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1.
OBJECTIVE: To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the cornea, eyelid, and third eyelid of healthy horses and those affected with squamous cell carcinoma (SCC) by use of immunohistochemical techniques. ANIMALS: 15 horses with SCC involving ocular tissues and 5 unaffected control horses. PROCEDURES: SCC-affected tissues were obtained from the cornea (n = 5 horses), eyelid (5), and third eyelid (5). Site-matched control tissues were obtained from 5 horses unaffected with SCC. Tissue sections of affected and control cornea, eyelid, and third eyelid were stained immunohistochemically for COX-1 and COX-2 via standard techniques. Stain uptake was quantified by use of computer-assisted image analysis of digital photomicrographs. RESULTS: Immunoreactivity for both COX-1 and COX-2 was significantly greater in equine corneas with SCC than in control corneas. No significant differences in COX-1 or COX-2 immunoreactivity were detected in eyelid and third-eyelid SCC, compared with site-matched control tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Immunoreactivity for COX-1 and COX-2 is high in equine corneal SCC, possibly indicating that COX plays a role in oncogenesis or progression of this tumor type at this site. Pharmacologic inhibition of COX may represent a useful adjunctive treatment for corneal SCC in horses.  相似文献   

2.
Expression of cyclooxygenase-2 in canine renal cell carcinoma   总被引：11，自引：0，他引：11  
Cyclooxygenase-2 (COX-2) has been shown to be the primary enzyme responsible for prostaglandin production during inflammation but is absent in most tissues under normal physiological states. High levels of COX-2 expression have been observed in the macula densa and thick ascending limbs of fetal kidneys; this expression declines to minimal levels during renal maturation. We hypothesized that the neoplastic cells of renal cell carcinoma (RCC) may revert to high expression of COX-2, and we evaluated its expression in three spontaneous cases of canine RCC by using immunohistochemical methods. The neoplastic cells of two of the three cases exhibited moderate to marked COX-2 immunoreactivity. These results suggest that some canine renal cell carcinomas express high levels of COX-2, which may play a role in the modulation of neoplastic cell growth.  相似文献   

3.
Four horses treated for ocular squamous cell carcinoma (SCC) that subsequently developed local tumour extension or local metastases without ocular recurrence are included in this study. Medical records were examined and long‐term follow‐up obtained through contact with owners and referring veterinarians. In 2 horses, SCC developed in the nasolacrimal duct and maxillary sinus one and 3.5 years, respectively, after treatment for SCC in the medial canthus of the eye. No recurrence of the SCC was noted in the ocular structures. Both were treated successfully with surgery and radiation therapy. Two additional horses had delayed metastasis of SCC to the parotid lymph node one and 2 years after excision of the ipsilateral third eyelid for SCC. No recurrence of the SCC was noted in the ocular structures. One was treated with surgery and radiation without success and one was not treated. Ocular SCC can spread to local tissues or lymph nodes without recurrence in the eye. The clinical manifestation of tumour recurrence may be delayed. Delayed local extension or local metastasis in horses after ocular SCC without recurrence in the eye itself has not been previously reported. Clinical signs of ocular squamous cell carcinoma should prompt immediate treatment and local recurrence despite successful treatment of the ocular disease is a possibility.  相似文献   

4.
Two Quarter Horse mares with hereditary equine regional dermal asthenia (HERDA) were diagnosed with metastatic squamous cell carcinoma (SCC) associated with chronic nonhealing wounds. The lesions were similar to the development of SCC from chronic nonhealing ulcers, known as Marjolin’s ulcers in humans. The horses showed recurrent skin wounds in the saddle and paralumbar regions and were confirmed by molecular techniques as having HERDA. Both horses were maintained as research animals for prolonged periods and received regular veterinary care and wound treatment. Both horses were ultimately euthanized because of their chronic progressive wounds, coupled with declining health. At necropsy, the nonhealing wounds were found to be complicated by infiltrative SCC; both horses had metastasis to lungs. Chronically inflamed, recurrent skin wounds that heal slowly and incompletely as a consequence of HERDA are proposed as a major pathogenetic factor in tumorigenesis. Consistent findings with respect to proliferation index (Ki-67) and mutations of p53 tumor suppressor gene were confirmed by immunohistochemistry in one horse. SCC consistent with Marjolin’s ulcer has been previously suggested in association with chronic ulcers or burn scars in horses, but this is the first report of an association with chronic poor healing wounds in HERDA horses.  相似文献   

