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1.
iScience ; 27(6): 109667, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38966570

RESUMO

Our work aimed to investigate the interactive roles of transforming growth factor ß1 (TGF-ß1), ubiquitin-specific-processing protease 7 (USP7), and Yes-associated protein (YAP) in ferroptosis during sepsis-secondary acute lung injury (ALI). Our study demonstrated that ferroptosis was aggravated by TGF-ß1 in both cellular and animal models of acute lung injury. Additionally, YAP upregulated glutathione peroxidase 4 (GPX4) and SLC7A11 by regulating the binding of TEAD4 to GPX4/SLC7A11 promoters. Furthermore, large tumor suppressor kinase 1 (LATS1) knockdown resulted in YAP expression stimulation, while USP7 downregulated YAP via deubiquitinating and stabilizing LATS1/2. YAP overexpression or USP7/LATS1 silencing reduced ferroptosis process, which regulated YAP through a feedback loop. However, TGF-ß1 annulled the repression of ferroptosis by YAP overexpression or LATS1/USP7 knockdown. By elucidating the molecular interactions between TGF-ß1, USP7, LATS1/2, and YAP, we identified a new regulatory axis of ferroptosis in sepsis-secondary ALI. Our study sheds light on the pathophysiology of ferroptosis and proposes a potential therapeutic approach for sepsis-induced ALI.

2.
Phytother Res ; 38(6): 3240-3267, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38739454

RESUMO

Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.


Assuntos
Neoplasias Pulmonares , Polifenóis , RNA Longo não Codificante , RNA Longo não Codificante/genética , Polifenóis/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Animais
3.
J Thorac Dis ; 16(2): 1234-1246, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505042

RESUMO

Background: Idiopathic pulmonary fibrosis (IPF) is an unrepairable disease that results in lung dysfunction and decreased quality of life. Prevention of pulmonary fibrosis is challenging, while its pathogenesis remains largely unknown. Herein, we investigated the effect and mechanism of long non-coding RNA (lncRNA) DNM3OS/Antisense RNA in the pathogenesis of pulmonary fibrosis. Methods: EdU (5-ethynyl-2'-deoxyuridine) and wound healing assays were employed to evaluate the role of DNM3OS on cell proliferation and migration. Western blot detected the proteins expressions of alpha-smooth muscle actin (α-SMA), vimentin, and fibronectin. The interactions among genes were evaluated by RNA pull-down, luciferase reporter, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and chromatin Isolation by RNA purification (ChIRP) assays. Results: DNM3OS was upregulated by transforming growth factor beta 1 (TGF-ß1) in a dose- and time-dependent manner. DNM3OS knockdown repressed the growth and migration of lung fibroblast, and fibrotic gene expression (CoL1α1, CoL3α1, α-SMA, vimentin, and fibronectin), while suppression of TSC2 accelerated the above process. DNM3OS recruited EZH2 to the promoter region of TSC2, increased the occupancy of EZH2 and H3K27me3, and thereby suppressed the expression of TSC2. HOXA5 promoted the transcription of DNM3OS. Conclusions: HOXA5-induced DNM3OS promoted the proliferation, migration, and expression of fibrosis-related genes in human embryo lung fibroblast via recruiting EZH2 to epigenetically suppress the expression of TSC2.

4.
Gynecol Oncol Rep ; 48: 101228, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37389134

RESUMO

Objective: For early-stage cervical cancer patients experiencing radical surgery, postoperative radiotherapy was recommended for patients with a combination of intermediate-risk factors. However, there was no consensus on whether to administer concurrent chemotherapy. The aim of the study was to confirm the clinical value of the controlling nutritional status (CONUT) score in guiding the use of concurrent chemotherapy during postoperative radiotherapy. Methods: A total of 969 patients with FIGO stage IB-IIA cervical cancer were retrospectively analyzed. Kaplan-Meier survival analysis was performed to compare disease-free survival (DFS) and cancer-specific survival (CSS) rates between different group. A Cox proportional hazards regression test was used to conduct multivariate analyses. Results: For the patients in the high CONUT group (≥3), the addition of concurrent chemotherapy had better 5-year DFS (91.2 % vs. 72.8 %, P = 0.005) and CSS (93.8 % vs. 77.4 %, P = 0.013) than those without it. Meanwhile, the patients with concurrent chemotherapy had less rate of locoregional recurrence (8.5 % vs 16.7 %, P = 0.034) and distant metastases (11.7 % vs 30.4 %, P = 0.015). The multivariate analysis showed that concurrent chemotherapy was detected to be a factor significantly associated with DFS (P = 0.011), local control (P = 0.041), distant metastasis (P = 0.005) and CSS (P = 0.023). For the patients in low CONUT group (<3), there was no difference in prognosis between patients. Conclusion: Pretreatment CONUT score may be a predictive factor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors during postoperative radiotherapy, and it can be helpful to determine the adjuvant treatment scheme.

