tbuckley/cabot-search huggingface dataset:
Patient-Reported Outcomes from the Phase III Randomized IMmotion151 Trial: Atezolizumab <b>+</b> Bevacizumab versus Sunitinib in Treatment-Naïve Metastatic Renal Cell Carcinoma
Authors: Michael B. Atkins, Brian I. Rini, Robert J. Motzer, Thomas Powles, David F. McDermott, Cristina Suarez, Sergio Bracarda, Walter M. Stadler, Frede Donskov, Howard Gurney, Stephane Oudard, Motohide Uemura, Elaine T. Lam, Carsten Grüllich, Caroleen Quach, Susheela Carroll, Beiying Ding, Qian (Cindy) Zhu, Elisabeth Piault-Louis, Christina Schiff, Bernard Escudier
Journal: Clinical Cancer Research (2020)

Patient-reported outcomes (PRO) were evaluated in the phase III IMmotion151 trial (NCT02420821) to inform overall treatment/disease burden of atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (mRCC).Patients were randomized 1:1 to receive atezolizumab 1,200 mg intravenous (i.v.) infusions every 3 weeks (q3w) plus bevacizumab 15 mg/kg i.v. q3w or sunitinib 50 mg per day orally 4 weeks on/2 weeks off. Patients completed the MD Anderson Symptom Inventory (MDASI), National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19), and Brief Fatigue Inventory (BFI) at baseline, q3w during treatment, at end of treatment, and during survival follow-up. Longitudinal and time to deterioration (TTD) analyses for core and RCC symptoms and their interference with daily life, treatment side-effect bother, and health-related quality of life (HRQOL) were evaluated.The intent-to-treat population included 454 and 461 patients in the atezolizumab plus bevacizumab and sunitinib arms, respectively. Completion rates for each instrument were 83% to 86% at baseline and ≥ 70% through week 54. Milder symptoms, less symptom interference and treatment side-effect bother, and better HRQOL at most visits were reported with atezolizumab plus bevacizumab versus sunitinib. The TTD HR (95% CI) favored atezolizumab plus bevacizumab for core (HR, 0.50; 0.40-0.62) and RCC symptoms (HR, 0.45; 0.37-0.55), symptom interference (HR, 0.56; 0.46-0.68), and HRQOL (HR, 0.68; 0.58-0.81).PROs in IMmotion151 suggest lower overall treatment burden with atezolizumab plus bevacizumab compared with sunitinib in patients with treatment-naïve mRCC and provide further evidence for clinical benefit of this regimen.
Dendritic cells loaded with XAGE-1b protein induce specific antitumor response against lung cancer
Authors: Q. Zhou, Y. L. Wu, A. L. Guo, K. Wang, C. R. Xu, Z. Wang, S. J. An, S. Q. Yang
Journal: Journal of Clinical Oncology (2007)

18080 Background: Dendritic cells (DCs) are the most potent antigen-presenting cells for initiating cellular immune response. Cancer-testis antigens (CTA) are the biggest tumor antigens family expressing only in some tumors and genital system but not in normal cells. XAGE-1b gene is one of CTA which highly expresses in lung cancer and has strong immunogenicity. Our study was to examine whether DCs loaded with XAGE-1b protein could induce specific antitumor response against lung cancer cells in vitro. Methods: Tumor tissues and normal lung tissues were obtained by operation from 30 non-small cell lung cancer patients. Cancer cells and normal lung epithelium cells were cultured and saved as target cells. Total RNA were isolated and RT-PCR was done to determine XAGE-1b gene expression. XAGE-1b gene was cloned by constructing expression vector and recombinant protein was expressed and purified by using BL21 (DE3) E. coli and AKTA-FPLC. Peripheral blood monocytes were isolated from 20ml blood and cultured to be DCs in serum-free DCs Medium. DCs were loaded with XAGE-1b protein through coculture and induced T lymphocytes into XAGE-1b-specific cytotoxic T lymphocytes (CTLs). The cytotoxicity of CTLs was then measured by cytotoxic assay. Results: 12/30(40%) lung cancer tissues expressed XAGE-1b gene, most of which were adenocarcinoma (11/12, 91.7%). None of normal tissues expressed it. Gene sequencing and western blot confirmed the expression vector construction and recombinant protein expression. Immunofluorescence identification showed the accumulation of XAGE-1b protein in immature DCs. T lymphocytes were stimulated twice with XAGE-1b protein-loaded DCs. Cytotoxic assay showed that the CTL cytotoxicity was much stronger for XAGE-1b positive tumor cells than for XAGE-1b negative tumor cells and it was almost none for normal lung epithelium cells. Conclusions: Our study indicates that DCs loaded with XAGE-1b protein could induce specific antitumor effect against lung cancer cells in vitro and this model offers a new approach to the immunotherapy for lung cancer. No significant financial relationships to disclose.