5.
Cyclooxygenase-2 expression in the cornea of dogs with keratitis   总被引：6，自引：0，他引：6  
Cyclooxygenase-2 (COX-2) can be overexpressed at inflammatory sites, leading to the generation of proinflammatory prostanoids. Selective inhibitors of COX-2 have potential use in treating inflammatory conditions including ophthalmic diseases in veterinary medicine. Keratitis is considered the most common inflammatory eye disease in dogs. In this study we evaluated the expression of COX-2 in normal dog eyes and in dog eyes with keratitis by immunohistochemistry using isoform-specific antibodies. In the normal eye (n = 4), no COX-2 immunoreactivity was observed in the cornea. In keratitis, COX-2 (n = 12) expression was observed in all corneal layers (epithelium, stromal cells, and endothelium). COX-2 immunoreactivity was also noted in the stromal and epithelial cells of the iris and the stromal cells of the trabecular meshwork. These data indicate that COX-2 may play a pathophysiologic role in keratitis and suggest potential therapeutic implications of prostaglandin modulation in inflammatory eye diseases.  相似文献   

6.
Ovarian tumours among domestic animals are frequently encountered in bitch. Cyclooxygenase-2 (COX-2) expression has been evaluated in different kind of canine primary epithelial neoplasms. Eleven canine ovarian carcinomas and two normal samples were evaluated immunohistochemically for COX-2 expression. Nine of 11 carcinoma samples (81%) expressed COX-2 enzyme isoform. The immunoreactivity was intracytoplasmically recorded and the intensity ranged from faint to strong. Our results show that COX-2 is expressed in canine ovarian carcinoma, suggesting a potential role of COX-2 in canine ovarian carcinogenesis.  相似文献   

7.
A perception exists amongst referring veterinarians and the lay public that blue‐eyed horses have increased frequency of ocular disease. The aim of this retrospective study was to assess the prevalence of ocular disease in horses with blue or heterochromic eyes relative to those with brown eyes. The medical records of horses presenting to either the Comparative Ophthalmology services or Equine Medicine/Surgery services at 2 institutions were reviewed. Signalment, ocular and nonocular diagnoses were recorded. Ocular disease was divided into 4 categories: adnexa, cornea, intraocular/orbit and squamous cell carcinoma (SCC). Owners were contacted by telephone to confirm iris colour. Chi‐square analysis was used to compare group proportions. A total of 164 eyes of horses with ocular disease and 212 eyes of horses without ocular disease were included. Blue eyes were equally common in the ocular disease and nonocular disease groups (P = 0.265). There was no significant difference in the proportion of blue‐ and brown‐eyed horses when comparing the adnexal and corneal (P = 0.548), corneal and intraocular/orbit (P = 0.379) and adnexal and intraocular/orbit (P = 0.843) categories. A significant difference was detected in the proportion of blue‐eyed horses between the adnexal (P = 0.000), corneal (P = 0.033), intraocular/orbital (P = 0.000) and SCC categories, with a higher proportion of blue‐eyed horses in the SCC than in the other 3 groups. Horses with blue or heterochromic irides are more likely to develop ocular SCC than horses with brown irides, but are not more likely to have adnexal, corneal or intraocular/orbital disease or to be presented for evaluation of ophthalmic disease. Veterinarians should consider the results of this study when answering questions from the lay public regarding the predisposition of blue‐eyed horses to ocular disease.  相似文献   

8.
Identification of regional and/or distant metastasis following treatment and local resolution of primary ocular squamous cell carcinoma (SCC) was observed in 5 horses. In all cases, identification of metastasis occurred at least 18 months following treatment of the primary ocular lesions. In 3 cases, invasion of blood or lymphatic vessels by neoplastic cells was identified in the excisional biopsies of the primary tumour. Two horses developed SCC at 2 or more separate sites. At the time metastases were identified, there was no evidence of local recurrence of the ocular tumour in any of the horses. These cases confirm the importance of long‐term monitoring of horses for metastatic disease following treatment of ocular SCC even in the absence of local recurrence.  相似文献   

