tbuckley/cabot-search huggingface dataset:
Abstract 2543: Venue-based recruitment to increase colorectal screening rates using fecal immunochemical test in Essex County, New Jersey
Authors: Luis Alzate-Duque, Pamela Valera, Vivian Cueto, Ashna Shome, Ana Natale-Pereira
Journal: Cancer Research (2021)

Abstract Background: Overall, Essex County, New Jersey's age-adjusted prevalence for completion of colorectal cancer screening is 71.5%; however, Black and Latinx residents have a lower colorectal cancer screening rate of 65%. To increase urban residents' colorectal screening rates, we used venue-based recruitment to educate the community about fecal immunochemical testing. Methods: Education about fecal immunochemical testing was implemented at community-based events following a colorectal cancer education session. These sessions were carried out in English, Spanish, and Portuguese. Eligibility criteria included the following: (1) between the ages of 45-85 and (2) not current with U.S. Preventive Services Task Force recommended colorectal cancer screening. Eligible participants who agreed to participate were provided a fecal immunochemical testing kit and instructed to complete these kits to be returned within two weeks. Patient navigators followed up with study participants to explore barriers to completion and facilitate the fecal immunochemical testing kit's timely return. Results: Approximately 132 participants received the fecal immunochemical testing kit, and 55% were returned. On average, participants who received the fecal immunochemical testing kit were at least 60 years of age, 11% were men, 71% indicated no primary care provider, 72% reported no health insurance, and 81% reported no prior colorectal cancer screening. Of the 55% of the fecal immunochemical testing kit that was returned, 9 (12%) were positive for occult blood, and two diagnostic colonoscopies were completed. Participants noted several barriers to completing and returning the fecal immunochemical testing kit. They noted the following barriers: misplaced or loss of fecal immunochemical testing kit, limited time, and perceived comfortability of handling a stool sample. Discussion: Targeting study participants at community-based events may increase access to colorectal screening for underserved populations. Barriers to colorectal cancer screening could be mitigated by co-locating colorectal cancer screening education in the community. Citation Format: Luis Alzate-Duque, Pamela Valera, Vivian Cueto, Ashna Shome, Ana Natale-Pereira. Venue-based recruitment to increase colorectal screening rates using fecal immunochemical test in Essex County, New Jersey [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2543.
Nemertean, Brachiopod, and Phoronid Neuropeptidomics Reveals Ancestral Spiralian Signaling Systems
Authors: Daniel Thiel, Luis A Yañez-Guerra, Mirita Franz-Wachtel, Andreas Hejnol, Gáspár Jékely
Journal: Molecular Biology and Evolution (2021)

Neuropeptides are diverse signaling molecules in animals commonly acting through G-protein coupled receptors (GPCRs). Neuropeptides and their receptors underwent extensive diversification in bilaterians and the relationships of many peptide-receptor systems have been clarified. However, we lack a detailed picture of neuropeptide evolution in lophotrochozoans as in-depth studies only exist for mollusks and annelids. Here, we analyze peptidergic systems in Nemertea, Brachiopoda, and Phoronida. We screened transcriptomes from 13 nemertean, 6 brachiopod, and 4 phoronid species for proneuropeptides and neuropeptide GPCRs. With mass spectrometry from the nemertean Lineus longissimus, we validated several predicted peptides and identified novel ones. Molecular phylogeny combined with peptide-sequence and gene-structure comparisons allowed us to comprehensively map spiralian neuropeptide evolution. We found most mollusk and annelid peptidergic systems also in nemerteans, brachiopods, and phoronids. We uncovered previously hidden relationships including the orthologies of spiralian CCWamides to arthropod agatoxin-like peptides and of mollusk APGWamides to RGWamides from annelids, with ortholog systems in nemerteans, brachiopods, and phoronids. We found that pleurin neuropeptides previously only found in mollusks are also present in nemerteans and brachiopods. We also identified cases of gene family duplications and losses. These include a protostome-specific expansion of RFamide/Wamide signaling, a spiralian expansion of GnRH-related peptides, and duplications of vasopressin/oxytocin before the divergence of brachiopods, phoronids, and nemerteans. This analysis expands our knowledge of peptidergic signaling in spiralians and other protostomes. Our annotated data set of nearly 1,300 proneuropeptide sequences and 600 GPCRs presents a useful resource for further studies of neuropeptide signaling.
Abstract 3070: Lung cancer TTFields treatment planning sensitivity to errors in torso segmentation
Authors: Hadas Ben Atya, Oren Peles, Reuben Shamir, Zeev Bomzon
Journal: Cancer Research (2021)

