tbuckley/cabot-search huggingface dataset:
Benchmarking surgical systems 2015–30: application of indicators from The Lancet Commission on Global Surgery for an indicator-based, near real-time capacity-building index
Authors: Jonathan W Meadows, Kelly McQueen
Journal: The Lancet Global Health (2016)

Background Safe, timely and accessible global essential surgery and anaesthesia, once neglected in global health, is now an integral part of universal health coverage with the passage of the WHO Resolution 68/15. In the past, hospital-based surgical assessment surveys and indices were important for advocacy and to identify real infrastructure deficits and needs. The Lancet Commission on Global Surgery indicators, however, necessitate a new evaluation approach to anaesthesia, obstetrics, and surgery in low-income countries. Here, we aimed to use indicators from the Lancet Commissions on Global Surgery and other common indicators in global health to create a new global surgery index, which could be used to inform key stakeholders working toward Lancet Commission on Global Surgery goals for 2030.
Abstract 27: Chemotherapy-induced Akt survival signaling is regulated by CD44- Ezrin/Radaxin Moesin (ERM) scaffolding, dependent on EGFR activity
Authors: Aaron J. Goldman, Ishwarya Shunmugam, Ashish Kulkarni, Fernando Rivera, Shiladitya Sengupta
Journal: Cancer Research (2012)

Abstract Akt survival signaling has emerged as a predictor of poor prognosis in tumors resistant to chemotherapy. Despite the firm correlation between enhanced Akt survival signaling in resistant tumor tissue, there is a poor understanding of the exact mechanisms which elicit this robust pathway activation. In the present study we sought to uncover the full pathway of Akt activation in response to chemotherapy in order to fully elucidate mechanisms and proteins involved in chemotherapy resistance. Using breast and ovarian cancer cells, immunoprecipitations revealed that the CD44 glycoprotein initiates a unique scaffolding effect with the Ezrin/Radixin/Moesin (ERM) proteins and Akt in response to the anti-tubulin chemotherapies, docetaxel and vincrisine. Knockdown of CD44 using siRNA revealed that the activation of Akt(ser473) and ERM(tyr353) by chemotherapy are abolished in a time and dose dependent manner. Flow cytometry, caspase activation and cell viability assays confirmed that loss of Akt signaling sensitizes cancer cells to chemotherapy-induced apoptosis and a similar sensitivity was observed in the absence of CD44 expression. Furthermore, immunoprecipitations revealed that inhibition of EGFR using the small molecule inhibitor, Erlotinib, prevented CD44/ERM/Akt scaffolding in response to chemotherapy. In summary, CD44 and ERM scaffolding is responsible for the activation of Akt survival signaling induced by chemotherapy, in-vitro. Loss of CD44 sensitizes cancer cells to apoptosis. This scaffolding effect is dependent on the activity of EGFR, suggesting that a unique interaction exists between this ErbB1 receptor tyrosine kinase and the CD44 glyco-protein. This is the first evidence for cell surface events which precipitate survival signaling in cancer cells as a consequence of chemotherapy. These findings elucidate novel biomarker interactions for translation in the clinical setting. 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 27. doi:1538-7445.AM2012-27
Bone Marrow Scan Using Tc-99m–Labeled Anti-Granulocyte Antibody To Evaluate Hematopoiesis in Osteomyelofibrosis
Authors: THOMAS GRÜNING, WOLF-GUNTER FRANKE
Journal: Clinical Nuclear Medicine (2000)

A 66-year-old woman who had known splenomegaly caused by osteomyelofibrosis for several years was referred for evaluation of hematopoietic bone marrow and extrasplenic hematopoiesis before splenectomy. Bone marrow scanning was performed using a Tc-99m–labeled anti-granulocyte antibody. The most prominent uptake was seen in a grossly enlarged spleen. There was normal uptake in the liver, kidneys, and bladder, but no bone marrow uptake. Despite the known limitations of anti-granulocyte antibodies for evaluating splenic hematopoiesis, the total absence of functioning bone marrow allowed the authors to conclude that any remaining hematopoiesis (a clinical judgment) must be splenic.
Abstract 2648: Gene-asbestos interaction and lung cancer risk from a genome-wide association study
Authors: Chen-Yu Liu
Journal: Cancer Research (2012)

Abstract Occupational asbestos exposure has been found to increase lung cancer risk based on epidemiologic studies. In order to clarify the respective roles of genetic factors and asbestos exposure on lung cancer risk, we conducted the asbestos exposure-gene interaction analyses. The first discovery stage included 745 Caucasian cases and 839 Caucasian controls using Illumina Human 610-Quad BeadChips. Several independent populations were included in the second replication stage. Cumulative lifetime asbestos exposure score (AES), which was previously developed and validated in our study population, was calculated from self-reported duration and intensity of occupational and nonoccupational exposures. We have found several suggested interesting / significant regions that might be associated with lung cancer risk in our SNP-asbestos exposure interaction tests, especially on 2p25.3, which has been replicated in another independent population. Further replication is still in process. 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 2648. doi:1538-7445.AM2012-2648
IMPROVED CASE MIX INDEX DUE TO EMBEDDING CLINICAL DOCUMENTATION IMPROVEMENT SPECIALISTS ON AN INPATIENT CARDIOLOGY SERVICE AT A TERTIARY MEDICAL CENTER
Authors: James C. Blankenship, William A. Vandermark, John Pfeifer, Susan M. Krex, TyAnn A. Schneider, Peter Berger
Journal: Journal of the American College of Cardiology (2015)
Abstract 5268: Standardized and validated ATCC breast cancer panels: A tool for the rapid validation of biological hypotheses.
Authors: Chengkang (CK) Zhang, Michal Elias-Bachrach, Sherry Challberg, David Bettoun
Journal: Cancer Research (2012)

Abstract Advances in personalized medicine rely on knowledge of validated markers that predict response to treatment. The availability of such information could significantly impact preclinical drug optimization and reduce the cost of clinical trials. Conversely, improving drug efficacy based on clinical data requires performing studies in defined biological systems. These defined systems typically are clonal cell lines, which have been key in advancing our understanding of numerous disease states, including cancer. A number of recent comprehensive studies have demonstrated that individual cell lines are restricted along discreet lineages and therefore do not recapitulate tumor heterogeneity observed in patients However, the use of a combination of such cell lines reflected the clinical diversity observed in patient. (Neve et al, 2006; Kao J et al, 2006; Keller PJ et al 2010). We postulated that the use of carefully characterized cell lines combined into biologically relevant panels might provide valuable insights into studies on target validation, lead optimization, mechanisms of action and evaluation of efficacy in various patient subgroups. The lack of uniform culture conditions among various tumor cell lines hampers the design and conduct of experiments using such cell line panels and complicates the interpretation of the results obtained from them. We therefore undertook to combine panels of breast cancer cell lines that represented major clinical manifestations of the disease and culture them under standardized conditions. We were able to establish culture conditions that maintained the expression of mRNA and cell surface proteins for validated therapeutic and clinical markers. Using a small collection of clinically validated and investigational compounds we provide several example about how carefully selected and characterized cell panels can be used to carry out pharmacology studies and address questions pertinent to tumor biology and anti-cancer drug development. 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 5268. doi:1538-7445.AM2012-5268
Resistance to Parvovirus B19 Infection Due to Lack of Virus Receptor (Erythrocyte P Antigen)
Authors: Kevin E. Brown, Jonathan R. Hibbs, Giorgio Gallinella, Stacie M. Anderson, Elton D. Lehman, Peggy McCarthy, Neal S. Young
Journal: New England Journal of Medicine (1994)

The presence of a specific cellular receptor is thought to be necessary for susceptibility to viral infection. The erythrocyte P antigen is the cellular receptor for parvovirus B19. We hypothesized that the rare persons with the p phenotype, whose erythrocytes do not have this receptor, would be naturally resistant to B19 infection, which causes erythema infectiosum.
Improvement in overall survival (OS) observed in higher doses of internal hepatic radiation with lipiodol I131 combined with intra-arterial chemotherapy in advanced hepatocelullar carcinoma (AHC) and refractory hepatic metastasis (HM)
Authors: L. Viana, F. Costa, O. F. Costa, P. A. Costa, C. Albertotti, A. C. Buzaid, F. C. Maluf, R. Marques, S. Martins
Journal: Journal of Clinical Oncology (2005)

