tbuckley/cabot-search huggingface dataset:
Abstract CN4-2: Genetic polymorphisms of ABC transporters in cancer chemotherapy: Development of SmartAmp2 method for clinical genetic testing
Authors: Toshihisa Ishikawa, Wanping Aw, Alexander Lezhava, Yoshihide Hayashizaki
Journal: Clinical Cancer Research (2010)

Abstract Pharmacogenomics data can facilitate our understanding of the sources of variability in drug response, which can potentially lead to improved safety and efficacy of chemotherapy for individual patients. Genetic polymorphisms of human ABC transporter genes are reportedly related to the risk of diseases or patients' responses to medication. However, a key requirement for the development of individualized medicine or personalized therapy is the ability to rapidly and conveniently test patients for genetic polymorphisms and/or mutations. For rapid genetic diagnosis, we have recently developed a rapid and cost-effective method named “SmartAmp2” that enables us to clinically test genotypes. Since ABCB1, ABCG2, ABCC4, and ABCC11 genes are known to be critically involved in cancer chemotherapy, we have examined whether the SmartAmp2 method could detect SNPs in those ABC transporter genes. In our study using clinical samples, the SmartAmp2 method has been proven to accurately detect and discriminate all possible homozygotes and heterozygotes of the SNPs we tested. Furthermore, we developed SmartAmp2 primers to detect mutations of K-RAS and EGFR genes in colon and lung cancers. Since the SmartAmp2 method enables us to detect genetic polymorphisms or mutations within 30 to 45 min under isothermal conditions without DNA isolation and PCR amplification, this method would provide a practical tool of genetic testing in cancer chemotherapy. Citation Information: Clin Cancer Res 2010;16(7 Suppl):CN4-2
Low frequency of TEL-AML1 in relapsed acute lymphoblastic leukemia supports a favorable prognosis for this genetic subgroup
Authors: JE Rubnitz, FG Behm, D Wichlan, C Ryan, JT Sandlund, RC Ribeiro, GK Rivera, ML Hancock, MV Relling, WE Evans, C-H Pui, JR Downing
Journal: Leukemia (1999)
MCF-7 cells selected for acquired resistance to an anti IGF-IR antibody remain sensitive to fulvestrant and to an IGFIR tyrosine kinase inhibitor (TKI).
Authors: X Zhang, B Seidel, KS LaPara, D Yee
Journal: Cancer Research (2009)

Abstract Abstract #72 Monoclonal antibodies and tyrosine kinase inhibitors (TKI) targeting the type-1 Insulin-like growth factor receptor (IGFIR) are currently in clinical trials. Resistance to several targeted therapies has been observed and is not well understood. Estrogen receptor (ER) has been shown to interact with IGFIR signaling to promote cell growth. To examine acquired resistance to IGF1R monoclonal antibodies, we selected ER positive MCF7L cells in increasing concentrations of an IGFIR inhibitory antibody (scFvFc, treated over 2 years). These cells (MCF7L-scFvFc) had downregulated IGFIR levels, increased basal phosphorylation of IRS-1 with constitutive activation of Akt. MCF7L-scFvFc cells had enhanced basal growth and were no longer responsive to IGF-I and estradiol (E2). To examine the relationship between IGF1R and ER function, we used the pure steroidal anti-estrogen fulvestrant to examine effects on growth of the parent and antibody-resistance cells. In parent MCF7L cells, fulvestrant inhibited growth responses to IGF-I and E2 treatment when each ligand was given individually, but when both ligands were given together, the growth inhibition was reversed. In MCF7L-scFvFc, fulvestrant inhibited growth response to IGF-I, but cells still responded to E2 even in the presence of fulvestrant. Fulvestrant inhibition of MCF7L-scFvFc basal growth was associated with downregulation of ER and IGFIR system components. Fulvestrant treatment induced PARP cleavage in MCF7L, but not in MCF7L-scFvFc cells. IGF-I partially protected cells against fulvestrant induced PARP cleavage, and E2 treatment has full protective effects on these cells. These data suggest that MCF7L-scFvFc cells were more resistant to cell apoptosis induced by fulvestrant. Other monoclonal antibodies directed against IGF1R were ineffective in reversing the resistance in MCF7L-scFvFc cells. To determine if activated IGF1R was responsible for the behavior of MCF7L-scFvFc cells, we used the IGF1R TKI AEW541. AEW541 inhibited growth of these antibody resistant cells and a combination of fulvestrant and AEW541 completely inhibited cell growth and IGF signaling in both MCF7L and MCF7L-scFvFc cells. Thus, activated IGFIR signaling was still required for the growth of MCF7L-scFvFc cells. In conclusion, MCF7L-scFvFc had low levels of IGF1R but retained activated IGF1R signaling that was inhibited by TKI (AEW541). In addition, the ER antagonist fulvestrant also inhibited growth of these cells. In these ER-positive cells, combined blockade of ER and IGF1R could provide a more prolonged inhibition of cell growth. Moreover, cells selected for resistance to an IGF1R antibody remain sensitive to IGF1R TKIs. Thus, concurrent or sequential targeting of IGF1R and ER function should be examined in breast cancer clinical trials of ER positive breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 72.
Abstract 1866: Polymorphisms in DNA double-strand break repair genes and end-joining capacity from sisters discordant for breast cancer from the New York site of the BCFR
Authors: Hui-Chen Wu, Nicola Machella, Qiao Wang, Ruby T. Senie, Regina M. Santella, Mary Beth Terry
Journal: Cancer Research (2010)

