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5-Hydroxy-3′,4′,6,7-tetramethoxyflavone (TMF) is a plant-origin flavone known for its anti-cancer properties. In the present study, the cytotoxic effect of TMF was evaluated in the U87MG and T98G glioblastoma (GBM) cell lines. The effect of TMF on cell viability was assessed with trypan blue exclusion assay and crystal violet staining. In addition, flow cytometry was performed to examine its effect on the different phases of the cell cycle, and in vitro scratch wound assay assessed the migratory capacity of the treated cells. Furthermore, the effect of in vitro radiotherapy was also evaluated with a combination of TMF and radiation. In both cell lines, TMF treatment resulted in G0/G1 cell cycle arrest, reduced cell viability, and reduced cell migratory capacity. In contrast, there was an antagonistic property of TMF treatment with radiotherapy. These results demonstrated the antineoplastic effect of TMF in GBM cells in vitro, but the antagonistic effect with radiotherapy indicated that TMF should be further evaluated for its possible antitumor role post-radiotherapy.

Background/Objectives: Glioblastoma (GBM) is the most aggressive type of brain tumor in adults. Currently, the only treatments available are surgery, radiotherapy, and chemotherapy based on temozolomide (TMZ); however, the prognosis is dismal. Several natural substances are under investigation for cancer treatment. 8α-O-(3,4-dihydroxy-2-methylenebutanoyloxy) dehydromelitensine (Isocnicin) is a natural compound derived from Centaurea species and was found to exhibit cytostatic/cytotoxic effect against different cell lines. In this study, we investigated the anti-glioma effects of isocnicin in U87 and T98 glioblastoma cell lines, as well as the effects of combined treatment with radiotherapy. Methods: Cell viability was evaluated with the trypan blue exclusion assay, cell cycle distribution was examined using flow cytometry, and the effects of the combination treatment were analyzed with CompuSyn software(1.0). Results: The result showed that isocnicin significantly reduced cell viability in U87 and T98 cell lines in a dose-dependent manner and IC50 values were calculated. Administration of isocnicin alone induced both S and G2/M cell cycle arrest in U87 and T98 cells in a dose-dependent manner. Moreover, when cells were treated with increasing concentrations of isocnicin, followed by 2 or 4 Gy of radiation, the percentage distribution of the cells in the G2/M phase was increased considerably in both U87 and T98 cell lines. Conclusions: Here, we show for the first time that co-treatment of isocnicin with radiation exerts a synergistic antiproliferative effect in glioblastoma cell lines. Natural compounds are promising for glioblastoma treatment. Further studies will be necessary to unravel isocnicin's mechanism of action and its synergistic effect with radiation on glioblastoma treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer has a major impact on societies across the world. In an attempt to find new treatment options for cancer, attention has shifted to natural compounds. Curcumin is a polyphenol isolated from the roots of turmeric that possesses many biological properties. It acts on the regulation of different aspects of tumor development and interconnects with major signaling pathways that are dysregulated in cancer, such as the phosphatidylinositol-3-kinase/protein kinase B pathway. In this review, the diverse effects of curcumin on the regulation of this pathway in different malignancies will be discussed. Cancer is a life-threatening disease and one of the leading causes of death worldwide. Despite significant advancements in therapeutic options, most available anti-cancer agents have limited efficacy. In this context, natural compounds with diverse chemical structures have been investigated for their multimodal anti-cancer properties. Curcumin is a polyphenol isolated from the rhizomes of Curcuma longa and has been widely studied for its anti-inflammatory, anti-oxidant, and anti-cancer effects. Curcumin acts on the regulation of different aspects of cancer development, including initiation, metastasis, angiogenesis, and progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway is a key target in cancer therapy, since it is implicated in initiation, proliferation, and cancer cell survival. Curcumin has been found to inhibit the PI3K/Akt pathway in tumor cells, primarily via the regulation of different key mediators, including growth factors, protein kinases, and cytokines. This review presents the therapeutic potential of curcumin in different malignancies, such as glioblastoma, prostate and breast cancer, and head and neck cancers, through the targeting of the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

