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Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating the natural production environment, ongoing studies are currently setting various strategies to significantly manipulate the quantity of anticancer molecules in plants. This review focuses on the recently studied secondary metabolite agents that have shown promising anticancer activity, outlining their potential mechanisms of action and pathways.

Introduction: One of the most frequently encountered intracranial tumours are the pituitary adenomas, these accounting for 5% to 20%. Therapeutic strategies vary largely, from medical therapy to complex neurosurgical procedures. The transsphenoidal approach can solve most of the lesions of the pituitary area, as long as the invasion of the adjacent structures is not significant. The transcranial approach is indicated in tumours with extensive invasion Materials and methods: We performed a retrospective study in the Bagdasar-Arseni Emergency Hospital Neurosurgery that aimed to analyze the demographics, signs and symptoms, therapeutic strategy, surgical approach, complications, and histopathology, from 2010 to 2019. Results: The total number of hospitalization records, including the follow-up hospitalization and/or second surgery hospitalization, was of 1107. Furthermore, there were 704 unique patients. The most common signs and symptoms encountered for the first admission were headache (245 – 34.56%), optic chiasm deficits (153 – 21.58%), acromegaly (85 – 11.99%). However, the majority of patients (507 – 71.51%) presented with some sort of hormonal imbalance or diabetes insipidus. On the one hand, a number of 325 (45.84%) patients had non-surgical treatment. On the other hand, a total of 384 (54.16%) surgeries for pituitary tumours were performed in this period. Discussion: In our study, the patients who underwent surgery benefited from either microsurgical transsphenoidal or transcranial surgeries. Even if the transsphenoidal approach was used far more, there was a greater relapse proportion in these patients. Transcranial surgery, even if followed by a far less proportion of relapse surgery, carried with it the burden of more days spent in hospital (most of the time twice as much as for the transsphenoidal patients). Conclusion: Both transsphenoidal and transcranial approaches have advantages and disadvantages, thus the best strategy would be to tailor each surgery to each patient, keeping an open mind to all available approaches.

Synchronous tumours can be found all along the entire neuraxis, however, some lesions are far less likely to coexist. One of these extremely rare associations is between GH-pituitary adenomas and suprasellar meningiomas. A wide spectrum of transcranial and transsphenoidal approaches were described in the literature for either sellar, suprasellar and parasellar lesions, but no agreement has been reached for the cases of simultaneous occurring lesions. We present a rare case of a woman with GH-secreting pituitary adenoma and concomitant suprasellar meningioma. The strategy chosen was sequential transsphenoidal surgeries. However, after the first surgery, the remaining tumour mass did not mobilize as expected due to gravity, hence we decided to perform a transcranial subfrontal unilateral approach. Surprisingly, the second surgery revealed a different histopathological result. Association of a GH-pituitary adenoma and suprasellar meningioma is very rare, only 17 cases being reported in the relevant literature so far. Different authors prefer different strategies, ranging from only transsphenoidal to simultaneous transsphenoidal and transcranial approaches, but no general consensus was established. In conclusion, the existence of synchronous tumours of the sellar region should be taken into account when imaging studies reveal an intracranial mass developing both sellar and suprasellar. The surgical strategy should be tailored to every specific patient and experience of the neurosurgeon.

Due to its localisation, rapid onset, high relapse rate and resistance to most currently available treatment methods, glioblastoma multiforme (GBM) is considered to be the deadliest type of all gliomas. Although surgical resection, chemotherapy and radiotherapy are among the therapeutic strategies used for the treatment of GBM, the survival rates achieved are not satisfactory, and there is an urgent need for novel effective therapeutic options. In addition to single-target therapy, multi-target therapies are currently under development. Furthermore, drugs are being optimised to improve their ability to cross the blood-brain barrier. In the present review, the main strategies applied for GBM treatment in terms of the most recent therapeutic agents and approaches that are currently under pre-clinical and clinical testing were discussed. In addition, the most recently reported experimental data following the testing of novel therapies, including stem cell therapy, immunotherapy, gene therapy, genomic correction and precision medicine, were reviewed, and their advantages and drawbacks were also summarised.

