tbuckley/cabot-search huggingface dataset:
Abstract 295: PPARγ-induced KLF4 in regulation of cell growth and migration in human hepatoma cells.
Authors: Hui-Tzu Hsu, Ming-Ta Sung, Chin-Wen Chi
Journal: Cancer Research (2013)

Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recently, a zinc finger transcription factor Krüppel-like factor 4 (KLF4) was found to be reduced in tumors of HCC patients. Additionally, results from our laboratory showed that overexpressed KLF4 repressed epithelial-mesenchymal transition (EMT) process and cell motility by induction of E-cadherin expression and reduction of EMT markers in hepatoma cells. Interestingly, it has been found that PPARγ agonists upregulated KLF4 in colorectal cancer cells. However, the mechanism of PPARγ-induced KLF4 in the EMT process of HCC remains unclear. In this study, Hep3B, PLC/PRF/5, and Mahlavu human hepatoma cells were treated with PPARγ agonists rosiglitazone, troglitazone, and PPARγ antagonist GW9662, respectively. After rosiglitazone or troglitazone treatment for various time periods, growth inhibition was observed in both Hep3B and PLC/PRF/5 cells at 48 hours by surforhodamine B assay. Mahlavu cells showed less response to rosiglitazone and troglitazone treatment as compared to the other two cell lines. However, pretreatment of GW9662, a PPARγ antagonist, prior to PPARγ agonists treatment did not block the PPARγ agonists-induced cell growth inhibition. Moreover, cotreatment of PPARγ agonist and antagonist showed additive growth inhibition effect. In addition, rosiglitazone and troglitazone inhibited the migration of Hep3B, PLC/PRF/5 and Mahlavu cells differentially in transwell assay. Western blotting analysis showed upregulation of KLF4 and E-cadherin in Hep3B and PLC/PRF/5 cells after rosiglitazone and troglitazone treatment. Interestingly, decreased KLF4 and E-cadherin were observed in Hep3B, PLC/PRF/5, and Mahlavu cells after GW9662 treatment, indicating that the regulation of KLF4 and E-cadherin were PPARγ-dependent. Moreover, GW9662 also inhibited cell migration of Hep3B, PLC/PRF/5, and Mahlavu cells, with a concomitant decrease of vimentin. These results together suggested that PPARγ agonists and antagonist not only inhibited the growth but also decreased migration of hepatoma cells. Modulation of the PPARγ agonists induced expression of KLF4 and E-cadherin played important role in migration of hepatoma cells. Citation Format: Hui-Tzu Hsu, Ming-Ta Sung, Chin-Wen Chi. PPARγ-induced KLF4 in regulation of cell growth and migration in human hepatoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 295. doi:10.1158/1538-7445.AM2013-295
Lumpectomy Compared with Lumpectomy and Radiation Therapy for the Treatment of Intraductal Breast Cancer
Authors: Bernard Fisher, Joseph Costantino, Carol Redmond, Edwin Fisher, Richard Margolese, Nikolay Dimitrov, Norman Wolmark, D. Lawrence Wickerham, Melvin Deutsch, Liora Ore, Eleftherios Mamounas, William Poller, Maureen Kavanah
Journal: New England Journal of Medicine (1993)

Women with ductal carcinoma in situ have been treated both by lumpectomy and by lumpectomy followed by radiation therapy, but the benefit of combined therapy is uncertain. A group of 818 women with ductal carcinoma in situ were randomly assigned to undergo lumpectomy or lumpectomy followed by breast irradiation (50 Gy). Sufficient tissue was removed that the margins of the resected specimens were histologically tumor-free. The mean duration of follow-up was 43 months (range, 11 to 86). The principal end point of the study was event-free survival, as defined by the presence of no new ipsilateral or contralateral breast cancers, regional or distant metastases, or other cancers and by no deaths from causes other than cancer.
