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Glioblastoma multiforme (GBM) is caused by the central nervous system-derived glial cells, and represents the most common (50%-60%) form of primary brain tumors. The aim of this study was to investigate the in vitro effects of selenium on human GBM cells. In the present study, GMS-10 and DBTRG-05MG human GBM cell lines were used as a model to examine selenium entering the cell, cell proliferation, cytotoxicity, DNA fragmentation and Ki-67 protein expression in selenomethionine treated and non-treated groups. Seleno-L-methionine (SeMet) as the organic source of selenium exerted effects on cell proliferation and cytotoxicity, as assessed with WST-1 and lactate dehydrogenase (LDH) tests, respectively. Apoptosis was assessed by DNA fragmentation with an enzyme-linked immunosorbent assay. Ki-67 protein expression was determined by Western blotting, while selenium measurements were performed in the supernatants and lysates by using Graphite Furnace Atomic Absorption Spectrometry. Th is is the first study to examine the effects of SeMet on cell proliferation and death in GMS-10 and DBTRG-05MG cells. Both GBM cell lines responded to SeMet in a dose- and time-dependent manner. WST-1 test showed that low-dose SeMet treatment (50 and 100 μM) increased cell proliferation. Analysis of intracellular SeMet levels by using AAS showed results consistent with viability and cytotoxicity tests. SeMet treatment for 72 h caused increased DNA fragmentation in both cell lines. In conclusion, our results suggest that SeMet induces cell death at high doses, while increasing cell proliferation at low doses. In the view of the data obtained in this investigation, further studies focusing on the possibility of using SeMet against different types of GBM and in combination with prospect synergic compounds are considered to be worthwhile.

In addition to the metabolic role of vitamin D, which is well known and clearly defined, there have been many hypotheses regarding its anti-proliferative and pro-apoptotic role. Epidemiology and Significance of Prostate Cancer. Prostate cancer is the second most common malignancy in men. Long period of cancerogenesis, available tumor markers and high incidence make this cancer ideal for preventive measures. Physiological Role of Vitamin D and its Effect on Prostate Cancer Cells. In vitro and in vivo studies have shown the anti-proliferative and pro-apoptopic role of vitamin D. Disorders of vitamin D metabolism are noted in vitamin D gene level, vitamin D receptor, vitamin D responsive elements and androgen receptors. We present the most important effect of those changes on vitamin D metabolism. Conclusion. Available studies on vitamin D level in serum, prostate tissue, observed activity of vitamin D enzymes and genetic changes give us only a slight insight into the basic mechanisms of vitamin D action in the development of prostate cancer; therefore, further investigations are needed. [ABSTRACT FROM AUTHOR]

Calotropin is a pharmacologically active compound isolated from milkweed plants like Calotropis procera, Calotropis gigantea, and Asclepias currasavica that belong to the Asclepiadaceae family. All of these plants are recognised as medical traditional plants used in Asian countries. Calotropin is identified as a highly potent cardenolide that has a similar chemical structure to cardiac glycosides (such as digoxin and digitoxin). During the last few years, cytotoxic and antitumor effects of cardenolides glycosides have been reported more frequently. Among cardenolides, calotropin is identified as the most promising agent. In this updated and comprehensive review, we aimed to analyze and discuss the specific mechanisms and molecular targets of calotropin in cancer treatment to open new perspectives for the adjuvant treatment of different types of cancer. The effects of calotropin on cancer have been extensively studied in preclinical pharmacological studies in vitro using cancer cell lines and in vivo in experimental animal models that have targeted antitumor mechanisms and anticancer signaling pathways. The analyzed information from the specialized literature was obtained from scientific databases until December 2022, mainly from PubMed/MedLine, Google Scholar, Scopus, Web of Science, and Science Direct databases using specific MeSH search terms. The results of our analysis demonstrate that calotropin can be a potential chemotherapeutic/ chemopreventive adjunctive agent in cancer pharmacotherapeutic management. [ABSTRACT FROM AUTHOR]

The gaps between the complex nature of cancer and therapeutics have been narrowed down due to extensive research in molecular oncology. Despite gathering massive insight into the mysteries of tumor heterogeneity and the molecular framework of tumor cells, therapy resistance and adverse side effects of current therapeutic remain the major challenge. This has shifted the attention towards therapeutics with less toxicity and high efficacy. Myricetin a natural flavonoid has been under the spotlight for its anti-cancer, anti-oxidant, and anti-inflammatory properties. The cutting-edge molecular techniques have shed light on the interplay between myricetin and dysregulated signaling cascades in cancer progression, invasion, and metastasis. However, there are limited data available regarding the nano-delivery platforms composed of myricetin in cancer. In this review, we have provided a comprehensive detail of myricetin-mediated regulation of different cellular pathways, its implications in cancer prevention, preclinical and clinical trials, and its current available nano-formulations for the treatment of various cancers. [ABSTRACT FROM AUTHOR]

