Nomogram to predict the risk of adverse outcomes in patients with residual stones following percutaneous nephrolithotomy.

PURPOSE: To investigate the risk factors associated with adverse outcomes in patients with residual stones after percutaneous nephrolithotomy (PCNL) and to establish a nomogram to predict the probability of adverse outcomes based on these risk factors. METHODS: We conducted a retrospective review of 233 patients who underwent PCNL for upper urinary tract calculi and had postoperative residual stones. The patients were divided into two groups according to whether adverse outcomes occurred, and the risk factors for adverse outcomes were explored by univariate and multivariate analyses. Finally, we created a nomogram for predicting the risk of adverse outcomes in patients with residual stones after PCNL. RESULTS: In this study, adverse outcomes occurred in 125 (53.6%) patients. Multivariate logistic regression analysis indicated that the independent risk factors for adverse outcomes were the diameter of the postoperative residual stones (P < 0.001), a positive urine culture (P = 0.022), and previous stone surgery (P = 0.004). The above independent risk factors were used as variables to construct the nomogram. The nomogram model was internally validated. The calculated concordance index was 0.772. The Hosmer-Lemeshow goodness-of-fit test was performed (P > 0.05). The area under the ROC curve of this model was 0.772. CONCLUSIONS: Larger diameter of residual stones, positive urine culture, and previous stone surgery were significant predictors associated with adverse outcomes in patients with residual stones after PCNL. Our nomogram could help to assess the risk of adverse outcomes quickly and effectively in patients with residual stones after PCNL.

The safety and efficiency of a 1470 nm laser in obtaining tract hemostasis in tubeless percutaneous nephrolithotomy: a retrospective cross-sectional study.

OBJECTIVE: It is challenging to perform a tubeless percutaneous nephrolithotomy (PNL) in patients with tract bleeding. The present study was designed to study the safety and efficacy of the 1470 nm laser for hemostatic completion in tubeless PNL patients with tract bleeding. PATIENTS AND METHODS: Between January 2020 and October 2021, 120 patients were retrospectively included and divided into two groups. The hemostasis group included 60 patients receiving tubeless PNL, in which a 1470 nm laser was used to manage tract bleeding. The other group included 60 patients receiving tubeless PNL in which the hemostasis procedure was not performed, serving as the control group. The differences in the patients' demographic characteristics, procedural information, and posttreatment outcomes between the two groups were statistically compared. RESULTS: The differences associated with sex, age, weight, body mass index, urine culture, stone burden, calyx of puncture, degree of hydronephrosis and comorbidities between the two groups were not statistically significant. Compared with the control group, the hemostasis group showed greatly reduced blood loss (0.61 ± 0.31 vs. 0.85 ± 0.46 g/dL) and decreased postoperative hospitalization duration (2.83 ± 0.81 vs. 4.45 ± 0.91 days). The differences in operative time, stone-free rate, Visual Analogue Score and postoperative complications between the two groups were not statistically significant. In the subgroup analysis, the obese patients and patients with moderate to severe hydronephrosis in the hemostasis group also showed a significantly less blood loss (0.51 ± 0.22 vs. 0.83 ± 0.48 g/dL; 0.54 ± 0.27 vs. 0.85 ± 0.47 g/dL, respectively) and shorter length of postoperative hospitalization (2.62 ± 0.51 vs. 4.47 ± 1.19 days; 2.97 ± 0.63 vs. 4.41 ± 0.91 days, respectively) than those in the control group. CONCLUSIONS: Our results demonstrated that 1470 nm laser is a safe, feasible and effective method to obtain tract hemostasis in tubeless PNL.

NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo.

