tbuckley/cabot-search huggingface dataset:
Abstract 2142: Retrospective analysis of 13160 clinically sequenced tumor samples reveals potential cancer drivers
Authors: Cheng Yan, Hongwei Wu, Junhui Yang, Weihua Guo, Yufei Yang
Journal: Cancer Research (2021)

Abstract Background: High Throughput Sequencing (HTS) has generated tones of sequencing data that is almost unbearable to interpret. Adequate data mining strategy is in need to take huge volume of sequencing data and be able to derive clinically meaningful information. The positional distribution of somatic mutation on corresponding gene has strong implication of oncogenic involvement. We purpose a framework of cancer gene prioritization. Our aim is to derive candidate cancer genes by leveraging large volume of cancer samples. Methods: We retrospectively analyzed 13160 clinically derived tumor samples consisting of five cancer types. These samples were previously subjected to captured sequencing covering either entire exome or major cancer related genes. To predict genes with oncogenic property, a modified version of 20/20 rule adapted from Bert's study was applied. After pan-cancer analysis, samples of each cancer type were analyzed separately to obtain cancer type specific candidate genes. Candidate genes uniquely predicted by our study were annotated in terms of molecular function and thoroughly assessed through literature curation. Results: Using the modified 20/20 rule, pan-cancer analysis reported a total number of 186 candidate genes. 29 of them were uniquely reported by our analysis (absence in Bert's list, CGC list and our internal curation list) including 1 oncogene and 28 tumor suppressors. Their oncogenic involvements were further confirmed using random forest classifier 20/20+. 29 novel cancer candidate genes were significantly enriched in well-established cancer pathways described in Sanchez-Vega, et's study (pval&amp;lt;0.01). For instance, Ras GTPase-activating protein 1 (RASA1) is an inhibitory regulator of the Ras-cyclic AMP pathway. Our data revealed that RASA1 is enriched with inactivating mutations across its coding region: a typical mutational pattern of tumor suppressor. However, literature mining showed limited understanding regarding the its oncogenic rule. In cancer type specific analysis, 14 additional candidate cancer genes were uniquely reported by our analysis including known driver genes such as HDAC4 in gastric cancer and KLF5 in intestinal cancer. However, some reported candidate genes were less studied, such as oncogene WNT10A in liver cancer, probably due to low mutation frequency in western population (&amp;lt;0.5% according to TCGA). However, it mutated in 5.29% (59/1115) of our liver cancer cohort and highly recurrent mutations were identified at R171C and G213S. Citation Format: Cheng Yan, Hongwei Wu, Junhui Yang, Weihua Guo, Yufei Yang. Retrospective analysis of 13160 clinically sequenced tumor samples reveals potential cancer drivers [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 2142.
Evaluation of Retrograde Ejaculation (RE) and overall satisfaction with sexual function before and after Holmium Laser Enucleation of the Prostate (HoLEP)
Authors: M-N. Welte, M. Deuker, S. Banek, L.A. Kluth, F.C. Roos, P. Mandel, M. Wenzel, F.K.H. Chun, A. Becker
Journal: European Urology (2021)
Intense androgen receptor inhibition with neoadjuvant apalutamide does not complicate robotic prostatectomy outcomes
Authors: X.Y. Yang, R. Tiwari, E.J. Aslim, K.J. Tay, J.S.P. Yuen, T.W. Chong, H.S.S. Ho, L.S. Lee
Journal: European Urology (2021)
Abstract 2088: The effect of sorghum on epigenetic modifications in colon cancer
Authors: Zeguela Kamagate, Dmitriy Smolensky, Petra Tsuji
Journal: Cancer Research (2021)

Abstract Colorectal cancer is a major public health issue, accounting for nearly 150,000 cases annually. Because colorectal cancer is correlated with inflammation and oxidative cellular stress, it would be highly beneficial to exploit bioactive components in our diet that could potentially inhibit cancer promotion. Certain varieties of the dietary grain sorghum (S. bicolor) contain high amounts bioactive polyphenols, which may contribute to the prevention of colon cancer due to their antioxidant properties, anti-inflammatory, and anti-carcinogenesis effects, some of which may be mediated by epigenetic mechanisms. Tumor suppressor genes are often hyper-methylated in tumors. Therefore, DNA methylation and histone acetylation patterns may affect