tbuckley/cabot-search huggingface dataset:
Abstract 382: Identification and characterization of circulating tumor cells with multiplexed Quantum Dot conjugated antibodies
Authors: Lanlan Zhou, Elizabeth M. Matthew, David T. Dicker, Wafik S. El-Deiry
Journal: Cancer Research (2015)

Abstract As non-invasive real-time liquid biopsy, circulating tumor cell (CTC) detection and characterization is one of the most active areas in translational cancer research, with 627 clinical trials having that include analysis of CTCs as a biomarker. We used breast cancer cells, prostate cancer cells and melanoma cells spiked into normal donor whole blood and captured with high porosity micro-filters followed by immunofluorescence staining. DAPI, CD45 conjugated with QDot525, CK8/18/19 conjugated with QDot605 and high molecular weight-melanoma associated antigen (HMW-MAA) conjugated with QDot705 were stained to identify CTCs. ER conjugated with QDot800 and PSA conjugated with QDot655 were stained to characterize CTCs. The CTC recovery rate was compared with the report from the US Food and Drug Administration- approved CellSearch® system (Veridex). Multiplexed tumor marker staining results were compared with single staining with fluorescently-labeled secondary antibody. Our study demonstrates that CTC multiplexed analysis has the potential for further genetic characterization of CTCs and offers potential insights into therapeutic targeting and resistance mechanisms. Citation Format: Lanlan Zhou, Elizabeth M. Matthew, David T. Dicker, Wafik S. El-Deiry. Identification and characterization of circulating tumor cells with multiplexed Quantum Dot conjugated antibodies. [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 382. doi:10.1158/1538-7445.AM2015-382
The impact of chemotherapy on cognition: A longitudinal study in testicular cancer.
Authors: Guy C. Toner, Hayley S. Whitford, Pawel Kalinowski, Peter S. Grimison, Martin R. Stockler, Andrew James Martin, Ian D. Davis, Ian N. Olver
Journal: Journal of Clinical Oncology (2016)

487 Background: Neuropsychological assessments suggest chemotherapy may lead to cognitive impairment but causal links remain unclear. Prospective longitudinal studies are needed to address methodological limitations, with different chemotherapy regimens, appropriate controls and adjusting confounders. Methods: This 16 centre, prospective observational study accrued 145 patients with testicular cancer treated with surgery, or surgery + chemotherapy, as determined by disease staging. Cognition was assessed by CogHealth, a 10-minute online playing-card format tool designed to overcome language limitations, assessment burden, and practice/ceiling effects. Quality of life, fatigue, anxiety, depression and self-perceived cognitive function were also assessed. Comparisons were made between baseline (≤6 months from orchidectomy/pre-chemotherapy) and follow-Up (12-18 months), for 3 groups with sufficient data; cisplatin-based chemotherapy (BEP/EP, n=41), carboplatin (n=20), and controls (n=41). Results: With age as a covariate, linear mixed models were used to compare the 3 groups over time. There were no significant differences between groups over time for cognitive tasks assessing psychomotor function, complex decision making, visual learning, working memory, and visual attention; self-perceived cognitive function matched actual performance. At baseline, for fatigue (p = 0.008), BEP/EP scored significantly worse than carboplatin (d = -0.75) and control groups (d = -0.80). For anxiety (p = 0.005), BEP/EP scored worse than controls (d = -0.91). For all groups anxiety (p = 0.03), emotional (p = 0.001) and functional wellbeing (p = 0.002), improved over time. BEP/EP with poorest scores at baseline, improved the most by follow-up (d = 0.63, -1.24, -1.17, respectively). Only physical wellbeing showed significant effects (p ≤ 0.03) for group, time, and a differing pattern of change across groups; the BEP/EP group scoring worse at baseline compared to carboplatin (d = -0.94) and control groups (d = -1.16), improving by follow-Up (d = -1.21). Conclusions: For patients with testicular cancer there were no statistically significant differences between groups for cognition scores or self-reported cognitive function. Clinical trial information: 12609000545268.
Safety and clinical activity of durvalumab (MEDI4736), an anti-PD-L1 antibody, in treatment-naïve patients with advanced non‒small-cell lung cancer.
Authors: Scott Joseph Antonia, Sang-We Kim, Alexander I. Spira, Myung-Ju Ahn, Sai-Hong Ignatius Ou, Neda Stjepanovic, Angela Fasolo, Dirk Jäger, Patrick Alexander Ott, Zev A. Wainberg, Heather A. Wakelee, Jonathan Wade Goldman, John Kurland, Marlon C. Rebelatto, Wenliang Yao, Ashok Kumar Gupta, John A. Blake-Haskins, Neil Howard Segal
Journal: Journal of Clinical Oncology (2016)