5.
Jpn J Clin Oncol ; 53(2): 122-129, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36408720

RESUMO

OBJECTIVE: Studies determining which early-stage cervical cancer patients with high-risk factors benefit from consolidation chemotherapy after postoperative concurrent chemoradiotherapy (CCRT) are limited and inconsistent. The aim of this study was to evaluate the value of consolidation chemotherapy in early-stage cervical cancer. METHODS: From 2010 to 2019, a retrospective review was conducted among high-risk early-stage cervical cancer patients who were treated with postoperative CCRT or consolidation chemotherapy after postoperative CCRT. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 293 patients with early-stage cervical cancer were included in this study. A total of 188 patients were in the consolidation chemotherapy group, and 105 patients were in the postoperative CCRT alone group. The median follow-up was 48.3 months (range: 3-123 months). In the survival analyses, no significant differences in DFS (P = 0.21) or OS (P = 0.15) were observed between the groups. The grade 3-4 leukopenia and neutropenia rates in the consolidation group were higher than those in the concurrent chemoradiotherapy alone group (54.8% vs. 28.6%, P = 0.02; 49.4% vs. 10.5%, P = 0.001, respectively). For patients with ≥2 positive lymph nodes or ≥2 high-risk factors, consolidation chemotherapy significantly improved DFS (P = 0.013 and P = 0.002) and OS (P < 0.001 and P < 0.001) compared with CCRT alone. CONCLUSION: For early-stage cervical cancer, consolidation chemotherapy after postoperative CCRT improved survival outcomes in patients with ≥2 positive lymph nodes or ≥2 high-risk factors.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Quimioterapia de Consolidação/métodos , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Estudos Retrospectivos
6.
J Clin Med ; 11(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36498728

RESUMO

OBJECTIVE: The process of normal cervix changing into high grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer is long and the mechanisms are still not completely clear. This study aimed to reveal the protein profiles related to HSIL and cervical cancer and find the diagnostic and prognostic molecular changes. METHODS: Data-independent acquisition (DIA) analysis was performed to identify 20 healthy female volunteers, 20 HSIL and 20 cervical patients in a cohort to screen differentially expressed proteins (DEPs) for the HSIL and cervical cancer. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional annotation of DEPs; the protein-protein interaction (PPI) and weighted gene co-expression network analysis (WGCNA) were performed for detection of key molecular modules and hub proteins. They were validated using the Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: A total of 243 DEPs were identified in the study groups. GO and KEGG analysis showed that DEPs were mainly enriched in the complement and coagulation pathway, cholesterol metabolism pathway, the IL-17 signaling pathway as well as the viral protein interaction with cytokine and cytokine receptor pathway. Subsequently, the WGCNA analysis showed that the green module was highly correlated with the cervical cancer stage. Additionally, six interesting core DEPs were verified by ELISA, APOF and ORM1, showing nearly the same expression pattern with DIA. The area under the curve (AUC) of 0.978 was obtained by using ORM1 combined with APOF to predict CK and HSIL+CC, and in the diagnosis of HSIL and CC, the AUC can reach to 0.982. The high expression of ORM1 is related to lymph node metastasis and the clinical stage of cervical cancer patients as well as the poor prognosis. CONCLUSION: DIA-ELSIA combined analysis screened and validated two previously unexplored but potentially useful biomarkers for early diagnosis of HSIL and cervical cancer, as well as possible new pathogenic pathways and therapeutic targets.

