tbuckley/cabot-search huggingface dataset:
Adoptive cell therapy with tumor-infiltrating lymphocytes supported by checkpoint inhibition across multiple solid cancer types
Authors: Anders Handrup Kverneland, Christopher Aled Chamberlain, Troels Holz Borch, Morten Nielsen, Sofie Kirial Mørk, Julie Westerlin Kjeldsen, Cathrine Lund Lorentzen, Lise Pyndt Jørgensen, Lene Buhl Riis, Christina Westmose Yde, Özcan Met, Marco Donia, Inge Marie Svane
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has shown remarkable results in malignant melanoma (MM), while studies on the potential in other cancer diagnoses are sparse. Further, the prospect of using checkpoint inhibitors (CPIs) to support TIL production and therapy remains to be explored. Study design TIL-based ACT with CPIs was evaluated in a clinical phase I/II trial. Ipilimumab (3 mg/kg) was administered prior to tumor resection and nivolumab (3 mg/kg, every 2 weeks ×4) in relation to TIL infusion. Preconditioning chemotherapy was given before TIL infusion and followed by low-dose (2 10e6 international units (UI) ×1 subcutaneous for 14 days) interleukin-2 stimulation. Results Twenty-five patients covering 10 different cancer diagnoses were treated with in vitro expanded TILs. Expansion of TILs was successful in 97% of recruited patients. Five patients had sizeable tumor regressions of 30%–63%, including two confirmed partial responses in patients with head-and-neck cancer and cholangiocarcinoma. Safety and feasibility were comparable to MM trials of ACT with the addition of expected CPI toxicity. In an exploratory analysis, tumor mutational burden and expression of the alpha-integrin CD103 (p=0.025) were associated with increased disease control. In vitro tumor reactivity was seen in both patients with an objective response and was associated with regressions in tumor size (p=0.028). Conclusion High success rates of TIL expansion were demonstrated across multiple solid cancers. TIL ACTs were found feasible, independent of previous therapy. Tumor regressions after ACT combined with CPIs were demonstrated in several cancer types supported by in vitro antitumor reactivity of the TILs. Trial registration numbers NCT03296137 , and EudraCT No. 2017-002323-25.
Design, synthesis and structure activity relationship within a series of pyrimidopyrimidine dual DKR/FGFR tyrosine kinase inhibitors.
Authors: P. Rossman, K. Luk, J. Cai, Y. Chen, A. Daniewski, A. Dermatakis, T. Flynn, L. Garofalo, P. Gillespie, R. Goodnow, B. Graves, W. Harris, N. Huby, N. Jackson, M. Kabat, F. Konzelmann, S. Li, Jj Liu, W. Liu, C. Lukacs, C. Michoud, A. Perrotta, L. Portland
Journal: Cancer Research (2004)

2478  The pyrimidopyrimidine moiety represents a core structure that is a useful template for the design of a variety of tyrosine kinase inhibitors. From high throughput screening, a pyrimidopyrimidine analogue was identified as a dual inhibitor of the growth factor receptors KDR (IC50 = 40 nM) and FGFR-1 (IC50 = 210 nM). This analogue was a significantly less potent inhibitor of other kinases tested (LCK, IC50 = 8 μM; CDK2 and p38, IC50 > 25 μM). The crystal structure of the src-family tyrosine kinase LCK with a closely related analogue bound was determined, elucidating the binding mode of the pyrimidopyrimidines. From these data, the ligand was docked into the ATP binding pocket of KDR. Based on this model a series of analogues were designed and synthesized to study the structure activity relationship. These compounds showed excellent activity in in vitro kinase assays and also in growth-factor stimulated HUVEC proliferation assays. In vivo experiments demonstrated significant inhibition of angiogenesis in the corneal pocket assay (CPA) and tumor growth inhibition in xenograft models for a number of these compounds. Structure activity relationship of these pyrimidopyrimidine compounds will be discussed.
