Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 34.873
Filter
1.
Scand J Urol ; 59: 126-130, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896070

ABSTRACT

INTRODUCTION: Surgical video review is an emerging tool for assessing patient outcomes, especially in complex surgeries such as robot-assisted partial nephrectomy (RAPN). Assessing and measuring warm ischaemia time (WIT) during RAPN by dividing it into the time used for tumour excision time (ExcT), time used for kidney reconstruction time (RecT) and intermediate time (IntT) has not been performed before. This study aimed to analyse the factors that can influence all surgical times and assess their impact on positive surgical margins (PSMs) and complication rates. METHODS: We evaluated 32 surgical video recordings from patients undergoing RAPN and measured WIT, ExcT, RecT and IntT with a stopwatch. Factors such as tumour characteristics and surgeon experience were also recorded. SPSS software was used to identify the predictors for all surgical times and to correlate ExcT with PSM and RecT with complication rate. RESULTS: We recorded a median WIT of 1,048 s (17 min and 28 s). The median of ExcT, RecT and IntT was 398 s (37.1% of WIT), 518 s (46.7% of WIT) and 180 s (16.2% of WIT), respectively. We found a significant correlation (P < 0.001) between R.E.N.A.L. score and all surgical times. No correlation was found between ExcT and PSM (P = 0.488) and between RecT and the probability of developing complications (P = 0.544). CONCLUSION: Tumour morphology influences all surgical times, and surgeon experience influences only ExcT. We observed a short RecT during RAPN though at the cost of increased ExcT, and we believe that improving surgical experience, especially for the excision of more complex tumours, can reduce WIT during RAPN.


Subject(s)
Kidney Neoplasms , Nephrectomy , Operative Time , Robotic Surgical Procedures , Warm Ischemia , Humans , Nephrectomy/methods , Robotic Surgical Procedures/methods , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Middle Aged , Male , Female , Aged , Video Recording , Kidney/surgery , Margins of Excision , Adult , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Plastic Surgery Procedures/methods
2.
Scand J Urol ; 59: 131-136, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896113

ABSTRACT

OBJECTIVE: Disease recurrence, particularly intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), is common. We investigated whether violations of onco-surgical principles before or during RNU, collectively referred to as surgical violation (SV), were associated with survival outcomes.  Material and methods: Data from a consecutive series of patients who underwent RNU for UTUC 2001-2012 at Skåne University Hospital Lund/Malmö were collected. Preoperative insertion of a nephrostomy tube, opening the urinary tract during surgery or refraining from excising the distal ureter were considered as SVs. Survival outcomes in patients with and without SV (IVR-free [IVRFS], disease-specific [DSS] and overall survival [OS]) were assessed using multivariate Cox regression analyses (adjusted for tumour stage group, prior or concomitant bladder cancer, comorbidity and preoperative urinary cytology). RESULTS: Of 150 patients, 47 (31%) were subjected to at least one SV. Overall, SV was not associated with IVRFS (HR 0.81, 95% CI 0.4-1.6) but with worse DSS (HR 1.9, 95% CI 1.03-3.7) and OS (HR 1.9, 95% CI 1.2-3) in multivariable analysis. Additional analyses with a broader definition of SV including also preoperative instrumentation of the upper urinary tract (ureteroscopy and/or double J stenting) showed similar outcomes for DSS (HR 2.1, 95% CI 1.1-4.3). CONCLUSION: Worse survival outcomes, despite no difference in IVR, for patients that were subjected to the violation of sound onco-surgical principles before or during RNU for UTUC strengthen the notion that adhering to such principles is a cornerstone in upper tract urothelial cancer surgery.


Subject(s)
Carcinoma, Transitional Cell , Kidney Neoplasms , Nephroureterectomy , Ureteral Neoplasms , Humans , Nephroureterectomy/methods , Female , Male , Aged , Ureteral Neoplasms/surgery , Ureteral Neoplasms/mortality , Ureteral Neoplasms/pathology , Carcinoma, Transitional Cell/surgery , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Middle Aged , Survival Rate , Retrospective Studies , Neoplasm Recurrence, Local/epidemiology , Aged, 80 and over , Ureter/surgery
5.
Cell Death Dis ; 15(6): 427, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890303

