Inorganic nanoparticle-cored dendrimers for biomedical applications: A review.

Hybrid nanostructures exhibit a synergistic combination of features derived from their individual components, showcasing novel characteristics resulting from their distinctive structure and chemical/physical properties. Surface modifiers play a pivotal role in shaping INPs' primary attributes, influencing their physicochemical properties, stability, and functional applications. Among these modifiers, dendrimers have gained attention as highly effective multifunctional agents for INPs, owing to their unique structural qualities, dendritic effects, and physicochemical properties. Dendrimers can be seamlessly integrated with diverse inorganic nanostructures, including metal NPs, carbon nanostructures, silica NPs, and QDs. Two viable approaches to achieving this integration involve either growing or grafting dendrimers, resulting in inorganic nanostructure-cored dendrimers. The initial step involves functionalizing the nanostructures' surface, followed by the generation of dendrimers through stepwise growth or attachment of pre-synthesized dendrimer branches. This hybridization imparts superior qualities to the resulting structure, including biocompatibility, solubility, high cargo loading capacity, and substantial functionalization potential. Combining the unique properties of dendrimers with those of the inorganic nanostructure cores creates a multifunctional system suitable for diverse applications such as theranostics, bio-sensing, component isolation, chemotherapy, and cargo-carrying applications. This review summarizes the recent developments, with a specific focus on the last five years, within the realm of dendrimers. It delves into their role as modifiers of INPs and explores the potential applications of INP-cored dendrimers in the biomedical applications.

Review of Recent Improvements in Carbon Ion Radiation Therapy in the Treatment of Glioblastoma.

Purpose: This article provides an overview of the physical and biologic properties of carbon ions, followed by an examination of the latest clinical outcomes in patients with glioma who have received carbon ion radiation therapy. Methods and Materials: According to thee articles that have been reviewed, glioma represents the predominant form of neoplastic growth in the brain, accounting for approximately 51% of all malignancies affecting the nervous system. Currently, high-grade glioma, specifically glioblastoma, comprises 15% of cases and is associated with a high mortality rate. The development of novel drugs for the treatment of high-grade tumors has been impeded by various factors, such as the blood-brain barrier and tumor heterogeneity, despite numerous endeavors. According to the definition of tumor grade established by the World Health Organization, the conventional treatment involves surgical resection followed by adjuvant radiation and chemotherapy. Despite numerous attempts in photon radiation therapy to apply the highest possible dose to the tumor site while minimizing damage to healthy tissue, there has been no success in increasing patient survival. The primary cause of resistance to conventional radiation therapy methods, namely x-ray and gamma-ray, is attributed to the survival of radio-resistant glioma stem cells, which have the potential to trigger a recurrence of tumors. Particle beams, such as protons and carbon ions, can deposit the highest dose to a confined region, thus offering a more accurate dose distribution compared with photon beams. Results: Carbon ions exhibit higher linear energy transfer and relative biologic effectiveness compared with photons, potentially enabling them to overcome radio-resistant tumor cells. Conclusions: Therefore, it can be hypothesized that carbon ion radiation therapy may show superior efficacy in destroying neoplastic cells with reduced negative outcomes compared with x-ray radiation therapy.

Therapeutic Effects of Melatonin in the Regulation of Ferroptosis: A Review of Current Evidence.

Ferroptosis is implicated in the pathogenesis of multiple diseases, including neurodegenerative diseases, cardiovascular diseases, kidney pathologies, ischemia-reperfusion injury, and cancer. The current review article highlights the involvement of ferroptosis in traumatic brain injury, acute kidney damage, ethanol-induced liver injury, and PM2.5-induced lung injury. Melatonin, a molecule produced by the pineal gland and many other organs, is well known for its anti- aging, anti-inflammatory, and anticancer properties and is used in the treatment of different diseases. Melatonin's ability to activate anti-ferroptosis pathways including sirtuin (SIRT)6/p- nuclear factor erythroid 2-related factor 2 (Nrf2), Nrf2/ antioxidant responsive element (ARE)/ heme oxygenase (HO-1)/SLC7A11/glutathione peroxidase (GPX4)/ prostaglandin-endoperoxide synthase 2 (PTGS2), extracellular signal-regulated kinase (ERK)/Nrf2, ferroportin (FPN), Hippo/ Yes-associated protein (YAP), Phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) and SIRT6/ nuclear receptor coactivator 4 (NCOA4)/ ferritin heavy chain 1 (FTH1) signaling pathways suggests that it could serve as a valuable therapeutic agent for preventing cell death associated with ferroptosis in various diseases. Further research is needed to fully understand the precise mechanisms by which melatonin regulates ferroptosis and its potential as a therapeutic target.

