tbuckley/cabot-search huggingface dataset:
Challenges with the ODAC-proposed independent audit of site investigator assessments.
Authors: Oliver Bohnsack, Annette Maria Schmid, Liddy Chen, Barbara Chandler
Journal: Journal of Clinical Oncology (2013)

e22161 Background: The ODAC (Oncologic Drug Advisory Committee) Meeting, July 24 th , 2012, on “Evaluation of Radiologic Review of Progression-free Survival in Non-hematologic Malignancies” discussed the merits of implementing an audit process of the investigator assessments in certain oncology trials with PFS endpoint instead of a full Blinded Independent Central Review (BICR) of all cases. The discussion centered around two potential methods (Dodd et al., 2008, 2011 and Amit et al., 2011) – their methods aimed to reduce the risk of informative censoring based on site central discordance, streamline trial conduct and provide cost savings. Both methods provide novel and interesting approaches. However, based on logistical and especially statistical challenges we found that both proposed methods in their current form can not achieve either goal of reducing cost, complexity, time and data censoring challenges inherent in the BICR process. Methods: This paper criticially evaluate the proposed methods and challenge the proposed processes and provide detailed explanations to obstacles inherent logistically, timewise, statistically, operationally. Results: Both of the proposed methods increase the complexity of conducting Oncology trials. As such the study duration will not be shortened but rather extended in certain scenarios. The statistical consequences of a discrepancy rate between Local Evaluations (LE) and BICR are not fully foreseeable and not defined. Operationally, both sponsor and imaging CRO need to implement new and forego well established processes, increasing risk, complexity and the chance for errors. Conclusions: This paper gives examples why the proposed methods are not suitable in their current form to be implemented in Oncology trials and rather put sponsors and study data at risk.
Multiple Myeloma Drivers of High Risk and Response to Stem Cell Transplantation Identified By Causal Machine Learning: Out-of-Cohort and Experimental Validation
Authors: Leon Furchtgott, Arnold Bolomsky, Fred Gruber, Mehmet Kemal Samur, Jonathan J. Keats, Jennifer Yesil, Kathrin Stangelberger, Michel Attal, Philippe Moreau, Hervé Avet-Loiseau, Karl Runge, Diane Wuest, Kelly Rich, Iya Khalil, Boris Hayete, Heinz Ludwig, Nikhil Munshi, Daniel Auclair
Journal: Blood (2017)
Thulium laser to manage a difficult biliary lithiasis: a first case report
Authors: Massimiliano Mutignani, Lorenzo Dioscoridi, Angelo Italia, Edoardo Forti, Francesco Pugliese, Marcello Cintolo, Giulia Bonato, Aurora Giannetti, Mutaz Massad
Journal: Endoscopy (2019)

The thulium laser, a new therapeutic laser, has recently been introduced in the field of endoscopy to overcome the limitations of classic thermoablative therapies, particularly in terms of the precision of the technique and the risks associated with the procedure [1].
Reconfigurable open microfluidics for studying the spatiotemporal dynamics of paracrine signalling
Authors: Jiaquan Yu, Erwin Berthier, Alexandria Craig, Theodorus E. de Groot, Sidney Sparks, Patrick N. Ingram, David F. Jarrard, Wei Huang, David J. Beebe, Ashleigh B. Theberge
Journal: Nature Biomedical Engineering (2019)
Preliminary Results from a Phase Ib Study Evaluating BCL-2 Inhibitor Venetoclax in Combination with MEK Inhibitor Cobimetinib or MDM2 Inhibitor Idasanutlin in Patients with Relapsed or Refractory (R/R) AML
Authors: Naval Daver, Daniel A. Pollyea, Karen W.L. Yee, Pierre Fenaux, Joseph M. Brandwein, Norbert Vey, Giovanni Martinelli, Kevin R Kelly, Gail J. Roboz, Jacqueline S. Garcia, Arnaud Pigneux, Smita Kshirsagar, Monique Dail, Jue Wang, Mehrdad Mobasher, Lin-Chi Chen, Wan-Jen Hong, Marina Konopleva, Michael Andreeff
Journal: Blood (2017)
Identification and characterization of microRNAs in human cervical cancer cell lines.
Authors: Weng-Onn Lui, Nader Pourmand, Andrew Fire
Journal: Cancer Research (2006)

