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1.
BACKGROUND: We hypothesized that keyhole limpet hemocyanin (KLH) would reduce cellular proliferation and effect apoptosis of melanoma cell lines in vitro. METHODS: Two human melanoma cell lines (HTB68 and HTB72) were subjected to a dose-response treatment regimen of KLH (0.4 microg to 100 microg/well). Cell viability was tested by MTT assay (SIGMA, St Louis, MO) at 72 hours. Apoptosis and necrosis were measured by the Annexin V FITC assay (Biovision Inc, Mountain View, CA). RESULTS: Melanoma cell proliferation was significantly reduced in the HTB68 cell line treated with 6.3 microg or higher doses of KLH. A significant reduction in cell growth was also observed in the HTB72 cells at 50 and 100 microg of KLH. KLH increased early apoptotic activity, whereas both late apoptosis and necrosis were decreased by the addition of KLH. CONCLUSIONS: KLH significantly reduces cellular proliferation in vitro in melanoma, via early apoptotic pathways. The results warrant in vivo studies into the effects of KLH in melanoma. 相似文献
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Somasundar P Riggs DR Jackson BJ Cunningham C Vona-Davis L McFadden DW 《The Journal of surgical research》2005,126(2):199-203
BACKGROUND: Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate found in food sources high in fiber content. IP6 has been reported to have significant inhibitory effects against a variety of primary tumors including breast and colon. The effects of IP6 have not been evaluated in pancreatic cancer. We hypothesized that IP6 would significantly inhibit cell growth and increase the apoptotic rate of pancreatic cancer in vitro. MATERIALS AND METHODS: Two pancreatic cancer cell lines (MIAPACA and PANC1) were cultured using standard techniques and treated with IP6 at doses of 0.5, 1.0, and 5.0 mm. Cell viability was measured by MTT at 24 and 72 h. Apoptosis was evaluated by Annexin V-FITC and results calculated using FACS analysis. Statistical analysis was performed by ANOVA. RESULTS: Significant reductions (P < 0.01) in cellular proliferation were observed with all IP6 concentrations tested in both cell lines and at both time points. Reductions in cell proliferation ranged from 37.1 to 91.5%. IP6 increased early and late apoptotic activity (P < 0.01). CONCLUSIONS: Treatment of pancreatic cancer with the common dietary polyphosphorylated carbohydrate IP6 significantly decreased cellular growth and increased apoptosis. Our findings suggest that IP6 has the potential to become an effective adjunct for pancreatic cancer treatment. Further in vivo and human studies are needed to evaluate safety and clinical utility of this agent in patients with pancreatic cancer. 相似文献
3.
Leptin induces cell migration and the expression of growth factors in human prostate cancer cells 总被引:15,自引:0,他引:15
Frankenberry KA Somasundar P McFadden DW Vona-Davis LC 《American journal of surgery》2004,188(5):560-565
BACKGROUND: The adipocyte hormone leptin has been shown to increase migration and angiogenesis in epithelial cells. Therefore, we hypothesized that leptin would induce prostate cancer cell migration and growth factor expression in vitro. METHODS: Prostate cancer cell lines DU145 and PC-3 (androgen-resistant) were treated with leptin over time. Supernatants were assayed for growth factor expression via enzyme-linked immunosorbent assay (ELISA). Becton Dickinson-Falcon Transwell systems were used to assay leptin-induced migration. RESULTS: Leptin significantly induced expression of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) in DU145 and PC-3 cells. Prostate cancer cell migration was enhanced by leptin and inhibited 50% to 70% with the addition of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) inhibitors. CONCLUSIONS: The mitogenic effects of leptin on cancer cells, in combination with the increased migration and expression of growth factors, overall likely contributes to the progression of prostate cancer. Therefore, obesity associated with high leptin levels should be considered a risk factor in prostate cancer patients. 相似文献
4.
