Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations

Samaras, Vassilis; Tsopanomichalou, Maria; Stamatelli, Angeliki; Arnaoutoglou, Christos; Samaras, Efstathios; Arnaoutoglou, Marianthi; Poulias, Hercules; Barbatis, Calypso

doi:10.1186/1746-1596-4-7

Cited by 13 publications

(8 citation statements)

References 37 publications

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“…Increased p38-MAPK and SPOP expression in primary culture indicates their role in tumour progression. These findings were found consistent with earlier results, wherein p-p38 expression was shown to be high in high grade of RCC 16 . High expression of SPOP in metastatic RCC compared to normal kidney tissue can be used for diagnosis of primary site by immunohistochemistry/RT-PCR of metastatic lesion 5 .…”

supporting

confidence: 83%

Speckle-Type POZ Protein Acts as a Predictive Biomarker for MTOR Target Therapy in Renal Cell Carcinoma

et al. 2016

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Renal cell carcinoma (RCC) develops resistance to most of the conventional therapies. In recent years inhibitors are being used to interfere with growth of cancer cells at molecular level and are found to be the most effective treatment option. However, some patients have to deal with severe side effects. Till date there have been no specific predictive biomarkers available to predict the target response and patient's stratification. We evaluate the expression of speckletype POZ protein (SPOP) as a predictive biomarker in the presence of mTOR target therapy. Tissue samples were collected after nephrectomies from patients with RCC. Further primary culture was established from tissues of low-and high-grade RCC. Working concentration of inhibitors (CCI-779 and SB203580) was selected by MTT assay on A-498 cell line. Western blot was performed to study the p38MAPK, mTOR and SPOP protein expression. Primary culture showed more than 70% positivity for pan-cytokeratin. The concentration of 20 M of CCI-799 and 25 M SB203580 caused 30% and 20% cell death respectively. Expression of SPOP protein was decreased in CCI-779-treated cells. The combined treatment of CCI-779 and SB203580 had more inhibitory effects on SPOP in all cells types. However, SB203580 had no effect on SPOP expression. The results underline that, SPOP could be used as a potential predictive biomarker to assess the response of therapy with mTOR inhibitor (CCI-779).

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confidence: 83%

Speckle-Type POZ Protein Acts as a Predictive Biomarker for MTOR Target Therapy in Renal Cell Carcinoma

et al. 2016

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“…Actually, low expression of caspase‐8 due to promoter methylation was shown to be associated with poor survival in neuroblastoma20 and medulloblastoma12 as well as relapse of glioblastoma multiforme 21. In clear cell renal cell, caspase‐8 expression is linked to Fuhrman's grade and survival 22. Interestingly, a recently described 6‐nucleotide insertion–deletion polymorphism in the CASP8 promoter leading to decreased caspase‐8 expression may be associated with reduced risk of developing many types of human cancers, including colorectal carcinoma, possibly because of increased T‐cell resistance to activation‐induced apoptosis by cancer cells 23…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic significance of APAF‐1, caspase‐8 and caspase‐9 in stage II/III colon carcinoma: Caspase‐8 and caspase‐9 is associated with poor prognosis

Sträter

Herter

Merkel

et al. 2010

Intl Journal of Cancer

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Apoptosis protease activating factor-1 (APAF-1), caspase-8 and caspase-9 are important factors in the execution of death signals. To study their prognostic influence in colon carcinoma, expression of APAF-1, caspase-8 and caspase-9 was determined by immunohistochemistry in normal colon mucosa (n 5 8) and R0-resected stage II/III colon carcinomas (n ! 124) using a semiquantitative score. Staining results were correlated with disease-free survival by Kaplan-Meier estimates, and multivariate Cox analyses were performed. In normal colon, APAF-1 and caspase-8 are most strongly expressed in the luminal surface epithelium, whereas caspase-9 is expressed all along the crypt axis. In colon carcinomas, there is considerable variability in the expression of these proapoptotic factors, although complete loss of caspase-8 and caspase-9 is rare. APAF-1 expression did not correlate with disease-free survival. Instead, both expression of caspase-9 and high-level expression of caspase-8 in a majority of tumor cells were significantly associated with adverse prognosis (p 5 0.004 and p 5 0.029, respectively). The influence of caspase-8 expression was mainly seen in patients with stage III colon carcinoma (p 5 0.011), whereas the prognostic influence of caspase-9 expression was significant in stage II cases (p 5 0.037) and just failed to be significant in stage III tumors (p 5 0.0581). After adjusting for confounding factors in a multivariate Cox analysis, the effect of caspase-9 in predicting disease-free survival was confirmed (p 5 0.003). Our data suggest that, in colon carcinomas, expression of caspase-8 and caspase-9 is significantly associated with poor survival. Caspase-9 may be an independent prognosticator in colon carcinoma.

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“…It was reported that either ERK1/2 or p38 can phosphorylate HIF-1 [111][112][113], while inhibition of these two MAPKs was capable of blocking the expression of reporter genes of the HIF-1 activity [114]. More recently, the use of p38 as a potential biomarker of ccRCC, which correlates well with Fuhrman grade, has been proposed [115]. In short, there is noticeable evidence suggesting that MAPK signaling pathways may be critical in the biological effects of the HIF in ccRCC and that the activation of MAPK signaling pathways plays a crucial role in tumorigenesis, metastasis, and angiogenesis of RCC.…”

Section: Renal Tumorigenesismentioning

confidence: 99%

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Luo

Shi

et al. 2016

Cell Physiol Biochem

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Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis. However, the underlying signaling mechanisms, whereby hypoxia alters cellular behaviors, remain poorly understood. Mitogen-activated protein kinases (MAPKs) are key signal-transducing enzymes activated by a wide range of extracellular stimuli, including hypoxia/ischemia. There are four major family members of MAPKs: the extracellular signal-regulated kinases-1 and -2 (ERK1/2), the c-Jun N-terminal kinases (JNK), p38 MAPKs, and extracellular signal-regulated kinase-5 (ERK5/BMK1). Recent studies, including ours, suggest that these MAPKs are differentially involved in renal responses to hypoxic/ischemic stress. This review will discuss their changes in hypoxic/ischemic pathophysiology with acute kidney injury, chronic kidney diseases and renal carcinoma.

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Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations

Cited by 13 publications

References 37 publications

Speckle-Type POZ Protein Acts as a Predictive Biomarker for MTOR Target Therapy in Renal Cell Carcinoma

Speckle-Type POZ Protein Acts as a Predictive Biomarker for MTOR Target Therapy in Renal Cell Carcinoma

Expression and prognostic significance of APAF‐1, caspase‐8 and caspase‐9 in stage II/III colon carcinoma: Caspase‐8 and caspase‐9 is associated with poor prognosis

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

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