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1.
Artigo em Inglês | MEDLINE | ID: mdl-38265406

RESUMO

Bladder cancer (BC) is a common malignant tumor of the urinary system. While current approaches involving adjuvant chemotherapy, radiotherapy, and immunotherapy have shown significant progress in BC treatment, challenges, such as recurrence and drug resistance, persist, especially in the case of muscle-invasive bladder cancer (MIBC). This is mainly due to the lack of pre-existing immune response cells in the tumor immune microenvironment. Micro-environmental changes (such as hypoxia and under-nutrition) can cause the aggregation of unfolded and misfolded proteins in the lumen, which induces endoplasmic reticulum (ER) stress. ER stress and its downstream signaling pathways are closely related to immunogenicity and tumor drug resistance. ER stress plays a pivotal role in a spectrum of processes within immune cells and the progression of BC cells, encompassing cell proliferation, autophagy, apoptosis, and resistance to therapies. Recent studies have increasingly recognized the potential of natural compounds to exhibit anti-BC properties through ER stress induction. Still, the efficacy of these natural compounds remains less than that of immune checkpoint inhibitors (ICIs). Currently, the ER stress-mediated immunogenic cell death (ICD) pathway is more encouraging, which can enhance ICI responses by mediating immune stemness. This article provides an overview of the recent developments in understanding how ER stress influences tumor immunity and its implications for BC. Targeting this pathway may soon emerge as a compelling therapeutic strategy for BC.

2.
J Pharm Biomed Anal ; 236: 115694, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37696190

RESUMO

BACKGROUND: Bladder cancer (BC) caused by Human papillomavirus (HPV) infection remains a complex public health problem in developing countries. Although the HPV vaccine effectively prevents HPV infection, it does not benefit patients with BC who already have HPV. METHODS: Firstly, the differential genes of HPV-related BC patients were screened by transcriptomics, and then the prognostic and clinical characteristics of the differential genes were analyzed to screen out the valuable protein signatures. Furthermore, the compound components and targets of Astragali Radix (AR) were analyzed by network pharmacology, and the intersection targets of drug components and HPV_BC were screened out for pathway analysis. In addition, the binding ability of the compound to the Astragali-HPV_BC target was verified by molecular docking and virtual simulation. Finally, to identify potential targets in BC patients through urine proteomics and in vitro experiments. RESULTS: Eleven HPV_BC-related protein signatures were screened out, among which high expression of EGFR, CTNNB1, MYC, GSTM1, MMP9, CXCR4, NOTCH1, JUN, CXCL12, and KRT14 had a poor prognosis, while low expression of CASP3 had a poor prognosis. In the analysis of clinical characteristics, it was found that high-risk scores, EGFR, MMP9, CXCR4, JUN, and CXCL12 tended to have higher T stage, pathological stage, and grade. Pharmacological and molecular docking analysis identified a natural component of AR (Quercetin) and it corresponding core targets (EGFR). The OB of the natural component was 46.43, and the DL was 0.28, respectively. In addition, EGFR-Quercetin has high affinity. Urine proteomics and RT-PCR showed that EGFR was expressed explicitly in BC patients. Mechanism analysis revealed that AR component targets might affect HPV_BC patients through Proteoglycans in the cancer pathway. CONCLUSION: AR can target EGFR through its active component (Quercetin), and has a therapeutic effect on HPV_BC patients.


Assuntos
Astrágalo , Medicamentos de Ervas Chinesas , Infecções por Papillomavirus , Neoplasias da Bexiga Urinária , Humanos , Metaloproteinase 9 da Matriz , Farmacologia em Rede , Simulação de Acoplamento Molecular , Infecções por Papillomavirus/tratamento farmacológico , Proteômica , Quercetina , Receptores ErbB/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
3.
Front Oncol ; 13: 1205604, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37538114

