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1.
Medicine (Baltimore) ; 99(45): e22950, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157935

RESUMO

INTRODUCTION: Cervical cancer is the second largest tumor disease threatening female reproductive tract health. AS2O3 is a multi-directional and multi-target anti-cervical cancer drug. It can be combined with platinum drugs to treat cervical cancer. The literatures of AS2O3 combined with platinum drugs related to cervical cancer have shown inconsistent results, and there is currently no high quality of systematic review to evaluate the effects of AS2O3 combined with platinum drugs in cervical cancer patients. METHODS AND ANALYSIS: English and Chinese literature about AS2O3 combined with platinum drugs treatment for cervical cancer published before August 31, 2020 will be systematic searched in PubMed, Embase, Web of Science, Cochrane Library, Open Grey, Clinicaltrials.gov, Chinese Clinical Trial Registry, WANFANG, VIP Chinese Science and Technology Journal Database, CNKI, Chinese biomedical document service system (SinoMed). Only randomized controlled trials (RCTs) of patients with cervical cancer will be included. Literature screening, data extraction, and the assessment of risk of bias will be independently conducted by 2 reviewers, and the 3rd reviewer will be consulted if any different opinions existed. Clinical total effective rate, adverse events, SCCAg, CYFRA21-1, quality of life, and immune function will be evaluated. Systematic review and meta-analysis will be produced by RevMan 5.3 and Stata 14.0. This protocol reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement. RESULTS: The current study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings in the fourth quarter of 2021. CONCLUSION: Efficacy and safety of AS2O3 combined with platinum drugs in the treatment of cervical cancer will be assessed. The results will be published in a public issue journal to provide evidence-based medical evidence for Obstetrician and Gynecologists to make clinical decisions. ETHICS AND DISSEMINATION: Ethical approval is not required as the review is a secondary study based on published literature. The results of the study will be published in peer-reviewed publications and disseminated electronically or in print. PROTOCOL REGISTRATION NUMBER: INPLASY202080130.


Assuntos
Trióxido de Arsênio/administração & dosagem , Compostos de Platina/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
2.
Oncology ; 98(11): 807-813, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32892198

RESUMO

INTRODUCTION: Different imaging techniques were introduced to improve preoperative clinical staging of locally advanced cervical cancer (LACC) with transvaginal ultrasound (TV-US) or transrectal ultrasound (TR-US) representing a promising staging technique in the evaluation of the local extension of the disease for invasive tumors. The aim of this study was to evaluate the response to neoadjuvant chemotherapy (NACT) in LACC by 2D/3D ultrasound examination. MATERIALS AND METHODS: We prospectively enrolled patients affected by histologically and clinically confirmed LACC. All patients were scheduled for 3 cycles of platinum-based NACT followed by radical surgery. The ultrasound examination was performed at every cycle and within 10 days before surgery. The parameters evaluated were: the volume (automatically computed by the VOCAL software) and the mass vascularization. RESULTS: From March 2010 to March 2019, 157 women were recruited. Among these patients, 12 of them were excluded: 6 for the presence of distant metastases, 4 for rare histology, and 2 for severe comorbidities not allowing the protocol treatment. Seventeen patients after NACT were excluded because they were not amenable to radical surgery. Thus, 128 were considered for the final analysis of whom 106 (83%) were considered responders to NACT by histology. The sensibility and specificity of ultrasound with regard to the response to chemotherapy compared to histological specimen were 94 and 82%, respectively, with an accuracy of 92%. The positive predictive value and negative predictive value were 96 and 75%, respectively. Finally, we found that nonetheless there was a trend towards a continuous response to chemotherapy among patients who were considered responders to NACT at pathological examination; the major volume and vascularization index (VI) reduction were observed during the first 2 cycles (74, 71% and 47, 63%, respectively). On the contrary, non-responders showed an initial reduction of the VI (4.86 consisting of 33%, 95% CI 0.79-8.92, p = 0.013), but no significant modification in tumour volume along NACT. CONCLUSION: 2D/3D ultrasound is useful in assessing early response to NACT in patients with LACC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Prospectivos , Ultrassonografia/métodos , Neoplasias do Colo do Útero/cirurgia
3.
Int J Nanomedicine ; 15: 6409-6420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922008

