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Methods We systematically reviewed the mRNA expression of 34 molecules associated with the four pathways in 227 GEP-NEN samples from five datasets, finding them consistently. We sorted the samples into two expression patterns of pathway-related molecules by unsupervised clustering technique. We investigated the specific cell-related genes responsible for the various types of tumor subtypes, particularly immune and stromal cells using the WGCNA technique, which gave us a new way to identify the pathway-related genes responsible for the various variations of pathway-related molecules, and then the PC_Score and PI_Score scoring systems were also developed using obtained specific cell-related molecules. In addition, we performed the matching of pathway-related subtypes with features of immune landscape in primary and metastatic GEP-NENs. We also identified the fibroblast-related molecules ASPN, COL10A1, EDNRA, MYL9, PRELP, RAB31, SPARC, and THBS2, as well as immune-related molecules including CASP1, CCL5, CTSS, PMP22, and TFEC, using WGCNA. I/FE was positively correlated with the immune landscape of T-cell activation and immunosuppression. In addition, the I/FE classified GEP-NENs with raised immune activation scores. Also though IE, FE, and I/FD were all present in the liver metastatic site, the four key pathway subtypes were not conserved in any of the tumor sites, but I/FE was not preserved in the liver metastatic site, and I/FD was also present. Conclusions This report was the first to conduct a comprehensive review of the four key pathways in GEP-NENs. Our results showed that the primary and metastatic GEP-NENs had distinct antitumor phenotypes.
Source link: https://doi.org/10.3389/fonc.2022.808448
Abstract Background Cytotoxic chemotherapy mixtures and targeted agents represent well-established treatment options in advanced pancreatic neuroendocrine tumors. In early PNET patients with progressive advanced PNET patients, the RamuNET trial aims to determine the effectiveness of dual therapy with DTIC and ramucirumab. Methods The RamuNET study, conducted by an investigator-initiated multicenter prospective single-arm trial to determine the toxicity of ramucirumab and dacarbazine in combination with dacarbazine over a period of at least 6 months. The sample size estimation was based on an exact binomial single-stage model, with the assumption that 80% of the patients will achieve disease control after 6 months. Discussion This paper explores a new therapeutic strategy that uses a combination of cytotoxic and targeted antiangiogenic therapy in advanced PNET. This trial, if positive, will provide the basis for a double-arm research to investigate the interaction of ramucirumab and DTIC in PNET's combination of ramucirumab and DTIC against other commonly used drugs.
Source link: https://doi.org/10.1186/s12885-021-08900-7
177Lu-Dotatate is used in the treatment of somatostatin-receptor-positive inoperable progressive gastroenteropancreatic neuroendocrine tumors. 177Lu-Dotatate's pharmacokinetics and toxicity were determined by this research. Method: Four injections of 7400 MBq 177Lu-Dotatate were given per patient with either Primene® 10% or Lysakare® containing them, according to the study. Result: 1,678 177Lu-Dotatate plasma concentrations were determined versus time from 83 consecutive patients with Primene® or Lysakare®. Primene® significantly increased the elimination rate constant of 177Lu-Dotatate over Lysakare®, according to a population pharmacokinetic study. Primitathera® plasma exposure by 34% was also reduced by 44%, while Lysakare® raised AUC by 7%. Lymphopenia was found in AUC with a trend toward increased toxicity with Lysakare®. Conclusions: Unlike Primene®, Lysakare® does not raise 177Lu-Dotatate elimination, which is not increased. The latter parameter has high interpatient variability but low intrapatient variability, which may have important clinical implications for treatment tailoring.
Source link: https://doi.org/10.2174/1874471015666211228123525
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