E2F8 Induces Cell Proliferation and Invasion through the Epithelial-Mesenchymal Transition and Notch Signaling Pathways in Ovarian Cancer.

BACKGROUND: Despite the recent research implicating E2F8 (E2F Transcription Factor 8) in cancer, the role of E2F8 in the progression of ovarian cancer has remained unclear. Hence, we explored the bio-functional effects of E2F8 knockdown on ovarian cancer cell lines in vitro and in vivo. METHODS: The expression of E2F8 was compared between ovarian cancer and noncancer tissues, and its association with the progression-free survival of ovarian cancer patients was analyzed. To demonstrate the function of E2F8 in cell proliferation, migration, and invasion, we employed RNA interference to suppress E2F8 expression in ovarian cancer cell lines. Finally, the effect of E2F8 knockdown was investigated in a xenograft mouse model of ovarian cancer. RESULTS: Ovarian cancer tissue exhibited significantly higher E2F8 expression compared to that of normal ovarian tissue. Clinical data showed that E2F8 was a significant predictor of progression-free survival. Moreover, the prognosis of the ovarian cancer patients with high E2F8 expression was poorer than that of the patients with low E2F8 expression. In vitro experiments using E2F8-knockdown ovarian cancer cell lines demonstrated that E2F8 knockdown inhibited cell proliferation, migration, and tumor invasion. Additionally, E2F8 was a potent inducer and modulator of the expression of epithelial-mesenchymal transition and Notch signaling pathway-related markers. We confirmed the function of E2F8 in vivo, signifying that E2F8 knockdown was significantly correlated with reduced tumor size and weight. CONCLUSIONS: Our findings indicate that E2F8 is highly correlated with ovarian cancer progression. Hence, E2F8 can be utilized as a prognostic marker and therapeutic target against ovarian malignancy.

Evaluation of novel orthotopic nude mouse models for human small-cell lung cancer.

INTRODUCTION: Although subcutaneous xenograft models have been widely used to evaluate the antitumor activity of new compounds, these models present a major disadvantage because the tumors do not accurately represent the cancer biology, especially with regard to metastasis and drug sensitivity. Effective murine models of small-cell lung cancer (SCLC) are needed. METHODS: To provide strategies for studying new therapies and tumor biology, we developed three orthotopic models of human SCLC (H69A, a variant of the National Cancer Institute [NCI]-H69 cell line selected for invasiveness in vitro, NCI-H187, and NCI-N417) in nude mice. Tumor cells were injected into their lungs and new cell lines were established from these tumors (H69ALu, H187Lu, and N417Lu) to select for a reproducible tumor growth pattern and minimize variations in tumor size. RESULTS: In all three models tumors started as a solitary mass in the left lung and spread to mediastinal and axillary lymph nodes and to the right lung in a pattern similar to that observed in human SCLC. To test the accuracy of this model in representing SCLC as seen in the clinic, we compared the efficacy of chemotherapeutic agents in each model. Irinotecan significantly inhibited the growth and progression of all three human SCLC tumors, and cisplatin, paclitaxel, and etoposide significantly inhibited the growth and progression of H69ALu tumors over the control agent. CONCLUSIONS: We have established three orthotopic murine models of human SCLC closely resembling the course of human SCLC seen in the clinic including metastasis to lymph nodes and distant organs. They provide a means for better understanding the biology of this disease and will enable evaluation of novel therapeutic strategies.

Addressing stakeholders' needs: economics and patient satisfaction.

PURPOSE: The economics of acute post-operative pain management are discussed. Studies identifying cost drivers in post-operative pain treatment and the economic sequelae of undertreated pain are reviewed. The relative costs of intermittent intramuscular analgesia, intravenous patient-controlled analgesia, and epidural analgesia are described. Medication errors and their consequences are addressed. The importance of patient satisfaction and data on its correlation with acute post-operative pain are reviewed. SUMMARY: Although the economics of acute post-operative pain treatment are difficult to accurately assess, studies have demonstrated that pharmacy acquisition costs represent as little as 1% of the total hospital cost of surgical treatment. Costs of analgesia are driven largely by staff time. Inadequate treatment of post-operative pain can have important economic ramifications associated with increased patient morbidity, extended hospital stays, and readmissions. Inadequate treatment of post-operative pain is also associated with reduced patient satisfaction, a measure of increasing importance to health systems and pharmacists who practice within them. CONCLUSION: Undertreatment of acute post-operative pain has important implications for health systems from the standpoints of economics and patient satisfaction.

Postoperative pain management with a patient-controlled transdermal delivery system for fentanyl.

PURPOSE: The efficacy and safety of fentanyl hydrochloride patient-controlled trans-dermal system (PCTS) for management of acute postoperative pain are discussed. SUMMARY: Fentanyl hydrochloride PCTS is a self-contained, needle-free, credit-card-sized fentanyl-delivery system that is worn on the patient's arm or chest. The system uses iontophoretic technology to actively deliver preprogrammed doses of fentanyl into the systemic circulation when activated by the patient on demand. PCTS is as safe and effective as i.v. morphine patient-controlled analgesia and superior to placebo for managing acute postoperative pain. Fentanyl absorption from PCTS is clinically insignificant when the device is not activated. This contrasts with the transdermal fentanyl patch, which delivers fentanyl continuously for 72 hours via passive absorption and is indicated only for use in the management of chronic pain. CONCLUSION: Fentanyl hydrochloride PCTS is a self-contained iontophoretic fentanyl-delivery system that provides patients control over pain management and consistent management of pain without analgesic peaks and troughs.