tbuckley/cabot-search huggingface dataset:
Abstract 1611: A novel anti-human CD47 antibody prodrug as cancer therapeutics to lower on-target side effects
Authors: Richard Zhang, Hunter Drobenaire, Huey Li, Veronica Pizzarella, Haishan Lin
Journal: Cancer Research (2021)

Abstract CD47 is highly expressed in many types of cancers, including human acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL), and solid tumors such as small-cell lung cancer (SCLC). Binding of CD47 to its receptor, SIRPα, on macrophages leads to inhibition of macrophage activation and phagocytosis. CD47 overexpression is one of the mechanisms cancer cells employ to evade immune surveillance and correlates with poor prognosis in cancers. Several strategies have been used to block CD47 binding to SIRPα, including anti-CD47 blocking antibodies and SIRPα-Fc fusion proteins. However, since CD47 is also expressed on normal cells, a major concern is that anti-CD47 antibodies could also cause on-target side effects, such as red blood cell hemagglutination and anemia. We have identified a panel of high affinity anti-human CD47 blocking antibodies. The lead antibodies bound to human CD47 with sub-nanomolar affinities and displayed a range of activities in blocking CD47:SIRPα interaction. These antibodies showed robust activities in stimulating macrophage-mediated phagocytosis of cancer cells. To minimize the on-target side effects of anti-CD47 antibodies, we have taken an antibody prodrug approach in which the antibody is inactive for normal cells while it becomes functional in the tumor microenvironment enriched with proteases. By screening a phage peptide library, we identified peptides that specifically block the anti-CD47 antibody binding activity. These peptides were fused to the humanized anti-CD47 antibody via a linker containing protease substrate sequences to derive the anti-CD47 antibody prodrug. We demonstrated that the anti-CD47 antibody prodrug lacked CD47 binding activity and was unable to block CD47:SIRPα interaction. Upon cleavage of the anti-CD47 antibody prodrug with proteases, the antibody regained full activities in both CD47 binding and blocking CD47:SIRPα interaction. Importantly, we showed that the anti-CD47 antibody prodrug had minimal hemagglutination and RBC binding activities. These data suggest that the novel anti-CD47 antibody prodrug is a promising candidate for the next generation anti-CD47 therapeutics with improved safety profile. Citation Format: Richard Zhang, Hunter Drobenaire, Huey Li, Veronica Pizzarella, Haishan Lin. A novel anti-human CD47 antibody prodrug as cancer therapeutics to lower on-target side effects [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 1611.
Abstract 12453: A Mood Stabilizer Inflames the Pericardium
Authors: Wajdi Bader, Muhammad Siddiqui, Mohammad Alaoua, Jasmine Botello
Journal: Circulation (2019)

Introduction: Lamotrigine is an anticonvulsant used in treating bipolar disorder. In addition, it is a medication that can be associated with infrequent but severe side effects such as HLH, DRESS, ...
Risks and benefits of phase I liver dysfunction studies: Should patients with severe liver dysfunction be included in these trials?
Authors: Selena Juarez Stuart, John Sarantopoulos, Anand B. Karnad, Devalingam Mahalingam, Sukeshi R. Patel, Steven D. Weitman
Journal: Journal of Clinical Oncology (2014)