Analysis of the molecular alterations in cancer cells following nanotechnology-assisted targeted radiotherapy using Raman spectroscopy.

The study unveiled an innovative strategy for precise radiation targeting in cancer treatment, along with the monitoring of molecular changes induced by this therapeutic approach. In this research, we explored the impact of administering anti-HER2-AgNPs nanoconjugates either individually or in conjunction with gamma irradiation on the viability of SKBR3 breast cancer cells. The utilization of nanoconjugates resulted in an enhancement of cellular sensitivity toward radiation. The viability of the cells exhibited a decline as the dose of irradiation increased, and this decrease was further exacerbated by the passage of time following irradiation. The analysis of RS revealed distinct cellular responses in varying conditions. The observed increase in SERS intensity, resulting from the increment in dose from 0 to 2 Gy, can be attributed to the probable upregulation of HER2 expression induced by irradiation. The observed decrease in SERS intensity at doses of 4 and 6 Gy can be attributed to the likely reduction in HER2 expression. It was illustrated that the analysis of Raman spectroscopy data can aid in the identification of radiation-induced biochemical alterations in cancer cells during the application of nanoconjugates-based radiotherapy. The findings revealed that nanoconjugates have the potential to enhance cellular sensitivity to radiation along with facilitating the detection of radiation-induced biochemical alterations within cancer cells.

Protective and therapeutic potential of melatonin against intestinal diseases: updated review of current data based on molecular mechanisms.

INTRODUCTION: Intestinal diseases, a leading global cause of mortality and morbidity, carry a substantial socioeconomic burden. Small and large intestines play pivotal roles in gastrointestinal physiology and food digestion. Pathological conditions, such as gut dysbiosis, inflammation, cancer, therapy-related complications, ulcers, and ischemia, necessitate the urgent exploration of safe and effective complementary therapeutic strategies for optimal intestinal health. AREAS COVERED: This article evaluates the potential therapeutic effects of melatonin, a molecule with a wide range of physiological actions, on intestinal diseases including inflammatory bowel disease, irritable bowel syndrome, colon cancer, gastric/duodenal ulcers and other intestinal disorders. EXPERT OPINION: Due to anti-inflammatory and antioxidant properties as well as various biological actions, melatonin could be a therapeutic option for improving digestive disorders. However, more researches are needed to fully understand the potential benefits and risks of using melatonin for digestive disorders.

Melatonin and bone-related diseases: an updated mechanistic overview of current evidence and future prospects.

PURPOSE: Bone diseases account for an enormous cost burden on health systems. Bone disorders are considered as age-dependent diseases. The aging of world population has encouraged scientists to further explore the most effective preventive modalities and therapeutic strategies to overcome and reduce the high cost of bone disorders. Herein, we review the current evidence of melatonin's therapeutic effects on bone-related diseases. METHODS: This review summarized evidences from in vitro, in vivo, and clinical studies regarding the effects of melatonin on bone-related diseases, with a focus on the molecular mechanisms. Electronically, Scopus and MEDLINE®/PubMed databases were searched for articles published on melatonin and bone-related diseases from inception to June 2023. RESULTS: The findings demonstrated that melatonin has beneficial effect in bone- and cartilage-related disorders such as osteoporosis, bone fracture healing, osteoarthritis, and rheumatoid arthritis, in addition to the control of sleep and circadian rhythms. CONCLUSION: A number of animal and clinical studies have indicated that various biological effects of melatonin may suggest this molecule as an effective therapeutic agent for controlling, diminishing, or suppressing bone-related disorders. Therefore, further clinical studies are required to clarify whether melatonin can be effective in patients with bone-related diseases.

Chemo-radiation therapy of U87-MG glioblastoma cells using SPIO@AuNP-Cisplatin-Alginate nanocomplex.

