tbuckley/cabot-search huggingface dataset:
Abstract P2-01-01: Mammography and Patient or Physician Detected Breast Cancer in 21-39 Year Old Women
Authors: HG Kaplan, JA Malmgren, MK Atwood
Journal: Cancer Research (2010)

Abstract Background: Mammography screening is not recommended for women under age 40. The American Cancer Society recommends clinical breast exam about every 3 years and breast self-exam as an option for women starting in their 20s. It is not clear what method is best for women at high risk. Methods: We conducted a prospective cohort study of all women presenting with primary breast cancer, aged 21-39, biopsy confirmed Stage 0-IV from 1990-2008 identified and tracked by our registry. Clinical presentation characteristics including age, race, TNM stage converted to AJCC 6, first degree relative, family and pregnancy history, histologic type and method of detection by patient (PtD), physician (PhysD) or mammography (MgD) were chart abstracted at the time of diagnosis. A first degree relative is a mother, father, son, daughter or sibling with a BC diagnosis. Cases with unknown or other method of detection (n=7) were removed (n=602). For analysis purposes patient and physician detected cases were combined into one manually detected category. Forward conditional stepwise regression was used to test association significance with detection method and the Kaplan-Meier method was used for disease free survival (DFS) analysis. Results: Women aged 21-39 represented 7% of the patients in our community based cancer center registry database. We did not observe any change in detection method over time with 12% MgD, 7% PhysD and 81% PtD. The majority of MgD cases were in the 30-34 (26%) and 35-39 (65%) year old age groups (Pearson chi square = 11.11, p=.011). 81% of the PhysD/PtD breast cancers were visible on subsequent mammography. 31% of the 74 MgD cases were stage 0 vs. 2.5% of the 528 PhysD/PtD cases. In a conditional logistic regression model with MgD BC yes/no as the binary outcome, age at diagnosis and having a first degree relative with breast cancer were significantly associated with mammography detection. DFS was significantly better in the MgD group (log rank test = 6.10, p=.014). Conclusions: Mammography detection in 20-39 year old breast cancer patients is associated with age &amp;gt; 30 years and presence of a BC affected first degree relative. Disease specific survival is significantly better in the mammography detected group largely due to lower stage at diagnosis. These results indicate mammography may be a reasonable option for screening high risk women aged 30-39. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-01-01.
Abstract 1886: Metabolic alterations associated with pancreatic cancer-induced cachexia.
Authors: Surendra K. Shukla, Pankaj K. Singh
Journal: Cancer Research (2013)

Abstract Cachexia, a metabolic syndrome, leads to loss of muscle weight and fat tissues. Cancer-induced cachexia accounts for nearly 20% of all cancer-related deaths and is most prevalent in patients with gastric, pancreatic, colon and lung cancer. Although association of cachexia with various types of cancers has been known for a long time, the molecular mechanism of cancer-induced cachexia is still not well understood. Better understanding of the cancer-related cachexia syndrome may provide novel therapeutic targets and improved health care for cancer patients. By culturing differentiated C2C12 and 3T3-L1 cells in the presence of pancreatic adenocarcinoma cell or immortalized epithelial cell supernatants, we established cell culture-based cachexia model systems to investigate the depletion of muscle mass and fatty acid storage. Progressive physiological and biochemical alterations during muscle fibre breakdown and adipocyte fat depletion were assayed by utilizing western blotting, real-time PCR and cell imaging. We then investigated metabolomic alterations in C2C12 and 3T3-L1 cell lines in response to the cachectic factors secreted by the tumor cells. We performed differential metabolomic analyses on tumor cell supernatant-treated or control treated differentiated C2C12 muscle fibers and 3T3-L1-derived adipocytes by utilizing 2D 1H-13C HSQC NMR technique. Alterations in metabolic pathways were also investigated by evaluating the expression of metabolic genes in the corresponding pathways by performing quantitative real-time PCR. To obtain further insights into the metabolic alterations that trigger cachexia, we extended our studies to in vivo mouse orthotopic xenograft models and investigated alterations in metabolic gene expression and metabolite flux in muscle and fat tissues of tumor-bearing mice. Our results identify crucial nodes in metabolite flux that can be targeted to regulate cell growth, proliferation, and turnover in muscle and fat tissues during cancer-induced cachexia. Citation Format: Surendra K. Shukla, Pankaj K. Singh. Metabolic alterations associated with pancreatic cancer-induced cachexia. [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 1886. doi:10.1158/1538-7445.AM2013-1886
Detection of Early Cardiac Dysfunction in Patients with Severe Beta-Thalassemia and Chronic Iron Overload
Authors: Martin B. Leon, Jeffrey S. Borer, Stephen L. Bacharach, Michael V. Green, Edward J. Benz, Patricia Griffith, Arthur W. Nienhuis
Journal: New England Journal of Medicine (1979)

