tbuckley/cabot-search huggingface dataset:
AB0757 Noninvasive ultrasound measurements of absolute soft tissue stiffness in systemic sclerosis
Authors: T. Santiago, B. Alcacer-Pitarch, F. Del Galdo, M. Buch, A. C. Redmond
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Elastography Ultrasound (EUS) is an ultrasound-based method, which allows the qualitative or quantitative measurements of the biomechanical properties of tissues. EUS can be performed using compression-wave or more recently, shear-wave propagation, using acoustic radiation force impulse (ARFI) imaging and associated new virtual touch imaging (VTI) and virtual touch quantification (VTQ) technologies. ARFI estimates tissue stiffness in real time and is quantitative and user independent. The use of VTQ technology has never before been reported in patients with systemic sclerosis (SSc). <h3>Objectives</h3> To compare the relative and absolute soft tissue stiffness in patients with SSc and healthy controls using compression EUS and ARFI. <h3>Methods</h3> Twenty-six patients with SSc and twenty-five age and gender matched healthy controls were included in the study. Relative and absolute stiffness of soft tissue were measured on the palmar aspect of the third metacarpophalangeal joint, plantar aspect of the third metatarsophalangeal joint and over the heel. All these sites have an anatomical features associated withbiomechanical stress. <h3>Results</h3> There was a trend towards greater tissues stiffness values in SSc patients and controls using all three technologies. VTQ was the most consistent measure and provided absolute outputs (Table 1). <h3>Conclusions</h3> Measurements of tissue stiffness by EUS add a new dimension to the assessment of soft tissues in SSc. The compression EUS and VTI technologies have some limitations for the real-world application in SSc. VTQ however, is a promising technique that provides absolute and objective quantification of tissue stiffness. In the longer term VTQ and similar technologies may offer an objective and quantitative alternative tools to clinical measures such as the modified Rodnan Skin Score. <h3>References</h3> -Clements PJ, et al Arthritis Rheum. 1990; 33:1256-63; -Drakonaki EE, et al. Br J Radiol. 2012; 85:1435-45; -Iagnocco A, et al J Rheumatol. 2010;37:1688-91; -Di Geso L, et al Clin Exp Rheumatol. 2011; 29:926-32; -Porta F, et al Rheumatology (Oxford). 2012;51:S7. <h3>Disclosure of Interest</h3> None Declared
P3-03-01: Low Expression of microRNA-210 Is an Independent Good Prognostic Factor in Japanese Triple-Negative Breast Cancer Patients.
Authors: T Toyama, N Kondo, Y Endo, H Sugiura, N Yoshimoto, M Iwasa, S Takahashi, H Iwase, Y Fujii, H Yamashita
Journal: Cancer Research (2011)

Abstract Background: microRNAs (miRNAs) have emerged as a new class of non-coding genes involved in regulating cell proliferation, differentiation, and viability. Recent studies have identified miR-210 among a set of hypoxia-regulated miRNAs and demonstrated a direct regulatory role of hypoxia-inducible factor-1 alpha (HIF-1 a) in its transcription. High expression of miR-210 has been reported to be a poor prognostic factor in several types of cancers including breast. Materials and Methods: TaqMan MicroRNA assays for miR-210 expression were performed in 219 breast cancers (58 triple-negative (TNBCs), and 161 ER-positive and HER2−negative). Correlations between miR-210 expression and clinicopathological factors were analyzed. The effects of several variables on survival were tested by Cox proportional hazards regression analysis. Results: miR-210 expression in TNBCs was significantly higher than in ER-positive and HER2−negative breast cancers (p&amp;lt;0.001). Patients whose TNBCs had low miR-210 expression experienced significantly better disease-free and overall survival compared with high miR-210 expressors (p=0.02 and p=0.05, respectively). Notably, among 40 node-negative TNBCs, 5-year disease-free survival was approximately 60% in patients whose tumors had high or intermediate miR-210 expression (n=26), while no patients with low miR-210 expression (n=14) suffered recurrent disease. Cox univariate and multivariate analyses demonstrated that low expression of miR-210 was an independent good prognostic factor in TNBCs. Discussion: Although prognosis of patients with TNBCs is poor, those whose tumors expressed low levels of miR-210 had a more favorable prognosis. Thus, the degree of miR-210 expression might be a clinically useful prognostic factor for decision-making regarding treatment in the adjuvant setting, especially in node-negative TNBC patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-03-01.
Abstract 3473: Beta catenin inhibitor ICG-001 attenuates proliferation of hepatic tumor initiating cells in Pten deficient models
Authors: Vivian Galicia Medina, Anketse D. Kassa, Bangyan L. Stiles
Journal: Cancer Research (2012)