BACKGROUND: NEAT1 has been shown to play an oncogenic role in many kinds of cancers. However, detailed roles of NEAT1 in bladder cancer are largely unknown. METHODS: In the present study, the expression of NEAT1, miR-101 and VEGF-C was detected in human bladder cancer samples. The relationship between NEAT1 and the prognosis of patients with bladder cancer was analysed. In vitro experiments explored the effects of NEAT1 on biological behaviours of bladder cancer T24 and 5637 cells. Bioinformatics prediction and luciferase assays were used to assay the regulatory mechanism of action of NEAT1 and miR-101. Loss and gain of the expression of miR-101 and VEGF-C were used to explore the effects of the NEAT1/miR-101/VEGF-C pathway on T24 and 5637 cells. The effect of NEAT1 on the growth of bladder cancer in vivo was explored using an orthotopic tumourigenesis model. RESULTS: NEAT1 and VEGF-C were significantly upregulated in bladder cancer samples, and miR-101 was significantly downregulated. NEAT1 upregulation was associated with poorer recurrence-free survival of patients with bladder cancer. Overexpression of NEAT1 promoted the proliferation, migration and invasion of bladder cancer cells. The results of the luciferase assay indicated that miR-101 was a target of NEAT1. The promoting effects of NEAT1 on bladder cancer cells were reversed by miR-101 upregulation, and inhibition of miR-101 enhanced the effects of NEAT1. Overexpression of VEGF-C had a clear synergistic effect with the action of NEAT1. Overexpression of NEAT1 increased tumour growth and induced the development of liver metastasis. CONCLUSIONS: In conclusion, our data indicated that NEAT1 was expressed at high levels in bladder cancer patients and correlated with unfavourable prognosis. NEAT1 promoted malignant development of bladder cancer in vitro and in vivo by regulating the miR-101/VEGF-C pathway.

Genetically-modified bone mesenchymal stem cells with TGF-ß3 improve wound healing and reduce scar tissue formation in a rabbit model.

Extensive scar tissue formation often occurs after severe burn injury, trauma, or as one of complications after surgical intervention. Despite significant therapeutic advances, it is still a significant challenge to manage massive scar tissue formation while also promoting normal wound healing. The goal of this study was to investigate the therapeutic effect of bone mesenchymal stem cells (BMSCs) that were genetically modified to overexpress transforming growth factor-beta 3 (TGF-ß3), an inhibitor of myofibroblast proliferation and collagen type I deposition, on full-thickness cutaneous wound healing in a rabbit model. Twenty-four rabbits with surgically-induced full-thickness cutaneous wounds created on the external ear (1.5 × 1.5 cm, two wounds/ear) were randomized into four groups: (G1), wounds with no special treatment but common serum-free culture medium as negative controls; (G2), topically-applied recombinant adenovirus, expressing TGF-ß3/GFP; (G3), topically-applied BMSCs alone; (G4), topically-applied BMSCs transfected with Ad-TGF-ß3/GFP (BMSCsTGF-ß3); and (G5), an additional normal control (n = 2) with neither wound nor treatment on the external ear skin. The sizes of wounds on the ear tissues were grossly examined, and the scar depth and density of wounds were histologically evaluated 21, 45, and 90 days after surgical wound creation. Our results demonstrated that G4 significantly reduced the wound scar depth and density, compared to G1~3. Numbers of cells expressing GFP significantly increased in G4, compared to G2. The protein expression of TGF-ß3 and type III collagen in G4 significantly increased, while the ratio of type I to type III collagen was also significantly reduced, which is similar to the tissue architecture found in G5, as compared the other treatment groups. In conclusion, transplantation of BMSCsTGF-ß3 remarkably improves wound healing and reduces skin scar tissue formation in an animal model, which may potentially provide an alternative in the treatment of extensive scar tissue formation after soft tissue injury.

Increased miR-141 expression is associated with diagnosis and favorable prognosis of patients with bladder cancer.