To detect early left ventricular dysfunction, we used radionuclide cineangiography to determine left ventricular ejection fraction during exercise in 24 patients with transfusion-dependent, congenital anemias, 21 of whom had severe beta thalassemia. Ejection fraction at rest was normal in 21 patients (greater than 45 per cent) and in all patients was 53 +/- 2 per cent (mean +/- S.E.M.)--not significantly different from the value in normal subjects. However, ejection fraction during exercise was normal in only 11 patients (53 +/- 3 per cent in all patients, P less than 0.001 as compared with the normal value). All eight patients who had received fewer than 100 transfusions but only three of 16 (19 per cent, P less than 0.001) who had received 100 or more transfusions had normal responses during exercise. Whereas echocardiographic fractional shortening at rest was normal in 16 of 19 patients studied, eight patients with normal fractional shortening had abnormal ejection-fraction responses to exercise. Thus, radionuclide cineangiography during exercise is a highly sensitive technique for detecting preclinical myocardial dysfunction in patients with systemic iron overload.
Urinary-Bladder Fibrosis and Telangiectasia Associated with Long-Term Cyclophosphamide Therapy
Authors: Warren W. Johnson, David C. Meadows
Journal: New England Journal of Medicine (1971)

Forty urinary bladders from patients treated with cyclophosphamide for neoplastic disease were examined at autopsy. Ten bladders were fibrotic; three also exhibited mucosal telangiectasia. The 10 were from patients who had received the largest quantities of the drug over the longest periods. Nine of the 10 had received the drug intravenously; the tenth had received it intravenously and orally. Five had gross hematuria, but five had been asymptomatic. Urinary-bladder fibrosis occurred when total dosage exceeded 6 g/m2 of body-surface area. Adequate hydration of the patient and, when feasible, oral rather than intravenous administration of the drug may reduce urinary-bladder fibrosis associated with cyclophosphamide therapy.
Health at the Crossroads: Transport Policy and Urban Health, by Ed T Fletcher, A J McMichael
Authors: D. Trichopoulos
Journal: BMJ (1997)

Ed T Fletcher, A J McMichael: John Wiley and Sons, £35, pp 340 ISBN 0 471 96272 4

This is an unusual and valuable book. It has long been known that urban residents have, as a rule, higher overall mortality than rural populations in the same country, but there have been few attempts to address this problem in an integrated and practical way. The book's thesis is that a major determinant of the harmful effects of …
PD02-08: Validation over Time of a Nomogram Predicting the Sentinel Node Positivity in Early Breast Carcinoma According to the Molecular Subtypes Classification.
Authors: C Ngô, Y De Rycke, D Mouttet, F Reyal, V Fourchotte, F Hugonnet, M-C Falcou, F-C Bidard, A Vincent-Salomon, A Fourquet, B Sigal-Zafrani, S Alran
Journal: Cancer Research (2011)

