RESUMO
This study assessed the efficacy of ThinPrep cytologic test and human papillomavirus (HPV) co-test in cervical cancer screening during pregnancy. A cohort of 8,712 pregnant women from Ren Ji Hospital participated in the study. Among them, 601 (6.90%) tested positive for high-risk HPV (HR-HPV) and 38 (0.44%) exhibited abnormal cytology results (ASCUS+). Following positive HR-HPV findings, 423 patients underwent colposcopy, and 114 individuals suspected of having high-grade squamous intraepithelial lesion and cervical cancer (HSIL+) underwent cervical biopsy. Histological examination revealed 60 cases of normal pathology (52.63%), 35 cases of low-grade squamous intraepithelial lesion (30.70%), 17 cases of HSIL (14.91%), and 2 cases of cervical cancer (1.75%). The incidence of HSIL+ in HPV 16/18 group was significantly higher than that in non-HPV16/18 group (10.53% vs. 6.14%, P < 0.05). Subsequent evaluation of the clinical performance of cytology alone, primary HPV screening, and co-testing for HSIL+ detection revealed that the HSIL+ detection rate was lowest with cytology alone. These findings suggest that HPV testing, either alone or combined with cytology, presents an efficient screening strategy for pregnant women, underscoring the potential for improved sensitivity in cervical cancer screening during pregnancy. The significantly higher incidence of HSIL+ in the HPV16/18 group emphasizes the importance of genotype-specific considerations.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Gravidez , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Papillomavirus Humano 16/genética , Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Papillomavirus Humano 18/genética , Papillomaviridae/genética , DNARESUMO
OBJECTIVE: Our study aimed to investigate the relationship between vascular endothelial growth factor (VEGF), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory complex, erythropoietin (EPO) levels, and ocular hemodynamics in patients diagnosed with primary open-angle glaucoma (POAG). METHODS: This is a prospective observational study. Patients diagnosed with POAG at The Sixth Hospital of Wuhan hospital between November 2022 and February 2023were enrolled.The patients were categorized into three groups based on the average visual field defect (mean deviation, MD) value: severe injury group (MD > 12 dB, 93 cases), moderate injury group (7 ≤ MD ≤ 12 dB, 89 cases), and mild injury group (MD < 7 dB, 85 cases). The levels of VEGF, NLRP3 inflammatory complex, EPO, and ocular hemodynamics were compared among the groups. Furthermore, the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG was analyzed using Pearson correlation analysis. After adjusting for confounding factors such as age and gender, multivariate Logistic regression analysis was performed with the ocular hemodynamics indexes being used as dependent variables, and VEGF, NLRP3, ASC, Caspase-1, and EPO being used as independent variables. RESULTS: A total of267 patients with POAG were enrolled. There were no significant differences in sex, age, body mass index, systolic blood pressure, diastolic blood pressure, smoking, alcohol consumption, and blood glucose between the two groups (P > 0.05). The levels of NLRP3, ASC, Caspase-1, and EPO in the severe and moderate injury groups were higher than those in the mild injury group, whereas the VEGF levels were lower in the severe and moderate groups compared to the mild group, showing significant differences (P < 0.05). The severe group exhibited higher levels of NLRP3, ASC, Caspase-1, and EPO than the moderate group, while the VEGF levels were lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). The peak systolic velocity(PSV) and resistance index (RI) were higher in the severe and moderate groups than in the mild group, whereas the EDV was significantly lower in the severe and moderate groups compared to the mild group (P < 0.05). The severe group exhibited higher PSV and RI values compared to the moderate group, while the EDV was lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). Pearson correlation analysis was performed to examine the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG. VEGF, NLRP3, ASC, Caspase-1, and EPO showed positive correlations with PSV and RI, and negative correlations with EDV in patients with POAG. Regression analysis showed that VEGF, NLRP3, ASC, Caspase-1 and EPO were significantly correlated with ocular hemodynamics in POAG (all P < 0.001). CONCLUSION: We demonstrated that the levels of VEGF, NLRP3 inflammatory complex, and EPO were highly associated with ocular hemodynamics in patients diagnosed with POAG.
