Investigating the reproducibility of radiomics features extracted from ultrasound images as diagnostic biomarkers in patients with hepatocellular carcinoma

Background: Radiomics is a noninvasive method that reveals information from medical images that are not recognizable by the naked eye. Radiomics has shown a high potential in the accurate diagnosis and prognosis of liver lesions in ultrasound images. Despite this high potential, changes in imaging parameters affect the reproducibility of ultrasound radiomics results. Therefore, the present study aims to investigate the reproducibility of the radiomics features extracted from the images of patients with hepatocellular carcinoma under changes in ultrasound scan parameters. Methods: This was a cross-sectional study conducted from July 2020 to July 2021 in the radiology department of Tabriz Paramedical Faculty. The images of 20 patients with hepatocellular carcinoma were obtained from the Cancer Imaging Archive database. These images were taken under different imaging conditions and parameters. The areas related to the lesion were manually extracted from the images with software tools. Then, in order to radiomics analysis, different radiomics features, including 24 gray level co-occurrence matrix (GLCM) and 16 gray level run length matrix (GLRLM), were extracted from the images. Then, using the coefficient of variation (CV%) and intraclass correlation coefficient (ICC) statistical tests, the reproducibility of radiomics features under changes in scan parameters was investigated. The values of ICC≥0.90 and CV<20% were considered reproducible in this study. Results: Among the 40 features extracted from ultrasound images, eight showed high reproducibility in both CV% and ICC tests. These features were joint entropy, Idmn, Imc2, correlation, MCC, sum entropy, gray level non-uniformity normalized, and run entropy in which the two features, Idmn and gray level non-uniformity normalized, showed the highest (CV%=0.24) and the lowest (CV%=14.90) stability against the changes of ultrasound scan parameters, respectively. The average ICC value of these features was obtained at 0.977. Conclusion: Despite the high potential of radiomics in diagnosing liver lesions, changes in imaging parameters directly affect the reproducibility of results. However, some radiomics features still show high stability and reproducibility under changes in imaging parameters

Conformal fields in prostate radiotherapy: A comparison between measurement, calculation and simulation

Aims: The objective of this study is to evaluate the accuracy of a treatment planning system (TPS) for calculating the dose distribution parameters in conformal fields (CF). Dosimetric parameters of CF′s were compared between measurement, Monte Carlo simulation (MCNP4C) and TPS calculation. Materials and Methods: Field analyzer water phantom was used for obtaining percentage depth dose (PDD) curves and beam profiles (BP) of different conformal fields. MCNP4C was used to model conformal fields dose specification factors and head of linear accelerator varian model 2100C/D. Results: Results showed that the distance to agreement (DTA) and dose difference (DD) of our findings were well within the acceptance criteria of 3 mm and 3%, respectively. Conclusions: According to this study it can be revealed that TPS using equivalent tissue air ratio calculation method is still convenient for dose prediction in non small conformal fields normally used in prostate radiotherapy. It was also showed that, since there is a close correlation with Monte Carlo simulation, measurements and TPS, Monte Carlo can be further confirmed for implementation and calculation dose distribution in non standard and complex conformal irradiation field for treatment planning systems

CuFe2O4 decorated with BSA as a potential nanoradioenhancer for enhanced X-ray radiation therapy of brain tumor

Glioblastoma (GBM) is a type of the central nervous system malignancy and considered as the most lethal and aggressive primary brain tumor. Adjuvant radiotherapy (RT) along with temozolomide (TMZ) is considered as the standard treatment regimen for GBM. However, implementation of RT in tumor suppression is frequently accompanied by several side effects. Additionally, dose limitation and radioresistance are other major drawbacks associated with radiation therapy. To this end, nanoradioenhancer/or nanoradiosensitizer based on high-Z metallic elements has emerged as a powerful treatment modality in GBM therapy. In this study, CuFe2O4 decorated with BSA nanoplatforms (CuFe2O4 @BSA) was fabricated to improve the theraputics potential of RT through sensitizing the U-87 GBM cells to X-ray radiation. The characterization techniques such as FTIR, XRD, EDS and UV–Vis spectroscopy confirmed successful fabrication of CuFe2O4 @BSA radioenhancer, while also TEM images indicated the prepared nanoradiosensitizers are uniform, homogenous, and spherical with an average size of about 5 nm. In vitro hemocompatibility and cytocompatibility of developed CuFe2O4 @BSA nanoradiosensitizers were also investigated by hemolysis and MTT assay, respectively. The merits of CuFe2O4 @BSA nanoplatforms in sensitizing the U-87 cells to the ionizing radiation were also exploited using intracellular ROS generation and MTT assay. It was found that CuFe2O4 @BSA nanoradiosensitizers did not cause any deleterious effects on primary human umbilical vein endothelial cells (HUVEC) of which the cell viability of all treated group was beyond 95%, endorsing the cytocompatibility and safety of these nanoplatforms for further assessment. Hemolysis assay also confirms the biosafety of CuFe2O4 @BSA nanoradiosensitizers, exhibiting no significant toxicity against human red blood cells in which the degree of hemolysis was less than 4%. In vitro cancer radiotherapy also demonstrated that the cell viability of U-87 GBM was considerably decreased once co-modality of X-ray and CuFe2O4 @BSA nanoradiosensitizers were used simultaneously. Radiosensitizing ability of these nanoparticles was also proved by intracellular ROS generation, of which implementation of CuFe2O4 @BSA nanoradiosensitizers upon X-ray irradiation resulted in superior ROS production. Overall, these findings provide vital evidence for applicability of prepared CuFe2O4 @BSA nanoradiosensitizers in killing the primary brain tumor cells specifically GBM