To date, many potent compounds have been found which are derived from plants and herbs and possess anticancer properties due to their antioxidant effects. 9″-Lithospermic acid methyl ester is an effective natural compound derived from the Thymus thracicus Velen. It has been proven that this compound has substantial properties in different diseases, but its effects in cancer have not been thoroughly evaluated. The aim of this work was to study the effects of 9″-Lithospermic acid methyl ester (9″-methyl lithospermate) in U87 and T98 glioblastoma cell lines. Its effects on cellular viability were assessed via Trypan Blue and Crystal Violet stains, the cell cycle analysis through flow cytometry, and cell migration by employing the scratch wound healing assay. The results demonstrated that 9″-methyl lithospermate was able to inhibit cellular proliferation, induce cellular death, and inhibit cell migration. Furthermore, these results were intensified by the addition of temozolomide, the most prominent chemotherapeutic drug in glioblastoma tumors. Further studies are needed to reproduce these findings in animal models and investigate if 9″-lithospermic acid methyl ester represents a potential new therapeutic addition for gliomas. [ABSTRACT FROM AUTHOR]

Background: Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coronary heart disease. We investigated the relationship of CRP with findings from myocardial perfusion imaging (MPI). Methods: In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) who underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6 mg/L) within 1 month from MPI were included. The patients had no infection or recent acute coronary syndrome. Results: The median CRP level was 4 mg/L (2, 10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (p = 0.006) and summed rest score (SRS) (p = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03–42.13, p = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (p = 0.027 and p = 0.005, respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). Conclusion: a high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI. [ABSTRACT FROM AUTHOR]

Background and Objectives: Previous studies revealed the anti-angiogenic, antiproliferative, and anti-inflammatory effects of Vitamin D (VitD) on cancer cells. Although this body of evidence supported the correlation of high VitD levels with reduced incidence rates for various malignancies, contradictory results were reported regarding non-melanoma skin cancer (NMSC). The aim of this overview was to summarize the available evidence from the existing pool of systematic reviews and meta-analyses, focusing on VitD serum status, dietary intake, and VitD receptor (VDR) polymorphisms in correlation to NMSC incidence. Materials and Methods: A literature search in electronic databases was conducted from inception to January 2023. The inclusion criteria were systematic reviews and meta-analyses published in peer-reviewed journals, evaluating VitD serum levels, dietary and/or supplementary intake, or VDR gene polymorphisms, and reporting data on NMSC. Results: A total of 10 studies were included in the data analysis models. A positive association between VitD serum levels and NMSC is highlighted. However, dietary/supplementation of VitD does not exhibit a likewise strong linkage to NMSC. Despite the contradictory findings, VDR polymorphisms may play a crucial role in the intricate NMSC pathogenesis. Conclusions: This umbrella review shows that high VitD levels are associated with increased NMSC incidence, potentially due to its direct correlation with increased sun exposure. Further research on VDR polymorphisms is suggested to explore their true effect size on NMSC risk. [ABSTRACT FROM AUTHOR]

Cancer theragnostics is a novel approach that combines diagnostic imaging and radionuclide therapy. It is based on the use of a pair of radiopharmaceuticals, one optimized for positron emission tomography imaging through linkage to a proper radionuclide, and the other bearing an alpha- or beta-emitter isotope that can induce significant damage to cancer cells. In recent years, the use of theragnostics in nuclear medicine clinical practice has increased considerably, and thus investigation has focused on the identification of novel radionuclides that can bind to molecular targets that are typically dysregulated in different cancers. The major advantages of the theragnostic approach include the elimination of multi-step procedures, reduced adverse effects to normal tissues, early diagnosis, better predictive responses, and personalized patient care. This review aims to discuss emerging theragnostic molecules that have been investigated in a series of human malignancies, including gliomas, thyroid cancer, neuroendocrine tumors, cholangiocarcinoma, and prostate cancer, as well as potent and recently introduced molecular targets, like cell-surface receptors, kinases, and cell adhesion proteins. Furthermore, special reference has been made to copper radionuclides as theragnostic agents and their radiopharmaceutical applications since they present promising alternatives to the well-studied gallium-68 and lutetium-177. [ABSTRACT FROM AUTHOR]

