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1.
Environ Monit Assess ; 196(5): 421, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38570395

RESUMO

This study aimed to estimate the carcinogenic and non-carcinogenic risk as well as the attributable cases due to exposure to organochlorine pesticides (OCPs): hexachlorobenzene (HCB), dichlorophenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), heptachlor, and chlordane. From serum concentrations of pesticides of interest in a sample of 908 women from Northern Mexico, the risk for both cancer and non-cancer health effects was evaluated. The population attributable fraction (PAF) was also calculated based on summary association estimates between exposure to OCPs and different health events. Findings revealed that due to their OCP exposure slightly less than half of the women in the sample were at increased risk of developing non-cancerous diseases. Moreover, approximately 25% and 75% of participants were at risk of develop some type of cancer associated with their HCB and DDE concentrations, respectively. In addition, it was estimated that 40.5% of type 2 diabetes, 18.7% of endometriosis, and 23.1% of non-Hodgkin's lymphoma cases could have been prevented if women had not been exposed to these OCPs. Results suggest that the use of OCPs may have contributed to the disease burden in the study area and, based on the time required for these substances to be eliminated from the body, there are probably some women who are still at elevated risk of developing diseases associated to OCPs.


Assuntos
Diabetes Mellitus Tipo 2 , Hidrocarbonetos Clorados , Neoplasias , Praguicidas , Humanos , Feminino , Hexaclorobenzeno/análise , Carcinógenos , México/epidemiologia , Monitoramento Ambiental , Praguicidas/análise , Hidrocarbonetos Clorados/análise , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia
2.
Front Endocrinol (Lausanne) ; 15: 1360139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505755

RESUMO

Background: Increased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are limited. Methods: A nationwide population-based cohort study in Sweden of patients treated with rhGH during childhood between 1985-2010, due to isolated growth hormone deficiency (GHD), small for gestational age (SGA) and idiopathic short stature (ISS). The comparison group consisted of 15 age-, sex-, and region-matched controls per patient, randomly selected from the general population. Data on neoplastic events and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height at study start, were collected through linkage with population-based registers. The cohort was followed for neoplastic events until the end of 2020. Results: 53,444 individuals (3,408 patients; 50,036 controls) were followed for up to 35 years, with a median follow-up of 19.8 years and a total of 1,050,977 person-years. Patients showed a moderately increased hazard ratio (HR) for neoplastic events overall compared to controls (HR 1.28, 95% CI: 1.12-1.46), but only significant for males (HR 1.39, 95% CI: 1.17-1.66) and not females (HR 1.15, 95% CI: 0.94-1.41). Longer treatment duration was associated with an increased HR, but no association was found between neoplastic events and mean or cumulative dose. No increased risk of malignant neoplasms was observed for the patients compared to matched controls (HR 0.91 95% CI: 0.66-1.26). Conclusion: No association was found between rhGH treatment during childhood for GHD, SGA, or ISS and malignant neoplastic events in early to mid-adulthood. A moderate increase in overall neoplastic events was observed due to an increased number of events in male patients.


Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Neoplasias , Humanos , Masculino , Adulto , Hormônio do Crescimento , Suécia/epidemiologia , Estudos de Coortes , Peso ao Nascer , Nanismo Hipofisário/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia
3.
Eur J Pharmacol ; 970: 176484, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38467235

