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1.
Artigo em Inglês | MEDLINE | ID: mdl-32462235

RESUMO

OBJECTIVE: White matter lesions (WMLs) are the most common central nervous system changes observed during cochlear implant evaluation. However, its clinical significance in cochlear implantation (CI) remains unclear. The purpose of this study is to explore the effects of WMLs on hearing and speech rehabilitation of prelingually deaf children after CI. METHODS: The data of forty-five children with WMLs who received CI from 2011 to 2014 were retrospectively reviewed. All patients underwent magnetic resonance imaging examination preoperatively. The categories of auditory performance (CAP) and speech intelligibility rating (SIR) scales were used to evaluate changes in the auditory and speech abilities of the patients, and the Fazekas scale was adopted to assess the extent of WMLs. The degree of WMLs was divided into four grades (none, mild, moderate, severe). We assessed hearing and speech abilities at the following time points: 6, 12, 24, 36, 48 and 60-months post-operation. RESULTS: No significant differences in CAP scores were observed between WMLs groups and the control group at 12 months post-CI (p = 0.099), but marked between-group differences were found at 6, 24, 48- and 60-months post-CI. (p < 0.05). Similarly, no significant differences in the SIR scores were observed at 6 months post-CI (p = 0.087), but marked between-group differences were found at 12, 24, 48- and 60- months post-CI. (p < 0.05). Analysis of stratified group results revealed improvements in hearing and speech development for all the subgroups, including the severe WMLs subgroup following CI. However, hearing and speech ability of the severe WMLs subgroup was much slower than that of other groups. CONCLUSIONS: The auditory and speech abilities of prelingually deaf children with WMLs and those without WMLs can improve after CI. Therefore, WMLs should not be considered a contraindication for CI. However, the decision to perform CI in such patients needs a comprehensive evaluation because the post-surgery effects on children with severe WMLs are not ideal.

2.
Eur Arch Otorhinolaryngol ; 277(5): 1281-1287, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32002612

RESUMO

OBJECTIVE: This study aimed to clarify the role and safety of balloon eustachian tuboplasty (BET) in the treatment of otitis media with effusion (OME) in children. METHODS: This retrospective study was performed between January 2017 and February 2018. The study covered 25 OME patients treated with BET combined with myringotomy and tube insertion (MTI), designated as the BET group, and 24 OME patients treated with MTI during the same period considered as the controls. In addition, all patients received adenoidectomy if found with adenoid hypertrophy. The air-bone conduction gap (ABG) and curative effect were compared between the two groups. Tubomanometry (TMM) results were recorded preoperatively to confirm existence of eustachian tube dysfunction (ETD). Otologic history and examination results of all patients were carefully recorded before the operation, at 6, 12 and 18 months postoperatively. RESULTS: Six months after surgery, ABG difference between the two groups was less than 1 dB HL. At 12 months after the operation, ABG in the BET group was smaller than that in the control group. There was a marked ABG deterioration (from 10.1 to 15.9 dB HL) in the control group compared to that in BET. Statistically significant differences in ABG difference between the two groups were observed 18 months after surgery with cured and total effective rates of BET at 76.1 and 93.5%, respectively. In the control group, these rates were 60.9 and 89.1% respectively. No serious complications and tympanic perforations were found in all subjects. CONCLUSION: MTI combined with BET is effective and safe in the treatment of children with OME. Compared to simple MTI, application of BET can effectively extend improvement period and increase cured rate, especially after removal of the ventilation tube. Directly benefit from the ventilation tube, the curative effect was close during the period of tube retention. Considering the sample size and follow-up time of this study, related studies targeting large cohorts are needed in the future to validate the benefits of BET in children with OME.

3.
Cell Res ; 30(1): 34-49, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31811277

RESUMO

Metastasis, the development of secondary malignant growths at a distance from a primary tumor, is the cause of death for 90% of cancer patients, but little is known about how metastatic cancer cells adapt to and colonize new tissue environments. Here, using clinical samples, patient-derived xenograft (PDX) samples, PDX cells, and primary/metastatic cell lines, we discovered that liver metastatic colorectal cancer (CRC) cells lose their colon-specific gene transcription program yet gain a liver-specific gene transcription program. We showed that this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical enhancers and super-enhancers. Further, we identified that the liver-specific transcription factors FOXA2 and HNF1A can bind to the gained enhancers and activate the liver-specific gene transcription, thereby driving CRC liver metastasis. Importantly, similar transcription reprogramming can be observed in multiple cancer types. Our data suggest that reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically.

