tbuckley/cabot-search huggingface dataset:
Abstract 1130: Cultural and socioeconomic factors affecting breast cancer screening in an Argentine city
Authors: Maria Virginia Croce, Luciano Cermignani, Martin E. Rabassa
Journal: Cancer Research (2020)

Abstract In Argentina, there are no studies evaluating cultural and socioeconomic factors affecting breast cancer screening. Argentina presents social and economic disparities, and there is a mixture of features of both developed and developing societies. The goal of this research was to analyze cultural and social factors in advantaged and disadvantaged women of a metropolitan area in order to improve breast cancer screening by increasing the understanding of the complex society. A cross-sectional study was performed; a total of 739 women was included, being 379 of low economic power (ow group, LG) and 360 of middle economic power (MG); women were personally interviewed within three months. A structured previously validated questionnaire was employed considering socially shared values, beliefs, expectations, motivations, and emotions relevant to health behaviors, interactions with the health care system, educational level, occupation, and information about breast cancer and mammographic screening. Previous research in this area suggested that theoretical models and multivariate methods were needed in order to account for the complexity of relations among psychological, social structural, and cultural determinants of health behaviors. In this sense, an exhaustive statistical analysis was performed by multivariate analysis and logistic regression model. A Principal Component Analysis was performed employing previously selected variables; 3 factors were extracted which accounted for 35.8% of the total variance. Factor 1 was associated with fatalistic responses in association to attitudes to life and/or mammography screening while Factor 2 was related to concerns about cancer and exposition to radiation. These two factors and the covariates age, social group, education, health system, and primary doctor were use in a logistic regression model to assess mammographic adherence. Low score Factor 2 (p=0.003), MG (p=0.024) and the availability of a primary doctor (p=0.000) were associated with high mammographic adherence. Conclusions: This study highlights that mammographic screening is highly influenced by socioeconomic power, health system, and access to primary doctor. It appears that, some psychological factors related to concerns about cancer and exposition to radiation are also important. These data would be important to plan specific prevention and early diagnosis programs to be implemented by governmental entities. Citation Format: Maria Virginia Croce, Luciano Cermignani, Martin E. Rabassa. Cultural and socioeconomic factors affecting breast cancer screening in an Argentine city [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1130.
International consensus recommendations on the diagnostic work-up for malformations of cortical development
Authors: Renske Oegema, Tahsin Stefan Barakat, Martina Wilke, Katrien Stouffs, Dina Amrom, Eleonora Aronica, Nadia Bahi-Buisson, Valerio Conti, Andrew E. Fry, Tobias Geis, David Gomez Andres, Elena Parrini, Ivana Pogledic, Edith Said, Doriette Soler, Luis M. Valor, Maha S. Zaki, Ghayda Mirzaa, William B. Dobyns, Orly Reiner, Renzo Guerrini, Daniela T. Pilz, Ute Hehr, Richard J. Leventer, Anna C. Jansen, Grazia M. S. Mancini, Nataliya Di Donato
Journal: Nature Reviews Neurology (2020)

Abstract Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. MCDs place a substantial burden on affected individuals, their families and societies worldwide, as these individuals can experience lifelong drug-resistant epilepsy, cerebral palsy, feeding difficulties, intellectual disability and other neurological and behavioural anomalies. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and aetiology, thereby hampering timely and adequate management. In this article, the international MCD network Neuro-MIG provides consensus recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs with the aim of improving patient management worldwide. We reviewed the literature on clinical presentation, aetiology and diagnostic approaches for the main MCD subtypes and collected data on current practices and recommendations from clinicians and diagnostic laboratories within Neuro-MIG. We reached consensus by 42 professionals from 20 countries, using expert discussions and a Delphi consensus process. We present a diagnostic workflow that can be applied to any individual with MCD and a comprehensive list of MCD-related genes with their associated phenotypes. The workflow is designed to maximize the diagnostic yield and increase the number of patients receiving personalized care and counselling on prognosis and recurrence risk.
Abstract 1660: Reflectance confocal microscopy modeling of lentigo maligna
Authors: Katharine L. Hanlon, James M. Grichnik
Journal: Cancer Research (2020)

