Analysis of two single nucleotide polymorphisms and loss of heterozygosity detection in the VHL gene in Chinese patients with sporadic renal cell carcinoma.
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Publications and source records attributed to Yan-qun Na.
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OBJECTIVE: To investigate the association between A49T polymorphism of SRD5A2 gene and risk of prostate cancer. METHODS: PCR was used to examine the A49T polymorphisms of SRD5A2 gene in the tissues of prostate cancer resected from 112 patients (CaP group) and the specimens of benign prostate hyperplasia (BPH group) resected from 89 patients. The association of A49T polymorphism with age of onset, FPSA, TPSA, F/T, T stage, and Gleason score were analyzed. RESULTS: There was no significant difference in A49T polymorphism between the CaP and BPH groups (P > 0.05). The average age of CaP patients was significantly higher than that of the BPH patients (P < 0.05). In the CaP patients, the Gleason score was significantly higher, and the age of onset was significantly lower in the AT + TT genotype than in the AA genotype (both P < 0.05) 2. The age of onset of the AA + AT group was significantly lower than that of the AA group (P < 0.05). CONCLUSION: AA + AT genotype may be of worse prognosis, however, without significant difference. Rank scoring may reflect the relation between Gleason score and A49T genotype and estimate the prognosis better than two-level discrete evaluation.
OBJECTIVE: To evaluate the significance of melanoma antigen (MAGE) gene expression in bladder transitional cell carcinoma (TCC). METHODS: MAGE-A1, A2, A3, A4 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR) in 3 clusters bladder TCC cells and 20 samples of bladder TCC patients (T(1) 7 samples, T(2) 5 samples, T(3) 6 samples, T(4) 2 samples, G(1) 1 samples, G(2) 11 samples, G(3) 8 samples). MAGE-A4 protein was detected by immunohistochemistry in 105 samples of bladder TCC patients (T(1) 35 samples, T(2) 12 samples, T(3) 26 samples, T(4) 13 samples, G(1) 13 samples, G(2) 44 samples, G(3) 48 samples). RESULTS: Three clusters bladder TCC cells had MAGE gene mRNA expression. In detection of MAGE mRNA of 20 samples of bladder TCC patients, 12 samples (60%) expressed MAGE-A1, 16 samples (80%) expressed MAGE-A2, 11 samples (55%) expressed MAGE-A3, 18 samples (90%) expressed MAGE-A4, 8 samples (40%) expressed all of MAGE-A1--A4. In 105 bladder TCC samples, 53 samples (50%) expressed MAGE-A4 protein. Strong expression (++ or +++) was significant higher in higher grade (13 samples/48 samples) or stage (14 samples/51 samples) than in lower grade (2 samples/57 samples) or stage (0 samples/35 samples). CONCLUSION: MAGE gene highly expresses in bladder TCC. Bladder TCC of high grade or high stage has higher MAGE-A4 protein strong expression.
OBJECTIVE: To investigated the value of homologous dermal acellular matrix graft (AMG) for urethral reconstruction in man, and found an ideal replacement material to simplify the urethroplastic surgery. METHODS: 16 male patients, aged 18-46 (mean 26.5), with urethral diseases were treated with allograft of tissue engineering material AMG. The causes of urethroplasty were complex urethral stricture followed by pelvic fracture (13 cases), anterior urethral stricture (2 cases), hypospadia (1 case). During the operation, AMG was sutured to a tubular graft and replaced the defect urethra. A 18-22 Fr silicone catheter was inserted in the reconstructed urethra for 4-6 weeks. RESULTS: All 16 patients were voiding well after removing the catheter, urethrography reveal excellent caliber of the reconstructed urethra. Urethroscopic examination showed the graft urethra was covered by epithelial tissue and grew into the native tissue. But stenosis was developed in 3 patients postoperatively, 1 patients received transurethral incision, another 2 needed urethral sounding. The patients were followed-up for 12-72 months (mean 45.6), no rejection was observed, all patients voided normally except 4 cases needed urethral dilatation periodically. CONCLUSION: The homologous dermal acellular matrix graft may serve as an ideal replacement material for complex urethral stricture or defect, without concern of rejection.