5619  Emerging data highlights the important roles of a class of small non-coding RNA species, including a large number of known microRNAs (miRNAs), in various biological processes. These small RNAs can control gene function through combinations of mRNA degradation, translational inhibition, and chromatin-based silencing mechanisms. Recent studies have revealed differential expression of miRNAs in cancer and the effects of miRNAs on cancer development and progression. Since the immense potential of miRNAs as regulators of gene networks is just beginning to unfold, a detailed molecular analysis of small RNA expression in the process of cancer development is of great interest. Here, we describe the profiles of miRNAs and other small RNA segments for six human cervical carcinoma cell lines obtained from large-scale sequencing of small RNA libraries. A total of 131 distinct miRNAs were expressed in these cell lines. The profiles were similar among the six cervical cancer cell lines, although significant differences were observed. A subset of miRNAs is highly expressed in all cell lines (eg. miR-21, let-7b, let-7a, let-7f, miR-23a, miR-125b and miR-151*). In addition to the known miRNAs, we identified 28 novel candidate miRNAs. These novel miRNAs can be specific or highly enriched in this tumor type. Although precise roles have not been assigned to these miRNAs, it nonetheless remains an intriguing possibility that they are indicative of important in the development or progression of cervical cancer.
Use of Natural Language Processing to Extract Clinical Cancer Phenotypes from Electronic Medical Records
Authors: Guergana K. Savova, Ioana Danciu, Folami Alamudun, Timothy Miller, Chen Lin, Danielle S. Bitterman, Georgia Tourassi, Jeremy L. Warner
Journal: Cancer Research (2019)

Current models for correlating electronic medical records with -omics data largely ignore clinical text, which is an important source of phenotype information for patients with cancer. This data convergence has the potential to reveal new insights about cancer initiation, progression, metastasis, and response to treatment. Insights from this real-world data will catalyze clinical care, research, and regulatory activities. Natural language processing (NLP) methods are needed to extract these rich cancer phenotypes from clinical text. Here, we review the advances of NLP and information extraction methods relevant to oncology based on publications from PubMed as well as NLP and machine learning conference proceedings in the last 3 years. Given the interdisciplinary nature of the fields of oncology and information extraction, this analysis serves as a critical trail marker on the path to higher fidelity oncology phenotypes from real-world data.
Natural product-based nanoformulations for cancer therapy: Opportunities and challenges
Authors: Dharambir Kashyap, Hardeep Singh Tuli, Mukerrem Betul Yerer, Ajay Sharma, Katrin Sak, Saumya Srivastava, Anjana Pandey, Vivek Kumar Garg, Gautam Sethi, Anupam Bishayee
Journal: Seminars in Cancer Biology (2019)
Abstract #420: From the basal apoptotic rate to the apoptotic threshold: Tumor cell's road to death
Authors: Lian Zhang, Christina Menke, Jakie Thorburn, Andrew Thorburn, Ross Camidge
Journal: Cancer Research (2009)

Apoptosis is believed to be the main route of cell death induced by chemo- and radiation therapy. Within the cell, the battle between the anti-apoptotic and prosurvival signals and how far away the cell is to its apoptotic threshold determines whether the cell commits irreversible caspase activation and apoptotic cell death. We propose that cancer cells have different basal apoptotic rates and proximity to the apoptotic threshold that determines their responses to chemo- and radiation therapy. To test this hypothesis, we have developed a basal apoptotic rate (BAR) assay to measure the accumulated apoptotic events for cultured lung cancer cells to increase their number from n to N. In this assay, we use M30 ELISA to measure caspase cleaved CK18 Asp396 neo-epitope. The assay provides a clinically feasible measurement to potentially assess the basal apoptotic rate of a patient\#8217;s tumor as well as chemotherapeutic response. NSCLC and SCLC cell lines exhibit significantly difference in their basal apoptotic rates determined by the BAR assay. Serum deprivation not only prolongs the time to increase cell number from n to N, but also increases the accumulated apoptotic events to get the same number. Downregulation of anti-apoptotic factor XIAP by siRNA also increases the basal apoptotic rate compare to the isogenic WT cells. These results indicate that it is possible to alter the basal apoptotic rate and overcome the endogenous anti-apoptotic signals. Manipulations of the basal apoptotic rate combined with chemotherapeutic agents may enhance the efficacy of anti-cancer drugs allowing for reduced dosage and side effects.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 420.
Molecular profiling (MP) for malignancies: Knowledge gaps and variable practice patterns among United States oncologists (Onc).
Authors: Bhavana Pendurthi Singh, Susan Lynne Britton, Petra Prins, Chao Yin, Maria L. Lankford, Joanne P. Willey, Arden Buettner, Brynn Tiscione, Mitchell Scharf, Jan Blancato, John Marshall
Journal: Journal of Clinical Oncology (2019)

