Prognostic Factors for Survival in Glioblastoma: A Retrospective Analysis Focused on the Role of Hemoglobin.

: Although several prognostic factors for survival have been identified in glioblastoma, there are numerous other potential markers (such as hemoglobin) whose role has not yet been confirmed. The aim of this study was to evaluate a wide range of potential prognostic factors, including HIF-1α and hemoglobin levels, for survival in glioblastoma. A secondary aim was to determine whether hemoglobin levels were associated with HIF-1α expression.

Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients.

Background: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients.

Comparative Analysis of miRNA and EMT Markers in Metastatic Colorectal Cancer.

Colorectal cancer (CRC) is the fourth most commonly diagnosed malignant condition in the world. Micro RNAs (miRNAs) as well as epithelial to mesenchymal transition (EMT) play an important role in the pathogenesis of CRC. We performed a comparative analysis of the expression of selected miRNA genes and EMT markers in bioptic samples from patients (n = 45) with primary CRC or metastatic (m)CRC to the regional lymph node using reverse transcription-quantitative PCR and IHC staining.

Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest.

Glioblastoma multiforme (GBM) belongs to most aggressive and invasive primary brain tumor in adults whose prognosis and survival remains poor. Potential new treatment modalities include targeting the cytoskeleton. In our study, we demonstrated that repurposed drug flubendazole (FLU) significantly inhibits proliferation and survival of GBM cells.

Increased Intracellular Free Zinc Has Pleiotropic Effects on Doxorubicin-Induced Cytotoxicity in hiPCS-CMs Cells.

(1) the mechanisms and outcomes of doxorubicin (DOX)-dependent toxicity upon changed intracellular zinc (Zn) concentrations in the cardiomyocytes obtained from human-induced pluripotent stem cells (hiPCS-CMs) were investigated; (2) cells exposed to the DOX were pretreated or cotreated with zinc pyrythione (ZnPyr) and various cellular endpoints and mechanisms were analyzed via cytometric methods; (3) both DOX concentrations (0.3 and 1 µM) induced a concentration-dependent loss of viability, an activation of autophagy, cell death, and the appearance of senescence. These phenotypes were preceded by an oxidative burst, DNA damage, and a loss of mitochondrial and lysosomal integrity.

Role of N-Cadherin in Epithelial-to-Mesenchymal Transition and Chemosensitivity of Colon Carcinoma Cells.

(1) Background: N-cadherin expression, epithelial-to-mesenchymal transition (EMT) and aggressive biological phenotype of tumor cells are linked although the underlying mechanisms are not entirely clear. (2) Methods: In this study, we used two different in vitro cell models with varying N-cadherin expression (stabilized lines and primocultures) and investigated their select biological features including the degree of their chemoresistance both in vitro as well as in vivo. (3) Results: We report that although enforced N-cadherin expression changes select morphological and behavioral characteristics of exposed cells, it fails to successfully reprogram cells to the aggressive, chemoresistant phenotype both in vitro as well as in vivo as verified by implantation of those cells into athymic mice.

Evaluating the Use of TiO Nanoparticles for Toxicity Testing in Pulmonary A549 Cells.

Purpose: Titanium dioxide nanoparticles, 25 nm in size of crystallites (TiO P25), are among the most produced nanomaterials worldwide. The broad use of TiO P25 in material science has implied a request to evaluate their biological effects, especially in the lungs. Hence, the pulmonary A549 cell line has been used to estimate the effects of TiO P25.

Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells.

Zinc levels in serum and/or tissue are reported to be altered in melanoma with unknown effects on melanoma development and biology. The purpose of this study was to examine the effects of acute chelation of free intracellular zinc pools in melanoma cell lines Bowes and A375, as well as selected melanoma tissue explants with high or low intracellular free zinc. Zinc chelating agent TPEN at the concentration of 25 µM was employed during 48 h, which significantly reduced intracellular free zinc while decreasing melanoma cell proliferation, inducing G1/S arrest and cell damage leading to mitochondrial, caspase-dependent apoptosis.

The Effect of Chronic Exposure of Graphene Nanoplates on the Viability and Motility of A549 Cells.

Graphene and its derivatives are popular nanomaterials used worldwide in many technical fields and biomedical applications. Due to such massive use, their anticipated accumulation in the environment is inevitable, with a largely unknown chronic influence on living organisms. Although repeatedly tested in chronic in vivo studies, long-term cell culture experiments that explain the biological response to these nanomaterials are still scarce.

Silencing of E-cadherin expression leads to increased chemosensitivity to irinotecan and oxaliplatin in colorectal cancer cell lines.

Colorectal carcinoma (CRC) is a leading malignant disease in most developed countries. In advanced stages it presents with metastatic dissemination and significant chemoresistance. Despite intensive studies, no convincing evidence has been published concerning the association of cadherins and epithelial-mesenchymal transition (EMT) as a direct cause of acquired chemoresistance in CRC.

Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model.

Sarcomas are a heterogeneous group of mesenchymal tumours, with a great variability in their clinical behaviour. While our knowledge of sarcoma initiation has advanced rapidly in recent years, relatively little is known about mechanisms of sarcoma progression. JUN-murine fibrosarcoma progression series consists of four sarcoma cell lines, JUN-1, JUN-2, JUN-2fos-3, and JUN-3.

Acute Increases in Intracellular Zinc Lead to an Increased Lysosomal and Mitochondrial Autophagy and Subsequent Cell Demise in Malignant Melanoma.

