916 research outputs found
Veronica Davis Gerald on Gullah Culture
No full textVeronica Davis Gerald is Director of the Charles Joyner Institute for Gullah and African Diaspora Studies at Coastal Carolina University. In this video abstract, she discusses her identity as both a scholar and native of the Gullah culture. This informs her collaborative work with the Charles Joyner Institute and Gullah communities of the Waccamaw Neck region of South Carolina. Keywords: Gullah Culture, Charles Joyner Institute, South Carolina, GUL
Trifluridine/tipiracil plus bevacizumab for third-line management of metastatic colorectal cancer: SUNLIGHT study design
No full textTrifluridine/tipiracil (FTD/TPI) is an orally active formulation of trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor that increases the bioavailability of trifluridine. Preliminary studies of FTD/TPI plus bevacizumab have produced encouraging results in the treatment of refractory metastatic colorectal cancer. Here, we describe the design of the multinational Phase III SUNLIGHT, an open-label study of FTD/TPI plus bevacizumab as third-line treatment for patients with unresectable metastatic colorectal cancer. A total of 490 patients will be randomized 1:1 to receive either FTD/TPI plus bevacizumab, or FTD/TPI monotherapy. The primary objective is to significantly improve overall survival with FTD/TPI plus bevacizumab compared with FTD/TPI monotherapy. The first patient was enrolled in November 2020.sponsorship: The SUNLIGHT study is funded by Servier. J Tabernero has received fees for advisory/consultancy roles from Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Genmab A/S, Halozyme, Imugene, Inflection Biosciences, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F Hoffmann-La Roche, Sanofi, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. J Taieb has received fees for advisory/consultancy roles from Lilly, MSD, AMGEN, Merck Serono, Novartis, Roche, Sanofi, Servier, HalioDX SAS and Pierre Fabre. F Ciardiello has received honoraria or consultation fees for speaker, consultancy or advisory roles from Amgen, Bayer, Bristol-Myers Squibb, Celgene, Merck Serono, Pfizer, Roche and Servier, direct research funding as the principal investigator for institutional research projects from Amgen, Bayer, Merck Serono, Roche and Ipsen, and has institutional financial interests, or received financial support for clinical trials or contracted research from Merck Serono, Roche, Symphogen and Array. M Fakih has received honoraria from Amgen, has received fees for speaker, consultancy or advisory roles from Amgen, Array BioPharma, Bayer, Guardant360 and Pfizer, and has received research grant support from Amgen, Novartis and AstraZeneca. GW Prager had participated in advisory board meetings/symposia for Merck Serono, Roche, Amgen, Sanofi, Lilly, Servier, Taiho, Bayer, Halozyme, BMS, MSD, Celgene, Shire and Terumo. EV Cutsem has received fees for consultancy or advisory roles from Bayer, Lilly, Roche, Servier, Bristol Myers Squibb, Celgene, Merck Sharp & Dohme, Merck KGaA, Novartis, AstraZeneca, Halozyme, Array BioPharma, Biocartis, GlaxoSmithKline, Daiichi Sankyo, Pierre Fabre, Sirtex Medical, Taiho Pharmaceutical and Incyte and has received research funding from Amgen, Bayer, Boehringer Ingelheim, Lilly, Novartis, Roche, Celgene, Ipsen, Merck, Merck KGaA, Servier and Bristol Myers Squibb. C Leger, R Fougeray and N Amellal are employed by Servier. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. (Servier, Amgen, Bayer, Merck Serono, Roche, Ipsen, Symphogen, Array, Novartis, AstraZeneca, Boehringer Ingelheim, Lilly, Celgene, Merck, Merck KGaA, Bristol Myers Squibb)status: Publishe
Predicting resistance to first-line FOLFOX plus bevacizumab in metastatic colorectal cancer: Final results of the multicenter, international PERMAD trial.
