Comparison of S‐phase fractions measured by flow cytometry and autoradiography in human transplant tumors

Feichter, G. E.; Czech, Wolfgang; Haag, D.; Futterman, G; Loehrke, Heinz; Abel, Ulrich

doi:10.1002/cyto.990090615

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…A number of previous authors have compared FCM DNA analysis to other methods of assessing proliferative fraction in mammary neoplasia [4,8,10,12,14,20,25], including one which analyzed PCNA staining [3]. These studies report statistically significant, but imperfect, associations between various proliferation indices, with overall correlations similar to ours.…”

Section: Discussionsupporting

confidence: 74%

Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer

Visscher

Wykes

Kubus

et al. 1992

Breast Cancer Res Tr

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Kinetic index determined by enumeration of neoplastic cells positive for proliferative cell nuclear antigen (PCNA) in 70 breast carcinomas (avidin-biotin immunoperoxidase technique) was compared to synthesis-phase fraction (S-phase, or SPF) values obtained by flow cytometry (FCM) using a multiparametric, 2 color method (dual-label propidium iodide/cytokeratin-FITC). The percent PCNA positive tumor cells (12.5% mean, range 1-28%) was significantly greater in aneuploid tumors (14.2% mean, N = 35) compared to diploid range tumors (10.7% mean, N = 35) (p less than 0.05), and was correlated with SPF derived from ungated DNA histograms (12.5% mean +/- 5.5%, r = 0.45, p less than 0.001). Marginally stronger statistical correlations were observed between the PCNA index and SPF values calculated from cytokeratin-gated (15.8% mean, r = 0.53, p less than 0.001) DNA histograms or from SPF values obtained following linear baseline debris subtraction (mean = 8.1%, r = 0.48, p less than 0.001). Significant associations were identified between PCNA index and prognostically important clinicopathologic parameters including nuclear grade (p = 0.014), presence of necrosis (p = 0.005), and angiolymphatic invasion (p = 0.003). We conclude: 1) PCNA index is comparable to FCM SPF and correlates with factors of known prognostic importance in carcinoma of the breast; 2) baseline debris and contaminating events derived from non-epithelial cells both represent significant artifacts in proliferative fraction estimates derived from FCM DNA histograms; and 3) multiparametric analysis may represent one means of improving the specificity and clinical value of FCM SPF determinations.

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Section: Discussionsupporting

confidence: 74%

Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer

Visscher

Wykes

Kubus

et al. 1992

Breast Cancer Res Tr

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“…These were calculated auto matically. Only in a few cases was a background subtraction necessary [13] Based on our data (table 2) a significantly (p< 0.0005) increased relapse rate can be expected in cases with more than 15% S phase. However, such a high rate is significantly (p< 0.0005) correlated with aneuploidy ( fig.…”

Section: Resultsmentioning

confidence: 95%

“…The question of whether and from which percentage on it may influence the prognosis depends on the tumor type and preparation methods [21][22][23][24], Also, background correction influences the data [13,25] and can even falsify them when the "debris' contains microcells [26]. In melanoma, S phases exceeding 15% seem to be of prognostic signifi cance.…”

Section: Discussionmentioning

confidence: 99%

DNA Flow Cytometry in the Prognosis of Primary Malignant Melanoma

Bartkowiak¹,

Schümann²,

Otto³

et al. 1991

Oncology

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DNA flow cytometry was carried out on 804 primary melanomas. The data were analyzed with a follow-up of 24–96 months. 57% of the cases were diploid, 32% had one abnormal cell population, and 11% were multiclonal. In 8% of the aneuploid tumors there were cell lines in the hypertetraploid range. A reliable S phase determination was possible in 524 cases. Among these 11 % had an S phase exceeding 15%. Using an increased tumor thickness, relapse rate and mortality as criteria of tumor progression, aneuploidy and multiclonality, the occurrence of hypertetraploid cell lines and a high S phase ( > 15%) proved to be correlated with a poor prognosis.

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“…The Dean-Jett model was applied to evaluate G1/S/G2-phase DNA content (%). 62 Analysis of cell cycle was performed with asynchronous population of cells because serum-starvation led to the induction of cell fusion into multinucleated cells, thereby directly affecting their cell cycle.…”

Section: Methodsmentioning

confidence: 99%

Functional KCa1.1 channels are crucial for regulating the proliferation, migration and differentiation of human primary skeletal myoblasts

Tajhya

Tanner

et al. 2016

Cell Death Dis

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Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1.1 (BK, Slo1, KCNMA1), regulates myoblast proliferation, migration, and fusion. We also show a loss of plasma membrane expression of the pore-forming α subunit of KCa1.1 in DM1 myoblasts. Inhibiting the function of KCa1.1 in healthy myoblasts induced an increase in cytosolic calcium levels and altered nuclear factor kappa B (NFκB) levels without affecting cell survival. In these normal cells, KCa1.1 block resulted in enhanced proliferation and decreased matrix metalloproteinase secretion, migration, and myotube fusion, phenotypes all observed in DM1 myoblasts and associated with disease pathogenesis. In contrast, introducing functional KCa1.1 α-subunits into DM1 myoblasts normalized their proliferation and rescued expression of the late myogenic marker Mef2. Our results identify KCa1.1 channels as crucial regulators of skeletal myogenesis and suggest these channels as novel therapeutic targets in DM1.

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Comparison of S‐phase fractions measured by flow cytometry and autoradiography in human transplant tumors

Cited by 11 publications

References 22 publications

Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer

Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer

DNA Flow Cytometry in the Prognosis of Primary Malignant Melanoma

Functional KCa1.1 channels are crucial for regulating the proliferation, migration and differentiation of human primary skeletal myoblasts

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