7.
Front Cell Dev Biol ; 8: 561804, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33163485

RESUMO

BACKGROUND: Ovarian cancer has the highest mortality rate among gynecologic cancers, and most patients are diagnosed in advanced stages. Enhancer of zeste homolog 2 (EZH2) is a major tumor marker and an effective therapeutic target for ovarian cancer, but the underlying molecular mechanism remains unclear. The present study investigated the biological effects of EZH2 knockout in SKOV3 cells in vitro and in vivo and explored the molecular mechanism by integrated analysis of messenger RNA sequencing (mRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) data. METHODS: The CRISPR/Cas9 system was used to establish EZH2 knockout SKOV3 cells. Protein expression was evaluated by Western blotting. The effect of EZH2 on ovarian cancer was evaluated in vitro with MTT, wound healing, Transwell, and apoptosis assays and in vivo with a xenograft model. mRNA-seq and ChIP-seq were performed to explore the molecular mechanism underlying the biological function of EZH2. Immunohistochemical staining (IHC) of tissue arrays was used to analyze the correlations among EZH2 and CYP27B1 expressions and prognosis. RESULTS: We obtained three EZH2 knockout subclones. EZH2 knockout SKOV3 cells exhibited significantly suppressed proliferation, migration, and invasion and a significantly increased apoptosis rate. The subcutaneous tumor formation rate decreased from 100 to 0% in the EZH2 knockout group. Integrated analysis of the mRNA-seq and ChIP-seq data identified 1,455 significantly upregulated genes with matching downregulated trimethylation of histone H3 lysine 27 (H3K27me3) methylation binding sites in 1b11H cells compared to SKOV3 cells. The set of downregulated genes in EZH2 knockout cells was highly enriched in genes regulating the activation of steroid biosynthesis; the top-ranked hub gene was CYP27B1. The EZH2 and CYP27B1 expression levels showed a statistically significant inverse correlation, which was also associated with unfavorable prognosis. The in vitro experiment demonstrated that CYP27B1 can suppress the proliferation, migration, and invasion of ovarian cancer cells. Moreover, the levels of AKT and p-AKT were significantly increased, whereas STAT3 was downregulated, in 1b11H cells compared to SKOV3 cells. Moreover, STAT3 and AKT overexpression was observed in 1b11H siRNA for CYP27B1 (siCYP27B1) cells. CONCLUSION: EZH2 plays an important role in promoting cell proliferation, migration, and invasion in ovarian cancer by regulating the core steroid biosynthesis gene via H3K27me3 methylation. Moreover, CYP27B1, the steroid biosynthesis hub gene, might be a novel therapeutic target for ovarian cancer.

8.
Cancer Manag Res ; 11: 8081-8093, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507330

RESUMO

BACKGROUND: It is unclear whether low density lipoprotein receptor-related protein 11 (LRP11), a newly found lipoprotein receptor regulatory protein, has the carcinogenic effects in cervical cancer. METHODS: Bioinformatics analysis, immunohistochemical (IHC) staining and evaluation, cell proliferation assay, flow cytometry, transwell migration and invasion assays, Western blotting, growth of LRP11-silenced cells in athymic nude mice were performed in this research. RESULTS: We found that LRP11 expression was higher in high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissue than in normal cervix, and high expression of LRP11 was associated with differentiation degree (P=0.0266), indicating poor prognosis (P=0.0210). The silencing of LRP11 in SiHa and CaSki cell lines inhibited cell proliferation, reduced migration and invasion and suppressed cell growth in nude mice, which possibly related to cell cycle protein regulation of CDK 2/4, cyclin D1/E1, MMP-2/9, and VEGF. Furthermore, LRP11 showed substantial positive correlation with P16 in vivo and in vitro. CONCLUSION: LRP11 plays important roles in proliferation, migration and invasion, with the potential to be a useful prognostic marker and therapeutic target for patients with HSIL and cervical cancer.

