tbuckley/cabot-search huggingface dataset:
MUC1-specific immunity and tumor inhibition induced by a recombinant BCG-MUC1-IL2 cancer vaccine in a MUC1-Tg mouse model.
Authors: Jianbo He, Dejun Shen, Scott Chandler, Helena R. Chang
Journal: Cancer Research (2004)

2160  We have constructed a recombinant vaccine BCG-MUC1-IL2, which expresses high level of human MUC1 VNTR core protein and secretes functional IL2. MUC1 is a breast cancer-associated antigen that is known to stimulate immunological responses in human. Interleukin 2 (IL2) is a lymphocyte activator and growth factor. BCG is a strong immune adjuvant that has been used safely and effectively in preventing tuberculosis and treating multiple human cancers. We hypothesized that, by combining the cancer-associated antigen with immunologic activators, recombinant BCG-MUC1-IL2 will augment the MUC1-specific immune responses and tumor inhibition. A mouse melanoma cell line transfected with human MUC1 (B16/hMUC1) grown in a human MUC1 transgenic mouse (MUC1-Tg) was selected for testing this hypothesis. The mice were immunized subcutaneously with 3×104 CFU of BCG-MUC1-IL2 and boosted four weeks later. The immunized animals were then challenged with 1,000 B16/hMUC1 melanoma cells the day after the last immunization. Control animals received either BCG-vector or PBS according to the same schedule. The tumor growths in all three groups were monitored. The animals were sacrificed when the tumor reached the maximal allowed size or four weeks after control animal died of tumor growth. The splenocytes and serum were collected from individual animals and were used to study the MUC1-specific immunities by ELISPOT and ELISA. We found that mice immunized with BCG-MUC1-IL2 had significant delay in tumor appearance. The mice in PBS group all developed tumors (four out of four) in three weeks and were scarificed by the fifth week because tumor reached the maximum size (1.5 cm3) allowed by the approved protocol. Mice in the BCG-vector group developed tumor one week later than PBS group. In BCG -MUC1-IL2 group, only one mouse developed tumor after fifth week and no tumor was observed in remaining three mice. These mice were sacrificed for immunological study at the end of eighth week after tumor challenge. The BCG-MUC1-IL2 vaccine mediated immunity was determined by ELISPOT and ELISA. The results of ELISPOT indicated that the MUC1-specific INF-γ expressing splenocytes were increased only in mice immunized with BCG-MUC1-IL2, but not in mice treated with BCG-vector or PBS. The IL4 expressing splenocytes were induced by both BCG-MUC1-IL2 and BCG-vector. A high level of MUC1-specific IgG production was detected by ELISA in BCG-MUC1-IL2 group. These results suggest that the recombinant BCG-MUC1-IL2 induces not only MUC1-specific cellular and humoral immune responses but also tumor inhibition and it may serve as a vaccine for breast cancer prevention and treatment.
Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study
Authors: Christoph U. Correll, John W. Newcomer, Bernard Silverman, Lauren DiPetrillo, Christine Graham, Ying Jiang, Yangchun Du, Adam Simmons, Craig Hopkinson, David McDonnell, René S. Kahn
Journal: American Journal of Psychiatry (2020)

