SOX11 as a prognostic biomarker linked to m6A modification and immune infiltration in renal clear cell carcinoma.

Background: The prognosis for patients with kidney renal clear cell carcinoma (KIRC) remains unfavorable, and the understanding of SRY-box transcription factor 11 (SOX11) in KIRC is still limited. The purpose of this paper is to explore the role of SOX11 in the prognosis of KIRC. Methods: We analyzed SOX11 expression in KIRC and adjacent normal tissues using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Our study aims to establish a correlation between SOX11 expression and clinical pathological features. Differentially expressed genes (DEGs) were assessed using R software. Furthermore, we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). Integration of data from the Tumor Immune Estimation Resource (TIMER) and TCGA databases allowed us to assess the association between SOX11 expression and immune infiltration in KIRC. Additionally, we analyzed the association between SOX11 gene expression and N6-methyladenosine (m6A) modification in KIRC using TCGA and GEO data. Results: Our findings revealed high SOX11 expression in KIRC, which showed a significant correlation with tumor staging and prognosis. GO/KEGG and GSEA analyses indicated that SOX11 was closely associated with sodium ion transport, synaptic vesicle circulation, and oxidative phosphorylation. Analysis of the TIMER and TCGA databases demonstrated correlations of SOX11 expression levels with the presence of CD8+ T lymphocytes, neutrophils, CD4+ T cells, as well as B cells. Moreover, both the TCGA and GEO datasets showed a substantial association between SOX11 and m6A modification-related genes, namely ZC3H13, FTO, METTL14, YTHDC1, IGF2BP1, and IGF2BP2. Conclusions: SOX11 exhibits a correlation with m6A modification and immune infiltration, suggesting its potential as a prognostic biomarker for KIRC.

Preparation of polyphenol-structural colored silk fabrics with bright colors.

Conventional textile dyeing relies on the use of dyes and pigments, which can cause severe environmental contamination and waste a large amount of water. Structural coloring is one of the effective ways to achieve environmentally friendly coloring of textiles. In this work, three plant polyphenols with the same o-benzenetriol structure (tannic acid (TA), gallic acid (GA), and tea polyphenol (TP)) were selected as raw materials. Three plant polyphenols can quickly form nanofilms at the gas-liquid interface through a Schiff base reaction with polyethyleneimine (PEI) under mildly alkaline conditions, which were deposited to the surface of silk fabric, allowing precise control over the thickness of film by adjusting the time, resulting in various structurally colored silk fabric. This method for creating structural colors is not substrate-specific and enables the quick production of structural colors on various textile substrates. Furthermore, the structural color silk fabric based on plant polyphenol has antibacterial performance. This textile coloring method is simple, cost-effective and environmentally friendly, providing a new approach to eco-friendly textile dyeing.

Fabrication of Robust Superhydrophobic Polyester Fabrics with Photothermal Conversion and Oil-Water Separation Performance through Deposition of Natural Polyphenols.

Superhydrophobic polyester (PET) fabrics were created by increasing fabric surface roughness and decreasing surface energy through interactions between natural polyphenols, ferrous sulfate heptahydrate, and hexadecyltrimethoxysilane. The superhydrophobic fabric can be obtained with different natural polyphenols, including tannic acid, ferulic acid, gallic acid, guaiacol, and caffeic acid. Durability tests were carried out on the superhydrophobic PET fabric, investigating resistance to washing, rubbing, UV aging, acids, alkalis, and organic reagents. The results demonstrate the stability and versatility of modified PET in complex environments. The modified superhydrophobic PET fabric exhibited exceptional oil-water separation and self-cleaning properties, exhibiting a water contact angle of 161.3° and a sliding angle of 4°. In addition, the modified fabric demonstrated a remarkable photothermal conversion efficiency, with the surface temperature increasing from 29.1 to 72 °C in 300 s, and it maintained a degree of photothermal conversion capability even upon completion of four cycles. This study offers novel perspectives on extending the utilization of natural polyphenols for constructing durable, robust, and multifunctional superhydrophobic fabrics.

Static sitting posture control during writing tasks in idiopathic scoliosis among freshmen.