the expression of genes that play a role in the promotion or prevention of colon cancer. Our objective is to investigate how high-polyphenol sorghum varietals impact epigenetic mechanisms in human colon cancer cells, including quantitating global DNA methylation and histone acetylation. We treated HCT116 human colon cancer cells with high-polyphenol sorghum extracts or solvent control, or 5 µM epigallocatechin gallate as a positive control, as it's known to decrease DNA methylation. Total RNA, protein, and DNA were harvested after 24 and 48 hours. mRNA expression of DNA methyltransferases (DNMT) were quantitated with qPCR. Our preliminary results suggest that high polyphenol sorghum may decrease the mRNA expression of DNMT1, the key enzyme that upholds methylation patterns after DNA synthesis. Furthermore, mRNA expression of DNMT 3A, which is the enzyme responsible for de novo DNA methylation, also indicated a decrease. We further plan to assess protein expression and catalytic activity of DNMTs and histone acetyltransferases in addition to global DNA methylation and histone acetylation to investigate the impact of these high polyphenol sorghum varietals on relevant epigenetic mechanisms in both HCT116 and CACO-2 cells. Consumption of high-polyphenol sorghum as part of the human diet may lead to global or gene-specific hypo-methylation or hyper-acetylation, and this may be of importance in the prevention of colon cancer. Research supported by USDA ARS Kansas. Citation Format: Zeguela Kamagate, Dmitriy Smolensky, Petra Tsuji. The effect of sorghum on epigenetic modifications in colon 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 2088.
Sociodemographic Characteristics and Inequities Associated With Access to In-Person and Remote Elementary Schooling During the COVID-19 Pandemic in New York State
Authors: Ashley M. Fox, Jun Soo Lee, Lucy C. Sorensen, Erika G. Martin
Journal: JAMA Network Open (2021)

score declines of Black students were approximately 50% larger than White students, with the highest achievement declines in districts with fully remote instruction.Beyond implications for learning, in-person instruction is vital to provide vulnerable students with access to technology, nutrition, physical health, and behavioral health services. 6Study limitations include a cross-sectional ecological design that may mask variation within districts, generalizability beyond NYS, and reliance on administrative data, which may have misclassifications.
IncobotulinumtoxinA is not inferior to OnabotulinumtoxinA intradetrusor injections in the treatment of neurogenic detrusor overactivity incontinence: A multicentre, randomized, double-blind, clinical trial
Authors: A.G. Giannantoni, M. Gubbiotti, E. Rubilotta, M. Balzarro, A. Antonelli, V. Bini
Journal: European Urology (2021)
Radical nephroureterectomy pentafecta: A proposal for standardisation of oncologic outcomes reporting following open, laparoscopic or robot-assisted radical nephroureterectomy
Authors: F. Soria, R. Hurle, D. D’Andrea, S. Albisinni, E. Laukhtina, B. Pradere, E. Di Trapani, A. Aziz, W. Krajewski, J.Y. Teoh, A. Mari, M. Moschini, R. Autorino, A. Porreca, M. Marchioni, G. Liguori, G. Lucarelli, G.M. Busetto, A. Antonelli, G.I. Russo, N. Crisan, A. Veccia, O. De Cobelli, P. Gontero, M. Ferro
Journal: European Urology (2021)
Abstract 911: <i>In vitro</i> and <i>in vivo</i> activity of DHES0815A, an antibody-drug conjugate targeting HER2/neu in uterine serous carcinoma
Authors: Joan Tymon R. Tymon-Rosario, Elena Bonazzoli, Stefania Bellone, Arancha Manzano, Paola Manara, Luca Zammataro, Silvia Pelligra, Adele Guglielmi, Barbara Gnutti, Burak Zeybek, Justin Harold, Dennis Mauricio, Elena Ratner, Peter Schwartz, Alessandro D. Santin
Journal: Cancer Research (2021)

Abstract Objective: Uterine serous carcinoma (USC) is an aggressive histologic variant of endometrial cancer which portends a poor prognosis. DHES0815A is a novel antibody-drug-conjugate (ADC) which binds specifically to HER2 overexpressing tumors at a distinct epitope from that bound by trastuzumab and pertuzumab after which it delivers the toxic payload, PBD-MA, a DNA mono-alkylating agent. The objective of this study was to evaluate the preclinical activity of DHES0815A against primary USC cell lines and xenografts. Methods: Twelve primary USC cell lines were assessed by immunohistochemistry (IHC) for HER2 protein expression and for C-erbB2 gene amplification using fluorescent in situ hybridization (FISH) analysis. Cell viability and bystander killing in USC cell lines after exposure to DHES0815A, the non-targeted ADC, and the unconjugated antibody (i.e. MHES0488A) were evaluated using flow cytometry-based-assays. In vivo activity of DHES0815A was tested against HER2/neu overexpressing USC xenografts. Results: High HER2/neu protein expression was seen in 25% (3/12) of the primary USC cell lines. USC cell lines overexpressing HER2/neu were significantly more sensitive to DHES0815A when compared to the non-targeted control ADC (p&amp;lt;0.001). DHES0815A did not induce significant bystander killing of HER2/neu negative tumors when admixed with HER2/neu positive tumors. DHES0815A caused growth-inhibition and increased survival in USC HER2/neu overexpressing xenografts when compared to controls (p&amp;lt;0.01). Conclusions: DHES0815A is both highly selective and toxic to USC tumors overexpressing HER2/neu both in vitro and in vivo. HER2-directed ADCs, alone or in combination with other HER2/neu targeted agents may represent a novel treatment option for patients with tumors harboring HER2/neu overexpression refractory to trastuzumab and traditional chemotherapy. Citation Format: Joan Tymon R. Tymon-Rosario, Elena Bonazzoli, Stefania Bellone, Arancha Manzano, Paola Manara, Luca Zammataro, Silvia Pelligra, Adele Guglielmi, Barbara Gnutti, Burak Zeybek, Justin Harold, Dennis Mauricio, Elena Ratner, Peter Schwartz, Alessandro D. Santin. In vitro and in vivo activity of DHES0815A, an antibody-drug conjugate targeting HER2/neu in uterine serous carcinoma [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 911.
Reducing Hospital Use of Urban Sickle Cell Adults Using Multidisciplinary Adult Care and Instrumental Support
Authors: Daniel Sop Mouaffo, Wally R. Smith, Zakiya Owens, Thokozeni Lipato, Marla Brannon, Stefani Vaughan-Sams, Nyssa Towsley, Ding-Yu Fei, Shirley Johnson
Journal: Blood (2017)
Re: Paul Abrams, Lynda D. Constable, David Cooper, et al. Outcomes of a Noninferiority Randomised Controlled Trial of Surgery for Men with Urodynamic Stress Incontinence After Prostate Surgery (MASTER). Eur Urol 2021;79:812–23
Authors: Frank Van der Aa, Yves Deruyver, Manuela Tutolo
Journal: European Urology (2021)
Abstract 2501: Functional properties and regulation of the catechol-O-methyltransferase gene in prostate cancer
Authors: Yuichiro Tanaka, Yutaka Hashimoto, Marisa Shiina, Varahram Shahryari, Priyanka Kulkarni, Soichiro Yamamura, Shahana Majid, Z Laura Tabatabai, Rajvir Dahiya
Journal: Cancer Research (2021)

Abstract The catechol-O-methylase (COMT) gene has been shown to play a protective role in the cell by reducing catechol-compounds that can cause genetic mutations and enhance the carcinogenesis process. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both The Cancer Genome Atlas (TCGA) and immunohistochemical analysis of clinical specimens demonstrated a reduction of COMT expression in prostate cancer. Also, western analyses of prostate cancer cell lines show COMT levels to be minimal in DuPro and DU145 and thus, these cells were used for further analyses. Re-expression of COMT led to suppressed migration ability (wound healing assay) and enhanced apoptosis (flow cytometric analyses), and when challenged with 4-hydroxyestradiol, a marked reduction of cell proliferation (MTT assay) was observed. Xenograft growth in athymic mice also resulted in inhibition due to COMT. As a mechanism, western analyses show cleaved CASP3 and BID were increased whereas XIAP and cIAP2 were reduced due to COMT. As COMT expression is low in prostate cancer, its regulation was determined. Databases identified several miRNAs capable of binding COMT and of these, miR-195 was observed to be increased in prostate cancer according to TCGA. Real-time PCR validated upregulation of miR-195 in clinical prostate cancer specimens as well as DuPro and DU145 and interestingly, luciferase reporter showed miR-195 capable of binding COMT. These results demonstrate COMT to play a protective role by activating the apoptosis pathway and for miR-195 to regulate its expression. COMT may thus be a potential biomarker or a therapeutic target for prostate cancer. Citation Format: Yuichiro Tanaka, Yutaka Hashimoto, Marisa Shiina, Varahram Shahryari, Priyanka Kulkarni, Soichiro Yamamura, Shahana Majid, Z Laura Tabatabai, Rajvir Dahiya. Functional properties and regulation of the catechol-O-methyltransferase gene in prostate 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 2501.
Non-invasive Detection of Immunotherapy-Induced Adverse Events
Authors: Carolina A. Ferreira, Pedram Heidari, Bahar Ataeinia, Nicoleta Sinevici, Meghan E. Sise, Robert B. Colvin, Eric Wehrenberg-Klee, Umar Mahmood
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Cancer immunotherapy has markedly improved the prognosis of patients with a broad variety of malignancies. However, benefits are weighed against unique toxicities, with immune-related adverse events (irAE) that are frequent and potentially life-threatening. The diagnosis and management of these events are challenging due to heterogeneity of timing onset, multiplicity of affected organs, and lack of non-invasive monitoring techniques. We demonstrate the use of a granzyme B–targeted PET imaging agent (GZP) for irAE identification in a murine model. Experimental Design: We generated a model of immunotherapy-induced adverse events in Foxp3–DTR–GFP mice bearing MC38 tumors. GZP PET imaging was performed to evaluate organs non-invasively. We validated imaging with ex vivo analysis, correlating the establishment of these events with the presence of immune infiltrates and granzyme B upregulation in tissue. To demonstrate the clinical relevance of our findings, the presence of granzyme B was identified through immunofluorescence staining in tissue samples of patients with confirmed checkpoint inhibitor–associated adverse events. Results: GZP PET imaging revealed differential uptake in organs affected by irAEs, such as colon, spleen, and kidney, which significantly diminished after administration of the immunosuppressor dexamethasone. The presence of granzyme B and immune infiltrates were confirmed histologically and correlated with significantly higher uptake in PET imaging. The presence of granzyme B was also confirmed in samples from patients that presented with clinical irAEs. Conclusions: We demonstrate an interconnection between the establishment of irAEs and granzyme B presence and, for the first time, the visualization of those events through PET imaging.
Abstract 1219: Deep mutational scanning of PDE3A identifies residues required for DNMDP response
Authors: Xiaoyun Wu, Malvina Papanastasiou, Gavin Schnitzler, Colin Garvie, Stephanie Hoyt, Terry Zhang, James Mullahoo, Andrew Baker, Joseph McGaunn, Bethany Kaplan, Sooncheol Lee, Martin Lange, Steven Carr, Xiaoping Yang, Federica Piccioni, Andrew Cherniack, Matthew Meyerson, Heidi Greulich
Journal: Cancer Research (2021)

Abstract PDE3A-SLFN12 complex formation is induced by a class of compounds, now called “velcrins”, exemplified by the small molecule, DNMDP. Cancer cells that express elevated levels of PDE3A and SLFN12 are sensitive to a velcrin-mediated cytotoxic response, which is independent of PDE3A inhibition. However, the details of complex formation have not yet been revealed. We solved the crystal structure of PDE3A with a series of ligands bound to the active site and found that PDE3A exists as a dimer, and velcrin binding does not cause any obvious structural changes in the PDE3A protein structure. Hydrogen-deuterium exchange (HDX-MS) experiments with velcrin-bound PDE3A in the absence and presence of SLFN12 identified three regions of PDE3A that are shielded from solvent as a result of velcrin-induced SLFN12 binding. Two of these regions are near the velcrin binding site, and the third region lies at the PDE3A homodimerization interface. In order to further investigate the structural relationship between PDE3A, DNMDP, and SLFN12, we took a deep-mutation scanning (DMS) approach to identify residues of PDE3A that impact DNMDP sensitivity. A library of PDE3A alleles was developed in which the sequence encoding amino acids 668-1141, including the PDE3A catalytic domain, was substituted with a codon for every other possible amino acid or a stop codon in the context of the full-length cDNA. The library was transduced into PDE3A-knockout GB1 glioblastoma cells and assessed for survival in the presence of DMSO or DNMDP. Corroborating the HDX-MS data, we identified three regions of PDE3A in which missense mutations abrogated DNMDP response: the active site, the homodimerization surface, and an alpha helix containing amino acid F914. We confirmed that mutations of F914 and the homodimer interface retain the ability to bind resin-conjugated compound but fail to complex with SLFN12. Taken together, the HDX and DMS results suggest that PDE3A dimerization is required to stabilize velcrin-induced SLFN12 binding and implicate the alpha helix containing F914 as the SLFN12 binding interface of PDE3A. Citation Format: Xiaoyun Wu, Malvina Papanastasiou, Gavin Schnitzler, Colin Garvie, Stephanie Hoyt, Terry Zhang, James Mullahoo, Andrew Baker, Joseph McGaunn, Bethany Kaplan, Sooncheol Lee, Martin Lange, Steven Carr, Xiaoping Yang, Federica Piccioni, Andrew Cherniack, Matthew Meyerson, Heidi Greulich. Deep mutational scanning of PDE3A identifies residues required for DNMDP response [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 1219.