9.
Exp Cell Res ; 371(1): 222-230, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30099052

RESUMO

Although persistent human papilloma virus (HPV) infection exerts a crucial influence on cervical carcinogenesis, other factors are also involved in its development, such as intraepithelial lesions and cervical cancer. B7-H3 and B7-H4, which have been reported to be co-regulatory ligands in the B7 family, had been found to be overexpressed in cervical cancer and correlated with adverse clinicopathological features and poor prognosis in our previous studies. In this study, we sought to explore the effects of B7-H3 and B7-H4 on the cervical microenvironment. Among several immune cytokines, interleukin-10 (IL-10) and transforming growth factor (TGF) ß1 stand out as important immunosuppressive factors. Our studies found that IL-10 expression increased with pathological change levels and significantly correlated with cervical cancer differentiation (P < 0.05). TGF-ß1 correlated with lymph node metastasis (LNM) (P < 0.01). Expression of B7-H3 and B7-H4 positively correlated with the expression of IL-10 and TGF-ß1. After co-culture, we found that overexpression of B7-H3 and B7-H4 in cervical cancer cell lines resulted in activation of the cell cycle and decreased apoptosis of U-937 cells. In addition, the contents of IL-10 and TGF-ß1, as well as their protein expression levels, increased in co-culture supernatants in U-937 cells, suggesting regulation by the p-JAK2/STAT3 pathway. The in vivo results demonstrated that with the increasing expression of B7-H3/B7-H4, the expression of IL-10 and TGF-ß1 also increased significantly. Overall, the expression of B7-H3 and B7-H4 favored an immunosuppressive microenvironment by promoting the production of IL-10 and TGF-ß1, thereby resulting in progression of cervical carcinogenesis.


Assuntos
Antígenos B7/genética , Regulação Neoplásica da Expressão Gênica , Interleucina-10/genética , Fator de Crescimento Transformador beta1/genética , Microambiente Tumoral/genética , Neoplasias do Colo do Útero/genética , Inibidor 1 da Ativação de Células T com Domínio V-Set/genética , Adulto , Animais , Apoptose/genética , Antígenos B7/imunologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Células HeLa , Xenoenxertos , Humanos , Interleucina-10/imunologia , Metástase Linfática , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Transdução de Sinais , Análise de Sobrevida , Fator de Crescimento Transformador beta1/imunologia , Microambiente Tumoral/imunologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Inibidor 1 da Ativação de Células T com Domínio V-Set/imunologia
10.
J Cancer ; 9(15): 2612-2624, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30087701

RESUMO

B7-H3, which has been reported to be a co-regulatory ligand of the B7 family, can suppress T cell-mediated immunity and has also been reported to be expressed in many malignancies. In this study, we found that B7-H3 was primarily expressed in the cytoplasm of cervical cancer cells and was associated with deep stromal invasion (P=0.0013). The disease-free survival data showed that cervical cancer patients whose tumours were positive for B7-H3 expression had higher mortality rates compared with patients whose tumours lacked B7-H3 expression (P=0.0317), representing an advantage over P16 (P=0.3486). In contrast, the level of serum B7-H3 was low in cases of cervical intraepithelial neoplasia and cervical cancer. The silencing of B7-H3 in the SiHa, CaSki and H8 cell lines inhibited cell proliferation and enhanced apoptosis, while the over-expression of B7-H3 in HeLa cells showed inverse changes. These changes were partially due to the regulation of cell cycle- and apoptosis-related proteins, such as E2F, P21, P16, PARP-1, Caspase-8, Bax, Bcl-2 and Bcl-xl. The results of in vivo experiments revealed that the knockdown of B7-H3 in tumour cells suppressed SiHa cell growth in nude mice. Overall, B7-H3 is involved in the development and progression of cervical intraepithelial neoplasia and cervical cancer through its effects on the cell cycle and apoptosis, which are mediated via the E7/Rb pathway. B7-H3 also has the potential to be a useful prognostic marker for patients with cervical cancer.

11.
J Ovarian Res ; 11(1): 31, 2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29685168

RESUMO

BACKGROUND: B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) might be an appropriate biomarker in the management of epithelial ovarian cancer (EOC). However, the biological role of BMI1 and its relevant molecular mechanism needs further elaboration. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is an excellent genome-editing tool and is scarcely used in EOC studies. METHODS: We first applied CRISPR/Cas9 technique to silence BMI1 in EOC cells; thereafter we accomplished various in vivo and in vitro experiments to detect biological behaviors of ovarian cancer cells, including MTT, flow cytometry, Transwell, real-time polymerase chain reaction and western blotting assays, etc.; eventually, we used RNA sequencing to reveal the underlying molecular traits driven by BMI1 in EOC. RESULTS: We successfully shut off the expression of BMI1 in EOC cells using CRISPR/Cas9 system, providing an ideal cellular model for investigations of target gene. Silencing BMI1 could reduce cell growth and metastasis, promote cell apoptosis, and enhance the platinum sensitivity of EOC cells. BMI1 might alter extracellular matrix structure and angiogenesis of tumor cells through regulating Focal adhesion and PI3K/AKT pathways. CONCLUSION: BMI1 is a potential biomarker in EOC management, especially for tumor progression and chemo-resistance. Molecular traits, including BMI1 and core genes in Focal adhesion and PI3K/AKT pathways, might be alternatives as therapeutic targets for EOC.


