Staging of Liver Fibrosis Based on Energy Valley Optimization Multiple Stacking (EVO-MS) Model.

Currently, staging the degree of liver fibrosis predominantly relies on liver biopsy, a method fraught with potential risks, such as bleeding and infection. With the rapid development of medical imaging devices, quantification of liver fibrosis through image processing technology has become feasible. Stacking technology is one of the effective ensemble techniques for potential usage, but precise tuning to find the optimal configuration manually is challenging. Therefore, this paper proposes a novel EVO-MS model-a multiple stacking ensemble learning model optimized by the energy valley optimization (EVO) algorithm to select most informatic features for fibrosis quantification. Liver contours are profiled from 415 biopsied proven CT cases, from which 10 shape features are calculated and inputted into a Support Vector Machine (SVM) classifier to generate the accurate predictions, then the EVO algorithm is applied to find the optimal parameter combination to fuse six base models: K-Nearest Neighbors (KNNs), Decision Tree (DT), Naive Bayes (NB), Extreme Gradient Boosting (XGB), Gradient Boosting Decision Tree (GBDT), and Random Forest (RF), to create a well-performing ensemble model. Experimental results indicate that selecting 3-5 feature parameters yields satisfactory results in classification, with features such as the contour roundness non-uniformity (Rmax), maximum peak height of contour (Rp), and maximum valley depth of contour (Rm) significantly influencing classification accuracy. The improved EVO algorithm, combined with a multiple stacking model, achieves an accuracy of 0.864, a precision of 0.813, a sensitivity of 0.912, a specificity of 0.824, and an F1-score of 0.860, which demonstrates the effectiveness of our EVO-MS model in staging the degree of liver fibrosis.

Validation and identification of anoikis-related lncRNA signatures for improving prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell carcinoma (ccRCC) usually has a high metastasis rate and high mortality rate. To enable precise risk stratification, there is a need for novel biomarkers. As one form of apoptosis, anoikis results from the disruption of cell-cell connection or cell-ECM attachment. However, the impact of anoikis-related lncRNAs on ccRCC has not yet received adequate attention. METHODS: The study utilized univariate Cox regression analysis in order to identify the overall survival (OS) associated anoikis-related lncRNAs (ARLs), followed by the LASSO algorithm for selection. On this basis, a risk model was subsequently established using five anoikis-related lncRNAs. To dig the inner molecular mechanism, KEGG, GO, and GSVA analyses were conducted. Additionally, the immune infiltration landscape was estimated using the ESTIMATE, CIBERSORT, and ssGSEA algorithms. RESULTS: The study constructed a novel risk model based on five ARLs (AC092611.2, AC027601.2, AC103809.1, AL133215.2, and AL162586.1). Patients categorized as low-risk exhibited significantly better OS. Notably, the study observed marked different immune infiltration landscapes and drug sensitivity by risk stratification. Additionally, the study preliminarily explored potential signal pathways associated with risk stratification. CONCLUSION: The study exhibited the crucial role of ARLs in the carcinogenesis of ccRCC, potentially through differential immune infiltration. Furthermore, the established risk model could serve as a valuable stratification factor for predicting OS prognosis.

A Zinc Oxide Nanowire-Modified Mineralized Collagen Scaffold Promotes Infectious Bone Regeneration.

Bone infection poses a major clinical challenge that can hinder patient recovery and exacerbate postoperative complications. This study has developed a bioactive composite scaffold through the co-assembly and intrafibrillar mineralization of collagen fibrils and zinc oxide (ZnO) nanowires (IMC/ZnO). The IMC/ZnO exhibits bone-like hierarchical structures and enhances capabilities for osteogenesis, antibacterial activity, and bacteria-infected bone healing. During co-cultivation with human bone marrow mesenchymal stem cells (BMMSCs), the IMC/ZnO improves BMMSC adhesion, proliferation, and osteogenic differentiation even under inflammatory conditions. Moreover, it suppresses the activity of Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans by releasing zinc ions within the acidic infectious microenvironment. In vivo, the IMC/ZnO enables near-complete healing of infected bone defects within the intricate oral bacterial milieu, which is attributed to IMC/ZnO orchestrating M2 macrophage polarization, and fostering an osteogenic and anti-inflammatory microenvironment. Overall, these findings demonstrate the promise of the bioactive scaffold IMC/ZnO for treating bacteria-infected bone defects.

Economic evaluation of stent retrievers in basilar artery occlusion: An analysis from Chinese healthcare system perspective.

PURPOSE: This study aimed to investigate the cost-effectiveness of stent retriever (SR) versus best medical management (BMM) in patients with basilar artery occlusion (BAO) in China. METHODS: We used a two-step approach to compare the cost-effectiveness of SR plus BMM with that of BMM alone over 20 years. A decision tree was initially constructed for the first 3 months, followed by a Markov model for the subsequent period. Collected data on clinical aspects were extracted from the BAOCHE investigation, while costs-related information was sourced from previously published research. The key metric for evaluating the primary outcome was the incremental cost-effectiveness ratio (ICER), achieved $/QALY. The threshold for identifying SR as highly cost-effective was set at an ICER below $12,551/QALY, SR was deemed cost-effective if the ICER ranged from $12,551 to $37,654 per QALY. Uncertainty was addressed using scenario, one-way sensitivity, and probabilistic sensitivity analyses (PSA). FINDINGS: For Chinese patients with BAO, the 20-year cost per patient was $8678 with BMM alone and $21,988 for SR plus BMM. Effectiveness was 1.45 QALY for BMM alone, and 2.77 QALY for SR plus BMM. The ICER of SR + BMM versus BMM alone was $10,050 per QALY. The scenario and one-way sensitivity analyses revealed that in certain situations the ICER could exceed $12,551 per QALY, but remain below $37,654 per QALY. Results from the PSA suggested that SR was likely to be cost-effective for Chinese patients with BAO, with a probability exceeding 98% when considering a willingness-to-pay (WTP) threshold of $12,551 per QALY. IMPLICATIONS: Our study indicates that SR is an intervention option that is highly likely to be cost-effective for Chinese patients with BAO, with a probability of over 98% under the current WTP threshold of $12,551 per QALY.

PIK3C2A is a prognostic biomarker that is linked to immune infiltrates in kidney renal clear cell carcinoma.

Background: Phosphoinositide 3-kinases (PI3Ks) are lipid enzymes that regulate a wide range of intracellular functions. In contrast to Class I and Class III PI3K, which have more detailed descriptions, Class II PI3K has only recently become the focus of functional research. PIK3C2A is a classical member of the PI3Ks class II. However, the role of PIK3C2A in cancer prognosis and progression remains unknown. Methods: The expression pattern and prognostic significance of PIK3C2A in human malignancies were investigated using multiple datasets and scRNA-seq data. The PIK3C2A expression in renal clear cell carcinoma (KIRC) was then validated utilizing Western blot. The functional role of PIK3C2A in KIRC was assessed using combined function loss experiments with in vitro experiments. Furthermore, the correlation of PIK3C2A expression with tumor immunity was investigated in KIRC. The TCGA database was employed to investigate PIK3C2A functional networks. Results: Significant decrease in PIK3C2A expression in KIRC, demonstrated that it potentially influences the prognosis of diverse tumors, particularly KIRC. In addition, PIK3C2A was significantly correlated with the T stage, M stage, pathologic stage, and histologic grade of KIRC. Nomogram models were constructed and used to predict patient survival based on the results of multivariate Cox regression analysis. PIK3C2A knockdown resulted in significantly increased KIRC cell proliferation. Of note, PIK3C2A expression demonstrated a significant correlation with the infiltrating levels of primary immune cells in KIRC. Conclusion: These findings support the hypothesis that PIK3C2A is a novel biomarker for tumor progression and indicates dynamic shifts in immune infiltration in KIRC. Furthermore, aberrant PIK3C2A expression can influence the biological activity of cancer cells.

Autophagy-related gene LAPTM4B promotes the progression of renal clear cell carcinoma and is associated with immunity.

