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1.
Clin Nephrol ; 101(2): 71-81, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38126728

ABSTRACT

BACKGROUND: The status of mineral and bone disorder (MBD) after kidney transplantation is not fully understood, and the assessment of abnormal mineral and bone metabolism in kidney transplant recipients (KTRs) has not been standardized. MATERIALS AND METHODS: We performed a retrospective analysis of 292 KTRs in our center. The levels of biochemical markers of bone metabolism and bone mineral density (BMD) were assessed. We evaluated the influencing factors of BMD using linear regression analysis. And correlation test was used for the correlation analysis between bone metabolism indicators and other indicators. RESULTS: Postoperative MBD mainly manifested as hypercalcemia (8.9%), hypophosphatemia (27.1%), low levels of 25-hydroxyvitamin D(25(OH)vitD) (67.0%), hyperparathyroidism (50.6%), and high levels of bone turnover markers (BTMs). The prevalence of osteopenia/osteoporosis in the femoral neck (FN) and lumbar spine (LS) was 20.1%/2.8% and 26.1%/3.6%, respectively. Multivariate analysis indicated that FN BMD was positively associated with body mass index (BMI) and negatively associated with acute rejection history (p < 0.05); while LS BMD was positively associated with BMI, and negatively associated with intact parathyroid hormone (iPTH) (p < 0.05). Biochemical markers of bone metabolism were affected by age, sex, preoperative dialysis mode and time, postoperative time, transplanted kidney function, and iPTH levels. LS BMD was negatively correlated with iPTH and BTMs (p < 0.05). CONCLUSION: MBD persisted after kidney transplantation. Decreased bone mass was associated with persistent hyperparathyroidism, acute rejection history, low BMI, advanced age, and menopause. Dynamic monitoring of bone metabolism index and BMD helps to assess MBD after kidney transplantation.


Subject(s)
Hyperparathyroidism , Kidney Transplantation , Female , Humans , Retrospective Studies , Kidney Transplantation/adverse effects , Renal Dialysis , Bone Density , Parathyroid Hormone , Biomarkers , Hyperparathyroidism/epidemiology , Hyperparathyroidism/etiology
2.
Ren Fail ; 46(1): 2300303, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38263697

ABSTRACT

BACKGROUND: The assessment of left ventricular (LV) remodeling and its association with mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate LV remodeling changes one year after kidney transplantation (KT) and identify their influencing factors. METHODS: Ninety-five KTRs (68 males; ages 40.2 ± 10.8 years) were followed before and one year after KT. Traditional risk factors and bone metabolism indicators were assessed. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and left ventricular diastolic dysfunction (LVDD) were measured using two-dimensional transthoracic echocardiography. The relationship between MBD and LV remodeling and the factors influencing LV remodeling were analyzed. RESULTS: One year after KT, MBD was partially improved, mainly characterized by hypercalcemia, hypophosphatemia, hyperparathyroidism, 25-(OH) vitamin D deficiency, elevated bone turnover markers, and bone loss. LVMI, the prevalence of left ventricular hypertrophy (LVH), and the prevalence of LVDD decreased, while LVEF increased. LVH was positively associated with postoperative intact parathyroid hormone (iPTH) and iPTH nonnormalization. △LVMI was positively associated with preoperative type-I collagen N-terminal peptide and postoperative iPTH. LVEF was negatively associated with postoperative phosphorous. △LVEF was negatively associated with postoperative iPTH. LVDD was positively associated with postoperative lumbar spine osteoporosis. Preoperative LVMI was negatively associated with △LVMI and positively associated with △LVEF. Advanced age, increased BMI, diabetes, longer dialysis time, lower albumin level, and higher total cholesterol and low-density lipoprotein levels were associated with LV remodeling. CONCLUSIONS: LV remodeling partially improved after KT, showing a close relationship with MBD.


Subject(s)
Kidney Transplantation , Male , Humans , Stroke Volume , Ventricular Function, Left , Ventricular Remodeling , Minerals , Hypertrophy, Left Ventricular
3.
Ren Fail ; 45(2): 2276382, 2023.
Article in English | MEDLINE | ID: mdl-37936391

ABSTRACT

BACKGROUND: The assessment and prevention of vascular calcification (VC) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate VC change one year after kidney transplantation (KT) and identify their influencing factors. METHODS: 95 KTRs (68 males; ages 40.2 ± 10.8 years) were followed one year after KT. Changes in bone mineral density (BMD) and bone metabolism biomarkers were assessed. Coronary artery calcification (CAC) and thoracic aortic calcification (TAC) were measured using 192-slice third-generation dual-source CT. The relationship between bone metabolism indicators and VC and the factors influencing VC were analyzed. RESULTS: Postoperative estimated glomerular filtration rate was 79.96 ± 24.18 mL/min*1.73 m2. One year after KT, serum phosphorus, intact parathyroid hormone (iPTH), osteocalcin, type I collagen N-terminal peptide (NTx), type I collagen C-terminal peptide, and BMD decreased, 25-hydroxyvitamin D remained low, and VC increased. Post-CAC and TAC were negatively correlated with pre-femoral neck BMD, and TAC was positively correlated with post-calcium. CAC and TAC change were positively correlated with post-calcium and 25-hydroxyvitamin D. Increased CAC was positively associated with hemodialysis and pre-femoral neck osteopenia. CAC change was positively associated with prediabetes, post-calcium, and pre-CAC and negatively associated with preoperative and postoperative femoral neck BMD, and NTx change. Increased TAC was positively associated with age, prediabetes, preoperative parathyroid hyperplasia/nodule, post-calcium, and post-femoral neck osteopenia. TAC change was positively associated with age, diabetes, pre-triglyceride, pre-TAC, dialysis time, post-calcium and post-iPTH, and negatively associated with post-femoral neck BMD. CONCLUSIONS: Mineral and bone disorders persisted, and VC progressed after KT, showing a close relationship.


Subject(s)
Bone Diseases, Metabolic , Kidney Transplantation , Prediabetic State , Vascular Calcification , Male , Humans , Kidney Transplantation/adverse effects , Calcium , Collagen Type I , Vascular Calcification/diagnostic imaging , Vascular Calcification/etiology , Vascular Calcification/metabolism , Bone Density , Minerals , Peptides
4.
Ren Fail ; 45(2): 2256418, 2023.
Article in English | MEDLINE | ID: mdl-37905940

ABSTRACT

BACKGROUND: Iguratimod has been shown to promote bone formation and inhibit bone resorption in rheumatoid arthritis patients. We aimed to explore its effect on bone metabolism and vascular calcification (VC) in kidney transplant recipients (KTRs). METHODS: A post hoc analysis was conducted among the subjects in our previous randomized clinical trial (NCT02839941). Forty-three KTRs completing bone metabolism 52 weeks after enrollment were selected for this analysis, among whom 27 patients received VC examinations. In the iguratimod group, iguratimod (25 mg twice daily) was added adjuvant to the traditional triple regimen. At the 52-week follow-up, the following parameters were assessed: serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), osteocalcin, type I collagen N-terminal peptide (NTx), type I collagen C-terminal peptide (CTx), bone mineral density (BMD) of the femoral neck and lumbar spine, coronary artery calcification (CAC) and thoracic aortic calcification (TAC). Bone metabolic and VC indices were compared between the two groups using the independent samples t test and Wilcoxon nonparametric test. RESULTS: At 52 weeks after enrollment, the iguratimod group had lower osteocalcin (p = 0.010), BALP (p = 0.015), NTx (p = 0.007), CTx (p = 0.012), CAC (p = 0.080) and TAC scores (p = 0.036) than the control group. There was no significant difference in serum calcium, phosphorus, 25-hydroxyvitamin D, iPTH and BMD between the groups. Iguratimod could reduce bone turnover markers (BTMs) at both high and low iPTH levels. The adverse effect of iguratimod was mild and tolerable. CONCLUSION: Iguratimod is safe, can reduce BTMs and may could attenuate VC in the first year after KT.


Subject(s)
Collagen Type I , Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Calcium , Osteocalcin , Bone Density , Peptides , Parathyroid Hormone , Biomarkers , Minerals , Phosphorus , Bone Remodeling
5.
Ren Fail ; 45(1): 2210231, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37183797

ABSTRACT

BACKGROUND: The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD. METHODS: A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared. RESULTS: MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia. CONCLUSIONS: MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation.


Subject(s)
Chronic Kidney Disease-Mineral and Bone Disorder , Hyperparathyroidism , Kidney Transplantation , Humans , Biomarkers , Bone Density , Bone Remodeling , Cohort Studies , Collagen Type I , Glucocorticoids , Kidney Transplantation/adverse effects , Parathyroid Hormone , Peptides , Osteoporosis
6.
Clin Transplant ; 36(4): e14565, 2022 04.
Article in English | MEDLINE | ID: mdl-34931720

ABSTRACT

OBJECTIVE: To evaluate the clinical efficacy and safety of iguratimod (IGU) for reducing panel reactive antibody (PRA) in high-mismatched renal transplant recipients. METHODS: Eligible recipients positive for PRAs who received or did not receive IGU treatment were enrolled. We retrospectively reviewed, collected, and analyzed statistically the clinical data of the recipients. RESULTS: A total of 80 recipients were included for further analysis. After IGU was administered for 9 months, no significant difference was found in the change rates of donor specific antibodies between two groups. Meanwhile, the reduction in the PRAs in the IGU group was greater than that in the non-IGU group in anti-human leukocyte antigen (HLA) class I and class II, anti-HLA class I, anti-HLA class II, anti-HLA A, and anti-HLA DR antibodies. However, no differences were found in the anti-HLA B, anti-HLA Cw, anti-HLA DP, and anti-HLA DQ antibodies between the two groups. No serious adverse events were reported, and the incidence of adverse events was comparable between the two groups. CONCLUSION: PRA levels in high-mismatched renal transplant recipients were significantly reduced after the administration of IGU. The high safety of IGU was also determined.


Subject(s)
Kidney Transplantation , Chromones , HLA Antigens , Histocompatibility Antigens Class I , Histocompatibility Testing , Humans , Isoantibodies , Kidney Transplantation/adverse effects , Retrospective Studies , Sulfonamides
7.
Med Sci Monit ; 25: 9138-9158, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31786580

ABSTRACT

BACKGROUND Acute rejection (AR) is a common complication of kidney transplantation. The transforming growth factor beta (TGF-ß) signaling pathway has been observed to be involved in several cellular functions. Our study aimed to investigate the correlations between single-nucleotide polymorphisms (SNPs) in TGF-ß-related genes and the risk of AR in renal transplant recipients. MATERIAL AND METHODS This retrospective, single-center study included 200 Chinese renal transplant recipients. All exons, exon/intron boundaries, and flanking regions of the TGF-ß signaling pathway were detected by targeting sequencing (TS) based on next-generation sequencing technology. Tagger SNPs and haplotypes were identified after adjustment. A general linear model (GLM) was used to explore the confounding effect of clinical variables. Five adjusted inheritance models were utilized to investigate the influence of SNPs on AR, and Banff score was applied to evaluate the effect of related SNPs on pathological changes. RESULTS A total of 188 SNPs on TGF-ß genes were detected. Analysis of adjustment led to identification of 31 tagger SNPs and 10 haplotype blocks. After the analysis of a general linear model and 5 sirolimus-adjusted multiple inheritance models, 1 of the SNPs - rs1131243 on the TGF-ßR3 gene - was observed to be significantly associated with the occurrence of AR. Based on Banff score, no significant association was observed between SNPs and pathological changes. CONCLUSIONS In this study, we observed that the SNP rs1131243 on the TGF-ßR3 gene was significantly associated with the occurrence of AR in Chinese renal transplant recipients.


Subject(s)
Graft Rejection , Transforming Growth Factor beta , Adult , Female , Humans , Male , Middle Aged , Asian People/genetics , China , Genotype , Graft Rejection/genetics , Haplotypes/genetics , Kidney/pathology , Kidney Transplantation/methods , Polymorphism, Single Nucleotide/genetics , Retrospective Studies , Risk Factors , Transforming Growth Factor beta/genetics , Transplant Recipients
8.
Urol Int ; 98(1): 102-110, 2017.
Article in English | MEDLINE | ID: mdl-27074041

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs (18-25 nucleotides) which post-transcriptionally regulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. This study aimed to determine the function of miR-154-5p in prostate cancer (PCa) cells and identify the novel molecular targets regulated by miR-154-5p. MATERIALS AND METHODS: The effects of forced miR-154-5p expression or E2F transcription factor 5 (E2F5) knockdown on PCa cells were evaluated by cell proliferation, flow cytometry, cell migration and invasion assays as well as by Western blot analysis. Dual-luciferase reporter assay was performed to verify the precise target of miR-154-5p. RESULTS: The forced expression of miR-154-5p or E2F5 knockdown significantly restrained cell growth, as well as the migratory and invasive capabilities. Such expression also induced G1 cell cycle arrest of PCa cells in vitro. Hence, E2F5 is a direct target gene of miR-154-5p. CONCLUSIONS: miR-154-5p may play an important role as an inhibitor of proliferation, migration and invasion of PCa by targeting E2F5 in PCa cell lines.