Megavoltage radiotherapy and cisplatin-based chemotherapy are the primary glioblastoma treatments. Novel nanoparticles have been designed to reduce adverse effects and boost therapeutic effectiveness. In the present study, we synthesized the SPIO@AuNP-Cisplatin-Alginate (SACA) nanocomplex, composed of a SPIO core, a gold shell, and an alginate coating. SACA was characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). U87-MG human glioblastoma cells and the HGF cell line (a healthy primary gingival fibroblast) were treated in multiple groups by a combination of SACA, cisplatin, and 6 MV X-ray. The MTT assay was used to assess the cytotoxicity of cisplatin and SACA (at various concentrations and for 4 h). Following the treatments, apoptosis and cell viability were evaluated in each treatment group using flow cytometry and the MTT assay, respectively. The findings demonstrated that the combination of SACA and 6 MV X-rays (at the doses of 2 and 4 Gy) drastically decreased the viability of U87MG cells, whereas the viability of HGF cells remained unchanged. Moreover, U87MG cells treated with SACA in combination with radiation exhibited a significant increase in apoptosis, demonstrating that this nanocomplex effectively boosted the radiosensitivity of cancer cells. Even though additional in vivo studies are needed, these findings suggest that SACA might be used as a radiosensitizer nanoparticle in the therapy of brain tumors.

COVID-19 diagnostic approaches with an extensive focus on computed tomography in accurate diagnosis, prognosis, staging, and follow-up.

Although a long time has passed since its outbreak, there is currently no specific treatment for COVID-19, and it seems that the most appropriate strategy to combat this pandemic is to identify and isolate infected individuals. Various clinical diagnosis methods such as molecular techniques, serologic assays, and imaging techniques have been developed to identify suspected patients. Although reverse transcription-quantitative PCR (RT-qPCR) has emerged as a reference standard method for diagnosis of SARS-CoV-2, the high rate of false-negative results and limited supplies to meet current demand are the main shortcoming of this technique. Based on a comprehensive literature review, imaging techniques, particularly computed tomography (CT), show an acceptable level of sensitivity in the diagnosis and follow-up of COVID-19. Indeed, because lung infection or pneumonia is a common complication of COVID-19, the chest CT scan can be an alternative testing method in the early diagnosis and treatment assessment of the disease. In this review, we summarize all the currently available frontline diagnostic tools for the detection of SARS-CoV-2-infected individuals and highlight the value of chest CT scan in the diagnosis, prognosis, staging, management, and follow-up of infected patients.

Evaluation of Dose-Painting in the Dominant Intraprostatic Lesions by Radiobiological Parameters using 68Ga- PSMA PET/CT.

Background: Patients diagnosed with dominant intraprostatic lesions (DIL) may need radiation doses over than 80 Gy. Dose-painting by contours (DPC) is a useful technique which helps the patients. Dose-painting approach need to be evaluated. Objective: To evaluate the DCP technique in the case of boosting the DILs by radiobiological parameters, tumor control probability (TCP), and normal tissue complication probability (NTCP) via PET/CT images traced by 68Ga-PSMA. Material and Methods: In this analytical study, 68Ga-PSMA PET/CT images were obtained from patients with DILs that were delineated using the Fuzzy c-mean (FCM) algorithm and thresholding methods. The protocol of therapy included two phases; at the first phase (ph1), a total dose of 72 Gy in 36 fractions were delivered to the planning target volume (PTV1); the seconds phase consisted of the application of variable doses to the PTV2. Moreover, two concepts were also considered to calculate the TCP using the Zaider-Minerbo model. Results: The lowest volume in DILs belonged to the DIL1 extracted by the FCM method. According to dose-volume parameters of the rectum and bladder, by the increase in the PTV dose higher than 92 Gy, the amounts of rectum and bladder doses are increased. There was no difference between the TCPs of DILs at doses higher than 86 Gy and 100 Gy for ordinary and high clone density, respectively. Conclusion: Consequently, our dose-painting approach for DILs, extracted by the FCM method via PET/CT images, can reduce the total dose for prostate radiation with 100% tumor control and less normal tissue complications.

Melatonin effect on platelets and coagulation: Implications for a prophylactic indication in COVID-19.