OBJECTIVE: To investigate the expression of SSX(2)gene in human renal cell carcinoma and urinary transitional cell carcinoma. METHODS: Reverse-transcription polymerase chain reaction (RT-PCR) was used for detecting SSX(2) gene in the specimens from renal cell carcinoma (n = 26), urinary transitional cell carcinoma (n = 27) and in 15 specimens taken from the tumor surrounding tissues. RESULTS: Positive expression of SSX(2) gene at mRNA was detected in 69% renal cell carcinomas (18/26), in 81% urinary transitional cell carcinomas (22/27). The mRNA of SSX(2) was not detected in the 15 specimens from tumor surrounding tissues. CONCLUSION: The SSX(2) gene is highly expressed in human renal cell carcinoma and urinary transitional cell carcinoma.
OBJECTIVE: To investigate relationship between benign prostatic hyperplasia (BPH) and hyperlipemia, and to clear out possible factors related to BPH etiology. METHODS: A total of 462 cases of BPH diagnosed by pathological examination were studied retrospectively. RESULTS: Of 462 cases, BPH with hyperlipemia was noted in 232 cases (50.22%). In comparison with the data of simple BPH, both prostate volume (P = 0.029) and residual urine (P = 0.03) were significantly increased in the BPH patients with hyperlipemia. Statistical analysis regarding the effects of different components of serum lipid on BPH clinical factors showed that the level of high density lipoprotein was significantly associated with both the enlargement of prostate volume (P < 0.05) and increasing of serum PSA (P < 0.05) Further study indicated that hypertension was demonstrated in 39.2% patients of BPH with hyperlipemia. Hyperlipemia accompanied with hypertension in BPH patients was significantly related to increased IPSS (P = 0.004). CONCLUSION: The situation of BPH with hyperlipemia is frequently noted in clinics, and the decreased level of high-density lipoprotein is significantly associated with the enlargement of prostate volume. Co-existence of hypertension with hyperlipemia in BPH patients greatly worsens the lower urinary tract symptoms (LUTS) of BPH. Hyperlipemia may be one of the risk factors in the processes of BPH growth and progression.
OBJECTIVE: To evaluate the expression of hypoxia inducible factor (HIF)-1alpha, 2alpha in sporadic clear cell renal cell carcinoma and their relationships to the mutations of von Hippel-Lindau (VHL) gene. METHODS: Mutations of VHL gene, expression of HIF-1alpha and 2alpha were detected by polymerase chain reaction (PCR), direct DNA sequencing and immunohistochemistry in 77 cases of Chinese sporadic clear cell renal cell carcinoma (CCRCC). The stage was pT(1)N(0)M(0)in 55 patients (71%), pT(2)N(0)M(0) in 7 patients (9%), pT(3)N(0)M(0) in 14 patients (18%), and pT(4)N(0)M(0) in 1 patient (1%). The classification according to the tumor nuclear grading system showed 15 carcinomas (19%) of tumor nuclear grade 1, 56 (73%) of tumor nuclear grade 2 and 6 (8%) of tumor nuclear grade 3. RESULTS: None of the VHL gene mutations were found in all the normal tissue specimens. VHL gene mutations were detected in 40 (52%) cases of CCRCC. The positive rate of HIF-2alpha (81%) was higher than that of HIF-1alpha (66%) (chi(2) = 23.310, P < 0.01); The positive rate of HIF-1alpha and HIF-2alpha in the cases of mutations (98% and 93% respectively) was higher than that of them in non-mutations (32% and 68% respectively) (chi(2) = 36.386, 7.617, P < 0.01); The correlation between HIF-1alpha and VHL gene mutations was closer than that between HIF-2alpha and VHL gene mutations (partial correlation coefficiency was 4.481 and 2.027 respectively, P < 0.01). The expression of HIF-1alpha and 2alpha in different pathological grade and stage of CCRCC showed no significant difference (P > 0.05). CONCLUSIONS: Our study suggests that VHL gene mutations are frequent in sporadic CCRCC, and the high expression of HIF-1alpha and 2alpha are found in the group of VHL mutations. However, we have not found significant correlation between the expression of HIF-1alpha and 2alpha and pathological grade and stage of CCRCC in our study.
OBJECTIVE: To define changes in clusterin expression following short-term neoadjuvant hormone therapy (NHT) and its biological significance in prostate cancer tissues. METHODS: Twenty-six archival radical prostatectomy (RP) specimens without receiving NHT, 19 needle biopsies and corresponding 19 RP specimens following 3-month NHT, were subjected to immunohistochemical clusterin staining. RESULTS: Staining for clusterin was mainly found in cytoplasm and part of extracellular matrix. Clusterin expression was significantly greater in RP specimens with preoperative NHT (t = 2.91, P < 0.01); Needle biopsies obtained before NHT consistently demonstrated lower staining intensity (1.42 +/- 0.51) than corresponding RP specimens (2.16 +/- 0.60) following 3-month NHT (t = 7.10, P < 0.01). CONCLUSIONS: Upregulation of clusterin in part accounts for malignant progression of prostate cancer through its anti-apoptotic action following androgen withdrawal. These findings support that adjuvant therapy targeting clusterin may enhance androgen ablation therapy in advanced prostate cancer.
