Enhancing surgical outcomes: accurate identification and removal of prostate cancer with B7-H3-targeted NIR-II molecular imaging.

PURPOSE: One of the main reasons for prostate cancer (PCa) recurrence is the difficulty in identifying and removing cancerous lesions during surgery. Accurately localizing and excising cancerous tissue remains a significant challenge. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence offers enhanced resolution, a high signal-to-noise ratio, and the potential for deeper tissue penetration. However, this technology is not currently employed for intraoperative imaging of PCa. This study aims to construct a new NIR-II probe targeting B7-H3 (AbB7-H3-800CW) for accurate intraoperative identification and resection of PCa. METHODS: Based on the differential expression of B7-H3 in PCa, we designed a novel imaging probe to accurately identify and guide the resection of preclinical PCa models and ex vivo human PCa tissues using NIR-II fluorescence imaging technology. RESULTS: Analyzing tissue samples from 60 clinical cases of PCa, along with benign prostatic hyperplasia and normal prostate tissue from 22 cases, we observed a significant difference in B7-H3 protein expression levels (P < 0.001). Subcutaneous and orthotopic mouse models of PCa were imaged using NIR-II fluorescence after AbB7-H3-800CW injection, showing promising results with successful tumor targeting and high-contrast images achieved within 24-48 h post-injection. The imaging also enabled the detection of occult PCa lesions approximately 1 mm in diameter. In addition, imaging analysis of human PCa and adjacent tissues using AbB7-H3-800CW incubation revealed that cancer tissues exhibited a significantly higher fluorescence intensity than adjacent tissues (P < 0.05), which was conducive to the evaluation of tumor resection margin in vitro. CONCLUSION: The findings revealed that B7-H3 was a compelling imaging target for PCa. The AbB7-H3-800CW molecular imaging probe is capable of accurately identifying PCa lesions and guiding their removal. This approach can potentially reduce the rate of surgical margins under NIR-II fluorescence guidance.

Fisetin decreases TET1 activity and CCNY/CDK16 promoter 5hmC levels to inhibit the proliferation and invasion of renal cancer stem cell.

As a natural flavonol, fisetin has significant inhibitory effects on many cancers. Although fisetin can inhibit kidney cancer, its effects on kidney renal stem cells (HuRCSCs) remain unknown. Our study found that renal cancer tissues and CD44+/CD105+ HuRCSCs both show high TET1 protein expression. Both in vivo and in vitro experiments showed that fisetin can effectively inhibit HuRCSC cell division and proliferation, invasion, in vivo tumourigenesis and angiogenesis. Our findings showed that fisetin can significantly decrease TET1 expression levels in HuRCSCs and overall 5hmC levels in the genomes of these cells. At the same time, ChIP-PCR results showed that fisetin can effectively inhibit 5hmC modification levels at the CpG islands in cyclin Y (CCNY) and CDK16 and reduce their transcription and activity. Thus, we conclude that fisetin inhibits the epigenetic mechanism in renal cancer stem cells, that is, fisetin inhibits TET1 expression and reduces 5hmC modification in specific loci in the promoters of CCNY/CDK16 in HuRSCs. This in turn inhibits transcription of these genes, causing cell cycle arrest and ultimately inhibiting renal cancer stem cell activity.

The prognostic value of vascular endothelial growth factor in patients with renal cell carcinoma: a systematic review of the literature and meta-analysis.