RESUMO

Background: Uterine corpus endometrial carcinoma (UCEC) belongs to a group of epithelial malignant tumors. Icaritin is the main active compound of Epimedii Folium. Icaritin has been utilized to induce UCEC cells to death. Methods: We wished to identify potential targets for icaritin in the treatment of UCEC, as well as to provide a groundwork for future studies into its pharmacologic mechanism of action. Network pharmacology was employed to conduct investigations on icaritin. Target proteins were chosen from the components of icaritin for UCEC treatment. A protein-protein interaction (PPI) network was established using overlapping genes. Analyses of enrichment of function and signaling pathways were undertaken using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, to select "hub genes". Finally, experiments were carried out to ascertain the effect of icaritin on endometrial cancer (HEC-1-A) cells. Results: We demonstrated that icaritin has bioactive components and putative targets that are therapeutically important. Icaritin treatment induced sustained activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt pathway) and inhibited growth of HEC-1-A cells. Conclusion: Our data provide a rationale for preclinical and clinical evaluations of icaritin for UCEC therapy.

4.
Int J Surg ; 109(9): 2762-2773, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37526108

RESUMO

BACKGROUND: The present study aimed to conduct a pooled analysis to compare the perioperative and oncologic outcomes of minimally-invasive radical nephrectomy with tumor thrombus (MI-RNTT) with open radical nephrectomy with tumor thrombus (O-RNTT). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to December 2022. The primary outcomes were perioperative results, complications, and oncologic outcomes. Review Manager 5.4 was used for this analysis. RESULTS: In total, eight retrospective trials with a total of 563 patients were included. Compared to O-RNTT, MI-RNTT had shorter hospitalization time [weighted mean difference (WMD) -3.58 days, 95% CI: -4.56 to -2.59; P <0.00001), lower volumes of blood loss (WMD -663.32 ml, 95% CI: -822.22 to -504.42; P <0.00001), fewer transfusion rates (OR 0.18, 95% CI: 0.09-0.35; P <0.00001), fewer overall complications (OR 0.33, 95% CI: 0.22-0.49; P <0.00001), and fewer major complications s (OR 0.49, 95% CI: 0.24-1.00; P =0.05). However, operative time, intraoperative complications, mortality rate (intraoperative, within 30 days, and total mortality), overall survival, recurrence-free survival, and cancer-specific survival did not significantly differ between the two groups. CONCLUSIONS: MI-RNTT possesses more benefits than O-RNTT in terms of length of hospital stay, blood loss, and complications and provides comparable mortality rates and oncologic outcomes. However, more comprehensive and rigorous research is warranted to further validate the outcomes, which should include a larger sample size and comprehensive data from high-volume medical centers.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/complicações , Estudos Retrospectivos , Resultado do Tratamento , Veias , Neoplasias Renais/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
6.
Int J Surg ; 109(10): 3178-3188, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37462997

RESUMO

BACKGROUND: This study aimed to conduct a pooled analysis to compare the outcomes of patients with metastatic renal cell carcinoma who received presurgical systemic therapy [(ST); including immunotherapy and/or targeted therapy] followed by cytoreductive nephrectomy (CN) [(deferred CN; (dCN)] with those who underwent upfront CN (uCN) followed by ST. METHODS: The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive search was conducted in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library database to identify eligible comparative studies up to April 2023. To evaluate their relevance, pooled hazard ratio with 95% CIs were calculated. RESULTS: A total of 3157 patients were included in nine studies. The dCN group was observed to be correlated with superior overall survival (OS) compared to the uCN group (hazard ratio =0.71, 95% CI 0.57-0.89, P =0.003). Moreover, the authors conducted subgroup analyses according to the type of ST, sample size, sex, age, and risk score, and observed similar outcomes for OS across most subgroups. CONCLUSIONS: The results of this study demonstrated that dCN may be associated with improved OS compared to uCN in patients with metastatic renal cell carcinoma receiving ST. However, no significant differences were found between the uCN and dCN groups in the immunotherapy-based combinations subgroup. Further research is needed to confirm these results.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução , Modelos de Riscos Proporcionais , Nefrectomia/métodos , Estudos Retrospectivos
7.
Int J Surg ; 109(6): 1769-1782, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37094827

