The traditional two-dimensional (2D) in vitro cell culture system (on a flat support) has long been used in cancer research. However, this system cannot be fully translated into clinical trials to ideally represent physiological conditions. This culture cannot mimic the natural tumor microenvironment due to the lack of cellular communication (cell-cell) and interaction (cell-cell and cell-matrix). To overcome these limitations, three-dimensional (3D) culture systems are increasingly developed in research and have become essential for tumor research, tissue engineering, and basic biology research. 3D culture has received much attention in the field of biomedicine due to its ability to mimic tissue structure and function. The 3D matrix presents a highly dynamic framework where its components are deposited, degraded, or modified to delineate functions and provide a platform where cells attach to perform their specific functions, including adhesion, proliferation, communication, and apoptosis. So far, various types of models belong to this culture: either the culture based on natural or synthetic adherent matrices used to design 3D scaffolds as biomaterials to form a 3D matrix or based on non-adherent and/or matrix-free matrices to form the spheroids. In this review, we first summarize a comparison between 2D and 3D cultures. Then, we focus on the different components of the natural extracellular matrix that can be used as supports in 3D culture. Then we detail different types of natural supports such as matrigel, hydrogels, hard supports, and different synthetic strategies of 3D matrices such as lyophilization, electrospiding, stereolithography, microfluid by citing the advantages and disadvantages of each of them. Finally, we summarize the different methods of generating normal and tumor spheroids, citing their respective advantages and disadvantages in order to obtain an ideal 3D model (matrix) that retains the following characteristics: better biocompatibility, good mechanical properties corresponding to the tumor tissue, degradability, controllable microstructure and chemical components like the tumor tissue, favorable nutrient exchange and easy separation of the cells from the matrix.

Several immune and immunocompetent cells, including dendritic cells, macrophages, adipocytes, natural killer cells, T cells, and B cells, are significantly correlated with the complex discipline of oncology. Cytotoxic innate and adaptive immune cells can block tumor proliferation, and others can prevent the immune system from rejecting malignant cells and provide a favorable environment for tumor progression. These cells communicate with the microenvironment through cytokines, a chemical messenger, in an endocrine, paracrine, or autocrine manner. These cytokines play an important role in health and disease, particularly in host immune responses to infection and inflammation. They include chemokines, interleukins (ILs), adipokines, interferons, colony-stimulating factors (CSFs), and tumor necrosis factor (TNF), which are produced by a wide range of cells, including immune cells, such as macrophages, B-cells, T-cells, and mast cells, as well as endothelial cells, fibroblasts, a variety of stromal cells, and some cancer cells. Cytokines play a crucial role in cancer and cancer-related inflammation, with direct and indirect effects on tumor antagonistic or tumor promoting functions. They have been extensively researched as immunostimulatory mediators to promote the generation, migration and recruitment of immune cells that contribute to an effective antitumor immune response or pro-tumor microenvironment. Thus, in many cancers such as breast cancer, cytokines including leptin, IL-1B, IL-6, IL-8, IL-23, IL-17, and IL-10 stimulate while others including IL-2, IL-12, and IFN-γ, inhibit cancer proliferation and/or invasion and enhance the body’s anti-tumor defense. Indeed, the multifactorial functions of cytokines in tumorigenesis will advance our understanding of cytokine crosstalk pathways in the tumor microenvironment, such as JAK/STAT, PI3K, AKT, Rac, MAPK, NF-κB, JunB, cFos, and mTOR, which are involved in angiogenesis, cancer proliferation and metastasis. Accordingly, targeting and blocking tumor-promoting cytokines or activating and amplifying tumor-inhibiting cytokines are considered cancer-directed therapies. Here, we focus on the role of the inflammatory cytokine system in pro- and anti-tumor immune responses, discuss cytokine pathways involved in immune responses to cancer and some anti-cancer therapeutic applications.