OBJECTIVE: Vascular endothelial growth factor (VEGF) serum level or tumor expression may be prognostic in renal cell carcinoma (RCC). The purpose of this meta-analysis was to examine the prognostic value of serum VEGF level and tumor expression in patients with RCC. METHODS: PubMed and EMBASE databases were searched until September 26, 2016. Prospective and retrospective studies of RCC patients that had VEGF levels measured were included. Outcome measures were overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). RESULTS: A total of 14 studies were included in the meta-analysis. In patients with RCC, elevated serum VEGF level was not associated with OS (pooled hazard ratio [HR] = 1.16; 95% confidence interval [CI]: 0.52 to 2.60; p = 0.716), but was associated with poor DSS (pooled HR = 4.22; 95% CI: 2.02 to 8.79; p < 0.001) and PFS (pooled HR = 1.50; 95% CI: 1.22 to 1.85; p < 0.001). Removal of one study, however, resulted in elevated serum level being associated with poorer OS. Tumor VEGF expression was not associated with OS (pooled HR = 1.48; 95% CI: 0.74 to 2.95; p = 0.263), but was associated with worse DSS (pooled HR = 1.83; 95% CI: 1.24 to 2.71; p = 0.003). CONCLUSION: In patients with RCC, elevated serum VEGF level is associated with worse OS, DSS, and PFS, while tumor expression is only associated with worse DSS. The number of studies, however, was limited and the results should be interpreted with caution.

CXCL5 is a potential diagnostic and prognostic marker for bladder cancer patients.

Chemokine C-X-C motif ligand 5 (CXCL5) is critical for bladder cancer growth and progression. Our previous study demonstrated that increase of CXCL5 in bladder cancer cell lines had an effect on tumor growth and progression. This study aims to investigate the expression of CXCL5 in tissue and urine of bladder cancer patients, in relation to clinicopathologic parameters, and as a predictive value in diagnosing and evaluating bladder cancer. Urothelial bladder cancer tissues from 255 patients were profiled for CXCL5 alterations by immunohistochemistry. Urine samples collected from patients with bladder cancer and urinary tract infections as well as healthy volunteers were analyzed by ELISA. High expression of CXCL5 in bladder cancer tissue was correlated with TNM stage (P = 0.012), cancer grade (P = 0.001), and lymph node metastasis (P = 0.007). CXCL5 alterations were associated with overall survival (P = 0.007), progression free survival (P = 0.004), and recurrence free survival in muscle invasive bladder cancers (P = 0.026). CXCL5 expression in the urine of bladder cancer patients was significantly different from urinary tract infection patients (P = 0.001) and healthy volunteers. However, urine leukocytes may predict CXCL5 levels (ß = 0.56, P < 0.001, R (2) = 0.314). CXCL5 expression in urine was also related to bladder cancer TNM stage (P = 0.039), lymph node metastasis (P = 0.023), tumor size (P = 0.007), and tumor grade (P = 0.005). The sensitivity and specificity for CXCL5/creatinine in predicting bladder cancer were 80.4 and 61.3 %, respectively. These results suggest increased CXCL5 expression in cancer tissue predicts poor survival in bladder cancer patients. CXCL5 expression in urine is useful in a minimally invasive modality for bladder cancer diagnosis. However, urine leukocytes are significant predictors of CXCL5 levels and may affect its result in bladder cancer diagnosis.

Protein interactions of cortactin in relation to invadopodia formation in metastatic renal clear cell carcinoma.

In the present study, we wanted to examine the predominant factor/s in the initiation of metastasis. We used samples of advanced grades of renal clear cell carcinoma with documented clinical history of vena caval spread as the experimental group. The major rationale for this selection is the fact that renal cell carcinoma metastasize extensively through the inferior vena cava up to the pulmonary bed and often exist as a continuous mass of metastatic tissue. As cortactin plays a significant role in invadopodia formation during initiation of metastasis, in the present study, we tested expression of cortactin and phospho(tyr421)-cortactin in different grades of renal cell clear carcinoma and examined its property to bind to actin. The findings of the present study suggest that the variations of the local physiological milieu are the driving forces for metastasis by enhancing molecular mechanisms for lamellipodia formation. We conclude that localization of cortactin in cancer cells and interaction between actin and its nucleators are crucial for cancer progression.

Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification.