Abstract Background: The molecular subtypes of breast cancer have different axillary status. A new nomogram including the interaction covariate between estrogen receptor (ER) and HER2 status has been recently published (Reyal et al. PLOSone, may 2011) and allows to identify before surgery the patients with a high risk of positive sentinel lymph node (SLN). The purpose of our study was to validate this model on an independent population. Patients and methods: We studied 755 consecutive patients treated for operable breast cancer with sentinel node biopsies in 2009, from the Institut Curie breast cancer prospective database. Baseline characteristics were compared between our population and the population used to build the model, using Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables. The multivariate model, including age, tumor size, lymphovascular invasion and interaction covariate between ER and HER2 status, was used to calculate the theoretical risk of positive sentinel lymph node (SLN) for all patients. The performance of the model on our population was then evaluated in terms of discrimination (area under the curve AUC) and of calibration (Hosmer-Lemeshow HL test). Results: Characteristics of our population were significantly different from the training population for the following variables: tumor size (median 12mm [1-60] versus 13mm [1-100] p=0.005), lymphovascular invasion (18.6% versus 23.7% p=0.006), positive ER (91.4% versus 87% p=0.002) and age as followed: 56.7% of patients ≤ 60 versus 63.1%, 17.5% of patients between 60 and 65 versus 14.1% and 25.8% of patients above 65 versus 22.8% p=0.01. The nomogram showed similar results in our population than in the training population in terms of discrimination (AUC= 0.72 [0.68−0.76] versus 0.73 [0.7−0.75] and calibration (HL p= 0.4 versus p=0.35). Conclusions: Despite significant differences between the two populations concerning variables which are part of the nomogram, the model was validated in our population. Our study shows that this nomogram is efficient and robust over time to predict the likelihood of positive SLN according to molecular subtypes defined by surrogate markers ER and HER2 determined by immunohistochemistry in clinical practice. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD02-08.
Abstract 4873: Comprehensive analysis of 160 whole-genome sequences reveals striking telomere alteration patterns in 9 pediatric cancers
Authors: Matthew D. Parker, Gang Wu, Xiang Chen, Michael Rusch, Armita Bahrami, Li Ding, Elaine Mardis, Charles Mullighan, Richard Gilbertson, Michael A. Dyer, Richard K. Wilson, James Downing, Jinghui Zhang
Journal: Cancer Research (2012)

Abstract Although telomere shortening has long been recognized as a feature of cancer genomes, a comprehensive characterization of telomere alteration in pediatric cancer has not yet been performed. As part of the St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project (PCGP), we are performing whole genome sequence analysis on 600 pediatric cancers and matched germ line samples. This database will allow us to carry out a systematic investigation of telomere alteration across a broad range of pediatric cancers. To characterize the relative level of telomere length within a tumor, we have developed an approach that utilizes the WGS data and identifies all sequencing reads containing the telomeric repeat (TTAGGG)4. This read count is then normalized for genome-wide coverage and compared to the result from the matched germline sample to define the relative level of telomere amplification or loss in the tumor. To date we have analyzed 160 tumor/normal pairs collected from 9 distinct pediatric cancers types (Early T Progenitor Acute Lymphoblastic Leukemia (ALL), Infant ALL, Hypo-diploid ALL, Medulloblastoma, Retinoblastoma, Neuroblastoma, Osteosarcoma, Rhabdomyosarcoma, and Adrenocortical Carcinoma). Our analysis revealed normal telomere length or minimal loss in Early T Progenitor Acute Lymphoblastic Leukemia (ALL), Hypo-Diploid ALL, Infant-ALL, Medulloblastoma, Retinoblastoma, and Rhabdomyosarcoma. By contrast a subset of three distinct tumor types (Neurobalstoma, Oteosarcoma, and Adrenocortical Carcinoma) were characterized by marked increases in the number of telomere reads in the tumor consistent with telomere lengthening. These latter findings were validated in neuroblastoma by quantitative polymerase chain reaction (13/14) and fluorescence in situ hybridization (7/7). The presence of long telomeres was statistically associated with an increase in the number of somatic structural variations in tumor, with this association most evident in osteosarcoma. These data suggest that some pediatric cancers are associated with marked abnormalities in telomere maintenance leading to expansion in the telomere repeats. Defining the specific mutational processes that are responsible for these telomere defects and expanding the dataset to all 600 cancers in the project should help to define the mechanisms through which these alterations contribute to the transformed phenotypes. 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 4873. doi:1538-7445.AM2012-4873
The value of endoscopic ultrasonography in the diagnosis and treatment of duodenum protuberances lesions
Authors: Yu Xiqiu, Liu Jintao
Journal: Endoscopy (2011)