Site-specific PEGylation of interleukin-2 enhances immunosuppression via the sustained activation of regulatory T cells
Authors: Bo Zhang, Jiaqi Sun, Yan Wang, Dezhong Ji, Yeshuang Yuan, Shengjie Li, Yeting Sun, Yingqin Hou, Pengchong Li, Lidan Zhao, Fei Yu, Wenxiao Ma, Boyang Cheng, Ling Wu, Jin Hu, Min Wang, Wei Song, Xiaogang Li, Hao Li, Yunyun Fei, Hua Chen, Lihe Zhang, George C. Tsokos, Demin Zhou, Xuan Zhang
Journal: Nature Biomedical Engineering (2021)
299P MicroRNAs-449 regulate doxorubicin response through ACSL4 modulation in TNBC
Authors: S. Torres Ruiz, I. Garrido Cano, R. Cervera Vidal, C. Hernando Melia, M.T.M. Martinez, S. Zazo, O. Burgués, F. Rojo Todo, B. Bermejo, A. Lluch-Hernandez, J.M. Cejalvo Andujar, P. Eroles, E. Tormo Martin
Journal: Annals of Oncology (2021)
Targeting cholesterol homeostasis in hematopoietic malignancies
Authors: Andrea Brendolan, Vincenzo Russo
Journal: Blood (2021)

Cholesterol is a vital lipid for cellular functions. It is necessary for membrane biogenesis, cell proliferation, and differentiation. In addition to maintaining cell integrity and permeability, increasing evidence indicates a strict link between cholesterol homeostasis, inflammation, and hematological tumors. This makes cholesterol homeostasis an optimal therapeutic target for hematopoietic malignancies. Manipulating cholesterol homeostasis by either interfering with its synthesis or activating the reverse cholesterol transport via the engagement of liver X receptors affects the integrity of tumor cells both in vitro and in vivo. Cholesterol homeostasis has also been manipulated to restore antitumor immune responses in preclinical models. These observations have prompted clinical trials involving acute myeloid leukemia to test the combination of chemotherapy with drugs interfering with cholesterol synthesis (ie, statins). We review the role of cholesterol homeostasis in hematopoietic malignancies as well as in cells of the tumor microenvironment and discuss the potential use of lipid modulators for therapeutic purposes.
Positive rates of various clinical parameters in cardiac sarcoidosis
Authors: A Uemura, Shin-ichiro Morimoto, Shinya Hiramitsu, Masatsugu Ohtsuki, Yasuchika Katoh, Shigeru Katoh, Atsushi Sugiura, Kenji Miyagishima, Nami Mori, Hitoshi Hishida
Journal: Circulation (2004)
71P Searching for predictive biomarkers of efficacy in small cell lung cancer (SCLC) patients treated with chemotherapy-immunotherapy combination using imaging mass cytometry (the HYPE study)
Authors: P. Le Noac'h, P. Hemon, D. Benguigui, G. Robinet, R. Descourt, G. Quere, H. Babey, J. Annic, A. Bourhis, U. Schick, J-O. Pers, A. Uguen, M. Geier
Journal: Annals of Oncology (2021)
Drainage for Infected Pancreatic Necrosis — Is the Waiting the Hardest Part?
Authors: Todd H. Baron
Journal: New England Journal of Medicine (2021)

Acute necrotizing pancreatitis, which occurs in up to 30% of episodes of acute pancreatitis, can be a devastating, life-threatening disease. For many years, acute necrotizing pancreatitis (the cause of clinically severe pancreatitis) was managed with open surgical necrosectomy. Surgeons eventually realized that necrosectomy was largely not beneficial for patients with sterile necrosis and that delay in surgery to allow for demarcation of the necrotic process from healthy, viable tissue resulted in better outcomes, including lower surgical mortality.1 The focus then shifted to recognition of and intervention for infected necrosis, as well as determination of the appropriate timing of surgery. Parallel . . .