9029 Background: The PD-1/PD-L1 axis is an important immune inhibitory pathway contributing to tumor cell escape from immunosurveillance. A Phase 1/2 dose escalation and dose expansion study is ongoing to evaluate the safety and efficacy of durvalumab, a modified human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, in patients with advanced non‒small-cell lung cancer (NSCLC) or other solid tumor types. Methods: Durvalumab 10 mg/kg is given q2w for up to 12 months to treatment-naïve patients with histologically or cytologically documented Stage IIIB/IV squamous (SQ) or non-SQ NSCLC. Retreatment is permitted if disease progresses after 12 months of therapy. Response is investigator-assessed per RECIST v1.1, and the results are presented by histology and PD-L1 status with the Ventana SP263 assay (PD-L1+ defined as ≥ 25% of tumor cells expressing membrane PD-L1). Fifteen patients were initially enrolled regardless of PD-L1 status. After a protocol amendment, enrollment was restricted to PD-L1+ patients. Results: As of 14 Dec 2015, 59 patients (48 PD-L1+; 9 PD-L1-; 58 EGFR WT; 57 ALK WT; 55 KRAS WT; 29 SQ; 30 non-SQ; median age 66 years [range 31-83]; 64% male; 96% current/prior smokers; ECOG 0/1: 37%/63%) received a median of 8 doses (range 1-27). Drug-related AEs were reported in 51% of patients; most frequent were fatigue (15%), diarrhea (12%), and decreased appetite (10%). Grade ≥ 3 drug-related AEs were reported in 9% of patients. Drug-related AEs led to discontinuation in 4 patients (7%); most frequent was diarrhea (2 patients). Fifty-two patients (23 SQ; 29 non-SQ) were evaluable for response with ≥ 12 weeks of follow-up. ORR (confirmed CR and PR) was 25% (11/43 PD-L1+; 1/8 PD-L1-), and disease control rate at ≥ 12 weeks was 56% (24/43 PD-L1+; 4/8 PD-L1-). ORR was similar for SQ (26%) and non-SQ (24%). Responses are ongoing in 9/13 responding patients (duration of response range: 5.7+ to 70.1+ weeks). Conclusions: Durvalumab monotherapy has a manageable safety profile with early evidence of clinical benefit in treatment-naïve SQ or non-SQ advanced NSCLC. A development program of durvalumab alone and in combination is ongoing in advanced NSCLC. Clinical trial information: NCT01693562.
Abstract 5084: Real-time, quantitative cellular analysis of migration and invasion
Authors: Meagan Roddy, John Rauch, Lindy O’Clair, Daniel M. Appledorn
Journal: Cancer Research (2016)

Abstract Chemotactic-driven cell migration is an important biological process impacting many areas of life science research including immunology, cancer and developmental biology. The dominant high-throughput solution for measuring cellular chemotaxis in vitro is the Boyden-chamber. However, traditional Boyden chamber products have inherent liabilities including: a) the inability to directly visualize the cell migration process, b) a requirement of tens of thousands of cells per well, c) the need to label cells for quantitation, d) a relative insensitivity to surface integrin signaling, and e) high random migration artifacts. Microfluidic solutions have sought to eliminate some of these deficiencies, specifically by providing the ability to visualize the cell migration process, but at the expense of relatively low throughput and cumbersome quantitation methods. Using a live-cell imaging approach and real-time image analysis quantitation, we have developed a new technology which eliminates most of the deficiencies of existing Boyden chambers and most importantly, provides direct visualization of both migration and invasion as it occurs. Integrated metrics precisely quantify the chemotactic response using significantly fewer cells (500-5000 cells per well) in a 96-well format. We exemplify this novel image based technique by studying the migration and invasion of both non-tumor and tumor-derived cell lines. Using Fetal bovine serum (FBS) as a chemoattractant, HT-1080 and NIH-3T3 cells were evaluated for their ability to directionally migrate across a coated surface or invade through a basement membrane extract by embedding the cells in an extracellular matrix prior to seeding. Qualitatively, we observed significant morphological differences between migrating and invading cells, the latter adopting a mesenchymal morphology reminiscent of cells that have undergone epithelial-mesenchymal transition (EMT) and exhibiting thinner, spindle-like morphology as they invade through the matrix. Using both cell count and cell area metrics, we observed a significant difference between migration and invasion kinetics of the relatively non-invasive cell line, NIH-3T3, and the highly invasive human fibrosarcoma derived cell line, HT-1080. Moreover, we observed significant and selective inhibition of HT-1080 cell invasion in the presence of GM6001, a broad inhibitor of Matrix Metalloproteinases (MMPs) with an IC50 of 25.7 nM. This new, real-time, quantitative cellular analysis technique illustrates a novel method to simultaneously study migration and invasion of tumor cells. Citation Format: Meagan Roddy, John Rauch, Lindy O’Clair, Daniel M. Appledorn. Real-time, quantitative cellular analysis of migration and invasion. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5084.
R-CHOP VERSUS R-FC FOLLOWED BY MAINTENANCE WITH RITUXIMAB OR IFN
Authors: Johanna Kluin-Nelemans, E. Hoster, O. Hermine, J. Walewski, M. Trneny, C. H. Geisler, W. Klapper, U. Vehling-Kaiser, M. Szymczyk, C. Gisselbrecht, S. Stilgenbauer, B. Coiffier, L. Kanz, J. K. Doorduijn, M. Untherhalt, M. Dreyling
Journal: Annals of Oncology (2011)
Abstract 4813: Magnetic iron oxide nanoparticles enhance anti-tumor effect of docetaxel on prostate cancer cells via ROS generation and NF-kappa B signaling
Authors: Kanako Kojima, Saho Hashimoto, Rina Sakamaki, Sanai Takahashi, Risa Kasakura, Ryo Maruyama, Tadashi Nittami, Hitoshi Ishiguro, Hiroji Uemura, Masatoshi Watanabe
Journal: Cancer Research (2016)

