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1.
Transl Androl Urol ; 11(9): 1292-1303, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36217405

ABSTRACT

Background: Compound aluminum sulfate injection (CASI) originated from a Chinese traditional medicine, "Kuzhiye", and has been used in treating non-muscle invasive bladder cancer (NMIBC). Previous studies suggested that CASI was a potential monotherapeutic drug for NMIBC. However, the efficacy and safety of CASI in the treatment of NMIBC, as well as the long-term recurrence after treatment, need to be further evaluated. Methods: A multicenter retrospective single-arm cohort study was conducted. From 2006 to 2009, 101 patients (74 men and 27 women, aged 58.9±11.9 years) with T1 or benign NMIBC were enrolled. Each patient was directly injected with CASI through catheter needle into the root of NMIBC. Vital signs, electrocardiography, blood count, blood biochemistry, and urine analysis were re-examined on day 2 and day 14 after CASI injection, together with a cystoscopic examination 4 weeks after CASI treatment was performed for all patients to assess the clinical activity and safety of CASI. To study long-term efficacy, patients in center 2 were followed up for recurrence with a median follow-up time of 13.8 years. Results: For the 101 patients enrolled in this study, demographic characteristics in the 3 centers showed no significant differences. After CASI, 2 patients showed administration site-dependent, but not dose-dependent, increase in their aluminum concentration in 24 hours without obvious abnormality in blood biochemistry. The overall effective rate was 97.03%, including complete tumor necrosis in 94 patients. Treatment-related adverse events occurred in 20 patients (19.80%), including 9 drug-related and 11 cystoscopy-related adverse events (AEs). All AEs were endurable and disappeared within 2 weeks without any treatment. The maximum tolerated single dose of CASI was 21 mL. Among the 43 patients at center 2, 3 patients were excluded because they changed to other treatment regimen. As of April 2022, of the 40 patients enrolled, 22 had no recurrence and 7 relapsed. The follow-up time was 2-16.2 years. The other 11 patients were lost to follow up. Conclusions: CASI may be an effective and safe option for the treatment of NMIBC and is expected to be a potential monotherapy regimen for NMIBC.

2.
J Cancer Res Ther ; 14(Supplement): S616-S621, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30249877

ABSTRACT

PURPOSE: Pyruvate kinase M2 (PKM2) was found overexpressed in tumor cells and played a significant role in tumor formation and growth. We sought to explore the correlation of PKM2 expression with cell proliferation, invasion, and apoptosis in bladder cancer cell line. MATERIALS AND METHODS: Real-time polymerase chain reaction and Western blot were performed to determine the expression level of PKM2 at mRNA and protein level. MTT and flow cytometry were respectively used to explore the proliferation, invasion, and apoptosis in bladder cancer cell line in vitro. RESULTS: The results suggested that suppression of PKM2 significantly decreased the proliferation rate, invasive cell number, and migration ability of bladder cancer cells compared with blank group. Moreover, proteins such as MMP2 and MMP9 as well as P38 expression were also affected by the PKM2 expression changes. These results proved that PKM2 could be involved in the progression of bladder cancer by mitogen-activated protein kinases signaling pathway. CONCLUSION: The data presented in this study revealed that PKM2 up-regulation may promote the development and metastasis of bladder cancer through promoting cell proliferation, migration and invasion via MAPK signal pathway.


Subject(s)
Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Pyruvate Kinase/genetics , Urinary Bladder Neoplasms/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Flow Cytometry , Gene Expression Regulation, Neoplastic/genetics , Humans , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Signal Transduction/genetics , Urinary Bladder Neoplasms/pathology , p38 Mitogen-Activated Protein Kinases/genetics
3.
Int J Clin Exp Pathol ; 8(5): 4725-34, 2015.
Article in English | MEDLINE | ID: mdl-26191162

ABSTRACT

OBJECTIVES: Rutin, a polyphenolic flavonoid, was reported to have beneficial effect on drug induced nephropathy. The present study aimed to introduce 5/6 nephrectomized rat model to further evaluate its renal protective effect. METHODS: Adult Wistar rats were induced to develop chronic renal failure through 5/6 nephrectomy (5/6 Nx). After that, animals were treated orally with saline, rutin at 15 and 45 mg/kg, and losartan (10 mg/kg) daily for 20 weeks; sham-operated animals were also involved as control. After treatment for 8 and 20 weeks, blood and urine samples were collected for biochemical examination; all the kidney remnants were collected for histological examination. The protein levels of TGF-ß1, smad2 and phosphorylated-smad2 (p-smad2) in kidney were measured. Immunohistochemistry was used to analyze the expression of TGF-ß1, fibronectin and collagen IV in kidney tissues. RESULTS: Results suggested that rutin could reduce the proteinurea, blood urine nitrogen and blood creatinine in 5/6 Nx animals significantly, as well as oxidation stress in the kidney. By histological examination, rutin administration alleviated glomerular sclerosis scores and tubulointerstitial injuries in a dose-dependent manner (P<0.01). Immunohistochemistry also suggested rutin could reduce the expression of TGF-ß1, fibronectin and collagen IV in kidney tissues. By western blot, we found the rutin could reduce the TGF-ß1, p-smad2 expression in the kidney tissues of rats. CONCLUSIONS: This study suggests that the rutin can improve renal function in 5/6 Nx rats effectively. Its effect may be due to its anti-oxidation and inhibiting TGFß1-Smad signaling.


