Ocular Squamous Cell Carcinoma Research Articles

Association between solar radiation and ocular squamous cell carcinoma in cattle

SUMMARY The association between ocular squamous cell tumors and various measures of solar radiation was evaluated for 2,775 contemporaneous Hereford cattle. The animals were from 34 herds located in 21 states in the United States and in one Canadian province. Examinations and photographs were made of the eyes of all cows and heifers in a herd; 33 herds were examined between June and August 1957 and 1 herd was examined in 1958. Solar radiation was measured by altitude and mean annual hours of sunshine applying to an individual herd, and global radiation, a cloudiness index, and elevation of nearby National Weather Service stations. All measures of solar radiation provided evidence of a significant association between increasing risks of developing cancer eye and increasing levels of radiation; adjustments were made for possible confounding effects of age and corneoscleral pigmentation. Associations were evident whether affliction was defined as the occurrence of any type of tumor (ie, plaque, papilloma, or carcinoma), or as the occurrence of only papilloma or carcinoma. Average ages of affected cattle also tended to be lower at high radiation levels than at low levels, further supporting the hypothesis that solar radiation has an important role in the development of this disease. In view of the heritability of eye pigmentation and its inhibitory effect on lesions, cancer eye may be controlled by selective breeding for increased pigmentation in and around the eye to afford protection against the harmful effects of incident uv radiation.

Combined treatment of ocular squamous cell carcinoma in a horse, using radiofrequency hyperthermia and interstitial 198Au implants

Combined treatment of ocular squamous cell carcinoma in a horse, using radiofrequency hyperthermia and interstitial 198Au implants

Ocular Surgery for Squamous Cell Carcinoma

In treating ocular squamous cell carcinoma in cattle, certainly enucleation or exenteration have been the time honored methods of choice. In many cases they may still be the methods of choice, however, as they leave a unilaterally blind animal, other less radical methods of therapy should be used whenever possible. Less radical therapeutic approaches should include: 1) immunotherapy, 2) cryosurgery, 3) radiofrequency hyperthermia, 4) Beta radiation, and 5) surgical removal of the tumor tissue without complete enucleation.

Local interleukin-2 therapy in bovine ocular squamous cell carcinoma. A pilot study.

Five cows bearing bovine ocular squamous cell carcinoma (BOSCC) were treated with low doses of recombinant human interleukin-2 (rhIL-2). A dose of 2500 U rhIL-2 was injected intralesionally and another 2500 U were injected into the subparotid regional lymph node once a day during a period of 5 consecutive days. This cycle of 5 days was repeated after an interval of 2 days. Total regression of the tumor was observed in three out of five animals. One cow showed tumor regression (greater than 80%) accompanied by metastases to the regional lymph node that were observed from the fifth week after the beginning of the treatment. Growth of the tumor of the fifth animal was retarded after treatment. In vitro proliferation of peripheral blood lymphocytes was investigated in two animals and tumor-infiltrating lymphocytes in one animal during incubation in various rhIL-2 concentrations. Cytotoxic activity of both cell populations against P815, Yac-1 and BOSCC-derived cell lines increased during incubation with rhIL-2. Cultured BOSCC-infiltrating lymphocytes showed predominant killing of the BOSCC-derived autologous cell line after 4 weeks of culture. Preliminary phenotype analysis did not give conclusive results with respect to the types of cells responsible for killing.

Depression of cell-mediated immunity by tumour cell products: induction of resistance by immunotherapeutically active extracts of bovine ocular squamous cell carcinoma.

Tumours produce substances that inhibit the expression of cell-mediated immunity, in the form of delayed-type hypersensitivity in mice. Phenol-saline extracts of bovine ocular squamous cell carcinoma (BOSCC) which have immunotherapeutic activity in cattle were able to immunize mice against this depressive effect. Such immunization was effective against products of BOSCC, a spontaneous rat tumour, three of four human tumour cell lines and (in other experiments) mouse tumours. Phenol-saline extracts of mouse tumour cell lines were immunogenic (protective against depression of delayed-type hypersensitivity) in mice. Fractions of BOSCC phenol-saline extracts which were immunotherapeutically active in cattle were generally also protective in mice. The protective activity was lost after treatment with proteinase K, and was present in the supernatant after precipitation with 55% ammonium sulphate. It was not affected by treatment with RNase or DNase or by heating to 50 degrees C for 2 h. It was present in gel filtration fractions with an apparent molecular weight of 10,000-37,000 daltons. The immunogenic factor in mice and the immunotherapeutic factor in cattle may be related to each other.

