tbuckley/cabot-search huggingface dataset:
Abstract 3186: Differential expression of PD-L1 between primary and metastatic Middle-Eastern epithelial ovarian carcinoma and its clinico-pathological correlation
Authors: Sandeep K. Parvathareddy, Abdul K. Siraj, Padmanaban Annaiyappanaidu, Felisa De Vera, Yan Kong, Zeeshan Qadri, Saeeda O. Ahmed, Hassan AlDossari, Khawla S. Al-Kuraya
Journal: Cancer Research (2021)

Abstract Ovarian cancer (OC) is one of the most common gynecologic cancer, which has the worst prognosis and highest mortality rate. The lack of curative treatment and the high relapse rate, especially in advanced OC, continues to present a clinical challenge, highlighting the need for new therapeutic strategies. This study was conducted to compare the expression of PD-L1 in Middle-Eastern primary epithelial ovarian carcinoma to that in peritoneal metastases and its correlation with clinico-pathological parameters. In total, 194 treatment naïve paired EOC and peritoneal metastases were analyzed by immunohistochemistry for PD-L1 expression. Clinico-pathological information was available for all patients. Significant differences in PD-L1 expression were found between primary EOC and peritoneal metastasis (p &amp;lt; 0.0001). We found discordant tumor cell PD-L1 expression between primary tumors and corresponding peritoneal metastasis in 34% (66/194) of cases. Furthermore, PD-L1 expression in peritoneal metastasis samples was significantly associated with adverse prognostic factors, such as high proliferative index (Ki67) (p = 0.0039) and high histologic grade (p = 0.0330). In conclusion, the heterogeneity of PD-L1 expression in EOC suggests its assessment as a potential biomarker for PD-L1 blockade may require analysis of metastatic lesions. Citation Format: Sandeep K. Parvathareddy, Abdul K. Siraj, Padmanaban Annaiyappanaidu, Felisa De Vera, Yan Kong, Zeeshan Qadri, Saeeda O. Ahmed, Hassan AlDossari, Khawla S. Al-Kuraya. Differential expression of PD-L1 between primary and metastatic Middle-Eastern epithelial ovarian carcinoma and its clinico-pathological correlation [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 3186.
Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing
Authors: Daniel Bradshaw, David F Bibby, Carmen F Manso, Renata Piorkowska, Hodan Mohamed, Juan Ledesma, Laura Bubba, Yuen T Chan, Siew Lin Ngui, Simon Carne, Jean L Mbisa
Journal: Clinical Microbiology and Infection (2021)
Combination topotecan and bevacizumab causes growth inhibition of ovarian cancer cells that express VEGF.
Authors: Shiying Cui, Johnathan M. Lancaster, Gina Chan, Robert M. Wenham
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5275 

The great majority of women diagnosed with epithelial ovarian cancer (EOC) will die of the disease. To date, the most significant results have come from advances in chemotherapy. There is considerable hope that novel biologically targeted therapy in combination with chemotherapy will improve survival. Bevacizumab, an antibody directed against the proangiogenic molecule vascular endothelial growth factor (VEGF) (Burger et al. 2005) shows great promise in ovarian cancer. There is little data, especially in human ovarian cancer cell lines, looking at how antiangiogenic agents and chemotherapy work together in combination. It is the specific purpose of this study to examine the growth inhibition that results from combination topotecan and bevacizumab in topotecan-resistant ovarian cancer cell lines that either did or did not express VEGF. To test the effect of chemotherapy on human ovarian cancer cells, seventeen ovarian cancer cell lines were treated with topotecan at different concentrations and time periods. Three pairs of these cell lines were further selected for assessing cell survival in the presence of bevacizumab alone or in combination with topotecan. Nine of seventeen cell lines showed resistant to topotecan treatment with a range of 62 to 100% cell survival. Three of these (OVCAR3; OVCAR5; SKOV3) have been previously shown to produce soluble VEGF (VEGF+). These cell lines were demonstrated relatively high resistance to 96-hours treatment with 0.3uM topotecan. When compared with a non-VEGF expressing cell line,A2780CP (VEGF-), VEGF+ cell lines (OVCAR3; OVCAR5; SKOV3) showed were significantly inhibited by bevacizumab when combined with topotecan after 24, 48 and 96 hours administration. This response was greater than the response to bevacizumab alone, suggesting synergy. This study demonstrates that topotecan resistant ovarian cancer cells that produce VEGF have a synergistic response to combination bevacizumab and topotecan. This opens further investigation into how other chemotherapeutics may behave when combined with antiangiogenic therapy in ovarian cancer.
Abstract 1191: Differences in gene mutation characteristics of gastric, intestinal and colorectal stromal tumors
Authors: Qian Wang, Hushan Zhang, Sihui Zhao, Jianxun Wang, Ning Ma, Jun Zhu
Journal: Cancer Research (2021)

