Evolution Of Solid Tumors Research Articles

Standardized Assessment of the Tumor-Stroma Ratio in Colorectal Cancer: Interobserver Validation and Reproducibility of a Potential Prognostic Factor.

The tumor stroma plays a relevant role in the initiation and evolution of solid tumors. Tumor-stroma ratio (TSR) is a histological feature that expresses the proportion of the stromal component that surrounds cancer cells. In different studies, the TSR represents a potential prognostic factor: a rich stroma in tumor tissue can promote invasion and aggressiveness. The aim of this study was to evaluate the reproducibility and determine the interobserver agreement in the TSR score. The stromal estimate was evaluated in patients diagnosed with colorectal adenocarcinoma (CRA), who underwent surgical resection. We also evaluated age, gender, and other anatomopathological features. Tumor-stroma ratio was calculated based on the slide used in routine diagnostic pathology to determine the T-status. Stromal percentages were separated into 2 categories: ⩽50%—low stroma and >50%—high stroma. The interobserver agreement in the TSR scoring was evaluated among 4 pathologists at different stages of professional experience, using 2 different ways to learn the scoring system. In total, 98 patients were included in this study; 54.1% were male, with a mean age of 61.9 years. Localized disease was diagnosed in 60.2% of patients. Stromal-poor CRA was predominant. The concordance between the TSR percentages of the 4 pathologists was substantial (Kappa > 0.6). There was greater agreement among pathologists for stromal-poor tumors. Substantial agreement and high reproducibility were observed in the determination of TSR score. The TSR score is feasible, suggesting that the presented methodology can be used to facilitate the determination of the stromal proportion of potential prognostic factor.

Consistent Inclusion of Mesenchymal Stem Cells into In Vitro Tumor Models.

Over recent years, the role of distinct mesenchymal stem cell populations in cancer progression has become increasingly evident. In this regard, developing in vitro preclinical tumor models capable of portraying tumor-associated mesenchymal stem cells (TA-MSCs) interactions with the tumor microenvironment (TME), cellular and extracellular components, would allow to improve the predictive potential of these platforms and expedite preclinical drug screening. Although recent studies successfully developed in vitro tumor models in which the biomolecular and cellular behaviors of TA-MSCs were recapitulated in the context of their interactions with specific TME components, no consensus has yet been reached regarding distinct TA-MSCs influence in the evolution of solid tumors. The paradoxical observations regarding the roles of MSCs on in vitro tumor models can in part be associated to a lack of standardization in how MSCs integration is performed. Herein, we summarize some of the main parameters linked to phenotypic variations established upon MSCs inclusion and interaction within in vitro tumor models. Acritical overview of recent studies and how standardization of key parameters could improve the reproducibility and predictability of current preclinical validation models containing MSCsis also provided.

The role of carbonic anhydrase IX in hypoxia control in OSCC

Tumoral microenvironments play a key role in the evolution of solid tumors. Tumor hypoxia is actively involved in the promotion of genetic instability, the invasive capacity of tumor cells, metastasis, and a worsening of the clinical evolution. Endogenous hypoxia markers are controlled by hypoxia-related genes, formed by HIF-1, which is related to several target genes that involve the energy metabolism, angiogenesis, and transmembrane carbonic anhydrases (CAs), mainly CA-IX that is one of the tumor-related carbonic anhydrases. The goal of this paper is to establish the role of CA-IX as a hypoxia marker in OSCC, while analyzing its expression in this type of tumors and its relationship with several clinical and pathological parameters and prognosis, evaluating its relationship with angiogenesis, other hypoxia markers, and clarifying its role in chemotherapy and radiotherapy resistance.

Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of a family of glycoprotein hormones that stimulate the proliferation and differentiation of hemopoietic cells in vitro and in vivo. We now report that human GM-CSF can also stimulate the proliferation of two osteogenic sarcoma cell lines, a breast carcinoma cell line, a simian virus 40-transformed marrow stromal cell line, and normal marrow fibroblast precursors. These findings suggest a more general regulatory function of GM-CSF on nonhemopoietic cell types than previously anticipated. They also raise the possibility of adverse side effects of GM-CSF therapy in patients whose malignant cells may be directly stimulated by this molecule and suggest a previously unanticipated role of GM-CSF gene activation in the evolution of solid tumors and in the pathogenesis of myelofibrosis.