An integrated multiomics analysis of rectal cancer patients identified POU2F3 as a putative druggable target and entinostat as a cytotoxic enhancer of 5-fluorouracil.

Rectal cancer (RC) accounts for one-third of colorectal cancers (CRC), and 40% of these are locally advanced rectal cancers (LARC). The use of neoadjuvant chemoradiotherapy (nCRT) significantly reduces the rate of local recurrence compared to adjuvant therapy or surgery alone. However, after nCRT, up to 40%-60% of patients show a poor pathological response, while only about 20% achieve a pathological complete response.

The Study of the Extracellular Matrix in Chronic Inflammation: A Way to Prevent Cancer Initiation?

Bidirectional communication between cells and their microenvironment has a key function in normal tissue homeostasis, and in disease initiation, progression and a patient's prognosis, at the very least. The extracellular matrix (ECM), as an element of all tissues and cellular microenvironment, is a frequently overlooked component implicated in the pathogenesis and progression of several diseases. In the inflammatory microenvironment (IME), different alterations resulting from remodeling processes can affect ECM, progressively inducing cancer initiation and the passage toward a tumor microenvironment (TME).

Bio-Engineered Scaffolds Derived from Decellularized Human Esophagus for Functional Organ Reconstruction.

Esophageal reconstruction through bio-engineered allografts that highly resemble the peculiar properties of the tissue extracellular matrix (ECM) is a prospective strategy to overcome the limitations of current surgical approaches. In this work, human esophagus was decellularized for the first time in the literature by comparing three detergent-enzymatic protocols. After decellularization, residual DNA quantification and histological analyses showed that all protocols efficiently removed cells, DNA (<50 ng/mg of tissue) and muscle fibers, preserving collagen/elastin components.

Establishment of a human 3D pancreatic adenocarcinoma model based on a patient-derived extracellular matrix scaffold.

Pancreatic cancer is likely to become one of the leading causes of cancer-related death in many countries within the next decade. Surgery is the potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC), although only 10%-20% of patients have a resectable disease after diagnosis. Despite recent advances in curative surgery the current prognosis ranges from 6% to 10% globally.

Optimization of Biomimetic, Leukocyte-Mimicking Nanovesicles for Drug Delivery Against Colorectal Cancer Using a Design of Experiment Approach.

The development of biomimetic nanoparticles (NPs) has revolutionized the concept of nanomedicine by offering a completely new set of biocompatible materials to formulate innovative drug delivery systems capable of imitating the behavior of cells. Specifically, the use of leukocyte-derived membrane proteins to functionalize nanovesicles (leukosomes) can enable their long circulation and target the inflamed endothelium present in many inflammatory pathologies and tumors, making them a promising and versatile drug delivery system. However, these studies did not elucidate the critical experimental parameters involved in leukosomes formulation.

An investigation on [5 fluorouracil and epigallocatechin-3-gallate] complex activity on HT-29 cell death and its stability in gastrointestinal fluid.

Recently an enhancement of the sensitivity of colorectal cancer (CRC) cells by 5-fluorouracil (5FU) due to the concurrent treatment with epigallocatechin-3-gallate (EGCG) has been found. In the present paper, to investigate on this aspect, adenocarcinoma cells HT29 were treated with 5FU, EGCG and an equimolar mixture of 5FU and EGCG ([5FU+EGCG]) and cell viability was determined. While 5FU exhibits a clear activity, EGCG alone does not express any activity.

Tumor Cells and the Extracellular Matrix Dictate the Pro-Tumoral Profile of Macrophages in CRC.

Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment. In colorectal cancer (CRC), a strong infiltration of TAMs is accompanied by a decrease in effector T cells and an increase in the metastatic potential of CRC. We investigated the functional profile of TAMs infiltrating CRC tissue by immunohistochemistry, flow cytometry, ELISA, and qRT-PCR and their involvement in impairing the activation of effector T cells.