tbuckley/cabot-search huggingface dataset:
Cell-Cycle-Specific Chromosome Damage Following Treatment of Cultured Chinese Hamster Cells With 4′-[(9-Acridinyl-amino] methanesulphon-m-anisidide-HCl2
Authors: Larry L. Deaven, Melvin S. Oka, Robert A. Tobey
Journal: JNCI Journal of the National Cancer Institute (1978)

The induction of chromosome damage in Chinese hamster (line CHO) cells by 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl (MAC) (NSC-141549) was studied in cell populations growing exponentially and at various stages of the cell cycle following release from isoleucine-deficient G1-arrest. Autoradiographic analysis demonstrated that cells in S-phase at time of drug addition (2 microgram MAC/ml for 2 hr) were delayed 8 hours before entering mitosis. Cells in G1 at the time of MAC treatment were not as severely delayed, which resulted in a rather sharp increase and decrease in a percent labeled mitosis curve. Chromosome damage occurred differentially during the cell cycle. Cells in late G2 during MAC treatment contained incompletely condensed chromosomes with occasional chromosome interchanges at the next mitosis. Early G2 cells were severely damaged (greater than 20 breaks/cell). Damage to cells in S or G1 at the time of MAC addition was less severe, whereas cells in G1-S traverse had intermediate levels of chromosome breaks. Thus MAC appeared to be particularly effective at times when chromatin was undergoing structural modifications (G1-S and S-G2 boundaries). Low concentrations of MAC (0.05 microgram/ml) increased the rate of sister chromatid exchange to almost eight times the background rate. The cellular effects of MAC were compared with previously reported studies of other antitumor agents.
Reproductive Technology -- The Price of Progress
Authors: John A. Collins
Journal: New England Journal of Medicine (1994)

Each year more than a million American women use infertility services, but fewer than 50 percent of them go on to deliver a live baby1. Standard treatments for infertility include induction of ovulation, artificial insemination, and surgery for tubal disease or endometriosis. Little is known about why success with standard treatment for infertility is so limited; in many cases there may be reproductive deficiencies that are undetectable with current methods. Many couples are unable to reconcile themselves to the prospect of childlessness, and for them the scope of treatment has been altered dramatically by new techniques of assisted reproduction. . . .
Increased Glucose Transport–Phosphorylation and Muscle Glycogen Synthesis after Exercise Training in Insulin-Resistant Subjects
Authors: Gianluca Perseghin, Thomas B. Price, Kitt Falk Petersen, Michael Roden, Gary W. Cline, Karynn Gerow, Douglas L. Rothman, Gerald I. Shulman
Journal: New England Journal of Medicine (1996)

Insulin resistance in the offspring of parents with non-insulin-dependent diabetes mellitus (NIDDM) is the best predictor of development of the disease and probably plays an important part in its pathogenesis. We studied the mechanism and degree to which exercise training improves insulin sensitivity in these subjects.
PWE-161 Platelet activation in acute upper gastrointestinal bleeding
Authors: B R Disney, R Watson, A Blann, G Lip, C Tselepis, M Anderson
Journal: Gut (2012)