No full text115 Background: Antiangiogenic agents, in particular monoclonal antibodies (mAbs) against VEGF, a major driver of tumor angiogenesis, are widely used in cancer therapy including metastatic colorectal cancer (mCRC). However, some patients do not profit from antiangiogenic treatments (AT), other patients benefit initially, but subsequently develop resistance not only to chemotherapy but also to AT. So far, no biomarkers are available to predict resistance to AT. Having an accurate assessment of imminent resistance to an AT may e.g. enable to respond by treating the patient with a more broadly acting antiangiogenic agent and thereby further delay resistance to the treatment and at the same time avoid employing a not anymore efficacious treatment. We hypothesized that repeated analysis of multiple cytokines related to angiogenesis together with machine learning approaches may enable an accurate prediction of anti-VEGF resistance during first-line treatment of mCRC patients with FOLFOX plus bevacizumab. The PERMAD trial aimed at establishing a CAF marker combination that enables the prediction of treatment resistance of patients with mCRC receiving Bevacizumab plus mFOLFOX6 in a palliative first-line setting about three months prior to radiological progress using an omics approach and bioinformatics. Methods: A phase I/II biomarker trial was conducted, including 15 centers in Germany and Austria. All mCRC patients included were treatment naïve and received FOLFOX plus Bevacizumab treatment. 102 different, preselected CAFs were prospectively collected and centrally analyzed in plasma samples (n = 647) obtained prior to treatment and biweekly until radiological progress determined by CT scan every 2 months. The values of CAFs affected in a similar fashion by both chemotherapy and disease progress were excluded. Using the remaining CAFs we employed a random forest predictor to define a combination of 5 CAF (CAF marker combination) whose change in values/pattern correlated with subsequent progress 3 months prior to radiological progress according to RECIST 1.1. Results: Using the samples described above and a random forest predictor we established a CAF marker combination comprising 5 CAF whose specific change in value/pattern over time indicated treatment resistance 3 months prior to radiological progress. The model allowed to differentiate timepoints without progress from timepoints predicting progress 100 days before radiological progress with an accuracy of 83%, a sensitivity of 76% and specificity of 88%. Conclusions: Using advanced bioinformatics, we identified a CAF marker combination that points out treatment resistance to FOLFOX plus Bevacizumab in patients with mCRC 3 months prior to radiological progress. Clinical trial information: NCT02331927
Clinical Trial Data Review of the Combination FTD/TPI + Bevacizumab in the Treatment Landscape of Unresectable Metastatic Colorectal Cancer
No full textRecommended first and second line treatments for unresectable metastatic colorectal cancer (mCRC) include fluorouracil-based chemotherapy, anti-vascular endothelial growth factor (VEGF)-based therapy, and anti-epidermal growth factor receptor-targeted therapies. In third line, the SUNLIGHT trial showed that trifluridine/tipiracil + bevacizumab (FTD/TPI + BEV) provided significant survival benefits and as such is now a recommended third line regimen in patients with refractory mCRC, irrespective of RAS mutational status and previous anti-VEGF treatment. Some patients are not candidates for intensive combination chemotherapy as first-line therapy due to age, low tumor burden, performance status and/or comorbidities. Capecitabine (CAP) + BEV is recommended in these patients. In the SOLSTICE trial, FTD/TPI + BEV as a first line regimen in patients not eligible for intensive therapy was not superior to CAP + BEV in terms of progression-free survival (PFS). However, in SOLSTICE, FTD/TPI + BEV resulted in similar PFS, overall survival, and maintenance of quality of life as CAP + BEV, with a different safety profile. FTD/TPI + BEV offers a possible first line alternative in patients for whom CAP + BEV is an unsuitable treatment. This narrative review explores and summarizes the clinical trial data on FTD/TPI + BEV.</p
Prediction of resistance to bevacizumab plus FOLFOX in metastatic colorectal cancer using a multi-marker panel and a machine-learning approach: Final results of the prospective multicenter PERMAD trial.
No full text204 Background: Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are widely used for tumor treatment, including metastatic colorectal cancer (mCRC). So far, there are no biomarkers that reliably predict resistance to anti-VEGF mAbs like bevacizumab. A biomarker-guided strategy for early and accurate assessment of resistance could avoid the use of non-effective treatment and improve patient outcomes. We hypothesized that repeated analysis of multiple cytokines and angiogenic growth factors (CAFs) before and during treatment using machine learning could provide an accurate and earlier, i.e., 100 days before conventional radiologic staging, prediction of resistance to first-line mCRC treatment with FOLFOX plus bevacizumab. Methods: 15 German and Austrian centers prospectively recruited 154 mCRC patients receiving FOLFOX plus bevacizumab as first-line treatment. Plasma samples were collected every two weeks until radiologic progression (RECIST 1.1) as determined by CT scans performed every 2 months. 102 pre-selected CAFs were centrally analyzed using a cytokine multiplex assay (Luminex, Myriad RBM). Results: Using random forest machine learning, we developed a predictive model that discriminated between the situations of ”no progress within 100 days before radiological progress” and ”progress within 100 days before radiological progress”. Into this we incorporated a combination of ten out of the 102 CAF markers, which fulfilled this task with 81% accuracy, 72% sensitivity, and 88% specificity. Conclusions: Using artificial intelligence we identified a CAF marker combination that indicates treatment resistance to FOLFOX plus bevacizumab in patients with mCRC within 100 days prior to radiologic progress. Further studies are required to show its clinical value. Clinical trial information: NCT02331927 .Sanofi Aventis 10000433
Compression of finite group actions and covariant dimension, II
No full textAbstractLet G be a finite group and φ:V→W an equivariant polynomial map between finite dimensional G-modules. We say that φ is faithful if G acts faithfully on φ(V). The covariant dimension of G is the minimum of the dimension of φ(V)¯ taken over all faithful φ. In [Hanspeter Kraft, Gerald W. Schwarz, Compression of finite group actions and covariant dimension, J. Algebra 313 (1) (2007) 268–291] we investigated covariant dimension and were able to determine it in many cases. Our techniques largely depended upon finding homogeneous faithful covariants. After publication of the paper, the junior author of this article pointed out several gaps in our proofs. Fortunately, this inspired us to find better techniques, involving multihomogeneous covariants, which have enabled us to extend and complete the results, simplify the proofs and fill the gaps of our previous work
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