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Simple Summary: Intraoperative Flow Cytometry (iFC) is a new technique that can help assess the malignancy grade, diagnose tumor type, and evaluate resection margins during solid tumor surgery. This study focuses on the role of iFC in grading gliomas and evaluating resection margins. iFC can analyze tissue samples within 5–6 min and was utilized to evaluate samples from patients with gliomas who underwent surgery over an 8-year period. The study found that high-grade gliomas had a significantly higher tumor index than low-grade gliomas. A cut-off value of 17% in the tumor index was identified as being able to accurately differentiate low- from high-grade gliomas. All low-grade gliomas were diploid, while 22 high-grade gliomas were aneuploid. iFC was also able to verify the presence of malignant tissue in every case when evaluating glioma margins. The study concludes that iFC is a promising intraoperative technique for glioma grading and resection margin assessment. Background: Intraoperative Flow Cytometry (iFC) is a novel technique for the assessment of the grade of malignancy and the diagnosis of tumor type and resection margins during solid tumor surgery. Herein, we set out to analyze the role of iFC in the grading of gliomas and the evaluation of resection margins. Material and Methods: iFC uses a fast cell cycle analysis protocol (Ioannina Protocol) that permits the analysis of tissue samples within 5–6 min. Cell cycle analysis evaluated the G0/G1 phase, S-phase, mitosis, and tumor index (S + mitosis phase fraction) and ploidy status. In the current study, we evaluated tumor samples and samples from the peripheral borders from patients with gliomas who underwent surgery over an 8-year period. Results: Eighty-one patients were included in the study. There were sixty-eight glioblastoma cases, five anaplastic astrocytomas, two anaplastic oligodendrogliomas, one pilocytic astrocytoma, three oligodendrogliomas and two diffuse astrocytomas. High-grade gliomas had a significantly higher tumor index than low grade gliomas (median value 22 vs. 7.5, respectively, p = 0.002). Using ROC curve analysis, a cut-off value of 17% in the tumor index could differentiate low- from high-grade gliomas with a 61.4% sensitivity and 100% specificity. All low-grade gliomas were diploid. From the high-grade gliomas, 22 tumors were aneuploid. In glioblastomas, aneuploid tumors had a significantly higher tumor index (p = 0.0018). Twenty-three samples from glioma margins were evaluated. iFC verified the presence of malignant tissue in every case, using histology as the gold standard. Conclusion: iFC constitutes a promising intraoperative technique for glioma grading and resection margin assessment. Comparative studies with additional intraoperative adjuncts are necessary. [ABSTRACT FROM AUTHOR]

Radiotherapy may be used alone or in combination with chemotherapy for cancer treatment. There are many mechanisms of radiation treatment exposure to toxicities. Our aim was to summarize the literature about known mechanisms of radiation-induced cardiac toxicities. We performed a systematic review of the literature on the PubMed database until October 2022 about cardiovascular toxicities and radiation therapy exposure. Only systematic reviews, meta-analyses, and reviews were selected. Out of 1429 publications screened, 43 papers met inclusion criteria and were selected for the umbrella review process. Microvascular and macrovascular complications could lead to adverse cardiac effects. Many radiotherapy-associated risk factors were responsible, such as the site of radiation treatment, beam proximity to heart tissues, total dosage, the number of radiotherapy sessions, adjuvant chemotherapeutic agents used, and patient traditional cardiovascular risk factors, patient age, and gender. Moreover, important dosage cutoff values could increase the incidence of cardiac toxicities. Finally, the time from radiation exposure to cardiac side effects was assessed. Our report highlighted mechanisms, radiation dosage values, and the timeline of cardiovascular toxicities after radiation therapy. All of the above may be used for the assessment of cardiovascular risk factors and the development of screening programs for cancer patients. [ABSTRACT FROM AUTHOR]