CuFe₂O₄ decorated with BSA as a potential nanoradioenhancer for enhanced X-ray radiation therapy of brain tumor

Glioblastoma (GBM) is a type of the central nervous system malignancy and considered as the most lethal and aggressive primary brain tumor. Adjuvant radiotherapy (RT) along with temozolomide (TMZ) is considered as the standard treatment regimen for GBM. However, implementation of RT in tumor suppression is frequently accompanied by several side effects. Additionally, dose limitation and radioresistance are other major drawbacks associated with radiation therapy. To this end, nanoradioenhancer/or nanoradiosensitizer based on high-Z metallic elements has emerged as a powerful treatment modality in GBM therapy. In this study, CuFe2O4 decorated with BSA nanoplatforms (CuFe2O4 @BSA) was fabricated to improve the theraputics potential of RT through sensitizing the U-87 GBM cells to X-ray radiation. The characterization techniques such as FTIR, XRD, EDS and UV-Vis spectroscopy confirmed successful fabrication of CuFe2O4 @BSA radioenhancer, while also TEM images indicated the prepared nanoradiosensitizers are uniform, homogenous, and spherical with an average size of about 5 nm. In vitro hemocompatibility and cytocompatibility of developed CuFe2O4 @BSA nanoradiosensitizers were also investigated by hemolysis and MTT assay, respectively. The merits of CuFe2O4 @BSA nanoplatforms in sensitizing the U-87 cells to the ionizing radiation were also exploited using intracellular ROS generation and MTT assay. It was found that CuFe2O4 @BSA nanoradiosensitizers did not cause any deleterious effects on primary human umbilical vein endothelial cells (HUVEC) of which the cell viability of all treated group was beyond 95%, endorsing the cytocompatibility and safety of these nanoplatforms for further assessment. Hemolysis assay also confirms the biosafety of CuFe2O4 @BSA nanoradiosensitizers, exhibiting no significant toxicity against human red blood cells in which the degree of hemolysis was less than 4%. In vitro cancer radiotherapy also demonstrated that the cell viability of U-87 GBM was considerably decreased once co-modality of X-ray and CuFe2O4 @BSA nanoradiosensitizers were used simultaneously. Radiosensitizing ability of these nanoparticles was also proved by intracellular ROS generation, of which implementation of CuFe2O4@BSA nanoradiosensitizers upon X-ray irradiation resulted in superior ROS production. Overall, these findings provide vital evidence for applicability of prepared CuFe2O4 @BSA nanoradiosensitizers in killing the primary brain tumor cells specifically GBM

Complete ablation of tumors using synchronous chemoradiation with bimetallic theranostic nanoparticles

Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi2S3–Au, with deep level defects (DLDs) in Bi2S3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi2S3–Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications

Facile preparation of silver based radiosensitizers via biomineralization method for enhanced in vivo breast cancer radiotherapy

Abstract To solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag2S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2S@BSA to impart active targeting capability to the final formulation (Ag-Ag2S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet–visible spectroscopy (UV–Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy

Modulation of radiation-induced base excision repair pathway gene expression by melatonin