Assuntos
Sistemas CRISPR-Cas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Complexo Repressor Polycomb 1/genética , Animais , Apoptose , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Movimento Celular/genética , Citometria de Fluxo , Adesões Focais/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Camundongos , Invasividade Neoplásica/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Complexo Repressor Polycomb 1/antagonistas & inibidores , Análise de Sequência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Oncol Rep ; 38(4): 2426-2434, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765941

RESUMO

B7-H3, a co-stimulatory molecule, has been found expressed in ovarian cancer, but its role and mechanism is not clear. In this study, we further verified the expression of B7-H3 in ovarian carcinoma and normal epithelial ovarian tissues. Three ovarian cancer cell lines, A2780, SKOV3 and HO8910 were selected to explore the effects of B7-H3 on proliferation, apoptosis, migration and invasion. We found that B7-H3 was mainly located in the cytoplasm of ovarian cancer cells as determined by immunofluorescence staining. The ability of cell invasion, migration, proliferation decreased after silencing B7-H3 whereas the apoptosis increased, which was related to the upregulation of Bax, caspase-8, cleaved caspase-8 and the downregulation of Bcl-2, Bcl-xl, matrix metalloproteinase-2 (MMP2) by western blotting. In addition, B7-H3 enhanced the H08910 cell capacities in invasion, migration and proliferation. Expression of the phosphorylation signal transducer and activator of transcription 3 (pStat3) molecules and their upstream molecules phosphorylation Janus kinase 2 (pJak2) were significantly increased. In order to investigate whether B7-H3 plays a role in this pathway, we treated the overexpressed HO8910 cells with AG490 (inhibitors of Jak2). Our findings revealed that B7-H3 affect ovarian cancer progression through the Jak2/Stat3 pathway, indicating that B7-H3 has the potential to be a useful prognostic marker.


Assuntos
Antígenos B7/genética , Biomarcadores Tumorais/genética , Janus Quinase 2/genética , Neoplasias Ovarianas/genética , Fator de Transcrição STAT3/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Janus Quinase 2/antagonistas & inibidores , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Ovarianas/patologia , Transdução de Sinais/genética , Tirfostinas/administração & dosagem
13.
Oncol Rep ; 38(2): 1043-1050, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28627681

RESUMO

B7-H3 is an immune regulatory molecule whose aberrant expression in tumors is associated with adverse outcomes. Upregulation of B7-H3 may promote tumor cell proliferation and metastasis in vitro, but the role of B7-H3 in cervical cancer has not yet been investigated. We measured B7-H3 expression in 90 cervical cancer patient and 20 non­cervical lesion patient tissues using immunohistochemistry and in 30 cervical cancer patient and 30 healthy donor blood samples using ELISA. The association of B7-H3 expression and the prognosis of cervical cancer patients was investigated. B7-H3 knockdown in CaSki and SiHa cell lines was performed using small hairpin (sh)RNA lentiviral transfection and B7-H3 overexpression in CaSki and HeLa cell lines was performed using plasmid-vector lentivirus transduction. Cell proliferation, invasion and migration were then measured using MTT and Transwell assays in vitro. B7-H3 expression was significantly higher in the cervical cancer tissues compared to that noted in the normal cervical tissues (mean 72.22 vs. 15.00%; p<0.001). Using Kaplan­Meier and Cox analyses, our data revealed that patients with strong intensity staining were significantly more likely to have a worse prognosis. The B7-H3 level in cervical cancer patient blood was significantly higher than that in the normal donors (13.41±6.12 vs. 9.90±3.16 ng/ml; p=0.007). MTT assay revealed that high expression of B7-H3 promoted cervical cancer cell proliferation. Transwell assay data revealed that high expression of B7-H3 enhanced cervical cancer cell migration and invasion (CaSki, p=0.003; HeLa, p=0.03). In conclusion, expression of B7-H3 was significantly higher in cervical cancer tissues compared to normal cervical tissues, and this high expression was associated with worse prognosis for cervical cancer patients. In addition, B7-H3 promoted proliferation, invasion and migration of cervical cancer and may be a potential target for treating cervical cancer.