RESUMO

Aim: Tumor cell-derived microparticles (MP) can function as a targeted delivery carrier for anti-tumor drugs. Here, we aimed to generate paclitaxel-loaded microparticles (MP-PTX) from HeLa cells and examined its therapeutic potential on human cervical carcinoma. Methods: MP-PTX was generated from HeLa cells by ultraviolet radiation and subsequent centrifugation. The particle size, drug loading rate, and stability of MP-PTX were examined in vitro. Flow cytometry and the MTT assay were performed to test the inhibitory effect of MP-PTX using different cell lines. Immunodeficient mice bearing HeLa cervical carcinoma were treated with 0.9% normal saline, MP, paclitaxel (PTX) (2.5 mg/kg), or MP-PTX (PTX content identical to PTX group) every day for 6 consecutive days. Tumor volume and animal survival were observed. Micro 18F-FDG PET/CT was performed to monitor the therapeutic efficacy. The proliferation activity of cells and microvessel density in tumor tissues were determined by immunohistochemical staining using Ki-67 and CD31, respectively. Results: Dynamic laser scattering measurements showed that the particle size of MP-PTX was 285.58 ± 2.95 nm and the polydispersity index was 0.104 ± 0.106. And the particle size of MP-PTX was not change at 4°C for at least one week. More than 1% of PTX in the medium could be successfully encapsulated into HeLa cell-derived MP. When compared with PTX, MP-PTX treatment significantly increased apoptosis of tumor cells and reduced their proliferation. In addition, MP-PTX showed lower toxicity to normal human umbilical vein endothelial cells (HUVEC) than PTX. In vivo studies further demonstrated that MP-PTX treatment significantly inhibited the growth of cervical carcinoma, prolonged the survival of tumor-bearing mice, and reduced the toxicity of PTX. Immunohistochemical staining revealed that MP-PTX treatment led to decreased Ki-67 positive tumor cells and decreased microvessel density in tumor tissues. Conclusion: Our results demonstrated that HeLa-derived MP-PTX significantly enhanced the anti-cancer effects of PTX with reduced toxicity, which may provide a novel strategy for the treatment of cervical carcinoma.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Paclitaxel/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Micropartículas Derivadas de Células/efeitos dos fármacos , Portadores de Fármacos/química , Células Endoteliais/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Fisiológica/efeitos dos fármacos , Paclitaxel/farmacologia , Tamanho da Partícula
4.
Anticancer Res ; 40(9): 4819-4828, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878770

RESUMO

Concurrent cisplatin-based chemotherapy and radiotherapy (CCRT) plus brachytherapy is standard treatment for locally advanced cervical cancer. Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy has been proposed as an alternative approach, especially for patients with stage Ib2-IIb disease. This review analyzes the most commonly used combination regimens in this clinical setting and the randomized trials comparing chemo-surgery versus definitive radiotherapy or CCRT. The combination of paclitaxel plus ifosfamide plus cisplatin (TIP regimen) obtained the highest rates of optimal pathological response, associated with elevated hematological toxicity. In a recent phase II study, a dose-dense regimen consisting of weekly paclitaxel plus carboplatin for 9 cycles has achieved optimal pathological response rates similar to those of TIP with better toxicity profile. Further studies are strongly warranted to better define the optimal regimen for the patients selected to receive NACT followed by radical surgery.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Quimioterapia Adjuvante , Feminino , Humanos , Histerectomia , Terapia Neoadjuvante , Prognóstico , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
5.
Anticancer Res ; 40(10): 5497-5502, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988872

RESUMO

BACKGROUND/AIM: The cell-killing and radiosensitizing effects of carbon-ion (C-ion) beams with low linear energy transfer (LET) are underexplored. We aimed to demonstrate the cell-killing effects of 60Co gamma rays and C-ion beams at various LET values and the radiosensitizing effect of C-ion beams at various LET and cisplatin levels. MATERIALS AND METHODS: Human uterine cervical cancer cells were irradiated with 60Co gamma rays and C-ion beams at different levels of LET, with and without cisplatin treatment. RESULTS: Low-LET C-ion beams had a superior cell-killing effect compared to 60Co gamma rays. Survival curves under low-LET C-ion beams were more similar to that of 60Co gamma rays than that of high-LET C-ion beams. Cisplatin significantly reduced cell survival after 1, 2, and 3 Gy C-ion beam irradiations at LET values of 13/30/70 keV/µm, 13/30 keV/µm, and 13 keV/µm, respectively. CONCLUSION: Low-LET C-ion beams combined with cisplatin have higher radiosensitizing effects than high-LET C-ion beams.


