tbuckley/cabot-search huggingface dataset:
Lactate Consumption via Cascaded Enzymes Combined VEGF siRNA for Synergistic Anti‐Proliferation and Anti‐Angiogenesis Therapy of Tumors
Authors: Yan Tang, Changhao Jia, Yu Wang, Wenjun Wan, Hui Li, Gui Huang, Xuenong Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract Lactate, as the most abundant component with concentrations of 4–40 m m in tumors, contributes to the regulation of metabolic pathways, angiogenesis, and immunosuppression, exhibiting remarkable potential in cancer treatment. Therefore, a codelivery strategy that combined the cascaded enzymes Lactate oxidase/Catalase (LOx/CAT) and vascular endothelial growth factor (VEGF) siRNA (siVEGF) to suppress tumor proliferation and angiogenesis synergistically is creatively proposed. In brief, the cationic liposomes (LIP) encapsulated with LOx/CAT and siVEGF via hydrophilic interaction and electrostatic adsorption followed by coating with PEGylated phenylboronic acid (PP) is established (PPL@[LOX+CAT]). Moreover, a simple 3‐aminophenylboronic acid (PBA)‐shielded strategy via fructose (Fru) is applied to further enhance the targeting efficiency in the tumor site. The obtained co‐encapsulated nanoparticles (NPs) can simultaneous intracellular release of LOx/CAT and siVEGF, and the collaborative use of LOx and CAT can promote lactate consumption even under a hypoxic tumor microenvironment (TME) without producing systemic toxicity. The combined application of lactate depletion and VEGF silencing demonstrated the efficient migration suppression of 4T1 cells in vitro and superior antitumor and antimetastatic properties in vivo. This work offers a promising tumor treatment strategy via integrating cascaded enzymes and gene therapy, and explores a promising therapy regimen for 4T1 triple‐negative breast cancer.
P56-7 A case of Nuclear protein in testis (NUT) midline carcinoma with response to Ewing sarcoma-based chemotherapy regimen
Authors: Yuki Nakatani, Yuko Akaisi, Furutama Junko, Asuka Okada, Kohei Akiyoshi, Shinya Tokunaga, Gen Kawa, Haruko Daga
Journal: Annals of Oncology (2021)
Autosomic dominant polycystic kidney disease and metformin: Old knowledge and new insights on retarding progression of chronic kidney disease
Authors: Alessandro Casarella, Ramona Nicotera, Maria T. Zicarelli, Alessandra Urso, Pierangela Presta, Francesca Deodato, Davide Bolignano, Giovambattista De Sarro, Michele Andreucci, Emilio Russo, Giuseppe Coppolino
Journal: Medicinal Research Reviews (2021)

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most common congenital kidney disorder, generally caused by mutations in the PKD1 and PKD2 genes, coding for polycystins 1 and 2. Its pathogenesis is accompanied by alterations of the cAMP, mTOR, MAPK/ERK, and JAK/STAT pathways. ADPKD is clinically characterized by the formation of many growing cysts with kidney enlargement and a progressive damage to the parenchyma, up to its complete loss of function, and the onset of end‐stage renal disease (ESRD). The current aim of ADPKD therapy is the inhibition of cyst development and retardation of chronic kidney disease progression. Several drugs have been recently included as potential therapies for ADPKD including metformin, the drug of choice for the treatment of type 2 diabetes mellitus, according to its potential inhibitory effects on cystogenesis. In this review, we summarize preclinical and clinical evidence endorsing or rejecting metformin administration in ADPKD evolution and pathological mechanisms. We explored the biology of APDKD and the role of metformin in slowing down cystogenesis searching PubMed and Clinical Trials to identify relevant data from the database inception to December 2020. From our research analysis, evidence for metformin as emerging cure for ADPKD mainly arise from preclinical studies. In fact, clinical studies are still scanty and stronger evidence is awaited. Its effects are likely mediated by inhibition of the ERK pathway and increase of AMPK levels, which are both linked to ADPKD pathogenesis.
The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey
Authors: Simon Mark Dahl Baunwall, Elisabeth M Terveer, Jens Frederik Dahlerup, Christian Erikstrup, Perttu Arkkila, Maria JGT Vehreschild, Gianluca Ianiro, Antonio Gasbarrini, Harry Sokol, Patrizia K Kump, Reetta Satokari, Danny De Looze, Séverine Vermeire, Radislav Nakov, Jan Brezina, Morten Helms, Jens Kjeldsen, Anne A Rode, Sabrina Just Kousgaard, Laurent Alric, Caroline Trang-Poisson, Julien Scanzi, Alexander Link, Andreas Stallmach, Juozas Kupcinskas, Peter Holger Johnsen, Kjetil Garborg, Eugenia Sánchez Rodríguez, Lena Serrander, Robert J Brummer, Katerina Tatiana Galpérine, Simon D Goldenberg, Benjamin H Mullish, Horace RT Williams, Tariq H Iqbal, Cyriel Ponsioen, Ed J Kuijper, Giovanni Cammarota, Josbert J Keller, Christian Lodberg Hvas
Journal: The Lancet Regional Health - Europe (2021)

Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).
Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA
Authors: Michele Cavo, Jesus San-Miguel, Saad Z. Usmani, Katja Weisel, Meletios A. Dimopoulos, Hervé Avet-Loiseau, Bruno Paiva, Nizar J. Bahlis, Torben Plesner, Vania Hungria, Philippe Moreau, Maria-Victoria Mateos, Aurore Perrot, Shinsuke Iida, Thierry Facon, Shaji Kumar, Niels W. C. J. van de Donk, Pieter Sonneveld, Andrew Spencer, Maria Krevvata, Christoph Heuck, Jianping Wang, Jon Ukropec, Rachel Kobos, Steven Sun, Mia Qi, Nikhil Munshi
Journal: Blood (2021)
Abstract 12290: Effect of High Intensity Interval Training on Extracellular Matrix-regulating Enzymes in Women With Breast Cancer Receiving Anthracycline-based Chemotherapy
Authors: Kyuwan Lee, Christina Dieli-Conwright
Journal: Circulation (2019)

Introduction: Increased levels of certain extracellular matrix (ECM)-regulating enzymes contribute to the development of atherosclerosis. Anthracycline chemotherapy is commonly used in all stages o...
MO20-2 Phase I study of BI 754091 plus BI 754111 in Asian patients with gastric/gastroesophageal junction or esophageal cancer
Authors: Do-Youn Oh, Yoon-Koo Kang, Kensei Yamaguchi, Shunsuke Kondo, Sun Young Rha, Yasutoshi Kuboki, Manabu Morimoto, Hiroki Hara, Chia-Chi Lin, Yoshifumi Tachibana, Jianrui Hou, Mabrouk Elgadi, Shigehisa Kitano
Journal: Annals of Oncology (2021)
Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy
Authors: Yuhan Zhou, Ting Ye, Chengzhi Ye, Chao Wan, Siyue Yuan, Yushuai Liu, Tianyu Li, Fagang Jiang, Jonathan F. Lovell, Honglin Jin, Jing Chen
Journal: Bioactive Materials (2021)

Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl). In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia, cisplatin, radiotherapy or photodynamic therapy. To improve HOCl-CDS activity at the tumor site, we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold. When injected intratumorally, the HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration, and tumor-associated macrophage reprogramming towards an M1 phenotype. The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-F10 melanoma. Furthermore, hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade. These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.
Preparing for the NASH Epidemic: A Call to Action
Authors: Fasiha Kanwal, Jay H. Shubrook, Zobair Younossi, Yamini Natarajan, Elisabetta Bugianesi, Mary E. Rinella, Stephen A. Harrison, Christos Mantzoros, Kim Pfotenhauer, Samuel Klein, Robert H. Eckel, Davida Kruger, Hashem El-Serag, Kenneth Cusi
Journal: Diabetes Care (2021)