RESUMO

BACKGROUND: The present study aimed to conduct a pooled analysis to compare the efficacy and safety of minimally invasive partial nephrectomy (MIPN) with open partial nephrectomy (OPN) in patients with complex renal tumors (defined as PADUA or RENAL score ≥7). METHODS: The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, Supplemental Digital Content 1, http://links.lww.com/JS9/A394 . We conducted a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases until October 2022. MIPN and OPN-controlled trials for complex renal tumors were included. The primary outcomes were perioperative results, complications, renal function, and oncologic outcomes. RESULTS: A total of 2405 patients were included in 13 studies. MIPN outperformed OPN in terms of hospital stay [weighted mean difference (WMD) -1.84 days, 95% CI -2.35 to -1.33; P <0.00001], blood loss (WMD -52.42 ml, 95% CI -71.43 to -33.41; P <0.00001), transfusion rates [odds ratio (OR) 0.34, 95% CI 0.17-0.67; P =0.002], major complications (OR 0.59, 95% CI 0.40-0.86; P =0.007) and overall complications (OR 0.43, 95% CI 0.31-0.59; P <0.0001), while operative time, warm ischemia time, conversion to radical nephrectomy rates, estimated glomerular decline, positive surgical margins, local recurrence, overall survival, recurrence-free survival, and cancer-specific survival were not significantly different. CONCLUSIONS: The present study demonstrated that MIPN was associated with a shorter length of hospital stay, less blood loss, and fewer complications in treating complex renal tumors. MIPN may be considered a better treatment for patients with complex tumors when technically feasible.


Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Neoplasias Renais/patologia , Procedimentos Cirúrgicos Robóticos/métodos , Nefrectomia/efeitos adversos , Nefrectomia/métodos
8.
J Robot Surg ; 17(4): 1227-1238, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36884204

RESUMO

The present study aimed to compare the efficacy and safety between robot-assisted nephroureterectomy (RANU) and open nephroureterectomy (ONU) for the treatment of upper tract urothelial carcinoma (UTUC). We systematically searched four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) to locate pertinent studies published in English up to January 2023. The primary outcomes evaluated included perioperative results, complications, and oncologic outcomes. Statistical analyses and calculations were performed using Review Manager 5.4. The study was registered with PROSPERO (ID: CRD42022383035). In total, eight comparative trials, including 37,984 patients were enrolled. Compared to ONU, RANU was associated with a significantly shorter length of stay (weighted mean difference [WMD] - 1.63 days, 95% confidence interval [CI] - 2.90, - 0.35; p = 0.01), less blood loss (WMD - 107.04 mL, 95% CI - 204.97, - 9.11; p = 0.03), less major complication(OR 0.78, 95% CI 0.70, 0.88; p < 0.0001), and lower positive surgical margin (PSM) (OR 0.33, 95% CI 0.12, 0.92; p = 0.03). However, no statistically significant differences were observed between the two groups in operative time, transfusion rates, rate of lymph node dissection, lymph node yield, overall complications, overall survival, cancer-specific survival, recurrence-free survival, and progression-free survival. RANU has superior advantages compared to ONU in terms of length of hospital stay, blood loss, postoperative complications, and PSM, while providing comparable oncologic outcomes in patients with UTUC.


Assuntos
Carcinoma de Células de Transição , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/cirurgia , Nefroureterectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia
9.
Front Immunol ; 14: 1132466, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36999026

RESUMO

Purpose: The prognostic impact of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immunotherapy is yet to be determined. The aim of our study is to evaluate the correlation between CN and outcomes in the setting of mRCC treated with immunotherapy. Methods: We conducted a systematic search of the Science, PubMed, Web of Science, and Cochrane Library databases to identify relevant studies published in English up to December 2022. The results were presented as hazard ratio (HR) with 95% confidence intervals (CIs) for overall survival (OS) was extracted to assess their relevance. The study was registered with PROSPERO (CRD42022383026). Results: A total of 2397 patients were included in eight studies. The CN group was observed to be correlated with superior OS compared to the No CN group (HR = 0.53, 95% CI 0.39-0.71, p < 0.0001). Subgroup analysis according to the type of immunotherapy, sample size, and treatment line of immune checkpoint inhibitor revealed that CN group had a superior OS in all subgroups. Conclusion: CN is associated with a better outcome in terms of OS benefit in selected patients with mRCC treated by immunotherapy, but further studies are required to verify the conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022383026.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Imunoterapia , Neoplasias Renais/patologia , Nefrectomia/métodos
10.
J Robot Surg ; 17(4): 1247-1258, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36913056