9.
The enzyme cyclooxygenase-2 (COX-2) is expressed in some tumor and stromal tissues, and catalyzes production of prostaglandins with growth stimulatory, antiapoptotic, proangiogenic, and immunosuppressive properties. Pharmacologic inhibition of COX-2 is associated with antitumor activity in various human and canine malignancies. The purpose of this study was to assess COX-2 expression in a series of equine sarcoids, melanomas, and squamous-cell carcinomas (SCC). COX-2 expression was assessed in formalin-fixed paraffin-embedded tissues from 14 sarcoids, 11 melanomas, and 37 SCC that represent various anatomic sites by using standard immunohistochemical methods. COX-2 was expressed in 2 of 14 sarcoids, 7 of 11 melanomas, and 32 of 37 SCC, 56% of which demonstrated moderate-to-strong immunoreactivity. There were no differences in expression between anatomic sites. In conclusion, most equine SCC and many melanomas appear to express COX-2 and thus could respond to COX-2 inhibitor therapy.  相似文献   

10.
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11.
Between January 1978 and December 1988, 147 horses with ocular/adnexal squamous cell carcinoma (SCC) were admitted to the Colorado State University Veterinary Teaching Hospital (CSU-VTH). Diagnosis was confirmed by histologic examination of appropriate tissue specimens. Medical records and communication with owners, referring veterinarians, or both provided information regarding initial examination, treatment at the CSU-VTH, and final outcome. At initial examination, 123 (83.7%) horses had unilateral involvement and 24 (16.3%) horses had bilateral involvement. The nictitating membrane, nasal canthus, or both (28.1%); limbus (27.5%); and eyelid (22.8%) were most commonly affected. In addition to the ocular/adnexal location, SCC was found elsewhere in 14 (9.5%) horses at initial examination. Adequate follow-up (greater than or equal to 4 months) for examination of tumor recurrence and survival analysis was obtained for 125 (85.0%) cases. After treatment at the CSU-VTH, tumor recurred in 30.4% of the cases. Tumor location, multiple vs single tumors at initial diagnosis, and CSU-VTH treatment modality influenced the recurrence of tumors. Survival analysis revealed a good prognosis for horses with ocular/adnexal SCC. Although undefined, a conservative estimate of the median survival time was 47 months. Six factors (treatment prior to referral, tumor location, tumor size, single or multiple tumors, treatment modality at the CSU-VTH, and recurrence or nonrecurrence) were analyzed to determine their relation with survival. Treatment prior to referral, multiple vs single tumors at initial examination, and treatment modality used at the CSU-VTH did not influence survival. Tumor location influenced survival; SCC involving the eyelid or orbit was associated with the poorest prognosis. Tumor stage (maximal dimension) was inversely related with survival.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

12.
Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotheraputic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis.  相似文献   

13.
In this retrospective study, medical records of 26 horses whose eyelids were tattooed were analyzed, and data regarding age, breed, eyelid pigment, eye color, sex, and reproductive status of the horses were compiled. Owners of the horses were contacted by telephone and questioned about their horses. Twenty-six horses were tattooed at Colorado State University (CSU), and one of them was tattooed twice. Records were available for 26 horses, and follow-up results by telephone were completed for 22 of those. Telephone follow-up times ranged from 3 months to 17 years after tattooing. American Paint Horses constituted 62% (16/26) of the cases, followed by Appaloosas (19% = 5/26), and Quarter Horses (8% = 2/26). In 100% (22/22) of cases, the reason for presenting the horse for a tattoo was lack of periocular pigmentation. Only two horses developed ocular or periocular squamous cell carcinoma (SCC) after their tattoos. Although the results of this study suggest that tattooing may be protective against SCC and solar blepharitis, it is by no means conclusive. However it appears to have no deleterious effects, and often owners like the appearance of the tattooed eyelid.  相似文献   