Dyes are an important class of natural and synthetic compounds, recently studied as potential anticancer drugs. Among various natural dye molecules, Curcumin was extensively studied in treatment of malignant gliomas, a highly incurable disease. Curcumin was reported to induce cell death in malignant gliomas by induction autophagy and apoptosis. We have previously reported that Helianthin, a synthetic dye compound, also induced apoptotic cell death in high grade glioma cells. In this study we evaluated the antiproliferative and the apoptotic effect of Curcumin and Helianthin on a human low passage glioblastoma cell line. We found that both compounds displayed antiproliferative properties on glioblastoma cells, however, at equimolar concentrations, Helianthin induced more cytotoxic effect than Curcumin. IC50 value is considered a good indicator of drug efficacy. We found that Helianthin required a lower concentration to achieve IC50 (16.9.735 �14.8 mM) than Curcumin (68.5 �12.3 mM). We also found that Curcumin and Helianthin treatment induced caspase 3, 8 and 9 activation in glioblastoma cells. This study may lead to a widespread search for dye agents that may represent an untapped source of drugs for cancer treatment.

In recent years, immunotherapy has raised the interest of many studies and provided different perspectives for the therapeutic management of high grade glioma. Our meta-analysis focused on the effectiveness of dendritic cell (DC) therapy and viral therapy (VT) in clinical trials. Fourteen eligible studies have been evaluated and the results suggest the improvement of both OS (HR = 0.65) (p

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.

Cancer and viruses have a long history that has evolved over many decades. Much information about the interplay between viruses and cell proliferation and metabolism has come from the history of clinical cases of patients infected with virus-induced cancer. In addition, information from viruses used to treat some types of cancer is valuable. Now, since the global coronavirus pandemic erupted almost a year ago, the scientific community has invested countless time and resources to slow down the infection rate and diminish the number of casualties produced by this highly infectious pathogen. A large percentage of cancer cases diagnosed are strongly related to dysregulations of the tyrosine kinase receptor (TKR) family and its downstream signaling pathways. As such, many therapeutic agents have been developed to strategically target these structures in order to hinder certain mechanisms pertaining to the phenotypic characteristics of cancer cells such as division, invasion or metastatic potential. Interestingly, several authors have pointed out that a correlation between coronaviruses such as the SARS-CoV-1 and -2 or MERS viruses and dysregulations of signaling pathways activated by TKRs can be established. This information may help to accelerate the repurposing of clinically developed anti-TKR cancer drugs in COVID-19 management. Because the need for treatment is critical, drug repurposing may be an advantageous choice in the search for new and efficient therapeutic compounds. This approach would be advantageous from a financial point of view as well, given that the resources used for research and development would no longer be required and can be potentially redirected towards other key projects. This review aims to provide an overview of how SARS-CoV-2 interacts with different TKRs and their respective downstream signaling pathway and how several therapeutic agents targeted against these receptors can interfere with the viral infection. Additionally, this review aims to identify if SARS-CoV-2 can be repurposed to be a potential viral vector against different cancer types.