ABSTRACT

As the second most common malignant tumor in the urinary system, renal cell carcinoma (RCC) is imperative to explore its early diagnostic markers and therapeutic targets. Numerous studies have shown that AURKB promotes tumor development by phosphorylating downstream substrates. However, the functional effects and regulatory mechanisms of AURKB on clear cell renal cell carcinoma (ccRCC) progression remain largely unknown. In the current study, we identified AURKB as a novel key gene in ccRCC progression based on bioinformatics analysis. Meanwhile, we observed that AURKB was highly expressed in ccRCC tissue and cell lines and knockdown AURKB in ccRCC cells inhibit cell proliferation and migration in vitro and in vivo. Identified CDC37 as a kinase molecular chaperone for AURKB, which phenocopy AURKB in ccRCC. AURKB/CDC37 complex mediate the stabilization of MYC protein by directly phosphorylating MYC at S67 and S373 to promote ccRCC development. At the same time, we demonstrated that the AURKB/CDC37 complex activates MYC to transcribe CCND1, enhances Rb phosphorylation, and promotes E2F1 release, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. Collectively, our study identified AURKB as a novel marker of ccRCC, revealed a new mechanism by which the AURKB/CDC37 complex promotes ccRCC by directly phosphorylating MYC to enhance its stability, and first proposed AURKB/E2F1-positive feedforward loop, highlighting AURKB may be a promising therapeutic target for ccRCC.


Subject(s)
Aurora Kinase B , Carcinoma, Renal Cell , Cell Cycle Proteins , Disease Progression , E2F1 Transcription Factor , Kidney Neoplasms , Proto-Oncogene Proteins c-myc , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , E2F1 Transcription Factor/metabolism , E2F1 Transcription Factor/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Line, Tumor , Phosphorylation , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Aurora Kinase B/metabolism , Aurora Kinase B/genetics , Cell Proliferation , Animals , Gene Expression Regulation, Neoplastic , Mice, Nude , Mice , Cell Movement/genetics , Chaperonins
6.
Sci Rep ; 14(1): 13556, 2024 06 12.
Article in English | MEDLINE | ID: mdl-38866930

ABSTRACT

Abnormalities in the extracellular matrix (ECM) play important roles in the regulation and progression of clear cell renal cell carcinoma (ccRCC). The cysteine cathepsin is one of the major proteases involved in ECM remodeling and has been shown to be aberrantly expressed in multiple cancer types. However, the clinical significance and biological function of distinct cysteine cathepsins in ccRCC remain poorly understood. In this study, several bioinformatics databases, including UALCAN, TIMER, GEPIA and the Human Protein Atlas datasets, were used to analyze the expression and prognostic value of different cysteine cathepsin family members in ccRCC. We found that the expression level of CTSF was downregulated in tumor tissues and closely related to the poor survival of ccRCC patients. Further in vitro experiments suggested that CTSF overexpression suppressed the proliferation and migration of ccRCC cells. Moreover, the expression of CTSF was shown to be associated with several immune-infiltrating cells and immunomodulators in ccRCC. These results indicated that CTSF might be a promising diagnostic and prognostic marker in ccRCC.


Subject(s)
Carcinoma, Renal Cell , Cathepsin F , Cell Proliferation , Gene Expression Regulation, Neoplastic , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/mortality , Prognosis , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Kidney Neoplasms/mortality , Female , Male , Cathepsin F/metabolism , Cathepsin F/genetics , Cell Line, Tumor , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Cell Movement/genetics , Middle Aged , Down-Regulation
7.
Sci Rep ; 14(1): 13475, 2024 06 12.
Article in English | MEDLINE | ID: mdl-38866983

ABSTRACT

Kidney renal clear cell carcinoma (KIRC) is the most common histological type of renal cancer, enhancer RNA plays a significant role in tumor growth, however, it has been less studied in renal cancer. The aim of this study was to investigate the role of eRNA AC003092.1 in KIRC. Clinical and RNA expression data were downloaded from a TCGA database, and performed bioinformatics analysis, including expression level analysis, survival analysis, clinical correlation analysis, immune correlation analysis. We further confirmed the expression level of AC003092.1 between normal and tumor cell, predicted the biological role of AC003092.1 in KIRC, and performed cell proliferation and wound healing assays, followed by GSEA enrichment analysis and western blot to detect the proteins of the enriched pathway. Bioinformatics results showed that AC003092.1 expression was elevated in tumor tissues, and knockdown of AC003092.1 expression inhibited cell proliferation and migration. GSEA and western blot results showed that knockdown AC003092.1 expression alleviated the extracellular matrix (ECM) process in KIRC cell lines. Our study provides evidence that AC003092.1 play an important role in KIRC, and AC003092.1 may promote tumor cell progression by affecting the ECM process during tumor development.


