The receptor for advanced glycation end products (RAGE) and its ligands are involved in the pathogenesis of cancer. Glyoxalase I (GLO1) is an enzyme which detoxifies advanced glycation end product (AGE) precursors. The aim of the study was to find out the relationship between four polymorphisms (single nucleotide polymorphism, SNP) of the RAGE gene (AGER) and one SNP of the GLO1 gene and clear cell renal cancer (ccRCC). All polymorphisms (rs1800625 RAGE -429T/C, rs1800624 -374T/A, rs3134940 2184A/G, rs2070600 557G/A (G82S), and GLO1 rs4746 419A/C(E111A)) were determined by PCR-RFLP in 214 patients with ccRCC. A group of 154 healthy subjects was used as control. We found significant differences in the allelic and genotype frequencies of GLO1 E111A (419A/C) SNP between patients and controls-higher frequency of the C allele in ccRCC-58.6 vs. 44.5% in controls, OR (95% CI) 1.77 (1.32-2.38), p = 0.0002 (corrected p = 0.001); OR (95% CI) CC vs. AA 2.76 (1.5-4.80), p = 0.0004 (corrected p = 0.002); and AC+CC vs. AA 2.03 (1.23-3.30), p = 0.0034 (corrected p = 0.017). High aggressiveness of the tumor (grade 4) was associated with the presence of C allele RAGE -429T/C SNP (original p = 0.001, corrected p = 0.005) and G allele RAGE 2184A/G SNP (p < 0.001 and p < 0.005), and for genotypes RAGE -429CC (original p = 0.008, corrected p = 0.04) and RAGE 2184GG SNP (original p = 0.005, corrected p = 0.025). Our results demonstrate the link of E111A GLO1 SNP to the presence of the tumor and the connection of RAGE -429T/C and 2184A/G SNPs with the aggressiveness of the tumor. Further studies are required, especially with respect to potential therapeutic implications.
High-flow priapism is a rare condition mainly caused by perineal trauma. Laceration of cavernosal artery results in a formation of arterial-lacunar fistula with unregulated blood flow causing prolonged erection. We present a case of a 25-year-old man with high-flow priapism and concurrent erectile dysfunction treated with repeated selective embolisation with only a partial effect. When no further embolisation was possible, we assumed on conservative management even through the fistula was still present. Spontaneous detumescence occurred 9 months, and erectile function has fully restored 24 months after the injury. To the best of our knowledge, spontaneous detumescence with full restoration of erection even through the persistent arterial-lacunar fistula has not been reported previously. Therefore, we propose conservative approach after embolisation to be an option.
Preoperative somatic symptoms and performance status in patients with RCC provide readily available prognostic information in addition to tumour size, stage and grade.
Background/Aim: Proteinase pregnancyassociated plasma protein A (PAPP-A) modulates the cell growth and carcinogenesis process. Its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to evaluate the significance of PAPP-A serum concentration in diagnosis, follow-up and prognosis of ccRCC patients. Materials and Methods: In a prospective study including 121 patients who underwent radical or partial nephrectomy for ccRCC [localized ccRCC without relapse (n=80), localized ccRCC with later relapse (n=26), primary metastatic cancer (n=15)] PAPP-A serum concentration was assessed preoperatively and in certain subgroups also postoperatively. Results: PAPP-A serum concentration showed no statistically significant difference between ccRCC and controls and among ccRCC subgroups, respectively. Disease stage and Fuhrman's grade were not shown to affect PAPP-A concentration. The dynamics of postoperative PAPP-A concentrations did not reveal any significance and PAPP-A was not a prognostic factor for cancer related or overall survival. Conclusion: PAPP-A serum concentration does not seem to be a useful biomarker in ccRCC.Renal cell carcinoma (RCC) accounts for 2-3% of all adult malignancies presenting the highest incidence in the Western world (1). Incidence of RCC has been continuously increasing over the last years. Clear cell RCC (ccRCC) represents the most prevalent histopathological subtype, which is diagnosed in more than 80% of patients. The exact process of the formation and progression of ccRCC in not known. There are no recommended genetic or biochemical markers for diagnosis and prediction of relapse before surgical removal of the tumour or during follow-up.Despite advances in diagnosis, especially in imaging techniques and higher rates of incidentally diagnosed tumours with imaging for unrelated complaints, still, in up to 30% of patient's, distant metastases are present at the time of initial diagnosis (2, 3). Furthermore, recurrence occurs in 20-30% patients with an initially localized disease during the follow-up (4). RCC is potentially curative with surgery and it is generally resistant to chemotherapy and radiotherapy. Despite progress in targeted therapy, prognosis of metastatic RCC remains poor with median survival less than one year (3). Therefore, detection of a biomarker suitable for early diagnosis and, even more, for accurate determination of the risk of relapse after partial or radical nephrectomy is of great importance.Pregnancy-associated plasma protein A (PAPP-A), also referred to as pappalysine-1 is a proteolytic enzyme that belongs to the zinc metalloproteinase superfamily. PAPP-A increases bioavailability of insulin like growth factor 1 (IGF-1) for receptor activation via proteolysis of inhibitory IGF binding proteins (IGFBPs), in particular IGFBP-4. Targeting IGF-1 receptor (IGF-1R) IGF-1 affects proteosynthesis (5). PAPP-A is expressed predominantly during pregnancy in placental syncythiotrophoblast and is required for normal foetal development and growth. Routinel...
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