-treated patients.ConclusionsFirst-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.
Role of tubulointerstitial injury in ANCA-associated vasculitis is underestimated
Authors: Nikolai Bulanov, Natalia V Chebotareva, Pavel I Novikov, Sergey V Moiseev
Journal: Annals of the Rheumatic Diseases (2018)

Available evidence suggests that epidermal growth factor (EGF) is decreased in patients with kidney diseases and may predict deterioration of kidney function.1 2 In the kidney, EGF is expressed in the ascending portion of the Henle’s loop and the distal tubule. EGF binds to the specific EGF receptors and is involved in the regulation of cell proliferation, migration, growth and differentiation. EGF is a main trophic factor for tubular cells and modulates tissue response to injury. In the recently published study, Wu et al 3 showed that a lower urinary EGF level was associated with a more severe renal disease, refractoriness to the immunosuppressive treatment, and a higher risk of progression to the composite endpoint that included end-stage renal disease and at least 30% decline in estimated glomerular filtration rate (eGFR) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In a multivariable Cox regression analysis, urinary EGF/creatinine remained an independent predictor for the composite endpoint (HR 0.61, 95% CI 0.45 to 0.83, p=0.001) after adjusting for age, gender, eGFR, urinary protein at renal biopsy, type of ANCA and treatment protocols. The authors suggested that urinary EGF/creatinine …
Apoptosis in Human Acute Myocardial Infarction
Authors: AnttiSaraste, KariPulkki, MarkkuKallajoki, KenthHenriksen, MarttiParvinen, Liisa-MariaVoipio-Pulkki
Journal: Circulation (1997)

Background After reopening of the infarct-related coronary artery, cardiomyocytes continue to die during reperfusion. The mechanisms of cell death have been subject to debate. We studied whether an apoptotic type of cell death occurs in human acute myocardial infarction (AMI). Methods and Results We studied myocardial samples of eight patients who died of AMI and had patent infarct-related arteries at autopsy. Six of the patients had received initially successful thrombolysis. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the in situ DNA end-labeling method. Apoptotic cardiomyocytes were observed particularly in the border zones of histologically infarcted myocardium, whereas very few apoptotic cells were present in the remote noninfarcted myocardium. Internucleosomal fragmentation was confirmed by agarose gel electrophoresis of DNA isolated from the representative myocardial areas. Conclusions This study provides evidence that in addi...
Effects of HIV Protease Inhibitors on Progression of Monocrotaline- and Hypoxia-Induced Pulmonary Hypertension in Rats
Authors: GuillaumeGary-Bobo, AmalHoussaini, ValerieAmsellem, DominiqueRideau, PierrePacaud, AlinePerrin, JérémyBrégeon, ElisabethMarcos, Jean-LucDubois-Randé, OlivierSitbon, LaurentSavale, SergeAdnot
Journal: Circulation (2010)

Background—Pulmonary hypertension (PH) is among the complications of HIV infection. Combination antiretroviral therapy may influence the progression of HIV-related PH. Because Akt signaling is a potential molecular target of HIV protease inhibitors (HPIs), we hypothesized that these drugs altered monocrotaline- and hypoxia-induced PH in rats by downregulating the Akt pathway, thereby inhibiting pulmonary artery smooth muscle cell proliferation. Methods and Results—Daily treatment with each of 3 first-generation HPIs (ritonavir 30 mg/kg, amprenavir 100 mg/kg, and nelfinavir 500 mg/kg) started 3 weeks after a subcutaneous monocrotaline injection (60 mg/kg) substantially diminished pulmonary artery pressure, right ventricular hypertrophy, number of muscularized pulmonary vessels, pulmonary arterial wall thickness, and proliferating pulmonary vascular Ki67-labeled cells without affecting vessel caspase 3 staining. HPI treatment partially prevented the development of hypoxia- and monocrotaline-induced PH. Mono...
Inhibition of Semaphorin As a Novel Strategy for Therapeutic Angiogenesis
Authors: JunjiMoriya, TohruMinamino, KaoruTateno, ShoOkada, AkiyoshiUemura, IppeiShimizu, MasatakaYokoyama, AikaNojima, MitsuhiroOkada, HisashiKoga, IsseiKomuro
Journal: Circulation Research (2010)

Rationale: The axon-guiding molecules known as semaphorins and their receptors (plexins) regulate the vascular pattern and play an important role in the development of vascular network during embryogenesis. Semaphorin (Sema)3E is one of the class 3 semaphorins, and plexinD1 is known to be its receptor. Although these molecules have a role in embryonic vascular development, it remains unclear whether the Sema3E/plexinD1 axis is involved in postnatal angiogenesis. Objective: The objective of this study was to elucidate the role of Sema3E/plexinD1 in postnatal angiogenesis. Methods and Results: Sema3E inhibited cell growth and tube formation by suppressing the vascular endothelial growth factor (VEGF) signaling pathway. Expression of Sema3E and plexinD1 was markedly upregulated in ischemic limbs of mice (2.5- and 4.5-fold increase for Sema3E and plexinD1, respectively), and inhibition of this pathway by introduction of the plexinD1-Fc gene or disruption of Sema3E led to a significant increase of blood flow r...