Abstract Dysfunction in DNA double strand break (DSB) repair increases breast cancer risk. Genetic variation could be an important factor in determining DSB capacity. However, data on the association of single nucleotide polymorphisms (SNPs) of DSB repair genes with phenotype and with breast cancer risk are limited. We determined genotypes for 25 DSB repair SNPs in a total of 298 families with discordant sisters for breast cancer, including 85 families with end-joining (EJ) capacity data available from the New York site of the Breast Cancer Family Registry (BCFR). We observed that XRCC4 variant (rs1056503) was associated with increased breast cancer risk with age-adjusted odds ratios (OR) of 1.67 (95% confidence interval (CI)=1.02-2.74) and a significant inverse effect of an XRCC5 variant (rs1051677) with an age-adjusted OR of 0.07 (95% CI=0.009-0.58). EJ capacities differed by different genotypes of BRCA1 among controls, and different genotypes of XRCC5 among cases and controls. However, in a final multivariable conditional logistic model, including RAD52 (rs11226), XRCC4 (rs1056503) and XRCC5 (rs3834), we did not observed any statistically significant genetic effect of DSB repair genes on breast cancer risk. Although these findings suggest that selected polymorphisms of DSB pathway genes were associated with EJ capacity, there were no main associations with breast cancer suggesting that DSB phenotype rather than genotype may be more important in predicting breast cancer. 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 1866.
Abstract 3451: Lack of CD47 in the tumor microenvironment enhances anti-tumor adaptive immune responses when combined with ionizing radiation
Authors: David R. Soto Pantoja, Terabe Masaki, Lisa A. Ridnour, William DeGraff, Jay A. Berzofsky, David D. Roberts
Journal: Cancer Research (2012)

Abstract Over half of the new cancer patients diagnosed this year in the United States will require ionizing radiation (IR) therapy as part of their course of treatment. Achieving a curative response, however, is limited by detrimental side effects and off-target toxicities of IR to normal cells. We previously demonstrated that CD47 null mice or blockade of CD47 confers radioprotection to normal tissues including radiosensitive hematopoietic progenitors. On the other hand, blockade of CD47 enhanced the radiation-induced tumor growth delay in two syngenic mouse models. One possible explanation for this observation is that, by protecting tumor-associated immune cells, CD47 suppression increases tumor immune surveillance. To examine the role of T cell immunity, we used the F15-12 RM mouse fibrosarcoma model in athymic mice. Blockade of CD47 in combination with IR did not alter tumor growth in these T-cell deficient mice versus IR alone. However, adoptive transfer of CD8+ T-cells in combination with CD47 blockade and IR significantly enhanced the reduction in tumor growth when compared to tumors of mice irradiated in combination with the T cell transfer alone (186 ± 50 vs. 370 ± 123 mm3 respectively, N=8). In vitro experiments showed that blockade of CD47 enhances antigen dependent CD8+ mediated cytotoxicity of tumor cells. Furthermore, in a syngeneic tumor model of B16 melanoma we observed over a 50% reduction in volume of irradiated tumors in a CD47-/- host versus a WT host. Immunohistochemical staining indicated an increase of intratumoral CD8+ cytotoxic T-cells. Further analysis indicated that lack or blockade of CD47 in combination with IR resulted in a significant increase in granzyme B expression, further indicating that the increased target cell death may be mediated by this pathway. CD47 suppression may also reduce tumor growth by altering the immunosuppressive factor VEGF. In both tumor models, either blockade of or lack of CD47 in combination with IR was associated with a reduction in VEGF. VEGF is a potent pro-angiogenic factor and a potent immunosuppressive factor that inhibits activation of cytotoxic T-cells. Our findings indicate that agents targeting CD47 enhance anti-tumor T cell immunity when combined with radiation. Combining CD47 suppression with IR and adoptive T cell transfer may increase the percentage of curative responses. 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 3451. doi:1538-7445.AM2012-3451
SP0196 Picturing the problem: Cardiovascular disease impact in inflammatory rheumatic diseases
Authors: G. Kitas
Journal: Annals of the Rheumatic Diseases (2013)