Over the past decade, a nonoperative approach toward the management of blunt hepatic trauma has become prevalent at most major urban trauma centers. To determine the applicability of the nonoperative approach in a rural setting, a 10-year retrospective review was conducted at a level I rural university-based trauma center. The Census Bureau defines ruralized areas to provide a better separation of urban and rural territory and population. A ruralized area is composed of one or more places and the adjacent surrounding territory that together have a maximum of 50,000 persons. West Virginia University is classified as a rural academic medical center and is situated in Morgantown, whose permanent population does not exceed 35,000. All patients with documented blunt hepatic trauma between July 1990 and June 2000 were identified and reviewed. To evaluate evolving trends, the patients were divided into two groups: group A (July 1, 1990-June 30, 1995) and group B (July 1, 1995-June 30, 2000). There were 236 patients with documented blunt hepatic trauma identified between July 1, 1990, and June 30, 2000). Overall, 70 per cent of patients were managed conservatively. When comparing the two groups, statistical significance was obtained in mean hospital length of stay (LOS) [19.8 days A vs. 9.1 days B (P < 0.0001)]; mean intensive care unit (ICU) days [15.2 days A vs. 5.3 days B (P < 0.0001)], blood transfusion [10 units A vs. 4.2 units B (P < 0.0016)], number of patients requiring surgery [52 (46%) A vs. 37 (30%) B (P < 0.022)]. There was only one death associated with nonoperative management. We have shown a definite trend toward nonoperative management of blunt hepatic trauma in a rural setting over the past decade. More than 70 per cent of our liver injury patients over the past 5 years have been managed nonoperatively, with statistically significant reductions in hospital LOS, ICU LOS, and transfusion requirements. We have found a definite trend over the past decade toward nonoperative management of blunt hepatic trauma in a rural setting. The rural setting with a delay in transport time to level I trauma center also did not significantly affect the outcome of the patients with nonoperative management of liver injuries. Approximately 78 per cent of our liver injury patients over the past 5 years have been managed nonoperatively and are associated with statistically significant reductions in hospital and ICU LOS and transfusion requirements. 相似文献
5.
Leptin is a growth factor in cancer 总被引:22,自引:0,他引:22
Somasundar P McFadden DW Hileman SM Vona-Davis L 《The Journal of surgical research》2004,116(2):337-349
6.
Somasundar P Riggs D Jackson B Vona-Davis L McFadden DW 《American journal of surgery》2003,186(5):575-578
BACKGROUND: Leptin is a hormone primarily produced by adipocytes and serum leptin is elevated in obese persons. One risk factor associated with adenocarcinoma of the esophagus is obesity. We hypothesized that leptin would have stimulatory effects on esophageal adenocarcinoma and alter apoptosis in vitro. METHODS: Barrett's esophageal adenocarcinoma cells (BIC-1 and SEG-1) were cultured with human recombinant leptin (80 ng/mL) for 24 hours. Cell growth was determined by MTT assay. Apoptosis and necrosis was measured after 16 hours of treatment with leptin using a Cell Death Kit. RESULTS: Exogenous leptin stimulated cell proliferation in both cell lines. No changes in apoptosis or necrosis resulted between control and leptin-treated groups. CONCLUSIONS: We have shown that leptin increases the proliferation of human esophageal adenocarcinoma, but does not alter cell apoptosis or necrosis. The data suggest that leptin stimulates esophageal adenocarcinoma growth by nonapoptotic mechanisms. Leptin antagonism may have potential efficacy in esophageal cancer therapy. 相似文献
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Frankenberry KA Skinner H Somasundar P McFadden DW Vona-Davis LC 《International journal of oncology》2006,28(4):985-993
