Background: Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods: We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results: In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion: Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical

Glioblastoma multiforme (GBM) has several distinctive characteristics linked to a poor early-stage prognosis. The crucial obstacle in the treatment of GBM is the inability of chemo drugs or other anticancer medicines to reach brain tumors due to the blood–brain tumor barrier (BBTB), leading to weak cytotoxic activity and drug resistance. Additionally, there is a limited number of clinically approved anticancer medicines for GBM because of the heterogeneity of this type of tumor. Presently, four FDA-approved drugs are available for the treatment of GBM, i.e., temozolomide, lomustine, carmustine, and bevacizumab. These drugs are primarily used to treat recurrent high-grade gliomas and their symptoms. Unfortunately, despite efforts to treat GBM over the last 60 years, no significant progress has been made in extending the overall survival (OS) of patients with this disease. Therefore, possible treatments and accessible drugs must be modified or advanced medicines developed to treat GBM. Several innovative strategies have been used to overcome these challenges, such as combining traditional therapies with emerging nanoscale-based biomaterials for multifunctional characteristics. These modified nanoscale biomaterials can cross the blood–brain barrier (BBB) and increase chemo-drug sensitivity through improved accumulation and efficiency. Herein, we review the recent developments in organic and inorganic biomaterial-based nanoparticles for GBM drug delivery. Firstly, we present a brief overview of the FDA-approved drugs and some additional chemo drugs for treating GBM, followed by a discussion on the drawbacks of the delivery of these drugs in GBM. Further, the current challenges in the field of GBM drug delivery, significant advancements in biomaterials research to overcome these obstacles, and subsequent considerations and opportunities for the application of biomaterials in the clinical treatment of GBM are highlighted.

Background and Objective: The ratio of live cells to total cells in a sample is a definition for cell viability or cell toxicity. The assessment of the viable cells plays a critical role in all processes of the cell culture workflows. Overall, they are used to evaluate the survival of cells and also to optimize culture or experimental conditions following treatment with different agents or compounds, like during a drug screen. In most cases, the measurement of cell viability is the primary purpose of the experiments, for example, in pharmaceutical studies to evaluate agents' toxicity. Methods: A literature research was conducted on cell viability assays in MEDLINE (PubMed), Web of Science and Scopus. Results: There is a wide range of cell viability assays and different parameters such as cost, speed, and complexity of a test effect to determine the choosing method. However each method has some advantages and disadvantages and none of them is not 100% perfect method. Conclusion: Accordingly, it seems that the simultaneous utility of at least two assays will cover each other disadvantages to demonstrate the effects of different agents on different cell types. For instance, when one assay measures cell metabolic health, the other one checks cells permeability. Therefore by this strategy a researcher can report with more confidence the effective doses of the examined therapeutic agents.

Bacterial nanocellulose (BNC) is one of the natural biopolymers with unique features, such as nontoxicity, biocompatibility, high tensile profile, nanofiber structure, and purity. The current review aimed to summarize the latest development in BNC-based biomaterials in cancer drug delivery. The original articles were found by searching key databases, including PubMed, Scopus, and Web of Scientific and using key terms such as “bacterial nanocellulose OR bacterial cellulose OR BNC” AND “cancer OR carcinoma OR tumor”. The obtained data were in a wide timeframe and the English language. Totally, 350 articles were found from the three main databases (i.e., 106, 251, and 173 articles from PubMed, Scopus, and the Web of Science, respectively). In general, 32 articles met the inclusion criteria after duplicate removal and screening according to the aim of the study. In this review study, different applications of the BNC were considered for cancer drug delivery in addition to describing advanced methods that may be applied to improve therapeutic potency while reducing the adverse effects of chemodrugs by decreasing their dosages. The high ratio of the surface area-to-volume and easy modifications of their chemical components lead to BNC potential use as an appropriate matrix structure for the binding and controlled release of various pharmaceutical agents, specifically for topical or transdermal administrations. In addition, BNC-based products regulate the release of hydrophobic and hydrophilic compounds, thus providing appropriate materials related to cancer drug delivery. However, undoubtedly, further developments of BNC-based products as cancer drug delivery systems require more extensive investigations.

Background: Gene silence via methylation of the CpG islands is cancer's most common epigenetic modification. Given the highly significant role of NIS in thyroid cancer (TC) differentiation, this cross-sectional study aimed to investigate the DNA methylation pattern in seven CpG islands (CpG1-7 including +846, +918, +929, +947, +953, +955, and +963, respectively) of the NIS promoter in patients diagnosed with papillary (PTC), follicular (FTC), and multinodular goiter (MNG). Additionally, a systematic review of the literature was conducted to compare our results with studies concerning methylation of the NIS gene promoter. Methods: Thyroid specimens from 64 patients met the eligibility criteria, consisting of 28 PTC, 9 FTC, and 27 benign MNG cases. The mRNA of NIS was tested by qRT-PCR. The bisulfite sequencing PCR (BSP) technique was performed to evaluate the promoter methylation pattern of the NIS gene. Sequencing results were received in chromatograph, FASTA, SEQ, and pdf formats and were analyzed using Chromas. The methylation percentage at each position and for each sample was calculated by mC/(mC+C) formula for all examined CpGs; following that, the methylation percentage was also calculated at each CpG site. Besides, a literature search was conducted without restricting publication dates. Nine studies met the eligibility criteria after removing duplicates, unrelated articles, and reviews. Results: NIS mRNA levels decreased in tumoral tissues of PTC (P = 0.04) and FTC (P = 0.03) patients compared to their matched non-tumoral ones. The methylation of NIS promoter was not common in PTC samples, but it was frequent in FTC (P < 0.05). Significant differences were observed in the methylation levels in the 4th(+ 947), 6th(+ 955), and 7th(+ 963) CpGs sites in the forward strand of NIS promoter between FTC and MNG tissues (76.34 ± 3.12 vs 40.43 ± 8.42, P = 0.004, 69.63 ± 3.03 vs 23.29 ± 6.84, P = 0.001 and 50.33 ± 5.65 vs 24 ± 6.89, P = 0.030, respectively). There was no significant correlation between the expression and methylation status of NIS in PTC and FTC tissues. Conclusion: Perturbation in NIS promoter’s methylation individually may have a potential utility in differentiating MNG and FTC tissues. The absence of a distinct methylation pattern implies the importance of other epigenetic processes, which may alter the production of NIS mRNA. In addition, according to the reversibility of DNA methylation, it is anticipated that the design of particular targeted demethylation medicines will lead to a novel cancer therapeutic strategy.