Peptide-based nanomaterials: Self-assembly, properties and applications
Authors: Tong Li, Xian-Mao Lu, Ming-Rong Zhang, Kuan Hu, Zhou Li
Journal: Bioactive Materials (2021)

Peptide-based materials that have diverse structures and functionalities are an important type of biomaterials. In former times, peptide-based nanomaterials with excellent stability were constructed through self-assembly. Compared with individual peptides, peptide-based self-assembly nanomaterials that form well-ordered superstructures possess many advantages such as good thermo- and mechanical stability, semiconductivity, piezoelectricity and optical properties. Moreover, due to their excellent biocompatibility and biological activity, peptide-based self-assembly nanomaterials have been vastly used in different fields. In this review, we provide the advances of peptide-based self-assembly nanostructures, focusing on the driving forces that dominate peptide self-assembly and assembly mechanisms of peptides. After that, we outline the synthesis and properties of peptide-based nanomaterials, followed by the applications of functional peptide nanomaterials. Finally, we provide perspectives on the challenges and future of peptide-based nanomaterials.
I期非小細胞肺癌への小分割定位照射(HypoFXSRT):日本での多施設試験257例の最新結果
Authors: Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, Niibe Y, Karasawa K, Hayakawa K, Takai Y, Kimura T, Takeda A, Ouchi A, Hareyama M, Kokubo M, Hara R, Itami J, Yamada K, Araki T
Journal: Journal of Thoracic Oncology (2007)
Tetralogy of Fallot
Authors: Y. d’Udekem, C. Ovaert, F. Grandjean, V. Gerin, M. Cailteux, P. Shango-Lody, A. Vliers, T. Sluysmans, A. Robert, J. Rubay
Journal: Circulation (2000)

Background —In tetralogy of Fallot, transannular patching is suspected to be responsible for late right ventricular dilatation. Methods and Results —In our institution, 191 patients survived a tetralogy of Fallot repair between 1964 and 1984. Transannular patching was used in 99 patients (52%), patch closure of a right ventriculotomy in 35, and direct closure of a right ventriculotomy in 55. Two had a transatrial-transpulmonary approach. To identify predictive factors of adverse long-term outcome related to right ventricular dilatation, the following events were investigated: cardiac death, reoperation for symptomatic right ventricular dilatation, and NYHA class II or III by Cox regression analysis. Mean follow-up reached 22±5 years. The 30-year survival was 86±5%. Right ventricular patching, whether transannular or not, was the most significant independent predictor of late adverse event (improvement χ 2 =16.6, P &lt;0.001). In patients who had direct closure, the ratio between end-diastolic right and left ventricular dimensions on echocardiography was smaller (0.61±0.017 versus 0.75±0.23, P =0.007), with a smaller proportion presenting severe pulmonary insufficiency (9% versus 40%, P =0.005). There was no difference between right ventricular and transannular patching concerning late outcome (log rank P value=0.6), right ventricular size (0.70±0.28 versus 0.76±0.26, P =0.4), or incidence of severe pulmonary insufficiency (30% versus 43%, P =0.3). Conclusions —In tetralogy of Fallot, transannular patching does not result in a worse late functional outcome than patching of an incision limited to the right ventricle. Both are responsible for a similar degree of long-term pulmonary insufficiency and right ventricular dilatation.
