Overcoming multidrug resistance in cancer: Recent progress in nanotechnology and new horizons.

Multidrug resistance (MDR), defined as the ability of cancer cells to gain resistance to both conventional and novel chemotherapy agents, is an important barrier in treating malignancies. Initially, it was discovered that cellular pumps dependent on ATP were the cause of resistance to chemotherapy, and further studies have found that other mechanisms such as increased metabolism of drugs, decreased drug entry, and defective apoptotic pathways are involved in this process. MDR has been the focus of numerous initiatives and countless studies have been undertaken to better understand MDR and formulate strategies to overcome its effects. The current review highlights various nano-drug delivery systems including polymeric/solid lipid/mesoporous silica/metal nanoparticles, dendrimers, liposomes, micelles, and nanostructured lipid carriers to overcome the mechanism of MDR. Nanoparticles are novel gateways to enhance the therapeutic efficacy of anticancer agents at the target site of action due to their tumor-targeting abilities, which can limit the unwanted systemic effects of chemotherapy agents and also reduce drug resistance. Additionally, other innovative strategies including RNA interference as a biological process used to inhibit or silence specific gene expression, natural products as MDR modulators with little systemic toxic effects, which interfere with the functions of proteins involved in drug efflux, and physical approaches such as combination of conventional drug administration with thermal/ultrasound/photodynamic strategies are also highlighted.

New potentials for 3-hydroxy-3-methyl-glutaryl-coenzymeA reductase inhibitors: Possible applications in retarding diabetic complications.

The prevalence of diabetes mellitus is increasing all over the world and it is apparent that treatment of diabetic complications has the same importance as primary diabetes treatment and glycemic control. Diabetic complications occur as a result of prolonged hyperglycemia and its consequences, such as advanced glycation end products and reactive oxygen species. Impairment of lipid profile is also contributed to worsening diabetic complications. Therefore, it seems that the application of lipid-lowering agents may have positive effects on reversing diabetic complications besides glycemic control. Statins, a group of lipid-lowering compounds, have been shown to exert antioxidant, immunomodulatory, anti-inflammatory, and antiproliferative properties beyond their lipid-lowering effects. Furthermore, they have been reported to improve diabetic complications with different pathways. In this review, we will discuss the clinical importance, molecular biology of the most important microvascular/macrovascular diabetic complications, possible application of statins and their mechanism of action in retarding these complications.

Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model.

PURPOSE: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems. METHODS: A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues. RESULTS: The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization. CONCLUSION: Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.

Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI).

PURPOSE: Amplified magnetic resonance imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video-processing algorithm, Eulerian video magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here, we strive to improve aMRI by incorporating a phase-based motion amplification algorithm. METHODS: Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output. RESULTS: Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient. CONCLUSION: Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion and may reveal subtle physiological variations of the brain as a result of pathology using processing of the fundamental harmonic or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.

Reversion of Multidrug Resistance by Co-Encapsulation of Doxorubicin and Metformin in Poly(lactide-co-glycolide)-d-α-tocopheryl Polyethylene Glycol 1000 Succinate Nanoparticles.

PURPOSE: P-glycoprotein (P-gp) mediated multidrug resistance (MDR) has been recognized as the main obstacle against successful cancer treatment. To address this problem, co-encapsulated doxorubicin (DOX) and metformin (Met) in a biodegradable polymer composed of poly(lactide-co-glycolide) (PLGA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared. We reported in our previous study that Met inhibits P-gp in DOX resistant breast cancer (MCF-7/DOX) cells. TPGS is a bioactive compound which has also been shown to inhibit P-gp, further to its pharmaceutical advantages. METHODS: The DOX/Met loaded PLGA-TPGS nanoparticles (NPs) were prepared by double emulsion method and characterized for their surface morphology, size and size distribution, and encapsulation efficiencies of drugs in NPs. RESULTS: All NPs were found to be spherical-shaped with the size distribution below 100 nm and encapsulation efficiencies were 42.26 ± 2.14% for DOX and 7.04 ± 0.52% for Met. Dual drug loaded NPs showed higher cytotoxicity and apoptosis in MCF-7/DOX cells in comparison to corresponding free drugs. The higher cytotoxicity of dual drug loaded NPs was attributed to the enhanced intracellular drug accumulation due to enhanced cellular uptake and reduced drug efflux which was obtained by combined effects of Met and TPGS in reducing cellular ATP content and inhibiting P-gp. CONCLUSION: Simultaneous delivery of DOX and Met via PLGA-TPGS NPs would be a promising approach to overcome MDR in breast cancer chemotherapy.

Thrombus-mimicking artifacts in two-point Dixon MRI: Prevalence, appearance, and severity.

