Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study was aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS: Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS: A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received GnRH antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS: Prostate cancer patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Assessment tool based on fatty acid metabolic signatures for predicting the prognosis and treatment response in bladder cancer.

Background: Fatty acid metabolism (FAM) is closely connected with tumorigenesis as well as disease progression and affects the efficacy of platinum-based drugs. Exploring biomarkers related to FAM in bladder cancer (BLCA) is essential to improve cancer prognosis. Methods: High-throughput sequencing data from The Cancer Genome Atlas (TCGA) were bioinformatically resolved to identify molecular subtypes of fatty acid metabolic profiles in BLCA using coherent clustering analysis. Based on fatty acid metabolic profile, a prognostic model was created using COX and LASSO COX models. CIBERSORT, Estimation of STromal and Immune cells in MAlignant Tumours using Expression (ESTIMATE), MCP-Count, and single sample gene set enrichment analysis (ssGSEA) were used to assess the differences in tumor microenvironment (TME) among different molecular subtypes, prognostic groups. Kaplan-Meier (K-M) survival curve was plotted to assess patients' prognosis. Receiver operating characteristic curve (ROC) and the clinical prognostic value of prognostic models was evaluated by the Nomogram. Results: Three molecular subtypes (FAMC1, FAMC2, FAMC3) of fatty acid metabolic patterns were determined. FAMC1 showed significant prognostic advantage with immunoreactivity. Five key prognostic FAMGs were identified and RiskScore was developed. We found that patients with low RiskScore showed significantly better immune microenvironment status, survival and response to immunotherapy. Similarly, both Nomogram and RiskScore demonstrated excellent prognostic value. Conclusions: In conclusion, our study showed that the RiskScore was closely related to the clinical traits of BLCA patients. The RiskScore may provide essential clinical guidance for predicting prognosis and treatment response in bladder cancer.

Optimized titanium dioxide nanotubes for dental implants: Estimation of mechanical properties and effects on the biological behaviors of human gingival fibroblasts and oral bacteria.

The long-term successes of implant restorations rely on both appropriate osseointegration and robust soft tissue integration (STI). Numerous studies have reported that titanium dioxide nanotube (TNT) arrays formed by electrochemical anodization (EA) can promote early osteogenesis, but the mechanical stability of such modifications is often ignored and remains underexplored. In addition, relatively little research has been done on their effects on soft tissues integration. In this study, we developed mechanically robust TNT arrays using an optimized EA system. Subsequently, we immobilized a peptide, specifically D-amino K122-4, onto the anodized TNTs via polydopamine (PDA) films to enhance their mechanical properties. Surface morphology and composition were characterized by scanning electron microscopy (SEM), atomic force microscopy, and X-ray photoelectron spectroscopy. Mechanical properties, including the elastic modulus and hardness of TNTs modified Ti surfaces, were assessed using the nano-indention test. The adhesive strength of TNTs films to the substrate was measured using the nano scratch test. Furthermore, we evaluated the adhesion, spreading, and proliferation of human gingival fibroblasts (HGFs) and periodontal pathogenic bacteria such as Streptococcus mutans (S.m) and F. nucleatum (F.n) on the surface. Results showed that the elastic modulus, hardness, and adhesive strength of anodized TNTs were significantly enhanced by the incorporation of the D-amino K122-4 peptide. Live-dead staining and SEM observation suggested a decreased surface colonization by both bacterial species. The antibacterial rate of S.m and F. n was 81.5% and 71.7%, respectively, evaluated by colony counting method. Additionally, results of CCK8 assay showed that modified TNTs slightly stimulated HGFs attachment and proliferation while producing enhanced fluorescence of integrin ß1 and F-actin, confirmed by laser confocal microscopy observation. Thus, D-amino K122-4 biofunctionalized TNTs present significantly improved mechanical properties, and the mechanically robust structures modulate HGFs proliferation and alignment, resulting in decreased bacteria growth. This novel strategy has the potential to create a surface coating for implants that exhibits superior mechanical robustness and enhanced surface-to-implant interactions.

Comparison of tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma with rhabdoid and sarcomatoid differentiations.