Abstract Progenitor or tumor initiating cells (TICs) are “altered” stem cells with the capacity to form solid tumors. Tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome ten) is aberrantly expressed in liver cancers. Liver specific Pten (Pm) mice develop liver cancer following an extensive phase of chronic lipid accumulation and demonstrate escalating levels of hepatic injury markers from 6-12M, prior to hepatic progenitor cell proliferation. In addition, TUNEL analysis revealed that hepatocytes from Pm mice undergo extensive apoptosis relative to control mice. We hypothesize that hepatocyte cell death induced by hepatic injury presents an opportunity for TICs to proliferate and consequently form mixed lineage tumors. Attenuation of hepatic injury by Akt2 deletion reduces progenitor cell proliferation and delays tumor development. Our analyses also revealed that the Wnt/β-Catenin signaling pathway is the likely molecular mediator of TIC proliferation in our Pm model. Wnt ligands including 7a and 10a as well as Wnt signaling receptor Fzd 2 are induced. In this study, we investigate the role of the Wnt/β-Catenin pathway in the activation of hepatic progenitor cells in the Pten deletion liver cancer model using novel Wnt/β-catenin inhibitor ICG-001. ICG-001 is a small molecule which specifically inhibits β-Catenin/CBP interaction. Coactivator CBP/β-Catenin/T cell factor (TCF) mediated transcription has been reported as critical for stem cell/progenitor cell proliferation. Here we demonstrate that ICG-001 significantly attenuates proliferation of hepatic cancer stem cell line P0 in vitro and also inhibits hepatotoxin induced proliferation of hepatic TICs in vivo in liver Pten null mice. Our preliminary results indicate that targeting the cancer stem cell niche may prove to be a viable approach to inhibit liver tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3473. doi:1538-7445.AM2012-3473
ENDOLIFTER COMO FACILITADOR DE LA D.S.E. EN MODELO PORCINO. VALOR DE LA EXPERIENCIA DEL ENDOSCOPISTA
Authors: JC Marín-Gabriel, J Díaz-Tasende, S Rodríguez-Muñoz, AJ Del Pozo-García, F Sánchez-Gómez, M Pérez-Carreras, J Aranda-Hernández, M Grau-Sanz, M Gracia-García, G Castellano-Tortajada
Journal: Endoscopy (2011)

Introducción: La disección submucosa endoscópica (D.S.E.) es un procedimiento muy complejo que requiere de una elevada destreza técnica por parte del endoscopista.
Abstract 1880: Sun exposure and the risk of prostate cancer in an Asian population: The Singapore Prostate Study
Authors: Sin-Eng Chia, Kin Yoke Wong, Weber Lau, Christopher Cheng
Journal: Cancer Research (2011)