Factors influencing morbidity and outcome of equine ocular squamous cell carcinoma.

A retrospective review of 41 cases of equine ocular squamous cell carcinoma with follow up information for 33 horses is presented. An apparent prevalence in heavy horse breeds was identified. Age and sex distribution were similar to those previously reported. High recurrence (42.4 per cent) and low metastasis (6 per cent) rates were seen. Initial tumour location, primary treatment used, or patient case history had no apparent influence on final outcome. The willingness of owners to pursue with continuous treatment correlated with a high degree of success.

TWO‐YEAR NON‐RECURRENCE RATES FOR EQUINE OCULAR AND PERIORBITAL SQUAMOUS CELL CARCINOMA FOLLOWING RADIOTHERAPY

Seventeen horses with a total of 18 ocular or periorbital squamous cell carcinomas were irradiated with Strontium‐90 surface therapy, or Radon‐222, Iodine‐125, or Iridium‐192 interstitial implants. Tumors were surgically cytoreduced prior to irradiation in all but two horses. Follow‐up data was obtained for 2 years in each horse. Two‐year‐non‐recurrence rates (no grossly visible evidence of tumor) were 87.5% for 90Sr beta therapy, and 60% (70% when corrected for non‐tumor‐related deaths) for interstitial implant therapy. Data regarding frequency of occurrence, location of lesions, age of onset, and non‐recurrence rates were similar to previous literature reports utilizing variable or shorter follow‐up periods. The effects of cytoreductive surgery of the tumors was not studied.

Controlling ocular squamous cell carcinoma in Hereford cattle

In 3 herds 737 Hereford cattle were examined for neoplastic ocular lesions at intervals ranging from 20 to 242 days. Initially all lesions greater than 3 mm diameter were treated by cryosurgery; smaller lesions were left untreated. At subsequent inspections, lesions which had increased to 5 mm diameter were treated. The prevalence of ocular lesions in the herds ranged from 8.1 to 45.7% at the commencement of the study, and from 1.5 to 8.8% after 3.5 years. In treated cattle 71% of lesions regressed after one or two treatments. Seventy-five percent of the small untreated lesions regressed. The progression of lesions and occurrence of new lesions was highest during summer and lowest during winter. It was concluded that inspection of eyes for lesions should be at intervals of 3 to 4 months, and include one during the summer. It is feasible for owners to detect and identify cattle with ocular lesions and to present for treatment those that have grown since the preceding inspection to a size nearing or exceeding 5 mm diameter.

Immune reactivity in cattle with ocular squamous cell carcinoma after intralesional BCG immunotherapy.

Lymphocyte stimulation with Con A and specific immune reactivity to BCG (antibody formation to BCG and DTH reaction to PPD) were determined in BCG-treated, surgically treated and untreated cows with ocular squamous cell carcinoma. In tumor-bearing cows the Con A-induced proliferation of lymphocytes was reduced when compared to healthy controls. This suppression consisted of a reduced blastogenic response to Con A of lymphocytes from tumor-bearing cows, and the presence of a factor in the sera of these animals, as these sera suppressed the blastogenic response of lymphocytes from healthy cows. BCG had only a minor influence on the suppressive activity. Antibodies to BCG were demonstrated in 50% of the BCG-treated animals. The formation of antibodies was not influenced by intradermal injection of PPD of Mycobacterium bovis. Absorption of a BCG antibody containing serum with BOSCC tumor extracts did not reveal the existence of cross reacting antigens between BCG and BOSCC. Pretherapeutic and posttherapeutic Con A reactivity could not be correlated with clinical response. Of the 30 BCG treated cows 29 developed a positive DTH reaction to PPD. Correlation between clinical response and immune reactivity was seen only with regard to the DTH reaction to PPD: this reaction remained positive for a longer period after treatment in animals with a favorable clinical outcome than in nonresponding animals.

Clinico-pathological aspects of immunotherapy by intralesional injection of BCG cell walls or live BCG in bovine ocular squamous cell carcinoma.