Severe COVID-19 is associated with the dynamic changes in coagulation parameters. Coagulopathy is considered as a major extra-pulmonary risk factor for severity and mortality of COVID-19; patients with elevated levels of coagulation biomarkers have poorer in-hospital outcomes. Oxidative stress, alterations in the activity of cytochrome P450 enzymes, development of the cytokine storm and inflammation, endothelial dysfunction, angiotensin-converting enzyme 2 (ACE2) enzyme malfunction and renin-angiotensin system (RAS) imbalance are among other mechanisms suggested to be involved in the coagulopathy induced by severe acute respiratory syndrome coronavirus (SARS-CoV-2). The activity and function of coagulation factors are reported to have a circadian component. Melatonin, a multipotential neurohormone secreted by the pineal gland exclusively at night, regulates the cytokine system and the coagulation cascade in infections such as those caused by coronaviruses. Herein, we review the mechanisms and beneficial effects of melatonin against coagulopathy induced by SARS-CoV-2 infection.

The Application of ATR Kinase Inhibitor AZD6738 in Combination with Radiotherapy for the Treatment of Melanoma.

Background: Melanoma is categorized as one of the most malignant, severe, and lethal cancers of the skin. Regarding the lack of efficiency of conventional therapies for most patients, novel therapeutic strategies are strongly required. Objective: The current study aimed to assess the impact of AZD6738- an ATR kinase inhibitor- in combination with 6 MV X-ray on the human melanoma cell line (A375). Material and Methods: In this experimental study, cells were treated with different concentrations of AZD6738 for 24 and 48 h in the presence and absence of radiation (2 Gy, 4 Gy, and 6 Gy). The cell viability and cell proliferation assay were examined in both experimental and control groups by MTT and colony formation techniques, respectively. Results: The results indicated that by increasing the concentration of AZD6738, the cell viability was markedly diminished in all treatment groups. As expected, the cell viability of the cells treated with AZD6738 and radiation was significantly lower than the group treated with AZD6738 alone. Besides, the combinatory treatment significantly decreased cell proliferation in the melanoma cell line. The combination of AZD6738 with radiation resulted in a significant increase in cytotoxicity by a 50% increase in cell death when used at concentrations of 0.3 µM, 1 µM, 1.51 µM, and 1.61 µM, respectively. Conclusion: The combination of AZD6738 with radiation possesses a synergistic effect on the reduction of the cell viability and proliferation of melanoma cells. This present study provides insight into the impact of Ataxia Telangiectasia and Rad3-related kinase (ATR) inhibition on the potential role of this kinase in the suppression of melanoma cell proliferation.

Investigating Radioprotective Effect of Hesperidin/Diosmin Compound Against 99mTc-MIBI-Induced Cardiotoxicity: Animal Study.

This study was designed to indicate the cardiotoxicity due to 99mTc-MIBI injection in myocardial perfusion imaging in wistar Rats. In addition, protective effect of hesperidin/diosmin compound (HDC) against the cardiotoxicity was evaluated. Twenty five male rats were randomly divided into five groups. The rats in Group 1 (control) only received PBS. For Group 2 (HDC only) the rats treated with only HDC. The rats in Group 3 (radiation) received PBS before injection and exposure to 1 mCi 99mTc-MIBI. The rats in Group 4 (HDC + radiation) treated with HDC before exposure. For Group 5 (radiation + HDC) the rats were exposed and thereafter administered HDC. The Animals of this study were orally administered 100 mg/kg/day of the HDC for 7 days. Then, the rats were sacrificed and afterwards their heart tissues were carefully extracted for biochemical and histopathological evaluations. According to our results in the radiation group, the rate of rupture of cardiomyocyte fibers was higher than other groups, and in some fibers, the presence of lymphocytes was observed. Relative improvement was observed in radiation + HDC group compared to the radiation group and also a small number of cardiomyocyte fibers were torn and in some fibers, the presence of lymphocytes was observed, which was less than the model group. Collagen deposition significantly increased in radiation group compared to control group (P < 0.05). It can be seen that the percentage of collagen deposition decreased substantially in the group treated with HDC before or after radiation compared to radiation group (P < 0.05). The MDA activities significantly reduced (P < 0.05) in both (HDC + radiation) and (radiation + HDC) groups. SOD activity significantly increased in both (radiation + HDC) and (HDC + radiation) groups compared to that of radiation group (P < 0.05). It could be concluded that the HDC is safe and promising useful therapeutic agent in radiation induced cardiotoxicity for patients undergoing nuclear medicine procedures.