HIGH GLUCOSE INCREASES GAMMA-GLUTAMYLTRANSFERASE-INDUCED TISSUE FACTOR EXPRESSION IN HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS
Authors: Valentina Scalise, Cristina Balia, Silvana Cianchetti, Vittoria Carnicelli, Francesca Faita, Tommaso Neri, Riccardo Zucchi, Alessandro Corti, Alessandro Celi, Roberto Pedrinelli
Journal: Journal of the American College of Cardiology (2016)
Abstract 1887: Distinct molecular targets of blueberry and black raspberry in breast cancer prevention
Authors: Srivani Ravoori, Hina Kausar, Farrukh Aqil, Ramesh C. Gupta
Journal: Cancer Research (2010)

Abstract We previously demonstrated protection with berries in diet, against estrogen-induced ACI rat mammary tumorigenesis, by inhibition of proliferation as early as 3 weeks of estrogen administration. In this study, blueberry (BB) and black raspberry (BRB) were administered in diet at 5% 2 weeks prior to implantation with 1.2 cm silastic implants containing 9 mg 17β-estradiol. Rats were killed at 3 weeks, 3 months and ∼7 months, when the tumor incidence in control group reached 80%. Analysis revealed significant reduction (p&amp;lt;0.05) in tumor volume (Control: 801.2±105.3 mm3; BB: 395±97.9 mm3; BRB: 461±109.8 mm3) and tumor multiplicity (Control: 6.9±0.9; BB: 4.4±0.6; BRB: 4.3±0.6) by the berry diets. Most important finding is that while BB was more effective in reducing the tumor volume, BRB was more efficient in delaying the first tumor incidence, by 5 weeks (p&amp;lt;0.05). We also investigated the key molecules of cell-cycle regulation, cell proliferation and transcription. The cell-cycle regulatory molecule cyclin D1 which was up-regulated by 3-4-fold in mammary tissues with estrogen treatment, was significantly down-regulated by BB diet as early as 3 weeks and remained down-regulated during the entire tumorigenesis period (p&amp;lt;0.05), as detected by western blot. BRB diet did not show any significant down-regulation of cyclin D1. Estrogen receptor α, on the other hand, which was significantly overexpressed with estrogen treatment at all the three time points, was significantly offset by BRB diet, but it was not well pronounced with BB diet. Molecules downstream of these effector proteins are currently being explored. While BB contains five distinct anthocyanidins (delphinidin, cyanidin, malvidin, peonidin, and petunidin) and insignificant levels of ellagic acid, BRB contains chiefly cyanidin and high levels of ellagic acid. Thus, the distinct and specific molecular targets and pathways involved in the protective actions of the two berries corroborate their distinct phytochemical signatures. (Supported by CA-118114 and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1887.
A prospective randomized study on the benefits of a new small-caliber colonoscope
Authors: K. Sato, S. Ito, F. Shigiyama, T. Kitagawa, K. Hirahata, K. Tominaga, I. Maetani
Journal: Endoscopy (2012)

We compared the performance efficiency of a newly developed small-caliber colonoscope (PCF-PQ260 L) with passive bending, high force transmission, and an outer diameter of 9.2 mm with that of a standard colonoscope, in female and male patients, particularly with regard to passage through acute angulations or into the proximal colon.A total of 330 patients were randomly allocated to undergo small-caliber (n = 164) or standard (n = 166) colonoscopy. The patients were assessed for pain using a visual analogue scale (0 = none, 100 = extremely painful), and for cecal intubation, withdrawal time, difficulty of colonoscopy, dosage and level of sedation used, and any complications.Median maximum pain and overall pain during colonoscopy were significantly lower in the small-caliber group than in the standard group in women (25 vs. 45, P < 0.001 and 15 vs. 26, P = 0.001, respectively), whereas no significant differences were seen in men (8 vs. 10, P = 0.103 and 16 vs. 20, P = 0.166, respectively). Furthermore, no significant differences were seen between groups in cecal intubation rate or time to cecum in all patients or by sex.Use of the small-caliber colonoscope reduced pain in female patients, but offered no advantage over standard colonoscopy in male patients. The performance of the small-caliber colonoscope was equivalent to that of the standard colonoscope in terms of cecal intubation rate and time to cecum, regardless of the sex of the patient.