2536 Background: Liver dysfunction studies on novel oncologic agents are necessary to evaluate effects of metabolism and pharmacokinetics, but data regarding risks and benefits of these trials in cancer patients with liver dysfunction is lacking. Our objective was to evaluate clinical benefit rates (CBR), death on study (DOS) rates, and rates of G3/4 toxicity for patients enrolled on liver dysfunction Phase I studies. Methods: We performed a retrospective review of non-pediatric Phase I hepatic dysfunction studies in patients with solid tumors from 2003-2013 at a single institution. We report the CBR, defined as response rate (RR) plus rate of stable disease (SD), rates of DOS from all causes, and rates of drug related G3/4 toxicity. Results: We analyzed 10 trials involving a total of 126 patients. In 9 of the 10 studies, patients were stratified based on degree of hepatic dysfunction according to the NCI Organ Dysfunction Working Group (NCI-ODWG) criteria. The most common tumor types were colorectal cancer (37%), hepatocellular carcinoma (18%), pancreatic adenocarcinoma (7%), and lung cancer (5%). Median age was 58 years (23-81). Liver dysfunction was from liver metastases in 61% and underlying cirrhosis in 19%. Therapeutic classes included targeted therapies in 7 trials and cytotoxics in 3 studies. The ORR among all patients was 2% (CR 0%/PR 2%). An additional 21% of patients had SD. The overall DOS rate was 15%. Overall G3/4 toxicity rate was 34% with hematologic toxicity being most common (21%). The CBR, DOS rates, and G3/4 toxicity rates were calculated for each group of patients by degree of liver dysfunction (see Table). Conclusions: In patients with severe liver dysfunction, CBR from Phase I studies was <1% while risk of death on study was 25%. Therefore, patients with severe liver dysfunction may not be ideal candidates for these types of trials. Further analysis of the data is needed to identify prognostic factors that further predict risk of death on study. Degree of liver dysfunction # of patients (%) CBR (%) DOS rate (%) #cycles completed median (range) G3/4 toxicity (%) Normal 17 (13) 53 12 4 (1-62) 24 Mild 40 (32) 30 10 2 (1-26) 48 Moderate 48 (38) 13 17 1 (1-10) 33 Severe 20 (16) <1 25 1 (1-4) 15
Radical hemiscrotectomy and en-bloc orchidectomy: Surgical technique, perioperative and oncologic outcomes of a supra-regional UK referral centre
Authors: C.D. Fankhauser, A. Issa, E.W.C. Lee, C. Oing, P. Oliveira, A. Parnham, J. Oates, V. Sangar, A. Gulamhusein, N.W. Clarke
Journal: European Urology (2021)
Choosing Wisely for COVID-19: ten evidence-based recommendations for patients and physicians
Authors: C. S. Pramesh, Giridhara R. Babu, Joyeeta Basu, Indu Bhushan, Christopher M. Booth, Girish Chinnaswamy, Randeep Guleria, S. P. Kalantri, Gagandeep Kang, Pavitra Mohan, Nachiket Mor, Madhukar Pai, Manu Prakash, Priscilla Rupali, Priya Sampathkumar, Manju Sengar, Richard Sullivan, Priya Ranganathan
Journal: Nature Medicine (2021)
Abstract 2931: Pharmacological inhibition of 17β-hydroxysteroid dehydrogenase impairs endometrial cancer growth in an orthotopic xenograft mouse model
Authors: Sofia Xanthoulea, Gonda Konings, Niina Saarinen, Bert Delvoux, Loes Kooreman, Pasi Koskimies, Merja Häkkinen, Seppo Auriola, Elisabetta d'Avanzo, Youssef Walid, Frank Verhaegen, Natasja Lieuwes, Florian Caiment, Roy Kruitwagen, Andrea Romano
Journal: Cancer Research (2021)