Assuntos
Eritropoetina , Glaucoma de Ângulo Aberto , Hemodinâmica , Pressão Intraocular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fator A de Crescimento do Endotélio Vascular , Humanos , Masculino , Feminino , Eritropoetina/sangue , Eritropoetina/metabolismo , Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Ângulo Aberto/sangue , Glaucoma de Ângulo Aberto/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Hemodinâmica/fisiologia , Pressão Intraocular/fisiologia , Idoso , Campos Visuais/fisiologia , Biomarcadores/sangueRESUMO
OBJECTIVE: The purpose of this study was to identify the clinical characteristics of patients with high-grade squamous intraepithelial lesions (HSIL) with abnormal endocervical curettage (ECC) and to evaluate the efficacy of abnormal preoperative ECC in predicting recurrence after a loop electrosurgical excision procedure (LEEP). METHODS: We retrospectively analyzed a total of 210 cases of histological HSIL in female patients diagnosed using cervical biopsy and/or indiscriminating ECC, and these included 137 cases with normal ECC and 63 cases with abnormal ECC. We also collected preoperative information and data on postoperative human papillomavirus (HPV) and histological outcomes within 2 years. RESULTS: The additional detection rate of HSIL using indiscriminating ECC was 5%. Patients with abnormal ECC were older (P < 0.001), predominantly menopausal (P = 0.001), had high-grade cytology (P = 0.032), a type 3 transformation zone (P = 0.046), and a higher proportion of HPV type 16/18 infection (P = 0.023). Moreover, age (odds ratio [OR] = 1.078, 95% confidence interval [CI] = 1.0325-1.1333, P = 0.003) and HPV 16/18 infection (OR = 2.082, 95% CI = 1.042-4.2163, P = 0.038) were independent risk factors for abnormal ECC. With an observed residual lesion/recurrence rate of 9.5% over the 24-month follow-up, we noted a 9.3% higher rate in the abnormal ECC group when compared with the normal ECC group. Abnormal preoperative ECC (OR = 4.06, 95% CI = 1.09-15.14, P = 0.037) and positive HPV at the 12-month follow-up (OR = 16.55, 95% CI = 3.54-77.37, P = 0.000) were independent risk factors for residual disease/recurrence. CONCLUSION: Preoperative ECC was one of the risk factors for post-LEEP residual/recurrent HSIL, and detecting abnormal ECC when managing older patients or patients with HPV 16/18 infection during colposcopy is critical.
Assuntos
Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Eletrocirurgia/métodos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Papillomavirus Humano 16 , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Papillomavirus Humano 18 , Curetagem , Lesões Intraepiteliais Escamosas/cirurgia , Papillomavirus Humano , PapillomaviridaeRESUMO
Data regarding human papillomavirus (HPV) prevalence, its associated risk factors, and women's knowledge about this disease before the HPV vaccine was approved are limited in Shanghai, China. Therefore, we investigated these questions among females in Shanghai and aimed to provide comprehensive data to guide HPV vaccination and present the biopsychosocial risk factors that impact high-risk HPV infection, and evaluate the level of knowledge and awareness of this disease among women aged 21-65 years old. A total of 6619 (aged from 21 to 65) women from different communities volunteered to participate in the HPV screening and complete questionnaires from December 2016 to December 2017 in the Department of Obstetrics and Gynecology of nine hospitals in Shanghai. Data were analyzed using sample logistic regression to assess biopsychosocial risk factors that impact high-risk HPV infection and knowledge of HPV infection. A total of 632 (9.5%) cases were positive for high-risk HPV test, 22.6% of them were HPV 16/18 infection, 77.4% of them were non HPV 16/18 infection. 40 potential risk factors may be related to high-risk HPV infection, and there were 19 factors' p value < 0.1 from single factor logistic analysis. Finally, multivariable regression revealed education level, type of vaginitis, history of hyperlipidemias, family history of cancer, number of pregnancies, number of sex partners were independent risk factors for high-risk HPV infection (p < 0.05). When stratified by education level, women who finished graduate school had significantly greater knowledge of cervical cancer, cervical screening, and the relationship between HPV and cervical cancer than other groups (p < 0.05). The prevalence rate of high-risk HPV was a little lower than other regions in China and other countries, which may be related to regions, races, living habits, and economy. A less reported finding is that the history of vaginitis and the history of hyperlipidemias in our study were related to HPV infection. The majority of the participants had poor knowledge regarding cervical cancer, cervical screening, and the relationship between HPV and cervical cancer. Hence, these results should be served as a wake-up call for the government to increase knowledge and awareness via the media and doctors.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Papillomavirus Humano 16/fisiologia , Papillomavirus Humano 18/fisiologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
Database screening indicated that microRNAs (miRNAs) are involved in pathogenesis of endometrial cancer. Among these miRNAs, miR-449a might be involved in tumorigenesis and lower expression of miR-449a was associated with poor prognosis. However, the role of miR-449a and its underlying molecular mechanism in endometrial cancer (EC) has not been investigated. In this study, our analysis found that miR-449a expression is inversely correlated with the stage of EC. Downregulation of miR-449a was correlated with tumor progression and poor prognosis in the EC patients. Results of functional analyses revealed that overexpression of miR-449a in human EC cells alleviated cell proliferation, invasion and metastasis. Conversely, loss of miR-449a in EC cancer cells facilitated all these cellular activities. Moreover, we identified N-myc downstream-regulated gene 1 (NDRG1) as a direct and functional target gene of miR-449a in EC cells, and the expression of NDRG1 in 87â¯EC specimens were inversely correlated with that of miR-449a. Additionally, further studies show that the down-regulation of NDRG1 expression inhibited proliferation and metastasis of EC cells through the PTEN/AKT pathway. Therefore, these results suggest that miR-449a suppresses the growth and metastasis of EC by directly targeting the NDRG1 gene and that the activation of miR-449a may represent an effective therapeutic strategy in EC.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias do Endométrio/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Sequência de Bases , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Fenótipo , PrognósticoRESUMO
