tbuckley/cabot-search huggingface dataset:
Abstract LB-39: Phenotypic switching and molecular anatomy of malignant progression <i>(E-M-T/M-E-T).</i>
Authors: Chong-Feng Gao, George F. Vande woude
Journal: Cancer Research (2011)

Abstract Proliferation and invasion are two fundamental phenotypes required for malignancy while phenotypic switching is required for malignant progression. Thus, during malignant progression primary tumor cells switch from proliferative to invasive phenotypes and switch again to form proliferating metastases. The acquisition of the invasive phenotype through epithelial-mesenchymal-transition (E-M-T) is a crucial step in tumor progression, as is mesenchymal-epithelial-transition (M-E-T) or switching to become tumor metastases. Using a reductionist approach, we have been able to reproduce these steps through a combination of in vitro and in vivo methods: Beginning with prostate and ovarian carcinoma cells, we show that the majority are epithelial (E) cells, grow as acini in three dimensional (3D) Matrigel and are nonresponsive to hepatocyte growth factor/scatter factor (HGF/SF). These E cells grow in soft agar and are tumorigenic in immunocompromised mice. However, there is a second cell population which also grows as acini in 3D Matrigel, but display extensive branching morphogenesis when HGF/SF is present. These subclones are mesenchymal (M), are highly invasive in response to HGF/SF, but do not grow in soft agar and display low or no tumorigenicity in vivo. We show that M cells can originate in vitro from the non-invasive E subclones. However, M subclones undergo M-E-T only in vivo, at low frequency mimicking tumor progression to proliferating metastases. We show that E-M-T switching events occur with loss of E-Cadherin and the gain of c-MET expression. Expression of β-Catenin does not change with phenotypic switching, but with the loss of E-Cadherin, its localization shifts from the cell membrane to nuclear/cytoplasmic location, activating β-Catenin dependent expression. Moreover, depleting E-Cadherin in E cells triggers nuclear/cytoplasmic shift of β-Catenin and enhanced HGF/SF-c-Met signaling, while ectopic expression of E-Cadherin in M cells restores E phenotype and decreases HGF/SF-Met signaling. Importantly, we show that phenotypic switching occurs with distinct changes in karyotype that dictate changes in the chromosome transcriptome and the expression of genes that account for changes to M or to E phenotypes, thereby implicating chromosome instability as a key mechanism for phenotypic switching. We conclude that chromosome instability generates the transcriptome diversity in vitro or in vivo, which in the appropriate environment, leads to expansion of clonal variants responsible for phenotypic switching. 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 LB-39. doi:10.1158/1538-7445.AM2011-LB-39
Dominant Inheritance of Adenomatous Colonic Polyps and Colorectal Cancer
Authors: Randall W. Burt, D. Timothy Bishop, Lisa A. Cannon, Mark A. Dowdle, Randall G. Lee, Mark H. Skolnick
Journal: New England Journal of Medicine (1985)

Except in the rare polyposis syndromes, the contribution of heritable factors to the genesis of colorectal cancer and adenomatous polyps is not well understood. We examined the inheritance of susceptibility to colonic polyps and cancer in a large Utah pedigree with multiple cases of common colorectal cancer but no recognizable inheritance pattern among them. Inheritance was clarified, however, by systematic screening for colonic polyps in pedigree members and spouse controls, using flexible proctosigmoidoscopy. One or more adenomatous polyps were found in 21 per cent of family members (41 of 191) but in only 9 per cent of controls (12 of 132) (P<0.005). Pedigree analysis was performed with likelihood methods that compared random occurrence of cancer and polyps with autosomal recessive and autosomal dominant patterns of inheritance. The analysis suggested that the observed excess of discrete adenomatous polyps and colorectal cancers was the result of an inherited autosomal dominant gene for susceptibility, rather than an inherited recessive gene for susceptibility or a chance occurrence. This type of inheritance of colorectal polyps and cancer may be more common than previously recognized. (N Engl J Med 1985; 312:1540–4.)
Prediction of Mortality in Patients with Cystic Fibrosis
Authors: Eitan Kerem, Joseph Reisman, Mary Corey, Gerard J. Canny, Henry Levison
Journal: New England Journal of Medicine (1992)

The majority of patients with cystic fibrosis die in early adulthood of lung disease. Lung transplantation is a treatment option for patients with advanced pulmonary disease, although the waiting period for organs may be as long as two years. Our purpose was to determine whether the risk of death due to respiratory failure could be predicted one or two years in advance on the basis of pulmonary function, blood gas levels, and nutritional status.
PET in Oncology. Basics and Clinical Applications
Authors: Yusuf Menda, Mark T. Madsen, David L. Bushnell
Journal: Clinical Nuclear Medicine (2000)

Department of Radiology; University of Iowa Hospitals and Clinics; Iowa City, Iowa Diagnostic Imaging and Radioisotope Therapy Service; Veterans Affairs Medical Center Iowa City; Iowa City, Iowa CLINICAL NUCLEAR MEDICINE publishes in each issue a section of references to articles of interest to its readers taken from the world medical literature. Articles below were selected from listings received through September 15, 2000. Slavic and Oriental language articles have English summaries unless marked with an asterisk after language abbreviation.
S72 RAGE Activation and Endothelial Cell Injury Associated with Cardiopulmonary Bypass
Authors: M Patel, T Svermova, L Ramakrishnan, BC Creagh-Brown, M Griffiths, A Burke-Gaffney
Journal: Thorax (2012)

<h3>Introduction and objectives</h3> The systemic inflammatory response syndrome (SIRS) which complicates most cases of surgery necessitating cardiopulmonary bypass (snCPB) is associated with endothelial cell injury and activation of the receptor for advanced glycation end products (RAGE). We hypothesised that RAGE activation leads to endothelial cell damage and that plasma levels of RAGE ligands, S100A8/A9 and S100A12, increased following snCPB will be positively associated with raised plasma syndecan-1 shed from damaged endothelial cells. We also hypothesised that S100 proteins and for comparison TNFα directly modulate syndecan-1 expression in cultured endothelial cells. <h3>Methods</h3> Enzyme-linked immunosorbent assay measurements of syndecan-1, S100A8/A9 and S100A12 in plasma samples collected from patients pre- and post-snCPB (n=12); real-time-PCR determination of syndecan-1 expression and the house-keeping gene, GAPDH, in human umbilical vein endothelial cells (HUVEC) following incubation with TNFα (20ng/ml), S100A8/A9 (2µg/ml) and S100A12 (2µg/ml) for 3 to 24h. <h3>Results</h3> Plasma levels of syndecan-1, S100A12 and S100A8/A9 levels increased following snCPB. Post-snCPB levels of syndecan-1 (86.1±16.2ng/ml) correlated, positively (r2=0.437, p=0.019; and r2=0.729, p=0.0004, respectively) with post-snCPB levels of S100A8/A9 (4.5±0.6ng/ml) and S100A12 (92.9±22.8ng/ml). In cultured HUVEC, TNFα significantly (p&lt;0.01, n=3) decreased syndecan-1 mRNA expression by 75% at 6h and expression remained suppressed at 24h. By contrast, neither S100A8/A9 nor S100A12, under the conditions investigated in this study, significantly altered syndecan-1 mRNA expression. <h3>Conclusion</h3> A positive association between post-operative plasma levels of RAGE ligands, S100A8/A9 and S100A12, and syndecan-1 is suggestive of a link between RAGE activation and endothelial injury, key feature of SIRS following snCPB. However, in cultured endothelial cells only TNFα and not S100A8/A9 or S100A12 decreased syndecan-1 mRNA expression; where decreased expression is indicative of reduced endothelial protective function. Possible explanations for the differences with S100A8/A9 and S100A12 in vivo and in vitro are that effects on syndecan-1 shedding in patients undergoing snCPB are indirect; and/or that in vitro, pre-activation of endothelial cells is required to up-regulate RAGE expression in order for S100 proteins to modulate syndecan-1 expression. These questions are the subject of on-going studies into the role of RAGE activation in endothelial dysfunction in SIRS.
Transmissibility of Pseudomonas cepacia Infection in Clinic Patients and Lung-Transplant Recipients with Cystic Fibrosis
Authors: Suzanne Steinbach, Li Sun, Ru-Zhang Jiang, Patrick Flume, Peter Gilligan, Thomas M. Egan, Richard Goldstein
Journal: New England Journal of Medicine (1994)

In patients with cystic fibrosis, infection with Pseudomonas cepacia is associated with poor outcomes. However, the extent of person-to-person transmission and the source of P. cepacia infection after lung transplantation are not well defined. Using DNA-based typing systems, we sought to determine the genetic relatedness of P. cepacia infection at one cystic fibrosis center.
Cerebral predominance in the monkey?
Authors: G. Ettlinger
Journal: Behavioral and Brain Sciences (1981)

The issues raised by Dr. Denenberg are complex, not least because the apparent communalities of hemispheric specialization among birds, rodents, monkeys, and human beings are also associated with negative instances (e.g., for parrots, Nottebohm 1976; for Macaco , other than fuscata , Petersen et al. 1978). To extend the available evidence I would like to refer to the preliminary findings of Garcha et al. (1980) on the monkey.
Abstract ES7-1: Next Generation Sequencing for the Clinician: A Breast Cancer Study
Authors: ER Mardis, L Ding, D Shen, J Wallis, K Chen, M Watson, J Hoog, MJ Ellis, Wilson RK
Journal: Cancer Research (2010)

