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1.
J Med Virol ; 96(3): e29426, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38420851

RESUMO

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.


Assuntos
Infecções por Papillomavirus , Médicos , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Papillomavirus Humano , Detecção Precoce de Câncer/métodos , Papillomaviridae/genética , Manejo de Espécimes/métodos , Esfregaço Vaginal/métodos , Sensibilidade e Especificidade
2.
Ecotoxicol Environ Saf ; 281: 116625, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38908056

RESUMO

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35-775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060-20.096], p = 0.042; 3.053 [1.075-8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m2 (95 % CI, -8.127--0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2'-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.


Assuntos
Retardadores de Chama , Organofosfatos , Insuficiência Renal Crônica , Humanos , Retardadores de Chama/toxicidade , Estudos Longitudinais , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/urina , Masculino , Feminino , Pessoa de Meia-Idade , Organofosfatos/toxicidade , Organofosfatos/urina , Idoso , Adulto , Rim/efeitos dos fármacos , Exposição Ambiental/estatística & dados numéricos , Compostos Organofosforados/urina , Compostos Organofosforados/toxicidade , Monitoramento Ambiental , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urina
3.
Int J Mol Sci ; 25(14)2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39063185

RESUMO

Ovarian clear cell carcinoma (OCCC) is often considered a relatively platinum-resistant malignancy. The aim of this study was to explore the influence of progesterone receptor (PR) expression levels on platinum sensitivity and survival outcomes in people with OCCC. A retrospective analysis was conducted with 80 people with OCCC who underwent surgery followed by adjuvant chemotherapy. PR expression was assessed via immunohistochemical (IHC) staining and quantified using the H score. The platinum sensitivity and survival outcomes of patients with weak and strong PR expression were compared. Additionally, cisplatin viability and migration experiments were conducted with OCCC cell lines (ES-2 and TOV-21G) with varying PR isoform expressions. Among the 80 patients, 62 were classified as having platinum-sensitive disease, while 18 had platinum-resistant disease. The mean total PR H- score of platinum-sensitive tumors was significantly higher than that of platinum-resistant tumors (p = 0.002). Although no significant differences in progression-free and overall survival were observed between patients with high and low PR expression, those with high PR expression tended to have longer survival. While PR protein was only weakly detectable in ES-2 and TOV-21G cells, a transfection of the PR-A or PR-B gene resulted in a strong expression of PR-A or PR-B, which led to significantly reduced proliferation and migration in ES-2 and TOV-21G cells. Furthermore, overexpression of PR-A or PR-B enhanced cisplatin cytotoxicity in these cell lines. In conclusion, strong PR expression was associated with improved platinum sensitivity and survival outcomes, consistent with our experimental findings. The potential of PR as a tumor sensitizer to cisplatin in OCCC warrants further investigation.


Assuntos
Adenocarcinoma de Células Claras , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas , Receptores de Progesterona , Humanos , Feminino , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Pessoa de Meia-Idade , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/genética , Resistencia a Medicamentos Antineoplásicos/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Linhagem Celular Tumoral , Idoso , Adulto , Estudos Retrospectivos , Movimento Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Platina/farmacologia , Platina/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
4.
Taiwan J Obstet Gynecol ; 63(4): 471-478, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39004472

RESUMO

Platinum-resistant ovarian cancer (PROC) refers to disease progression within 6 months after the completion of platinum-based chemotherapy. Historically, treatment options for PROC were limited with a poor prognosis and non-platinum single agent plus bevacizumab has been the mainstay of treatment. Fortunately, there have been notable advancements in recent years, leading to an advance in treatment paradigms for this challenging disease. Various combinations of chemotherapy, targeted agents such as poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapy are being explored for an improved treatment outcome. Antibody-drug conjugates targeting folate receptor alpha, which deliver a cytotoxic payload directly to cancer cells, have emerged as a promising therapeutic approach for PROC. WEE1 inhibitors, such as adavosertib, function by inhibiting the WEE1 kinase activity, leading to premature entry of a cell into mitosis phase and thus increased DNA damage. It has been observed that cancer cells with TP53 mutations may be more sensitive to WEE1 inhibitors. Biomarker testing such as analysis of the expression level of folate receptor alpha or mutation in TP53 may be applicable for identifying patients who are more likely to respond to the specific therapy, enabling a more personalized treatment approach. This overview summarizes key clinical findings on the efficacy and safety of theses novel biomarker-driven therapeutic approaches.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Receptor 1 de Folato/antagonistas & inibidores , Proteínas de Ciclo Celular/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia/métodos , Imunoconjugados/uso terapêutico , Pirazóis/uso terapêutico , Proteína Supressora de Tumor p53 , Pirimidinonas/uso terapêutico
5.
Taiwan J Obstet Gynecol ; 63(1): 29-36, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38216265