Abstract Early melanoma detection in sun-damaged skin can be a challenge. Clinically, some solar lentigines or flat seborrheic keratoses may be relatively indistinguishable from Lentigo Maligna. Reflectance Confocal Microscopy can now be used in the clinic to evaluate these lesions in vivo and increase biopsy accuracy. Spatial relationships of cells and architecture of associated skin structures play a critical role in appropriate diagnoses. As we move toward artificial intelligence using computer diagnostic platforms, it will be important to base algorithms on data with high diagnostic yield. We have undertaken efforts to create 3D reconstructions from sequential depths of confocal images of skin lesion in vivo in order to allow for more precise definition spatial relationships. These efforts have facilitated clearer evaluation of architectural changes at the dermal epidermal junction, location of cells around adnexal structures, and extent of melanocytic dendricity and diversity within the lesion. The use of color maps for efficient identification and accurate localization of cellular and architectural features of interest is another approach to advanced evaluation of confocal image data. We anticipate that these efforts will further improve accuracy for both human and computer diagnoses from reflectance confocal images. We appreciate generous support of the Theodora B Betz Foundation. Citation Format: Katharine L. Hanlon, James M. Grichnik. Reflectance confocal microscopy modeling of lentigo maligna [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1660.
Abstract 2844: New breast cancer protein as a potential biomarker in liquid biopsies
Authors: Safaa A. Ibrahim, Valerie riehl, Kenneth D. Beaman
Journal: Cancer Research (2020)

Abstract The decline in breast cancer mortality over the past 2 decades is primarily the result of advances in early detection and treatment. However, the five year relative survival rate of metastatic breast cancer (MBC) patients is only 27%. This requires the need of new biomarkers for early detection of MBC. Tumors secrete microvesicles (MV) in large quantities to blood circulation in order to communicate with distant cells such as immune cells and prepare the metastatic niche. Our recent studies showed that MV from metastatic breast cancer cells contain a specific peptide from the a2 isoform vacuolar ATPase (a2NTD). This a2NTD is undetectable in mammary epithelial cells MV but expressed abundantly by MV produced by breast tumor cells. We have previously shown that the MV containing a2NTD modulate immune cells, promotes tumor growth, metastasis and positively correlates with the invasiveness of breast cancer cells. Identifying the role of a2NTD in regulating immune cells in liquid biopsy will provide a new biomarker for breast cancer. Treatment of whole blood from healthy volunteers with MDA MB-231 MV or recombinant a2NTD drives the neutrophil transition from High density neutrophils (HDN) to Low density neutrophils (LDN). Flow cytometrical analysis showed that LDN possess the PMN-MDSCs markers CD11b+ CD15+ CD14- CD33- HLA-DR-. In addition a2NTD treatment was associated with decreased internal staining of Arg-1 in neutrophils that suggests the release of Arg-1. This data suggest that a2NTD can reprogram neutrophils to exert immunosuppressive phenotype. Further characterization of surface markers as well as functional assays demonstrate the exact phenotype of neutrophils. Together studying the impact of a2NTD present in MV on immune alteration during metastasis can be potential predictors of the growth and metastasis of breast cancer. Citation Format: Safaa A. Ibrahim, Valerie riehl, Kenneth D. Beaman. New breast cancer protein as a potential biomarker in liquid biopsies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2844.
Abstract 62: Destabilization of <i>NOXA</i> mRNA as a common resistance mechanism to targeted therapies
Authors: Joan Montero, Cecile Gstalder, Daniel J. Kim, Dorota Sadowicz, Wayne Miles, Michael Manos, Justin R. Cidado, J. Paul Secrist, Adriana E. Tron, Keith Flaherty, F. Stephen Hodi, Charles H. Yoon, Anthony Letai, David E. Fisher, Rizwan Haq
Journal: Cancer Research (2020)