Subject(s)
Fibrosis/drug therapy , Kidney/drug effects , Oxidative Stress/drug effects , Proteinuria/drug therapy , Rutin/therapeutic use , Signal Transduction/drug effects , Smad Proteins/metabolism , Transforming Growth Factor beta1/metabolism , Animals , Fibrosis/metabolism , Fibrosis/pathology , Kidney/metabolism , Kidney/pathology , Male , Nephrectomy , Phosphorylation/drug effects , Proteinuria/metabolism , Proteinuria/pathology , Rats , Rats, Wistar , Rutin/pharmacology
4.
PLoS One ; 10(3): e0118951, 2015.
Article in English | MEDLINE | ID: mdl-25790284

ABSTRACT

The aim of the present study was to examine whether hypoxia preconditioning could improve therapeutic effects of adipose derived mesenchymal stem cells (AMSCs) for diabetes induced erectile dysfunction (DED). AMSCs were pretreated with normoxia (20% O2, N-AMSCs) or sub-lethal hypoxia (1% O2, H-AMSCs). The hypoxia exposure up-regulated the expression of several angiogenesis and neuroprotection related cytokines in AMSCs, including vascular endothelial growth factor (VEGF) and its receptor FIK-1, angiotensin (Ang-1), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), stromal derived factor-1 (SDF-1) and its CXC chemokine receptor 4 (CXCR4). DED rats were induced via intraperitoneal injection of streptozotocin (60 mg/kg) and were randomly divided into three groups-Saline group: intracavernous injection with phosphate buffer saline; N-AMSCs group: N-AMSCs injection; H-AMSCs group: H-AMSCs injection. Ten rats without any treatment were used as normal control. Four weeks after injection, the mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured. The contents of endothelial, smooth muscle, dorsal nerve in cavernoursal tissue were assessed. Compared with N-AMSCs and saline, intracavernosum injection of H-AMSCs significantly raised ICP and ICP/MAP (p<0.05). Immunofluorescent staining analysis demonstrated that improved erectile function by MSCs was significantly associated with increased expression of endothelial markers (CD31 and vWF) (p<0.01) and smooth muscle markers (α-SMA) (p<0.01). Meanwhile, the expression of nNOS was also significantly higher in rats receiving H-AMSCs injection than those receiving N-AMSCs or saline injection. The results suggested that hypoxic preconditioning of MSCs was an effective approach to enhance their therapeutic effect for DED, which may be due to their augmented angiogenesis and neuroprotection.


Subject(s)
Adipose Tissue/cytology , Cell Hypoxia/physiology , Diabetes Complications/therapy , Erectile Dysfunction/therapy , Mesenchymal Stem Cell Transplantation/methods , Neovascularization, Physiologic/physiology , Neuroprotection/physiology , Analysis of Variance , Animals , Blotting, Western , Cell Differentiation/physiology , DNA Primers/genetics , Erectile Dysfunction/etiology , Immunohistochemistry , Male , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction
5.
Int J Clin Exp Med ; 8(11): 20454-62, 2015.
Article in English | MEDLINE | ID: mdl-26884961

ABSTRACT

BACKGROUND: Genetic variation of SNPs in the PTGS2 gene is reported to be capable of creating tissue milieu favoring tumorigenesis. Some studies have implicated the common SNP rs20417 has association with PCa risk, while others showed reverse results. The study was performed with an aim to reconcile the existing controversy by performing a meta-analysis. METHODS: We searched databases of Embase and PubMed and identified 8 publications fulfilling the specified inclusion criteria. X(2)-based Q-test and I(2) statistic were quantified to measure the heterogeneity across studies. The pooled ORs and 95% CIs were calculated to estimate the association between SNP rs20417 and PCa risk. RESULTS: Based on an enlarged sample size by combining the data from published meta-analyses and those missed in them, the results of the present meta-analysis revealed the association of SNP rs20417 and overall PCa risk was not significant. Subgroup analyses according to ethnicity and source of controls did not show any significant results, either. CONCLUSIONS: The meta-analysis suggests that the presence of SNP rs20417 is unlikely to be associated with PCa risk. Our understanding of the genetic risk for PCa should be further expanded and refined through future research in a much larger number of participants.

