tbuckley/cabot-search huggingface dataset:
Abstract B13: OncoPredictor: An integrative genomics platform to systematically predict responsive tumor populations from <i>in vitro</i> drug response data
Authors: Daniel R. Rhodes, Gary Daubresse, Peter Wyngaard, Mark Tomilo, Paul Williams, Christine O'Day, Yulia Ovechkina, Usha Warrior, Seth Sadis
Journal: Clinical Cancer Research (2010)

Abstract A key challenge in drug development is identifying clinically relevant genomic biomarkers from preclinical data. Here, we developed OncoPredictor, a cellular screening and bioinformatics platform to (1) evaluate multiple types of genomic biomarkers for association with in vitro drug response and (2) analyze identified biomarkers in clinical tumor populations, thereby suggesting potential drug development strategies. We examined data for 18 targeted, anticancer agents tested across more than 200 cancer cell lines for which detailed genomic data were collected. To support association analysis of drug response and genomic biomarkers, a cell line biomarker catalog was constructed including gene and pathway mutations, copy number aberrations and gene expression changes, in addition to tumor-derived gene expression molecular subtypes. Similarly, to support the rapid translation of in vitro biomarkers to clinical tumor populations, a tumor biomarker catalog was developed, characterizing the frequency of biomarkers across the Oncomine database, which includes more than 40,000 genomic profiles from tumor specimens. Notably, our analysis uncovered several known and novel drug- biomarker-tumor population associations providing a series of cancer treatment hypotheses. For example, within Ras/Raf mutant cell lines, overexpression of a novel biomarker associated with sensitivity to CI-1040, a MEK inhibitor, and identified a sub-population of Ras/Raf mutant colorectal cancer and melanoma that may be more likely to benefit from MEK inhibitors. Similarly, we showed that a growth factor activation network associated with a dramatic response to sunitinib and identified a fraction of glioblastoma and particular types of sarcoma with activation, suggesting that these indications may benefit from a tumor intrinsic response to sunitinib. Finally, for everolimus, an mTOR inhibitor, we found that a gene expression-based molecular subtype of breast cancer were particularly sensitive and demonstrated that the while subtype-positive breast cancers have a good prognosis, 10% of breast cancers that metastasize are subtype-positive, suggesting a defined clinical population that could benefit from mTOR inhibitors. In summary, our platform provides a comprehensive and clinically relevant framework to discover and apply genomic biomarkers of drug response. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B13.
P357Adipose tissue specific adipose triglyceride lipase as a major determinant for the development of pressure overload-induced heart failure
Authors: J Salatzki, S Brix, Z Ban, V Benz, E Kershaw, U Kintscher, A Foryst-Ludwig
Journal: Cardiovascular Research (2014)

Introduction: Myocardial metabolism undergoes a change in response to pathological hypertrophy, characterized by increased reliance on glucose oxidation, decreased free fatty acid oxidation, and a loss of metabolic flexibility. Cardiac metabolism is determined by whole-body metabolism and influenced by other organs such as adipose tissue. However, the molecular interaction between adipose tissue and the development of pathological hypertrophy is not well understood. Hence, we aimed to investigate the effect of Adipose Triglyceride Lipase (ATGL) in adipose tissue on the development of myocardial hypertrophy and heart failure in a pressure overload-induced cardiac hypertrophy model in mice.
Idiopathic Pulmonary Hemorrhage in Pregnancy
Authors: Victor Gurewich, Martin A. Thomas
Journal: New England Journal of Medicine (1959)

THE following is a report of a young, seven-month-pregnant woman who was gravely ill with cough, breathlessness, cyanosis, bilateral pulmonary infiltration on x-ray study and a hemoglobin of only 4.8 gm. per 100 ml. Because of the characteristic clinical picture and the absence of any other cause of blood loss, the diagnosis of idiopathic pulmonary hemorrhage or of so-called idiopathic pulmonary hemosiderosis was tentatively made, and appropriate treatment was instituted. Of particular interest is the fact that complete remission rapidly followed the use of steroids in this critically ill patient.A biopsy of the lung was obtained on the tenth . . .
Susan Elizabeth Jean ("Sue") Munby Rachael Mary Rosser Robert Spencer ("Bob") Rudland Sankar Das Sarkar Roger Sauvan-Smith
Authors: A. Lewis, V. Watts, J. Keenan, S. Sarkar, N. Paros
Journal: BMJ (1998)

