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The Oncologist 2012Recent advancements in the molecular characterization of renal cell carcinoma altered the classification system and now kidney cancer is divided into several distinct... (Review)
Review
Recent advancements in the molecular characterization of renal cell carcinoma altered the classification system and now kidney cancer is divided into several distinct histologic subtypes. Although once a separate histologic category, sarcomatoid renal cell carcinoma is no longer considered a separate tumor type because it can occur with all histologic subtypes. Limited research on tumors with sarcomatoid change has led to minimal progress in the understanding and treatment of these tumors. Because the sarcomatoid variant of renal cell carcinoma can account for approximately one in six cases of advanced kidney cancer, we hope to familiarize clinicians with these tumors by describing the historic background, histologic features, molecular characterization, diagnosis, prognosis, treatment strategies, and active clinical trials of this aggressive type of tumor.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms
PubMed: 22234634
DOI: 10.1634/theoncologist.2011-0227 -
Morphologie : Bulletin de L'Association... Mar 2014Renal carcinomas are histologically and prognostically heterogeneous. Genomic as well as chromosomal studies of these tumors have permitted a better comprehension of... (Review)
Review
Renal carcinomas are histologically and prognostically heterogeneous. Genomic as well as chromosomal studies of these tumors have permitted a better comprehension of molecular mechanisms implicated in their development and progression. The most frequent histological subtypes are characterized by recurrent cytogenetic abnormalities, such as the loss of the chromosome 3 short arm involving a VHL gene copy in clear cell renal carcinomas, or trisomies 7 and 17 in papillary renal cell carcinomas. New histological subtypes like renal carcinomas associated with Xp11.2 translocations have also been individualized. Besides diagnosis, some chromosomal aberrations like the loss of a short arm of chromosome 9 in different renal carcinoma histological subtypes have a worse prognostic impact. The identification of chromosomal shuffles contributes in backing histological diagnosis and in precising the individual prognosis of patients. This review describes chromosomal abnormalities associated to renal carcinomas and their impact for an accurate classification of these tumors and the evaluation of their prognosis.
Topics: Carcinoma; Carcinoma, Renal Cell; Cytogenetic Analysis; Humans; Karyotyping; Kidney Neoplasms
PubMed: 24656859
DOI: 10.1016/j.morpho.2014.02.006 -
Medical Science Monitor : International... May 2021Renal cell carcinoma (RCC) is a most common type of urologic neoplasms; it accounts for 3% of malignant tumors, with high rates of relapse and mortality. The most common... (Review)
Review
Renal cell carcinoma (RCC) is a most common type of urologic neoplasms; it accounts for 3% of malignant tumors, with high rates of relapse and mortality. The most common types of renal cancer are clear cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal carcinoma (chRCC), which account for 90%, 6-15%, and 2-5%, respectively, of all renal malignancies. Although surgical resection, chemotherapy, and radiotherapy are the most common treatment method for those diseases, their effects remain dissatisfactory. Furthermore, recent research shows that the treatment efficacy of checkpoint inhibitors in advanced RCC patients is widely variable. Hence, patients urgently need a new molecular biomarker for early diagnosis and evaluating the prognosis of RCC. MicroRNAs (miRNAs) belong to a family of short, non-coding RNAs that are highly conserved, have long half-life evolution, and post-transcriptionally regulate gene expression; they have been predicted to play crucial roles in tumor metastasis, invasion, angiogenesis, proliferation, apoptosis, epithelial-mesenchymal transition, differentiation, metabolism, cancer occurrence, and treatment resistance. Although some previous papers demonstrated that miRNAs play vital roles in renal cancer, such as pathogenesis, diagnosis, and prognosis, the roles of miRNAs in kidney cancer are still unclear. Therefore, we reviewed studies indexed in PubMed from 2017 to 2020, and found several studies suggesting that there are more than 82 miRNAs involved in renal cancers. The present review describes the current status of miRNAs in RCC and their roles in progression, diagnosis, therapy targeting, and prognosis of RCC.