OBJECTIVE: To investigate the efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell carcinoma (mRCC) with rhabdoid (mRCC-R) and sarcomatoid (mRCC-S) differentiations. MATERIALS AND METHODS: In this single-institutional cohort study, we included patients with RCC with rhabdoid (RCC-R) and sarcomatoid (RCC-S) differentiation, who were treated with TKIs after metastasis at our institute from 2013 to 2021. Patient characteristics, treatments, and clinical outcomes were recorded and analyzed. RESULTS: We identified 111 patients with RCC-R or RCC-S differentiations, of which 23 patients were included in the final analysis. Of the 23 patients, 10 (43.5%) were grouped as mRCC-R and 13 (56.5%) as mRCC-S. At a median follow-up of 40 months, mRCC-R and mRCC-S progressed in 7 of 10 and 12 of 13 patients, respectively. In addition, four and eight patients died in the mRCC-R and mRCC-S groups, respectively. The median progression-free survival (PFS) of the two groups was 19 months (mRCC-R: 95% confidence interval [CI] 4.08-33.92) and 7 months (mRCC-S: 95% CI 2.03-11.96), while the median overall survival (OS) was 32 months and 21 months, respectively. mRCC-S had a worse prognosis than mRCC-R. Based on the univariate Cox regression model, single metastasis or multiple metastasis of tumor, rhabdoid differentiation, and sarcomatoid differentiation were predictors of PFS but not OS. CONCLUSION: The efficacy of TKIs in the treatment of mRCC-R and mRCC-S may be different.

Use of PARP inhibitors in prostate cancer: from specific to broader application.

Prostate cancer (PC) is one of the major health issues of elderly men in the word. It is showed that there were approximately 1.414 million patients with PC in 2020 worldwide, with a high mortality rate in metastatic cases. In the present choices of treatment in PC, androgen deprivation therapy has long been as a backbone of them. But the clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) were not ideal because of their poor prognosis, more effective therapeutic approaches are still necessary to further improve this problem. Poly (ADP-ribose) polymerase (PARP) inhibitors lead to the single-strand DNA breaks and/or double-strand DNA breaks, and result in synthetic lethality in cancer cells with impaired homologous recombination genes. It is estimated that approximately 20~25% of patients with mCRPC have a somatic or germinal DNA damage repair gene mutation. Furthermore, in "BRCAness" cases, which has been used to describe as tumors that have not arisen from a germline BRCA1 or BRCA2 mutation, there were also a number of studies sought to extend these promising results of PARP inhibitors. It is worth noting that an interaction between androgen receptor signaling and synthetic lethality with PARP inhibitors has been proposed. In this review, we discussed the mechanism of action and clinical research of PARP inhibitors, which may benefit population from "specific" to the "all-comer" in patients with PC when combined with novel hormonal therapies.

The significance of EphA2-regulated Wnt/ß-catenin signal pathway in promoting the metastasis of HBV-related hepatocellular carcinoma.

BACKGROUND: Hepatitis B virus (HBV) infection is closely associated with the malignant progression of hepatocellular carcinoma (HCC). However, the mechanism involved in the HBV-related HCC development remains poorly understood. Hence, the aim of this study is to investigate the regulatory mechanism of EphA2-induced epithelial-mesenchymal transition (EMT) in the metastasis of HBV-related HCC cells. METHODS AND RESULTS: The expression level of EphA2 was determined in HBV-related human HCC cells. Then, the effects of EphA2 silencing on the EMT-associated proteins, the Wnt/ß-catenin signal pathway and the metastatic potential of HBV-related HCC cells were evaluated. Finally, the inhibitory role of Entecavir (a potent antiviral drug for HBV) on EphA2-induced EMT was explored. The present study revealed that the EphA2 expression level was increased in HBV-related HCC cells compared with non-related HCC cells. Following EphA2 knockdown, the downregulation of Vimentin, ß-catenin and p-GSK-3ßSer9 expressions, the upregulation of E-cadherin expression, and the suppressed migration and invasion ability of HBV-related HCC cells were found. Additionally, Entecavir was proved to have a significant inhibitory effect on EphA2-induced EMT via attenuating the Wnt/ß-catenin signal pathway. CONCLUSIONS: In this study, we found that EphA2-induced EMT was involved in the enhanced metastatic potential of HBV-related HCC cells through the activation of the Wnt/ß-catenin signal pathway.

Semi-Supervised Cell Detection with Reliable Pseudo-Labels.