Abstract Chemotherapy is one of treatment options for castration-resistant prostate cancer. Especially, docetaxel-based chemotherapy has been shown to improve the quality of life in patients with the advanced disease. However, this needs to be improved because of limitations by lack of specificity, toxicity, and progression of docetaxel-resistance. Thus, combination of docetaxel with other compounds or drugs is needed to overcome these problems. Magnetic iron oxide nanoparticles (MgNPs, Fe3O4) have been investigated for nanomedicine such as drug delivery, cancer diagnosis and therapy. We have also shown that MgNPs would modify the effect of chemotherapy in prostate cancer cells in vitro. The purpose of this study was to analyze the combined effect of docetaxel and non-/carboxyl-modified magnetic nanoparticles (MgNPs/MgNPs-COOH) on a prostate cancer cell line, DU145 and clarify their mechanisms. While only MgNPs produced reactive oxygen species (ROS) and 8-OHdG, MgNPs-COOH did neither produce ROS nor 8-OHdG. The combination of docetaxel and MgNPs-COOH more effectively inhibited cancer cell growth and induced apoptosis compared with combination of docetaxel and MgNPs. Although docetaxel induced NF-kappa B expression, combination of docetaxel and MgNPs inhibited NF-kappa B expression compared with combination of MgNPs-COOH and docetaxel. However, both combinations increased p-Akt expression. These results suggest that MgNPs/MgNPs-COOH may enhance effect of docetaxel on prostate cancer cells via NF-kappa B signaling, however different factors may be involved in these phenomena, leading to new tumor ablation therapies. Citation Format: Kanako Kojima, Saho Hashimoto, Rina Sakamaki, Sanai Takahashi, Risa Kasakura, Ryo Maruyama, Tadashi Nittami, Hitoshi Ishiguro, Hiroji Uemura, Masatoshi Watanabe. Magnetic iron oxide nanoparticles enhance anti-tumor effect of docetaxel on prostate cancer cells via ROS generation and NF-kappa B signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4813.
Abstract 1846: Gene expression analysis of P-glycoprotein and LMWPTP in chronic myeloid leukemia cells treated with metformin and imatinib mesylate
Authors: Ligia P. Oliveira, Rafael G. Ferro, Ana CSS Galvão.
Journal: Cancer Research (2016)