Topics: Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Epithelial-Mesenchymal Transition; Humans; Kidney Neoplasms; MicroRNAs; Neovascularization, Pathologic; Prognosis
PubMed: 33963171
DOI: 10.12659/MSM.930639 -
Oncology Research 2023As a common tumor of the urinary system, the morbidity and mortality related to renal carcinoma, are increasing annually. Clear cell renal cell carcinoma (CCRCC) is the... (Review)
Review
As a common tumor of the urinary system, the morbidity and mortality related to renal carcinoma, are increasing annually. Clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell carcinoma, accounting for approximately 75% of the total number of patients with renal cell carcinoma. Currently, the clinical treatment of ccRCC involves targeted therapy, immunotherapy, and a combination of the two. In immunotherapy, PD-1/PD-L1 blocking of activated T cells to kill cancer cells is the most common treatment. However, as treatment progresses, some patients gradually develop resistance to immunotherapy. Meanwhile, other patients experience great side effects after immunotherapy, resulting in a survival status far lower than the expected survival rate. Based on these clinical problems, many researchers have been working on the improvement of tumor immunotherapy in recent years and have accumulated numerous research results. We hope to find a more suitable direction for future immunotherapy for ccRCC by combining these results and the latest research progress.
Topics: Humans; Carcinoma, Renal Cell; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Kidney Neoplasms
PubMed: 37305384
DOI: 10.32604/or.2023.027942 -
Journal of Experimental & Clinical... Jun 2021Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC).... (Review)
Review
Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported. One of the mechanisms of VEGF-TKIs is inhibition of the classical angiogenesis pathway. However, recent studies have shown the restoration of an alternative angiogenesis pathway in modulating resistance. Further, in the last 5 years, immune checkpoint inhibitors (ICIs) have revolutionized RCC treatment. Although some patients exhibit potent responses, a non-negligible number of patients are innately resistant or develop resistance within a few months to ICI therapy. Hence, an understanding of the mechanisms of VEGF-TKI and ICI resistance will help in formulating useful knowledge about developing effective treatment strategies for patients with advanced RCC. In this article, we review recent findings on the emerging understanding of RCC pathology, VEGF-TKI and ICI resistance mechanisms, and potential avenues to overcome these resistance mechanisms through rationally designed combination therapies.
Topics: Carcinoma, Renal Cell; Disease-Free Survival; Drug Resistance, Neoplasm; Immune Checkpoint Inhibitors; Neoplasm Metastasis; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Vascular Endothelial Growth Factor A
PubMed: 34099013
DOI: 10.1186/s13046-021-01961-3 -
Medicina (Kaunas, Lithuania) Oct 2023: Metastasis is a major cause of death in renal cell carcinoma (RCC) patients; therefore, a better understanding of the metastatic process and the ability to predict...
: Metastasis is a major cause of death in renal cell carcinoma (RCC) patients; therefore, a better understanding of the metastatic process and the ability to predict metastasis in advance is important for treating patients with RCC. This study aimed to investigate whether histological subtypes of RCC and other factors, such as nuclear grade and sarcomatoid differentiation, could predict the probability and location of metastases in patients with RCC. : Cases of clear-cell, papillary, chromophobe, and sarcomatoid RCC were retrieved and analyzed from the Surveillance, Epidemiology, and End Results databases. : When comparing the metastatic patterns among the three histologic subtypes, patients with clear-cell RCC were significantly more likely to have brain and lung metastases. Moreover, patients with papillary RCC were significantly less likely to develop bone metastases and more likely to develop lymph node metastases. Patients with chromophobe RCC are significantly more likely to develop liver metastases. As the nuclear grade increased, there was also a significantly increased tendency for clear-cell RCC to metastasize to the lungs. Patients with sarcomatoid RCC had a higher rate of metastasis, with a significantly higher probability of metastasis to the bone and lungs, than those with all three histological subtypes did. : Histological subtype, nuclear grade, and sarcomatoid differentiation were significant predictors of metastasis in patients with RCC.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Lymphatic Metastasis; Lung Neoplasms; Cell Differentiation
PubMed: 37893563
DOI: 10.3390/medicina59101845 -
German Medical Science : GMS E-journal 2016We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects... (Comparative Study)
Comparative Study
We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.
Topics: Apoptosis; Carcinoma, Renal Cell; Cell Line; Cell Line, Tumor; Cytokine-Induced Killer Cells; Dose-Response Relationship, Drug; Humans; Kidney Neoplasms; Piperazines; Treatment Outcome
PubMed: 27141211
DOI: 10.3205/000231 -
Frontiers in Immunology 2022Clear Cell Renal Carcinoma (ccRCC) accounts for nearly 80% of renal carcinoma cases, and immunotherapy plays an important role in ccRCC therapy. However, the responses...
Clear Cell Renal Carcinoma (ccRCC) accounts for nearly 80% of renal carcinoma cases, and immunotherapy plays an important role in ccRCC therapy. However, the responses to immunotherapy and overall survival for ccRCC patients are still hard to predict. Here, we constructed an immune-related predictive signature using 19 genes based on TCGA datasets. We also analyzed its relationships between disease prognosis, infiltrating immune cells, immune subtypes, mutation load, immune dysfunction, immune escape, etc. We found that our signature can distinguish immune characteristics and predict immunotherapeutic response for ccRCC patients with better prognostic prediction value than other immune scores. The expression levels of prognostic genes were determined by RT-qPCR assay. This signature may help to predict overall survival and guide the treatment for patients with ccRCC.
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Immunotherapy; Kidney Neoplasms; Prognosis
PubMed: 35936012
DOI: 10.3389/fimmu.2022.869297 -
Current Oncology Reports Sep 2022Historically, kidney cancer was diagnosed as either clear cell renal carcinoma (ccRCC) or non-clear cell renal carcinoma (nccRCC). With further research into the... (Review)
Review
PURPOSE OF REVIEW
Historically, kidney cancer was diagnosed as either clear cell renal carcinoma (ccRCC) or non-clear cell renal carcinoma (nccRCC). With further research into the pathophysiology of nccRCC, multiple distinct subtypes have emerged creating distinct diagnosis, such as papillary renal cell carcinoma (PRCC), chromophobe renal cell carcinoma (crRCC), or unclassified carcinoma (cRCC). Many other kidney cancer subtypes are now included in the WHO classification system.
RECENT FINDINGS
The prognosis for each of the more frequently diagnosed types is discussed here along with treatment recommendations. The available clinical trial results and salient retrospective studies of each subtype are reviewed here to guide clinicians on the optimal treatment selection for patients with these rare histologic types or RCC. Many nccRCC types are now recognized and each has unique molecular drivers which are different than ccRCC. The optimal treatment strategy is different for each subtype. The prognosis also differs based on the histology.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Prognosis; Retrospective Studies
PubMed: 35438388
DOI: 10.1007/s11912-022-01269-1 -
Bioengineered Feb 2022This study investigated the role of ADAM metallopeptidase domain 12 (ADAM12) in clear cell renal cell carcinoma (ccRCC). The mRNA expression of ADAM12 was analyzed using...
This study investigated the role of ADAM metallopeptidase domain 12 (ADAM12) in clear cell renal cell carcinoma (ccRCC). The mRNA expression of ADAM12 was analyzed using The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database, and the protein expression level of ADAM12 in renal clear cell carcinoma cell lines was detected by Western blot analysis. The Wilcoxon rank-sum test, logistic regression analysis, Cox regression analysis, and Kaplan-Meier analysis were used to assess the relationship between the clinicopathological characteristics and the prognosis of ccRCC patients and ADAM12 expression. The miRNAs and lncRNAs associated with ADAM12 were predicted, and a ceRNA network was constructed using the Starbase database. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analysis were used to identify relevant pathways. The relationship between ADAM12 and immune infiltration and checkpoints was analyzed using the TIMER and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The results showed that ADAM12 expression was increased in ccRCC tissues and cells and significantly correlated with patient gender, Tumor stage, Metastasis stage, Node stage, and clinical grade. Survival analysis showed that ccRCC patients with high ADAM12 expression had a low overall survival rate. Univariate and multivariate Cox regression analyses showed that ADAM12 was an independent prognostic factor. Enrichment analysis showed that ADAM12 expression was associated with immune-related pathways. Immune infiltration analysis showed that ADAM12 expression was related to immune cell infiltration, PD-1, PD-L1, and CTLA4. These results suggest that ADAM12 may be a potential diagnostic and prognostic biomarker for ccRCC.
Topics: ADAM12 Protein; Carcinoma, Renal Cell; Cell Line, Tumor; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Neoplasm Proteins; Prognosis
PubMed: 35094638
DOI: 10.1080/21655979.2021.2010313