Pathological images play an important role in the diagnosis, treatment, and prognosis of cancer. Usually, pathological images contain complex environments and cells of different shapes. Pathologists consume a lot of time and labor costs when analyzing and discriminating the cells in the images. Therefore, fully annotated pathological image data sets are not easy to obtain. In view of the problem of insufficient labeled data, we input a large number of unlabeled images into the pretrained model to generate accurate pseudo-labels. In this article, we propose two methods to improve the quality of pseudo-labels, namely, the pseudo-labeling based on adaptive threshold and the pseudo-labeling based on cell count. These two pseudo-labeling methods take into account the distribution of cells in different pathological images when removing background noise, and ensure that accurate pseudo-labels are generated for each unlabeled image. Meanwhile, when pseudo-labels are used for model retraining, we perform data distillation on the feature maps of unlabeled images through an attention mechanism, which further improves the quality of training data. In addition, we also propose a multi-task learning model, which learns the cell detection task and the cell count task simultaneously, and improves the performance of cell detection through feature sharing. We verified the above methods on three different data sets, and the results show that the detection effect of the model with a large number of unlabeled images involved in retraining is improved by 9%-13% compared with the model that only uses a small number of labeled images for pretraining. Moreover, our methods have good applicability on the three data sets.

Context-aware learning for cancer cell nucleus recognition in pathology images.

MOTIVATION: Nucleus identification supports many quantitative analysis studies that rely on nuclei positions or categories. Contextual information in pathology images refers to information near the to-be-recognized cell, which can be very helpful for nucleus subtyping. Current CNN-based methods do not explicitly encode contextual information within the input images and point annotations. RESULTS: In this article, we propose a novel framework with context to locate and classify nuclei in microscopy image data. Specifically, first we use state-of-the-art network architectures to extract multi-scale feature representations from multi-field-of-view, multi-resolution input images and then conduct feature aggregation on-the-fly with stacked convolutional operations. Then, two auxiliary tasks are added to the model to effectively utilize the contextual information. One for predicting the frequencies of nuclei, and the other for extracting the regional distribution information of the same kind of nuclei. The entire framework is trained in an end-to-end, pixel-to-pixel fashion. We evaluate our method on two histopathological image datasets with different tissue and stain preparations, and experimental results demonstrate that our method outperforms other recent state-of-the-art models in nucleus identification. AVAILABILITY AND IMPLEMENTATION: The source code of our method is freely available at https://github.com/qjxjy123/DonRabbit. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

DNA-repair status should be assessed in treatment-emergent neuroendocrine prostate cancer before platinum-based therapy.

OBJECTIVES: This study sought to provide contemporary data from a multi-institution with respect to DNA-repair genes (DRGs) status and its impact on effects of platinum-based chemotherapy in treatment-emergent neuroendocrine prostate cancer (t-NEPC), for which little data exist. PATIENTS AND METHODS: All patients were retrospectively collected with eligible biopsied tissues for targeted next generation sequencing (NGS). The main outcomes were radiologic progression-free survival and overall survival according to Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Among the 43 NEPC patients, 13/43 (30%) harbored homozygous deletions, deleterious mutations, or both in DRGs. Eleven patients (11/13, 85%) with DRGs aberrations had effective response, including 7 patients with BRCA1/2 defects and 2 with mismatch repair-deficient caused by MSH2 alterations. While significantly fewer responders (30%) were detected in patients without DRGs aberrations (odds ratio = 12.83, p = 0.003). Compared with patients without genomic DRGs aberrations, the hazard ratio (HR) for radiologic progression in those with DRGs defects was 0.42 (95% confidence interval [CI]: 0.19-0.93), and the HR for death was 0.65 (95% CI: 0.24-1.72). The most common adverse event of Grade 3 or 4 was anemia, as noted in 7 patients (16%). CONCLUSION: The DRGs status is therapeutically meaningful in t-NEPC. Given the potential responses to platinum-based chemotherapy, our findings support the clinical use of NGS in t-NEPC patients to identify DRGs aberrations.

Association of tumor mutational burden with genomic alterations in Chinese urothelial carcinoma.