Assuntos
Carbono/uso terapêutico , Radioisótopos de Cobalto/uso terapêutico , Radiossensibilizantes/uso terapêutico , Neoplasias do Colo do Útero/radioterapia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cisplatino/farmacologia , Relação Dose-Resposta à Radiação , Feminino , Raios gama , Humanos , Transferência Linear de Energia/efeitos da radiação , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia
6.
Life Sci ; 255: 117858, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497635

RESUMO

At present, cervical cancer is the fourth leading cause of cancer among women worldwide with no effective treatment options. In this study we aimed to evaluate the efficacy of hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) photodynamic therapy (PDT) in a comprehensive panel of human cervical cancer-derived cell lines, including HeLa (HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and 18-positive), and C33A (HPV-negative), compared to a nontumorigenic human epithelial cell line (HaCaT). Were investigated: (i) cell cytotoxicity and phototoxicity, cellular uptake and subcellular distribution; (ii) cell death pathway and cellular oxidative stress; (iii) migration and invasion. Our results showed that HYP/P123 micelles had effective and selective time- and dose-dependent phototoxic effects on cervical cancer cells but not in HaCaT. Moreover, HYP/P123 micelles accumulated in endoplasmic reticulum, mitochondria and lysosomes, resulting in photodynamic cell death mainly by necrosis. HYP/P123 induced cellular oxidative stress mainly via type II mechanism of PDT and inhibited cancer cell migration and invasion mainly via MMP-2 inhibition. Taken together, our results indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat cervical cancers through PDT, suggesting they are worthy for in vivo preclinical evaluations.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Feminino , Células HeLa , Humanos , Micelas , Invasividade Neoplásica , Estresse Oxidativo/efeitos dos fármacos , Perileno/administração & dosagem , Perileno/farmacologia , Poloxaleno/química , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
7.
Medicine (Baltimore) ; 99(24): e20558, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541479

RESUMO

BACKGROUND: Cervical cancer (CC) is a very common and malignant tumor in female population. Although a variety of single medications are reported to treat this condition, they all have limited efficacy. Previous studies have reported the combination of paclitaxel, carboplatin, and bevacizumab (PCB) can be used for the treatment of patients with CC effectively. However, no systematic review has explored its efficacy and safety. This study will address its efficacy and safety systematically and comprehensively. METHODS: The following electronic databases will be retrieved from their inceptions to the January 1, 2020 to identify all potential associated studies: MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Google scholar, and Chinese Biomedical Literature Database. We will include randomized controlled trials (RCTs) of adult women (≥18 years) with CC globally. Eligible interventions will target any forms of PCB. The study methodological quality of all included studies will be appraised using Cochrane risk of bias tool. Statistical analysis will be undertaken using RevMan 5.3 software. In addition, we will perform a narrative synthesis to describe quality and content of the evidence. RESULTS: This study will summarize recent evidence and provide quality evidence for the efficacy and safety of PCB on CC. CONCLUSION: The findings of this study will seek to identify the efficacy and safety of PCB and suggest future directions for research efforts targeting CC among this population. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040195.


Assuntos
Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Carboplatina/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
8.
Anticancer Res ; 40(6): 3031-3037, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487596

RESUMO

Perineural invasion (PNI) is detected in 7.0-35.1% of cervical carcinomas. This histological finding correlates with cervical invasion, lymph-vascular space invasion (LVSI), tumor size, positive resection margins, parametrial invasion, node metastases and advanced stage. Some authors have reported that PNI has no prognostic relevance, others have found that PNI is related to disease-free survival or overall survival (OS) at univariate analysis, and others have observed that it is an independent poor prognostic factor for OS. The evaluation of PNI status should be included in the decision-making process for planning adjuvant treatment. PNI has been found in 7.6-52.4% of vulvar carcinomas. This feature, which is strongly associated with depth of invasion, LVSI, tumor size, advanced stage and nodal involvement, is an independent prognostic variable for the risk of recurrence and death in most series. PNI should be evaluated routinely in histopathology reports of vulvar carcinoma and could help clinicians to tailor adjuvant treatment.