Assuntos
Adenocarcinoma/secundário , Antígenos B7/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/secundário , Movimento Celular , Proliferação de Células , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/metabolismo , Adolescente , Adulto , Idoso , Apoptose , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
14.
Oncol Rep ; 37(4): 2308-2316, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28260085

RESUMO

Recent studies have reported that the immune-regulatory protein B7-H4 is highly expressed in various types of cancer, but little is known concerning its roles in cervical cancer. In the present study, we investigated the expression of B7-H4 in human tissues and serum samples, and explored the effects of B7-H4 on proliferation, apoptosis, migration and invasion of cervical cancer cell lines, including SiHa and HeLa. We found that B7-H4 was mainly located in the cytoplasm of cervical cancer cells as determined by immunofluorescence staining. Serum B7-H4 (sB7-H4) was overexpressed in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer, and the area under the ROC curve (AUC) was 0.955. There was no statistical significance between B7-H4 expression and clinicopathological factors in cervical cancer tissue samples. B7-H4 promoted the proliferation of SiHa and HeLa cells, and protected them from apoptosis, which was related to the upregulation of E7, phosphorylated Rb (pRb), E2F, P16, P21, Bcl-2 and the downregulation of Rb, cleaved PARP and cleaved caspase-3 as determined by western blotting. In addition, B7-H4 increased the ability of cell migration and invasion by targeting angiogenic factors, matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF) as determined by RT-PCR. Our findings revealed that B7-H4 has the potential to be a useful prognostic marker. In addition, B7-H4 plays important roles in proliferation, apoptosis, migration and invasion, indicating that B7-H4 can serve as a new therapeutic target for cervical cancer.


Assuntos
Regulação para Cima , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Inibidor 1 da Ativação de Células T com Domínio V-Set/genética , Inibidor 1 da Ativação de Células T com Domínio V-Set/metabolismo , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Invasividade Neoplásica , Transdução de Sinais , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/metabolismo
15.
Wei Sheng Yan Jiu ; 46(6): 861-867, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29903192

RESUMO

OBJECTIVE: To study the differences in food consumption among rural residents in various regions of China, and to analyze the climatic factors that affect the food consumption of rural residents. METHODS: Based on the consumption data of 13 kinds of food of rural residents including wheat, rice, other grain, fresh vegetables, pork, beef and mutton, poultry, eggs and related products, milk and related products, aquatic products, edible oil, sugar and liquor collected from the China Statistical Yearbook and China's Economic and social data research platform during 2000 to 2012, cluster analysis was conducted to partition the dietary structure and compare the differences in food consumption in each geographical area. Selecting the average temperature, annual temperature difference, daily temperature difference, average air pressure, average daily precipitation, average wind speed, average relative humidity, average sunshine duration, 8 climatic factors as independent variables from the "Dataset of daily surface observations values in individual years( 1981-2010) in China "and "Dataset of annual values of climate data from Chinese surface stations for global exchange " released by China Meteorological Data Service Center to establish a multivariate linear regression model to study the correlation between food consumption and climate. RESULTS: The geographical partition of dietary structure of rural residents in China was as follows: Beijing-Tianjin region, northeast region, upstream and downstream parts of the Yellow River region, southeast coastal area, the part middle and lower reaches of the Yangtze River region, Lingnan area, southwest region, Inner Mongolia, Tibet, Qing-Xin( Qinghai and Xinjiang)region. In the comparison of annual per capita food consumption in various regions: the consumption of eggs and related products( 12. 96 kg) and edible oil( 10. 18 kg) in BeijingTianjin region, vegetable( 128. 20 kg) in northeastern region, aquatic products( 15. 81 kg) and liquor( 19. 04 kg) in the southeastern coastal areas, rice( 189. 36 kg) and poultry( 10. 17 kg) in Lingnan area, pork( 26. 46 kg) in southwest China, other food( 126. 31 kg), milk and related products( 32. 38 kg), beef and mutton( 12. 87 kg) and sugar( 2. 65 kg) in Tibet, and wheat( 184. 63 kg) in Qingxin region was the highest in China. While the consumption of sugar( 0. 79 kg) in northeastern region, other food( 10. 64 kg) in the southeastern coastal areas, wheat( 0. 60 kg) and milk and related products( 0. 33 kg) in Lingnan area, beef and mutton( 0. 43 kg) in southwest China, edible oil( 4. 21 kg) in Inner Mongolia, vegetables( 19. 21 kg), eggs and related products( 0. 60 kg), aquatic products( 0. 01 kg), pork( 2. 23 kg) and poultry( 0. 03 kg) in Tibet, and rice( 13. 00 kg)and liquor( 2. 25 kg) in Qing-Xin regions was the lowest in China. The result of multiple linear regression analysis of climate and food consumption showed that consumption of wheat in staple foods was negatively correlated with average daily precipitation( P < 0. 01, Adj. R~2= 0. 632); and there was a positive correlation between rice consumption and average daily precipitation, and a negative correlation with average temperature and daily temperature difference( P < 0. 01, Adj. R~2= 0. 839). There was a positive correlation between vegetable consumption and annual temperature difference, and negative correlation with average sunshine duration( P < 0. 01, Adj. R~2= 0. 450). The pork consumption was negatively correlated with the average sunshine duration( P < 0. 01, Adj. R~2= 0. 386). CONCLUSION: The dietary structure of rural residents in China can bedivided into 10 kinds of geographical partitions. Average daily precipitation is negatively and positively correlated with consumption of wheat and rice, respectively. Average sunshine duration has negative impact on vegetable and pork consumption. Average temperature and daily temperature difference are negatively correlated with rice consumption. And annual temperature difference has positive impact on vegetable consumption.