Subject(s)
Cell Movement , Cell Proliferation , MicroRNAs/physiology , Prostatic Neoplasms/pathology , Aged , Humans , Male , Middle Aged , Neoplasm Invasiveness , Tumor Cells, Cultured
9.
BJU Int ; 118(4): 610-7, 2016 10.
Article in English | MEDLINE | ID: mdl-27207733

ABSTRACT

OBJECTIVE: To evaluate the feasibility and efficiency of laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping, and to analyse the factors affecting postoperative renal function. PATIENTS AND METHODS: We conducted a retrospective analysis of 466 consecutive patients undergoing LPN using main renal artery clamping (group A, n = 152) or segmental artery clamping (group B, n = 314) between September 2007 and July 2015 in our department. Blood loss, operating time, warm ischaemia time (WIT) and renal function were compared between groups. Univariable and multivariable linear regression analyses were applied to assess the correlations of selected variables with postoperative glomerular filtration rate (GFR) reduction. Volumetric data and estimated GFR of a subset of 60 patients in group B were compared with GFR to evaluate the correlation between these functional variables and preserved renal function after LPN. RESULTS: The novel technique slightly increased operating time, WIT and intra-operative blood loss (P < 0.001), while it provided better postoperative renal function (P < 0.001) compared with the conventional technique. The blocking method and tumour characteristics were independent factors affecting GFR reduction, while WIT was not an independent factor. Correlation analysis showed that estimated GFR presented better correlation with GFR compared with kidney volume (R(2) = 0.794 cf. R(2) = 0.199) in predicting renal function after LPN. CONCLUSIONS: LPN with segmental artery clamping minimizes warm ischaemia injury and provides better early postoperative renal function compared with clamping the main renal artery. Kidney volume has a significantly inferior role compared with eGFR in predicting preserved renal function.


Subject(s)
Kidney Neoplasms/surgery , Laparoscopy , Nephrectomy/methods , Renal Artery/surgery , Constriction , Feasibility Studies , Female , Glomerular Filtration Rate , Humans , Kidney/pathology , Kidney/physiology , Male , Middle Aged , Organ Size , Prognosis , Recovery of Function , Retrospective Studies
10.
Urol Int ; 97(4): 473-479, 2016.
Article in English | MEDLINE | ID: mdl-27732979

ABSTRACT

OBJECTIVE: To assess the feasibility of retroperitoneal laparoscopic nephrectomy combined with bench surgery and autotransplantation in treating complex renal tumor. PATIENTS AND METHODS: Six patients with complex renal tumor were seen in our institution between 2010 and 2014. Three patients with bilateral renal cell carcinoma underwent retroperitoneal laparoscopic nephrectomy on both sides. Extracorporeal tumorectomy and renal reconstruction were performed on the side of the smaller tumor and then kidney autotransplantation was performed. The other 3 patients with tumor involving the solitary kidney underwent laparoscopic nephrectomy combined with bench surgery and autotransplantation. RESULT: The total time of the operation was 287 ± 25 min; warm ischemia time 3.1 ± 0.7 min; cold ischemia time 47 ± 8.1 min; and kidney autotransplantation required time 86 ± 8.6 min. Estimated blood loss was 232 ± 45.8 ml. Serum creatinine levels were 179 ± 44.7 µmol/l upon hospital discharge. Two patients received temporary hemodialysis. No patient needed further hemodialysis during follow-up. One patient died of multiple metastases 18 months after surgery. The other 5 patients survived without recurrence or metastasis during follow-up. CONCLUSIONS: Retroperitoneal laparoscopic radical nephrectomy combined with bench surgery and autotransplantation is a feasible choice for patients with complex renal cell carcinoma in bilateral kidneys and tumor involving the solitary kidney.


Subject(s)
Nephrectomy , Carcinoma, Renal Cell , Humans , Kidney Neoplasms , Laparoscopy , Neoplasm Recurrence, Local , Solitary Kidney , Transplantation, Autologous
11.
Urol Int ; 94(1): 74-8, 2015.
Article in English | MEDLINE | ID: mdl-25139177

ABSTRACT

OBJECTIVE: To describe the feasibility of retroperitoneal laparoscopic reimplantation of the left renal vein (LRV) for nutcracker syndrome (NCS). PATIENTS AND METHODS: Two patients with NCS underwent the surgery. Both patients complained of gross hematuria and flank discomfort that could not be relieved by resting. They were placed in a supine position and 5 ports were placed in the right abdominal wall. The procedures were performed with a retroperitoneal approach. The LRV was transected and then reimplanted into the distal inferior vena cava. RESULTS: The procedures were performed successfully without any major complications. The total operation time was 105 and 120 min, respectively. Hematuria and flank discomfort were resolved after the surgery. Ultrasonography revealed a patent lumen without compression. CONCLUSIONS: Retroperitoneal laparoscopic reimplantation of the LRV appears to be a feasible procedure with satisfactory short-term outcomes.