BACKGROUND: In this study, the association between high-risk human papillomavirus (hrHPV) infection and the vaginal microbiome in pregnant women was evaluated in Chinese cohorts. METHODS: The vaginal bacterial composition of four groups, 38 hrHPV-infected pregnant women (PHR, n = 38), pregnant women without HPV infection (PN, n = 48), nonpregnant women with hrHPV infection (NPHR, n = 19) and nonpregnant women without HPV infection (NPN, n = 30), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS: The results revealed that both pregnancy and HPV infection can increase vaginal bacterial microbial richness and diversity, with the bacterial composition being most influenced by pregnancy. Lactobacillus was the most dominant genus among all samples. NPN samples were dominated by CST (community state type) III, mainly composed of Lactobacillus iners. Both pregnancy and hrHPV infection were accompanied by an increased proportion of CST I (dominated by Lactobacillus crispatus), as opposed to CST III. Bifidobacterium, Bacillus, Megasphaera, Sneathia, Prevotella, Gardnerella, Fastidiosipila and Dialister were found to be biomarkers for hrHPV-infected women, though different genera (Bifidobacterium, Megasphaera, Bacillus, Acidovorax, Oceanobacillus and Lactococcus) were associated with hrHPV-infected pregnant women. CONCLUSIONS: This work uncovered a probable synergistic effect of hrHPV infection and pregnancy on the vaginal microbial composition. HPV infection in pregnant women was associated with a more complex and diverse microbial environment.
Assuntos
Microbiota , Infecções por Papillomavirus/microbiologia , Vagina/microbiologia , Vagina/virologia , Adulto , Povo Asiático , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Microbiota/genética , Infecções por Papillomavirus/virologia , Gravidez , RNA Ribossômico 16S/genéticaRESUMO
OBJECTIVE: To retrospectively analyse the incidence of high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinoma (SCC) in women of different ages with high-risk (HR) human papillomavirus (HPV) but with normal cytology test results stratified by age and HPV genotype. METHODS: In total, 1858 women with HR-HPV infection but with a normal smear who received a colposcopy and biopsy between 2015 and 2016 at our institution were included. The pathological results were retrospectively analysed after stratifying by age and HPV genotype. RESULTS: Among the 1858 cases, the HSIL% in women aged 21-29 years (10.54%) was significantly different from that in women aged 40-49 years (19.85%; P < 0.05), whereas there was no significant difference in the HSIL% among women aged 21-29 years and those in the other age groups (P > 0.05). In total, 295 cases had single HPV16 infection. The HSIL% in patients with HPV16/18 infection was >15%, and the 40-49-year age group had the highest percentage at 48.48%. For other HR-HPV infections, the HSIL and SCC incidence rate was 10.41%, and there was no significant difference among the age groups; thus, women with other types of viral infections, regardless of age, should be referred to colposcopy. CONCLUSIONS: Although HPV16 is the HPV with the highest risk, other HR-HPV infections can also cause a high percentage of HSILs and SCC in women with normal cytology. Therefore, it is necessary to refer HR-HPV-infected women aged ≥21 years for colposcopy in a timely manner to exclude potential cervical intraepithelial neoplasia and cervical cancer.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Citodiagnóstico , Infecções por Papillomavirus/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Adulto , Idoso , Células Escamosas Atípicas do Colo do Útero/patologia , Células Escamosas Atípicas do Colo do Útero/virologia , Biópsia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Colposcopia , Detecção Precoce de Câncer , Feminino , Papillomavirus Humano 16/patogenicidade , Papillomavirus Humano 18/patogenicidade , Humanos , Pessoa de Meia-Idade , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Esfregaço Vaginal/métodos , Adulto Jovem , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: Vaginal intraepithelial neoplasia (VaIN) is a group of diseases of squamous epithelial dysplasia and carcinoma in situ occurring in the vagina, which is associated with high-risk human papillomavirus (HR-HPV) infection. OBJECTIVES: To evaluate the efficacy and safety of Carbon dioxide (CO2) laser, 5-aminolevulinic acid photodynamic therapy (PDT) and PDT combined with CO2 laser pretreatment for VaIN1 with HR-HPV infection, and analyze the factors affecting the clearance of HR-HPV. METHODS: Patients with HR-HPV infection and pathological diagnosis of VaIN1 and received laser or PDT or PDT combined with laser pretreatment were recruited. A total of 45 patients received one to three times CO2 laser (laser Group), 15 patients received three times PDT (PDT Group) and 15 patients received CO2 laser once and PDT three times (laser + PDT Group). HPV testing, cytology and colposcopy examinations at 3-6 months and 9-12 months after treatment were analyzed to assess the outcomes of the treatment. RESULTS: There was no significant difference in regression rate of VaIN1 among the laser Group, the PDT Group and the laser + PDT Group (3-6 month follow-up: 57.78% vs 73.3% vs 80 %, 9-12 month follow-up: 68.89% vs 80% vs 86.67 %, P>0.05). HR-HPV remission rates were also similar in the three groups (3-6 month follow-up: 26.67% vs 46.67% vs 46.67 %, 9-12 month follow-up: 40 % in all groups, P>0.05). Compared to HR-HPV negative group, patients in the HR-HPV positive group were older and had more pregnancies. Menopause and multiple vaginal lesions were more common in the HR-HPV positive group. Adverse reactions were mild in the PDT Group. The laser Group and the laser + PDT Group had more adverse effects, such as increased vaginal secretion, vaginal bleeding, scarring and local pain. CONCLUSION: For patients with VaIN1 at risk of progression, ALA-PDT presents itself as a viable choice for those who are well-informed and can consent to its costs and benefits. The addition of CO2 laser pretreatment may not increase the benefit of ALA-PDT treatment of VaIN1. Older age, menopause, more times of pregnancies, and multiple vaginal lesions might affect HR-HPV regression.