RESUMO

Probiotics, live microorganisms that confer health benefits to the host when administered in adequate amounts, have gained considerable attention for their potential role in maintaining women's health. This overview summarizes key clinical findings on the beneficial effects of probiotics in various aspects of women's health. Probiotics, particularly Lactobacillus species, contribute to vaginal health by promoting a balanced vaginal microbiome to prevent infections and maintain an acidic environment. In gynecologic conditions, probiotics show potential in preventing and managing bacterial vaginosis, vulvovaginal candidiasis, and sexually transmitted infections. Probiotic supplementation has also been associated with improvements in metabolic parameters and menstrual irregularities in polycystic ovary syndrome patients. During pregnancy, probiotics may be helpful in reducing the risk of gestational diabetes, maternal group B streptococcal colonization, obstetric anemia, and postpartum mastitis. In recent years, the potential role of probiotics in the prevention and management of gynecologic cancer has gained attention. Further research is needed to better understand the specific mechanisms and determine the optimal Lactobacillus strains and dosages regimens for gynecologic cancer prevention and therapy. In conclusion, probiotics offer a non-invasive and cost-effective approach to support women's health and prevent obstetric and gynecologic complications.


Assuntos
Síndrome do Ovário Policístico , Probióticos , Vaginose Bacteriana , Gravidez , Feminino , Humanos , Saúde da Mulher , Vagina/microbiologia , Vaginose Bacteriana/prevenção & controle , Probióticos/uso terapêutico , Lactobacillus
6.
Int J Gynaecol Obstet ; 165(3): 1244-1256, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38287783

RESUMO

OBJECTIVE: Traditionally, the prognosis of patients with FIGO stage I endometrial cancer is determined by clinicopathological risk factors. In this study, we assessed the potential contribution of pretreatment carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) levels to estimating the prognosis of these patients and aimed to develop and validate a prognostic nomogram. METHODS: This retrospective study included patients with FIGO stage I endometrial cancer who underwent treatment between January 2009 and December 2021 in the four institutes of Chang Gung Memorial Hospital. To identify optimal cutoff values of CEA and CA-125 for predicting survival, receiver operating characteristic (ROC) curves were generated, the Kaplan-Meier method was used to estimate survival, and a Cox regression model was used to analyze the independent prognostic factors. Finally, a nomogram and calibration curve were constructed to predict patient survival probability. RESULTS: Of the 1559 patients evaluated, the optimal cutoff values of CEA and CA-125 were 1.44 ng/mL (area under the ROC curve [AUC] 0.601) and 39.77 U/mL (AUC 0.503), respectively. Multivariate Cox regression analysis showed that pretreatment CEA (hazard ratio [HR] 2.11, 95% confidence interval [95% CI] 1.35-3.28), CA-125 (HR 2.07, 95% CI 1.31-3.27), age >70 years (HR 12.54, 95% CI 5.05-31.11), myometrial invasion >50% (HR 1.69, 95% CI 1.03-2.73), non-endometrioid histology (HR 1.83, 95% CI 1.14-2.95), high-grade tumor (HR 2.41, 95% CI 1.46-3.97), and lymphovascular space invasion (HR 2.32, 95% CI 1.26-4.25) were significant variables associated with overall survival. These factors were used to construct the nomogram model, which showed good concordance and accuracy. CONCLUSIONS: Integration of pretreatment CEA and CA-125 in a prognostic nomogram is feasible. Our prediction model has the potential to assist clinicians in guiding appropriate clinical practice.