Stefan-Alexandru Artene,1 Adina Turcu-Stiolica,2 Richard Hartley,1 Marius Eugen Ciurea,3 Oana Daianu,1 Corina Brindusa,1 Oana Alexandru,4 Ligia Gabriela Tataranu,5 Stefana Oana Purcaru,1 Anica Dricu1 1Unit of Biochemistry, 2Department of Biostatistics, 3Department of Plastic and Reconstructive Surgery, 4Department of Neurology, University of Medicine and Pharmacy of Craiova, Craiova, 5Department of Neurosurgery, “Bagdasar–Arseni” Emergency Hospital, Bucharest, Romania Background: The bevacizumab and irinotecan protocol is considered a standard treatment regimen for recurrent malignant glioma. Recent advances in immunotherapy have hinted that vaccination with dendritic cells could become an alternative salvage therapy for the treatment of recurrent malignant glioma.Methods: A search was performed on PubMed, Cochrane Library, Web of Science, ScienceDirect, and Embase in order to identify studies with patients receiving bevacizumab plus irinotecan or dendritic cell therapy for recurrent malignant gliomas. The data obtained from these studies were used to perform a systematic review and survival gain analysis.Results: Fourteen clinical studies with patients receiving either bevacizumab plus irinotecan or dendritic cell vaccination were identified. Seven studies followed patients that received bevacizumab plus irinotecan (302 patients) and seven studies included patients that received dendritic cell immunotherapy (80 patients). For the patients who received bevacizumab plus irinotecan, the mean reported median overall survival was 7.5 (95% confidence interval [CI] 4.84–10.16) months. For the patients who received dendritic cell immunotherapy, the mean reported median overall survival was 17.9 (95% CI 11.34–24.46) months. For irinotecan + bevacizumab group, the mean survival gain was -0.02±2.00, while that for the dendritic cell immunotherapy group was -0.01±4.54.Conclusion: For patients with recurrent malignant gliomas, dendritic cell immunotherapy treatment does not have a significantly different effect when compared with bevacizumab and irinotecan in terms of survival gain (P=0.535) and does not improve weighted survival gain (P=0.620). Keywords: malignant glioma, irinotecan, bevacizumab, dendritic cell, systematic analysis

Immunotherapy holds great promise in the treatment of high grade glioma (HGG). We performed a comprehensive meta-analysis of clinical trials involving dendritic cell (DC) therapy and viral therapy (VT) for the treatment of HGG, in order to assess their clinical impact in comparison to standard treatments in terms of overall survival (OS) and progression-free survival (PFS). To our knowledge, this is the first meta-analysis to evaluate VT for the treatment of HGG, allowing comparison of different immunotherapeutic approaches. Thirteen eligible studies of 1043 cases were included in the meta-analysis. For DC vaccination, in terms of OS, both newly diagnosed patients (HR, 0.65) and patients who suffered from recurrent HGGs (HR = 0.63) presented markedly improved results compared to the control groups. PFS was also improved (HR = 0.49) but was not statistically significant (p = 0.1). A slight improvement was observed for newly diagnosed patients receiving VT in terms of OS (HR = 0.88) while PFS was inferior for patients in the experimental arm (HR = 1.16). Our results show that DC therapy greatly improves OS for patients with both newly diagnosed and recurrent HGGs. VT, however, did not provide any statistically significant improvements in terms of OS and PFS for patients with newly diagnosed HGGs.

Introduction. Meningiomas are benign tumors which originate from the cells of the arachnoid granules. Meningiomas represent a special pathologic entity for neurosurgeons due to the fact that they can grow silently for a long time, and can affect important neural structures when they become symptomatic. The total resection of meningiomas is curative. For the meningiomas which are not surgically accessible and for reoccurrence. Gamma Knife radiosurgery (GKS) is a very efficient solution. Materials and methods. The study below presents the experience of the authors regarding the use of GKS for the treatment of meningiomas. The authors focus on a population of 550 patients diagnosed and treated for meningiomas over a period of 10 years at the „Bagdasar-Arseni“ University Hospital in Bucharest. This study compares the impact of GKS when performed alone or in association with open microneurosurgery. The authors assessed patients with tumors ranging between 1 and 42 cm3 in volume. GKS is used successfully to treat meningiomas, both independently and in association with open microsurgery. Results. The major complications of the treatment are represented by lack of response to treatment (7% of patients) and transient cerebral edema (22% of patients). A disturbing phenomenon happens in a few meningiomas of the convexity, with malignant edema (

Not only pituitary adenomas, but also a number of tumors may arise from within the sella presenting a diagnostic and therapeutic challenge at a multidisciplinary specialist level. This article presents a case of a colloid cyst located in sellar region, with overlapping symptoms of a nonfunctioning pituitary adenoma.

