scholarly journals Immunotherapy-Related Publications in Colorectal Cancer: A Bibliometric Analysis

Healthcare ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 75
Author(s):  
Daniel Sur ◽  
Cristina Lungulescu ◽  
Irina-Ioana Puscariu ◽  
Simona Ruxandra Volovat ◽  
Madalina Preda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
New England ◽  
Microsatellite Instability ◽  
Checkpoint Inhibitors ◽  
University Of Texas ◽  
Publication Patterns ◽  
Johns Hopkins University ◽  
The Us ◽  
Recherche Médicale ◽  
The University

Patients with microsatellite-instability-high (MSI-H) or mismatched repair-deficient colorectal cancer (CRC) appear to be responsive to checkpoint inhibitors. This study aimed to assess research trends in CRC immunotherapy. Publication patterns of articles covering immunotherapies in CRC in the Web of Science Core Collection database were retrospectively examined using VOS viewer software (version 1.6.16) prior to 25 May 2021. Ultimately, 3977 records were identified that were published between 1975 and 2021, which received a total of 128,681 citations (an average of 32.36 citations per item), with a noticeable rise in 2014. The majority of articles were published in the US (35.8%), China (17.7%), and Germany (9.4%). Publications mainly originated from the Institut National de la Santé Et De La Recherche Medicale Inserm, followed by the University of Texas System and Harvard University; however, Johns Hopkins University received the most citations (18,666 for 69 publications). The Journal of Clinical Oncology issued the most publications (n = 146), while the most referenced item (7724 citations) was published in the New England Journal of Medicine in 2012. The most common keywords were associated with tumors (expression and microsatellite instability) or immune system components (t-cells/dendritic cells). The findings demonstrate the scientific community’s interest in the MSI-H subtype of colorectal tumors and how immunotherapy may be employed more successfully to treat metastatic CRC.

scholarly journals Beyond Microsatellite Instability: Evolving Strategies Integrating Immunotherapy for Microsatellite Stable Colorectal Cancer

2021 ◽  
Vol 22 (8) ◽  
Author(s):  
Federica Pecci ◽  
Luca Cantini ◽  
Alessandro Bittoni ◽  
Edoardo Lenci ◽  
Alessio Lupi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Cancer Progression ◽  
Checkpoint Inhibitors ◽  
Tnm Classification ◽  
Standard Of Care ◽  
First Line Therapy ◽  
Combination Strategies ◽  
The Impact

Opinion statementAdvanced colorectal cancer (CRC) is a heterogeneous disease, characterized by several subtypes with distinctive genetic and epigenetic patterns. During the last years, immune checkpoint inhibitors (ICIs) have revamped the standard of care of several tumors such as non-small cell lung cancer and melanoma, highlighting the role of immune cells in tumor microenvironment (TME) and their impact on cancer progression and treatment efficacy. An “immunoscore,” based on the percentage of two lymphocyte populations both at tumor core and invasive margin, has been shown to improve prediction of treatment outcome when added to UICC-TNM classification. To date, pembrolizumab, an anti-programmed death protein 1 (PD1) inhibitor, has gained approval as first-line therapy for mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) advanced CRC. On the other hand, no reports of efficacy have been presented in mismatch-repair-proficient (pMMR) and microsatellite instability-low (MSI-L) or microsatellite stable (MSS) CRC. This group includes roughly 95% of all advanced CRC, and standard chemotherapy, in addition to anti-EGFR or anti-angiogenesis drugs, still represents first treatment choice. Hopefully, deeper understanding of CRC immune landscape and of the impact of specific genetic and epigenetic alterations on tumor immunogenicity might lead to the development of new drug combination strategies to overcome ICIs resistance in pMMR CRC, thus paving the way for immunotherapy even in this subgroup.

Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors

2021 ◽  
Vol 22 ◽  
Author(s):  
Csongor György Lengyel
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Primary Objective ◽  
Dna Mismatch ◽  
Dominant Component ◽  
Colon Cancers

: The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate professionals to offer better survival options for patients with CRC.

scholarly journals Developing Taiwan Studies Teaching Programmes in Europe and the US: The Experience of SOAS University of London and University of Texas at Austin

2019 ◽  
Vol 240 ◽  
pp. 1108-1134 ◽  
Author(s):  
Dafydd Fell ◽  
Sung-sheng Yvonne Chang
Keyword(s):  
Rapid Expansion ◽  
Academic Environment ◽  
University Of Texas ◽  
The Us ◽  
Key Features ◽  
The University ◽  
Development Trajectories

AbstractOver the last two decades, there has been a rapid expansion in the number of Taiwan programmes at universities in America and Europe; however, few of these Taiwan programmes have attempted to develop teaching courses. Where Taiwan courses have been introduced, they have tended to be in isolation and not well integrated into existing academic programmes. Among the universities with Taiwan programmes, only two have attempted to create comprehensive teaching programmes through which students can graduate with a degree in Taiwan studies: SOAS University of London and the University of Texas at Austin. The purpose of this paper is to compare the experiences of these two institutions in developing such niche teaching programmes. It begins with a discussion of how these two programmes first emerged and then goes on to review their distinct development trajectories and key features. The paper offers an analysis of how these two programmes were able not only to survive but also to expand their offerings and thrive in an academic environment that should be hostile to such niche programmes. It concludes with a review of the remaining challenges facing these teaching programmes.

scholarly journals Universities as Embedded Knowledge Hubs and the Challenge of Local Development. The US Lessons and the Italian Case

2010 ◽  
Vol 16 (2) ◽  
pp. 5-22 ◽  
Author(s):  
Lorenzo Ciapetti
Keyword(s):  
Local Development ◽  
New Paradigm ◽  
Modal Shift ◽  
University System ◽  
Italian Case ◽  
Development Section ◽  
Johns Hopkins University ◽  
The Us ◽  
Recent Project ◽  
The University

This article discusses the claim of a new paradigm in the knowledge production and diffusion process, and the need to assess the regional and local implications of this modal shift. After introductory remarks included in the first part of the paper, its next section introduces the theme of localisation of knowledge as a source of regional development; section three examines the lessons we can extract from the US university system (with a particular regard to the case of Johns Hopkins University and the recent project for a biotech park in the city of Baltimore); in section four an illustration of the Italian University system leads to a description of the current evolution of the University of Bologna toward a new entrepreneurial role. The last part of the paper discusses the embedded role of universities in the light of the two cases presented in the previous sections and draws the conclusions in terms of regional policy.

scholarly journals More Gasoline from Crude

2003 ◽  
Vol 125 (12) ◽  
pp. 45-46
Author(s):  
John DeGaspari
Keyword(s):  
Crude Oil ◽  
Distillation Column ◽  
Department Of Energy ◽  
Cooperative Research ◽  
University Of Texas ◽  
Ongoing Work ◽  
The Us ◽  
Development Agreement ◽  
The University ◽  
Cooperative Research And Development

This article highlights that pushing a refinery distillation column to its limits to meet heightened demand is a tricky undertaking that could result in an unwanted phenomenon called column flooding. As petroleum is distilled, various components of the crude oil remain separated from each other on porous trays inside the column. During a flood, butane, gasoline, asphalt, and other distilled crude oil products begin to commingle with each other inside the column. By knowing the actual beginnings of flooding, the operator knows how much he can push the column to distill more products. The flooding predictor will identify the incipient flood point regardless of the grade of crude oil and will provide the operator with information to reduce throughput when necessary. The US Department of Energy has awarded a cooperative research and development agreement to second point. The Motiva refinery in Norco has signed on as a partner to run the flooding predictor on a commercial-scale distillation column. Data from those tests will be fed into the ongoing work at the University of Texas.

scholarly journals Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Joseph D Butner ◽  
Geoffrey V Martin ◽  
Zhihui Wang ◽  
Bruna Corradetti ◽  
Mauro Ferrari ◽  
...  
Keyword(s):  
Tumor Response ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Cancer Center ◽  
Model Parameters ◽  
University Of Texas ◽  
Checkpoint Inhibitor Therapy ◽  
Tumor Types ◽  
The University

Background: Checkpoint inhibitor therapy of cancer has led to markedly improved survival of a subset of patients in multiple solid malignant tumor types, yet the factors driving these clinical responses or lack thereof are not known. We have developed a mechanistic mathematical model for better understanding these factors and their relations in order to predict treatment outcome and optimize personal treatment strategies.Methods: Here, we present a translational mathematical model dependent on three key parameters for describing efficacy of checkpoint inhibitors in human cancer: tumor growth rate (α), tumor immune infiltration (Λ), and immunotherapy-mediated amplification of anti-tumor response (µ). The model was calibrated by fitting it to a compiled clinical tumor response dataset (n = 189 patients) obtained from published anti-PD-1 and anti-PD-L1 clinical trials, and then validated on an additional validation cohort (n = 64 patients) obtained from our in-house clinical trials.Results: The derived parameters Λ and µ were both significantly different between responding versus non-responding patients. Of note, our model appropriately classified response in 81.4% of patients by using only tumor volume measurements and within two months of treatment initiation in a retrospective analysis. The model reliably predicted clinical response to the PD-1/PD-L1 class of checkpoint inhibitors across multiple solid malignant tumor types. Comparison of model parameters to immunohistochemical measurement of PD-L1 and CD8+ T cells confirmed robust relationships between model parameters and their underlying biology.Conclusion: These results have demonstrated reliable methods to inform model parameters directly from biopsy samples, which are conveniently obtainable as early as the start of treatment. Together, these suggest that the model parameters may serve as early and robust biomarkers of the efficacy of checkpoint inhibitor therapy on an individualized per-patient basis.Funding: We gratefully acknowledge support from the Andrew Sabin Family Fellowship, Center for Radiation Oncology Research, Sheikh Ahmed Center for Pancreatic Cancer Research, GE Healthcare, Philips Healthcare, and institutional funds from the University of Texas M.D. Anderson Cancer Center. We have also received Cancer Center Support Grants from the National Cancer Institute (P30CA016672 to the University of Texas M.D. Anderson Cancer Center and P30CA072720 the Rutgers Cancer Institute of New Jersey). This research has also been supported in part by grants from the National Science Foundation Grant DMS-1930583 (Z.W., V.C.), the National Institutes of Health (NIH) 1R01CA253865 (Z.W., V.C.), 1U01CA196403 (Z.W., V.C.), 1U01CA213759 (Z.W., V.C.), 1R01CA226537 (Z.W., R.P., W.A., V.C.), 1R01CA222007 (Z.W., V.C.), U54CA210181 (Z.W., V.C.), and the University of Texas System STARS Award (V.C.). B.C. acknowledges support through the SER Cymru II Programme, funded by the European Commission through the Horizon 2020 Marie Skłodowska-Curie Actions (MSCA) COFUND scheme and the Welsh European Funding Office (WEFO) under the European Regional Development Fund (ERDF). E.K. has also received support from the Project Purple, NIH (U54CA210181, U01CA200468, and U01CA196403), and the Pancreatic Cancer Action Network (16-65-SING). M.F. was supported through NIH/NCI center grant U54CA210181, R01CA222959, DoD Breast Cancer Research Breakthrough Level IV Award W81XWH-17-1-0389, and the Ernest Cockrell Jr. Presidential Distinguished Chair at Houston Methodist Research Institute. R.P. and W.A. received serial research awards from AngelWorks, the Gillson-Longenbaugh Foundation, and the Marcus Foundation. This work was also supported in part by grants from the National Cancer Institute to S.H.C. (R01CA109322, R01CA127483, R01CA208703, and U54CA210181 CITO pilot grant) and to P.Y.P. (R01CA140243, R01CA188610, and U54CA210181 CITO pilot grant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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