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1.
Acta Cytol ; 65(5): 385-392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34482310

RESUMO

OBJECTIVE: The objective of this study was to evaluate the application of DNA ploidy analysis in large-scale population screening for cervical cancer. METHODS: From March 2016 to March 2019, eligible subjects were enrolled and recommended to undergo DNA ploidy analysis, the ThinPrep cytology test (TCT), and high-risk human papillomavirus (hrHPV) detection concurrently. Patients with positive results were recommended for colposcopy, and biopsy diagnosis was regarded as the "gold standard." We compared the test efficiencies of the 3 methods and compared the efficiency and accuracy of the TCT in our hospital and the "2-cancer screening" project in Hubei Province during the same period. RESULTS: Among 20,574 women, the positive rates of DNA ploidy analysis, cytology, and hrHPV testing were 4.01%, 4.71%, and 16.28%, respectively. The sensitivities of these methods for screening for grade 2+ cervical intraepithelial neoplasia were 0.70, 0.68, and 0.96, and their specificities were 0.79, 0.82, and 0.45, respectively. On comparing DNA ploidy analysis with the TCT, there was no significant difference in the sensitivity, specificity, positive predictive value, negative predictive value, and missed diagnosis rate. In opportunistic screening and the 2-cancer screening project, the positive rates of cytology were 4.71% and 2.87%, respectively. And the efficiency and accuracy of the TCT in opportunistic screening were higher than in the 2-cancer screening project. CONCLUSION: Therefore, DNA ploidy analysis, which is of low-cost and does not depend on cytopathologists, can replace cytology and be applied in large-scale population screening for cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Programas de Rastreamento , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Adulto , Biópsia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Citodiagnóstico/métodos , DNA , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Papillomaviridae/genética , Gravidez , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Adulto Jovem
2.
Anticancer Res ; 41(9): 4431-4438, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475065

RESUMO

BACKGROUND/AIM: Although still controversial, the current treatment for locally advanced neuroendocrine carcinoma of the cervix (NECC) relies on chemoradiation (CRT). The aim of this study is to evaluate the alternative role of combined chemotherapy and surgery in treating NECC. PATIENTS AND METHODS: This is a retrospective series of patients undergoing radical surgery after neoadjuvant chemotherapy (NACT) for locally advanced NECC (stages IIB-IVA). Histological examination and immunohistochemistry were performed on surgical specimens to confirm diagnosis. Systematic literature search was conducted to identify other cases treated with chemotherapy and surgery. RESULTS: Seven patients with a mean age of 49 years were identified. The mean greatest diameter at diagnosis was 59.3±24.7 mm. FIGO stage was IIB in 14.3% of patients, IIIB in 28.6%, IIIC in 42.9%, and IVA in 14.3%. The response to NACT was partial, ranging from 50% to 80%. Neuroendocrine markers were expressed in all cases. The mean progression-free survival (PFS) and overall survival (OS) were 15.0±30.6 months and 26.3±36.4 months, respectively. Eleven studies encompassing a total of 27 patients met eligibility criteria for the systematic review. CONCLUSION: Surgery after NACT for locally advanced NECC may yield similar outcomes compared to CRT. The benefit of performing surgery as a primary approach could lie in the possibility of reserving CRT for recurrences. Since randomized clinical trials are difficult to be designed, an expert consensus is required to address the non-inferiority of radical surgery over CRT.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
3.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445562

