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1.
World J Clin Oncol ; 15(2): 302-316, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38455139

ABSTRACT

BACKGROUND: Bladder cancer (BC) is the most common urological tumor. It has a high recurrence rate, displays tutor heterogeneity, and resists chemotherapy. Furthermore, the long-term survival rate of BC patients has remained unchanged for decades, which seriously affects the quality of patient survival. To improve the survival rate and prognosis of BC patients, it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention. Transmembrane 9 superfamily member 1 (TM9SF1), also known as MP70 and HMP70, is a member of a family of nine transmembrane superfamily proteins, which was first identified in 1997. TM9SF1 can be expressed in BC, but its biological function and mechanism in BC are not clear. AIM: To investigate the biological function and mechanism of TM9SF1 in BC. METHODS: Cells at 60%-80% confluence were transfected with lentiviral vectors for 48-72 h to achieve stable TM9SF1 overexpression or silencing in three BC cell lines (5637, T24, and UM-UC-3). The effect of TM9SF1 on the biological behavior of BC cells was then investigated through CCK8, wound-healing assay, transwell assay, and flow cytometry. RESULTS: Overexpression of TM9SF1 increased the in vitro proliferation, migration, and invasion of BC cells by promoting the entry of BC cells into the G2/M phase. Silencing of TM9SF1 inhibited in vitro proliferation, migration, and invasion of BC cells and blocked BC cells in the G1 phase. CONCLUSION: TM9SF1 may be an oncogene in BC.

2.
World J Clin Oncol ; 14(10): 420-439, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37970109

ABSTRACT

BACKGROUND: Since the start of the 21st century, prostate cancer with lung metastasis (PCLM) has accumulated significant scientific research output. However, a systematic knowledge framework for PCLM is still lacking. AIM: To reconstruct the global knowledge system in the field of PCLM, sort out hot research directions, and provide reference for the clinical and mechanism research of PCLM. METHODS: We retrieved 280 high-quality papers from the Web of Science Core Collection and conducted a bibliometric analysis of keywords, publication volume, and citation frequency. Additionally, we selected differentially expressed genes from global high-throughput datasets and performed enrichment analysis and protein-protein interaction analysis to further summarize and explore the mechanisms of PCLM. RESULTS: PCLM has received extensive attention over the past 22 years, but there is an uneven spatial distribution in PCLM research. In the clinical aspect, the treatment of PCLM is mainly based on chemotherapy and immunotherapy, while diagnosis relies on methods such as prostate-specific membrane antigen positron emission tomography/computed tomography. In the basic research aspect, the focus is on cell adhesion molecules and signal transducer and activator of transcription 3, among others. Traditional treatments, such as chemotherapy, remain the mainstay of PCLM treatment, while novel approaches such as immunotherapy have limited effectiveness in PCLM. This study reveals for the first time that pathways related to coronavirus disease 2019, cytokine-cytokine receptor interaction, and ribosome are closely associated with PCLM. CONCLUSION: Future research should focus on exploring and enhancing mechanisms such as cytokine-cytokine receptor interaction and ribosome and improve existing mechanisms like cadherin binding and cell adhesion molecules.

3.
Int J Urol ; 30(12): 1122-1132, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37602677

ABSTRACT

OBJECTIVES: This study aims to reveal immunophenotypes associated with immunotherapy response in bladder cancer, identify the signature genes of immune subtypes, and provide new molecular targets for improving immunotherapy response. METHODS: Bladder cancer immunophenotypes were characterized in the bulk RNA sequencing dataset GSE32894 and Imvigor210, and gene expression signatures were established to identify the immunophenotypes. Expression of gene signatures were validated in single-cell RNA sequencing dataset GSE145140 and human proteins expression data source. Investigation of Immunotherapy Response was performed in IMvigor210 dataset. Prognosis of tumor immunophenotypes was further analyzed. RESULTS: Inflamed and immune-excluded immunophenotypes were characterized based on the tumor immune cell scores. Risk score models that were established rely on RNA sequencing profiles and overall survival of bladder cancer cohorts. The inflamed tumors had lower risk scores, and the low-risk tumors were more likely to respond to atezolizumab, receiving complete response/partial response (CR/PR). Patients who responded to atezolizumab had higher SRRM4 and lower NPHS1 and TMEM72 expression than the non-responders. SRRM4 expression was a protective factor for bladder cancer prognosis, while the NPHS1 and TMEM72 showed the opposite pattern. CONCLUSION: This study provided a novel classification method for tumor immunophenotypes. Bladder cancer immunophenotypes can predict the response to immune checkpoint blockade. The immunophenotypes can be identified by the expression of signature genes.


Subject(s)
Nephrotic Syndrome , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Urinary Bladder , Immunotherapy , Tumor Microenvironment , Prognosis , Nerve Tissue Proteins
4.
IET Syst Biol ; 17(2): 70-82, 2023 04.
Article in English | MEDLINE | ID: mdl-36854874

ABSTRACT

Bladder cancer (BC) is a common cancer worldwide with a high prevalence. This study was conducted to elucidate the expression and clinical significance of Sorbin and SH3 domain-containing protein 1 (SORBS1) in BC as well as to explore its molecular mechanism in BC tumourigenesis. RNA-sequencing data, microarray, and Immunohistochemistry (IHC) were applied to elucidated the SORBS1 expression at multiple levels. After that, the relationship between tumour-immune infiltration and SORBS1 was also explored. Finally, SORBS1-related genes in BC were identified to perform functional enrichment analyses. The expression integration revealed that the comprehensive expression of SORBS1 at the mRNA level was -1.02 and that at the protein level was -3.73, based on 12 platforms, including 1221 BC and 187 non-BC samples. SORBS1 was negatively correlated with tumour purity (correlation = -0.342, p < 0.001) and positively correlated with macrophage (correlation = 0.358, p < 0.001). The results of enrichment analyses revealed that the most significant biological pathways of SORBS1-related genes were epithelial-mesenchymal transition. SORBS1 was significantly down-regulated in BC and may play a role as tumour suppressor. This study provides new directions and biomarkers for future BC diagnosis.


Subject(s)
Clinical Relevance , Urinary Bladder Neoplasms , Humans , Down-Regulation , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Urinary Bladder Neoplasms/genetics , Gene Expression Regulation, Neoplastic
5.
Naunyn Schmiedebergs Arch Pharmacol ; 396(9): 2071-2085, 2023 09.
Article in English | MEDLINE | ID: mdl-36914902

ABSTRACT

Nitidine chloride (NC) is effective on cancer in many tumors, but its effect on bladder cancer (BC) is unknown. We conducted cell function experiments to verify the antineoplastic effect of NC on BC cell lines (5637, T24, and UM-UC-3) in vitro. Then, mRNAs of NC-treated and NC-untreated BC cells were extracted for mRNA sequencing. Differentially expressed genes (DEGs), expression analysis, and drug molecular docking were conducted to discover the target gene of NC. Finally, functional enrichment was analyzed to explore the underlying mechanisms. NC dramatically inhibited proliferation, migration, and invasion, and it induced apoptosis and arrested the S and G2/M phases of BC cell lines. Lymphocyte antigen 75 (LY75) appeared to be the target of NC. LY75 was highly expressed and had the ability to distinguish BC tissue from non-cancerous tissue. Then, drug molecular docking confirmed the targeting relationship between NC and LY75. Gene enrichment analysis showed that the downregulated genes, after being treated with NC, were mainly enriched in pathways relevant to cell pathophysiological processes. NC inhibits BC cell proliferation, migration, and invasion, induces apoptosis, and arrests cell cycles by downregulating the expression of LY75. This study provides molecular and theoretical bases for NC treatment of BC.


Subject(s)
Signal Transduction , Urinary Bladder Neoplasms , Humans , Molecular Docking Simulation , Cell Line, Tumor , Cell Proliferation , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Apoptosis , Lymphocytes , Cell Movement
6.
Pathol Res Pract ; 233: 153847, 2022 May.
Article in English | MEDLINE | ID: mdl-35430506