<h3>Introduction</h3> Acute upper gastrointestinal bleeding (AUGIB) is a common reason for medical admissions and is associated with significant morbidity and mortality. Studies have previously noted an excess of cardiovascular events in patients who have suffered from AUGIB. Patients who have aspirin withheld for 8 weeks following admission with AUGIB have significantly higher rates of CVS events. The aim of the study was to assess the level of platelet activation, and platelet reactivity, in patients presenting with AUGIB. <h3>Methods</h3> Patients admitted to Sandwell and West Birmingham Hospitals NHS Trust with AUGIB were recruited. Dyspeptic patients attending for diagnostic OGD were used as controls. To assess platelet activation citrated whole blood was incubated at room temperature with monoclonal mouse antibodies against constitutively expressed platelet marker CD42a-PerCP, and markers of platelet activation PAC1-FITC, and CD62P-APC. Negative controls were run in parallel. Incubation was terminated after 15 min. Platelet reactivity to an agonist, in this case ADP, was assessed by stimulating blood with ADP for 2 min prior to incubation with antibodies as described above. Samples were analysed using a FACSCalibur flow cytometer. Platelets were identified on the basis of their forward and side scatter properties and the presence of the CD42a platelet-specific marker. CD62P and PAC1 expression were measured by the percentage of platelets expressing these markers. Statistical significance of mean platelet activation was determined by the t-test. The Mann–Whitney U test was utilised for non-normally distributed data. Statistical analysis was performed using SPSS V.18.0 software. <h3>Results</h3> A total of 31 patients with AUGIB and 25 controls were recruited. The groups were age and gender matched. The mean age of the AUGIB group is 66.4±18.2 years, and the control group 62.8±6.1 years. There was a significant differences in the level of CD62P positivity between the study groups (18.4±5.8% in AUGIB group and 13.9±3.7% in the control group, p=0.001) and in those staining positive for both CD62P and PAC1 (1.9±1.45% in AUGIB group and 1.2±1.0% in the control group, p=0.027). No differences were seen in PAC1 positivity between the groups (7.1±5.2 vs 5.1±4.2, p=0.127). No differences were seen in the response of platelets to ADP between the study and control groups. <h3>Conclusion</h3> Patients presenting with AUGIB have higher levels of platelet activation when compared to controls. Platelet reactivity to ADP was similar between the two groups. In patients with high cardiovascular risk profiles early re-introduction of aspirin or other anti-platelet agents should be considered. <h3>Competing interests</h3> None declared.
Abstract 1871: Role of CYP1B1 gene polymorphisms in anticancer drug cytotoxicity as studied on isogenic cell lines
Authors: Valérie Le Morvan, Elodie Richard, Ricardo Bellott, Alban Pasquies, Jacques Robert, Amélie Lansiaux
Journal: Cancer Research (2012)

Abstract Cytochrome P450 1B1 (CYP1B1) is found in tumour tissue and is suspected to play a role in oncogenesis and drug resistance. CYP1B1 gene polymorphisms have been associated with the risk of developing lung and other cancers. We have recently shown that one of them (rs1056836, 1697C&amp;gt;G, L432V) was significantly associated with the cytotoxicity of DNA-damaging anticancer drugs in two independent panels of tumour cell lines, the NCI-60 panel and the JFCR-45 panel (Mol Cancer Ther 2010; 9: 3315-21). The present study was aimed at identifying the molecular mechanisms involved in anticancer drug resistance associated with this polymorphic variation. We have cloned the wild-type human CYP1B1 cDNA (1697C) in a lentiviral vector pDesti-pGK and obtained the variant cDNA (1697G) by directed mutagenesis. The two polymorphic variants were then used for the generation of viruses and the infection of cell lines. The CYP1B1 viruses were produced by cotransfection of 293T cells with viral plasmid DNA and either pER51CYP1B1WT-pGK or pER51CYP1B1VAR-pGK plasmid DNA in the presence of calcium phosphate. Cell supernatants containing the virus were harvested 24 h after transfection, filtered through a 0.45 μm membrane and stored at −80°C. Five different cell lines devoid of CYP1B1 expression were infected (COS-1 [Fibroblastic cell line], SW620 [colorectal cancer cell line], CAL27, CAL33 and SQ20B [HNSCC cell lines]). We thus generated five pairs of isogenic cell lines differing only by the polymorphic status of one nucleotide in the CYP1B1 gene. mRNA and protein expression were evaluated by qRT-PCR and western blotting, respectively. The cytotoxicity of a panel of anticancer drugs was evaluated on these cell lines (cisplatin, oxaliplatin, gemcitabine, doxorubicin, etoposide, camptothecin, irinotecan and its active metabolite [SN38]). A systematically higher IC50 was noticed for the cell lines harbouring the variant cDNA as compared to those harbouring the wild-type cDNA, the variant cell lines being 2-3-fold resistant to all agents. These results obtained on isogenic cell lines were in perfect agreement with what could be expected from the study of the cell line panels. The catalytic activity of the two CYP1B1 variants is being studied using ethoxyresorufine O-deethylation. A population of 125 head-and-neck cancer patients treated by chemotherapy in the palliative setting has been prospectively constituted and will be used for the clinical validation of the interest of CYP1B1 genotyping for predicting anticancer drug activity. 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 1871. doi:1538-7445.AM2012-1871
Prevalence of BRCA1 and BRCA2 genes mutations in a sample of families with high risk of breast and ovarian cancer in Brazil.
Authors: VF Esteves, LS Thuler, L Amendola, PP Frankel, RJ Vieira, RJ Koifman, S Koifman
Journal: Cancer Research (2009)

