Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) remains one of the most common cancer types globally, and while it has been extensively studied, the molecular basis for its pathology remains incompletely understood. Herein, we profiled three previously published datasets (GSE66272, GSE100666, and GSE105261) in a single integrated analysis aimed at identifying disease-associated patterns of gene expression that may offer mechanistic insight into the drivers of this disease. We pooled expression data from 39 normal kidney samples and 39 kidney tumors, leading us to identify 310 differentially expressed genes (DEGs) that were linked to kidney cancer in all three analyzed datasets. Of these genes, 133 and 177 were up- and down-regulated, respectively, in cancer samples. We then incorporated these DEGs into a protein-protein interaction network with the STRING and Cytoscape tools, and we were able to identify signaling pathways significantly enriched for these DEGs. The relationship between DEG expression and ccRCC patient survival was further evaluated using a Kaplan-Meier approach, leading us to identify TIMP1 as an independent prognostic factor in ccRCC patients. When TIMP1 expression was disrupted in ccRCC cell lines, this impaired their migratory and invasive capabilities. In summary, we employed an integrative bioinformatics approach to identify ccRCC-related DEGs and associated signaling pathways. Together these findings offer novel insight into the mechanistic basis for ccRCC, potentially helping to identify novel therapeutic targets for the treatment of this deadly disease.

Autologous granulation tissue tubes for replacement of urethral defects: An experimental study in male rabbits.

INTRODUCTION: Tubularized urethroplasty is commonly performed in clinical practice using genital skin flaps, bladder mucosa, and buccal mucosa. However, the long-term effects are not satisfying, and donor site morbidities remain a problem. Besides, those grafts are unavailable with malignant conditions of the urinary tract, a history of lichen sclerosis, or oral disease. OBJECTIVE: An autologous granulation tissue tube of any required length and diameter can be produced by implanting foreign objects subcutaneously (Summary Fig.). The current study aimed to investigate to what extent of length this fully autologous tissue could be used for tubularized urethroplasty, satisfying urethral patency and tissue regeneration, in male rabbits. STUDY DESIGN: Twenty-seven New Zealand male rabbits were randomly divided into three groups. Silastic tubes were implanted subcutaneously in Group 1 and Group 2. By 2 weeks the granulation tissue encapsulating the tubes was harvested. In Group 1, pendulous urethral segments of 1 cm were excised, and urethroplasty was performed with the granulation tissue tube in an end-to-end fashion. In Group 2, a pendulous urethral segment of 1.5 cm was replaced with the tissue tube. In Group 3, a pendulous urethral defect of 1 cm was repaired by re-anastomosis as control. Serial urethrograms were performed at 1, 2 and 6 months postoperatively. Meanwhile, the neo-urethra were harvested and analyzed grossly and histologically. RESULTS: The urethrograms showed that all animals in Group 1 maintained a wide urethral caliber. In contrast, animals in Group 2 and Group 3 developed progressive strictures. Histologically, an intact urothelium with one to two cell layers lined the graft by 1 month, which was surrounded by increasing organized smooth muscle in Group 1. By 6 months, the grafts were completely integrated into native urethra. Nevertheless, extensive fibrosis occurred in Group 2 and Group 3. DISCUSSION: The tissue successfully maintained patency and guided urethral regeneration across a distance of 1 cm. As an epithelium-free graft, the tissue showed better results than acellular matrix for tubularized urethroplasty compared with previous studies. Nevertheless, several limitations existed: (1) the urethral defect was created in healthy urethra, which could not fully simulate the clinical situation; (2) as a small animal model, rabbit was less informative for clinical problems; (3) the tissue was inadequate for long segmental urethral replacement. Further study is needed before the procedure is used clinically. CONCLUSION: An autologous granulation tissue tube grown subcutaneously could be successfully used to repair urethral defects of 1 cm in male rabbits.

[Primary cutaneous T-cell lymphoma of the penis complicated by Fournier gangrene: a case report].

OBJECTIVE: To explore the clinical presentation, pathologic characteristics, diagnosis and treatment of cutaneous T-cell lymphoma of the penis. METHODS: A 49-year-old man presented with painful swelling and inflammation of the foreskin, failed to respond to antibiotic treatment and dorsal incision, and was instead complicated by Fournier gangrene. Then he underwent debridement and pathological examination. RESULTS: Pathological results indicated cutaneous T-cell lymphoma of the penis. Immunohistochemistry showed CD3 and CD45 RO to be positive, but CD30, CD79a, CD20 and HMB negative. The patient was treated by interferon alpha and ultraviolet B for 2 weeks, followed by total removal of the external genitalia because of necrosis of the corpus spongiosum, which involved the scrotum and right testis on pathological examination. CONCLUSION: Cutaneous T-cell lymphoma of the penis is a rare condition and easily mis diagnosed in the early phase. Definitive diagnosis depends on pathological study.