6.
Cell Tissue Bank ; 16(1): 143-50, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24777650

ABSTRACT

Human adipose-derived stem cells (hADSCs) have the ability to influence immune response, and hence are key cell sources for tissue repair and regeneration. In this study we explored the effect of continuous passage on the immunomodulatory properties of hADSCs to provide some advises for large-scale production of hADSCs for clinical applications. We found that after continuous passage, the specific surface markers expression levels as well as the adipogenic and osteogenic differentiation capacities of hADSCs had no obvious changes. However, the secretion levels of IL-10 and HGF reduced dramatically along with passage numbers. Furthermore, the INF-γ level was found higher in which medium peripheral blood mononuclear cells were co-cultured with hADSCs with higher passage numbers. Also, the in vivo experiments showed that the peritonitis model mice, which were injected with higher passage numbers of hADSCs, tended to have higher levels of inflammation. All these together indicated that continuous passage has only minor effect on the cell phenotypes but will impair the immunomodulatory properties of hADSCs. This suggests that hADSCs could be prepared by continuous passage, but only those cells of lower passage numbers would be ideal therapeutic tools.


Subject(s)
Adipose Tissue/cytology , Immunomodulation , Stem Cells/immunology , Adipose Tissue/metabolism , Animals , Cell Differentiation , Coculture Techniques , Cytokines/metabolism , Humans , Mice , Mice, Inbred C57BL , Stem Cells/cytology
7.
J Cell Mol Med ; 18(3): 434-43, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24460735

ABSTRACT

Tissue engineering has brought new hopes for urethral reconstruction. However, the absence of pre-vascularization and the subsequent degradation of materials often lead to the failure of in vivo application. In this study, with the assistance of hypoxia-activated human umbilical cord mesenchymal stem cells (hUCMSCs), pedicled muscle flaps were used as materials and pre-incubated in ventral penile subcutaneous cavity of rabbit for 3 weeks to prepare a pre-vascularized urethral construct. We found that small vessels and muscle fibres were scattered in the construct after 3 weeks' pre-incubation. The construct presented a fibrous reticular structure, which was similar to that of the corpus spongiosum under microscope examination. The produced constructs were then used as a patch graft for reconstruction of the defective rabbit urethra (experimental group), natural muscular patch was used as control (control group). Twelve weeks after the reconstructive surgery, urethrography and urethroscope inspections showed wide calibres of the reconstructed urethra in the experimental group. Histopathological studies revealed that fibrous connective tissues and abundant muscle fibres constituted the main body of the patch-grafted urethra. In contrast, in the control group, only adipose tissue was found in the stenosis-reconstructed urethra, replacing the originally grafted muscular tissue. To our knowledge, this is the first report that successfully constructed a pre-vascularized urethral construct by using hypoxia-activated hUCMSC and pedicled muscle flaps. More importantly, the pre-vascularized construct showed a good performance in urethral reconstruction when applied in vivo. The study provided a novel strategy for tissue engineering of pre-vascularized urethral construct for the defective urethra, representing a further advancement in urethral reconstruction.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Muscles/blood supply , Surgical Flaps/blood supply , Tissue Engineering/methods , Umbilical Cord/cytology , Urethra/blood supply , Angiogenesis Inducing Agents/metabolism , Animals , Blotting, Western , Cell Hypoxia , Cell Separation , Cytokines/metabolism , Humans , Male , Rabbits , Radiography , Plastic Surgery Procedures , Subcutaneous Tissue/physiology , Urethra/diagnostic imaging , Urethra/surgery
8.
Zhonghua Wai Ke Za Zhi ; 51(2): 119-22, 2013 Feb 01.
Article in Chinese | MEDLINE | ID: mdl-23711003

