tbuckley/cabot-search huggingface dataset:
Vascular and lymphatic phenotype of HER2+ breast cancer.
Authors: S. Tannenbaum, M. Rampurwala, P. Hegde, N. Jabbour, N. Phoenix, K. Claffey
Journal: Journal of Clinical Oncology (2011)

e11046 Background: Increased tumor vascularity is associated with poor prognosis in breast cancer and has been a feature associated with HER2 positive (+) disease. Distinction between HER2+ and HER2 negative (-) breast cancers can be equivocal, making therapy decisions difficult. The current study evaluated lymphatic (LV) and blood vessel (BV) density in HER2+ versus HER2- tumors as a potential strategy to distinguish these important groups of patients. Vascular endothelial growth factor-C (VEGF-C), a lymphangiogenic growth factor found in tumor cells, and lymphoid tumor infiltrates were also quantitated in matching cases. Methods: Primary tumor sections (7mm) were cut from archived formalin-fixed paraffin embedded tissue. 17 tumors were selected for each group with HER2 FISH ratios of 10:1 (HER2+) and 1.3:1 (HER2-). Post-analysis separated out estrogen receptor positive (ER+) and negative (ER-) status. Immunohistochemical analysis used the following antibodies: CD31 (BV marker) D2-40 (LV marker) and VEGF-C. Digital images (4/tumor) were captured and vessels counted in hot spots within the tumor (intratumoral, IT) and surrounding non-tumor stroma (peritumoral, PT). VEGF-C and lymphoid infiltrates were scored as low, intermediate or high based on staining intensity and presence of infiltrating lymphocytes in either IT or PT locations. Results: There was no statistical relationship between the degree of FISH positivity and BV or LV counts: CD31: HER2+: IT9, PT8; HER2-: IT7, PT9. D2-40: HER2+: IT1, PT3; HER2-: IT1, PT4. Differences were noted for VEGF-C staining; 80% of HER2+ER- cases showed strong positivity, 50% of HER2-ER- cases and <25% in the ER+ cases. Lymphoid infiltrates were dramatically increased in the HER2+ER- group as compared to all others. Vessel hot spots were highly correlated to areas of lymphoid infiltration. Conclusions: Vascular number is one mechanism of tumor spread to lymphatics; they were not increased in HER2+ samples in this study. VEGF-C has been shown to increase tumor invasion toward lymphatics particularly in conjunction with tumor expression of specific receptors. VEGF-C expression was elevated in the HER2+ER- cases in this study and may offer an alternative mechanism for tumor invasiveness in this subtype of breast cancer.
Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels
Authors: Connor A. Emdin, Amit V. Khera, Pradeep Natarajan, Derek Klarin, Hong-Hee Won, Gina M. Peloso, Nathan O. Stitziel, Akihiro Nomura, Seyedeh M. Zekavat, Alexander G. Bick, Namrata Gupta, Rosanna Asselta, Stefano Duga, Piera Angelica Merlini, Adolfo Correa, Thorsten Kessler, James G. Wilson, Matthew J. Bown, Alistair S. Hall, Peter S. Braund, Nilesh J. Samani, Heribert Schunkert, Jaume Marrugat, Roberto Elosua, Ruth McPherson, Martin Farrall, Hugh Watkins, Cristen Willer, Gonçalo R. Abecasis, Janine F. Felix, Ramachandran S. Vasan, Eric Lander, Daniel J. Rader, John Danesh, Diego Ardissino, Stacey Gabriel, Danish Saleheen, Sekar Kathiresan
Journal: Journal of the American College of Cardiology (2016)
Both G0/G1 Cell Cycle Arrest and Continuous Activation of MAPK Induce Autophagic Cell Death in bcr-abl-Positive Leukemic Cells.
Authors: Yuko Mishima, Yasuhito Terui, Yuji Mishima, Toshihiro Takizawa, Shinya Kimura, Taira Maekawa, Kiyohiko Hatake
Journal: Blood (2005)
Abstract LB-167: The role of Sirt1 in tumorigenesis
Authors: Natalie Shunxiang Ren
Journal: Cancer Research (2015)