RESUMO

Synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, has been implicated in cancer progression, and therapeutic resistance, as well as cancer stem cell (CSC)-like properties. Previously, we demonstrated that SCP3 promotes these aggressive phenotypes via hyperactivation of the AKT signaling pathway; however, the underlying mechanisms responsible for SCP3-induced AKT activation remain to be elucidated. In this study, we demonstrated that the EGF-EGFR axis is the primary route through which SCP3 acts to activate AKT signaling. SCP3 triggers the EGFR-AKT pathway through transcriptional activation of EGF. Notably, neutralization of secreted EGF by its specific monoclonal antibody reversed SCP3-mediated aggressive phenotypes with a concomitant reversal of EGFR-AKT activation. In an effort to elucidate the molecular mechanisms underlying SCP3-induced transcriptional activation of EGF, we identified Jun activation domain-binding protein 1 (JAB1) as a binding partner of SCP3 using a yeast two-hybrid (Y2H) assay system, and we demonstrated that SCP3 induces EGF transcription through physical interaction with JAB1. Thus, our findings establish a firm molecular link among SCP3, EGFR, and AKT by identifying the novel roles of SCP3 in transcriptional regulation. We believe that these findings hold important implications for controlling SCP3high therapeutic-refractory cancer.


Assuntos
Complexo do Signalossomo COP9/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fator de Crescimento Epidérmico/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Peptídeo Hidrolases/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Complexo do Signalossomo COP9/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Fator de Crescimento Epidérmico/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Peptídeo Hidrolases/genética , Fosforilação , Domínios e Motivos de Interação entre Proteínas , Transdução de Sinais , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
4.
Molecules ; 26(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34443546

RESUMO

Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.


Assuntos
Antineoplásicos/farmacologia , Propionatos/farmacologia , Neoplasias do Colo do Útero/patologia , Antineoplásicos/química , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , NF-kappa B/metabolismo , Propionatos/química , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo
5.
Photochem Photobiol Sci ; 20(8): 1087-1098, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34398442

RESUMO

In this study, C-doped TiO2 nanoparticles (C-TiO2) were prepared and tested as a photosensitizer for visible-light-driven photodynamic therapy against cervical cancer cells (HeLa). X-ray diffraction and Transmission Electron Microscopy confirmed the anatase form of nanoparticles, spherical shape, and size distribution from 5 to 15 nm. Ultraviolet-visible light spectroscopy showed that C doping of TiO2 enhances the optical absorption in the visible light range caused by a bandgap narrowing. The photo-cytotoxic activity of C-TiO2 was investigated in vitro against HeLa cells. The lack of dark cytotoxicity indicates good biocompatibility of C-TiO2. In contrast, a combination with blue light significantly reduced the survival of HeLa cells: illumination only decreased cell viability by 30% (15 min of illumination, 120 µW power), and 60% when HeLa cells were preincubated with C-TiO2. We have also confirmed blue light-induced C-TiO2-catalyzed generation of reactive oxygen species in vitro and intracellularly. Oxidative stress triggered by C-TiO2/blue light was the leading cause of HeLa cell death. Fluorescent labeling of treated HeLa cells showed distinct morphological changes after the C-TiO2/blue light treatment. Unlike blue light illumination, which caused the appearance of large necrotic cells with deformed nuclei, cytoplasm swelling, and membrane blebbing, a combination of C-TiO2/blue light leads to controlled cell death, thus providing a better outcome of local anticancer therapy.


Assuntos
Carbono/química , Nanopartículas , Fototerapia , Titânio/química , Titânio/farmacologia , Neoplasias do Colo do Útero/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Terapia Combinada , Feminino , Células HeLa , Humanos
6.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445466

RESUMO

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core-shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core-shell microparticles were of spherical appearance, with an average size of 14.65 µm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core-shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Microesferas , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Camundongos , Paclitaxel/administração & dosagem , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Medicine (Baltimore) ; 100(31): e26844, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397857

RESUMO

RATIONALE: Primary signet ring cell carcinoma of the uterine cervix is extremely rare and the clinical characteristics and prognosis are not well known and there are no specific guidelines for treatment. PATIENT CONCERNS: A 43-year-old woman was referred to our hospital for abnormal uterine bleeding lasting 1 month. DIAGNOSES: Histological examination revealed a signet ring cell carcinoma of the uterine cervix. After evaluation of extragenital origin, the patient was diagnosed International Federation of Gynecology and Obstetrics stage IIIC1 primary signet ring cell carcinoma or the uterine cervix. INTERVENTION: The patient was prescribed concomitant chemo-radiation followed by intracavitary brachytherapy. OUTCOMES: She showed no evidence of disease after treatment but, it recurred after 7 months of last treatment. LESSONS: Different approaches to diagnosis and treatment of this rare disease are needed and molecular pathological studies related to the onset of the disease are required.