4.
Cancer Lett ; 466: 49-60, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31542354

RESUMO

Acquired resistance to 5-fluorouracil (5-FU) is a major barrier to benefit from chemotherapy in colon cancer patients. Hydrogen sulfide (H2S), mainly produced by cystathionine-ß-synthase (CBS), has been reported to promote the proliferation and migration of colon cancer cells. In this study, the effect of inhibiting H2S synthesis on the sensitivity of colon cancer cell lines to 5-FU was investigated. Increased expression of CBS was validated in online database and tissue microarrays. Inhibiting H2S synthesis significantly sensitized colon cancer cell lines to 5-FU both in vitro and in vivo. Decreasing H2S synthesis utilizing shRNA lentiviruses significantly reversed the acquired resistance to 5-FU. MicroRNA sequencing was performed and miR-215-5p was revealed as one of the miRNAs with most significantly altered expression levels after CBS knock down. Epiregulin (EREG) and thymidylate synthetase (TYMS) were predicted to be potential targets of miR-215-5p. Decreasing H2S synthesis significantly decreased the expression of EREG and TYMS. These results demonstrate that inhibiting H2S synthesis can reverse the acquired resistance to 5-FU in colon cancer cells.

5.
Mediators Inflamm ; 2019: 5796491, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354386

RESUMO

Escherichia coli Nissle 1917 (EcN), a kind of probiotic, has been reported to have a protective effect on the intestinal barrier function and can ameliorate certain gastrointestinal disorders. In this study, the potential protective effect of EcN on the intestinal barrier function in a septic mouse model induced by cecal ligation and puncture (CLP) operation was investigated. FITC-Dextran 4,000 Da (FD-4) flux and the expression levels of tight junction (TJ) proteins were measured to evaluate the protective effect of EcN on the intestinal barrier function. Then, Caco-2 monolayers were utilized to further investigate the protective effect of the EcN supernatant (EcNsup) on the barrier dysfunction induced by TNF-α and IFN-γ in vitro; the plasma level of both the cytokines increased significantly during sepsis. Transepithelial electrical resistance (TEER) and FD-4 transmembrane flux were measured, and the localization of ZO-1 and Occludin was investigated by immunofluorescence. The expression of MLCK and the phosphorylation of MLC were detected by western blot. The activation of NF-κB was explored by immunofluorescence, and CHIP assays were performed to investigate the conjunction of NF-κB with the promoter of MLCK. The results indicated that EcN protected the intestinal barrier function in sepsis by ameliorating the altered expression and localization of TJ proteins and inhibiting the NF-κB-mediated activation of the MLCK-P-MLC signaling pathway which might be one of the mechanisms underlying the effect of EcN.


Assuntos
Escherichia coli/fisiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , NF-kappa B/metabolismo , Animais , Western Blotting , Células CACO-2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Fosforilação/fisiologia , Sepse/metabolismo , Transdução de Sinais , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Fator de Transcrição RelA/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
6.
Life Sci ; 231: 116529, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31173781

