Paraneoplastic digital ischemia in clear-cell renal-cell carcinoma: Report of a case and review of the literature

2018 ◽  
Vol 86 (3) ◽  
pp. 156-160
Author(s):  
Katerina Kampoli ◽  
Dimitra Gardeli ◽  
Maria Mouktaroudi ◽  
Antonis Fanouriakis ◽  
Andreas M Lazaris ◽  
...  
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Early Recognition ◽  
Treatment Options ◽  
Cell Cancer ◽  
Critical Ischemia ◽  
Cell Renal Cell Carcinoma ◽  
Digital Ischemia ◽  
History Of

Digital ischemia has been rarely associated, as a paraneoplastic syndrome, with renal cancer. Since it can severely compromise the patients’ quality of life, early recognition is important, in order to optimally address it with currently available treatment options, such as tyrosine inhibitors. Digital ischemia may occur in the general population and it can be the result of other non-cancerous diseases; accordingly, a thorough and aggressive work-up is mandatory, together with appropriate therapeutic steps such as tyrosine kinase inhibitors, vasodilators, and antiaggregants. Herein, we report a 78-year-old male patient with a history of clear-cell renal-cell cancer, who presented in the emergency department with critical ischemia in the upper limbs.

scholarly journals Characteristics and Treatment Challenges of Non-Clear Cell Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3807
Author(s):  
Pierangela Sepe ◽  
Arianna Ottini ◽  
Chiara Carlotta Pircher ◽  
Andrea Franza ◽  
Melanie Claps ◽  
...  
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Case Reports ◽  
Treatment Options ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Mtor Inhibitors ◽  
Cell Renal Cell Carcinoma ◽  
Clear Cell Rcc

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

scholarly journals Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Louis Y. El Khoury ◽  
Shuang Fu ◽  
Ryan A. Hlady ◽  
Ryan T. Wagner ◽  
Liguo Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell ◽  
Lower Risk ◽  
Clear Cell ◽  
Cell Cancer ◽  
Low Risk ◽  
Cell Renal Cell Carcinoma ◽  
A Genome ◽  
Size Grade ◽  
Prognostic Power

Abstract Background Despite using prognostic algorithms and standard surveillance guidelines, 17% of patients initially diagnosed with low risk clear cell renal cell carcinoma (ccRCC) ultimately relapse and die of recurrent disease, indicating additional molecular parameters are needed for improved prognosis. Results To address the gap in ccRCC prognostication in the lower risk population, we performed a genome-wide analysis for methylation signatures capable of distinguishing recurrent and non-recurrent ccRCCs within the subgroup classified as ‘low risk’ by the Mayo Clinic Stage, Size, Grade, and Necrosis score (SSIGN 0–3). This approach revealed that recurrent patients have globally hypermethylated tumors and differ in methylation significantly at 5929 CpGs. Differentially methylated CpGs (DMCpGs) were enriched in regulatory regions and genes modulating cell growth and invasion. A subset of DMCpGs stratified low SSIGN groups into high and low risk of recurrence in independent data sets, indicating that DNA methylation enhances the prognostic power of the SSIGN score. Conclusions This study reports a global DNA hypermethylation in tumors of recurrent ccRCC patients. Furthermore, DMCpGs were capable of discriminating between aggressive and less aggressive tumors, in addition to SSIGN score. Therefore, DNA methylation presents itself as a potentially strong biomarker to further improve prognostic power in patients with low risk SSIGN score (0–3).

scholarly journals The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory?

2021 ◽  
Vol 22 (12) ◽  
pp. 6237
Author(s):  
Andrea Marchetti ◽  
Matteo Rosellini ◽  
Veronica Mollica ◽  
Alessandro Rizzo ◽  
Elisa Tassinari ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Treatment Algorithm ◽  
Morning Glory ◽  
Molecular Characteristics ◽  
Cell Renal Cell Carcinoma ◽  
Low Incidence

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.

scholarly journals Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11880
Author(s):  
Hui Zhao ◽  
Junjun Zhang ◽  
Xiaoliang Fu ◽  
Dongdong Mao ◽  
Xuesen Qi ◽  
...  
Keyword(s):  
Renal Cell ◽  
Prognostic Model ◽  
Cox Regression ◽  
Clear Cell ◽  
Cell Cancer ◽  
Data Sets ◽  
Potential Therapeutic Target ◽  
Cell Renal Cell Carcinoma ◽  
Cellular Energy ◽  
Testing Data

The members of the Nedd4-like E3 family participate in various biological processes. However, their role in clear cell renal cell carcinoma (ccRCC) is not clear. This study systematically analyzed the Nedd4-like E3 family members in ccRCC data sets from multiple publicly available databases. NEDD4L was identified as the only NEDD4 family member differentially expressed in ccRCC compared with normal samples. Bioinformatics tools were used to characterize the function of NEDD4L in ccRCC. It indicated that NEDD4L might regulate cellular energy metabolism by co-expression analysis, and subsequent gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A prognostic model developed by the LASSO Cox regression method showed a relatively good predictive value in training and testing data sets. The result revealed that NEDD4L was associated with biosynthesis and metabolism of ccRCC. Since NEDD4L is downregulated and dysregulation of metabolism is involved in tumor progression, NEDD4L might be a potential therapeutic target in ccRCC.

scholarly journals Canadian guideline on genetic screening for hereditary renal cell cancers

2013 ◽  
Vol 7 (9-10) ◽  
pp. 319 ◽  
Author(s):  
M. Neil Reaume ◽  
Gail E. Graham ◽  
Eva Tomiak ◽  
Suzanne Kamel-Reid ◽  
Michael A.S. Jewett ◽  
...  
Keyword(s):  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Healthcare Providers ◽  
Specific Reference ◽  
Ideal Model ◽  
Canadian Guideline ◽  
Referral Criteria ◽  
Consensus Statements ◽  
History Of

Background: Hereditary renal cell cancer (RCC) is an ideal model for germline genetic testing. We propose a guideline of hereditary RCC specific criteria to suggest referral for genetic assessment.Methods: A review of the literature and stakeholder resources for existing guidelines or consensus statements was performed. Referral criteria were developed by expert consensus.Results: The criteria included characteristics for patients with RCC (age ≤45 years, bilateral or multifocal tumours, associated medical conditions and non-clear cell histologies with unusual features) and for patients with or without RCC, but a family history of specific clinical or genetic diagnoses.Conclusions: This guideline represents a practical RCC-specific reference to allow healthcare providers to identify patients who may have a hereditary RCC syndrome, without extensive knowledge of each syndrome. RCC survivors and their families can also use the document to guide their discussions with healthcare providers about their need for referral. The criteria refer to the most common hereditary renal tumour syndromes and do not represent a comprehensive or exclusive list. Prospective validation of the criteria is warranted.

scholarly journals Newly-presented potential targeted drugs in the treatment of renal cell cancer

2016 ◽  
Vol 11 (1) ◽  
pp. 122-129
Author(s):  
Jingfeng Zhang ◽  
Qinsi He ◽  
Zhi Zheng
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibody ◽  
Cell Carcinoma ◽  
Small Molecule ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Targeted Drugs ◽  
Cell Renal Cell Carcinoma ◽  
Targeted Treatments

AbstractRenal cell carcinoma (RCC) is the most frequent form of renal cancer, and is associated with a high frequency of metastasis. While, there is few therapeutic methods can substantially prolong survival. Superior to cytokine therapy with IL-2 and/or IFN-a, several newer targeted treatments are available for the treatment of patients with advanced conventional (clear cell) renal cell carcinoma (RCC), which received improved outcomes. These newer targeted treatments include the multi-targeted tyrosine kinase inhibitors (TKIs, sorafenib, sunitinib, pazopanib, and axitinib), the humanised antivascular endothelial growth factor (VEGF) monoclonal antibody [bevacizumab combined with interferon (IFN)-a], and mTOR (mammalian target of rapamycin) complex 1 kinase inhibitors (everolimus and temsirolimus). However, these targeted drugs are still associated with limited efficacy and high toxicity, so there is still a strong need for further discovery of new targeted drugs. In the present manuscript, we summarize newly-presented potential targeted drugs for RCC, classified by drug characteristic, small molecule, small molecule combination, monoclonal antibody, polysaccharides, organometals and peptides.

scholarly journals The Role of Everolimus in Renal Cell Carcinoma

2015 ◽  
Vol 2 (4) ◽  
pp. 187-194
Author(s):  
Malek Meskawi ◽  
Roger Valdivieso ◽  
Paolo Dell’Oglio ◽  
Vincent Trudeau ◽  
Alessandro Larcher ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Phase Iii ◽  
Current Evidence ◽  
Second Line ◽  
Cell Renal Cell Carcinoma ◽  
Line Therapy

Everolimus (RAD001) is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC). In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs). However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib), which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

scholarly journals Ubiquitin-specific protease 44 inhibits cell proliferation and migration via inhibition of JNK pathway in clear cell renal cell cancer

2019 ◽  
Author(s):  
Jiangqiao Zhou ◽  
Tianyu Wang ◽  
Tao Qiu ◽  
Zhongbao Chen ◽  
Xiaoxiong Ma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Cell Renal Cell Carcinoma ◽  
Jnk Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Ccrcc Cell ◽  
Proliferation And Migration

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. USP44 has been reported to be involved in various cancers. This study aimed to investigate the function role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from TCGA data portal and GSO database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. The function of USP44 in cell proliferation and migration was assessed by cellular and molecular analysis. Results: USP44 was lowly expressed in the ccRCC cancer tissues compared to the normal tissue. Further, USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival . USP44 overexpression significantly inhibited tumor cell proliferation and migration of 786-O cell as well as Caki-1 cell. In addition, USP44 overexpression also prohibited cell proliferation by up-regulating P21, down-regulating Cyclin D1 expression, and inhibited cell migration by up-regulating MMP2 and MMP9 expression. In contrast, USP44 knockdown enhances ccRCC cell proliferation and migration. Furthermore, the USP44 function in inhibiting ccRCC cell proliferation and migration is associated with the phosphorylation level of JNK. Conclusion: In summary, this study showed that USP44 may be a marker in predicting the ccRCC progression and USP44 inhibits ccRCC cell proliferation and migration dependent on the JNK pathway.

scholarly journals Combination of pembrolizumab and axitinib: a new gold standard in the first-line therapy for metastatic clear-cell renal-cell carcinoma?

2020 ◽  
Vol 16 (3) ◽  
pp. 29-37
Author(s):  
R. A. Gafanov ◽  
A. G. Dzidzaria ◽  
I. B. Kravtsov ◽  
S. V. Fastovets
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Clinical Results ◽  
First Line ◽  
Cell Renal Cell Carcinoma

The treatment strategy for metastatic renal cell carcinoma (mRCC) has evolved with the emergence of anti-angiogenic drugs, in particular tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors (ICIs). Both treatment options improved patient outcomes and altered the natural history of mRCC. Clinical studies have focused on evaluating combination regimens containing ICI and VEGFR-targeted TKIs. The combination of axitinib with pembrolizumab (KEYNOTE-426) showed better results compared to sunitinib in patients with mRCC who had not previously received systemic therapy. In this article, we discuss the rationale for the combination of ICI and TKI based on preclinical data, as well as the clinical results obtained with the combination of axitinib with pembrolizumab in first-line patients in clinical trials.

scholarly journals Metastatic Lesion of the Tibia from Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Piotr Młodożeniec ◽  
Krzysztof Balawender ◽  
Mateusz Zasadny
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Local Therapy ◽  
X Rays ◽  
Cell Renal Cell Carcinoma ◽  
Lower Limb Pain

Introduction. Renal cell carcinoma is responsible for 3% of all cancers, with the highest incidence occurring in Western countries. Additionally, in patients with osseous metastasis, only 3% occur within the tibia. Rarely, a patient presents with a primary complaint of lower limb pain in advanced metastatic renal cell carcinoma. Case Presentation. The patient arrived at the emergency department with a primary complaint of left ankle pain. Ankle X-rays demonstrated a lytic lesion involving the medial malleolus with possible metastatic disease. CT scan confirmed a tumor within the right kidney. The patient was treated with a laparoscopic radical nephrectomy with histopathologic confirmation of clear cell renal cell carcinoma. Biopsy was then performed of the tibial lesion, confirming metastatic clear cell renal cell carcinoma. The tibial lesion was treated with local radiotherapy, and because of the progression of the tibia lesion, a decision was made to amputate the leg. Additionally, the patient was enrolled to sunitinib treatment and was disease free at one year of follow-up. 13 months after diagnosis of cancer, she was suffering a major stroke of the brain that caused her to die. Conclusion. The treatment of patients with osseous metastases of renal cell cancer depends on the number of metastases, location of metastases, and overall health of the patient. We performed an overview of available literature and provided a summary regarding the use of cytoreductive nephrectomy, local therapy, target therapy, and bone-targeting agents in the treatment of metastatic renal cell cancer.

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