Meningiomas are the most frequent central nervous system tumors in adults. The majority of these tumors are benign. Nevertheless, the intraoperative identification of meningioma grade is important for modifying surgical strategy in order to reduce postoperative complications. Here, we set out to investigate the role of intraoperative flow cytometry for the differentiation of low-grade (grade 1) from high-grade (grade 2–3) meningiomas. The study included 59 patients. Intraoperative flow cytometry analysis was performed using the 'Ioannina Protocol' which evaluates the G0/G1 phase, S-phase, mitosis and tumor index (S + mitosis phase fraction) of a tumor sample. The results are available within 5 min of sample receipt. There were 41 grade 1, 15 grade 2 and 3 grade 3 meningiomas. High-grade meningiomas had significantly higher S-phase fraction, mitosis fraction and tumor index compared to low-grade meningiomas. High-grade meningiomas had significantly lower G0/G1 phase fraction compared to low-grade meningiomas. Thirty-eight tumors were diploids and twenty-one were aneuploids. No significant difference was found between ploidy status and meningioma grade. ROC analysis indicated 11.4% of tumor index as the optimal cutoff value thresholding the discrimination between low- and high-grade meningiomas with 90.2% sensitivity and 72.2% specificity. In conclusion, intraoperative flow cytometry permits the detection of high-grade meningiomas within 5 min. Thus, surgeons may modify tumor removal strategy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Obesity has been linked to various cardiovascular risk factors, increased incidence of coronary artery disease, and myocardial perfusion defects. The aim of this study was to investigate if body mass index (BMI) and waist circumference (WC) were associated with myocardial perfusion defects. Materials and Methods: A total of 308 consecutive patients who had myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) and a complete medical record on file were studied retrospectively. Results: The median age was 69 (61–76) years, the BMI was 27.6 (24.4–30.7) kg/m2, and the WC was 110 (102–118) cm. Of the 308 patients, 239 patients (77.6%) had myocardial ischemia. A positive test for ischemia was more frequent in men compared to women (72 vs. 28%, p < 0.001). Within the male group, BMI and WC were not significantly different between the ischemia and non-ischemia groups. In contrast, within the female group, both BMI (30.2 vs. 27.1 kg/m2, p = 0.002) and WC (112 vs. 105.5 cm, p = 0.020) were significantly higher in the ischemia group. Multivariable logistic regression showed that male sex and BMI were the only two independent predictors of ischemia in our patient population. Conclusions: This study showed that BMI was an independent predictor of ischemia in our patient population. [ABSTRACT FROM AUTHOR]

A 69-year-old male was admitted to our hospital because of left facial trauma with bone fractures, including the maxillary sinus, zygomatic arch, and ethmoid and sphenoid bones. Brain computed tomography was unremarkable but regional cerebral blood flow with hexamethyl-propyleneamine oxime single-photon emission computed tomography (SPECT) showed hypoperfusion of the left hemisphere, which was reversible since a repeat SPECT 4 months later was substantially improved. Brain perfusion SPECT may provide information on cerebrovascular status in some cases of facial injury. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to compare the myocardial perfusion imaging (MPI) with [99mTc]tetrofosmin stress -- rest single-photon emission computer tomography (SPECT) of patients with epilepsy with matched control individuals. Material and methods: All 29 adult epileptic patients were receiving antiepileptic drugs (AEDs) for epilepsy. Thirty-two individuals matched for gender and age consisted of the control group. MPIs SPECT were performed, and myocardial summed scores were obtained during stress (SSS) and rest (SRS) images. Abnormal MPI was considered when SSS was ≥ 4. In addition, the difference (SDS) between SSS and SRS was also assessed, which represents a rate of reversibility after stress. Results: Twenty of 29 (68.97%) patients with epilepsy had abnormal MPI and 14/32 (43.75%) of the controls (p = 0.04). Among males, 18/23 patients and 11/25 controls had abnormal MPI (p = 0.01), with quite a significant difference for mean SSS between male patients and controls (p = 0.002). Furthermore, SDS comparison showed that irreversible abnormalities were more common in patients than in control individuals. A difference of inadequately compensated myocardial ischemia between patients treated with enzyme inducing AEDs and patients treated with valproic acid was also detected. Conclusions: Single-photon emission computer tomography (SPECT) may detect increased risk for coronary artery disease and further cardiovascular events in patients with epilepsy. Our findings favor the conclusion that SPECT could be used for the early identification of cardiovascular comorbidity in epilepsy. [ABSTRACT FROM AUTHOR]