4232 Background: Our experience with intrahepatic Lipiodol I131 (L131) combined with oxaliplatin (OHP) IA, infusion FUDR and LV IA in 19 AHC and 20 HM pts were published (Proc ASCO 22:4133,2004). In this treatment program, the dose of L131 was planned for each pt, with median dose of 50 mCi (range: 25 - 80). This abstract reviews the impact of the dose of L131 in the OS of all 43 patients treated from Dec 2001 to Sep 2004. Methods: All pts, 19 AHC and 24 HM had predominant hepatic disease and symptomatic progression prior to inclusion. The first 39 pts were treated with a cycle of L131 intra-hepatic infusion dose followed by OHP 100 mg/m2 IA over 2h on D1, and FUDR 60 mg/m2/d + LV 15 mg/m2/d IA by 96h infusion (D1–4). In the last 4 pts, FUDR and LV were substituted by Capecitabine 3000 mg/m2/d PO for 4 days. The program was scheduled to deliver only one cycle. The single dose of L131 was calculated based on the distribution of 1 mCi of L131 to the target liver parenchyma and its volumetry. The planned dose of radiation should be < 50 Gy to the whole liver or < 60 Gy to a single lobe. To date, 55 treatment cycles were delivered. 8 pts were allowed to be retreated due to tumor accumulated dose < 120 Gy or tumor progression in prior responders. Results: After a median follow up of 160 days (mean 237 days), 39 pts (91%) were already dead. The median OS for all pts was 160 days. Pts treated with an accumulated dose of L131 > 50 mCi had a significant higher OS compared to pts treated with 50 mCi (130 days vs 495 days, log rank p=0.058; breslow p=0.21). The difference between log rank and breslow may be due to acute treatment mortality in Child C and advanced Child B pts. In the HM pts, there was no significant difference in OS regarding the accumulated dose of L131 (> 50 mCi: median 160 days vs < 50 mCi: 80 days, p=0.15). Conclusion: Internal radiation combined with IA chemotherapy can increase OS in AHC and refractory HM if appropriate dose of L131 can be delivered safely. This data encourages strategies to increase the accumulated dose of L131. No significant financial relationships to disclose.
GW25-e2475 Prvention of contrast-induced Nephropathy with l-carnitine in Coronary Heart Disease Patients with Diabetes Mellitus undergoing percutaneous coronary intervention
Authors: Li Wenhua, He Haiyan, Wang Lin, Chen Jing, Yu Yaren, Qian Wenhao, Liu Jiali, Li Dongye
Journal: Journal of the American College of Cardiology (2014)
Male fertility in hot environment [letter]
Authors: Levine Rj
Journal: JAMA (1984)

The American Medical Association Council on Scientific Affairs has recently noted that adequate studies of adverse effects on male reproductive function from working in hot environments do not exist.  Unfortunately the Council has also made the premaute judgment that such effects are not to be expected under normal working conditions.  It cites a study of workers in sugar refineries and railroads by Fonio et al which is poorly documented and lacks a control group.  Although Fonio et al state that heat had no negative influence on fertility since 94% of surveyed persons were reported to have had children during exposure no attempt was made to determine if the number of children conceived might have been fewer than usual.  While temporary hot exposures should as the Council has concluded cause no permanent effects and no substantial decrease in fertility exposures of up to several hours experienced regularly may indeed produce infertility.  Watanabe has shown that the sperm counts of volunteers can be suppressed to a very low level for a considerable time by repeating heat treatments at 3- or 4-week intervals.  The Council Report moreover fails to mention data on the effects of modest elevation of temperature.  During hot summers the breeding efficiency of cattle and sheep is known to decline concurrent with a reduction in semen quality.  Similarly in men semen specimens obtained in Houston revealed a circannual rhythm of sperm concentration and total count with lowest values in the summer months.  This may explain why throughout the world the pattern of births in tropical and subtropical climates is consistent with a deficit of conceptions during the hot season.  Large reductions is sperm counts without change in libido have been noted in studies of healthy volunteers who wore padded athletic supporters during waking hours for 3 weeks or more.  The devices increased intrascrotal temperatures in nude men by approximately 1 degree celsius but their influence on the temperatures of clothed men would be even less.  The maximum decrease in sperm counts was achieved after supporters had been worn about 6 weeks when on the average counts were 14% of pretreatment levels.  In my opinion the evidence accumulated to date suggests that occupational exposure to heat at currently acceptable limits may decrease male fertility.  Whether in fact it does should be determine now.  (full text)
META-ANALYSIS OF RISK OF STROKE AND THROMBO-EMBOLISM WITH RIVAROXABAN VERSUS VITAMIN K ANTAGONISTS IN ABLATION AND CARDIOVERSION OF ATRIAL FIBRILLATION
Authors: Ramez S. Nairooz, Partha Sardar, Maria Pino, Hossam Amin, Asif Sewani, Waddah Maskoun, Hakan Paydak
Journal: Journal of the American College of Cardiology (2015)
Abstract 2888: SOCS3-deficient cells are defective in the DNA damage response
Authors: Nicholas A. Cacalano, Sisi Jiang
Journal: Cancer Research (2011)