BACKGROUND: The posture control deficit is one important dysfunction in adolescent idiopathic scoliosis (AIS) patients, which is related to the development of the disease. However, it is not apparent whether AIS could affect static sitting posture control in late adolescence. OBJECTIVE: This study aims to compare static sitting posture control in idiopathic scoliosis freshmen with normal peers to reveal possible differences in posture stability between them during writing tasks. METHODS: In total, there were 10 AIS patients and 11 normal college students chosen for the writing task test. Data on the distribution of gluteal pressure during sitting were gathered. The comparison between these two groups was made using the independent sample t-test. RESULTS: The total excursion (TE) of the center of pressure (COP) of the AIS group considerably increased in comparison with the control group (CON) (p = 0.029). The AIS group's average COP velocity in the anteroposterior (AP) direction was significantly higher than the CON group (p = 0.048). The peak gluteal pressure on the right side was significantly higher in the AIS group than in the CON group (p = 0.039). The right gluteal contact area dynamic variation was significantly higher in the AIS group compared to the CON group (p = 0.025). CONCLUSIONS: AIS patients showed increased gluteal pressure and lower sitting posture stability during writing tasks.

Esterase D interacts with metallothionein 2A and inhibits the migration of A549 lung cancer cells in vitro.

Esterase D (ESD) is a nonspecific esterase widely distributed in various organisms. ESD plays an important role in regulating cholesterol efflux, inhibiting viral replication and lung cancer growth. MT2A (metallothionein 2A) is the most important isoform of metallothionein (MTs) in human and high expression of MT2A in tumors represents poor prognosis and metastatic behavior. However, there are no reports about the molecular mechanism of ESD in the regulation of tumor metastasis. In this study, we found for the first time that activation ESD promoted its interaction with MT2A and decreased the protein level of MT2A, which resulting in the concentration of free zinc ions up-regulated, and inhibited the migration of A549 lung cancer cells in vitro.

Increased Metallothionein-1 Associated with Gout Activity and Tophi.

BACKGROUND AND AIMS: Gout is a chronic self-limiting inflammatory arthritis. An increase in metallothionein-1 (MT-1) has been reported in rheumatoid arthritis and osteoarthritis, and it attenuates inflammation and the pathology of diseases. This study aims to detect MT-1 levels in patients with gout and to explore its correlation with disease activity, clinical indexes, and inflammatory cytokines. METHODS: The expression of MT-1 messenger RNAs (mRNAs) and protein levels in patients with gout were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Correlations between MT-1 and clinical indexes or inflammatory mediators were analyzed using Spearman's correlation test. RESULTS: Compared with healthy controls (HCs, n = 43), patients with active gout (n = 27) showed higher levels of MT-1 mRNA in peripheral blood mononuclear cells and protein in serum, particularly those with tophi. No significant difference in serum MT-1 levels was observed among patients with inactive gout, HCs, and patients with hyperuricemia without gout. Furthermore, no significant difference was observed between patients with gout with kidney damage and HCs. In addition, serum interleukin (IL)-1ß, IL-6, and IL-8 levels were significantly increased in patients with active gout, particularly in those with tophi. The serum MT-1 level was positively correlated with C-reactive protein, as well as with IL-1ß, IL-6, and IL-18. CONCLUSION: The higher levels of MT-1 were found in patients with gout, which were correlated with disease activity and gout related pro-inflammatory cytokines. Indicating MT-1 may serve as a new marker for predicting disease activity.Abbreviations: IL-1ß: Interleukin 1ß; MT-1: Metallothionein-1; CRP: C-Reactive Protein; ROS: Reactive Oxygen Species; IL-10: Interleukin 10; TGF-ß: Transforming Growth Factor Beta.

HAPLN3 inhibits apoptosis and promotes EMT of clear cell renal cell carcinoma via ERK and Bcl-2 signal pathways.