Abstract Background: Gastrointestinal stromal tumors (GIST), which were thought to originate from interstitial cells of Cajal,is the most common malignant mesenchymal neoplasm, and account for 1%-3% of digestive tract tumors. Drug development in GIST has successfully utilized the KIT/PDGFRA oncogenic mutation. At the same time, drug sensitivity and resistance, such as imatinib resistance, is a problem should be paid more attention. We analyzed features of kit/pdgfra mutation in different region GIST of Chinese patients, which will provide reference information for the use of targeted drugs among patients with gastric, intestinal or colorectal stromal tumors. Methods: Tumor samples of 201 HCC patients were consecutively collected in China from January 2018 to June 2020, next generation sequencing (NGS) was performed to detect gene mutation by 3D Medicines, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA. Results: All these tissue samples were divided as stomach (n=109), small intestine (n=79), colon and the rectum (n=13). The average age of three group were 57, 55 and 50, the proportion of males in gastric, intestinal and colorectal stromal tumor were 64.2% (79/109), 60.8% (48/79) and 61.5%(8/13), respectively. NGS analysis showed that, frequency of kit were 71.5% (78/109), 83.5% (66/79) and 61.5% (8/13), among witch, mutation of exon 9 were 1.8%(2/109), 27.8% (22/79), 30.7% (4/13), and exon 11 were 66.1%(72/109), 53.2%(42/79), 30.8%(4/13); frequency of pdgfra were 14.7%(16/109), 3.8%(3/79) and 7.7%(1/13), and mutation frequency of pdgfra exon 18 were 11.9% (13/109), 1.3%(1/79), 7.7%(1/13). Conclusions: GIST is more inclined to occur in male. kit was the main mutation in GIST, however, only 1.8% of gastric GIST carry exon 9 mutations, a large proportion (66.1% and 53.2%) of gastric and intestinal GISTs carry exon 11 mutations. Besides, more mutation of pdgfra happened in gastric GIST than intestinal and colorectal GISTs. These results demonstrate that GIST occurred in different location may show different sensitivity or resistance to drugs targeting KIT/PDGFRA signals. Citation Format: Qian Wang, Hushan Zhang, Sihui Zhao, Jianxun Wang, Ning Ma, Jun Zhu. Differences in gene mutation characteristics of gastric, intestinal and colorectal stromal tumors [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 1191.
Abstract 3105: 4-Methylumbelliferone (4Mu) turns CD133+ lung cancer stem cells (CSCs) more susceptible to conventional chemotherapy
Authors: Ana L. Bezazian, Maria Amanda Escribano, Marco A. Diaz Gutierrez, Mariel Fusco, Paula Roselló, Juan Braga Menendez, Esteban J. Fiore, Juan M. Bayo Fina, Manglio M. Rizzo, Mariana Malvicini
Journal: Cancer Research (2021)

