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Curcumin is a polyphenol extracted from the rhizomes of the turmeric plant, Curcuma longa which has anti-inflammatory, and anticancer properties. Chronic inflammation is associated with the development of cancer. Curcumin acts on the regulation of various immune modulators, including cytokines, cyclooxygenase-2 (COX-2), and reactive oxygen species (ROS), which partly explains its anticancer effects. It also takes part in the downregulation of growth factors, protein kinases, oncogenic molecules and various signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (STAT3) signaling. Clinical trials of curcumin have been completed or are ongoing for various types of cancer. This review presents the molecular mechanisms of curcumin in different types of cancer and the evidence from the most recent clinical trials.

Glioblastoma is the most common and lethal type of tumor of the central nervous system, with an average survival of 15 months after first diagnosis. Immune checkpoint inhibitors (ICIs) have been largely investigated for their ability to harness the immune system to combat tumors. However, their efficacy varies a lot depending on tumor type. In glioblastoma, PD-1/PD-L1 immunotherapy has been explored in various studies; however, the unique immunosuppressive environment in the brain and the presence of the blood–brain barrier as well as the large intratumoral heterogeneity have limited its efficacy considerably. In order to improve the clinical efficacy of ICIs, it is important to delve into the different factors affecting the response rate in GBM. Herewith, we summarize the most common causes of resistance to anti-PD-1/PD-L1 immunotherapy as well as possible ways of enhancing its efficacy, particularly through combination with other therapeutic agents in the preclinical and clinical setting. Furthermore, we provide an insight into the most promising methods for modulating the blood–brain barrier, as well as the growing role of molecular imaging and radiogenomics in this field.

Radiation therapy plays an important role in almost every cancer treatment. However, radiation toxicity to normal tissues, mainly due to the generation of reactive free radicals, has limited the efficacy of radiotherapy in clinical practice. Curcumin has been reported to possess significant antitumor properties. Although curcumin can sensitize cancer cells to irradiation, healthy cells are much less sensitive to this effect, and thus, curcumin is thought to be a potent, yet safe anti-cancer agent. In this review, a summary of the role of curcumin as both a radiosensitizer and radioprotector has been presented, based on the most recent data from the experimental and clinical evaluation of curcumin in different cancer cell lines, animal models, and human patients.

Difluoromethylornithine (DFMO; eflornithine) is an irreversible suicide inhibitor of the enzyme ornithine decarboxylase which is involved in polyamine synthesis. Polyamines are important for cell survival, thus DFMO was studied as an anticancer agent and as a chemoprevention agent. DFMO exhibited mainly cytostatic activity and had single agent efficacy as well as activity in combination with other chemotherapeutic drugs for some cancers and leukemias. Herewith, we summarize the current knowledge of the anticancer and chemopreventive properties of DFMO and assess the status of clinical trials.

Curcumin, a bioactive polyphenol, is known to have anticancer properties. In this study, the effectiveness of curcumin pretreatment as a strategy for radio-sensitizing glioblastoma cell lines was explored. For this, U87 and T98 cells were treated with curcumin, exposed to 2 Gy or 4 Gy of irradiation, and the combined effect was compared to the antiproliferative effect of each agent when given individually. Cell viability and proliferation were evaluated with the trypan blue exclusion assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic effects of the combination treatment were analyzed with CompuSyn software. To examine how the co-treatment affected different phases of cell-cycle progression, a cell-cycle analysis via flow cytometry was performed. Treatment with curcumin and radiation significantly reduced cell viability in both U87 and T98 cell lines. The combination treatment arrested both cell lines at the G2/M phase to a higher extent than radiation or curcumin treatment alone. The synergistic effect of curcumin when combined with temozolomide resulted in increased tumor cell death. Our results demonstrate for the first time that low doses of curcumin and irradiation exhibit a strong synergistic anti-proliferative effect on glioblastoma cells in vitro. Therefore, this combination may represent an innovative and promising strategy for the treatment of glioblastoma, and further studies are needed to fully understand the molecular mechanism underlying this effect.

Aims : To highlight possible correlations of type 2 diabetes mellitus (T2DM) with microscopic / macroscopic characteristics of colorectal cancer tissues, along with the expression of Ten-Eleven Translocation 2 (TET2) and glutathione-S-transferase pi (GST-pi) proteins. Materials and methods : Tumors from 46 patients were embedded in paraffin blocks, stained with hematoxylin-eosin and studied microscopically. Immunohistochemical study of TET2 and GST-pi expression was performed. The results were analyzed and correlated with T2DM as comorbidity. Results : All tumors expressed GST-pi at three levels (weak, moderate, and strong); two out of three tumors showed either weak or moderate TET2 expression. Patients without T2DM tended to have tumors with weak or no expression of TET2 ( p =0.038) whereas diabetic patients’ tumors showed a significantly higher percentage of strong or moderate GST-pi expression ( p =0.034). On binomial logistic regression, tumors excised from T2DM patients were 6.9 times more likely to show moderate (rather than weak and none) TET2 expression compared to tumors from non-diabetic patients (95% CI [1.33, 35.75]), and a 2.7-fold higher relative likelihood of showing strong (rather than moderate and weak) GST-pi expression (95% CI [0.63, 12.09]), taking into account sex, age, and tumor size. The association between T2DM and TET2 expression remains statistically significant in additional binomial analysis that was performed taking into account certain histological tumor characteristics. Conclusions : TET2 and GST-pi are expressed in malignant colon tumors. T2DM in CRC patients was associated with the highest observed GST-pi expression; absence of T2DM was associated with the lowest observed TET2 expression. T2DM increases the probability of observing GST-pi and TET2 expression at maximum levels, independent of specific tumor microscopic features and certain patient characteristics.