Abstract Most targeted cancer therapies fail to achieve complete tumor regressions or attain durable remissions. To understand why these treatments fail to induce robust cytotoxic responses despite appropriately targeting oncogenic drivers, here we systematically interrogated the dependence of cancer cells on the BCL-2 family of apoptotic proteins after drug treatment. We observe that multiple targeted therapies, including BRAF or EGFR inhibitors, rapidly deplete the pro-apoptotic factor NOXA, thus creating a dependence on the anti-apoptotic protein MCL-1. This adaptation requires a pathway leading to the destabilization of the NOXA mRNA transcript. We find that interruption of this mechanism of anti-apoptotic adaptive resistance dramatically increases cytotoxic responses in cell lines and a murine melanoma model. Durable control of disease in vivo can be achieved with combinations of targeted therapy with an MCL-1 inhibitor. However, consistent with an adaptive resistance mechanism we have identified, the timing of drug treatment strongly influences the efficacy of the combination therapy. Collectively, our results identify NOXA mRNA destabilization/MCL-1 adaptation as a non-genomic mechanism that limits apoptotic responses. Our data indicate that optimal sequencing of MCL-1 inhibitors with targeted therapies could overcome widespread and clinically important therapeutic resistance, and achieve prolonged tumor responses in solid tumors. Citation Format: Joan Montero, Cecile Gstalder, Daniel J. Kim, Dorota Sadowicz, Wayne Miles, Michael Manos, Justin R. Cidado, J. Paul Secrist, Adriana E. Tron, Keith Flaherty, F. Stephen Hodi, Charles H. Yoon, Anthony Letai, David E. Fisher, Rizwan Haq. Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 62.
Osteoconductive hybrid hyaluronic acid hydrogel patch for effective bone formation
Authors: Soojeong Choi, Jong Seung Lee, Jisoo Shin, Min Suk Lee, Donyoung Kang, Nathaniel S. Hwang, Hyungsuk Lee, Hee Seok Yang, Seung-Woo Cho
Journal: Journal of Controlled Release (2020)
Abstract 6351: A novel NSC small molecule inhibitor, inhibits proliferation and invasion of triple-negative breast cancer cells
Authors: Hassan Yousefi
Journal: Cancer Research (2020)

Abstract Treatment of patients with Triple-negative breast cancer (TNBC) has been challenging due to the absence of well-defined molecular targets and high invasive and proliferative capacities of these cells. Current treatments against TNBC have shown minimal activity due to the high recurrence rate in the patients. There is, therefore, a pressing need for novel and efficacious therapies against TNBC. Here, we found a novel small molecule inhibitor with potent anti-tumor activity against TNBC cells. Anti-proliferative effects of NSC small molecule inhibitor were determined using 2D and 3D culture cell proliferation. Propium iodide staining was performed to analyze cell cycle distribution and Annexin/PI assay was carried out to evaluate the induction of apoptosis. Western blot analyses, proteomic and gene array techniques were applied to elucidate the molecular mechanisms underlying the anti-tumor activity of the small molecule inhibitor. Our data show that our NSC small molecule inhibitor, reduced the proliferation of a panel of breast cancer cells, particularly, TNBC cells through the induction of apoptosis but not cell cycle arrest. Proteomic and gene array analysis implicated a myriad of canonical signaling pathways including cell death, and cell survival. Furthermore, we found that treatment with NSC small molecule inhibitor impaired TNBC cell migration and invasion via expression reduction of the epithelial-to-mesenchymal transition (EMT) markers. In addition, we found that NSC small molecule inhibitor decreased TNBC cell proliferation and clonogenic survival and induced apoptotic cell death through inhibition of the anti-apoptotic proteins. Altogether, our data indicate that NSC small molecule inhibitor may exhibit anti-tumor activity in TNBC cells and provide a rationale for further investigation of the potential of NSC small molecule inhibitor as an attractive therapeutic drug for TNBC. We are currently in the process of validating our proteomic data. Further in-depth investigations are required to evaluate the exact targets and mechanism of this potent small molecule inhibitor, and its anti-neoplasm effects on TNBC in vivo. Citation Format: Hassan Yousefi. A novel NSC small molecule inhibitor, inhibits proliferation and invasion of triple-negative breast cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6351.
Abstract LB-315: Oncology research applications on an electrical impedance based, high accuracy sequencing platform
Authors: Saurabh Paliwal, Mohammad Fallahi, Ali Nabi, Tyson A. Clark, Bin Dong, Srijeeta Bagchi, Maryam Jouzi, Hannah Ritchie, Lydia Bonar, Anthony Thomas, Narin Tangprasertchai, Meysam R. Barmi, Xavier Gomes, Subra Sankar, Hesaam Esfandyarpour
Journal: Cancer Research (2020)