Abstract Abstract #6020 Introduction: Of all malignant neoplasia among women, breast cancer has the highest incidence rate in Brazil. The objective of the present study was to ascertain the frequency of genetic modifications in a high risk population for breast and ovarian cancer from different regions of Brazil. Methods: An exploratory, descriptive study was carried out on the prevalence of the BRCA1 and BRCA2 mutations in case series of high risk families to breast and/or ovarian cancer. Following the respective heredogram construction, a sample of blood was taken and DNA extraction was performed to all index cases. The protein truncation test (PTT) was used to screen for truncated mutations in exon 11 of the BRCA1 gene and in exons 10 and 11 of the BRCA2 gene. Results: Of the 612 individuals submitted to genetic testing, 21 (3.4%), 19 women and 2 men, had mutations in the BRCA1 or BRCA2 genes. BRCA1 mutations consisted of ins6kb, 5382insC, 2156delGinsCC, 185delAG, C1201G, C3522T and 3450del4 mutations, while BRCA2 mutations were 5878del10, 5036delA and 4232insA. Conclusion: The prevalence of germline mutations in the BRCA1 and BRCA2 genes found in the present study was lower than reported by other studies in Brazil. The inclusion of individuals with medium risk may have contributed towards the lower observed prevalence. Nevertheless, individuals with a high probability of carrying mutations should be advised with respect to the possibility of undergoing genetic testing, and of the risks, benefits and limitations of these tests. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6020.
A 1-h Combination Algorithm Allows Fast Rule-Out and Rule-In of Major Adverse Cardiac Events
Authors: Arash Mokhtari, Catharina Borna, Patrik Gilje, Patrik Tydén, Bertil Lindahl, Hans-Jörgen Nilsson, Ardavan Khoshnood, Jonas Björk, Ulf Ekelund
Journal: Journal of the American College of Cardiology (2016)
The effects of being conscious: Looking for the right evidence
Authors: Marco Mazzone
Journal: Behavioral and Brain Sciences (2014)

Abstract Huang &amp; Bargh's (H&amp;B's) general picture might underestimate the role played by conscious self and overestimate the behavioral inconsistencies at the personal level. This follows from how they delimit the goals under consideration: Their theses that goals are not consciously selected and that the conscious self is involved just in post hoc rationalization should also be tested against concrete and long-term goals.
PC0003 Prevalence of musculoskeletal diseases and its treatment in the elderly
Authors: R. Julian, V. Castell, I. Gomez, C. Mateo, M. Sanchez, P. Lopez-Gonzalez, P. Sanchez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Aging population means an increase in the prevalence of degenerative diseases like osteoarthritis and other musculoskeletal conditions and therefore an increased consumption of drugs for these diseases. <h3>Objectives</h3> To determine the prevalence of musculoskeletal diseases in general (particularly osteoarthritis) and drugs used for its treatment in a cohort of over 65 years designed in Primary Care <h3>Methods</h3> Descriptive cross-sectional study with a stratified random sampling, weighted by age and sex. Information about sociodemographic and health variables was obtained by a semi-structured interview. Participants were invited by mail and then were recruited in the medical office or by telephone. Other variables were obtained from computerized medical records used in Primary Care <h3>Results</h3> Sample: 814 individuals ≥65 years. Mean age =77±7.6 years (65-103 years), 51.5% were women. Polypharmacy (≥6 drugs) was present only in the 3.2% of them. Subjective musculoskeletal condition was declared by 66.8% of the subjects, but a musculoskeletal disease diagnosed in medical records was present in 58.1% of them. The prevalence of the different musculoskeletal diseases was: osteoarthritis =49%, rheumatoid arthritis and other rheumatisms =5.5%, gout =4.8%; osteoporosis =17.6%, and other musculoskeletal disease =5.9%. The 4.2% from them had suffered some fracture in the last 10 years, being hip fractures in 1.1%. Medication utilization: 53.8% of the sample did not take any drug to combat these diseases, 29.9% used a single drug chronically, 11.5% 2 drugs and only 4.8% used 3 or more drugs. Medication profile: Analgesics were consumed in 57.9% of them (46.1% paracetamol and other painkillers = 11.8%); nonsteroidalanti-inflammatory drugs (NSAIDs) = 28.1%; corticosteroids =1.7%; drugs for gout = 6.4%, symptomatic slow action drugs in osteoarthritis (SYSADOA) = 6.4% and drugs for osteoporosis (vitamin D, calcium and antiresorptives) = 4.3% <h3>Conclusions</h3> The prevalence of musculoskeletal diseases in the elderly of our community is high (especially osteoarthritis) Nearly half of the individuals over 65 years (43.2%) chronically consume any drugs related to musculoskeletal diseases. Among these the most widely used is paracetamol followed by nonsteroidalanti-inflammatory drugs <h3>References</h3> Carmona G, Ballina R, Lafflon A. EPISER 2000: prevalence of rheumatic disease in the Spanish population. Rev Esp Reumatol. 2001; 28 (1):18-25. Peña A, Fernández-Lόpez JC. Prevalence and risk factors in osteoartritis. Reumatol Clin 2007; 3 Supl 3: S6-12. De Miguel E, Dominguez A, Morales FJ, Varela C, Riesgo Y. Study of medication in osteoarthritis. Rev Esp Reumatol 2003; 30(1): 12-9. <h3>Disclosure of Interest</h3> None Declared
Case 85-1961
Journal: New England Journal of Medicine (1961)