Objective: To explore the clincic and endoscopic ultrasonography (EUS) features of duodenum protuberances lesions and to evaluate the value of EUS in the diagnosis and treatment of duodenum protuberances lesions. Methods: 106 cases of duodenum protuberances lesions found by endoscopy from May 2003 to May 2009, 48 cases which could not diagnosised by gastroscopy were examined by EUS or endoscopic ultrasonography miniature probe (UMP) with high frequency. To confirmed diagnosis and chosed treating methods according to their internal echo pattern, size, layer of origin and boundary. Results: Through EUS, of which 10 cases were diagnosed with gastrointestinal stromal tumors, 12 with Brunner's gland adenoma, 2 with lipomas, 6 with polyps, 2 with cyst, 1 with ectopic pancreas, 2 with duodenum cancer, 1 with primary malignant lymphoma of duodenum, 3 with extrinsic compression, 7 with minor papilla, 2 with normal cases. After EUS examinations, 16 lesions that located in mucosa (m) or mucosa muscularis (mm) or submucosa (sm) were performed endoscopic resection, their pathology showed: 6 inflammatory polyps, 4 stromal tumors, 2 adenomatous polyps, 3 Brunner's gland adenoma, 1 ectopic pancreas, 1 lipoma. 2 of 6 lesions located in muscularis propria (mp were resected surgical operation, their pathology showed stromal tumors. 4 were followed up by EUS. The histological results of 18 patients were consistent with the preoperative diagnosis of EUS, with 85.7% (18/21) diagnostic accuracy. Conclusion: EUS can clearly show five layers of duodenums and histologic structure of adjacent organs, EUS is quite a valuable means for the definite diagnosis of duodenum protuberances lesions, and helpful in choosing the effective treating methods.
GE-01 * MOLECULAR AND PATHOLOGIC SUBSETS OF LOW GRADE GLIOMAS AND GLIONEURONAL TUMORS IDENTIFIED BY microRNA PROFILING
Authors: H. Ames, M. A. Vizcaino, F. Rodriguez
Journal: Neuro-Oncology (2014)

Low-grade (WHO I-II) gliomas represent the most frequent primary tumors of the central nervous system in children. They often have a good prognosis following total resection, however they can create many neurological complications due to mass effect, and may be difficult to resect depending on anatomic location. MicroRNAs have been identified as molecular regulators of protein expression that can repress multiple mRNAs concurrently through base pairing. Specific microRNAs are often suppressed during early cell differentiation to promote the expression of mitogenic proteins that are associated with the maintenance of specific stem cell types, a mechanism for growth and survival that is frequently exploited in cancer cells. Identification of these microRNA signatures present in low grade glioma and glioneuronal tumor sub-types could therefore lead to a wealth of candidate biomarkers. We used NanoString technology to analyze the expression levels of 800 microRNAs in nine low-grade glial and glioneuronal tumor subtypes (n = 45) using formalin-fixed paraffin-embedded tissue. We then generated hierarchical clusters following evaluation via significant analysis of microarrays (SAMs). Hierarchical clustering separated tumors from non-neoplastic brain. When looking at individual tumors, subependymal giant cell astrocytomas (SEGA) clustered sharply together, consistent with a unique microRNA expression signature in this tuberous sclerosis associated tumor subtype, compared to other low grade glial and glioneuronal tumors. Candidate microRNAs were validated using qRT-PCR. In SEGAs, microRNAs miR-219-5p, miR-129-2-3p, miR-338-3p, miR-487b, miR-885-5p, and miR-323-3p were significantly down-regulated by more than 15 fold as compared to normal brain and were also significantly down-regulated as compared to other low grade gliomas. In summary, altered microRNA expression is a feature of low grade glial and glioneuronal tumors. MicroRNA profiling may therefore be useful in subtyping these tumors and to provide important insights into their biology.
TCT- 121 Relationship Between On-treatment Platelet Reactivity Prior to Coronary Artery Bypass Surgery and In-Hospital Major Bleeding The Surgical Timing based On Platelet Reactivity for Coronary Artery Bypass Graft surgery (STOP-CABG) trial
Authors: Ron Waksman, lakshmana Pendyala, Rebecca Torguson, Augusto Pichard, Lowell F. Satler
Journal: Journal of the American College of Cardiology (2014)
Abstract 636: C-Met antibodies with distinctive characteristics including induction of receptor degradation without activation and tumor specificity
Authors: Sameer Greenall, Ermanno Gherardi, Andrew Scott, Terrance G. Johns
Journal: Cancer Research (2011)

