mobic and Prostatic-Neoplasms

Canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) of prostate and urinary bladder are highly invasive and metastatic tumors of closely neighbored organs. Cell lines are valuable tools to investigate tumor mechanisms and therapeutic approaches in vitro. PAC in dogs is infrequent, difficult to differentiate from TCC and usually characterized by poor prognosis, enhancing the value of the few available cell lines. However, as cell lines adapt to culturing conditions, a thorough characterization, ideally compared to original tissue, is indispensable. Herein, six canine PAC cell lines and three TCC cell lines were profiled by immunophenotype in comparison to respective original tumor tissues. Three of the six PAC cell lines were derived from primary tumor and metastases of the same patient. Further, two of the three TCC cell lines were derived from TCCs invading into or originating from the prostate. Cell biologic parameters as doubling times and chemoresistances to commonly used drugs in cancer treatment (doxorubicin, carboplatin and meloxicam) were assessed. All cell lines were immunohistochemically close to the respective original tissue. Compared to primary tumor cell lines, metastasis-derived cell lines were more chemoresistant to doxorubicin, but equally susceptive to carboplatin treatment. Two cell lines were multiresistant. COX-2 enzyme activity was demonstrated in all cell lines. However, meloxicam inhibited prostaglandin E2 production in only seven of nine cell lines and did neither influence metabolic activity, nor proliferation. The characterized nine cell lines represent excellent tools to investigate PAC as well as TCC in prostate and urinary bladder of the dog. Furthermore, the profiled paired cell lines from PAC primary tumor and metastasis provide the unique opportunity to investigate metastasis-associated changes PAC cells undergo in tumor progression. The combination of nine differently chemoresistant PAC and TCC cell lines resembles the heterogeneity of canine lower urinary tract cancer.

Topics: Adenocarcinoma; Animals; Carboplatin; Carcinoma, Transitional Cell; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Dog Diseases; Dogs; Doxorubicin; Gene Expression Regulation, Neoplastic; Immunophenotyping; Male; Meloxicam; Neoplasm Metastasis; Prostatic Neoplasms; Urinary Bladder Neoplasms

A 12-year-old neutered male Springer Spaniel was referred with a 1-year history of recurring urinary tract infections. Repeated treatment with appropriate antimicrobials selected on the basis of bacterial culture and antimicrobial susceptibility results would result in clinical improvement, but recurrence of clinical signs was observed within days after discontinuation of treatment.. Ultrasound examination revealed a tubular, fluid-filled structure dorsal to the bladder that extended from the midlevel of the bladder to the cranial pole of the prostate. Mineralized foci within a heterogeneous prostatic parenchyma were also noted. Dilation of the right ductus deferens (DD) was observed during exploratory laparotomy.. Both DD were surgically removed, and the prostate was biopsied. The histopathological diagnosis was transitional cell carcinoma involving the right DD and the prostate. The dog was treated with meloxicam (0.1 mg/kg [0.05 mg/lb], p.o., q 24 h) for 9 months after diagnosis before being euthanized.. Because the normal DD is rarely visualized during abdominal ultrasonography in dogs, identification of a tubular, fluid-filled structure dorsal to the bladder may indicate an abnormal DD. Transitional cell carcinoma of the DD should be included in the differential diagnoses of affected patients examined for clinical signs involving the urinary tract.

Topics: Animals; Carcinoma, Transitional Cell; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Euthanasia, Animal; Male; Meloxicam; Prostatic Neoplasms; Testicular Neoplasms; Thiazines; Thiazoles; Vas Deferens

Recent studies have shown that COX-2 inhibitors, such as meloxicam, have demonstrated promising results when used with chemotherapy. Based on these findings, this is the first study in which the antiproliferative effect of meloxicam is investigated on two prostate cancer cell lines (PC3 and DU-145). We have also evaluated if this antiproliferative effect is dose- and/or time-dependent. Meloxicam is assayed at a concentration range of 10-800 microM for 24, 48 and 72 h. Our results reveal that meloxicam has a selective dose- and time-dependent antiproliferative effect against PC3 but not against DU-145 cells. In PC3 cells the IC(50) decreased from 740 microM at 24 h to 515 microM at 72 h after meloxicam treatment. Chemoembolization based on microspheres has been emerged as a novel and promising way for antitumoural therapy; therefore, in our study we have developed and characterized a new controlled release system consisting of biodegradable PLGA/PEG-derivative meloxicam microspheres. The optimized formulation has a mean particle size of 13.06+/-0.09 microm, mean encapsulation efficiency of 58.44+/-4.53% and releases 0.45+/-0.05 microg meloxicam/day/mg microspheres between days 3 and 28 of the in vitro release assay. In conclusion, we should consider meloxicam as a possible adjuvant agent in the treatment of prostate cancer.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2 Inhibitors; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Inhibitory Concentration 50; Lactic Acid; Male; Meloxicam; Particle Size; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Prostatic Neoplasms; Thiazines; Thiazoles; Time Factors

Hypoxia-induced up-regulation of vascular endothelial growth factor (VEGF) expression is a critical event leading to tumor neovascularization. Hypoxia stimulates hypoxia-inducible factor-1alpha (HIF-1alpha), a transcriptional activator of VEGF. Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the formation of prostaglandins (PGs) from arachidonic acid, is also induced by hypoxia. We reported previously that COX-2 inhibition prevents hypoxic up-regulation of VEGF in human prostate cancer cells and that prostaglandin E(2) (PGE(2)) restores hypoxic effects on VEGF. We hypothesized that PGE(2) mediates hypoxic effects on VEGF by modulating HIF-1alpha expression. Addition of PGE(2) to PC-3ML human prostate cancer cells had no effect on HIF-1alpha mRNA levels. However, PGE(2) significantly increased HIF-1alpha protein levels, particularly in the nucleus. This effect of PGE(2) largely results from the promotion of HIF-1alpha translocation from the cytosol to the nucleus. PGE(2) addition to PC-3 ML cells transfected with a GFP-HIF-1alpha vector induced a time-dependent nuclear accumulation of the HIF-1alpha protein. Two selective COX-2 inhibitors, meloxicam and NS398, decreased HIF-1alpha levels and nuclear localization, under both normoxic and hypoxic conditions. Of several prostaglandins tested, only PGE(2) reversed the effects of a COX-2 inhibitor in hypoxic cells. Finally, PGE(2) effects on HIF-1alpha were specifically inhibited by PD98059 (a MAPK inhibitor). These data demonstrate that PGE(2) production via COX-2-catalyzed pathway plays a critical role in HIF-1alpha regulation by hypoxia and imply that COX-2 inhibitors can prevent hypoxic induction of HIF-mediated gene transcription in cancer cells.

Topics: Active Transport, Cell Nucleus; Arachidonic Acid; Catalysis; Cell Nucleus; Culture Media, Serum-Free; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Cytosol; Dinoprostone; Endothelial Growth Factors; Enzyme Inhibitors; Flavonoids; Green Fluorescent Proteins; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoblotting; Intercellular Signaling Peptides and Proteins; Isoenzymes; Luminescent Proteins; Lymphokines; Male; MAP Kinase Signaling System; Meloxicam; Membrane Proteins; Nitrobenzenes; Phosphatidylinositol 3-Kinases; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfonamides; Thiazines; Thiazoles; Time Factors; Transcription Factors; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors