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Background: This study provides a comprehensive examination of the histological features of non-neoplastic parenchyma in renal cell carcinoma (RCC). We prospectively collected radical nephrectomy (RN) specimens, to analyze the histological changes within peritumoral and distant parenchyma.Methods: Data of patients who underwent RN and had no known history of diabetes, hypertension, hyperlipidemia, or chronic kidney disease etc., were prospectively collected. Tumor pseudo-capsule (PC), and parenchyma within 2 cm from tumor margin, were pathologically assessed. The parenchyma beyond PC or tumor margin was divided into 20 subsections of 1 mm in width. Histological changes, including chronic inflammation, glomerulosclerosis, arteriosclerosis and nephrosclerosis, were given scores of 0, 1, 2 or 3 for each subsection of each specimen, according to their severity. The 20 subsections of each specimen were further divided into four groups according to the distance from the tumor edge (group 1: 0-2 mm; group 2: 2-5 mm; group 3: 5-10 mm; group 4: 10-20 mm), to better compare the peritumoral parenchyma with the distant parenchyma.Results: In total, 53 patients were involved in this study. All tumors were confirmed RCCs (clear cell vs. papillary vs. chromophobe were 83% vs. 5.7% vs. 11.3%, respectively), with a mean size of 5.6 cm. Histological changes were more severe in peritumoral parenchyma close to PC or tumor edge (0-5 mm), and less common within parenchyma more distant from the tumor (5-20 mm) (p < 0.001). chronic inflammation and nephrosclerosis were the most common changes especially in peritumoral parenchyma (0-2 mm). PC was present in 49 tumors (92.5%), and PC invasion occurred in 5 cases (10.2%). Mean PC thickness was 0.7 mm. PCs were more likely to be present in clear cell RCC or papillary RCC than in chromophobe RCC (100% vs. 100% vs. 33.3%, respectively; p < 0.001).Conclusions: Most RCCs have a well-developed PC, especially clear cell RCC. Histological changes mainly occur in peritumoral parenchyma, being rather uncommon in distant parenchyma. A compression band filled with severe histological changes was typically observed in renal parenchyma close to the tumor. Its preservation while performing an enucleation margin may not be entirely necessary. [ABSTRACT FROM AUTHOR]

Background: Protein sequence clustering has been widely used as a part of the analysis of protein structure and function. In most cases single linkage orgraph-based clustering algorithms have been applied. OPTICS (Ordering Points To Identify the Clustering Structure) is an attractive approach due to its emphasis on visualization of results and support for interactive work, e.g., in choosing parameters. However, OPTICS has not been used, as far as we know, for protein sequence clustering. Results: In this paper, a system of clustering proteins, SEQOPTICS (SEQuence clustering with OPTICS) is demonstrated. The system is implemented with Smith-Waterman as protein distance measurement and OPTICS at its core to perform protein sequence clustering. SEQOPTICS is tested with four data sets from different data sources. Visualization of the sequence clustering structure is demonstrated as well. Conclusion: The system was evaluated by comparison with other existing methods. Analysis of the results demonstrates that SEQOPTICS performs better based on some evaluation criteria including Jaccard coefficient, Precision, and Recall. It is a promising protein sequence clustering method with future possible improvement on parallel computing and other protein distance measurements. [ABSTRACT FROM AUTHOR]

Background: Previous study demonstrated that extracellular ATP could promote cell migration and invasion in multiple human cancers. Till now, the pro-invasive mechanisms of ATP and P2RX6, a preferred receptor for ATP, are still poorly studied in RCC. Methods: Bioinformatics analysis was performed to identify the differentially expressed genes during RCC different stages. Tissue microarray, IHC staining and survival analysis was respectively used to evaluate potential clinical function. In vitro and in vivo assays were performed to explore the P2RX6 biological effects in RCC progression. Results: We found that ATP might increase RCC cells migration and invasion through P2RX6. Mechanism dissection revealed that ATP-P2RX6 might modulate the Ca2+-mediated p-ERK1/2/MMP9 signaling to increase the RCC cells migration and invasion. Furthermore, METTL14 implicated m6A modification in RCC and down-regulated P2RX6 protein translation. In addition, human clinical survey also indicated the positive correlation of this newly identified signaling in RCC progression and prognosis. Conclusions: Our findings revealed that the newly identified ATP-P2RX6-Ca2+-p-ERK1/2-MMP9 signaling facilitates RCC cell invasion and metastasis. Targeting this novel signaling pathway with small molecules might help us to develop a new approach to better suppress RCC progression. [ABSTRACT FROM AUTHOR]