ABSTRACT

OBJECTIVE: To summarize the 5-year follow-up to 2 micron continuous wave laser vaporesection for the treatment of patients with low urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), and evaluate the safety and clinical effects of the treatment. METHODS: From October 2006 to September 2007, 236 cases with low urinary tract symptom secondary to BPH were treated transurethrally under epidural or general anesthesia using the 70 Watt 2 micron laser system. Vaporesection of the prostate was performed with the traditional "U" or the "dividing" method. The 210 cases who met the inclusion criteria in this study were selected for further observation. Baseline and perioperative data were recorded and evaluated in resection time, transfusion rate, catheter-time, improvements in maximal urinary flow rate (Qmax), international prostate symptom scores (IPSS), quality of life (QoL), and post voiding residual volume (PVR). RESULTS: Out of the 210 cases, 179 cases were followed up to 5 years finally. All the surgical procedures were successfully conducted under epidural or general anesthesia. Mean operation time was (80 ± 22) minutes, and mean retrieved prostatic tissue was (24.9 ± 4.2) g. Resected prostatic tissues could be easily flashed out of the bladder. There were no significant differences in serum sodium concentrations and hemoglobin levels before and after the surgery. Mean catheter time and hospital stay was (114 ± 35) hours and (5.7 ± 1.9) days respectively. Only one postoperative secondary hemorrhage was found and treated with blood transfusion. During the 5-year follow-up, Qmax increased from (8.6 ± 3.5) ml/s preoperatively to (23.6 ± 4.2) ml/s by the end of the follow-up (P < 0.01), IPSS and QoL-Score improved from 25.3 ± 5.2 and 4.1 ± 1.3 to 6.1 ± 3.0 and 1.4 ± 0.8 respectively (P < 0.01), and PVR decreased from (248 ± 89) ml to (15 ± 13) ml. The 3 patients developed urinary incontinence and recovered 3 months later through functional exercises with the help of acupuncture. Five patients were found to have urethral stricture 3 months after the surgery and recovered with the treatment of urethral dilatation (3 cases) or internal urethrotomy (2 cases) respectively. CONCLUSIONS: Transurethral vaporesection of prostate using the 2 micron continuous wave laser system is a safe and effective treatment for benign prostatic hyperplasia with obvious improvements in subjective and objective voiding parameters, which were evident at 3 months after the surgery and were sustained throughout the 5-year long-term follow-up.


Subject(s)
Laser Therapy , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/methods , Aged , Aged, 80 and over , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications
9.
Exp Ther Med ; 5(4): 1097-1100, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23596476

ABSTRACT

The present study aimed to evaluate the method and clinical effects of transurethral dividing vaporesection of the prostate in the management of benign prostatic hyperplasia (BPH) using the RevoIix 70 W 2-µm continuous wave (cw) laser. A total of 155 BPH patients were treated transurethrally under epidural or sacral anesthesia using the dividing vaporesection technique. Of these, 80 had a prostate volume of ≤80 ml and 75 had a prostate volume of >80 ml. Pre- and post-operative data were evaluated for prostate-specific antigens (PSAs), post-void residual volume (PVR), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS) and quality of life (QoL). Statistical analyses were performed using the SPSS 16.0 software. Treatment effectiveness evaluations were also conducted. In the ≤80 ml prostate volume group, the mean PSA level decreased from 3.8±0.9 to 2.6±1.3 ng/ml. The PVR, mean Qmax, IPSS and QoL score improved significantly (P<0.05) in each group but no statistically significant difference was identified between the two groups. With a shorter surgery duration, safe use and high cutting efficiency and rapid vaporization ability, the 2-µm laser vaporesection technique shows superiority compared to standard techniques in the treatment of BPH.

10.
J Cancer Res Clin Oncol ; 139(7): 1189-98, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23568547

ABSTRACT

PURPOSE: Bladder cancer is one of the world's top ten malignant tumors. The crucial role of microRNA in carcinogenesis has been well emphasized. Considering miRNA expression was tumor stage-, tissue-, or even development-specific, more experimental evidences about the functions of miRNAs in bladder cancer should be discovered to advance applying of miRNA in the diagnosis or therapy of cancer. METHODS: MiR-708 level in bladder carcinoma and adjacent noncancerous tissues was tested by real-time qPCR. Cell apoptosis was analyzed by using flow cytometry. The tumorigenicity of bladder carcinoma cells was evaluated in nude mice model. Luciferase reporter gene assays were performed to identify the interaction between miR-708 and 3'UTR of Caspase-2 mRNA. The protein level of Caspase-2 was determined by western blotting. RESULTS: In this study, we reported that miR-708 was frequently dysregulated in human bladder carcinoma tissues compared to normal tissues. In addition, we found that silencing of miR-708 could promote the T24 and 5637 cells to apoptosis and inhibit the bladder tumor growth in vivo. Also, Caspase-2 was proved to be one of direct targets of miR-708 in T24 and 5637 cells. Further results showed that Caspase-2 was involved in the miR-708 regulated cell apoptosis. CONCLUSIONS: All together, these results suggest miR-708 may act as an oncogene and induce the carcinogenicity of bladder cancer by down-regulating Caspase-2 level.