14.
OBJECTIVE: To assess expression of cyclooxygenase (COX)-1 and -2 in naturally occurring squamous cell carcinomas (SCCs) and the analogous normal tissues in horses. SAMPLE POPULATION: Tissue samples collected from 3 conjunctival, 2 vulvar, 4 preputial, and 5 penile SCCs during surgical excision in 14 horses and from corresponding body regions (conjunctiva [n = 5 horses], vulva [2], prepuce [3], and penis [3]) in 5 horses euthanized for reasons unrelated to neoplasia. PROCEDURES: Tissue samples were snap frozen in liquid nitrogen and stored at -80 degrees C until analysis. Protein was extracted from the frozen tissues, and western blot analyses were performed. Nonneoplastic and abnormal tissues from each body region were run on the same blot, and blots were run in triplicate. Molecular-weight markers and COX-1 and 2 ovine standards (positive control samples) were run concurrently on the gels; negative control samples were not used. RESULTS: All tissues, including the nonneoplastic and SCC tissues, expressed both COX-1 and -2 proteins. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the expression of COX proteins in both nonneoplastic and SCC-affected tissues in horses is markedly different from that in other species. The reason for the potential benefit of COX-2 inhibitors in horses and other species is unknown. Further research needs to be performed to evaluate the efficacy of COX-2 inhibitors as cancer treatments in horses. Investigation of the mechanisms of tumor development in horses should be performed to increase understanding of this disease and ascertain how the mechanisms differ from those in other animals.  相似文献   

15.
OBJECTIVE: To determine the effects of treatment with and without adjuvant radiation therapy on recurrence of ocular and adnexal squamous cell carcinoma (SCC) at specific anatomic locations in horses. DESIGN: Retrospective study. ANIMALS: 91 horses. PROCEDURES: Medical records of horses with histologically confirmed ocular and adnexal SCC evaluated from 1985 to 2002 were reviewed. Sex, breed, age, type of treatment, location, and recurrence of SCC were recorded. Two treatment groups determined by recurrence of SCCs treated with and without adjuvant radiation therapy were established. RESULTS: The anatomic site with the highest recurrence rate was the limbus (junction of the cornea and sclera) or bulbar conjunctiva (477%), independent of treatment group. There was a significant difference in recurrence rates of ocular and adnexal SCCs between the 2 treatment groups, independent of anatomic location. Recurrence rates of SCCs treated with and without adjuvant radiation therapy were 11.9% and 44.1%, respectively. Recurrence rates for SCCs of the eyelid, limbus or bulbar conjunctiva, and cornea treated with adjuvant radiation therapy were significantly different from those for SCCs treated without adjuvant radiation therapy. The most frequently represented anatomic site for ocular and adnexal SCCs was the eyelid (28.7%). Coat color, breed, and the interaction of age and breed had a significant effect on tumor recurrence regardless of treatment type and anatomic location. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that ocular and adnexal SCCs treated with adjuvant radiation therapy had a significantly lower recurrence rate, compared with SCCs treated without adjuvant radiation therapy, independent of anatomic location.  相似文献   

16.
Cryopreserved equine ocular squamous cell carcinoma (SCC) was inoculated subcutaneously into 15 athymic nude and 15 SCID mice. Xenotransplantation resulted in tumor growth in two athymic nude mice and 1 SCID mouse. Histological appearance and immunohistochemical characterization using cytokeratin 5/6 markers and p53 markers of the tumor grown in mice was in full accord with the original equine tumors. No evidence of metastasis was noted in any mouse. This model may serve as a relevant in vivo model for studying the biology of equine ocular SCC and for the testing of new therapeutic modalities.  相似文献   

17.
Cyclooxygenase (COX) performs the critical initial reaction in the arachidonic metabolic cascade, leading to formation of proinflammatory prostaglandins, thromboxanes, and prostacyclins. The discovery of a second COX isoform (COX-2) associated with inflammation led to agents that selectively inhibit COX-2. Cyclooxygenase-2 inhibitors are also being developed for canine applications. To assess the compound potency on canine enzymes, canine COX-1 and COX-2 were cloned, expressed, and purified. Cyclooxygenase-1 was cloned from a canine kidney complementary DNA (cDNA) library, with 96 % sequence homology to human COX-1. Cyclooxygenase-2 was cloned from canine kidney and lipopolysaccharide-stimulated macrophage cDNA libraries, with a 93 % sequence homology to human COX-2. The arachidonic acid Michaelis constants for canine COX-1 and COX-2 were 4.8 and 6.6 micrometer, respectively, compared with 9.6 and 10.2 micrometer for ovine. Inhibition results indicated that, for all compounds tested, there was no significant difference between potencies determined for canine enzymes and those for human enzymes.  相似文献   