Abstract Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide. Taxane-platin chemotherapy is widely used for NSCLC treatment; however, the majority of patients will ultimately progress or relapse. In the tumor microenvironment (TME) cancer cells co-exist with cellular and non-cellular components that drive tumor processes such as chemotherapy resistance. A small group of tumor cells called cancer stem cells (CSCs) that express some markers such as CD133, CD44 and ALHD1 have particularly different proliferative, differentiation and self-renewal potential. In fact, CD133+ NSCLC cells showed significantly higher abilities of self-renewal and drug resistance characteristics when compared to CD133- cells. It has been partly described how the TME component hyaluronan (HA) regulates CSCs function. We have previously demonstrated that 4-Methylumbelliferone (4Mu), a modulator of HA synthesis, reduces CSCs properties in hepatocarcinoma. Here, we observed that HA was present Lewis Lung Carcinoma (LLC) tumors from mice. We found HA+ LLC cells; thus cancer cells produced, at least in part, the HA observed in tumors. We also observed about 6.58 ± 0.83 % of CD133+ CSCs on in vitro cultured LLC cells. Isolated CD133+ cells showed higher expression of HA and CD44 in comparison with non-CSCs population (p&amp;lt;0.05). Analysis of HA synthases (HAS), hyaluronidases (HYAL) and the CSCs transcription factors KLF4 and SOX2 expression from NSCLC patients using The Cancer Genome Atlas data showed that while HAS3 positively correlates with levels of KLF4 and SOX2, HYAL2 inversely correlates with SOX2 expression. Also, 4Mu treatment of whole, CD133+ or CD133- LLC cells showed an inhibitory concentration 50 (IC50) of 0.90mM, 0.60mM and 1.06mM respectively, while non tumor cells showed an IC50 of 4.22mM (p&amp;lt;0.01). When CD133+ cells were treated with 4Mu plus pemetrexed or paclitaxel we observed a significant decrease in viability with an IC50 of 0.4nM pemetrexed (Pe) vs. 0.05nM Pe+4M, and 9.3nM paclitaxel (Pa) vs. 0.80nM Pa + 4Mu. (p&amp;lt;0.05). Our results suggest that HA a principal ligand of CD44 is involved in CD133+ cells phenotype and their modulation by 4Mu could increases chemo sensibility of lung cancer stem cells. Citation Format: Ana L. Bezazian, Maria Amanda Escribano, Marco A. Diaz Gutierrez, Mariel Fusco, Paula Roselló, Juan Braga Menendez, Esteban J. Fiore, Juan M. Bayo Fina, Manglio M. Rizzo, Mariana Malvicini. 4-Methylumbelliferone (4Mu) turns CD133+ lung cancer stem cells (CSCs) more susceptible to conventional chemotherapy [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 3105.
Annals Graphic Medicine - Impostor Syndrome
Authors: Utkarsh Goel
Journal: Annals of Internal Medicine (2021)

Web ExclusivesJuly 2021Annals Graphic Medicine - Impostor SyndromeFREEUtkarsh Goel, MBBSUtkarsh Goel, MBBSAll India Institute of Medical Sciences, New Delhi, India (U.G.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0093 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: All India Institute of Medical Sciences, New Delhi, India (U.G.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G20-0093.Author/Illustrator Information: Utkarsh Goel, MBBS, is a graduate of All India Institute of Medical Sciences, New Delhi (e-mail, [email protected]com).This article was published at Annals.org on 13 July 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics July 2021Volume 174, Issue 7Page: W66-W67 ePublished: 13 July 2021 Issue Published: July 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 600: Liquid biopsy for neuroendocrine differentiation: Validation of a circulating tumor cell assay for synaptophysin
Authors: Jennifer Chow, A Anders Tevis, Edward Lo, Alisa Clein, Daniel E. Sabath, Arturo B. Ramirez, Eric P. Kaldjian, Tad George
Journal: Cancer Research (2021)