Renal cell carcinoma (RCC) is the most common type of primary renal parenchymal malignancy in adults, with a high degree of malignancy and poor prognosis. Human renal cancer stem cells (HuRCSCs) are reported to be the main cause of drug resistance, metastasis, recurrence, and poor prognosis. Erianin is a low molecular-weight bibenzyl natural product extracted from Dendrobium chrysotoxum, which inhibits the in vitro and in vivo activity of a variety of cancer cells. However, the molecular mechanisms of Erianin's therapeutic effect on HuRCSCs are unknown. Here, we isolated CD44+/CD105+ HuRCSCs from patients with renal cell carcinoma. The experiments confirmed that Erianin significantly inhibited the proliferation, invasion, angiogenesis, and tumorigenesis of HuRCSCs, and induced oxidative stress injury and Fe2+ accumulation. qRT-PCR and western blotting showed that Erianin significantly reduced the expression levels of cellular Ferroptosis protective factors, and upregulated the expression of METTL3 and downregulated that of FTO. Dot blotting results indicated that Erianin significantly upregulated the mRNA N6-methyladenosine (m6A) modification of HuRCSCs. The results of RNA immunoprecipitation-PCR also indicated that Erianin significantly enhanced the m6A modification level of the 3' untranslated region of ALOX12 and P53 mRNA in HuRCSCs, resulting in increased stability, prolonged half-life, and improved translation activity. In addition, clinical data analysis showed that the expression of FTO correlated negatively with adverse events in patient with renal cell carcinoma. Thus, this study suggested that Erianin can induce Ferroptosis in renal cancer stem cells by promoting N6-methyladenosine modification of ALOX12/P53 mRNA, ultimately achieving a therapeutic effect on renal cancer.

Clinical benefits of scarless endoscopic thyroidectomy: an expert's experience.

BACKGROUND: By comparison with the conventional surgical approach to thyroidectomy, scarless (in the neck) endoscopic thyroidectomy (SET) has a superior cosmetic result but a very long learning curve. The objective of the present study was to compare surgical outcomes of SET performed by an experienced surgeon with the outcomes of conventional thyroidectomy. METHOD: Enrolled in this study were 25 patients who underwent SET and 18 who underwent conventional surgery. Differences in size of tumor, length of incision, duration of operation, volume of blood loss, pathological findings, postoperative pain, complications, and cosmetic result were investigated. RESULTS: The two groups were well matched. The total length of incisions and volume of blood loss of SET were significantly lower than those of conventional surgery. In addition to the superior cosmetic result, postoperative pain was significantly less severe and rates of hypesthesia or paresthesia and discomfort while swallowing were significantly lower in the endoscopy group. CONCLUSIONS: In experienced hands, SET offers more benefits than the conventional approach, including less postoperative pain and discomfort and a better cosmetic outcome.

Prehospital aortic blood flow control techniques for non-compressible traumatic hemorrhage.

Non-compressible hemorrhage in the junctional areas and torso could be life-threatening and its prehospital control remains extremely challenging. The aim of this review was to compare commonly used techniques for the control of non-compressible hemorrhage in prehospital settings, and thereby provide evidence for further improvements in emergency care of traumatic injuries. Three techniques were reviewed including external aortic compression (EAC), abdominal aortic junctional tourniquet (AAJT), and resuscitative endovascular balloon occlusion of the aorta (REBOA). In prehospital settings, all three techniques have demonstrated clinical effectiveness for the control of severe hemorrhage. EAC is a cost- and equipment-free, easy-to-teach, and immediately available technique. In contrast, AAJT and REBOA are expensive and require detailed instructions or systematic training. Compared with EAC, AAJT and REBOA have greater potentials in the management of traumatic hemorrhage. AAJT can be used not only in the junctional areas but also in pelvic and bilateral lower limb injuries. However, both AAJT and REBOA should be used for a limited time (less than 1 hour) due to possible consequences of ischemia and reperfusion. Compared with EAC and AAJT, REBOA is invasive, requiring femoral arterial access and intravascular guidance and inflation. Mortality from non-compressible hemorrhage could be reduced through the prehospital application of aortic blood flow control techniques. EAC should be considered as the first-line choice for many non-compressible injuries that cannot be managed with conventional junctional tourniquets. In comparison, AAJT or REBOA is recommended for better control of the aorta blood flow in prehospital settings. Although these three techniques each have advantages, their use in trauma is not widespread. Future studies are warranted to provide more data about their safety and efficacy.

Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival.

Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30-40% decrease in prostate cancer cell growth and a 60-65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60-75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications.

Discovery of pyrrole derivatives for the treatment of glioblastoma and chronic myeloid leukemia.

Long-term survivors of glioblastoma multiforme (GBM) are at high risk of developing second primary neoplasms, including leukemia. For these patients, the use of classic tyrosine kinase inhibitors (TKIs), such as imatinib mesylate, is strongly discouraged, since this treatment causes a tremendous increase of tumor and stem cell migration and invasion. We aimed to develop agents useful for the treatment of patients with GBM and chronic myeloid leukemia (CML) using an alternative mechanism of action from the TKIs, specifically based on the inhibition of tubulin polymerization. Compounds 7 and 25, as planned, not only inhibited tubulin polymerization, but also inhibited the proliferation of both GMB and CML cells, including those expressing the T315I mutation, at nanomolar concentrations. In in vivo experiments in BALB/cnu/nu mice injected subcutaneously with U87MG cells, in vivo, 7 significantly inhibited GBM cancer cell proliferation, in vivo tumorigenesis, and tumor growth, tumorigenesis and angiogenesis. Compound 7 was found to block human topoisomerase II (hTopoII) selectively and completely, at a concentration of 100 µM.

The minimally invasive effect of breast approach endoscopic thyroidectomy: an expert's experience.

We evaluated the invasiveness of breast approach endoscopic thyroidectomy (BAET) carried out by surgeon very experienced in this procedure. Twenty-four patients who underwent BAET and 19 patients who underwent conventional thyroidectomy were the study population. Postoperative pain was assessed by a visual analog scale (VAS). The values 2, 12, and 24 h after surgery were significantly lower in the BAET group than those in the conventional group. Serum IL-6 and CRP levels were measured by an ELISA preoperatively and at 2, 12, 24 and 48 h after operation. Their values increased significantly after both procedures when compared to preoperative levels with significant differences between the two groups detected at the 24-hour and 48-hour time points. Subjective and objective evidence supported the notion that BAET could become a minimally invasive procedure if the surgeon gained sufficient experience.

Comparison of the Detection Windows of Heroin Metabolites in Human Urine Using Online SPE and LC-MS/MS: Importance of Morphine-3-Glucuronide.

Heroin abuse is a serious problem that endangers human health and affects social stability. Though often being used as confirmation of heroin use, 6-monoacetylmorphine (6-MAM) has limitations due to its short detection window. To compare the detection windows of heroin metabolites (morphine (MOR), 6-MAM, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G)) in human urine, an automated online solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated. The limits of detections (LODs) of the four metabolites were in the range of 1.25-5 ng/mL. Intra and inter-day precision for all the metabolites was 0.4-6.7% and 1.8-7.3%, respectively. Accuracy ranged from 92.9 to 101.7%. This method was then applied to the analysis of urine samples of 20 male heroin abusers. M3G was detected 9-11 days after admission to the drug rehabilitation institute in 40% of heroin users while MOR or M6G was not always detected. The detection window of M3G was thus the longest. Furthermore, M3G had a much higher concentration than MOR and M6G. Therefore, M3G could provide diagnostic information with regard to heroin exposure in the combination with other clues (e.g., heroin seizures at the scene).

ZSCAN16 promotes proliferation, migration and invasion of bladder cancer via regulating NF-kB, AKT, mTOR, P38 and other genes.