The tumor mutational burden (TMB) calculated by whole-exome sequencing (WES) is a promising biomarker for the response to immune checkpoint inhibition (ICIs) in solid tumors. However, WES is not feasible in the routine clinical setting. In addition, the characteristics of the TMB in Chinese urothelial carcinoma (UC) are unclear. The aim of this study was to demonstrate the reliability of an Acornmed 808 panel and analyze the characteristics of the TMB in Chinese UC. An Acornmed 808 panel was designed and virtually validated using UC data from the cancer genome atlas (TCGA). Comprehensive analysis of sequencing and clinical data was performed to explore the characteristics of the TMB for 143 Chinese UC patients. Compared to the TMB calculated with random 808-, 500-, and 250-gene panels, the TMB calculated with the Acornmed 808 panel was closer to that calculated by WES. There were marked disparities in the mutational landscape and TMB between Chinese and TCGA UC data. The TMB was negatively associated with copy number variation (CNV). In contrast, the TMB was positive correlation with numbers of mutated DDR genes. Exposure to aristolochic acid signature was observed only in the TMB-high groups. The Acornmed 808 panel is a clinically practical method to assess the TMB. The TMB was associated with the DDR gene status and CNV counts and might be a biomarker for further stratification of UC patients. The study suggested that patients with high TMB may have a unique carcinogenic mechanism.

The immunogenic reaction and bone defect repair function of ε-poly-L-lysine (EPL)-coated nanoscale PCL/HA scaffold in rabbit calvarial bone defect.

Tissue engineering is a promising strategy for bone tissue defect reconstruction. Immunogenic reaction, which was induced by scaffolds degradation or contaminating microorganism, influence cellular activity, compromise the efficiency of tissue engineering, or eventually lead to the failure of regeneration. Inhibiting excessive immune response through modulating scaffold is critical important to promote tissue regeneration. Our previous study showed that ε-poly-L-lysine (EPL)-coated nanoscale polycaprolactone/hydroxyapatite (EPL/PCL/HA) composite scaffold has enhanced antibacterial and osteogenic properties in vitro. However, the bone defect repair function and immunogenic reaction of EPL/PCL/HA scaffolds in vivo remains unclear. In the present study, three nanoscale scaffolds (EPL/PCL/HA, PCL and PCL/HA) were transplanted into rabbit paraspinal muscle pouches, and T helper type 1 (Th1), T helper type 2 (Th2), T helper type 17 (Th17), and macrophage infiltration were analyzed after 1 week and 2 weeks to detect their immunogenic reaction. Then, the different scaffolds were transplanted into rabbit calvarial bone defect to compare the bone defect repair capacities. The results showed that EPL/PCL/HA composite scaffolds decreased pro-inflammatory Th1, Th17, and type I macrophage infiltration from 1 to 2 weeks, and increased anti-inflammatory Th2 infiltration into the regenerated area at 2 weeks in vivo, when compared to PCL and PCL/HA. In addition, EPL/PCL/HA showed an enhanced bone repair capacity compared to PCL and PCL/HA when transplanted into rabbit calvarial bone defects at both 4 and 8 weeks. Hence, our results suggest that EPL could regulate the immunogenic reaction and promote bone defect repair function of PCL/HA, which is a promising agent for tissue engineering scaffold modulation.

Study on antibacterial properties and cytocompatibility of EPL coated 3D printed PCL/HA composite scaffolds.

Biomaterial scaffolds play a critical role in bone tissue engineering. Moreover, 3D printing technology has enormous advantage in the manufacture of bioengineering scaffolds for patient-specific bone defect treatments. In order to provide an aseptic environment for bone regeneration, ε-poly-l-lysine (EPL), an antimicrobic cationic polypeptide, was used for surface modification of 3D printed polycaprolactone/hydroxyapatite (PCL/HA) scaffolds which were fabricated by fused deposition modeling (FDM) technology. The scaffold morphology and micro-structure were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and transform infrared spectroscopy (FT-IR). The release profile surface roughness, open porosity, and mechanical properties of the scaffolds were evaluated. Cell adhesion, proliferation, differentiation potential and antibacterial properties were also examined. As a result, 3D printed PCL/HA scaffolds with interconnected pores showed a slightly rough surface and improved mechanical properties due to adding hydroxyapatite (HA) particles. After being modified by EPL, favorable biocompatibility and osteoconductivity of ε-poly-l-lysine/polycaprolactone/hydroxyapatite (EPL/PCL/HA) scaffolds were observed. Moreover, antibacterial activity of the EPL/PCL/HA scaffolds was apparent. As a consequence, the EPL/PCL/HA scaffolds had great potential for bone regeneration and prevention of infections. This would yield a patient-specific bioactive and antibacterial composite scaffold for advanced bone tissue engineering applications.

