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

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

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

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 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

Anticancer Agent Shikonin Is an Incompetent Inducer of Cancer Drug Resistance

<div><h3>Purpose</h3><p>Cancer drug resistance is a major obstacle for the success of chemotherapy. Since most clinical anticancer drugs could induce drug resistance, it is desired to develop candidate drugs that are highly efficacious but incompetent to induce drug resistance. Numerous previous studies have proven that shikonin and its analogs not only are highly tumoricidal but also can bypass drug-transporter and apoptotic defect mediated drug resistance. The purpose of this study is to investigate if or not shikonin is a weak inducer of cancer drug resistance.</p> <h3>Experimental Design</h3><p>Different cell lines (K562, MCF-7, and a MDR cell line K562/Adr), after repeatedly treated with shikonin for 18 months, were assayed for drug resistance and gene expression profiling.</p> <h3>Results</h3><p>After 18-month treatment, cells only developed a mere 2-fold resistance to shikonin and a marginal resistance to cisplatin and paclitaxel, without cross resistance to shikonin analogs and other anticancer agents. Gene expression profiles demonstrated that cancer cells did strongly respond to shikonin treatment but failed to effectively mobilize drug resistant machineries. Shikonin-induced weak resistance was associated with the up-regulation of βII-tubulin, which physically interacted with shikonin.</p> <h3>Conclusion</h3><p>Taken together, apart from potent anticancer activity, shikonin and its analogs are weak inducers of cancer drug resistance and can circumvent cancer drug resistance. These merits make shikonin and its analogs potential candidates for cancer therapy with advantages of avoiding induction of drug resistance and bypassing existing drug resistance.</p> </div

Schisandrin B Attenuates Cancer Invasion and Metastasis Via Inhibiting Epithelial-Mesenchymal Transition

<div><h3>Background</h3><p>Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposed as a strategy to combat cancer. Therefore, to develop candidate drugs that target the process of metastasis is very important. In the preliminary studies, we found that schisandrin B (Sch B), a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could suppress cancer metastasis.</p> <h3>Methodology</h3><p>BALB/c mice were inoculated subcutaneously or injected via tail vein with murine breast cancer 4T1 cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-β induced epithelial-mesenchymal transition (EMT) of 4T1 and primary human breast cancer cells was assayed.</p> <h3>Principal Findings</h3><p>Sch B significantly suppressed the spontaneous lung and bone metastasis of 4T1 cells inoculated s.c. without significant effect on primary tumor growth and significantly extended the survival time of these mice. Sch B did not inhibit lung metastasis of 4T1 cells that were injected via tail vein. Delayed start of treatment with Sch B in mice with pre-existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. Histopathological evidences demonstrated that the primary tumors in Sch B group were significantly less locally invasive than control tumors. In vitro assays demonstrated that Sch B could inhibit TGF-β induced EMT of 4T1 cells and of primary human breast cancer cells.</p> <h3>Conclusions</h3><p>Sch B significantly suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT, suggesting its potential application in targeting the process of cancer metastasis.</p> </div