RESUMO

AIMS: The present study investigated the effect of Escherichia coli Nissle 1917 (EcN) on irinotecan-induced intestinal barrier dysfunction and gut microbial dysbiosis in a mouse model and in the human colonic cells lines Caco-2. MATERIALS AND METHODS: Male BALB/c mice received irinotecan intraperitoneal injection with or without EcN administration intragastrically. Body weight, diarrhea severity, intestinal permeability and histopathological analysis of ileum epithelia of mice from different groups were assessed. The expression and localization of tight junction proteins were examined using western blot and immunofluorescence. Gut microbiota structure and diversity were measured with 16 S rRNA sequencing. Caco-2 monolayers were incubated with EcN culture supernatant (EcNsup) or SN-38 and the monolayer barrier function was assessed by transepithelial electrical resistance (TER) and FITC-dextran 4000 Da (FD-4) flux. KEY FINDINGS: Pretreatment with EcN significantly attenuated irinotecan-induced weight loss and diarrhea in mice. In addition, EcN inhibited the increased intestinal permeability and decreased Claudin-1 expression in irinotecan-treated mice. Furthermore, irinotecan treatment decreased the diversity of gut microbiota and increased the relative abundance of Proteobacteria compared to control group. EcN administration ameliorated the gut microbiota dysbiosis. In Caco-2 monolayers, EcNsup ameliorated the decreased TER and increased FD-4 flux elicited by SN-38. Moreover, EcNsup attenuated SN-38-induced altered localization and distribution of Claudin-1 in Caco-2 monolayers. SIGNIFICANCE: Our results indicated that the administration of EcN protected against irinotecan-induced intestinal injury by regulating intestinal barrier function and gut microbiota.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Animais , Células CACO-2 , Claudina-1/metabolismo , Diarreia/patologia , Disbiose/tratamento farmacológico , Escherichia coli/metabolismo , Gastroenteropatias/metabolismo , Microbioma Gastrointestinal/genética , Humanos , Enteropatias/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Irinotecano/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Probióticos/farmacologia , Proteínas de Junções Íntimas/metabolismo
7.
Cancer Cell Int ; 19: 137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31139014

RESUMO

Background: The aim of the present study was to clarify the correlations between SPARC expression in gastric cancer-associated fibroblasts (GCAFs) and the prognosis of patients with gastric cancer and to elucidate the role of GCAF-derived SPARC in stemness transformation and 5-fluorouracil resistance in gastric cancer. Methods: One hundred ninety-two patients were enrolled in the present study. SPARC expression levels were evaluated by immunohistochemical staining. Primary GCAFs were obtained and cultured from cancer patients for in vitro study, and a lentivirus infection method was employed to knock down SPARC expression in GCAFs. The stemness phenotype and 5-fluorouracil (5-FU) response of gastric cancer cells were assessed via a 3D co-culture model. The apoptotic status and stemness alterations were monitored by flow cytometry and western blotting. Additionally, label-free quantification proteomics was used to identify the differentially expressed proteins and potential pathways in gastric cancer cells treated with GCAF-derived SPARC. Results: Low expression of GCAF-derived SPARC was associated with decreased differentiation and reduced 5-year overall survival and was an independent predictive factor for prognosis in gastric cancer. The 3D tumour growth and 5-FU resistance abilities of gastric cancer cells were elevated after treatment with GCAFs with SPARC knockdown relative to these abilities in negative control cells. Additionally, suppressing SPARC expression in GCAFs facilitated the phenotypic alteration of gastric cancer cells towards CD44+/CD24- cancer stem cell (CSC)-like cells. Quantification proteomics analysis revealed that the differentially expressed proteins in gastric cancer cells were mainly involved in the AKT/mTOR and MEK/ERK signalling pathways. Conclusions: SPARC expression in GCAFs is a useful prognostic factor in patients with gastric cancer. Low expression of GCAF-derived SPARC can lead to CSC transformation and 5-FU resistance. Additionally, the AKT/mTOR and MEK/ERK signalling pathways may participate in the malignant process.

9.
J Crohns Colitis ; 13(8): 1067-1080, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30722010

RESUMO

BACKGROUND AND AIMS: Endogenous H2S regulates multiple physiological and pathological processes in colon epithelial tissues. The current study investigated the role of cystathionine ß-synthase [CBS], a major producer of H2S in colon epithelial cells, in the pathogenesis of ulcerative colitis [UC]-related intestinal barrier injury. The expression and DNA methylation level of CBS were investigated in inflamed and non-inflamed colon tissues collected from UC patients, and the effect of decreased CBS levels on Caco-2 monolayer barrier injury and altered status of tight junctions elicited by tumour necrosis factor/interferon [TNF/IFN] was determined. METHODS: The expression of CBS and the methylation level of the CBS promoter were assessed in non-inflamed and inflamed colon epithelial tissue samples collected from UC patients. Barrier function, status of tight junction proteins and activation of the NF-κB p65-mediated MLCK-P-MLC signalling pathway were further investigated in Caco-2 monolayers. RESULTS: Decreased expression of CBS and elevated methylation levels of the CBS promoter were observed in inflamed sites compared with in non-inflamed sites in the colon epithelial samples from UC patients. In Caco-2 monolayers, decreased expression of CBS exacerbated TNF/IFN-induced barrier injury and altered localization of tight junction proteins. Decreased expression of CBS predisposed Caco-2 monolayers to injury elicited by TNF/IFN via augmentation of the NF-κB p65-mediated MLCK-P-MLC signalling pathway. CONCLUSIONS: Decreased expression of CBS propagates the pathogenesis of UC by exacerbating inflammation-induced intestinal barrier injury. Elevated methylation of the CBS promoter might be one of the mechanisms underlying the decreased expression of CBS in inflamed sites of colon epithelial tissues from UC patients.