Presentation of Case A sixty-nine-year-old Negro woman was admitted to the hospital because of abdominal masses. For the past sixteen years the patient had diabetes mellitus, which was well controlled on 20 to 40 units of NPH insulin daily. Two and a half years before entry she began to experience progressive weight loss, tremor, heat intolerance and nervousness. The thyroid gland was markedly enlarged; the protein-bound iodine was 20.7 microgm. per 100 ml., and the radioactive-iodine uptake was 90.5 per cent in twenty-four hours. After methimazole (Tapazole) and two courses of radioactive sodium iodide she became euthyroid; subsequently, the diabetes . . .
Abstract 5277: S100A7 modulates EGFR signaling in estrogen receptor negative breast cancer cell lines
Authors: Zahida Qamri, Mohd W. Nasser, Abdalla Abdussamad, Nancy Lill, Ramesh K. Ganju
Journal: Cancer Research (2010)

Abstract Purpose of Study: S100A7 (psoriasin) is highly expressed in estrogen receptor alpha negative (ER-α−) and EGFR+ basal like phenotype, especially triple negative, that have been associated with worse prognosis and outcome. However, not much is known about the role of S100A7 in promoting tumorigenesis of ER-α− and EGFR+ breast cancers. We hypothesize that S100A7 secreted by tumor cells may modulate tumor growth by binding to receptor for advanced glycation end-products (RAGE) and activating EGFR in ER-α−. In the present study, we analyzed recombinant S100A7-mediated EGFR signaling that enhances breast tumorigenesis and metastasis in ER-α− cells. Methods: We examined the effect of recombinant S100A7 on cell migration and motility of ER-α− MDA-MB231 and MDA-MB453 breast cancer cell lines. In addition, we analyzed S100A7-mediated signaling mechanisms by monitoring changes in phosphorylation and expression of various signaling molecules by Western blot, immunoprecipitation and immunofluorescence. We also co-transfected HEK-293 with EGFR and RAGE plasmids to analyze crosstalk between S100A7/RAGE and EGF/EGFR in these cells. Results: We observed high expression of RAGE in ER-α− MB-231 and MB-453 breast cancer cell lines by FACS analysis. We have also shown that S100A7 is secreted in the conditioned media of ER-α− MB-231 overexpressing S100A7 cells. Recombinant soluble S100A7 was shown to induce cell migration and wound healing in MB-231 and MB-453 cells. These effects were mediated through RAGE, as RAGE neutralizing antibody blocked S100A7-mediated functional effects. To further analyze the molecular mechanism of S100A7-mediated signaling, we observed that recombinant S100A7 transactivates EGFR. Further analysis of molecular mechanism revealed that S100A7 enhances AKT and Erk phosphorylation as well as increases association between Jab-1 and EGFR. The crosstalk between S100A7/RAGE and EGF/EGFR was further confirmed by co-transfecting HEK-293 cells with EGFR and RAGE. Recombinant S100A7 was shown to induce EGFR phosphorylation in these transfected cells, confirming S100A7 may transactivate EGFR by binding to RAGE. Conclusion: These studies reveal that S100A7 may enhance metastatic potential of ER-α− cells by binding to RAGE and activating EGFR signaling. Furthermore, these studies may help in the development of S100A7/RAGE as novel therapies target for ER-α− breast cancer, especially triple-negative and EGFR+ basal-like cancers, which are highly aggressive and difficult to treat. 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 5277.
Abstract LB-371: Evaluating the protein SUMOylation pathway as a potential cancer therapeutic target using inducible RNA interference
Authors: Xingyue He, Neil Bence, Larry Dick, Petter Veiby, Joe Bolen
Journal: Cancer Research (2011)