RESUMO

This study aims to assess the efficacy and safety of robot-assisted partial nephrectomy (RAPN) compared with open partial nephrectomy (OPN) in the management of complex renal tumors (defined as RENAL score ≥ 7). We conducted a comprehensive literature search in PubMed, Embase, Web of Science, and Cochrane Library to identify relevant comparative studies up to January 2023. This study was conducted with the Review Manager 5.4 software, and included RAPN and OPN-controlled trials for complex renal tumors. The prime outcomes were to assess the perioperative results, complications, renal function, and oncologic outcomes. A total of 1493 patients were included in seven studies. Compared to OPN, RAPN was associated with a significantly shorter hospital stay (weighted mean difference [WMD] - 1.53 days, 95% confidence interval [CI] - 2.44, - 0.62; p = 0.001), less blood loss (WMD - 95.88 mL, 95% CI - 144.19, - 47.56; p = 0.0001), lower transfusion rates (OR 0.33, 95% CI 0.15, 0.71; p = 0.005), fewer major complications (OR 0.63, 95% CI 0.39, 1.01; p = 0.05), and fewer overall complications (OR 0.49, 95% CI 0.36, 0.65; p < 0.00001). Nevertheless, no statistically significant differences were found between the two groups in operative time, warm ischemia time, estimated glomerular decline, intraoperative complications, positive surgical margins, local recurrence, overall survival, and recurrence-free survival. The study demonstrated that RAPN had superior perioperative parameters and fewer complications when compared to OPN for complex renal tumors. However, no significant differences were found in terms of renal function and oncologic outcomes.


Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Tempo de Internação , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Rim/fisiologia , Rim/patologia , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
11.
J Robot Surg ; 17(3): 765-777, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36469187

RESUMO

This study aims to evaluate the effectiveness and safety between single-port robotic-assisted partial nephrectomy (da Vinci SP system) with conventional robotic-assisted partial nephrectomy (da Vinci Si or Xi system). We systematically searched PubMed, Science Embase, Web of Science and Cochrane Library database for articles comparing single-port robotic-assisted partial nephrectomies (SP-RAPN) and conventional robotic-assisted partial nephrectomy (Con-RAPN) till September 2022. The principal outcomes included perioperative outcomes, complications, and oncologic outcomes were evaluated. A total of 586 patients were included in six studies. There were no significant differences in operative time (p = 0.19), transfusion rates (p = 0.11), off-clamp (p = 0.32), total perioperative milligram morphine equivalents (MME) (p = 0.44), intraoperative complications (p = 0.60), major complications (p = 0.84), overall complications (p = 0.90), positive surgical margins (PSM) (p = 0.75) and local recurrence (p = 0.50) between SP-RAPN and Con-RAPN. In addition, the marginal results were recorded in length of hospital stay subgroup (WMD - 0.35 days, 95% CI - 0.70, 0.01; p = 0.06) and blood loss (WMD - 27.16 ml, 95% CI - 56.90, 2.58; p = 0.07). However, SP-RAPN had longer warm ischemia time compared to Con-RAPN (WMD 3.42 min, 95% CI 1.71, 5.13; p < 0.0001). The results of this study demonstrated that SP-RAPN provided similar effectiveness and safety to Con-RAPN, while SP-RAPN might be associated with a marginally shorter length of hospital stay and less blood loss.


Assuntos
Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Complicações Intraoperatórias/etiologia , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos
12.
World J Surg Oncol ; 20(1): 21, 2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35065650

RESUMO

BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.