Assuntos
Colite Ulcerativa , Cistationina beta-Sintase , Metilação de DNA , Mucosa Intestinal , Junções Íntimas/fisiologia , Adulto , Células CACO-2/metabolismo , Células Cultivadas , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Colite Ulcerativa/cirurgia , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Feminino , Humanos , Interferons/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Transdução de Sinais , Fator de Transcrição RelA , Transcriptoma , Fator de Necrose Tumoral alfa/metabolismo
10.
Complement Ther Med ; 42: 381-388, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30670271

RESUMO

BACKGROUND: Acupuncture as an alternative treatment method is widely used in the treatment of sudden sensorineural hearing loss(SSNHL) in China. We performed a systematic review and meta-analysis to assess the clinical efficacy of acupuncture for the management of SSNHL patients. MATERIALS AND METHODS: The PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and WanFang databases were searched. Searches were performed on April 27, 2018 and without language and publication year restrictions. We collected and analyzed the randomized controlled trials (RCTs) of acupuncture for the treatment of SSNHL patients to assess its efficacy and safety. The RevMan5.3 software was used for analysis. The fixed-effects model can be applied to calculate the risk ratio (RR) or weighted mean difference (WMD) if the chi-square test shows there was no significance of heterogeneity (p > 0.10, I2<50%). Otherwise, the random effects mode was used. RESULTS: Twenty randomized controlled trials met our inclusion criteria. The electroacupuncture(EA), manual acupuncture(MA) plus western medicine(WM) and EA plus WM groups lead to significantly better pure tone audiometry(PTA) than WM alone in cured rate (P = 0.01; P < 00,001; P < 0.006, respectively). However, no significant differences were observed between MA and WM (p = 0.27). In terms of total effective rate, all of them showed significant improvement compared to WM alone (MA: P = 0.03; EA: P = 0.01; MA + WM: P < 0.00001; EA + WM: P = 0.04). In addition, no significant difference was found between the MA plus WM and WM alone groups in the improvement of tinnitus (P = 0.37). No trials reported serious adverse events. CONCLUSION: Acupuncture could be a valid treatment option for SSNHL, especially for patients who could not be cured by drugs alone. However, the outcome was limited temporarily due to the lack of high-quality research support. High-quality evidence is needed to clarify the future efficacy and safety of acupuncture for SSNHL.


Assuntos
Terapia por Acupuntura , Perda Auditiva Neurossensorial/terapia , Adolescente , Adulto , Idoso , Eletroacupuntura , Humanos , Pessoa de Meia-Idade , Adulto Jovem
11.
Oncol Res ; 27(7): 739-750, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30180922

RESUMO

The activated form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], regulates numerous cellular processes, including inhibition of cancer progression. IL-1ß has been reported to facilitate cancer development, especially by inducing an epithelial-to-mesenchymal transition (EMT) in several malignant tumors. However, the underlying mechanism of 1,25(OH)2D3 and IL-1ß in colorectal cancer (CRC) still remains largely unknown. To fill in this knowledge gap, we measured cell proliferation and invasion by CCK-8 and Transwell assays after stimulation with 1,25(OH)2D3 and IL-1ß. E-cadherin and vimentin were chosen as markers of EMT measured by immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blot. The expression and function of the vitamin D receptor (VDR) was evaluated by Western blot and luciferase reporter assay. qRT-PCR and RNA-FISH were performed to detect the expression and location of lncTCF7 in vitro. The binding sites of VDR in the lncTCF7 promoter were confirmed by a chromatin immunoprecipitation assay. Based on the above experiments, we found that 1,25(OH)2D3 attenuates IL-1ß-induced increased proliferation and invasion in colorectal cancer through enhancing VDR, which inhibits the expression of lncTCF7 by directly binding to its promoter region.