Abstract Protein SUMOylation is a conserved ubiquitin-like protein posttranslational modification pathway catalyzed by the SUMO enzymatic cascade. Previous studies have indicated SUMO pathway genes are highly expressed in cancer and are required for development and cell viability. We applied lentivirus based shRNA methods to efficiently knockdown SUMO pathway components in human cancer cells. shRNAs for SAE2 and UBC9 lead to reduced SUMO pathway activity as measured by cell based reporter assays. Knockdown of SUMO enzymes suppresses proliferation of human cancer cells including U2OS, HCT116 and HeLa cells. Multiple shRNAs for each gene showed a similar growth arrest phenotype suggesting that the results are not RNAi off target effects. Furthermore, SUMO pathway inhibition by RNAi sensitize U2OS cells to the DNA damage agent Camptothecin, indicating a chemo-sensitizing effect of SUMO pathway inhibition. To improve the reproducibility of our experiments and avoid an observed negative selection for the constitutively expressed shRNAs, we established a doxycycline inducible conditional shRNA (tet-on) system to achieve acute and reversible SUMO enzyme knockdown. Acute SAE2 knockdown in U2OS and HCT116 cells reduces S phase and slows cell growth in vitro. Our data demonstrate SUMO pathway is a potential therapeutic target to treat cancer and this study demonstrates that inducible shRNA systems are valuable for early stage drug discovery. 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-371. doi:10.1158/1538-7445.AM2011-LB-371
PD03-08: BRCA1-Like Triple Negative Tumors: Clinicopathological Variables and Chemosensitivity to Alkylating Agents.
Authors: J Wesseling, EH Lips, AMM Oonk, RM Smits, CCM van Rijn, L Mulder, N Laddach, SS Savola, LFA Wessels, PM Nederlof, S Rodenhuis, ALT Imholz
Journal: Cancer Research (2011)

Abstract Background Our group has previously employed array Comparative Genomic Hybridization (aCGH) to assess the genomic patterns of BRCA1-mutated breast cancers. It is reasonable to assume that this pattern indicates ‘BRCAness’ and thus serves as a marker for homologous recombination deficiency. This BRCA1-like aCGH profile is also present in about half of all triple negative sporadic breast cancers and has been shown to be predictive for benefit from intensive chemotherapy with DNA crosslinking agents. To study BRCA1-like tumors and conventional dose chemotherapy sensitivity in more detail, we compared clinical factors and survival rates in a uniform cohort of triple negative breast tumors treated with alkylating agents. Patients and methods 103 patients with triple negative tumors received conventional dose adjuvant chemotherapy with doxorubicin/cyclophosphamide. DNA was extracted from tumor samples and BRCA1-like profiles were assessed. Tumors were classified as BRCA1 -like or non-BRCA1-like. Standard clinical and histopathological factors were determined and compared between both groups. Relapse free survival (RFS), disease specific survival (DSS) and overall survival (OS) after diagnosis were compared between BRCA1-like and non-BRCA1-like tumors. Results 66 tumors (65%) had a BRCA1-like profile, while 35 tumors (35%) did not show such a profile. Patients with BRCA1-like tumors tended to be younger and had more often node-negative disease compared to the patients with non-BRCA1-like tumors (p=0.058 and p=0.034, respectively). There was no significant difference in survival between BRCA1-like and non BRCA1-like patients after treatment with alkylating agents: the median RFS was 121 vs. 109 months, median DSS was 129 vs. 114 months and OS was 127 vs. 110 months, for BRCA1-like versus non-BRCA1-like tumors. T-stage was the only variable significantly associated with survival. Conclusion BRCA1-like tumors occurred in younger patients and were more often node negative, which are features shared with tumors in BRCA1-mutation carriers. We did not observe a difference in survival between BRCA1-like and non-BRCA1-like triple negative breast cancers after treatment with conventional dose chemotherapy with alkylating agents. These results confirm our previous findings that BRCA1-like tumors have similar sensitivity to anthracycline-based adjuvant chemotherapy as other triple-negative tumors. It will be important to establish whether BRCA1-like tumors also share the exquisite sensitivity of BRCA-mutated tumors to PARP-inhibitors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD03-08.