The positive effect of selective prostaglandin E2 receptor EP2 and EP4 blockade on cystogenesis in vitro is counteracted by increased kidney inflammation in vivo
Authors: Morgane Lannoy, Manoj K. Valluru, Lijun Chang, Fatima Abdela-Ali, Dorien J.M. Peters, Andrew J. Streets, Albert C.M. Ong
Journal: Kidney International (2020)
Targeting of inflammatory pathways with R2CHOP in high-risk DLBCL
Authors: Keenan T. Hartert, Kerstin Wenzl, Jordan E. Krull, Michelle Manske, Vivekananda Sarangi, Yan Asmann, Melissa C. Larson, Matthew J. Maurer, Susan Slager, William R. Macon, Rebecca L. King, Andrew L. Feldman, Anita K. Gandhi, Brian K. Link, Thomas M. Habermann, Zhi-Zhang Yang, Stephen M. Ansell, James R. Cerhan, Thomas E. Witzig, Grzegorz S. Nowakowski, Anne J. Novak
Journal: Leukemia (2020)
Abstract P4-04-02: Epigenomic analysis of cancer stem cells (CSCs) from triple-negative breast cancer (TNBC) reveals p63 and p73 as core metastasis drivers
Authors: Arthur Lambert, Christopher Fiore, Yogesh Chutake, Elisha Verhaar, Mei Wei Chen, Joana Donaher, Ferenc Reinhardt, Ian Engstrom, Bingbing Yuan, Brian Bierie, Daneyal Farouq, John Carulli, Eric Olson, Matthew Guenther, Robert Weinberg
Journal: Cancer Research (2020)

Abstract Cancer stem cells (CSCs) are key drivers of cancer metastasis, drug resistance, and disease recurrence. While the transcriptional regulatory circuitry that underlies the generation and propagation of the breast CSC state is not completely understood, defining the core regulators of the CSC state has the potential to reveal how these cells arise and point to potential targetable pathways for therapeutic intervention. We isolated CSCs by selecting for surface expression of integrin β4 (ITGB4). ITGB4-hi cells are highly enriched for CSCs and display cellular and molecular features indicative of their residence in an intermediate EMT state, including the ability to seed metastasis in vivo. Using ITGB4-hi CSCs isolated from the SUM159 breast cancer cell line, we deployed epigenome mapping by H3K27ac ChIP-seq, nucleosome occupancy by ATAC-seq, and transcriptome analysis by RNA-seq. Using comparative analysis of enhancer usage and DNA accessibility, we identified the transcriptional regulatory circuitry of breast cancer CSCs and pinpointed the master transcription factors that control the CSC state. We find that p63/p73 proteins function as master transcriptional regulators in breast CSCs and establish super-enhancers at critical CSC state genes. Loss of p63 and p73 disrupts the transcriptional circuitry of CSCs and leads to a highly mesenchymal state that is incompatible with metastatic colonization. Re-introduction of p63/p73 expression into non-CSCs leads to reactivation of the CSC transcriptional program and enables metastasis. These findings reveal the unique transcriptional circuitry of CSCs and suggest potential dependencies and pathways for therapeutic targeting of cells in the CSC state. Citation Format: Arthur Lambert, Christopher Fiore, Yogesh Chutake, Elisha Verhaar, Mei Wei Chen, Joana Donaher, Ferenc Reinhardt, Ian Engstrom, Bingbing Yuan, Brian Bierie, Daneyal Farouq, John Carulli, Eric Olson, Matthew Guenther, Robert Weinberg. Epigenomic analysis of cancer stem cells (CSCs) from triple-negative breast cancer (TNBC) reveals p63 and p73 as core metastasis drivers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-04-02.