Inflammatory rheumatic diseases, particularly rheumatoid arthritis but also the spondyloarthropathies (SpA), associate with increased cardiovascular disease (CVD) morbidity and mortality. There appears to be a gradient, with the risk of CVD death being increased by 50-70% in RA compared to the general population, followed by smaller, but still significant increases in Psoriatic Arthritis and then Ankylosing spondylitis. The reasons for this have been subject to intensive scrutiny in the last decade, and a picture appears to be emerging. Classical CVD risk factors, including hypertension, dyslipidaemia, insulin resistance, altered body composition/obesity and decreased physical activity are more prevalent in these conditions and may contribute to the increased risk. Systemic inflammation, characteristic of all these conditions, also plays a role but it remains unclear whether this is due to direct effects on the vasculature or mediated through effects on the classical risk factors. Observational studies suggest that the more effective the control of inflammation, the better the cardiovascular outcomes appear to be, but this needs to be confirmed in prospective studies designed specifically for the purpose. Assessment of CVD risk in these conditions remains a challenge, as the widely used in the general population risk algorithms all underestimate actual risk in people with inflammatory rheumatic diseases: disease specific risk algorithms need to be developed and validated, so that they can then be used to inform effective prevention strategies. Such strategies also remain elusive and not validated at present, but they are likely to include a two-pronged approach: systematic identification and management of classical CVD risk factors, together with effective control of systemic inflammation. <h3>Disclosure of Interest</h3> None Declared
Should Liver Metastases of Breast Cancer Be Biopsied To Improve Treatment Choice?
Authors: L. Fumagalli, G. Curigliano, V. Bagnardi, M. Locatelli, G. Aurilio, P. Della Vigna, L. Monfardini, S. Giudici, G. Viale, L. Toppo, A. Goldhirsch
Journal: Cancer Research (2009)

Abstract Background: Decision making on systemic treatment of women with metastatic breast cancer is based on features like estrogen receptor (ER), progesterone receptor (PgR), and HER2 status assessed on the primary tumor. We evaluated the concordance of receptor status between primary tumor and liver metastases and estimated the potential change of these pathological features and its impact on treatment choice.Materials and methods: We retrospectively analyzed a database including ultrasound guided liver biopsies performed from 1995 to 2008. All tissue samples, both from primary tumor and liver metastases, were analyzed for ER, PgR and HER2 status. Clinical and biological data were obtained from medical charts (including treatments before and after liver biopsy). Differences between proportions were evaluated using the Pearson chi-square test.Results: We identified 215 consecutive patients with matched primary and liver tissue samples. Median time from primary diagnosis to liver biopsy was 4.1 years (range 0-18.3 years). Changes in ER status were observed in 38/215 patients (17.7%). 15/47 patients (31.9%) changed from ER negative to positive and 23/168 patients (13.7%) changed from ER positive to negative [p= 0.0038]. Changes in PgR status were observed in 111/215 patients (51.6%). 16/74 patients (21.6%) changed from PgR negative to positive and 95/141 patients (67.4%) from PgR positive to negative [p &amp;lt;0.0001]. 11/41 patients (26.8%) changed from ER and PgR negative to ER or PgR positive [Group A] and 25/174 patients (14.4%) changed from ER or PgR positive to ER and PgR negative [Group B] [p=0.054]. In the Group A the treatment of 4/11 patients (36.4%) was changed after biopsy: 2/4 started endocrine treatment (HT) and 2/4 stopped it. In Group B the treatment of 16/25 patients (64%) was changed after biopsy: 15/16 stopped HT. Changes in HER2 status were observed in 19/131 patients (14.5%): 5/93 patients (5.4%) changed from HER2 negative to positive and 14/38 patients (36.8%) changed from HER2 positive to negative [p= &amp;lt;0.0001]. In this group 5/5 patients started a trastuzumab containing treatment after biopsy.Conclusions: There was a substantial discordance in receptor status between primary tumor and liver metastases, which led to change in therapy for 21.8 % of patients. Biopsy of metastases for reassessment of biological features should be considered in all patients when safe and easy to perform, since it might impact treatment choice for many. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6003.
A Nomogram To Predict Breast Cancer Probability in Patients with Nipple Discharge.
Authors: C. Mazouni, P. Bonnier, C. Uzan, O. Haddad, S. Delaloge, F. Rimareix, J. Garbay
Journal: Cancer Research (2009)