Abstract INTRODUCTION: Recent epidemiological studies have reported an inverse association between sun exposure and prostate cancer which may be related to vitamin D or other factors, but these studies have been conducted almost exclusively in the Western countries, and in temperate locations. The objective of this paper is to study the association of sun exposure and risk of prostate cancer (PC). METHODS: The Singapore Prostate Cancer study is a hospital-based, case-control study conducted in Singapore between April 2007 and May 2009. Singapore residents (ethnic Chinese/Malays/Indians) aged 50 and above formed the study population. Detailed information on outdoor activities under sun (for recreational or occupational purposes) during childhood and in adulthood, skin color and sun sensitivity, and other information on other possible risk factors were collected in personal interviews. A total of 240 incident prostate cancer cases and 268 controls were recruited. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis, adjusted for age, ethnicity, education, family history of any cancers, BMI and skin color. RESULTS: Subjects with black/dark brown eye compared with light brown pigmentation have an adjusted OR of 5.88 (3.17-10.92) of getting PC. The adjusted ORs for skin color “Light Tan” and “Tan/Dark brown/black” subjects when compared with of “very white/white” subjects were 4.43 (2.26-8.69) and 7.62 (3.41-17.03); respectively. Sunburn frequency is associated with increase risk of PC. The adjusted ORs with “Never” sunburn as referent were 1.30 (0.71-2.39) for “Seldom”; 2.27 (0.96-5.35) for “Occasionally”; 4.30 (1.66-11.16) for “Frequently”. This trend was significant (p=0.001). Sun exposure in adulthood (hrs/week) is also associated with increase risk of PC. The adjusted ORs with “0 hrs” sunburn as referent were 1.71 (0.90-3.25) for “0.1-10hrs” and 2.03 (1.09-3.81) for “&amp;gt;10 hrs”. This trend was significant (p=0.017). CONCLUSION: Pigment characteristics (eye and skin color) and sun exposure and possible sensitivity showed association with risk of PC, after adjusting for likely confounders. We observed an overall risk of PC among subjects who reported spending time outdoors regularly. 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 1880. doi:10.1158/1538-7445.AM2011-1880
Abstract 2144: An integrated genomic and transcriptomic analysis of human uterine leiomyomas
Authors: Priscila D.R Cirilo, Fabio A. Marchi, Alex F. Carvalho, Anagloria Pontes, Silvia R. Rogatto
Journal: Cancer Research (2010)

Abstract Uterine leiomyoma (UL) are tumors that arise from the uterine smooth muscle wall. Despite their nonmalignant nature, UL represent a major concern in women's health through their induction of significant morbidity in more than 25% of reproductive-age. The etiology of UL remains unknown. Cytogenetic studies have been identified recurrent aberrations involving the t(12;14); del(7)(q22q32); trisomy 12; and 6p21 rearrangements. The aim of this study was integrate genomic and gene expression microarray data to identify genes with altered function due to genomic instability. DNA and RNA were extracted from 24 UL from women at proliferative (n=14) and secretory (n=10) phase of the menstrual cycle. Normal control RNA was obtained from adjacent myometrium from all cases. Array CGH and gene expression microarray was done using the Human 44K Agilent oligoarrays according to manufacturer's instructions. Data were extracted and flagged with Feature Extraction software (version 10.1.1.1) and processed using Genomic Workbench Standard (version.5.0.14). Non-supervised analysis of gene expression revealed clustering of all cases independent of the phase of menstrual cycle. It was observed a significant correlation between deletion and down expression at 1q32.2-q44 and 7q11.22-q33. Although deletions at 1q and 7q had been described previously as involved in UL, the genes mapped at these regions were poorly studied. These genes are involved in Wnt signaling pathway, induction of apoptosis, transforming growth factor signaling pathway, fumarate hydratase activity, and fibrinolysis. Furthermore, it was observed correlation between amplification and increased gene expression at 11p15.5, 14q32.33, and 16p13.3. These regions harboring genes with function associated with regulation of cell proliferation and regulation of JNK cascade. Our results provide strong circumstantial evidence that different patterns of genomic imbalances contribute to their specific transcriptomic profiles. In the future, new therapies based on these findings can be applied in a subgroup of patients with specific genomic imbalances. Supported by the FAPESP (07/51643-8) and CNPq (485032/2007-4), Brazil. 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 2144.
Abstract 262: Upregulation of neutrophil gelatinase-associated lipocalin by ErbB2 through NF-κB activation
Authors: Shau-Hsuan Li, Valerie S. Hawthorne, Christopher L. Neal, Sartaj Sanghera, Jia Xu, Jun Yang, Hua Guo, Patricia S. Steeg, Dihua Yu
Journal: Cancer Research (2010)