Assuntos
Carcinoma de Células em Anel de Sinete , Colo do Útero , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Neoplasias do Colo do Útero , Esfregaço Vaginal/métodos , Adulto , Antineoplásicos/administração & dosagem , Biópsia/métodos , Braquiterapia/métodos , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/fisiopatologia , Carcinoma de Células em Anel de Sinete/terapia , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Evolução Fatal , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Papillomaviridae/isolamento & purificação , Retratamento/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/fisiopatologia , Neoplasias do Colo do Útero/terapia , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/etiologia
8.
Medicine (Baltimore) ; 100(34): e27035, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449483

RESUMO

BACKGROUND: The value of sentinel lymph node (SLN) mapping for early-stage cervical cancer remains controversial. Therefore, we collected data to investigate the feasibility and diagnostic accuracy of SLN in patients with early-stage (IA-IIA) cervical cancer. METHODS: We searched Embase, PubMed, and the Cochrane Library databases issued before June 1, 2020. The sample size of the selected study was at least 10 patients with early-stage (IA-IIA) cervical cancer, the pooled detection rates and the separate detection rate (overall detection rate, bilateral detection rate) using blue dye with Tc, technetium 99 (Tc) and indocyanine green (ICG) technique of early-stage cervical cancer was reported. R-3.6.1 software was used to evaluate pooled detection rate and sensitivity. RESULTS: Two thousand one hundred sixty-four patients included for analysis in 28 studies ranging from 12 to 405 patients. The combined overall detection rate of SLN mapping was 95% with a 72% pooled bilateral detection rate. The sensitivity of the combined overall detection rate of SLN mapping was 94.99% as well as a sensitivity of 72.43% bilateral detection rate. The overall detection rate of SLN was 96% for blue dye with Tc, 95% for Tc, 98% for ICG technique. The bilateral detection rate of SLN was 76% for blue dye with Tc, 63% for Tc, 85% for ICG technique. The sensitivity of the overall detection rate of SLN mapping was 97.76% as well as a sensitivity of 84.96% bilateral detection rate of ICG technique. CONCLUSION: In early-stage cervical cancer, overall detection rate of SLN mapping is elevated while bilateral detection rate is lower. The overall detection rate (98%) as well as bilateral rate (85%) of ICG seems to be a better SLN mapping technique among the method of SLN mapping (using blue dye with Tc, Tc or ICG). We believe SLN mapping may be considered contemporary technique which could provide additional benefits over traditional pelvic lymphadenectomy. While promising results in SLN mapping has been found, larger patient samples, including randomized studies, are required at the same time.


Assuntos
Linfonodo Sentinela/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Corantes , Feminino , Humanos , Verde de Indocianina , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela/métodos , Tecnécio
9.
BMJ Open ; 11(8): e042364, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380711