Abstract Protein expression of synaptophysin (SYP) is characteristic of neuroendocrine subtype tumors. In prostate cancer, neuroendocrine differentiation is correlated with disease progression, poor prognosis, and treatment resistance. Analysis of circulating tumor cells (CTCs) by multiparameter immunofluorescence (IF) microscopy allows non-invasive characterization of cancer cell biomarker expression in real time. This information can be helpful in prognosis, treatment selection, and patient stratification. Here we describe the validation of a biomarker IF assay for enumeration of CTCs and characterization of their SYP expression. The 0920-VB SYP CTC assay workflow includes processing blood samples to slides (AccuCyte® Sample Preparation System), staining slides with a panel of fluorescent markers (RarePlex® Staining Kit and Ventana® DISCOVERY® ULTRA immunostaining system), and multiparameter imaging and analysis (CyteFinder® Instrument). The panel consists of a nuclear dye, and antibodies against cytokeratins and EpCAM (to identify epithelial CTCs), CD45 (to exclude white blood cells) and SYP. Both clinical and spike-in samples were used for assay validation. The model CTCs used to generate spike-in samples included 22Rv1 (prostate carcinoma, SYP positive) and BT-474 (breast carcinoma, SYP negative). Performance metrics for the assay included accuracy, sensitivity, specificity, repeatability, and intermediate precision of SYP detection and CTC enumeration. Single-cell SYP mean fluorescence intensities (MFI) were analyzed to determine protein expression levels. An MFI threshold for SYP positivity was established by maximizing the classification accuracy of the positive and negative cell lines. Using this threshold, 98.7% of 22Rv1 cells were correctly classified as SYP-positive, and 99.7% of BT474 cells were correctly classified as SYP-negative with an inter-run coefficient of variation of 13.9% for the 22Rv1 cell line. In clinical prostate, breast and colon cancer patient samples, subsets of CTCs were found to be SYP positive with the expected cytoplasmic localization of the marker. In summary, this liquid biopsy assay provides an analytically sensitive and specific method for CTC enumeration and SYP biomarker expression analysis, allowing non-invasive detection of neuroendocrine differentiation. Citation Format: Jennifer Chow, A Anders Tevis, Edward Lo, Alisa Clein, Daniel E. Sabath, Arturo B. Ramirez, Eric P. Kaldjian, Tad George. Liquid biopsy for neuroendocrine differentiation: Validation of a circulating tumor cell assay for synaptophysin [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 600.
THE MUNICIPALIZATION OF HOSPITALS: THE BRADFORD EXPERIMENT
Authors: C. Buttar
Journal: BMJ (1920)

<h3>Abstract</h3> Dynamical systems on graphs allow to describe multiple phenomena from different areas of Science. In particular, many complex systems in Ecology are studied by this approach. In this paper we analize the mathematical framework for the study of the structural stability of each stationary point, feasible or not, introducing a generalization for this concept, defined as <i>Global Structural Stability</i>. This approach would fit with the proper mathematical concept of structural stability, in which we find a full description of the complex dynamics on the phase space due to nonlinear dynamics. This fact can be analyzed as an informational field grounded in a global attractor whose structure can be completely characterized. These attractors are stable under perturbation and suppose the minimal structurally stable sets. We also study in detail, mathematically and computationally, the zones characterizing different levels of biodiversity in bipartite graphs describing mutualistic antagonistic systems of population dynamics. In particular, we investigate the dependence of the region of maximal biodiversity of a system on its connectivity matrix. On the other hand, as the network topology does not completely determine the robustness of the dynamics of a complex network, we study the correlation between structural stability and several graph measures. A systematic study on synthetic and biological graphs is presented, including 10 mutualistic networks of plants and seed-dispersal and 1000 random synthetic networks. We compare the role of centrality measures and modularity, concluding the importance of just cooperation strength among nodes when describing areas of maximal biodiversity. Indeed, we show that cooperation parameters are the central role for biodiversity while other measures act as secondary supporting functions. <h3>Author summary</h3> We introduce the concept of Global Structural Stability as a proper mathematical concept to fully understand biodiversity in some ecological systems. Our concept retakes the definitions in the classical works of R. Thom [1] and Andronov-Pontryagin [2]. Moreover, there exists a close relation between the structure of a complex network, described as a graph, and its associated dynamics. Mutualistic networks introduce cooperation links between two groups of species, as plant and pollinators or seed-dispersal. The understanding of organizational aspects leading to maximizing biodiversity is one of the more important research areas in Theoretical and Applied Ecology. In this work we introduce a systematic study on different graph measures in order to identify optimal organization for maximal biodiversity (defined as structural stability). Our results conclude that, for mutualistic systems, the strength in cooperation parameters are the core fact, i.e., cooperation is the real fact optimizing biodiversity among other possible structural configurations.
Abstract 730: Annual hazard rate of recurrence in Middle-Eastern papillary thyroid cancer over a long-term follow-up
Authors: Abdul K. Siraj, Sandeep K. Parvathareddy, Zeeshan Qadri, Saud Azam, Felisa De Vera, Maha Al-Rasheed, Wael Haqawi, Hassan AlDossari, Khawla S. Al-Kuraya
Journal: Cancer Research (2021)