BACKGROUND: As one of the most common genitourinary malignancies worldwide, bladder cancer affects about 3.4 million people globally, with 430,000 new cases a year since 2015. Despite the advances in bladder cancer diagnosis and therapy, there has been little progress in the patients' overall survival in nearly 30 years. Therefore, investigating novel molecular therapeutic targets is required to gain insight into the tumorigenesis of bladder cancer, which ultimately may be used to develop more effective therapeutic strategies. METHODS: Herein, we used gene knockdown in vitro and in vivo to unveil the unknown roles of ZSCAN16 in bladder cancer. Afterward, to decipher the unknown regulatory role of ZSCAN16 in tumor progression, we verified that a bunch of genes including NF-κB, AKT, mTOR, and P38 were the key downstream regulators of ZSCAN16 by western blot and rescue experiments. RESULTS: We found high expression of ZSCAN16 transcripts in bladder cancer cells and tumor samples from the TCGA database and tissue microarray bank, demonstrated in correlation with poor prognosis for bladder cancer patients. The in vitro experiments indicated that the silencing of ZSCAN16 by shRNA lentivirus promoted apoptosis and inhibited proliferation, colony formation, as well as migration and invasion in T24 cells. By investigating the signaling pathways, we proved ZSCAN16 play a novel role as oncogenic gene in bladder cancer by regulating NF-κB, AKT, mTOR, P38 and other genes. Furthermore, the in vivo experiments identified that ZSCAN16 knockdown retarded the tumor growth in nude mice. CONCLUSIONS: In summary, these findings revealed that ZSCAN16 is a potential novel oncogene in the development and progression of bladder cancer. This study will shed light on developing novel therapeutic targets in the future treatment of bladder cancer.

LncRNA NR2F2-AS1 Upregulates Rac1 to Increase Cancer Stemness in Clear Cell Renal Cell Carcinoma.

Background: Zhang et al. characterized a novel oncogenic long noncoding RNA (lncRNA) named NR2F2-AS1 in lung cancer. In this study, the role of lncRNA NR2F2-AS1 in clear cell renal cell carcinoma (ccRCC) was explored. Materials and Methods: Levels of NR2F2-AS1 and Rac1 mRNA expression in both cancer and noncancer tissues from 60 patients with ccRCC were measured by performing RT-qPCR. NR2F2-AS1 siRNA silencing and overexpression experiments were performed to analyze the role of NR2F2-AS1 in regulating Rac1 expression. Cell stemness was analyzed by stemness assay. Results: NR2F2-AS1 was upregulated in ccRCC, and high NR2F2-AS1 expression levels in ccRCC tissues were associated with poor survival. Rac1 was also upregulated in ccRCC and positively correlated with NR2F2-AS1. In ccRCC cells, NR2F2-AS1 overexpression mediated the upregulation of Rac1, whereas NR2F2-AS1 siRNA was accompanied by Rac1 downregulation. NR2F2-AS1 and Rac1 overexpression resulted in the increased ccRCC cell stemness, whereas NR2F2-AS1 and Rac1 siRNA silencing played an opposite role. Rac1 overexpression inhibited the role of NR2F2-AS1 siRNA silencing. Conclusions: NR2F2-AS1 may upregulate Rac1 to increase cancer stemness in ccRCC.

Structure-activity relationship studies and in vitro and in vivo anticancer activity of novel 3-aroyl-1,4-diarylpyrroles against solid tumors and hematological malignancies.

Novel 3-aroyl-1,4-diarylpyrrole derivatives were synthesized to explore structure-activity relationships at the phenyls at positions 1 and 4 of the pyrrole. The presence of amino phenyl rings at positions 1 and 4 of the pyrrole ring were found to be a crucial requirement for potent antitumor activity. Several compounds strongly inhibited tubulin assembly through binding to the colchicine site. Compounds 42, 44, 48, 62 and 69 showed antitumor activity with low nanomolar IC50 values in several cancer cell lines. Compound 48 was generally more effective as an inhibitor of glioblastoma, colorectal and urinary bladder cancer cell lines; 69 consistently inhibited CML cell lines and demonstrated superiority in nilotinib and imatinib resistant LAMA84-R and KBM5-T315I cells. In animal models, compound 48 exhibited significant inhibition of the growth of T24 bladder carcinoma and ES-2 ovarian clear cell carcinoma tumors. Compounds 48 and 69 represent robust lead compounds for the design of new broad-spectrum anticancer agents active in different types of solid and hematological tumors.

