Prognostic value of the apoptotic index analysed jointly with selected cell cycle regulators and proliferation markers in non-small cell lung cancer

Dworakowska, Dorota; Jassem, Ewa; Jassem, Jacek; Karmolinski, Andrzej; Łapiński, M; Tomaszewski, Dariusz; Rzyman, Witold; Jaskiewicz, K; Sworczak, Krzysztof; Grossman, Ashley

doi:10.1016/j.lungcan.2009.01.008

Cited by 19 publications

(16 citation statements)

References 36 publications

(58 reference statements)

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“…This method supports the identification of ovarian cells with characteristic symptoms of apoptosis, including those in early stages of suicide when morphological changes are not clearly pronounced (Jiang et al 2011). In most studies (including the present work), the presence of apoptotic cells is determined with the use of the AI, which indicates the percentage of apoptotic cells in 1000 cells (Dworakowska 2005). In our experiment, the AI median for the entire group of 30 bitches reached 13.…”

Section: Discussionsupporting

confidence: 72%

“…Multiple fields must be evaluated when positively stained nuclei are not evenly distributed. PCNA expression varies in different sections of the same ovarian tissue; therefore, the final percentage of stained nuclei is strictly determined by the size of the analysed specimen and the number of viewed fields (Dworakowska 2005). The proliferative activity of the ovarian follicles studied was less pronounced in both experimental groups, as demonstrated by the overall PI median of 25.49.…”

Section: Discussionmentioning

confidence: 92%

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The effect of experimental low zearalenone intoxication on ovarian follicles in pre-pubertal bitches

Gajęcka¹

2013

Polish Journal of Veterinary Sciences

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Companion animals, including bitches, may be exposed to zearalenone (ZEN) toxins that are often present in feed, and ZEN intoxication may lead to ovarian dysfunction. This study involved evaluation of the degree of ZEN-induced hypo stimulation of ovary by determination of proliferative and apoptotic indices and description of the ultra-structural organization of ovarian follicles in pre-pubertal bitches subjected to experimental, long-term exposure to low-dose ZEN mycotoxicosis. The experiment involved 30 clinically healthy, immature Beagle bitches aged approximately 70 days with initial average body weight of 8 kg, randomly divided into three groups of 10 animals each: two experimental groups (EI and EII) and a control group (C). Over a period of 42 days, ZEN was administered per os to EI animals at a dose of 50 μg/kg BW, and to EII bitches at a dose of 75 μg/kg BW. Control group animals were fed placebo containing no ZEN for 42 days. Analytical samples of the mycotoxin were administered daily in gelatin capsules before morning feeding. All the bitches were subjected to ovario-hysterectomy at the end of the experiment. Proliferation index (PCNA method) and apoptotic index (TUNEL test) values were determined by immune-histological analyses. The median for apoptotic index was determined at 13.45 for group EI, 17.84 for group EII, and 8.59 for group C. The median for proliferation index was determined at 35.25 for group EII, 42.44 for group EI, and 70.60 for group C. The results of ultra-structural examinations of the ovaries revealed that experimental, ZEN-induced hyperestrogenism enhanced apoptosis and lowered the proliferative ability of follicular cells what contributed to organelle destruction in pre-pubertal bitches. The changes observed were particularly advanced in EII animals, which were administered a higher dose of ZEN.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 92%

The effect of experimental low zearalenone intoxication on ovarian follicles in pre-pubertal bitches

Gajęcka¹

2013

Polish Journal of Veterinary Sciences

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“…However, we found that lncRNA DLEU2 promoted the proliferation and invasion of NSCLC cells, but inhibition of lncRNA DLEU2 reversed these effects. PCNA and MMP‐2, tumour proliferation and invasion related markers, act as the poor prognostic factors in NSCLC . We found that lncRNA DLEU2 induced their expression levels and acted as an oncogene in NSCLC.…”

Section: Discussionmentioning

confidence: 78%

LncRNA DLEU2 accelerates the tumorigenesis and invasion of non–small cell lung cancer by sponging miR‐30a‐5p