Assuntos
Fator 1-alfa Nuclear de Hepatócito/metabolismo , Interleucina-1beta/metabolismo , Vitamina D/análogos & derivados , Animais , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos , Masculino , Camundongos , Camundongos Nus , Vitamina D/farmacologia , Vitamina D/uso terapêutico
12.
Int J Clin Oncol ; 24(3): 296-305, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30334174

RESUMO

OBJECTIVES: To evaluate the survival benefits that lymph node dissection (LND) brought to clinically node-negative upper tract urothelial carcinoma (UTUC) patients. METHODS: Non-metastatic node-negative UTUC patients were identified from the Surveillance, Epidemiology and End Results database. N0 patients were naturally divided as cN0-pNx group (clinically diagnosed as N0 without LND performed) and cNx-pN0 group (pathologically diagnosed as node-negative no matter what clinical node status they have). RESULTS: Of the 2731 patients included, 2240 and 491 cases were cN0-pNx and cNx-pN0, respectively. The overall survival (OS) of cNx-pN0 patients was significantly better than that of cNx-pN0 patients (p = 0.022). After propensity score matching, the survival of cNx-pN0 patients was still significantly better than cN0-pNx group. Besides, multivariate analyses showed cNx-pN0 (received LND) was an independent favorable prognostic factor for OS and CSS compared with cN0-pNx (no LND). Survival advantages of pN0 group were more significant in ≥ T2 patients and patients with tumor size ≤ 5 cm. Even in N0 patients who received adjuvant treatment, LND still brought obvious survival improvement (HRos = 0.565, p = 0.013; HRcss = 0.607, p = 0.046). CONCLUSION: LND could improve survival outcomes in patients with clinically node-negative UTUC, especially for those with muscle-invasive diseases (T2-4 stages) or smaller tumor size (≤ 5 cm). Adjuvant treatment after nephroureterectomy is incapable of replacing the therapeutic role of LND.


Assuntos
Excisão de Linfonodo/métodos , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefroureterectomia , Prognóstico , Pontuação de Propensão , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/patologia , Neoplasias Ureterais/cirurgia , Neoplasias Urológicas/cirurgia , Urotélio/patologia
13.
Eur Arch Otorhinolaryngol ; 276(2): 297-304, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30460401

RESUMO

OBJECTIVES: Transoral endoscopic/robotic thyroidectomy vestibule approach (TOETVA/TORTVA) is a novel technology that has been proposed for the treatment of thyroid disease. Its adoption has increased because of its satisfying cosmetic effects. The primary aim of this systematic review was to assess the feasibility and safety of this approach, and the secondary aim was to discuss the indications for this technology. MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, we searched Pubmed, Embase and the Cochrane databases for published studies on the feasibility and safety of TOETVA or TORTVA. RESULTS: 11 articles containing 864 patients met the inclusion criteria after full-text screening, of which two were reports of randomized controlled trial (RCT), two were retrospective cohort studies and the remaining seven studies were case series. Only studies that evaluated the feasibility and safety of this approach were included. TOETVA/TORTVA was successfully performed in 857 out of the 864 cases (99.2%). The mean operative time ranged from 60.4 to 265.4 min. In most articles, blood loss was less than 50 mL and the mean hospital stay ranged from 1.1 to 8.2 days. The safety outcomes were presented in all articles. The total incidence of adverse events was 14.5%, of which the main complications were transient hypoparathyroidism (5.6%) and transient recurrent laryngeal nerve (RLN) injury (3.1%). CONCLUSIONS: This review preliminarily suggests that TOETVA or TORTVA could be an effective and safe treatment for thyroidectomy. Due to the small sample size and low level of evidence, further large-scale, well-designed RCTs are required to validate our findings.