The aims of this study are to analyze the association of microRNA-141 (miR-141) with the clinicopathological parameters of bladder cancer and evaluate the value of miR-141 in predicting the prognosis of bladder cancer. In this study, 114 patients with bladder cancer were enrolled in the study, and tissue specimens were obtained from the tumor zone and from adjacent normal area. miR-141 expression was determined using SYRB Green quantitative real-time polymerase chain reaction assay and was further correlated with patients' clinicopathological parameters and the follow-up data. The results indicated that miR-141 was upregulated in malignant bladder specimens compared with normal ones (P < 0.001). miR-141 expression was significantly associated with tumor stage (P < 0.001), tumor grade (P < 0.001), and muscle invasion status (P < 0.001). Log-rank test showed that the higher miR-141 expression was associated with longer disease-specific survival of the patients with bladder cancer (P < 0.001), which was also proven by univariate and multivariate Cox regression analysis (P < 0.001 and P = 0.039, respectively). Focusing on patients with non-muscle invasive bladder cancer, univariate analysis using log-rank test and Cox regression analysis found that patients with high miR-141 expression experienced longer disease-free survival (P = 0.031 and P = 0.040, respectively) and disease-specific survival (P = 0.028 and P = 0.038, respectively), which was confirmed by multivariate Cox regression analysis (P = 0.036 and P = 0.042, respectively). In conclusion, this study showed that miR-141 may contribute to the progression of bladder cancer and its upregulation may be independently associated with favorable prognosis of bladder cancer, suggesting that miR-141 might serve as a promising biological marker for further risk stratification in the management of bladder cancer.

Synthesis of novel galactose functionalized gold nanoparticles and its radiosensitizing mechanism.

BACKGROUND: Biocompatible gold nanoparticles (GNPs) are potentially practical and efficient agents in cancer radiotherapy applications. In this study, we demonstrated that GNPs can significantly modulate irradiation response of hepatocellular carcinoma cells in vitro and investigated the underlying mechanisms. We co-grafted galactose (GAL) targeting hepatocyte specific asialoglycoprotein receptor and Polyethylene Glycol (PEG) onto GNPs surfaces to increase GNPs targeting specificity and stability. RESULTS: This novel GAL-PEG-GNPs and bare GNPs show similar appearance and cytotoxicity profiles, while more GAL-PEG-GNPs can be effectively uptaken and could enhance cancer cell killing. CONCLUSION: GAL-PEG-GNPs have better radiosensitization to HepG2. The sensitization mechanism of GAL-PEG-GNPs is related to the apoptotic gene process activated by generation of a large amount of free radicals induced by GNPs.

Accelerating effects of growing-season warming on tree seasonal activities are progressively disappearing.

The phenological changes induced by climate warming have profound effects on water, energy, and carbon cycling in forest ecosystems. In addition to pre-season warming, growing-season warming may drive tree phenology by altering photosynthetic carbon uptake. It has been reported that the effect of pre-season warming on tree phenology is decreasing. However, temporal change in the effect of growing-season warming on tree phenology is not yet clear. Combining long-term ground observations and remote-sensing data, here we show that spring and autumn phenology were advanced by growing-season warming, while the accelerating effects of growing-season warming on tree phenology were progressively disappearing, manifesting as phenological events converted from being advanced to being delayed, in the temperate deciduous broadleaved forests across the Northern Hemisphere between 1983 and 2014. We further observed that the effect of growing-season warming on photosynthetic productivity showed a synchronized decline over the same period. The responses of phenology and photosynthetic productivity had a strong linear relationship with each other, and both showed significant negative correlations with the elevated temperature and vapor pressure deficit during the growing season. These findings indicate that warming-induced water stress may drive the observed decline in the responses of tree phenology to growing-season warming by decelerating photosynthetic productivity. Our results not only demonstrate a close link between photosynthetic carbon uptake and tree seasonal activities but also provide a physiological perspective of the nonlinear phenological responses to climate warming.

International Alliance of Urolithiasis Guideline on Shockwave Lithotripsy.

Different international associations have proposed their own guidelines on urolithiasis. However, the focus is primarily on an overview of the principles of urolithiasis management rather than step-by-step technical details for the procedure. The International Alliance of Urolithiasis (IAU) is releasing a series of guidelines on the management of urolithiasis. The current guideline on shockwave lithotripsy (SWL) is the third in the IAU guidelines series and provides a clinical framework for urologists and technicians performing SWL. A total of 49 recommendations are summarized and graded, covering the following aspects: indications and contraindications; preoperative patient evaluation; preoperative medication; prestenting; intraoperative analgesia or anesthesia; intraoperative position; stone localization and monitoring; machine and energy settings; intraoperative lithotripsy strategies; auxiliary therapy following SWL; evaluation of stone clearance; complications; and quality of life. The recommendations, tips, and tricks regarding SWL procedures summarized here provide important and necessary guidance for urologists along with technicians performing SWL. PATIENT SUMMARY: For kidney and urinary stones of less than 20 mm in size, shockwave lithotripsy (SWL) is an approach in which the stone is treated with shockwaves applied to the skin, without the need for surgery. Our recommendations on technical aspects of the procedure provide guidance for urologists and technicians performing SWL.

LncRNA CASC9 Affects Cell Proliferation, Migration, and Invasion of Tongue Squamous cell Carcinoma via Regulating miR-423-5p/SOX12 Axes.

INTRODUCTION: The incidence of tongue squamous cell carcinoma (TSCC) has increased in recent decades. However, the function of long non-coding RNA (lncRNA) CASC9 in the occurrence and progression of TSCC is unclear. In this work, we attempted to clarify the role of lncRNA CASC9 in determining the phenotype of TSCC cells, and to clarify the underlying mechanisms. METHODS: We used qRT-PCR analysis to identify the level of CASC9 mRNA expression in TSCC clinical samples and cell lines. We investigated cell proliferation, and cell migration and invasion of TSCC cells transfected with siCASC9 or siNC using CCK-8 and transwell assays. Bioinformatics analysis and a luciferase reporter assay were employed to predict and verify the target microRNA (miRNA). RESULTS: CASC9 was up-regulated in the TSCC tissues and cells, and predicted a poor prognosis. CASC9 silencing significantly inhibited cell proliferation, migration, and invasion of the TSCC cells compared with the non-targeting control small interfering RNA (siCtrl) treatment. miR-423-5p was predicted as the targeting miRNA of CASC9; this was verified by a luciferase reporter assay. CASC9 expression showed a negative correlation with miR-423-5p expression and a positive correlation with SOX12 expression. The miR-423-5p inhibitor can rescue the carcinogenesis effect of CASC9 on TSCC cells. CONCLUSION: Our work indicates that CASC9 plays a role in TSCC tumorigenesis; this novel information will improve TSCC molecular targeting therapy.

circHIPK3 Promotes Cell Proliferation and Migration of Gastric Cancer by Sponging miR-107 and Regulating BDNF Expression.

BACKGROUND: Circular RNAs (circRNAs) play important regulatory roles in cancer development. However, the mechanisms by which circRNAs regulate gene expression in gastric cancer (GC) remain unclear. METHODS: Human GC samples and their matched normal adjacent tissues were obtained from 30 patients to assess the expression of circHIPK3 and its relationship with GC proliferation and migration. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circHIPK3 in GC proliferation and migration, and its underlying molecular mechanisms. RESULTS: Using a circRNA microarray we found a circRNA termed circHIPK3 that performed a significant regulatory role in GC. circHIPK3 was further confirmed to be upregulated in all GC tissues and cells tested. Furthermore, circHIPK3 levels were associated with Tumor & Lymph Node & Metastasis(TNM) stage (P = 0.032). The area under the receiver operating characteristic curve (ROC) was 0.743 (95% confidence interval 0.615-0.872; P = 0.001). CCK-8, colony formation, Transwell and EdU assays were performed to evaluate the effects of circHIPK3 on cell proliferation and migration in GC. Moreover, circHIPK3 was identified as a sponge of miR-107, and as such it regulated brain-derived neurotrophic factor (BDNF), which plays a pivotal role in the development of GC. CONCLUSION: circHIPK3 represents a novel potential biomarker and therapeutic target of GC.