Hyaluronan and proteoglycan link protein 3 (HAPLN3) is a member of the hyaluronan and proteoglycan link protein family expressed in the extracellular matrix closely associated with the development and occurrence of various malignant tumors; yet, its function in clear cell renal cell cancer (ccRCC) is still poorly understood. The following study investigated the progress and mechanism of HAPLN3 on ccRCC using bioinformatics analysis and in vitro experiments. In order to determine whether HAPLN3 is differentially expressed in ccRCC, we analyzed data from the Cancer Genome Atlas (TCGA) and GSE40435 and further validated them in the Human Protein Atlas (HPA) database. Simultaneously, the TCGA dataset was utilized to study the relationship between HAPLN3 expression and the progression of ccRCC and its prognostic value in ccRCC. Gene enrichment analysis (GSEA) was used to explore HAPLN3-related signaling pathways in ccRCC. The TIMER database investigates the link for both HAPLN3 and immune cell infiltration. Different ccRCC cell lines the role of HAPLN3 on cell biological behavior in vitro. HAPLN3 was increased in ccRCC, and its high expression was related to the patients' survival rates and clinical characteristics. GSEA showed that HAPLN3 is mainly enriched in proliferative and metastatic pathways. In addition, HAPLN3 was an independently associated significant predictor in patients with ccRCC. Functional experiments demonstrated that HAPLN3 could promote the proliferation, migration, and invasion of ccRCC cells through the ERK1/2 signaling pathway. To sum up, our data suggest that HAPLN3 may serve as a new prognostic biomarker and potential therapeutic target for ccRCC.

Predictive Value of the Log Odds of Negative Lymph Nodes/T Stage as a Novel Prognostic Factor in Bladder Cancer Patients After Radical Cystectomy.

Background: The effect of lymph node resection on the prognosis of bladder cancer (BLCA) patients receiving radical cystectomy should not be ignored. Our aim was to explore the prognostic value of the log odds of negative lymph nodes/T stage (LONT) and construct a more effective nomogram based on LONT to predict cancer-specific survival (CSS) in postoperative BLCA patients. Methods: Patients diagnosed with BLCA after radical cystectomy between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. We randomly split (7:3) these patients into the primary cohort and internal validation cohort. 86 patients from the First Affiliated Hospital of Nanchang University were collected as the external validation set. Univariate and multivariate cox regression analyses were carried out to seek prognostic factors of postoperative BLCA patients. According to these significantly prognostic factors, a simple-to-use nomogram was established for predicting CSS. Their performances were evaluated by using calibration curves, the concordance index (C-index), the receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). In addition, different risk groups were tested by Kaplan-Meier curves and log-rank tests. Result: Whether in cancer-specific survival (CSS) or overall survival (OS), LONT was an independent and significant prognostic factor. Through further screening, the ultimate nomogram of CSS was composed of nine independent prognostic factors including LONT, age, race, tumor size, histologic type, T stage, N stage, summary stage and chemotherapy. The C-index of nomogram in the primary cohort, internal and external validation cohort were 0.734, 0.720 and 0.728, respectively. The AUC of predicting CSS at 3 and 5 years were 0.783 and 0.774 in the primary cohort and 0.781 and 0.781 in the validation cohort. The results of calibration and DCA showed good concordance and clinical applicability. Significant differences (P < 0.05) were displayed in CSS among different risk groups. Conclusion: LONT was regarded as a novel and reliable prognostic factor. Compared with the AJCC staging system, the established nomogram based on LONT can more effectively predict the prognosis of BLCA patients after radical cystectomy.

Activation of Esterase D by FPD5 Inhibits Growth of A549 Lung Cancer Cells via JAB1/p53 Pathway.

Esterase D (ESD) is widely distributed in mammals, and it plays an important role in drug metabolism, detoxification, and biomarkers and is closely related to the development of tumors. In our previous work, we found that a chemical small-molecule fluorescent pyrazoline derivative, FPD5, an ESD activator, could inhibit tumor growth by activating ESD, but its molecular mechanism is still unclear. Here, by using RNA interference (RNAi), andco-immunoprecipitation techniques, we found that ESD suppressed the nucleus exportation of p53 through reducing the interaction between p53 and JAB1. The protein level of p53 in the nucleus was upregulated and the downstream targets of p53 were found by Human Gene Expression Array. p53 inhibited the expression of CDCA8 and CDC20. Lastly, the cell cycle of A549 cells was arrested at the G0/G1 phase. Together, our data suggest that ESD inhibited the cancer cell growth by arresting the cell cycle of A549 cells via the JAB1/p53 signaling pathway. Our findings provide a new insight into how to inhibit the growth of lung cancer with the activation of ESD by FPD5.

Esterase D stabilizes FKBP25 to suppress mTORC1.