Assuntos
Ácido Aminolevulínico , Lasers de Gás , Infecções por Papillomavirus , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Feminino , Fotoquimioterapia/métodos , Lasers de Gás/uso terapêutico , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/complicações , Ácido Aminolevulínico/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Pessoa de Meia-Idade , Adulto , Neoplasias Vaginais/tratamento farmacológico , Lesões Intraepiteliais Escamosas , Terapia CombinadaRESUMO
BACKGROUND: Patients after hysterectomy are at higher risk for developing VaIN. However, there are no standard treatments for HPV infection and VaIN after hysterectomy and relative studies are limited. Thus we aim to evaluate the feasibility of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) for the treatment of persistent vaginal infection with high-risk HPV (HR-HPV) in post-hysterectomy patients. METHODS: Thirty-eight patients aged 43-70 years old with persistent vaginal stump HR-HPV infection with or without histological vaginal intraepithelial neoplasia (VaIN1) during follow-up after hysterectomy were recruited. Twenty patients received three times of ALA-PDT (PDT Group). Eighteen patients did not receive any treatments (Control Group). HPV testing, cytology, and colposcopy were performed in all patients 4-6 months and 12 months after treatment. RESULTS: HR-HPV remission rates of the PDT Group were 40% (8/20) and 66.67% (12/18) at the 4-6 month and 12-month follow-up, respectively, both were significantly higher than that of the Control Group (11.11% (2/18) and 6.23% (1/16), respectively; P < 0.05). For the PDT Group, the regression rate of VaIN1 was 100% (7/7) at 4-6 months, while VaIN1 recurred in two cases (28.6%) at the 12-month due to persistent HR-HPV infection. No persistence or progression of VaIN1 was noted. For the Control group, the spontaneous regression rate of VaIN1 was 50% (3/6) at 4-6 months and one patient progressed into VaIN2. At the 12-month follow-up point, one patient reccurred and the disease regression, persistence and recurrence rates were 40% (2/5), 40% (2/5) and 20% (1/5), respectively. Adverse reactions were mild after PDT treatment. CONCLUSION: 5-ALA-PDT is a safe, non-invasive, and effective option for post-hysterectomy patients who have persistent HR-HPV infection.
Assuntos
Infecções por Papillomavirus , Fotoquimioterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Ácido Aminolevulínico/uso terapêutico , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/patologia , Estudos de Viabilidade , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Histerectomia/efeitos adversos , Neoplasias do Colo do Útero/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Cervical cancer the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020 for high rates of recurrence and metastasis. Identification of novel targets could aid in the prediction and treatment of cervical cancer. NADPH oxidase 1 (NOX1) gene-mediated production of reactive oxygen species (ROS) could induce migration and invasion of cervical cancer cells. Tumor-associated macrophages (TAMs) play important roles in cervical cancer. Tumor cell-derived exosomes mediate signal transduction between the tumor and tumor microenvironment. Elucidation of the mechanisms of NOX1-carrying exosomes involved in the regulation of TAMs may provide valuable insights into the progression of cervical cancer. METHODS: Uniformly standardized mRNA data of pan-carcinoma from the UCSC database were downloaded. Expression of NOX1 in tumor and adjacent normal tissues for each tumor type was calculated using R language software and significant differences were analyzed. SNP data set were downloaded for all TCGA samples processed using MuTect2 software from GDC. Cell experiment and animal tumor formation experiment were used to evaluate whether exosomal NOX1 stimulating ROS production to promote M2 polarization of TAM in cervical cancer. RESULTS: NOX1 is highly expressed with a low mutational frequency in pan-carcinoma. Upregulation of NOX1 may be associated with infiltration of M2-type macrophages in cervical cancer tissues, and NOX1 promotes malignant features of cervical cancer cells by stimulating ROS production. Exosomal NOX1 promotes M2 polarization of by stimulating ROS production. Exosomal NOX1 enhances progression of cervical cancer and M2 polarization in vivo by stimulating ROS production. CONCLUSION: Exosomal NOX1 promotes TAM M2 polarization-mediated cancer progression through stimulating ROS production in cervical cancer.