Abstract SIRT1 is a highly conserved NAD+-dependent protein deacetylase. Homologs of SIRT1 in lower model organisms are able to delay the aging process in response to nutrients. Although the SIRT1 protein deacetylase activities have been shown to regulate numerous transcription factors and co-factors (eg. PCG-1, p53), modulate cellular metabolism and promote cell survival and stress resistance, the role of SIRT1 in cancer metabolism, growth and survival is still highly controversial. Colorectal cancer is one of the most common malignancies in the world. However, there are few studies revealing the clinical relevance of the expression of SIRT1 and related markers in colorectal cancer with human tissue. Although recent studies have revealed that SIRT1 plays an important role in colorectal tumorigenesis, the exact role of SIRT1 in colorectal tumorigenesis is still controversial. Thus far, our data demonstrates that knocking out SIRT1 induces the acetylation of p53 and alters cellular metabolism. Deletion of SIRT1 in MEFs decreases glutamine uptake and increases cell death by trigging apoptosis pathways. As a result, SIRT1 KO MEFs fails to induce tumors in a xenograft model in nude mice. We have recently generated a mouse colon cancer model on SIRT1 intestine knockout mouse strains (SIRT1 iKO) and discovered that SIRT1 iKO mice display a reduced rate of tumorigenesis. To further confirm the role of SIRT1 on colon cancer, we propose to analyze the association of SIRT1 expression and the prognosis in colorectal cancer. Citation Format: Natalie Shunxiang Ren. The role of Sirt1 in tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-167. doi:10.1158/1538-7445.AM2015-LB-167
Acute Myeloid Leukemia with Mutated NPM1 Presenting with Life-Threatening, Either Arterial or Venous, Thromboembolism: a Report of 4 Cases.
Authors: Maria Paola Martelli, Lorenzo Brunetti, Luca De Carolis, Elisabetta Agliani, Laura Berchicci, Elisabetta Bonifacio, Valentina Pettirossi, Ilaria Gionfriddo, Debora Cecchini, Alessia Tabarrini, Roberta Rossi, Stelvio Ballanti, Massimo F Martelli, Brunangelo Falini
Journal: Blood (2009)
Pharmacokinetic-pharmacodynamic analysis of hepatic artery infusion of three-drug chronomodulated chemotherapy and intravenous cetuximab in patients with liver metastases from colorectal cancer registered in OPTILIV, a European multicenter phase II trial.
Authors: F. Levi, A. Karaboué, M. Etienne-Grimaldi, E. Chatelut, P. F. Innominato, G. Paintaud, P. Loukakos, R. Adam, M. Bouchahda, G. Milano
Journal: Journal of Clinical Oncology (2011)

e14134 Background: Hepatic artery infusion (HAI) of chemotherapy effectively downstages liver metastases from colorectal cancer (lmCRC). A major drawback is extra-hepatic progression, due to poor systemic drug exposure. Purpose: To relate the occurrence of adverse events to circulating plasma drug levels in lmCRC patients (pts) receiving iv Cet and triplet chrono HAI (Bouchahda Cancer 2009). Methods: The plasma pharmacokinetics of iv Cet (500 mg/m², D1 10:00-12:30) and HAI of irinotecan (Ir, 180 mg/m² D1 02:00-08:00, peak at 05:00), 5-fluorouracil (Fu, 900 mg/m²/d D2-4, 22:15-09:45, peak at 04:00), and oxaliplatin (Ox, 28 mg/m²/d D2-4, 10:15-21:45, peak at 16:00) were determined during the 1st course in 5/35 pts registered. Maximum concentration (Cmax) and Area Under the concentration Curve (AUC) were compared with 1st course and maximum toxicities. Results: Pt characteristics: 2F, 3M aged 33-70 y, with 3-30 lesions (median, m=17) involving both lobes (largest lesion diameter, 39-110 mm); 3 pts with >25% liver involvement; one prior chemotherapy regimen (2 pts), ≥two (3 pts). Three pts displayed grade 3-4 toxicities, involving 3 targets for 2 of them after 2-4 courses. The AUCs of Cet and SN38 were both correlated with maximum leukopenia (p = 0.001 and 0.002), neutropenia (p = 0.03 and 0.07), thrombocytopenia (p = 0.06 and 0.018), fatigue (p = 0.06 and 0.025) and diarrhea (p = 0.06 and 0.018). Conclusions: Chronomodulated triplet HAI resulted in significant systemic exposure to chemotherapy. Circulating levels of Cet and SN-38 were jointly associated with main toxicities. [Drug] Cmax a (mg/L) at Tmax (clock hour) Trapezoidal AUC a (g*min/L) [Cet] 419 (232-510) at 12:30 323.7 (234.1-468.9) [Ir] 813 (622-1220) at 6:00 700.9 (417.5–1179) [Free SN38] 16 (11-36) at 6:00-8:00 13.1 (2.6–38.5) [Fu] 587 (427-845) at 4:00 161.4 (105.7–218.6) [Total Ox] 1018 (579-1106) at 19:15-04:00 628.6 (370.3–722.5) [Free Ox] 182 (92-439) at 16:15-21:45 95.3 (51.2–173.2) a Median (range)
The mTOR Complex Controls HIV Latency
Authors: Emilie Besnard, Shweta Hakre, Martin Kampmann, Hyung W. Lim, Nina N. Hosmane, Alyssa Martin, Michael C. Bassik, Erik Verschueren, Emilie Battivelli, Jonathan Chan, J. Peter Svensson, Andrea Gramatica, Ryan J. Conrad, Melanie Ott, Warner C. Greene, Nevan J. Krogan, Robert F. Siliciano, Jonathan S. Weissman, Eric Verdin
Journal: Cell Host & Microbe (2016)
The Serum Levels of N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) Is a Strong Indicator of Pulmonary Hypertension in Patients with Sickle Cell/Beta Thalassemia.
Authors: Ersi Voskaridou, Antonios Tsoutsias, George Tsetsos, Evgenia Spyropoulou, Evangelos Terpos
Journal: Blood (2006)
EULAR/EFORT recommendations for management of patients older than 50 years with a fragility fracture and prevention of subsequent fractures
Authors: W F Lems, K E Dreinhöfer, H Bischoff-Ferrari, M Blauth, E Czerwinski, JAP da Silva, A Herrera, P Hoffmeyer, T Kvien, G Maalouf, D Marsh, J Puget, W Puhl, G Poor, L Rasch, C Roux, S Schüler, B Seriolo, U Tarantino, T van Geel, A Woolf, C Wyers, P Geusens
Journal: Annals of the Rheumatic Diseases (2016)

