Tumour-associated Angiogenesis and Intermediate Blood Vessels in Renal Cell Carcinoma

Background/Aim: Renal cell carcinoma is strongly vascularized, and formation of new blood vessels is a complex and multi-step process. In this study, we analysed the subtypes of intermediate blood vessels, as shown by double immunohistochemistry. Materials and Methods: Tumour-associated blood vessels were identified by double immunostaining based on CD34 and smooth muscle cell actin. Blood vessels were classified both quantitatively and qualitatively based on the expression of the aforementioned two markers. The main criteria to sub-classify intermediate blood vessels was the presence, distribution, and arrangement of perivascular cells. Results: We described three subtypes of intermediate blood vessels found particularly in the tumour area: Subtype 1 lacked perivascular cells, subtype 2 showed scattered pericytes attached to the vascular wall, and subtype 3 showed a continuous layer of perivascular cells on one side. Conclusion: We describe for the first time three subtypes of renal cell carcinoma-associated intermediate blood vessels, which could be important in prognosis and as potential targets for anti-vascular therapy.

Download Full-text

MP70-14 THE ONCOLOGIC IMPACT OF POSITIVE VASCULAR WALL SURGICAL MARGINS IN PATIENTS WITH RENAL CELL CARCINOMA AND VENOUS TUMOR THROMBUS UNDERGOING NEPHRECTOMY

The Journal of Urology ◽

10.1016/j.juro.2015.02.2539 ◽

2015 ◽

Vol 193 (4S) ◽

Author(s):

Sarah Psutka ◽

R. Houston Thompson ◽

Stephen Boorjian ◽

Christine Lohse ◽

Suzanne Stewart ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Tumor Thrombus ◽

Vascular Wall ◽

Surgical Margins ◽

Venous Tumor Thrombus

Download Full-text

Downregulation of Smac/DIABLO Expression in Renal Cell Carcinoma and Its Prognostic Significance

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.191 ◽

2005 ◽

Vol 23 (3) ◽

pp. 448-454 ◽

Cited By ~ 63

Author(s):

Yoichi Mizutani ◽

Hiroyuki Nakanishi ◽

Kosuke Yamamoto ◽

Yong Nan Li ◽

Hiroki Matsubara ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Significance ◽

Inhibitor Of Apoptosis ◽

Normal Kidney ◽

Drug Induced ◽

Fresh Frozen ◽

Induced Apoptosis ◽

First Time

Purpose Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) was recently identified as a protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune- and drug-induced apoptosis. However, little is known about the clinical significance of Smac/DIABLO in various cancers, including renal cell carcinoma (RCC). This study examined Smac/DIABLO expression in 78 healthy kidneys and 78 RCCs. Materials and Methods The level of Smac/DIABLO expression was quantified by Western blot analysis using nonfixed fresh frozen tissues. Results The expression of Smac/DIABLO was lower in RCC compared with the autologous normal kidney. Sixty-four (82%) of 78 of RCC expressed Smac/DIABLO, and 18% were negative, whereas 100% of normal kidney tissues were positive. In stage I/II RCC, 96% expressed Smac/DIABLO, whereas only 50% expressed Smac/DIABLO in stage III/IV. Smac/DIABLO expression inversely correlated with the grade of RCC. Patients with RCC expressing Smac/DIABLO had a longer postoperative disease-specific survival than those without Smac/DIABLO expression in the 5-year follow-up. Transfection with Smac/DIABLO cDNA enhanced tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) –mediated and cisplatin-mediated cytotoxicity in RCC. Conclusion The present study demonstrates for the first time that Smac/DIABLO expression was downregulated in RCC and that no Smac/DIABLO expression in RCC predicted a worse prognosis. In addition, transfection with Smac/DIABLO sensitized RCC to TRAIL/cisplatin-induced apoptosis. These results suggest that Smac/DIABLO expression in RCC may be used as a prognostic parameter, and that enhancement of Smac/DIABLO expression in RCC may potentiate immunotherapy and chemotherapy.

Download Full-text

Translocation Renal Cell Carcinoma in a Child Previously Treated for Infantile Fibrosarcoma

Pediatric and Developmental Pathology ◽

10.1177/1093526617707849 ◽

2017 ◽

Vol 21 (4) ◽

pp. 418-422 ◽

Cited By ~ 1

Author(s):

Jing Ma ◽

Ci Pan ◽

Minzhi Yin

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Previous Treatment ◽

Final Diagnosis ◽

Infantile Fibrosarcoma ◽

Disease Spectrum ◽

Previously Treated ◽

Xp11.2 Translocation ◽

First Time

We report a child who developed a TFE3/Xp11.2 translocation renal cell carcinoma (RCC) when he was 3 years and 3 months old, after previous treatment for infantile fibrosarcoma (IFS). When he was 3 months old, a left axilla mass has been detected, which was tan and solid, was 1.5 cm in greatest dimension, and composed of sheets of spindle cells that was positive for vimentin and fibronectin. Fluorescence in situ hybridization showed positive result in ETV6 gene rearrangements. The final diagnosis was IFS. After surgery and chemotherapy, he remained disease-free until 3 years; later, he was detected to have a tumor in right kidney which measured 2.5 × 2 × 1.5 cm. The tumor comprised clear-cell features that were arranged in papillary and adenoid architecture. The tumor cells were positive for TFE3 and CK. The diagnosis was TFE3/Xp11.2 translocation RCC. Previous research has reported that the radio/chemotherapy for the first tumor might be involved in the pathogenesis of translocation RCC. In our report, this is the first time the IFS is included in the disease spectrum which can cause secondary translocation RCC.

Download Full-text

SETD2 deficiency impairs β-catenin destruction complex to facilitate renal cell carcinoma formation

10.1101/2020.07.13.200220 ◽

2020 ◽

Author(s):

Hanyu Rao ◽

Xiaoxue Li ◽

Min Liu ◽

Jing Liu ◽

Wenxin Feng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Molecular Mechanisms ◽

Clear Cell ◽

Set Domain ◽

Cell Renal Cell Carcinoma ◽

Incurable Disease ◽

First Time

AbstractClear cell renal cell carcinoma (ccRCC) is a largely incurable disease that is highly relevant to epigenetic regulation including histone modification and DNA methylation. SET domain–containing 2 (SETD2) is a predominant histone methyltransferase catalyzing the trimethylation of histone H3 Lysine 36 (H3K36me3) and its mutations are highly relevant to clear cell renal cell carcinoma (ccRCC). However, its physiology role in ccRCC remains largely unexplored. Here we report that Setd2 deletion impairs the β-catenin destruction complex to facilitate ccRCC formation in a c-MYC-generated polycystic kidney disease (PKD) model, which can be relieved by an inhibitor of β-catenin-responsive transcription. Clinically, SETD2 loss is widely observed in ccRCC samples, and negatively correlated with expression of some members of β-catenin destruction complex, but positively correlated with the activation of Wnt/β-catenin signaling. Our findings thus highlight a previously unrecognized role of SETD2-mediated H3K36me3 modification in regulation of Wnt/β-catenin pathway in ccRCC.SummaryOur findings for the first time reveal a previously unrecognized role of the SETD2-mediated H3K36me3 modification in regulation of the Wnt/β-catenin pathway in ccRCC and shed light on the molecular mechanisms underlying the formation of renal cell carcinoma with epigenetic disorders.

Download Full-text

Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials

Lab on a Chip ◽

10.1039/d0lc00252f ◽

2020 ◽

Vol 20 (23) ◽

pp. 4420-4432

Author(s):

María Virumbrales-Muñoz ◽

Jiong Chen ◽

Jose Ayuso ◽

Moonhee Lee ◽

E. Jason Abel ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Trials ◽

Blood Vessel ◽

Cell Carcinoma ◽

Blood Vessels ◽

Renal Cell ◽

Clear Cell ◽

Single Patient ◽

Cell Renal Cell Carcinoma

Identification and testing of personalized anti-angiogenic treatments for clear cell renal cell carcinoma using patient-derived microfluidic models of normal and tumor-associated blood vessels.

Download Full-text

Erythropoietin levels in the course of a patient with erythropoietin- producing renal cell carcinoma and transplantation of this tumor in nude mice

Blood ◽

10.1182/blood.v54.1.245.bloodjournal541245 ◽

1979 ◽

Vol 54 (1) ◽

pp. 245-253 ◽

Cited By ~ 1

Author(s):

K Toyama ◽

N Fujiyama ◽

H Suzuki ◽

TP Chen ◽

N Tamaoki ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Lung Metastasis ◽

Nude Mice ◽

Renal Cell ◽

Primary Renal Cell Carcinoma ◽

First Time ◽

Serum Erythropoietin

Erythropoietin was measured by exhypoxic polycythemic mouse method in the course of a 64-yr-old male with renal cell carcinoma associated with erythrocytosis. Serum erythropoietin fluctuated with progression of the disease. Preoperative elevated erythropoietin (0.11 U/ml, p greater than 0.05) subsided after nephrectomy and again increased with developing lung metastasis (0.1 U/ml, p greater than 0.02). Erythropoietin was markedly increased in the tumorous extracts from primary renal cell carcinoma in the kidney (0.2 U/g, p greater than 0.01) and lung metastasis (0.8 U/g, p greater than 0.01). Renal cell carcinoma from the lung metastasis was transplanted into nude mice, resulting in erythrocytosis in some of these mic. In the erythrocytotic mice, erythropoietin was elevated to levels of 0.25--0.9 U/g (p greater than 0.01) in the tumorous extracts and increased (0.67 U/ml, p greater than 0.02) in the serum. These results indicate that this renal cell carcinoma is an erythropoietin-producing tumor, and this tumor has been successfully transplanted in nude mice for the first time.

Download Full-text