Background: This study provides a comprehensive examination of the histological features of non-neoplastic parenchyma in renal cell carcinoma (RCC). We prospectively collected radical nephrectomy (RN) specimens, to analyze the histological changes within peritumoral and distant parenchyma., Methods: Data of patients who underwent RN and had no known history of diabetes, hypertension, hyperlipidemia, or chronic kidney disease etc., were prospectively collected. Tumor pseudo-capsule (PC), and parenchyma within 2 cm from tumor margin, were pathologically assessed. The parenchyma beyond PC or tumor margin was divided into 20 subsections of 1 mm in width. Histological changes, including chronic inflammation, glomerulosclerosis, arteriosclerosis and nephrosclerosis, were given scores of 0, 1, 2 or 3 for each subsection of each specimen, according to their severity. The 20 subsections of each specimen were further divided into four groups according to the distance from the tumor edge (group 1: 0-2 mm; group 2: 2-5 mm; group 3: 5-10 mm; group 4: 10-20 mm), to better compare the peritumoral parenchyma with the distant parenchyma., Results: In total, 53 patients were involved in this study. All tumors were confirmed RCCs (clear cell vs. papillary vs. chromophobe were 83% vs. 5.7% vs. 11.3%, respectively), with a mean size of 5.6 cm. Histological changes were more severe in peritumoral parenchyma close to PC or tumor edge (0-5 mm), and less common within parenchyma more distant from the tumor (5-20 mm) (p < 0.001). chronic inflammation and nephrosclerosis were the most common changes especially in peritumoral parenchyma (0-2 mm). PC was present in 49 tumors (92.5%), and PC invasion occurred in 5 cases (10.2%). Mean PC thickness was 0.7 mm. PCs were more likely to be present in clear cell RCC or papillary RCC than in chromophobe RCC (100% vs. 100% vs. 33.3%, respectively; p < 0.001)., Conclusions: Most RCCs have a well-developed PC, especially clear cell RCC. Histological changes mainly occur in peritumoral parenchyma, being rather uncommon in distant parenchyma. A compression band filled with severe histological changes was typically observed in renal parenchyma close to the tumor. Its preservation while performing an enucleation margin may not be entirely necessary.

Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma (mRCC) in China. This study aimed to compare the efficacy, safety, and quality of life (QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy., Methods: Clinical data of patients with mRCC who received sorafenib (400 mg twice daily; 4 weeks) or sunitinib (50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival (OS), progression-free survival (PFS), adverse events (AEs), and QoL (SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL., Results: Medical records of 184 patients (110 in the sorafenib group and 74 in the sunitinib group) were reviewed. PFS and OS were comparable between the sorafenib and sunitinib groups (both P > 0.05). The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group (36.5% vs. 10.9%, P < 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group (62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs (P = 0.017 and 0.005)., Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.

Background: Hypoalbuminemia adversely affects the clinical outcomes of various cancers. The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma (mRCC) who received sorafenib or sunitinib as first-line treatment., Methods: In this single-center, retrospective study, we assessed the progression-free survival (PFS) and overall survival (OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment. PFS and OS were compared between patients with post-treatment hypoalbuminemia (post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level (albumin level ≥36.4 g/L). The Memorial Sloan Kettering Cancer Center (MSKCC) risk model stratified mRCC patients into three risk categories. Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models. Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis., Results: The median PFS and OS of the 184 patients were 11 months (95% confidence interval [CI] 9-12 months) and 23 months (95% CI 19-33 months), respectively. Patients with post-treatment hypoalbuminemia had significantly shorter median PFS (6 months [95% CI 5-7 months]) and OS (11 months [95% CI 9-15 months]) than patients who had normal post-treatment albumin levels (PFS: 12 months [95% CI 11-16 months], P < 0.001; OS: 31 months [95% CI 24-42 months], P < 0.001), respectively. Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS (hazard ratio [HR], 2.113; 95% CI 1.390-3.212; P < 0.001) and OS (HR, 2.388; 95% CI 1.591-3.585; P < 0.001). Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS. The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS (c-index: 0.68 and 0.73, respectively) compared with the basic MSKCC risk model (c-index: 0.67 and 0.70, respectively). The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis (both P < 0.001)., Conclusions: Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors. Additionally, integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.

Background: Transitional cell carcinoma (TCC) originating from the renal pelvis with a venous tumor thrombus is a rare entity. However, clinicians should be aware of it because of its high malignancy and poor prognosis., Case Presentation: Here, we report three cases of pathologically confirmed TCC originating from the renal pelvis with extension into the renal vein or inferior vena cava (IVC). Of these patients, two are males and one is female (58~73 years old). Their main symptom is flank pain; besides, gross hematuria and weight loss is observed in one of the patients. Computed tomography (CT) scan of the first patient revealed multiple space-occupying lesions in the left renal pelvis and left medium and lower ureter with a tumor thrombus in the left renal vein. CT scan of the second patient revealed a right renal mass and extension into the IVC. Abdominal magnetic resonance imaging (MRI) of the third patient showed a soft tissue mass in the region of the left renal sinus, and the signal of the soft tissue was observed in the left renal vein. The preoperative diagnoses of the first and third patient were TCC, while the second patient was renal cell carcinoma (RCC). Two patients with the preoperative diagnosis of TCC underwent laparoscopic radical nephroureterectomy with thrombectomy, and the other patient underwent radical nephrectomy with thrombectomy. The surgeries were successful. Although two of our patients underwent chemotherapy and radiotherapy, they died 2 and 19 months after the surgery, respectively. The other patient refused any adjuvant therapy and died 3 months after the operation., Conclusions: Compared to the extension of RCC to the renal vein or IVC, extension of TCC to the renal vein or IVC is rare. TCC with a venous tumor thrombus is often misdiagnosed as RCC. However, a correct preoperative or intraoperative diagnosis is of great importance to decide surgical strategy. Laparoscopic radical nephroureterectomy with thrombectomy may be a safe and feasible operative method in treatment of TCC with a renal vein thrombus. The prognosis of such cases is poor even if chemotherapy and radiotherapy are scheduled.