ABSTRACT

Bladder cancer (BC) ranks as the ninth most commonly diagnosed cancer worldwide. The presence of a transcription factor (TF) has been uncovered as a significant contributor to the pathophysiological changes of cancers. In present study, we elucidated the expression and clinical significance of Homeobox A11 (HOXA11) in BC for the first time, and originally investigated HOXA11 as a TF. Employing in-house immunohistochemistry (IHC), we incorporated 137 BC and 34 non-BC cases to detect the expression of HOXA11 protein in BC tissues. HOXA11-related RNA-sequencing (RNA-seq) expression and RNA microarrays were collected from public databases, the "sva" and "limma" R packages were implemented to integrate and normalize the RNA-seq data and microarrays separately. Integration expression was carried out to further evaluate the HOXA11 expression by utilizing the standard mean difference (SMD). The expression level of HOXA11 in various BC cell lines was also evaluated. We further systematically analyzed the downstream target genes of HOXA11 in BC by utilizing Chromatin Immunoprecipitation Sequencing (ChIP-seq) profiles, differentially expressed genes (DEGs), and HOXA11-related genes. Modification of histone marks on the promoter region of target genes were also discovered by histone ChIP-seq data. Results of the IHC and RNA-seq revealed the protein and mRNA expression of HOXA11 was significantly decreased in BC tissues compared to non-BC tissues (2.98 ± 1.48 vs. 8.23 ± 2.64; 6.87 ± 1.54 vs. 8.38 ± 1.42). Five platforms significantly revealed the down-regulation of HOXA11 expression in BC (GPL96, GPL570, GPL6102, GPL6884, and GPL13497). A similar decreased trend was discovered in BC tissues in expression integration with the incorporated SMD reaching -0.843 (-1.362 ~ -0.325, p = 0.001) and -1.051 (-1.674 ~ -0.428, p = 0.001). Expression of HOXA11 was down-regulated in most of the BC cell lines. COL1A1 was considered as a final HOXA11 target gene and positively related to HOXA11 with the correlation coefficient as 0.584 (95% CI: 0.371-0.739, p < 0.001). HOXA11 regulates COL1A1 expression in BC via H3K27ac modification. The expression of COL1A1 was down-regulated with the SMD reached -0.312 (p < 0.001). In conclusion, HOXA11 expression is markedly decreased and might promote the transcription of COL1A1 to inhibit BC.


Subject(s)
Genes, Homeobox , Urinary Bladder Neoplasms , Gene Expression Regulation , Homeodomain Proteins , Humans , RNA , Transcription Factors/genetics , Urinary Bladder Neoplasms/genetics
7.
Cell Biosci ; 11(1): 87, 2021 May 17.
Article in English | MEDLINE | ID: mdl-34001269

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) play a crucial role in cancer development and tumor resistance to therapy in prostate cancer, but the influence of MSCs on the stemness potential of PCa cells by cell-cell contact remains unclear. In this study, we investigated the effect of direct contact of PCa cells with MSCs on the stemness of PCa and its mechanisms. METHODS: First, the flow cytometry, colony formation, and sphere formation were performed to determine the stemness of PCaMSCs, and the expression of stemness-related molecules (Sox2, Oct4, and Nanog) was investigated by western blot analysis. Then, we used western blot and qPCR to determine the activity levels of two candidate pathways and their downstream stemness-associated pathway. Finally, we verified the role of the significantly changed pathway by assessing the key factors in this pathway via in vitro and in vivo experiments. RESULTS: We established that MSCs promoted the stemness of PCa cells by cell-cell contact. We here established that the enhanced stemness of PCaMSCs was independent of the CCL5/CCR5 pathway. We also found that PCaMSCs up-regulated the expression of Notch signaling-related genes, and inhibition of Jagged1-Notch1 signaling in PCaMSCs cells significantly inhibited MSCs-induced stemness and tumorigenesis in vitro and in vivo. CONCLUSIONS: Our results reveal a novel interaction between MSCs and PCa cells in promoting tumorigenesis through activation of the Jagged1/Notch1 pathway, providing a new therapeutic target for the treatment of PCa.

