pulmicort and Colonic-Neoplasms

Complicated diverticulitis is an uncommon endoscopic finding. We report an unusual case of complicated diverticulitis in a 53-year-old man suffering from chronic constipation, abdominal pain and a recent episode of subocclusion. He underwent to colonoscopy that showed left-sided diverticulosis and a 3 cm irregular mass in the sigmoid. During biopsy sampling due to the suspect of colonic carcinoma, pus and bleeding came out from the lesion. After lavage, a large diverticulum with visible vessel at the bottom was found, which was clipped with stopping bleeding. After a short course of in-hospital treatment, at discharging the patient was treated with budesonide MMX9 mg/day for 8 weeks. At that time, colonoscopy did not show sign of diverticular inflammation, and inflammatory indexes were normal. This case demonstrates that the use of a topical steroid, combined with an endoscopic approach, may easily resolve an unusual endoscopic complication in patients suffering from complicated diverticular disease.

Topics: Anti-Inflammatory Agents; Budesonide; Colonic Neoplasms; Colonoscopy; Diagnosis, Differential; Diverticulitis, Colonic; Drug Administration Schedule; Humans; Male; Middle Aged

Topics: Budesonide; Colectomy; Colitis; Colonic Diseases; Colonic Neoplasms; Diagnosis, Differential; Emergencies; Eosinophilia; Humans; Intestinal Obstruction; Male; Middle Aged; Sigmoid Diseases

This study evaluates whether the inhibitory effects of prednisolone phosphate (PLP) encapsulated in long-circulating liposomes (LCL-PLP) on tumor growth and tumor angiogenesis described previously can be generalized to other types of glucocorticoids (GC) encapsulated in LCL (LCL-GC). Four types of synthetic GC, i.e. budesonide disodium phosphate (BUP), dexamethasone disodium phosphate (DXP), methylprednisolone disodium phosphate (MPLP), and PLP, were selected based on the difference in their potency to activate the human glucocorticoid receptor. The effects of all LCL-GC on the production of angiogenic/inflammatory factors in vivo in the B16.F10 murine melanoma model as well as on the viability and proliferation of tumor cells and endothelial cells in vitro were investigated. Our results show that all four selected LCL-GC formulations inhibit tumor growth, albeit to different degrees. The differences in antitumor activity of LCL-GC correlate with their efficacy to suppress tumor angiogenesis and inflammation. The strongest antitumor effect is achieved by LCL-encapsulated BUP (LCL-BUP), due to the highest potency of BUP versus the other three GC types. The in vitro results presented herein suggest that LCL-BUP has strong cytotoxic effects on B16.F10 melanoma cells and the anti-proliferative effects of all LCL-GC towards angiogenic endothelial cells play a role in their antitumor activity.

Topics: Animals; Budesonide; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cells, Cultured; Colonic Neoplasms; Dexamethasone; Dose-Response Relationship, Drug; Drug Delivery Systems; Endothelium, Vascular; Glucocorticoids; Inflammation; Injections, Subcutaneous; Liposomes; Male; Melanoma, Experimental; Methylprednisolone; Mice; Mice, Inbred C57BL; Nanomedicine; Neovascularization, Pathologic; Prednisolone; Receptors, Glucocorticoid; Time Factors; Tumor Burden; Umbilical Veins

Allergen-induced respiratory inflammation facilitates and/or elicits the extravasation of proinflammatory leukocytes by well-understood mechanisms that mediate the movement of multiple cell types. The nonspecific character of these pathways led us to hypothesize that circulating cancer cells use similar mechanisms, promoting secondary tumor formation at distal sites. To test this hypothesis, the frequency of metastasis to the lung as a function of allergic pulmonary inflammation was assessed following the i.v. injection of B16-F10 melanoma cells in mice. These studies showed that allergen-induced pulmonary inflammation resulted in a >3-fold increase in lung metastases. This increase was dependent on CD4(+) T-cell activities; however, it occurred independent of the induced eosinophilia associated with allergen provocation. Interventional strategies showed that existing therapeutic modalities for asthma, such as inhaled corticosteroids, were sufficient to block the enhanced pulmonary recruitment of cancer cells from circulation. Additional mechanistic studies further suggested that the ability of circulating cancer cells to extravasate to surrounding lung tissues was linked to the activation of the vascular endothelium via one or more Galpha(i)-coupled receptors. Interestingly, a survey of a clinical breast cancer surgical database showed that the incidence of asthma was higher among patients with lung metastases. Thus, our data show that allergic respiratory inflammation may represent a risk factor for the development of lung metastases and suggest that amelioration of the pulmonary inflammation associated with asthma will have a direct and immediate benefit to the 7% to 8% of breast cancer patients with this lung disease.