PURPOSE: To evaluate the incidence and severity of potentially thrombus mimicking, flow-induced misallocation artifacts in a clinical setting. Two-point "Dixon" fat-water separation methods, with bipolar readout gradients, may suffer from flow-induced fat-water misallocation artifacts. If these artifacts occur within blood vessels, they may mimic thrombus. MATERIALS AND METHODS: Two-point Dixon coronal and axial images acquired in 102 consecutive patients were retrospectively evaluated for the presence of flow-induced artifacts in arteries and veins. Artifacts were graded on a 3-point scale (none, mild, severe) by two independent readers. Interreader agreement was evaluated with kappa statistics. RESULTS: Reader 1 reported 63 artifacts in 46 (45%) of the cases (severe in 19 cases, 18.6%). Reader 2 reported 51 artifacts in 43 (42.2%) of the cases (severe in 18 cases, 17.6%). Misallocation of fat and water was apparent in all datasets with severe artifacts, whereas variable signal intensity changes in water and fat images were observed in mild artifacts. Interreader agreement was good for artifacts appearing in coronal images (κ = 0.7) and fair for artifact appearance in axial images (κ = 0.24). CONCLUSION: Our study shows a high incidence of flow-induced mild and severe artifacts in a two-point Dixon method with bipolar readout gradients. This artifact should not be misinterpreted as intravascular thrombus. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:229-236.

HtrA3 stromal expression is correlated with tumor budding in stage II colorectal cancer.

Tumor budding is a well-established adverse prognostic factor in colorectal carcinoma (CRC). It may represent a form of epithelial-to-mesenchymal transition (EMT), although the underlying mechanisms remain unclear. High-temperature requirement A3 (HtrA3) is an inhibitor of the bone morphogenetic protein pathway, the suppression of which has been linked to EMT. Since HtrA3 is highly expressed in the desmoplastic stroma at the CRC invasive front, we sought to evaluate the relationship between tumor budding and HtrA3 expression in 172 stage II CRC resection specimens. All tumors were evaluated for tumor budding, with the highest budding slide selected for pan-keratin (CK) and HtrA3 immunohistochemistry. Representative areas of tumor core and invasive front, including budding and non-budding areas, were marked on CK stained slides, and then evaluated on HtrA3 stained slides. HtrA3 expression in tumor cells (tHtrA3) and peritumoral stroma (sHtrA3) was assessed for staining percentage and intensity (the product yielding a final score). Tumors with high-grade tumor budding (HGTB) showed increased expression of sHtrA3 in budding areas compared to non-budding areas at the invasive front (P<0.001). In addition, sHtrA3 expression at the invasive front was significantly higher in HGTB tumors compared to minimally budding tumors (P<0.05). tHtrA3 expression at the invasive front was significantly associated with high histological grade (P<0.05). Higher sHtrA3 expression in the tumor core (but not invasive front) was significantly associated with decreased 5-year overall survival on univariate analysis (P<0.05), but not multivariate analysis. HtrA3 expression in the peritumoral stroma of patients with stage II CRC is associated with HGTB and may be a novel marker of poor outcome.

Amplified magnetic resonance imaging (aMRI).

PURPOSE: This work describes a new method called amplified MRI (aMRI), which uses Eulerian video magnification to amplify the subtle spatial variations in cardiac-gated brain MRI scans and enables better visualization of brain motion. METHODS: The aMRI method takes retrospective cardiac-gated cine MRI data as input, applies a spatial decomposition, followed by temporal filtering and frequency-selective amplification of the MRI cardiac-gated frames before synthesizing a motion-amplified cine data set. RESULTS: This approach reveals deformations of the brain parenchyma and displacements of arteries due to cardiac pulsatility, especially in the brainstem, cerebellum, and spinal cord. CONCLUSION: aMRI has the potential for widespread neuro- and non-neuro clinical use because it can amplify and characterize small, often barely perceptible motion and can visualize the biomechanical response of tissues using the heartbeat as an endogenous mechanical driver. Magn Reson Med 75:2245-2254, 2016. © 2016 Wiley Periodicals, Inc.

Combined gadoxetic acid and gadofosveset enhanced liver MRI: A feasibility and parameter optimization study.

