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Glioblastoma (GBM) is an aggressive brain cancer characterized by significant molecular and cellular heterogeneity, which complicates treatment efforts. Current standard therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, often fail to achieve long-term remission due to tumor recurrence and resistance. A pro-oxidant environment is involved in glioma progression, with oxidative stress contributing to the genetic instability that leads to gliomagenesis. Evaluating pro-oxidant therapies in brain tumors is crucial due to their potential to selectively target and eradicate cancer cells by exploiting the elevated oxidative stress levels inherent in these malignant cells, thereby offering a novel and effective strategy for overcoming resistance to conventional therapies. This study investigates the therapeutic potential of doxorubicin (DOX) and photodynamic therapy (PDT) with Me-ALA, focusing on their effects on redox homeostasis. Basal ROS levels and antioxidant gene expression (NFE2L2, CAT, GSR) were quantitatively assessed across GBM cell lines, revealing significant variability probably linked to genetic differences. DOX and PDT treatments, both individually and in combination, were analyzed for their efficacy in inducing oxidative stress and cytotoxicity. An in silico analysis further explored the relationship between gene mutations and oxidative stress in GBM patients, providing insights into the molecular mechanisms underlying treatment responses. Our findings suggest that pro-oxidant therapies, such as DOX and PDT in combination, could selectively target GBM cells, highlighting a promising avenue for improving therapeutic outcomes in GBM.
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Neoplasias Encefálicas , Doxorrubicina , Glioblastoma , Estresse Oxidativo , Fotoquimioterapia , Espécies Reativas de Oxigênio , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , Humanos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Fotoquimioterapia/métodos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Sinergismo Farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
PURPOSE: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy. METHODS: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated. RESULTS: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles. CONCLUSION: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy.
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Carboplatina , Dislipidemias , Hipertensão , Hipogonadismo , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Estudos Retrospectivos , Hipogonadismo/epidemiologia , Hipogonadismo/complicações , Dislipidemias/epidemiologia , Dislipidemias/complicações , Hipertensão/epidemiologia , Hipertensão/complicações , Adulto , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/patologia , Seminoma/complicações , Seminoma/epidemiologia , Seminoma/patologia , Pessoa de Meia-Idade , Incidência , Espanha/epidemiologia , Carboplatina/administração & dosagem , Adulto Jovem , Estadiamento de Neoplasias , Fatores de Risco , IdosoRESUMO
PURPOSE: Breast cancer is the leading cause of cancer death in Brazil and in many countries around the world. In order to minimize the risk of recurrence and death, adjuvant endocrine therapy (AET) is used in women whose tumors express hormone receptors; however, the therapy is associated with low rates of compliance. Therefore, we sought to evaluate the proportion of patients who are adherent/non-adherent to AET at the beginning of the therapy (1st year) and at its end (5th year). METHODS: Cross-sectional study assessing adherence through the Brief Medication Questionnaire. RESULTS: It was identified that eventual failures in maintaining the correct adherence to the treatment have risen from 23% of patients in the 1st year of treatment to 35% of patients in the 5th year (p = 0.005). In both groups, use of aromatase inhibitors, polypharmacy of at least 3 mediations and the previous diagnosis of diabetes mellitus (DM) or systemic arterial hypertension (SAH) have contributed to low adherence among patients. CONCLUSION: The proportion of patients who are not adherent to AET was high in both cohorts, and the rate of non-adherent patients rises over time. It is essential to incorporate screening methods for lack of compliance to AET, as well as measures to try to reduce non-persistence to the treatment, such as educating the patients on the benefits of the treatment, managing comorbidities through lifestyle changes and, therefore, reducing polypharmacy and, above all, detecting and treating very early the adverse effects of AET that might interfere with its correct use.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Antineoplásicos Hormonais/efeitos adversos , Estudos Transversais , Países em Desenvolvimento , Adesão à Medicação , Quimioterapia AdjuvanteRESUMO
Introduction melanoma patients who become stage III after a positive sentinel node biopsy (SNB) may have several patterns of recurrence patients and methods retrospective analysis of melanoma patients who have undergone SNB in a single institution from 2000 to 2015. Results There were 111 recurrences (45.1%) among 246 (20.3%) SNB positive patients and median DRFS was 77.7 months. After initial treatment, further recurrences occurred in 68 (77.3%) patients, regardless the site of initial recurrence conclusions multimodal strategies are recommended to achieve better results when managing stage III melanoma patients after a positive SNB.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/cirurgia , Melanoma/patologia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Excisão de LinfonodoRESUMO
Buthionine sulfoximine (BSO) is a synthetic amino acid that blocks the biosynthesis of reduced glutathione (GSH), an endogenous antioxidant cellular component present in tumor cells. GSH levels have been associated with tumor cell resistance to chemotherapeutic drugs and platinum compounds. Consequently, by depleting GSH, BSO enhances the cytotoxicity of chemotherapeutic agents in drug-resistant tumors. Therefore, the aim of this study was to conduct a systematic review with meta-analysis of preclinical studies utilizing BSO in cancer treatments. The systematic search was carried out using the following databases: PubMed, Web of Science, Scopus, and EMBASE up until March 20, 2023, in order to collect preclinical studies that evaluated BSO, alone or in association, as a strategy for antineoplastic therapy. One hundred nine investigations were found to assess the cytotoxic potential of BSO alone or in combination with other compounds. Twenty-one of these met the criteria for performing the meta-analysis. The evidence gathered indicated that BSO alone exhibits cytotoxic activity. However, this compound is generally used in combination with other antineoplastic strategies, mainly chemotherapy ones, to improve cytotoxicity to carcinogenic cells and treatment efficacy. Finally, this review provides important considerations regarding BSO use in cancer treatment conditions, which might optimize future studies as a potential adjuvant antineoplastic therapeutic tool.