8.
IET Syst Biol ; 15(1): 1-13, 2021 02.
Article in English | MEDLINE | ID: mdl-33527765

ABSTRACT

The clinicopathological implication and prospective molecular mechanisms of miRNA-145-5p in the metastasis of prostate cancer (PCa) stand unclear. Herein, it is found that miRNA-145-5p expression was remarkably reduced in 131 cases of metastatic PCa than 1371 cases of localised ones, as the standardised mean differences (SMD) was -1.26 and the area under the curve (AUC) was 0.86, based on miRNA-chip and miRNA-sequencing datasets. The potential targets of miRNA-145-5p in metastatic PCa (n = 414) was achieved from the intersection of miRNA-145-5p transfected metastatic PCa cell line data, differential expression of metastatic PCa upregulated genes and online prediction databases. TOP2A was screened as one of the target hub genes by PPI network analysis, which was adversely related to miRNA-145-5p expression in both metastatic PCa (r = -0.504) and primary PCa (r = -0.281). Gene-chip and RNA-sequencing datasets, as well as IHC performed on clinical PCa samples, showed consistent upregulated expression of TOP2A mRNA and protein in PCa compared with non-PCa. The expression of TOP2A mRNA was also significantly higher in metastatic than localised PCa with the SMD being 1.72 and the AUC of sROC being 0.91. In summary, miRNA-145-5p may participate in PCa metastasis by binding TOP2A and be useful as a biomarker for the detection of metastatic PCa.


Subject(s)
MicroRNAs , Neoplasm Metastasis/genetics , Prostatic Neoplasms , Gene Expression Regulation, Neoplastic , Humans , Male , MicroRNAs/genetics , Prospective Studies , Prostatic Neoplasms/genetics , RNA, Messenger
9.
Zhonghua Nan Ke Xue ; 26(8): 751-758, 2020 Aug.
Article in Chinese | MEDLINE | ID: mdl-33377740

ABSTRACT

Robot surgical system is the most advanced laparoscopic surgery technology, with obvious advantages in urology. Training in robotic surgery is essential for the application of future surgical techniques. A standardized training program should be established for robotic surgery in urology and andrology and form a disciplinary consensus of expert ideas based on the actual conditions of China and successful experience abroad. This article summarizes the development status, standardized training, training curriculum and evaluation tools in robotic surgery at home and abroad, exploring the bridging of the gaps in the training program, prospects, and establishment of a training system for robotic surgery operating standards in urology and andrology in China.


Subject(s)
Andrology , Robotic Surgical Procedures/education , Urology , Andrology/education , China , Clinical Competence , Humans , Urology/education
10.
Biomed Res Int ; 2020: 6037434, 2020.
Article in English | MEDLINE | ID: mdl-33178832

ABSTRACT

BACKGROUND: The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. MATERIALS AND METHODS: The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. RESULTS: The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. CONCLUSION: miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.


Subject(s)
Bone Neoplasms/secondary , Carcinogenesis/genetics , Down-Regulation/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , CDC2 Protein Kinase/metabolism , Gene Ontology , Gene Regulatory Networks , Humans , Kaplan-Meier Estimate , Male , MicroRNAs/metabolism , Middle Aged , Prognosis , Prostatic Neoplasms/diagnosis , Protein Interaction Maps/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , ROC Curve , Reproducibility of Results
11.
Med Sci Monit ; 26: e926273, 2020 Oct 26.
Article in English | MEDLINE | ID: mdl-33104528

ABSTRACT

BACKGROUND Bladder carcinoma (BLCA) is a leading cause of cancer-related deaths worldwide. The aim of this work was to develop an accurate stratification in predicting the prognosis and directing the treatment of BLCA patients based on small nucleolar RNAs (snoRNAs). MATERIAL AND METHODS Expression profiles of snoRNAs were downloaded from the SNORic database. The expression profiles and clinical outcomes of BLCA patients were analyzed. Survival-associated snoRNAs were identified and used to develop a novel risk score classifier. Genes in the whole genome that were significantly correlated with the included prognostic snoRNAs were used for functional enrichment analysis. RESULTS The results showed that age, American Joint Committee on Cancer (AJCC) stage, and tumor status were significantly correlated with overall survival (OS) of BLCA patients. We selected 12 survival-associated snoRNAs to build a prognostic signature. Patients were separated into high- and low-risk groups based on the median value of the risk score. Patients in the high-risk group and low-risk group have distinct clinical outcomes. The AJCC TNM stage showed moderate utility as a prognostic indicator for clinical outcome prediction. Then, clinical parameters and risk scores were entered in multivariate Cox analysis. Notably, the prognostic signature remained an independent significant prognostic risk factor. The pathway analysis suggested that these genes were enriched in several types of cancer and "Focal adhesion" pathways. CONCLUSIONS The prognostic signature defined by expression profiles of 12 survival-associated snoRNAs appears to be an excellent predictor of the clinical outcome of BLCA patients.