Subject(s)
Laparoscopy , Renal Nutcracker Syndrome/surgery , Renal Veins/surgery , Replantation , Vascular Surgical Procedures/methods , Vena Cava, Inferior/surgery , Adult , Blood Loss, Surgical , Female , Flank Pain/etiology , Hematuria/etiology , Humans , Length of Stay , Male , Operative Time , Patient Positioning , Phlebography/methods , Renal Nutcracker Syndrome/complications , Renal Nutcracker Syndrome/diagnosis , Renal Veins/diagnostic imaging , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonography , Young Adult
12.
Zhonghua Wai Ke Za Zhi ; 53(11): 847-51, 2015 Nov 01.
Article in Zh | MEDLINE | ID: mdl-26813840

ABSTRACT

OBJECTIVE: To study the technique and clinical outcomes of laparoscopic radical prostatectomy for high risk prostate cancer. METHODS: A total of 65 patients with high risk prostate cancer were treated with surgery in the First Affiliated Hospital of Nanjing Medical University from January 2011 to June 2013. The mean age was 67 years (range 45-75 years). The mean preoperative prostate specific antigen (PSA) level was 26.7 µg/L (range 11.2-65.5 µg/L). The transrectal biopsy revealed Gleason score of 3+3 in 4 patients, Gleason 3+4 in 27 patients, Gleason 4+3 in 11 patients, Gleason 4+4 in 21 patients and Gleason 4+5 in 2 patients. The bone metastasis was excluded by scintigraphy examination. The surgical procedures were performed through transperitoneal approach. Extended pelvic lymph nodes dissection was performed after the removal of the prostate. Adjuvant radiotherapy or hormonal therapy was administrated according to the pathological results. Serum PSA was detected every 1 to 2 month and urinary continence was evaluated every 3 month in the first year, and then serum PSA was detected every 2 to 3 month. RESULTS: The mean operative time was (134±21) minutes and the median blood loss was (300±146) ml. Bladder neck reconstruction was performed in 15 cases. The drainage was removed on postoperative day 4 and the catheter was removed on day 7. Pathologic results demonstrated pT2 in 25 patients, pT3a in 28 patients, pT3b in 9 patients and pT4 in 3 patients. Positive surgical margin was presented in 15 patients. A median of 19 lymph nodes (range 11-24 nodes) were retrieved during lymphadenectomy and 11 patients had lymph nodes metastasis with a total of 19 positive nodes. Forty-three patients recovered continence after the removal of catheter. Eleven patients received adjuvant hormonal therapy and 19 patients received adjuvant radiation therapy. With the median of 20 months follow-up (range 12-30 months), 5 patients got biochemical recurrence. CONCLUSIONS: Laparoscopic radical prostatectomy with extended lymph nodes dissection for high risk prostate cancer is safe and technical feasible. It provides accurate information on tumor stage and grade. It is an important component of multimodality for the treatment of high risk prostate cancer.


Subject(s)
Laparoscopy , Prostatectomy , Prostatic Neoplasms/surgery , Aged , Biopsy , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Postoperative Period , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis
13.
Zhonghua Nan Ke Xue ; 21(12): 1098-101, 2015 Dec.
Article in Zh | MEDLINE | ID: mdl-26817302

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia (BPH). METHODS: We conducted a multi-centered open clinical study on 165 BPH patients treated with Saw Palmetto Extract Capsules at a dose of 160 mg qd for 12 weeks. At the baseline and after 6 and 12 weeks of medication, we compared the International Prostate Symptom Scores (IPSS), prostate volume, postvoid residual urine volume, urinary flow rate, quality of life scores (QOL), and adverse events between the two groups of patients. RESULTS: Compared with the baseline, both IPSS and QOL were improved after 6 weeks of medication, and at 12 weeks, significant improvement was found in IPSS, QOL, urinary flow rate, and postvoid residual urine. Mild stomachache occurred in 1 case, which necessitated no treatment. CONCLUSION: Saw Palmetto Extract Capsules were safe and effective for the treatment of BPH.