We performed a retrospective study, including patients operated for brain AVMs between 1999 and 2014, in the Clinic of Neurosurgery, Emergency Clinical Hospital Bagdasar-Arseni, Bucharest. 277 patients underwent surgery for brain AVMs. Mean age was 29.82 years. 195 patients (70.40%) presented with hemorrhage and 86 cases (31.05%) were admitted with seizures. We performed total resection of AVMs in 228 cases (82.31%) and subtotal resection in 49 cases (17.69%). Regarding patients with residual nidus, 16 of them underwent second surgery, 27 stereotactic radiosurgery Gamma Knife, 3 embolization and 3 refused further treatment. Modified Rankin Scale (mRS) improved following surgery (Z = -9.248, p = 0.000). Early complications (0-30 days) were encountered in 84 patients (30.32%). We found the following risk factors for postoperative complications occurrence: motor deficit (p = 0.006), co-morbidities (p = 0.023), higher mRS (p = 0.005), lower Karnofsky score (p = 0.003), lower GCS (p = 0.016), profound nidus (p = 0.001), eloquent aria (p = 0.000), large nidus (p = 0.000), multiple arterial territory (p = 0.000), deep feeding arteries (p = 0.000), higher number of feeding arteries (p = 0.000), deep venous drainage (p = 0.000), multiple draining veins (p = 0.000), higher Spetzler- Martin grade (p = 0.006), high flow (p = 0.000), vascular steel (p = 0.000), associated aneurysms (p = 0.010) and decompressive craniectomy (p = 0.019). Mortality was 6.1%. Microsurgery is the treatment of choice for brain AVMs. Surgical results are excellent, with low morbidity and mortality. Patients with poor surgical results belonged to the group admitted with severe altered general state, state of consciousness, massive hematomas and acute brainstem dysfunction. If part of the nidus cannot be safely surgical resected, stereotactic radiosurgery can provide definitive cure of the lesion.

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 failure of therapies targeting tumor angiogenesis may be caused by anti-angiogenic resistance mechanisms induced by VEGF and non-VEGF pathways alterations. Anti-angiogenic therapy failure is also attributed to immune system, acting by tumor-associated macrophages that release pro-angiogenic factors and a consequent increase of blood vessels. Recently, in a study by Rheal et al., a new angiogenic receptor, epidermal growth factor, latrophilin, and 7 trans-membrane domain-containing protein 1 on chromosome 1(ELTD1) has been identified as a promising glioma biomarker. In this study we aim to analyse whether this receptor may be used as a target molecule in glioblastoma therapy. Our results showed that small interfering RNA silencing ELTD1 caused cytotoxicity in glioblastoma cells. We also found that PDGFR, VEGFR, and their common PI3K/mTOR intracellular pathway inactivation-induced cytotoxicity in glioblastoma cells. Further, we found high percent of cytotoxicity in a low passage glioblastoma cell line after BEZ235 (a dual inhibitor of PI3K/mTOR pathway) treatment at nanomolar concentrations, compared to AG1433 (a PDGFR inhibitor) and SU1498 (a VEGFR inhibitor) that were only cytotoxic at micromolar ranges. In the future, these could prove as attractive therapeutic targets in single therapy or coupled with classic therapeutic approaches such as chemotherapy of radiotherapy.