Antibacterial activity and cytocompatibility of an implant coating consisting of TiO2 nanotubes combined with a GL13K antimicrobial peptide.

Prevention of implant-associated infections at an early stage of surgery is highly desirable for the long-term efficacy of implants in dentistry and orthopedics. Infection prophylaxis using conventional antibiotics is becoming less effective due to the development of bacteria resistant to multiple antibiotics. An ideal strategy to conquer bacterial infections is the local delivery of antibacterial agents. Therefore, antimicrobial peptide (AMP) eluting coatings on implant surfaces is a promising alternative. In this study, the feasibility of utilizing TiO2 nanotubes (TNTs), processed using anodization, as carriers to deliver a candidate AMP on titanium surfaces for the prevention of implant-associated infections is assessed. The broad-spectrum GL13K (GKIIKLKASLKLL-CONH2) AMP derived from human parotid secretory protein was selected and immobilized to TNTs using a simple soaking technique. Field emission scanning electron microscope, X-ray diffraction, Fourier transform infrared spectroscopy, and liquid chromatography-mass spectrometry analyses confirmed the successful immobilization of GL13K to anatase TNTs. The drug-loaded coatings demonstrated a sustained and slow drug release profile in vitro and eradicated the growth of Fusobacterium nucleatum and Porphyromonas gingivalis within 5 days of culture, as assessed by disk-diffusion assay. The GL13K-immobilized TNT (GL13K-TNT) coating demonstrated greater biocompatibility, compared with a coating produced by incubating TNTs with equimolar concentrations of metronidazole. GL13K-TNTs produced no observable cytotoxicity to preosteoblastic cells (MC3T3-E1). The coating may also have an immune regulatory effect, in support of rapid osseointegration around implants. Therefore, the combination of TNTs and AMP GL13K may achieve simultaneous antimicrobial and osteoconductive activities.

c-Met-mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma.

Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase-14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor-derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors.

MicroRNA-30a as a prognostic factor in urothelial carcinoma of bladder inhibits cellular malignancy by antagonising Notch1.

OBJECTIVE: To explore the relation between microRNA-30a (miR-30a) and Notch1, and to evaluate the potential prognostic role of miR-30a in invasive urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: In all, 50 invasive UCB tissue specimens, along with the adjacent bladder tissue specimens were obtained, and the clinical parameters of the 50 patients were analysed. Bioinformatics analysis was performed and miR-30a was selected as a potential miRNA targeting Notch1, with a luciferase assay performed to verify the binding site between miR-30a and Notch1. Quantitative real-time reverse transcriptase-polymerase chain reaction was used to assess the RNA expressions of miR-30a and Notch1, while Western Blotting and immunohistochemical staining were used to assess the protein expression of Notch1. Finally, cell proliferation, cell cycle, cell migration and invasion assays were used to evaluate the cellular effects of miR-30a and Notch1 on the UCB cell lines T24 and 5637. RESULTS: MiR-30a was downregulated in tumour tissues when compared with adjacent bladder tissues (P < 0.001), negatively correlating with Notch1 messenger RNA (R(2) 0.106, P = 0.021) in invasive UCB, and miR-30a expression further decreased in patients with shorter overall survival and disease-free survival (P = 0.039 and P = 0.037, respectively). The luciferase assay showed that miR-30a inhibited the Notch1 3'-untranslated region reporter activities in the T24 and 5637 cell lines (both P < 0.001). Both miR-30a and small interfering RNA Notch1 negatively regulated cell proliferation (P = 0.002 and P = 0.035 in T24; P = 0.029 and P = 0.037 in 5637 cell lines), activated cell cycle arrest (both P < 0.001 in T24; both P < 0.001 in 5637 cell lines), and prevented cellular migration (both P < 0.001 in T24; P = 0.003 and P < 0.001 in 5637 cell lines) and invasion (P = 0.009 and P = 0.006 in T24; P = 0.006 and P = 0.002 in 5637 cell lines) abilities. Ectopic Notch1 without the 3'untranslated region partially rescued the above-mentioned cellular effects of over-expressed miR-30a on T24 and 5637 cells. CONCLUSIONS: MiR-30a lessens cellular malignancy by antagonising oncogene Notch1 and plays an effective prognostic role in invasive UCB.

[Effect of platelet derived growth factor-B and its receptor expression on the proliferation of renal cell carcinoma ACHN cells].

OBJECTIVE: To study the effect of platelet derived growth factor-B and its receptor expression on the proliferation of renal cell carcinoma ACHN cells in vitro and in vivo. METHODS: PDGF-B gene was transfected into human renal carcinoma cell line ACHN cells, and the proliferation capability of ACHN cells transfected with or without PDGF-B was assessed by MTT assay. The effect of PDGF-B on the expression of p-PDGFR-ß in endothelial cells and vascular smooth muscle cells (VSMC) was detected by Western blot. ACHN cells transfected with PDGF-B were injected into mice (untransfected ACHN as control) to induce tumor formation. Immunohistochemical staining was used to detect the expression of Ki-67 in tumor cells and the tumor volume was measured to compare the tumor growth in the two groups. RESULTS: The PDGF-B expression of ACHN cells in transfected group was significantly increased than that in the untransfected group. MTT assay showed that the proliferation capability of ACHN cells in the transfected and untransfected groups had no significant differences at different time points (P>0.05). The expression of p-PDGFR-ß in VSMC was significantly increased when cultured with PDGF-B overexpression culture medium. The mean tumor size of the PDGF-B group and control group was (0.305±0.108) cm(3) and (0.577±0.218) cm(3), respectively (P=0.007). Ki-67-positive tumor cells were (41.00±5.34)/HPF in the PDGF-B-transfected group and (55.80±2.95)/HPF in the untransfected group (P=0.001). CONCLUSION: PDGF-B overexpression may up-regulate p-PDGFR-ß expression of VSMC in renal cell carcinoma, and inhibit the tumor cell proliferation and tumor growth through paracrine signaling.

Antibacterial and osteogenic stem cell differentiation properties of photoinduced TiO2 nanoparticle-decorated TiO2 nanotubes.

AIM: To improve the antibacterial and mammalian cell compatibility properties of titania nanotubes (TNTs) anodized into titanium (Ti). MATERIALS & METHODS: 3-8-nm TiO2 nanoparticles were decorated on the surface and inside TNT (TNT-TiO2) through a hydrothermal method. After UV light treatment, two types of oral bacteria and stem cells were cultured on the samples to determine antibacterial and compatibility properties. RESULTS: TiO2 nanoparticles increased the surface area and photocatalysis of TNTs. Based on the photocatalysis effect and prolonged photo-induced wettability, the numbers of Streptococcus mutans and Porphyromonas gingivalis were lower on the surface of TNT-TiO2 than pure Ti and TNTs after the first 7 days. Specifically, for S. mutans, the glycosytransferase (gtf) genes were downregulated 0.1-0.2-fold on TNT-TiO2. Due to the different topography and high surface energy of TNT-TiO2, stem cells also showed improved osteogenic functions on TNT-TiO2. CONCLUSION: In this study, we demonstrated for the first time improved antibacterial properties and, at the same time, greater stem cell osteogenic capacity when decorating TNTs with nanosized TiO2 particles, which may significantly improve orthopedic and dental implant efficacy.

Effect of platelet-derived growth factor-B on renal cell carcinoma growth and progression.

BACKGROUND: Platelet-derived growth factor-B (PDGF-B) expression promotes the proliferation of mural cells surrounding the blood vessels during angiogenesis. The effect of PDGF-B involved in angiogenesis on tumor growth and progression in clear cell renal cell carcinoma (ccRCC) is unknown. METHODS: We examined the expression of PDGF-B and its receptor PDGFR-ß in 174 patients with ccRCC by microarray analysis. Cancer-specific survival was estimated using the Kaplan-Meier method. PDGF-B-transfected and mock-transfected ACHN cells were implanted into mice to induce tumor formation and tumor growth, respectively, and progression in mice models was assessed using immunohistochemistry and histomorphology. The role of PDGF-B during angiogenesis in vitro was evaluated by flow cytometry analysis, cell migration, and tube formation assay. RESULTS: High expression of PDGF-B was associated with significantly decreased risk of cancer-specific mortality (P ≤ 0.001). The data indicated significant inhibition of tumor growth (P ≤ 0.05) and a reduction in proliferating tumor cells (P = 0.019) in vivo. PDGF-B also inhibits tumor metastasis and invasion events in tumor-bearing mice models. In vitro studies revealed that the tube formation capability of vascular smooth muscle cells (VSMCs), which are believed to be the precursors to pericytes in vivo, significantly induced by PDGF-B. The PDGF-B overexpression also results in a tendency to reside in S and G2/M phases of the cell cycle (P = 0.001) and increasing migration capability of VSMCs (P ≤ 0.001). CONCLUSION: Our results demonstrated that PDGF-B, which increased VSMCs proliferation and migration capability during angiogenesis, limited tumor growth and progression in ccRCC. Therefore, PDGF-B may be a novel and promising prognostic marker.