Changes in zinc content and dysregulated zinc homeostatic mechanisms have been recognized in several solid malignancies such as prostate cancer, breast cancer, or pancreatic cancer. Moreover, it has been shown that zinc serum and/or tissue levels are altered in melanoma with varying effects on melanoma development and biology. This study was conducted to explore the effects of acute increases of intracellular zinc in a set of melanoma tissue explants obtained from clinical samples.

Biology of Glioblastoma Multiforme-Exploration of Mitotic Catastrophe as a Potential Treatment Modality.

Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM cells with emphasis on cell cycle and cytoskeletal apparatus of these cells, in particular microtubules.

The Evaluation of Glioblastoma Cell Dissociation and Its Influence on Its Behavior.

Purpose: Primary cell lines are a valuable tool for evaluation of tumor behavior or sensitivity to anticancer treatment and appropriate dissociation of cells could preserve genomic profile of the original tissue. The main aim of our study was to compare the influence of two methods of glioblastoma multiforme (GBM) cell derivation (mechanic-MD; enzymatic-ED) on basic biological properties of thus derived cells and correlate them to the ones obtained from stabilized GBM cell line A-172.

Methods: Cell proliferation and migration (xCELLigence Real-Time Cell Analysis), expression of microRNAs and protein markers (RT-PCR and Western blotting), morphology (phase contrast and fluorescent microscopy), and accumulation of temozolomide (TMZ) and its metabolite 5-aminoimidazole-4-carboxamide (AIC) inside the cells (LC-MS analysis) were carried out in five different samples of GBM (GBM1, GBM2, GBM32, GBM33, GBM34), with each of them processed by MD and ED types of isolations.

Cardiac Troponins are Among Targets of Doxorubicin-Induced Cardiotoxicity in hiPCS-CMs.

Modern diagnostic strategies for early recognition of cancer therapeutics-related cardiac dysfunction involve cardiac troponins measurement. Still, the role of other markers of cardiotoxicity is still unclear. The present study was designed to investigate dynamics of response of human cardiomyocytes derived from induced pluripotent stem cells (hiPCS-CMs) to doxorubicin with the special emphasis on their morphological changes in relation to expression and organization of troponins.

Selected Aspects of Chemoresistance Mechanisms in Colorectal Carcinoma-A Focus on Epithelial-to-Mesenchymal Transition, Autophagy, and Apoptosis.

Chemoresistance has been found in all malignant tumors including colorectal carcinoma (CRC). Nowadays chemoresistance is understood as a major reason for therapy failure, with consequent tumor growth and spreading leading ultimately to the patient's premature death. The chemotherapy-related resistance of malignant colonocytes may be manifested in diverse mechanisms that may exist both prior to the onset of the therapy or after it.

The effect of sodium butyrate and cisplatin on expression of EMT markers.

Histone modifications play a key role in the epigenetic regulation of gene transcription in cancer cells. Histone acetylations are regulated by two classes of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are increased in ovarian carcinomas and they are involved in carcinogenesis and resistance to chemotherapeutic agents.

Flubendazole and mebendazole impair migration and epithelial to mesenchymal transition in oral cell lines.

Benzimidazole anthelmintics flubendazole and mebendazole are microtubule-targeting drugs that showed considerable anti-cancer activity in different preclinical models. In this study, the effects of flubendazole and mebendazole on proliferation, migration and cadherin switching were studied in a panel of oral cell lines in vitro. Both compounds reduced the viability of the PE/CA-PJ15 and H376 oral squamous carcinoma cells and of the premalignant oral keratinocytes DOK with the IC values in the range of 0.

Inositol hexaphosphate limits the migration and the invasiveness of colorectal carcinoma cells in vitro.

Inositol hexaphosphate (IP6), also known as phytic acid, has been shown to exhibit anticancer effects in a number of preclinical tumor models. IP6 decreases proliferation by arresting cells in the G0/G1 phase, inhibits iron-mediated oxidative reactions, enhances differentiation and stimulates apoptosis. The present study attempted to characterize the effect of IP6 on the migration and adhesion of colon cancer SW620 cells.

Oxaliplatin and irinotecan induce heterogenous changes in the EMT markers of metastasizing colorectal carcinoma cells.

In patients with advanced colorectal cancer (CRC), surgery is complemented with systemic therapy - chemotherapy and radiochemotherapy. Although the patients' overall survival has been significantly improved, tumor resistance is still a frequent cause of chemotherapy failure. Several factors contribute to chemoresistance of tumor cells including changes related with epithelial-mesenchymal transition (EMT).

Increases in Intracellular Zinc Enhance Proliferative Signaling as well as Mitochondrial and Endolysosomal Activity in Human Melanocytes.

Background/aims: Zinc (Zn) is an important microelement required by skin cells for a variety of biological processes. The role of Zn in melanocyte proliferation and homeostasis has to date not been investigated.

Methods: Human dermal melanocytes were isolated from patients and their proliferative activity determined along with both total and labile Zn content.

Anthelmintic Flubendazole and Its Potential Use in Anticancer Therapy.

Flubendazole is a widely used anthelmintic drug belonging to benzimidazole group. The molecular mechanism of action of flubendazole is based on its specific binding to tubulin, which results in disruption of microtubule structure and function, and in the interference with the microtubule-mediated transport of secretory vesicles in absorptive tissues of helminths. The microtubule-disrupting properties of benzimidazole derivatives raised recently interest in these compounds as possible anti-cancer agents.

Boldine Inhibits Mouse Mammary Carcinoma In Vivo and Human MCF-7 Breast Cancer Cells In Vitro.

Boldine is an aporphine alkaloid widely consumed in the folk medicine of some regions. Its anticancer potential has been shown but not yet elucidated. We compared the antitumor effect of orally and parenterally applied boldine in mice bearing solid Ehrlich tumor.