BACKGROUND: Esterase D (ESD) is a nonspecific esterase that detoxifies formaldehyde. Many reports have stated that ESD activity is associated with a variety of physiological and pathological processes. However, the detailed signaling pathway of ESD remains poorly understood. METHODS: Considering the advantages of the small chemical molecule, our recent work demonstrated that 4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl) phenol (FPD5) activates ESD, and will be a good tool for studying ESD further. Firstly, we determined the interaction between ESD and FK506 binding protein 25 (FKBP25) by yeast two-hybrid assay and co-immunoprecipitation (CO-IP) and analyzed the phosphorylation levels of mTORC1, P70S6K and 4EBP1 by western blot. Furthermore, we used the sulforhodamine B (SRB) and chick chorioallantoic membrane (CAM) assay to analyze cell viability in vitro and in vivo after treatment with ESD activator FPD5. RESULTS: We screened FKBP25 as a candidate protein to interact with ESD by yeast two-hybrid assay. Then we verified the interaction between ESD and endogenous FKBP25 or ectopically expressed GFP-FKBP25 by CO-IP. Moreover, the N-terminus (1-90 aa) domain of FKBP25 served as the crucial element for their interaction. More importantly, ESD reduced the K48-linked poly-ubiquitin chains of FKBP25 and thus stabilized cytoplasmic FKBP25. ESD also promoted FKBP25 to bind more mTORC1, suppressing the activity of mTORC1. In addition, ESD suppressed tumor cell growth in vitro and in vivo through autophagy. CONCLUSIONS: These findings provide novel evidence for elucidating the molecular mechanism of ESD and ubiquitination of FKBP25 to regulate autophagy and cancer cell growth. The ESD/FKBP25/mTORC1 signaling pathway is involved in inhibiting tumor cell growth via regulating autophagy.

The prognosis and clinicopathological features of different distant metastases patterns in renal cell carcinoma: analysis based on the SEER database.

Existing data on the prognosis and clinicopathological features of patients with metastatic renal cell carcinoma (mRCC) are limited. This study aims to investigate the prognostic value and clinicopathological features of different metastatic sites in patients with mRCC. A dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database consisting of 18 registries (1973-2015) was selected for a retrospective mRCC cohort study. Information was included on the metastatic sites in lung, bone, liver, and brain. Kaplan-Meier analysis was applied to compare the survival distribution. Univariate and multivariate Cox regression models were used to analyze survival outcomes. From the SEER database, a total of 10,410 patients with primary mRCC from 2010 to 2015 were enrolled in this cohort study. Analysis indicated that 54.9%, 37.7%, 19.5%, and 10.4% of patients were found to have lung, bone, liver, and brain metastasis, respectively. There was a significantly higher risk for sarcomatoid RCC patients to develop liver metastasis as compared to patients with clear cell RCC. The median survival for patients with lung, bone, liver, or brain metastasis was 7 months, 7 months, 4 months, and 5 months, respectively. Various clinicopathological features and prognostic values are associated with different metastatic sites. Understanding these differences may enable targeted pre-treatment assessment of primary mRCC and personalized curative intervention for patients.

USP31 acetylation at Lys1264 is essential for its activity and cervical cancer cell growth.

Ubiquitin-specific protease 31 (USP31) is a member of deubiquitinase family that is involved in nuclear factor-κB activation and sarcomagenesis. However, little is known about posttranslational modification in the regulation of its activity and cervical cancer cell growth. In our study, we found that the Lys1264 residue of USP31 can be modified with an acetyl group by high-resolution mass spectrometry in HeLa cell line, and site-specific mutagenesis can significantly increase USP31 ubiquitin hydrolase activity and decrease the expression of p65. When being transfected with a plasmid expressing mutated USP31, the number of cancer cells was significantly decreased. We also observed that mutated USP31 could promote apoptosis but not cell cycle by flow cytometer analysis. Overexpression of mutated USP31 could reverse the effect in USP31 knockdown cell line. To further investigate its activity in tumorigenesis, deacetylase sirtuin 1 (Sirt1) was shown to interact with USP31 by co-immunoprecipitation and blocking the function of Sirt1 by knockdown or the inhibitor nicotinamide could increase the acetylation of USP31. When Lys1264 of USP31 mutated, Sirt1 could not remove its acetylation and alter the expression level of p65. Finally, inhibition or knockdown of Sirt1 suppressed USP31 activity in HeLa cell line, leading to cisplatin-induced apoptosis resistance. Therefore, acetylation at Lys1264 suppresses USP31 activity and plays a protective role in cancer cell growth. Our study contributes to understanding the mechanism of USP31 activity regulation and its role in tumorigenesis.