TCT-308 Impact of Coronary Artery Spasm on Development of New-onset Diabetes Mellitus in Asian Population
Authors: Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Yoonjee Park, Raghavender Goud Akkala, Sunki Lee, Ji Bak Kim, Sung Il Im, Jin oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2013)
A2.28 Characterisation and potential function of HMGB1 in juvenile idiopathic arthritis
Authors: H Erlandsson Harris, P Lundbäck, P Stridh, L Klevenvall, R Jenkins, M Fischer, E Sundberg, U Andersson, DJ Antoine
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> High mobility group box protein 1 (HMGB1) is a prototypic alarmin being released from activated, stressed or dying cells. Extracellular HMGB1 has the ability to induce cell migration as well as cytokine production. Pathogenic effects of HMGB1 have been described in several inflammatory diseases, including arthritis, and HMGB1-specific blockade is beneficial in multiple experimental disease models. Recent reports have underlined the importance of post-translational modifications (PTMs) in determination of HMGB1 function and release mechanisms. We investigated the occurrence of PTMs of HMGB1 obtained from synovial fluid (SF) of juvenile idiopathic arthritis patients (JIA). <h3>Materials and methods</h3> Synovial fluid was obtained from 17 JIA patients. Total Levels of HMGB1 were determined by ELISA. PTMs of HMGB1 were determined HMGB1-specific immunoprecipitation followed by Liquid chromatography tandem mass-spectrometry (LC-MS/MS). <h3>Results</h3> Analyses of 17 JIA patients confirmed high HMGB1 levels in SF. Liquid chromatography tandem mass-spectrometry (LC-MS/MS) analyses of PTMs revealed that total HMGB1 levels did not associate with increased LDH activity but strongly correlated with nuclear location sequence 2 (NLS2) hyperacetylation, indicating active release of HMGB1. The correlation between total HMGB1 levels and NLS2 hypoacetylation suggests additional, acetylation-independent release mechanisms. Monomethylation of lysine 43 (K43), a proposed neutrophil-specific PTM, strongly associated with high HMGB1 levels, implying that neutrophils are a source of released HMGB1. Analysis of cysteine redox isoforms: fully reduced HMGB1, disulfide HMGB1 and oxidised HMGB1 revealed that HMGB1 acts as both a chemotactic and a cytokine-inducing mediator. These properties were associated with actively released HMGB1. <h3>Conclusions</h3> This is the first report that characterises HMGB1-specific PTMs during a chronic inflammatory condition. HMGB1 in SF from JIA patients is actively released through both acetylation- and non-acetylation-dependent manners. The presence of various functional HMGB1 redox isoforms confirms the complexity of its pathogenic role during chronic inflammation. Defining HMGB1 release pathways and redox isoforms is critical for the understanding of the contribution of HMGB1 during inflammatory processes.
Abstract 1651: Targeting Vav3 oncogene enhances docetaxel-induced apoptosis in LNCaP cells under chronic hypoxia
Authors: Takeo Nomura, Kenichi Hirai, Mutsushi Yamasaki, Fuminori Sato, Hiromitsu Mimata
Journal: Cancer Research (2011)

Abstract Introduction and Objective: We previously reported that chronic hypoxic condition (1% oxygen for over six months) induced Vav3 oncogene expression with androgen-independent growth and malignant behavior in LNCaP cells. And overexpression of Vav3 oncogene promoted the growth of LNCaP cells with increased invasion and migration under normoxic condition. The objective of this study was to examine the effect of Vav3 siRNA on cell proliferation and apoptosis in docetaxel-treated LNCaP cells under chronic hypoxic condition. Methods: We analyzed the sensitivity of docetaxel in LNCaP cells under normoxic and chronic hypoxic conditions by 2-(4-lodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1) and flow cytometric analyses. The effects of Vav3 siRNA on cell growth and apoptosis were examined under chronic hypoxia with or without docetaxel treatment. To seek a molecular understanding of Vav3 siRNA induced apoptosis, we analyzed alterations in the growth signaling components in the PI3K/Akt and ERK mediated pathways by immunoblot analysis. Results: Overexpression of Vav3 was observed in LNCaP cells under chronic hypoxia compared with its expression under normoxia. Although the growth rates were reduced in a dose- and time-dependent manner by docetaxel in LNCaP cells under both normoxic and chronic hypoxic conditions, these effects were significantly decreased in LNCaP cells under chronic hypoxia. In addition, we found that docetaxel induced apoptosis following activation of caspase-3 and cleaved poly (ADP-ribose) polymerase, and that the interrupting the Vav3 signaling pathway using siRNA enhanced docetaxel sensitivity of LNCaP cells under chronic hypoxia and led to apoptosis. A profound activation of PI3K/Akt pathway was observed under chronic hypoxic condition. Treatment with Vav3 siRNA showed weak inhibition of Akt phosphorylation and treatment with Vav3 siRNA plus docetaxel strongly inhibited this signaling. Conclusions: Our results showed that Vav3 siRNA enhances docetaxel-induced apoptosis in LNCaP cells under chronic hypoxia and that targeting Vav3 oncogene may have important practical implications for managing hormone refractory prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1651. doi:10.1158/1538-7445.AM2011-1651
Effect of asbestos on the P388D1 macrophagelike cell line: preliminary ultrastructural observations.