Abstract Chemotherapy is an effective treatment for many tumors; however, some tumors begin to exhibit a wide range of resistance after a few cycles of chemotherapy, which is known as phenotype of resistance to multiple drugs (multidrug resistance - MDR). The MDR phenotype arises through various mechanisms, but often is associated with an increased efflux of hydrophobic cytotoxic drugs. Therefore, the search for more selective and efficient antitumor compounds in the elimination of cancer cells boosts the research in oncology area. Studies of genes and pathways that are deregulated in tumors and that are essential to their growth may provide new strategies that lead to the development of therapeutic agents that target these pathways. Previous data from our research group have shown potent toxic activity of metformin, an oral hypoglycemic used for more than 30 years for the treatment of type II diabetes, on chronic myeloid leukemia cells (CML), potentiating the effects of imatinib mesylate, the standard chemotherapy used in the treatment of CML. CML cells treated with these agents showed changes in expression of proteins associated with the MDR phenotype. In this way, this project aimed to evaluate the expression of ABCB1 (Pgp) e ACP1 (LMWPTP) by Polymerase Chain Reaction in real time (qPCR) in LCM K562 cells and Lucena before and after treatment with metformin and/or imatinib mesylate, seeking to verify the effects of metformin, alone or in combination with Imatinib mesylate in the expression of these genes in Lucena in K562 cells. We found statistically significant differences in expression between treatments compared to control and between K562 and Lucena cells. It is possible to conclude that these genes may be associated with MDR phenotype. Citation Format: Ligia P. Oliveira, Rafael G. Ferro, Ana CSS Galvão. Gene expression analysis of P-glycoprotein and LMWPTP in chronic myeloid leukemia cells treated with metformin and imatinib mesylate. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1846.
Experience of the use of trabectedin (ET-743) in patients with advanced soft tissue sarcoma failing doxorubicin and/or ifosfamide in Korea.
Authors: H. Kim, J. Ahn, H. Lee, T. M. Kim, J. Lee, K. Park, S. Sym, Y. Choi, K. Lee, S. Y. Rha
Journal: Journal of Clinical Oncology (2010)

e20518 Background: Trabectedin (ET-743, Yondelis) has emerged as a novel and effective treatment option for patients failing doxorubicin and/or ifosfamide, the current standard treatment for advanced metastatic sarcoma. Recently, as the ethnic differences become the major issues in introducing novel agents, the information of efficacy and toxicity profile in Asian population is essential. Methods: We present the retrospective results obtained from trabectedin use in patients with advanced refractory soft tissue sarcoma (STS) from multi-centers in Korea. From December 2008 to December 2009, 21 patients received trabectedin at a schedule with dose of 1.5 milligrams/m2 every 3 weeks by continuous 24h infusion. Results: All patients had received prior treatment with an anthracycline and/or ifosfamide, and ECOG status was 0 or 1. Patients were treated with more than two previous chemotherapy lines (2-6 lines). Lung and liver were most common metastatic site. The patients received a median of 2 cycles (1-6 cycles) of treatment and total 57 cycles. Objective partial response was observed in one patient and seven patients achieved stable disease with 38% of disease control rate. The median progression-free survival was only 2 months (20–207 days). Seven patients experienced early disease progression (within 30 days). Four patients died while on treatment, three from disease progression and one from treatment-related toxicity of G4 hepatic toxicity. The common toxicities included neutropenia, anemia, thrombocytopenia, transiently increased transaminase concentrations. Grade 3-4 neutropenia were encounted in 35% and grade 3-4 transaminitis in 15%. Febrile neutropenia was infrequent (<10%). Other significant toxicities were nausea, vomiting and asthenia. Both treatment delays and/or dose reductions were needed in 33% of patients. Conclusions: Although this result have many limitations of retrospective analysis, it supports the necessity of further investigations of this drug for the modification of dose or schedule, or for the combination with other drugs, or identification of pharmacogenomic biomarkers to improve the outcome of advanced soft tissue sarcomas in Korea. No significant financial relationships to disclose.
Does agent sequencing matter across multiple lines of chemotherapy in metastatic breast cancer (MBC)?: A single institution retrospective analysis of 550 women.
Authors: Antonio Bernardo, Federico Sottotetti, Cristina Teragni, Barbara Tagliaferri, Emma Pozzi, Luca Licata, Raffaella Palumbo
Journal: Journal of Clinical Oncology (2015)