Abstract Predicting the pattern of recurrence is necessary to establish optimal surveillance and treatment strategies. We identified patient population that remain at risk for an event and clarify changes in the hazard rate (HR) for tumor recurrence overtime in Middle Eastern patients with Papillary Thyroid Cancer (PTC). Data for 1201 PTC patients from single institute with median follow-up of 9.5 years were analyzed. Estimated HR were plotted overtime for the entire cohort, as well as for radioactive iodine (RAI) ablation in patients separately. The changes in risk were further analyzed according to clinical variable and factors predictive of early (≤ 5years) and late (&amp;gt;5 years) recurrence were explored using Cox regression analysis. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 - 2 years (3.7%), with a second smaller peak between 13 - 14 years (3.2%). Patients receiving RAI therapy had a lower hazard of recurrence compared to those who did not receive RAI therapy (1.5% vs 2.7%, p = 0.0001). Importantly, this difference was significant even in the intermediate-risk PTC patients (0.7% vs 2.3%; p = 0.0001). Interestingly, PTC patients who were male, aged ≥ 55 years, with lymph node involvement and advanced stage disease were still at high risk for late recurrence. In conclusion, we confirmed the validity of double-peaked time-varying pattern for risk of recurrence in Middle-Eastern PTC patients. Furthermore, according to the time distribution of recurrence hazard, we could formulate individualized treatment and surveillance plans in PTC patients. Citation Format: Abdul K. Siraj, Sandeep K. Parvathareddy, Zeeshan Qadri, Saud Azam, Felisa De Vera, Maha Al-Rasheed, Wael Haqawi, Hassan AlDossari, Khawla S. Al-Kuraya. Annual hazard rate of recurrence in Middle-Eastern papillary thyroid cancer over a long-term follow-up [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 730.
Abstract LB182: Vaccination by liposomes and synthetic short peptide eradicated HPV-associated tumor
Authors: Xuedan He, Shiqi Zhou, Breandan Quinn, Dushyant Jahagirdar, Joaquin Ortega, Scott I. Abrams, Jonathan F. Lovell
Journal: Cancer Research (2021)

Abstract Human papilloma virus (HPV)-16 is associated with cervical cancers and induces expression of the E6 and E7 oncogenes. 6 major histocompatibility complex (MHC) class I (MHC-I) epitopes were predicted to be immunogenic by sequencing a murine cell line that expresses E6/E7. A liposomal vaccine made of cobalt-porphyrin-phospholipid (CoPoP) and synthetic 9-mer epitopes appended with 3 histidine residues, resulting in rapid formation of stable peptide-liposome particles. Immunization with these predicted 6 peptides led to protection from tumor challenge on mice. Of the 6 peptides screened, only the previously identified E749-57 epitope has anti-tumor efficacy. The peptide-liposome particles that formed upon mixing E7HHH49-57 with CoPoP liposomes were stable in serum and avidly taken up by immune cells in vitro and rapidly released in lysosome. As a prophylactic vaccine, liposomal E7HHH49-57 vaccine protected mice from tumor challenge and re-challenge. As a therapeutic vaccine, immunization with the synthetic short peptide at a dose of 100 ng protected mice when admixed with CoPoP liposomes, whereas 200-fold higher peptide doses were ineffective with the Poly(I:C) adjuvant. CoPoP induced strong infiltrating CD8+ T response within the tumor microenvironment with improved functional profile. Vaccine monotherapy using nanogram dosing of the E7HHH49-57 peptide admixed with CoPoP reversed the growth of large established tumors, permanently eradicating subcutaneous tumors upwards of 100 mm3, and also completely eradicated lung tumors in a metastasis model. Citation Format: Xuedan He, Shiqi Zhou, Breandan Quinn, Dushyant Jahagirdar, Joaquin Ortega, Scott I. Abrams, Jonathan F. Lovell. Vaccination by liposomes and synthetic short peptide eradicated HPV-associated tumor [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 LB182.