The Interface of Cancer, Their Microenvironment and Nanotechnology

Cancer is one of the deadliest diseases with a cure far from being found. Despite the extraordinary advances in the therapy approaches, only a few patients respond to treatments. The tumor microenvironment (TME) plays a crucial role in cancer progression by contributing to the chemoresistance. Thus, emerging efforts are being made in nanotechnology research focusing on nanoparticles' potential role and their application in immune system modulation. Moreover, the omics have contributed to bioengineering and nanotechnology development by elucidating the mechanisms of cancer and specific biomarkers that could be used as new therapeutic targets. Furthermore, the non-coding microRNA as a target for cancer treatment and creation of organoids for the study of new treatments helped for the new therapeutics' era called personalized medicine. Here we will discuss the role played by TME in tumor initiation and progression we will describe the recent nanotechnology applied to cancer treatment. Specifically, we will describe the potential role of nanoparticles (NPs) and their application in immune system modulation, ultimately leading to circumventing tumor cell proliferation.publishersversionpublishe

Microglia/Astrocytes–Glioblastoma Crosstalk: Crucial Molecular Mechanisms and Microenvironmental Factors

In recent years, the functions of glial cells, namely, astrocytes and microglia, have gained prominence in several diseases of the central nervous system, especially in glioblastoma (GB), the most malignant primary brain tumor that leads to poor clinical outcomes. Studies showed that microglial cells or astrocytes play a critical role in promoting GB growth. Based on the recent findings, the complex network of the interaction between microglial/astrocytes cells and GB may constitute a potential therapeutic target to overcome tumor malignancy. In the present review, we summarize the most important mechanisms and functions of the molecular factors involved in the microglia or astrocytes–GB interactions, which is particularly the alterations that occur in the cell’s extracellular matrix and the cytoskeleton. We overview the cytokines, chemokines, neurotrophic, morphogenic, metabolic factors, and non-coding RNAs actions crucial to these interactions. We have also discussed the most recent studies regarding the mechanisms of transportation and communication between microglial/astrocytes – GB cells, namely through the ABC transporters or by extracellular vesicles. Lastly, we highlight the therapeutic challenges and improvements regarding the crosstalk between these glial cells and GB

A highlight on Sonic hedgehog pathway

Abstract Hedgehog (Hh) signaling pathway plays an essential role during vertebrate embryonic development and tumorigenesis. It is already known that Sonic hedgehog (Shh) pathway is important for the evolution of radio and chemo-resistance of several types of tumors. Most of the brain tumors are resistant to chemotherapeutic drugs, consequently, they have a poor prognosis. So, a better knowledge of the Shh pathway opens an opportunity for targeted therapies against brain tumors considering a multi-factorial molecular overview. Therefore, emerging studies are being conducted in order to find new inhibitors for Shh signaling pathway, which could be safely used in clinical trials. Shh can signal through a canonical and non-canonical way, and it also has important points of interaction with other pathways during brain tumorigenesis. So, a better knowledge of Shh signaling pathway opens an avenue of possibilities for the treatment of not only for brain tumors but also for other types of cancers. In this review, we will also highlight some clinical trials that use the Shh pathway as a target for treating brain cancer

Evaluation of miRNA Expression in Glioblastoma Stem-Like Cells: A Comparison between Normoxia and Hypoxia Microenvironment

Purpose: Glioblastoma is an aggressive and incurable brain tumor whose progression is driven in part by glioblastoma stem cells, which are also responsible for the tumor’s low therapy efficacy. The maintenance and expansion of the stem cell population is promoted by the hypoxic microenvironment, where miRNAs play fundamental roles in their survival. Methods: GBM stem-like cells were isolated from three GBM parental cell lines. The stem-like cells were then cultured under normoxic and hypoxic microenvironments followed by investigation of the in vitro “stemness” of the cells. Results: We found miR-128a-3p, 34-5p and 181a-3p to be downregulated and miR-17-5p and miR-221-3p to be upregulated in our stem-like cells compared to the GBMs. When a comparison was made between normoxia and hypoxia, a further fold downregulation was observed for miR-34-5p, miR-128a-3p and miR-181a-3p and a further upregulation was observed for miR-221-3p and 17-5p. There was an increased expression of HIF-1/2, SOX2, OCT4, VEGF, GLUT-1, BCL2 and survivin under hypoxia. Conclusion: Our data suggest that our GBMs were able to grow as stem-like cells and as spheroids. There was a differential expression of miRNAs between the stems and the GBMs and the hypoxia microenvironment influenced further dysregulation of the miRNAs and some selected genes

Gliomas and the vascular fragility of the blood brain barrier

Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB). By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM), characterized by a highly heterogeneous cell population (including tumor stem cells), extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the blood brain barrier and the concerns that arise when this barrier is affected