Subject(s)
Carcinoma, Renal Cell , Cell Proliferation , Gene Expression Regulation, Neoplastic , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Prognosis , Cell Proliferation/genetics , Cell Line, Tumor , Down-Regulation/genetics , Cell Movement/genetics , Female , Male , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Computational Biology/methods , Middle Aged , Enhancer RNAs
8.
Proc Natl Acad Sci U S A ; 121(25): e2310793121, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38861592

ABSTRACT

mTORC1 is aberrantly activated in renal cell carcinoma (RCC) and is targeted by rapalogs. As for other targeted therapies, rapalogs clinical utility is limited by the development of resistance. Resistance often results from target mutation, but mTOR mutations are rarely found in RCC. As in humans, prolonged rapalog treatment of RCC tumorgrafts (TGs) led to resistance. Unexpectedly, explants from resistant tumors became sensitive both in culture and in subsequent transplants in mice. Notably, resistance developed despite persistent mTORC1 inhibition in tumor cells. In contrast, mTORC1 became reactivated in the tumor microenvironment (TME). To test the role of the TME, we engineered immunocompromised recipient mice with a resistance mTOR mutation (S2035T). Interestingly, TGs became resistant to rapalogs in mTORS2035T mice. Resistance occurred despite mTORC1 inhibition in tumor cells and could be induced by coculturing tumor cells with mutant fibroblasts. Thus, enforced mTORC1 activation in the TME is sufficient to confer resistance to rapalogs. These studies highlight the importance of mTORC1 inhibition in nontumor cells for rapalog antitumor activity and provide an explanation for the lack of mTOR resistance mutations in RCC patients.


Subject(s)
Carcinoma, Renal Cell , Drug Resistance, Neoplasm , Kidney Neoplasms , Mechanistic Target of Rapamycin Complex 1 , TOR Serine-Threonine Kinases , Animals , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Mice , Humans , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Mechanistic Target of Rapamycin Complex 1/metabolism , TOR Serine-Threonine Kinases/metabolism , Tumor Microenvironment/drug effects , Cell Line, Tumor , Sirolimus/pharmacology , Mutation , MTOR Inhibitors/pharmacology , MTOR Inhibitors/therapeutic use
9.
J Immunother Cancer ; 12(6)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862251

ABSTRACT

BACKGROUND: A combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC. METHODS: This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis. RESULTS: A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24-0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1-2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size. CONCLUSION: Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT04118855.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Axitinib , Carcinoma, Renal Cell , Kidney Neoplasms , Neoadjuvant Therapy , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Axitinib/therapeutic use , Axitinib/pharmacology , Male , Female , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Middle Aged , Neoadjuvant Therapy/methods , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Prospective Studies , Nephrectomy/methods
10.
Sci Rep ; 14(1): 13390, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38862642

ABSTRACT

The tumor microenvironment (TME) comprises immune-infiltrating cells that are closely linked to tumor development. By screening and analyzing genes associated with tumor-infiltrating M0 cells, we developed a risk model to provide therapeutic and prognostic guidance in clear cell renal cell carcinoma (ccRCC). First, the infiltration abundance of each immune cell type and its correlation with patient prognosis were analyzed. After assessing the potential link between the depth of immune cell infiltration and prognosis, we screened the infiltrating M0 cells to establish a risk model centered on three key genes (TMEN174, LRRC19, and SAA1). The correlation analysis indicated a positive correlation between the risk score and various stages of the tumor immune cycle, including B-cell recruitment. Furthermore, the risk score was positively correlated with CD8 expression and several popular immune checkpoints (ICs) (TIGIT, CTLA4, CD274, LAG3, and PDCD1). Additionally, the high-risk group (HRG) had higher scores for tumor immune dysfunction and exclusion (TIDE) and exclusion than the low-risk group (LRG). Importantly, the risk score was negatively correlated with the immunotherapy-related pathway enrichment scores, and the LRG showed a greater therapeutic benefit than the HRG. Differences in sensitivity to targeted drugs between the HRG and LRG were analyzed. For commonly used targeted drugs in RCC, including axitinib, pazopanib, temsirolimus, and sunitinib, LRG had lower IC50 values, indicating increased sensitivity. Finally, immunohistochemistry results of 66 paraffin-embedded specimens indicated that SAA1 was strongly expressed in the tumor samples and was associated with tumor metastasis, stage, and grade. SAA1 was found to have a significant pro-tumorigenic effect by experimental validation. In summary, these data confirmed that tumor-infiltrating M0 cells play a key role in the prognosis and treatment of patients with ccRCC. This discovery offers new insights and directions for the prognostic prediction and treatment of ccRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/genetics , Prognosis , Tumor Microenvironment/immunology , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Female , Male , Risk Assessment/methods , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Middle Aged , Immunotherapy/methods , Sulfonamides/therapeutic use
12.
BMC Med Imaging ; 24(1): 135, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844837