Renal cell carcinoma (RCC) is a common urologic disease. Currently, surgery is the primary treatment for renal cancer; immunotherapy is not as effective a treatment strategy as expected. Hence, understanding the mechanism in the tumor immune microenvironment (TME) and exploring novel immunotherapeutic targets are considered important. Recent studies have demonstrated that autophagy could affect the immune environment of renal cell carcinoma and induce proliferation and apoptosis of cancer cells. By comparing lysosomal genes and regulating autophagy genes, we identified the LAPTM4B gene to be related to RCC autophagy. By analyzing the TCGA-KIRC cohort using bioinformatics, we found M2 macrophages associated with tumor metastasis to be significantly increased in the immune microenvironment of patients with high expression of LAPTM4B. GO/KEGG/GSEA/GSVA results showed significant differences in tumor autophagy- and metastasis-related pathways. Single-cell sequencing was used to compare the expression of LAPTM4B in different cell types and obtain the differences in lysosomal and autophagy pathway activities in different ccRCC cells. Subsequently, we confirmed the differential expression of LAPTM4B in renal cell carcinoma of different Fuhrman grades using western blotting. Downregulation of LAPTM4B expression significantly reduced the proliferation of renal cell carcinoma cells and promoted cell apoptosis through cell experiments. Overall, our study demonstrated that the autophagy-related gene LAPTM4B plays a critical role in the TME of RCC, and suggested that LAPTM4B is a potential therapeutic target for RCC immunotherapy.

Meta-Analysis of the Diagnostic Value of Cell-free DNA for Renal Cancer.

Cell-free DNA (cf-DNA) has been reported to represent a suitable material for liquid biopsy in the diagnosis and prognosis of various cancers. We performed a meta-analysis of published data to investigate the diagnostic value of cf-DNA for renal cancer (RCa). Systematic searches were conducted using Pubmed, Embase databases, Web of Science, Medline and Cochrane Library to identify relevant publications until the 31st March 2021. For all patients, we evaluated the true diagnostic value of cf-DNA by calculating the number of true positive, false positive, true negative, and false negative, diagnoses by extracting specificity and sensitivity data from the selected literature. In total, 8 studies, featuring 754 RCa patients, and 355 healthy controls, met our inclusion criteria. The overall diagnostic sensitivity and specificity for cf-DNA was 0.71 (95% confidence interval (CI), 0.55-0.83) and 0.79 (95% CI, 0.66-0.88), respectively. The pooled positive likelihood ratio and pooled negative likelihood ratio were 3.42 (95% CI, 2.04-5.72) and 0.36 (95% CI, 0.23-0.58), respectively. The area under the summary receiver operating characteristic curve was 0.82 (95% CI, 0.79-0.85), and the diagnostic odds ratio was 7.80 (95% CI, 4.40-13.85). Collectively, our data demonstrate that cf-DNA has high specificity and sensitivity for diagnosing RCa. Therefore, cf-DNA is a useful biomarker for the diagnosis of RCa.

ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through m6A-PKM2-Mediated Glycolysis and Enhances Chemosensitivity.

OBJECTIVE: N6-Methyladenosine (m6A) is the most prevalent RNA epigenetic modulation in eukaryotic cells, which serves a critical role in diverse physiological processes. Emerging evidences indicate the prognostic significance of m6A regulator ZC3H13 in hepatocellular carcinoma (HCC). Herein, this study was conducted for revealing biological functions and mechanisms of ZC3H13 in HCC. METHODS: Expression of ZC3H13 was examined in collected HCC and normal tissues, and its prognostic significance was investigated in a public database. Gain/loss of functional assays were presented for defining the roles of ZC3H13 in HCC progression. The specific interactions of ZC3H13 with PKM2 were validated in HCC cells via mRNA stability, RNA immunoprecipitation, and luciferase reporter and MeRIP-qPCR assays. Moreover, rescue experiments were carried out for uncovering the mechanisms. RESULTS: ZC3H13 expression was downregulated in HCC, and its loss was in relation to dismal survival outcomes. Functionally, overexpressed ZC3H13 suppressed proliferation, migration, and invasion and elevated apoptotic levels of HCC cells. Moreover, ZC3H13 overexpression sensitized to cisplatin and weakened metabolism reprogramming of HCC cells. Mechanically, ZC3H13-induced m6A modified patterns substantially abolished PKM2 mRNA stability. ZC3H13 facilitated malignant behaviors of HCC cells through PKM2-dependent glycolytic signaling. CONCLUSION: Collectively, ZC3H13 suppressed the progression of HCC through m6A-PKM2-mediated glycolysis and sensitized HCC cells to cisplatin, which offered a fresh insight into HCC therapy.

