The use of nanoparticles (NPs) in treatment of diseases have increased exponentially recently, giving rise to the science of nanomedicine. The safety of these NPs in humans has also led to the science of nanotoxicology. Due to a dearth of both readily available models and precise bio-dispersion characterization techniques, nanotoxicological research has obviously been constrained. However, the ensuing years were notable for the emergence of improved synthesis methods and characterization tools. Major advances have been made in linking certain physical variables, paralleling improvements in characterization size, shape, or coating factors to the resulting physiological reactions. Although significant progress has been a contribution to the development of nanotoxicology, however, it faces numerous difficulties and technical constraints distinct from those of conventional toxicological assessment as it attempts to improve the therapeutic effects of medicines. Determining thorough characterization standards, standardizing dosimetry, assessing the kinetics of ions dissolving and enhancing the accuracy of in vitro-in vivo correlation efficiency, also defining restrictions on exposure protection are some of the most important and pressing concerns. This article will explore the past advancement and potential prospects of nanotoxicology, standard models, emphasizing significant findings from earlier studies and examining current challenges, giving insight on the way forward.

BACKGROUND:Glioblastomas are characterized by aggressive behavior. Surgery, radiotherapy, and alkylating agents, including temozolomide are the most common treatment options for glioblastoma. Often, conventional therapies fail to treat these tumors since they develop drug resistance. There is a need for newer agents to combat this deadly tumor. Natural products such as gedunin have shown efficacy in several human diseases. A comprehensive study of gedunin, an heat shock protein (HSP)90 inhibitor, has not been thoroughly investigated in glioblastoma cell lines with different genetic modifications. AIMS:A key objective of this study was to determine how gedunin affects the biological and signaling mechanisms in glioblastoma cells, and to determine how those mechanisms affect the proliferation and apoptosis of glioblastoma cells. METHODS:The viability potentials of gedunin were tested using MTT, cell counts, and wound healing assays. Gedunin's effects on glioma cells were further validated using LDH and colony formation assays. In addition, we investigated the survival and apoptotic molecular signaling targets perturbed by gedunin using Western blot analysis and flow cytometry. RESULTS:Our results show that there was a reduction in cell viability and inhibition of wound healing in the cells tested. Western blot analysis of the gene expression data revealed genes such as EGFR and mTOR/Akt/NF kappa B to be associated with gedunin sensitivity. Gedunin treatment induced apoptosis by cleaving poly ADP-ribose polymerase, activating caspases, and downregulating BCL-xL. Based on these results, gedunin suppressed cell growth and HSP client proteins, resulting in apoptosis in glioblastoma cell lines. CONCLUSION:Our data provide in vitro support for the anticancer activity of gedunin in glioma cells by downregulating cancer survival proteins.

The present study investigated the combined effects of erlotinib and luteolin on the proliferation and apoptosis of glioblastoma cell lines overexpressing EGFR or glioma cells expressing truncated EGFR (ΔEGFR). Glioblastomas are the most malignant form of astrocytoma and represent about 50% of all adult primary brain tumors. The multimodal approach to treating glioblastomas includes surgery, radiotherapy, and chemotherapy. However, the prognosis for glioblastomas is very poor because of their invasiveness and chemo- and radio-therapeutic resistance

The epidermal growth factor (EGFR) receptor is frequently overexpressed in glioblastoma multiforme IV (GBM). Increased expression of EGFR leads to increased proliferation, decreased apoptosis, and increased resistance to chemotherapeutic agents. A small molecule called erlotinib inhibits EGFR receptors by binding to their adenosine triphosphate (ATP) binding sites. It is FDA approved to treat a variety of EGFR-mediated cancers. Several clinical trials have explored a combination of erlotinib with other agents to treat glioblastoma since it is believed that erlotinib would benefit patients with GBM with EGFR mutations or expression. Luteolin, a natural flavonoid, inhibits cell growth and induces apoptosis in cancer cells. We investigated the combined effects of erlotinib and luteolin on proliferation and apoptosis on glioblastoma cell lines overexpressing EGFR or glioma cells expressing truncated EGFR (ΔEGFR). In a concentration-dependent fashion, the combination of luteolin and erlotinib reduced cell proliferation (p < 0.05) and induced apoptosis by cleaving PARP and increasing caspase expression. In addition, the combination of luteolin and erlotinib reduced the phosphorylation of downstream EGFR cell signaling molecules such as Akt, NF kappa B, and STAT3 in a concentration-dependent manner. These findings suggest that combining luteolin with erlotinib offers a potential treatment strategy for glioblastoma multiforme IV.