Subject(s)
Carcinoma/enzymology , Caspase 2/genetics , Cell Transformation, Neoplastic/genetics , Cysteine Endopeptidases/genetics , MicroRNAs/metabolism , RNA Interference , Urinary Bladder Neoplasms/enzymology , Animals , Apoptosis/genetics , Base Sequence , Carcinoma/genetics , Carcinoma/pathology , Caspase 2/metabolism , Cell Line, Tumor , Cysteine Endopeptidases/metabolism , Enzyme Repression , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , MicroRNAs/physiology , Neoplasm Transplantation , Tumor Burden , Up-Regulation , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology
11.
J Mol Histol ; 44(3): 347-56, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23436000

ABSTRACT

Estrogens and their receptors are important factors involved in periodontal ligament (PDL) tissue health. As a regulator of estrogen receptors (ER), the proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) may play a role in alveolar bone formation and PDL homeostasis. The aim of the present study was to observe PELP1 expression in rat PDL tissue during estrogen levels manipulations. Twenty-one 8-week old normal female Sprague-Dawley rats were randomly divided into three equal groups: sham-operated controls, ovariectomized (OVX) group, and OVX given 17ß-estradiol intraperitoneally (OVX + E2) for 16 weeks. PELP1 expression was down-regulated in the OVX group and was up-regulated in the OVX + E2 group. Periodontal ligament fibroblast cells (PDLFCs) were isolated from PDL tissue, and characterized by immunohistochemical staining. Estradiol treatment of PDLFCs induced PELP1 protein level compared to untreated cells. PELP1 mRNA expression in estradiol-treated cells was relatively low at the beginning of treatment and then steadily increased from hour 4. In conclusion, results indicate that PELP1 is expressed in rat PDL tissue and PDLFCs, and that its expression is up-regulated during estrogen treatment.


Subject(s)
Estradiol/pharmacology , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Nuclear Proteins/biosynthesis , Nuclear Proteins/genetics , Periodontal Ligament/drug effects , Periodontal Ligament/metabolism , Animals , Down-Regulation , Estradiol/metabolism , Estrogens/blood , Estrogens/metabolism , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Nerve Tissue Proteins/metabolism , Nuclear Proteins/metabolism , Ovariectomy/methods , RNA, Messenger/genetics , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Receptors, Estrogen/metabolism , Up-Regulation
12.
J Biomed Mater Res A ; 100(10): 2612-22, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22615210

ABSTRACT

The study is aimed to evaluate the differentiation potential of human adipose-derived stem cells (hADSCs) into urothelial lineage, and to assess possibility of constructing ureteral grafts using the differentiated hADSCs and a novel polylactic acid (PLA)/collagen scaffolds. HADSCs were indirectly cocultured with urothelial cells in a transwell coculture system for urothelial differentiation. After 14 days coculturing, differentiation was evaluated by detecting urothelial lineage markers (cytokeratin-18 and uroplakin 2) in mRNA and protein level. Then the differentiated hADSCs were seeded onto PLA/collagen ureteral scaffolds and cultured in vitro for 1 week. The biocompatibility of the scaffolds was tested by scanning electron microscopy (SEM) and MTT analysis. At last, the cell/scafflod grafts were subcutaneously implanted into 4-week-old female athymic mice for 14 days. The results demonstrated that the hADSCs could be efficiently induced into urothelial lineage by indirect coculture. The differentiated cells seeded onto the PLA/collagen ureteral scaffolds survived up to 7 days and maintained proliferation in vitro, which indicated that the scaffolds displayed good biocompatibility. In vivo study showed that the differentiated cells in the grafts survived, formed multiple layers on the scaffolds and expressed urothelial lineage markers. In conclusion, hADSCs may serve as an alternative cell resource in cell-based tissue engineering for ureteral reconstruction. These cells could be employed to construct a model of ureteral engineering grafts and be effectively applied in vivo, which could be a new strategy on ureteral replacement with applicable potential in clinical research.


Subject(s)
Biocompatible Materials/pharmacology , Cell Differentiation/drug effects , Stem Cells/cytology , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Ureter/transplantation , Urothelium/cytology , Adipose Tissue/cytology , Adult , Aged , Animals , Biodegradation, Environmental , Biomarkers/metabolism , Cell Lineage/drug effects , Cell Separation , Cell Tracking , Coculture Techniques , Female , Humans , Materials Testing , Mice , Middle Aged , Prosthesis Implantation , Stem Cells/drug effects , Surface Properties , Ureter/ultrastructure , Young Adult
13.
Cell Tissue Res ; 347(3): 737-746, 2012 03.
Article in English | MEDLINE | ID: mdl-22290635