Assuntos
Cirurgia Endoscópica por Orifício Natural , Procedimentos Cirúrgicos Robóticos , Doenças da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Perda Sanguínea Cirúrgica , Humanos , Tempo de Internação , Duração da Cirurgia , Complicações Pós-Operatórias
14.
Oncol Rep ; 40(5): 2445-2454, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30106121

RESUMO

Poor response and chemotherapy resistance to cisplatin (DDP)­based therapy frequently lead to treatment failure in advanced bladder cancer; however the underlying mechanism is extremely complex and unclear. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A), a recently identified human oncoprotein, has been shown to play important regulatory roles in cancer cell survival. The present study aimed to investigate the correlation of CIP2A with sensitivity to DDP in bladder cancer cells. In the present study, knockdown of CIP2A was performed using short hairpin­RNA. IC50 determination was used to estimate the chemosensitivity of cells to DDP. Apoptosis and DNA damage indicators were tested in vitro and in vivo to clarify the role of CIP2A in enhancing DDP sensitivity. We observed that CIP2A knockdown enhanced DDP sensitivity. CIP2A depletion accelerated the process of DNA damage caused by DDP treatment. Furthermore, DDP triggered inhibition of CIP2A by preventing AKT Ser473 phosphorylation. In vivo, CIP2A suppression increased the cytotoxicity of DDP, which resulted in a decrease in the subcutaneous tumor growth in a xenograft mouse model. Our findings revealed that the mechanism underlying the involvement of CIP2A in DDP sensitivity enhancement is that CIP2A mediates DDP­induced cell apoptosis and DNA damage. CIP2A is a potential target to improve the response to DDP­based therapy in bladder cancer patients.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autoantígenos/metabolismo , Cisplatino/farmacocinética , Proteínas de Membrana/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Apoptose/genética , Autoantígenos/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Cisplatino/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Concentração Inibidora 50 , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Morfolinas/farmacologia , Proteínas Oncogênicas/genética , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Serina/metabolismo , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Jpn J Clin Oncol ; 48(10): 942-949, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137442

RESUMO

Objective: To evaluate the prognostic value of lymph node (LN) involvement for patients with chromophobe renal cell carcinoma (chRCC) and ascertain the minimum number of LNs that need to be pathologically examined to reliably diagnose a patient with node negative chRCC. Methods: From 2004 to 2014, non-metastatic chRCC patients receiving radical nephrectomy together with lymphadenectomy were identified from the Surveillance, Epidemiology and End Results (SEER) database. The primary outcome was overall survival (OS). Results: Two hundred and forty-six patients received lymph node dissection during the surgery. Of the patients, 24 (10%) had pathologically confirmed positive LN. Multivariate Cox regression model showed that positive LN was an independent unfavorable predictor for OS (HR = 2.83, 95%CI = 1.14-6.98, P = 0.024). More importantly, LN(-) patients with at least three LNs dissected had significantly better OS compared with when 1-2 LNs were examined (P = 0.048). Multivariate analysis confirmed that in LN(-) patients, the examination of three or more LNs could independently predict better OS compared with patients with only 1-2 LNs dissected (HR≥3LNs = 0.362, 95% CI = 0.135-0.972, P = 0.044). Additionally, the likelihood of finding at least one positive LN was significantly higher on dissection of ≥3 LNs compared with examination of 1-2 LNs (15% vs 5%, P = 0.018). Decision curve analysis found a better clinical validity of the '3 LNs examined'-based classification compared with the traditional LN(-)/LN(+) classification. Conclusion: The proportion of positive LNs in chRCC was far from neglectable and LN metastasis could independently predict unfavorable OS. We recommended a minimum of three LNs should be pathologically examined in order to reliably determine node negative.


Assuntos
Carcinoma de Células Renais/patologia , Linfonodos/patologia , Adulto , Carcinoma de Células Renais/mortalidade , Estudos de Coortes , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 21(6): 710-715, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29968247