Assuntos
Quimioterapia Adjuvante/métodos , Invasividade Neoplásica/patologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/cirurgia , Feminino , Humanos , Prognóstico , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Neoplasias Vulvares/complicações , Neoplasias Vulvares/patologia
9.
Am J Surg Pathol ; 44(9): 1184-1191, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32496434

RESUMO

Tumor cell expression of major histocompatibility complex (MHC) class I is required for antigen presentation and adaptive immune recognition. Absent or diminished MHC class I expression is thought to contribute to immunotherapeutic resistance in some epithelial tumors but has not been previously studied in cervical and vulvar carcinoma. Given that anti-programmed cell death 1 (PD-1) checkpoint inhibition is deployed for programmed cell death ligand 1 (PD-L1)-positive recurrent and metastatic cervical squamous carcinomas, identifying tumors with loss of MHC class I is of clinical interest to optimize the selection of immunotherapeutic candidates. Immunohistochemistry for PD-L1 and MHC class I combined A, B, and C heavy chains (MHC class I) was assessed in 58 human papillomavirus-associated cervical and vulvar lesions, including 27 squamous intraepithelial lesions (SILs) and 31 invasive squamous cell carcinoma (SCC). Although 84% of SCC and 22% of SIL were PD-L1-positive, 35.5% (11/31) of SCC and 18.5% (5/27) of SIL also showed clonal or complete loss of MHC class I. Loss of MHC class I expression was more common in PD-L1-positive (10/26, 38%) versus PD-L1-negative SCC (1/5, 20%). In summary, over one third of human papillomavirus-associated cervical and vulvar SCC show clonal or complete loss of MHC class I expression, including many PD-L1-positive cases. This suggests that the efficacy of checkpoint inhibitors targeting the PD-1/PD-L1 axis may be limited in a subset of cervical and vulvar squamous neoplasms due to an impaired ability to engage with the adaptive immune system related to loss of MHC class I expression.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Escamosas/virologia , Resistencia a Medicamentos Antineoplásicos , Antígenos de Histocompatibilidade Classe I/imunologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/virologia , Neoplasias Vulvares/virologia , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Regulação para Baixo , Feminino , Interações Hospedeiro-Patógeno , Humanos , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Lesões Intraepiteliais Escamosas Cervicais/tratamento farmacológico , Lesões Intraepiteliais Escamosas Cervicais/imunologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/imunologia , Neoplasias Vulvares/patologia
10.
Oncology ; 98(9): 603-611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492692

RESUMO

OBJECTIVES: To analyze the diagnostic accuracy of two-dimensional (2D) and three-dimensional transvaginal ultrasound (3D TV-US) for evaluation of parametrial status in locally advanced cervical cancer patients after neoadjuvant chemotherapy (NACT), using histology as the gold standard. METHODS: Consecutive patients with histologically confirmed cervical cancer were staged according to FIGO (International Federation of Gynaecology and Obstetrics) criteria. All IB2-IIIB FIGO stage patients were examined by 2D and 3D TV-US and magnetic resonance imaging (MRI) at the diagnosis time (T0) and after NACT. At T0, the US evaluation of parametrial involvement was compared to MRI before treatment. The results of US and MRI examinations of parametrial status after NACT were compared with the histological specimen. RESULTS: We enroled 51 consecutive patients in the study. Before chemotherapy, clinical examination under anaesthesia identified parametrial involvement in 48 patients, ultrasonography in 46 patients, and MRI in 49 patients. The agreement between US and MRI was 94%. The sensitivity of US for parametrial status was 93.8%, with a positive predictive value of 97.8%, using MRI as the standard. The correlation between US and MRI was statistically significant (p = 0). After chemotherapy, histological examination of surgical specimens identified parametrial involvement in 3 patients. Ultrasonography correctly identified those cases with parametrial infiltration, recording a sensitivity of 100%, specificity of 90.9%, positive predictive value of 50%, and negative predictive value of 100%. The MRI had a sensitivity of 100%, specificity of 45.5%, positive predictive value of 14.3%, and negative predictive value of 100%, respectively. The concordance in the identification of the presence/absence of infiltration between US and MRI with histology was 90% (p = 0.001) and 61%, respectively, after chemotherapy treatment. Particularly, in defining the degree of infiltration, the agreement between US and MRI with histology was 90 and 58%, respectively. CONCLUSION: In locally advanced cervical cancer patients, 2D/3D TV-US can be considered accurate in the evaluation of parametrial infiltration to assess the response to NACT. It could be included as a diagnostic method in the preoperative work-up of cervical cancer.


Assuntos
Imageamento Tridimensional/métodos , Ultrassonografia Doppler/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Neoplasias do Colo do Útero/patologia
11.
J Cancer Res Clin Oncol ; 146(9): 2189-2203, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32488496

RESUMO

PURPOSE: Cervical cancer metastasis results in poor prognosis and increased mortality, which is not separated from inflammatory reactions accumulated by prostaglandin E2 (PGE2). As a specific G-protein coupled PGE2 receptor, EP3 is demonstrated as a negative prognosticator of cervical malignancy. Now, we aimed to investigate the pathological mechanism of EP3 in modulating cervical cancer carcinogenesis. METHODS: Bioinformatics analysis was used to identify PAI-1 and uPAR correlations with EP3 expression, as well as the prognosis of cervical cancer patients. In vitro analyses were carried out to investigate the role of EP3 on cervical cancer proliferation and migration. RESULTS: In vitro studies showed that sulprostone (an EP3 agonist) enhanced the proliferation and migration of cervical cancer cells, whereas silencing of EP3 inhibited their proliferation and migration. Furthermore, EP3 knockdown increased the expression of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator receptor (uPAR), and phosphorylated extracellular signal-regulated kinases 1/2 (p-ERK1/2), but decreased p53 expression. Bioinformatics analysis showed that both PAI-1 and uPAR were correlated with EP3 expression, as well as the prognosis of cervical cancer patients. The survival analysis further showed that uPAR overexpression (IRS≥2) was correlated with a lower overall survival rate of cervical cancer patients with advanced stages (FIGO III-IV). CONCLUSION: These results indicated that EP3 signaling pathway might facilitate the migration of cervical cancer cells through modulating uPAR expression. Therefore, EP3 and uPAR could represent novel therapeutic targets in the treatment of cervical cancer in advantaged stages.


Assuntos
Movimento Celular/genética , Dinoprostona/genética , Receptores de Prostaglandina E Subtipo EP3/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Transdução de Sinais/genética , Neoplasias do Colo do Útero/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Biologia Computacional/métodos , Dinoprostona/análogos & derivados , Dinoprostona/farmacologia , Feminino , Células HeLa , Humanos , Prognóstico , Transdução de Sinais/efeitos dos fármacos , Análise de Sobrevida , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia
12.
Radiol Med ; 125(12): 1233-1242, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32424659

RESUMO

PURPOSE: To explore the value of histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantitative parameters and apparent diffusion coefficient (ADC) values in predicting the neoadjuvant chemotherapy (NACT) response for cervical cancers. METHODS: Sixty-three patients with pathologically proved stage IB2-IIA2 cervical cancer from March 2013 to January 2017 were retrospectively analyzed. They were divided into two groups on the basis of therapeutic response: the significant response (SR) group, which contains complete response patients and partial response patients, and nonsignificant response (non-SR) group, which contains progressive diseases and stable diseases. Clinical characteristics, DCE-MRI parameters (Ktrans, Kep, Ve), and ADC values before NACT were analyzed and compared between the two groups. RESULTS: SR group and non-SR group were documented in 35 and 28 patients. The mean Ktrans value, 90th percentile Ktrans value, maximal Ktrans value, and 90th percentile ADC value of tumors in SR were significantly higher than those in non-SR group (P = 0.012, P = 0.022, P = 0.005, P = 0.033, respectively), and the mean Ve value and 10th percentile Ve value of tumors were significantly lower in SR group (P = 0.041, P = 0.033, respectively). Kep values did not significantly differ between SR and non-SR. The 90th percentile Ktrans value combined with the 90th percentile ADC value had the highest area under the curve at 0.740 (P = 0.003) to predict NACT effectiveness. CONCLUSION: Histogram analysis of DCE-MRI multi-parameters combined with ADC values may serve as sensitive indicators for predicting NACT effectiveness in cervical cancers.