Abstract Introduction: Tumor Treating Fields (TTFields) is a treatment modality for glioblastoma multiforme (GBM) and other malignant tumors, utilizing low-intensity, intermediate frequency (100-300kHz) alternating electric field delivered through noninvasive transducer arrays. TTFields are currently being tested in a phase III clinical trial for the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Previous studies have demonstrated that the treatment efficacy increases when the dose of TTFields delivered to the tumor is at least 1 V/cm. Thus, personalized simulations to estimate the dose are performed as part of the patient treatment planning. For NSCLC treatment, these simulations require the segmentation of torso tissues. We are currently developing a semi-automatic software for the segmentation of these tissues. Achieving highly accurate segmentation is time consuming and not always necessary. Therefore, in this study we assess the level of segmentation accuracy that is required for TTFields dose estimation. Methods: We introduce a novel pipeline for evaluating the sensitivity of TTFields treatment planning errors in the segmentation of torso tissues. To this end, we incorporated an expert-segmented torso volume and artificially placed NSCLC tumors of different sizes in the vicinity of the tested torso tissue. We employed relaxations to the segmentation algorithm and derived the TTFields distribution with and without the simulated segmentation errors. We then computed the treatment planning error as the per-voxel average deviation of the TTFields dose computed over the erroneous segmentation from the reference one. The dose was calculated over the simulated tumor location and over the entire lung volume. Results: We have evaluated our sensitivity analysis pipeline on 9 different test cases. Based on previous analysis, we have set our tolerable target error to be 0.1 V/cm. Our results show that 6 out of the 9 tests were within the target, whereas the other 3 exceeded the target, requiring algorithmic refinements. Conclusions: We have presented a method for estimating the sensitivity of lung cancer TTFields treatment planning to segmentation errors. This method is used to evaluate the required accuracy of the semi-automatic torso segmentation tool that we are currently developing. Our method can be further extended to other types of tumors in different regions of the body. Citation Format: Hadas Ben Atya, Oren Peles, Reuben Shamir, Zeev Bomzon. Lung cancer TTFields treatment planning sensitivity to errors in torso segmentation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3070.
NTRK and RET fusion–directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake
Authors: Young Ah Lee, Hyunjung Lee, Sun-Wha Im, Young Shin Song, Do-Youn Oh, Hyoung Jin Kang, Jae-Kyung Won, Kyeong Cheon Jung, Dohee Kwon, Eun-Jae Chung, J. Hun Hah, Jin Chul Paeng, Ji-hoon Kim, Jaeyong Choi, Ok-Hee Kim, Ji Min Oh, Byeong-Cheol Ahn, Lori J. Wirth, Choong Ho Shin, Jong-Il Kim, Young Joo Park
Journal: Journal of Clinical Investigation (2021)

BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983-March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison.RESULTSWe identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAFV600E in 41 patients, TERTC228T in 2 patients [1 of whom had a coexisting BRAFV600E], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAFV600E PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients <10 years of age) had lower expression of thyroid differentiation genes, including SLC5A5, than did adult fusion PTCs. Two girls with progressive 131I-refractory lung metastases harboring a TPR-NTRK1 or CCDC6-RET fusion oncogene received fusion-targeted therapy; larotrectinib and selpercatinib decreased the size of the tumor and restored 125I radioiodine uptake. The girl with the CCDC6-RET fusion oncogene received 131I therapy combined with selpercatinib, resulting in a tumor response. In vitro 125I uptake and 131I clonogenic assays showed that larotrectinib inhibited tumor growth and restored radioiodine avidity.CONCLUSIONSIn pediatric patients with fusion oncogene PTC who have 131I-refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric patients with PTC.FUNDINGThe Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4012417 and 2019R1A2C2084332); the Korean Ministry of Health and Welfare (H14C1277); the Ministry of Education (2020R1A6A1A03047972); and the SNUH Research Fund (04-2015-0830).TRIAL REGISTRATIONTwo patients received fusion-targeted therapy with larotrectinib (NCT02576431; NAVIGATE) or selpercatinib (LOXO-RET-18018).
68Ga-PSMA PET/CT for Recurrent Prostate Cancer after Radical Prostatectomy: What’s next? Analysis from a single, high volume tertiary referral center
Authors: D. Robesti, G. Gandaglia, N. Fossati, A. Stabile, E. Mazzone, V. Cucchiara, G. Rosiello, R. Leni, E. Camisassa, M. Moschini, R. Colombo, A. Necchi, P.I. Karakiewicz, F. Montorsi, A. Briganti
Journal: European Urology (2021)
Abstract 3104: EMT and CSC Enrichment Induced by ERK Inhibition in NSCLC
Authors: Shurui Cai, Xuetao Bai, Na Li, Ananya Banerjee, Kousalya Lavudi, Tejinder Pal
Journal: Cancer Research (2021)

Abstract The activation of Mitogen-activated protein kinase pathway (MAPK/ERK pathway) has been found to play an important role in many cancers including lung cancer, and multiple inhibitors targeting this pathway have been developed. Several ERK inhibitors (ERKi, e.g., Ulixertinib, SCH772984) have been shown to be active against different cancers harboring RAS, BRAF, or MEK mutations, as well as cancers with developed BRAF/MEK inhibitor resistance. Nevertheless, sustained inhibition of ERK can lead to resistance and is likely to cause tumor relapse as well. Studies over the years have shown that a small portion of cells within tumors, which can reproduce themselves and sustain cancer, being called “cancer stem cells (CSCs)”, is the cause of tumor initiation and progression. Many reports have implicated the association of Epithelial-to-Mesenchymal Transition (EMT) program with CSCs and identified EMT-transcription factors (TFs) as CSC regulators. Here, we demonstrated that ERKi treatment induces EMT in non-small cell lung cancer cells (NSCLC), probably by inducing Slug expression. We also found that ERKi treatment can enrich the cancer stem cell (CSC) like population in NSCLC cells, evidenced by increased ALDH+ cells, enhanced in vitro sphere formation capability, and enhanced tumorigenicity in immunodeficient mice. Moreover, in NSCLC cells, we proved ERK knockdown or ERKi treatment can reduce C/EBPα expression, which is believed to be a master epithelial “gatekeeper” whose expression is required to prevent unwarranted mesenchymal transition. Our findings reveal a novel mechanism underlying the tumor relapse after ERKi treatment in NSCLC, and ultimately will help us improve current NSCLC therapeutic methods. Citation Format: Shurui Cai, Xuetao Bai, Na Li, Ananya Banerjee, Kousalya Lavudi, Tejinder Pal. EMT and CSC Enrichment Induced by ERK Inhibition in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3104.
Latent class analysis-derived subphenotypes are generalisable to observational cohorts of acute respiratory distress syndrome: a prospective study
Authors: Pratik Sinha, Kevin L Delucchi, Yue Chen, Hanjing Zhuo, Jason Abbott, Chunxue Wang, Nancy Wickersham, J Brennan McNeil, Alejandra Jauregui, Serena Ke, Kathryn Vessel, Antonio Gomez, Carolyn M Hendrickson, Kirsten N Kangelaris, Aartik Sarma, Aleksandra Leligdowicz, Kathleen D Liu, Michael A Matthay, Lorraine B Ware, Carolyn S Calfee
Journal: Thorax (2021)