Assuntos
Clima , Dieta , Alimentos , População Rural , Pequim , China , Humanos , Tibet , Verduras
16.
Onco Targets Ther ; 9: 5203-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27578986

RESUMO

Epithelial ovarian cancer, a vexing challenge for clinical management, still lacks biomarkers for early diagnosis, precise stratification, and prognostic evaluation of patients. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), a member of the polycomb group of proteins, engages in diverse cellular processes, including proliferation, differentiation, senescence, and stem cell renewal. In addition, BMI1, as a cancer stem-cell marker, participates in tumorigenesis through various pathways. Rewardingly, recent studies have also revealed a relationship between BMI1 expression and the clinical grade/stage, therapy response, and survival outcome in a majority of human malignancies, including epithelial ovarian cancer. Therefore, BMI1 might serve as a potential stratification factor and treatment target for epithelial ovarian cancer, pending evidence from further investigations.

17.
BMC Cancer ; 16: 73, 2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26858203

RESUMO

BACKGROUND: Intravenous leiomyomatosis (IVL) extending to inferior vena cava and heart is one of the most challenging conditions for surgical treatment. We explored the use of computerized tomography angiography (CTA) in preoperative assessment for this disease. METHODS: A cohort of 31 patients with IVL extending to inferior vena cava and heart were reviewed from the year 2002 to 2014, focusing on the preoperative CTA imaging characteristics and the surgical procedures in clinical treatment. RESULTS: All patients were diagnosed correctly combining the clinical medical history and CTA imaging. Thirteen patients had tumors confined within the inferior vena cava, and 18 patients had tumors intruding into the right heart. Furthermore, 15 tumors were located in the right atrium alone, and 3 tumors involved both the right atrium and the right ventricle. All patients had simple or multiple soft tissue masses from the pelvis, with 22 tumors extending into inferior vena cava through the iliac veins and 9 tumors through the ovarian veins. Three patients had tumors invading into lung and underwent tumor thrombus resection in the pulmonary artery. Patients received either one-stage surgery or two-stage surgery dependent on patient general condition and tumor status. All operations were successfully performed by multidisciplinary cooperation, including gynecology, cardiac surgery, and vascular surgery, without severe surgical-related complications or deaths. CONCLUSIONS: CTA imaging can present location, size, and full-scale extension pathway of IVL lesions, and can be used as first-line imaging technique in preoperative assessment, having great significance in making surgical plan and obtaining successful outcome.