A LYSA Phase Ib Study of Tazemetostat (EPZ-6438) plus R-CHOP in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) with Poor Prognosis Features
Authors: Clémentine Sarkozy, Franck Morschhauser, Sydney Dubois, Thierry Molina, Jean Marie Michot, Peggy Cullières-Dartigues, Benjamin Suttle, Lionel Karlin, Steven Le Gouill, Jean-Michel Picquenot, Romain Dubois, Hervé Tilly, Charles Herbaux, Fabrice Jardin, Gilles Salles, Vincent Ribrag
Journal: Clinical Cancer Research (2020)

The histone-methyl transferase EZH2, catalytic subunit of the PRC2 complex involved in transcriptional regulation, is mutated in approximately 25% of germinal center B-cell lymphomas. Aberrant proliferative dependency on EZH2 activity can be targeted by the orally available EZH2 inhibitor tazemetostat (EPZ-6438). We report the results of the phase Ib tazemetostat plus R-CHOP combination (NCT02889523), in patients 60 to 80 years of age with newly diagnosed diffuse large B-cell lymphoma.The primary objective of this dose-escalation study was to evaluate the safety of the combination and to determine the recommended phase II dose (RP2D) of tazemetostat.A total of 17 patients were enrolled. During C1 and C2, two dose-limiting toxicities were observed: one grade 3 constipation at 400 mg and one grade 5 pulmonary infection at 800 mg. Grade 3 or more toxicities observed in more than 10% of the patients were constipation (24%), nausea (12%), and hypokalemia (12%). Grade 3 to 4 hematologic adverse events were recorded in 8 patients (47%): neutropenia (47%), leukopenia (29%), anemia (18%), and thrombocytopenia (12%). The tazemetostat RP2D was 800 mg. No organ-oriented toxicity increased with tazemetostat dosage escalation (severity and incidence). At 800 mg, AUC and Cmax of tazemetostat were similar compared with the single-agent study (E7438-G000-101).The RP2D of tazemetostat combined with R-CHOP is 800 mg twice a day. The association presents safety and PK comparable with R-CHOP alone. Preliminary efficacy data are encouraging and further investigations in phase II trial are warranted.
Human leukocyte antigen class I-restricted activation of CD8( ) T cells provides the immunogenetic basis of a systemic drug hypersensitivity (vol 28, pg 822, 2008)
Authors: Diana Chessman, Lyudmila Kostenko, Tessa Lethborg, Anthony W Purcell, Nicholas A Williamson, Zhenjun Chen, Lars Kjer-Nielsen, Nicole A Mifsud, Brian D Tait, Rhonda Holdsworth, Coral Ann Almeida, David Nolan, Whitney A Macdonald, Julia K Archbold, Anthony D Kellerher, Debbie Marriott, Simon Mallal, Mandvi Bharadwaj, Jamie Rossjohn, James McCluskey
Journal: Immunity (2008)
A retrospective exploratory study of the variability of radiologists’ measurements in a selected subgroup of subjects enrolled in a clinical trial
Authors: R. W. Ford, R. R. Ford, K. Zhou
Journal: Journal of Clinical Oncology (2007)

6523 A retrospective exploratory study of the variability of radiologists’ measurements in a selected subgroup of subjects enrolled in a clinical trial Background: Independent centralized review of imaging studies is an established means of validating data used in support of corporate ‘go-no go‘ decisions, regulatory approval, and post marketing claims. Despite best efforts at standardizing this process using the Response Evaluation Criteria in Solid Tumors (RECIST), there will be inherent differences in radiologic measurements. To define a concise value for the variation between a specific set of radiologists, the following study was performed. Methods: An experienced radiologist and a research intern reviewed digital Computerized Tomographic (CT) scans from 31 subjects to identify 150 primary and metastatic tumors. Tumors were categorized into 4 categories. [Category (Cat.) 1 - Defined Edge/Radially Symmetric, Cat. 2 - Defined Edge/Irregular Shape, Cat. 3 - Blurred Edge/Radially Symmetric, Cat. 4 - Blurred Edge/Irregular Shape] Fifteen radiologists independently measured each tumor. Mixed effects models controlling for different tumors were used to assess the variance. Results Overall, the between reader variations accounted for 4.15% percent of total errors for the length. The respective between reader and the random errors are 0.32 (95% CI: 0.14, 0.77) and 7.51 (95%CI: 7.08, 8.01). The data shows that the variances are smallest for category 1 tumors (total error: 1.45) and largest for category 4 tumors (total error: 20.79). The total error for categories 2 and 3 are listed in Table 1 below. Conclusions The (low reader error) / (total error) verifies that the radiologists were only responsible for a small portion of the total error, and suggests these 15 radiologists measuring a tumor will be comparable to one of these radiologists measuring the tumor many times. No significant financial relationships to disclose. [Table: see text]