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Antineoplásicos , Neoplasias , Humanos , Butionina Sulfoximina/farmacologia , Butionina Sulfoximina/uso terapêutico , Metionina Sulfoximina/uso terapêutico , Metionina Sulfoximina/toxicidade , Resistencia a Medicamentos Antineoplásicos , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Prognostic and predictive factors for early and late distant distance recurrence risk in estrogen-receptor positive and HER2-receptor negative early breast cancer are well known, but not all these variables work equally for the prediction. The following are the most widely accepted variables for categorizing risk levels: clinic-pathologic features (tumor size, lymph node involvement, histological grade, age, menopausal status, Ki-67 expression, estrogen, and progesterone expression), primary systemic treatment response (pathologic response and/or Ki-67 downstaging), and gene expression signatures stratification. Treatment guidelines from cancer societies and collaborative groups, online predict-tools, real-world data and experts' opinion recommends different adjuvant strategies (chemotherapy, endocrine therapy, ovarian suppression, olaparib, or abemaciclib) depending on the low (< 10%), intermediate (10%-20%) or high-risk of distance recurrence at least in the first 5 years. Multiple randomized prospective trials were updated in 2022, that evidence allow us to perform a stratification of risk in pre- and postmenopausal women with estrogen-receptor positive and HER2-receptor negative early breast cancer based on a combination of clinic-pathologic features and genomic assays and guide the adjuvant systemic treatment recommendation for those with high risk.
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INTRODUCTION: The KEYNOTE-054 trial found that adjuvant treatment with pembrolizumab improved recurrence-free survival versus placebo in completely resected high-risk stage III melanoma patients. We assessed the cost-effectiveness of adjuvant pembrolizumab in Colombia compared with watchful waiting, a widely used strategy despite the high risk of recurrence with surgery alone. METHODS: A four-health state [recurrence-free (RF), locoregional recurrence (LR), distant metastases (DM), and death) Markov model was developed to assess the lifetime medical costs and outcomes (3% annual discount), along with cost-effectiveness ratios (ICERs). The transitions from the RF and LR states were modeled using KEYNOTE-054 data, and those from the DM state were modeled using data from the KEYNOTE-006 trial and a network meta-analysis of advanced treatments received after adjuvant pembrolizumab and watchful waiting. The health state utilities were derived from KEYNOTE-054 Euro-QoL data and literature. Costs are expressed in 2021 Colombian pesos (COP). RESULTS: Over a 46-year time horizon, patients on adjuvant pembrolizumab and watchful waiting were estimated to gain 9.69 and 7.56 quality-adjusted life-years (QALYs), 10.83 and 8.65 life-years (LYs), and incur costs of COP 663,595,726 and COP 563,237,206, respectively. The proportion of LYs spent in RF state was 84.63% for pembrolizumab and 72.13% for watchful waiting, yielding lower subsequent treatment, disease management, and terminal care costs for pembrolizumab. Adjuvant pembrolizumab improved survival by 2.18 LYs and 2.13 QALYs versus watchful waiting. The ICER per QALY was COP 47,081,917, primarily driven by recurrence rates and advanced melanoma treatments. The deterministic sensitivity analysis results were robust and consistent across various reasonable inputs and alternative scenarios. At a willingness-to-pay threshold of COP 69,150,201 per QALY, the probability of pembrolizumab being cost-effective was 65.70%. CONCLUSION: Pembrolizumab is cost-effective as an adjuvant treatment compared to watchful waiting among patients with high-risk stage III melanoma after complete resection in Colombia.