Bovine ocular squamous cell carcinoma (BOSCC) of clinical stage I, mostly situated in the third eyelid, was chosen as a therapy model for squamous cell carcinoma of the head and neck in humans. Block resection was found to be the best method of treatment. Regression was noticed in 19 out of 30 cows treated intratumourously with a single injection of live BCG or BCG cell wall vaccine, followed by recurrence in 8 cases. In 2 untreated cows, complete lasting regression occurred. Regression was significantly more frequently encountered in intratumourously treated cows than in controls. Regression was associated with a high mitotic index, severe infiltrating growth and small amounts of cellular (lymphoid) infiltration. Metastasis was found in 14 out of 50 cows: 5 in 10 untreated controls, 8 in 30 BCG treated cows and 1 in 10 surgically treated cows. The growth rate of progressively growing untreated and of some treated tumours was not associated with the mitotic index nor with other morphological characteristics tested. The mitotic index was found to be higher in the deep infiltrating layer than in the superficial layer of the primary tumour, suggesting that a single biopsy is not sufficiently representative for cell kinetic studies.

Tumour-associated antigens in bovine ocular squamous cell carcinoma: Studies with sera from tumour-bearing animals

Sera from 21 cattle (10 bovine ocular squamous cell carcinoma (BOSCC) bearing and 11 controls) were tested for antibody reactivity against various cultured cells (BOSCC, normal skin and tumours other than BOSCC), by an indirect immunofluorescence technique. Most of the BOSCC sera reacted with autologous and allogeneic BOSCC cells and did not show any significant reactivity with normal skin cells (autologous or allogeneic). These sera when further tested on 7 different allogeneic or xenogeneic tumour cell types (other than BOSCC), showed significant reactivity only with cultured equine sarcoid and cutaneous papilloma cells. Three of the BOSCC sera did not react with autologous BOSCC cells but reacted indiscriminately with all other allogeneic BOSCC, normal cells and other tumour cells. Most of the control sera did not show any significant reactivity against BOSCC cells except sera from one cow bearing ocular papilloma and 2 healthy normals that were in contact with BOSCC bearing animals. This study suggests that BOSCC cells possess tumour associated antigens that are common to most (if not all) BOSCC cells.

Radical Surgery of Bovine Ocular Squamous Cell Carcinoma (Cancer Eye) Complications and Results

Radical Surgery of Bovine Ocular Squamous Cell Carcinoma (Cancer Eye) Complications and Results

Bovine ocular squamous cell carcinoma: ultrastructural characteristics in vitro.

The ultrastructure of cells obtained from bovine ocular squamous cell carcinoma is described. Cells were observed in pelleted form and in monolayer in situ on film liners. Both preparations consistently showed the ultrastructural features of transformed epithelium in vitro.

Immunoprophylaxis of an Ocular Solid Malignant Tumor in Cattle<xref ref-type="fn" rid="fn2">2</xref><xref ref-type="fn" rid="fn3">3</xref><xref ref-type="fn" rid="fn4">4</xref>

Individual Hereford cows bearing benign precursor lesions of ocular squamous cell carcinoma were treated by intralesional injection of mycobacterial cell walls in an oil-in-water emulsion in an attempt to interrupt neoplastic progression. Thirty-one months after treatment, statistical analysis of data indicated that intralesional BCG cell wall vaccine can interrupt this process and provides effective immunoprophylactic prevention of malignant disease.

Bovine Ocular Squamous Cell Carcinoma: Tumor-Associated Immunity Detected by E-Rosette Augmentation Test<xref ref-type="fn" rid="fn2">2</xref>

The E-rosette augmentation (ERA) assay was used to study cell-mediated immunity with blood leukocytes from cattle with bovine ocular squamous cell carcinoma (BOSCC), from cattle with benign ocular or cutaneous lesions, and from healthy controls. Potassium chloride extracts (3 M) of BOSCC and skin from the same donor, cutaneous bovine papillomas, allogeneic lymphosarcoma, and xenogeneic sheep squamous cell carcinoma were used as antigens. Of the 21 animals with BOSCC, leukocytes of 19 gave positive ERA reactions to BOSCC extract and only those of 4 reacted nonspecifically to other extracts. Of 21 animals in the control group, only 3 gave positive ERA reactions. In reciprocal tests, cattle with BOSCC showed ERA reactivity only against extracts of BOSCC, and cattle with cutaneous papillomas showed reactivity only against extracts of cutaneous papillomas. Blood leukocytes from tumor-bearing cattle stimulated with related tumor extracts released a soluble factor that enhanced E-rosette formation when tested on normal bovine leukocytes.