Life expectancy has drastically increased over the last few decades worldwide, with important social and medical burdens and costs. To stay healthy longer and to avoid chronic disease have become essential issues. Organismal aging is a complex process that involves progressive destruction of tissue functionality and loss of regenerative capacity. One of the most important aging hallmarks is cellular senescence, which is a stable state of cell cycle arrest that occurs in response to cumulated cell stresses and damages. Cellular senescence is a physiological mechanism that has both beneficial and detrimental consequences. Senescence limits tumorigenesis, lifelong tissue damage, and is involved in different biological processes, such as morphogenesis, regeneration, and wound healing. However, in the elderly, senescent cells increasingly accumulate in several organs and secrete a combination of senescence associated factors, contributing to the development of various age-related diseases, including cancer. Several studies have revealed major molecular pathways controlling the senescent phenotype, as well as the ones regulating its interactions with the immune system. Attenuating the senescence-associated secretory phenotype (SASP) or eliminating senescent cells have emerged as attractive strategies aiming to reverse or delay the onset of aging diseases. Here, we review current senotherapies designed to suppress the deleterious effect of SASP by senomorphics or to selectively kill senescent cells by “senolytics” or by immune system-based approaches. These recent investigations are promising as radical new controls of aging pathologies and associated multimorbidities.

The tumor microenvironment plays a major role in tumor growth, invasion and resistance to chemotherapy, however understanding how all actors from microenvironment interact together remains a complex issue. The tumor microenvironment is classically represented as three closely connected components including the stromal cells such as immune cells, fibroblasts, adipocytes and endothelial cells, the extracellular matrix (ECM) and the cytokine/growth factors. Within this space, proteins of the adamalysin family (ADAM for a disintegrin and metalloproteinase; ADAMTS for ADAM with thrombospondin motifs; ADAMTSL for ADAMTS-like) play critical roles by modulating cell–cell and cell–ECM communication. During last decade, the implication of adamalysins in the development of hepatocellular carcinoma (HCC) has been supported by numerous studies however the functional characterization of most of them remain unsettled. In the present review we propose both an overview of the literature and a meta-analysis of adamalysins expression in HCC using data generated by The Cancer Genome Atlas (TCGA) Research Network.

Brain tumors can present with various psychiatric symptoms, with or without neurological symptoms, an aspect that complicates the clinical picture. However, no systematic description of symptoms that should prompt a neurological investigation has been provided. This review aims to summarize available case reports describing patients with brain tumors showing psychiatric symptoms before brain tumor diagnosis, in order to provide a comprehensive description of these symptoms as well as their potential relationship with delay in the diagnosis. A systematic literature review on case reports of brain tumors and psychiatric symptoms from 1970 to 2020 was conducted on PubMed, Ovid, Psych Info, and MEDLINE. Exclusion criteria comprised tumors not included in the World Health Organization (WHO) Classification 4^th edition and cases in which psychiatric symptoms were absent or followed the diagnosis. A total of 165 case reports were analyzed. In a subset of patients with brain tumors, psychiatric symptoms can be the only manifestation or precede focal neurological signs by months or even years. The appearance of focal or generalized neurological symptoms after, rather than along with, psychiatric symptoms was associated with a significant delay in the diagnosis in adults. A timely assessment of psychiatric symptoms might help to improve early diagnosis of brain tumors.

Obesity and breast cancer are two major health issues that could be categorized as sincere threats to human health. In the last few decades, the relationship between obesity and cancer has been well established and extensively investigated. There is strong evidence that overweight and obesity increase the risk of postmenopausal breast cancer, and adipokines are the central players in this relationship. Produced and secreted predominantly by white adipose tissue, adiponectin is a bioactive molecule that exhibits numerous protective effects and is considered the guardian angel of adipokine. In the obesity–cancer relationship, more and more evidence shows that adiponectin may prevent and protect individuals from developing breast cancer. Recently, several updates have been published on the implication of adiponectin in regulating tumor development, progression, and metastases. In this review, we provide an updated overview of the metabolic signaling linking adiponectin and breast cancer in all its stages. On the other hand, we critically summarize all the available promising candidates that may reactivate these pathways mainly by targeting adiponectin receptors. These molecules could be synthetic small molecules or plant-based proteins. Interestingly, the advances in genomics have made it possible to create peptide sequences that could specifically replace human adiponectin, activate its receptor, and mimic its function. Thus, the obvious anti-cancer activity of adiponectin on breast cancer should be better exploited, and adiponectin must be regarded as a serious biomarker that should be targeted in order to confront this threatening disease.