A combination of olanzapine and the opioid receptor antagonist samidorphan is under development for the treatment of schizophrenia and bipolar I disorder. The single-tablet combination treatment is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. In this phase 3 double-blind trial, the authors evaluated the weight profile of combined olanzapine/samidorphan compared with olanzapine in patients with schizophrenia.Adults (ages 18‒55 years) with schizophrenia were randomly assigned to receive either combination treatment with olanzapine and samidorphan or olanzapine treatment for 24 weeks. Primary endpoints were percent change from baseline in body weight and proportion of patients with ≥10% weight gain at week 24. The key secondary endpoint was the proportion of patients with ≥7% weight gain. Waist circumference and fasting metabolic laboratory parameters were also measured.Of 561 patients who underwent randomization (olanzapine/samidorphan combination, N=280; olanzapine, N=281), 538 had at least one postbaseline weight assessment. At week 24, the least squares mean percent weight change from baseline was 4.21% (SE=0.68) in the olanzapine/samidorphan group and 6.59% (SE=0.67) in the olanzapine group (the difference of -2.38% [SE=0.76] was significant). Significantly fewer patients in the olanzapine/samidorphan combination group compared with the olanzapine group had weight gain ≥10% (17.8% and 29.8%, respectively; number needed to treat [NNT]=7.29; odds ratio=0.50) and weight gain ≥7% (27.5% and 42.7%, respectively; NNT=6.29; odds ratio=0.50). Increases in waist circumference were smaller in the olanzapine/samidorphan combination group compared with the olanzapine group. Schizophrenia symptom improvement was similar between treatment groups. Adverse events (in ≥10% of the groups) in the olanzapine/samidorphan and olanzapine groups included weight gain (24.8% and 36.2%), somnolence (21.2% and 18.1%), dry mouth (12.8% and 8.0%), and increased appetite (10.9% and 12.3%). Metabolic changes were small and similar between treatments.Olanzapine/samidorphan combination treatment was associated with significantly less weight gain and smaller increases in waist circumference than olanzapine and was well tolerated. The antipsychotic efficacy of the combination treatment was similar to that of olanzapine monotherapy.
Oncologist Burnout Syndrome in Eastern Europe: Results of the Multinational Survey
Authors: Davor Kust, Jure Murgić, Petra Vuković, Ivan Kruljac, Marin Prpić, Ana Zilić, Csongor Lengyel, Kamil Wdowiak, Linda Simaskaite, Ulug Mutlu Gunaydin, Ivana Tica Sedlar, Elena Fountzilas, Urska Janzic, Iulia Coroian, Ivana Durutovic, Pellegrino, Benedetta, Mila Petrova, Emiljana Huti, Elena Napolskaia, Bostjan Seruga, Antonija Balenović, Ana Frobe, Krešimir Luetić
Journal: Journal of Clinical Oncology (2020)
Abstract IA17: Patient-derived organoid models of bladder cancer
Authors: Michael M. Shen
Journal: Clinical Cancer Research (2020)

Abstract The molecular mechanisms of bladder tumorigenesis are poorly understood, in part due to the lack of suitable model systems that reflect the biology of human bladder cancer. In our studies, we have used three-dimensional culture approaches to establish a novel biobank of human patient-derived organoids from primary bladder tumors. These organoid lines recapitulate the histopathologic and molecular diversity of non-muscle invasive bladder cancer as well as muscle-invasive bladder cancer, and can be readily converted into xenografts by orthotopic transplantation. These organoid lines can be propagated by serial passaging in culture while maintaining their tumor properties and display mutational profiles that are highly concordant with their parental tumors. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Furthermore, we have shown that these organoid lines are highly amenable for analyses of drug response, which can be validated in vivo using orthotopic xenografts. I will discuss our recent findings using patient-derived tumor organoid lines to investigate bladder cancer biology and drug response, including ongoing analyses of tumor plasticity and the basis for tumor recurrence. Citation Format: Michael M. Shen. Patient-derived organoid models of bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA17.
Penetrating Injuries from “Less Lethal” Beanbag Munitions
Authors: Kristofor A Olson, Laura E Haselden, R Daniel Zaunbrecher, Adam Weinfeld, Lawrence H Brown, Jason A Bradley, Tatiana C P Cardenas, Marc D Trust, Ben Coopwood, Pedro G Teixeira, Carlos V R Brown, Jayson D Aydelotte
Journal: New England Journal of Medicine (2020)

Penetrating Injuries from “Less Lethal” Beanbag Munitions This report from a level 1 trauma center located near the site of protests describes several serious injuries resulting from use of beanbag...
Ozone: a natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders
Authors: Catia Scassellati, Antonio Carlo Galoforo, Cristian Bonvicini, Ciro Esposito, Giovanni Ricevuti
Journal: Ageing Research Reviews (2020)