e11557 Background: The role of drug sequencing in the global therapeutic strategy to MBC remains a debated issue. We aimed to analyze different treatment patterns and outcomes of women receiving multiple chemotherapy (CT) lines, focusing on the potential impact of early taxane exposure in advanced treatment lines, across different histologic subtypes. Methods: Data of 550 patients (pts) who had received at least 3 CT lines for MBC from January 2004 to December 2013 were collected from the electronic institutional database to the aim of this retrospective analysis. Overall survival (OS) and time to treatment failure (TTF) were calculated according to the Kaplan-Meyer method for each CT line. Cox proportional hazards model was used to identify factors that could influence TTF and OS. Results: We identified 312 with HR+/HER2- disease (Cohort A), 145 with HER2+ (Cohort B) and 93 with HR-/HER2- disease (Cohort C). All women had received taxane-based CT for MBC, 35% of them were taxane-pretreated in the adjuvant setting. The median follow-up was 65 months (range 21-122). Median OS, evaluated from day 1 of each CT line, decreased from 36.4 (1st line) to 10.2 months ( ≥ 4 lines) in cohort A, from 35.6 months to 9.6 months in cohort B, and from 20.2 to 5.8 months in cohort C. When calculated in function of early (1st-2nd line) versus late ( ≥ 3rd) taxane treatment, OS was 35.2 vs 31.4, 33.4 vs 26.5, and 18.6 vs 13.2, respectively. In the univariate analysis absence of liver metastasis, prior adjuvant taxane-and/or trastuzumab-based CT and number of CT lines were positively linked to a longer OS in each cohort. In the multivariate analysis the taxane exposure in early lines of treatment and the number of received CT were significantly correlated with TTF and OS in the whole population (p < 0.01). Conclusions: Our results show that the use of taxane-based CT in early (1st-2nd) lines of treatment is associated with OS improvement in all the analyzed subgroups. Within the modern ‘sequential continuum of care strategy’ in MBC, the choice of the most active agents in earlier disease phases could be a good way to invest in the “best” CT regimen also across unfavorable tumor subtypes.
Abstract 4368: High-throughput phenotyping of lung cancer somatic mutations
Authors: Alice H. Berger, Angela N. Brooks, Xiaoyun Wu, Yashaswi Shrestha, Candace Chouinard, Federica Piccioni, Mukta Bagul, Atanas Kamburov, Marcin Imielinski, Larson Hogstrom, Cong Zhu, Xiaoping Yang, Sasha Pantel, Ryo Sakai, Nathan Kaplan, David Root, Rajiv Narayan, Ted Natoli, David Lahr, Itay Tirosh, Pablo Tamayo, Gad Getz, Bang Wong, John Doench, Aravind Subramanian, Todd R. Golub, Matthew Meyerson, Jesse S. Boehm
Journal: Cancer Research (2016)

Abstract Recent cancer genome sequencing and analysis has identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood, limiting the use of this genetic knowledge for clinical decision-making. Here we describe a new high-throughput approach, expression-based variant impact phenotyping (eVIP), which uses gene expression changes to infer somatic mutation impact. We generated a lentiviral expression library representing 53 genes and 194 somatic mutations identified in primary lung adenocarcinomas. Next, we introduced this library into A549 lung adenocarcinoma cells and 96 hours later performed gene expression profiling using Luminex-based L1000 profiling. We built a computational pipeline, eVIP, to compare mutant and wild-type expression signatures to infer whether variants were gain-of-function, change-of-function, loss-of-function, or neutral. Overall, eVIP identified 69% of mutations as impactful whereas 31% appeared functionally neutral. A very high rate, 92%, of missense mutations in the KEAP1 and STK11 tumor suppressor genes were found to inactivate or diminish protein function. As a complementary approach, we assessed which mutations are epistatic to EGFR or capable of initiating xenograft tumor formation in vivo. A subset of the impactful mutations identified by eVIP could induce xenograft tumor formation in mice and/or confer resistance to cellular EGFR inhibition. Among these mutations were 20 rare or non-canonical somatic variants in clinically-actionable or -relevant oncogenes including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and PIK3CA E600K. eVIP can, in principle, characterize any genetic variant, independent of prior knowledge of gene function. Further application of eVIP should significantly advance the pace of functional characterization of mutations identified from genome sequencing. Citation Format: Alice H. Berger, Angela N. Brooks, Xiaoyun Wu, Yashaswi Shrestha, Candace Chouinard, Federica Piccioni, Mukta Bagul, Atanas Kamburov, Marcin Imielinski, Larson Hogstrom, Cong Zhu, Xiaoping Yang, Sasha Pantel, Ryo Sakai, Nathan Kaplan, David Root, Rajiv Narayan, Ted Natoli, David Lahr, Itay Tirosh, Pablo Tamayo, Gad Getz, Bang Wong, John Doench, Aravind Subramanian, Todd R. Golub, Matthew Meyerson, Jesse S. Boehm. High-throughput phenotyping of lung cancer somatic mutations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4368.
The 3-OH Derivative of the Polychlorinated Biphenyl (PCB)-28 Inhibits Telomerase Expression and Accelerates Telomere Shortening in Vitro: A Rationale for the Significantly Shortened Telomere Length Found in Peripheral Blood Lymphocytes of Workers Exposed to High Doses of Lower Chlorinated PCBs
Authors: Patrick Ziegler, Thomas Schettgen, Stefan Wilop, Natalia Soares Quintete, Susanne Ziegler, Fabian Beier, Monica S.V. Ferreira, Peter Uciechowski, Lothar Rink, Thomas Kraus, Tim H. Brümmendorf
Journal: Blood (2014)