Objective: Approximately 70% of all cancer patients receive radiotherapy. Although radiotherapy is effective in killing cancer cells, it has adverse effects on normal cells as well. Melatonin (MLT) as a potent antioxidant and anti-inflammatory agent has been proposed to stimulate DNA repair capacity. We investigated the capability of MLT in the modification of radiation-induced DNA damage in rat peripheral blood cells. Materials and Methods: In this experimental study, male rats (n = 162) were divided into 27 groups (n = 6 in each group) including: irradiation only, vehicle only, vehicle with irradiation, 100 mg/kg MLT alone, 100 mg/kg MLT plus irradiation in 3 different time points, and control. Subsequently, they were irradiated with a single whole-body X-ray radiation dose of 2 and 8 Gy at a dose rate of 200 MU/min. Rats were given an intraperitoneal injection of MLT or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were also taken 8, 24, and 48 h postirradiation, in order to measure the 8-oxoguanine glycosylase1 (Ogg1), Apex1, and Xrcc1 expression using quantitative real-time-polymerase chain reaction. Results: Exposing to the ionizing radiation resulted in downregulation of Ogg1, Apex1, and Xrcc1 gene expression. The most obvious suppression was observed in 8 h after exposure. Pretreatments with MLT were able to upregulate these genes when compared to the irradiation-only and vehicle plus irradiation groups (P < 0.05) in all time points. Conclusion: Our results suggested that MLT in mentioned dose may result in modulation of Ogg1, Apex1, and Xrcc1 gene expression in peripheral blood cells to reduce X-ray irradiation-induced DNA damage. Therefore, administration of MLT may increase the normal tissue tolerance to radiation through enhancing the cell DNA repair capacity. We believed that MLT could play a radiation toxicity reduction role in patients who have undergone radiation treatment as a part of cancer radiotherapy

Synthesis of curcumin loaded single walled carbon nanotubes: Characterization and anticancer effects in vitro

Curcumin, derived from Curcuma longa, is a widely used natural compound in anticancer treatments. Single-walled carbon nanotubes (SWCNTs), a significant class of nanomaterials known for their unique physicochemical properties, serve as effective carriers for curcumin. This allows for the utilization of curcumin's antitumor capabilities while overcoming its conventional drawbacks of low aqueous solubility and instability under physiological conditions. In the current study, SWCNTs were cultivated without hydrogen gas, utilizing a Fe-Mo/Al2O3 catalyst. Once prepared by the Chemical Vapor Deposition (CVD) method under ideal conditions, they were combined with curcumin. Various techniques, including Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), UV–Vis, Fourier Transform Infrared (FTIR), Raman, and X-Ray Diffraction (XRD), were employed to characterize the system. The quality of the SWCNT was determined by the ID/IG ratio in Raman spectroscopy. The DLS technique revealed that the ζ-potential of SWCNT and SWCNT-Cur was approximately −13.9 and −25.5 mV, respectively. The Nano-formulation had a loading capacity of 14/87 %. The rate of hemolysis caused by SWCNT-Cur was less than 10 %, and the high rate of cell viability observed in HFF-2 cells following the MTT test indicates the high safety of the Nano-formulation. To validate the therapeutic effects of the SWCNT-Cur on the 4T1 cell line, both in the presence and absence of X-ray radiation, the MTT assay method was used in vitro. The results showed a significant increase in toxicity on breast cancer cells with increasing concentration

Targeted CuFe2O4 hybrid nanoradiosensitizers for synchronous chemoradiotherapy

© 2022 Elsevier B.V.Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe2O4@BSA-FA-CUR, loaded with curcumin (CUR) and modified by bovine serum albumin (BSA) and folic acid (FA) was developed to enhance tumor accumulation and promote the anti-cancer activity while attenuating adverse effects. Both copper (Cu) and iron (Fe) were utilized in the construction of these submicron scale entities, therefore strong radiosensitization effect is anticipated by implementation of these two metals. The structure–function relationships between constituents of nanomaterials and their function led to the development of nanoscale materials with great radiosensitizing capacity and biosafety. BSA was used to anchor Fe and Cu ions but also to improve colloidal stability, blood circulation time, biocompatibility, and further functionalization. Moreover, to specifically target tumor sites and enhance cellular uptake, FA was conjugated onto the surface of hybrid bimetallic nanoparticles. Finally, CUR as a natural chemotherapeutic agent was encapsulated into the developed bimetallic nanoparticles. With incorporation of all abovementioned stages into one multifunctional nanoplatform, CuFe2O4@BSA-FA-CUR is produced for synergistic chemoradiotherapy with positive outcomes. In vitro investigation revealed that these nanoplatforms bear excellent biosafety, great tumor cell killing ability and radiosensitizing capacity. In addition, high cancer-suppression efficiency was observed through in vivo studies. It is worth mentioning that co-use of CuFe2O4@BSA-FA-CUR nanoplatforms and X-ray radiation led to complete tumor ablation in almost all of the treated mice. No mortality or radiation-induced normal tissue toxicity were observed following administration of CuFe2O4@BSA-FA-CUR nanoparticles which highlights the biosafety of these submicron scale entities. These results offer powerful evidence for the potential capability of CuFe2O4@BSA-FA-CUR in radiosensitization of malignant tumors and opens up a new avenue of research in this area