Systems medicine is founded on a mechanism-based approach and identifies in this way specific therapeutic targets. This approach has been applied for the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Nrf2 plays a central role in different pathologies including neurodegenerative disorders (NDs), which are characterized by common pathogenetic features. We here present wide scientific background indicating how a natural bioactive molecule with antioxidant/anti-apoptotic and pro-autophagy properties such as the ozone (O3) can represent a potential new strategy to delay neurodegeneration. Our hypothesis is based on different evidence demonstrating the interaction between O3 and Nrf2 system. Through a meta-analytic approach, we found a significant modulation of O3 on endogenous antioxidant-Nrf2 (p < 0.00001, Odd Ratio (OR) = 1.71 95%CI:1.17-2.25) and vitagene-Nrf2 systems (p < 0.00001, OR = 1.80 95%CI:1.05-2.55). O3 activates also immune, anti-inflammatory signalling, proteasome, releases growth factors, improves blood circulation, and has antimicrobial activity, with potential effects on gut microbiota. Thus, we provide a consistent rationale to implement future clinical studies to apply the oxygen-ozone (O2-O3) therapy in an early phase of aging decline, when it is still possible to intervene before to potentially develop a more severe neurodegenerative pathology. We suggest that O3 along with other antioxidants (polyphenols, mushrooms) implicated in the same Nrf2-mechanisms, can show neurogenic potential, providing evidence as new preventive strategies in aging and in NDs.
Abstract 6483: Performance characteristics of the first FDA-cleared droplet digital PCR (ddPCR) IVD assay for monitoring chronic myelogenous leukemia
Authors: Dawne N. Shelton, Prasanthi Bhagavatula, Nathan Sepulveda, Lan Beppu, Jerald Radich
Journal: Cancer Research (2020)

Abstract Introduction: Chronic myelogenous leukemia (CML) is a cancer of myeloid cells that accounts for 15-20% of all cases of leukemia. Most CML cases are caused by a translocation between chromosomes 9 and 22 which creates an abnormal fusion gene, BCR-ABL1. The BCR-ABL1 gene expresses an abnormal tyrosine kinase protein that causes unregulated growth and survival of granulocytes. CML is treated with TKIs (tyrosine kinase inhibitors). The concentration of BCR-ABL1 transcript RNA is a marker of disease progression and the effectiveness of TKI treatment.Bio-Rad's QXDx BCR-ABL %IS Kit is an in vitro diagnostic test for the quantification of BCR-ABL transcripts in total RNA from whole blood from individuals diagnosed with Chronic Myeloid Leukemia expressing BCR-ABL1 Fusion transcript types e13a2 and/or e14a2. Materials and Methods: The QXDx BCR-ABL %IS Kit is a newly launched FDA-approved ddPCR assay from Bio-Rad Laboratories. Reproducibility of results across multiple sites, days, instruments, and users was evaluated using contrived samples consisting of BCR-ABL positive patient samples mixed with negative patient samples. Clinical performance of the kit was evaluated on patient samples, and compared to an already existing FDA-approved test. Clinical performance was further tested in the College of American Pathologists challenge. Results: The reproducibility study noted negligible contributions to variance from site, instrument, day, and user for samples spanning from MR 0.7-4.2. The mean between the QXDx™ BCR-ABL %IS Kit and the comparator test using a Bland-Altman analysis was 0.16 MR units. The limits of agreement between the two methods indicate that the difference between the two methods should be between 0.47 and -0.14 MR on 95% of tested samples. The QXDx™ BCR-ABL %IS assay demonstrated excellent correlation with the comparator test using a Weighted Deming regression with a Pearson R correlation coefficient of 0.99, slope 1.037 and intercept of 0.1084. College of American Pathologists(CAP) challenges (n=6) were conducted from 2016-2019, QXDx™ BCR-ABL %IS system results were regressed vs the mean values published by CAP yielded a slope of 1 and R2=0.99. Conclusions: The QXDx™ BCR-ABL %IS Kit on the QXDx™ AutoDG™ Droplet Digital PCR System can be used safely and effectively in the laboratory on t(9;22) positive CML patients for monitoring of treatment with Tyrosine Kinase Inhibitors (TKIs). Citation Format: Dawne N. Shelton, Prasanthi Bhagavatula, Nathan Sepulveda, Lan Beppu, Jerald Radich. Performance characteristics of the first FDA-cleared droplet digital PCR (ddPCR) IVD assay for monitoring chronic myelogenous leukemia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6483.
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Authors: Steven P Marso, Anders G Holst, Tina Vilsbøll
Journal: New England Journal of Medicine (2017)