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.
Beating the Clock in T-cell Acute Lymphoblastic Leukemia
Authors: William L. Carroll, Iannis Aifantis, Elizabeth Raetz
Journal: Clinical Cancer Research (2016)

Abstract CDK4/6 inhibition was synergistic with dexamethasone and everolimus but antagonistic with conventional chemotherapy in T-cell acute lymphoblastic leukemia (T-ALL) preclinical models. Cyclin-dependent kinase inhibition in combination with glucocorticoids and mTOR inhibition offers a unique therapeutic opportunity in T-ALL. Clin Cancer Res; 23(4); 873–5. ©2016 AACR. See related article by Pikman et al., p. 1012
Abstract 4282: All-trans retinoic acid enhances the effector functions of the anti-CD38 antibody SAR650984
Authors: Lucas Bush, David Harper, Rita Greco, Zhili Song, Guang Yang, Francisco Adrian
Journal: Cancer Research (2015)

Abstract SAR650984 is a humanized IgG1 monoclonal antibody selectively targeting CD38 that is in clinical development for the treatment of multiple myeloma (MM). SAR650984 eliminates MM cells through different mechanisms, including antibody dependent cytotoxicity and phagocytosis (ADCC and ADCP, respectively), complement dependent cytotoxicity (CDC), and direct induction of apoptosis. The aim of this study was to assess the cell killing activity of SAR650984 following genetic and chemical manipulation of CD38 expression in MM cells. We established several MM cell lines engineered to overexpress CD38; median levels of CD38 were 537,000 receptors/cell, versus 29,000 receptors/cell in the parental cell lines. ADCC, ADCP, CDC, and apoptosis induced by SAR650984 treatment were all significantly increased in the CD38-overexpressing lines compared with the parental cell lines. Based on these data, we hypothesized that pre-treatment of MM cells with all-trans retinoic acid (ATRA) would enhance the activity of SAR650984, since ATRA can induce up-regulation of CD38 expression. Treatment of the MM cell lines JJN-3, ARH-77, U266, Karpas-620, SKMM-2, RPMI-8226, NCI-H929, KMS-12PE and MOLP-8 with ATRA resulted in a dose-dependent 1.4- to 6.7-fold up-regulation of cell surface expressed CD38. Pretreatment of MM cells with ATRA for 48 hours resulted in enhanced SAR650984-mediated ADCC and ADCP compared to non-pretreated cells. The enhancement of ADCC and ADCP activity by ATRA pretreatment was recorded in all the cell lines tested. In conclusion, these in vitro data are supportive of further evaluation of the combination of SAR650984 and ATRA for the treatment of MM. Citation Format: Lucas Bush, David Harper, Rita Greco, Zhili Song, Guang Yang, Francisco Adrian. All-trans retinoic acid enhances the effector functions of the anti-CD38 antibody SAR650984. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4282. doi:10.1158/1538-7445.AM2015-4282
Abstract 5310: Prognostic and predictive biomarkers of clinical response to Bevacizumab in recurrent WHO grade 3 malignant glioma patients
Authors: Anders Toft, Thomas Urup, Kirsten Grunnet, Ib J. Christensen, Signe R. Michaelsen, Helle Broholm, Vibeke A. Larsen, Michael Kosteljanetz, Ulrik Lassen, Hans S. Poulsen
Journal: Cancer Research (2015)

