mobic and Carcinoma--Transitional-Cell

Urothelial carcinoma (UC) is the most common tumour of the canine urinary bladder. Recently, BRAF mutation testing emerged as a diagnostic option, but its prognostic significance is unknown. This study investigates the relationship between BRAF (variant V595E) mutation status and overall survival in UC-bearing dogs. Seventy-nine patients histologically diagnosed with UC of the bladder and/or urethra between 2006 and 2019 were included in this retrospective single-centre-study. Treatment consisted of meloxicam (n = 39, group 1 'Melox'), mitoxantrone and meloxicam (+/- followed by metronomic chlorambucil; n = 23, group 2 'Chemo') or partial cystectomy followed by meloxicam +/- mitoxantrone (n = 17, group 3 'Sx'). Survival was significantly influenced by treatment (p = .0002) and tumour location (p < .001) in both uni- and multivariable analyses. BRAF mutation was identified in 51 tumours (=64.6%) and had no statistically significant influence on overall survival: MST for BRAF-negative patients 359 versus 214 days for BRAF-positive dogs (p = .055). However, in BRAF-positive dogs, survival depended significantly on type of treatment in univariable analysis: MSTs for groups 1-3 were 151, 244 and 853 days, respectively (p = .006); In BRAF-positive group 2 ('Chemo')-patients, adjuvant metronomic chlorambucil after mitoxantrone more than doubled MST compared to patients receiving mitoxantrone alone (588 vs. 216 days; p = .030). In contrast, MSTs were not significantly different in BRAF-negative patients among the three treatment groups (p = .069). Multivariate analysis of these data was not possible due to group size limitations. This study identified tumour location and treatment type, but not BRAF mutation status, as independent prognostic factors for overall survival.

Topics: Animals; Carcinoma, Transitional Cell; Chlorambucil; Dog Diseases; Dogs; Female; Male; Meloxicam; Mitoxantrone; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Retrospective Studies; Urinary Bladder 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

Records of 11 cats with transitional cell carcinoma of the urinary bladder, which had been treated with meloxicam, were reviewed for signalment, duration of clinical signs prior to diagnosis, results of diagnostic imaging, whether or not concurrent surgery was performed and survival. Immunohistochemical expression of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) was assessed in the tumours of seven cats. Tumour location varied greatly. The cats had a mean age of 13 years. Three cats had a previous diagnosis of feline idiopathic cystitis of up to 2008 days duration. Ten of the cats showed clinical improvement (reduction of haematuria and/or dysuria), with a mean survival time (MST) of 311 days (range 10-1064); 1-year survival of 50%. All seven bladders assessed for COX staining were COX-1 positive and five were COX-2 positive. The MST for the COX-2-positive cats was 123 days, the MST for the COX-2-negative cases was 375 days.

Topics: Animals; Carcinoma, Transitional Cell; Cat Diseases; Cats; Cyclooxygenase 1; Cyclooxygenase 2; Female; Immunochemistry; Isoenzymes; Male; Meloxicam; Neoplasm Proteins; Survival Analysis; Thiazines; Thiazoles; Urinary Bladder Neoplasms

To examine the chemopreventive effects of a selective cyclooxygenase (COX)-2 inhibitor, meloxicam, and a selective epidermal growth factor (EGF)-receptor tyrosine kinase inhibitor, gefitinib (as a single agent) on a carcinogen-induced rodent bladder carcinogenesis model.. The study comprised 103 male Fisher-344 rats (8 weeks old); after initial carcinogen treatment for 8 weeks with 0.05%N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water, the rats were divided into five groups, i.e. group 1, control (vehicle only); group 2, gefitinib high-dose (15 mg/kg by gavage once daily); group 3, gefitinib low-dose (5 mg/kg); group 4, meloxicam high-dose (1.8 mg/kg by gavage once daily); and group 5, meloxicam low-dose (0.6 mg/kg). Twelve weeks later the rats were killed; after fixing the bladder in 10% formalin, the number and size of hyperplasia and carcinoma foci were recorded microscopically in sections stained with haematoxylin and eosin, submitted entirely as multiple strips.. The incidence of carcinoma, confirmed microscopically, was: control 14/20 (70%); high-dose gefitinib, 7/20 (35%); low-dose gefitinib, 7/20 (35%); high-dose meloxicam 7/21 (33%); and low-dose meloxicam, 12/20 (60%). The mean numbers of carcinomas per bladder in groups 1-5 were 1.2, 0.5, 0.4, 0.5 and 1.1, respectively. The incidence and the mean number of carcinomas per bladder were significantly lower in the treatment groups (P < 0.05) than in the control group, except in the low-dose meloxicam group. There were no significant adverse effects.. Both meloxicam and gefitinib have inhibitory effects on rat bladder carcinogenesis with no significant adverse effects. A combination of these drugs would be worth studying for their synergistic effects.

Topics: Animals; Anticarcinogenic Agents; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma, Transitional Cell; Cyclooxygenase Inhibitors; Gefitinib; Male; Meloxicam; Protein Kinase Inhibitors; Quinazolines; Rats; Rats, Inbred F344; Thiazines; Thiazoles; Treatment Outcome; Urinary Bladder Neoplasms