The interferons (IFNs) are a family of cytokines with diverse cellular actions such as control of cell proliferation and regulation of immune responses; therefore, they have been extensively studied as antitumor agents for a variety of malignancies, including gliomas. Type I IFNs exert their antitumor effects either directly, by targeting the tumor cells or the tumor stem cells, or indirectly, by regulating the anticancer activities of the immune system. More specifically, IFN-beta and IFN-alpha exhibit antiproliferative effects by p53 induction, CD8+ T-lymphocyte and macrophage activation, chemokine secretion, and miR-21 downregulation. In vitro and in vivo studies provide evidence that immunotherapy could have a role in glioma treatment, especially when first-line therapeutic interventions fail to produce durable responses. These effects are more obvious when combining IFN-beta with classical antitumor therapies such as temozolamide, an oral chemotherapeutic, for both newly diagnosed and recurrent gliomas. However, further clinical studies are needed to determine whether IFNs will have a definite place in the management of gliomas.

Although several antipsychotic drugs have been shown to possess anticancer activities, haloperidol, a “first-generation” antipsychotic drug, has not been extensively evaluated for potential antineoplastic properties. The aim of this study was to investigate the antitumoral effects of haloperidol in glioblastoma (GBM) U87, U251 and T98 cell lines, and the effects of combined treatment with temozolomide (TMZ) and/or radiotherapy, using 4 Gy of irradiation. The viability and proliferation of the cells were evaluated with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis, using the annexin-propidium iodide (PI), and cell cycle, cluster of differentiation (CD) expression and caspase-8 activation were measured using flow cytometry. Treatment with haloperidol significantly reduced cell viability in U87, U251 and T98 GBM cell lines. Haloperidol induced apoptosis in a dose-dependent manner, inhibited cell migration and produced an alteration in the expression of CD24/CD44. The additional effect of haloperidol, combined with temozolomide and radiation therapy, increased tumor cell death. Haloperidol was observed to induce apoptosis and to increase caspase-8 activation. In conclusion, haloperidol may represent an innovative strategy for the treatment of GBM and further studies are warranted in glioma xenograft models and other malignancies.

The objective of this study was to analyze the characteristics that contribute to the successful dissemination of VIM-producing Pseudomonas aeruginosa (P. aeruginosa), belonging to ST111 and ST235, in a Greek hospital. A total of 120 non-repetitive P. aeruginosa, which had meropenem minimal inhibitory concentrations (MICs) greater than 2 mg/L, were studied. VIM-encoding genes were amplified and sequenced within their integrons. Isolates were typed by multilocus sequence typing (MLST). Six VIM-producers, representative of different integron structures and sequence types (STs), were completely sequenced using Illumina platform. Sixty-one P. aeruginosa were confirmed to produce VIM-type carbapenemases. ST111 dominated (n = 34) among VIM-producers, while 15 VIM-producers belonged to ST235. The blaVIM-like genes were located in three integron types, including In59, In595 and In1760, which were integrated into P. aeruginosa chromosomes. Whole genome sequencing (WGS) data demonstrated that ST111 and ST235 MBL producers carried several resistance and virulence genes. Additionally, the presence of type I-C and type I-E clustered regularly interspaced short palindromic repeats (CRISPR)/Cas locus was observed in ST235 and ST395 isolates, respectively. In conclusion, our findings confirmed the clonal spread of ST111 P. aeruginosa, carrying the VIM-2-encoding integron In59, in the University Hospital of Larissa (UHL). In addition, they highlighted the important role of high-risk clones, ST111 and ST235, in the successful dissemination and establishment into hospital settings of clinically important pathogens carrying resistance determinants.

Glioblastoma (GBM) is the most aggressive primary central nervous system (CNS) tumor in adults with dismal prognosis. Currently, the therapeutic interventions include gross total resection, when possible, followed by radiotherapy and chemotherapy. However, despite treatment, tumor usually recurs within 7–9 months. The presence of glioma cells with stem-like properties and tumor’s heterogeneity have been identified as the most important factors driving recurrence. Recently, research efforts have been focused on the use of natural substances as treatment for GBM. Siderol is an ent-kaurane diterpenoid, isolated from the genus Sideritis. Sideritis extracts have already been investigated for their anti-inflammatory, antioxidant, and anticancer effects. In this study, we investigated the antitumoral effects of siderol in GBM T98 and U87 cell lines, as well as the effects of combined treatment with temozolomide (TMZ). Cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue exclusion assay. Different concentrations of siderol were used in order to calculate the IC50 values at 72 h after treatment. Flow cytometry used for the DNA cell cycle analysis after treatment with siderol in concentrations of IC50 and twice the IC50 values for 72 h. Furthermore, the effect of siderol in cell’s migratory ability was tested using wound healing assay. Cell viability and proliferation, after combined treatment with siderol and TMZ, also were evaluated with the trypan blue exclusion assay and the effects of the combination treatment were analyzed with CompuSyn software. Treatment with siderol significantly reduced cell viability in T98 and U87 cell lines in a dose-dependent manner and IC50 values were calculated, 18 μM and 13 μM, respectively. Moreover, siderol induced G0/G1 cell cycle arrest in a dose-dependent manner and inhibited the migration in both cell lines. In addition, siderol and TMZ seem to have synergistic action in the majority of tested concentrations in both T98 and U87 cells. In conclusion, siderol may represent an innovative strategy for the treatment of GBM, and further studies are needed on siderol’s efficacy and mode of action.