Targeting Glypican-1 Reverses Resistance to 5-Fluorouracil in Esophageal Adenocarcinoma Cells.

BACKGROUND/AIM: The primary mode of therapy for individuals with locally advanced esophageal adenocarcinoma (EAC) is neoadjuvant chemotherapy, commonly 5-Fluorouracil (5-FU). However, approximately 30% of these patients develop resistance to therapy. Glypican-1 (GPC-1) has been identified as one of the key drivers of chemoresistance in cancer; however, its role in EAC cells has not been explored. The objective of the present study was to evaluate the role of GPC-1 in chemoresistance to 5-FU in EAC cells. MATERIALS AND METHODS: Cell viability to 5-FU was measured with CCK-8 assay, and GPC-1 expression was validated using western blot. 5-FU resistant cell lines were generated. The effect of lentivirus-mediated GPC-1 knockdown on FLO-1 cell viability, cell cycle, and apoptosis was evaluated. RESULTS: 5-FU resistant EAC cells showed increased GPC-1 expression and knockdown of GPC-1 increased cell death and apoptosis. Importantly, the knockdown of GPC-1 enhanced the antitumor effects of 5-FU in vitro via down-regulating AKT/ERK/ß-catenin signaling. CONCLUSION: Silencing GPC-1 has the potential to augment the efficacy of 5-FU chemotherapy in resistant EAC tumors.

Human Papillomavirus (HPV) Detection by Chromogenic In Situ Hybridization (CISH) and p16 Immunohistochemistry (IHC) in Breast Intraductal Papilloma and Breast Carcinoma.

PURPOSE: This study explored human papillomavirus (HPV) amplification in breast benign and malignant lesions by chromogenic in situ hybridization (CISH) and the concordance of p16 expression by immunohistochemistry. PATIENTS AND METHODS: The presence of HPV6/11 and HPV16/18 in 33 cases of intraductal papilloma, 34 cases of ductal carcinoma in situ (DCIS), and 56 cases of invasive breast carcinoma (IBC) was evaluated using matched-background breast parenchyma and breast reduction as control groups. Association with clinicopathologic factors including prognosis was assessed. RESULTS: HPV 6/11 was observed in 0 cases (0%) of breast reduction, one case (3%) of intraductal papilloma, 11 cases (32.4%) of DCIS, and eight cases (14.3%) of IBC. HPV 16/18 was detected in three cases of (9.1%) breast reduction, six cases (18.8%) of intraductal papillomas, 14 cases (41.2%) of DCIS, and 25 cases (44.6%) of IBC. There was no difference in the HPV status between intraductal papilloma and breast reduction. HPV amplification in intraductal papilloma did not associate with developing atypia or carcinoma after long-term follow-up. However, HPV 6/11 and HPV 16/18 amplification was significantly higher in both DCIS and IBC when compared with breast reduction (P < .05). Compared with background breast parenchyma, HPV 16/18 amplification was significantly higher in both DCIS and IBC (P = .003 and P = .013, respectively). No correlation between p16 immunohistochemical staining and either of the HPV CISH testing was found (P > .05). CONCLUSION: HPV infection was detected in both breast lesions and background parenchyma. HPV infection may play a role in the pathogenesis of breast cancer but is not associated with intraductal papilloma. Immunohistochemical stain for p16 is not a good surrogate marker for HPV infection in breast lesions.

A retrospective analysis of the incidence of hemolysis in type and screen specimens from trauma patients.

BACKGROUND: Hemolysis of blood samples has been a concern in hospitals. Currently, residents and nurses have replaced traditional teams of skilled phlebotomists for both routine and 'stat' blood draws. Although this leads to a decreased operating cost for institutions, the lack of skill and experience leads to a higher percentage of hemolyzed specimens. OBJECTIVE: To determine the incidence of hemolyzed 'type and screen' blood samples at Staten Island University Hospital (SIUH) (New York, USA). METHODS: The study group comprised 615 consecutive trauma patients at SIUH between July 2006 and June 2007. Patients were treated according to the Advanced Trauma Life Support protocol. The primary survey for a trauma patient consists of 'airway', 'breathing' and 'circulation'. The primary objective of 'circulation' is to establish vascular access and collect blood samples for analysis. The SIUH in-house laboratory provided all of the reports. RESULTS: Of the 615 samples collected, 155 samples (25.2%) were hemolyzed. CONCLUSIONS: The hemolysis rate of 25.2% for type and screen samples is higher than previously reported in the literature. The data suggest that the high rate of hemolysis in these trauma patients is due to the residents' lack of experience and skills required to obtain an adequate blood draw.