Biologicals have become an integral part of cancer treatment both as therapeutic agents and as supportive care agents. It is important to know that biologics are large, complex molecular entities requiring extensive immunogenicity testing and pharmacovigilance strategies to ensure no immune response is evoked in the body. Oncology's pharmacological market is dominated by biologics; however, their high development and manufacturing costs are burdensome to health care systems. Biologics being the most expensive prescription drugs on the market limit the accessibility for necessary treatment in the case of many patients. As biologics patents expire, the development of biosimilars is underway in an effort to lower costs and enable patients to access new cancer therapies. Regulatory guidelines for biosimilars have now been established and are constantly being revised to address any issues, facilitating their robust development. Moreover, many scientific societies offer guidance to help stakeholders better understand current regulations and biosimilar's safety. Despite the potential cost benefits, lack of knowledge about biosimilars, and the possibility of immunogenicity have created an uncertain environment for healthcare professionals and patients. In this review, we provide an overview of relevant legislation and regulations, pharmacoeconomics, and stakeholder perceptions regarding biosimilars. The article also describes biosimilars in development, as well as the ones currently available on the market.

Background: Medicinal plants serve as sources of compounds used to treat other types of cancers. The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in brain tumor cells. Objective: This study aimed to examine the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival. Methods: The methanolic fraction of Lophira alata (LAM) was subjected to high-performance liquid chroma-tography to determine the fingerprints of the active molecules. The antiproliferative effects of Lophira alata were assessed using the MTT and LDH assays. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways, such as Akt, mTOR, and apoptotic markers such as PARP and caspases. Results: The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-depen-dent decrease in glioma cell proliferation. In addition, LAM attenuated phorbol ester-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha attenuated LAM-me-diated downregulation of Akt. In addition, LAM induced both PARP and caspase cleavages. The HPLC finger-print of the fraction indicates the presence of flavonoids. Conclusion: LAM decreases cell proliferation and induces apoptosis in glioma cell lines and thus could serve as a therapeutic molecule in the management of gliomas.

Glioblastoma multiforme (GBM) is an aggressive neoplasm characterized by an elevated, aberrant, proliferative capacity accompanied by diffuse patterns of brain invasion. It has been estimated that in 2018 there were 17,000 deaths out of 24,000 newly diagnosed cases of GBM. The average life expectancy of patients with GBM is only slightly over one year. Current guideline‐recommended therapy consisting of tumor resection followed by chemotherapy with temozolomide and radiation has shown limited efficacy due to resistance and high recurrence rates. There is a critical need for the development of new drugs and combination treatment modalities that will considerably increase patient survival and improve the poor prognosis of the disease. Natural products have long served as a source of chemotherapeutic agents. Gedunin is a naturally occurring molecule with clinical potential as an HSP90 inhibitor. Gedunin was isolated from the neem tree, Azadirachta indica A. Juss. (Meliaceae). A. Indica, traditionally used for the treatment of malaria, has been shown to possess some anticancer activity. Our primary objective was to determine the antiproliferative and apoptotic effects of gedunin in glioblastoma cell lines, with the goal of also determining the key signaling pathways affected by gedunin.

Glioblastomas are a subtype of gliomas, which are the most aggressive and deadly form of brain tumours. The epidermal growth factor receptor (EGFR) is over-expressed and amplified in glioblastomas. Luteolin is a common bioflavonoid found in a variety of fruits and vegetables. The aim of this study was to explore the molecular and biological effects of luteolin on EGF-induced cell proliferation and the potential of luteolin to induce apoptosis in glioblastoma cells. In vitro cell viability assays demonstrated that luteolin decreased cell proliferation in the presence or absence of EGF. Immunoblots revealed that luteolin decreased the protein expression levels of phosphorylated Akt, mTOR, p70S6K and MAPK in the presence of EGF. Furthermore, our results revealed the ability of luteolin to induce caspase and PARP cleavages in glioblastoma cells in addition to promoting cell cycle arrest. Our results demonstrated that luteolin has an inhibitory effect on downstream signalling molecules activated by EGFR, particularly the Akt and MAPK signalling pathways, and provided a rationale for further clinical investigation into the use of luteolin as a therapeutic molecule in the management of glioblastoma.

Background: The leaf, fruit ,and bark of Momordica charantia (MC)(Common name. Bitter Melon). (Cucurbitaceae) has been used extensively in folk medicine as a remedy for diabetes. Biological and pharmacological activities attributed to different parts and extracts of these plants include anti-HIV, wound healing, anti-helmintic, anti-genotoxicity, larvicidal, antiviral, antimicrobial, anti-obesity, antifertility, anticancer, antidiabetes, antidiarrheal .In Nigeria, a decoction of the leaves or bark is used in folk medicine to manage diabetes. Pregnant and lactating women have been observed, consuming the extract of MC for its folkloric belief as an antidiabetic agent. But its potential for toxicity when administered during pregnancy, lactation and breast feeding has not been completely investigated. The present study was aimed to review the literature for evidence on the use, safety, efficacy and pharmacology of Momordica charantia during pregnancy and lactation.Methods: Seven electronic databases including the Napralert database were searched. Data were compiled based on the grade and evidence found.Results: There were no scientific evidence to support the use of Momordica charantia during pregnancy and lactation. However animal studies in both rodents and primates show that the plant extract, induce abortion. In males, seed extracts of M.charantia, showed indirect evidence of reduced availability of pituitary gonadotrophs necessary for spermatogenesis.Conclusion: Caution should be exercised with the use of Momordica charantia during pregnancy and lactation till human research is conducted to determine its safety. There is a need to be cautious when using preparations containing Momordica charantia. Implications for Nursing: Findings can be utilized by community health nurses and policy makers to advice on the use of Momordica charantia during pregnancy, lactation and in males in their reproductive life.