10510 Background: Clinically impactful therapies for malignancies require the identification of specific molecular alterations. Onc must be aware of these targets and how to interpret them to provide optimum care. The use of MP has become the standard of care for many cancers, and is recently FDA approved. Using 2 data sets, we assessed the current awareness and incorporation of MP in the treatment of cancer; comparing data from community based Onc (C) to academic Onc (A). Methods: C consisted of 292 physicians polled using an audience response system during 6 case-based research events across the US. Questions focused on various aspects of molecular testing. Data for A was obtained from a chart review focused on timing and extent of MP in disease specific academic practices (lung, breast, GI) (N = 59). Results: Within C, 257 (88%) were Onc from community-based practices. The frequency at which Onc ordered MP significantly varied depending on tumor type; 33% in lung cancer (LC), 18% in colorectal cancer (CRC) and less commonly in breast cancer (BC) (8%). In A, MP was ordered more frequently; 74% in LC, 27% in CRC and 0% in BC. These results reflect a gap in practice among community versus academic Onc, as C had lower utilization of MP for both LC and CRC. In C, Onc were also asked to match the molecular alteration with the appropriate targeted therapy. Onc incorrectly matched the molecular alteration to the targeted therapy or marked unknown in up to 69%. This reflects a large knowledge gap among community Onc with regards to the correct application of MP to currently FDA approved targeted therapies. Conclusions: Given the significant knowledge and practice gap, we conclude there is an urgent need for focused educational activities that facilitate improved knowledge of MP and corresponding personalized therapeutic strategies for Onc in the US.
Replacement Therapy for Inherited Enzyme Deficiency
Authors: Roscoe O. Brady, Peter G. Pentchev, Andrew E. Gal, Sue R. Hibbert, Anatole S. Dekaban
Journal: New England Journal of Medicine (1974)

The effect of intravenous administration of glucocerebrosidase isolated from human placenta was investigated in two patients with Gaucher's disease who are deficient in this enzyme. The first received one injection of 1.5 x 106 units of glucocerebrosidase, and the second an injection of 1.65 x 106 units on two successive days. Liver biopsies were obtained before and 24 hours after injection of enzyme. Glucocerebroside in the liver of the first patient decreased from 702 to 519 μg per gram wet weight and from 1634 to 1214 μg per gram in the second after infusion of glucocerebrosidase. The quantity of glucocerebroside in erythrocytes of the two patients before infusion was 7.4 and 6.2 μg per milliliter of cells respectively and 2.9 and 2.6 μg per milliliter of cells 72 hours afterward. These findings indicate that exogenous glucocerebrosidase causes definite decreases in the quantity of accumulated lipid in patients with Gaucher's disease. (N Engl J Med 291:989–993, 1974)
Underserved African-American and white women with breast cancer have similar prognostic profiles for estrogen receptor and tumor grade
Authors: Keith A. Dookeran, Karen Ferrer, Marin Sekosan, Xuezhi Gao, Yu Wang, Lorena Diaz de Leon, Barbara Lukaszczyk, Rocio De La Torre, George Roman, Erika K. Radeke, Neena Muthyala, Wendy A. Rogowski, Howard A. Zaren
Journal: Cancer Research (2006)