Using latent class analysis (LCA), two subphenotypes of acute respiratory distress syndrome (ARDS) have consistently been identified in five randomised controlled trials (RCTs), with distinct biological characteristics, divergent outcomes and differential treatment responses to randomised interventions. Their existence in unselected populations of ARDS remains unknown. We sought to identify subphenotypes in observational cohorts of ARDS using LCA.LCA was independently applied to patients with ARDS from two prospective observational cohorts of patients admitted to the intensive care unit, derived from the Validating Acute Lung Injury markers for Diagnosis (VALID) (n=624) and Early Assessment of Renal and Lung Injury (EARLI) (n=335) studies. Clinical and biological data were used as class-defining variables. To test for concordance with prior ARDS subphenotypes, the performance metrics of parsimonious classifier models (interleukin 8, bicarbonate, protein C and vasopressor-use), previously developed in RCTs, were evaluated in EARLI and VALID with LCA-derived subphenotypes as the gold-standard.A 2-class model best fit the population in VALID (p=0.0010) and in EARLI (p<0.0001). Class 2 comprised 27% and 37% of the populations in VALID and EARLI, respectively. Consistent with the previously described 'hyperinflammatory' subphenotype, Class 2 was characterised by higher proinflammatory biomarkers, acidosis and increased shock and worse clinical outcomes. The similarities between these and prior RCT-derived subphenotypes were further substantiated by the performance of the parsimonious classifier models in both cohorts (area under the curves 0.92-0.94). The hyperinflammatory subphenotype was associated with increased prevalence of chronic liver disease and neutropenia and reduced incidence of chronic obstructive pulmonary disease. Measurement of novel biomarkers showed significantly higher levels of matrix metalloproteinase-8 and markers of endothelial injury in the hyperinflammatory subphenotype, whereas, matrix metalloproteinase-9 was significantly lower.Previously described subphenotypes are generalisable to unselected populations of non-trauma ARDS.
Abstract 729: Prognostic significance of COX-2 over-expression in <i>BRAF</i> mutated Middle Eastern PTC
Authors: Rong Bu, Sandeep K. Parvathareddy, Abdul K. Siraj, Padmanaban Annaiyappanaidu, Kaleem Iqbal, Maha Al Rasheed, Wael Haqawi, Khawla S. Al-Kuraya
Journal: Cancer Research (2021)

Abstract The cyclooxygenase-2 (COX-2) - prostaglandin E2 (PGE2) pathway has been implicated in carcinogenesis with BRAF mutation shown to promote PGE2 synthesis. This study was conducted to evaluate COX-2 expression in a large cohort of Middle Eastern Papillary Thyroid Carcinoma (PTC) and further evaluate the prognostic significance of COX-2 expression in strata of BRAF mutation status. BRAF mutation analysis was performed by Sanger sequencing and COX-2 expression was evaluated immunohistochemically using tissue microarray. COX-2 over-expression was noted in 43.2% (567/1314) of cases and was significantly associated with poor prognostic markers such as extra-thyroidal extension, lymph node metastasis and higher tumor stage. COX-2 was also an independent predictor of poor disease-free survival (DFS). Most notably, the association of COX-2 expression with DFS differed by BRAF mutation status. COX-2 over-expression was associated with poor DFS in BRAF mutant but not BRAF wild-type PTCs with the multivariate-adjusted hazard ratio of 2.10 (95% CI = 1.52 - 2.92; p &amp;lt; 0.0001) for COX-2 over-expressed tumors in BRAF mutant PTC. In conclusion, the current study shows that COX-2 plays a key role in prognosis of PTC patients. Furthermore, a significant association of COX-2 expression with poor DFS was noted in BRAF mutated tumors. Our data suggests the potential therapeutic role of COX-2 inhibition in patients with BRAF mutated PTC. Citation Format: Rong Bu, Sandeep K. Parvathareddy, Abdul K. Siraj, Padmanaban Annaiyappanaidu, Kaleem Iqbal, Maha Al Rasheed, Wael Haqawi, Khawla S. Al-Kuraya. Prognostic significance of COX-2 over-expression in BRAF mutated Middle Eastern PTC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 729.
Advantages of using jaimy robotic system in sacrocolpopexy for bladder prolaps
Authors: G. Stoica, J. Lakssir, Y. Himmi, H. Dergamoun, C. Balsanu, T. Coroi, S. Regragui, P. Maulaz, H. Benhard, M.E. De Tinguy, M. Haydar
Journal: European Urology (2021)
Abstract 511: Clonal lineage and somatic hypermutation analysis comparing DNA and RNA as input material by long amplicon IGH chain sequencing
Authors: Michelle Toro, Geoffrey Lowman, Loni Pickle, Stephanie Ostresh, Mark Andersen, Shrutii Sarda, Chenchen Yang
Journal: Cancer Research (2021)