Subject(s)
Plant Extracts/therapeutic use , Prostatic Hyperplasia/drug therapy , Capsules , Humans , Male , Plant Extracts/adverse effects , Quality of Life , Serenoa
14.
Mutagenesis ; 29(6): 419-25, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25239121

ABSTRACT

Angiogenesis is fundamentally important to the pathogenesis of clear cell renal cell carcinoma (ccRCC). We investigated the association between variations of genes related to angiogenesis and the risk of ccRCC. In a case-control study of 859 ccRCC patients and 1004 cancer-free subjects, we genotyped 24 potentially functional single nucleotide polymorphisms (SNPs) in seven angiogenesis-related genes (HIF1A, EPAS1, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) using the TaqMan or Snapshot method. Unconditional logistic regression, adjusted for potential confounding factors, was used to assess the risk associations. The functionality of selected SNPs was assessed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and luciferase reporter gene assays. We found two SNPs (VEGFA rs2010963 and VEGFR3 rs448012) that were significantly associated with increased risk of ccRCC, after adjusting for multiple comparisons [rs2010963 CC/GC cf. GG: false discovery rate (FDR) = 0.048, odds ratio (OR) = 1.36, 95% confidence interval (95% CI) = 1.12-1.66; rs448012 CC/GC cf. GG: FDR = 0.048, OR = 1.38, 95% CI =1.13-1.69]. Real-time quantitative PCR revealed that the variant genotypes of rs2010963, but not rs448012, were associated with increased gene expression in normal tissues of ccRCC patients (CC/GC cf. GG: P = 0.036). The luciferase reporter assay showed that the rs2010963 C allele significantly increased luciferase activity over that of the rs2010963 G allele. Our results indicate that VEGFA rs2010963 and VEGFR3 rs448012 are associated with risk of ccRCC. Furthermore, rs2010963 is a functional SNP that may affect ccRCC susceptibility by modulating endogenous VEGFA expression.


Subject(s)
Carcinoma, Renal Cell/blood supply , Carcinoma, Renal Cell/genetics , Genetic Predisposition to Disease , Kidney Neoplasms/blood supply , Kidney Neoplasms/genetics , Neovascularization, Pathologic/genetics , Carcinoma, Renal Cell/pathology , Case-Control Studies , Gene Expression Regulation, Neoplastic , Genes, Reporter , Genetic Association Studies , Humans , Kidney Neoplasms/pathology , Luciferases/metabolism , Middle Aged , Plasmids/metabolism , Polymorphism, Single Nucleotide/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Risk Factors , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor Receptor-3/genetics
15.
Mutagenesis ; 29(2): 149-54, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24503183

ABSTRACT

Members of the miR-34 family have been shown to be transcriptional targets of the tumour suppressor gene P53. Aberration expression of miR-34 impairs p53-mediated cell cycle arrest and apoptosis. A single nucleotide polymorphism T > C (rs4938723) located within the CpG island in the promoter region of pri-miR-34b/c may affect its expression and has been suggested to influence cancer risk. In this study, we genotyped rs4938723 using the TaqMan method to explore the relationship between this polymorphism and the risk of renal cell cancer (RCC) in a case-control study of 710 RCC patients and 760 control subjects. We found that individuals carrying the CC genotype had a significantly increased RCC risk compared with those with TT or TT/TC genotypes [odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.06-2.21 for CC vs. TT and OR = 1.48, 95% CI = 1.05-2.10 for CC vs. TT/TC). Furthermore, the increased risk was more evident in the subgroups of older subjects (OR = 1.80, 95% CI = 1.08-3.01), males (OR = 1.64, 95% CI = 1.08-2.51), smokers (OR = 2.07, 95% CI = 1.16-3.69) and drinkers (OR = 1.94, 95% CI = 1.01-3.73), although no interaction between rs4938723 and these characteristics was observed. Twenty-seven normal tissues adjacent to tumour were used to evaluate the association between the expression level of miR-34b/c and the polymorphism, which revealed higher expression levels of miR-34b/c in normal renal tissues with TT+TC genotypes than in those with CC genotypes (P < 0.01). Furthermore, a luciferase gene assay in 293-T cells showed that the luciferase activities with rs4938723 T allele are higher than that with C allele (P < 0.05). These results suggest that the miR-34b/c rs4938723 C allele may increase susceptibility to RCC by decreasing the activity of pri-miR-34b/c promoter.