3696  Background: Survival disparity for African-American (AA) women with breast cancer has been associated with more frequent biological characteristics of poor-prognosis, including high tumor grade of differentiation (grade) and estrogen receptor (ER) negative status. However, AA women are more commonly underserved and have low socioeconomic status (SES), and other studies suggest that low SES, not simply race, is associated with this prognostic profile. We hypothesized that low SES AA and non-Hispanic white (white) women with breast cancer, who received standardized care at a single public institution, would demonstrate similar poor prognostic profiles regarding tumor grade and ER status. Methods: Clinical-pathological features were examined in 341 AA and 94 white, consecutive low SES women, diagnosed and treated for breast cancer between 2000-05, at the MBCCOP, Stroger Hospital of Cook County, in Chicago. Univariate and multivariate logistic regression analyses were used to predict associations with ER status and tumor grade, and to evaluate differences between races. Survival was estimated using the Kaplan-Meier method. Results: Univariate analysis predicted that ER negative status was associated with younger age, tumor size > 2cm, node positive status, AJCC stage ≥ 2B, and grade 3 tumors, in AA women. In white women however, ER negative status was only associated with grade 3 tumors. Multivariate analysis demonstrated that high tumor grade was the only significant predictive factor for ER negative status in both races (p
Extreme Levels of Air Pollution Associated With Changes in Biomarkers of Atherosclerotic Plaque Vulnerability and Thrombogenicity in Healthy Adults
Authors: Hongbing Xu, Tong Wang, Shengcong Liu, Robert D. Brook, Baihuan Feng, Qian Zhao, Xiaoming Song, Tieci Yi, Jie Chen, Yi Zhang, Yang Wang, Lemin Zheng, Sanjay Rajagopalan, Jianping Li, Wei Huang
Journal: Circulation Research (2019)

Rationale: The pathophysiologic mechanisms of air pollution–associated exacerbation of cardiovascular events remain incompletely understood. Objective: To assess whether ambient air pollution can be a trigger of the vulnerable plaque and heightened thrombogenicity through systemic inflammatory pathways. Methods and Results: In Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunctions in Healthy Adults Living in Beijing), 73 healthy adults (mean±SD, 23.3±5.4 years) were followed up in 2014 to 2016. We estimated associations between air pollutants and biomarkers relevant to atherosclerotic plaque vulnerability, thrombogenicity, and inflammation using linear mixed-effects models and elucidated the biological pathways involved using mediation analyses. Receiver operating characteristic analyses were conducted to assess the ability of each biomarker to predict ambient air pollution exposures. High average concentrations of particulate matter in diameter &lt;2.5 μm (91.8±63.8 µg/m 3 ) were observed during the study period. Significant increases in circulating biomarkers of plaque vulnerability, namely MMPs (matrix metalloproteinases; MMP-1, 2, 3, 7, 8, and 9), of 8.6% (95% CI, 0.1–17.8) to 141.4% (95% CI, 111.8–171.0) were associated with interquartile range increases in moving averages of particulate matter in diameter &lt;2.5 μm, number concentrations of particles in sizes of 5 to 560 nm and black carbon, during the last 1 to 7 days before each participant’s clinic visit. Higher air pollutant levels were also significantly associated with decreases in TIMP (tissue inhibitors of MMPs; TIMP-1 and 2), heightened thrombogenicity (shortened prothrombin time and increases in sCD40L [soluble CD40 ligand], sCD62P [soluble P-selectin], and fibrinogen/fibrin degradation products), and elevations in systemic inflammation (IL-1β [interleukin-1β], CRP [C-reactive protein], MIP-1α/β [macrophage inflammatory protein-1α/β], sRAGE [soluble receptor for advanced glycation end products], and IGFBP [insulin-like growth factor–binding protein]-1 and 3). Receiver operating characteristic curves showed that several biomarkers can serve as robust pollutant-specific predictors with high versus low black carbon exposure (area under the receiver operating characteristic curve of 0.974 [95% CI, 0.955–0.992] for MMP-8 and 0.962 [95% CI, 0.935–0.988] for sRAGE). Mediation analysis further showed that systemic inflammation can mediate ≤46% of the changes in MMPs and thrombogenicity associated with interquartile range increases in air pollutants. Conclusions: Our results suggest that air pollution may prompt cardiovascular events by triggering vulnerable plaque along with heightened thrombogenicity possibly through systemic inflammatory pathways.
Safety and efficacy of dasatinib in patients with advanced gastrointestinal stromal tumors refractory to imatinib and sunitinib: A single arm, multicenters, phase 2 trial.
Authors: Jian Li, Ye Zhou, Xinhua Zhang, Xiaojun WU, Yongjian Zhou, Xiufeng Liu, Bo Zhang, Xin Wu, Shen Lin
Journal: Journal of Clinical Oncology (2019)

