tbuckley/cabot-search huggingface dataset:
Abstract 663: Targeting autophagy potentiates the anti-tumoral action of crizotinib in ALK-positive anaplastic large cell lymphoma
Authors: Géraldine MITOU, Julie FRENTZEL, Laurence LAMANT, Fabienne MEGGETTO, Estelle ESPINOS, Patrice CODOGNO, Pierre BROUSSET, Sylvie GIURIATO
Journal: Cancer Research (2015)

Abstract ALK (Anaplastic Lymphoma Kinase)-positive Anaplastic Large Cell Lymphoma (ALCL) occurs predominantly in children and young adults. Their chemotherapeutic treatment leads to a 5-year overall survival amounted to 70-80%. The tumor relapses are often very aggressive and lethal and their underlying mechanisms are unknown. Therefore, there is still a need to improve current therapy. Crizotinib is the most advanced ALK tyrosine kinase inhibitor already used in clinics for ALK-associated lung cancers. However, mechanisms of escape to crizotinib have been reported in cell lines and patients submitted to continuous crizotinib treatment. Thus, its use in frontline treatment for ALCL is hampered by the emergence of resistance. As autophagy has been proposed as a cell survival mechanism potentially involved in the acquisition of resistance to tyrosine kinase inhibitor, we investigated here whether autophagy was activated during ALCL treatment. We demonstrated in ALCL that autophagy is induced upon ALK inactivation, as a pro-survival response. We found that different ALK inhibition approaches (crizotinib or ALK-targeting siRNA) combined with autophagy inhibition (chloroquine, 3-methyladenine or ATG7-targeting siRNA) compromised cell survival and cell growth. Altogether, our results suggest that crizotinib and chloroquine (two drugs already used in clinics) co-treatment could be beneficial for ALK-positive ALCL patients. Citation Format: Géraldine MITOU, Julie FRENTZEL, Laurence LAMANT, Fabienne MEGGETTO, Estelle ESPINOS, Patrice CODOGNO, Pierre BROUSSET, Sylvie GIURIATO. Targeting autophagy potentiates the anti-tumoral action of crizotinib in ALK-positive anaplastic large cell lymphoma. [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 663. doi:10.1158/1538-7445.AM2015-663
Abstract 1367: Anti-angiogenesis promotes venous thromboembolism through inducing PAI-1 in a mouse xenograft model of human lung carcinoma
Authors: Ni Chen, Meiping Ren, Rong Li, Xin Deng, Yongjie Li, Kai Yan, Lamei Xiao, Yan Yang, Liqun Wang, Mao Luo, Jianbo Wu
Journal: Cancer Research (2015)

Abstract Thromboembolism is a major source of morbidity and mortality in patients with cancer. Increased incidence of venous thromboembolism (VTE) was associated with anti-vascular endothelial growth factor (VEGF) treatment in cancer. However, the mechanism of VTE initiation remains elusive. In this study, we addressed the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A on either an inferior vena cava stenosis or a saphenous vein model using a xenograft mouse model. We found that treatment of bevacizumab accelerated thrombosis in a saphenous vein model with an increased thrombus weight in an inferior vena cava stenosis model. Administration of bevacizumab inhibited the growth of lung tumor by suppressing angiogenesis. Both intrathrombotic PAI-1 expression and plasma PAI-1 level was significantly increased by the treatment of bevacizumab. Furthermore, pharmacologic inhibition of PAI-1 with PAI-039 blocked the bevacizumab-induced venous thrombosis, but showed no change in tumor growth. Collectively, these findings indicate that PAI-1 plays a role in VET with anti-angiogenesis therapy, and have efficacy as a therapeutic strategy to prevent VET. Citation Format: Ni Chen, Meiping Ren, Rong Li, Xin Deng, Yongjie Li, Kai Yan, Lamei Xiao, Yan Yang, Liqun Wang, Mao Luo, Jianbo Wu. Anti-angiogenesis promotes venous thromboembolism through inducing PAI-1 in a mouse xenograft model of human lung carcinoma. [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 1367. doi:10.1158/1538-7445.AM2015-1367
Outcomes Following Discontinuation of E. coli- asparaginase upon Severe Allergic Reactions in Children with Acute Lymphoblastic Leukemia
Authors: Der-Cherng Liang, Hsiu-Ju Yen, Wan-Hui Chang, Hsi-Che Liu, Ting-Chi Yeh, Giun-Yi Hung, Kang-Hsi Wu, Ching-Tien Peng, Yu-Hsiang Chang, Te-Kao Chang, Chih-Cheng Hsiao, Jiunn-Ming Sheen, Yu-Hua Chao, Tai-Tsung Chang, Shyh-Shin Chiou, Pei-Chin Lin, Shih-Chung Wang, Ming-Tsan Lin, Wan-Ling Ho, Yu-Chieh Chen
Journal: Blood (2015)
Serologic Screening for Genital Herpes Infection
Authors: Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry, Karina W. Davidson, John W. Epling, Francisco A. R. García, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, William R. Phillips, Maureen G. Phipps, Michael P. Pignone, Michael Silverstein, Chien-Wen Tseng
Journal: JAMA (2016)