Abstract The ability to study genome-wide sequence alterations in cancer genomes has transformed our understanding of the intricacies of this disease. We have applied whole genome sequencing and analysis to tease apart the genomic predictors of aromatase inhibitor (AI) response, by selecting luminal breast cancer cases obtained within a clinical trial of aromatase inhibitor treatment (ACOSOG Z1031). Our study compared the constitutional genome to the cancer genome for patients that exhibit either a response or a resistance phenotype, based on their Ki67 IHC score following 4 month AI treatment and resection. My talk will highlight the process by which these genomes are sequenced and analyzed, and will provide our most recent insights into how the combination of the constitutional and somatic genomes determine whether a patient will respond to AI treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES7-1.
Abstract 987: Researching policy proposals aimed at placing cancer on the global health agenda
Authors: Norie Kawahara
Journal: Cancer Research (2010)

Abstract Deaths caused by cancer continue to increase around the world. People living in low- and middle-income countries are in greater danger than people living in high-income countries of succumbing to risks that can be relatively easily avoided by man-made interventions. These risks include smoking, unhealthy eating and lifestyle, lack of exercise, excessive intake of alcohol, and chronic infections such as HPV or hepatitis. The World Health Organization projects that if the challenges facing low- and middle-income countries are not addressed, by 2015 an estimated 5.7 million people will die annually in those countries, rising to 8.9 million by 2030. With limited medical resources, the priority challenges for the global health agenda remain focused on HIV/AIDS and malaria. Now, however, is the time to transform global health policies. The U.S. Commitment to Global Health clearly states that “Cancer Should Be Raised Onto the Global Health Agenda” and yet cancer remains to be recognized by the global health community as a priority issue. What is the positioning given to cancer on the global health agenda? What factors are preventing is inclusion in global health? What are the primary mechanisms that inform and decide the global health agenda? In contrast to infectious diseases, cancer slowly yet perniciously attacks the very roots of people's lives. This long time-frame means that we must consider a wide-range of factors, including economic, cultural and domestic and international policies. This policy-based research was implemented in the form of interviews with people from various sectors, encompassing various perspectives, including social determinants of health, health equity and solidarity and human rights. The results and analysis of this research are broken down into: (1) Top-down mechanisms, (2) Bottom-up mechanisms, and (3) the formation of new values through an IT network that functions to meld (1) and (2) and promote them in tandem. The results will be used to present the challenges and outlook for raising cancer onto the global health agenda. In order to ensure the global advancement of cancer research, in accordance with the principles and theory enshrined in the Universal Declaration of Human Rights, which stipulates that all people have the right to enjoy the benefits of science and technology, an urgent prerequisite is to promote strategic analysis with the objective of including cancer in the United Nations Millennium Development Goals (MDGs). Achieving the inclusion of cancer in the MDGs would significantly raise the profile of cancer in the global health agenda. 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 987.
Case 30-1961
Journal: New England Journal of Medicine (1961)

Presentation of Case A sixty-two-year-old man was admitted to the hospital because of an abdominal mass. Thirty years previously a perforated duodenal ulcer was sutured at another hospital. One year later a gastroenterostomy was performed. The patient remained well until two years before entry, when he noticed an uncomfortable sensation in the abdomen that was relieved by eating. Three months before admission acute, severe pain occurred in the left side of the mid-portion of the abdomen and epigastrium. An aortogram was suggested, but the patient refused. The abdominal distress continued, and anorexia developed. Two days before entry black stools were . . .
Abstract LB-54: Gap Junction Enhancer Increases Efficacy of Cisplatin to Attenuate Mammary Tumor Growth
Authors: Stephanie N. Shishido, Thu A. Nguyen
Journal: Cancer Research (2011)

Abstract INTRODUCTION: Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors (Knapp et al. 1988). Increasing gap junction activity or enhancing GJIC in tumor cells provides the targets to enhance antineoplastic therapies. A new class of substituted quinolines (PQs) possesses inhibitory activities against breast cancer cells through the enhancement of gap junctional intercellular communication. We examined the effect of combinational treatment of PQ and antineoplastic drugs in an animal model to show an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions. MATERIALS AND METHODS: Mice were implanted with estradiol-17ß (1.7 mg/pellet) before the injection of 1 × 107 T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control), Cisplatin (3.5mg/kg), PQ (25mg/kg), or a combining treatment of Cisplatin and PQ. RESULTS: Cisplatin alone decreased mammary tumor growth by 29% while combinational treatment of Cisplatin and PQ showed a 36% reduction after 7 treatments at every 2 days. Histological results showed a significant increase of gap junction proteins, Cx43 and Cx26, in PQ-treated tissues compared to control or Cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinational treatment (PQ and Cisplatin) was seen compared to Cisplatin alone. CONCLUSIONS: We have showed for the first time an increase in the efficacy of antineoplastic drugs via the enhancement of gap junctions with PQs, a specific class of gap junction enhancers. 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 LB-54. doi:10.1158/1538-7445.AM2011-LB-54
Effects of Arsenic on Osteoblast Differentiation <i>in Vitro</i> and on Bone Mineral Density and Microstructure in Rats
Authors: Cheng-Tien Wu, Tung-Ying Lu, Ding-Cheng Chan, Keh-Sung Tsai, Rong-Sen Yang, Shing-Hwa Liu
Journal: Environmental Health Perspectives (2014)