Abstract The hepatocyte growth factor receptor (c-Met) is a cell surface, disulphide linked heterodimeric receptor tyrosine kinase consisting of an extracellular 50 kDa α-chain and an extracellular/intracellular 145 kDa β-chain containing the tyrosine kinase domain. The two chains of the mature c-Met arise from the proteolytic cleavage of a single-chain precursor. The α-chain and N-terminal part of the β-chain associate to form the SEMA domain which contains the binding site for hepatocyte growth factor (HGF). Aberrant signalling due to dysregulation of the c-Met receptor is often associated with more aggressive cancers in a range of tumor types, making it a target for cancer drug development. Mice were immunized with the SEMA domain of c-Met followed by cancer cells expressing c-Met in order to generate antibodies that target this receptor. We created 3 antibodies that exclusively bound the unprocessed form of c-Met. Fine epitope mapping using overlapping linear peptides showed all 3 antibodies had distinct binding sites; one each for the α- and β-chain and one with a conformational epitope. Since this unprocessed form of c-Met is only found on the surface of cancer cells, and not normal cells, these antibodies are tumor specific and may be extremely valuable as targeting agents. We also identified a series of antibodies that bind a defined peptide on the α-chain of c-Met and stimulate c-Met degradation without concurrent activation of the receptor; a problem with previous antibodies that enhance c-Met degradation. Through their ability to down-regulate c-Met, these antibodies inhibited HGF induced migration of SK-OV-3 ovarian cancer cells, inhibited ligand-independent proliferation of A549 lung cancer cells and had anti-tumor activity against U87MG glioma xenografts that possess a HGF/c-Met autocrine loop. The generation of cancer-specific c-Met antibodies and novel antagonist antibodies opens up new strategies for targeting this crucial receptor in range of cancer types. 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 636. doi:10.1158/1538-7445.AM2011-636
Abstract 5202: MUC1 oncogene is required for EGF/Src-driven carcinoma cell metastasis
Authors: Steven K. M. Lau, David J. Shields, Eric A. Murphy, David A. Cheresh
Journal: Cancer Research (2010)

Abstract Epidermal growth factor receptor (EGFR) and Src tyrosine kinase signaling promote epithelial to mesenchymal transition (EMT) and have been associated with increased metastatic capacity of tumor cells. We observed that EGFR/Src signaling leads to the activation of integrin αvβ5 on carcinoma cells, resulting in an increased invasive capacity without influencing primary tumor growth in vivo (Ricono, et al 2009). We explored potential downstream effectors of Src that may influence this metastatic cascade using an in silico screening approach. Leads were selected based on their ability to influence EGFR/Src/αvβ5-dependent invasion in vitro and metastasis in vivo in a chicken chorioallantoic membrane model. Here, we report the transmembrane glycoprotein mucin-1 (MUC1) as an essential mediator of the EGFR/Src/αvβ5 signaling axis leading to the metastasis of carcinoma cells in vivo. Disruption of MUC1 expression selectively abolished EGF/Src/αvβ5-dependent migration in vitro and metastasis in vivo without influencing primary tumor growth. Importantly, EGFR- and Src-dependent phosphorylation of the cytoplasmic tail of MUC1 (MUC1-CT) facilitated cleavage of MUC1-CT. Once cleaved, MUC1-CT was able to associate with β-catenin, enter the nucleus and modulate gene expression relevant to the metastatic properties of these cells. These findings support a critical role for MUC1 in the regulation of EGFR/Src/αvβ5-dependent metastasis of a wide range of carcinomas. 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 5202.