Enhancing the Anticancer and Anti-Inflammatory Properties of Curcumin in Combination with Quercetin, for the Prevention and Treatment of Prostate Cancer.

Prostate cancer is the second most common cancer in men. Although epidemiologic studies show that a higher intake of polyphenols, curcumin (CUR), and quercetin (QRT), in particular, result in lower prostate cancer risk, the chemopreventive mechanisms underlying the effects of CUR and QRT have not been fully understood yet, and most investigations were conducted with individual compounds. Here, we investigated the anticancer and anti-inflammatory effects of CUR in combination with QRT, respectively, in a human prostate cancer cell line, PC-3, and in LPS-stimulated RAW 264.7 cells, and found that their combination significantly inhibited proliferation and arrested the cell cycle, inducing apoptosis, so exhibiting synergic activities stronger than single drug use. Moreover, via their antioxidant effects, the combination of CUR and QRT modulated several inflammation-mediated signaling pathways (ROS, nitric oxide, and pro-inflammatory cytokines) thus helping protect cells from undergoing molecular changes that trigger carcinogenesis. Although additional studies, including in vivo experiments and translational studies, are required, this study raises the possibility of their use as a safe, effective, and affordable therapeutic approach to prostate cancer.

TiO2-NPs Toxicity and Safety: An Update of the Findings Published over the Last Six Years.

Nanotechnology has greatly impacted our daily life and has certainly yielded many promising benefits. Titanium dioxide nanoparticles (TiO2-NPs) are among those produced on a large industrial scale that have found many practical applications in industry and daily life. Due to their presence in products such as food, cosmetics, sunscreens, medications, paints or textiles, contact with TiO2-NPs in our daily life is inevitable. The small size, together with the corresponding large specific surface area, make nanoparticles able to penetrate through cellular barriers and reach various parts of the body through different routes of exposure, including inhalation, injection, dermal penetration, and gastrointestinal tract absorption. Furthermore, after long-term exposure, the TiO2-NPs could accumulate in tissues leading to chronic diseases. This raises serious doubts about their potentially harmful effects on human health. In the past, TiO2-NPs have been considered inert, however, many in vitro studies have shown that they were cyto- and genotoxic, leading to the production of reactive oxygen species (ROS) and to the activation of signaling pathways involved in inflammation and cell death. Several in vivo studies have also demonstrated that TiO2-NPs, once in the bloodstream, could reach and accumulate in important organs causing toxic effects. Very recently, the International Agency for Research on Cancer (IARC) has classified these nanoparticles as possibly carcinogenic to humans. In this survey, we summarize the latest advances in acknowledging the toxicity and safety of TiO2-NPs. Since the literature is often controversial, further studies are still needed to define the risk/benefit ratio of using these nanoparticles. Overall, the data herein reported are critical for assessing human risk after exposure to TiO2-NPs.

The Potential of MicroRNAs as Non-Invasive Prostate Cancer Biomarkers: A Systematic Literature Review Based on a Machine Learning Approach.

Background: Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Although the prostate-specific antigen (PSA) test is used in clinical practice for screening and/or early detection of PCa, it is not specific, thus resulting in high false-positive rates. MicroRNAs (miRs) provide an opportunity as biomarkers for diagnosis, prognosis, and recurrence of PCa. Because the size of the literature on it is increasing and often controversial, this study aims to consolidate the state-of-art of relevant published research. Methods: A Systematic Literature Review (SLR) approach was applied to analyze a set of 213 scientific publications through a text mining method that makes use of the Latent Dirichlet Allocation (LDA) algorithm. Results and Conclusions: The result of this activity, performed through the MySLR digital platform, allowed us to identify a set of three relevant topics characterizing the investigated research area. We analyzed and discussed all the papers clustered into them. We highlighted that several miRs are associated with PCa progression, and that their detection in patients' urine seems to be the more reliable and promising non-invasive tool for PCa diagnosis. Finally, we proposed some future research directions to help future scientists advance the field further.

Role of MicroRNAs in the Development and Progression of the Four Medulloblastoma Subgroups.

Medulloblastoma is the most frequent malignant brain tumour in children. Medulloblastoma originate during the embryonic stage. They are located in the cerebellum, which is the area of the central nervous system (CNS) responsible for controlling equilibrium and coordination of movements. In 2012, medulloblastoma were divided into four subgroups based on a genome-wide analysis of RNA expression. These subgroups are named Wingless, Sonic Hedgehog, Group 3 and Group 4. Each subgroup has a different cell of origin, prognosis, and response to therapies. Wingless and Sonic Hedgehog medulloblastoma are so named based on the main mutation originating these tumours. Group 3 and Group 4 have generic names because we do not know the key mutation driving these tumours. Gene expression at the post-transcriptional level is regulated by a group of small single-stranded non-coding RNAs. These microRNA (miRNAs or miRs) play a central role in several cellular functions such as cell differentiation and, therefore, any malfunction in this regulatory system leads to a variety of disorders such as cancer. The role of miRNAs in medulloblastoma is still a topic of intense clinical research; previous studies have mostly concentrated on the clinical entity of the single disease rather than in the four molecular subgroups. In this review, we summarize the latest discoveries on miRNAs in the four medulloblastoma subgroups.

Dextran-Curcumin Nanosystems Inhibit Cell Growth and Migration Regulating the Epithelial to Mesenchymal Transition in Prostate Cancer Cells.

Functional nanocarriers which are able to simultaneously vectorize drugs to the site of interest and exert their own cytotoxic activity represent a significant breakthrough in the search for effective anticancer strategies with fewer side effects than conventional chemotherapeutics. Here, we propose previously developed, self-assembling dextran-curcumin nanoparticles for the treatment of prostate cancer in combination therapy with Doxorubicin (DOXO). Biological effectiveness was investigated by evaluating the cell viability in either cancer and normal cells, reactive oxygen species (ROS) production, apoptotic effect, interference with the cell cycle, and the ability to inhibit cell migration and reverse the epithelial to mesenchymal transition (EMT). The results proved a significant enhancement of curcumin efficiency upon immobilization in nanoparticles: IC50 reduced by a half, induction of apoptotic effect, and improved ROS production (from 67 to 134%) at low concentrations. Nanoparticles guaranteed a pH-dependent DOXO release, with a more efficient release in acidic environments. Finally, a synergistic effect between nanoparticles and Doxorubicin was demonstrated, with the free curcumin showing additive activity. Although in vivo studies are required to support the findings of this study, these preliminary in vitro data can be considered a proof of principle for the design of an effective therapy for prostate cancer treatment.

Dextran-Curcumin Nanoparticles as a Methotrexate Delivery Vehicle: A Step Forward in Breast Cancer Combination Therapy.

With the aim to effectively deliver methotrexate (MTX) to breast cancer cells, we designed a nanocarrier system (DC) derived from the self-assembly of a dextran-curcumin conjugate prepared via enzyme chemistry with immobilized laccase acting as a solid biocatalyst. Nanoparticles consisted of homogeneously dispersed nanospheres with a mean diameter of 290 nm, as characterized by combined transmission electron microscopy and dynamic light scattering investigations. DC was able to control the MTX release overtime (t1/2 value of 310 min), with cell internalization studies proving its presence inside MCF-7 cytoplasm. Finally, improved MTX efficacy was obtained in viability assays, and attributed to the synergy of curcumin moieties and loaded MTX as underlined by a combination index (CI) < 1.