21 research outputs found
Laparoscopic diagnostic peritoneal lavage (L-DPL): A method for evaluation of penetrating abdominal stab wounds
BACKGROUND: The management of penetrating abdominal stab wounds has been the subject of continued reappraisal and controversy. In the present study a novel method which combines the use of diagnostic laparoscopy and DPL, termed laparoscopic diagnostic peritoneal lavage (L-DPL) is described METHOD: Five trauma patients with penetrating injuries to the lower chest or abdomen were included. Standard videoscopic equipment is utilized for the laparoscopic trauma evaluation of the injured patient. When no significant injury is detected, the videoscope is withdrawn and 1000 mL of normal saline is infused through the abdominal trochar into the peritoneal cavity, and the effluent fluid studied for RBCs, WBC, amylase debry, bile as it is uced in regular diagnostic peritoneal lavage RESULTS: Laparoscopic peritoneal lavage (L-DPL) was then performed and proved to be negative in all 5 patients. RBC lavage counts above 100,000/mcrl were not considered as a positive lavage result, because the bleeding source was directly observed and controlled laparoscopically. All patients recovered uneventfully and were released within 3 days. This procedure combines the visual advantages of laparoscopy together with the sensitivity and specificty of DPL for the diagnosis of significant penetrating intra-abdominal injury, when the diagnostic strategy of selective consevatism for abdominal stab wounds is adopted. CONCLUSION: A method of laparoscopic diagnostic peritoneal lavage (L-DPL) in hemodynamically stable patients with penetrating lower thoracic or abdominal stab wounds is described. The method is especially applicable for trauma surgeons with only basic experience in laparoscopic technique. This procedure is used to obtain conclusive evidence of significant intra-abdominal injury, confirm peritoneal penetration, control intra-abdominal bleeding, and repair lacerations to the diaphragm and abdominal wall. The combination of laparoscopy and DPL afforded by the L-DPL method adds to the sensitivity and specificity of DPL, and avoids under or over sesitivty, that have limited the use of DPL in the hemodynamically stable trauma patients with suspicious or proven peritoneal penetration
The expression of the ubiquitin ligase subunit Cks1 in human breast cancer
INTRODUCTION: Loss of the cell-cycle inhibitory protein p27(Kip1 )is associated with a poor prognosis in breast cancer. The decrease in the levels of this protein is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1). Skp2 was recently found to be overexpressed in breast cancers, but the role of Cks1 in these cancers is unknown. The present study was undertaken to examine the role of Cks1 expression in breast cancer and its relation to p27(Kip1 )and Skp2 expression and to tumor aggressiveness. METHODS: The expressions of Cks1, Skp2, and p27(Kip1 )were examined immunohistochemically on formalin-fixed, paraffin-wax-embedded tissue sections from 50 patients with breast cancer and by immunoblot analysis on breast cancer cell lines. The relation between Cks1 levels and patients' clinical and histological parameters were examined by Cox regression and the Kaplan–Meier method. RESULTS: The expression of Cks1 was strongly associated with Skp2 expression (r = 0.477; P = 0.001) and inversely with p27(Kip1 )(r = -0.726; P < 0.0001). Overexpression of Cks1 was associated with loss of tumor differentiation, young age, lack of expression of estrogen receptors and of progesterone receptors, and decreased disease-free (P = 0.0007) and overall (P = 0.041) survival. In addition, Cks1 and Skp2 expression were increased by estradiol in estrogen-dependent cell lines but were down-regulated by tamoxifen. CONCLUSION: These results suggest that Cks1 is involved in p27(Kip1 )down-regulation and may have an important role in the development of aggressive tumor behavior in breast cancer
Over-expression of Skp2 is associated with resistance to preoperative doxorubicin-based chemotherapy in primary breast cancer
The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells
INTRODUCTION: Loss of the cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in breast cancer. The decrease in p27 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S phase kinase protein 2 (Skp2). The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer. Rapamycin was found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression is unknown. METHODS: The expression of Skp2 mRNA and protein levels were examined in rapamycin-treated breast cancer cell lines. The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1. RESULTS: Rapamycin significantly decreased Skp2 mRNA and protein levels in a dose and time-dependent fashion, depending on the sensitivity of the cell line to rapamycin. The decrease in Skp2 levels in the different cell lines was followed by cell growth arrest at G1. In addition, rapamycin enhanced the degradation rate of Skp2 and down-regulated the expression of the APC\C inhibitor Emi1. CONCLUSION: These results suggest that Skp2, an important oncogene in the development and progression of breast cancer, may be a novel target for rapamycin treatment
