Blockade of dual-specificity phosphatase 28 decreases chemo-resistance and migration in human pancreatic cancer cells.

Pancreatic cancer remains one of the most deadly cancers, with a grave prognosis. Despite numerous endeavors to improve treatment of the neoplasm, limited progress has been made. In the present study, we investigated the role of dual specificity phosphatase 28 (DUSP28) in relation to anti-cancer drug sensitivity and migratory activity in human pancreatic cancer cells for the first time. Analysis using Universal exPress Codes (UPCs) with the GEO database showed significantly higher DUSP28 mRNA expression in pancreatic cancers. We found that DUSP28 was highly expressed in several human pancreatic cancer cell lines that showed resistance to anti-cancer drugs. Overexpression of DUSP28 decreased anti-cancer drug-sensitivity and enhanced cellular migration via the ERK1/2 pathway in DUSP28-negative cell lines. Knockdown of DUSP28 re-sensitized cells to anti-cancer drugs even at sublethal doses by inducing an apoptotic pathway and significantly reduced migration in DUSP28-positive human pancreatic cancer cell lines. Furthermore, DUSP28-positive cell line (Panc-1) xenograft models were more resistant to gemcitabine treatment than DUSP28-negative cell line (SNU-213) xenograft models. Collectively, these results indicate that DUSP28 plays a key role in drug resistance and migratory activity in human pancreatic cells, and suggest that targeting DUSP28 might have clinical relevance in eradicating malignant pancreatic cancers.

The influence of time intervals between loop electrosurgical excision and subsequent hysterectomy on the morbidity of patients with cervical neoplasia.

OBJECTIVE: To improve clinical prospects by reducing intraoperative or postoperative complications, subsequent hysterectomy is generally conducted within 48 h or 6 weeks after cervical cold-knife conization. The loop electrosurgical excision procedure (LEEP) is widely used for cervical conization. However, no study has ever been undertaken on the relation between postoperative sequelae and the time between LEEP and hysterectomy. Therefore, this study was undertaken to evaluate the correlations between postoperative sequelae and the interval between LEEP and hysterectomy. METHODS: The medical records of 338 patients, who underwent type 1 extended hysterectomy after LEEP at the Department of Obstetrics and Gynecology, Yonsei University College of Medicine, were retrospectively reviewed. The subjects were divided into three groups according to time from LEEP to hysterectomy: group 1 (within 48 h, n = 210), group 2 (between 48 h and 6 weeks, n = 88), and group 3 (>6 weeks, n = 40). RESULTS: The three groups showed no significant differences with respect to patient characteristics (age, delivery history, body mass index, and a history of surgery). Postoperative complications such as fever, dysuria, and surgical region complications (effraction, infection, and rubefaction) were not significantly different among the three groups. Other complications, namely, ureter injury and abdominal wall hematoma, were found in one case in each group 1. CONCLUSION: The postoperative clinical courses were not significantly different regardless of time interval between LEEP and subsequent hysterectomy. Therefore, hysterectomies can be conducted at any time when the patient is in an appropriate condition, i.e., not precisely within 48 h or >6 weeks after LEEP.