RESUMO
Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.
RESUMO
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.
RESUMO
To date, many potent compounds have been found which are derived from plants and herbs and possess anticancer properties due to their antioxidant effects. 9â³-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 9â³-Lithospermic acid methyl ester (9â³-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 9â³-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 9â³-lithospermic acid methyl ester represents a potential new therapeutic addition for gliomas.
Assuntos
Antineoplásicos , Benzofuranos , Neoplasias Encefálicas , Depsídeos , Glioblastoma , Animais , Glioblastoma/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Temozolomida/farmacologia , Benzofuranos/farmacologia , Proliferação de Células , Linhagem Celular Tumoral , Apoptose , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologiaRESUMO
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.
Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Glioblastoma/metabolismo , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Apoptose , Sobrevivência CelularRESUMO
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.
RESUMO
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.
Assuntos
Neoplasias Cutâneas , Vitamina D , Humanos , Revisões Sistemáticas como Assunto , Vitaminas , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Receptores de Calcitriol/genética , Polimorfismo GenéticoRESUMO
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.
RESUMO
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-propylene-amine 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.
RESUMO
Bone scintigraphy with Tc-99m-diphosphonate analogs are widely used in staging, restaging, and monitoring the therapy effectiveness of various cancer types. Bone-seeking agents are excreted through urination, resulting in the visualization of either anatomical abnormalities or pathological conditions of the kidneys and bladder. We present a case of a 63-year-old man with urinary bladder carcinoma depicted on whole body planar and single-photon emission computed tomography/computed tomography images.
RESUMO
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.
RESUMO
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.
Assuntos
Cardiotoxicidade , Neoplasias , Humanos , Cardiotoxicidade/etiologia , Coração/efeitos da radiação , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Neoplasias/complicações , Fatores de Risco , Doses de RadiaçãoRESUMO
Introduction: Meningiomas are the most common central nervous system tumor in adults. Knowledge of the tumor grade can guide optimal treatment timing and shape personalized follow-up strategies. Positron emission tomography (PET) has been utilized for the metabolic assessment of various intracranial space-occupying lesions. Herewith, we set out to evaluate the diagnostic accuracy of PET for the noninvasive assessment of meningioma's grade. Materials and methods: The Medline, Scopus and Cochrane databases were systematically searched in March 2022 for studies that evaluated the sensitivity and specificity of PET compared to the gold standard of histological diagnosis in the grading of meningiomas. Summary statistics will be calculated and scatter plots, summary curve from the HSROC model and posterior predictions by empirical Bayes estimates will be presented. Results: Five studies consisting of 242 patients with a total of 196 low-grade (Grade 1) and 46 high grade (Grade 2/3) meningiomas were included in our analysis. Three of the included studies used 18F-FDG, one study used 18F-FLT and one used(Whiting et al., 2011) 18 F-FET as PET tracers. The pooled sensitivity was 76% (95% CI: 52%-91%) and the pooled specificity was 89% (95% CI: 83%-93%). The diagnostic odds ratio was 27.17 (95% CI: 9.22-80.06), the positive likelihood ratio was 7.18 (95% CI: 4.54-11.34) and the negative likelihood ratio was 0.26 (95% CI: 0.11-0.61). Conclusion: PET is a promising and viable option as a noninvasive imaging tool to differentiate the meningioma grades. However, currently it cannot overtake the gold standard of histological grade confirmation. More studies are required for further validation and refinement of this imaging technique and assessment of other radiotracers as well.
RESUMO
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.
Assuntos
Neoplasias Meníngeas , Meningioma , Adulto , Humanos , Meningioma/cirurgia , Meningioma/patologia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Citometria de Fluxo , AneuploidiaRESUMO
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.
Assuntos
Doença da Artéria Coronariana , Epilepsia , Isquemia Miocárdica , Imagem de Perfusão do Miocárdio , Adulto , Epilepsia/complicações , Epilepsia/diagnóstico por imagem , Teste de Esforço , Humanos , Masculino , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
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.
Assuntos
Doença da Artéria Coronariana , Isquemia Miocárdica , Imagem de Perfusão do Miocárdio , Idoso , Índice de Massa Corporal , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/etiologia , Imagem de Perfusão do Miocárdio/métodos , Estudos Retrospectivos , Fatores de RiscoRESUMO
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.
RESUMO
BACKGROUND: 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.