Distinct genes related to drug response identified in ER positive and ER negative breast cancer cell lines
Breast cancer patients have different responses to chemotherapeutic treatments. Genes associated with drug response can provide insight to understand the mechanisms of drug resistance, identify promising therapeutic opportunities, and facilitate personalized treatment. Estrogen receptor (ER) positive and ER negative breast cancer have distinct clinical behavior and molecular properties. However, to date, few studies have rigorously assessed drug response genes in them. In this study, our goal was to systematically identify genes associated with multidrug response in ER positive and ER negative breast cancer cell lines. We tested 27 human breast cell lines for response to seven chemotherapeutic agents (cyclophosphamide, docetaxel, doxorubicin, epirubicin, fluorouracil, gemcitabine, and paclitaxel). We integrated publicly available gene expression profiles of these cell lines with their in vitro drug response patterns, then applied meta-analysis to identify genes related to multidrug response in ER positive and ER negative cells separately. One hundred eighty-eight genes were identified as related to multidrug response in ER positive and 32 genes in ER negative breast cell lines. Of these, only three genes (DBI, TOP2A, and PMVK) were common to both cell types. TOP2A was positively associated with drug response, and DBI was negatively associated with drug response. Interestingly, PMVK was positively associated with drug response in ER positive cells and negatively in ER negative cells. Functional analysis showed that while cell cycle affects drug response in both ER positive and negative cells, most biological processes that are involved in drug response are distinct. A number of signaling pathways that are uniquely enriched in ER positive cells have complex cross talk with ER signaling, while in ER negative cells, enriched pathways are related to metabolic functions. Taken together, our analysis indicates that distinct mechanisms are involved in multidrug response in ER positive and ER negative breast cells. © 2012 Shen et al
Correction to: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells
Correction to: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells
After the publication of this work [1], an error was noticed in Fig. 2b, Fig. 3a and Fig. 5b. The Skp1 loading control was accidentally duplicated. We apologize for this error, which did not affect any of the interpretations or conclusions of the article
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The role of selective computed tomography in the diagnosis and management of suspected acute appendicitis
The negative appendectomy rate in patients with clinically diagnosed acute appendicitis is 20 to 40 per cent. Recently CT has emerged as a powerful diagnostic tool in the evaluation of suspected appendicitis and its routine use has been advocated. The objective of this study was to evaluate the impact of selective use of abdominal CT on the negative appendectomy rate. Three hundred eight patients were enrolled in this prospective study. Abdominal CT was performed in patients with uncertain clinical signs of appendicitis. CT was not performed in patients with either a very high or a very low index of suspicion. The results were compared with a retrospective analysis of 85 consecutive patients operated by clinical diagnosis alone. One hundred twenty-seven patients had a final diagnosis of acute appendicitis. CT was performed in 198 patients (64%). The sensitivity, specificity, and accuracy of CT scans were 91, 92, and 91 per cent, respectively. Surgical management plans were altered in 54 patients after obtaining the CT results; unnecessary delay in surgical treatment or unnecessary operations were prevented in 28 and 26 patients, respectively. In addition CT detected unrelated pathologies in 23 patients. CT was not performed in patients with low index of suspicion and none were found to suffer from acute appendicitis. The negative appendectomy rate was 17 per cent (7% men and 24% women) in patients selected for surgery on the basis of very high clinical suspicion alone. Overall the negative appendectomy rate with the selective use of CT was 16 per cent, which is significantly lower than the rate achieved by diagnosing patients on clinical grounds alone (24%). CT is highly accurate in diagnosing or ruling out acute appendicitis and may substantially decrease the negative appendectomy rate as well as unnecessary delayed observation. We believe that CT should be performed routinely in women with suspected appendicitis and selectively in men