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common conditions with a rising burden. Yet there are significant management gaps between clinical guidelines and practice in patients with NAFLD and NASH. Further, there is no single global guiding strategy for the management of NAFLD and NASH. The American Gastroenterological Association, in collaboration with 7 professional associations, convened an international conference comprising 32 experts in gastroenterology, hepatology, endocrinology, and primary care providers from the United States, Europe, Asia, and Australia. Conference content was informed by the results of a national NASH Needs Assessment Survey. The participants reviewed and discussed published literature on global burden, screening, risk stratification, diagnosis, and management of individuals with NAFLD, including those with NASH. Participants identified promising approaches for clinical practice and prepared a comprehensive, unified strategy for primary care providers and relevant specialists encompassing the full spectrum of NAFLD/NASH care. They also identified specific high-yield targets for clinical research and called for a unified, international public health response to NAFLD and NASH.
<i>Chop</i> / <i>Ddit3</i> depletion in β cells alleviates ER stress and corrects hepatic steatosis in mice
Authors: Jing Yong, Vishal S. Parekh, Shannon M. Reilly, Jonamani Nayak, Zhouji Chen, Cynthia Lebeaupin, Insook Jang, Jiangwei Zhang, Thazha P. Prakash, Hong Sun, Sue Murray, Shuling Guo, Julio E. Ayala, Leslie S. Satin, Alan R. Saltiel, Randal J. Kaufman
Journal: Science Translational Medicine (2021)

Depletion of Chop in pancreatic β cells optimizes insulin secretion and reduces fatty liver in preclinical models.
Efficacy and safety of <scp>CD19</scp>‐directed <scp>CAR‐T</scp> cell therapies in patients with relapsed/refractory aggressive B‐cell lymphomas: Observations from the <scp>JULIET</scp>, <scp>ZUMA</scp>‐1, and <scp>TRANSCEND</scp> trials
Authors: Jason R. Westin, Marie José Kersten, Gilles Salles, Jeremy S. Abramson, Stephen J. Schuster, Frederick L. Locke, Charalambos Andreadis
Journal: American Journal of Hematology (2021)

Abstract Chimeric antigen receptor (CAR)‐T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B‐cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR‐T cell products for patients with high‐grade B‐cell lymphomas or diffuse large B‐cell lymphoma (DLBCL) who are relapsed or refractory to ≥ 2 prior lines of therapy; lisocabtagene maraleucel was approved in 2021. Safety and efficacy outcomes from the pivotal trials of each CAR‐T cell therapy have been reported. Despite addressing a common unmet need in the large B‐cell lymphoma population and utilizing similar CAR technologies, there are differences between CAR‐T cell products in manufacturing, pivotal clinical trial designs, and data reporting. Early reports of commercial use of axicabtagene ciloleucel and tisagenlecleucel provide the first opportunities to validate the impact of patient characteristics on the efficacy and safety of these CAR‐T cell therapies in the real world. Going forward, caring for patients after CAR‐T cell therapy will require strategies to monitor patients for sustained responses and potential long‐term side effects. In this review, product attributes, protocol designs, and clinical outcomes of the key clinical trials are presented. We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world. Finally, we discuss postinfusion management and preview upcoming clinical trials of CAR‐T cell therapies.
Single-Cell Long Non-Coding RNA Landscape of T Cells in Human Cancer Immunity
Authors: Haitao Luo, Dechao Bu, Lijuan Shao, Yang Li, Liang Sun, Ce Wang, Jing Wang, Wei Yang, Xiaofei Yang, Jun Dong, Yi Zhao, Furong Li
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep understanding of T cells. To date, the complete landscape and systematic characterization of long noncoding RNAs (lncRNAs) in T cells in cancer immunity are lacking. Here, by systematically analyzing full-length single-cell RNA sequencing (scRNA-seq) data of more than 20,000 libraries of T cells across three cancer types, we provided the first comprehensive catalog and the functional repertoires of lncRNAs in human T cells. Specifically, we developed a custom pipeline for de novotranscriptome assembly and obtained a novel lncRNA catalog containing 9433 genes. This increased the number of current human lncRNA catalog by 16% and nearly doubled the number of lncRNAs expressed in T cells. We found that a portion of expressed genes in single T cells were lncRNAs which had been overlooked by the majority of previous studies. Based on metacell maps constructed by the MetaCell algorithm that partitions scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNA genes were identified. They were associated with effector, exhausted, and regulatory T cell states. Moreover, 84 of them were functionally annotated based on the co-expression networks, indicating that lncRNAs might broadly participate in the regulation of T cell functions. Our findings provide a new point of view and resource for investigating the mechanisms of T cell regulation in cancer immunity as well as for novel cancer-immune biomarker development and cancer immunotherapies
SARS-CoV-2-specific cellular and humoral immunity in COVID-19 convalescence after liver transplantation
Authors: T. Kirchner, H. Sauer, A. Bonifacius, R. Louisa, I. Pink, B. Engel, E. Saunders, J. Martens, M. M. Hoeper, R. Blasczyk, H. Wedemeyer, E. Jaeckel, C. Falk, B. Eiz-Vesper, R. Taubert
Journal: Journal of Hepatology (2021)
Endothelial cell infection and dysfunction, immune activation in severe COVID-19
Authors: Zhongnan Qin, Fengming Liu, Robert Blair, Chenxiao Wang, Haoran Yang, Joseph Mudd, Joshua M Currey, Naoki Iwanaga, Jibao He, Ren Mi, Kun Han, Cecily C. Midkiff, Mohammad Afaque Alam, Bertal H Aktas, Richard S Vander Heide, Ronald Veazey, Giovanni Piedimonte, Nicholas J Maness, Süleyman Ergün, Franck Mauvais-Jarvis, Jay Rappaport, Jay K. Kolls, Xuebin Qin
Journal: Theranostics (2021)