RESUMO

OBJECTIVE: We aimed to analyse the clinical value of primary site surgery in improving the cancer-specific survival (CSS) and overall survival (OS) of initial metastatic cervical cancer patients. DESIGN: A population-based retrospective study. SETTING: National Cancer Institute's Surveillance, Epidemiology and End Results database. PARTICIPANTS: We analysed 1390 patients with the International Federation of Gynecology and Obstetrics 2009 stage IVB cervical cancer with complete clinical data treated between 2010 and 2016. INTERVENTIONS: Primary site surgery. MEASURES: Propensity score matching (PSM) with a ratio of 1:2 was used to balance measure covariates of comparison groups. Survival time was calculated using Kaplan-Meier methods and compared by the log-rank test. To eliminate the bias of site-specific metastasis, clinicopathological factors and subsequent therapy on survival analysis, subgroup analyses stratified by metastasis type, clinicopathological factors and subsequent therapy were employed to evaluate the effect of cervical surgery on survival. Combination of directed acyclic graph and change-in-estimate procedures was performed to indentified confounders, and Cox regression was used to assess the survival benefit of cervical surgery for primary metastatic cervical cancer patients. The consistency of our findings was evaluated through sensitivity analysis. RESULTS: Matching resulted in two comparison groups with minor differences in most variables. Pre-and-post-PSM, the median CSS and OS in the surgery group were 1.3 and 1.5, 1.1 and 1.2 times of those in the non-surgery group, respectively. Primary site surgery conferred prognosis superiority for patients with metastases to distant lymph node and other sites rather than organ metastases. After PSM and adjusting confounders, local surgery reduced the cancer related and overall mortality rates by 31% and 30%, respectively. CONCLUSIONS: Surgical procedures could promote survival in patients with primary metastatic cervical cancer and should be considered a therapeutic option for carefully chosen patients.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
10.
Medicine (Baltimore) ; 100(32): e26845, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397891

RESUMO

RATIONALE: Despite the development of human papillomavirus vaccines and significant improvement in cervical cancer screening over the past few years, cervical cancer remains the fourth most common cancer in women of childbearing age after breast cancer, melanoma, and thyroid cancer. PATIENT CONCERNS: In this case report, the patients are all cervical cancer with stage IB2 and IB3 during pregnancy, the management constitutes a major medical challenge related to the impact of treatment on both maternal and fetal outcomes. Neoadjuvant chemotherapy (NACT) is an innovative option for cervical cancer patients with stage IB2 and IB3 before cesarean delivery and radical hysterectomy, and many chemotherapeutic agents are available, cisplatin plus paclitaxel yielded good maternal and fetal outcomes to the authors' knowledge. DIAGNOSES: Masses were discovered in the cervix of 4 pregnant women with a history of vaginal bleeding. Biopsy examination of the masses revealed cervical carcinoma, which was staged in accordance with the International Federation of Gynecology and Obstetrics (i.e., FIGO) system. INTERVENTIONS: The patients were treated with paclitaxel plus cisplatin, followed by cesarean delivery and radical hysterectomy. OUTCOMES: The 4 patients were treated successfully, with no recurrence during follow-up periods of 14 to 56 months, and all of the children were doing well with no anomalies. LESSONS: Although further data are required, in pregnant women with invasive cervical cancer, NACT with cisplatin plus paclitaxel followed by cesarean delivery and radical hysterectomy was a practical treatment option.


Assuntos
Cisplatino , Histerectomia/métodos , Paclitaxel , Complicações Neoplásicas na Gravidez , Neoplasias do Colo do Útero , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biópsia/métodos , Colo do Útero/patologia , Cesárea/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/cirurgia , Resultado da Gravidez , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
11.
Medicine (Baltimore) ; 100(33): e26960, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414964