Abstract Background: Nipple discharge is a symptoms of breast disease that lead to the diagnosis of breast cancer in 5% of cases. Our objective was to develop a scoring system based on clinical and radiological factors to predict the risk of breast cancer (BC).Methods: Predictive factors of breast cancer were identified in a population of 90 women operated for unilateral nipple discharge, at Institut Beauregard, in France. A scoring system that gives individual probability of BC was developed based on univariate and multivariate logistic regression models. This model was validated in an external independent data set of 263 patients treated at Institut Gustave Roussy, in France.Results: The frequency of BC was 50% and 19.1%, respectively in the training set and in the validation. set. Factors associated with BC were age (p=0.04), presence of a clinical tumor (p=0,03), presence of a nodular lesion (p=0,03) or microcalcifications (p= 0.006) at mammography, in univariate analysis. In multivariate analysis. Only age (p= 0.03), microcalcifications (p= 0,007), or nodular lesion (p=0.06) at mammography were significance or tend to reach significance in multivariate analysis. Based on AIC, factors entered in the model were: age, clinical mass, abnormal images at mammography. The model has a good auc (76.6%). In the validation set, the auc was lower (66.6%).Conclusion: A clinico-radiological model can be built to predict BC in women with nipple discharge to help the decision-making and plan the suitable surgery. A further validation and testing of biological parameters might improve our model. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5031.
782 THE aa15–17 AMINO ACID SEQUENCE IN THE TERMINAL PROTEIN DOMAIN OF HBV POLYMERASE AS A VIRAL FACTOR AFFECTING IN VIVO REPLICATION ACTIVITY OF THE VIRUS
Authors: K. Yoshino, K. Sugawara, Y. Uchida, J. Kouyama, K. Naiki, N. Nakayama, S. Mochida
Journal: Journal of Hepatology (2013)
Hypoglycemia in Hospitalized Patients
Authors: Kathleen F. Fischer, Joel A. Lees, John H. Newman
Journal: New England Journal of Medicine (1986)

We analyzed 137 episodes of hypoglycemia (serum glucose ≤49 mg per deciliter) occurring in 94 adult patients hospitalized during a six-month period at a tertiary care hospital. Forty-five percent of the patients had diabetes mellitus, and administered insulin was implicated in 90 percent of episodes in diabetics. Hypoglycemia in diabetic patients occurred under a variety of circumstances, frequently because of decreased caloric intake related to illness or hospital routine. Insulin-induced hypoglycemia also occurred during treatment of hyperkalemia (eight patients) or during hyperglycemia related to total parenteral nutrition (six patients). Forty-six of the 94 patients had chronic renal insufficiency, and 20 of these 46 had underlying diabetes mellitus. Thus, renal insufficiency unrelated to diabetes mellitus was the second most frequent diagnosis associated with hypoglycemia. The majority of other cases of hypoglycemia were related to liver disease, infections, shock, pregnancy, neoplasia, or burns. Hypoglycemia was not the apparent cause of death in any patient, but the overall hospital mortality was 27 percent and was related to the degree of hypoglycemia and the number of risk factors for hypoglycemia. We conclude that hypoglycemia is a common problem in hospitalized patients, is common in renal insufficiency, is usually iatrogenic, and correlates with high mortality in severely ill patients. (N Engl J Med 1986; 315:1245–50.)
Abstract 430: MiRNA profiling of prostate cancer cell-derived large oncosomes identifies a signature of invasion and metastasis
Authors: Matteo Morello, Andrew C. Dudley, Peter Schow, Rosalyn M. Adam, Samantha Morley, David Mulholland, Luigi Insabato, Hong Wu, Michael Klagsbrun, Neil A. Bhowmick, Mark A. Rubin, Crislyn D'Souza-Schorey, Michael R. Freeman, Dolores Di Vizio
Journal: Cancer Research (2012)

