LINS1 (Lines Homolog 1)

The newly proposed BIA equation demonstrated potential for predicting SMACT as the reference standard. Our hypothesis requires further investigation in both healthy and clinical populations.

The knockdown of hsa_circ_0002346 resulted in increased tumor cell proliferation, invasion, migration and decreased apoptosis. Additionally, alterations in the expression of EMT-associated proteins further support the hypothesis that hsa_circ_0002346 is implicated in the metastatic processes of breast cancer.Conclusionhsa_circ_0002346 emerges as a promising biomarker for breast cancer and a potential therapeutic target for future treatment strategies.

We also provide evidence that the mammalian homologs of Hyd (UBR5, known to be recurrently dysregulated in various human cancers), Lin (LINS1), and Bowl (OSR1/2) constitute an analogous protein degradation pathway in human cells, and that OSR2 promotes prostate cancer tumorigenesis. Altogether, these findings define a previously unrecognized tumor suppressor pathway that links epigenetic program to regulated protein degradation in tissue growth control and tumorigenesis.

Furthermore, while all the essayed compounds showed antitumoral properties, LINS01022 and LINS01023 exhibited the most potent antiproliferative effects by: i) inducing cell apoptosis and suppressing cell migration in 4T1 and MDA-MB-231 TNBC cells, and ii) inhibiting cell growth in paclitaxel-resistant 4T1 cells (potentiating the paclitaxel antiproliferative effect). Moreover, 20 mg/kg LINS01022 reduced tumor size in 4T1 tumor-bearing mice, exhibiting a safe toxicological profile and potential for druggability estimated by ADME calculations. We conclude that the H3R is involved in the regulation of TNBC progression, offering promising therapeutic potential for the novel LINS01 series of H3R antagonists.

This study showed good statistical correlations between early and late scintigraphy in most patients. However, in 35% of women late scintigraphy detected more nodes. In case of poor visualization after the first scintigraphy, re-injection should be considered. Late scintigraphy is probably helpful in confirming successful re-injection and in showing deviating lymph flow in women with failed mapping after the first injection and successful re-injection. Because missing metastatic sentinel lymph nodes often leads to a poor prognosis, we prefer optimal correlations between imaging and intraoperative identification. Hence, late scintigraphy cannot be safely omitted.

P3, N=395, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2022 --> Oct 2025 | Trial primary completion date: Jan 2022 --> Oct 2025

P3, N=395, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2021 --> Jan 2022 | Trial primary completion date: Jan 2021 --> Jan 2022

Legal entity responsible for the study: Sujin Yang. Funding: Has not received any funding.