The RBP1-CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma.

Retinol-binding protein 1 (RBP1) is involved in several physiological functions, including the regulation of the metabolism and retinol transport. Studies have shown that it plays an important role in the pathogenesis of several types of cancer. However, the role of RBP1 and its correlation with autophagy in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown. In this study, RBP1 was identified as the most significantly upregulated DEPs with a >2-fold change in OSCC samples when compared to normal tissues through iTRAQ-based proteomics analysis coupled with 2D LC-MS/MS. RBP1 overexpression was significantly associated with malignant phenotypes (differentiation, TNM stage, and lymphatic metastasis) of OSCC. In vitro experiments demonstrated that RBP1 was significantly increased in OSCC tissues and cell lines compared with control group. RBP1 overexpression promoted cell growth, migration, and invasion of OSCC cells. Silencing of RBP1 suppressed tumor formation in xenografted mice. We further demonstrated that the RBP1-CKAP4 axis was a critical regulator of the autophagic machinery in OSCC, inactivation of autophagy rescued the RBP1-CKAP4-mediated malignant biological behaviors of OSCC cells. Overall, a mechanistic link was provided by RBP1-CKAP4 between primary oncogenic features and the induction of autophagy, which may provide a potential therapeutic target that warrants further investigation for treatment of OSCC.

circ-PKD2 inhibits carcinogenesis via the miR-204-3p/APC2 axis in oral squamous cell carcinoma.

Recent findings have shown that dysregulation of circular RNAs (circRNAs) is implicated in various cancers. However, the contribution of circRNAs in oral squamous cell carcinoma (OSCC) remains largely unexplored. We screened circRNA expression profiles using a circRNA microarray in paired OSCC and normal tissues and explored the clinical significance of a downregulated circRNA, circ-PKD2. Moreover, the biological function of circ-PKD2 in OSCC was investigated both in vitro and in vivo. We found that downregulation of circ-PKD2 in OSCC correlated significantly with aggressive characteristics. Further analysis revealed that overexpression of circ-PKD2 inhibited OSCC cell proliferation, migration and invasion, induced apoptosis and cell cycle arrest, which were promoted by knockdown of circ-PKD2. In addition, circ-PKD2 was identified as a sponge for miR-204-3p and upregulated the expression of adenomatous polyposis coli 2 (APC2), which was the functional target of miR-204-3p. Moreover, circ-PKD2 attenuated the oncogenic effects of miR-204-3p-mediated APC2 on OSCC progression via multiple signaling pathways. These results demonstrate that the circ-PKD2/miR-204-3p/APC2 axis represents a novel pathway involved in the pathogenesis of OSCC and may serve as a novel therapeutic target of OSCC.

Decreased expression of hsa_circ_0072387 as a valuable predictor for oral squamous cell carcinoma.

OBJECTIVE: Increasing evidence points toward the key function of circular RNAs (circRNAs) in various carcinomas. This study aimed to identify aberrant expression of hsa_circ_0072387 in oral squamous cell carcinoma and probe its clinical significance. MATERIALS AND METHODS: Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to assess hsa_circ_0072387 expression levels in 63 paired OSCC tissues and three OSCC cell lines. The area under the receiver operator characteristic (ROC) curve was plotted to assess any potential clinical significance. RESULTS: Our data showed that hsa_circ_0072387 expression in OSCC was significantly downregulated compared with adjacent normal tissues (p < 0.001). Compared to human normal oral keratinocyte cell, the levels of hsa_circ_0072387 were lower in three OSCC cell lines (SCC25, SCC15, CAL27). More significantly, hsa_circ_0072387 expression was associated with the TNM stage in OSCC (p = 0.050). The area under the ROC curve reached up to 0.746. Based on bioinformatics, hsa-miR-129-3p, hsa-miR-141-3p, and hsa-miR-29-3p were predicted to be potential miRNAs binding with hsa_circ_0072387. Furthermore, hsa-miR-129-3p, hsa-miR-141-3p, and hsa-miR-29-3p were involved in multiple tumor-related signaling pathways. CONCLUSION: Our finding suggested that lower expression of has_circ_0072387 could be a key circRNA in OSCC and serve as a potential biomarker in OSCC diagnosis and therapeutic targets.