The effect of iodine-131 beta-particles in combination with A-966492 and Topotecan on radio-sensitization of glioblastoma: An in-vitro study.

Glioblastoma tumors are resistant to radiotherapy, and the need for drugs to induce radio-sensitization in tumor cells has always been a challenge. Besides, radiotherapy using targeted radionuclide would be effective even for resistant tumors. It has been shown topoisomerase I and poly (ADP-ribose) polymerase (PARP) enzymes have critical roles in the repair process of DNA injury in cells. Therefore, the inhibition of the activity of these enzymes can halt this process and result in the accumulation of damaged DNA in cells and the induction of cell death in tumors. In the present research, the impact of beta-particles of iodine-131 in combination with Topotecan (TPT), as the inhibitor of topoisomerase I, and A-966492, as the inhibitor of the PARP enzyme on the possible increase of radio-sensitivity of glioblastoma cells was assessed. For this purpose, a human glioblastoma cell line, U87MG, was cultured in flasks coated with Poly-Hema to achieve 300 µm-diameter spheroids. Then, nontoxic concentrations of A-966492 and TPT were applied in the cell culture media. The viability of the cells treated with iodine131 in combination with A-966492 and TPT was determined by the clonogenic assay. The expression rate of gamma-H2AX, as a biomarker of DNA double-strand breaks, was analyzed using immunofluorescence microscopy to unravel the effect of TPT, A-966492 (1 µM), and radiation on the cell death induction. The combination of each TPT or A-966492 with radiation resulted in the increased rate of cell death, and the ratios of sensitizer enhancement at 50% survival (SER50) were elevated by 1.45 and 1.25, respectively. Chemo- and radio-sensitization were promoted when iodine-131 was combined with A-966492 and TPT, with the SER50 of 1.68. Also, the expression of γ-H2AX was significantly increased in cells treated with A-966492 and TPT combined with radiation. The results demonstrated that iodine-131, in combination with A-966492 and TPT, had marked effects on radio-sensitizing and can be used as a targeted radionuclide for targeting radiotherapy in combination with topoisomerase I and PARP inhibitors to enhance radiotherapy in clinics.

Low-dose radiotherapy (LD-RT) for COVID-19-induced pneumopathy: a worth considering approach.

PURPOSE: It seems that 2020 would be always remembered by the name of novel coronavirus (designated as SARS-CoV-2), which exerted its deteriorating effects on the health care, economy, education, and political relationships. In August 2020 more than eight hundred thousand patients lost their lives due to acute respiratory syndrome. In the limited list of therapeutic approaches, the effectiveness of low-dose radiation therapy (LD-RT) for curing inflammatory-related diseases have sparkled a light that probably this approach would bring promising advantages for COVID-19 patients. LD-RT owns its reputation from its ability to modulate the host inflammatory responses by blocking the production of pro-inflammatory cytokines and hampering the activity of leukocytes. Moreover, the cost-effective and availability of this method allow it to be applied to a large number of patients, especially those who could not receive anti-IL-6 treatments in low-income countries. But enthusiasm for applying LD-RT for the treatment of COVID-19 patients has been muted yet. CONCLUSION: In this review, we take a look at LD-RT mechanisms of action in the treatment of nonmalignant diseases, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if LD-RT might be a promising therapeutic approach in COVID-19 patients.

The Effects of Calligonum Extract and Low-Intensity Ultrasound on Motility, Viability, and DNA Fragmentation of Human Frozen-Thawed Semen Samples.

BACKGROUND: The study aimed to evaluate the impact of Calligonum extract and US radiation on sperm parameters of cryopreserved human semen samples. MATERIALS AND METHODS: In this experimental study, twenty-five semen specimens were obtained from healthy semen donors and incubated in human tubal fluid (HTF) medium supplemented with 10% human serum albumin (HSA) for 45 minutes. Samples were treated with Calligonum extract (10 µg/ml) alone (CGM group) and US radiation (LIPUSexposed group) alone or a combination of both treatments (CGM+LIPUS). The US group received US stimulation (in both continuous and pulsed wave modes) at a frequency of 1 MHZ and intensity of 200 mW/cm2 for 200 seconds. Sperm morphology was assessed by Diff-Quik staining. The DNA fragmentation was evaluated the Halo sperm kit. Sperm parameters was analyzed by a computer-assisted semen analysis system. Reactive oxygen species (ROS) was assessed by flow cytometry. RESULTS: The results showed that the treatment with Calligonum extract significantly (P<0.05) increased the progressive motility of spermatozoa in the CGM group as compared with the control group. The application of low-intensity US significantly (P<0.05) decreased the motility and viability of spermatozoa in the US group when compared with the control group. Our findings also indicated that the use of both low-intensity US in continuous mode and Calligonum extract slightly increased progressive motility; however, such an increase was not statistically significant. The rate of DNA fragmentation was considerably higher (P<0.05) in control and LIPUS-exposed groups than the other groups. CONCLUSION: Treatment of spermatozoa with Calligonum extract slightly improved the sperm parameters due to its antioxidant activity, on the other hand, according to our results, US radiation did not improve sperm parameters which may be due to interference with the motility of sperm, as well as its physical effects on spermatozoa.