Authors: N F Johnson, R Davies
Journal: Environmental Health Perspectives (1983)

The ultrastructural effects of mineral dusts on a macrophagelike cell line (P388D1) were studied by transmission electron microscopy. The cells were found to contain virus particles which probably did not exert a cytopathic effect toward the cells. During mitosis the asbestos fibers appeared to be pushed to the periphery of the cell. The distribution of the asbestos in the P388D1 cells was similar to that seen previously in cultured peritoneal macrophages, and it was concluded that the cytotoxic effect of asbestos towards the cells was due to mechanical effects, e.g., by penetrating structures such as the nucleus or phagosomes, by preventing the ordered movement of organelles with the cell or by disrupting the cytoskeletal framework of the cell.
P8 Objective Cough Frequency Monitoring In Bronchiectasis
Authors: A. Spinou, R. Garrod, K. Lee, C. Elston, M. Loebinger, K. Chung, R. Wilson, S. Birring
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Cough is a major symptom in bronchiectasis. Cough monitors are emerging as an important tool that assesses cough objectively. The aim of this cross-sectional study was to assess cough frequency in non-cystic fibrosis bronchiectasis, investigate its association with patient-reported symptoms and health-related quality of life (HRQOL), and investigate potential factors of cough frequency variability. <h3>Methods</h3> Patients with non-cystic fibrosis bronchiectasis were recruited from 2 outpatient bronchiectasis clinics. All patients underwent 24-hour ambulatory cough monitoring with the Leicester Cough Monitor, and reported sleeping time in a diary. The patients also completed the Leicester Cough Questionnaire (HRQOL), and visual analogue score (VAS) for sputum and cough severity. Sputum bacteria colonisation status was assessed, and defined as at least 2 positive cultures, minimum 3 months apart and within one year. <h3>Results</h3> 49 patients were recruited; median (IQR) age 65 (52, 70) years, 64% female. The aetiology of bronchiectasis were: idiopathic (45%), post infective (29%) and other (25%). The prevalence of sputum colonisation were: pseudomonas aeruginosa 38% and other organisms 29% of patients. Median (IQR) 24-hour, day time and night time cough counts were: 249 (112, 438), 240 (109, 404.5) and 24 (5, 56.5) coughs respectively. There was diurnal variation in cough frequency (Figure 1). Day time cough frequency was significantly greater than night time (Wilcoxon signed rank test p &lt; 0.01). 24-hour total coughs were significantly associated with HRQOL (Spearman ρ=-0.54, p &lt; 0.01), cough VAS (ρ=0.56, p &lt; 0.01) and sputum VAS (ρ=0.48, p &lt; 0.01). There was an association between 24-hour cough counts and gender (linear regression p = 0.05), but no association with bronchiectasis aetiology, sputum colonisation status or age. <h3>Conclusions</h3> Cough frequency monitoring in patients with bronchiectasis is feasible. Higher cough frequency was associated with poorer HRQOL and worse patient-reported symptoms of cough and sputum. Patients coughed more during the day than at night. 24-hour cough frequency was variable and gender was identified as an influential factor. Future studies should investigate other potential factors for cough variability in bronchiectasis and evaluate the potential of cough frequency as an outcome measure for assessing the efficacy of therapy.
Abstract 3708: Effects of black raspberry and related components on DB[<i>a,l</i>]P-induced DNA adduct formation in mouse oral tissues.