OBJECTIVE: To investigate the impact of primary hypertension on angiogenesis in the tissues of benign prostatic hyperplasia (BPH). METHODS: Immunohistochemistry was carried out to examine the expression of CD34, so as to calculate the microvassel density (MVD), and the expression of vascular endothelial growth factor (VEGF) in the tissues of prostatic gland, resected during operation, of 50 simple BPH patients, aged 68.3 (56 approximately 83), and 50 patients with BPH with hypertension, aged 69.0 (55 approximately 91) with a course of hypertension of 16.5 +/- 11.9 years (1 - 41 years). RESULTS: The MVD of the simple BPH group was 23.1 +/- 9.2, significantly lower than that of the BPH complicated with hypertension group (28.2 +/- 9.5, P < 0.01), especially the BPH complicated with hypertension group with a course >/= 15 years (31.3 +/- 8.5). The MVD of the BPH complicated with hypertension group with a course >/= 15 years was significantly higher than that of the BPH complicated with hypertension group with a course < 15 years (25.7 +/- 9.7, P < 0.05). The VEGF positive rate of the stroma of the simple BPH group was 46.0%, significantly lower than that of the BPH complicated with hypertension group (66.0%, P < 0.05), especially that of the BPH complicated with hypertension group with a course >/= 15 years (81.8%). The VEGF positive rate of the stroma of the BPH complicated with hypertension group with a course >/= 15 years was significantly higher than that of the BPH complicated with hypertension group with a course < 15 years (53.6%, P < 0.05). In the group of BPH with hypertension, MVD was positively correlated with the expression of VEGF in the stromal tissue (R = 0.11, P < 0.05). CONCLUSION: Hypertension may be closely related to the increased expression of VEGF in prostatic stroma. The increased expression of VEGF may induce angiogenesis and consequently lead to clinical progression of BPH in patients with hypertension.
OBJECTIVE: To investigate the diagnosis and management of primary hyperparathyroidism with urolithiasis. METHODS: The clinical data of 12 patients who were diagnosed with primary hyperparathyroidism with urolithiasis from January 1998 to June 2004 were analyzed retrospectively. RESULTS: Four male and five female patients were demonstrated pathologically as parathyroid adenoma, with a mean age of 45.7 +/- 11.8 years (26 approximately 57) and a stone history of 8.3 +/- 6.4 years (0.5 approximately 22). Their serum calcium and PTH level were elevated obviously, while serum phosphate of 66% patients were lowered. The positive rate and accuracy of ultrasound, CT and (99m)TC-MIBI imaging were 67%, 100%, and 100% and 67%, 75%, 100% respectively. After resection of the parathyroid adenoma, the patients' serum calcium and PTH returned to normal. The other data of 3 cases without parathyroid adenoma. all males aged 45 approximately 54, were also investigated. CONCLUSIONS: Serum calcium level above 2.96 mmol/L and PTH 3.9 or more times as normal in patients with recurrent or bilateral urolithiasis should be suspected with primary hyperparathyroidism. (99m)TC-MIBI image functions best in preoperative localization of the abnormal gland. Parathyroidectomy is the curative approach for the disease. Stones should be followed up after operation and appropriate treatment should be employed when needed.