ABSTRACT

Autologous urothelial cells (UCs) provide a cell source for urinary tissue engineering because they can be used safely due to their lack of immunogenicity. However, these cells cannot be harvested under the following circumstances: malignancy, infection and organ loss, etc. Human adipose-derived stem cells (HADSCs) possess the traits of high differentiation potential and ease of isolation, representing a promising resource for tissue engineering and regenerative medicine. Nevertheless, HADSCs have been poorly investigated in urology and the optimal approaches to induce HADSCs into urothelium are still under investigation. In this study, we hypothesized that the change of microenvironment by a conditioned medium was essential for the transdifferentiation of HADSCs into UCs. We then used a conditioned medium derived from urothelium to alternate the microenvironment of HADSCs. After 14 days of culture in a conditioned medium, about 25-50% HADSCs changed their morphology into polygonal epithelium-like shapes. In addition, these cells expressed up-regulating of urothelial lineage-specific markers (uroplakin 2and cytokeratin-18) and down-regulating of mesenchymal marker (vimentin) in RNA and protein level, respectively, which confirmed that HADSCs were induced into urothelial lineage cells. We also measured the growth factors in the conditioned medium in order to analyze the molecular mechanisms regulating transdifferentiation. We observed that the expression levels of PDGF-BB and VEGF were significantly higher than those of the control group after 14 days induction, suggesting they were abundantly secreted into the medium during the culturing period. In conclusion, HADSCs showed in vitro the upregulation of markers for differentiation towards urothelial cells by culturing in an urothelial-conditioned medium, which provides an alternative cell source for potential use in urinary tract tissue engineering.

14.
Arch Surg ; 147(2): 159-67, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22351911

ABSTRACT

OBJECTIVES: To study the clinical anatomy of the transversalis fascia (TF) and to explore the intertransversalis fascia approach in urologic laparoscopic operations (ULOs). DESIGN: Prospective study. SETTING: Two academic hospitals. OTHER PARTICIPANTS: Data from 1217 urologic laparoscopic or open operations and 10 laparoscopic hernia repairs were analyzed between January 1, 2009, and April 30, 2011. Findings from 3 fresh autopsies were also included. MAIN OUTCOME MEASURES: The anatomy of the TF was studied and the intertransversalis fascia approach was explored in ULOs; furthermore, they were proved in the open operations and fresh autopsies. Photographs were taken from the intertransversalis fascia approach in ULOs, micrographs were obtained to examine the microscopic structure of the TF, and the color atlas of TF anatomy (cross and sagittal sections) was drawn. RESULTS: The TF is a general plane of connective tissue lying between the inner surface of the transversus abdominis and the extraperitoneal fat. It can be divided into 2 layers (superficial and deep), with an amorphous fibroareolar space between them. The intertransversalis fascia approach in ULOs is the approach between the 2 layers of the TF. CONCLUSIONS: The intertransversalis fascia approach is described for the first time, to our knowledge. Surgeons can obtain a clean, clear, and bloodless operating space in ULOs using the intertransversalis fascia approach.


Subject(s)
Fasciotomy , Laparoscopy , Urologic Surgical Procedures , Adipose Tissue/anatomy & histology , Adrenalectomy/methods , Cystectomy/methods , Fascia/anatomy & histology , Hernia, Inguinal/surgery , Humans , Nephrectomy/methods , Peritoneum/anatomy & histology , Prostatectomy/methods , Urologic Surgical Procedures/methods
15.
Chin Med J (Engl) ; 124(19): 3087-92, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22040561

ABSTRACT

BACKGROUND: Efficient cell adhesion and proliferation is a central issue in cell-based tissue engineering, which offers great promise for repair of urethral defects or strictures. This study evaluated the adhesion and growth of rabbit uroepithelium on a surface-modified three-dimensional poly-L-lactic acid (PLLA) scaffold. METHODS: Urethral mucosa were harvested from male New Zealand rabbits and the urothelium were dissociated and then cultured. Immunocytochemistry on cultured uroepithelium for pancytokeratin and uroplakin II and TE-7 confirmed pure populations. After in vitro proliferation, cells were seeded onto a surface-modified urethral scaffold with non-knitted filaments. The morphology and viability of the cells were examined by immunohistochemical and fluorescence staining. Inverted and scanning microscopes were used to document cell growth and adhesion. RESULTS: Three to five days after primary culture, the uroepithelial cells gradually became confluent, assuming a cobblestone pattern. The filaments of the urethral scaffold had excellent biocompatibility and allowed growth of the uroepithelium, without affecting viability. The uroepithelial cells adhered to and grew well on the scaffold. After 3 - 7 days, the cells grew vigorously and meshes of the scaffold were full of uroepitheliums. CONCLUSIONS: The surface-modified urethral scaffold with non-knitted filaments allows the growth of uroepithelium and can serve as a carrier for the tissue engineering of urethra.


Subject(s)
Absorbable Implants , Epithelial Cells/physiology , Tissue Engineering/methods , Urethra/cytology , Animals , Cells, Cultured , Lactic Acid , Male , Polyesters , Polymers , Rabbits
16.
Asian Pac J Cancer Prev ; 12(5): 1307-11, 2011.
Article in English | MEDLINE | ID: mdl-21875287

ABSTRACT

OBJECTIVES: Hypoxia-inducible factor-1alpha (HIF-1a) is widely considered to be one of the key regulators in cancer cells. Here, we investigated a microRNA regulating expression of HIF-1a and explored its functions in clear cell renal cell carcinoma (ccRCC) cells. METHODS AND MATERIALS: Western blot and reporter assays were used to assess HIF-1a as a direct target of miR-138. The effects of miR-138 or si-HIF-1a on ccRCC 786-O cells were also estimated by apoptosis analysis and cell migration assay. RESULTS: The data showed HIF-1a to be one target of miR-138. Futhermore, inhibition of the expression of HIF-1a with specific siRNA or miR-138 could increase apoptosis and reduce the migration of 786-O cells. CONCLUSIONS: miR-138 could inhibit the expression of HIF-1a and regulate the apoptosis and migration of ccRCC cells.