Subject(s)
Carcinoma/diagnosis , RNA, Small Nucleolar/metabolism , Urinary Bladder Neoplasms/diagnosis , Aged , Biomarkers, Tumor/metabolism , Carcinoma/epidemiology , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Risk Factors , Survival Rate , Urinary Bladder Neoplasms/epidemiology
12.
Cancer Biomark ; 27(2): 265-275, 2020.
Article in English | MEDLINE | ID: mdl-31929144

ABSTRACT

BACKGROUND: Tumor-infiltrating immune cells are indispensable to the progression and prognosis of clear cell renal cell carcinoma (ccRCC). OBJECTIVE: The aim of this study was to explore the clinical implications of immune cell infiltrates in ccRCC. METHODS: The Cancer Genome Atlas (TCGA) database (N= 515) and E-MTAB-1980 cohort of patients (N= 101) were adopted to estimate the prognostic value of immune cell infiltration. Twenty-four types of immune cells were evaluated using single-sample gene set enrichment analysis. Cox regression analyses were conducted to develop an immune risk score. RESULTS: Survival analyses revealed that 13 genes significantly associated with the overall survival (OS). Furthermore, multivariate Cox analysis identified an immune risk score on the basis of mast cells, natural killer CD56bright cells, T helper 17 (Th17) cells, and Th2 cells. The immune risk score was associated with OS, with hazard ratios of 2.72 (95% CI 2.17-3.40) and 3.24 (95% CI 1.64-6.44) in TCGA and E-MTAB-1980 datasets, respectively. This immune risk score was significantly correlated with some immunotherapy-related biomarkers. CONCLUSIONS: We profiled a prognostic signature and established an immune risk score model for ccRCC, which could provide novel predictive markers for patients with ccRCC and an indicator for immunotherapy response measurement.


Subject(s)
Carcinoma, Renal Cell/immunology , Kidney Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Carcinoma, Renal Cell/classification , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Cohort Studies , Female , Gene Expression Profiling , Humans , Kidney Neoplasms/classification , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Prognosis , RNA, Neoplasm/genetics , RNA, Neoplasm/immunology , Survival Rate
13.
BMC Cancer ; 17(1): 878, 2017 12 21.
Article in English | MEDLINE | ID: mdl-29268703

ABSTRACT

BACKGROUND: Prostate is susceptible to infection and pro-inflammatory agents in a man's whole life. Chronic inflammation might play important roles in the development and progression of prostate cancer. Mesenchymal stem cells (MSCs) are often recruited to the tumor microenvironment due to local inflammation. We have asked whether stimulation of MSCs by pro-inflammatory cytokines could promote prostate tumor growth. The current study investigated the possible involvement of MSCs stimulated by pro-inflammatory cytokines in promotion and angiogenesis of prostate cancer through relative pathway in vitro and in vivo. METHODS: A syngeneic mouse model of C57 was established. The murine prostate cancer cells (RM-1) mixing with MSCs treated with tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) or vehicle were subcutaneously injected into C57 mice. Tumor volume of C57 mouse model was estimated and serum level of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) was test by Enzyme-linked Immunosorbent Assay (ELISA). A hen egg test-chorioallantoic membrane (HET-CAM) assay was applied to test the effect of conditioned media of stimulated MSCs in chorioallantoic membrane angiogenesis. Short interfering RNA (siRNA) knocked down either hypoxia-inducible factor-1alpha (HIF-1α) or nuclear factor-erythroid-2-related factor 2 (NRF2) were employed. mRNA of PDGF and VEGF in MSCs, as well as NRF2 and HIF-1α was test by Real time polymerase chain reaction (PCR) analyses. Protein expression levels of PDGF and VEGF from conditioned medium, NRF2, HIF-1α, as well as PDGF and VEGF in MSCs were detected by Western blot analysis. RESULTS: MSCs treated with TNF-α and IFN-γ promote tumor growth in C57 syngeneic mouse model, correlating with increased serum level of PDGF, VEGF. HET-CAM assay shows the angiogenic effect of conditioned medium of MSCs pre-treated with the pro-inflammatory cytokines. mRNA and protein levels of two pro-angiogenic factors (PDGF and VEGF) and key hypoxia regulators (HIF-1α and NRF2) in MSCs were induced after MSCs' pretreatment. siRNA knockdown either HIF-1α or NRF2 results reduction of PDGF and VEGF expression. CONCLUSIONS: MSCs stimulated by pro-inflammatory cytokines increase the expression of PDGF and VEGF via the NRF2-HIF-1α pathway and accelerate prostate cancer growth in mice.