RESUMO

ABSTRACT: To explore the predictive value of preoperative serum squamous cell carcinoma antigen (SCC-Ag) level for lymph node metastasis (LNM), particularly, in patients surgically treated for early-stage cervical squamous cell carcinoma.We enrolled 162 patients with cervical squamous cell carcinoma stages IB to IIA following the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. The patients had previously undergone radical surgery. Correlation of the SCC-Ag level with clinicopathological features and the predictive value of SCC-Ag for LNM were analyzed.High preoperative SCC-Ag level was correlated with FIGO stage (P = .001), tumor diameter >4 cm (P < .001), stromal infiltration (P < .001), LNM (P < .001) and lymphovascular space invasion (LVSI), (P = .045). However, it was not correlated with age, histological differentiation, parametrial involvement, and positive vaginal margin (P > .05). Univariate analysis revealed that FIGO stage (P = .015), tumor diameter (P = .044), stromal infiltration (χ2 = 10.436, P = .005), SCC-Ag ≧ 2.75 ng/mL (χ2 = 14.339, P < .001), LVSI (χ2 = 12.866, P  < .001), parametrial involvement (χ2 = 13.784, P < .001) were correlated with LNM, but not with age, histological differentiation, and positive vaginal margin. Moreover, multivariate analysis demonstrated that SCC-Ag ≧2.75 ng/mL (P = .011, OR = 3.287) and LVSI (P = .009, OR = 7.559) were independent factors affecting LNM. The area under the receiver operator characteristic curve of SCC-Ag was 0.703 (P < .001), while 2.75 ng/mL was the best cutoff value for predicting LNM. The sensitivity and specificity of diagnosis were 69.4% and 65.9%, respectively.High SCC-Ag level was revealed to be an independent risk factor for the prognosis of squamous carcinoma of the cervix before an operation. Besides, SCC-Ag (2.75 ng/mL) can be utilized as a potential marker to predict LNM in early stage cervical cancer before an operation.


Assuntos
Antígenos de Neoplasias/sangue , Carcinoma de Células Escamosas/diagnóstico , Metástase Linfática/diagnóstico , Serpinas/sangue , Neoplasias do Colo do Útero/diagnóstico , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
12.
Medicine (Baltimore) ; 100(34): e27056, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449496

RESUMO

ABSTRACT: Chromobox homolog 8 (CBX8) plays an important role in the occurrence and development of various tumors, and is closely related to the prognosis of patients with cancer. However, the occurrence, development, and prognostic value of CBX8 in cervical cancer have not been reported yet.In this study, immunohistochemistry was used to detect the expression of CBX8 in cervical cancer tissues and the corresponding normal tissues adjacent to the tumor. Furthermore, the relationship between CBX8 and programmed death-ligand 1 (PD-L1) expression, clinicopathological characteristics, and prognosis of cervical cancer were explored, and the prognostic value of CBX8 in cervical cancer was clarified.In this study, the results of immunohistochemistry using tissue chips obtained from patients with cervical cancer showed that CBX8 was highly expressed in cervical cancer tissues, and its expression was proportional to the international federation of gynecology and obstetrics (FIGO) stage. Disease-free and overall survival of patients with high CBX8 expression in cervical cancer were significantly shorter than those of patients with low CBX8 expression. Thus, CBX8 was found to be an independent prognostic factor for patients with cervical cancer. In addition, CBX8 and PD-L1 co-expression model could better predict the prognosis of patients with cervical cancer, and its area under the receiver operating characteristic curve was similar to that of FIGO stage.CBX8 may be an independent prognostic factor for cervical cancer. Moreover, the CBX8 and PD-L1 co-expression model could predict the postoperative survival of patients with cervical cancer objectively and reliably, which will aid clinicians to shunt patients with cervical cancer based on the risk of death, develop a reasonable treatment plan, and provide personalized prognosis.


Assuntos
Antígeno B7-H1/biossíntese , Complexo Repressor Polycomb 1/biossíntese , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
13.
Acta Cytol ; 65(5): 448-452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34293740

RESUMO

INTRODUCTION: Seborrheic keratosis-like lesion of the cervix and vagina is a rare lesion and shows similar morphology to vulvar seborrheic keratosis; 3 of the 7 previously reported cases were associated with low-risk human papillomavirus (HPV) type 42. We report a case of seborrheic keratosis-like lesion of the cervix and provide the first description of the cytological features of this lesion. CASE PRESENTATION: A woman in her late forties presented with postcoital bleeding. She had a cervical screening test following which she underwent cervical biopsy, endocervical and endometrial curettage, large loop excision of the transformation zone of the cervix, and hysterectomy. RESULTS: The liquid-based cytology preparation showed cohesive groups of mildly atypical squamoid cells with a spindle cell morphology, mildly increased nuclear to cytoplasmic ratio, prominent nucleoli, and occasional nuclear grooves. No koilocytes were identified. Molecular genotyping revealed positivity for HPV type 42. DISCUSSION/CONCLUSION: This represents the first description of the cytological features of a seborrheic keratosis-like lesion of the cervix, which are distinctive and unusual. Whilst the mild squamous atypia raised the possibility of a low-grade squamous intraepithelial lesion, no koilocytes were identified. The association in our case with a low-risk HPV type, HPV 42, provides further evidence for a role of this HPV type in the pathogenesis of these lesions.