Zhao

Gao

et al. 2019

J Cellular Molecular Medi

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Long non‐coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of non–small cell lung cancer (NSCLC). However, how lncRNA deleted in lymphocytic leukaemia 2 (DLEU2) contributes to NSCLC remains undocumented. The clinical significance of lncRNA DLEU2 and miR‐30a‐5p expression in NSCLC was analysed by using fluorescence in situ hybridization and TCGA cohorts. Gain‐ and loss‐of‐function experiments as well as a NSCLC tumour model were executed to determine the role of lncRNA DLEU2 in NSCLC. DLEU2‐sponged miR‐30a‐5p was verified by luciferase reporter, and RIP assays. Herein, the expression of lncRNA DLEU2 was elevated in NSCLC tissues, and its high expression or low expression of miR‐30a‐5p acted as an independent prognostic factor of poor survival and tumour recurrence in NSCLC. Silencing of lncRNA DLEU2 repressed the tumorigenesis and invasive potential of NSCLC, whereas re‐expression of lncRNA DLEU2 showed the opposite effects. Furthermore, lncRNA DLEU2 harboured a negative correlation with miR‐30a‐5p expression in NSCLC tissues and acted as a sponge of miR‐30a‐5p, which reversed the tumour‐promoting effects of lncRNA DLEU2 by targeting putative homeodomain transcription factor 2 in NSCLC. Altogether, lncRNA DLEU2 promoted the tumorigenesis and invasion of NSCLC by sponging miR‐30a‐5p.

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“…In another study by Langendijk et al (Langendijk et al 2000), high AI was associated with worse local control, more distant metastases and a significantly worse overall survival in patients with inoperable NSCLC treated with high-dose radiotherapy. Furthermore, Dworakowska et al (Dworakowska et al 2009) found that NSCLC patients with very high AI values combined with very high PCNA (proliferating cell nuclear antigen) labeling index had a particularly poor prognosis and concluded that joint analysis of several apoptosis, proliferation and cell cycle regulation biomarkers may provide more useful prognostic information as compared to AI alone. On the other hand, other researchers failed to reveal any association between AI and survival in patients with NSCLC (Gorgoulis et al 2000).…”

Section: Reviewmentioning

confidence: 99%

“…The aim of this study was to perform a review of the MEDLINE literature in an attempt to determine the exact clinical value of tumor necrosis and apoptotic index (AI) as prognostic biomarkers in NSCLC. We retrieved 28 papers, investigating the prognostic significance of necrosis and/or apoptosis in patients with primary NSCLC (Tables 1 and 2) (Lipford et al 1984; Elson et al 1988; Lee et al 1989; Roeslin et al 1991; Roberts et al 1992; Shahab et al 1992; Tormanen et al 1995; Kessler et al 1996; Goldstein et al 1999; Swinson et al 2002; Poleri et al 2003; Khan et al 2004; Rena et al 2007; Inoue et al 2008; Cho et al 2008; Sardari Nia et al 2010; Kiliçgün et al 2010; Park et al 2011; Pataer et al 2012; Tantraworasin et al 2013; Komaki et al 1996; Tanaka et al 1999; Matturi et al 1999; Langendijk et al 2000; Gorgoulis et al 2000; Hwang et al 2001; Puglisi et al 2002; Dworakowska et al 2009). Studies on apoptosis-related genes were excluded.…”

Section: Introductionmentioning

confidence: 99%

Necrosis and apoptotic index as prognostic factors in non-small cell lung carcinoma: a review

et al. 2014

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Necrosis and apoptosis represent two pathogenetically distinct types of cell death. Necrosis is associated with pathologic conditions while apoptosis is a physiological process of programmed cell death, which is associated with normal tissue growth and is frequently impaired in various forms of cancer. Tumor necrosis and apoptotic index (AI) have been previously evaluated as prognostic biomarkers in lung cancer, but their exact clinical value remains unclear. The aim of this study was to perform a systematic review of the MEDLINE literature on the prognostic significance of these histopathological markers in patients with non-small cell lung carcinoma (NSCLC). Although a substantial body of evidence suggests that tumor necrosis may be a strong predictor of aggressive tumor behavior and reduced survival in patients with NSCLC, the independent prognostic value of this biomarker remains to be firmly established. Furthermore, previous data on the prognostic significance of apoptotic index in NSCLC are relatively limited and largely controversial. More prospective studies are necessary in order to further validate tumor necrosis and AI as prognostic markers in NSCLC.

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Prognostic value of the apoptotic index analysed jointly with selected cell cycle regulators and proliferation markers in non-small cell lung cancer

Cited by 19 publications

References 36 publications

The effect of experimental low zearalenone intoxication on ovarian follicles in pre-pubertal bitches

The effect of experimental low zearalenone intoxication on ovarian follicles in pre-pubertal bitches

LncRNA DLEU2 accelerates the tumorigenesis and invasion of non–small cell lung cancer by sponging miR‐30a‐5p

Necrosis and apoptotic index as prognostic factors in non-small cell lung carcinoma: a review

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