Authors: Kun-Ming Chen, Shang-Min Zhang, Cesar Aliaga, Yuan-Wan Sun, Arthur Berg, Arun Sharma, Shantu Amin, Gary Stoner, Karam El-Bayoumy
Journal: Cancer Research (2013)

Abstract Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region; in the USA, over 45,000 cases and about 11,000 deaths from the disease occur annually. Progress in the prevention and control of OSCC has been hampered by the lack of appropriate animal models that would reflect human exposure. Tobacco smoking is considered a major etiological factor in the development of oral cancer. Previous studies have demonstrated the ability of diets containing 5-10% freeze-dried black raspberry (BRB) powder to inhibit the development of chemically-induced cancers in multiple organ sites in rodents including 7,12-dimethylbenz(a)anthracene (DMBA) induced squamous cell carcinomas (SCC) in the hamster cheek pouch. DMBA, however, is not present in the environment and the hamster cheek pouch model may not be applicable to humans. Recently, we developed a relevant animal model (Int. J. Cancer, 2012, 2783-90) and showed that dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and a tobacco smoke component, induces SCC in oral tissues of mice. In the current study, we evaluated the effects of BRB and related components including kaempferol and resveratrol on DNA adducts induced by DB[a,l]P in mouse oral cavity as an initial step to explore the potential preventive activity of BRB and its related components on DB[a,l]P-induced oral cancer. The DB[a,l]PDE-DNA adduct levels were quantified by our recently developed LC-MS/MS method (Chem. Res. Toxicol. 2011, 1297-303). We demonstrated that the administration of BRB (5%), kaempferol (0.025%) or resveratrol (0.002%) in the diet, starting 2 weeks before DB[a,l]P (24 nmol, 3 times a week for 5 weeks) resulted in 27%, 36% or 65% reduction of the level of (-)-anti-trans-DB[a,l]PDE-dA in murine oral tissues, respectively. In conclusion, our results support that dietary consumption of BRB and its related components can inhibit the metabolic activation of DB[a,l]P, and may prevent the subsequent mutagenesis and carcinogenesis resulting from exposure to DB[a,l]P. Citation Format: Kun-Ming Chen, Shang-Min Zhang, Cesar Aliaga, Yuan-Wan Sun, Arthur Berg, Arun Sharma, Shantu Amin, Gary Stoner, Karam El-Bayoumy. Effects of black raspberry and related components on DB[a,l]P-induced DNA adduct formation in mouse oral tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3708. doi:10.1158/1538-7445.AM2013-3708
Abstract 2882: Penta-O-galloyl-beta-D-glucose induces DNA replicative S arrest and G1 arrest independent of p21Cip1, p27Kip1 and p53 in human breast cancer cells and is orally active against breast cancer xenograft
Authors: Yubo Chai, Hyo-Jeong Lee, Ahmad Shaik, Katai NKhata, Chengguo Xing, Sung-Hoon Kim, Junxuan Lü
Journal: Cancer Research (2010)

Abstract Natural herbal compounds with novel actions different from existing breast cancer targeting modalities are attractive for improving treatment and prevention efficacy and safety. We have recently shown that penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG), a naturally occurring gallotannin polyphenol compound, induced S-phase arrest in prostate cancer cells through inhibiting DNA replicative synthesis, in addition to the induction of G1 arrest and cell deaths at higher levels of exposure. We and others have shown that PGG through i.p. injection exerts a strong in vivo growth suppression of human prostate cancer xenograft models in athymic nude mice. We hypothesize that the novel DNA replication targeting action and the cellular arrest and death effects of PGG are applicable to breast cancer cells and PGG could be a novel agent for treatment or prevention of breast cancer, especially those without proven drugable targets such as triple-negative breast cancer. In cell culture studies, exposure to serum achievable level of PGG induced rapid S arrest in p53-wild type ER-dependent MCF-7 breast cancer cells and in p53-mutant ER-/PR- and Her2-negative (triple-negative) MDA-MB-231 breast cancer cells as indicated by the lack of BrdU incorporation into S-phase cells. Higher levels of PGG induced more caspase-mediated apoptosis in MCF-7 than in MDA-MB-231 cells. In addition to S-arrest, PGG induced G1 arrest in both cell lines. Contrary to a study by others with questionable design, we have found no induction of CDK inhibitory proteins p21Cip1 and p27Kip1 with G1 arrest. PGG treatment led to decreased cyclin D1 in both cell lines and over-expressing cyclin D1 abolished G1 arrest and hastened S arrest. In serum-starvation synchronized MCF-7 cells, we observed a close association of down-regulation of cyclin D1 and de-phosphorylation of Rb by PGG shortly before G1-S transition stimulated by serum. Though PGG inhibited estrogen-stimulated cell growth in MCF-7 cells, it had little effect on estrogen receptor-alpha level. To test the in vivo efficacy of PGG, we treated female athymic mice inoculated with MDA-MB-231 xenograft with 10 mg/kg body weight by daily gavage and compared with weekly paclitaxel treatment at the same dosage. Oral administration of PGG led to a better growth inhibitory efficacy than the taxane drug. Together, our in vitro and in vivo data support PGG as a potential chemopreventve or treatment agent for breast cancer with novel targeting actions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2882.