OBJECTIVE: To assess whether primary hypertension affects the occurrence and progression of benign prostatic hyperplasia (BPH). METHODS: A total of 423 cases of BPH, undergoing transurethral resection of prostate (TURP) or open surgery due to severe low urinary tract symptoms, were reviewed and analyzed. All cases were verified to be BPH postoperatively following histopathological examination. RESULTS: Of 423 patients, 295 cases (69.7%) were simple BPH (group BPH-NT); 128 cases (30.3%) were BPH with hypertension (group BPH-HT). The mean age and the incidence of haematuria were significantly higher in group BPH-HT than those in group BPH-NT (P < 0.05). The time of BPH occurrence and surgical treatment in group BPH-HT with mean diastolic blood pressure >/= 90 mmHg was significantly earlier than those with diastolic blood pressure < 90 mmHg (P < 0.05; P < 0.01). As compared with group BPH-NT, the time of BPH occurrence was significantly earlier in group BPH-HT with more than 10 years hypertension; the rate of urinary retention and haematuria was significantly higher and prostatic volume was significantly greater in group BPH-HT with more than 20 years hypertension; (all P < 0.05). Additionally, prostatic volume was positively correlated with the years of hypertension in group BPH-HT (Rsq = 0.056, P = 0.009). CONCLUSIONS: The present results demonstrate that BPH may be frequently accompanied by the disease of hypertension. A long-term hypertension, particularly the condition of high diastolic blood pressure may improve the occurrence and clinical progression of BPH.
OBJECTIVE: To investigate biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) in patient of renal cell carcinoma (RCC) patient. METHODS: We extracted tumor and normal DNA from 41 RCC patients. Mutation of VHL gene from tumor tissue was detected from tumor tissue by polymerase chain reaction (PCR) and direct sequencing. Two single nucleotide polymorphism (SNP) sites located in VHL gene were analyzed by PCR restriction fragment length polymorphism, and loss of heterozygosity (LOH) was analyzed for VHL gene by comparing between tumor with normal tissue. RESULTS: Mutation and LOH of VHL gene was found in 51% (21/41) and 42% (8/19) of RCC patients respectively. LOH was highly associated with mutation positive tumors (r = 0.78) and VHL biallelic inactivation was detected in 37% of RCC patients. CONCLUSION: Biallelic inactivation of VHL gene occurs in RCC due to VHL mutation and LOH, and its frequency rate is 37%.
OBJECTIVE: To exam two single nucleotide polymorphism(SNP) in VHL gene and intragenic loss of heterozygosity (LOH) of VHL gene in 79 Chinese sporadic renal cell carcinomas(RCCs), and to analyze the relationships between VHL LOH and clinicopathological parameters. METHODS: The authors extracted tumor and normal tissue DNA and detected two genotypes of intragenic SNP sites, rs779805 in the 5'terminal and rs 1642742 in the 3'terminal of VHL gene by polymerase chain reaction-restriction frament length polymorphism, then analyzed VHL LOH by comparing tumor tissue versus normal tissue in heterozygosities. Subsequently the relationships between VHL LOH and clinicopathological parameters of RCCs were analyzed. RESULTS: The computed heritage parameters of two SNPs, included genotype frequency, allele frequency, heterozygosity, and polymorphism information content. Twenty-nine heterozygosities were detected in 79 RCCs. LOH was found in 41.4%(12/29) of RCCs. No significant relationships between VHL LOH and age, sex, tumor stage, pathological grade were found. CONCLUSION: LOH of VHL gene is an important genetic event in Chinese sporadic renal carcinoma, and the LOH frequency is 41.4%. VHL LOH has no influence on stage and grade of RCC.
OBJECTIVE: To evaluate the relationship between the deformation of penile artery and the primary artery erectile dysfunction, and to improve the treatment and diagnosis of primary artery erectile dysfunction. METHODS: One case of primary artery erectile dysfunction was presented with its primary clinic data. RESULTS: The dorsal artery of the penis was thin and the bilateral penile arteries were lacking by arteriography. The implantation of a penile prosthesis significantly improved the patient's erectile function. CONCLUSION: The primary artery erectile dysfunction is a relatively rare disease. The possibility of primary artery erectile dysfunction should be kept in mind. Penile prosthesis implantation is an effective means for the treatment of primary artery erectile dysfunction.
OBJECTIVE: To study the efficacy and safety of Eviprostat for the treatment of benign prostatic hyperplasia (BPH). METHODS: An open, multicentral clinical trial was conducted in 100 patients with BPH. Patients received a 12-week oral administration of Eviprostat 2 tablets per-time, 3 times a day. The main indexes of efficacy include international prostatic symptom score (IPSS), maximum urinary flow rate (Qmax), residual urine ( Ru) and prostatic volume (V). The additional indexes are quality of life score (QOL) and average urinary flow rate (Qave). RESULTS: After a 12-week therapy, IPSS, QOL score, Qmax and Qave were significantly improved. IPSS was averagely decreased by 5.67 (P < 0.001); QOL score was averagely decreased by 1.44 (P < 0.001); Qmax was averagely increased by 1.70 ml/s (P <0.001); Qave was averagely increased by 1.15 ml/s (P < 0.001); Ru was averagely decreased by 5.07 ml (P = 0.046) , PSA level was averagely decreased by 0.129 microg/L (P < 0.017). The clinical adverse event rate was 1%. CONCLUSION: Eviprostat is a kind of safe, effective and preferable drug for treating BPH. It can improve the subjective symptoms and objective measures of the patients.