Expression of CX3CR1 associates with cellular migration, metastasis, and prognosis in human clear cell renal cell carcinoma.

OBJECTIVES: The identification of critical proteins regulating cancer cell metastasis, in clear cell renal cell carcinoma (CCRCC), is important for prediction of prognosis, prevention of metastasis, and treatment of this lethal malignancy. In the present study, we evaluated the role of CX3CR1 in cellular adhesion, migration, and metastasis in CCRCC. We further investigated the downstream molecular signaling mechanism of fractalkine (FKN)-CX3CR1-induced migration and metastasis. MATERIALS AND METHODS: The expression and localization of CX3CR1 in RCC cell lines were assessed by immunofluorescence analysis. The migration of cancer cells was examined by wound healing and transwell migration assay. The expression level of CX3CR1 and FKN in 78 CCRCC individual samples, 16 normal kidney cortex tissue samples, and 16 cases of metastatic lesions of CCRCC were evaluated using immunohistochemical analysis on tissue microarray. The signal pathway of functional FKN was analyzed by the use of the western-blotting method and inhibitory migration assay. RESULTS: CX3CR1 was expressed in human RCC cell lines, and only membrane positive cells were responsible for FKN-induced cell migration. Extracellular signal-related kinases (ERK1/2) and phosphatidyl-inositide 3 kinase/Akt (PI3K/Akt) were each activated upon soluble FKN stimulation in a time-dependent manner, whereas blockades of MEK, PI3K, and G proteins prevented FKN-mediated cellular migration. Furthermore, CCRCC tissue microarray immunohistochemistry data revealed a clear association of strong CX3CR1 expression with tumor metastasis and poor prognosis. CONCLUSIONS: CX3CR1 expression is associated with the process of cellular migration in vitro and tumor metastasis of CCRCC in vivo. Both clinical and molecular cellular evidence suggest that CX3CR1 is a potential marker and therapeutic target for CCRCC prognostic prediction and treatment.

[Loss of expression and mechanism of early growth response gene-3 in human oral squamous carcinoma].

OBJECTIVE: To evaluate the expression of early growth response gene-3 (EGR3) in human oral squamous carcinoma tissue, non-adjacent tissue and oral carcinoma cell lines and detect the effects of EGR3 expression on the biological behaviors of oral squamous carcinoma cell lines. METHODS: From October 2008 to December 2009, the expression of EGR3 was detected in 20 human oral squamous carcinoma tissue, non-tumor adjacent tissue and 2 oral carcinoma cell lines. The total-length plasmid of EGR3 was constructed and transfected into oral squamous carcinoma line Tca-8113 to observe the proliferation and apoptosis. RESULTS: There was a high-level expression of EGR3 mRNA in normal oral squamous epithelial and non-tumor adjacent tissues (2.108 ± 0.996 and 1.721 ± 1.196). And a low-level expression or a loss of EGR3 mRNA in human oral squamous carcinoma tissue and oral carcinoma cell lines (0.007 ± 0.005 and 0.007 ± 0.001) (both P < 0.05). Tca-8113 transfected by EGR3 plasmid had a high-level expression of EGR3 mRNA capable of inhibiting the proliferation of Tca-8113 and promoting its apoptosis dramatically. The stimulating index in overexpression of EGR3 was lower than control group (0.35 ± 0.11 vs 0.82 ± 0.21, P < 0.05). After overexpression of EGR3 in Tca-8113, the frequency of middle-Late stage of apoptosis (Annexin-V/PI double positive) was higher than the frequency of vector group (23.12% ± 6.65% vs 5.96% ± 0.98%, P < 0.05). CONCLUSION: A low-level expression or a loss of EGR3 in human oral squamous carcinoma and an over-expression of EGR3 in human oral squamous carcinoma may inhibit the proliferation and promote apoptosis of oral squamous carcinoma.