To the Editor: In reporting the results of the Trial to Evaluate Cardiovascular and Other Longterm Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6), Marso et al. (Nov.10 issue) 1 describe a lower rate of cardiovascular events among patients with type 2 diabetes mellitus who received the glucagon-like peptide 1 (GLP-1) analogue semaglutide than among patients who received placebo.Their results are consistent with those in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, 2 which assessed the effects of another GLP-1 analogue, liraglutide.In SUSTAIN-6, the use of insulin at trial entry was similar between the two groups.However, during the LEADER trial, the use of insulin was approximately two times higher in the placebo group than in the liraglutide group, and during SUSTAIN-6, the use of insulin was approximately three times higher in the placebo group than in the semaglutide group.The significantly greater use of insulin in the placebo groups in these two trials may, at least in part, explain the increase in the risk of death from any cause as well as the increase in the risks of heart failure, cardiovascular events, renal failure, and hypoglycemia in these two groups.Hazard ratios for these events associated with increased use of insulin range from 1.23 to 4.57, as shown in two cohort studies in primary care. 3,4Thus, we wonder whether the greater use of insulin in the placebo groups than in the liraglutide and semaglutide groups during these trials may have amplified the beneficial effects of liraglutide and semaglutide.
Life and Death of Selfish Genes: Comparative Genomics Reveals the Dynamic Evolution of Cytoplasmic Incompatibility
Authors: Julien Martinez, Lisa Klasson, John J Welch, Francis M Jiggins
Journal: Molecular Biology and Evolution (2020)

Abstract Cytoplasmic incompatibility is a selfish reproductive manipulation induced by the endosymbiont Wolbachia in arthropods. In males Wolbachia modifies sperm, leading to embryonic mortality in crosses with Wolbachia-free females. In females, Wolbachia rescues the cross and allows development to proceed normally. This provides a reproductive advantage to infected females, allowing the maternally transmitted symbiont to spread rapidly through host populations. We identified homologs of the genes underlying this phenotype, cifA and cifB, in 52 of 71 new and published Wolbachia genome sequences. They are strongly associated with cytoplasmic incompatibility. There are up to seven copies of the genes in each genome, and phylogenetic analysis shows that Wolbachia frequently acquires new copies due to pervasive horizontal transfer between strains. In many cases, the genes have subsequently acquired loss-of-function mutations to become pseudogenes. As predicted by theory, this tends to occur first in cifB, whose sole function is to modify sperm, and then in cifA, which is required to rescue the cross in females. Although cif genes recombine, recombination is largely restricted to closely related homologs. This is predicted under a model of coevolution between sperm modification and embryonic rescue, where recombination between distantly related pairs of genes would create a self-incompatible strain. Together, these patterns of gene gain, loss, and recombination support evolutionary models of cytoplasmic incompatibility.
Infertile Men Have Higher Prostate-specific Antigen Values than Fertile Individuals of Comparable Age
Authors: Luca Boeri, Paolo Capogrosso, Walter Cazzaniga, Eugenio Ventimiglia, Edoardo Pozzi, Federico Belladelli, Nicolò Schifano, Luigi Candela, Massimo Alfano, Filippo Pederzoli, Costantino Abbate, Emanuele Montanari, Luca Valsecchi, Enrico Papaleo, Paola Viganò, Patrizia Rovere-Querini, Francesco Montorsi, Andrea Salonia
Journal: European Urology (2020)
Common Susceptibility Loci for Male Breast Cancer
Authors: Sarah Maguire, Eleni Perraki, Katarzyna Tomczyk, Michael E Jones, Olivia Fletcher, Matthew Pugh, Timothy Winter, Kyle Thompson, Rosie Cooke, Alison Trainer, Paul James, Stig Bojesen, Henrik Flyger, Heli Nevanlinna, Johanna Mattson, Eitan Friedman, Yael Laitman, Domenico Palli, Giovanna Masala, Ines Zanna, Laura Ottini, Valentina Silvestri, Antoinette Hollestelle, Maartje J Hooning, Srdjan Novaković, Mateja Krajc, Manuela Gago-Dominguez, Jose Esteban Castelao, Hakan Olsson, Ingrid Hedenfalk, Emmanouil Saloustros, Vasilios Georgoulias, Douglas F Easton, Paul Pharoah, Alison M Dunning, D Timothy Bishop, Susan L Neuhausen, Linda Steele, Alan Ashworth, Montserrat Garcia Closas, Richard Houlston, Anthony Swerdlow, Nick Orr
Journal: JNCI Journal of the National Cancer Institute (2020)