138 Background: Regorafenib is recommended to treat advanced gastrointestinal stromal tumor (GIST) refractory to imatinib and sunitinib. However, the efficacy is not satisfied, other active agents need to be explored to advanced patients. Methods: In this single arm, multi-center, phase 2 trial, we enrolled patients aged 18 years and older with advanced GIST who had received previous imatinib and sunitinib treatment. Participants were treated with oral dasatinib 50mg twice a day for 2 weeks. If patients were tolerable, then they received dasatinib 70mg twice a day treatment, to tumor progression or intolerable toxicities. The primary endpoint was RECIST-based progression-free survival (PFS) in the intention-to-treat population. The secondary endpoints included response rate, overall survival (OS) and advent events. ctDNA will be analysis in some patients to explore the sensitive biomarker to dasatinib. Results: From May 2016 to June 2018, 58 patients from nine medical centers were enrolled in this study. Two patients had partial response and disease control rate was 62.0%. The median PFS was 3.0 months (95% CI, 2.6-3.4 months). There was no statistic difference of PFS in both subgroup with different primary mutations and in subgroup with different secondary mutations. The patients with wild type GIST had a trend of longer PFS of 5.5 months. In 4 patients with PDGFRA D842V mutation, two patients had stable disease. The median OS was 14.0 months (95% CI, 10.8-17.2 months). The most frequently observed grade 3 adverse events included anemia (10.3%), diarrhea (1.7%). The analysis of ct DNA is ongoing. Conclusions: Dasatinib is an active treatment for patients with GIST who are refractory to imatinib and sunitnib. This study is registered with ClinicalTrials.gov, NCT02776878 . Clinical trial information: NCT02776878.
Outcome of Patients Receiving Extracorporeal Photopheresis for Steroid Resistant Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies
Authors: Mauricette Michallet, Mohamad Sobh, Alexandre Deloire, Daniela Revesz, Youcef Chelgoum, Mohamed El-Hamri, Franck-Emmanuel Nicolini, Hélène Labussière, Olivier Hequet
Journal: Blood (2018)
High-Dose TSLP Induces Co-Receptor Internalization and Signal Shutdown in Ph-like B-ALL with Overexpression of CRLF2
Authors: WayAnne B. Watson, Hossam Alkashgari, Cornelia Stoian, Jacqueline S. Coats, Ineavely Baez, Hannah Choi, Benjamin Becerra, Rishikesh Chavan, Muhammad Omair Kamal, Shadi Farzin Gohar, Xianmei Meng, Sinisa Dovat, Kimberly J. Payne, Hoda Erjaee
Journal: Blood (2018)
VEGF-VEGFR pathway and its activitation in renal cell carcinoma: Role in sunitinib response.
Authors: Gustavo Rubio, Victoria Casado, Ana Leon, Manuel Domine, Sandra Zazo, Francisco Lobo, Yann Izarzugaza, Juan Luis Arranz, Jose Ignacio Martin-Valades, Gloria Serrano, Cristina Carames, Juan Madoz, Raul Rincon, Carmen Canadas, Nuria Perez-Gonzalez, Maria Jesus Fernandez-Acenero, Sharon Cordova, Angel Campos, Federico Rojo, Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2012)

e15094 Background: Activation of VEGFR through its phosphorylation at specific tyrosine residues promotes changes in the microvasculature density. Inhibition of this mechanism targeting kinase activity has demonstrated an impact on clinical benefit in renal cell carcinoma. Methods: Fifty renal cell carcinomas have been assessed to evaluate the role of VEGF-VEGFR pathway and its impact on microvascular density (MVD). In order to identify parameters of potential clinical benefit to sunitinib a control group was included. IHC of VEGF, VEGFR (KDR), phosphorylated VEGFR-Y1175 and microvascular density assessment were performed. Results: All cases show VEGF expression; using a ROC curve a threshold was identified with a statistical significant worse PFS in those cases with higher VEGF expression in the whole series of patients treated with sunitinib (p=0.037) and in the subgroup with clear cell histology only (p=0.011). pKDR was positive in 40%: with an AUC=0.9 and according to this threshold statistical significance was found in PFS in the whole series (p=0.016) and in the clear cell subgroup (p=0.007). Microvascular density showed a statistical significance when was evaluated in terms of PFS in the group including all histologies (p=0.011) and those cases with clear cell subtype only (p=0.005). Conclusions: Our data suggest that VEGF, pKDR-Y1175 and MVD may identify the patients with significant clinical benefit to sunitinib in terms of statistically longer PFS.