Single nucleotide polymorphisms (SNPs) analysis of CYP2C8, GSTT1, GSTP1, MDR1(A), MDR1(B) and ERCC1 as predictor of survival after weekly paclitaxel for relapsed advanced head &amp; neck cancer patients (AHNCP)
Authors: J. J. Grau, M. Monzo, M. Vargas, S. Jansa, m. Campayo, L. Alos, J. Domingo-Domenech, E. Verger
Journal: Journal of Clinical Oncology (2007)

2540 Background: Gene SNPs correlate with survival in cancer patients (pts) treated with chemotherapy (CHM). CYP2C8 and GSTT1, GTSP1 genes are involved in phase 1 and 2 drug cellular metabolisms respectively; MDR1(A) and MDR1(B) are involved in drug membrane transport and ERCC1 in DNA repair Methods: We evaluated the presence of SNPs of these 6 genes and the survival of AHNCP treated with weekly paclitaxel, 80 mg/m 2 iv for 6 weeks. Responding pts continue CHM till progression. All pts were cisplatin resistant and no other local therapies were available. We analysed paraffin-embedded biopsies from 47 consecutive AHNCP for SNPs of the mentioned genes. The status of the alleles wild type (wt) or at least 1 SNP was compared with response rate (RR), time to progression (TTP) and overall survival (OS) Results: Of 47 pts, 43 were male and 4 female. The median of age was 57 yr (46–80). RR was 45% (21/47) and the TTP in responders was 5 months of median. OS for all pts was 5.6 months. Wild type vs at least 1 SNPs frequencies according the genes were: CYP2C8 23/24; GSTT1 45/2; GSTP1 36/11; MDR1(A) 21/28; MDR1(B) 13/34; and ERCC1 27/20. OS was significantly better in pts with 2 or more SNPs accumulated (p=0.0455). No other significant differences were observed in RR, TTP or OS in SNPs vs wild type pts. Conclusions: SNPs of CYP2C8, MDR1(A) and MDR1(B) genes were more frequent than wt in our pts. OS was significantly better in pts with 2 or more SNPs accumulated. Paclitaxel provides high rate of responses of short duration in AHNC pts No significant financial relationships to disclose.
Association Between Rotavirus Vaccination and Type 1 Diabetes in Children
Authors: Jason M. Glanz, Christina L. Clarke, Stanley Xu, Matthew F. Daley, Jo Ann Shoup, Emily B. Schroeder, Bruno J. Lewin, David L. McClure, Elyse Kharbanda, Nicola P. Klein, Frank DeStefano
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Because rotavirus infection is a hypothesized risk factor for type 1 diabetes, live attenuated rotavirus vaccination could increase or decrease the risk of type 1 diabetes in children. <h3>Objective</h3> To examine whether there is an association between rotavirus vaccination and incidence of type 1 diabetes in children aged 8 months to 11 years. <h3>Design, Setting, and Participants</h3> A retrospective cohort study of 386 937 children born between January 1, 2006, and December 31, 2014, was conducted in 7 US health care organizations of the Vaccine Safety Datalink. Eligible children were followed up until a diagnosis of type 1 diabetes, disenrollment, or December 31, 2017. <h3>Exposures</h3> Rotavirus vaccination for children aged 2 to 8 months. Three exposure groups were created. The first group included children who received all recommended doses of rotavirus vaccine by 8 months of age (fully exposed to rotavirus vaccination). The second group had received some, but not all, recommended rotavirus vaccines (partially exposed to rotavirus vaccination). The third group did not receive any doses of rotavirus vaccines (unexposed to rotavirus vaccination). <h3>Main Outcomes and Measures</h3> Incidence of type 1 diabetes among children aged 8 months to 11 years. Type 1 diabetes was identified by<i>International Classification of Diseases</i>codes: 250.x1, 250.x3, or E10.xx in the outpatient setting. Cox proportional hazards regression models were used to analyze time to type 1 diabetes incidence from 8 months to 11 years. Hazard ratios and 95% CIs were calculated. Models were adjusted for sex, race/ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and Vaccine Safety Datalink site. <h3>Results</h3> In a cohort of 386 937 children (51.1% boys and 41.9% non-Hispanic white), 360 169 (93.1%) were fully exposed to rotavirus vaccination, 15 765 (4.1%) were partially exposed to rotavirus vaccination, and 11 003 (2.8%) were unexposed to rotavirus vaccination. Children were followed up a median of 5.4 years (interquartile range, 3.8-7.8 years). The total person-time follow-up in the cohort was 2 253 879 years. There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20.6 cases per 100 000 person-years. Compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio was 1.03 (95% CI, 0.62-1.72) for children fully exposed to rotavirus vaccination and 1.50 (95% CI, 0.81-2.77) for children partially exposed to rotavirus vaccination. <h3>Conclusions and Relevance</h3> The findings of this study suggest that rotavirus vaccination does not appear to be associated with type 1 diabetes in children.