Assuntos
Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Imagem por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Gadolínio DTPA , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
14.
Phytother Res ; 34(9): 2366-2384, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32364634

RESUMO

Apoptosis and autophagy are important processes that control cellular homeostasis and have been highlighted as promising targets for novel anticancer drugs. This study aims to investigate the inhibitory effects and mechanisms of Neferine (Nef), an alkaloid from the lotus seed embryos of Nelumbo nucifera (N. nucifera), as a dual inducer of apoptosis and autophagy through the reactive oxygen species (ROS) activation in cervical cancer cells. Nef and N. nucifera extract suppressed the cell viability of HeLa and SiHa cells in a dose-dependent manner. Importantly, Nef showed minimal toxicity to normal cells. Furthermore, Nef inhibited anchorage-independent growth, colony formation and migration ability of cervical cancer cells. Nef induces mitochondrial apoptosis by increasing pro-apoptotic protein bax, cytochrome-c, cleaved caspase-3 and caspase-9, poly-ADP ribose polymerase (PARP) cleavage, DNA damage (pH2 AX) while downregulating Bcl-2, procaspase-3 and procaspase-9, and TCTP. Of note, apoptotic effect by Nef was significantly attenuated in the presence of N-acetylcysteine (NAC), suggesting pro-oxidant activity of this compound. Nef also promoted autophagy induction through increasing beclin-1, atg-4, atg-5 and atg-12, LC-3 activation, and P 62/SQSTM1 as determined by western blot analysis. Collectively, these results demonstrate that Nef is a potent anticancer compound against cervical cancer cells through inducing apoptosis and autophagic pathway involving ROS.


Assuntos
Apoptose/efeitos dos fármacos , Benzilisoquinolinas/química , Produtos Biológicos/química , Células HeLa/efeitos dos fármacos , Lotus/química , Sementes/química , Neoplasias do Colo do Útero/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Transfecção
15.
Tumori ; 106(5): 413-423, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32403994

RESUMO

BACKGROUND: Primary cervical leiomyosarcomas (CLMS) constitute 21% of all cervical sarcomas. Because of their rarity, to our knowledge, fewer than 40 cases have been reported. The aim of this study is to evaluate the clinical and surgical-pathological features, prognosis, treatment options, and survival of primary CLMS. METHODS: A systematic review of the medical literature was conducted to evaluate articles about primary CLMS. The literature was searched between 1959 and May 2019. On final evaluation, there were 29 articles (one consisted of 8 cases; one consisted of 3 cases) and 42 cases with the addition of our 4 cases. RESULTS: Age (⩾48 versus ⩽47 years) (hazard ratio.HR], 4.528; 95% confidence interval.CI], 1.550-13.227; p=0.006) and mitoses count (<10/10 high-power field [HPF] versus ⩾10/10 HPF) (HR, 3.865; 95% CI, 1.046-14.278; p=0.043) are independent prognostic factors for recurrence and age (HR, 5.318; 95% CI, 1.671-16.920; p=0.005) and hysterectomy (performed versus not performed) (HR, 4.377; 95% CI, 1.341-14.283; p=0.014) are independent prognostic factors for death because of disease on multivariate analysis. CONCLUSIONS: Information on primary CLMS is sparse and obtained from rare case reports and case series. Hysterectomy must be the first choice of treatment in these patients according to our results on multivariate analysis. The type of hysterectomy does not have an effect on oncologic outcome. Radical hysterectomy is not obligatory and more data are needed to make more accurate conclusions.


Assuntos
Colo do Útero/patologia , Leiomiossarcoma/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Histerectomia , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/patologia , Leiomiossarcoma/radioterapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Radioterapia Adjuvante/efeitos adversos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
17.
Obstet Gynecol ; 135(5): 1070-1083, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32282601