[Relationship of transforming growth factor beta1 and basic fibroblast growth factor to detrusor underactivity following bladder outlet obstruction: experiment with rats].

OBJECTIVE: To investigate the relationship of transforming growth factor beta1 (TGFbeta1) and basic fibroblast growth factor (bFGF) to detrusor underactivity following bladder outlet obstruction (BOO). METHODS: Female Wistar rats underwent ligation of the urethra to establish BOO models and were divided into BOO model 2-week group (11 rats) and BOO model 6-week group (10 rats). 8 rats underwent sham operation as control group. The detrusor urine was taken out and stimulated by carbachol to measure the detrusor contraction force (DCF). RT-PCR method was employed to measure the mRNA expression of TGFbeta1 and bFGF in the detrusor urine. Urine TGFbeta1 and bFGF were determined by ELISA. RESULTS: The maximum DCF levels of the BOO 2-week group under the 1 x 10(-4) mmol/L and 1 x 10(-3) mmol/L carbachol concentrations were 0.96 g +/- 0.11 g and 1.98 g +/- 0.21 g respectively, both significantly higher than those of the sham operation group (0.85 g +/- 0.18 g and 1.82 g +/- 0.19 g respectively, both P < 0.05). The maximum DCF levels of the BOO 6-week group under the 1 x 10(-5), 1 x 10(-4), 1 x 10(-3) and 1 x 10 (-2) mmol/L carbachol concentrations were 0.19 g +/- 0.02 g, 0.65 g +/- 0.06 g, 1.12 g +/- 0.08 g, and 1.40 g +/- 0.19 g respectively, all significantly lower than those of the BOO 2-week group (0.24 g +/- 0.03 g, 0.96 g +/- 0.11 g, 1.98 g +/- 0.21 g, and 2.16 g +/- 0.21 g respectively, all P < 0.05) and those of the sham operation group (0.23 g +/- 0.04 g, 0.85 g +/- 0.18 g, 1.82 g +/- 0.19 g, and 2.12 g +/- 0.26 g respectively, all P < 0.05). The mRNA expression of TGFbeta1 of the BOO 6-week group, BOO 2-week group, and sham operation group was 0.72 +/- 0.21, 0.34 +/- 0.10, and 0.32 +/- 0.01 respectively, there was a significant difference between the BOO 6-week group and the BOO 2-week group (P < 0.01). The mRNA expression level of bFGF of the BOO 6-week group was 0.38 +/- 0.13, significantly higher than those of the BOO 2-week group and sham operation group (0.21 +/- 0.07 and 0.10 +/- 0.05 respectively, both P <0.05). DCF was negatively correlated with the mNRA expression of TGFbeta1 and the mNRA expression bFGF in detrusor (both P < 0.05). The urine TGFbeta1 of the BOO 6-week group was (606 +/- 216) microg/mol Cr, significantly higher than that of the BOO 2-week group [(131 +/- 49) microg/mol Cr] and that of the sham operation group [(107 +/- 22) microg/mol Cr, both P <0.05]. CONCLUSION: With the progression of BOO, there is a sustained rise of bFGF mRNA expression in detrusor; however, the TGFbeta1 mRNA expression only increases during the decompensation stage. Urine TGFbeta1 level is very high 6 weeks after BOO, which may help predict the contraction function of bladder after BOO.

[Establishment of a new model of neurogenic bladder dysfunction caused by lumbar intervertebral diskhernia and its urodynamic evaluation].