Topics: Animals; Asthma; Breast Neoplasms; Budesonide; CD4-Positive T-Lymphocytes; Cell Adhesion; Cell Line, Tumor; Cell Movement; Colonic Neoplasms; Endothelial Cells; Eosinophilia; Female; GTP-Binding Protein alpha Subunits, Gi-Go; Humans; Lung; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplastic Cells, Circulating; Vascular Cell Adhesion Molecule-1

Lung and colon tumors were induced in A/J, C3H, and A/J X C3H (AC3) mice by administering 16 mg/kg vinyl carbamate followed by 6 weekly doses of 12 mg/kg azoxymethane (AOM). Beginning 1 week after carcinogen treatment, the mice received chemopreventive agents, dexamethasone or piroxicam, at 0.1 and 75 mg/kg in the diet, respectively. Both AOM and vinyl carbamate induces lung tumors, but only AOM induced colon tumors. The strain sensitivity for both colon and lung tumors was A/J > AC3 > C3H mice. Dexamethasone and piroxicam reduced the multiplicity of colon and lung tumors in A/J and AC3 mice, demonstrating the advantage of a combined colon and lung bioassay. The ability of budesonide, a drug that prevents mouse lung tumors, to modulate DNA methylation in vinyl carbamate-induced lung tumors was also determined. Budesonide administered for only 7 days prior to sacrifice caused a dose-dependent (0.6 to 2.4 mg/kg diet) reversal in tumors of DNA hypomethylation and hypomethylation of the insulin-like growth factor (IGF)-II gene in the differentially methylated region (DMR) 2 region of exons 4 to 5. Longer treatment with budesonide reversed hypomethylation when administered up to the time of sacrifice. These results indicate that reversal of the hypomethylation of DNA and of specific genes in lung tumors may be applicable as a surrogate end-point biomarker for chemoprevention.

Topics: Animals; Azoxymethane; Biological Assay; Biomarkers; Budesonide; Carcinogens; Chemoprevention; Colonic Neoplasms; Dexamethasone; DNA Methylation; Dose-Response Relationship, Drug; Glucocorticoids; Insulin-Like Growth Factor II; Lung Neoplasms; Mice; Mice, Inbred Strains; Piroxicam; Urethane

Steroid resistance is a major problem in the management of patients with inflammatory bowel disease. In Crohn disease, poor response to corticosteroids has been related to increased expression of the drug efflux pump, P-glycoprotein. However, it has not been investigated thoroughly whether corticosteroids commonly used for drug therapy in inflammatory bowel disease are substrates of P-glycoprotein. We tested the hypothesis that budesonide and prednisone are substrates of P-glycoprotein thereby possibly contributing to variable therapeutic effects. Polarized, basal to apical transport of [3H]budesonide and [3H]prednisone was studied in monolayers of L-MDR1 cells (LLC-PK1 cells stably transfected with human MDR1 cDNA) and Caco-2 cells, both of which express P-glycoprotein in their apical membrane. Drug transport was measured during 4 hours at substrate concentrations of 5 microM. Net transport rates and permeability coefficients were calculated. Inhibition of P-glycoprotein-mediated transport across Caco-2 monolayers was determined after addition of the P-glycoprotein inhibitor PSC-833. The net transport rate from the basolateral to the apical side was significantly higher in L-MDR1 than in LLC-PK1 cells for both budesonide and prednisone. Apparent permeability coefficients of budesonide and prednisone reflected polarized transport from basal to apical. PSC-833 inhibited the polarized transport of both corticosteroids. In conclusion, budesonide and prednisone were identified as substrates of the intestinal drug efflux pump, P-glycoprotein. Therefore, drug secretion via P-glyco-protein into gut lumen might play a more important role in pharmacokinetics and pharmacodynamics of these corticosteroids than currently appreciated in gastroenterological practice.

Topics: Anti-Inflammatory Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Budesonide; Cell Culture Techniques; Colonic Neoplasms; Crohn Disease; Drug Resistance, Multiple; Humans; Permeability; Prednisone; Tumor Cells, Cultured