OBJECTIVE: The correlation were studied between testosterone 5-alpha-reductase II (SRD5A2) gene polymorphisms and prognosis factors. METHODS: V89L and A49T variants was identified with Mwo1 and Rsa1. The differences of V89L and A49T between cancer of prostate (CaP) and benign prostatic hyperplasia (BPH) were studied. In addition, we also researched the association of polymorphisms with age of onset, free prostate specific antigen (FPSA), total PSA (TPSA), FPSA/TPSA (F/T), Gleason score, and T stage in cancer group. RESULTS: We found no differences of V89L and A49T polymorphisms between CaP and BPH. In CaP group the A49T variant was associated with lower age of onset (P = 0.03) and higher Gleason score (P = 0.015). There were no differences between VV and VL+LL polymorphisms with any of the characteristics studied. When the characteristics above were regarded as two-level discrete variable, there were no differences by A49T and V89Lvariants. CONCLUSION: In CaP group, the AT+TT genotype was perhaps associated with poor prognosis. VL+LL genotype has no relation with prognosis.
OBJECTIVE: To study the paracrine effect of the neuroendocrine differentiation cells and its influence on androgen receptor expression of prostate carcinoma cells. METHODS: Established an in vitro induced model of neuroendocrine differentiation of prostate carcinoma (LNCaP(NE), PC-3M(NE)), and investigate the proliferation effect of neuroendocrine phenotype cells (LNCaP(NE), PC-3M(NE)) on other non-neuroendocrine phenotype cells (LNCaP, PC-3M) by feeding non-neuroendocrine phenotype cells with the medium pre-incubated with induced neuroendocrine phenotype cells. It was also tested the regulation of androgen receptor mRNA and androgen receptor protein expression of LNCaP(NE) cells on LNCaP cells by reverse transcriptase polymerase chain reaction and Western Blot in the presence or absence of androgens. RESULTS: The medium pre-incubated with PC-3M(NE) cells could promote the proliferation of PC-3M cells. The medium pre-incubated with LNCaP(NE) cells could promote the proliferation of LNCaP cells, and reduce the expression of androgen receptor in the latter in the absence of androgens, but the negative results were observed in the presence of androgens. CONCLUSIONS: The neuroendocrine phenotype cells of prostate cancer can reduce the expression of androgen receptor in prostate cancer cells and promote them to proliferate by means of paracrine in the blockade of androgens.
OBJECTIVE: To evaluate the relationship between the mutation of the von Hippel-Lindau (VHL) gene and expression of vascular endothelial growth factor (VEGF) in sporadic clear cell renal cell carcinoma (CCRCC) and angiogenesis. METHODS: Polymerase chain reaction (PCR) was used to detect the mutation of VHL gene in the specimens of cancerous tissue and normal tissues away from tumor from 77 patients with CCRCC. Immunohistochemistry was used to examine the expression of VEGF. CD34 staining was used to measure the microvascular density (MVD). RESULTS: VHL gene mutations were detected in 40 cases (51.9%). The expression rate of VEGF was 79.2% (61 cases). The positive rate of VEGF in the cases with VHL mutation was 92.5%, significantly higher than that in the cases without VHL mutation (64.9%, P = 0.003). The levels of MVD was higher in the cases with VHL mutation and those with VEGF expression were 760.80/mm2 and 715.95/mm2 respectively, both significantly higher than those in the cases without VHL-mutation and those without VEGF expression (547.03/mm2 and 437.44/mm2 respectively, all P = 0.001). The cases with expression of VEGF were divided into two groups according the presence or absence of VHL gene mutations or not. The MVD of the cases with VEGF expression and VHL mutation was 760.80 mm2, significantly higher than that of the cases with VEGF expression and without VHL mutation (547.03 mm2, P = 0.011). CONCLUSION: The mutation rate of VHL gene is high among the Chinese with sporadic CCRCC. VHL gene mutation increases significantly the VEGF expression, thus, and perhaps via other mechanism too, promoting the angiogenesis in tumor. The high level of MVD of the cases with VHL gene mutation may be related to the high malignant potential of CCRCC.