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2 results on '"Pipinikas C"'

1. High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial.

Author

van Dorp J, Pipinikas C, Suelmann BBM, Mehra N, van Dijk N, Marsico G, van Montfoort ML, Hackinger S, Braaf LM, Amarante T, van Steenis C, McLay K, Daletzakis A, van den Broek D, van de Kamp MW, Hendricksen K, de Feijter JM, Boellaard TN, Meijer RP, van der Heijden AG, Rosenfeld N, van Rhijn BWG, Jones G, and van der Heijden MS

Subjects
Humans, Ipilimumab adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Progression-Free Survival, Nivolumab adverse effects, Neoplasms chemically induced
Abstract

Cohort 1 of the phase 1B NABUCCO trial showed high pathological complete response (pCR) rates with preoperative ipilimumab plus nivolumab in stage III urothelial cancer (UC). In cohort 2, the aim was dose adjustment to optimize responses. Additionally, we report secondary endpoints, including efficacy and tolerability, in cohort 2 and the association of presurgical absence of circulating tumor DNA (ctDNA) in urine and plasma with clinical outcome in both cohorts. Thirty patients received two cycles of either ipilimumab 3 mg kg -1 plus nivolumab 1 mg kg -1 (cohort 2A) or ipilimumab 1 mg kg -1 plus nivolumab 3 mg kg -1 (cohort 2B), both followed by nivolumab 3 mg kg -1 . We observed a pCR in six (43%) patients in cohort 2A and a pCR in one (7%) patient in cohort 2B. Absence of urinary ctDNA correlated with pCR in the bladder (ypT0Nx) but not with progression-free survival (PFS). Absence of plasma ctDNA correlated with pCR (odds ratio: 45.0; 95% confidence interval (CI): 4.9-416.5) and PFS (hazard ratio: 10.4; 95% CI: 2.9-37.5). Our data suggest that high-dose ipilimumab plus nivolumab is required in stage III UC and that absence of ctDNA in plasma can predict PFS. ClinicalTrials.gov registration: NCT03387761 ., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2023
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2. Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes

Author

Tubio, J. M., Li, Y., Ju, Y. S., Martincorena, I., Cooke, S. L., Tojo Castro, Marta, Gundem, G., Pipinikas, C. P., Zamora, J., Raine, K., Menzies, A., Roman-Garcia, P., Fullam, A., Gerstung, M., Shlien, A., Tarpey, P. S., Papaemmanuil, E., Knappskog, S., Van Loo, P., Ramakrishna, M., Davies, H. R., Marshall, J., Wedge, D. C., Teague, J. W., Butler, A. P., Nik-Zainal, S., Alexandrov, L., Behjati, S., Yates, L. R., Bolli, N., Mudie, L., Hardy, C., Martin, S., McLaren, S., O'Meara, S., Anderson, E., Maddison, M., Gamble, S., Foster, C., Warren, A. Y., Whitaker, H., Brewer, D., Eeles, R., Cooper, C., Neal, D., Lynch, A. G., Visakorpi, T., Isaacs, W. B., van't Veer, L., Caldas, C., Desmedt, C., Sotiriou, C., Aparicio, S., Foekens, J. A., Eyfjörd, J. E., Lakhani, S. R., Thomas, G., Myklebost, O., Span, P. N., Børresen-Dale, A. L., Richardson, A. L., Van de Vijver, M., Vincent-Salomon, A., Van den Eynden, G. G., Flanagan, A. M., Futreal, P. A., Janes, S. M., Bova, G. S., Stratton, M. R., McDermott, U., Campbell, P. J., Group, ICGC Breast Cancer, Group, ICGC Bone Cancer, and Group, ICGC Prostate Cancer

Subjects
Mutagenesis, Insertional, Long Interspersed Nucleotide Elements, Carcinogenesis, Genome, Human, Transduction, Genetic, Neoplasms, DNA Transposable Elements, food and beverages, Humans, Exons, Chromatin, Translocation, Genetic
Abstract

Long interspersed nuclear element-1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3' transduction. Because 3' transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3' transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3' transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3' transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome.

Published
2014

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