Abstract The SOCS family of proteins are negative feedback inhibitors of cytokine and growth factor signal transduction, targeting primarily the STAT family of transcription factors. Several SOCS genes, including SOCS1 and SOCS3 are hypermethylated and silenced in solid tumors, which is believed to impart a growth advantage via hyperactivation of the STAT pathway. Despite the growing role of SOCS in the pathogenesis of cancer, very little is known of their role in modulating tumor cell responses to therapy. We recently identified an unexpected function for SOCS3 in the context of the DNA damage response. We found that cells lacking SOCS3 are sensitive to ionizing radiation (IR) in a clonogenic survival assay due to impaired p21 (Cip1/Waf-1) upregulation, which results in failure of the radiation-induced G1-S checkpoint. Normal cell cycle arrest and p21 upregulation could be restored in SOCS3-/- MEFs by overexpression of a phosphorylation-deficient, dominant-negative (DN) mutant of STAT3. Two STAT3-dependent genes known to suppress p21 expression, c-Myc and BCL6 are overrepresented in SOCS3-deficient MEFs. Likewise, human tumor cells that repress SOCS3 expression by epigenetic silencing are also more radiosensitive than their SOCS3+ counterparts. In agreemwnt with our data in MEFs, c-Myc and BCL6 are overexpressed in human tumor cells that silence SOCS3 expression by promoter hypermethulation, suggesting that tumors lacking SOCS3 may be more vulnerable to IR-based therapies due to impaired cell cycle arrest and DNA repair. Our data suggest that therapeutic targeting of SOCS3 in tumor cells could sensitize cells to IR and improve the effectiveness of radiotherapy. 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 2888. doi:10.1158/1538-7445.AM2011-2888
UNDERUSE OF FULL DOSE FACTOR XA INHIBITION IN ATRIAL FIBRILLATION: INSIGHT FROM THE SPRINT-AF REGISTRY
Authors: Milan Gupta, Narendra Singh, Michelle Tsigoulis, Mahesh Kajil, Jafna Cox, Paul Dorian, G. B. John Mancini, Andrew C.T. Ha
Journal: Journal of the American College of Cardiology (2015)
Breakpoint analysis by fluorescence in situ hybridization in myelodysplastic syndromes with t(3;12)(q26;p13) and expression of EVI1
Authors: AA van de Loosdrecht, K Kok, B de Vries, AY van der Veen, E van den Berg, MT Esselink, P Marynen, E Vellenga, GW van Imhoff
Journal: Leukemia (2000)
Evaluation of Radioactive Iodine (I<sup>131</sup>) as a Treatment for Hyperthyroidism
Authors: Carl E. Cassidy, E. B. Astwood
Journal: New England Journal of Medicine (1959)

RADIOACTIVE iodine, although an effective form of treatment for hyperthyroidism, has the disadvantage that response of patients to a selected dose varies widely. As yet no method has been devised to select a dose that would be uniformly satisfactory. A quantity that may restore normal thyroid function in one patient may prove entirely ineffective in another, and a similar dose may even induce lasting myxedema in a seemingly comparable case. Myxedema is an undesirable therapeutic result, and, on the other hand, repeated trials with doses that prove inadequate may delay recovery for a year or longer. The current study was . . .
P3-05-05: Cyclin D1 Gene Amplification Is Rarely Heterogeneous in Breast Cancer.
Authors: E Burandt, M Grünert, M Choschzick, V Müller, C Bokemeyer, R Simon, G Sauter, A Lebeau, F Jänicke, W Wilczak
Journal: Cancer Research (2011)