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Melanoma , Qualidade de Vida , Humanos , Análise Custo-Benefício , Colômbia , Recidiva Local de Neoplasia/tratamento farmacológico , Melanoma/tratamento farmacológico , Melanoma/cirurgia , Anos de Vida Ajustados por Qualidade de Vida , Adjuvantes Imunológicos/uso terapêutico , Linfonodos/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma Maligno CutâneoRESUMO
This study aimed to investigate the effect of chemotherapy (CT) and its different types of regimens on the anthropometry and body composition of women with breast cancer. Three-hundred-and-four women with breast cancer were enrolled in this multicenter study. The participants were evaluated before the infusion of the first cycle of CT (pre-CT), and until two weeks after CT completion (post-CT), regarding body weight, body mass index (BMI); waist circumference (WC); waist-to-height ratio (WHtR); conicity index (C-index); fat mass index (FMI); and fat-free mass index (FFMI). CT regimens were classified as anthracycline-based (AC-doxorubicin or epirubicin); anthracyclines and taxane (ACT); cyclophosphamide, methotrexate, and 5-fluorouracil (CMF); or isolated taxanes (paclitaxel or docetaxel). Women significantly increased BMI and FMI post-CT (p < 0.001 and p = 0.007, respectively). The ACT regimen increased FMI (p < 0.001), while FFMI increased after AC (p = 0.007). It is concluded that the CT negatively impacted body composition and the type of regime had a strong influence. The ACT regimen promoted an increase in FMI compared to other regimens, and the AC increased FFMI. These findings reinforce the importance of nutritional monitoring of breast cancer patients throughout the entire CT treatment.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Brasil , Composição Corporal , Docetaxel/uso terapêutico , Ciclofosfamida/uso terapêutico , Fluoruracila/uso terapêutico , Índice de Massa Corporal , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Adequate adherence to the 2018 diet and exercise recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) can possibly result in less oxidative stress, lower risk to chemo- and radiotoxicity, lower risk of relapse, and increased quality of life in breast cancer survivors. This observational study aims to investigate the influence of adherence to updated recommendations of the WCRF/AICR on oxidative stress biomarkers in women with breast cancer undergoing adjuvant treatment (AT). We hypothesized that adherence to WCRF/AICR recommendations is inversely related to oxidative damage biomarkers and directly associated with antioxidant status. Women (n = 78) were evaluated before (T0) and after AT. After collecting anthropometric, physical activity, and food consumption data, a standardized score of adherence to WCRF/AICR recommendations was applied. The sample was divided into low-medium adherence and high adherence groups. Blood samples were collected at both timepoints for oxidative stress biomarkers analysis. Multiple linear regression analyzes were applied to verify associations between WCRF/AICR score and biomarkers. We found that low-medium adherence to WCRF/AICR recommendations at T0 affected lower levels of reduced glutathione (P= .003) and higher levels of lipid hydroperoxides (P= .002) and plasma carbonylated proteins (P= .001) after AT. The WCRF/AICR score at T0 was inversely associated with changes in plasma carbonylated protein concentrations after AT (adjusted ß = -0.359; P= .01). Our findings suggest that high WCRF/AICR score before and during AT may provide greater stability of antioxidant capacity and protection against exacerbated oxidative stress.
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Neoplasias da Mama , Humanos , Feminino , Estados Unidos , Neoplasias da Mama/prevenção & controle , Qualidade de Vida , Espécies Reativas de Oxigênio , Antioxidantes , Fatores de Risco , Dieta , Exercício FísicoRESUMO
Malaria is a disease that affects thousands of people around the world every year. Its pathogenesis is associated with the production of reactive oxygen and nitrogen species (RONS) and lower levels of micronutrients and antioxidants. Patients under drug treatment have high levels of oxidative stress biomarkers in the body tissues, which limits the use of these drugs. Therefore, several studies have suggested that RONS inhibition may represent an adjuvant therapeutic strategy in the treatment of these patients by increasing the antioxidant capacity of the host. In this sense, supplementation with antioxidant compounds such as zinc, selenium, and vitamins A, C, and E has been suggested as part of the treatment. Among dietary antioxidants, lycopene is the most powerful antioxidant among the main carotenoids. This review aimed to describe the main mechanisms inducing oxidative stress during malaria, highlighting the production of RONS as a defense mechanism against the infection induced by the ischemia-reperfusion syndrome, the metabolism of the parasite, and the metabolism of antimalarial drugs. Furthermore, the effects of lycopene on several diseases in which oxidative stress is implicated as a cause are outlined, providing information about its mechanism of action, and providing an evidence-based justification for its supplementation in malaria.