Abstract Background: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A), has proven activity in treatment of recurrent high-grade glioma. High response rates have been demonstrated, but particularly in WHO grade 3 malignant gliomas, efforts to identify predictors of clinical response have been limited. Predictive biomarkers and prognostic models are required in order to individualize treatment for this patient population. The primary end-point of this study was identification of prognostic and potentially predictive clinical and paraclinical factors of response. The secondary end-point was to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Materials and methods: A total of 64 recurrent grade 3 glioma patients treated with bevacizumab and irinotecan were retrospectively evaluated. Eligible patients from our center had a WHO performance status of 0-2 and were administered bevacizumab and irinotecan between December 2005 and November 2014 according to a previously published clinical protocol. The possibly relevant prognostic baseline factors screened for included: Age, gender, WHO grade 3 diagnosis, tumor size and location, multifocal disease, extent of resection, number of prior chemotherapy regiments, response to prior chemotherapy, first-line treatment, number of previous recurrences, neurological deficit, corticosteroid use, performance status, necrosis, vascular proliferation, neutrophil-to-lymphocyte ratio, and expression of p53, EGFR, Mib-1, MGMT, IDH-1 and ATRX. Candidate factors were subjected to univariate analysis and factors with P-values below 0.10 were considered for multivariate analysis. Prognostic models were generated by logistic regression and Cox regression, modeling response and survival end-points. P-values below 0.05 were considered statistically significant. Results will be presented. Citation Format: Anders Toft, Thomas Urup, Kirsten Grunnet, Ib J. Christensen, Signe R. Michaelsen, Helle Broholm, Vibeke A. Larsen, Michael Kosteljanetz, Ulrik Lassen, Hans S. Poulsen. Prognostic and predictive biomarkers of clinical response to Bevacizumab in recurrent WHO grade 3 malignant glioma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5310. doi:10.1158/1538-7445.AM2015-5310
A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework
Authors: George D. Thurston, Howard Kipen, Isabella Annesi-Maesano, John Balmes, Robert D. Brook, Kevin Cromar, Sara De Matteis, Francesco Forastiere, Bertil Forsberg, Mark W. Frampton, Jonathan Grigg, Dick Heederik, Frank J. Kelly, Nino Kuenzli, Robert Laumbach, Annette Peters, Sanjay T. Rajagopalan, David Rich, Beate Ritz, Jonathan M. Samet, Thomas Sandstrom, Torben Sigsgaard, Jordi Sunyer, Bert Brunekreef
Journal: European Respiratory Journal (2016)

The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies. This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.
Tolerability and hematologic improvement assessed using three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes
Authors: R. M. Lyons, T. Cosgriff, S. Modi, H. McIntyre, C. L. Beach, J. T. Backstrom
Journal: Journal of Clinical Oncology (2007)

