Dear Sir, Intravenous cyclophosphamide (CPA) pulse-therapy is one of the best methods for the lupus nephritis (LN) treatment [1]. Possible severe complications considered that this treatment should be applied only to patients with a high likelihood of success. Thus, prediction of response to therapy ob tains considerable significance. The data from renal biopsy, activity (AI) and chronicity (Cl) indices, together with certain clinical signs, were found to be prognostic markers in LN patients treated with immunosuppres sants [1,2], but the predictive value of these signs was not supported by other studies (3,4]. We tried to determine the best predictors among different clinical and morphological variables using a stepwise multiple linear re gression analysis of the CPA pulse therapy results.Thirty-four patients with severe LN (fe male 32, male 2, nephrotic syndrome in 31, high blood pressure in 23, elevated serum creatinine (Scr) in 15) were treated with CPA pulses (10-20 mg/kg body weight i.v. every 3-4 weeks) combined with high-or middledose prednisolone; total CPA dose was 3-20 g. Renal biopsy performed in 21 patients revealed diffuse proliferative LN (DPLN) in 13, focal proliferative LN (FPLN) in 2, mem branous gonadotropin (GN) in 3 and scle rosing G N in 3 patients. For further anal ysis of morphological data biopsis were di vided in 3 groups according to the degree of severity: membranous GN 1st degree, D PL N /FPL N 2nd degree, sclerosing GN 3rd degree, and semiquantitative AI and Cl [1] were scored. Patients were followed for 3-45 months (mean 15.6). The outcomethe rate of renal functional deteriorationwas calculated a s:(1/Scr0-1/Scrl)/T, where ScrO and Scrl were the Scr levels before treatment and at the end of the follow up period, respectively, and T was the dura tion of follow-up (months).By the end of the follow-up period posi tive results were noted in 72% of patients (remission in 19, improvement in 5), negative results in 28% (deterioration in 1, uremia in 4, death in 5). The results were positive in all 3 patients with membranous GN and in 11 pa tients with D PLN /FPLN ; the results were negative in all 3 patients with sclerosing GN and in 4 with DPLN/FPLN.The prognostic value of clinical and mor phological signs was evaluated by comparing three statistical models which related the prognostic variables to the outcome with multiple linear regression. The first model included eight clinical variables: sex, age, LN duration, duration of exacerbation, Scr level, the presence of high blood pressure and he maturia, and total CPA dose; according to the stepwise multiple regression procedure two of them, LN duration and the Scr level, were chosen as forming the most powerful prog nostic clinical model (model 1, table 1), the predictive power of which was 87.6% (R2 x 100%). At the second stage one morpho logical variable (the degree of histological lesions severity) was added to the eight clini cal variables. The degree of histological se verity and the Scr level were chosen from this set by stepwise re...
NTRK gene fusions are drivers of tumorigenesis events that specific Trk-inhibitors can target. Current knowledge of the downstream pathways activated has been previously limited to the pathways of regulator proteins phosphorylated directly by Trk receptors. Here, we aimed to detect genes whose expression is increased in response to the activation of these pathways. We identified and analyzed differentially expressed genes in thyroid cancer samples with NTRK1 or NTRK3 gene fusions, and without any NTRK fusions, versus normal thyroid gland tissues, using data from the Cancer Genome Atlas, the DESeq2 tool, and the Genome Enhancer and geneXplain platforms. Searching for the genes activated only in samples with an NTRK fusion as opposed to those without NTRK fusions, we identified 29 genes involved in nervous system development, including AUTS2, DTNA, ERBB4, FLRT2, FLRT3, RPH3A, and SCN4A. We found that genes regulating the expression of the upregulated genes (i.e., upstream regulators) were enriched in the “signaling by ERBB4” pathway. ERBB4 was also one of three genes encoding master regulators whose expression was increased only in samples with an NTRK fusion. Moreover, the algorithm searching for positive feedback loops for gene promoters and transcription factors (a so-called “walking pathways” algorithm) identified the ErbB4 protein as the key master regulator. ERBB4 upregulation (p-value = 0.004) was confirmed in an independent sample of ETV6-NTRK3-positive FFPE specimens. Thus, ErbB4 is the potential key regulator of the pathways activated by NTRK gene fusions in thyroid cancer. These results are preliminary and require additional biochemical validation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.