DNA Flow Cytometric Studies of 66 Human Lung Tumors Analyzed Before Treatment

Salvati, Franco; Teodori, Laura; Gagliardi, Luigi; Signora, M; Aquilini, Mauro; Storniello, G

doi:10.1378/chest.96.5.1092

Cited by 41 publications

(11 citation statements)

References 22 publications

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“…One study (Del Carlo Bernardi et al, 1997) defined diploid tumours as tumours presenting a DI ≤ 1.2 a feature shared by hypodiploid tumours Stipa et al, 1993). 3 publications were preliminary reports of DNA content-survival relationship (Salvati et al, 1989;Ichinose et al, 1991;Ogawa et al, 1991) but otherwise subsequently reported by the respective groups (Ogawa et al, 1992;Ichinose et al, 1993; Three studies included less than 10% small cell lung cancers.…”

Section: Resultsmentioning

confidence: 99%

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

Choma

Daurès²,

Quantin

et al. 2001

Br J Cancer

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Ploidy status predicts disease-free intervals and short-term survival in numerous human malignancies (Barlogie et al 1983; Friedlander et al 1984). In lung cancer, the prognostic value of ploidy is controversial. The effect of ploidy status on patient outcome has been investigated particularly in non-small-cell lung cancers (NSCLC), a group of different histologies including squamous cell carcinoma (SQC), adenocarcinoma (ADC) and large cell carcinoma (LCC). Although authors from different laboratories have suggested that patients presenting an aneuploid tumour have a shorter survival than patients presenting a nearly diploid tumour, others did not find such a difference. Many factors could explain the differences in estimating the ploidy-survival relationship. Possible interpretation could lie in the heterogeneity of the abnormal DNA patterns gathered under the common term of aneuploidy, i.e. hyperdiploidy, hypodiploidy and multiploidy . Differences in methods used to analyse DNA content could also have been responsible for the above-mentioned controversy inasmuch as some studies were founded on flow cytometry data whereas others used static cytometry. Finally, the difference might be related to the histological and clinical characteristics of the studied patient population.We therefore made a meta-analysis of published studies aimed at determining the prognostic effect of aneuploidy in surgically resected NSCLC. TRIALS AND METHODS Eligibility criteriaThe most conventional definition of ploidy status is as follows: ploidy was determined for each specimen using DNA index which represents the ratio of the cell DNA content of tumour G 0/1 cells to the diploid G 0/1 peak (2n). A coefficient of variation (CV) for this DNA index (DI) has been specifically defined for each study. Thus, a DNA index = 1 defined a near diploid specimen i.e. only one peak of G 0/1 cells in the near diploid region (2n, DNA index = 1) with few G 2 M tumour cells in the tetraploid region (4n Summary In lung cancer, DNA content abnormalities have been described as a heterogeneous spectrum of impaired tumour cell DNA histogram patterns. They are merged into the common term of aneuploidy and probably reflect a high genotypic instability. In non-small-cell lung cancer, the negative effect of aneuploidy has been a subject of controversy inasmuch as studies aimed at determining the survival-DNA content relationship have reported conflicting results. We made a meta-analysis of published studies aimed at determining the prognostic effect of aneuploidy in surgically resected non-small-cell lung cancer. 35 trials have been identified in the literature. A comprehensive collection of data has been constructed taking into account the following parameters: quality of specimen, DNA content assessment method, aneuploidy definition, histology and stage grouping, quality of surgical resection and demographic characteristics of the analysed population. Among the 4033 assessable patients, 2626 suffered from non-small-cell lung cancer with aneuploid DNA content ...

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Section: Resultsmentioning

confidence: 99%

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

Choma

Daurès²,

Quantin

et al. 2001

Br J Cancer

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“…Together, these results indicate that SP600125 promotes inactive p53 accumulation in A549 cells and that effective p53 degradation could not occur upon treatment with SP600125 in both the cytosol and nucleus in spite of the significant increase of the formation of the Mdm2ep53 complex. For example, an aneuploid cell population was detected at a high frequency from lung cancer tissue but not in normal tissue (Salvati et al, 1989) 3. Expression of cell cycle-associated proteins in SP600125-treated A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Induction of endoreduplication by a JNK inhibitor SP600125 in human lung carcinoma A 549 cells

Miyamoto-Yamasaki

Yamasaki

Tachibana

et al. 2007

Cell Biology International

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The effect of the pan c-Jun N-terminal kinase (JNK) inhibitor SP600125 on the proliferation of human lung carcinoma A549 cells has been evaluated. We have shown that SP600125 completely inhibited the proliferation of A549 cells, the cycle arrest being in G2/M phase. When cells were treated with SP600125 for >12h, a cell population with DNA content of 4n to 8n was detected. Moreover, the effect of SP600125 on the expression of cell cycle related proteins was an upregulation of p53 protein accompanied by an increase in its molecular mass. Prolonged SP600125 treatment downregulated p21, Bax and Mdm2 expression, but increased the level of the cellular p53-Mdm2 complex. Taken together, we show that SP600125 could induce G2/M cell cycle arrest and endoreduplication in a p21 independent manner, and that SP600125 could also post-translationally modify p53 to modify its function. Our data show that basic JNK activity plays an important role in the progression of the cell cycle at G2/M cell phase.

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“…A multiploidy or a hyperdiploidy had no effect on prognosis. Bengtsson, 1981;Volm et al, 1985;Abe et al, 1985;Zimmerman et al, 1987;Salvati et al, 1988;Dazzi et al, 1990), whereas others failed to demonstrate this relationship (Bunn et al, 1983;Cibas et al, 1989;Cheon et al, 1993 …”

Section: Surgerymentioning

confidence: 99%

“…The effect of ploidy status on patient outcome has been investigated particularly in non-small-cell lung cancers (NSCLCs), a group of different histologies including squamous cell carcinoma (SQC), adenocarcinoma and large-cell carcinoma (LCC). Although authors from different laboratories have suggested that patients presenting an aneuploid tumour have a shorter survival than patients presenting a nearly diploid tumour (Blondal et al, 1981;Volm et al, 1985;Zimmerman et al, 1987;Salvati et al, 1988;Dazzi et al, 1990), others did not find such a difference (Bunn et al, 1983;Cibas et al, 1989;Cheon et al, 1993). It is noteworthy that aneuploidy defines a heterogeneous group of tumours differing by their patterns of DNA histograms, namely: hyperdiploidy, hypodiploidy and multiploidy (Barlogie et al, 1980).…”

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confidence: 99%

Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers

Pujol

Simony²,

Jolimoy³

et al. 1996

Br J Cancer

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Summary One hundred and thirty-seven lung cancer patients (123 non-small-cell lung cancers (NSCLC), 10 small-cell lung cancers (SCLC) and four carcinoid tumours) who underwent surgery in an attempt at complete resection were prospectively entered in a study whose aim was to determine the prognostic significance of a hypodiploidy or a multiploidy pattern of tumour cell DNA content and a high immunohistochemical reactivity of a

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DNA Flow Cytometric Studies of 66 Human Lung Tumors Analyzed Before Treatment

Cited by 41 publications

References 22 publications

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

Induction of endoreduplication by a JNK inhibitor SP600125 in human lung carcinoma A 549 cells

Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers

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