Abstract Introduction: We recently demonstrated that amoeboid prostate cancer (PCa) cells shed large (1-10µm diameter), bioactive membrane particles, representing a new class of tumor microvesicles termed large oncosomes (LO). LO can transfer oncogenic signals horizontally within the tumor microenvironment, as demonstrated by activation of phospho-tyrosines and Akt in recipient cells. Methods: We used differential ultracentrifugation and immuno-flow cytometry with size beads to isolate oncosomes in the 1-10µm diameter range. The method was applied to culture medium as well as to the plasma of mice with prostate cancer. In order to identify oncosome miRNAs relevant to metastasis, we performed a GeneChip® miRNA 2.0 Array screen of oncosomes shed by tumorigenic RWPE-2 PCa cells. Non-tumorigenic RWPE-1 cells were also analyzed. Results: LO contained protease and significantly stimulated migration of tumor and endothelial cells. LO also contained Caveolin-1, the GTPase ARF6 and other proteins that we used as markers to identify them in the circulation of mice with PCa, and in murine and human tissues with metastatic disease. Oncosomes also contained RNA. The miRNA profile of the oncosomes was compared to the miRNA profile of the cells of origin. While the miRNA profile of RWPE-2 almost completely matched the profile of RWPE-1 cells, the profiles differed significantly between LO isolated from the two cell lines. In particular, RWPE-2-derived LO contained miR-1228*, miR-150*, miR-373*, miR-135a*, miR-34b and miR-491-3p, which have been implicated in cancer cell proliferation and migration. In particular, the miRNAs miR-135a* and miR-373* target and inhibit the focal adhesion kinase (FAK), which plays a role in promoting a mesenchymal to amoeboid transition. miR-135a* and miR-373* have also been demonstrated to stimulate cell invasion, and are up-regulated in metastatic prostate and breast cancer. Target prediction analysis identified members of pathways involved in metabolic deregulation, and in oncogenic intercellular signaling and cell-cell interaction specifically in the LO purified from the tumorigenic cell line. Conclusions: Collectively, our results indicate that tumor cells can use oncosome formation to actively export pro-oncogenic miRNAs and that oncosomes therefore serve as a potential source of biomarkers of tumor progression. 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 430. doi:1538-7445.AM2012-430
Elevated Plasma Dopamine-β-Hydroxylase Activity in Autosomal Dominant Torsion Dystonia
Authors: G. Frederick Wooten, Roswell Eldridge, Julius Axelrod, Robert S. Stern
Journal: New England Journal of Medicine (1973)

Abstract Dopamine-β-hydroxylase, the enzyme that converts dopamine to norepinephrine, was measured in the plasma of 41 normal subjects, 24 patients with a clinical and genetic pattern compatible wi...
Soft-Tissue Uptake of Tc-99m DPD (Dicarboxypropane Diphosphonate) in Amyloidosis
Authors: F. JAVIER DE HARO, IGNACIO CASTEJON, ELDA BESADA, JOSE ORTIZ BERROCAL
Journal: Clinical Nuclear Medicine (1996)

A case of systemic light-chain-derived amyloidosis (AL amyloidosis) is presented in which a Tc-99m DPD bone scan demonstrated the uptake of tracer in the heart, thyroid, parotid glands, uterus, and intestinal tract. The presence of amyloid deposits was confirmed by biopsy specimens.
USING 4D ECHOCARDIOGRAPHY IMAGING TO EVALUATE THE EFFECT OF STROKE VOLUME ON MYOCARDIAL STRAIN
Authors: David Sahn, Priyanka Mathur, Hao Chuan Lei, Katie Hastie, Gabriella Farland, Muhammad Ashraf, Cole Streiff, Meihua Zhu
Journal: Journal of the American College of Cardiology (2015)
Value of Electron-Beam Computed Tomography for the Noninvasive Detection of High-Grade Coronary-Artery Stenoses and Occlusions
Authors: Stephan Achenbach, Werner Moshage, Dieter Ropers, Jörg Nossen, Werner G. Daniel
Journal: New England Journal of Medicine (1998)

Reliable noninvasive assessment of coronary-artery stenoses and occlusions would constitute an advantage in the care of patients with known or suspected coronary artery disease. We investigated the accuracy of contrast-enhanced electron-beam computed tomography (CT) for the detection of high-grade coronary-artery stenoses and occlusions.