RESUMO

The clinical application of novel chemotherapeutic drugs including oral 5-FU and targeted drugs and preoperatively accurate imaging grading has brought challenges to the indication criteria developed by NCCN and ESMO for neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC). Extended hotspots have focused on the effectiveness of using capecitabine instead of fluorouracil infusion, the combination of multiple drugs and the feasibility of using neoadjuvant chemotherapy instead of neoadjuvant chemoradiotherapy for selective patients. Traditionally, the evaluation of the effect of neoadjuvant therapy has been based on the effect on the pathological complete remission (pCR) rate. However, current studies recommend the disease-free survival (DFS) as a more important outcome. Besides, seeking for effective biomarkers as predictive markers for neoadjuvant therapies or as prognostic markers remains a hotspot in the field of neoadjuvant chemoradiotherapy. The "watch and wait" approach refers to taking a close follow-up strategy instead of direct operation for patients achieving clinically complete remission (cCR) after neoadjuvant therapy. However, there is no unified evaluation criteria and time point for the evaluation of cCR following neoadjuvant therapy. Therefore, there remain a lot of controversies regarding the clinical application of neoadjuvant chemoradiotherapy in LARC. In this manuscript, research progress in the indication for neoadjuvant therapy, improvement in the neoadjuvant therapeutic schedule, advancement of the efficacy evaluation criteria of neoadjuvant therapy, the "watch and wait" approach and other hot topics is summarized to provide references for clinical practice.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Terapia Neoadjuvante , Neoplasias Retais/terapia , Capecitabina/uso terapêutico , Quimiorradioterapia , Fluoruracila/uso terapêutico , Humanos , Estadiamento de Neoplasias , Resultado do Tratamento
17.
Cancer Cell Int ; 18: 104, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30038550

RESUMO

Background: Cancer-associated fibroblasts (CAFs) play important roles in tumor progression. However, the behaviors of activated CAFs in gastric cancer remain to be determined. The aim of the present study was to investigate the correlations between activated gastric CAFs and the prognosis of patients with gastric cancer, and to determine the effects of activated CAFs on the malignant phenotype and 5-fluorouracil resistance in this cancer. Methods: Ninety-five patients with primary gastric cancer were enrolled in this study. Activation states of gastric CAFs were evaluated by immunohistochemistry. A modified method for the primary culture of gastric CAFs was employed. Types of CAFs and activation states were identified by immunocytochemical and immunofluorescent staining. Cell co-culture and gastric CAF conditioned medium transfer models were established to investigate the paracrine effects of activated CAFs on the migration and invasion of gastric cell lines. The half maximal inhibitory concentration of 5-fluorouracil and levels of cell apoptosis were examined using cell viability assay and flow cytometry, respectively. Protein expression levels of associated molecules were measured by Western blotting. Results: Kaplan-Meier survival curves showed that activated gastric CAFs identified via fibroblast activation protein were significantly related to poorer cumulative survival in gastric cancer patients. Five strains of CAFs were successfully cultured via the modified culture method, and three gastric CAFs strains were identified as activated gastric CAFs. The migration and invasion abilities of gastric cells were significantly enhanced in both the co-culture group and the conditioned medium group. The half maximal inhibitory concentration for 5-fluorouracil in BGC-823 cells was elevated after treatment with conditioned medium, and early apoptosis was inhibited. Additionally, an obvious elevation of epithelial-mesenchymal transition level was observed in the conditioned medium group. Conclusions: Activated gastric CAFs correlate with a poor prognosis of cancer patients and may contribute to the malignant phenotype and the development of resistance to 5-fluorouracil via paracrine action in gastric cancer. Gastric CAFs with a specific activation state might be used as a tumor biomarker within the microenvironment for prognosis and as a new therapeutic target for chemoresistant gastric cancer.

18.
J Cancer ; 9(7): 1152-1164, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29675096

RESUMO

Objectives: To develop reliable nomograms to estimate individualized overall survival (OS) and cancer specific survival (CSS) for patients with primary small cell carcinoma of the bladder (SCCB) and compare the predictive value with the AJCC stages. Patients and Methods: 582 eligible SCCB patients identified in the Surveillance, Epidemiology, and End Results (SEER) dataset were randomly divided into training (n=482) and validation (n=100) cohorts. Akaike information criterion was used to select the clinically important variables in multivariate Cox models when establishing nomograms. The performance of nomograms was bootstrapped validated internally and externally using the concordance index (C-index) with 95% confidence interval (95% CI) and calibration curves and was compared with that of the AJCC stages using C-index, Kaplan-Meier curves and decision curve analysis (DCA). Results: Two nomograms shared common indicators including age, tumor size, T stage, lymph node ratio, metastases, chemotherapy, radiation and radical cystectomy, while marriage and gender were only incorporated in the OS nomogram. The C-indices of nomograms for OS and CSS were 0.736 (95%CI 0.711-0.761) and 0.731(95%CI 0.704-0.758), respectively, indicating considerable predictive accuracy. Calibration curves showed consistency between the nomograms and the actual observation. The results remained reproducible when nomograms were applied to the validation cohort. Additionally, comparisons between C-indices, Kaplan-Meier curves and DCA proved that the nomograms obtained obvious superiority over the AJCC stages with wide practical threshold probabilities. Conclusions: We proposed the first two nomograms for individualized prediction of OS and CSS in SCCB patients with satisfactory predictive accuracy, good robustness and wide applicability.

19.
World J Surg Oncol ; 16(1): 61, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29562940

RESUMO

BACKGROUND: Previous researches pointed out that the measurement of urine fibronectin (Fn) could be a potential diagnostic test for bladder cancer (BCa). We conducted this meta-analysis to fully assess the diagnostic value of urine Fn for BCa detection. METHODS: A systematic literature search in PubMed, ISI Web of Science, EMBASE, Cochrane library, and CBM was carried out to identify eligible studies evaluating the urine Fn in diagnosing BCa. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with their 95% confidence intervals (CIs) were calculated, and summary receiver operating characteristic (SROC) curves were established. We applied the STATA 13.0, Meta-Disc 1.4, and RevMan 5.3 software to the meta-analysis. RESULTS: Eight separate studies with 744 bladder cancer patients were enrolled in this meta-analysis. The pooled sensitivity, specificity, and DOR were 0.80 (95%CI = 0.77-0.83), 0.79 (95%CI = 0.73-0.84), and 15.18 (95%CI = 10.07-22.87), respectively, and the area under the curve (AUC) of SROC was 0.83 (95%CI = 0.79-0.86). The diagnostic power of a combined method (urine Fn combined with urine cytology) was also evaluated, and its sensitivity and AUC were significantly higher (0.86 (95%CI = 0.82-0.90) and 0.89 (95%CI = 0.86-0.92), respectively). Meta-regression along with subgroup analysis based on various covariates revealed the potential sources of the heterogeneity and the detailed diagnostic value of each subgroup. Sensitivity analysis supported that the result was robust. No threshold effect and publication bias were found in this meta-analysis. CONCLUSIONS: Urine Fn may become a promising non-invasive biomarker for bladder cancer with a relatively satisfactory diagnostic power. And the combination of urine Fn with cytology could be an alternative option for detecting BCa in clinical practice. The potential value of urine Fn still needs to be validated in large, multi-center, and prospective studies.


Assuntos
Biomarcadores Tumorais/urina , Fibronectinas/urina , Neoplasias da Bexiga Urinária/diagnóstico , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/urina
20.
Cancer Manag Res ; 9: 611-626, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29180897

RESUMO

Background: We aimed to evaluate the prognostic value of site-specific metastases in patients with metastatic bladder cancer and analyze the roles that surgeries play in the treatment of this malignancy. Materials and methods: A population-based retrospective study using Surveillance, Epidemiology and End Results dataset was performed and metastatic bladder cancer patients were classified according to the sites of metastases (bone, brain, liver, lung and distant lymph nodes). Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS). Results: A total of 1862 patients with metastatic bladder cancer from 2010 to 2014 were identified. Bone, lung and distant lymph nodes were the most common metastatic sites. Patients with bone, brain, liver and lung involvement had worse OS and CSS compared to patients without the corresponding sites of metastases. Multivariate analysis showed that bone, brain, liver and lung metastases were independent prognostic factors for both OS and CSS, while distant node metastasis was not. Moreover, patients with a single metastatic site had more favorable OS (p<0.001) and CSS (p<0.001) than patients with multisite metastases. Among single-site metastatic patients, distant nodes and liver metastases represented the best and the worst prognosis, respectively. Moreover, radical cystectomy was an independent predictor for better OS and CSS, while in patients with liver metastasis and multiple metastatic sites, RC did not bring benefits. Besides, in patients with a single metastatic site, metastasectomy seemed to be associated with favorable OS (p=0.042), especially for patients with age <65 years (p=0.006) and for muscle-invasive bladder cancer patients (p=0.031). Conclusion: Distant metastatic sites have differential impact on survival outcomes in patients with metastatic bladder cancer. Surgeries, including radical cystectomy and metastasectomy, might still lead to survival benefits for highly selected patients.

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