Abstract ErbB2 (HER2, neu) is a receptor tyrosine kinase overexpressed in about 25% of invasive breast carcinomas. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted glycoprotein expressed in a variety of cancers including breast carcinomas. NGAL can inhibit erythroid cell production leading to anemia. Anemia usually occurs in cancer patients and negatively impacts quality of life. However, current treatment for cancer-related anemia has potential complications. ErbB2, NGAL, and anemia have all been associated with increased metastasis and poor prognosis in breast cancer patients, although the relationship between ErbB2 and NGAL expression is not clear. Here, using breast cancer cell lines in vitro and transgenic mice carrying the activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV-neu) in vivo, we demonstrate that ErbB2 overexpression leads to NGAL upregulation, which is dependent on nuclear factor kappa B (NF-κB) activity. MMTV-neu transgenic mice developed anemia after tumor onset, and anemia progression could be partially arrested by an NF-κB inhibitor and an ErbB2-targeted therapy. Taken together, upregulation of NGAL by ErbB2 through NF-κB activation is involved in cancer-related anemia, and ErbB2, NF-κB, NGAL pathway may serve as potential therapeutic targets for cancer-related anemia. 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 262.
BRAIN TUMOUR INITIATING CELLS AND TARGETING STAT3 ONCOGENIC SIGNALLING IN GBM
Authors: S. Weiss, S. Nguyen, A. Luchman, N. Grinshtein, O. Stechishin, A. Aman, D. Uehling, R. al-Awar, D. Kaplan
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma (GBM) is a devastating disease and the most lethal of adult brain tumours. Despite standard surgery, radiation and chemotherapy, the median survival is 15 months, thought to be due, in part, to recurrence from a small reservoir of brain tumour initiating cells. Our laboratory discovered adult neural stem cells, now found to be present in the brains of all adult mammals, through the development of the clonal neurosphere assay. This assay has contributed to the identification of adult human brain tumour initiating cells (BTICs), which may represent a reservoir that leads to GBM recurrence and death. Building upon the identification of growth factors and cytokines that converge on the cytoplasmic signal transducer and activator of transcription 3 (STAT3) to maintain the adult neural stem cell undifferentiated state, and the fact that STAT3 is abnormally active in GBM and may be one of the causes of tumour growth and therapeutic resistance, targeting the janus kinase (JAK)/STAT3 signalling pathway has become a major research focus for our laboratory. Here, we report the GBM translational potential of R333, a JAK/SYK inhibitor in development for other indications by Rigel Pharmaceuticals. METHODS: We have developed a cellular resource of more than 100 BTIC lines derived from GBM patients. Collaborative studies with academic and industry partners has resulted in the identification of promising therapeutic candidates that target JAK/STAT3 signalling in GBM. These compounds are tested for their ability to attenuate growth of BTICs in cell culture, on target activity in vitro and in vivo, and for their impact on the the survival of immunocompromised mice that have received BTIC xenografts. We employed this approach to examine the therapeutic potential of R333. RESULTS: In a collection of diverse patient-derived BTIC lines, R333 demonstrated potent, on-target JAK/STAT3 inhibition at low micromolar doses that effectively decreased BTIC viability and clonogenic potential, without affecting human fetal astrocytes. Importantly, R333 could be co-administered with temozolomide without reducing therapeutic response. Using phosphoproteomics, we confirmed the primary target of R333 in BTSCs as activated STAT3. In a BTIC orthotopic xenograft model, systemic treatment with R348, the pro-drug form of R333, resulted in BBB penetration and significant increased overall median survival without major side effects. CONCLUSIONS: These data suggest that R333 (R348) is a potent, BBB-permeable JAK/STAT3 inhibitor, worthy of further clinical evaluation for GBM treatment. These findings support our overall hypothesis that targeting the STAT3 signalling pathway may represent an effective therapeutic approach to managing GBM. SECONDARY CATEGORY: Tumor Biology.
Amylase-Resistant Starch plus Oral Rehydration Solution for Cholera
Authors: B.S. Ramakrishna, S. Venkataraman, P. Srinivasan, Pratap Dash, Graeme P. Young, Henry J. Binder
Journal: New England Journal of Medicine (2000)