RESUMO

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the efficacy of adjuvant human papillomavirus (HPV) vaccination in preventing recurrent cervical intraepithelial neoplasia (CIN) 2 or greater after surgical excision. DATA SOURCES: Electronic databases (Cochrane, PubMed, EMBASE, MEDLINE, Scopus, and ClinicalTrials.gov) were searched for studies comparing surgical excision alone to surgical excision with adjuvant HPV vaccination for CIN 2 or greater. Studies published from January 1990 to January 2019 were included. METHODS: A total of 5,901 studies were reviewed. The primary outcomes evaluated included: recurrence of CIN 2 or greater, CIN 1 or greater, and HPV 16,18 associated CIN within 6-48 months. We used Covidence software to assist with screening, and meta-analysis was performed using Review Manager. TABULATION, INTEGRATION, AND RESULTS: Six studies met inclusion criteria and were included in the final analysis. In total 2,984 women were included; 1,360 (45.6%) received adjuvant HPV vaccination after surgical excision, and 1,624 (54.4%) received either placebo or surgical management alone for CIN 2 or greater. Recurrence of CIN 2 or greater occurred within 6-48 months in 115 women (3.9%) overall; however, recurrence was significantly lower for vaccinated women: 26 of 1,360 women (1.9%) vs 89 of 1,624 unvaccinated women (5.9%) (relative risk [RR] 0.36 95% CI 0.23-0.55). The risk of CIN 1 or greater was also significantly lower with adjuvant HPV vaccination, occurring in 86 of 1,360 vaccinated women (6.3%) vs 157 of 1,624 unvaccinated women (9.7%) (RR 0.67 95% CI 0.52-0.85). Thirty-five women developed recurrent CIN 2 or greater lesions specific to HPV 16,18; nine received adjuvant vaccination (0.9%) vs 26 who were unvaccinated (2.0%) (RR 0.41 95% CI 0.20-0.85). CONCLUSION: Adjuvant HPV vaccination in the setting of surgical excision for CIN 2 or greater is associated with a reduced risk of recurrent cervical dysplasia overall and a reduction in the risk of recurrent lesions caused by the most oncogenic strains (HPV 16,18). Human papillomavirus vaccination should therefore be considered for adjuvant treatment in patients undergoing surgical excision for CIN 2 or greater. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019123786.


Assuntos
Neoplasia Intraepitelial Cervical/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Infecções por Papillomavirus/complicações , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Neoplasia Intraepitelial Cervical/cirurgia , Neoplasia Intraepitelial Cervical/virologia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/virologia , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
18.
Cancer Chemother Pharmacol ; 85(4): 731-739, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32146495

RESUMO

Lack of cancer-targeted delivery of chemotherapeutics is one of the major obstacles for successful cancer therapy. Nanostructured lipid carriers (NLC) have shown great promise in drug-delivery applications since they are highly scalable, biodegradable nanocarriers with high-drug-loading capacity. However, traditional method prepared NLC, the diameter of which range from 80 to 200 nm, is easily blocked and trapped in perivascular regions without further penetration. As a result, ultrasmall NLC with size under 100 nm or lower range are reported to be ideally tumor targeting carrier as it allows for superior tumor accumulation and permeation. Moreover, surface modification of NLC with folic acid (FA) could significantly increase the drug-delivery efficiency through active targeting effect. In our study, an ultrasmall NLC with FA modification (FA-NLC) was prepared to load docetaxel (DTX) for cancer therapy. Our results showed that DTX-loaded FA-NLC comprised of homogeneous particles with size around 30 nm. In addition, it exhibited great colloidal stability, satisfactory drug-loading efficiency, and high biocompatibility in vitro. Meanwhile, in vivo studies indicated that ultrasmall FA-NLC exhibited greater tumor retention and enhanced antitumor effect compared with control.


Assuntos
Docetaxel/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanoestruturas/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose , Proliferação de Células , Docetaxel/farmacocinética , Feminino , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoestruturas/química , Tamanho da Partícula , Distribuição Tecidual , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Cancer Cytopathol ; 128(7): 491-498, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32125771