PURPOSE: Demonstration of feasibility and protocol optimization for the combined use of gadofosveset trisodium with gadoxetic acid for delayed T1-weighted liver MRI. METHODS: Eleven healthy volunteers underwent hepatobiliary phase imaging at 3 Tesla (T) using gadoxetic acid. Multiple breathheld T1-weighted three-dimensional spoiled gradient echo sequences were performed at varying flip angles before and after injection of gadofosveset. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured to determine optimal T1-weighting. Examples of three patients with focal liver lesions were acquired. RESULTS: The addition of gadofosveset to the hepatobiliary phase of gadoxetic acid renders vessels isointense to liver tissue at low flip angles due to increased vessel SNR (P < 0.001). The lowest CNR of liver relative to portal vein (CNR = 15; 95% confidence interval [CI]: -14-44) was observed at a 10º flip angle. The highest CNR of liver relative to muscle (CNR = 214; 95% CI: 191-237) was observed at a 20º flip angle. The combined enhancement leads to homogenously enhanced liver tissue and liver vasculature. Cysts were detected in three volunteers and metastases were detected in two patients. In these anecdotal cases the cysts and metastases stood out as conspicuous focal hypointensities on combined gadoxetic acid and gadofosveset enhanced images. CONCLUSION: Combined gadoxetic acid and gadofosveset enhanced liver MRI is feasible, with low flip angles minimizing contrast between vessels and liver. Further clinical studies are needed to confirm that low flip angles provide an optimal combination of sensitivity and specificity for lesion detection in patients.

Flow-induced signal misallocation artifacts in two-point fat-water chemical shift MRI.

PURPOSE: Two-point fat-water separation methods are increasingly being used for chest and abdominal MRI and have recently been introduced for use in MR angiography of the lower extremities. With these methods, flowing spins can accumulate unintended phase shifts between the echo times. The purpose of this study is to demonstrate that these phase shifts can lead to inaccurate signals in the water and fat images. THEORY AND METHODS: In vitro experiments were conducted at 1.5T and 3.0T using a stenosis-mimicking phantom and a computer-controlled pump to image a range of physiologically relevant velocities. RESULTS: In the phantom images acquired using bipolar readout gradients, fat-water signal inaccuracies were visible in regions of flow, with increasing severity as the flow rate was increased. Additionally, similar effects were observed in regions of high flow in clinical chest and liver exams. In the phantom images, the effect was eliminated by using a dual-pass method without bipolar readout gradients. CONCLUSION: When using fat-water separation methods with bipolar readout gradients, phase shifts caused by the motion of spins can lead to signal inaccuracies in the fat and water images. These artifacts can be mitigated by using approaches that do not use bipolar readout gradients.

Combined dynamic contrast-enhanced liver MRI and MRA using interleaved variable density sampling.

PURPOSE: To develop and evaluate a method for volumetric contrast-enhanced MRI of the liver, with high spatial and temporal resolutions, for combined dynamic imaging and MR angiography (MRA) using a single injection of contrast agent. METHODS: An interleaved variable density (IVD) undersampling pattern was implemented in combination with a real-time-triggered, time-resolved, dual-echo 3D spoiled gradient echo sequence. Parallel imaging autocalibration lines were acquired only once during the first time frame. Imaging was performed in 10 subjects with focal nodular hyperplasia (FNH) and compared with their clinical MRI. The angiographic phase of the proposed method was compared with a dedicated MR angiogram acquired during a second injection of contrast. RESULTS: A total of 21 FNH, three cavernous hemangiomas, and 109 arterial segments were visualized in 10 subjects. The temporally resolved images depicted the characteristic arterial enhancement pattern of the lesions with a 4-s update rate. Images were graded as having significantly higher quality compared with the clinical MRI. Angiograms produced from the IVD method provided noninferior diagnostic assessment compared with the dedicated MR angiogram. CONCLUSION: Using an undersampled IVD imaging method, we have demonstrated the feasibility of obtaining high spatial and temporal resolution dynamic contrast-enhanced imaging and simultaneous MRA of the liver.

Use of a computer-controlled motion phantom to investigate the temporal and spatial fidelity of HYPR processing.

PURPOSE: In this work, we investigate the spatial and temporal fidelity of highly constrained backPRojection (HYPR) processing using a computer-controlled motion phantom. The goal of this experimental set-up was to provide not only well-defined temporal dynamics and spatial characteristics of the motion phantom, but also circumstances that imitate in vivo scenarios. METHODS: The phantom was designed to represent an artery flanked on both sides by vein. Both arterial and venous components have different temporal dynamics but are confluent, which corresponds to a difficult scenario for HYPR. Spatial and temporal fidelity was investigated by measuring signal intensity profiles through the phantom both orthogonal to as well as along the direction of motion. RESULTS: Spatial fidelity profiles measured from the HYPR processed images yielded full-width-at-half-maximum values very similar to those measured in non-HYPR-processed images. Furthermore, there was no significant spreading of the motion phantom leading edge in HYPR processed images. CONCLUSION: Although HYPR processing has certain characteristic artifacts that are discussed, the technique can be used to improve image quality of highly undersampled time frame images with minimal loss of spatial or temporal fidelity.

