Metformin represses the carcinogenesis potentially induced by 50 Hz magnetic fields in aged mouse fibroblasts via inhibition of NF-kB.

Aging is a risk factor for various human disorders, including cancer. Current literature advocates that the primary principles of aging depend on the endogenous stress-induced DNA damage caused by reactive oxygen species 50 Hz low-frequency magnetic field was suggested to induce DNA damage and chromosomal instability. NF-kB, activated by DNA damage, is upregulated in age-related cancers and inhibition of NF-kB results in aging-related delayed pathologies.

Midkine: A Cancer Biomarker Candidate and Innovative Therapeutic Approaches.

Midkine (MDK) is a protein that contributes to both physiological and pathological processes. Several studies provide insight into the different roles of MDK in development, tissue repair, neural plasticity, and health and disease processes. This research further examined how MDK contributed to conditions, including neurological diseases, inflammation, and ischaemia.

In vitro effects of heparin-binding epidermal growth factor on adhesion stage of implantation.

A member of the epidermal growth factor (EGF) family, the heparin-binding EGF (HB-EGF) is expressed in the uteri of both humans and mice during the implantation process. To study the effects of HB-EGF on adhesion stage, we developed an in vitro implantation model employing Ishikawa cell line and JAR cell line, which may attach to Ishikawa cells. For 1, 6, 12, and 24 hours, co-cultures of JAR spheroids grown on Ishikawa monolayers were treated with 1, 10, and 100 ng∕mL doses of HB-EGF.

The Possible Interactions and Therapeutic Roles of Lithium Chloride and Midkine on Cancer Treatment.

Midkine (MK) is a heparin-binding anti-apoptotic growth factor or cytokine also known as neurite growth-promoting factor 2 (NEGF2). It is developmentally an important retinoic acid-responsive gene product strongly induced during the mid-gestation stage. Midkine promotes different cellular events such as cell growth, differentiation, survival, gene expression, and drug resistence.

Inhibition of midkine by metformin can contribute to its anticancer effects in malignancies: A proposal mechanism of action of metformin in context of endometrial cancer prevention and therapy.

Metformin, a drug widely used in the treatment of type II diabetes mellitus (T2DM), has been the focus of interest as a potential therapeutic agent for certain types of malignancies, including gynaecological cancers [i.e. endometrial cancer (EC)].

Gemcitabine, vinorelbine and cyclooxygenase inhibitors in the treatment of glioblastoma. Ultrastructural analyses in C6 glioma in vitro.

Objectives: To define ultrastructural features accompanying to antitumor effects of gemcitabine, vinorelbine and cyclooxygenase inhibitors in C6 glioma cells in vitro. Vinorelbine is a semisynthetic vinca alkaloid and recent studies showed its antitumor activity in pediatric optic and pontine gliomas. Vinorelbine infusion induces a severe tumor site-pain in systemic cancers, but it is unknown whether algesia and inflammation contribute to its antitumor effects.

Midkine silencing enhances the anti-prostate cancer stem cell activity of the flavone apigenin: cooperation on signaling pathways regulated by ERK, p38, PTEN, PARP, and NF-κB.

Prostate cancer (PCa) is the most common cancer in men worldwide. Midkine (MK) is overexpressed in PCa, as well as in tumor-initiating cells termed cancer stem cells (CSCs). Apigenin is a dietary flavone with considerable anti-tumor activities.

Methylation Changes of Primary Tumors, Monolayer, and Spheroid Tissue Culture Environments in Malignant Melanoma and Breast Carcinoma.

Epigenetic changes have major role in the normal development and programming of gene expression. Aberrant methylation results in carcinogenesis. The primary objective of our study is to determine whether primary tumor tissue and cultured tumor cells in 2D and 3D tissue culture systems have the same methylation signature for , , and .

Medroxyprogesterone effects on colony growth, autophagy and mitochondria of C6 glioma cells are augmented with tibolone and temozolomide: Cell kinetic and electron microscopical studies with a broad review of the literature.

