ABSTRACT
Ceftriaxone is a commonly used antibiotic due to some of its advantages. Reversible gallbladder (GB) sludge or stone has been reported after ceftriaxone therapy. Most of these patients have no symptom, but the GB sludge or stone can sometimes cause cholecystitis. We experienced two patients who had newly developed GB stones after ceftriaxone therapy for diverticulitis and pneumonia, and this resolved spontaneously 1 month after discontinuation of the drug. Awareness of this complication could help to prevent unnecessary cholecystectomy.
Subject(s)
Humans , Young Adult , Ceftriaxone , Cholecystectomy , Cholecystitis , Cholecystolithiasis , Diverticulitis , Gallbladder , Gallstones , Pneumonia , SewageABSTRACT
PURPOSE: Phenylbutyrate is an effective redifferentiating agent in several human cancers. Recently phenylbutyrate has been reported to inhibit histone deacetylase activity. We investigated the effects of sodium 4-henylbutyrate (Na-4-PB) on cell proliferation in a human pancreatic cancer cell line. METHODS: A human pancreatic cancer cell line, Aspc-1 was purchased from Korean Cell Line Bank. Antiproliferative effects of sodium 4-phenylbutyrate were measured by MTT assay and their mechanisms were evaluated by apoptosis assay and cell cycle analysis. RESULTS: After 3 days of treatment with Na-4-PB at the concentration of 2.5, 5, 7.5, and 10 mM, relative growth inhibition compared to control was 21.3+/-8.3% (mean+/-SD), 37.8+/-2.3%, 46.7+/-0.5%, and 56.7+/-1.7% respectively (p < 0.05). Antiproliferative effect of Na-4-PB was also time-dependent. Combination treatment with Na-4-PB and troglitazone, a PPARg agonist, increased antiproliferative effects but was not synergistic. After 48 hour treatment with Na-4-PB, early apoptotic cell population in control, 2.5, and 5 mM of Na-4-PB was 29.6%, 44.2%, and 65.9%, respectively. After 24 hour treatment with Na-4- PB, G0/G1 phase population in control, 2.5, and 5 mM of Na-4-PB was 55.0%, 67.4%, and 65.8%, respectively. CONCLUSION: Na-4-PB inhibited pancreatic cancer cell proliferation by inducing apoptosis and cell cycle arrest at G0/G1 phase in time- and dose-dependent manner. Combination treatment with Na-4-PB and other chemotherapeutic agents such as troglitazone, a PPARg agonist, can enhance antiproliferative effects. Na-4-PB might be a promising potential therapeutic agent for patients with pancreatic cancer.
Subject(s)
Humans , Apoptosis , Cell Cycle , Cell Cycle Checkpoints , Cell Line , Cell Proliferation , Histone Deacetylases , Pancreatic Neoplasms , SodiumABSTRACT
PURPOSE: Selective cyclooxygenase (COX)-2 inhibitors have been reported to inhibit cancer cell proliferation. We investigated the effects of NS-398, a selective COX-2 inhibitor, on cell proliferation in human pancreatic cancer cell lines. METHODS: Human pancreatic cancer cell lines, Aspc-1, Capan-1, and Capan-2 were used. We used western blot and/or RT-PCR to evaluate COX-2 and vascular endothelial growth factor expression. Antiproliferative effects were measured by MTT assay, apoptosis assay and cell cycle analysis. Epidermal growth factor (EGF) and troglitazone were used for combined treatment. RESULTS: COX-2 was relatively overexpressed in Capan-1 and Capan- 2, but minimal in Aspc-1 cell line. COX-2 mRNA expression was upregulated by 50 microM of NS-398 in Aspc-1 cell line but was downregulated at 100 microM in all cell lines. Treatment with NS-398 increased cell population of G0/G1 phase and also induced early apoptotic changes in a dose-dependent manner in all three cell lines. Combined treatment with EGF or troglitazone did not seem to affect antiproliferative effects of NS-398. All three cell lines expressed vascular endothelial growth factor constitutively and its expression was downregulated by treatment with NS-398. Pretreatment with NS-398 prior to radiation exposure increased radiosensitivity in Capan-2 cells. CONCLUSION: COX-2 expression was variable in pancreatic cancer cell lines. NS-398 inhibited pancreatic cancer cell proliferation by inducing apoptosis and cell cycle arrest in a dose-dependent manner. Treatment with NS-398 also inhibited expression of VEGF and enhanced radiosensitivity in pancreatic cancer cell lines. COX-2 inhibitors might be promising potential therapeutic agents for patients with pancreatic cancer.