Westminster 1978; DRCOG, MRCGP), died of metastatic cancer of the colon on 20 May 1998.She followed her mother into general practice and became a partner in her training practice, with her identical twin sister in practice nearby.She moved to Kenilworth when her husband was appointed a consultant clinical oncologist.A woman with high standards in everything she tackled, she was a superb cook and hostess, while her practical gardening knowledge was immense.Bird watching, walking, tennis, and skiing (latterly) were all among her interests.
SC-14 * ASYMMETRY-DEFECTIVE OLIGODENDROCYTE PROGENITORS AS POTENTIAL CELL-OF-ORIGIN OF HYPERACTIVATED RAF-INDUCED MALIGNANT ASTROCYTOMAS
Authors: B. Kadkhodaei, R. G. Lerner, M. Sidorov, S. Gomez-Lopez, M. McMahon, D. James, C. Petritsch
Journal: Neuro-Oncology (2014)

BACKGROUND: Studies show that the expression of an activating mutation of BRAF (BRAFV600E) in conjunction with Ink4a/Arf deletion, but not each alteration by itself, lead to formation of malignant astrocytoma (MA)-like tumors. Importantly, BRAFV600E occurs in 39% of pediatric MA and in 7.7% of adult glioblastomas with a preference for young adult patients, and the majority coincides with homozygous deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) encoding Ink4a/Arf. Responses to pharmacologic inhibition of BRAFV600E in melanoma patients were stunning but led to rapid resistance. A better understanding of the molecular mechanism by which activated Raf signaling transforms adult neural progenitors into high-grade MA cells is needed to overcome resistance. APPROACH AND RESULTS: We hypothesize that BRAFV600E transforms Ink4a/Arf-depleted neural progenitor cells, by disrupting their asymmetric cell division, thereby initiating a cascade of events that fails to restrict cell fate determinants during division, alters cell fate, enhances proliferation and allows for other changes associated with neoplastic transformation. We use a Cre inducible mouse model of BRAFV600E, the BRafCA allele, and of Ink4a/ARf (Ink4a/Arf-loxP) in combination with fluorescence-activated cell sorting to isolate neural progenitor cells from the adult mouse brain subventricular zone. Enriched neural progenitor populations are subjected in vitro modified to express BRAFV600E and deleted Ink4a/Arf by adenovirus-Cre infection. Cell-culture-based assays determine their rate of asymmetric cell division, self-renewal, proliferation and their differentiation capacity. CONCLUSION: BRAFV600E expression causes a cell-type specific decrease in asymmetric cell division in oligodendrocyte progenitor cells (OPC). Asymmetry-defective in vitro modified OPC and OPC-like cells isolated from a tumor cell line are capable of forming tumors when injected into mice. We will present data from our ongoing search for critical molecular regulators and pathway(s) associated with BRAFVE-mediated disruption of asymmetric cell division and malignant transformation.
EG-10 * LONG NON-CODING RNAs IN GLIOBLASTOMA
Authors: C. Pastori, P. Kapranov, C. Penas, G. S. Laurent, N. Ayad, C. Wahlestedt
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM) is the most common, aggressive and incurable primary brain tumor in adults. Genome studies have confirmed that GBM is extremely heterogeneous with many genetically different subgroups. Consequently, there is much current interest in epigenetic drugs that may be active across genetically distinct tumors. In support of this, some epigenetic drugs has recently shown efficacy against several cancers including glioblastoma. Much recent interest has also been devoted to long non-coding RNAs (lncRNAs), which can modulate gene expression regulating chromatin architecture, in part through the interaction with epigenetic protein machineries. To date, however, only a few lncRNAs have been studied in human cancer. We therefore embarked on a comprehensive genomic and functional analysis of lncRNAs in GBM. Using the Helicos Single Molecule Sequencing platform glioblastoma samples were sequenced resulting in the identification of hundreds of dysregulated lncRNAs. Among these the lncRNA HOTAIR was found massively increased in GBM. This observation parallels findings in other cancers where HOTAIR's increased expression has been linked to poor prognosis due to metastatic events. Interestingly, here we show that in glioblastoma HOTAIR does not promote metastasis, but instead sustains the ability of these cells to proliferate. In fact, we demonstrate that HOTAIR knockdown in GBM strongly impairs cell proliferation and induces apoptosis in vitro and in vivo. Further, we implicate HOTAIR in the mechanism of action of certain epigenetic drugs. In summary, long noncoding RNAs (newly discovered epigenomic factors) play a vital role in GBM and deserve attention as entirely novel drug targets as well as biomarkers.
ASCO/AACR: Shared Emphases And Separate Meetings
Authors: J. McCann
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article ASCO/AACR: Shared Emphases And Separate Meetings Get access Jean McCann Jean McCann Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 12, 16 June 1993, Pages 939–942, https://doi.org/10.1093/jnci/85.12.939 Published: 16 June 1993
964 IMPLEMENTING EASL &amp; AASLD GUIDELINES FOR HEPATOCELLULAR CARCINOMA SCREENING IS COST-EFFECTIVE IN LONDON'S ETHNICALLY DIVERSE POPULATION
Authors: W. Alazawi, K. Abeysekera, J. Dearden, M. Glynn, Y. Kallis, P. Kennedy, R. Marley, G.R. Foster, P. Kooner
Journal: Journal of Hepatology (2013)
OC-128 The effect of obesity on the radicality of subtotal oesophagectomy for oesophageal adenocarcinoma
Authors: H V Jones, S Wahed, A Krishnan, J Shenfine, S M Griffin
Journal: Gut (2012)