Investigation of the Dose-Enhancement Effects of Spherical and Rod-Shaped Gold Nanoparticles on the HeLa Cell Line.

BACKGROUND: Cervical cancer cells are known as radioresistant cells. Current treatment methods have not improved the patients' survival efficiently; thus, new therapeutic strategies are needed to enhance the efficacy of radiotherapy. Gold nanomaterials with different shapes and sizes have been explored as radiosensitizers. The present study compared the radiosensitizing effects of gold nanorods (AuNRs) with spherical gold nanoparticles (AuNPs) on the HeLa cell line irradiated with megavoltage X-rays. MATERIALS AND METHODS: The cytotoxicity of AuNRs and AuNPs on HeLa cells in the presence and absence of 6-MV X-ray was investigated using the MTT assay. For this aim, HeLa cells were incubated with and AuNPs and AuNRs at various concentrations (5, 10, and 15 µg/mL) for 6 hours. Afterward, HeLa cells were irradiated with 6-MV X-ray at a single dose of 2 Gy. RESULTS: The results showed that the addition of AuNRs and AuNPs could enhance the radiosensitivity of HeLa cells. Both AuNRs and AuNPs showed low toxicity on HeLa cells, while AuNRs were more toxic than AuNPs at the examined concentrations. Moreover, it was found that AuNRs could enhance the radiosensitivity of HeLa cells more than spherical-shaped AuNPs. CONCLUSION: This study revealed that the shape of nanoparticles is an effective factor when they are used as radiosensitizing agents during radiotherapy.

CT imaging markers to improve radiation toxicity prediction in prostate cancer radiotherapy by stacking regression algorithm.

PURPOSE: Radiomic features, clinical and dosimetric factors have the potential to predict radiation-induced toxicity. The aim of this study was to develop prediction models of radiotherapy-induced toxicities in prostate cancer patients based on computed tomography (CT) radiomics, clinical and dosimetric parameters. METHODS: In this prospective study, prostate cancer patients were included, and radiotherapy-induced urinary and gastrointestinal (GI) toxicities were assessed by Common Terminology Criteria for adverse events. For each patient, clinical and dose volume parameters were obtained. Imaging features were extracted from pre-treatment rectal and bladder wall CT scan of patients. Stacking algorithm and elastic net penalized logistic regression were used in order to feature selection and prediction, simultaneously. The models were fitted by imaging (radiomics model) and clinical/dosimetric (clinical model) features alone and in combinations (clinical-radiomics model). Goodness of fit of the models and performance of classifications were assessed using Hosmer and Lemeshow test, - 2log (likelihood) and area under curve (AUC) of the receiver operator characteristic. RESULTS: Sixty-four prostate cancer patients were studied, and 33 and 52 patients developed ≥ grade 1 GI and urinary toxicities, respectively. In GI modeling, the AUC for clinical, radiomics and clinical-radiomics models was 0.66, 0.71 and 0.65, respectively. To predict urinary toxicity, the AUC for radiomics, clinical and clinical-radiomics models was 0.71, 0.67 and 0.77, respectively. CONCLUSIONS: We have shown that CT imaging features could predict radiation toxicities and combination of imaging and clinical/dosimetric features may enhance the predictive performance of radiotoxicity modeling.

The Use of ß-Elemene to Enhance Radio Sensitization of A375 Human Melanoma Cells.