Assuntos
Biomarcadores Tumorais , Antígeno Ca-125 , Antígeno Carcinoembrionário , Neoplasias do Endométrio , Estadiamento de Neoplasias , Nomogramas , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/sangue , Pessoa de Meia-Idade , Antígeno Ca-125/sangue , Estudos Retrospectivos , Antígeno Carcinoembrionário/sangue , Idoso , Prognóstico , Biomarcadores Tumorais/sangue , Adulto , Curva ROC , Modelos de Riscos Proporcionais , Estimativa de Kaplan-Meier , Idoso de 80 Anos ou mais
7.
J Cancer ; 15(5): 1213-1224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356716

RESUMO

Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer. Although studies have reported that downregulation of HOXD10 expression may contribute to the migration and invasion abilities in EOC, much about its regulation remains to be fully elucidated. The present study aimed to identify different gene expression profiles associated with HOXD10 overexpression in EOC cells. The present study confirmed that HOXD10 overexpression effectively inhibited the proliferation and motility of the TOV21G and TOV112D cells. Further, we overexpress HOXD10 in TOV112D cells, the different gene expression (DEGs) profiles induce by HOXD10 was analyze by the Human OneArray microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), ingenuity pathway analysis (IPA) was used to perform the pathway enrichment analysis for the DEGs. Integrated bioinformatics analysis showed that the DEGs were enriched for terms related to oxidative phosphorylation and mitochondrial function pathways. Dysfunction oxidative phosphorylation metabolic pathway occurs frequently in many tumors. We validated the expression of NDUFA7, UQCRB and CCL2 using qPCR, involving in metabolism-related pathway, were significantly changed by HOXD10 overexpression in EOC. The detailed regulatory mechanism that links HOXD10 and the oxidative phosphorylation genes is not yet fully understood, our findings provide novel insight into HOXD10-mediated pathways and their effects on cancer metabolism, carcinogenesis, and the progression of EOC. Thus, the data suggest that strategies to interfere with metabolism-related pathways associated with cancer drug resistance could be considered for the treatment of ovarian tumors.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38801238

RESUMO

OBJECTIVE: To investigate the associations between time interval from myomectomy to pregnancy (TIMP) and subsequent pregnancy and obstetric complications, and to explore whether these associations vary according to maternal age at birth. METHODS: A retrospective population-based cohort study was conducted from 2008 to 2017. Data were extracted from the National Health Insurance Research Database and the Taiwan Maternal and Child Health Database, comprising 2024 379 births from 1 391 856 pregnancies. Eligible cases were identified using diagnostic and procedure codes; 4006 first singleton births in 4006 women after their first laparotomic myomectomy were identified. We estimated the risks of pregnancy and obstetric outcomes according to TIMP (<6, 6-11, and ≥12 months). Subgroup analysis was performed by further dividing according to maternal age at birth (18-34 vs ≥35 years old). RESULTS: We observed higher risks of gestational hypertensive disorders (adjusted odds ratio [aOR] 1.97, 95% confidence interval [CI] 1.22-3.18, P = 0.005) and neonatal death (aOR 4.59, 95% CI 1.49-14.18, P = 0.008) for TIMP of <6 months versus TIMP of 6-11 months. Likewise, a TIMP ≥12 months was associated with increased risks of gestational hypertensive disorders (aOR 1.72, 95% CI 1.14-2.58, P = 0.010), and neonatal death (aOR 3.27, 95% CI 1.16-9.24, P = 0.025) versus a TIMP of 6-11 months. In subgroup analysis, women over 35 years old still had higher risks of gestational hypertensive disorders when TIMP was <6 months (aOR 2.26, 95% CI 1.17-4.37, P = 0.015) or ≥12 months (aOR 2.04, 95% CI 1.17-3.54, P = 0.012), and a higher risk of neonatal death when TIMP was <6 months (aOR 4.05, 95% CI 1.06-15.53, P = 0.041); whereas women aged 18-34 years old did not. CONCLUSIONS: This study suggests that a TIMP between 6 and 11 months is associated with lower risks of gestational hypertensive disorders and neonatal death compared with a TIMP <6 months or ≥12 months, especially for women over 35 years old.

9.
Thorac Cancer ; 15(24): 1805-1814, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39045786

RESUMO

BACKGROUND: Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. METHODS: The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. RESULTS: The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2-butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2-butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild-type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression. CONCLUSIONS: OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population.


Assuntos
Receptores ErbB , Retardadores de Chama , Neoplasias Pulmonares , Organofosfatos , Humanos , Masculino , Feminino , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Pessoa de Meia-Idade , Idoso , Exposição Ambiental/efeitos adversos , Mutação , Adulto
10.
Cancer Manag Res ; 16: 989-1001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39108298

RESUMO

Background: The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined. Results: The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3-T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥3 µg/L and clinical stage IVB were independent prognostic factors for worse OS. Conclusion: The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.

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