OBJECTIVE: To establish a new rat model of neurogenic bladder dysfunction caused by lumbar intervertebral disk hernia, and to confirm the model by urodynamic examination. METHODS: Twenty male Wistar rats were divided into two groups at random:experimental group (n = 15) and pseudo-operation group (n = 5). The rats underwent laparotomy to disclose the intervertebral disk of L(6)-S(1), and a 1.50 mm x 4.50 mm blunt screw with flat end was inserted into the intervertebral disk of L(6)-S(1) of the rats in the experimental group so as to establish the model of lumbar intervertebral disk hernia. Computed radiography (CR) was performed 3 days after the operation to conform the successful insertion of the screw. Combined behavioral score (CBS) was used 1 d, 3 d, 1 week, 2 weeks, and 4 weeks after the operation. Four weeks after the laparotomy a vesical fistula above the pubis was made in all of the rats, and then urodynamic examination was performed three days after this operation. RESULTS: CR after operation confirmed that the blunt screw had been inserted into the lumbar disk of L(6). The CBS scores of the 2 groups at different time points all decreased along with time, and basically remained unchanged 1 week after. The CBS scores of the experiment group were significantly higher than those of the pseudo-operation group (all P < 0.05). The spontaneous vesical contraction rate in the filling period of the experimental group was (4.37 +/- 2.13) times/min, significantly higher than that of the pseudo-operation group [(0.06 +/- 0.13) times/min, t = 4.425, P = 0.000], the maximum bladder capacity of the experimental group was (1.20 +/- 0.34) ml, significantly greater than that of the pseudo-operation group [(0.60 +/- 0.14) ml, t = 5.141, P = 0.002], and bladder compliance of the experimental group was (0.024 +/- 0.012) ml/cm H(2)O, significantly lower than that of the pseudo-operation group [(0.096 +/- 0.088) ml/cm H(2)O, t = 2.891, P = 0.011], and the leak point pressure of the experimental group was (75 +/- 27) cm H(2)O, not significantly different from that of the pseudo-operation group [(62 +/- 23) cm H(2)O]. The urodynamic examination on the conscious rats confirmed the successful establishment of the neurogenic bladder dysfunction caused by lumbar intervertebral disk hernia. CONCLUSION: A new model of neurogenic bladder dysfunction caused by lumbar intervertebral disk hernia has been established by insertion of a blunt screw into the lumbar intervertebral disk of L(6). The model is confirmed by urodynamic examination.

[Change of nerve growth factor mRNA in human detrusor in bladder outlet obstruction with benign prostatic hyperplasia and their implication].

OBJECTIVE: To investigate the change of nerve growth factor (NGF) mRNA in human detrusor in bladder outlet obstruction (BOO) with benign prostatic hyperplasia (BPH) and their implication. METHODS: Eight cases of bladder cancer and 40 patients with BPH were included in this study. All patients were divided into three groups, a control group, an obstructive detrusor stability group and an obstructive detrusor instability group. NGF mRNA in detrusor from all patients was measured using a RT-PCR. RESULTS: The RT-PCR study indicated that NGF mRNA was expressed in detrusor of three groups of patients. There were significant differences among the three groups (P < 0.01). The expression of NGF mRNA in the obstructive instability group was higher than that in the obstructive stability group and in the control group. The NGF mRNA level in the obstructive stability group was higher than that in the control group. CONCLUSION: The expression of NGF mRNA in detrusor was elevated in BOO with BPH. The elevated expression of NGF mRNA might be correlated with detrusor instability (DI) due to BOO.

[Association of uPA and uPAR expression with invasive behaviors of urinary transitional cell carcinoma].

BACKGROUND & OBJECTIVE: Urokinase-type plasminogen activator (uPA)/its receptor (uPAR), serine protease system, plays a key role in the degradation of extracellular matrix and basement membranes, and intensifying the tumor invasion. The study was designed to investigate the expression of uPA and uPAR in urinary transitional cell carcinoma. The correlation between their expression and tumor invasion was evaluated. METHODS: The expression and localization of uPA and uPAR were examined among 50 cases of renal pelvic and ureter carcinoma and 40 cases of bladder cancer using the PicTure(TM) current type of immunohistochemical two-step method. RESULTS: The normal pelvic, ureter, and bladder did not express uPA and uPAR. The positive expression of uPA and uPAR were concentrated in tumor tissues compared with that in the adjacent tissues. The positive rates of uPA and uPAR expressed the tissues were 33.33% and 50.00% in G1 grade; 88.47% and 96.15% in G3 grade; 37.50% and 50.00% in Ta-T1 tissues; 100.0% and 100.0% in T4 tissues, respectively. The positive rates of uPA and uPAR expression in tumor tissues with higher grade and stage were obviously increased (P< 0.05); meanwhile, there were close correlation between uPA and uPAR (rs=0.979). CONCLUSION: The co-expression of uPA and uPAR was one of the characteristics of urinary transitional cell carcinoma and significantly correlated with tumor stage and grade.

[The expression of urokinase-type plasminogen activator and its receptor in urinary transitional cell carcinoma].

OBJECTIVE: To probe into the expression and clinical significance of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in urinary transitional cell carcinoma. METHODS: Expression of uPA and uPAR were detected in 50 cases of renal pelvis and ureter carcinoma and 40 cases of bladder cancer immunohistochemically. RESULTS: The positive rates of uPA and uPAR were closely correlated to the grade and the stage of urinary transitional cell carcinoma (r = 0.979, P < 0.01), whereas uPA and uPAR were not detected in normal kidney, ureter and bladder tissue. CONCLUSION: uPA and uPAR are highly expressed in urinary transitional cell carcinoma and they may be responsible for the tumor invasion and metastasis.