Subject(s)
Angiogenesis Inducing Agents/metabolism , Bone Marrow/pathology , Cytokines/pharmacology , Inflammation Mediators/pharmacology , Mesenchymal Stem Cells/pathology , Prostatic Neoplasms/pathology , Animals , Apoptosis/drug effects , Bone Marrow/drug effects , Bone Marrow/immunology , Bone Marrow/metabolism , Cell Proliferation/drug effects , Chickens , Chorioallantoic Membrane/drug effects , Chorioallantoic Membrane/pathology , Culture Media, Conditioned/pharmacology , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , Prostatic Neoplasms/chemically induced , Prostatic Neoplasms/immunology , Prostatic Neoplasms/metabolism , Tumor Burden , Tumor Cells, Cultured , Tumor Microenvironment
14.
Eur J Gastroenterol Hepatol ; 26(4): 444-51, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24463566

ABSTRACT

BACKGROUND: Because of an increasing aging population worldwide, a greater number of elderly patients are being considered for hepatic resection. The objective of this retrospective pair-matched study was to assess the influence of age on postoperative outcomes after major hepatectomy (resection of three or more Couinaud segments) in elderly patients with hepatocellular carcinoma (HCC) and cirrhosis. PATIENTS AND METHODS: A retrospective review of patient demographics, diagnoses, surgical treatments, and early postoperative outcomes was performed. RESULTS: A total of 208 HCC patients with cirrhosis underwent major hepatectomy between 2007 and 2012. The mortality rate was 3.57% in patients aged 70 years or more (group E) compared with 1.32% in those aged below 70 years (group Y; P=0.630). The overall complication rates were 53.57% in group E and 47.37% in group Y (P=0.427). Increasing age was independently associated with postoperative pneumonia (P<0.001), bacteremia (P=0.026), and respiratory failure requiring reintubation (P=0.028). A total of 25.00% of patients had a Clavien-Dindo classification grade of 3a or more in group E compared with 13.16% in group Y (P=0.040). In multivariate analysis, intraoperative red blood cell transfusion of 5 U or more (P=0.016; hazard ratio 4.812; 95% confidence interval 1.332-17.384) was a predictor of higher morbidity in the elderly. CONCLUSION: With rigorous screening of patients and improvement of perioperative management and operative techniques, major hepatectomy can be safely performed on HCC patients aged 70 years or more with liver cirrhosis. Intraoperative red blood cell transfusion of 5 U or more was predictive of higher morbidity in the elderly. Surgeons should take care to minimize the likelihood of intraoperative blood transfusion in elderly patients.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Hepatitis B/complications , Hepatitis C/complications , Liver Cirrhosis/virology , Liver Neoplasms/surgery , Adult , Age Factors , Aged , Blood Loss, Surgical/prevention & control , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/virology , Chi-Square Distribution , Erythrocyte Transfusion , Female , Hepatectomy/adverse effects , Hepatitis B/diagnosis , Hepatitis C/diagnosis , Humans , Liver Cirrhosis/diagnosis , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Male , Middle Aged , Multivariate Analysis , Patient Safety , Postoperative Complications/etiology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
15.
Int J Cancer ; 134(10): 2403-13, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24122750

ABSTRACT

The prognostic role of inflammation index like neutrophil-to-lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta-analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression-free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499-2.193) and PFS (HR: 2.102, 95% CI: 1.554-2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226-2.022) and higher carcino-embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308-1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.


Subject(s)
Colorectal Neoplasms/pathology , Lymphocytes/pathology , Neutrophils/pathology , Carcinoembryonic Antigen/metabolism , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/therapy , Disease-Free Survival , Humans , Lymphocyte Count , Neoplasm Staging , Prognosis
16.
Int J Clin Exp Med ; 6(9): 845-50, 2013.
Article in English | MEDLINE | ID: mdl-24179582