Assuntos
Colo do Útero/patologia , Ceratose Seborreica/cirurgia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/cirurgia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Ceratose Seborreica/complicações , Ceratose Seborreica/patologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Risco , Lesões Intraepiteliais Escamosas/cirurgia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia
14.
Medicine (Baltimore) ; 100(28): e26593, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260540

RESUMO

ABSTRACT: Human papillomavirus (HPV) infection is a common sexually transmitted disease worldwide and the leading cause of cervical cancer. Current vaccines do not cover all HPV genotypes whereas the distribution of HPV genotypes varies in different geographic regions. The study aimed to investigate the distribution of HPV genotypes in patients with cervical squamous intraepithelial lesion (SIL) and cervical squamous cell carcinoma (SCC) in Taizhou City of Jiangsu Province, China. A total of 940 patients including 489 cases with cervical low-grade squamous intraepithelial lesions (LSIL), 356 cases with cervical high-grade squamous intraepithelial lesions (HSIL), and 95 cases with cervical SCC, underwent a biopsy or surgery in Taizhou People's Hospital between January 2019 and December 2019. The HPV testing results were retrospectively analyzed. The overall prevalence of any, high-risk, and low-risk HPV was 83.83%, 81.91%, and 12.13%, respectively. The 5 most common HPV genotypes were HPV16 (35.64%), HPV52 (16.91%), HPV58 (13.94%), HPV33 (8.94%), and HPV18 (7.98%). The prevalence of any and HR-HPV in SCC was significantly higher than those in LSIL and HSIL, while the prevalence of LR-HPV in SCC was significantly lower than those in LSIL and HSIL (P < .01). Single and dual HPV infections were prevalent in SCC, LSIL, and HSIL. Furthermore, the prevalence of dual HPV infection in SCC was significantly higher than those in LSIL and HSIL (P = .002). The HPV prevalence varied by age, being highest among women with SCC, LSIL, and HSIL aged 40 to 49 years, 40 to 49 years, and 50 to 59 years, respectively. In conclusion, the findings revealed a very high prevalence of HPV in women with cervical lesions in Taizhou. Routine HPV tests must cover all common HPV genotypes in clinical practice.


Assuntos
Alphapapillomavirus/genética , Carcinoma de Células Escamosas/virologia , Neoplasia Intraepitelial Cervical/virologia , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/virologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , China/epidemiologia , DNA Viral , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prevalência , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Adulto Jovem
15.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299115

RESUMO

A series of novel hybrid compounds containing benzofuroxan and 2-aminothiazole moieties are synthesized via aromatic nucleophilic substitution reaction. Possible reaction pathways have been considered quantum-chemically, which allowed us to suggest the most probable products. The quantum chemical results have been proved by X-ray data on one compound belonging to the synthesized series. It was shown that the introduction of substituents to both the thiazole and amine moieties of the compounds under study strongly influences their UV/Vis spectra. Initial substances and obtained hybrid compounds have been tested in vitro as anticancer agents. Target compounds showed selectivity towards M-HeLa tumor cell lines and were found to be more active than starting benzofuroxan and aminothiazoles. Furthermore, they are considerably less toxic to normal liver cells compared to Tamoxifen. The mechanism of action of the studied compounds can be associated with the induction of apoptosis, which proceeds along the mitochondrial pathway. Thus, new hybrids of benzofuroxan are promising candidates for further development as anticancer agents.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzoxazóis/química , Tiazóis/química , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Neoplasias do Colo do Útero/patologia
16.
Anticancer Res ; 41(7): 3543-3560, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230150