<h3>Introduction</h3> Obesity is on the increase in the UK and is a known risk factor for adenocarcinoma of the oesophagus. It is recognised that oesophagectomy in obese patients is more difficult with concerns that radicality of resection is reduced. The aims of this study were to evaluate body mass index (BMI) in patients with oesophageal adenocarcinoma who underwent subtotal oesophagectomy with radical lymphadenectomy and to evaluate the effect of obesity on lymph node (LN) dissection and survival. <h3>Methods</h3> All patients who underwent subtotal oesophagectomy for adenocarcinoma between January 2000 and December 2010 were identified from a prospectively maintained database. All other histological types were excluded. Patients were categorised according to BMI using the WHO criteria: underweight (2), normal (18.5–24.99 kg/m<sup>2</sup>), overweight (25-29.99 kg/m<sup>2</sup>) and obese (≥30 kg/m<sup>2</sup>). Demographics, presence of Barrett9s oesophagus or reflux disease, operative time, R0 resections, complications, LN resection and positivity were analysed. Long-term and disease free survival were calculated using the Kaplan–Meier method. <h3>Results</h3> 413 patients were identified. 23 had no BMI recorded and were excluded leaving 390 patients: eight underweight; 117 normal BMI; 172 overweight; 93 obese. BMI significantly increased over time (mean BMI 26.0 in 2000–2001, 27.8 in 2010, p=0.041). Obese patients were younger compared to normal BMI patients (mean age 60.1 and 64.4 respectively, p=0.003). The incidence of Barrett9s oesophagus and reflux disease were not significantly different between groups. Operating time was significantly longer for obese patients (p=0.018). R0 resections were similar between groups (normal patients 96.4% and obese 95.5%). The mean number of LNs resected (33 for both normal BMI and obese groups) and the LN ratio did not differ significantly between groups. Obese patients had significantly lower disease stages (32.3% stage 1 obese patients vs 16.2% stage 1 normal BMI patients, p=0.006). Overall survival was longer for obese patients compared with those of normal BMI (81 months vs 55 months, p=0.004). When matched for stage, this difference did not reach significance (p=0.236). Disease free survival did not differ between groups. The overall complication rate was similar between groups (70.1% for normal BMI, 66.3% for obese). <h3>Conclusion</h3> This is the first study to evaluate BMI in a homogenous group of patients with adenocarcinoma undergoing subtotal oesophagectomy with a standardised radical lymphadenectomy. BMI and obesity among these patients increased with time. The radicality of surgery, in terms of LN yields and R0 resections, did not reduce in the obesity group and this is further supported by equivalent stage-matched long-term survival. <h3>Competing interests</h3> None declared.
Abstract 3047A: Differential subcellular localization and trafficking of RET isoforms.
Authors: Mathieu J. F. Crupi, Douglas S. Richardson, Lois M. Mulligan
Journal: Cancer Research (2013)