RESUMO

Protein kinases play pivotal roles in various biological functions, influencing cell differentiation, promoting survival, and regulating the cell cycle. The disruption of protein kinase activity is intricately linked to pathways in tumor development. This manuscript explores the transformative impact of protein kinase inhibitors on cancer therapy, particularly their efficacy in cases driven by targeted mutations. Focusing on key tyrosine kinase inhibitors (TKIs) like Bcr-Abl, Epidermal Growth Factor Receptor (EGFR), and Vascular Endothelial Growth Factor Receptor (VEGFR), it targets critical kinase families in cancer progression. Clinical trial details of these TKIs offer insights into their therapeutic potentials. Learning from FDA-approved kinase inhibitors, the review dissects trends in kinase drug development since imatinib's paradigm-shifting approval in 2001. TKIs have evolved into pivotal drugs, extending beyond oncology. Ongoing clinical trials explore novel kinase targets, revealing the vast potential within the human kinome. The manuscript provides a detailed analysis of advancements until 2022, discussing the roles of specific oncogenic protein kinases in cancer development and carcinogenesis. Our exploration on PubMed for relevant and significant TKIs undergoing pre-FDA approval phase III clinical trials enriches the discussion with valuable findings. While kinase inhibitors exhibit lower toxicity than traditional chemotherapy in cancer treatment, challenges like resistance and side effects emphasize the necessity of understanding resistance mechanisms, prompting the development of novel inhibitors like osimertinib targeting specific mutant proteins. The review advocates thorough research on effective combination therapies, highlighting the future development of more selective RTKIs to optimize patient-specific cancer treatment and reduce adverse events.


Assuntos
Neoplasias Pulmonares , Neoplasias , Humanos , Fator A de Crescimento do Endotélio Vascular , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Quinases/metabolismo , Mutação , Neoplasias Pulmonares/tratamento farmacológico
4.
Arch Toxicol ; 98(5): 1241-1252, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38478087

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic persistent chemicals, which are used in many industrial and commercial applications. Hundreds of different PFAS have been identified in the environment and they are commonly found also in human blood. Due to the chemical stability and extensive use, PFAS pose a risk for human health and wildlife. Mounting evidence indicates that PFAS-exposure adversely affects many organs including liver, kidney, and reproductive tissues and induces tumors in laboratory rodents. Epidemiological studies show association between PFAS-exposure and some tumors also in humans. Effects of PFAS-exposure are complex and obviously do not depend only on the concentration and the structure of PFAS, but also on age and sex of the exposed individuals. It has been difficult to show a causal link between PFAS-exposure and tumors. Moreover, molecular mechanisms of the PFAS effects in different tissues are poorly understood. PFAS are not directly mutagenic and they do not induce formation of DNA binding metabolites, and thus are assumed to act more through non-genotoxic mechanisms. In this review, we discuss the involvement of PFAS-compounds in tumor development in tissues where PFAS exposure has been associated with cancer in epidemiological and animal studies (liver, kidney, testicle and breast). We will focus on molecular pathways and mechanisms related to tumor formation following PFAS-exposure.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Neoplasias , Animais , Humanos , Neoplasias/induzido quimicamente , Mutagênese , Rim , Fígado , Fluorocarbonos/toxicidade
5.
Circ Cardiovasc Qual Outcomes ; 17(3): e010279, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38440888

RESUMO

BACKGROUND: Transcatheter left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation, but the predictors of LAAO use in routine care are unclear. We aimed to assess the utilization trends of LAAO and compare the change in characteristics of LAAO users versus OACs since its marketing. METHODS: Using the US Medicare claims database (March 15, 2015, to December 31, 2020), we identified patients with atrial fibrillation, ≥65 years, and CHA2DS2-VASc score ≥2 (men) or ≥3 (women), with either first implantation of an LAAO device or initiation of OACs, including apixaban, dabigatran, rivaroxaban, edoxaban, or warfarin. Patient characteristics, measured 365 days before the first LAAO or OAC use date, were compared using logistic regression. RESULTS: There were 30 058 LAAO recipients (mean age, 77.74 years; female, 42.1%) and 792 600 OAC initiators (mean age, 78.48; female, 53.3%). In 2020, patients had higher odds of initiating LAAO use than in 2015 (0.52 versus 9.32%; adjusted odds ratio [aOR], 13.64 [95% CI, 12.56-14.81]). Old age (ie, >85 versus 65-75 years; aOR, 0.84 [95% CI, 0.80-0.88]), female sex (aOR, 0.74 [95% CI, 0.71-0.76]), Black race (aOR, 0.63 [95% CI, 0.58-0.68]) versus White race, and Medicaid eligibility (aOR, 0.61 [95% CI, 0.58-0.64]) were associated with lower odds of receiving LAAO. Among clinical characteristics, frailty, cancer, fractures, and venous thromboembolism were associated with lower odds of LAAO use, while history of intracranial and extracranial bleeding, coagulopathy, and falls were associated with higher odds of receiving LAAO. CONCLUSIONS: Among patients with atrial fibrillation receiving stroke-preventive therapy, LAAO use increased rapidly from 2015 to 2020 and was positively associated with the risk factors for OAC complications but negatively associated with old age, advanced frailty, and cancer. Black race and female sex were associated with a lower likelihood of receiving LAAO.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Fragilidade , Neoplasias , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Idoso , Estados Unidos/epidemiologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Medicare , Anticoagulantes/efeitos adversos , Neoplasias/induzido quimicamente , Resultado do Tratamento
6.
Pharmacol Res Perspect ; 12(2): e1182, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38429945

