Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.

Glioblastoma stem cells (GSCs) are cells with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked to tumor cell heterogeneity. Most standard treatments fail to completely eradicate GSCs, causing the recurrence of the disease. GSCs could represent one reason for the low efficacy of cancer therapy and for the short relapse time. Nonetheless, experimental data suggest that the presence of therapy-resistant GSCs could explain tumor recurrence. Therefore, to effectively target GSCs, a comprehensive understanding of their biology and the survival and developing mechanisms during treatment is mandatory. This review provides an overview of the molecular features, microenvironment, detection, and targeting strategies of GSCs, an essential information required for an efficient therapy. Despite the outstanding results in oncology, researchers are still developing novel strategies, of which one could be targeting the GSCs present in the hypoxic regions and invasive edge of the glioblastoma.

From all central nervous system tumors, gliomas are the most common. Nowadays, researchers are looking for more efficient treatments for these tumors, as well as ways for early diagnosis. Receptor tyrosine kinases (RTKs) are major targets for oncology and the development of small-molecule RTK...

Treatment of high grade gliomas (HGGs) has remained elusive due to their high heterogeneity and aggressiveness. Surgery followed by radiotherapy represents the mainstay of treatment for HGG. However, the unfavorable location of the tumor that usually limits total resection and the resistance to radiation therapy are the major therapeutic problems. Chemotherapy with DNA alkylating agent temozolomide is also used to treat HGG, despite modest effects on survival. Disregulation of several growth factor receptors (GFRs) were detected in HGG and receptor amplification in glioblastoma has been suggested to be responsible for heterogeneity propagation through clonal evolution. Molecularly targeted agents inhibiting these membrane proteins have demonstrated significant cytotoxicity in several types of cancer cells when tested in preclinical models. Platelet-derived growth factor receptors (PDGFRs) and associated signaling were found to be implicated in gliomagenesis, moreover, HGG commonly display a Platelet-derived growth factor (PDGF) autocrine pathway that is not present in normal brain tissues. We have previously shown that both the susceptibility towards PDGFR and the impact of the PDGFR inactivation on the radiation response were different in different HGG cell lines. Therefore, we decided to extend our investigation, using two other HGG cell lines that express PDGFR at the cell surface. Here, we investigated the effect of PDGFR inhibition alone or in combination with gamma radiation in 11 and 15 HGG cell lines. Our results showed that while targeting the PDGFR represents a good means of treatment in HGG, the combination of receptor inhibition with gamma radiation did not result in any discernable difference compared to the single treatment. The PI3K/PTEN/Akt/mTOR and Ras/Raf/MEK/ERK pathways are the major signaling pathways emerging from the GFRs, including PDGFR. Decreased sensitivity to radiation-induced cell death are often associated with redundancy in these pro-survival signaling pathways. Here we found that Phosphoinositide 3-kinases (PI3K), Extracellular-signal-regulated kinase 1/2 (ERK1/2), or c-Jun N-terminal kinase 1/2 (JNK1/2) inactivation induced radiosensitivity in HGG cells.

The aim of this work was to assess the analgesic effect of three Vitis vinifera L. leaf extracts and the anti-inflammatory effect of three gels obtained from Aesculus hippocastanum L. seed extracts using animal models, as a preliminary study for the future development of topical preparations based on the combination of extracts with synergistic therapeutic effects on hemorrhoid disease. The analgesic effect was determined by means of the writhing test in mice. The anti-inflammatory effect was determined after administration of carrageenan or kaolin in the rat paw. Extraction using glycerol yielded the highest amounts of flavonoids for both V. vinifera leaves (37.27 ± 1.174 mg/L) and A. hippocastanum seeds (53.48 ± 0.212 mg/L). The highest total phenolic contents were registered for the V. vinifera 20% ethanolic extract (615.3 ± 34.44 mg/L) and for the A. hippocastanum glycerolic extract (247.8 ± 6.991 mg/L). The writhing test revealed that the V. vinifera ethanolic extract induced the most efficient analgesia (57.20%, p < 0.01), better than that induced by the positive control. In the carrageenan inflammation model, only the gel obtained from the A. hippocastanum glycerolic extract significantly reduced paw edema (17.27%, p < 0.05). An anti-inflammatory effect was also observed in the kaolin inflammation model but was not statistically significant (10.12%, p > 0.05). Our findings indicate that V. vinifera and A. hippocastanum extracts may have potential uses for the treatment of pain and inflammation associated with hemorrhoid disease.

Cancer remains one of the most difficult to manage healthcare problems. The last two decades have been considered the golden age of cancer research, with major breakthroughs being announced on a regular basis. However, the major problem regarding cancer treatment is the incapability to selectively target cancer cells, with certain populations of tumors still remaining alive after treatment. The main focus of researchers is to develop treatments that are both effective and selective in targeting malignant cells. In this regard, bioavailability can be increased by overcoming the biological barriers encountered in the active agent’s pathway, creating carrier vehicles that have the ability to target malignant cells and effectively release the active agent. Since its appearance, nanomedicine has provided many answers to these challenges, but still, some expectations were not satisfied. In this review, we focused on the most recent developments in targeted drug delivery. Furthermore, a summary of different types of nanoparticles used to deliver active therapeutic agents in oncology is presented, along with details on the nanodrugs that were clinically approved by the Food and Drug Administration (FDA), until April 2019.