Rationale: Pulmonary vascular endotheliitis, perivascular inflammation, and immune activation are observed in COVID-19 patients.While the initial SARS-CoV-2 infection mainly infects lung epithelial cells, whether it also infects endothelial cells (ECs) and to what extent SARS-CoV-2-mediated pulmonary vascular endotheliitis is associated with immune activation remain to be determined.Methods: To address these questions, we studied SARS-CoV-2-infected K18-hACE2 (K18) mice, a severe COVID-19 mouse model, as well as lung samples from SARS-CoV-2-infected nonhuman primates (NHP) and patient deceased from COVID-19.We used immunostaining, RNAscope, and electron microscopy to analyze the organs collected from animals and patient.We conducted bulk and single cell (sc) RNA-seq analyses, and cytokine profiling of lungs or serum of the severe COVID-19 mice.Results: We show that SARS-CoV-2-infected K18 mice develop severe COVID-19, including progressive body weight loss and fatality at 7 days, severe lung interstitial inflammation, edema, hemorrhage, perivascular inflammation, systemic lymphocytopenia, and eosinopenia.Body weight loss in K18 mice correlated with the severity of pneumonia, but not with brain infection.We also observed endothelial activation and dysfunction in pulmonary vessels evidenced by the up-regulation of VCAM1 and ICAM1 and the downregulation of VE-cadherin.We detected SARS-CoV-2 in capillary ECs, activation and adhesion of platelets and immune cells to the vascular wall of the alveolar septa, and increased complement deposition in the lungs, in both COVID-19-murine and NHP models.We also revealed that pathways of coagulation, complement, K-ras signaling, and genes of ICAM1 and VCAM1 related to EC dysfunction and injury were upregulated, and were associated with massive immune activation in the lung and circulation.
The Need for Life-Course Study of Children Born to Mothers With Prior COVID-19 Infection
Authors: John McCarthy, Diane Liu, Frederick Kaskel
Journal: JAMA Pediatrics (2021)