RESUMO

Cancer medicines often have narrow therapeutic windows; toxicity can be severe and sometimes fatal, but inadequate dose intensity reduces efficacy and survival. Determining the optimal dose for each patient is difficult, with body-surface area used most commonly for chemotherapy and flat dosing for tyrosine kinase inhibitors, despite accumulating evidence of a wide range of exposures in individual patients with many receiving a suboptimal dose with these strategies. Therapeutic drug monitoring (measuring the drug concentration in a biological fluid, usually plasma) (TDM) is an accepted and well validated method to guide dose adjustments for individual patients to improve this. However, implementing TDM in routine care has been difficult outside a research context. The development of genotyping of various proteins involved in drug elimination and activity has gained prominence, with several but not all Guideline groups recommending dose reductions for particular variant genotypes. However, there is increasing concern that dosing recommendations are based on limited data sets and may lead to unnecessary underdosing and increased cancer mortality. This Review discusses the evidence surrounding genotyping and TDM to guide decisions around best practice.


Assuntos
Fluoruracila , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/induzido quimicamente , Fenótipo , Genótipo
7.
Crit Rev Toxicol ; 54(3): 153-173, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38470145

RESUMO

The Ramazzini Institute (RI) has been conducting animal carcinogenicity studies for decades, many of which have been considered by authoritative bodies to determine potential carcinogenicity in humans. Unlike other laboratories, such as the U.S. National Toxicology Program (NTP), the RI does not provide a report or record of historical control data. Transparently documenting historical control data is critical in the interpretation of individual study results within the same laboratory. Historical control data allow an assessment of significant trends, either increasing or decreasing, resulting from changes in laboratory methods or genetic drift. In this investigation: (1) we compiled a dataset of the tumors reported in control groups of Sprague-Dawley rats and Swiss mice based on data included in published RI studies on specific substances, and (2) conducted case studies to compare data from this RI control dataset to the findings from multiple RI studies on sweeteners and corresponding breakdown products. We found considerable variability in the tumor incidence across multiple tumor types when comparing across control groups from RI studies. When compared to the tumor incidence in treated groups from multiple studies, the incidence of some tumors considered to be treatment-related fell within the variability of background incidence from the RI control dataset.


Assuntos
Neoplasias , Ratos , Camundongos , Humanos , Animais , Ratos Sprague-Dawley , Incidência , Testes de Carcinogenicidade , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia
8.
Int J Mol Sci ; 25(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38339129