Abstract Background Traditional next generation sequencing methods for quantifying somatic hypermutation (SHM) rely on multiplex primers targeting either the framework 1 (FR1) or Leader regions of the IGH variable gene in combination with joining gene primers to amplify rearranged IGH chains from gDNA templates. Ion AmpliSeq primer panels for SHM evaluation were compared using both DNA and RNA input. Performance was compared using SHM values obtained from RNA samples amplified using FR1 variable gene primers in combination with constant gene primers to determine each IGH isotype and subtype in a single PCR reaction. Comparison of SHM frequencies measured from matched RNA and DNA samples were used to determine the feasibility for use of RNA in the study of SHM as well as comparison of the performance of Leader and FR1 gene primers in DNA studies. Methods Two multiplex primer panels were developed for DNA templates. These panels target the Leader or FR1 regions of the IGHV gene and the IGHJ gene. RNA samples were surveyed using FR1 and constant region primers. Comparisons of SHM frequency using 200ng of gDNA and 25ng of RNA from B cell lines and clinical research samples. Sequencing was accomplished using the Ion Gene Studio S5, while clonotyping, isotype determination, and somatic hypermutation analysis was performed using Ion Reporter 5.16 analysis software. Results Both RNA and DNA input assay workflows were able to correctly determine the SHM status of all rearrangements tested. IGHV SHM values were highly concordant between both RNA and DNA approaches. Additionally, SHM values derived from FR1 targeting variable gene primers delivered concordant results compared to Leader targeting variable gene primers when using DNA input across a wide range of SHM frequencies tested. Conclusions These results support the ability of highly multiplexed long-read NGS assays to accurately quantify SHM in either DNA or RNA samples. Concordant results were shown between FR1 and Leader targeting primers using DNA input. RNA based NGS methods benefit from lower sample requirements as well as the addition of isotype (and subtype) identification, opening new research areas for study of the B cell immune repertoire. Citation Format: Michelle Toro, Geoffrey Lowman, Loni Pickle, Stephanie Ostresh, Mark Andersen, Shrutii Sarda, Chenchen Yang. Clonal lineage and somatic hypermutation analysis comparing DNA and RNA as input material by long amplicon IGH chain sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 511.
Abstract 39: APOBEC3A drives acquired resistance to targeted therapies in non small cell lung cancer
Authors: Hideko Isozaki, Ammal Abbasi, Naveed Nikpour, Adam Langenbucher, Wenjia Su, Marcello Stanzione, Lecia V. Sequist, Rémi Buisson, Michael S. Lawrence, Aaron N. Hata
Journal: Cancer Research (2021)

Abstract Acquired drug resistance to even the most effective anti cancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified, the underlying molecular mechanisms shaping tumor evolution during treatment are incompletely understood. The extent to which therapy actively drives tumor evolution by promoting mutagenic processes or simply provides the selective pressure necessary for the outgrowth of drug resistant clones remains an open question. Here, we report that lung cancer targeted therapies commonly used in the clinic induce the expression of cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug tolerant cancer cells persisting during therapy. Induction of A3A facilitated the formation of double strand DNA breaks (DSBs) in cycling drug-treated cells, and fully resistant clones that evolved from drug tolerant intermediates exhibited an elevated burden of chromosomal aberrations such as copy number alterations and structural variations. Preventing therapy induced A3A mutagenesis either by gene deletion or RNAi mediated suppression delayed the emergence of drug resistance. Finally, we observed accumulation of A3A mutations in lung cancer patients who developed drug resistance after treatment with sequential targeted therapies. These data suggest that induction of A3A mutagenesis in response to targeted therapy treatment may facilitate the development of acquired resistance in non small cell lung cancer. Thus, suppressing expression or enzymatic activity of A3A may represent a potential therapeutic strategy to prevent or delay acquired resistance to lung cancer targeted therapy. Citation Format: Hideko Isozaki, Ammal Abbasi, Naveed Nikpour, Adam Langenbucher, Wenjia Su, Marcello Stanzione, Lecia V. Sequist, Rémi Buisson, Michael S. Lawrence, Aaron N. Hata. APOBEC3A drives acquired resistance to targeted therapies in non small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 39.