High-grade gliomas are among the most aggressive malignancies, with significantly low median survival. Recent experimental research in the field has highlighted the importance of natural substances as possible antiglioma agents, also known for their antioxidant and anti-inflammatory action. We have previously shown that natural substances target several surface cluster of differentiation (CD) markers in glioma cells, as part of their mechanism of action. We analyzed the genome-wide NF-κB binding sites residing in consensus regulatory elements, based on ENCODE data. We found that NF-κB binding sites reside adjacent to the promoter regions of genes encoding CD markers targeted by antiglioma agents (namely, CD15/FUT4, CD28, CD44, CD58, CD61/SELL, CD71/TFRC, and CD122/IL2RB). Network and pathway analysis revealed that the markers are associated with a core network of genes that, altogether, participate in processes that associate tumorigenesis with inflammation and immune evasion. Our results reveal a core regulatory network that can be targeted in glioblastoma, with apparent implications in individuals that suffer from this devastating malignancy. [ABSTRACT FROM AUTHOR]

Patients with illicit drug use may have deleterious acute and chronic cardiac effects. We present a case of a 42-year-old man, former alcohol and various illicit drugs user, who was admitted to the psychiatric unit for management of psychosis. Because of his previous drug and alcohol history, a cardiological evaluation was performed which revealed silent severe myocardial ischemia detected by myocardial perfusion imaging (MPI). The myocardial ischemia was attributed to coronary microvascular dysfunction, occurring several years after quitting the illicit drugs. This study highlights the potential myocardial ischemia that may occur in patients with previous alcohol and illicit drug use, and the role of MPI, a non-invasive test that can provide important information regarding the myocardial status of such patients, even without obvious cardiac symptoms or findings. [ABSTRACT FROM AUTHOR]

BACKGRAOUND: Langerhans cell histiocytosis is a rare hematological disorder. Skin rash is the typical early feature, and bony involvement is the second most common presentation. METHODS: We present a case of a 5-month-old female infant with left hemifacial swelling, initially treated for infection with antibiotics. However, due to persistence of swelling and new onset fever, further evaluation with ultrasonography, CT scan, FDG PET/CT and eventually biopsy was performed. RESULTS: Imaging methods revealed mandibular osteolysis indicative of either osteomyelitis or histiocytosis X. Tissue biopsy was diagnostic for Langerhans cell histiocytosis. CONCLUSION: Langerhans cell histiocytosis may present in infancy with a variety of symptoms, included an isolated bony lesion. Langerhans cell histiocytosis, despite its rarity, should be included in the differentiated diagnosis, when bone osteolysis is found. [ABSTRACT FROM AUTHOR]

Background and Objectives: Vitamin D (Vit D) deficiency has been implicated in various conditions, including cardiovascular disease. The purpose of this retrospective study was to investigate the incidence of patients with myocardial ischemia in relation to their serum levels of vitamin D. Materials and Methods: A 64-month search (January 2016 to April 2021) in our database of the Nuclear Medicine Laboratory revealed 113 patients who had both myocardial perfusion imaging with single photon emission computed tomography (MPI SPECT) and Vit D measurements. MPI SPECT obtained myocardial images during both stress (summed stress score, SSS) and rest (summed rest score, SRS). Abnormal MPI SPECT was when the SSS was ≤4. Vit D was determined by radioimmunoassay (RIA). Patients with Vit D values <10 ng/mL, 10-29 ng/mL and ≤30 ng/mL were defined as having a deficiency, insufficiency and sufficiency, respectively. Results: Among patients, 46/113 (40.7%) were male and 67/113 (59.3%) were female. Abnormal MPI was found in 58/113 (51.3%) patients. Vit D deficiency was noted in 20/113 (17.7%) patients, insufficiency in 86/113 (76.1%) patients, and normal Vit D was noted in only 7/113 (6.2%) patients. Sixteen of the 20 patients (80%) with Vit D deficiency, and 38/86 (44.2%) with insufficiency had an abnormal MPI SPECT. In contrast, only 1/7 (14.3%) patients with sufficient Vit D levels had an abnormal MPI SPECT. The Mann-Whitney U-test showed that ischemia reduced the values of Vit D. Correlation analysis showed a negative association of Vit D levels with SSS (rho = -0.232, p = 0.014) and SRS (rho = -0.250, p = 0.008). Further evaluation with a Vit D cut off 20 ng/mL retrieved no statistical significance. Finally, Vit D and gender were independently associated with myocardial ischemia. Conclusions: Low Vit D levels may represent a risk factor for myocardial ischemia. [ABSTRACT FROM AUTHOR]