<h3>Importance</h3> Genital herpes is a prevalent sexually transmitted infection in the United States, occurring in almost 1 in 6 persons aged 14 to 49 years. Infection is caused by 2 subtypes of the herpes simplex virus (HSV), HSV-1 and HSV-2. Antiviral medications may provide symptomatic relief from outbreaks but do not cure HSV infection. Neonatal herpes infection, while uncommon, can result in substantial morbidity and mortality. <h3>Objective</h3> To update the 2005 US Preventive Services Task Force (USPSTF) recommendation on screening for genital herpes. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on the accuracy, benefits, and harms of serologic screening for HSV-2 infection in asymptomatic persons, including those who are pregnant, as well as the effectiveness and harms of preventive medications and behavioral counseling interventions to reduce future symptomatic episodes and transmission to others. <h3>Findings</h3> Based on the natural history of HSV infection, its epidemiology, and the available evidence on the accuracy of serologic screening tests, the USPSTF concluded that the harms outweigh the benefits of serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant. <h3>Conclusions and Recommendation</h3> The USPSTF recommends against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant. (D recommendation)
Evolution of loading protocols in implant dentistry for partially dentate arches
Authors: Dean Morton, Adrien Pollini
Journal: Periodontology 2000 (2016)

Abstract Better outcomes for patients receiving dental implants as part of oral rehabilitation remains a constant goal. Advances in implant design, clinical protocols and biomaterials provide opportunities to accelerate treatment, increasing efficiency, predictability and patient satisfaction. It is important to understand that these changes can result in negative outcomes and increased risk. This article reviews the existing published evidence relating to accelerated clinical protocols and patient outcomes. Subsequent to the review, clinical recommendations are offered.
Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: Implications for treatment with anti-IL-17 agents
Authors: Łukasz Matusiak, Justyna Szczęch, Andrzej Bieniek, Danuta Nowicka-Suszko, Jacek C. Szepietowski
Journal: Journal of the American Academy of Dermatology (2016)
New Strategies in Metastatic Hormone Receptor–Positive Breast Cancer: Searching for Biomarkers to Tailor Endocrine and Other Targeted Therapies
Authors: Rachel C. Jankowitz, Steffi Oesterreich, Adrian V. Lee, Nancy E. Davidson
Journal: Clinical Cancer Research (2016)

