scholarly journals Tryptophan 2,3‐dioxygenase in tumor cells is associated with resistance to immunotherapy in renal cell carcinoma

2021 ◽  
Author(s):  
Makoto Sumitomo ◽  
Kiyoshi Takahara ◽  
Kenji Zennami ◽  
Tomomi Nagakawa ◽  
Yasuhiro Maeda ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell

Diagnostic ability of four cell-free miRNA signatures pre- and post-nephrectomy concordantly found in the tumor and blood from patients with renal cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16577-e16577
Author(s):  
Matias Bustos ◽  
Rebecca Gross ◽  
Rebeka Dejenie ◽  
Ryu Suyeon ◽  
Negin Rahimzadeh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Incidental Finding ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Ability ◽  
Paired Samples ◽  
Tumor Tissues

e16577 Background: Renal cell carcinoma (RCC) has shown an increase in incidence based on continued incidental finding of these tumors by imaging. There is a need for reliable biomarkers like MicroRNAs (miRNA) that are released by the tumor cells and can be detected in assays using blood or urine samples. The first aim of the present pilot study is to determine the diagnostic ability of cell-free miRNA (cfmiR) biomarkers released by RCC tumor cells in urine and plasma samples. The secondary aim was to determine cfmiRs utility in monitoring RCC before and after radical or partial nephrectomy. Methods: We profiled tumor tissues (n = 11), pre-operative (pre-P n = 18; pre-U n = 17) and post-operative (post-P n = 18; post-U n = 17) plasma and urine paired samples from 18 RCC patients with a median follow-up of 18.4 months. As a control, we utilized plasma (n = 73) and urine (n = 16) samples taken from normal healthy donors (NHD). All specimens (n = 170) were processed and analyzed using HTG EdgeSeq miRNA whole transcriptome assay. All of the samples were normalized and DESeq2. Only miRNAs with a FC < -1.5 or > 1.5, FDR < 0.05, normalized counts > 30 were considered Results: We assessed urine, plasma, and tissue for 2083 miRNAs. The pre-U profiles from patients with RCC and NHD were compared to find differentially expressed (DE) cfmiRs. We found 182 cfmiRs DE in pre-U RCC, of which 106 were upregulated and 76 were downregulated. Similarly, we found 830 cfmiRs DE in the pre-P from RCC compared to NHD, of which 192 were upregulated and 638 were downregulated. We then searched for the top 100 miRNAs most frequently detected and identified in the tumor and in pre-P and pre-U samples. Forty miRNAs were consistently found and highly detected in all of the specimens. Of those 40 miRNAs, 33 cfmiRs were found DE in pre-P and 9 cfmiRs significantly decreased in post-P samples after surgery to the level values observed in the plasma from NHD. In the pre-P and pre-U samples from RCC patients, let-7a-5p, let-7b-5p, miR-23b-3p, and miR-30d-5p were found to be consistently upregulated compared to their respective controls. By using receiving operating characteristic (ROC) curves we assessed the area under the curve (AUC) of all the four cfmiRs in detecting RCC patients. The values of AUC for the four cfmiRs detected in pre-P ranged from 76.2-81% [sensitivity, 61.1-83.3%; specificity, 74-86.3%] and in pre-U samples ranged from 76.1-82.4% [sensitivity, 64.7-70.6%; specificity, 100%]. We observed that the four cfmiRs significantly decreased in the post-U samples from RCC patients after surgery to the level values observed in urine from NHD. Conclusions: Our results propose a four cfmiR signature as a potential diagnostic/monitoring urine biomarker that is also detectable in the plasma and tumor tissues from RRC. Further studies to validate these cfmiRNAs as biomarkers for RCC in blood and urine are ongoing.

Antibodies to Cultured Tumor Cells Detected in Sera of Renal Cell Carcinoma Patients by a Quantitative Avidin-Biotin Method

1986 ◽  
Vol 136 (4) ◽  
pp. 795-798
Author(s):  
Jean B. deKernion ◽  
Laszlo Lovrekovich ◽  
Dominique Chopin ◽  
Urs E. Studer
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Cultured Tumor Cells

scholarly journals Histopathologic and Immunohistochemistry Findings in Feline Renal Cell Carcinoma

2018 ◽  
Vol 55 (5) ◽  
pp. 663-672 ◽  
Author(s):  
Isao Matsumoto ◽  
James K. Chambers ◽  
Kazumi Nibe ◽  
Ryohei Kinoshita ◽  
Ryohei Nishimura ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Biological Behavior ◽  
Nuclear Accumulation ◽  
Mesenchymal Transition ◽  
Marker Expression ◽  
Papillary Type ◽  
Columnar Cells

The biological behavior and immunohistochemical features of feline renal cell carcinoma (RCC) have not been well characterized. In the present study, immunohistochemical examinations were performed in 12 feline cases of RCC. The RCC consisted of solid ( n = 2), solid-tubular ( n = 2), tubular ( n = 3), papillary ( n = 2), tubulopapillary ( n = 2), and sarcomatoid ( n = 1) type lesions. Of the cases with RCC, 1 developed metastatic disease and 6 cases had no evidence of recurrence at 80 to 2292 days after surgery. One papillary-type tumor had cuboidal cells with scant cytoplasm and monomorphic nuclei, and the other had pseudostratified columnar cells with abundant cytoplasm. Immunohistochemistry revealed that the tumor cells in most cases were positive for cytokeratin (CK)7, CK20, KIT, and CD10, with the exception of cases of the solid type with clear cytoplasm (solid anaplastic), papillary type with columnar cells, and sarcomatoid types. A small number of tumor cells in the solid anaplastic and in the sarcomatoid types were positive for aquaporin-1. Increased expression of N-cadherin and Twist along with nuclear accumulation of β-catenin were observed in the sarcomatoid type. These results indicated that CK, KIT, and CD10 are relatively strongly expressed in most feline RCC. The solid anaplastic RCC exhibited CD10 expression with the absence of distal tubule marker expression. Although immunohistochemistry profiles were relatively consistent with those described in human RCC, the histopathologic features were different from those seen in humans. Epithelial-mesenchymal transition (EMT) marker expression in the current cases may suggest the involvement of an EMT-like mechanism in the development of sarcomatoid RCC in cats.

scholarly journals Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression

2020 ◽  
Vol 21 (4) ◽  
pp. 1475
Author(s):  
Vera Cappelletti ◽  
Elena Verzoni ◽  
Raffaele Ratta ◽  
Marta Vismara ◽  
Marco Silvestri ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Response Prediction ◽  
Surface Proteins ◽  
Cell Recovery ◽  
Epithelial Cell Surface

Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.

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