Abstract Background: Amplification of Cyclin D1 (CCND1) occurs in about 10–20% of breast cancers and has been suggested to predict resistance to anti-hormonal therapy. As the diagnostic accuracy of predictive biomarkers can be substantially limited by regional expression differences within tumors, heterogeneity of CCND1 amplification was assessed in this study. To assess heterogeneity, a novel tissue microarray based analysis platform was developed. Material and Methods: To comprehensively asses the three-dimensional molecular composition of breast cancers, a “heterogeneity TMA” was constructed containing 8 different tissue cylinders from as many different cancer containing tumor blocks as possible (at least 4) from 147 primary breast cancers. Additional tissue samples were taken from 1–4 corresponding nodal metastases from 35 of these patients. Dual labeling fluorescence in situ hybridization (FISH) with probes for CCND1 and centromere 11 was applied. Results: The analysis revealed amplification in 29 of 133 (21.8%) patients with interpretable FISH data. CCND1 amplification was more frequently seen in ductal (22 of 87; 25.29%) than in lobular type (5 of 32; 15.63%) (p=0.251). CCND1 amplification was also associated with high tumor grade with amplification rates of 1 of 18 (5.56%) in grade 1, 15 of 72 (20.83%) in grade 2 and 12 of 40 (30%) in grade 3 carcinoma (p=0.075). CCND1 amplification was more frequently seen in ER positive cases (27 of 110; 24.55%) than in ER negative cases (1 of 17; 5.88%) (p=0.052). No association could be found between CCND1 amplification and tumor stage (p=0.445) and CCND1 amplification and PR status (p=0.752). Heterogeneous amplification status was detected in 9 of 29 (31.0%) amplified tumors, i.e. in 6.8% of all informative cases. Heterogeneity was successfully validated on large sections in all 4 heterogeneous cases with high level amplification. In the remaining 5 “heterogeneous cases” discordant results were due to variable interpretation of borderline amplification results with CCND1/centromer 11 ratios between 1.7 and 2.3. There were no discrepancies seen between primary tumors and matched lymph node metastases. Discussion: The high degree of homogeneity seen for CCND1 amplification suggests that this alteration represents an early event in tumor development/progression in a subset of breast cancers. CCND1 status determined in a small biopsy will be highly representative of the entire tumor and will thus be appropriate for predicting treatment outcome. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-05.
Abstract 612: FOXO1A is a target for HER2 overexpressing breast tumors
Authors: Yanyuan Wu, Xiying Shang, Marianna Sarkissyan, Dennis Slamon, Jaydutt V. Vadgama
Journal: Cancer Research (2010)

Abstract Trastuzumab treatment has improved the overall survival of HER2 overexpressing breast cancer patients. However, many of these patients will eventually become resistant to treatment. It is unclear what mechanisms may contribute to resistance to Trastuzumab. In this study we have tested the hypothesis that targeting of the FKHR transcription factor FOXO1A in HER2 overexpressing breast tumor cells, can overcome the Trastuzumab resistance in vitro. We have demonstrated that overexpression of HER2 leads to activation of PI3K/Akt pathway and subsequent inactivation of FOXO1A in HER2 overexpressing breast cancer cells, SKBR3. In wildtype SKBR3 cells, Trastuzumab downregulates active Akt (pAkt) and increases FOXO1A expression that leads to increase in p27kip1, and decrease in cyclin D1, and finally inhibits SKBR3 cell proliferation. In contrast, the effect of Trastuzumab was eliminated by the reduction of FOXO1A in HER2 overexpressing cells with constitutively active Akt1 (Clone SKBR3/AA28). The down-regulation of FOXO1A in SKBR3/AA28 resulted in nuclear export of p27kip1. Blocking the constitutively active Akt by a specific Akt/protein kinase B signaling inhibitor-2 (API-2) significantly increased FOXO1A expression and rendered the SKBR3/AA28 cells more responsive to Trastuzumab induced growth inhibition. Re-activation of FOXO1A by stable transfection or transient transfection also restored the growth inhibitory effects of Trastuzumab in SKBR3/AA28 cells. In summary, Trastuzumab can inhibit proliferation of HER2 overexpressing breast cancer cells by re-activating FOXO1A through inhibition the PI3K/Akt pathway. FOXO1A may therefore serve as a target for HER2 overexpressing breast tumors, and its activation or increased expression may overcome resistance to Trastuzumab treatment. 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 612.
Conventional Compared with Individualized Chemotherapy for Childhood Acute Lymphoblastic Leukemia
Authors: William E. Evans, Mary V. Relling, John H. Rodman, William R. Crom, James M. Boyett, Ching-Hon Pui
Journal: New England Journal of Medicine (1998)

The rate of clearance of antileukemic agents differs by a factor of 3 to 10 among children with acute lymphoblastic leukemia. We hypothesized that the outcome of treatment would be improved if doses were individualized to prevent low systemic exposure to the drugs in patients with fast drug clearance.