Circular RNA hsa_circRNA_102958 may serve as a diagnostic marker for gastric cancer.

BACKGROUND: Circular RNAs (circRNA) play key regulatory roles in cancer progression. Human circRNA microarray was performed to screen for abnormally expressed circRNA in gastric cancer tissues. In this study, we found circRNA102958 was up-regulated in gastric cancer tissues and cell lines. METHODS: The hsa_circRNA_102958 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric tissue and cell. Then, the association between the expression level of hsa_circRNA_102958 and the clinicopathological features of patients with gastric cancer was further analyzed. Finally, a network of hsa_circRNA_102958-miRNA-mRNA interactions was predicated. RESULTS: In this study, we analyzed 30 patients and found that hsa_circRNA_102958 was significantly overexpressed in gastric cancer tissues compared with paired adjacent normal tissues. Clinicopathological features showed that hsa_circRNA_102958 level in GC tissues was positively associated with TNM stage (p= 0.032). The area under the ROC curve was 0.74. Finally, a total of 5 miRNAs were predicted to have an interaction with hsa_circRNA_102958. CONCLUSIONS: hsa_circRNA_102958 may be a potential novel and stable biomarker for the diagnosis of gastric carcinoma.

High expression of agrin is associated with tumor progression and poor prognosis in hepatocellular carcinoma.

The heparan sulfate proteoglycan agrin is known to accumulate in the context of hepatocellular carcinoma (HCC). Agrin is important for neoangiogenesis in HCC tissues, and is incorporated into newly formed vasculature, but exactly how agrin contributes to the pathology of HCC remains to be fully defined. We therefore examined the clinical relevance of agrin as it pertains to HCC progression and prognosis using tissue sections from a total of 313 HCC patients. We found that agrin expression was detectable in more HCC samples (25.4% vs. 77.1%; P < 0.05) compared to normal tissue controls. Agrin expression was notably linked to tumor size (P = 0.041) and metastasis (P = 0.034). The recurrence free survival rate of agrin-positive HCC patients was considerably lower than that of agrin-negative patients (P = 0.001). We further confirmed HCC survival to be independently correlated with tumor size, metastasis, microvascular invasion and edmondson Grade via a Cox regression analysis. Upregulation of Agrin may play a crucial role in HCC progression. Together our results suggest that Agrin has the potential to be used as a prognostic indicator in predicting HCC patient outcomes.

Nomogram to predict the risk of adverse outcomes in patients with residual stones following percutaneous nephrolithotomy

ABSTRACT Purpose: To investigate the risk factors associated with adverse outcomes in patients with residual stones after percutaneous nephrolithotomy (PCNL) and to establish a nomogram to predict the probability of adverse outcomes based on these risk factors. Methods: We conducted a retrospective review of 233 patients who underwent PCNL for upper urinary tract calculi and had postoperative residual stones. The patients were divided into two groups according to whether adverse outcomes occurred, and the risk factors for adverse outcomes were explored by univariate and multivariate analyses. Finally, we created a nomogram for predicting the risk of adverse outcomes in patients with residual stones after PCNL. Results: In this study, adverse outcomes occurred in 125 (53.6%) patients. Multivariate logistic regression analysis indicated that the independent risk factors for adverse outcomes were the diameter of the postoperative residual stones (P < 0.001), a positive urine culture (P = 0.022), and previous stone surgery (P = 0.004). The above independent risk factors were used as variables to construct the nomogram. The nomogram model was internally validated. The calculated concordance index was 0.772. The Hosmer- Lemeshow goodness-of-fit test was performed (P > 0.05). The area under the ROC curve of this model was 0.772. Conclusions: Larger diameter of residual stones, positive urine culture, and previous stone surgery were significant predictors associated with adverse outcomes in patients with residual stones after PCNL. Our nomogram could help to assess the risk of adverse outcomes quickly and effectively in patients with residual stones after PCNL

Enhanced radiation effect on SMCC7721 cells through endoplasmic reticulum stress induced by C225-GNPs in vitro and in vivo.