Assuntos
Neoplasias do Colo do Útero , Feminino , Animais , Humanos , Neoplasias do Colo do Útero/genética , NADPH Oxidase 1/genética , Espécies Reativas de Oxigênio , Macrófagos Associados a Tumor , Macrófagos , Microambiente TumoralRESUMO
Objective: To evaluate and elucidate the effects and mechanism of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the local immune response of women with cervical intraepithelial neoplasia grade 2 (CIN2). Materials and methods: Immunofluorescence staining was used to compare immune cells infiltration before and after ALA-PDT in 23 patients with CIN2. The infiltration of immune cells into the cervical tissues of patients with different outcomes was also compared at the 6-month follow-up period. Immune cell counts in samples collected before and after treatment were compared. Results: We found an increased number of CD8+ T cell infiltration, an increased proportion of CD8+ T cells expressing Granzyme B (GrB), Chemokine receptor 3 (CXCR3), and CD8+ tissue-resident memory T (TRM) cells, and a decreased proportion of CD8+ T cells expressing PD-1 in patients with CIN2 compared to that before ALA-PDT. Moreover, at the 6-month follow-up, there was higher infiltration of CD8+ T and CD8+ TRM cells, higher expression of GrB and CXCR3, and lower expression of PD-1 on CD8+ T cells in the HPV clearance and CIN2 disappearance groups than in the HPV-positive and CIN2 regression groups. However, no significant difference was observed in the number of CD8+ TSCM following ALA-PDT. Conclusion: ALA-PDT could activate CD8+ T cell responses by modulating the expression of CXCR3 and PD-1 in CD8+ T cells and increasing the infiltration of CD8+ TRM cells. And the infiltration of CD8+ T cells is correlated with the prognosis of CIN2.
Assuntos
Infecções por Papillomavirus , Fotoquimioterapia , Displasia do Colo do Útero , Humanos , Feminino , Ácido Aminolevulínico/uso terapêutico , Ácido Aminolevulínico/farmacologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Linfócitos T CD8-Positivos , Receptor de Morte Celular Programada 1RESUMO
OBJECTIVE: To evaluate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with CO2 laser pretreatment (Laser+ALA-PDT) on patients with cervical high-grade squamous intraepithelial lesions (HSILs). METHODS: A total of 114 patients treated by ALA-PDT or Laser+ALA-PDT at 3 centers were retrospectively reviewed. The effective rate, cure rate of lesions as well as high-risk human papillomavirus (HR-HPV) regression rate and persistent infection rate in the 2 groups were compared according to 3-6 month and 9-12 months follow-ups. The characteristics and risk factors for ineffective cases were evaluated by regression analysis. RESULTS: At the 3-6month follow-up, the effective rate was significantly higher in the Laser+ALA-PDT group than in the ALA-PDT group (96.6% vs. 81.3%, p = 0.048). A total of 79.3% of the laser+ALA-PDT patients achieved cure rate compared with 61.3% of the ALA-PDT patients (p = 0.082). In the Laser+ALA-PDT group, the HR-HPV-negative rate was significantly higher (72.4% vs. 50.7%, p = 0.045), while the persistence rate was significantly lower (20.7% vs. 42.7%, p = 0.037). At the 9-12month follow-up, the cure rate was 83% in the ALA-PDT group, 17% lower than that in the Laser+ALA-PDT group (p = 0.055). A total of 20.8% of patients in the ALA-PDT group and 5.3% in the Laser+ALA-PDT group showed persistent HR-HPV infection (p = 0.120). Pretreatment HR-HPV type, multiple infections and treatment modality were relevant factors for PDT outcome. CONCLUSIONS: For patients with cervical HSIL, laser+ALA-PDT shows better efficiency and HPV regression compared with ALA-PDT. HPV16/18 and multi-infection may be risk factors for ineffective treatment with ALA-PDT.