Early Medicaid Expansion and Cancer Mortality
Authors: Justin M Barnes, Kimberly J Johnson, Eric Adjei Boakye, Lidia Schapira, Tomi Akinyemiju, Eliza M Park, Evan M Graboyes, Nosayaba Osazuwa-Peters
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Although Medicaid expansion is associated with decreased uninsured rates and earlier cancer diagnoses, no study has demonstrated an association between Medicaid expansion and cancer mortality. Our primary objective was to quantify the relationship between early Medicaid expansion and changes in cancer mortality rates. Methods We obtained county-level data from the National Center for Health Statistics for adults aged 20-64 years who died from cancer from 2007 to 2009 (preexpansion) and 2012 to 2016 (postexpansion). We compared changes in cancer mortality rates in early Medicaid expansion states (CA, CT, DC, MN, NJ, and WA) vs nonexpansion states through a difference-in-differences analysis using hierarchical Bayesian regression. An exploratory analysis of cancer mortality changes associated with the larger-scale 2014 Medicaid expansions was also performed. Results In adjusted difference-in-differences analyses, we observed a statistically significant decrease of 3.07 (95% credible interval = 2.19 to 3.95) cancer deaths per 100 000 in early expansion vs nonexpansion states, which translates to an estimated decrease of 5276 cancer deaths in the early expansion states during the study period. Expansion-associated decreases in cancer mortality were observed for pancreatic cancer. Exploratory analyses of the 2014 Medicaid expansions showed a decrease in pancreatic cancer mortality (−0.18 deaths per 100 000, 95% confidence interval = −0.32 to −0.05) in states that expanded Medicaid by 2014 compared with nonexpansion states. Conclusions Early Medicaid expansion was associated with reduced cancer mortality rates, especially for pancreatic cancer, a cancer with short median survival where changes in prognosis would be most visible with limited follow-up.
Surviving maternal sepsis in low-income countries
Authors: Salome Maswime, Edward Buga
Journal: The Lancet Global Health (2021)

Maternal sepsis accounts for 11% of maternal deaths globally, making it the third leading cause of maternal mortality in the world, after haemorrhage and hypertension.1 A key finding from the Global Maternal Sepsis (GLOSS) substudy2 was that women in low-income countries who were admitted during the post-partum or post-abortion period were more likely to have a severe maternal outcome than women in upper-middle-income or high-income countries (adjusted odds ratio 1·84 [95% CI 1·05–3·22]). However, no other facility characteristics were associated with increased odds of severe maternal outcomes; most of these outcomes were associated with individual characteristics, such as pre-eclampsia.
PIKfyve Inhibitors for the Treatment of Multiple Myeloma
Authors: Cecilia Bonolo De Campos, Yuan Xiao Zhu, Chang-Xin Shi, Laura Ann Bruins, Joachim L Petit, Alysia N Polito, Meaghen E Sharik, Caleb K Stein, Gregory J Ahmann, Ilsel D Lopez Armenta, Nikolai Sepetov, Sergei Romanov, P. Leif Bergsagel, Marta Chesi, Nathalie Meurice, A. Keith Stewart
Journal: Blood (2017)
Difficulties of Differential Diagnosis of Abrikosov’s Tumor and Breast Cancer in the Outpatient Polyclinic Practice
Authors: E. V. Shivilov, Kh. S. Arslanov, G. E. Kvetenadze, A. L. Miftakhova, M. V. Rusakova, T. V. Pavlova
Journal: Radiology - Practice (2021)

The clinical example shows the difficulties of differential diagnosis at the outpatient policlinic stage of the granular cell tumor (Abrikosov’s tumor) and malignant neoplasm of the breast, which have similar semiotic signs. The final diagnosis of «granular cell tumor» is established only on the basis of pathomorphological and immunohistochemical studies obtained during core-biopsy of biological material.