The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC.
Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden
Authors: Long H Nguyen, Anne K Örtqvist, Yin Cao, Tracey G Simon, Bjorn Roelstraete, Mingyang Song, Amit D Joshi, Kyle Staller, Andrew T Chan, Hamed Khalili, Ola Olén, Jonas F Ludvigsson
Journal: The Lancet. Gastroenterology & hepatology (2020)
Abstract 6471: Variable expression of ZEB-1, Bcl-2, and E-cadherin in human hepatocholangio and renal cell carcinomas
Authors: Joeffrey J. Chahine, Kyungmin Ko, Bhaskar VS Kallakury, Pamela L. Tuma
Journal: Cancer Research (2020)

Abstract Although Epithelial-Mesenchymal Transition (EMT) in cancers remains controversial, its relevance in tumor progression is a subject of investigation. The presence of cellular changes associated with EMT in bladder tumor progression have been well investigated, unlike other human carcinomas with very little data available to date. ZEB-1 which targets E-Cadherin repression is a transcriptional regulator that has been implicated in EMT, and its nuclear expression in tumor cells has been associated with aggressive malignancies in some types of cancer. Recently, it was also reported that ZEB-1 inhibits the expression of proapoptotic factor B-cell lymphoma (Bcl)-2 interacting mediator of cell death (BIM) by binding directly to the BIM promoter and repressing its transcription. We tested this hypothesis with a human cohort of 24 Cholangiocarcinoma (CC), 18 Hepatocellular (HCC) and 31 Renal Cell (RCC) human carcinomas. Formalin fixed paraffin embedded tissue sections containing benign and tumor lesions were immunostained using the Dako Autostainers Link 48 along with ZEB-1 monoclonal OT13G6 (ABCAM), Bcl-2 monoclonal 124 (Agilent, Dako), and E-Cadherin monoclonal NCH-38 (Agilent, Dako) antibodies. Nuclear, membraneous and/or cytoplasmic immunoreactivity was scored based on the intensity and percentage of positive cells in both the benign epithelium and adjacent tumor in each case. E-Cadherin was highly expressed in both the adjacent benign and malignant components with no significant variability in all three carcinomas, with ZEB-1 and Bcl-2 evaluated for the any positivity staining in both components for all cases. Results are detailed in the table below.All positive ZEB-1 cases in HCC were in high grade cases unlike the positive ZEB-1 in RCC which were in low grade cases. But more noticeably, 8/10 (80%) positive ZEB-1 were also positive for Bcl-2 in all three carcinoma types. Despite the small number of cases analyzed in this cohort a trend in the expression of ZEB-1 and its co-expression with BCL-2 may have some prognostic implications. We are currently extending this analysis to a larger number of CC, HCC, and RCC to closely examine the significance of ZEB-1, and Bcl-2 expression across differently graded lesions to further test our hypothesis. Citation Format: Joeffrey J. Chahine, Kyungmin Ko, Bhaskar VS Kallakury, Pamela L. Tuma. Variable expression of ZEB-1, Bcl-2, and E-cadherin in human hepatocholangio and renal cell carcinomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6471.
Abstract 14630: The Predictive Factors Affecting Diagnostic Accuracy in On-Site Operated Novel CT-Fractional Flow Reserve Based on Fluid & Structrual Interaction
Authors: Etsuro Kato, Shinichiro Fujimoto, Yuko Kawaguchi, Kanako Kumamaru, Tomotaka Dohi, Kazuhisa Takamura, Chihiro Aoshima, Makoto Hiki, Yoshiteru Kato, Shinya Okazaki, Hiroyuki Daida
Journal: Circulation (2017)

Introduction: Using fluid and structural interaction in multiple cardiac phases into consideration, a novel algorism of CT-FFR analysis which enables to set conditions which are specific for indivi...