Abstract Next Generation Sequencing (NGS) technologies have revolutionized basic biological and clinical research, especially in oncology. NGS cancer assays are used to determine cancer predisposition, identify tumor mutations, monitor treatment response and develop personalized therapies. Here, GenapSys presents a scalable, low cost, and high accuracy sequencing platform based on electrical impedance detection. We demonstrate that a single run with a 16M sensor chip generates up to 2 Gb of data, with greater than 99% raw accuracy and an average read length of about 150 bp. We highlight its applications for oncology research, using diverse cancer panels on reference and clinical samples. We tested hybrid-capture and multiplex PCR-based cancer panels on a range of DNA sources, including oncology reference standards derived from cell line DNA, cfDNA standards, as well as clinical samples: FFPE, fresh frozen tumor tissue, and blood. For hybrid-capture libraries, we used the IDT xGen Pan Cancer 1.5 and Exome Research panels. We detected low frequency mutations in the range of 1%-24.5% across multiple reference standards with the cancer panel, and observed high correlation in allele frequency with expected values (R2 &amp;gt; 0.99). Similar results were obtained with an amplicon panel, the Ion AmpliSeq Cancer Hotspot Panel v2. Whole exome sequencing and pan cancer sequencing of clinical FFPE, fresh frozen and blood samples showed high concordance (F1-score &amp;gt; 95%) of SNV mutation calling with commonly used NGS technology. Thus, we demonstrate that the GenapSys Sequencing Platform is an accurate, scalable, and low cost solution for oncology research on a wide range of sample types and NGS assays. Citation Format: Saurabh Paliwal, Mohammad Fallahi, Ali Nabi, Tyson A. Clark, Bin Dong, Srijeeta Bagchi, Maryam Jouzi, Hannah Ritchie, Lydia Bonar, Anthony Thomas, Narin Tangprasertchai, Meysam R. Barmi, Xavier Gomes, Subra Sankar, Hesaam Esfandyarpour. Oncology research applications on an electrical impedance based, high accuracy sequencing platform [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-315.
Abstract LB-216: Frequent oncogenic tyrosine kinase gene fusions in supratentorial glioblastomas of young children
Authors: Torsten Pietsch, Christian Vokuhl, Gerrit H. Gielen, Andre O. von Bueren, Evelyn Dörner, Glen Kristiansen, Andreas Waha, Christof Kramm
Journal: Cancer Research (2020)