RESUMO

BACKGROUND: The cervical cancer screening recommendation for transgender female-to-male (FTM) patients is the same as that for cisgender females. A lack of literature on testosterone-induced changes in cervical cytology in these patients may result in interpretation errors, especially without a proper clinical history. The aim of this study was to delineate the Papanicolaou (Pap) test findings in this patient population. METHODS: A pathology laboratory information system was used to obtain a cohort of FTM transgender patients on testosterone therapy (2009-2019). A cohort of age-matched, atrophic, control cisgender female patients (postpartum or menopausal) was selected. A retrospective review of the cytomorphologic findings on cervical Pap smears, pertinent follow-up, and human papillomavirus (HPV) test results was performed. RESULTS: Fourteen transgender patients (age range, 21-64 years; mean age, 42.5 years) receiving testosterone therapy with 17 Pap smears were identified. One of the 5 available HPV tests was positive for HPV, and 4 were negative. A Pap smear review revealed the following: negative for intraepithelial lesion (NILM; 82.4%), unsatisfactory (5.9%), atypical squamous cells of undetermined significance (ASCUS; 5.9%), and low-grade squamous intraepithelial lesion (5.9%). The Pap smears of the atrophic cisgender cohort (102 patients) revealed the following: NILM (92.5%), unsatisfactory (0.9%), ASCUS (5.6%), and high-grade squamous intraepithelial lesion (0.9%). The difference between the rates of epithelial cell abnormality in the 2 cohorts was not statistically significant. Although atrophy was noted in both groups, cytomorphologic findings of transitional cell metaplasia (TCM; 88.2%) and "small cells" (82.4%) were characteristic of the testosterone-treated transgender cohort. Histologic correlates of TCM and small cells were noted in hysterectomy specimens from 6 patients. CONCLUSIONS: Small cells and TCM are common cytomorphologic findings in Pap smears of testosterone-treated transgender (FTM) patients. On the basis of histologic follow-up, small cells most likely represent atrophic parabasal cells of cervical-vaginal epithelium.


Assuntos
Carcinoma de Células de Transição/patologia , Neoplasia Intraepitelial Cervical/patologia , Citodiagnóstico/métodos , Teste de Papanicolaou/métodos , Infecções por Papillomavirus/complicações , Testosterona/administração & dosagem , Neoplasias do Colo do Útero/patologia , Adulto , Androgênios/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/virologia , Neoplasia Intraepitelial Cervical/tratamento farmacológico , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Pessoas Transgênero , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
20.
Int J Nanomedicine ; 15: 1283-1295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32161458

RESUMO

Background: Cervical cancer stem cells (CCSCs) represent a subpopulation of tumor cells that possess self-renewal capacity and numerous intrinsic mechanisms of resistance to conventional chemotherapy and radiotherapy. These cells play a crucial role in relapse and metastasis of cervical cancer. Therefore, eradication of CCSCs is the primary objective in cervical cancer therapy. Salinomycin (Sal) is an agent used for the elimination of cancer stem cells (CSCs); however, the occurrence of several side effects hinders its application. Nanoscale drug-delivery systems offer great promise for the diagnosis and treatment of tumors. These systems can be used to reduce the side effects of Sal and improve clinical benefit. Methods: Sal-loaded polyethylene glycol-peptide-polycaprolactone nanoparticles (Sal NPs) were fabricated under mild and non-toxic conditions. The real-time biodistribution of Sal NPs was investigated through non-invasive near-infrared fluorescent imaging. The efficacy of tumor growth inhibition by Sal NPs was evaluated using tumor xenografts in nude mice. Flow cytometry, immunohistochemistry, and Western blotting were used to detect the apoptosis of CSCs after treatment with Sal NPs. Immunohistochemistry and Western blotting were used to examine epithelial-mesenchymal transition (epithelial interstitial transformation) signal-related molecules. Results: Sal NPs exhibited antitumor efficacy against cervical cancers by inducing apoptosis of CCSCs and inhibiting the epithelial-mesenchymal transition pathway. Besides, tumor pieces resected from Sal NP-treated mice showed decreased reseeding ability and growth speed, further demonstrating the significant inhibitory ability of Sal NPs against CSCs. Moreover, owing to targeted delivery based on the gelatinase-responsive strategy, Sal NPs was more effective and tolerable than free Sal. Conclusion: To the best of our knowledge, this is the first study to show that CCSC-targeted Sal NPs provide a potential approach to selectively target and efficiently eradicate CCSCs. This renders them a promising strategy to improve the therapeutic effect against cervical cancer.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Piranos/administração & dosagem , Neoplasias do Colo do Útero/patologia , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Gelatinases/metabolismo , Células HeLa , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular , Nanopartículas/administração & dosagem , Células-Tronco Neoplásicas/patologia , Poliésteres/química , Polietilenoglicóis/química , Piranos/farmacocinética , Piranos/farmacologia , Distribuição Tecidual , Neoplasias do Colo do Útero/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
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