Objective: Risk of high grade gliomas is lower in young females and its incidence enhances after menopause suggesting likely protective roles of female hormones. Hormone replacement therapy (HRT) was widely employed to treat osteoporosis and some epidemiological studies showed that HRT regimes including progesterone analogs such as medroxyprogesterone acetate (MPA) decreased risk of glial tumors. Tibolone is a unique progesterone analog employed in HRT with tissue specific estrogenic effects and stimulates gene expressions very similar to those induced by MPA.

Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway.

Aims: To examine the functions of growth factor midkine (MK) and a flavonoid quercetin on survival, apoptosis and migration of prostate cancer (PCa) stem cells (CSCs).

Main Methods: CD44/CD133 and CD44 stem cells were isolated from PC3 and LNCaP cells, respectively by magnetic-activated cell sorting system. 3D cell culture was used to evaluate the ability of quercetin, MK siRNA, and the combination of both to inhibit spheroid formation, apoptosis and cell cycle arrest.

Erucic acid, a component of Lorenzo's oil and PPAR-δ ligand modifies C6 glioma growth and toxicity of doxorubicin. Experimental data and a comprehensive literature analysis.

Background: PPAR-δ is a transcription factor which has crucial roles in stimulating oligodendroglial differentiation and myelination and its activation was also shown to differentiate malignant C6 glioma cells into oligodendrocytes.

Objective: One of the ligands of PPAR-δ is erucic acid (EA), an edible omega-9 fatty acid consumed more by Asian populations and exists highly in Chinese womens milk. There exist epidemiological evidence that pediatric brain tumor incidence is among the lowest in the Chinese population.

Effects of different drug treatments on the proliferation of human ovarian carcinoma cell line MDAH-2774.

Background/aim: In this study, the effects of resveratrol as a natural polyphenol compound, gemcitabine as an antimetabolite that has nucleoside structure analogous to deoxycytidine, and para-aminophenol-derived paracetamol were investigated with single and combined applications in monolayers of the MDAH-2774 human ovarian cancer cell line. Materials and methods: Drugs were evaluated in cell culture with respect to cell proliferation, cell cytotoxicity (trypan blue dye exclusion test), synthesis phase of cell cycle, and cell structure in 24, 48, 72, and 96 h. Result: Resveratrol and gemcitabine diminished both cell proliferation and cell cycle synthesis phase indication in monolayer cell cultures (P < 0.

Dual inhibition of P-glycoprotein and midkine may increase therapeutic effects of anticancer drugs.

Multidrug resistance (MDR) to chemotherapy may significantly affect the outcome of cancer treatment. ATP-dependent drug efflux pumps, including P-glycoprotein (P-gp), contribute to the resistance of various chemotherapeutic agents. Overexpression of P-gp in tumor cells induces chemoresistance via pumping the anticancer drugs out of the cells.

1,25-Dihydroxyvitamin D stimulates odontoblastic differentiation of human dental pulp-stem cells in vitro.

Background: 1,25-Dihydroxyvitamin D (1,25-OH D) plays an important role in mineralized tissue metabolism, including teeth. However, few studies have addressed its role in odontoblastic differentiation of human dental pulp-stem cells (hDPSCs).

Aim: This study aimed to understand the influence of various concentrations of 1,25-OH D on the proliferation capacity and early dentinogenesis responses of hDPSCs.

Lithium chloride has a biphasic effect on prostate cancer stem cells and a proportional effect on midkine levels.

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide and the levels of differentiation growth factor midkine (MK) are increased in PCa. Cancer and/or the treatment process itself may lead to psychiatric disorders. Lithium chloride (LiCl) has anti-manic properties and has been used in cancer therapy; however, it has a queried safety profile.

The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling.

Aims: Cancer stem cells (CSCs) are involved in drug resistance, metastasis and recurrence of cancers. The efficacy of apigenin on cell survival, apoptosis, migration and stemness properties were analyzed in CSCs.