The high atomic number of gold nanoparticles (GNPs) enables them to offer potential as practical and efficient radiosensitizing agents for cancer radiotherapy applications. In the present study, it was demonstrated that GNPs can significantly modulate the irradiation response of hepatocellular carcinoma (HCC) cells in vitro and in vivo, of which the underlying mechanisms were investigated. Cetuximab (C225) is a targeting agent, which binds to the extracellular domain of epidermal growth factor receptor (EGFR). Hepatocyte-targeting, EGFR-specific C225 was synthesized onto GNP surfaces (C225-GNPs) to increase the GNP targeting specificity. C225-GNPs was synthesized successfully and characterized. The cytotoxicity was tested using a Cell Counting Kit-8 assay and 50% inhibition concentration of SMCC7721 cells was calculated. Cell uptake assay was detected using transmission electron microscopy. Radiosensitization was tested using a cell colony formation assay and cell cycle was detected using flow cytometry. The expression of a number of apoptotic proteins were tested by western blot analysis. Orthotropic SMCC7721 xenografts were used in order to verify its radiosensitizing effect. The results revealed that a higher number of C225-GNPs were effectively uptaken by SMCC7721 cells and markedly enhanced cancer cell death. The sensitization mechanism of C225-GNPs was associated with the apoptotic gene signalling process activated by endoplasmic reticulum stress and the unfolded protein response in cancer cells. In orthotopic SMCC7721 xenografts, the C225-GNPs significantly enhanced the radiation-induced suppression of tumour growth. The results of the present study provided evidence that C225-GNPs are potent radiosensitizers with radiotherapeutic value for HCC with the overexpression of EGFR.

Role of 5-Aza-CdR in mitomycin-C chemosensitivity of T24 bladder cancer cells.

Chemotherapeutic insensitivity is one of key obstacles to effectively treating muscle invasive bladder cancer. 5-Aza-2'-deoxycytidine (5-Aza-CdR) has been identified as a tumor suppressive agent in various types of cancer. The aim of the present study was to identify the effects of 5-Aza-CdR on the mitomycin-C (MMC) chemosensitivity of T24 bladder cancer cells and investigate the underlying mechanisms. T24 cells were treated with a combination of MMC and 5-Aza-CdR at various concentrations. The rates of proliferation and apoptosis were assessed by an MTT assay and flow cytometry, respectively. The expression of drug resistance-associated proteins, including P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), and autophagy-associated proteins, including beclin 1, nucleoporin 62 (p62) and autophagy protein 5 (ATG5) were detected with western blotting. Treatment with 5-Aza-CdR significantly promoted the MMC chemosensitivity of T24 cells. The proliferation of T24 cells was significantly inhibited with increasing 5-Aza-CdR concentration, whereas apoptosis was significantly increased. This was associated with the decreased expression of P-gp, MRP1, beclin 1, p62 and ATG5. In conclusion, 5-Aza-CdR enhanced MMC chemosensitivity in bladder cancer T24 cells, which may be caused by the suppression of drug resistance- and autophagy-associated proteins.

Expression of Wntless in colorectal carcinomas is associated with invasion, metastasis, and poor survival.