Combined inhibition of CXCL12 and PD-1 in MSS colorectal and pancreatic cancer: modulation of the microenvironment and clinical effects
Authors: Meggy Suarez-Carmona, Anja Williams, Jutta Schreiber, Nicolas Hohmann, Ulrike Pruefer, Jürgen Krauss, Dirk Jäger, Anna Frömming, Diana Beyer, Dirk Eulberg, Jarf Ulf Jungelius, Matthias Baumann, Aram Mangasarian, Niels Halama
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immunotherapy in microsatellite stable colorectal or pancreatic cancer has not shown promising results. It has been hypothesized that targeting immunosuppressive molecules like SDF1-alpha/CXCL12 could contribute to immunotherapy and animal models showed promising results on T cell activation and migration in combination with immune checkpoint inhibition. Methods Here, we describe the successful application of anti-CXCL12 (NOX-A12) in patients with advanced stage pretreated metastatic colorectal and pancreatic cancer (OPERA trial). The treatment consisted of 2 weeks of anti-CXCL12 monotherapy with NOX-A12 followed by combination therapy with pembrolizumab (n=20 patients) until progression or intolerable toxicity had occurred. Results The treatment was safe and well tolerated with 83.8% grade I/II, 15.5% grade III and 0.7% grade V adverse events. Of note, for a majority of patients, time on trial treatment was prolonged compared with their last standard treatment preceding trial participation. Systematic serial biopsies revealed distinct patterns of modulation. Tissue and clinical responses were associated with Th1-like tissue reactivity upon CXCL12 inhibition. A downregulation of a cytokine cassette of interleukin (IL)-2/IL-16/CXCL-10 was associated with tumor resistance and furthermore linked to a rare, CXCL12-associated CD14 + CD15 + promonocytic population. T cells showed aggregation and directed movement towards the tumor cells in responding tissues. Serum analyses detected homogeneous immunomodulatory patterns in all patients, regardless of tissue responses. Conclusions We demonstrate that the combination of CXCL12 inhibition and checkpoint inhibition is safe and grants further exploration of synergistic combinatorial strategies.
Tuberculosis outbreak associated with a homeless shelter - Kane County, Illinois, 2007-2011.
Authors: C. Dobbins, K. Marishta, P. Kuehnert, M. Arbisi, E. Darnall, C. Conover, J. Howland, K. Powell, S. Althomsons, S. Bamrah, D. Garrett, M. Haddad
Journal: MMWR Morbidity and Mortality Weekly Report (2012)
Genome edited B cells: a new frontier in immune cell therapies
Authors: Geoffrey L. Rogers, Paula M. Cannon
Journal: Molecular Therapy (2021)

Cell therapies based on reprogrammed adaptive immune cells have great potential as "living drugs." As first demonstrated clinically for engineered chimeric antigen receptor (CAR) T cells, the ability of such cells to undergo clonal expansion in response to an antigen promotes both self-renewal and self-regulation in vivo. B cells also have the potential to be developed as immune cell therapies, but engineering their specificity and functionality is more challenging than for T cells. In part, this is due to the complexity of the immunoglobulin (Ig) locus, as well as the requirement for regulated expression of both cell surface B cell receptor and secreted antibody isoforms, in order to fully recapitulate the features of natural antibody production. Recent advances in genome editing are now allowing reprogramming of B cells by site-specific engineering of the Ig locus with preformed antibodies. In this review, we discuss the potential of engineered B cells as a cell therapy, the challenges involved in editing the Ig locus and the advances that are making this possible, and envision future directions for this emerging field of immune cell engineering.
COVID-19 Vaccines: Adenoviral Vectors
Authors: Catherine Jacob-Dolan, Dan H. Barouch
Journal: Annual Review of Medicine (2021)

The worldwide pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the unprecedented pace of development of multiple vaccines. This review evaluates how adenovirus (Ad) vector platforms have been leveraged in response to this pandemic. Ad vectors have been used in the past for vaccines against other viruses, most notably HIV and Ebola, but they never have been produced, distributed, or administered to humans at such a large scale. Several different serotypes of Ads encoding SARS-CoV-2 Spike have been tested and found to be efficacious against COVID-19. As vaccine rollouts continue and the number of people receiving these vaccines increases, we will continue to learn about this vaccine platform for COVID-19 prevention and control.
