Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters











Database
Type of study
Language
Publication year range
1.
Pancreas ; 42(7): 1060-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23695799

ABSTRACT

OBJECTIVE: This study aimed to investigate whether the overexpression of protein kinase C ß1 (PKCß1) is able to modulate the malignant phenotype displayed by the human ductal pancreatic carcinoma cell line PANC1. METHODS: PKCß1 overexpression was achieved using a stable transfection approach. PANC1-PKCß1 and control cells were analyzed both in vitro and in vivo. RESULTS: PANC1-PKCß1 cells displayed a lower growth capacity associated with the down-regulation of the MEK/ERK pathway and cyclin expression. Furthermore, PKCß1 overexpression was associated with an enhancement of cell adhesion to fibronectin and with reduced migratory and invasive phenotypes. In agreement with these results, PANC1-PKCß1 cells showed an impaired ability to secrete proteolytic enzymes. We also found that PKCß1 overexpressing cells were more resistant to cell death induced by serum deprivation, an event associated with G0/G1 arrest and the modulation of PI3K/Akt and NF-κB pathways. Most notably, the overexpression of PKCß1 completely abolished the ability of PANC1 cells to induce tumors in nude mice. CONCLUSIONS: Our results established an important role for PKCß1 in PANC1 cells suggesting it would act as a suppressor of tumorigenic behavior in pancreatic cancer.


Subject(s)
Carcinoma, Pancreatic Ductal/enzymology , Carcinoma, Pancreatic Ductal/etiology , Pancreatic Neoplasms/enzymology , Pancreatic Neoplasms/etiology , Protein Kinase C beta/metabolism , Animals , Carcinoma, Pancreatic Ductal/pathology , Cell Adhesion , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Survival , Heterografts , Humans , MAP Kinase Signaling System , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Neoplasm Transplantation , Pancreatic Neoplasms/pathology , Peptide Hydrolases/metabolism , Protein Kinase C beta/genetics , Proto-Oncogene Proteins c-akt/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Up-Regulation
2.
Int J Cancer ; 110(6): 825-30, 2004 Jul 20.
Article in English | MEDLINE | ID: mdl-15170663

ABSTRACT

Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response. Our aim was to determine if treatment with NSAIDs would lower tumor and metastasis growth and their accompanying syndromes. The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of leukocytosis and the weight loss associated with LP07 progression. Serum levels of the inflammatory cytokines IL-1beta and IL-6, mediators of cachexia, were modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction in angiogenesis were attained when cells were treated with either indomethacin or celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells treated with celecoxib. These data suggest that several processes implicated in tumor progression can be modulated with NSAID treatment. Improvement in performance status through modulation of cachexia may offer a possibility for combining anti-inflammatory treatments with more aggressive therapies.


Subject(s)
Adenocarcinoma/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Lung Neoplasms/drug therapy , Paraneoplastic Syndromes/prevention & control , Adenocarcinoma/pathology , Animals , Cell Division/drug effects , Cell Survival/drug effects , Chemotaxis/drug effects , Cyclooxygenase Inhibitors/therapeutic use , Cytokines/analysis , Disease Progression , Female , Indomethacin/therapeutic use , Lactones/therapeutic use , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Neoplasm Invasiveness/prevention & control , Sulfones
3.
J Pain Symptom Manage ; 27(1): 85-95, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14711473

ABSTRACT

Systemic syndromes characterized by a persistent activity of circulating mediators (cytokines) are frequently present with advanced cancer. We grouped under the general heading of "Systemic Immune-Metabolic Syndrome (SIMS)" a particular variety of distressing systemic syndrome characterized by dysregulation of the psycho-neuro-immune-endocrine homeostasis, with overlapping clinical manifestations. SIMS may include cachexia, anorexia, nausea, early satiety, fatigue, tumor fever, cognitive changes and superinfection. The aim of this study was to ameliorate some of the SIMS symptoms in a homogeneous group of lung adenocarcinoma patients using a multitargeted therapy. Fifteen patients with evidence of SIMS were studied. SIMS was defined as the presence of weight loss, anorexia, fatigue performance status>/=2 and acute-phase protein response. Patients received medroxyprogesterone (MPA) (500 mg twice daily), celecoxib (200 mg twice daily), plus oral food supplementation for 6 weeks. After treatment, 13 patients either had stable weight (+/- 1%) or had gained weight. There were significant differences in improvement of body-weight-change rate, nausea, early satiety, fatigue, appetite and performance status. Patients who had any kind of lung infection showed higher levels of IL-10 compared to non-infected patients (P=0.039). Our results suggest that patients with advanced lung adenocarcinoma, treated with MPA, celecoxib and dietary intervention, might have considerable improvement in certain SIMS outcomes. This multitargeted symptomatic approach deserves further study.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antineoplastic Agents/therapeutic use , Cachexia/therapy , Fatigue/therapy , Medroxyprogesterone/therapeutic use , Sulfonamides/therapeutic use , Superinfection/therapy , Adenocarcinoma/complications , Adult , Aged , Cachexia/diet therapy , Cachexia/etiology , Celecoxib , Fatigue/diet therapy , Fatigue/etiology , Female , Humans , Lung Neoplasms/complications , Male , Middle Aged , Pilot Projects , Pyrazoles , Superinfection/diet therapy , Superinfection/etiology , Syndrome
SELECTION OF CITATIONS
SEARCH DETAIL