C-reactive Protein in Patients with Metastatic Clear Cell Renal Carcinoma: An Important Biomarker for Tumor-associated Inflammation

Two consecutive multi-center phase II trials were designed to prove the hypothesis, whether therapeutic modeling of tumor-associated inflammatory processes could result in improved tumor response. Therapy in both trials consisted of low-dose capecitabine 1g/m2 twice daily p.o. for 14 days, every 3 weeks, day 1+, and rofecoxib 25 mg daily p.o., day 1+ (from 11/04 etoricoxib 60 mg daily instead) plus pioglitazone 60 mg daily p.o., day 1+. In study II low-dose IFN-α 4.5 MU sc. three times a week, week 1+, was added until disease progression. Eighteen, and 33 patients, respectively, with clear cell renal carcinoma and progressive disease were enrolled. Objective response (48%) was exclusively observed in study II (PR 35%, CR 13%), and paralleled by a strong CRP response after 4 weeks on treatment, p = 0.0005, in all 29 pts (100%) with elevated CRP levels. Median progression-free survival could be more than doubled from a median of 4.7 months (95% CI, 1.0 to 10.4) to 11.5 months (6.8 to 16.2) in study II, p = 0.00001. Median overall survival of population II was 26 months. Efficacious negative regulation of tumor-associated inflammation by transcription modulators may result in a steep increase of tumor response and survival.

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Abstract A28: C-reactive protein as a predictive marker of response to sunitinib treatment in metastatic clear cell renal carcinoma

10.1158/1538-8514.tumang15-a28 ◽

2015 ◽

Author(s):

Martin Pilskog ◽

Christian Beisland ◽

Oddbjørn Straume

Keyword(s):

Renal Carcinoma ◽

Clear Cell ◽

Predictive Marker ◽

Clear Cell Renal Carcinoma ◽

C Reactive Protein ◽

Sunitinib Treatment ◽

Reactive Protein ◽

Cell Renal Carcinoma

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Antiangiogenic Therapy in Clear Cell Renal Carcinoma (CCRC): Pharmacological Basis and Clinical Results

Cancers ◽

10.3390/cancers13235896 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5896

Author(s):

Alessandro Comandone ◽

Federica Vana ◽

Tiziana Comandone ◽

Marcello Tucci

Keyword(s):

Renal Carcinoma ◽

Clear Cell ◽

Checkpoint Inhibitors ◽

Antiangiogenic Therapy ◽

Objective Response ◽

Predictive Biomarkers ◽

Clear Cell Renal Carcinoma ◽

Anticancer Activities ◽

Cell Renal Carcinoma ◽

Treatment Research

Angiogenesis has a direct stimulatory effect on tumor growth, duplication, invasion and metastatic development. A significant portion of conventional renal cell carcinomas are angiogenesis-dependent tumors and the pathways supporting this process have been thoroughly investigated over the last 20 years. As a consequence, many tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, pazopanib, axitinib, and cabozantinib), one monoclonal antibody (bevacizumab), and two mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus) have been investigated and approved for the treatment of advanced or metastatic clear cell renal carcinoma (metastatic CCRC) in first-line, as well as second-line, therapy, with impressive results in progression-free survival and in the objective response rate compared with previously available therapies or placebo. Recently, a new type of drug has been approved for metastatic CCRC: immunomodulatory checkpoint inhibitors (ICIs), alone or in combination with TKIs. However, many questions and areas to be explored still remain with regard to clear cell renal carcinoma (CCRC) treatment: research on predictive biomarkers, the best patient selection, how to overcome the mechanisms of resistance, and the best sequence of therapies in daily clinical practice. This review focuses on the pharmacological properties and anticancer activities of these drugs. The toxicity profile and clinical limitations of these therapies are also discussed.

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Long survival of a young patient with Xp11.2 translocation metastatic clear cell renal carcinoma: case report and review of the literature

Tumori Journal ◽

10.1177/03008916211049275 ◽

2021 ◽

pp. 030089162110492

Author(s):

Stefania Pipitone ◽

Maria Giuseppa Vitale ◽

Cinzia Baldessari ◽

Massimo Dominici ◽

Roberto Sabbatini

Keyword(s):

Case Report ◽

Renal Carcinoma ◽

Clear Cell ◽

Adult Population ◽

Progression Free Survival ◽

World Health ◽

Rapid Progression ◽

Clear Cell Renal Carcinoma ◽

Cell Renal Carcinoma ◽

Xp11.2 Translocation

Introduction: Xp11.2 translocation is a rare subtype of renal cell carcinoma (RCC), identified as a single entity only from 2004 by World Health Organization (WHO). These tumors involve pediatric age group and rarely patients over 40 years old. Children show indolent disease; adult population has invasive tumor at diagnosis with rapid progression. Case report: We describe a case report of a young woman affected by metastatic clear cell renal carcinoma with Xp11.2 translocation. She achieved a longer stable disease (SD) to first line treatment with atezolizumab plus bevacizumab, obtaining a progression free survival (PFS) of 21 months. After she received cabozantinib, sunitinib and then sorafenib. Conclusions: The patient had an overall survival (OS) of 51 months, which is much higher than that reported in literature data. Unfortunately, the biology of Xp11.2 translocation RCC and its therapeutic management are still unclear.

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1651: Molecular Prognostic Modeling Using Protein Expression Profile in Clear Cell Renal Carcinoma

The Journal of Urology ◽

10.1016/s0022-5347(18)38859-1 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 436-436 ◽

Cited By ~ 3

Author(s):

Hyung L. Kim ◽

David B. Seligson ◽

Nicolette Janzen ◽

Matthew H. Bui ◽

Robert A. Figlin ◽

...

Keyword(s):

Protein Expression ◽

Expression Profile ◽

Renal Carcinoma ◽

Clear Cell ◽

Clear Cell Renal Carcinoma ◽

Protein Expression Profile ◽

Cell Renal Carcinoma ◽

Prognostic Modeling

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The VHL tumor suppressor inhibits expression of the IGF1R and its loss induces IGF1R upregulation in human clear cell renal carcinoma

Oncogene ◽

10.1038/sj.onc.1210474 ◽

2007 ◽

Vol 26 (45) ◽

pp. 6499-6508 ◽

Cited By ~ 68

Author(s):

J S P Yuen ◽

M E Cockman ◽

M Sullivan ◽

A Protheroe ◽

G D H Turner ◽

...

Keyword(s):

Tumor Suppressor ◽

Renal Carcinoma ◽

Clear Cell ◽

Clear Cell Renal Carcinoma ◽

Cell Renal Carcinoma

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The Influence of the Extremely Low Frequency Electromagnetic Field on Clear Cell Renal Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms22031342 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1342

Author(s):

Aleksandra Cios ◽

Martyna Ciepielak ◽

Wanda Stankiewicz ◽

Łukasz Szymański

Keyword(s):

Electromagnetic Field ◽

Cancer Cells ◽

Cell Lines ◽

Renal Carcinoma ◽

Clear Cell ◽

Low Frequency ◽

Inhibitory Effect ◽

Hek293 Cells ◽

Clear Cell Renal Carcinoma ◽

Cell Renal Carcinoma

The development of new technologies and industry is conducive to the increase in the number and variety of electromagnetic field (EMF) sources in our environment. The main sources of EMF are high-voltage lines, household appliances, audio/video devices, mobile phones, radio stations, and radar devices. In the growing use of electronic devices, scientists are increasingly interested in the effects of EMF on human health. Even though many studies on the effects of EMF have already been carried out, none of them has shown a significant effect on mammals, including humans. Moreover, it is not entirely clear how EMF influences cell behavior. The International Agency for Research on Cancer on 31 May 2011, classified PEM as a possible carcinogenic factor. This study aimed to investigate the effect of the electromagnetic field on morphological and functional changes in clear cell renal carcinoma. The research was carried out on in vitro cultures of four cell lines: HEK293, 786-O 769-P, and Caki1. The results of the research showed that the EMF of low frequency had a slight effect on the viability of cells. EMF, which induced cell arrest in the G1 phase, increased the number of early apoptotic cells and decreased the number of viable cells in the 786-O line. EMF did not affect the proliferation and viability of HEK293 cells. Extreme low-frequency EMF (ELF-EMF) also showed an inhibitory effect on the migration and metastatic properties of clear cell kidney cancer cells. Moreover, shortly after the end of ELF-EMF exposure, significant increases in ROS levels were observed in all tested cell lines. As part of the work, it was shown that low-frequency EMF shows an inhibitory effect on the proliferation of primary cancer cells, diminishing their migratory, invasive, and metastatic abilities. It also increases the apoptosis of cancer cells and the amount of reactive oxygen species. Based on the results of our research, we want to point up that the effect of ELF-EMF depends on a specific metabolic state or at a specific stage in the cell cycle of the cells under study.

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