Enhanced bone regenerative properties of calcium phosphate ceramic granules in rabbit posterolateral spinal fusion through a reduction of grain size
Authors: Xiangfeng Li, Quan Zhou, Yonghao Wu, Cong Feng, Xi Yang, Linnan Wang, Yumei Xiao, Kai Zhang, Xiangdong Zhu, Limin Liu, Yueming Song, Xingdong Zhang
Journal: Bioactive Materials (2021)

Osteoinductivity is a crucial factor to determine the success and efficiency of posterolateral spinal fusion (PLF) by employing calcium phosphate (Ca-P) bioceramics. In this study, three kinds of Ca-P ceramics with microscale to nanoscale gain size (BCP-control, BCP-micro and BCP-nano) were prepared and their physicochemical properties were characterized. BCP-nano had the spherical shape and nanoscale gain size, BCP-micro had the spherical shape and microscale gain size, and BCP-control (BAM®) had the irregular shape and microscale gain size. The obtained BCP-nano with specific nanotopography could well regulate in vitro protein adsorption and osteogenic differentiation of MC3T3 cells. In vivo rabbit PLF procedures further confirmed that nanotopography of BCP-nano might be responsible for the stronger bone regenerative ability comparing with BCP-micro and BCP-control. Collectedly, due to nanocrystal similarity with natural bone apatite, BCP-nano has excellent efficacy in guiding bone regeneration of PLF, and holds great potentials to become an alternative to standard bone grafts for future clinical applications.
Differences in Breast and Colorectal Cancer Screening Adherence Among Women Residing in Urban and Rural Communities in the United States
Authors: Sanjay Shete, Yangyang Deng, Jackilen Shannon, Babalola Faseru, Deirdre Middleton, Ronaldo Iachan, Brittany Bernardo, Rajesh Balkrishnan, Sunny Jung Kim, Bin Huang, Morgan M. Millar, Bernard Fuemmler, Jakob D. Jensen, Jason A. Mendoza, Jinxiang Hu, DeAnn Lazovich, Linda Robertson, Wendy Demark-Wahnefried, Electra D. Paskett, Abigail Foulds, Andrew Mrkva, Todd Bear, Jian-Min Yuan, Amy Ferketich, Jay Fisher, Timothy Huerta, Ann McAlearney, Darrell Gray, Chasity Washington, Darla Fickle, Heather Aker, Stephanie Dickinson, Chen Lyu, Sina Kianersi, Heather Anderson, Ken Smith, Debra Ma, Helen Lillie, Sean Upshaw, Bassam Dahman, David Wheeler, Tamas Gal, Albert Ksinan, Bonny Morris, Carrie Miller, Elizabeth Do, Kendall Fugate-Laus, Westley Fallavollita, Gordon Ginder, Robert Winn, Thomas Loughran, Mona Fouad, Sejong Bae, Isabel Scarinci, Monica Baskin, Casey Daniel, Claudia Hardy, Paige Farris, Motomi Mori, Zhenzhen Zhang, Stacy McCrea-Robertson, Allen Greiner, David Doody, Roy Jensen, Edward Ellerbeck, Ronald Chen, Hope Krebill, Danny Kurz, Noelle Voges, George Batten, Roger Anderson, Lindsay Hauser, Thomas Guterbock, Rej Desai, Benjamin Haaland
Journal: JAMA Network Open (2021)

Screening for breast and colorectal cancer has resulted in reductions in mortality; however, questions remain regarding how these interventions are being diffused to all segments of the population. If an intervention is less amenable to diffusion, it could be associated with disparities in mortality rates, especially in rural vs urban areas.