The learning curve for endoscopic thyroidectomy: a single surgeon's experience.

BACKGROUND: Endoscopic thyroidectomy has been known to surgeons for only 20 years. Related studies still are needed to make up for the deficiency of clinical experience. Research on the learning curve for the endoscopic thyroidectomy could be the method for investigating the operation experience. METHODS: This retrospective study investigated 300 consecutive patients who underwent endoscopic thyroidectomy by a single endoscopist during the past 7 years. The study population was equally divided into 10 groups chronologically. Pearson's chi-square test and one-way analysis of variance were used to compare differences in the demographic data, operative time, operation score system, and follow-up data. RESULTS: The mean operative time was 98.07 min. The mean operation score was 6.00, and the rate of conversion to open surgery was 3.7%. There were no differences in demographic data or complications among the 10 groups. Subcutaneous edema occurred in five cases and transient recurrent laryngeal nerve palsy in five cases. There were significant differences in the mean operative time (p < 0.01) and the mean operation score (p < 0.01) among the 10 groups. Comparison of two neighboring groups showed differences in both operative time (p < 0.05) and operation score (p < 0.01) between groups 2 and 3 and in operation score between groups 5 and 6 (p < 0.05). CONCLUSIONS: The first 60 cases constitute the early stage of the learning curve for endoscopic thyroidectomy. The proficiency and stability of the operation reach the advanced level after 150 cases.

CDK5RAP3 Participates in Autophagy Regulation and Is Downregulated in Renal Cancer.

Renal cancer is one of the most common malignant urological tumors; however, its diagnosis and treatment are not well established. In the present study, we identified that CDK5 regulatory subunit-associated protein 3 (CDK5RAP3), a putative tumor suppressor in many cancers, was downregulated in renal cancer tissues. Through loss- and gain-of-function experiments, we observed that the action of CDK5RAP3 in renal cancer cells was different in Caki-1 and 769-P cell lines. Knockdown of endogenous CDK5RAP3 in Caki-1 slightly increased cell viability, whereas overexpression of CDK5RAP3 in 769-P cells inhibited cell viability. In addition, we observed that CDK5RAP3 participated in the regulation of autophagy in renal cancer. Knockdown of CDK5RAP3 induced significant inhibition of autophagy in Caki-1 cells but not in 769-P cells. In contrast, overexpression of CDK5RAP3 significantly activated autophagy in 769-P cells, as evidenced by increased LC3-II levels. However, the LC3-II could not be altered by CDK5RAP3 overexpression in Caki-1 cells. These findings demonstrated that CDK5RAP3 is downregulated in renal cancer and may be associated with autophagy.

Analysis of longissimus muscle quality characteristics and associations with DNA methylation status in cattle.

BACKGROUND: As cattle represent one of the most important livestock species for meat production, control of muscle development in regards to quality is an important research focus. OBJECTIVES: In this study, the phenotypic quality traits and its associations with DNA methylation levels of the longissimus muscle in two cattle breeds were studied. METHODS: The pH value, water loss rate, fat and protein and fatty acid content were measured in three beef cattle breeds of longissimus mucle; The longissimus mucle was analyzed by MethylRAD-seq and RNA-seq. The differentially methylated and differentially expressed related genes were subjected to BSP. RESULTS: Methylation status of longissimus mucle was analyzed by MethylRAD-seq. Compared with Simmental, there were 39 differentially methylated and expressed genes in muscle of Yunling cattle, and 123 differentially methylated and expressed genes in Wenshan muscle. A combined analysis of MethylRAD-seq and RNA-seq results revealed differential methylation and expression level of 18 genes between Simmental and Wenshan cattle, and 14 genes between Simmental and Yunling cattle. In addition, 28 genes were differentially methylated between Wenshan and Yunling cattle. Results of promoter methylation analysis of ACAD11, FADS6 and FASN showed that the overall degree of DNA methylation of FADS6 and FASN was negatively correlated with their expression levels. Methylation level of FASN in Simmental was greater than Yunling and Wenshan. The degree of methylation at the FADS6 CpG4 site was significantly higher in Simmental than that in Yunling. The levels of methylation at the CpG7 locus of the Simmental and Yunling breeds were greater than Wenshan cattle. A negative correlation was detected between the methylation levels and the expression of FASN CpG1, CpG2, CpG3, CpG5, CpG7, and CpG10. CONCLUSION: The functional and molecular regulatory mechanism of the genes related to meat quality can be revealed systematically from aspects of the genetic and epigenetic regulation. These studies will help to further explore the molecular mechanisms and phenotypic differences that regulate growth and quality of different breeds of cattle.