Subject(s)
Asian People/genetics , Carcinoma, Renal Cell/genetics , MicroRNAs/genetics , Promoter Regions, Genetic/genetics , DNA Primers/genetics , Gene Frequency , Genotype , Humans , Logistic Models , Luciferases , MicroRNAs/metabolism , Odds Ratio , Plasmids/genetics , Polymorphism, Single Nucleotide/genetics , Risk Factors
16.
BMC Urol ; 14: 2, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24387269

ABSTRACT

BACKGROUND: Although cystitis glandularis (CG) is a common benign urinary bladder epithelial abnormality, it remains unclear whether CG is a premalignant lesion. Cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) overexpression has recently been reported as a potential tumor initiator or promoter. We evaluated and compared COX-2 and Bcl-2 expression in CG, chronic cystitis (CC), and primary vesicle adenocarcinoma (ADC) tissues. METHODS: We conducted a retrospective study to investigate COX-2 and Bcl-2 levels in CG and ADC. We obtained tissue samples from 75 patients (including 11 cases of CC, 30 typical cases of CG (CGTP), 30 cases of intestinal CG (CGIT), and 4 cases of ADC) between 1989 and 2009 from the Surgical Pathology Archives of the No. 2 People's Hospital of Zhenjiang, affiliated with Jiangsu University. COX-2 and Bcl-2 immunohistochemical staining was performed on all tissues. Nine normal bladder epithelial specimens were evaluated as control samples. Correlations between COX-2 and Bcl-2 expression in CG were also analyzed. RESULTS: COX-2 and Bcl-2 expression was higher in the ADC group compared to other groups (p < 0.05). COX-2 and Bcl-2 levels were higher in the CGIT group compared to the CGTP group (p = 0.000 for both). The CGIT and CGTP groups both showed higher COX-2 expression compared to the CC group (p = 0.000 for both). There was no difference in Bcl-2 expression between the CGTP and CC groups (p = 0.452). Additionally, the difference in COX-2 and Bcl-2 expression between the control and CC groups was also insignificant (p = 0.668 and p = 0.097, respectively). Finally, we found that COX-2 and Bcl-2 levels were positively related (r = 0.648, p = 0.000). CONCLUSION: COX-2 and Bcl-2 overexpression in the CG group suggests that CG, particularly the intestinal type, may be a premalignant lesion that converts into a tumor in the presence of carcinogens.


Subject(s)
Adenocarcinoma/metabolism , Cyclooxygenase 2/metabolism , Cystitis/metabolism , Precancerous Conditions/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Urinary Bladder Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Cystitis/diagnosis , Female , Humans , Male , Retrospective Studies
17.
BMC Urol ; 14: 16, 2014 Feb 04.
Article in English | MEDLINE | ID: mdl-24491207

ABSTRACT

BACKGROUND: In most hospitals, several options for the management of renal stones are available: shockwave lithotripsy, endourologic treatment, or surgery. Choice of treatment is based on the anatomic characteristics of the patient, and the location and size of the stones. In this study we assessed a retroperitoneal laparoscopic technique for treatment of complex renal stones. METHODS: Seventy-five patients, including 53 men and 22 women with a mean age of 47.8 years (range 18-74 y), underwent retroperitoneal laparoscopy for the treatment of complex renal stones between July 2006 and November 2012 in our hospital. RESULTS: The retroperitoneal laparoscopic procedures for treatment of complex renal stones were completely successful in 73 cases, while 2 cases converted to open surgery. The operative time was 85-190 min with a mean of 96 min. The estimated blood lost was 20-400 mL with a mean of 80 mL. After the operation 7 patients experienced urinary leakage. Ultrasonography, x-ray of the kidney, ureter and bladder, and intravenous urography were reviewed at post-procedural follow-up at 6-82 months. No hydronephrosis aggravation was found, and there was no calculus recurrence. CONCLUSION: The merits of retroperitoneal laparoscopy for the treatment of complex renal stones include sparing the nephron, less bleeding, short hospitalization, quick postoperative recovery, and controllable procedure after training Success depends on the experience of surgeons and judicious selection of cases.