ABSTRACT

Hepatic tuberculosis is uncommon, lack of specific clinical manifestations and imaging features, so it can easily be misdiagnosed in clinical. Herein, we discuss variety of its forms and summarize the diagnosis and treatment of hepatic tuberculosis in this paper. Five cases of hepatic tuberculosis are described. The diagnosis, treatment and outcome of the patients are discussed. Image examination associated with image-guided fine needle aspiration biopsy is the best diagnostic method. In our center, three patients underwent needle biopsy and confirmed hepatic tuberculosis. In addition, two patients preoperative misdiagnosed as cholangiocarcinoma were confirmed hepatic tuberculosis by postoperative pathology. Three patients underwent surgical procedures along with anti-tubercular drug therapy, two patients received only anti-tubercular drug therapy. The renal post-transplantation patient with hepatic tuberculosis eventually died of multiple organ failure (MODS). The other four patients were followed for 48~120 months, yielding no recurrence of hepatic tuberculosis. In conclusion, hepatic tuberculosis usually associated with atypical clinical manifestations. Image examination associated with image-guided fine needle aspiration biopsy is the best diagnostic method. Anti-TB treatment is effective in most of cases. However, if there are indications for surgery or difficult to diagnose, surgical procedures along with anti-tubercular drug therapy could be adopted.

17.
Med Oncol ; 30(1): 381, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23292867

ABSTRACT

Many non-surgical treatments of hepatocellular carcinoma (HCC) have significantly improved in the last few decades and have shown survival benefits for selected patients with HCC. Today ablation can improve survival in individuals diagnosed in early HCC and even offer a curative treatment in selected candidates. Patients with intermediate-stage HCC benefit from transarterial chemoembolization (TACE). Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown a better combined ischemic and cytotoxic effect locally and less system toxicity when compared with conventional TACE. Those diagnosed at advanced stage benefit from sorafenib. In addition to TACE and sorafenib which could improve survival for selected patients, three-dimensional conformal radiotherapy treatment (3-DCRT), selection internal radiation therapy and systemic chemotherapy have also shown anti-tumor activity in the treatment of advanced HCC, but their survival benefit have not been proven. The limited effects of single therapy suggested that the combination would enhance the overall treatment effect. Other potential non-surgical therapies like gene therapy and immunotherapy are still in testing phases, except for some small-scale clinical trials which have been reported to show some beneficial effect. Here, we review the current non-surgical treatments in HCC and the new advances in this field.


Subject(s)
Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Ablation Techniques/methods , Chemoembolization, Therapeutic/methods , Combined Modality Therapy , Humans , Radiotherapy/methods
18.
Ai Zheng ; 28(3): 232-5, 2009 Mar.
Article in Chinese | MEDLINE | ID: mdl-19619435

ABSTRACT

BACKGROUND AND OBJECTIVE: Establishing ovarian cancer cell lines will benefit researches on biological characteristics of ovarian cancer stem cells and antitumor drugs. This study was to establish a human ovarian carcinoma cell line from peritoneal effusion, and explore its biological characteristics. METHODS: Cells were isolated from peritoneal effusion of an ovarian carcinoma patient, purified and cultured in vitro. The morphology of the cells was observed under electromicroscope. The growth curve of cells was drawn to calculate cell doubling time (TD). Cell karyotype was analyzed. The levels of sex hormone, and the expression of CA125 and CA19-9 in cell culture supernate were detected by radioimmunoassay. The cells were transplanted into nude mice to observe tumor formation. RESULTS: A new ovarian carcinoma cell line was established, which had been maintained in vitro for over 100 passages in two years. Abnormal nuclei were observed under electromicroscope. TD was 40.8 h. The karyotype of the cells was hyperdiploid with 63-120 chromosomes. The level of estradiol in cell culture supernate was 45.0 pg/mL; the level of testosterone was 0.03 ng/mL; pregnendione was undetected; the level of CA125 was 4.49 U/mL; the level of CA19-9 was 4.09 U/mL. Poorly differentiated ovarian adenocarcinoma was formed subcutaneously in nude mice after transplantation. CONCLUSION: The new ovarian carcinoma cell line is proved to be an immortalized and malignant cell line.


Subject(s)
Adenocarcinoma/pathology , Cell Line, Tumor , Disease Models, Animal , Ovarian Neoplasms/pathology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Animals , Ascitic Fluid/pathology , CA-125 Antigen/metabolism , CA-19-9 Antigen/metabolism , Estradiol/metabolism , Female , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Polyploidy , Progesterone/metabolism , Testosterone/metabolism
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