Assuntos
Neoplasias Colorretais , Metilação de DNA , Biomarcadores , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Análise de Sequência de DNA
13.
Int Immunopharmacol ; 87: 106771, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32683302

RESUMO

Acute pancreatitis during pregnancy (APIP) rarely occurs but may lead to preterm delivery and be associated with high fetal mortality. Macrophage migration inhibitory factor (MIF) participates in various inflammatory diseases as a pro-inflammatory cytokine. In this study, we aimed to explore the effects of (S, R)-3-(4-hydroxyphenyl)-4, 5dihydro-5-isoxazole acetic methyl ester (ISO-1), an inhibitor of MIF, on maternal thyroid injury associated with APIP and its potential mechanisms in a pregnant rat model. APIP model was induced by retrograde injection of sodium taurocholate. ISO-1 was injected intraperitoneally 30 min before model establishment. The severity of pancreatitis was assessed by levels of tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL-6 of maternal serum as well as histopathological score. Thyroid injury was determined by free triiodothyronine (FT3), free tetraiodothyronine (FT4) and thyroid histopathological score. Levels of MIF in maternal serum and the expression of MIF, CD68, CD3 and intercellular cell adhesion molecule-1 (ICAM-1) as well as oxidative stress status in maternal thyroid tissues were detected. Ultrastructure of maternal thyroid tissues was observed by transmission electron microscope. Thyroid injuries occurred in APIP and the lesions were attenuated with the pretreatment of ISO-1. Moreover, ISO-1 reduced the expression of MIF, attenuated the activations of CD68, CD3, ICAM-1 while improved oxidative stress status in maternal thyroid. Our research suggested a protective role of ISO-1 on thyroid injury and endocrine disorder during APIP, which may be associated with the inhibition of biological functions of MIF.


Assuntos
Oxirredutases Intramoleculares/antagonistas & inibidores , Isoxazóis/uso terapêutico , Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , Pancreatite/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Glândula Tireoide/efeitos dos fármacos , Animais , Citocinas/sangue , Feminino , Oxirredutases Intramoleculares/sangue , Oxirredutases Intramoleculares/imunologia , Isoxazóis/farmacologia , Fatores Inibidores da Migração de Macrófagos/sangue , Fatores Inibidores da Migração de Macrófagos/imunologia , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/sangue , Pancreatite/imunologia , Pancreatite/patologia , Gravidez , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Glândula Tireoide/ultraestrutura
15.
Am J Physiol Gastrointest Liver Physiol ; 315(5): G838-G847, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30138574

RESUMO

This study was conducted to investigate the effect of 4-phenylbutyric acid (4-PBA) on vital organ injury following sodium taurocholate-induced acute pancreatitis (AP) in rats and the pertinent mechanism. The serum biochemical indicators and key inflammatory cytokines, histopathological damage and apoptosis of vital organs in rat AP, were evaluated in the presence or absence of 4-PBA. Moreover, mRNA and protein levels of endoplasmic reticulum stress (ERS) markers were assessed. 4-PBA significantly attenuated the structural and functional damage of vital organs, including serum pancreatic enzymes, hepatic enzymes, creatinine, and urea. The morphological changes and infiltration of neutrophils and macrophages were reduced as well. These effects were accompanied by decreased serum levels of proinflammatory TNF-α and IL-1ß. Furthermore, 4-PBA diminished the expression of ERS markers (glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, protein kinase R-like ER kinase, activated transcription factor 6, and type-1 inositol requiring enzyme) in vital organs of AP rats. 4-PBA also reduced AP-induced apoptosis in lung, liver, and kidney tissues as shown by TUNEL assay. The present study demonstrated that 4-PBA protected pancreas, lung, liver, and kidney from injury in rat AP by regulating ERS and mitigating inflammatory response to restrain cell death and further suggested that 4-PBA may have potential therapeutic implications in the disease. NEW & NOTEWORTHY In this study, we suggest that endoplasmic reticulum stress (ERS) is an important player in the development of acute pancreatitis-induced multiorgan injury, providing additional evidence for the proinflammatory role of ERS. Because 4-phenylbutyric acid has been suggested to inhibit ERS in many pathological conditions, it is possible that this effect can be involved in alleviating inflammatory response and cell death to ameliorate vital organ damage following acute pancreatitis induced by sodium taurocholate in rats.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Pancreatite Necrosante Aguda/tratamento farmacológico , Fenilbutiratos/uso terapêutico , Animais , Apoptose , Interleucina-1beta/sangue , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite Necrosante Aguda/complicações , Fenilbutiratos/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue
16.
Medicine (Baltimore) ; 93(11): e58, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25192483