Abstract Although major advances in our understanding of the molecular underpinnings of hormone receptor–positive (HR+) breast cancer have led to new therapies that have substantially improved patient outcomes, endocrine-resistant disease still remains a leading cause of breast cancer mortality. Comprehensive molecular profiling of breast cancers has highlighted tremendous tumor heterogeneity, and analysis of paired primary and metastatic tumors has shown the evolution that can occur during acquired resistance to systemic therapies. Novel techniques for monitoring tumor load under treatment pressure, including “liquid biopsy” techniques, such as circulating free tumor DNA (cfDNA) and circulating tumor cells, have shown promise as biomarkers to direct treatment without invasive tumor biopsies. However, more research is needed to deepen our understanding of breast cancer alterations under treatment pressure to reveal mechanisms of drug resistance and apply precision medicine in biomarker-driven clinical trials. Clin Cancer Res; 23(5); 1126–31. ©2016 AACR.
Variations in Proteasome Enzymatic Activities in Plasma of Patients with Chronic Lymphocytic Leukemia and Their Value in Predicting Clinical Behavior.
Authors: Wanlong Ma, Susan O’Brien, Iman Jilani, Xi Zhang, Hagop Kantarjian, Zeev Estov, Alessandra Ferrajoli, Michael Keating, Francis Giles, Maher Albitar
Journal: Blood (2006)
Abstract 3352: Identification of factors that recruit tumor-associated neutrophils to head and neck squamous cell cancer
Authors: Hanan A. Niaz
Journal: Cancer Research (2015)

Abstract Recent immunohistological studies have shown that abundant tumour-associated neutrophils (TAN) are present within malignant tumours. TAN can have a significant impact on the tumour microenvironment via release of potent growth factots, chemokines and proteinases that influence tumour progression. The presence of TAN has been associated with poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to identify which factors are responsible for neutrophil recruitment into HNSCC. The number of TAN within human HNSCC tissue was evaluated by immunohistochemical staining for the neutrophil marker, myeloperoxidase (MPO). The factors secreted by FaDu HNSCC multi-cellular tumour spheroids (MCTS) were analysed by cytokine array and ELISA. Neutrophils isolated from the peripheral blood of healthy volunteers were used to measure neutrophil migration to factors identified from the array. Then the recruitment of neutrophils to MCTS was assessed overtime by flow cytometry in the absence and presence of small molecule inhibitors. FaDu xenograft mouse models were used to confirm the effect of these inhibitors on neutrophil recruitment in-vivo. MPO staining confirmed the presence of marked numbers of TAN in HNSCC compared to normal oral epithelium. HNSCC MCTS resemble in-vivo tumours, displaying areas of hypoxia, necrosis and cell proliferation. Neutrophils migrated to recombinant CXCL8, CXCL1 and MIF and these chemoattractants were found in the conditioned medium of FaDu MCTS. The recruitment of neutrophils to FaDu MCTS was significantly inhibited when neutrophils were pre-treated with antagonists for CXCR2 and CXCR4, the receptors for CXCL8, CXCL1 and MIF respectively. Moreover, use of the MIF inhibitor, ISO-1caused a dramatic reduction in the number of neutrophils recruited into FaDu MCTS. In-vivo, ISO-1 significantly reduced the number of TAN in xenograft FaDu tumours. Collectively, these data suggest that CXCL8, CXCL1 and MIF in particular are important in the recruitment of TAN into HNSCC. Citation Format: Hanan A. Niaz. Identification of factors that recruit tumor-associated neutrophils to head and neck squamous cell cancer. [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 3352. doi:10.1158/1538-7445.AM2015-3352
Abstract 1409: Whole-cell and local viscoelasticity of stem-like and non-stem-like breast cancer cells
Authors: Amina Alipour, Monica M. Burdick, David F.J. Tees
Journal: Cancer Research (2015)