ABSTRACT

BACKGROUND: This study aims to explore machine learning(ML) methods for non-invasive assessment of WHO/ISUP nuclear grading in clear cell renal cell carcinoma(ccRCC) using contrast-enhanced ultrasound(CEUS) radiomics. METHODS: This retrospective study included 122 patients diagnosed as ccRCC after surgical resection. They were divided into a training set (n = 86) and a testing set(n = 36). CEUS radiographic features were extracted from CEUS images, and XGBoost ML models (US, CP, and MP model) with independent features at different phases were established. Multivariate regression analysis was performed on the characteristics of different radiomics phases to determine the indicators used for developing the prediction model of the combined CEUS model and establishing the XGBoost model. The training set was used to train the above four kinds of radiomics models, which were then tested in the testing set. Radiologists evaluated tumor characteristics, established a CEUS reading model, and compared the diagnostic efficacy of CEUS reading model with independent characteristics and combined CEUS model prediction models. RESULTS: The combined CEUS radiomics model demonstrated the best performance in the training set, with an area under the curve (AUC) of 0.84, accuracy of 0.779, sensitivity of 0.717, specificity of 0.879, positive predictive value (PPV) of 0.905, and negative predictive value (NPV) of0.659. In the testing set, the AUC was 0.811, with an accuracy of 0.784, sensitivity of 0.783, specificity of 0.786, PPV of 0.857, and NPV of 0.688. CONCLUSIONS: The radiomics model based on CEUS exhibits high accuracy in non-invasive prediction of ccRCC. This model can be utilized for non-invasive detection of WHO/ISUP nuclear grading of ccRCC and can serve as an effective tool to assist clinical decision-making processes.


Subject(s)
Carcinoma, Renal Cell , Contrast Media , Kidney Neoplasms , Machine Learning , Neoplasm Grading , Ultrasonography , Humans , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Female , Retrospective Studies , Male , Middle Aged , Ultrasonography/methods , Aged , Adult , Radiomics
13.
Cancer Med ; 13(11): e7247, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38826126

ABSTRACT

OBJECTIVES: To examine real-world characteristics, journey, and outcomes among patients with locoregional, nonmetastatic renal cell carcinoma (RCC). METHODS: A retrospective analysis of medical records from the ConcertAI Oncology Dataset was performed on adults in the United States with newly diagnosed nonmetastatic RCC between January 2012-December 2017 who received surgical treatment, and were followed until August 2021. Patients were stratified based on the risk of recurrence after nephrectomy. Recurrence rate and survival outcomes were assessed. RESULTS: The cohort (n = 439) had a median age of 64 years, 66.1% were male, and 76.5% had clear-cell histology. The median follow-up time from nephrectomy was 39.3 months overall, 41.0 months for intermediate-high-risk patients (n = 377; 85.9%) and 24.1 months for high-risk patients (n = 62; 14.1%). For intermediate-high- and high-risk patients, respectively, 68.4% and 56.5% had ≥1 medical oncologist visit after nephrectomy. Of 260 patients with documentation of postoperative imaging assessments, 72% were ordered by medical oncologists, and the median time from initial nephrectomy to the first scan was 110 days (intermediate-high-risk) and 51 days (high-risk). Provider-documented recurrence occurred in 223 (50.8%) patients, of whom 41.7% had ≥1 medical oncologist visit before the recurrence. Three-year disease-free survival (DFS), and overall survival rates were 49.4% and 80.8% (all patients): 27.7% and 64.7% (high-risk); and 52.9% and 83.3% (intermediate-high-risk). CONCLUSIONS: Our study reports low DFS after nephrectomy for patients with intermediate-high- and high-risk RCC. Subsequent approval and use of new and newly approved adjuvant therapeutic options could potentially delay or prevent recurrence.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplasm Recurrence, Local , Nephrectomy , Humans , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Nephrectomy/methods , Male , Female , Middle Aged , Kidney Neoplasms/surgery , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Retrospective Studies , Aged , Neoplasm Staging , Risk Factors , Treatment Outcome , United States/epidemiology , Adult
14.
Cancer Immunol Immunother ; 73(8): 142, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832989