RESUMO

BACKGROUND/AIM: There is a lack of data concerning the surgical treatment of locally advanced squamous cell carcinoma of the uterine cervix (LACC) with neoadjuvant and adjuvant chemotherapy (NACT, ACT) as well as total mesometrial resection (TMMR). The aim of the study was to present a novel approach for treating LACC using a tumor response score for NACT. PATIENTS AND METHODS: A total of 12 patients with LACC were treated with NACT [cisplatin, ifosfamide, paclitaxel (TIP)], TMMR and ACT containing TIP. To measure the response during NACT, we scored i) the maximum tumor diameter (maxTD) in gynecological examination, ii) the MRI for radiologic maxTD, iii) the tumor volume and iv) the squamous cell carcinoma antigen before and after two applications of TIP. RESULTS: TIP reduced all score-parameters in 10 of 12 patients (p<0.005). We found a possible reduction of lymph node metastasis in 72.7%. The proposed score detected sufficient and insufficient tumor response. CONCLUSION: TIP followed by TMMR with ACT could be a possibility for patients denying radiochemotherapy. The tumor response score can detect patients with inadequate benefit from NACT.


Assuntos
Colo do Útero/efeitos dos fármacos , Colo do Útero/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Colo do Útero/patologia , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Histerectomia/métodos , Metástase Linfática/tratamento farmacológico , Metástase Linfática/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos
17.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198834

RESUMO

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC50 and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.


Assuntos
Anidrase Carbônica IX/genética , Inibidores da Anidrase Carbônica/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose/efeitos dos fármacos , Anidrase Carbônica IX/antagonistas & inibidores , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Compostos de Fenilureia/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sulfonamidas/farmacologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
18.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207106

RESUMO

Infection with human papillomavirus type 16 (HPV16) is one of the major risk factors for the development of cervical cancer. Our previous studies have demonstrated the involvement of the early oncoprotein E5 of HPV16 (16E5) in the altered isoform switch of fibroblast growth factor receptor 2 (FGFR2) and the consequent expression in human keratinocytes of the mesenchymal FGFR2c isoform, whose aberrant signaling leads to EMT, invasiveness, and dysregulated differentiation. Here, we aimed to establish the possible direct link between these pathological features or the appearance of FGFR2c and the expression of 16E5 in low-grade squamous intraepithelial lesions (LSILs). Molecular analysis showed that the FGFR2c expression displayed a statistically significant positive correlation with that of the viral oncoprotein, whereas the expression values of the epithelial FGR2b variant, as well as those of the differentiation markers keratin 10 (K10), loricrin (LOR) and involucrin (INV), were inversely linked to the 16E5 expression. In contrast, the expression of EMT-related transcription factors Snail1 and ZEB1 overlapped with that of 16E5, becoming a statistically significant positive correlation in the case of Snail2. Parallel analysis performed in human cervical LSIL-derived W12 cells, containing episomal HPV16, revealed that the depletion of 16E5 by siRNA was able to counteract these molecular events, proving to represent an effective strategy to identify the specific role of this viral oncoprotein in determining LSIL oncogenic and more aggressive profiles. Overall, coupling in vitro approaches to the molecular transcript analysis in ectocervical early lesions could significantly contribute to the characterization of specific gene expression profiles prognostic for those LSILs with a greater probability of direct neoplastic progression.