Abstract Endometrial cancer (EC) is the most common gynaecological tumor in developed countries and its incidence is increasing. Approximately 80% of newly diagnosed EC cases are estrogen-dependent. Type 1 17β-hydroxysteroid dehydrogenase (17β-HSD-1) is the enzyme that catalyzes the final step in estrogen biosynthesis by reducing the weak estrogen estrone (E1) to the potent estrogen 17β-estradiol (E2), and previous studies showed that this enzyme is implicated in the local E2 generation in EC. In the present study we employed a recently developed orthotopic and estrogen-dependent xenograft mouse model of EC to show that pharmacological inhibition of the 17β-HSD-1 enzyme inhibits disease development. Tumors were induced in one uterine horn of athymic nude mice by intra-uterine injection of the well-differentiated human endometrial adenocarcinoma Ishikawa cell line that was modified to express 17β-HSD-1 in levels comparable to humans and, in addition, the luciferase and green fluorescent protein reporter genes. After tumor engraftment, controlled estrogen exposure was achieved using subcutaneous MedRod implants that released either E1 or placebo. A subgroup of the E1 supplemented mice received daily gavage of FP4643, a well characterized 17β-HSD-1 inhibitor. Bioluminescence imaging (BLI) was used to measure tumor growth non-invasively. At sacrifice, mice receiving E1 and treated with the FP4643 inhibitor showed a significant reduction in tumor growth by approximately 65% compared to mice receiving E1 alone. Tumors exhibited metastatic spread to the peritoneum, to the lymphovascular space (LVI) and to the thoracic cavity. Metastatic spread and LVI were both reduced in the inhibitor treated group. Transcriptional profiling of tumors indicated that FP4643 treatment reduced the oncogenic potential at the mRNA level. In conclusion, we show that the FP4643 inhibition represents a potential promising novel endocrine treatment for EC Citation Format: Sofia Xanthoulea, Gonda Konings, Niina Saarinen, Bert Delvoux, Loes Kooreman, Pasi Koskimies, Merja Häkkinen, Seppo Auriola, Elisabetta d'Avanzo, Youssef Walid, Frank Verhaegen, Natasja Lieuwes, Florian Caiment, Roy Kruitwagen, Andrea Romano. Pharmacological inhibition of 17β-hydroxysteroid dehydrogenase impairs endometrial cancer growth in an orthotopic xenograft mouse model [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 2931.
Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer
Authors: Christian Rolfo, Philip Mack, Giorgio V. Scagliotti, Charu Aggarwal, Maria E. Arcila, Fabrice Barlesi, Trever Bivona, Maximilian Diehn, Caroline Dive, Rafal Dziadziuszko, Natasha Leighl, Umberto Malapelle, Tony Mok, Nir Peled, Luis E. Raez, Lecia Sequist, Lynette Sholl, Charles Swanton, Chris Abbosh, Daniel Tan, Heather Wakelee, Ignacio Wistuba, Rebecca Bunn, Janet Freeman-Daily, Murry Wynes, Chandra Belani, Tetsuya Mitsudomi, David Gandara
Journal: Journal of Thoracic Oncology (2021)
Automated sizing of colorectal polyps using computer vision
Authors: Mohamed Abdelrahim, Hiroyasu Saiga, Naoto Maeda, Ejaz Hossain, Hitoshi Ikeda, Pradeep Bhandari
Journal: Gut (2021)

Colorectal polyp size is an important biomarker that influences management decisions, but currently used subjective methods are flawed. We explored two computer vision (CV) techniques for binary classification of polyp size as either ≤5 mm or >5 mm. First, we used premeasured phantom polyps (22 such polyps’ videos) fixed on a pig colon model to explore the concept of automated sizing using structure from motion (SfM) approach and compared it with the sizing by 10 independent endoscopists: overall, average diagnostic accuracy of the SfM system (85.2%) was superior to endoscopists judgement (59.5%). Second, we developed a deep learning model based on convolutional neural networks (CNN) and found 80% accuracy in 10 videos of human polyps. Real-time automated polyp sizing when combined with artificial intelligence (AI) assissted polyp characterisation could improve polyp management strategies.

### CV techniques

CV can be defined as the ability of machines to process and understand visual data, automating the type of tasks the human eye would normally be required to do. In order to perform automated polyp size classification, we employed two types of CV techniques, SfM and deep learning (DL).