Subject(s)
Kidney Calculi/pathology , Kidney Calculi/surgery , Laparoscopy/methods , Nephrectomy/methods , Organ Sparing Treatments/methods , Adolescent , Adult , Aged , Blood Loss, Surgical/statistics & numerical data , Female , Humans , Laparoscopy/statistics & numerical data , Male , Middle Aged , Nephrectomy/statistics & numerical data , Operative Time , Organ Sparing Treatments/statistics & numerical data , Retroperitoneal Space/pathology , Retroperitoneal Space/surgery , Treatment Outcome , Young Adult
18.
World J Surg Oncol ; 12: 131, 2014 Apr 29.
Article in English | MEDLINE | ID: mdl-24774011

ABSTRACT

BACKGROUND: We aimed to evaluate the feasibility and clinical significance of using a modified liver-mobilization technique to treat renal cell carcinoma (RCC) combined with intrahepatic inferior vena cava (IVC) thrombosis. METHODS: A total of 11 level III thrombus patients underwent radical nephrectomy with resection of the tumor thrombus from intrahepatic IVC. A father clamp was used in combination with hepatic portal blocking to control the IVC. RESULTS: The intraoperative mortality and postoperative complications were reduced in 11 cases of RCC with intrahepatic IVC thrombosis. The mean blood loss was 800 mL, and mean patient hospital stay was 13 days. Follow-up was conducted for one to four months, with only two cases of recurrence recorded. CONCLUSIONS: The proposed modified liver-mobilization technique could safely and effectively treat RCC and reduce intrahepatic IVC thrombosis.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Liver/surgery , Nephrectomy/methods , Postoperative Complications/prevention & control , Thrombectomy/methods , Thrombosis/surgery , Vena Cava, Inferior/surgery , Adult , Aged , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/mortality , Feasibility Studies , Female , Follow-Up Studies , Humans , Kidney Neoplasms/complications , Kidney Neoplasms/mortality , Liver/pathology , Male , Middle Aged , Neoplasm Staging , Neoplastic Cells, Circulating , Postoperative Complications/mortality , Prognosis , Survival Rate , Thrombosis/complications , Thrombosis/mortality , Vena Cava, Inferior/pathology
19.
Urol Int ; 92(4): 396-9, 2014.
Article in English | MEDLINE | ID: mdl-24576978

ABSTRACT

OBJECTIVE: To report our initial experience in treating renal nutcracker syndrome by retroperitoneal laparoscopic extravascular stenting. PATIENTS AND METHODS: Two male patients, aged 13 and 16 years, were diagnosed with nutcracker syndrome and received retroperitoneal laparoscopic extravascular stent placement. The perioperative data were collected and evaluated. The follow-up was 10 and 18 months. RESULTS: Both procedures were successful without obvious complications. Total operative time was 65 and 50 min, estimated blood loss was 110 and 70 ml, and postoperative hospital stay was 4 and 6 days. The symptom of gross hematuria ceased 3 and 6 days after surgery. Both patients had normal findings during follow-up. CONCLUSIONS: Treatment of nutcracker syndrome by retroperitoneal laparoscopic extravascular stent placement is a safe and feasible procedure, especially for youngsters in the period of physical development. Longer follow-up and further experience are needed to evaluate the efficacy of this procedure.


Subject(s)
Laparoscopy/methods , Renal Nutcracker Syndrome/surgery , Stents , Adolescent , Humans , Male , Operative Time , Postoperative Period , Renal Nutcracker Syndrome/diagnostic imaging , Retroperitoneal Space , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonography
20.
Prostate ; 73(10): 1082-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23460133

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in diverse biological processes. Aberrant miR-152 expression has been frequently reported in various malignant tumors. However, the mechanism of miR-152 in prostate cancer (PCa) remains unclear. This study aims to determine the function of miR-152 in PCa cells and identify the novel molecular targets regulated by miR-152. METHODS: The expression levels of transforming growth factor-alpha (TGFα) were determined in three samples of PCa and adjacent non-tumorous tissues by Western blot analysis. miR-152 levels in 48 primary PCa and 15 non-malignant tissue samples were measured by qRT-PCR. The effects of forced miR-152 expression or TGFα knockdown on PCa cells were evaluated by cell migration and invasion assays, as well as Western blot analysis. Dual-luciferase reporter assay was used to identify binding sites between miR-152 and TGFα 3'-UTR. RESULTS: TGFα was upregulated in PCa tissue samples compared with that in adjacent normal ones. miR-152 expression was significantly decreased in primary PCa samples compared with that in non-malignant samples. Patients with Gleason scores >7 exhibited lower miR-152 levels than those with lower scores. Moreover, low miR-152 expression is correlated with advanced pathological T-stages. Forced miR-152 expression or TGFα knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro. TGFα is a direct target gene of miR-152. CONCLUSIONS: Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.


Subject(s)
Cell Movement/genetics , MicroRNAs/metabolism , Neoplasm Invasiveness/genetics , Prostatic Neoplasms/metabolism , Transforming Growth Factor alpha/metabolism , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Male , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Transforming Growth Factor alpha/genetics , Up-Regulation/genetics
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