LncRNA H19 induces immune dysregulation of BMMSCs, at least partly, by inhibiting IL-2 production.

BACKGROUND: Systemic lupus erythematosus (SLE) is a representative systemic autoimmune disease. LncRNA H19 has been identified to participate in various biological processes in human diseases. However, the role of H19 in SLE remains unclear. METHODS: In this study, we first examined H19 expression in SLE patients by RT-qPCR and found that H19 expression was significantly upregulated in the serum and bone marrow-derived mesenchymal stem cells (BMMSCs) of SLE patients and positively associated with SLE disease activity index. We then performed gain-of-function and loss-of-function using mimic-H19 (H19-OE) and inhibitor-H19 (H19-KD) to examine the effects of H19 on BMMSC differentiation, proliferation, migration, and apoptosis using flow cytometry, DAPI staining, and migration and apoptosis assays. RESULTS: The results showed that H19 inhibited proliferation and migration but promoted apoptosis of BMMSCs, interfered with BMMSCs-mediated Treg cell proliferation and differentiation, and regulated BMMSCs-mediated Tfh/Treg cell balance. Dual-luciferase reporter assay confirmed the in silico prediction of interaction between H19 and IL-2. Furthermore, RT-qPCR showed that H19 directly inhibited IL-2 transcription in BMMSCs. ELISA showed that both active and total IL-2 protein levels were significantly lower in SLE BMMSCs. More importantly, we found that IL-2 significantly enhanced H19-OE-induced Treg cell differentiation and migration of BMMSCs, and these effects were reversed by anti-IL-2 antibody. CONCLUSION: Overall, our study indicates that LncRNA H19 induces immune dysregulation of BMMSCs, at least partly, by inhibiting IL-2 production and might be a novel therapeutic target for SLE.

Percutaneous vs Laparoscopic Treatment for Simple Renal Cysts: A Meta-analysis.

Objective: To compare the percutaneous and laparoscopic treatment for renal cyst to determine the optimal therapy for patients with renal cyst. Materials and Methods: A systematic search of PubMed, Cochrane Library, Web of Science, and EMBASE databases was conducted for articles published through June 3, 2020, using the preferred reporting items for systematic reviews and meta-analyses guidelines. Results: We found 493 studies from databases, and 6 were considered for the evidence synthesis. A total of 1631 cases were included. Of these patients, 488 cases underwent laparoscopic treatment and 1143 cases underwent percutaneous treatment. Symptomatic and radiologic success were higher for laparoscopic treatment (odds ratio [OR], OR = 3.59, confidence interval [95% CI], 1.45-8.88, p = 0.006; and OR = 7.46, 95% CI 3.99-13.94, p < 0.00001, respectively). Minor or severe complications were similar between the two treatments (OR = 1.54, 95% CI 0.40-5.98, p = 0.53; OR = 3.13, 95% CI 0.03-359.76, p = 0.64, respectively). Conclusion: Laparoscopic treatment for renal cyst was associated with better symptomatic and radiologic success, and its complication was no more than percutaneous treatment.

Patients With Ankylosing Spondylitis Are Associated With High Risk of Fibromyalgia: A Nationwide Population-Based Cohort Study.

Objectives: The main purpose of this retrospective cohort study was to provide an evaluation of Ankylosing spondylitis (AS) patients' fibromyalgia risk in different age and sex subgroups by analyzing large study samples. Methods: Datasets from the National Taiwan Insurance Research Database (NHIRD) were retrieved in this retrospective cohort study. This study was approved by the Institutional Review Board of Chung Shan Medical University (IRB permit number CS15134). Within the Longitudinal Health Insurance Database (LHID), and the subset of NHIRD, we identified AS patients to explore the risk of further fibromyalgia. The exposure cohort included patients with newly-diagnosed AS (ICD-9-CM:720.0) during 2000-2013. After 1:4 age-sex matching and 1:2 propensity score matching, and adjusting potential confounders, individuals without AS were identified as a comparison cohort. The adjusted hazard ratio of subsequent development of fibromyalgia in people with AS was evaluated. Further stratification analyses of different ages and genders were then undertaken to validate the results. Results: In total, 17 088 individuals were included in the present study, including 5,696 patients with AS and 11,392 individuals without AS. Respective incidence rates (per 1,000 person-months) of fibromyalgia was 0.52 (95% CI, 0.46-0.59) in the AS cohort and 0.39 (95% CI, 0.35-0.44) in the non-AS cohort. Compared with the non-AS cohort, aHR of developing fibromyalgia was 1.32 (95% CI, 1.12-1.55) in people with AS. This association was consistent in both statistical models of 1:4 age-sex matching and 1:2 propensity score matching. Conclusion: Patients with AS were associated with a higher risk of fibromyalgia, especially those over 65 years old. In managing patients with AS, clinicians should be aware of this association, which could impact diagnosis, disease activity evaluation, and treatment.