A major focus of brain cancer research today is to translate understanding of glioma biology into advances in treatment, by exploring the potential of target therapy. Here we investigated the ability of three compounds belonging to the chemical class of azo dyes (methyl red, methyl yellow, and helianthin) to inhibit glioblastoma (GB) cell growth in vitro. Our results showed that helianthin induced cytotoxicity in two GB cell cultures, cell lines 18 and 38, whereas methyl red and methyl yellow were not cytotoxic. The effect of helianthin on EGFR, IGF-1R, and their common intracellular signaling via PI3-K and ERK1/2 was also analyzed. Treatment with helianthin down-regulated EGFR and IGF-1R activity in both cell lines. Helianthin treatment blocked ERK1/2 phosphorylation without affecting PI3K activity in cell line 18 and reduced both PI3K and ERK1/2 in GB 38 cell line. The cell death was accompanied by degradation of PARP without affecting BCL2 expression in both GB cell cultures. Because of the genetic heterogeneity of malignant gliomas, we tested the effect of helianthin on other two primary GB lines (11 and 15) and two early-passage GB cultures (BT1GB and BT2GB), to assess the general nature of the anti-tumor effect of the drug in GB cells. We found that helianthin treatment induced cell death in all the GB cell cultures analyzed. To our knowledge, this is the first report indicating that helianthin can reduce GB cell growth.

Lack of effectiveness of radiation therapy may arise from different factors such as radiation induced receptor tyrosine kinase activation and cell repopulation; cell capability to repair radiation induced DNA damage; high grade glioma (HGG) tumous heterogeneity, etc. In this study, we analyzed the potential of targeting epidermal growth factor receptor (EGFR) in inducing radiosensitivity in two human HGG cell lines (11 and 15) that displayed similar growth patterns and expressed the receptor protein at the cell surface. We found that 15 HGG cells that express more EGFR at the cell surface were more sensitive to AG556 (an EGFR inhibitor), compared to 11 HGG cells. Although in line 15 the effect of the inhibitor was greater than in line 11, it should be noted that the efficacy of this small-molecule EGFR inhibitor as monotherapy in both cell lines has been modest, at best. Our data showed a slight difference in the response to radiation of the HGG cell lines, three days after the treatment, with line 15 responding better than line 11. However, both cell lines responded to ionizing radiation in the same way, seven days after irradiation. EGFR inhibition induced radiosensitivity in 11 HGG cells, while, in 15 HGG cells, the effect of AG556 treatment on radiation response was almost nonexistent.

Increased expression and activation of receptor tyrosine kinases frequently occur in human brain tumors, mediating a variety of growth-promoting pathways and leading to radioresistance; however, little is known about their motogenic potency relative to one another. In this study, we found co-expression of Insulin like growth factor-1 receptor (IGF-1R) and platelet derived growth factor receptor (PDGFR) in two high-grade gliomas (HGG) cell lines 18 and 38. Dual targeting of IGF-1R and PDGFR increased cell death in both 18 and 38 cell lines in comparison to inhibition of either receptor alone. In addition, co-inhibition of IGF-1R and PDGFR increased radiosensitivity in 18 cells but failed to intensify the effect of radiation in 38 cells. In HGG cells, radiation-induced cell death has been connected to the activation of c-Jun-NH2-terminal kinase-1 (JNK1). We found that JNK1 was weakly expressed in 38 cells while it had an elevated expression in 18 cells. Exposure to ionizing radiation induced JNK1 activation only in 18 cells without affecting the protein activity in 38 cells. These results suggest that in 18 cell line radiation-activated JNK1 may provide an anti-proliferative signaling, parallel to receptors co-targeting. To test this hypothesis, HGG cells were treated with dominant negative JNK1 (dnJNK1) and the response to radiation was assayed in presence or absence of receptors co-inhibition. Indeed dnJNK protected 18 cells against gamma-irradiation-induced cell death. dnJNK treatment did not influence radiation response of the 38 cell line, which expressed low levels of JNK1. In conclusion we found that IGF-1R and PDGFR co-inhibition caused an increased cell death in two HGG cell line and induced the radiosensitization of the JNK1 expressing cell line.