Abstract The RET proto-oncogene encodes a receptor tyrosine kinase (RTK) necessary for development of the kidneys and enteric nervous system. Two distinct isoforms of the growth factor receptor arise through alternative splicing of the 3’ exons, and are termed RET9 and RET51 to denote the number of amino acids in each C-terminal tail. These isoforms induce unique transphosphorylation patterns on intracellular tyrosine residues, differentially bind downstream signalling proteins, and possess different intrinsic abilities to cause cellular transformation. Subcellular localization and trafficking of RTKs have increasingly been recognized as important post-receptor activation regulatory mechanisms, involving protein-protein interactions. Here, we explore the differential subcellular localization and trafficking of RET isoforms in human cell line models. We have observed that RET51 is efficiently matured and localized to the cell membrane, while immature RET9 accumulates in a perinuclear region and matures more slowly, leading to lower relative expression on the plasma membrane. Subsequent to RET activation, both isoforms at the cell surface are internalized through the clathrin coated-pit pathway into endosomes, where signaling persists. Although RET51 is internalized more rapidly than RET9, a portion of RET51 molecules recycles back to the plasma membrane, maintaining high expression levels at the cell surface. Recycling prevents efficient degradation of RET51, allowing for prolonged downstream signaling relative to RET9. We predict that progress through these trafficking steps is modulated by specific protein interactions between RET isoforms and sorting proteins, and these interactions are also determined at later stages by modifications on RET itself, most notably ubiquitination. Future studies could allow us to identify these key proteins/binding sites which may differ between RET9 and RET51. Since RET51 has a longer residency time in an endosomal compartment, where sustained Erk1/2 signaling promotes mitogenesis, this may in part explain the greater transforming potential of RET51. Together, our data suggest that differences in RET isoform subcellular localization and trafficking would lead to differences in signal transduction and may in part explain the functional differences observed between RET isoforms. Citation Format: Mathieu J. F. Crupi, Douglas S. Richardson, Lois M. Mulligan. Differential subcellular localization and trafficking of RET isoforms. [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 3047A. doi:10.1158/1538-7445.AM2013-3047A
ECOENDOSCOPIA Y RESONANCIA PÉLVICA EN EL ESTADIAJE DEL CANCER RECTAL. ESTUDIO COMPARATIVO
Authors: B Castro, G De las Heras, A Terán, J Cabezas, B Sampedro
Journal: Endoscopy (2010)

Introduccion: En el cáncer rectal (CR) el estadiaje locorregional es uno de los principales factores pronósticos. Tanto la Ecoendoscopia (USE) como la Resonancia Magnética Pélvica (RMP) son técnicas empleadas en su valoración prequirúrgica.
Father's Lifestyle Can Have Fetal Consequences
Authors: N. Volkers
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Father's Lifestyle Can Have Fetal Consequences Get access Nancy Volkers Nancy Volkers Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 22, 20 November 1991, Pages 1611–1612, https://doi.org/10.1093/jnci/83.22.1611 Published: 20 November 1991
P208 A prospective observational study to evaluate the effect of social and personality factors on CPAP compliance in OSA
Authors: A. Gulati, K. Jordan, M. Ali, R. Chadwick, I. E. Smith
Journal: Thorax (2010)

<h3>Introduction</h3> Continuous positive airway pressure (CPAP) treatment for Obstructive sleep apnoea (OSA) is associated with variable initial acceptance and subsequent compliance with no consistent association with the severity of symptoms or physiological variables. There are very few data on the role of socioeconomic status, level of education and personality type. A recent retrospective study showed type D personality to be associated with poor compliance.1 <h3>Methods</h3> All patients with a confirmed diagnosis of OSA, recommended CPAP were considered. Baseline questionnaires were completed to assess employment and socio-economic status and type D personality. Compliance was measured at 6–10 weeks and 6 months. <h3>Results</h3> 265 patients participated in the study. Seven switched to Bi-level PA, 2 were excluded and four withdrew their consent; 224 were still using CPAP at 6 months. At baseline mean age was 52.1 (SD 11.0)/y, M:F 205:60 (3.4:1), Epworth sleepiness score (ESS) 14 (SD 4.4), BMI 37.1 (SD 7.8), 4% Desaturation index (DI) 27.9 (SD 20.6)/h and AHI 28.0 (SD 18.6)/h. Mean compliance at 6–10 weeks and 6 months was 5.68 (SD 2.3) h and 5.31 (SD 2.3) h, respectively. 20.5% were using CPAP &lt;4 h/night at 6 weeks and 25.9% at 6 months. In comparison to individuals who were working (or retired from work), those who were long term unemployed (n=17) had a lower average CPAP usage at 6–10 weeks (4.08 h; SD 2.3) and 6 months (3.2 h; SD 2.6). This group was also more likely to use CPAP &lt;4 h/night at 6–10 weeks and 6 months (OR 5.06, p=0.001 and OR 3.62, p=0.01 respectively). No association was found between different Socio-economic classes for people in work, type D personality, education level, sex, age, baseline ESS, DI and AHI with 6–10 weeks or 6 month compliance. Compliance at 6–10 weeks correlated strongly with 6 months compliance (rs=0.82). <h3>Conclusion</h3> In our practice there is no significant association between CPAP compliance with socio-economic status, education level or the personality type. People who are long term unemployed may need more intensive support to get optimal benefit from CPAP.
Abstract 427: Targeted inhibition of the mTOR complex components, RAPTOR and RICTOR, attenuates progression of colorectal cancer
Authors: Gulhati Pat, Kanika A. Bowen, Jianyu Liu, Jing Li, Suimin Qiu, Heidi L. Weiss, Tianyan Gao, B. Mark Evers
Journal: Cancer Research (2010)