Obesity is considered a risk factor for many cancers, including breast cancer. Our laboratory has previously shown that leptin is mitogenic in many cancer cell lines, including breast. Information regarding the effects of high leptin levels on leptin receptor expression and signaling is lacking. The purpose of this study was to characterize leptin receptor expression in response to leptin in breast cancer cells. In addition, SOCS-3 expression (a leptin inducible inhibitor of leptin signaling), plus MAPK and PI3K signaling, were examined to determine their role in leptin-induced cell proliferation. Breast cancer cell lines, ZR75-1 and HTB-26, were treated with 0, 4, 40 or 80 ng/ml of leptin. Multiplex RT-PCR was performed to determine relative mRNA expression levels of the human short (huOB-Ra) or long (huOB-Rb) leptin receptor isoforms, or SOCS-3. MAPK and PI3K signaling was analyzed by phosphorylation of ERK and Akt, respectively, via Western blotting. Cell proliferation and inhibitor studies were analyzed by MTT assay. HTB-26 and ZR75-1 both expressed huOB-Ra, huOB-Rb and SOCS-3 mRNA; however, mRNA expression levels generally remained unchanged over time with leptin treatment. MAPK and PI3K pathways were activated in the presence of leptin over time. MAPK and PI3K inhibitors significantly blocked leptin-induced proliferation. Higher levels of circulating leptin contribute to breast cancer proliferation by activation of the MAPK and PI3K signaling pathways involved in cell growth and survival. The mitogenic effects of leptin are not a consequence of altered leptin receptor or SOCS-3 mRNA expression. 相似文献
9.
Jeffrey Reha Shiva Kumar Reddy Mukkamalla Ritesh Rathore Ponnandai Sadasivan Somasundar 《European journal of surgical oncology》2018,44(1):148-156
Background
Lymph node involvement (LNI) is an important prognostic factor in colon cancer. But, variations in LNI among different age groups are less known. Adequate lymph node evaluation (LNE) requires assessment of ≥12 nodes. In our previous study, using Surveillance, Epidemiology and End Results (SEER) data, we demonstrated that older patients are less likely to have LNI (Khan et al. 2014). Our current study validates those findings using National Cancer Data Base (NCDB).Methods
NCDB was queried for patients diagnosed with stages I–III colon adenocarcinoma from 2004 to 2008 who underwent surgical resections. Pearson Chi-square test and Cox proportional hazards regression model were utilized for statistical analysis.Results
A cohort of 97,831 patients was identified for analysis. Among patients belonging to 18–64, 65–74 and >75 years age groups, frequency of adequate LNE was 73.6%, 69% and 67.4% respectively, with pathologically confirmed LNI rates being 44.7%, 37.8% and 29.3% respectively (p < 0.0001). Adequate LNE was associated with improved 5-year overall survival (OS) regardless of age, gender, race, comorbidity index, insurance, income, year of diagnosis, pathologic tumor status, stage, grade, type of colectomy, adjuvant chemotherapy or academic level of facility. Rates of adequate LNE increased from 2004 to 2008, with a corresponding increase in survival outcomes (p < 0.0001).Conclusion
Adequate LNE is very crucial for appropriate staging of colon cancer, and carries a high prognostic value. This study validates our previous findings of lower rates of LNI in elderly and reiterates the importance of adequate LNE, which is associated with improved survival. Also identified were increasing rates of adequate LNE over the years, with corresponding improvement in OS. 相似文献10.
Sanjay Munireddy Steven Katz P. Somasundar N. Joseph Espat 《Journal of gastrointestinal oncology.》2012,3(1):69-77
Surgical resection for colorectal hepatic metastases (CRHM) is the preferred treatment for suitable candidates, and the only potentially curative modality. However, due to various limitations, the majority of patients with CRHM are not candidates for liver resection. In recent years, there has been an increasing interest in the role of thermal tumor ablation (TTA) as a component of combined resection-ablation strategies, staged hepatic resections, or as standalone adjunct treatment for patients with CRHM. Thus, ablative approaches have expanded the group of patients with CRHM that may benefit from liver-directed treatment strategies.Key Words: Colorectal liver metastasis, tumor ablation, thermal ablation 相似文献