Glycoprotein-130 Expression Is Associated with Aggressive Bladder Cancer and Is a Potential Therapeutic Target.

Predicting bladder cancer progression is important in selecting the optimal treatment for bladder cancer. Because current diagnostic factors regarding progression are lacking, new factors are needed to further stratify the curative potential of bladder cancer. Glycoprotein-130 (GP130), a transmembrane protein, is central to a number of signal transduction pathways involved in tumor aggressiveness, making it an attractive target. We hypothesize that if GP130 is found in an aggressive population of bladder tumors, then blocking GP130 expression may inhibit bladder cancer growth. Herein, we quantitatively show, using 11 patient samples and four bladder cancer cell lines, that GP130 is expressed in the aggressive human bladder tumors and in high-grade bladder cancer cell lines. Moreover, GP130 is significantly correlated with tumor grade, node category, tumor category, and patient outcome. We demonstrated a tumor-specific GP130 effect by blocking GP130 expression in bladder tumor cells, which resulted in decreased cell viability and reduced cell migration. Furthermore, we reduced tumor volume by approximately 70% compared with controls by downregulating GP130 expression using chitosan-functionalized nanoparticles encapsulating GP130 siRNA in an in vivo bladder cancer xenograft mouse model. Our results indicate that GP130 expression is linked to the aggressiveness of bladder tumors, and blocking GP130 has therapeutic potential in controlling tumor growth.

[Carcinoma recurrence rates after laparoscopic nephroureterectomy in patients undergoing transurethral incision of the ureteral orifice and open excision of bladder cuff].

OBJECTIVE: To compare the oncologic efficacy of transurethral incision of the ureteral orifice and open excision of bladder cuff in retroperitoneal laparoscopic nephroureterectomy (LNU) for patients with upper tract urothelium carcinoma. METHODS: The hospital records of 86 patients with upper tract urothelium carcinoma who underwent laparoscopic nephroureterectomy were reviewed retrospectively. 53 of the 86 patients, 22 males and 31 females, aged (68.6+/-14.1), underwent transurethral incision of the ureteral orifice (TUIUO), and 33, 14 males and 19 females, aged (72.4+/-15.2), underwent open excision of bladder cuff. Electric cauterization of the ureteral orifice was performed prior to resection. Follow-up was conducted for 28 (3-47) months. RESULTS: In all the specimens in the TUIUO group scar at the ureter orifice caused by electric excision could be seen. Test to check the pressure of distal ureter in 25 specimens proved that the ureters were all sealed. The distal ureter end began to leak at the water pressure of 135 cm in 1 case, at the water pressure of 167 cm in 1 case, and at 175 cm in 2 cases, but no leaking was seen even at 197 cm H2O in the other cases. Recurrence of bladder tumor was seen in 13 of the 53 patients of the TUIUO group and in 8 of the 33 patients of the open excision of bladder cuff group. Local recurrence developed in one case with the tumor at stage pT4N0M0 8 months after operation. CONCLUSION: Electric cauterization of the ureteral orifice prior to resection effectively ensures the leakproofness of the distal ureter end during LNU. As compared with open excision of bladder cuff, TUIUO does not increase the rate of neoplasm recurrence.