RESUMO

Sellar plasmacytoma is a rare cause of sellar lesions. Preoperative diagnosis remains a challenge. We present a 34-year-old Chinese woman with a 25-day history of headache and diplopia. A physical examination revealed incomplete left abducens nerve palsy. The initial diagnosis was invasive pituitary adenoma. The patient's condition deteriorated suddenly the day before the arranged operating date, with the hemoglobin level declining from 113 to 70 g/L. The operation was cancelled and further studies confirmed the diagnosis of sellar solitary plasmacytoma that progressed to multiple myeloma. After undergoing radiotherapy, high-dose chemotherapy, and autologous peripheral blood stem cell transplantation, complete remission was achieved on 4 years follow-up. We reviewed the pertinent literature and reached the following conclusions: sellar plasmacytomas with development of multiple myeloma on follow-up more likely happened in men than in women; and if the sellar plasmacytoma does not compress the cranial nerve, transsphenoidal resection should be cautious because the systemic treatment with radiotherapy, chemotherapy, and autologous peripheral blood stem cell transplantation may be more effective with little invasion.


Assuntos
Mieloma Múltiplo/diagnóstico , Plasmocitoma/diagnóstico , Neoplasias Cranianas/diagnóstico , Adulto , China , Diagnóstico Diferencial , Feminino , Humanos , Mieloma Múltiplo/fisiopatologia , Plasmocitoma/fisiopatologia , Sela Túrcica , Neoplasias Cranianas/fisiopatologia
18.
J Biol Chem ; 286(28): 25007-15, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21592963

RESUMO

Mesenchymal stem cells (MSCs), which are modulated by cytokines present in the tumor microenvironment, play an important role in tumor progression. It is well documented that inflammation is an important part of the tumor microenvironment, so we investigated whether stimulation of MSCs by inflammatory cytokines would contribute to their ability to promote tumor growth. We first showed that MSCs could increase C26 colon cancer growth in mice. This growth-promoting effect was further accelerated when the MSCs were pre-stimulated by inflammatory factors IFN-γ and TNF-α. At the same time, we demonstrated that MSCs pre-stimulated by both inflammatory factors could promote tumor angiogenesis in vivo to a greater degree than untreated MSCs or MSCs pre-stimulated by either IFN-γ or TNF-α alone. A hen egg test-chorioallantoic membrane (HET-CAM) assay showed that treatment of MSC-conditioned medium can promote chorioallantoic membrane angiogenesis in vitro, especially treatment with conditioned medium of MSCs pretreated with IFN-γ and TNF-α together. This mechanism of promoting angiogenesis appears to take place via an increase in the expression of vascular endothelial growth factor (VEGF), which itself takes place through an increase in signaling in the hypoxia-inducible factor 1α (HIF-1α)-dependent pathway. Inhibition of HIF-1α in MSCs by siRNA was found to effectively reduce the ability of MSC to affect the growth of colon cancer in vivo in the inflammatory microenviroment. These results indicate that MSCs stimulated by inflammatory cytokines such as IFN-γ and TNF-α in the tumor microenvironment express higher levels of VEGF via the HIF-1α signaling pathway and that these MSCs then enhance tumor angiogenesis, finally leading to colon cancer growth in mice.