Abstract Colorectal cancer (CRC) is the second leading cause of cancer deaths in the USA. The mammalian target of rapamycin (mTOR) acts downstream of PI3K to regulate cell growth, proliferation and survival. The mTOR kinase nucleates two distinct complexes, mTORC1 and mTORC2. The mTOR-RAPTOR complex (mTORC1) regulates translation initiation through the effectors S6K and 4E-BP1, while the mTOR-RICTOR complex (mTORC2) regulates the actin cytoskeleton and activates Akt, a key regulator of cell survival. Rapamycin inhibits the kinase activity of mTORC1; prolonged rapamycin treatment also inhibits mTORC2 assembly and Akt activation in certain cells. The purpose of the present study was to determine the effect of targeting mTORC1 and mTORC2 upon progression of CRCs. METHODS. HCT116 and SW480 human colon cancer cells were treated with rapamycin. Cells were also transfected with shRNA directed against RAPTOR or RICTOR. Effects on migration (measured by wound healing assay) and invasion (measured by transwell matrigel assay) were analyzed. Changes in actin cytoskeleton and cell-cell contacts were determined by immunofluorescence microscopy. RESULTS. (i) Immunohistochemical analysis showed that the mTORC1 and mTORC2 components, mTOR, RAPTOR and RICTOR, are overexpressed in primary CRCs and matched liver metastases compared to normal colonic tissue. (ii) Treatment with rapamycin significantly decreased the migration and invasion of HCT116 and SW480 cells. (iii) Stable shRNA-mediated knockdown of RAPTOR and RICTOR significantly decreased the migration and invasion of HCT116 and SW480 cells. (iv) Stable shRNA-mediated knockdown of RAPTOR and RICTOR leads to mesenchymal-to-epithelial transition, as evidenced by increased E-cadherin and decreased vimentin levels. (v) Stable shRNA-mediated knockdown of RAPTOR and RICTOR leads to characteristic rearrangements in actin cytoskeleton as well as increased cell-cell contact. CONCLUSIONS. The mTORC1 and mTORC2 components, mTOR, RAPTOR and RICTOR, are overexpressed in both primary CRCs as well as matched liver metastases. Although the mTOR signaling axis is primarily associated with growth of normal and cancer cells, we demonstrate that stable inhibition of both mTORC1 and mTORC2 decreases migration and invasion capabilities of CRC cells as well as causing a mesenchymal-to-epithelial change in phenotype. The mechanism for this decrease in migration and invasion may be via modulation of actin cytoskeletal rearrangement and cell-cell contact. Thus, targeted inhibition of mTOR signaling represents a novel therapeutic strategy to attenuate the progression and metastasis of CRCs. 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 427.
Groups as units of functional analysis, individuals as proximate mechanisms
Authors: David Sloan Wilson
Journal: Behavioral and Brain Sciences (2014)

Abstract Whenever selection operates at a given level of a multitier hierarchy, units at that level should become the object of functional analysis, and units at lower levels should be studied as proximate mechanisms. This intuition already exists for the study of genes in individuals, when individuals are the unit of selection. It is only beginning to be applied for the study of individuals in groups, when groups are the unit of selection. Smaldino's target article is an important step in this direction with an emphasis on human cultural evolution, but the same algorithm applies to all multilevel evolutionary processes.