RESUMO

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet is the main non-workplace Cd exposure source other than passive and active smoking. The intestinal absorption of Cd involves transporters for essential metals, notably iron and zinc. These transporters determine the Cd body burden because only a minuscule amount of Cd can be excreted each day. The International Agency for Research on Cancer listed Cd as a human lung carcinogen, but the current evidence suggests that the effects of Cd on cancer risk extend beyond the lung. A two-year bioassay demonstrated that Cd caused neoplasms in multiple tissues of mice. Also, several non-tumorigenic human cells transformed to malignant cells when they were exposed to a sublethal dose of Cd for a prolonged time. Cd does not directly damage DNA, but it influences gene expression through interactions with essential metals and various proteins. The present review highlights the epidemiological studies that connect an enhanced risk of various neoplastic diseases to chronic exposure to environmental Cd. Special emphasis is given to the impact of body iron stores on the absorption of Cd, and its implications for breast cancer prevention in highly susceptible groups of women. Resistance to cell death and other cancer phenotypes acquired during Cd-induced cancer cell transformation, under in vitro conditions, are briefly discussed. The potential role for the ZnT1 efflux transporter in the cellular acquisition of tolerance to Cd cytotoxicity is highlighted.


Assuntos
Cádmio , Neoplasias , Feminino , Humanos , Animais , Camundongos , Cádmio/toxicidade , Cádmio/metabolismo , Carcinogênese , Zinco , Transformação Celular Neoplásica , Ferro , Neoplasias/induzido quimicamente
9.
Int J Cancer ; 154(12): 2043-2053, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38345158

RESUMO

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.


Assuntos
Transplante de Rim , Neoplasias , Masculino , Feminino , Humanos , Adolescente , Tacrolimo/efeitos adversos , Estudos Retrospectivos , Prednisona/efeitos adversos , Transplante de Rim/efeitos adversos , Ácido Micofenólico/efeitos adversos , Rejeição de Enxerto/epidemiologia , Imunossupressores/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Inibidores Enzimáticos , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Transplantados
11.
BMC Public Health ; 24(1): 430, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341560

RESUMO

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011-2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.


Assuntos
Dietilexilftalato , Neoplasias , Ácidos Ftálicos , Humanos , Masculino , Feminino , Dietilexilftalato/toxicidade , Dietilexilftalato/análise , Inquéritos Nutricionais , Ácidos Ftálicos/toxicidade , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia
12.
PLoS One ; 19(2): e0297852, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38329982

RESUMO

BACKGROUND: Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not induce cancer, some randomized clinical trials (RCTs) found a pattern of increased cancer death under LLT. Our objective was to assess a possible shift from CV to cancer death in LLT trials (i.e. an increase in cancer and decrease in CV death) and to investigate potential subgroups at risk. METHODS: We performed a systematic review and meta-analysis. We retrieved RCTs from MEDLINE, Embase, and Cochrane Central until 08/2023. We extracted the number of CV and cancer deaths in the treatment vs. in the control arm, calculated the relative risk (RR) by dividing the risk of death in the treatment over the risk of death in the control group and then pooled them using random-effect meta-analysis. We performed subgroup analyses on primary and secondary prevention, and according to different age cut-offs. RESULTS: We included 27 trials with 188'259 participants (23 statin; 4 ezetimibe trials). The trials reported 4056 cancer deaths, 2061 under LLT and 1995 in control groups. Overall, there was no increased risk of cancer mortality (RR 1.03, 95% confidence interval 0.97-1.10), with no difference between primary and secondary prevention. In the subgroup analyses for RCTs with ≥15% of participants aged ≥75 years, the RR of cancer death was 1.11 (1.00-1.23), while the RR for CV death was 0.96 (0.91-1.01). For RCTs with a mean age ≥ 70 years, the RR for cancer death was 1.21 (0.99-1.47). CONCLUSION: LLT does not lead to a shift from CV to cancer death. However, there might be a possible shift with a pattern of increased cancer deaths in trials with more older adults, particularly ≥75 years. Individual participant data from LLT trials should be made public to allow further investigations. PROSPERO REGISTRATION: CRD42021271658.


Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias , Humanos , Idoso , Ezetimiba , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Lipídeos
13.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338912

RESUMO

Despite significant advancements in understanding the causes and progression of tumors, cancer remains one of the leading causes of death worldwide. In light of advances in cancer therapy, there has been a growing interest in drug repurposing, which involves exploring new uses for medications that are already approved for clinical use. One such medication is edaravone, which is currently used to manage patients with cerebral infarction and amyotrophic lateral sclerosis. Due to its antioxidant and anti-inflammatory properties, edaravone has also been investigated for its potential activities in treating cancer, notably as an anti-proliferative and cytoprotective drug against side effects induced by traditional cancer therapies. This comprehensive review aims to provide updates on the various applications of edaravone in cancer therapy. It explores its potential as a standalone antitumor drug, either used alone or in combination with other medications, as well as its role as an adjuvant to mitigate the side effects of conventional anticancer treatments.


Assuntos
Esclerose Amiotrófica Lateral , Neoplasias , Fármacos Neuroprotetores , Humanos , Edaravone/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Esclerose Amiotrófica Lateral/tratamento farmacológico , Antioxidantes/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Sequestradores de Radicais Livres/farmacologia
14.
Int J Mol Sci ; 25(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396649

RESUMO

The dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway can lead to uncontrolled cellular growth and tumorigenesis. Targeting PI3K and its downstream substrates has been shown to be effective in preclinical studies and phase III trials with the approval of several PI3K pathway inhibitors by the Food and Drug Administration (FDA) over the past decade. However, the limited clinical efficacy of these inhibitors, intolerable toxicities, and acquired resistances limit the clinical application of PI3K inhibitors. This review discusses the PI3K signaling pathway, alterations in the PI3K pathway causing carcinogenesis, current and novel PI3K pathway inhibitors, adverse effects, resistance mechanisms, challenging issues, and future directions of PI3K pathway inhibitors.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Carcinogênese/induzido quimicamente , Fosfatidilinositóis/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
15.
Biomolecules ; 14(2)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38397436

RESUMO

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this affects cardiovascular and tumor biomarkers; exploring the role of cardiovascular biomarkers in the risk stratification and in the identification of chemotherapy-induced cardiotoxicity; and providing a summary of the novel potential biomarkers in this clinical setting.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Cardiotoxicidade/etiologia , Cardiotoxicidade/diagnóstico , 60591 , Antineoplásicos/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Biomarcadores , Biomarcadores Tumorais
16.
Arthritis Res Ther ; 26(1): 48, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347556

RESUMO

BACKGROUND: Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk. METHODS: The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history. RESULTS: The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30-60 mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66). CONCLUSIONS: The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.


Assuntos
Lúpus Eritematoso Sistêmico , Neoplasias , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Inibidores de Calcineurina/efeitos adversos , Glucocorticoides/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Fatores de Risco , Sistema de Registros , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Índice de Gravidade de Doença
17.
Sci Total Environ ; 924: 171261, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38417520

RESUMO

The recent scientific focus on polycyclic aromatic hydrocarbons (PAHs) has stemmed from their recognized genotoxic, mutagenic, and carcinogenic properties. This systematic review seeks to evaluate the nexus between exposure to water sources contaminated with PAHs and the associated cancer risk among global populations, encompassing both children and adults. Web of Science (WoS), Cochrane Library, PubMed, ProQuest, Scopus, and Google Scholar, were searched following the PRISMA guidelines, until December 31, 2023. Quality assessment of the selected studies was performed using the Newcastle-Ottawa Scale. The increased lifetime cancer risk (ILCR) attributed to PAH exposure through ingestion and dermal absorption was thoroughly examined across diverse age groups. After extensive searching, screening, and eligibility, 30 articles were included in this review, which was conducted in different parts of the world, including Nigeria (n = 11), China (n = 7), India (n = 4), Iran (n = 3), South Africa (n = 2), Italy (n = 1), Colombia (n = 1), and Iraq (n = 1). Our analysis underscores Nigeria's alarming prevalence of PAH contamination in its rivers, groundwaters, and seawater. Remarkably, the highest cancer risk was identified among children and adults, notably in proximity to the Atlas Cove jetty (seawater) and various Nigerian rivers. This elevated risk is primarily attributed to the combined effects of ingestion and dermal absorption. Furthermore, our findings emphasize the prominent role of combustion-derived and pyrogenic sources of PAH in the examined aquatic ecosystems. This study unequivocally establishes that PAH-contaminated water sources significantly amplify the risk of cancer among both children and adults. The extent of risk variation is influenced by the specific water source, duration of exposure, and age group. Consequently, proactive identification of contaminated water sources and their pollution origins, coupled with targeted educational campaigns, holds promise for reducing the global burden of PAH-related cancer.


