<i>Caenorhabditis elegans</i>BMP Transcriptional Program Implicates Collagen Genes in Body Size Regulation

Madaan, Uday; Yzeiraj, Edlira; Meade, Michael; Ca, Rushlow; Savage-Dunn, Cathy

doi:10.1101/108225

Cited by 1 publication

(1 citation statement)

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“…Nematode cuticles mostly consist of collagen (more than 80%) [101]. It has been shown that epidermal collagen genes can act as positive regulators, dose-dependent regulators, and negative regulators of body size [102]. In connection with the damage to the cuticle, which was observed, disruption of epidermal gene expression may caused inhibition of C. elegans growth.…”

Section: Effect On the Worm Survivalmentioning

confidence: 99%

Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment

Uram,

Wróbel,

Walczak

et al. 2023

Molecules

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Fulvestrant (F), lapatinib (L), and paclitaxel (P) are hydrophobic, anticancer drugs used in the treatment of estrogen receptor (ER) and epidermal growth factor receptor (EGFR)-positive breast cancer. In this study, glycidylated PAMAM G4 dendrimers, substituted with F, L, and/or P and targeting tumor cells, were synthesized and characterized, and their antitumor activity against glioma U-118 MG and non-small cell lung cancer A549 cells was tested comparatively with human non-tumorogenic keratinocytes (HaCaT). All cell lines were ER+ and EGFR+. In addition, the described drugs were tested in the context of antinematode therapy on C. elegans. The results show that the water-soluble conjugates of G4P, G4F, G4L, and G4PFL actively entered the tested cells via endocytosis due to the positive zeta potential (between 13.57–40.29 mV) and the nanoparticle diameter of 99–138 nm. The conjugates of G4P and G4PFL at nanomolar concentrations were the most active, and the least active conjugate was G4F. The tested conjugates inhibited the proliferation of HaCaT and A549 cells; in glioma cells, cytotoxicity was associated mainly with cell damage (mitochondria and membrane transport). The toxicity of the conjugates was proportional to the number of drug residues attached, with the exception of G4L; its action was two- and eight-fold stronger against glioma and keratinocytes, respectively, than the equivalent of lapatinib alone. Unfortunately, non-cancer HaCaT cells were the most sensitive to the tested constructs, which forced a change in the approach to the use of ER and EGFR receptors as a goal in cancer therapy. In vivo studies on C. elegans have shown that all compounds, most notably G4PFL, may be potentially useful in anthelmintic therapy.

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Section: Effect On the Worm Survivalmentioning

confidence: 99%