Suppression of OSCC malignancy by oral glands derived-PIP identified by iTRAQ combined with 2D LC-MS/MS.

Oral squamous cell carcinoma (OSCC) is the most common malignancy in head and neck cancer and a global cause of cancer-related death. Due to the poor survival rates associated with OSCC, there is a growing need to develop novel technologies and predictive biomarkers to improve disease diagnosis. The identification of new cellular targets in OSCC tumors will benefit such developments. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics analysis combined with 2-dimensional liquid chromatography and tandem mass spectrometry (2D LC-MS/MS) were used to identify differentially expressed proteins (DEPs) between tumor and normal tissues. Of the DEPs detected, the most significantly downregulated protein in OSCC tissue was prolactin-inducible protein (PIP). Clonogenic and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) experiments showed that the proliferation capacity of OSCC cells overexpressing PIP decreased due to cell cycle arrest at the G0/G1 checkpoint. Wound-healing and transwell assay further showed that PIP overexpression also reduced the migration and invasion of OSCC cells. Immunohistochemistry (IHC) was used to analyze the expression in OSCC, indicating that PIP may be secreted by glandular cells and have an inhibitory effect on OSCC cells to produce. In western blot analysis, silencing studies confirmed that PIP mediates these effects through the AKT/mitogen-activated protein kinase (MAPK) signaling axis in OSCC cells. Taken together, this study reveals PIP as a key mediator of OSCC cell growth, migration, and invasion through its effect on AKT/MAPK signaling.

Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro.

BACKGROUND: The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC. METHODS: Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR. RESULTS: In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings. CONCLUSION: The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.

CBCT-based bone quality assessment in decompression of large odontogenic cystic lesions.

OBJECTIVES: Bone quality comprises bone mineral density and trabecular microstructure. The aim of this study was to explore the effectiveness of cone-beam computed tomography (CBCT) in evaluating bone quality of large odontogenic cystic lesions after decompression using CBCT and BoneJ software, and to determine whether secondary definitive surgery can be guided using CBCT data. METHODS: Twenty-seven patients with large odontogenic cystic lesions treated by decompression were evaluated by CBCT. Medical history and perioperative details were analyzed. RESULTS: The [Formula: see text]CT values for all patients with cystic lesions decreased after decompression, with no differences for age, sex, and histology (p > 0.05). Bone volume fraction and trabecular number of new cancellous bone (0.012%, 0.17/mm3) were lower than those of normal cancellous bone (0.189%, 0.47/mm3) (p < 0.05), while new cancellous bone trabecular separation (11.344 ± 2.556 mm) was stronger than normal cancellous bone trabecular separation (4.833 ± 2.232 mm) (p < 0.05). There were no differences in trabecular thickness between new cancellous bone (3.812 ± 1.593 mm) and normal cancellous bone (4.598 ± 3.573 mm) (p = 0.746). The [Formula: see text]CT values of five patients with favorable osteogenesis were - 72, -86, - 86, -47, and - 55, those of three patients with moderate osteogenesis were - 107, -120, and - 71, and those of two patients with poor osteogenesis were - 165 and - 127 during secondary definitive surgery. CONCLUSIONS: CBCT is considered beneficial for evaluating bone quality of large odontogenic cystic lesions after decompression, while providing potentially useful information for referral to secondary definitive surgery.

Kindlin-2-mediated upregulation of ZEB2 facilitates migration and invasion of oral squamous cell carcinoma in a miR-200b-dependent manner.