18.
Cryopreserved equine ocular squamous cell carcinoma (SCC) was inoculated subcutaneously into 15 athymic nude and 15 SCID mice. Xenotransplantation resulted in tumor growth in two athymic nude mice and 1 SCID mouse. Histological appearance and immunohistochemical characterization using cytokeratin 5/6 markers and p53 markers of the tumor grown in mice was in full accord with the original equine tumors. No evidence of metastasis was noted in any mouse. This model may serve as a relevant in vivo model for studying the biology of equine ocular SCC and for the testing of new therapeutic modalities.  相似文献   

19.
Objective To determine the complications and nonrecurrence rates following superficial lamellar keratectomy, bulbar conjunctivectomy, and adjunctive carbon dioxide (CO2) photoablation for corneolimbal squamous cell carcinoma (SCC) in the horse. Study design Retrospective study. Sample population Twenty‐four horses with corneolimbal SCC. Procedure Medical records of horses diagnosed with corneolimbal SCC that was surgically excised and where CO2 photoablation was used as an adjunctive therapy from 2000 to 2007 were reviewed. Signalment, prior therapy, tumor location and size, complications, and recurrence of SCC were recorded. Results The Thoroughbred was the most commonly (25%) represented breed. Lesions were >10 mm in diameter in 70.8% of cases. Eight horses (33.3%) had neoplastic cells extending to the deep margin of the keratectomy. All horses were available for follow‐up for an average ± standard deviation of 40.7 ± 25 months. Four horses (16.7%) developed a recurrence of SCC. Three of these four horses underwent repeat keratectomy and CO2 photoablation, one each, at 4 months, 1, and 2 years following the initial procedure. One horse underwent enucleation 8 months following the initial procedure. Conclusions and clinical relevance As an adjunctive therapy, CO2 photoablation was successful in 87.5% of the horses following a single procedure and in a total of 91.7% following a second therapeutic application. CO2 photoablation appears to be effective as an adjunctive therapy following removal of large corneolimbal SCC in the horse and in cases in which all tumor cells were not excised.  相似文献   

20.
OBJECTIVE: To determine the amount of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes induced in vitro in equine alveolar macrophages in response to lipopolysaccharide (LPS). Sample Population-Alveolar macrophages obtained from 12 horses. PROCEDURE: Alveolar macrophages were collected by bronchoalveolar lavage from 12 horses and incubated for 6 hours with LPS (0.001 to 10 microg/ml) or vehicle. Total RNA was extracted and purified. After first-strand cDNA synthesis, mRNA induction was measured, using a polymerase chain reaction (PCR) technique for COX-2, iNOS, and glyceraldehyde 3-phosphate dehydrogenase. In a second study, cells were incubated with LPS or vehicle for 24 hours. Culture medium was assayed for COX-2 and iNOS activity by determining prostaglandin E2 (PGE2) and total nitrite concentrations, respectively. RESULTS: Lipopolysaccharide induces COX-2 and iNOS mRNA in equine alveolar macrophages. Sequencing revealed that PCR products for COX-2 and iNOS had a high degree of nucleotide homology with the human sequences (91% COX-2, 93% iNOS). Production of mRNA for COX-2 and iNOS was accompanied by induction of enzyme activity. Comparing PCR fragment production, expression of mRNA for iNOS appeared to be less than that for COX-2. Induction of COX-2, but not iNOS, was LPS-concentration dependent. Conclusion-Lipopolysaccharide induces COX-2 and iNOS in equine macrophages. CLINICAL RELEVANCE: The induction of iNOS and COX-2 by LPS in equine macrophages suggests these enzymes may be important in the pathophysiology of sepsis. Pharmacologic modulation of iNOS and COX-2 activity may represent a novel therapeutic target in the management of endotoxemia in horses.  相似文献   

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