Subject(s)
Carcinoma, Renal Cell/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , MicroRNAs/genetics , Apoptosis , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Movement , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , MicroRNAs/metabolism , RNA Interference , RNA, Small Interfering
17.
Asian Pac J Cancer Prev ; 12(4): 929-33, 2011.
Article in English | MEDLINE | ID: mdl-21790228

ABSTRACT

Systemic chemotherapy is the only current modality that provides the potential for long-term survival in bladder carcinoma patients with metastatic disease. Overexpression of cyclooxygenase-2 COX-2 induces expression of immune- and cell proliferation-related genes and is associated with the grade, prognosis and recurrence of transitional cell carcinoma of the bladder. There is abundant evidence that aberrant expression of microRNAs (miRNAs) is implicated in numerous disease states and miRNAs have the potential to be used for cancer therapeutics. Here, we found expression of miR-143 to be low in a series of human bladder carcinomas as compared to background tissue. In addition, restoration of miR-143 by cell transfection in T24 cancer cells led to decreased COX-2 expression, reduced proliferation and mobility. Our findings will help to further understand the functions of miRNAs in cancer cells and point to a specific potential of miR-143 may be employed as a therapeutic agent for bladder carcinoma. The results provide insights into the development of novel tumor markers or new therapeutic strategies.


Subject(s)
Carcinoma, Transitional Cell/genetics , Cell Movement/genetics , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , MicroRNAs/genetics , Urinary Bladder Neoplasms/genetics , 3' Untranslated Regions , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Transitional Cell/metabolism , Carcinoma, Transitional Cell/pathology , Cell Line, Tumor , Cell Proliferation , Humans , MicroRNAs/biosynthesis , Neoplasm Metastasis , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Prognosis , Transfection/methods , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology
18.
BJU Int ; 108(6): 901-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21223480

ABSTRACT

OBJECTIVE: • To study the operability and effectiveness of a biodegradable ureteral stent for clinical treatment of ureteral war injury using a canine model. MATERIALS AND METHODS: • A device was designed and employed to generate firearm fragment wounds in unilateral ureters (on randomly chosen sides) of nine beagles (Group A). The wounded ureters were then debrided and sutured. • Intravenous pyelography (IVP) and radioactive renography were performed 40, 80 and 120 days postoperatively. In Group B, firearm fragment wounds were made to the bilateral ureters in nine beagles. A polylactic acid stent was placed unilaterally (on a randomly chosen side) whereas the ureter on the other side was debrided and sutured without stenting. • Both IVP and radioactive renography were performed 40, 80 and 120 days postoperatively. The operability and effectiveness of the biodegradable ureteral stent were studied thereafter. RESULTS: • In Group A, hydronephrosis and hydroureter occurred and worsened postoperatively on the wounded sides in all nine beagles. The ratio of the renal partial concentration indices (RPCI) between the kidneys (unwounded side : wounded side) increased. • The ratio of the kidney washout half-time between the kidneys (unwounded side : wounded side) decreased. In Group B, neither hydronephrosis nor hydroureter was found postoperatively in the stented ureters but both occurred in the unstented ureters in all nine beagles. • The ratio of RPCI between kidneys (stented side : unstented side) increased whereas the kidney washout half-time ratio between the stented and unstented sides decreased. Differences were significant. CONCLUSION: • In Group A, the new canine model for firearm fragment wounds was tested and proved to be operable and effective. In Group B, hydronephrosis and hydroureter were effectively prevented in ureters by biodegradable stent placement compared with the non-stented ureters where hydronephrosis and hydroureter occurred. The renal concentration capacity was effectively protected and the half-time of kidney washout was shortened.