The miR-200 family suppresses epithelial-mesenchymal transition by inhibiting ZEB1 and ZEB2 mRNA translation in several types of cancers. Kindlin-2 is a target gene of miR-200b and its expression level correlates positively to ZEB2 in oral squamous cell carcinoma (OSCC). Whether Kindlin-2 and ZEB2 share a competitive endogenous RNAs regulatory network in OSCC remains unclear. Here, we studied the expression levels of miR-200b, Kindlin-2, and ZEB2 and found direct interaction between miR-200b, ZEB2, and Kindlin-2 mRNA in OSCC. A series of experiments was performed to elucidate the role of miR-200b and Kindlin-2 in OSCC cells. To further investigate whether Kindlin-2 regulates ZEB2 as a "ceRNA", we utilized pools of siRNAs to deplete Kindlin-2 or ZEB2 in Tca-8113 cells. Significantly elevated expression levels of Kindlin-2 and ZEB2, down-regulated mRNA levels of miR-200b, and a positive correlation between Kindlin-2 and ZEB2 were found in OSCC cells. Additional results suggest that miR-200b directly targets ZEB2 and that Kindlin-2 3'UTR miR-200b repressed both the migration and invasive functionality of Tca-8113. Kindlin-2 and ZEB2 are involved in accelerated migration and invasion of Tca-113 cells in vitro and Kindlin-2 controlled ZEB2 expression. However, Kindlin-2-mediated ZEB2 regulation did not depend on miRNAs. These results indicate that Kindlin-2 does not act as ZEB2 ceRNA and modify the migration of Tca-8113 cells. Our results improve our understanding of the underlying molecular and cellular mechanisms of oral cancer metastasis.

Detection of Urothelial Bladder Carcinoma via Microfluidic Immunoassay and Single-Cell DNA Copy-Number Alteration Analysis of Captured Urinary-Exfoliated Tumor Cells.

The increasing incidence of bladder cancer and its high rate of recurrence over a 5-year period necessitate the need for diagnosis and surveillance amelioration. Cystoscopy and urinary cytology are the current tools, and molecular techniques such as BTA stat, NMP22, survivin mRNA, and urovysion FISH have attracted attention; however, they suffer from insufficient sensitivity or specificity. We developed a novel microfluidic approach for harvesting intact urinary-exfoliated tumor cells (UETC), either individually or in clusters, in a clean and segregated environment, which is crucial to minimize cross-contamination and misreads. To reliably and accurately identify UETC, our quantitative immunoassay involved concurrent use of two oncoproteins CK20 and CD44v6 antigen. CK20 is an intermediate filament protein overexpressed in urothelial tumors, and CD44v6 is a membrane adhesion molecule closely associated with cell invasion, tumor progression, and metastatic spread. Single-cell whole-genome sequencing on 12 captured UETCs and copy number alteration analysis showed that 11/12 (91.7%) of the immunofluorescence-identified UETCs possessed genomic instability. A total of 79 patients with bladder cancer and 43 age-matched normal controls (NC) were enrolled in the study. We detected considerably higher UETC counts in patients with bladder cancer versus the NC group [53.3 (10.7-1001.9) vs. 0.0 (0-3.0) UETCs/10 mL; P < 0.0001]. For bladder cancer detection, a stratified 10-fold cross-validation of training data reveals an overall predictive accuracy of 0.84 [95% confidence interval (CI), 0.76-0.93] with an 89.8% (95% CI, 71.5%-86.4%) for sensitivity and 71.5% (95% CI, 59.7%-83.3%) for specificity. Overall, the microfluidic immunoassay demonstrates increased sensitivity and specificity compared with other techniques for the detection of bladder cancer.Significance: A unique and promising diagnostic assay for bladder cancer is proposed with potential clinical utility as a complement for cytology. Cancer Res; 78(14); 4073-85. ©2018 AACR.

Effect of ß-carotene on immunity function and tumour growth in hepatocellular carcinoma rats.

The aim of the present study was to investigate the anticancer and immunity activity of ß-carotene in hepatocellular carcinoma (HCC) rats. Three days after transplantation, forty Wistar rats were randomly divided into four groups, each group consisting of 10 animals. These groups were control group (untreated), low-dose ß-carotene-treated group (20 mg/kg), middle-dose group (40 mg/kg) and high-dose (60 mg/kg) group. ß-Carotene-treated groups were fed with ß-carotene (20, 40, 60 mg/kg b.w.) orally for 30 days. Control group was treated with the same volume of physiological saline. Another ten rats were served as the normal group. Results showed that 30 days of ß-carotene treatment could significantly inhibit tumour growth, enhance blood NK, IL-2, TNF-α, WBC, TP, ALB and A/G levels, and decrease blood ALT, AST and ALP activities in HCC rats. Pathological analysis of liver tissue showed that ß-carotene treatment may decrease damage of liver tissue in HCC rats. It can be concluded that ß-carotene may improve the immunity function and inhibit tumour growth in HCC rats.