Prunus armeniaca L. (Rosaceae)-syn. Amygdalus armeniaca (L.) Dumort., Armeniaca armeniaca (L.) Huth, Armeniaca vulgaris Lam is commonly known as the apricot tree. The plant is thought to originate from the northern, north-western, and north-eastern provinces of China, although some data show that it may also come from Korea or Japan. The apricot fruit is used medicinally to treat a variety of ailments, including use as an antipyretic, antiseptic, anti-inflammatory, emetic, and ophthalmic remedy. The Chinese and Korean pharmacopeias describe the apricot seed as an herbal medicinal product. Various parts of the apricot plant are used worldwide for their anticancer properties, either as a primary remedy in traditional medicine or as a complementary or alternative medicine. The purpose of this review was to provide comprehensive and up-to-date information on ethnobotanical data, bioactive phytochemicals, anticancer potential, pharmacological applications, and toxicology of the genus Prunus armeniaca, thus providing new perspectives on future research directions. Included data were obtained from online databases such as PubMed/Medline, Google Scholar, Science direct, and Wiley Online Library. Multiple anticancer mechanisms have been identified in in vitro and in vivo studies, the most important mechanisms being apoptosis, antiproliferation, and cytotoxicity. The anticancer properties are probably mediated by the contained bioactive compounds, which can activate various anticancer mechanisms and signaling pathways such as tumor suppressor proteins that reduce the proliferation of tumor cells. Other pharmacological properties resulting from the analysis of experimental studies include neuroprotective, cardioprotective, antioxidant, immunostimulatory, antihyperlipidemic, antibacterial, and antifungal effects. In addition, data were provided on the toxicity of amygdalin, a compound found in apricot kernel seeds, which limits the long-term use of complementary/alternative products derived from P. armeniaca. This updated review showed that bioactive compounds derived from P. armeniaca are promising compounds for future research due to their important pharmacological properties, especially anticancer. A detailed analysis of the chemical structure of these compounds and their cytotoxicity should be carried out in future research. In addition, translational pharmacological studies are required for the correct determination of pharmacologically active doses in humans. [ABSTRACT FROM AUTHOR]

Background: In recent decades, the 5-year survival rate of osteosarcoma remains poor, despite the variety of operations, and exploration of drug therapy has become the key to improvement. This study investigates the contribution of different aspects in osteosarcoma and cure, and predicts research hotspots to benefit future clinical outcomes.Methods: The Web of Science and PubMed databases were queried to collect all relevant publications related to osteosarcoma and cure from 2009 to 2019. These data were imported into CiteSpace and the Online Analysis Platform of Literature Metrology for bibliometric analysis. Bi-clustering was performed on Bibliographic Item co-occurrence Matrix Builder (BICOMB) and gCLUTO to identify hotspots. Additionally, completed clinical trials on osteosarcoma with results past phase II were collated.Results: A total of 2258 publications were identified in osteosarcoma and cure from 2009 to 2019. China has the largest number of publications (38.49%), followed by the United States (23.03%) with the greatest impact (centrality = 0.44). The centrality of most institutions is < 0.1, and Central South University and Texas MD Anderson Cancer Center possess the highest average citation rates of 3.25 and 2.87. BMC cancer has the highest average citation rate of 3.26 in 772 journals. Four authors (Picci P, Gorlick R, Bielack SS and Bacci G) made the best contributions. We also identified eight hotspots and collected 41 clinical trials related to drug research on osteosarcoma.Conclusions: The urgent need exists to strengthen global academic exchanges. Overcoming multidrug resistance in osteosarcoma is the focus of past, present and future investigations. Transformation of the metastasis pattern, microenvironment genetics mechanism, alternative methods of systemic chemotherapy and exploration of traditional Chinese medicine is expected to contribute to a new upsurge of research. [ABSTRACT FROM AUTHOR]

Bufalin is an anticancer drug extract from traditional Chinese medicine. Several articles about bufalin have been published. However, the literature on bufalin has not yet been systematically studied. This study aimed to identify the study status and knowledge structures of bufalin and to summarize the antitumor mechanism. Data were retrieved and downloaded from the PubMed database. The softwares of BICOMB, gCLUTO, Ucinet 6.0, and NetDraw2.084 were used to analyze these publications. The bufalin related genes were recognized and tagged by ABNER software. Then these BF-related genes were performed by Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, and protein-protein interaction (PPI) network analysis. A total of 474 papers met the search criteria from 2000 to 2019. By biclustering clustering analysis, the 50 high-frequency main MeSH terms/subheadings were classified into 5 clusters. The clusters of drug therapy and the mechanism of bufalin were hotspot topics. A total of 50 genes were identified as BF-related genes. PPI network analysis showed that inducing apoptosis was the main effect of bufalin, and apoptosis-related gene Caspase 3 was the most reported by people. Bufalin could inhibit the proliferation, invasion, and metastasis of cancer cells through multiple signaling pathways, such as PI3K/AKT, Hedgehog, MAPK/JNK, Wnt/ β -catenin, TGF- β /Smad, Integrin signaling pathway, and NF-KB signaling pathway via KEGG analysis. Through the quantitative analysis of bufalin literature, we revealed the research status and hot spots in this field and provided some guidance for further research. [ABSTRACT FROM AUTHOR]