7083 Background: At a dosing schedule of 75 mg/m 2 /day SC for 7 days every 4 weeks, azacitidine is an effective and safe treatment (Tx) for patients (pts) with myelodysplastic syndromes (MDS) (JCO 2002; 20:2429). An alternative dosing schedule that eliminates the need for weekend dosing would be more convenient to pts and clinicians. Methods: In this phase II, multicenter, open-label trial, pts with MDS were randomized to 1 of 3 regimens that were repeated every 4 weeks: AZA 5–2-2 (75 mg/m 2 /day × 5 days, followed by 2 days no Tx, followed by 75 mg/m 2 /day × 2 days), AZA 5–2-5 (50 mg/m 2 /day × 5 days, followed by 2 days no Tx, followed by 50 mg/m 2 /day × 5 days) or AZA 5 (75 mg/m 2 /day × 5 days). To determine if response/improvement according to International Working Group criteria (Blood 2000; 96:3671) can be maintained after 6 cycles, the study was amended to include a 12-month maintenance comparing AZA 5 every 4 weeks with AZA 5 every 6 weeks. Results: As of Nov. 30, 2006, 138 pts have been randomized to AZA 5–2-2 (n=46), AZA 5–2-5 (n=47) and AZA 5 (n=45). Most pts are RA (43%) or RAEB (30%), based on FAB classification. Of 104 pts who have received =2 cycles of Tx, hematologic improvement (major or minor in at least 1 cell line) occurred in 63% (65) of the patients ( Table ). Of these pts, 14% had a bi-lineage (AZA 5–2-2: 11%, AZA 5–2-5: 10%, AZA 5: 22%) and 6% had a tri-lineage AZA 5–2-2: 6%, AZA 5–2-5: 7%, AZA 5: 5%) response (based on any improvement). Ongoing pts in the study include AZA 5–2-2: 41% (19/46), AZA 5–2-5: 47% (22/47), and AZA 5: 58% (26/45). No treatment-related mortality has been reported. Most Tx-related grade 3 or 4 events were hematological (AZA 5–2-2: 39%, AZA 5–2-5: 24%, AZA 5: 16%). Updated data, including several pts who have completed at least 6 cycles maintenance, will be available at the time of the meeting. Conclusions: These data indicate that the 3 alternative azacitidine dosing schedules are safe, effective, and similar in efficacy with the FDA-approved regimen. [Table: see text] [Table: see text]
Abstract 5195: A novel, multimodal theranostic nanoprobe is effectively incorporated into melanoma brain metastatic cells
Authors: Synnøve N. Aasen, Tilo W. Eichler, Martin Hruby, Aneta Pospisilova, Petr Stepanek, Endy Spriet, Daniel Jirak, Kai Ove Skaftnesmo, Frits Thorsen
Journal: Cancer Research (2015)

Abstract Metastatic cancer is a significant cause of death worldwide, despite continuing advances in research on diagnostics and therapy. To overcome unsuccessful drug delivery to the tumor tissue, several different nanoprobes have been designed, of which some have combined diagnostic and therapeutic properties. It is an advantage to use non-toxic, biodegradable materials in the design of nanoprobes, as such compounds are easily eliminated from the body. In this work we report for the first time the use of a recently developed nanoprobe to label melanoma metastatic cell lines, for multimodal imaging of cellular uptake and drug delivery. Our nanoprobe consisted of a backbone of glycogen, where the red fluorescent marker Dyo-615 for fluorescence microscopy and Gadolinium for MRI were incorporated. Fluorescence microscopy showed effective labeling of human melanoma metastatic cells over 24 hours and cell viability was not affected by the labeling. The nanoprobe was found in the cytosol of the cells, and a gradual degradation of the probe inside the lysosomes could be observed. In vitro MRI relaxivity measurements showed significant reduction in T1 mapping times, compared to unlabeled cells. In vivo MRI studies showed that subcutaneous melanoma tumors in mice could be effectively visualized with T1 weighted MRI after intravenous injection of the nanoprobe, and the contrast enhancement was comparable to what was seen after using standard Omniscan contrast agent. In summary, our biodegradable glycogen nanoprobe shows a high potential to be used further as a theranostic entity. The nanoprobe may offer additional advantages over MRI contrast agents, as tumor uptake of pharmaceuticals attached to the nanoprobe can be traced in real-time in vivo. Citation Format: Synnøve N. Aasen, Tilo W. Eichler, Martin Hruby, Aneta Pospisilova, Petr Stepanek, Endy Spriet, Daniel Jirak, Kai Ove Skaftnesmo, Frits Thorsen. A novel, multimodal theranostic nanoprobe is effectively incorporated into melanoma brain metastatic cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5195. doi:10.1158/1538-7445.AM2015-5195
Minimal Residual Disease Assessment By Flow Cytometry in AML Is an Independant Prognostic Factor Even after Adjusting for Cytogenetic/Molecular Abnormalities
Authors: Chezi Ganzel, Zhuoxin Sun, Mithat Gonen, Jay P. Patel, Omar Abdel-Wahab, Hugo F Fernandez, Jacob M. Rowe, Martin S. Tallman, Ross L. Levine, Elisabeth M. Paietta
Journal: Blood (2014)