Wntless also known as WLS, GPR177, or Evi, is a key modulator of Wnt protein secretion. Its overexpression is found in certain types of human cancers such as malignant astrocytoma and breast cancers. We hypothesized that this protein may be aberrantly expressed in colorectal carcinoma which also possesses aberrant Wnt signaling. To investigate the association between the expression of Wnt and clinicopathological parameters in colorectal carcinomas, a set of colorectal carcinoma tissue samples was analyzed for the expression of WLS using an anti-GPR177 monoclonal antibody specific for the WLS protein. High expression of WLS protein was observed in most colorectal carcinoma samples compared with nontumor mucosa in the same patients (117/201, 58.2%). High expression of WLS was associated with sex (p = 0.005), age (p = 0.009), depth of invasion (p < 0.001), lymph node metastasis (p = 0.026), and tumor-node-metastasis (TNM) stage (p = 0.003). No significant relationship between the expression of WLS and tumor location, size, and differentiation was found. The survival analyses showed WLS was an independent prognostic marker and that patients whose carcinoma exhibited high expression of WLS had a poorer outcome (p = 0.033). Our results indicate that WLS may play a role in invasion and metastasis of colorectal carcinoma. The WLS protein expression level may be used as a potential prognostic marker in colorectal carcinoma. Furthermore, the WLS gene may provide a novel target for therapy of colorectal carcinoma.

Genotoxicity of mesoporous silica nanoparticles in human embryonic kidney 293 cells.

Mesoporous silica nanoparticles (MSNs) have been widely evaluated for their potential use as carriers for cancer diagnosis and therapy. Understanding the toxicity of MSNs is crucial to their biomedical applications. Although several groups have reported the cytotoxicity of MSNs, the genotoxicity (inducing genetic aberrations) of MSNs in normal human cells has not been extensively investigated. Gene amplification and mutation may initiate and promote carcinogenesis, and changes in mRNA expression can affect normal human physical functions. In this study, human embryonic kidney 293 (HEK293) cells were treated overnight with MSNs at a concentration of 120 µg/mL. The cells were assayed with fluorescent in situ hybridization to check for chromosome changes and gene amplification. Mutations in the epidermal growth factor receptor 1 (EGFR1) and KRAS genes were checked with DNA sequencing. The effects of MSNs on mRNA expression were investigated with an Agilent human mRNA microarray. No chromosomal alterations or gene mutations in EGFR or KRAS were observed in the control HEK293 cells or HEK293 cells exposed to MSNs. The microarray analysis showed that MSNs significantly altered gene expression. The expression of 579 genes was upregulated and that of 1263 genes was downregulated in HEK293 cells treated with MSNs compared with the control HEK293 cells. Our findings suggest that exposure to MSNs is genotoxic to normal human cells, leading to changes in the expression of some genes. This genotoxicity may cause cellular dysfunction and certain benign diseases. We have not shown that MSN exposure induces serious genotoxicity involving carcinogenesis.

Expression of the EphA1 protein is associated with Fuhrman nuclear grade in clear cell renal cell carcinomas.

Aberrant expression of receptor tyrosine kinase EphA1 in malignant tissues has been reported. However, the expression profile of EphA1 in renal cell carcinoma (RCC) and its association with clinicopathological parameters remain unknown. The aim of this study was to determine the cancerous value of the EphA1 protein expression in patients with renal cell carcinomas. This study included 144 patients with clear cell RCC (ccRCC), 18 patients with chromophobe RCC and 6 patients with papillary RCC. The EphA1 protein was detected in RCC tissue samples by an immunohistochemical staining with a specific polycolonal antibody. The correlation of the expression of the EphA1 protein with clinicopathological parameters was evaluated. High level of the expression of EphA1 was observed in all normal renal tubes. The EphA1 protein was negatively or weakly expressed in 93 out of 144 ccRCC (64.6%) and positively expressed in 51 out of 144 ccRCC (35.4%). The high level expression of the EphA1 protein was significantly associated with younger patients (P<0.001), sex (P=0.016) and lower nuclear grade (P<0.001). No significant relation between the expression of EphA1 and tumor diameter was found (P=0.316). Positive expression of EphA1 was observed in all samples of chromophobe RCC and papillary RCC. Our data indicated that the EphA1 protein may be a new marker for the prognosis of ccRCC.

Targeting EGFL7 expression through RNA interference suppresses renal cell carcinoma growth by inhibiting angiogenesis.

Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis.