The Potential Value of Paraspinal Nerve Block (PVB) in Percutaneous Nephrolithotomy (PCNL) Compared with General Anesthesia and Epidural Anesthesia.

Objective: To analyze the potential value of paraspinal nerve block (PVB) in percutaneous nephrolithotomy (PCNL) and to compare it with general anesthesia and epidural anesthesia. Methods: 120 patients undergoing PCNL surgery in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2021 to June 2022 were selected and divided into PVB anesthesia group, general anesthesia group, and epidural anesthesia group according to different anesthesia methods, with 40 cases in each group. The anesthesia index (anesthesia operation time, anesthetic effect time, anesthesia time), the vital signs (heart rate, mean arterial pressure), postoperative pain [visual analog scale (VAS)], stress response index (cortisol and noradrenaline), the incidence of adverse reactions (nausea and vomiting, lethargy, dizziness, skin itching, bradycardia) were compared among the three groups. Results: The operation time of the anesthesia in the PVB anesthesia group was 5.72±1.25, which was significantly lower than that in the the general (7.95±1.15) and epidural anesthesia groups(8.23±1.43), and the differences were statistically significant (P = .000). The time of onset of anesthesia in the PVB anesthesia group was 6.63±1.87, which was significantly lower than that in the the general (9.84±2.41) and epidural anesthesia groups(10.14±2.89), and the differences were statistically significant (P = .000).The heart rate during percutaneous puncture and intraoperative lithotripsy in the PVB anesthesia group was statistically lower than in the general and epidural anesthesia groups (P < .05). The mean arterial pressure 20 minutes after anesthesia and at the end of operation in the PVB anesthesia group was higher than that in the general anesthesia group, and the mean arterial pressure during percutaneous puncture and intraoperative lithotomy was lower than that in the general anesthesia group (P < .05). The VAS scores of the PVB anesthesia group at 2, 6, 12, 24, and 48 hours after the operation were lower than those of general and epidural anesthesia groups (P < .05). The incidence of adverse reactions was 5.00% (2/40) in the PVB anesthesia group and 35.00% (14/40) in the general anesthesia group, which was lower than that of 27.50% (11/40) in the epidural anesthesia group. (P < .05). Conclusion: The potential value of PVB in PCNL is high is better than that of general anesthesia and epidural anesthesia, anesthesia can shorten operation time and work time, extend the time of anesthesia to maintain, and be helpful to the intraoperative vital signs in patients with stable, mild postoperative pain and stress, low incidence of adverse reactions, efficacy and safety are good, can be introduced.

Novel Nomograms Based on Gamma-Glutamyl Transpeptidase-to-Lymphocyte Ratio Predict Prognosis of Hepatocellular Carcinoma Patients After Hepatectomy.

Background: The prediction of prognosis of hepatocellular carcinoma (HCC) is of great significance in improving disease outcome and optimizing clinical management, while reliable prognostic indicators are lacking. This study was conducted to develop readily-to-use nomograms for prognosis prediction of HCC after hepatectomy. Materials and Methods: Data of eligible patients were collected and analyzed retrospectively. Independent prognostic factors were identified by Cox regression, and nomograms for the prediction of disease-free survival (DFS) and overall survival (OS) were developed. The performance of the nomograms was evaluated by receiver operating characteristics (ROC) curves, C-indexes and calibration curves and was verified by the validation cohort. The predictive value of the nomograms was also compared with the 8th edition of American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) and the Barcelona Clinic Liver Cancer (BCLC) staging systems. Results: In total, 599 patients were enrolled in the analysis: 420 in the training cohort and 179 in the validation cohort. The optimal cut-off value of Gamma-Glutamyl Transpeptidase-to-Lymphocyte Ratio (GLR) was 19.5. GLR contributed significantly to the nomograms with good predictive power. In ROC analyses, the areas under curve (AUCs) of the nomograms for 1-, 3- and 5-year DFS and OS prediction were 0.758, 0.756, 0.734 and 0.810, 0.799, 0.758, respectively. The C-indexes of the DFS nomogram were 0.697 (95% CI 0.665-0.729) in the training cohort and 0.710 (95% CI 0.664-0.756) in the validation cohort. For OS prediction, the C-indexes were 0.741 (95% CI 0.704-0.778) and 0.758 (95% CI 0.705-0.811) in the training and validation cohorts, respectively. The calibration curves demonstrated satisfactory agreement between nomogram predictions and actual observations. The nomograms demonstrated superior predictive performance to the TNM and the BCLC staging systems. Conclusion: Our novel nomograms showed adequate performance in the prediction of HCC prognosis after hepatectomy, which may facilitate the risk stratification and individualized management of HCC patients.