Application of direct virtual coil to dynamic contrast-enhanced MRI and MR angiography with data-driven parallel imaging.

PURPOSE: To demonstrate the feasibility of direct virtual coil (DVC) in the setting of 4D dynamic imaging used in multiple clinical applications. THEORY AND METHODS: Three dynamic imaging applications were chosen: pulmonary perfusion, liver perfusion, and peripheral MR angiography (MRA), with 18, 11, and 10 subjects, respectively. After view-sharing, the k-space data were reconstructed twice: once with channel-by-channel (CBC) followed by sum-of-squares coil combination and once with DVC. Images reconstructed using CBC and DVC were compared and scored based on overall image quality by two experienced radiologists using a five-point scale. RESULTS: The CBC and DVC showed similar image quality in image domain. Time course measurements also showed good agreement in the temporal domain. CBC and DVC images were scored as equivalent for all pulmonary perfusion cases, all liver perfusion cases, and four of the 10 peripheral MRA cases. For the remaining six peripheral MRA cases, DVC were scored as slightly better (not clinically significant) than the CBC images by Radiologist A and as equivalent by Radiologist B. CONCLUSION: For dynamic contrast-enhanced MR applications, it is clinically feasible to reduce image reconstruction time while maintaining image quality and time course measurement using the DVC technique.

Development of New Resolvin D1 Analogues for Osteoarthritis Therapy: Acellular and Computational Approaches to Study Their Antioxidant Activities.

In osteoarthritis (OA), oxidative stress plays a crucial role in maintaining and sustaining cartilage degradation. Current OA management requires a combination of pharmaceutical and non-pharmacological strategies, including intraarticular injections of hyaluronic acid (HA). However, several lines of evidence reported that HA oxidation by reactive oxygen species (ROS) is linked with HA cleavage and fragmentation, resulting in reduced HA viscosity. Resolvin D1 (RvD1) is a lipid mediator that is biosynthesized from omega-3 polyunsaturated fatty acids and is a good candidate with the potential to regulate a panoply of biological processes, including tissue repair, inflammation, oxidative stress, and cell death in OA. Herein, newly designed and synthesized imidazole-derived RvD1 analogues were introduced to compare their potential antioxidant properties with commercially available RvD1. Their antioxidant capacities were investigated by several in vitro chemical assays including oxygen radical absorbance capacity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, ferric ion reducing antioxidant power, hydroxyl radical scavenging, and HA fragmentation assay. All results proved that imidazole-derived RvD1 analogues showed excellent antioxidant performance compared to RvD1 due to their structural modifications. Interestingly, they scavenged the formed reactive oxygen species (ROS) and protected HA from degradation, as verified by agarose gel electrophoresis and gel permission chromatography. A computational study using Gaussian 09 with DFT calculations and a B3LYP/6-31 G (d, p) basis set was also employed to study the relationship between the antioxidant properties and chemical structures as well as calculation of the molecular structures, frontier orbital energy, molecular electrostatic potential, and bond length. The results showed that the antioxidant activity of our analogues was higher than that of RvD1. In conclusion, the findings suggest that imidazole-derived RvD1 analogues can be good candidates as antioxidant molecules for the treatment of oxidative stress-related diseases like OA. Therefore, they can prolong the longevity of HA in the knee and thus may improve the mobility of the articulation.

Bottlebrush Polymers for Articular Joint Lubrication: Influence of Anchoring Group Chemistry on Lubrication Properties.

The role of carboxylic, aldehyde, or epoxide groups incorporated into bottlebrush macromolecules as anchoring blocks (or cartilage-binding blocks) is investigated by measuring their lubricating properties and cartilage-binding effectiveness. Mica modified with amine groups is used to mimic the cartilage surface, while bottlebrush polymers functionalized with carboxylic, aldehyde, or epoxide groups played the role of the lubricant interacting with the cartilage surface. We demonstrate that bottlebrushes with anchoring blocks effectively reduce the friction coefficient on modified surfaces by 75-95% compared to unmodified mica. The most efficient polymer appears to be the one with epoxide groups, which can react spontaneously with amines at room temperature. In this case, the value of the friction coefficient is the lowest and equals 0.009 ± 0.001, representing a 95% reduction compared to measurements on nonmodified mica. These results show that the presence of the functional groups within the anchoring blocks has a significant influence on interactions between the bottlebrush polymer and cartilage surface. All synthesized bottlebrush polymers are also used in the preliminary lubrication tests carried out on animal cartilage surfaces. The developed materials are very promising for future in vivo studies to be used in osteoarthritis treatment.