OBJECTIVE: Melanoma is the most malignant and severe type of skin cancer. It is a tumor with a high risk of metastasis and resistant to conventional treatment methods (surgery, radiotherapy, and chemotherapy). ß-elemene is the most active constituent of Curcuma wenyujin which is a non-cytotoxic antitumor drug, proved to be effective in different types of cancers. The study aimed to investigate the therapeutic effects of ß-elemene in combination with radiotherapy on A375 human melanoma. MATERIALS AND METHODS: In this experimental study, human melanoma cells were grown in the monolayer culture model. The procedure of the treatment was performed by the addition of different concentrations of ß-elemene to the cells. Then, the cells were exposed to 2 and 4 Gy X-ray in different incubation times (24, 48, and 72 hours). The MTT assay was used for the determination of the cell viability. To study the rate of apoptosis response to treatments, the Annexin V/PI assay was carried out. RESULTS: The results of the MTT assay showed ß-elemene reduced the cell proliferation in dose- and time-dependent manners in cells exposed to radiation. Flow cytometry analysis indicated that ß-elemene was effective in the induction of apoptosis. Furthermore, the combination treatment with radiation remarkably decreased the cells proliferation ability and also enhanced apoptosis. For example, cell viability in a group exposed to 40 µg/ml of ß-elemene was 80%, but combination treatment with 6 MV X beam at a dose of 2 Gy reduced the viability to 61%. CONCLUSION: Our results showed that ß-elemene reduced the proliferation of human melanoma cancer cell through apoptosis. Also, the results demonstrated that the radio sensitivity of A375 cell line was significantly enhanced by ß-elemene. The findings of this study indicated the efficiency of ß-elemene in treating melanoma cells and the necessity for further research in this field.

The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells.

OBJECTIVE: Glioblastoma (GBM) is one of the devastating types of primary brain tumors with a negligible response to standard therapy. Repurposing drugs, such as disulfiram (DSF) and metformin (Met) have shown antitumor properties in different cell lines, including GBM. In the present study, we focused on the combinatory effect of Met and DSF-Cu on the induction of apoptosis in U87-MG cells exposed to 6-MV X-ray beams. MATERIALS AND METHODS: In this experimental study, the MTT assay was performed to evaluate the cytotoxicity of each drug, along with the combinatory use of both. After irradiation, the apoptotic cells were assessed using the flow cytometry, western blot, and real-time polymerase chain reaction (RT-PCR) to analyze the expression of some cell death markers such as BAX and BCL-2. RESULTS: The synergistic application of both Met and DSF had cytotoxic impacts on the U87-MG cell line and made them sensitized to irradiation. The combinatory usage of both drugs significantly decreased the cells growth, induced apoptosis, and caused the upregulation of BAX, P53, CASPASE-3, and it also markedly downregulated the expression of the anti-apoptotic protein BCL-2 at the gene and protein levels. CONCLUSION: It seems that the synergistic application of both Met and DSF with the support of irradiation can remarkably restrict the growth of the U87-MG cell line. This may trigger apoptosis via the stimulation of the intrinsic pathway. The combinatory use of Met and DSF in the presence of irradiation could be applied for patients afflicted with GBM.

Organ at risk dose calculation for left sided breast cancer treatments using intraoperative electron radiotherapy: A Monte Carlo-based feasibility study.

The present study aims to calculate the received dose by lungs and heart, as organs at risk (OAR), during intraoperative electron radiotherapy (IOERT) of left breast cancer at the presence and absence of shielding disk using Monte Carlo (MC) simulation. LIAC 12, a dedicated IOERT Linac, and an anthropomorphic phantom were considered in this study to simulate particle tracks of 6, 8, 10, and 12 MeV nominal electron energies using EGSnrc MC particle transport simulation code. The results showed that for increasing electron beam energies in the absence of shielding disk, left lung and heart dose would also be increasing so that, maximum left lung and heart dose respectively increases from 0.512 to 9.920 Gy and from 0 to 0.506 Gy with increment of electron energy from 6 to 12 MeV. Employing the shielding disk in 6 and 8 MeV energy can reduce the heart and left lung maximum dose to zero. On the other hand, this dose reduction at 10 and 12 MeV energy was respectively about 99% and 93.5% for heart and 99.9% and 92.9% for left lung. Right lung did not receive a remarkable dose both in presence and absence of shielding disk. From the results, it can be concluded that employing the shielding disk can effectively reduce the received dose to OARs.