Objective: Natural products have served as sources of lead compounds that are commonly used in the treatment of human diseases including cancer. Pavetta crassipes has been widely demonstrated to have ethnopharmacological potential in the management of malaria, gastrointestinal conditions, central nervous system behavioral disorders, hypertension, and cancer. The goal of our study was to evaluate the biological and molecular effects of Fraction G, obtained from the plant Pavetta crassipes, on glioblastoma invasive growth and survival. Methodology: The antiproliferative effects of Fraction G, obtained from Pavetta crassipes, was evaluated using the trypan blue exclusion, (3-(4, 5-Dimethylthiazol- 2yl)-2, 5-Diphenyltetrazolium Bromide; MTT), and lactate dehydrogenase (LDH) assays. Flow cytometry and Western blotting analyses were carried out to examine the effects of Fraction G on cell cycle check-points and its effects on epidermal growth factor receptor-mediated signaling of AKT and MAPK pathways. Results: In this paper, we report that the Fraction G obtained from the plant Pavetta crassipes induced a reduction in glioma cell viability and proliferation as well as induced an increase in apoptosis as evidenced by cleaved PARP, increased caspase 3/7 activity, and cell cycle arrest in the G0/G1 check point. Furthermore, we report that Fraction G inhibited the phosphorylation of AKT and MAPK following EGF treatment. Conclusion: Taken together, our results demonstrate that Fraction G has potent inhibitory effects on pathways involved in glioblastoma proliferation and survival.

Background: In Nigeria decoctions and aqueous extract of Azadirachta indica A. juss (AI), are commonly used in the treatment of malaria. Some women have been observed consuming aqueous extract of AI during pregnancy and lactation because of the folkloric belief that it is potentially harmless.Objectives: There is a paucity of data on the effects of consumption of AI during pregnancy and lactation.Its use by women during lactation and pregnancy, calls for an in-depth understanding of its efficacy and potential for harm during pregnancy and lactation.

Nature has provided a diverse array of secondary metabolites. Many of these metabolites have intricate molecular scaffolding and important pharmacological properties. Among the pharmacologically important secondary compounds found in plants are the lignins, lignans, polyketide, and polyacetylene compounds. A survey of the recent literature yielded a large number of manuscripts detailing the isolation and characterization of compounds belonging to these structural classes.

ObjectivesGlioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM.MethodsProliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses.Key findingsOur results showed that apigenin reduced cell viability and proliferation in a dose- and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL.ConclusionOur results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM.

Brittenham K, Choi R, Kapraly M, Kime B, Knoebel J Statement of the Research Problem: There is insufficient data available concerning the stability of promethazine in different intravenous (IV) formulations. Research Objective: To determine the stability of promethazine in different IV formulations with regard to temperature and light. H0: There is no statistically significant difference in the stability of promethazine in different IV formulations with regard to temperature and light. HA: There is a statistically significant difference in the stability of promethazine in different IV formulations with regard to temperature and light.

Progress in research on the molecular aspects of glioblastoma has yet to provide a medical therapy that significantly improves prognosis. Glioblastoma invariably progress through current treatment regimens with radiotherapy as a key component. Activation of several signaling pathways is thought to be associated with this resistance to radiotherapy. Ras activity is exceptionally high in glioblastoma and may regulate sensitivity to radiotherapy. Raf-1, a downstream effector of Ras, demonstrates a high amount of activity in glioblastoma. Therefore, Raf-1 inhibition should be considered as a mechanism to increase the effectiveness of radiotherapy in treatment regimen. In vitro analysis was performed with a novel Raf-1 kinase inhibitor (BAY 54-9085) in culture with the glioblastoma cell line U1242. The cell line was treated in serum-containing media and analyzed for the effect of the BAY 54-9085 alone and BAY 54-9085 combined with radiation on cell death. BAY 54-9085 displayed a cytocidal effect on glioblastoma cells following a 3 day incubation with the drug in serum-containing media. A dose of 2.5 μM displayed moderate cell death which significantly increased with a dose of 5.0 μM. In addition, glioblastoma cells treated with both the BAY 54-9085 and gamma radiation displayed a significant increase in cell death (85.5%) as compared to either BAY 54-9085 (73.1%) or radiation (34.4%) alone. Radiation therapy is a key component of treatment for glioblastoma. A novel Raf-1 inhibitor displayed in vitro evidence of synergistically increasing cell death of glioblastoma cells in combination with radiation.