SfM is a photogrammetric imaging technique that algorithmically recovers three-dimensional (3D) structure of an object from multiple two-dimensional (2D) images and is commonly used in topographic studies. SfM finds matching points in input images and recovers the 3D structure by solving the epipolar constraint equation derived from these matching points, as briefly illustrated in figure 1. The algorithm calculates a camera’s pose as a rotation matrix and a translation vector using matching points. Finally, we apply mathematical formulas to compute the distance between the polyp and endoscope, and that distance is used to compute polyp size in real time. Compared with DL, this SfM technique uses less data making it relatively easier and quicker to convert into a clinical …
A French cohort for assessing COVID-19 vaccine responses in specific populations
Authors: Paul Loubet, Linda Wittkop, Eric Tartour, Beatrice Parfait, Benoit Barrou, Jean-Yves Blay, Maryvonne Hourmant, Marie Lachâtre, David-Axel Laplaud, Martine Laville, Bruno Laviolle, Jean-Daniel Lelievre, Jacques Morel, Stéphanie Nguyen, Jean-Philippe Spano, Benjamin Terrier, Anne Thiebaut, Jean-Francois Viallard, François Vrtovsnik, Xavier de Lamballerie, Odile Launay
Journal: Nature Medicine (2021)
Active surveillance for prostate cancer: Comparison between incidental tumors vs. tumors diagnosed at prostate biopsies
Authors: M.L. Piccinelli, S. Luzzago, M. Fontana, F.M.G. Botticelli, F.A. Mistretta, M. Catellani, E. Di Trapani, R. Bianchi, G. Cozzi, A. Cioffi, P. Pricolo, S. Alessi, G. Cordima, M. Ferro, D.V. Matei, G. Petralia, G. Musi, O. De Cobelli
Journal: European Urology (2021)
Abstract 3027: Role of BCOR in retinoblastoma
Authors: Michelle Garying Zhang, Dawn Owens, Stefan Kurtenbach, Jeffim Kuznetsov, Matthew Fields, Daniel Pelaez, James W. Harbour
Journal: Cancer Research (2021)

Abstract Retinoblastoma, which is usually initiated by the biallelic mutational inactivation of RB1, is the most common primary eye cancer in children and is fatal if left untreated. While retinoblastoma is initially sensitive to chemotherapy, it demonstrates a strong propensity for therapeutic escape, which is a leading cause of ocular morbidity, eye loss, and reduced survival. This problem is exacerbated by a poor understanding of how retinoblastoma progresses after the initial loss of RB1. Genomic analysis of primary retinoblastoma tumors has revealed the corepressor BCOR as the second most common target of mutations in retinoblastoma. Here, we explored the role of BCOR in normal retinal development to provide insights into its role in retinoblastoma. Mass spectrometry following immunoprecipitation of wildtype BCOR in primary retinoblastoma cells revealed novel BCOR interacting proteins in the Polycomb and MiDAC epigenetic complexes. Subsequent studies revealed potential functional consequences of BCOR mutation that may promote retinoblastoma progression. This work reveals new insights the role of epigenetic deregulation in retinoblastoma progression, and they nominate new candidates for therapeutic intervention. Citation Format: Michelle Garying Zhang, Dawn Owens, Stefan Kurtenbach, Jeffim Kuznetsov, Matthew Fields, Daniel Pelaez, James W. Harbour. Role of BCOR in retinoblastoma [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 3027.
Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study
Authors: Reimar Wernich Thomsen, Anders Hammerich Riis, Esben Meulengracht Flachs, David H Garabrant, Jens Peter Ellekilde Bonde, Henrik Toft Sørensen
Journal: Thorax (2021)

Introduction The risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems. Methods We examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services). Results Our study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes. Conclusions We found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.
Variations of urodynamic parameters and bladder contractility in women with idiopathic OAB undergoing Onabotulinum Toxin A injection. A prospective multi-institutional study
Authors: G.D. De Rienzo, P. Minafra, E. Costantini, E. Illiano, E. Finazzi Agrò, M. Serati, A. Giammò, V. Pastoressa, F.P. Bianchi, P. Ditonno
Journal: European Urology (2021)
Abstract 948: Preclinical evaluation of VEGF Ang2 bispecific nanobody BI836880 in patient-derived xenograft models of nasopharyngeal carcinoma
Authors: Eric Chi Wong, Gigi Lam, Connie Wong, Rachel C. Lam, Kwok Wai Lo, Edwin Pun Hui, Anthony Tak Chan, Brigette B. Ma
Journal: Cancer Research (2021)