Assuntos
Transição Epitelial-Mesenquimal , Expressão Gênica , Papillomavirus Humano 16/genética , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/patologia , Linhagem Celular , Transformação Celular Viral , Colo do Útero/patologia , Colo do Útero/virologia , Suscetibilidade a Doenças , Células Epiteliais/metabolismo , Feminino , Humanos , Queratinócitos/metabolismo , Gradação de Tumores , Infecções por Papillomavirus/virologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Neoplasias do Colo do Útero/metabolismo
19.
World J Surg Oncol ; 19(1): 209, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253208

RESUMO

OBJECTIVE: This study aimed to evaluate the clinical outcomes for patients with stage IB2/IIA2 cervical squamous cell carcinoma treated with neoadjuvant chemotherapy combined with radical surgery. METHODS: A total of 68 patients with cervical squamous cell carcinoma were randomly divided into the experimental group (n = 35) and the control group (n = 33). The patients in the experimental group received paclitaxel plus cisplatin neoadjuvant chemotherapy for two cycles, then underwent radical hysterectomy and bilateral adnexectomy at 2 weeks post-chemotherapy. The control group only underwent radical hysterectomy and bilateral adnexectomy after the diagnosis of cervical squamous cell carcinoma. The toxic and side effects of chemotherapy in the experimental group were observed. Also, the operation method, operation time, blood loss, grade of wound healing, complications, and postoperative pathology were noted in the two groups. Primary foci and pelvic lymph node recurrence and distant metastasis were observed, and 3-year and 5-year survival rates were calculated. RESULTS: Only one patient in the experiment had grade III bone marrow suppression; no other grade III and IV chemotherapy toxic reactions were observed. The operation was successfully completed in all patients. The operation time, intraoperative blood loss, placement of the ureteral catheter, bladder injury, ureteric injury, postoperative urinary tub, pelvic drainage tube indwelling time, anal exhaust time, postoperative complications, and metastatic ratio of lymph nodes were not significantly different between the two groups (P > 0.05). The number of dissected lymph nodes, deep myometrial invasion, and vascular tumor emboli showed a significant difference in the experimental group compared with the control group (P < 0.05). The 3-year disease-free survival (82.9% vs 81.9%), 5-year disease-free survival (71.4% vs 60.6%), 3-year overall survival (91.4% vs 87.8%), and 5-year overall survival (82.9% vs 75.6%) were not statistically significantly different between the experimental group and the control group (P > 0.05). CONCLUSIONS: Neoadjuvant chemotherapy in IB2/IIA2 stage cervical squamous cell carcinoma showed low toxic side effects. Radical surgery after chemotherapy is safe and feasible. It plays a coordinating role in reducing the tumor infiltration depth of the deep muscle layer and the incidence of vascular tumor emboli, reducing the use of postoperative adjuvant therapy, and improving the quality of life of patients, but does not improve the 3-year/5-year survival rate.


Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Histerectomia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
20.
Cancer Sci ; 112(9): 3691-3698, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34252250

RESUMO

In Japan, the age-adjusted incidence of cervical cancer has been increasing constantly and rapidly among younger women. We set out to accurately confirm the effectiveness of the HPV vaccine in Japan. Data were collected for women born in the fiscal year (FY) 1990 to 1997, who became eligible for their 20-y-old cervical cancer screening between the FY 2010 to 2017. The adjusted incidence of cervical intraepithelial neoplasia (CIN)1+ in women born in FY 1990 to 1993, that is those who reached the national vaccination target age prior to the introduction of publicly subsidized HPV vaccinations, referred here after as "the pre-introduction generation", was 1.42% (242/17 040). The incidence in the "vaccination generation" (women born in FY 1994 to 1997, that is those who were heavily vaccinated as a group when they were of the nationally targeted age of 13-16) was 1.66% (135/8020). There was no significant difference between these incidence rates. However, our FY birth year-by-year analysis revealed that the incidence of CIN1+ was obviously lower than that predicted based on just the trend for CIN1+ seen in the pre-introduction generation. Our analysis revealed that the incidence of CIN3+ was obviously lower in the vaccination generation than in the pre-introduction generation (P = .0008). The incidence of CIN was already tending to increase in both the pre-introduction and vaccination generations. The changes in CIN incidence by individual birth FY must be examined to accurately determine the actual effects of the HPV vaccine for reducing mild cervical lesions.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Papillomaviridae/imunologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/métodos , Adolescente , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Adulto Jovem
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