Abstract It has been shown that the mechanical properties of pathological cells are different from healthy ones. Therefore, mechanical characterization of cells may be useful for investigating mechanisms and progression of diseases. In the case of cancer, the finding that cancerous cells are considerably more deformable than normal ones provides the motivation for investigating rheological differences between stem-like and non-stem-like cancer cells. In this study, the viscoelastic properties of six breast cancer cell lines, three of which have been regarded (based on surface markers) as stem-like and three considered less stem-like, were measured using micropipette aspiration and particle tracking microrheology. In micropipette experiments, cancer cells were aspirated one-by-one at controlled pressures into small glass micropipettes and the length of the aspirated section of the cells was tracked as a function of time. The applied pressure was either increased linearly or increased suddenly to different levels and then held constant. The homogeneous elastic half-space model was used to interpret the viscoelastic properties of the different cell lines. The effect of pressure loading rate on cell viscoelasticity was examined by applying three different aspiration pressure rates of 9, 6, and 3 Pa/s. The apparent Young's modulus was found to depend on pressure loading rate, which suggests a more complex rheology than a standard viscoelastic solid. Above a threshold force level, cells were also found to enter the micropipette continuously in a fashion that is analogous to white blood cells, i.e. as a liquid drop with constant cortical tension. A comparison between the Young's moduli showed that at least some of the stem-like breast cancer cell lines were less stiff than less stem-like cell lines and more likely to exhibit the liquid drop-like behavior. The reduction in stiffness and change in rheological regime might be the result of lower actin filament density which allowed the stem-like cancer cells to be more deformable while undergoing extravasation and intravasation during the metastatic process. Regional rheological differences were also found using particle tracking microrheology. Our hypothesis is that the differences in the rheological properties might help to distinguish between stem-like cancer cells and non-stem-like ones, which could eventually lead to a new detection and diagnostic method in cancer research. Citation Format: Amina Alipour, Monica M. Burdick, David F.J. Tees. Whole-cell and local viscoelasticity of stem-like and non-stem-like breast cancer 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 1409. doi:10.1158/1538-7445.AM2015-1409
Abstract 488: High DKC1 expression supports neuroblastoma tumor cell proliferation and is strongly associated with poor patient outcomes
Authors: Rosemary O'Brien, Michelle F. Maritz, Cheng Fei Kong, Stefania Purgato, Bing Liu, Chen Yang, Amanda Russell, Jayne Murray, Claudia Flemming, Michelle Haber, Giovanni Perini, Murray D. Norris, Jamie I. Fletcher, Karen L. Mackenzie
Journal: Cancer Research (2015)