Abstract BI836880 is a humanized bispecific nanobody directed against angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF)-derived peptides, with selective and potent antiangiogenic and antineoplastic activities. It comprises of blocking domains that bind to Ang2 and VEGF and prevents Ang2- and VEGF-mediated signalling; thus, inhibits both angiogenesis and tumour cell proliferation. Tumor angiogenesis contributes to progression of nasopharyngeal cancer (NPC) and VEGF/receptor inhibitors agents have activity in NPC patients. In this study, the preclinical activity of a novel VEGF/Ang-2 bi-specific nanobody, BI836880, was evaluated in two NPC-PDX models - Xeno-2117 and Xeno-666. The effect of BI836880 on tumor growth was compared with the control, bevacizumab - an anti-VEGF antibody which has been evaluated in NPC patients. Tumor-bearing mice were randomized into three groups: vehicle control, 15mg/kg bevacizumab (b.i.w) and 15mg/kg BI836880 (b.i.w.). Drug was administered by intraperitoneal injection and the treatment duration was four weeks. Tumor sizes and body weights were monitored by caliper and balance, respectively. The results showed that BI836880 was very well tolerated in mice, with no signs of stress and loss of weight observed during the treatment. At day 14, the mean tumor volumes of BI836880, bevacizumab vs vehicle control was 264.5±36.0, 290.0±32.4 vs 697.38±88.4 mm3 in Xeno-666 (p&amp;lt;0.001, BI836880 vs control), and 293.5±39.3, 319.6±37.6 vs 1016.8±107.6 mm3 in Xeno-2117 (p&amp;lt;0.0001, BI836880 vs control), respectively. Angiogenesis marker CD34 was analyzed by IHC staining and the microvessel densities were calculated by Image J. The results showed that BI836880 could significantly reduce the numbers of microvessels to a comparable extent as bevacizumab in NPC model. In addition, BI836880 had increased the tumor internal necrotic area by 118.7% compared to vehicle control in Xeno-2117 (p=0.0148), but the effect was insignificant in Xeno-666 (p=0.5467). In conclusion, BI836880 can inhibit NPC growth to an extent that is comparable to bevacizumab, further investigation in combination with cytotoxic or immunotherapeutic agents are warranted. Citation Format: Eric Chi Wong, Gigi Lam, Connie Wong, Rachel C. Lam, Kwok Wai Lo, Edwin Pun Hui, Anthony Tak Chan, Brigette B. Ma. Preclinical evaluation of VEGF Ang2 bispecific nanobody BI836880 in patient-derived xenograft models of nasopharyngeal 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 948.
Sequential Chemoradiotherapy vs Concurrent Chemoradiotherapy or Radiotherapy Alone in Adjuvant Treatment for Patients With Cervical Cancer
Authors: Sezin Yuce Sari, Alper Kahvecioglu, Ferah Yildiz
Journal: JAMA Oncology (2021)

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The diagnostic value of [18F]-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) for urachal cancer
Authors: L.E. Stokkel, M.P. Stokkel, M.L. Donswijk, M.J. Lahaye, B.W.G. Van Rhijn, L.S. Mertens
Journal: European Urology (2021)
Abstract 12144: Thirty-day Readmissions After Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure: Insights From the National Readmissions Database
Authors: Fabio V Lima, Kevin Kennedy, Lauren Rousseau, Antony F Chu
Journal: Circulation (2019)

Introduction: Catheter ablation (CA) is an established treatment for symptomatic atrial fibrillation (AF) resistant to medical therapy. In heart failure (HF), CA is associated with improved long-te...