Assuntos
Neoplasias Cardíacas/diagnóstico por imagem , Leiomiomatose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Neoplasias Uterinas/diagnóstico por imagem , Adulto , Angiografia/métodos , Feminino , Coração/diagnóstico por imagem , Coração/fisiopatologia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Leiomiomatose/complicações , Leiomiomatose/patologia , Leiomiomatose/cirurgia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Artéria Pulmonar/cirurgia , Neoplasias Uterinas/complicações , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia
18.
BMC Cancer ; 15: 270, 2015 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-25886261

RESUMO

BACKGROUND: Owing to the rarity of sex cord tumor with annular tubules (SCTAT), it is difficult to recognize SCTAT clinically and there is no standard treatment. The aim of our study was to investigate the treatment outcomes and prognosis of patients with ovarian SCTAT. METHODS: A cohort of 13 patients with SCTAT diagnosed and treated in Peking Union Medical College Hospital was studied. Data on clinicopathological characteristics, treatment, and prognosis were retrospectively reviewed and analyzed. RESULTS: SCTAT accounted for 1.4% of ovarian sex cord stromal tumors, with an average onset age of 22.6 years. All patients presented with menstrual disturbances or isosexual precocity at disease onset. Initial surgery was unilateral salpingo-oophorectomy in 11 cases. Recurrence rate was 46.2%, and 38.5% of patients experienced multiple recurrences. The disease free interval gradually shortened with increasing numbers of recurrences. Recurrent tumors were mostly ipsilateral to the primary tumor and located in retroperitoneum. Surgery remained the main treatment for recurrent cases. Serum estradiol and progesterone levels usually elevated at disease onset, decreased dramatically after operation, and they elevated again with the development of recurrence. The median progression-free survival (PFS) was 97.8 months, and the 1-year and 5-year PFS were 92% and 67%, respectively. Five-year overall survival (OS) was 100%. CONCLUSIONS: Unilateral salpingo-oophorectomy is a feasible treatment for primary SCTAT cases with intact capsules and without PJS. Complete tumor resection is suggested for recurrent cases and long-term follow-up is strongly recommended. Despite the high risk of recurrence, SCTAT prognosis is relatively favorable.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Síndrome de Peutz-Jeghers/cirurgia , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Ovariectomia , Síndrome de Peutz-Jeghers/patologia , Prognóstico , Estudos Retrospectivos , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Resultado do Tratamento
19.
J Gynecol Oncol ; 25(4): 293-300, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25142622

RESUMO

OBJECTIVE: To explore appropriate treatment modality of microinvasive cervical cancer (MIC) and to analyze prognosis and risk factors of recurrence. METHODS: A cohort of 324 Chinese patients with MIC diagnosed and treated at Peking Union Medical College Hospital was retrospectively reviewed. Demographic features, treatment modalities, pathologic parameters, risk factors of residual disease, survival and risk factors of recurrence were analyzed. RESULTS: Of all patients, 280 cases were staged IA1 and 44 cases staged IA2 MIC. Twenty-five cases (7.7%) were found to have lympho-vascular space involvement (LVSI), but no parametrial involvement or ovarian metastasis was detected. Only one staged IA2 patient with LVSI was found to have lymph node metastasis. 32.4% patients (82/253) had residual diseases after conization. No significant difference of LVSI, lymph node metastasis and residual disease after coniztion was found between stage IA1 and IA2 MIC patients. Multivariate logistic analysis showed positive margin was the only independent risk factor of residual disease after conization (odds ratio [OR], 4.18; p<0.001). Recurrence occurred in five cases, but no mortality was found. Progression-free survival for stage IA1 patients treated by conization or hysterectomy was similar (92.3% and 98.8%, p=0.07). Cox regression analysis revealed LVSI as an independent risk factor for recurrence in stage IA1 patients (OR, 12.14; p=0.01). CONCLUSION: For stage IA1 patients with negative resection margin and no LVSI, conization can be an ideal treatment modality. For stage IA2 patients, more conservative surgery such as simple hysterectomy may be considered. LVSI is an independent risk factor for recurrence in patients with stage IA1 cervical cancer.


Assuntos
Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Estudos de Coortes , Conização/métodos , Feminino , Humanos , Histerectomia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasia Residual , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Adulto Jovem
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