Clinicopathological characteristics and outcome of primary sarcomatoid carcinoma and carcinosarcoma of the liver.

BACKGROUND: Primary sarcomatoid carcinoma (SC) and carcinosarcoma (CS) of the liver are rare tumors. PATIENTS AND METHODS: From November 1999 to June 2011, clinicopathological features and outcome of 10 SC and 14 CS patients were retrospectively studied. RESULTS: In the SC group, six patients had hepatocellular carcinoma and four had cholangiocellular carcinoma, while in the CS group, it was nine and five patients, respectively. All cases of the sarcomatous components were vimentin-positive. Pan-cytokeratin were stained in sarcomatous components of the SC group, but not in the CS group. The sarcomatous component in the SC group was negative for desmin, myoglobin, HHF35, SMA, CD68, Mac387, AAT, CD34, and S100. In the CS group, the sarcomatous components in six cases were malignant fibrous histiocytomas, six were fibrosarcomas, and two were rhabdomyosarcomas. Median survival times were 9.6 and 4.8 months for the SC and CS groups, respectively (P = 0.483). In univariate analysis, favorable predictors of overall survival were asymptomatic, Child-Pugh class A, no distant metastasis, and radical resection. CONCLUSIONS: SC and CS were highly aggressive malignancies with similar poor survival regardless of the histological and immunohistochemical findings. Early detection through regular physical examination and treatment with radical resection may improve the outcome of those patients.

Effect of tea polyphenol on oxidative injury in S180 cells induced hepatocarcinoma mice.

The purpose of this study was to evaluate the antioxidant nature of tea polyphenol on S180 cells induced liver cancer in mice. In the present study, hepatocellular carcinoma was induced by tumor transplantation of liver in situ. The antitumor activity of tea polyphenol has been determined in vivo in hepatocellular carcinoma mice after treatment of drug (50, 100, 150 mg/kg body weight) by gavage for 20 days. Results showed that a significant increase in serum aspartate transaminase (AST), alkaline phosphatase (ALP), alanine aminotransfere (ALT), malondialdehyde (MDA) level, decrease in serum white blood cells (WBC), serum total protein (TP), albumin (ALB), A/G, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ), liver reduced glutathione (GSH) levels were observed. In addition, the levels of enzymic and non-enzymic antioxidants were decreased when subjected to S180 cells induction. These altered enzyme levels were ameliorated significantly by administration of tea polyphenol at the concentration of 50, 100, 150 mg/kg body weight in drug-treated animals. These results indicate that the protective effect of tea polyphenol was associated with inhibition of MDA induced by S180 cells and to maintain the antioxidant enzyme levels.

Antitumour activity of Lycium chinensis polysaccharides in liver cancer rats.

In the present study, polysaccharides were extracted from the Lycium chinensis (LCP). Rats were divided into four groups. Two groups (Groups A) were maintained on the basal diet, whereas the remaining three groups (Groups B, C and D) had free access to the basal diet and were orally fed with LCP at 200 mg/kg b.w. for Group B, 400 mg/kg b.w. for Group C and 600 mg/kg b.w. for Group D, respectively. Following 4 weeks of this dietary regimen, hepatocarcinogenesis was initiated in all animals by a single intraperitoneal DENA (Sigma-Aldrich, St. Louis, MO, USA) injection at a dose of 200 mg/kg body weight (mixed with peanut oil). Results still showed that L. chinensis polysaccharides (LCP) increased spleen, thymus indexs, antioxidant enzymes activities and decreased oxidative injury. In addition, LCP still significantly affect VEGF and Cyclin D1 proteins expression in liver cancer rats. It can be concluded that LCP exhibited remarkable protective effects against diethylnitrosamine (DEN)-induced oxidative hepatic injury in liver cancer rats.