Assuntos
Lasers de Gás , Infecções por Papillomavirus , Fotoquimioterapia , Lesões Intraepiteliais Escamosas , Humanos , Ácido Aminolevulínico/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Infecções por Papillomavirus/tratamento farmacológico , Lasers de Gás/uso terapêutico , Papillomavirus Humano 16 , Estudos Retrospectivos , Papillomavirus Humano 18RESUMO
Wnt/ß-Catenin signaling dysregulation is involved in tumorigenesis. Furthermore, epigenetic modification of the Dickkopf (DKK) family (DKK1-DKK4) has been shown to be important in Wnt signaling regulation. In this study, the role of DKK2, a Wnt antagonist, in epithelial ovarian cancer (EOC) was evaluated by examining the expression and methylation of DKK2 in SKOV3 and ES-2 ovarian cancer cell lines and 78 tissues collected from patients (50 ovarian carcinoma, 20 benign tumor and 8 normal ovarian tissues). DKK2 is highly downregulated in EOCs; however, DKK2 expression levels are higher in both normal tissues and benign tumors. In most cases of ovarian carcinoma, DKK2 is methylated, compared with the more common unmethylated form present in benign tumors and normal ovarian tissues. Additionally, DKK2 may be epigenetically silenced by methylation in higher grades and stages of EOC. Functional analysis revealed that overexpression of DKK2 suppressed malignant cell growth and invasion in SKOV3 and ES-2 cell lines. The expression of the downstream genes of Wnt signaling, including ß-catenin, c-Myc and cyclin D1, was decreased in DKK2-transfected cells compared with mock cells. The expression of matrix metalloproteinase-2 and focal adhesion kinase were also decreased in DKK2 transfectants, supporting findings indicating inhibition of cell migration and invasion. This report provides novel indications that DKK2 is a unique hypermethylated target gene in EOC and that DKK2 may contribute to tumorigenesis in EOC through the Wnt/ß-catenin signaling mechanisms.
Assuntos
Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Via de Sinalização Wnt/genética , Animais , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Decitabina , Feminino , Humanos , Camundongos , Invasividade Neoplásica , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologiaRESUMO
MicroRNAs have recently been identified as regulators that modulate target gene expression and are suggested to be involved in the development and progression of endometriosis. This study was undertaken to analyze the expression level of microRNA-199a (miR-199a) in paired ovarian endometrioma and eutopic endometrium from women with endometriosis, and to investigate the contribution of miR-199a to the invasive capability of endometrial stromal cells (ESCs). Cell adhesion, migration and Matrigel invasion assays were carried out to measure the invasiveness of ESCs. Bioinformatics prediction, reporter gene assay, PCR, western blotting and ELISA were performed to identify miR-199a targets and related signaling pathways. The results showed that the expression level of miR-199a was lower in the eutopic endometrium from women with endometriosis, and even lower in the paired ovarian endometrioma, compared with the expression in normal controls. Moreover, ectopic expression of miR-199a attenuated ESC adhesion, migration and invasiveness. MiR-199a targeted and inhibited IkappaB kinase beta (IKKß) in ESCs. Accompanied by IKKß reduction, miR-199a suppressed nuclear factor-kappa B (NF-κB) pathway activation and interleukin-8 (IL-8) production in ESCs. All these findings suggest that miR-199a, down-regulated in endometriosis, attenuates the invasive capability of ESCs in vitro partly through IKK/NF-κB pathway suppression and reduced IL-8 expression. In conclusion, miR-199a could be involved in the pathogenesis of endometriosis.
Assuntos
Endométrio/citologia , Quinase I-kappa B/metabolismo , Interleucina-8/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Células Estromais/citologia , Células Estromais/metabolismo , Adulto , Western Blotting , Adesão Celular/genética , Adesão Celular/fisiologia , Movimento Celular/genética , Movimento Celular/fisiologia , Células Cultivadas , Endometriose/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas In Vitro , Interleucina-8/genética , MicroRNAs/genética , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Adulto JovemRESUMO
Tripartite motif-containing 44 (TRIM44) is known to play an oncogenic role in multiple human cancers, including esophageal cancer. Sesamin possesses potent anti-inflammatory and anti-cancer properties for various cancers. This study is designed to unravel the biological functions of sesamin and TRIM44 in esophageal cancer. TRIM44 expression in esophageal squamous cell cancer (ESCC) cell lines and tissues was determined by RT-qPCR assay and Western blot. The effects of sesamin and TRIM44 on ESCC cell growth in vivo and in vitro were assessed by the mouse model and CCK-8 assay, respectively. We found that TRIM44 was significantly upregulated in ESCC cell lines and tissues when compared to their counterparts. Sesamin treatment or depletion of TRIM44 markedly reduced ESCC cell proliferation. The nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) signaling pathway may be involved in sesamin-mediated TRIM44 suppression. Finally, we showed that oral administration of sesamin dramatically inhibited tumor growth or ESCC in nude mice. Our results suggest that sesamin exerts anti-tumor activity in ESCC via inhibition of NF-κB signaling pathway, demonstrating its potential for the treatment of esophageal cancer.