The Need for Life-Course Study of Children Born to Mothers With Prior COVID-19 Infection Of the pandemics faced by the US in the 20th century, none were more severe than the influenza A/PR/8/34 (H1N1) outbreak of 1918-the so-called Spanish influenza.Emerging during World War I, this pandemic is estimated to have infected nearly one-third of the global population and killed approximately 50 million people, including 675 000 people in the US.While the pandemic was brief, some individuals experienced reaching effects.Women infected with the flu during pregnancy had children found to have higher rates of heart disease, kidney disease, and diabetes throughout their life course. 1The implications of such findings hold relevance today, as the novel coronavirus SARS-CoV-2 has spread throughout the world.Given the effects observed in the 1918 pandemic and reported birth outcomes related to maternal COVID-19 infection, it is prudent to use the lessons and epidemiology of the 1918 pandemic to inform practice and follow-up of potential long-term health effects associated with maternal COVID-19 infection.The 1918 influenza was unusual in the vigor with which it affected young adults, but other populations were not spared-including fetuses in utero.Birth rates declined along with an increased rate in stillbirths, but carrying a pregnancy to birth did not ensure that born children avoided the effects of influenza.Rates of congenital malformation and premature birth increased during all waves of the pandemic, contributing to increased infant mortality rates during the spring 1919 wave. 2 Premature birth from any cause is a risk for associated conditions, such as kidney or heart disease, later in life, 3,4 compounded by any risk that may be associated with in utero exposure to maternal infection.Like the influenza of 1918, maternal COVID-19 infection during pregnancy has been associated with increased risk of neonatal and perinatal complications.Notably, premature birth rates in mothers infected with COVID-19 have been observed to be significantly elevated from their pre-COVID-19 rate, and low birth weight in children of mothers infected with COVID-19 has also been observed, 5 although little evidence has supported that neonates are at major risk of direct harm through processes like vertical transmission. 6owever, such outcomes could have long-term effects even in the absence of direct neonatal infection.The Barker hypothesis postulates that interruptions in normal in utero development can have lasting health effects specific to the organ systems developing at that time. 3For example, the heart develops during the first trimester, and as such, children of mothers infected with a disease during this time may bear a higher risk of cardiovascular disease later in life.Conversely, children of mothers infected with a disease in their third trimester, VIEWPOINT
Comparison of best supportive care, CHOP, or R-CHOP for treatment of diffuse large B-cell lymphoma in Malawi: a cost-effectiveness analysis
Authors: Matthew S Painschab, Racquel Kohler, Stephen Kimani, Wilberforce Mhango, Bongani Kaimila, Takondwa Zuze, Victor Mithi, Edwards Kasonkanji, Noel Mumba, Richard Nyasosela, Stephanie Wheeler, Satish Gopal
Journal: The Lancet Global Health (2021)

Cost-effectiveness data for cancer treatment are needed from sub-Saharan Africa, where diffuse large B-cell lymphoma (DLBCL) is a common, curable cancer. In high-income countries, the standard of care for DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemoimmunotherapy. Rituximab is often not available in sub-Saharan Africa due to perceived unaffordability, and treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) is common. We aimed to evaluate the cost-effectiveness of treatment in Malawi, comparing best supportive care, CHOP, or R-CHOP in patients with DLBCL. For this cost-effectiveness analysis, we used published Malawi microcosting data, clinical data from a prospective cohort treated with CHOP, and clinical trial data evaluating R-CHOP. We used a decision-tree model to calculate costs per disability-adjusted life-year (DALY) averted from the health system perspective for the treatment of patients with DLBCL with best supportive care, CHOP, or R-CHOP, running the model on a per-patient basis and a Malawi population-level basis. We used the WHO definitions of cost-effective (three times the GDP per capita of the country) and extremely cost-effective (equal to the GDP per capita of the country) as willingness-to-pay thresholds for Malawi. On a per-patient level, compared with best supportive care, CHOP was estimated to avert a mean 7·4 DALYs at an incremental cost of US$1384, for an incremental cost-effectiveness ratio (ICER) of $189 per DALY averted, which is substantially lower than the willingness-to-pay threshold (extremely cost-effective). Compared with CHOP, R-CHOP was estimated to avert 2·8 DALYs at an incremental cost of $3324, resulting in an ICER of $1204 per DALY averted, which is slightly higher than the cost-effective willingness-to-pay threshold. In probabilistic sensitivity analyses, CHOP remained cost-effective for DLBCL treatment in more than 99% of simulations, whereas R-CHOP was lower than the threshold in 46% of simulations. We estimated CHOP to be cost-effective for DLBCL treatment in Malawi, and that the addition of rituximab might be cost-effective. Despite upfront costs, DLBCL treatment is probably a prudent investment relative to other accepted health interventions in sub-Saharan Africa. National Institutes of Health.