Thiol-Ene Synthesis of Cationic Carbosilane Dendrons: a New Family of Synthons

A variety of neutral and cationic carbosilane dendrons containing a wide range of active groups, such as −N₃, −OH, −NH₂, and −SH, at the focal points were synthesized from carbosilane vinyl dendrons BrG_<i>n</i>V_<i>m</i> from generations 1–3 by substitution of the bromine atom at the focal point and functionalization of the vinyl groups via thiol-ene click chemistry with HS­(CH₂)₂NMe₂·HCl. These dendritic wedges were characterized by NMR, MS, and elemental analysis

Improved Efficiency of Ibuprofen by Cationic Carbosilane Dendritic Conjugates

In order to improve the efficiency of the anti-inflammatory drug ibuprofen, cationic carbosilane dendrimers and dendrons with ibuprofen at their periphery or at their focal point, respectively, have been synthesized, and the release of the drug was studied using HPLC. Macrophages were used to evaluate the anti-inflammatory effect of the ibuprofen-conjugated dendritic systems and compared with mixtures of non-ibuprofen dendritic systems in the presence of the drug. The cationic ibuprofen-conjugated dendron was the compound that showed higher anti-inflammatory properties. It reduces the LPS-induced <i>COX-2</i> expression and decreases the release of several inflammatory cytokines such as TNFα, IL-1β, IL-6, and CCL3. These results open new perspectives in the use of these compounds as drug carriers

“Long-term oncologic outcomes and risk factors for distant recurrence after pathologic complete response following neoadjuvant treatment for locally advanced rectal cancer. A nationwide, multicentre study”

Background: Pathologic complete response (pCR) after multimodal treatment for locally advanced rectal cancer (LARC) is used as surrogate marker of success as it is assumed to correlate with improved oncologic outcome. However, long-term oncologic data are scarce.Methods: This retrospective, multicentre study updated the oncologic follow-up of prospectively collected data from the Spanish Rectal Cancer Project database. pCR was described as no evidence of tumour cells in the specimen. Endpoints were distant metastases-free survival (DMFS) and overall survival (OS). Multivariate regression analyses were run to identify factors associated with survival.Results: Overall, 32 different hospitals were involved, providing data on 815 patients with pCR. At a median follow-up of 73.4 (IQR 57.7-99.5) months, distant metastases occurred in 6.4% of patients. Abdominoperineal excision (APE) (HR 2.2, 95%CI 1.2-4.1, p = 0.008) and elevated CEA levels (HR = 1.9, 95% CI 1.0-3.7, p = 0.049) were independent risk factors for distant recurrence. Age (years) (HR 1.1; 95% CI 1.05-41.09; p &lt; 0.001) and ASA III-IV (HR = 2.0; 95%-CI 1.4-2.9; p &lt; 0.001), were the only factors associated with OS. The estimated 12, 36 and 60-months DMFS rates were 96.9%, 91.3%, and 86.8%. The estimated 12, 36 and 60-months OS rates were 99.1%, 94.9% and 89.3%.Conclusions: The incidence of metachronous distant metastases is low after pCR, with high rates of both DMFS and OS. The oncologic prognosis in LARC patients that achieve pCR after neoadjuvant chemoradiotherapy is excellent in the long term. (c) 2023 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved