Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy

Watanabe, Soichi; Miyata, Yasuyoshi; Kanda, Shigeru; Iwata, Tohru; Hayashi, Tomayoshi; Kanetake, Hiroshi; Sakai, Hideki

doi:10.1007/s00432-009-0718-x

Cited by 14 publications

(21 citation statements)

References 27 publications

(34 reference statements)

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“…Similarly, patients were divided according to age at operation, taking the median age as the cutoff value. To evaluate the apoptotic cells, we used 2 parameters: the proportions of cleaved caspase-3-positive and TUNELpositive cells [29]. All specimens were examined using a Nikon E-400 microscope, and digital images were captured (model DU100, Nikon, Tokyo, Japan).…”

Section: Discussionmentioning

confidence: 99%

“…A consecutive section from each sample processed without the primary antibody was used as a negative control. In situ labeling for detection of apoptotic cells was performed as described previously [29]. We used the Apop Tag In Situ Apoptosis Detection Kit (Intergen Company, Purchase, NY) based on terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL).…”

Section: Immunohistochemistry and Terminal Deoxynucleotidyl Transferamentioning

confidence: 99%

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High density of tryptase-positive mast cells in patients with renal cell carcinoma on hemodialysis: correlation with expression of stem cell factor and protease activated receptor-2

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemistry and Terminal Deoxynucleotidyl Transferamentioning

confidence: 99%

High density of tryptase-positive mast cells in patients with renal cell carcinoma on hemodialysis: correlation with expression of stem cell factor and protease activated receptor-2

et al. 2012

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“…As mentioned, the scenarios delineated above are difficult to reconcile with the significant spontaneous apoptosis rates observed in several human tumor types which often exceed those of corresponding normal tissues [138,139,140,141,142,143,144,145,146,147,148,149]. In fact, spontaneous apoptosis occurring in malignant neoplasms was already noted in the seminal publication of Kerr et al (1972) that coined the term apoptosis [150].…”

Section: The Occurrence Of Spontaneous Apoptosis In Tumorsmentioning

confidence: 99%

“…For small cell lung carcinoma an AI of 2.65% (mean) was reported [147], for prostate cancer an AI of 1.9% [148], and for gastric cancer an AI of 1.97% [146]. Several studies on breast cancer have even demonstrated a correlation between the rate of apoptosis and tumor progression [138,139,142].…”

Section: The Occurrence Of Spontaneous Apoptosis In Tumorsmentioning

confidence: 99%

The Enigmatic Roles of Caspases in Tumor Development

Jäger

Zwacka

2010

Cancers

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One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors.

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“…As positive control for the TUNEL method, prostate cancer tissue following hormone therapy was used. These prostate specimens were obtained from Nagasaki University Graduate School of Biomedical Sciences (Nagasaki, Japan) and their reliability was confirmed in our previous study (24). Positive and negative control sections were prepared.…”

Section: Methodsmentioning

confidence: 94%

Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

et al. 2016

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Abstract. Fps/Fes related (Fer) is a non-receptor tyrosine kinase that is expressed in fibroblasts, immune cells and endothelial cells. Fer serves an important pathological role in cell survival, angiogenesis and the immune system. However, the pathological role of Fer expression in the stromal cells surrounding renal cell carcinoma (RCC) has not been previously investigated. In the present study, immunohistochemical analysis of Fer was performed using the formalin-fixed tissue samples of 152 patients with RCC. The proliferative and apoptotic indices were used to represent the percentage of proliferation marker protein Ki-67-and cleaved caspase-3-positive cells, respectively. The microvessel density was defined as the number of cluster of differentiation (CD) 31-positively stained vessels/mm 2 . In addition, CD57 + and CD68 + cells were counted using semi-quantification of natural killer (NK) cells and macrophages. Fer expression in stromal cells was negatively associated with Fuhrman grade, pathological tumor stage and metastasis (P<0.001). Fer expression in stromal cells was negatively associated with CD68 + macrophage density, whereas it was positively associated with CD57 + NK cell density. Kaplan-Meier estimators indicated that decreased stromal Fer expression was a predictive marker of decreased cause-specific survival rate (P<0.001). Furthermore, low expression of Fer was identified as being an independent marker of decreased cause-specific survival using multivariate analysis (hazard ratio, 7.4; 95% confidence interval, 1.7-33.0; P<0.001). The results of the present study suggested that low Fer expression in stromal cells is associated with increased malignant aggressiveness and decreased survival in patients with RCC. CD57 + NK cell and CD68 + macrophage regulation in cancer-stromal tissue is considered to affect RCC pathology.

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Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy

Abstract: NHT did not influence XIAP expression. We speculate that the inhibition of XIAP expression may reinforce the apoptotic effect of NHT and improve the prognosis in patients with prostate cancer.

Cited by 14 publications

References 27 publications

High density of tryptase-positive mast cells in patients with renal cell carcinoma on hemodialysis: correlation with expression of stem cell factor and protease activated receptor-2

High density of tryptase-positive mast cells in patients with renal cell carcinoma on hemodialysis: correlation with expression of stem cell factor and protease activated receptor-2

The Enigmatic Roles of Caspases in Tumor Development

Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

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