ABSTRACT

BACKGROUND: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. METHOD: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. RESULTS: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). CONCLUSIONS: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Female , Male , Middle Aged , Kidney Neoplasms/mortality , Kidney Neoplasms/immunology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Adult , Aged , Young Adult , Adolescent , Sex Factors , Immune Checkpoint Inhibitors/therapeutic use , Prognosis , Immunotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival Rate , Aged, 80 and over
15.
Arch Esp Urol ; 77(4): 412-417, 2024 May.
Article in English | MEDLINE | ID: mdl-38840285

ABSTRACT

OBJECTIVE: Advancements in medical science have improved non-metastatic renal cell carcinoma (NM-RCC) treatment strategies, but long-term survival is influenced by various factors, including perioperative blood transfusion. This study aims to analyse prognostic factors in patients with NM-RCC after radical nephrectomy. METHODS: From January 2018 to December 2021, a total of 132 patients with NM-RCC after radical nephrectomy were studied. According to 2-year follow-up data, the patients were categorised into case (with poor outcomes, including pneumothorax, renal issues, recurrence or death) and control groups. Data on demographics, clinical characteristics and perioperative blood transfusion were collected, and key prognostic factors were identified through logistic regression. RESULTS: A total of 32 patients with poor prognosis were included in the case group, accounting for 24.24% (32/132), and 100 patients without poor prognosis were included in the control group, accounting for 75.76% (100/132). Tumour stage, tumour size and perioperative blood transfusion were all risk factors for the prognosis of patients, and odds ratio (OR) >1. The above indicators had high predictive value for the prognosis of patients after surgery. CONCLUSIONS: The prognostic factors of patients with NM-RCC after radical nephrectomy include tumour stage, tumour size and perioperative blood transfusion, and each factor had predictive value.


Subject(s)
Blood Transfusion , Carcinoma, Renal Cell , Kidney Neoplasms , Nephrectomy , Perioperative Care , Humans , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Kidney Neoplasms/mortality , Male , Female , Retrospective Studies , Middle Aged , Nephrectomy/methods , Prognosis , Blood Transfusion/statistics & numerical data , Aged
16.
BMC Med Genomics ; 17(1): 150, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822402

ABSTRACT

Long non-coding RNAs (lncRNAs) and cancer stem cells (CSCs) are crucial for the growth, migration, recurrence, and medication resistance of tumors. However, the impact of lncRNAs related to stemness on the outcome and tumor immune microenvironment (TIME) in clear cell renal cell carcinoma (ccRCC) is still unclear. In this study, we aimed to predict the outcome and TIME of ccRCC by constructing a stem related lncRNAs (SRlncRNAs) signature. We firstly downloaded ccRCC patients' clinical data and RNA sequencing data from UCSC and TCGA databases, and abtained the differentially expressed lncRNAs highly correlated with stem index in ccRCC through gene expression differential analysis and Pearson correlation analysis. Then, we selected suitable SRlncRNAs for constructing a prognostic signature of ccRCC patients by LASSO Cox regression. Further, we used nomogram and Kaplan Meier curves to evaluate the SRlncRNA signature for the prognose in ccRCC. At last, we used ssGSEA and GSVA to evaluate the correlation between the SRlncRNAs signature and TIME in ccRCC. Finally, We obtained a signtaure based on six SRlncRNAs, which are correlated with TIME and can effectively predict the ccRCC patients' prognosis. The SRlncRNAs signature may be a noval prognostic indicator in ccRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplastic Stem Cells , RNA, Long Noncoding , Tumor Microenvironment , Humans , RNA, Long Noncoding/genetics , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/immunology , Prognosis , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/immunology , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Female , Male , Kaplan-Meier Estimate , Gene Expression Profiling
18.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 129-134, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836670