Aim: To investigate the theme trends and knowledge structure of adipose-derived stem cells (ADSCs) related literatures by using bibliometric analysis. Materials & methods: Co-word analysis, strategic diagram and social network analysis were employed. Results: In line with strategic diagrams, ADSC differentiation and transplantation as main undeveloped themes in 2003–2007 were partially replaced by regeneration medicine and ADSCs for myocardial infarction in 2008 to 2012, and then partially replaced by miRNAs in ADSC genetics and nerve regeneration in 2013 to 2017. Based on social network analysis, regenerative medicine/methods, myocardial infarction/therapy, as well as miRNAs/genetics, and nerve regeneration/physiology were considered the emerging hot spots in 2008 to 2012 and 2013 to 2017. Conclusion: The undeveloped themes and emerging hot spots could be considered as new research topics. [ABSTRACT FROM AUTHOR]

In drug development, phase 1 first-in-human studies represent a major milestone as the drug moves from preclinical discovery to clinical development activities. The safety of human subjects is paramount to the conduct of these studies and regulatory considerations guide activities. Forces of evolution on the pharmaceutical industry are re-shaping the first-in-human dose selection strategy. Namely, high attrition rates in part due to lack of efficacy have led to the re-organization of research and development organizations around the umbrella of translational research. Translational research strives to bring basic research advances into the clinic and support the reverse transfer of information to enhance compound selection strategies. Pharmacokinetic/pharmacodynamic (PK/PD) modeling holds a unique position in translational research by attempting to integrate diverse sets of information. PK/PD modeling has demonstrated utility in dose selection and trial design for later stages of drug development and is now being employed with greater prevalence in the translational research setting to manage risk (i.e., oncology and inflammation/immunology). Moving from empirical E models to more mechanistic representations of the biological system, a higher fidelity of human predictions is expected. Strategies that have proven useful for PK predictions are being applied to PK/PD predictions. This review article examines examples of the application of PK/PD modeling in establishing target concentrations for supporting first-in-human study design. [ABSTRACT FROM AUTHOR]

Endothelial-cell function is important in the healing of damaged endothelium after percutaneous coronary artery damage. In 3 different animal models, we sought to determine whether rapamycin (sirolimus) affects the proliferation and migration of endothelial cells and endothelial progenitor cells. First, after we implanted stents in dogs, we found that re-endothelialization was impeded more by drug-eluting stents than by bare-metal stents, 30 days after percutaneous coronary intervention. Second, in vitro in rats, we found that 1-100 ng/mL of rapamycin time- and dose-dependently inhibited proliferation over 72 hr (with effects evident as early as 24 hr) and also dose-dependently induced endothelial progenitor-cell apoptosis. Finally, in vivo in rats, we observed that vascular endothelial growth factor expression was decreased after 5 days of rapamycin treatment. We conclude that rapamycin impedes reendothelialization after drug-eluting stent implantation by inhibiting the proliferation and migration of coronary endothelial cells, inducing endothelial progenitor-cell apoptosis, and decreasing vascular endothelial growth factor expression in the circulation. [ABSTRACT FROM AUTHOR]

Proteasome inhibitors represent a new class of antineoplastic drugs that are considered in the treatment of haematological malignancies. We compared the effects of the reversible proteasome inhibitor bortezomib (Velcade®) and the epoxomicin derivative PR-171, an irreversible inhibitor, on primary human acute myeloid leukaemia (AML) cells. Both drugs inhibited autocrine- and cytokine-dependent proliferation of primary AML blasts when tested at nanomolar levels (0·1–100 nmol/l). The antiproliferative effect was independent of basal chymotrypsin-like proteasome activity (showing a 20-fold variation between patients), genetic abnormalities, morphological differentiation and CD34 expression when testing a large group of consecutive patients ( n = 54). The effect was retained in cocultures with bone marrow stromal cells. In addition, both drugs enhanced apoptosis. The effect of PR-171 could be detected at lower concentrations than for bortezomib, especially when testing the influence on clonogenic AML cell proliferation. Both drugs had divergent effects on AML cells’ constitutive cytokine release. Furthermore, both drugs caused a decrease in proliferation and viability when tested in combination with idarubicin or cytarabine. An antiproliferative effect on primary human acute lymphoblastic leukaemia cells was also detected. We conclude that nanomolar levels of the proteasome inhibitors tested had dose-dependent antiproliferative and proapoptotic effects on primary AML cells in vitro. [ABSTRACT FROM AUTHOR]