Assuntos
Neoplasias do Colo/metabolismo , Mediadores da Inflamação/metabolismo , Interferon gama/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neovascularização Patológica/metabolismo , Microambiente Tumoral , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antivirais/metabolismo , Antivirais/farmacologia , Linhagem Celular Tumoral , Embrião de Galinha , Membrana Corioalantoide/metabolismo , Membrana Corioalantoide/patologia , Neoplasias do Colo/patologia , Meios de Cultivo Condicionados/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mediadores da Inflamação/farmacologia , Interferon gama/farmacologia , Masculino , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Chin Med J (Engl) ; 120(18): 1567-73, 2007 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-17908471

RESUMO

BACKGROUND: Neurophysiologic monitoring during surgery is to prevent permanent neurological injury resulting from surgical manipulation. To improve the accuracy and sensitivity of intraoperative neuromonitoring, combined monitoring of transcranial electrical stimulation motor evoked potentials (TES-MEPs), somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) was attempted in microsurgery for lesions adjacent to the brainstem and intracranial aneurysms. METHODS: Monitoring of combined TES-MEPs with SSEPs was attempted in 68 consecutive patients with lesions adjacent to the brainstem as well as intracranial aneurysms. Among them, 31 patients (31 operations, 28 of posterior cranial fossa tumors, 3 of posterior circulation aneurysms) were also subjected to monitoring of BAEPs. The correlation of monitoring results and clinical outcome was studied prospectively. RESULTS: Combined monitoring of evoked potentials (EPs) was done in 64 (94.1%) of the 68 patients. MEPs monitoring was impossible for 4 patients (5.9%). No complication was observed during the combined monitoring in all the patients. In 45 (66.2%) of the 68 patients, EPs were stable, and they were neurologically intact. Motor dysfunction was detected by MEPs in 8 patients, SSEPs in 5, and BAEPs in 4, respectively. CONCLUSIONS: A close relationship exists between postoperative motor function and the results of TES-MEPs monitoring. TES-MEPs are superior to SSEPs and BAEPs in detecting motor dysfunction, but combined EPs serve as a safe, effective and invasive method for intraoperative monitoring of the function of the motor nervous system. Monitoring of combined EPs during microsurgery for lesions adjacent to the brainstem and intracranial aneurysms may detect potentially hazardous maneuvers and improve the safety of subsequent procedures.


Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Aneurisma Intracraniano/cirurgia , Microcirurgia , Monitorização Intraoperatória , Adolescente , Adulto , Idoso , Tronco Encefálico/fisiopatologia , Feminino , Humanos , Aneurisma Intracraniano/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
20.
Zhonghua Nan Ke Xue ; 13(3): 206-11, 2007 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-17393780

RESUMO

OBJECTIVE: To establish rat models of FSH autoantibody and to investigate the effect of FSH autoantibody on the spermatogenic capability of rat testis. METHODS: Thirsty 21-day old SD rats were randomly divided into an experimental and a control group of equal number. A specific polypeptide corresponding to the rat FSHbeta subunit was synthesized and coupled to (keyhole limpet hemocyanin) KLH. The rats in the experimental group were immunized with polypeptide-KLH and these in the control group with KLH. Further immunization was performed every 2 weeks for 7 times. On the 77th, 91st and 105th day of the immunization, 5 rats from the experimental group and another 5 from the control group were killed. Then the structures of the seminiferous tubule and epididymal sperm were observed by light and electron microscope, respectively. Meanwhile, the counts of sperms and the percentage of swelled sperm were calculated. And the level of serum testosterone was detected by enzyme-linked immunospecific assay (ELISA). RESULTS: The titer of the anti-polypeptide antibody was 1:200 on the 49th day of the immunization, and reached 1:400 on the 63rd. Compared with the control group, the percentage of swelled sperm significantly decreased on the 91st day (60.4 +/- 6.23 vs 50.60 +/- 3.05, P < 0.05), and the number of spermatogenic cells and sperms in seminiferous tubules reduced on the 105th day in the experimental group, the counts of sperms (46.08 +/- 6.56 vs 32.53 +/- 3.41) and the percentage of swelled sperm (60.60 +/- 5.86 vs 48.60 +/- 3.85) significantly lower (P < 0.05), while the level of serum T significantly higher than that in the control group (P < 0.05). CONCLUSION: FSH autoantibody might cause testis dyszoospermia.


Assuntos
Autoanticorpos/fisiologia , Hormônio Foliculoestimulante/imunologia , Hemocianinas/imunologia , Espermatozoides/fisiologia , Testículo/fisiologia , Animais , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Contagem de Espermatozoides
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