Abstract Dyskerin is a nucleolar RNA-binding protein that functions as a core component of the telomerase holoenzyme, as well as in ribonuclear protein complexes involved in ribosome biogenesis and RNA processing. This study investigates the clinical and functional relevance of dyskerin expression in the paediatric cancer neuroblastoma. Here it is shown, in two independent neuroblastoma patient cohorts, that high expression of the gene encoding dyskerin (DKC1) very strongly correlates with poor event-free and overall survival. The prognostic power of DKC1 expression was independent of the established indicators used in the management of this disease, namely diagnosis age &amp;gt; 1.5 yr, stage of disease and amplification of the MYCN oncogene (P&amp;lt;0.0001). Dyskerin mRNA and protein expression were also found to be elevated, relative to normal cells, across a panel of neuroblastoma cell lines. Chromatin immunoprecipitation showed that the DKC1 promoter region was directly targeted by both MycN and c-Myc in neuroblastoma cells. Depletion of dyskerin using RNAi severely impaired proliferation, inhibited anchorage independent growth and dramatically slowed tumour growth in a mouse model of neuroblastoma (P&amp;lt;0.01, Two-way Anova). In p53 competent cells, the proliferative arrest induced by dyskerin depletion was accompanied by an accumulation of p53 and p21cip1, accumulation in G1 phase of the cell cycle and cell death. However in the absence of p53 function, an alternate mechanism operated to impair proliferation when dyskerin was downregulated. The mechanism responsible for the proliferative arrest also appeared to be telomerase-independent, as it was not rescued by ectopic overexpression of telomerase. Taken together, these data identify DKC1 is a crucial MYC target gene in neuroblastoma, and show that neuroblastoma cells become addicted to high DKC1 expression. The results support further investigation of DKC1 as a therapeutic target in the treatment of refractory neuroblastoma. Citation Format: Rosemary O'Brien, Michelle F. Maritz, Cheng Fei Kong, Stefania Purgato, Bing Liu, Chen Yang, Amanda Russell, Jayne Murray, Claudia Flemming, Michelle Haber, Giovanni Perini, Murray D. Norris, Jamie I. Fletcher, Karen L. Mackenzie. High DKC1 expression supports neuroblastoma tumor cell proliferation and is strongly associated with poor patient outcomes. [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 488. doi:10.1158/1538-7445.AM2015-488
18F-Fluoroestradiol PET/CT Measurement of Estrogen Receptor Suppression during a Phase I Trial of the Novel Estrogen Receptor-Targeted Therapeutic GDC-0810: Using an Imaging Biomarker to Guide Drug Dosage in Subsequent Trials
Authors: Yingbing Wang, Karen L. Ayres, Debra A. Goldman, Maura N. Dickler, Aditya Bardia, Ingrid A. Mayer, Eric Winer, Jill Fredrickson, Carlos L. Arteaga, José Baselga, Henry C. Manning, Umar Mahmood, Gary A. Ulaner
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Evaluate 18F-fluoroestradiol (FES) PET/CT as a biomarker of estrogen receptor (ER) occupancy and/or downregulation during phase I dose escalation of the novel ER targeting therapeutic GDC-0810 and help select drug dosage for subsequent clinical trials. Experimental Design: In a phase I clinical trial of GDC-0810, patients with ER-positive metastatic breast cancer underwent FES PET/CT before beginning therapy and at cycle 2, day 3 of GDC-0810 therapy. Up to five target lesions were selected per patient, and FES standardized uptake value (SUV) corrected for background was recorded for each lesion pretherapy and on-therapy. Complete ER downregulation was defined as ≥90% decrease in FES SUV. The effect of prior tamoxifen and fulvestrant therapy on FES SUV was assessed. Results: Of 30 patients who underwent paired FES-PET scans, 24 (80%) achieved ≥90% decrease in FES avidity, including 1 of 3 patients receiving 200 mg/day, 2 of 4 patients receiving 400 mg/day, 14 of 16 patients receiving 600 mg/day, and 7 of 7 patients receiving 800 mg/day. Withdrawal of tamoxifen 2 months prior to FES PET/CT and withdrawal of fulvestrant 6 months prior to FES PET/CT both appeared sufficient to prevent effects on FES SUV. A dosage of 600 mg GDC-0810 per day was selected for phase II in part due to decreases in FES SUV achieved in phase I. Conclusions: FES PET/CT was a useful biomarker of ER occupancy and/or downregulation in a phase I dose escalation trial of GDC-0810 and helped select the dosage of the ER antagonist/degrader for phase II trials. Clin Cancer Res; 23(12); 3053–60. ©2016 AACR.
Interest, attitudes, and participation in clinical trials among lymphoma patients with online access
Authors: K. Schwartz
Journal: Journal of Clinical Oncology (2009)

e19514 Background: There is an increasing number of investigational agents for lymphomas and a limited patient pool, approximately 5% of available patients. Thus, identifying and addressing obstacles to study enrollment is vital to making progress. Methods: This analysis was made from a non-random population of 251 lymphoma patients with online access to our survey. Results: In this cohort, 43% reported High Interest in clinical trials, 50% have Considered Trials, and 27% Have Participated. Patients who considered studies (126) ranked the following reasons for declining as significant: Randomization (70), Insurance (49), Study Risks / Toxicities (42), Travel and Lodging (30), Eligibility (28), Tests and Procedures (12), and a perception that Regular Treatment is superior (6). See Table 1 for associations with consideration of clinical trials and participation. Conclusions: In this cohort, interest in clinical trials and participation rates were much higher than generally cited. As expected, the discussion of clinical trials with the patient's oncologist was associated with the highest consideration (85%) and participation (53%) rates, suggesting a need to increase awareness of study protocols among treating physicians so that this discussion can become more routine. Patient issues and perceptions regarding randomization, study risk, eligibility, and tests and procedures suggest an opportunity to improve enrollment in clinical trials by focusing on these aspects of study design, specifically, attending to the rationale of the protocol as a treatment decision. [Table: see text] No significant financial relationships to disclose.