Tripartite Motif-Containing Protein 11 Reverses Paclitaxel Resistance in Prostate Cancer Drug-Resistant Cells by Mediating Family with Sequence Similarity 46B Expression.

Tripartite motif-containing protein 11 (TRIM11) and family with sequence similarity 46B (FAM46B) have been demonstrated to play roles in prostate cancer development, but their function in paclitaxel resistance remains unclear. The role of TRIM11 and FAM46B in paclitaxel resistance in prostate cancer was estimated. The paclitaxel-resistant cells were established with gradually increasing concentrations of paclitaxel in prostate cancer cells. The sensitivity to paclitaxel of established cells was assessed by the value of the median inhibitory concentration in the presence of 0-1000 nM paclitaxel. The expression level of TRIM11 and FAM46B was evaluated by real-time quantitative polymerase chain reaction. The proliferation, migration, and invasion of established cells were evaluated by CCK8 and Tran-swell assay. TRIM11 was upregulated in paclitaxel-resistant cells and promoted the proliferation, migration, and invasion of established cells. The significant downregulation of FAM46B was observed in paclitaxel-resistant cells. Although the overexpression of FAM46B suppressed the viability and metastasis of paclitaxel-resistant cells, which was reversed by the upregulation of TRIM11. Both the knockdown of TRIM11 and overexpression of FAM46B could enhance paclitaxel sensitivity of established resistant cells. The promoted effect of FAM46B overexpression was alleviated by the elevation of TRIM11. TRIM11 could improve the sensitivity to paclitaxel of resistant prostate cancer cells via regulating FAM46B.

Myricetin Induces Apoptosis and Protective Autophagy through Endoplasmic Reticulum Stress in Hepatocellular Carcinoma.

Myricetin, a natural flavonoid, exhibits diverse biological activities, including antitumor effects. The present study aimed to investigate the effects of myricetin on hepatocellular carcinoma (HCC) cells and explore the underlying molecular mechanisms. Our results showed that myricetin significantly inhibited cell proliferation and induced apoptosis in HCC cells. The apoptosis induced by myricetin was associated with the activation of endoplasmic reticulum (ER) stress. In addition, autophagy was enhanced in response to ER stress. Inhibition of autophagy by RNA interference or chemical inhibitors resulted in increased apoptosis in myricetin-treated HCC cells. The in vivo experiment also showed that myricetin effectively reduced tumor growth in an HCC xenograft model and that combination treatment with an autophagy inhibitor significantly enhanced this effect. These results indicated that myricetin induced apoptosis in HCC cells through the activation of ER stress. Protective autophagy was also upregulated during this process. Simultaneous inhibition of autophagy enhanced the anti-HCC activity of myricetin. Myricetin might be a promising drug candidate for HCC therapy, and the combined use of myricetin with autophagy inhibitors could be an effective therapeutic strategy.

Manipulation and Mechanical Deformation of Leukemia Cells by High-Frequency Ultrasound Single Beam.

Ultrasound single-beam acoustic tweezer system has attracted increasing attention in the field of biomechanics. Cell biomechanics play a pivotal role in leukemia cell functions. To better understand and compare the cell mechanics of the leukemia cells, herein, we fabricated an acoustic tweezer system in-house connected with a 50-MHz high-frequency cylinder ultrasound transducer. Selected leukemia cells (Jurkat, K562, and MV-411 cells) were cultured, trapped, and manipulated by high-frequency ultrasound single beam, which was transmitted from the ultrasound transducer without contacting any cells. The relative deformability of each leukemia cell was measured, characterized, and compared, and the leukemia cell (Jurkat cell) gaining the highest deformability was highlighted. Our results demonstrate that the high-frequency ultrasound single beam can be utilized to manipulate and characterize leukemia cells, which can be applied to study potential mechanisms in the immune system and cell biomechanics in other cell types.

Single-cell RNA sequencing identify SDCBP in ACE2-positive bronchial epithelial cells negatively correlates with COVID-19 severity.

The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in many deaths throughout the world. It is vital to identify the novel prognostic biomarkers and therapeutic targets to assist with the subsequent diagnosis and treatment plan to mitigate the expansion of COVID-19. Since angiotensin-converting enzyme 2 (ACE2)-positive cells are hosts for COVID-19, we focussed on this cell type to explore the underlying mechanisms of COVID-19. In this study, we identified that ACE2-positive cells from the bronchoalveolar lavage fluid (BALF) of patients with COVID-19 belong to bronchial epithelial cells. Comparing with patients of COVID-19 showing severe symptoms, the antigen processing and presentation pathway was increased and 12 typical genes, HLA-DRB5, HLA-DRB1, CD74, HLA-DRA, HLA-DPA1, HLA-DQA1, HSP90AA1, HSP90AB1, HLA-DPB1, HLA-DQB1, HLA-DQA2, and HLA-DMA, particularly HLA-DPB1, were obviously up-regulated in ACE2-positive bronchial epithelial cells of patients with mild disease. We further discovered SDCBP was positively correlated with above 12 genes particularly with HLA-DPB1 in ACE2-positive bronchial epithelial cells of COVID-19 patients. Moreover, SDCBP may increase the immune infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in different lung carcinoma. Moreover, we found the expression of SDCBP was positively correlated with the expression of antigen processing and presentation genes in post-mortem lung biopsies tissues, which is consistent with previous discoveries. These results suggest that SDCBP has good potential to be further developed as a novel diagnostic and therapeutic target in the treatment of COVID-19.

Pancancer Analysis of Neurovascular-Related NRP Family Genes as Potential Prognostic Biomarkers of Bladder Urothelial Carcinoma.

BACKGROUND: Neurovascular-related genes have been implicated in the development of cancer. Studies have shown that a high expression of neuropilins (NRPs) promotes tumourigenesis and tumour malignancy. METHOD: A multidimensional bioinformatics analysis was performed to examine the relationship between NRP genes and prognostic and pathological features, tumour mutational burden (TMB), microsatellite instability (MSI), and immunological features based on public databases and find the potential prognostic value of NRPs in pancancer. RESULTS: Survival analysis revealed that a low NRP1 expression in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), low-grade glioma (LGG), and stomach adenocarcinoma (STAD) was associated with poor prognosis. A high NRP2 expression in bladder urothelial carcinoma (BLCA), kidney renal papillary cell carcinoma (KIRP), and mesothelioma (MESO) was associated with poor prognosis. Moreover, NRP1 and NRP2 were associated with TMB and MSI. Subsequent analyses showed that NRP1 and NRP2 were correlated with immune infiltration and immune checkpoints. Genome-wide association analysis revealed that the NRP1 expression was strongly associated with kidney renal clear cell carcinoma (KIRC), whereas the NRP2 expression was closely associated with BLCA. Ultimately, NRP2 was found to be involved in the development of BLCA. CONCLUSIONS: Neurovascular-related NRP family genes are significantly correlated with cancer prognosis, TME, and immune infiltration, particularly in BLCA.

SphK2/S1P Promotes Metastasis of Triple-Negative Breast Cancer Through the PAK1/LIMK1/Cofilin1 Signaling Pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) features a poor prognosis, which is partially attributed to its high metastatic rate. However, there is no effective target for systemic TNBC therapy due to the absence of estrogen, progesterone, and human epidermal growth factor 2 receptors (ER, PR, and HER-2, respectively) in cancer. In the present study, we evaluated the role of sphingosine kinase 2 (SphK2) and its catalyst sphingosine-1-phosphate (S1P) in TNBC metastasis and the effect of the SphK2-specific inhibitor ABC294640 on TNBC metastasis. METHODS: The function of SphK2 and S1P in TNBC cell metastasis was evaluated using transwell migration and wound-healing assays. The molecular mechanism of SphK2/S1P mediating TNBC metastasis was investigated using Western blot, histological examination, and immunohistochemistry assays. The antitumor activity of ABC294640 was examined in an in vivo TNBC lung metastatic model. RESULTS: Sphingosine kinase 2 promoted TNBC cell migration through the generation of S1P. Targeting SphK2 with ABC294640 inhibited TNBC lung metastasis in vivo. p21-activated kinase 1 (PAK1), p-Lin-11/Isl-1/Mec-3 kinase 1 (LIMK1), and Cofilin1 were the downstream signaling molecules of SphK2/S1P. Inhibition of PAK1 suppressed SphK2/S1P-induced TNBC cell migration. CONCLUSION: Sphingosine kinase 2/sphingosine-1-phosphate promotes TNBC metastasis through the activation of the PAK1/LIMK1/Cofilin1 signaling pathway. ABC294640 inhibits TNBC metastasis in vivo and could be developed as a novel agent for the clinical treatment of TNBC.

FAM46B Promotes Apoptosis and Inhibits Glycolysis of Prostate Cancer Through Inhibition of the MYC-LDHA Axis.

OBJECTIVE: Increased dependence on glycolysis is a known element of cancer. This study was designed to examine critical glycolysis components including transcription factor MYC and its downstream target lactate dehydrogenase A (LDHA), potential upstream regulators of glycolysis such as family with sequence similarity 46 member B (FAM46B), and the impact of the abundance of these proteins on apoptosis and glycolysis in prostate cancer. MATERIALS AND METHODS: A total of 70 primary prostate cancer patient samples were compared to normal tissues for FAM46B and LDHA expression and the corresponding patients' survival was monitored for 60 months. Prostate cancer cell lines were employed for protein expression manipulation, glucose uptake and LDH assays, and apoptosis measurements. A xenograft mouse model was used to quantify the role of FAM46B and LDHA on tumor growth in vivo. RESULTS: FAM46B expression was reduced in prostate tumor tissue compared to normal tissue and prostate cancer patients who expressed low amounts of FAM46B had shortened average lifespans compared to those who expressed higher amounts of FAM46B (p=0.008). FAM46B overexpression reduced glucose uptake, decreased LDH activity, and induced apoptosis in prostate cancer cell lines while FAM46B shRNA increased MYC levels in a non-malignant prostate cell line (P69). Conversely, forced expression of LDHA in LNCaP cells produced an increase in glycolysis markers with a corresponding decrease in apoptosis. FAM46B-overexpressing xenografts had starkly blunted growth which was restored with co-overexpression of LDHA. CONCLUSION: FAM46B plays a central role in regulating glycolysis and apoptosis in prostate cancer and operates through the regulation of LDHA via MYC. FAM46B's keystone status in prostate cancer makes it a potential, robust biomarker for prostate cancer prognosis and a promising therapeutic target.

Targeting SphK2 Reverses Acquired Resistance of Regorafenib in Hepatocellular Carcinoma.

Background: Regorafenib is a second-line therapy drug used for advanced hepatocellular carcinoma (HCC). Unfortunately, the survival benefit of the patients receiving this treatment is modest, which may be attributed to drug resistance. In the present study, sphingosine kinase 2 (SphK2) was targeted to reverse regorafenib resistance in HCC. Methods: The functions of SphK2 and sphingosine-1-phosphate (S1P), the catalytic product of SphK2 in regorafenib resistance of HCC cells, were evaluated by cell counting kit-8 assay, colony formation, cell cycle evaluation, and annexin V-fluorescein isothiocyanate/propidium iodide double-staining assay. The antitumor activity of combined treatment of regorafenib and the SphK2-specific inhibitor ABC294640 was examined in HCC cells in vitro and xenograft model in vivo. The molecular mechanisms of SphK2/S1P-mediating regorafenib resistance were investigated using cell line establishment and Western blot analysis. Results: Well-developed regorafenib-resistant HCC cells indicated high expression levels of SphK2. The sensitivity to regorafenib of regorafenib-resistant HCC cells was restored following SphK2 knockdown or pharmacological inhibition by ABC294640. In addition, ectopic expression of SphK2 and exogenous addition of S1P decreased the sensitivity of HCC cells to regorafenib. Furthermore, the combination treatment with ABC294640 sensitized resistant tumor to regorafenib in xenograft model of HCC. The phosphorylation levels of nuclear factor κB (NF-κB), as well as those of signal transducer and activator of transcription 3 (STAT3), were positively associated with SphK2 and S1P. Conclusions: SphK2/S1P mediates regorafenib resistance of HCC through NF-κB and STAT3 activation. Targeting SphK2 by ABC294640 potently reduces regorafenib resistance of HCC cells both in vitro and in vivo. The combination of ABC294640 and regorafenib could be developed as a novel potential treatment strategy for advanced HCC.

DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.

BACKGROUND: With increasing incidence, pancreatic cancer (PC) is one of the most common digestive tract tumors. However, the prognosis of PC is particularly dismal due to the highly invasive and metastatic behavior of this deadly disease. DEP domain-containing protein 1B (DEPDC1B), which is overexpressed in multiple tumors, such as breast cancer, oral cancer and non-small cell lung cancer, plays a significant role in cell movement, cell cycle and cytoskeleton reorganization. However, the function of DEPDC1B in PC remains poorly understood. METHODS: The function of DEPDC1B in the migration and invasion of PC was evaluated by wound healing and Transwell assays in vitro and PC-derived liver metastasis models in vivo. The molecular mechanisms of DEPDC1B were investigated through cell line establishment, Western blotting, qRT-PCR, immunoprecipitation, histological examination and immunohistochemistry analysis. RESULTS: DEPDC1B was overexpressed in PC cell lines. DEPDC1B regulated cell migration and invasion. DEPDC1B regulated the Rac1/PAK1-LIMK1-cofilin1 signaling pathway by interacting with Rac1. Rac1 inhibition suppressed DEPDC1B-induced migration and invasion in PC in vitro and DEPDC1B-induced liver metastasis in vivo. CONCLUSION: DEPDC1B promoted cell migration and invasion by activating the Rac1/PAK1-LIMK1-cofilin1 signaling pathway, thus providing a potential therapeutic target against PC.

MSRB3 promotes the progression of clear cell renal cell carcinoma via regulating endoplasmic reticulum stress.

BACKGROUND: Renal cancer represents about 3 % of all human cancers. Clear cell renal cell carcinoma (ccRCC) is the main type of renal cancer. Methionine sulfoxide reductase B3 (MSRB3) is a protein repair enzyme that specifically catalyzes the reduction of methionine-R-sulfoxide residues and has an antioxidant function. However, MSRB3's role in ccRCC is still obscure. METHODS: Immunohistochemical staining and Real-time PCR were used to compare the expression level of MSRB3 in ccRCC tissues and adjacent tissues. Western blot was used to detect the expression of MSRB3 in cell lines. Chi-square test were applied to evaluate the potential of MSRB3 to function as a cancer biomarker. RNA interference was used to inhibit MSRB3 expression in ccRCC cells, followed by detecting cell proliferation, apoptosis, migration and invasion. The markers of endoplasmic reticulum stress were then detected by western blot. RESULTS: In this study, we validated that MSRB3 was significantly up-regulated in ccRCC samples and cell lines. It was also demonstrated that the up-regulation of MSRB3 was associated with several clinicopathologic features. Knockdown of MSRB3 remarkably arrested the proliferation, migration and invasion, while promoted apoptosis, and induced the changes of markers of endoplasmic reticulum stress. CONCLUSION: In conclusion, we demonstrated that MSRB3 was an oncogene of ccRCC associated with patients' pathological characteristics and modulated endoplasmic reticulum stress of cancer cells.

Biosynthesis of selenium nanoparticles and their effect on changes in urinary nanocrystallites in calcium oxalate stone formation.

Plant bio constituents have the ability to prepare nanoparticles, and usually, plant polyphenols are tested to reduce sodium selenite to selenium nanoparticles (SeNPs). In this work, we showed the biosynthesis of SeNPs using Ocimum tenuiflorum leaf extract. The as obtained SeNPs were in the size range of 15-20 nm and spherical in shape. Also, TEM microscopic images represented the aggregation of crystal structures as extracellular deposits. Moreover, scanning electron microscopy was performed to examine the chemical transition of calcium oxalate (CaC2O4) crystal's shape and structure due to the influence of SeNPs. SeNPs inhibited the aggregation and growth of CaC2O4 monohydrate crystals and hence the prepared SeNPs could have important prospects in medical and pharmaceutical applications as a potential inhibitor of CaC2O4 urinary stones.

Down-Regulation of Nfatc1 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Prostate Cancer Cells.

BACKGROUND Prostate cancer (PCa), accounting for 28% of all male cancer cases, is the second leading cause of cancer-related death among men. NFATc1, belonging to the NFAT family, is overexpressed in PCa and is correlated with the risk of recurrence after radical prostatectomy. MATERIAL AND METHODS In the present study, the expression of NFATc, c-myc, and PKM2 in PCa cells was regulated by lentiviruses and then detected by real-time PCR and Western blot analysis. Further, proliferation, invasion, and migration assays were performed. The glucose consumption and lactate production were assessed by biochemical detection. RESULTS We found that NFATc1 down-regulation significantly suppressed the proliferation and Warburg effect of PCa cells, concurrent with a decrease of c-myc and PKM2 expression. Likewise, the abilities of migration and invasion were also inhibited in NFATc1-silenced PCa cells. In addition, NFATc1 down-regulation-induced inhibition of cell proliferation, migration, invasion, and Warburg effect were counteracted by up-regulation of c-myc or PKM2. The expression of PKM2 was positively regulated by NFATc1 and c-myc expression. CONCLUSIONS These results indicate that NFATc1 down-regulation can suppress the proliferation, Warburg effect, and migration and invasion abilities of PCa cells, probably by regulating c-myc and PKM2 expression. NFATc1 may be a potential therapeutic target for PCa and could be used as a diagnosis or prognosis indicator of PCa.

FAM46B inhibits cell proliferation and cell cycle progression in prostate cancer through ubiquitination of ß-catenin.

FAM46B is a member of the family with sequence similarity 46. Little is known about the expression and functional role(s) of FAM46B in prostate cancer (PC). In this study, the expression of FAM46B expression in The Cancer Genome Atlas, GSE55945, and an independent hospital database was measured by bioinformatics and real-time PCR analysis. After PC cells were transfected with siRNA or a recombinant vector in the absence or presence of a ß-catenin signaling inhibitor (XAV-939), the expression levels of FAM46B, C-myc, Cyclin D1, and ß-catenin were measured by western blot and real-time PCR. Cell cycle progression and cell proliferation were measured by flow cytometry and the CCK-8 assay. The effects of FAM46B on tumor growth and protein expression in nude mice with PC tumor xenografts were also measured. Our results showed that FAM46B was downregulated but that ß-catenin was upregulated in patients with PC. FAM46B silencing promoted cell proliferation and cell cycle progression in PC, which were abrogated by XAV-939. Moreover, FAM46B overexpression inhibited PC cell cycle progression and cell proliferation in vitro and tumor growth in vivo. FAM46B silencing promoted ß-catenin protein expression through the inhibition of ß-catenin ubiquitination. Our data clearly show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of ß-catenin.

Overexpression of miR-155 in clear-cell renal cell carcinoma and its oncogenic effect through targeting FOXO3a.

MicroRNA-155 (miR-155) is overexpressed in numerous human cancer types and has an oncogenic role. Previous study has revealed that miR-155 serves an important role in the progression of clear-cell renal cell carcinoma (ccRCC); however, the underlying mechanism was not completely clarified. The present study aimed to investigate the biological role of miR-155 in ccRCC and the underlying molecular mechanisms. The expression of miR-155 in 20 ccRCC and adjacent normal kidney tissues was determined by PCR. After downregulation of miR-155 expression by miR-155 inhibitor, cell growth was assessed by MTT and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Cell invasion and migration was detected by wound healing and Transwell assays. Furthermore, forkhead box O3a (FOXO3a) mRNA and protein expression were detected by PCR and immunoblotting. The expression of FOXO3a in 20 ccRCC tissues was also examined by immunohistochemistry. The expression of miR-155 was upregulated in ccRCC tissues compared to that in adjacent normal tissues. Inhibition of miR-155 significantly suppressed the proliferation, colony formation, migration and invasion, and induced G1 arrest and apoptosis of ccRCC cells in vitro. Moreover, inhibition of miR-155 significantly upregulated FOXO3a expression, and miR-155 expression was inversely correlated with FOXO3a expression in ccRCC tissues. In conclusion, miR-155 may have an important role in the genesis of ccRCC through targeting FOXO3a and may be a potential target for ccRCC therapy.

Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway.

We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin.

RNF7 knockdown inhibits prostate cancer tumorigenesis by inactivation of ERK1/2 pathway.

Development of castration resistance is a key contributor to mortality in patients with prostate cancer. High expression of RING finger protein 7 (RNF7) in cancer cells is known to play a key role in tumor progression. However, the role of RNF7 in prostate cancer progression is not well elucidated. In this study, we silenced RNF7 by shRNA interference in two castration resistant prostate cancer (CRPC) cell lines, DU145 and PC3. RNF7 knockdown attenuated proliferation and enhanced sensitivity of prostate cancer cells to cisplatin treatment. Invasive property of DU145 and PC3 cells was also attenuated by RNF7 silencing. The underlying mechanisms appear to be associated with accumulation of tumor suppressive proteins p21, p27 and NOXA, while inactivation of ERK1/2 by RNF7 knockdown. We demonstrated that RNF7 knockdown induced growth suppression of prostate cancer cells and inactivated ERK1/2 pathway, which suggested RNF7 might be a potential novel therapeutic target for CRPC.

Lack of association of microvessel density with prognosis of renal cell carcinoma: evidence from meta-analysis.

To investigate microvessel density (MVD) and its association with prognosis of renal cell carcinoma (RCC) by means of a meta-analysis. We obtained published studies and extracted appropriate data, then did a meta-analysis to estimate the predictive role of MVD by combining estimated effect-size from individual studies. Analyses for overall survival (OS) and cancer-specific survival (CSS) were performed, separately. Subgroup analysis stratified by biomarkers were also performed for studies using CD34, factor VIII-related antigen (F VIII) and others, respectively. A total of 20 studies were included for meta-analyses including nine (four for F VIII, three for CD34, and two for others) for OS and 11 (two for F VIII, seven for CD34 and two for others) for CSS. There was no significance of MVD predicting OS or CSS of RCC. The pooled HR for OS was 0.910 (95% CI 0.824-1.006; P = 0.065) and CSS was 0.977 (95% CI: 0.915-1.043; P = 0.487). We failed to observe significant association between MVD and prognosis of RCC. Additional studies are needed to provide more precise evidences to support our results.

Multi-target lentivirus specific to hepatocellular carcinoma: in vitro and in vivo studies.

BACKGROUND & AIMS: We aimed at investigating the effects of the targeted transduction of the Wtp53-pPRIME-miR30-shRNA gene into liver cancer cells, under the mediation of anti-alpha fetoprotein scFv-directed lentivirus, and the inhibitory effect of this system on liver cancer cells. METHODS: The result of infection was observed by fluorescence microscopy. Polymerase chain reaction and Western blotting were used to demonstrate the successful transduction and transcription of the Wtp53-pPRIME-miR30-shRNA-IGF1R gene. Cell growth was observed via the Cell-Counting Kit-8 Method, and cell apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling. To observe further the effects of AFP-Wtp53-pPRIME-miR30-shRNA-IGF1R therapy in animals, models of BALB-C nude mice bearing subcutaneous human hepatocellular carcinoma were established. The influence of the growth of subcutaneously transplanted tumor, expression of Wtp53 protein, apoptosis, and microvessel formation on the overall level of AFP-Wtp53 pPRIME-miR30-shRNA-IGF1R were also evaluated. RESULTS: Recombinant lentivirus was successfully constructed, and its functional plaque-forming unit titer was determined as 4.58 × 10(9)plaque-forming units/ml. A positive strand was detected by polymerase chain reaction and Western blotting. Lentiviral construction worked effectively in AFP-positive liver cancer cells. In vitro and in vivo experiments showed that the recombinant lentivirus was more efficacious in inhibiting the proliferation of Hep3B cells. CONCLUSIONS: The Wtp53-pPRIME-miR30-shRNA gene can be subjected to targeted transduction into liver cancer cells under the mediation of anti-alpha fetoprotein scFv-directed lentivirus. The Wtp53-pPRIME-miR30-shRNA system has targeting ability and lethal effects on liver cancer cells.