Assuntos
Antineoplásicos/farmacologia , Dioxóis/farmacologia , Lignanas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dioxóis/química , Dioxóis/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lignanas/química , Lignanas/uso terapêutico , Camundongos , Camundongos Nus , NF-kappa B/metabolismo , Transplante Heterólogo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismoRESUMO
Erastin is a small molecule identified in chemical screen that is capable of inducing ferropotosis. There is collective evidence proving that erastin-induced ferroptosis exhibits anti-tumor potential within diverse caners, such as ovarian cancer (OC). However, most OC cells show relative resistance to ferroptosis induced by erastin. M2-polarized tumor-associated macrophages (TAMs) have an important effect on the OC tumor microenvironment (TME), which makes M2 polarization a noticeable part in the context of OC therapy. The immunomodulatory effects of erastin on ferroptosis-resistant OC cells remain poorly understood. Here, we found that low concentration of erastin greatly promoted ferroptosis-resistant OC cell invasion and migration via STAT3-mediated M2 polarization of macrophages. As revealed by in-vitro experimental results, erastin significantly increased metastases of ferroptosis-resistant OC, and the percentage of M2 macrophage infiltration was also raised after erastin treatment. Furthermore, erastin augmented IL-8 production of macrophages, and pharmacological blockage of IL-8 partially abrogated the stimulatory effect of erastin on ferroptosis-resistant OC cells. This study demonstrates a new mechanism undering the tumor-promoting activity of erastin and has implications for the STAT3/IL-8 axis as a potential target for ferroptosis-resistant OC cells to improve overall anti-tumor efficacy.
Assuntos
Ferroptose , Neoplasias Ovarianas , Feminino , Humanos , Interleucina-8 , Neoplasias Ovarianas/tratamento farmacológico , Piperazinas/farmacologia , Microambiente Tumoral , Fator de Transcrição STAT3RESUMO
OBJECTIVE: To study the regulation of microRNA 199a (miR-199a) on adhesion, migration and invasion ability of human eutopic endometrial stromal cells (ESC) from patients with endometriosis. METHODS: ESC were transfected with miR-199a mimics or negative control (NC) RNA by lipofectamine 2000. The adhesion, migration and invasion ability of ESC were detected by cell adhesion assay, scratch assay, cell migration assay and matrigel invasion assay, respectively. Luciferase reporter assay was used to evaluate whether IKKß was the target gene of miR-199a. The expression of ikappa B kinase beta (IKKß), inhibitory kappa B alpha (IκB-α), phospho-IκB-α(p-IκB-α) and nuclear factor-kappa B (NF-κB) protein were measured by western blot. RESULTS: (1) Adhesion potential: the adhesion inhibitory rates were (14 ± 4)% in miR-199a group and 0 in control group, which showed significant difference (P < 0.01). (2) Migration and invasion: in the scratch assay, ESC transfected with miR-199a exhibited a lower scratch closure rate than that of controls. In migration and invasion assays, the migration and invasion ability of miR-199a group were significantly decreased compared with those of NC group [130 ± 31 vs. 247 ± 36 (P < 0.01); 63 ± 15 vs. 133 ± 17 (P < 0.01), respectively]. (3) The luciferase activity of miR-199a group was significantly lowered than that of control group [0.160 ± 0.006 vs. 0.383 ± 0.083 (P < 0.01)]. The protein levels of IKKß, p-IκB-α, IκB-α and NF-κB of 0.350 ± 0.195, 0.443 ± 0.076, 1.970 ± 0.486 and 0.454 ± 0.147 in miR-199a group were significantly different compared with the NC group in which the protein levels were set at 1.000 (P < 0.01). CONCLUSIONS: miR-199a can inhibit the adhesion, migration and invasion of the ESC. IKKß is the target gene of miR-199a in ESC. One of the mechanisms of the inhibition effect is probably that miR-199a inhibits the activation of NF-κB signaling pathway by targeting IKKß gene.
Assuntos
Endometriose , Endométrio/citologia , MicroRNAs/genética , Células Estromais/metabolismo , Western Blotting , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Humanos , Proteínas I-kappa B , Inibidor de NF-kappaB alfa , NF-kappa B/genética , Transdução de Sinais/genéticaRESUMO
BACKGROUND: High-risk HPV infection is the main cause of cervical cancer and pre-cancerous lesions. The current principle of clinical management of cervical low-grade squamous intraepithelial lesion is observation for 2 years. Progression to high-grade squamous intraepithelial lesion warrants intervention. Primary treatment option is surgical excision which may have a negative impact on fertility. Topical photodynamic therapy is a non-invasive and targeted therapy. We investigated the clinical efficacy of this therapy for cervical low-grade squamous intraepithelial lesion with high-risk HPV infection. METHODS: A retrospective study consisting of 258 female patients aged 21-69 years with a histologically confirmed cervical low-grade squamous intraepithelial lesion with high-risk HPV infection was carried out. Subjects were treated with three sessions of 20 % 5-aminolevulinic acid photodynamic therapy at intervals of 7-14 days. Three months after treatment, the effect was evaluated through HPV typing, Thinprep cytology and colposcopy directed biopsy. Six months after treatment, the photodynamic therapy effect was evaluated by HPV genotyping and Thinprep cytology first, the pathological examination would be performed at the 6-month follow-up point if the cytological results indicated the risk of high-grade squamous intraepithelial lesions. RESULTS: Three months after treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, pâ¯=â¯0.081).The remission rates of the <50 age group was significantly higher than the >50 age group (67.28 %vs46.34 %, pâ¯=â¯0.001). The total lesion regression rate wa treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, pâ¯=â¯0.081).The remission rates of the <50 age group was significantly higher than the >50 age group (67.28 %vs46.34 %, pâ¯=â¯0.001). The total lesion regression rate was 84.88 % (219/258). 12.8 % (33/258) of patients did not progress. Only 2.33 % (6/258) patients progressed to high-grade squamous intraepithelial lesion and accepted loop electrosurgical excision procedure. The patients >50 age group had significant higher progression rate than the patients ï¼50 age group (pï¼0.05). Six months after treatment, except for 6 patients who progressed to high-grade squamous intraepithelial lesion and underwent surgical treatment, the total baseline HPV remission rates was up to 82.54 % (208/252). CONCLUSION: 5-aminolevulinic acid photodynamic therapy was highly effective and did not appear to create cervical damage.. It might be an ideal treatment for cervical low-grade squamous intraepithelial lesion with high-risk HPV infection, but this requires additional clinical trials.
Assuntos
Infecções por Papillomavirus , Fotoquimioterapia , Lesões Intraepiteliais Escamosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Idoso , Ácido Aminolevulínico/uso terapêutico , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Gravidez , Estudos Retrospectivos , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto Jovem , Displasia do Colo do Útero/tratamento farmacológicoRESUMO
BACKGROUND: High-risk HPV (hrHPV) not only increases the risk of cervical precancerous lesions and cervical cancer, but also adds psychological burden to HPV-positive women. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive and highly tissue-selective therapy. We aim to investigate the clinical efficacy of ALA-PDT for elimination of cervical hrHPV infection in HPV-positive women without cervical lesions. METHODS: A total of 57 hrHPV-positive women without pathologically proved cervical lesions received three treatments of ALA-PDT in total. HPV DNA testing and pap cytology were performed in all patients. Patients with positive HPV16/18 or abnormal TCT results received colposcopic biopsy during the follow-up. RESULTS: hrHPV clearance rate was 56.1 % (32/57) at 3-month follow-up and 68.1 % at 6-month follow-up. 100 % of HPV 18 and 87.5 % of HPV16 infections were cleared while the clearance rate was 48.8 % among those positive for 12 other high-risk types. Multivariate analysis showed HPV16/18 infection was associated with significantly higher clearance rate. HPV clearance rate in patients with multiple-type HPV infection was significantly lower than that in patients with single-type HPV infections. CONCLUSIONS: ALA-PDT is effective on treating hrHPV infection in patients with no cervical lesions. HPV16/18 positive cases can benefit most from ALA-PDT. Multitype-infected women need more sessions of 5- ALA-PDT to eradicate hrHPV infection.
Assuntos
Infecções por Papillomavirus , Fotoquimioterapia , Neoplasias do Colo do Útero , Ácido Aminolevulínico/uso terapêutico , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Infecções por Papillomavirus/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológicoRESUMO
BACKGROUND: There are insufficient studies comparing the efficacy of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) against CO2 laser therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with high-risk human papillomavirus (HR-HPV), especially for long-term efficacy. METHODS: Patients with cervical LSIL and HR-HPV infection were divided into two treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4-6 months and 12 months after the treatment. RESULTS: (1) Among 277 patients, 176 patients received 5-ALA PDT and 101 patients received CO2 laser therapy. (2) 4-6 months after treatment, there was no significant difference between two groups in the complete remission (CR) rates of cervical LSIL and the clearance rate of HR-HPV infection. (3) 12 months after treatment, compared with the CO2 laser group, the CR rates of cervical LSIL in the 5-ALA PDT group was significantly higher than the CO2 laser group. There was no statistical difference in the clearance rate of HR-HPV infection between the two groups. (4) 12 months after treatment, the recurrence rate of cervical lesions and the reinfection rate of HR-HPV infection in 5-ALA PDT group were significantly lower than those in CO2 laser group. CONCLUSION: The effect of 5-ALA PDT is similar to CO2 laser at 4-6 months. The long-term efficacy of 5-ALA PDT appears better than CO2 laser. As a non-invasive treatment, 5-ALA PDT is a highly effective therapeutic procedure for cervical LSIL with HR-HPV infection.