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is a lethal malignancy with high metastatic probability. Paired box 2 gene product (PAX2) carbonic anhydrase IX were biomolecules closely linked with ccRCC development and outcomes of multiple malignancies. We aim to explore the role of immunohistochemical staining of PAX2 and CAIX to predict ccRCC prognosis after nephrectomy. Surgical specimens of patients who were pathologically diagnosed as ccRCC were reviewed. Expression levels of PAX2 and CAIX were assessed via immunohistochemical staining. Recurrence-free survival (RFS) and overall survival were compared among different phenotypes. Inverse probability of treatment weighting (IPTW) was used for adjustment of confounding factors. 56 patients were included. Patients with PAX2 and CAIX high-expression (the two-high group, n=8) had significantly longer RFS and OS than those of simultaneously down-expression (the two-low group, n=31). Median RFS was 38.4 (95% CI: 32.3-NA) for the two-high group and 14.8 (95% CI: 13.4-39.0) months for the two-low group (P=0.043). IPTW confirmed PAX2 and CAIX co-expression is associated with less recurrence risk HR: 0.39, 95% CI: 0.17-0.92, P=0.031). Co-expression of PAX2 and CAIX is associated better prognosis of ccRCC. We are looking for validation by large cohort studies.


Subject(s)
Carbonic Anhydrase IX , Carcinoma, Renal Cell , Immunohistochemistry , Kidney Neoplasms , Nephrectomy , PAX2 Transcription Factor , Humans , PAX2 Transcription Factor/metabolism , PAX2 Transcription Factor/genetics , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/genetics , Male , Female , Carbonic Anhydrase IX/metabolism , Carbonic Anhydrase IX/genetics , Nephrectomy/methods , Middle Aged , Retrospective Studies , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Kidney Neoplasms/mortality , Kidney Neoplasms/genetics , Prognosis , Aged , Disease-Free Survival , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Adult , Antigens, Neoplasm
19.
Int J Mol Sci ; 25(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38892169

ABSTRACT

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel and uncommon type of renal cell carcinoma, which has been recently recognized and introduced as a distinct entity in the WHO 2022 kidney tumor classification. Previously known as "unclassified RCC", followed by "tuberous sclerosis complex (TSC)-associated RCC", ESC-RCC is now a distinct category of kidney tumor, with its own name, with specific clinical manifestations, and a unique morphological, immunohistochemical and molecular profile. Due to its recent introduction and the limited available data, the diagnosis of ESC-RCC is still a complex challenge, and it is probably frequently misdiagnosed. The secret of diagnosing this tumor lies in the pathologists' knowledge, and keeping it up to date through research, thereby limiting the use of outdated nomenclature. The aim of our case-based review is to provide a better understanding of this pathology and to enrich the literature with a new case report, which has some particularities compared to the existing cases.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/diagnosis , Kidney Neoplasms/pathology , Kidney Neoplasms/diagnosis , Eosinophilia/pathology , Eosinophilia/diagnosis , Male
20.
Int J Mol Sci ; 25(11)2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38892327

ABSTRACT

Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the progression of RCC in vitro and in vivo. Lead challenge of Renca cells with 0.5 µM lead acetate for 10 consecutive passages decreased E-cadherin expression and cell aggregation. Proliferation, colony formation, and wound healing were increased. When lead-challenged cells were injected into mice, tumor size at day 21 was increased; interestingly, this increase was seen in male but not female mice. When mice were challenged with 32 ppm lead in drinking water for 20 weeks prior to tumor cell injection, there was an increase in tumor size in male, but not female, mice at day 21. To investigate the mechanism underlying the sex differences, the expression of sex hormone receptors in Renca cells was examined. Control Renca cells expressed estrogen receptor (ER) alpha but not ER beta or androgen receptor (AR), as assessed by qPCR, and the expression of ERα was increased in tumors in both sexes. In tumor samples harvested from lead-challenged cells, both ERα and AR were detected by qPCR, yet there was a significant decrease in AR seen in lead-challenged tumor cells from male mice only. This was paralleled by a plate-based array demonstrating the same sex difference in BMP-7 gene expression, which was also significantly decreased in tumors harvested from male but not female mice; this finding was validated by immunohistochemistry. A similar expression pattern was seen in tumors harvested from the mice challenged with lead in the drinking water. These data suggest that lead promotes RCC progression in a sex-dependent via a mechanism that may involve sex-divergent changes in BMP-7 expression.


Subject(s)
Bone Morphogenetic Protein 7 , Carcinoma, Renal Cell , Cell Proliferation , Kidney Neoplasms , Animals , Female , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/genetics , Male , Bone Morphogenetic Protein 7/metabolism , Bone Morphogenetic Protein 7/genetics , Mice , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/chemically induced , Cell Line, Tumor , Cell Proliferation/drug effects , Lead/toxicity , Receptors, Androgen/metabolism , Receptors, Androgen/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Estrogen Receptor alpha/metabolism , Estrogen Receptor alpha/genetics , Sex Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...