Main Methods: Prostate CSCs (CD44(+)) were isolated from human prostate cancer (PCa) PC3 cells using a magnetic-activated cell sorting system.

Antagonist activity of the antipsychotic drug lithium chloride and the antileukemic drug imatinib mesylate during glioblastoma treatment in vitro.

Objectives: Glioblastoma (GBM), the most common primary tumour of the central nervous system, is characterised by a high malignancy and poor prognosis. The aims of this study were to investigate whether the combination of imatinib mesylate (IM) and lithium chloride (LiCl) exhibited a synergistic effect in treatment and to determine whether midkine (MK) affected the fate of this treatment in vitro.

Methods: Monolayer and spheroid cultures of the T98G human GBM cell line were treated with an IM and LiCl combination for 72 h.

Differences between Solution and Membrane Forms of Chitosan on the In Vitro Activity of Fibroblasts.

Background: Chitosan, a linear polysaccharide, has been recently used in biomedical applications. In vitro studies have demonstrated its effect on cellular growth and its stimulatory action on cellular layer formation.

Aims: The present study aims to compare the proliferative effects of chitosan in two forms, membranous and solution forms, on Swiss 3T3 mouse embryonic fibroblasts.

Effects of hemostatic agents on fibroblast cells.

Purpose: Hemostatic agents may be used topically to control hemorrhage, especially in patients with bleeding disorders. The agent used may have a negative effect on the tissue prolonging the healing time. The aim of this study was to compare the effects of 3 different hemostatic agents on fibroblast cells on a rat primary fibroblast cell culture model.

Ficus carica latex prevents invasion through induction of let-7d expression in GBM cell lines.

Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required.

Antibacterial effect of Kenger gum on mutans streptococci and its cytotoxic effect on the 3T3 fibroblast cell line.

Purpose: To evaluate the antibacterial effect of Kenger gum on mutans streptococci (in vivo) and Streptococcus mutans (in vitro) and its cytotoxic effect on the 3T3 fibroblast cell line.

Materials And Methods: In vitro antibacterial activity of Kenger gum extracts against S.mutans was determined by the disk-diffusion method.

Expression profiling of stem cell signaling alters with spheroid formation in CD133/CD44 prostate cancer stem cells.

Cancer stem cells (CSC) isolated from multiple tumor types differentiate and when cultured in serum; however, the factors responsible for their differentiation have not yet been identified. The first aim of the present study was to identify CD133/CD44 DU145 prostate CSCs and compare their profiles with non-CSCs as bulk counterparts of the population. Subsequently, the two populations continued to be three-dimensional multicellular spheroids.

WNT1 gene expression alters in heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+ prostate cancer stem cell spheroids.

Purpose: Established cancer cell lines contain cancer stem cells (CSCs) which can propagate to form three dimensional (3D) tumor spheroids in vitro. Aberrant activation of WNT signaling is strongly implicated in the progression of cancer and controls CSCs properties. In this study we hypothesized that when cells were maintained as spheroids, the structure of CSCs could show differentiation between CSCs and non- CSCs.

Sorafenib and lithium chloride combination treatment shows promising synergistic effects in human glioblastoma multiforme cells in vitro but midkine is not implicated.

Objectives: The objectives of this study were to test the effects of the new combination treatment modality, sorafenib (SOR) and lithium chloride (LiCl) and to assess whether midkine (MK) protein has a role in any potential effects.

Methods: Monolayer and spheroid cultures of T98G human glioblastoma multiforme (GBM) cells were treated with LiCl and SOR (inhibition concentration 50 value  =  100 μM), or their combination, or were left untreated (control). Cell proliferation and apoptotic indices, the mechanism of action, and the levels of apoptotic and anti-apoptotic proteins were evaluated in monolayer cultures and ultrastructure was evaluated by transmission electron microscopy (TEM) in spheroid cultures after for 72 hours.