Although standard glucose-based oral rehydration therapy corrects the dehydration caused by cholera, it does not reduce the diarrhea. Short-chain fatty acids, which are produced in the colon from nonabsorbed carbohydrates, enhance sodium absorption. We conducted a study to determine the effects of an orally administered, nonabsorbed starch (i.e., one resistant to digestion by amylase) on fecal fluid loss and the duration of diarrhea in patients with cholera.
Abstract 4009: Regulation of mTOR pathway by the orphan nuclear receptor NR4A1 (TR3/Nur77) in non-small cell lung cancer: Role of TR3 in AMPK activation
Authors: Syng-Ook Lee, Terrick Andey, Un-Ho Jin, Kyounghyun Kim, Mandip Singh, Stephen Safe
Journal: Cancer Research (2011)

Abstract The orphan nuclear receptor NR4A1 (TR3/Nur77) is overexpressed as a nuclear protein in multiple human tumors and this receptor exhibits pro-oncogenic activity in many tumor types. A recent study in this laboratory has shown that deactivation of TR3 decreases proliferation and induces apoptosis through inhibition of Sp1-dependent anti-apoptotic genes. In this study, we show that TR3 is overexpressed in human non-small cell lung cancer (NSCLC) tissues compared with adjacent normal lung tissues and high TR3 expression levels are correlated with shorter survival for patients with NSCLC (P = 0.0112). Treatment of NSCLC cells with small interfering RNAs for TR3 or the TR3 deactivator, 1,1-bis(3’-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH), decreased cell proliferation and induced apoptosis through dual-targeting of mTOR pathway and Sp1 transcription factor. Knockdown of TR3 inhibited mTOR and its two major downstream targets, p70S6K and 4E-BP1 through LKB1-independent activation of AMPK but not through inactivation of AKT nor Sp1. We also observed that AMPK activation by TR3 knockdown is primarily due to induction of sestrin2 by enhancing p53-dependent transactivation activity. Furthermore, DIM-C-pPhOH (30 mg/kg/day) induced apoptosis and inhibited tumor growth in an orthotopic mouse model of human NSCLC, and decreased tumor number and size in a lung metastatic tumor model using tail vein injection. These results demonstrate for the first time that endogenous nuclear TR3 regulates AMPK-mediated mTOR pathway and TR3 deactivation represents a novel approach for treatment of NSCLC. Grant support: National Institutes of Health (R01CA124998) 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 4009. doi:10.1158/1538-7445.AM2011-4009
TECHNIQUE FOR ASSESSMENT OF CRANIAL BONE GRAFT SURVIVAL USING CT and SPECT
Authors: C. B. Caldwell, O. L. Antonyshyn, M. P. Bernstein, K. Ma, P. W. Cooper, L. E. Ehrlich
Journal: Clinical Nuclear Medicine (1998)

Caldwell, C. B.; Antonyshyn, O. L.; Bernstein, M. P.; Ma, K.; Cooper, P. W.; Ehrlich, L. E.Author Information
Prognostic significance of <i>GSTP1 and MGMT</i> hypermethylation in invasive ductal breast carcinoma patients.
Authors: G Sharma, S Mirza, R Parshad, SD Gupta, P Pandaya, R Ralhan
Journal: Cancer Research (2009)

Abstract Abstract #4053 Purpose: Methylation-mediated suppression of detoxification, DNA repair and tumor suppressor genes has been implicated in cancer development, by shifting cells from the normal cellular cycle to a state of high proliferation that favors tumor development and progression. The current study was designed to analyze the methylation status of these genes in sera of breast cancer patients and determine the correlation of promoter hypermethylation of these genes with disease prognosis and patient survival.&amp;#x2028; Experimental design: To test the hypothesis that promoter methylation of GSTP1 and MGMT is associated with disease prognosis, the methylation status of these genes was analyzed in invasive ductal carcinoma tissues and corresponding sera of breast cancer patients and correlated with disease free survival of these patients.&amp;#x2028; Results: Promoter methylation of GSTP1 and MGMT was observed in 25% and 38% of breast tumor tissues, respectively and in 23% and 35% of the corresponding sera of breast cancer patients. There was significant association between methylation of GSTP1 and advanced tumor stage. Patients harboring methylated GSTP1 were more likely to have disease progression and reduced overall survival compared with patients who did not have the methylated gene.&amp;#x2028; Conclusion: GSTP1 methylation in tumor and sera may serve as a poor prognostic marker in patients with invasive ductal carcinoma. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4053.