Abstract P1-17-13: Design of a cognitive bias modification eHealth app to improve implicit vitality in breast cancer patients: A co-creation process
Authors: Roos G.M. Wolbers, Christina Bode, Ester J.M. Siemerink, Sabine Siesling, Marcel E. Pieterse
Journal: Cancer Research (2020)

Abstract Objective: More than 50% of all breast cancer patients experience fatigue symptoms during and after their treatment course. Recent evidence shows that fatigue is partly driven by cognitive biases, such as the self-as-fatigued identity bias, which may be corrected with computer-based Cognitive Bias Modification (CBM) techniques. The aim of the current study was the intervention design of such a CBM-training by adopting a co-creation approach. Methods: Semi-structured interviews were conducted with seven health professionals, three breast cancer patients and two patient advocates. Aim of the interviews was to collect input for the design of the CBM-training taking the attitude and preferences of the stakeholders into account and to determine the timing and implementation of the training in the treatment course. Results: Overall, the interviews showed that CBM was accepted among all stakeholders. Important requirements were revealed, such as that the training needs to be simple, undemanding, yet engaging and persuasive. Based on the results, eHealth app IVY (Implicit VitalitY) was created. Interviews suggested that IVY should be offered early in the treatment course and should be carefully aligned with clinical treatment. Conclusion: CBM training tasks seem to be suitable for targeting fatigue in breast cancer patients. It is innovative to use CBM techniques for cancer-related fatigue in a preventive approach. The current study suggests CBM has several benefits, such as being simple, time-effective and possibly increase levels of self-control in patients. In the next step, effectiveness of the CBM-training will be tested. Citation Format: Roos G.M. Wolbers, Christina Bode, Ester J.M. Siemerink, Sabine Siesling, Marcel E. Pieterse. Design of a cognitive bias modification eHealth app to improve implicit vitality in breast cancer patients: A co-creation process [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-13.
Clinical outcome of patients with thymic epithelial tumors
Authors: G. Palmieri, L. Montella, G. Merola, C. Merola, E. Matano, L. Petillo, A. Evoli
Journal: Journal of Clinical Oncology (2007)

14148 Advanced chemorefractory thymic epithelial tumors still represent a challenge in clinical oncology. Neoplastic thymoma cells express EGFR. We evaluated the clinical activity of Cetuximab, a chimeric human-mouse monoclonal IgG1 antibody blocking ligand binding to EGFR, in five cases of advanced chemorefractory thymic epithelial tumor. Materials and Methods: Patient Characteristics and response evaluation. Patients’ characteristics and responses to treatment are represented in the table . The patients were assessed for EGFR expression in the primitive tumor, being considered this data as a basis for an anti EGFR treatment. Moreover they were evaluated as concerns clinical status and biochemistry and imaged by a combined PET-CT. Treatment schedule: The patients received intravenous cetuximab (C225, Erbitux, Merck KgaA, Darmstadt, Germany) over 1 hour at 400 mg/m 2 loading dose followed by the weekly administration of 250 mg/m 2 . The first dose of 400 mg/m 2 was given during the course of 2 hours. Subsequent weekly treatments were given at a dose of 250 mg/m 2 during the course of 1 hour. This preliminary evaluation suggests for the first time that cetuximab may be a useful therapeutic choice in advanced pretreated thymic tumors. Despite the need for prolonged follow-up of the patients and further confirmatory studies, the EGF/EGFR pathway seems to play a pivotal role in thymic tumor. [Table: see text] No significant financial relationships to disclose.
Multicenter Study of Metastatic Lung Tumors Targeted by Interventional Cryoablation Evaluation (SOLSTICE)
Authors: Matthew R. Callstrom, David A. Woodrum, Francis C. Nichols, Jean Palussiere, Xavier Buy, Robert D. Suh, Fereidoun G. Abtin, Bradley B. Pua, David C. Madoff, Sandeep L. Bagla, Dimitrios C. Papadouris, Hiran C. Fernando, Damian E. Dupuy, Terrance T. Healey, William H. Moore, Thomas V. Bilfinger, Stephen B. Solomon, Hooman Yarmohammadi, Henry J. Krebs, Charles J. Fulp, Antoine Hakime, Lambros Tselikas, Thierry de Baere
Journal: Journal of Thoracic Oncology (2020)