Upregulation of Versican Associated with Tumor Progression, Metastasis, and Poor Prognosis in Bladder Carcinoma.

OBJECTIVE: This work analyzes the role of versican (VCAN) on bladder cancer (BLCA). Versican (VCAN) is a chondroitin sulfate proteoglycan which is important for tumorigenesis and the development of cancer. However, the expression of VCAN on human bladder cancer (BLCA) has been rarely reported. METHODS: The clinical significance of VCAN in BLCA has been determined by our bioinformatics tools. Then, we performed immunohistochemical staining (IHC) and analyzed the correlation between VCAN expression and clinicopathological features. RESULTS: The bioinformatics results reveal that a high VCAN mRNA level was significantly associated with stage, histological subtype, molecular subtype, and metastasis in BLCA. Furthermore, IHC reveals that expression of VCAN was significantly correlated with the number of tumors, invasion depth, lymph node metastasis, distant metastasis, and histological grade. Kaplan-Meier survival analysis reveals that patients with a high expression of VCAN have poor prognosis than those patients with a low expression of VCAN. According to our result from the bioinformatics database, the mechanism of VCAN in BLCA revealed that VCAN was related to FBN1 and genes of the ECM remodeling pathway (MMP1, MMP2). CONCLUSION: VCAN expression might be included in the process of carcinogenesis and prognosis. Hence, VCAN could be a reliable biomarker of the clinical prognosis on BLCA.

Facile fabrication of superhydrophobic polyester fabric based on rapid oxidation polymerization of dopamine for oil-water separation.

Through the special chemical structure of dopamine (DA), superhydrophobic polyester (PET) fabric was fabricated by introducing the low surface energy substance hexadecyltrimethoxysilane (HDS) into the PET fabric and chelating Fe ions with phenolic hydroxyl groups of polydopamine (PDA) to form a rough surface. The water contact angle (WCA) of the prepared PDA/Fe/HDS PET fabric was higher than 160° and the scrolling angle (SA) was lower than 2.09°. The excellent adhesion property of polydopamine (PDA) on the substrate is helpful to improve the stability of superhydrophobic PDA/Fe/HDS PET fabric. The tests results showed that the modified PET fabric maintains excellent mechanical properties. Its superhydrophobic property had good stability and durability in the harsh environment of washing, mechanical friction, UV irradiation, seawater immersion, acid-base and organic reagents erosion. The PDA/Fe/HDS PET fabric also had good self-cleaning and oil-water separation properties. It still had good oil-water separation performance after repeated use for 25 times, and the separation efficiency was more than 95%. The preparation method was facile, the treatment time can be shortened, the cost of the modified substrate was low, and fluorine-free substances were used in the process. This work provides a new way to expand the added value of PET fabrics and develop durable superhydrophobic fabrics in practical application.

Expression and Clinical Significance of MMP-28 in Bladder Cancer.

AIMS: The aim of this study to determine the expression of MMP-28 in bladder urothelial carcinoma and to analyze the correlation between MMP-28 and the clinicopathological characteristics of human bladder carcinoma, and its relationship with patient prognosis. METHODS: A total of 491 surgically resected bladder cancer samples and 80 normal tissue adjacent to the tumor were stained by immunohistochemistry. The expression of MMP-28 in these samples was quantitated, and the value of MMP-28 as a marker of bladder cancer and prognosis was assessed. RESULTS: The expression of MMP-28 in urinary bladder carcinoma was higher than in normal bladder mucosa. The high level of MMP-28 was significantly correlated with tumor histology grade, lymphatic metastasis, lymph node infiltration, and distant metastasis (P < 0.05). The upregulation of MMP-28 was also closely related to the risk of cancer progression and the survival of patients. Further analysis documented that high expression of MMP-28 was associated with decreased overall survival in bladder cancer patients. CONCLUSIONS: The abnormal expression of MMP-28 may be related to the initiation and development of urothelial carcinoma. The upregulation of MMP-28 can be used as one of the effective indicators to diagnose bladder cancer and predict tumor progression.