Rational design of smart nano-platforms based on antifouling-nanomaterials toward multifunctional bioanalysis.

The ability to design nanoprobe devices with the capability of quantitative/qualitative operation in complex media will probably underpin the main upcoming progress in healthcare research and development. However, the biomolecules abundances in real samples can considerably alter the interface performance, where unwanted adsorption/adhesion can block signal response and significantly decrease the specificity of the assay. Herein, this review firstly offers a brief outline of several significances of fabricating high-sensitivity and low-background interfaces to adjust various targets' behaviors induced via bioactive molecules on the surface. Besides, some important strategies to resist non-specific protein adsorption and cell adhesion, followed by imperative categories of antifouling reagents utilized in the construction of high-performance solid sensory interfaces, are discussed. The next section specifically highlights the various nanocomposite probes based on antifouling-nanomaterials for electrode modification containing carbon nanomaterials, noble metal nanoparticles, magnetic nanoparticles, polymer, and silicon-based materials in terms of nanoparticles, rods, or porous materials through optical or chemical strategies. We specially outline those nanoprobes that are capable of identification in complex media or those using new constructions/methods. Finally, the necessity and requirements for future advances in this emerging field are also presented, followed by opportunities and challenges.

Oncostatic activities of melatonin: Roles in cell cycle, apoptosis, and autophagy.

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Melatonin exerts oncostatic functions in numerous human malignancies. An increasing number of studies report that melatonin reduces the invasiveness of several human cancers such as prostate cancer, breast cancer, liver cancer, oral cancer, lung cancer, ovarian cancer, etc. Moreover, melatonin's oncostatic activities are exerted through different biological processes including antiproliferative actions, stimulation of anti-cancer immunity, modulation of the cell cycle, apoptosis, autophagy, the modulation of oncogene expression, and via antiangiogenic effects. This review focuses on the oncostatic activities of melatonin that targeted cell cycle control, with special attention to its modulatory effects on the key regulators of the cell cycle, apoptosis, and telomerase activity.

Chitosan-based biomaterials for the treatment of bone disorders.

Bone is an alive and dynamic organ that is well-differentiated and originated from mesenchymal tissues. Bone undergoes continuous remodeling during the lifetime of an individual. Although knowledge regarding bones and their disorders has been constantly growing, much attention has been devoted to effective treatments that can be used, both from materials and medical performance points of view. Polymers derived from natural sources, for example polysaccharides, are generally biocompatible and are therefore considered excellent candidates for various biomedical applications. This review outlines the development of chitosan-based biomaterials for the treatment of bone disorders including bone fracture, osteoporosis, osteoarthritis, arthritis rheumatoid, and osteosarcoma. Different examples of chitosan-based formulations in the form of gels, micro/nanoparticles, and films are discussed herein. The work also reviews recent patents and important developments related to the use of chitosan in the treatment of bone disorders. Although most of the cited research was accomplished before reaching the clinical application level, this manuscript summarizes the latest achievements within chitosan-based biomaterials used for the treatment of bone disorders and provides perspectives for future scientific activities.

Oncostatic activities of melatonin: Roles in cell cycle, apoptosis, and autophagy.

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Melatonin exerts oncostatic functions in numerous human malignancies. An increasing number of studies report that melatonin reduces the invasiveness of several human cancers such as prostate cancer, breast cancer, liver cancer, oral cancer, lung cancer, ovarian cancer, etc. Moreover, melatonin's oncostatic activities are exerted through different biological processes including antiproliferative actions, stimulation of anti-cancer immunity, modulation of the cell cycle, apoptosis, autophagy, the modulation of oncogene expression, and via antiangiogenic effects. This review focuses on the oncostatic activities of melatonin that targeted cell cycle control, with special attention to its modulatory effects on the key regulators of the cell cycle, apoptosis, and telomerase activity.

Were magnetic materials useful in cancer therapy?

Cancer is one of the major challenges fronting the biomedical basic researches in our time. The study and development of effective therapeutic strategies for cancer therapy are vital. Among the many probable core constituents of nanoparticles, magnetite-based nanoparticles have been widely studied for cancer therapy owing to their inherent magnetic features, multifunctional design, biodegradable and biocompatible properties. Magnetic nanoparticles have been also designed for utilizing as contrast enhancer agents for magnetic resonance imaging, drug delivery systems, and most recently as a therapeutic element in inducing cellular death in tumor ablation therapies. This review aimed to provide an overview of the various applications of magnetic nanoparticles and recent achievements in developing these advanced materials for cancer therapy.