Immunotherapy by Intralesional Injection of BCG Cell Walls or Live BCG in Bovine Ocular Squamous Cell Carcinoma: A Preliminary Report<xref ref-type="fn" rid="fn2">2</xref>

Cows of the Dutch Frisian and Maas-Rijn-IJssel breed with histologically confirmed ocular squamous cell carcinoma showed complete regression of the primary tumor in 70 or 60% of the cases after intralesional injection of a BCG cell wall or live BCG vaccine, respectively. Recurrence of the tumor was observed in 57% of the animals treated with BCG cell walls and in 25% of the animals treated with live BCG vaccine. Spontaneous regression was seen in 20% of the untreated cows. In a second control group, radical surgery, the most successful treatment for primary stage I tumors in humans, resulted in a 90% cure. Influence of immunotherapy on metastases could not yet be fully evaluated. White blood cell counts were not changed after therapy. It was not possible to link a favorable response to BCG therapy with the intensity of the delayed type hypersensitivity (DTH) reaction to purified protein derivative of mycobacteriae (PPD) or the formation of antibodies to BCG as determined by a micro-enzyme-linked immunosorbent assay. However, in animals that showed tumor regression, the DTH reaction to PPD had a tendency to persist for a longer period of time. It was concluded that 1) block resection was the best method of treatment for this tumor, 2) a single intralesional injection of a BCG cell wall vaccine was as effective as live BCG vaccine in the induction of complete regression of the primary tumor, 3) in this preliminary study BCG cell wall vaccine was less effective than live BCG vaccine in the prevention of recurrence, and 4) this naturally occurring tumor model is well suited for the study of the influence of BCG immunotherapy in a primary stage I tumor.

Ocular Involvement in Xeroderma Pigmentosum

A 37-year-old, white woman with xeroderma pigmentosum had reduced vision for many years because of primary and secondary corneal epithelial edema and stromal haze. Corneal grafting was required, but was not successful. Numerous primary dermal tumors of various types involving the lids of both eyes had been excised surgically or treated by freezing with liquid nitrogen. Squamous cell carcinomas involving the limbal area of the globe and adjacent tissues were excised from the left eye at age 12, the right eye at age 32, and the left eye (again) at age 36. The right limbal tumor soon recurred and invaded the orbit despite radiation treatment; this required right orbital exenteration. The second left limbal tumor recurred one year later, soon after the recurrence of a left lower lid basal cell carcinoma. Left orbital exenteration was required. Corneal graft failures and recurrent ocular squamous cell carcinoma involving the eye in xeroderma pigmentosum can be difficult management problems.

Tumor associated antigens of bovine cancer eye

A study was conducted to determine the presence of surface antigens on cultured cells of bovine ocular squamous cell carcinoma (BOSCC) by serological testing. Serum from cattle with plaque and malignant stages of disease were tested for reactivity with surface antigens of cultured autologous and allogeneic cells. Indirect immune fluorescence assays were conducted to determine the presence of antibodies towards these tumor cells. It was found that sera tested possessed antibodies to the cultured tumor cells. Further, no surface reactivity was observed when these sera were tested for reactivity with normal epithelial cells. Reactive sera were analyzed by absorption tests with autologous and allogeneic cells. Absorbed sera showed no reactivity to surface antigens or allogeneic cells. This study suggests that there might be a shared antigen among the cells from plaque and malignant lesions.

Evidence for papillomaviruses in ocular lesions in cattle

Negatively stained preparations of various ocular lesions, generally considered to be precursors to bovine ocular squamous cell carcinoma, were subjected to electron microscopic examination for viruses. Lesions examined included five conjunctival plaques, an acanthotic lesion from an eyelid, 15 conjunctival papillomas, two papillomas of the eyelid and two keratinised elongated proliferative lesions of the eyelid (cutaneous horns). Eight lesions contained particles that resembled papillomaviruses. These consisted of a conjunctival plaque, five conjunctival papillomas, a papilloma of the eyelid and one of the samples of cutaneous horn. The particles were present in small numbers and were found only after prolonged search. The finding of these particles suggests that papillomavirus may be involved in the aetiology of bovine ocular squamous cell carcinoma.

Efficacy of Intratumorally Administered Mycobacterial Cell Walls in the Treatment of Cattle With Ocular Carcinoma<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref><xref ref-type="fn" rid="FN4">4</xref>

Individual Hereford cows with naturally occurring ocular squamous cell carcinoma were treated by intralesional injections of mycobacterial cell walls in an oil-in-water emulsion. Six of 23 treated animals were alive (5 free of tumor and 1 with arrested disease) at a minimum of 2.5 years after treatment, as compared to 1 of 18 controls. A necropsy, lymph node metastases were found in most animals with progressive disease. The disease progressed to an advanced stage (which required death of the animals) at a faster rate for control animals than for treated animals.