Generalized Multi-Hit Model of Radiation-Induced Cell Survival with a Closed-Form Solution: An Alternative Method for Determining Isoeffect Doses in Practical Radiotherapy.

The standard linear-quadratic (LQ) model is currently the preferred model for describing the ionizing radiation-induced cell survival curves and tissue responses. And the LQ model is also widely used to calculate isoeffect doses for comparing different fractionated schemes in clinical radiotherapy. Despite its ubiquity, because the actual dose-response curve may appear linear at high doses in the semilogarithmic plot, the application of the LQ model is greatly challenged in the high-dose region, while the dose employed in stereotactic body radiotherapy (SBRT) is often in this area. Alternatively, the biophysical models of radiation-induced effects with a linear-quadratic-linear (LQL) characteristic can well fit the dose-survival curve of cells in vitro. However, most of these LQL models are phenomenological and have not fully considered the biophysical mechanism of radiation-induced damage and repair, and the fitting quality decreases in some high-dose ranges. In this work, to provide an alternative model to describe the cell survival curves in high-dose ranges and predict the biologically effective dose (BED) for SBRT, we propose a novel generalized multi-hit model with a closed-form solution by considering an upper bound on the number of lethal damages induced by radiation that can be repaired in a cell. This model has a clear biophysical basis and a simple expression, and also has the LQL characteristic under low- and high-dose approximate conditions. The experimental data fitting indicated that compared to the standard LQ model and our previously generalized target model, the current model can better fit the radiation-induced cell survival curves in the high-dose ranges (P < 0.05). The current model parameters and parameter ratios were determined from the fits in different kinds of cell lines irradiated with various dose rates and linear energy transfer (LET), which indicates that the model parameters significantly depend on the dose rate and LET. Based on the current model, we derived two equivalence formulae for the BED calculations in the low- and high-dose ranges, and then calculated the BED for the clinical data of SBRT from 17 selected studies. The correlation analysis showed that there were significant linear correlations between the BED at isocenter and planning target volume (PTV) edge calculated by this model and the LQ model (R > 0.86, P < 0.001). In conclusion, the generalized multi-hit model proposed in this work can be used as an alternative tool to handle in vitro radiation-induced cell survival curves in high-dose ranges, and calculate the in vivo BED for comparing the dose fractionation schemes in clinical radiotherapy.

Fitting the Generalized Target Model to Cell Survival Data of Proton Radiation Reveals Dose-Dependent RBE and Inspires an Alternative Method to Estimate RBE in High-Dose Regions.

The imprecise estimation of the relative biological effectiveness (RBE) of proton radiation has been one of the main challenges for further calculating the biologically effective dose in proton therapy. Since dose levels can greatly influence the proton RBE, the relationship between the two should be clarified first. In addition, since the dose-response curves are usually too complex to readily assess RBE in high-dose regions, a reliable and simple method is needed to predict the RBE of proton radiation accurately in clinically relevant doses. The standard linear-quadratic (LQ) model is widely used to determine the RBE of particles for clinical applications. However, there has been some debate over its use when modeling the cell survival curves in high-dose regions, since those survival curves usually show linear behavior in the semilogarithmic plot. By considering both cellular repair effects and indirect effects of radiation, we have proposed a generalized target model with linear-quadratic linear (LQL) characteristics. For the more accurate evaluation of proton RBE in radiotherapy, here we used this generalized target model to fit the cell survival data in V79 and C3H 10T1/2 cells exposed to proton radiation with different LETs. The fitting results show that the generalized target model works as well as the LQ model in general. Based on the fitting parameters of the generalized target model, the RBE of six given doses DT (RBET) could be calculated in the corresponding cell lines with different LETs. The results show that the RBET gradually decreases with increased dose in both cell types. In addition, inspired by the calculation method of the maximum values of RBE (RBEM) in the low-dose region, a novel method was proposed for estimating the RBE in the high-dose region (RBEH) based on the slope ratio of the dose-response curves in this region. Linear regression analysis indicated a significant linear correlation between the proposed RBEH and the RBET in high-dose regions, which suggests that the current method can be used as an alternative tool, which is both simple and robust, to estimate RBE in high-dose regions.