1647TiP Antiandrogen therapy and TMPRSS2 status: How prostate cancer patients are protected from COVID-19 pandemic
Authors: M. Claps, E. Jachetti, R. Ferri, F. Badenchini, E. Verzoni, R. Montone, P. Sepe, V. Guadalupi, A. Ottini, G. Baciarello, R. Valdagni, M.P. Colombo, F. de Braud, G. Procopio
Journal: Annals of Oncology (2021)
Intralesional TTI-621, a novel biologic targeting the innate immune checkpoint CD47, in patients with relapsed or refractory mycosis fungoides or Sézary syndrome: a multicentre, phase 1 study
Authors: Christiane Querfeld, John A Thompson, Matthew H Taylor, Jennifer A DeSimone, Jasmine M Zain, Andrei R Shustov, Carolyn Johns, Sue McCann, Gloria H Y Lin, Penka S Petrova, Robert A Uger, Naomi Molloy, Yaping Shou, Oleg E Akilov
Journal: The Lancet Haematology (2021)
1168P Clinical characteristics and survival in stage I-IIIA lung cancer resected patients in Spain, analyzed in the Thoracic Tumors Registry (TTR)
Authors: F.F. Franco, E. Carcereny, R. Lopez Castro, D. Rodriguez, M.A. Cobo Dols, R. Bernabe Caro, A. Blasco Cordellat, B. Massuti Sureda, A.L. Ortega Granados, E. del Barco, J. Bosch-Barrera, M. Guirado, J.L. Gonzalez-Larriba, O. Juan Vidal, J. Mosquera Martinez, J.M. Oramas Rodriguez, M.A. Sala Gonzalez, V. Calvo, A. Estival Gonzalez, M. Provencio
Journal: Annals of Oncology (2021)
957O Long-term follow-up of patients (pts) with human papillomavirus (HPV)–associated malignancies treated with bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1
Authors: J. Strauss, M. Gatti-Mays, B.C. Cho, A. Hill, S. Salas, E. McClay, J. Redman, H.A. Sater, E. Lamping, J.L. Marté, L. Cordes, M. Bilusic, F. Karzai, R. Madan, J. Schlom, G. Jehl, L.S. Ojalvo, J. Gulley
Journal: Annals of Oncology (2021)
Abstract 114: Association of Serum Potassium Levels With Favorable Neurological Outcome After Out-of-Hospital Cardiac Arrest: The CRITICAL Study in Osaka, Japan
Authors: Haruka Shida, Tasuku Matsuyama, Tetsuhisa Kitamura, Takefumi Kishimori, Kosuke Kiyohara, Satoe Okabayashi, Takashi Kawamura, Taku Iwami
Journal: Circulation (2018)

Background: Little is known about the association between serum potassium levels on hospital arrival and favorable neurological outcome after out-of-hospital cardiac arrest. Objective: The purpose of this study was to assess whether serum potassium levels on hospital arrival had prognostic indications for patients with out-of-hospital cardiac arrest (OHCA). Methods: The prospective, multicenter observational study conducted in Osaka, Japan (the CRITICAL study) enrolled all consecutive OHCA patients transported to 14 participating institutions from July 2012 through December 2015. We included adult patients aged ≥ 18 years with OHCA of cardiac origin who achieved return of spontaneous circulation (ROSC) and whose serum potassium level on hospital arrival was available. Based on the serum potassium level on hospital arrival, patients were divided into five quintiles (Q1-Q5), namely, Q1 (&lt;3.7mEq/l), Q2 (3.7-4.2mEq/l), Q3 (4.2-5.0mEq/l), Q4 (5.0-6.1mEq/l), and Q5 (&gt;6.1mEq/l). The primary outcome was one-month survival with favorable neurological outcome, which was defined as cerebral performance category scale 1 or 2. Results: During the study period, a total of 7373 patients were registered and 1148 of them were eligible for our analyses. The highest proportion of favorable neurological outcome was 42.2% (113/268) in the Q1, followed by 37.6% (76/202), 20.6% (50/243), 6.9% (15/216), and 2.7% (6/219) in the Q2, Q3, Q4, and Q5 (p&lt;0.001). In the multivariable logistic regression analysis, the adjusted proportion of favorable neurological outcome decreased as serum potassium level increased (p for trend &lt;0.001). In the subgroup analyses stratified by the first documented rhythm and estimated glomerular filtration rate, the adjusted proportions of favorable neurological outcome indicated similar tendency with those in the main analysis. Conclusion: Higher serum potassium level was significantly and independently associated with poor neurological outcome. Serum potassium on hospital arrival may be effective as a prognostic indication for out-of-hospital cardiac arrest achieving ROSC.
Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy
Authors: Moglie Le Quintrec, Maxime Teisseyre, Nicole Bec, Emilien Delmont, Ilan Szwarc, Hélène Perrochia, Marie Christine Machet, Anthony Chauvin, Nicolas Mavroudakis, Guillaume Taieb, Luca Lanfranco, Claire Rigothier, Boucraut José, Catalano Concetta, Clair Geneste, Vincent Pernin, Christian Larroque, Jérôme Devaux, Anaïs Beyze
Journal: Kidney International (2021)