How Can the European Federation for Colposcopy Promote High Quality Colposcopy Throughout Europe?

Since its inception in 1998, the European Federation for Colposcopy (EFC) now comprises 26 member societies. Its principle aim is to promote high quality colposcopy throughout Europe with special emphasis on training, education and treatment. This review summarises EFC’s activities and achievements to date

The effect of extracellular lactate concentration on intracellular lactate concentration and intracellular L/P ratio in Bcap-37 cells.

<p>Bcap-37 cells were incubated in complete RPMI-1640 medium containing 12 mM glucose supplemented with 20 mM lactate. At the indicated time point, intracellular lactate and pyruvate were measured. (A) Intracellular lactate; (B) Intracellular pyruvate; (C) Intracellular L/P ratio. Data are mean ± SD. Data were confirmed by 2 independent experiments.</p

The effect of oxygen levels on cytosolic free NAD/NADH ratios in Hela cells.

<p>Hela cells were incubated in complete RPMI-1640 medium containing 12 mM glucose supplemented with 20 mM lactate under oxygen levels between 21% to 1%. After 24-hour incubation, glucose consumption and lactate generation by Hela cells, cell growth, and intracellular lactate and pyruvate were measured. (A) Cell proliferation; (B) Glucose consumption; (C) Lactate generation; (D) L/G ratio; (E) Intracellular pyruvate; (F) Intracellular lactate; (G) Intracellular L/P ratio; (H) Cytosolic free NAD/NADH ratio estimated from the corresponding L/P ratio (see description in text). Data are mean±SD. Data were confirmed by 2 independent experiments.</p

Cytosolic free NAD/NADH ratio estimated at the conversion at equilibrium in Bcap-37 cells.

<p>Bcap-37 cells were incubated in complete RPMI-1640 medium containing 12 mM glucose supplemented with or without lactate (x axis). After 24-hour incubation, glucose consumption and lactate generation by Bcap-37 cells, cell growth, and intracellular lactate and pyruvate were measured. (A) Cell proliferation; (B) Glucose consumption; (C) Lactate generation; (D) L/G ratio; (E) Intracellular pyruvate; (F) Intracellular lactate; (G) Intracellular L/P ratio; (H) Cytosolic free NAD/NADH ratio estimated from the corresponding L/P ratio(see corresponding text). Data are mean±SD. Data were confirmed by 3 independent experiments.</p

The effect of oxygen levels on intracellular concentration of lactate and pyruvate in Hela cells.

<p>Hela cells were incubated in complete RPMI-1640 medium containing 12 mM glucose. After 24-hour incubation, glucose consumption and lactate generation by Hela cells, cell growth, and intracellular lactate and pyruvate were measured. (A) Cell proliferation; (B) Glucose consumption; (C) Lactate generation; (D) L/G ratio; (E) Intracellular pyruvate; (F) Intracellular lactate; (G) Intracellular L/P ratio; (H) Cytosolic free NAD/NADH ratio erroneously estimated from the corresponding L/P ratio. Data are mean±SD. Data were confirmed by 2 independent experiments.</p

Intracellular lactate concentration and L/P ratio are highly labile in Bcap-37 cells.

<p>Bcap-37 cells were incubated in complete RPMI-1640 medium containing 12 mM glucose and supplemented with 6 mM glucose every 24 hours. At the indicated time point, intracellular lactate and pyruvate, glucose consumption and lactate generation by Bcap-37 cells, and cell growth were monitored. (A) Intracellular lactate; (B) Intracellular pyruvate; (C) Intracellular L/P ratio; (D) Cytosolic free NAD/NADH ratio erroneously estimated from the corresponding L/P ratio; (E) Cell proliferation curves; (F) Glucose consumption; (G) Lactate generation; (H) L/G ratio (the generated lactate divided by the consumed glucose between 2 time points). Data are mean±SD. Data were confirmed by 2 independent experiments.</p

Sch B inhibits local invasion of 4T1 cells <i>in vivo</i>.

<p>Mice (n = 20 for each group) were treated with Sch B (100 mg/kg body weight) or vehicle intragastrically daily for 7 days. (A) Primary tumors and surrounding tissues were resected on day 15 for hematoxylin-eosin stain (upper, ×40, lower, ×100). (B) immunostaining of E-cadherin and vimentin.(×100).</p

Sch B prolongs mouse survival time in dose-dependent manner.

<p>Mice (n = 8 for each group) receiving Sch B (100, 30, 10 mg/kg body weight) or vehicle every day for total 7 doses, and primary tumors were resected on day 10. (A) Mouse survival time. (B) Mouse body weight. (C) Tumor weight resected on day 10. *, P<0.05, **, P<0.01, Sch B versus control group.</p

Sch B reduces 4T1 lung metastasis but does not affect the growth of primary tumor.

<p>5×10⁴ viable 4T1 cells were inoculated <i>s.c.</i> in the right second mammary fat pad area to establish the spontaneously metastatic model. Sch B (100 mg/kg body weight) or vehicle (0.5% paraxamer) was dosed intragastrically every day for a total of 7 doses. Mice (n = 20 for each group) were sacrificed on day 30. (A) The growth curves of primary tumor (B) Mouse body weight. (C) Primary tumor weight on the day sacrificed. (D) Numbers of visible lung metastatic nodules. (E) The lung metastatic index. *, P<0.05, **, P<0.01.</p

Sch B inhibits bone metastasis of 4T1 cells.

<p>Bone metastasis of 4T1 in mice demonstrated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040480#pone-0040480-g002" target="_blank">Figure 2</a> were evaluated using H&E staining as described in Materials and Methods. The incidence of bone metastasis was reflected by the visible osteolysis. (A) Representative photo of bone metastasis. Osteolysis was marked by arrow. (B) Representative photo of bones with no osteolysis. (C) Incidence of bone metastasis (n = 20) compared using chi-square analysis. *, P<0.05, Sch B versus control group.</p