Abstract Glioblastoma in infancy and early childhood is characterized by a more favorable outcome compared to older children. We have shown in previous studies that these tumors are characterized by a stable genome. The occurrence of tyrosine kinase gene fusions in glioblastomas of infancy may represent therapeutic targets. 50 glioblastomas (GBM) with supratentorial location occurring in children younger than four years were retrieved from the archives of the Brain Tumor Reference Center, Institute of Neuropathology, University of Bonn, Germany. DNA and RNA were extracted from FFPE tumor samples. Gene fusions were identified on the DNA level by FISH using break-apart probes for ALK, NTRK1, -2, -3, ROS1 and MET and Molecular Inversion Probe (MIP) methodology. For the detection of fusions on the RNA level, targeted RNA sequencing was performed as well as Nanostring-based detection with probes specific for recurrent fusions. 37 supratentorial GBM occurred in the first year of life, 13 GBM between one and four years. 18 cases showed fusions of ALK to different fusion partners; all occurred in the first year of life (18/37 cases, 48.6%). Fusions of ROS1 were found in 5, MET in 3, NTRK1, -2, -3 in 10 cases. 12 cases showed no and two novel fusions. The different methods led to comparable results. Only recurrent fusions with known fusion partners were detectable with probes designed for the fusion sequence, and library construction for targeted RNA sequencing was not successful in a fraction of cases. Break-apart FISH led to reliable results on the next day, and MIP technology represented the most sensitive method for analysis of FFPE samples. Gene fusions involving the tyrosine kinase genes ALK, MET, ROS1 and NTRK1, -2, -3 occurred in 72% of glioblastomas of children younger than four years; the most frequent were ALK fusions occurring in infant GBM. DNA based MIP technology represented the most robust and sensitive assay. Citation Format: Torsten Pietsch, Christian Vokuhl, Gerrit H. Gielen, Andre O. von Bueren, Evelyn Dörner, Glen Kristiansen, Andreas Waha, Christof Kramm. Frequent oncogenic tyrosine kinase gene fusions in supratentorial glioblastomas of young children [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-216.
Abstract 4508: Modulating the release rate of polyethylene glycol (PEG) polymers from interleukin-2 (IL-2) PEG conjugates to optimize anti-tumor efficacy
Authors: Hui Li, Yuntao Song, Haiping Zhou, Chuan Liao, Meng Xu, Chuang Li
Journal: Cancer Research (2020)

Abstract The cytokine interleukin-2 (IL-2) is an endogenous agonist of the IL-2 pathway that activates and expands tumor killing lymphocytes. High doses of IL-2 are needed to activate CD8 T cells and NK cells, through binding on low-affinity IL-2 receptor beta gamma subunits (IL-2Rβγ). Severe toxic side effects associated with high doses, as well as the poor PK profile of IL-2, have limited its clinical usage. In addition of the toxicities, IL-2 also stimulates proliferation and activation of regulatory T cells (Tregs) through binding on the high-affinity heterotrimeric IL-2 receptor alpha beta gamma subunits (IL-2Rαβγ), which may antagonize the intended anti-tumor immunity. We report on an IL-2 PEGylation strategy to improve the pharmacokinetic properties of IL-2. Utilizing our proprietary PEGylation technology, IL-2 was covalently connected with multiple polyethylene glycol (PEG) polymers through releasable linkers. Our technology enabled the conjugation of IL-2 with average of 5-6 polyethylene glycol (PEG) polymers in high efficiency and 80-90% isolated yield. Anti-tumor efficacy of IL-2 was optimized by modulating the hydrolysis rate of the releasable linkers connecting IL-2 and polymers. The releasable linkers used in the study had the hydrolysis rate in the range of 15 to 120 hours to release one PEG polymer from the conjugates. The conjugates with hydrolysis rate of 20-60 h showed the optimal anti-tumor efficacy in B16F10 animal model. These results suggest that our novel approach of IL-2 PEGylation may optimize IL-2 biological activity and anti-tumor efficacy. Modulating the releasable rate of the PEG polymer would optimize the pharmacokinetic properties of the released active IL-2 species and enable the optimized anti-tumor efficacy. We are currently exploring the usage of our technology platform to further engineer IL-2 as a non-IL2Rα binding conjugate for improved toxicity profile. Citation Format: Hui Li, Yuntao Song, Haiping Zhou, Chuan Liao, Meng Xu, Chuang Li. Modulating the release rate of polyethylene glycol (PEG) polymers from interleukin-2 (IL-2) PEG conjugates to optimize anti-tumor efficacy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4508.