Arsenic is a ubiquitous toxic element and is known to contaminate drinking water in many countries. Several epidemiological studies have shown that arsenic exposure augments the risk of bone disorders. However, the detailed effect and mechanism of inorganic arsenic on osteoblast differentiation of bone marrow stromal cells and bone loss still remain unclear. We investigated the effects and mechanism of arsenic on osteoblast differentiation in vitro and evaluated bone mineral density (BMD) and bone microstructure in rats at doses relevant to human exposure from drinking water. We used a cell model of rat primary bone marrow stromal cells (BMSCs) and a rat model of long-term exposure with arsenic-contaminated drinking water, and determined bone microstructure and BMD in rats by microcomputed tomography (μCT). We observed significant attenuation of osteoblast differentiation after exposure of BMSCs to arsenic trioxide (0.5 or 1 μM). After arsenic treatment during differentiation, expression of runt-related transcription factor-2 (Runx2), bone morphogenetic protein-2 (BMP-2), and osteocalcin in BMSCs was inhibited and phosphorylation of enhanced extracellular signal-regulated kinase (ERK) was increased. These altered differentiation-related molecules could be reversed by the ERK inhibitor PD98059. Exposure of rats to arsenic trioxide (0.05 or 0.5 ppm) in drinking water for 12 weeks altered BMD and microstructure, decreased Runx2 expression, and increased ERK phosphorylation in bones. In BMSCs isolated from arsenic-treated rats, osteoblast differentiation was inhibited. Our results suggest that arsenic is capable of inhibiting osteoblast differentiation of BMSCs via an ERK-dependent signaling pathway and thus increasing bone loss.
Abstract 1794: Cross-regulation of polycomb group protein BMI1 and WNT inhibitors.
Authors: Joon-Ho Cho, Manjari Dimri, Goberdhan P. Dimri
Journal: Cancer Research (2013)

Abstract Polycomb group (PcG) proteins are evolutionarily conserved gene silencers, which determine cell fate decisions during development. These proteins are often aberrantly expressed in cancer cells. In particular, BMI1 and EZH2 are known to be overexpressed in a number of human malignancies including breast and prostate cancers. In vitro models of cancer development strongly support oncogenic role of overexpressed BMI1 in cancer and metastasis. BMI1 is known to be required for self-renewal of neural, hematopoietic, intestinal and mammary stem cells. In addition, BMI1 is downregulated in senescent cells, and this downregulation may contribute to age-related pathologies. BMI1 is also suspected to play a role in cancer stem cell development and increase stem cell-ness of tumors to promote drug resistance. Despite its role in cancer, stem cell phenotype, development and aging, very little is known about the signaling pathways that regulate the expression of BMI1. Here we report that BMI1 activates WNT pathway and upregulates its target genes such as Cyclin D1 and c-Myc. Using promoter-reporter assays, quantitative RT-PCR and Western blot analyses, we show that BMI1 auto-activates its expression via an E-box present in its promoter. Because auto-activation of BMI1 depends on E-box sequences present in its promoter, we hypothesized that BMI1 may regulate expression of c-Myc directly or indirectly via activation of WNT pathway. Indeed, our data suggest that BMI1 upregulated expression of c-Myc via activation of WNT pathway. Further dissection of this regulation revealed that BMI1 represses expression of WNT inhibitors, in particular DKK family of proteins such as DKK1, DKK2 and DKK3. Interestingly, we also found that DKK1 inhibits expression of BMI1, which also depends on E-box present in BMI1 promoter. Thus BMI1 and WNT inhibitors such as DKK1 cross-regulate each other's expression. We speculate that such regulation might favor BMI1 overexpression in cancer cells via increased WNT activity and c-Myc expression. On the other hand, increased expression of WNT inhibitors such as DKK1 might favor BMI1 downregulation in senescent and aged tissues. Thus, a fine tuned positive feedback loop controls BMI1 expression via WNT signaling pathway, and this feedback loop may be relevant to the role of BMI1 in cancer, stem cells and senescence. Citation Format: Joon-Ho Cho, Manjari Dimri, Goberdhan P. Dimri. Cross-regulation of polycomb group protein BMI1 and WNT inhibitors. [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 1794. doi:10.1158/1538-7445.AM2013-1794