Subject(s)
Absorbable Implants , Lactic Acid/therapeutic use , Polymers/therapeutic use , Stents , Ureter/injuries , Warfare , Wounds, Gunshot/surgery , Animals , Dogs , Feasibility Studies , Female , Hydronephrosis/prevention & control , Male , Polyesters , Postoperative Complications/prevention & control , Radiography , Ureter/diagnostic imaging , Ureteral Diseases/prevention & control , Wounds, Gunshot/diagnostic imaging
19.
Zhonghua Yi Xue Za Zhi ; 91(38): 2706-9, 2011 Oct 18.
Article in Chinese | MEDLINE | ID: mdl-22321982

ABSTRACT

OBJECTIVE: To survey the incidence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in males aged ≥ 50 years and explore the correlation between LUTS and ED. METHODS: A cross-sectional study was performed at Beijing communities in 1644 males aged over 50 years. The International Index of Erectile Function-5 (IIEF-5) and International Prostate Symptom Score (IPSS) were recorded. Pearson's χ(2) test and Spearman correlation coefficients were used to analyze the results of IPSS, LUTS and their correlations with ED. RESULTS: The mean age was 64.5 years old (range: 50-93), the mean value of IPSS(9.9 ± 8.2), the prevalence of mild, moderate and severe LUTS 49.2% (809/1644), 36.4% (599/1644) and 14.4% (236/1644) respectively. The mean value of IIEF was (9.4 ± 8.6), the total incidence of ED 90.5% (1487/1644) and the incidence of ED of mild, moderate and severe LUTS 85.7% (694/809), 93.7% (561/599) and 97.9% (231/236) respectively. The total IIEF-5 score was found significantly correlated with the total IPSS score (r = -0.335, P < 0.01), the obstructive symptoms (r = -0.276, P < 0.01)and irritative symptoms (r = -0.326, P < 0.01). The severity of LUTS was correlated with the severity of ED (r = 0.304, P < 0.01). Correlations also existed between age and total IPSS score(r = 0.388, P < 0.01), LUTS severity (r = 0.457, P < 0.01), total IIEF score (r = -0.533, P < 0.01) or ED severity (r = 0.529, P < 0.01). CONCLUSION: The incidence of LUTS or ED in aging males increases with age. The severity of ED is positively correlated with the severity of LUTS. Irritative and obstructive symptoms influence the occurrence of ED in aging males.


Subject(s)
Erectile Dysfunction/epidemiology , Lower Urinary Tract Symptoms , Aged , Aged, 80 and over , Aging , China/epidemiology , Cross-Sectional Studies , Humans , Incidence , Male , Middle Aged , Prostatic Hyperplasia/epidemiology , Surveys and Questionnaires
20.
Zhonghua Wai Ke Za Zhi ; 48(17): 1328-31, 2010 Sep 01.
Article in Chinese | MEDLINE | ID: mdl-21092615

ABSTRACT

OBJECTIVE: To investigate whether whole tumor cell vaccination strategies in combination with bone marrow transplantation (BMT) can stimulate graft-versus-tumor effect (GVT). METHODS: Twenty-six BALB/c mice were randomly divided into 3 groups: BMT group (group A, n = 10), BMT + vaccination group (group B, n = 10), control group (group C, n = 6). (BALB/c × C57BL/6) F1 mice [CB6F1, H-2K(b/d)] were used as donors. BALB/c mice of group C were only inoculated with Renca cell (2.6 × 10(6)). Mice of group A and B were conditioned with 8 Gy irradiation, followed by infusion by bone marrow cell of CB6F1 mice on day 1, then inoculated with Renca cell (2.6 × 10(6)) on day 8. All mice of group B were immunized subcutaneous on the back with 5 × 10(5) irradiated Renca tumor cells on day 9 and day 16. All mice of group C were inoculated with Renca cell (2.6 × 10(6)) on day 8. In group A and B, all mice were analyzed by fluorescence activated cell sorter (FACS) on day 14, and 28 day after BMT. Mice were killed on day 32 after inoculation with tumor cell and collected blood sample. All tumors were taken out to be weighed and then fixed in 10% buffered formalin, embedded in paraffin, and cut into 5 µm slices. The slices were stained with HE and examined by TdT mediated-dUTP nick end labeling (TUNEL). Liver, skin, intestine, and spleen were biopsied for histopathological examination. RESULTS: The results of chimera showed that engraftments of group A, B were full donor chimerism, and the chimerism of those remained above 90% and preserved even after 28 days. The tumor weight, tumor volume increment in the group B was lower than group A and C (P < 0.05). The tumor suppressing rates of the group A and B were 54%, 60% respectively. The area ratio of tumor necrosis and apoptosis index (AI) of the tumor in the group B were higher than group A and C (P < 0.05). Graft-versus-host disease was not observed in each group. CONCLUSION: The mechanism of GVT after haploidentical allogeneic bone marrow transplantation with tumor vaccination may be the promotion of tumor necrosis and apoptosis.


Subject(s)
Bone Marrow Transplantation/immunology , Cancer Vaccines/immunology , Graft vs Tumor Effect/immunology , Kidney Neoplasms/therapy , Animals , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/therapy , Cells, Cultured , Disease Models, Animal , Kidney Neoplasms/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neoplasm Transplantation , Transplantation Chimera/immunology
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