Assuntos
Neoplasias , Hidrocarbonetos Policíclicos Aromáticos , Criança , Adulto , Humanos , Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise , Água , Ecossistema , Medição de Risco , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , China
18.
Cancer Sci ; 115(3): 752-762, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38254257

RESUMO

Immune checkpoint inhibitor discovery represents a turning point in cancer treatment. However, the response rates of solid tumors remain ~10%-30%; consequently, prognostic and immune-related adverse event (irAE) predictors are being explored. The programmed cell death protein 1 (PD-1) receptor occupancy (RO) of PD-1 inhibitors depends on the number of peripheral blood lymphocytes and their PD-1 expression levels, suggesting that the RO may be related to efficacy and adverse events. As PD-1 inhibition affects each T-cell subset differently, the RO of each cell population must be characterized. However, relevant data have not been reported, and the prognostic relevance of this parameter is not known. In this study, we aimed to clarify the association between the nivolumab RO in each T-cell population and patient prognosis and reveal the development of irAEs in nivolumab-treated patients. Thirty-two patients were included in the study, and the mean follow-up period was 364 days. The nivolumab RO on effector regulatory T cells (eTregs) was significantly lower in the group that presented clinical benefits, and a significant negative association was observed between PD-1 occupancy on eTregs and all-cause mortality. The results suggest that the nivolumab RO on eTregs may be a prognostic factor in PD-1 inhibitor therapy, implying that the inhibition of PD-1/PD-ligand 1 (PD-L1) signaling on eTregs may attenuate antitumor effects.


Assuntos
Neoplasias , Nivolumabe , Humanos , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1 , Linfócitos T Reguladores/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Inibidores de Checkpoint Imunológico
20.
J Neurol Sci ; 457: 122862, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38185015

RESUMO

INTRODUCTION: Upper-limb symptoms are often reported in the context of chemotherapy-induced peripheral neurotoxicity (CIPN), but objective quantification of functional deficits is often lacking. We examined and compared a range of neurophysiological and functional assessments of the upper-limb in the assessment of CIPN severity. METHODS: Cross-sectional assessment of neurotoxic chemotherapy-treated patients was undertaken using patient-reported and clinically-graded CIPN measures. Upper-limb functional assessments comprised of assessing fine motor skills, sensory perception, and neurophysiological measures of the median nerve. Group comparisons between participants who reported absence or presence of upper-limb functional deficits were investigated. RESULTS: 60 participants who were 11.5 (IQR = 4.0-26.0) months post-neurotoxic chemotherapy treatment reported CIPN. 65% (n = 39) reported upper-limb CIPN symptoms. Reduction in fine motor skills, sensory perception and median nerve SNAP amplitudes were associated with higher CIPN severity. Participants who self-reported presence of upper-limb functional deficits had worse CIPN severity across all measures, compared to participants who reported no upper-limb functional deficits. CONCLUSIONS: Participants who reported upper-limb symptoms and functional deficits had worse CIPN severity and quality-of-life. There is a high burden of upper-limb dysfunction long after neurotoxic chemotherapy treatment cessation. Focus on research into supportive care and rehabilitation options to improve upper-limb function is warranted to improve patient quality-of-life.


Assuntos
Antineoplásicos , Sobreviventes de Câncer , Neoplasias , Síndromes Neurotóxicas , Doenças do Sistema Nervoso Periférico , Humanos , Antineoplásicos/efeitos adversos , Estudos Transversais , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/complicações , Qualidade de Vida , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente
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