Calcified meningiomas have a slower growth rate and a better outcome than non-calcified meningiomas. Matrix Gla Protein (MGP) acts as an inhibitor of soft tissue calcification. Depending on its carboxylation status MGP may occur in two conformations: uncarboxylated (ucMGP) or carboxylated (cMGP). Low levels of serum ucMGP have been described to be a sign of tissue calcification. In calcified tumoral tissue samples we identified both ucMGP (r = 0.957, p[0.001) and cMGP (r = 1, p[0.001), while non-calcified tumors were negative for both MGP conformation deposits. The concentration of serum t-ucMGP in patients with calcified and non-calcified meningiomas were not significantly different (3499�1388 vs. 3882�2558).

Biobank is a very sophisticated system that consists of a programmed storage of biological material and corresponding data. Biobanks are created to be used in medical research, in clinical and translational medicine, and in healthcare. In the past 20 years, a large number of biobanks have been set up around the world, to support the modern research directions in medicine such as omix and personalized medicine. More recently, embryonic and adult stem cell banks have been developed. Stem cell banking was reported to be required for medical research as well as clinical transplant applications. The quality of the samples stored in a biobank is very important. The standardization is also important; the biological material stored in a biobank must be processed in a manner that allows compatibility with other biobanks that preserve samples in the same field. In this paper, we review some issues related to biobanks purposes, quality, harmonization, and their financial and ethical aspects.

In the past few years ‘cancer stem cells’ (CSCs) area has become an interesting field of cancer research. In 19th century, Durante and Conheim [6] and after one hundred year Sell and Pierce [6, 7] issued the hypothesis that stem cells could induce cancer in all type of tissues. Unlike normal tissue stem cells, cancer stem cells are characterized by an abnormal differen‐ tiation rate, which can lead to tumor [8, 9].

Background: Plant extract therapy has been the cornerstone of cancer treatment for many years. The natural component curcumin demonstrated antineoplastic effects on different type of tumor cells. In this study, we explored the effectiveness of curcumin against low-passage human primary glioblastoma (GB) cell cultures. Materials and Methods: Early passage GB cell cultures (GB3B, GB4B, and GB5B) were established from fresh samples tissue obtained from GB patients. Growth rate (GR) and doubling time (DT) was determined for each cell line. The cytotoxic effect of curcumin was quantified by hemocytometer cell counting, using trypan blue. To study the changes in cell shape, GB cells exposed to a concentration corresponding to inhibitory concentration 50 (IC50) of curcumin were studied by phase-contrast microscopy by capturing images during the treatment. Results: Our results showed that GB cells proliferate with a GR of 0.2872 and a DT of 2.41 days for GB3B, a GR of 0.2787 and a DT of 2.49 days for GB4B, and a GR of 0.2787 and a DT of 2.49 days for GB5B. Curcumin induced cell death in GB cells in a time- and dose-dependent manner. The IC50 for GB3B was 46.4 µM, for GB4B was 78,3 µM, and for GB5B was 47.7 µM. Phase contrast microscopy showed that cultures treated with curcumin in a concentration corresponding to IC50 contained rounded cells and cell fragments, 72 h after the treatment. Conclusions: The results of the present investigation proved that curcumin is a natural compound potentially useful in the fight against GB.

The development and function of the nervous system is dependent on many growth factors and their signaling. Tropomyosin-receptor-kinase receptor family controls synaptic strength and plasticity in the mammalian nervous system. Dysregulation of Tropomyosin-receptor-kinase receptors signaling can lead to neural developmental disorders and has been reported in certain diseases of the nervous system. Apart from their role in the nervous system, these tyrosine kinase receptors are also involved in cancer biology. Tropomyosin-receptor-kinases and their ligands, neurotrophins, are also involved in neural precursor stem cells differentiation. This review focuses on Tropomyosin-receptor-kinases, the most abundant receptors in mammalian nervous system.