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Biomedical subjects

G Shklar

Publications and source records attributed to G Shklar.

At least 55 records · Page 3Linked to original sources

Prevention of experimental oral cancer by extracts of Spirulina-Dunaliella algae.

An extract of Spirulina-Dunaliella algae was shown to prevent tumor development in hamster buccal pouch when a 0.1% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil was applied topically three times weekly for 28 weeks. The algae extract was delivered by mouth in continued dosages of 140 micrograms in 0.4 ml mineral oil three times per week. After 28 weeks, the animals given vehicle and untreated controls all presented gross tumors of the right buccal pouch. Animals fed canthaxanthin presented a notably and statistically significant reduction in tumor number and size compared with controls. Animals fed beta-carotene demonstrated a smaller but statistically significant reduction in tumor number and size. The algae animals presented a complete absence of gross tumors. However, microscopic sections of the buccal pouch in the algae group showed localized areas of dysplasia and early carcinoma-in-situ undergoing destruction.

9,10-Dimethyl-1,2-benzanthracene↗

Improvement of dental development in osteopetrotic mice by maternal vitamin D3 sulfate administration.

Utilizing the microphthalamic mouse, (mi/mi) as a model of osteopetrosis, vitamin D3 (cholecalciferol) was administered prenatally and postnatally to study its effects on tooth development and subsequent eruption. It has previously been reported that vitamin D3 crosses the placental barrier and is absorbed into mammary gland milk. Fifteen heterozygotes (+/mi) were used as breeders. There were three study groups: A) 5.0 ng/gm cholecalciferol sulfate; B) 2.5 ng/gm cholecalciferol sulfate; and C) no therapy. Intraperitoneal injections were administered three times per week, beginning when pregnancy was evident, and continuing for 4 additional weeks during lactation. Approximately half of the 59 offspring were sacrificed at age 1 day and the other half at 4 weeks. The former group was studied for crown development, and the latter group was studied for root development and eruption. When the osteopetrotic offspring of group A were compared with osteopetrotic offspring of group C, crown development and tooth eruption were substantially more advanced. Parameters examined were maturity of the ameloblasts and odontoblasts, dentin and enamel formation, root sheath development, status of eruption, and degree of apex closure. It was concluded that cholecalciferol sulfate significantly improves tooth development and subsequent eruption in the osteopetrotic mouse. A genetic disease has had its phenotype modified by vitamin therapy during gestation.

Animals↗

Lingual changes in ageing mice by light- and scanning electron-microscopy.

Tongues from young, old and senescent Swiss-Webster white mice were compared. Sections and tissues were taken from the anterior, posterior, and ventral regions. The epithelium became atrophic and hyperkeratotic in the senescent animals. The filiform papillae were blunted, atrophic and disorganized across the entire dorsal surface in the older animals. The ventral aspect in the senescent animals had thinning epithelium, a hyperchromatic germinal layer, and a roughened, disorganized surface.

Aging↗

GGT reduction in beta carotene-inhibition of hamster buccal pouch carcinogenesis.

Levels of activity for gamma glutamyl transpeptidase (GGT) were studied in hamster buccal pouches developing DMBA-induced epidermoid carcinomas and in pouches in which carcinogenesis was inhibited by topical application of beta carotene. The beta carotene acted to inhibit tumor development when applied topically on days alternate to the application of 0.25% DMBA in heavy mineral oil thrice weekly for 22 weeks. Forty male young adult Syrian hamsters were divided into four equal groups. Group 1 had DMBA applied to left buccal pouches thrice weekly. Group 2 had DMBA applied as in Group 1 but also beta carotene thrice weekly on days alternate to the DMBA application. Group 3 animals were painted with only beta carotene and Group 4 animals were untreated controls. The left buccal pouches were dissected at autopsy and divided in half. One half was fixed in formalin, sectioned in paraffin and stained with hematoxylin-eosin for histologic study. The other half was prepared for the histochemical demonstration of GGT activity using epithelial whole mount preparations. GGT activity was found to be reduced in the left buccal pouches of those animals treated with both beta carotene and DMBA when compared to those animals treated with DMBA alone.

9,10-Dimethyl-1,2-benzanthracene↗

Regression of experimental hamster cancer by beta carotene and algae extracts.

The effect of algae extract on tumor regression was studied. Phycotene (extract of Spirulina and Dunaliella algae) 250 micrograms in 0.1 ml MEM (minimum essential medium) was injected locally into DMBA (7, 12 dimethylbenz(a)anthracene)-induced squamous cell carcinomas of hamster buccal pouch in 20 animals. DMBA-induced carcinomas in 20 hamsters were injected locally with beta carotene 250 micrograms in 0.1 ml MEM; DMBA-induced carcinomas in 20 animals were injected locally with canthaxanthin, 250 micrograms in 0.1 ml MEM, and DMBA-induced carcinomas in 20 animals were injected locally with 13-cis-retinoic acid, 250 micrograms in 0.1 ml MEM. Twenty animals with DMBA-induced carcinomas were sham-injected controls using 0.1 ml MEM. The various agents were injected into the tumor bearing right buccal pouches twice-weekly for four weeks. Total tumor regression was found in 30% of phycotene animals, 20% of beta carotene animals and 15% of canthaxanthin animals after four weeks. Partial tumor regression was found in the remaining 70% of phycotene animals, 80% of beta carotene animals and 85% of canthaxanthin animals. None of the 13-cis-retinoic acid animals had total tumor regression, but 70% showed partial regression. No tumor regression was found in the DMBA control group and the sham-injected group.

Animals↗

Effects of onion extract on the development of hamster buccal pouch carcinomas as expressed in tumor burden.

One-hundred male, young-adult Syrian hamsters (Mesocricetus auratus) were divided into five equal groups of 20 animals each. Groups 1, 2, and 3 were painted three times a week in the left buccal pouches with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil. Group 1 animals also received a 20% onion extract in their drinking water and were also painted in left buccal pouches three times a week with a 50% onion extract in mineral oil. Group 2 animals received the onion extract in their drinking water, but they received only mineral oil in buccal pouches as a control for the painting with onion extract in mineral oil. Group 3 animals received DMBA but no onion extract. Group 4 animals received onion extract but no DMBA, and Group 5 animals were left untreated. Onion extract was found to significantly delay tumor formation in Groups 1 and 2 compared with Group 3 DMBA controls.

9,10-Dimethyl-1,2-benzanthracene↗

In vitro inhibitory effect of onion extract on hamster buccal pouch carcinogenesis.

In vitro studies were performed that used varying concentrations of onion extract added to cell cultures of an epidermoid carcinoma cell line derived from hamster buccal pouch carcinoma (HCPC-1). The studies demonstrated tumor growth inhibition beginning after 24 hours of incubation at an onion extract concentration of 25% and above in culture media. After 4 days and 10 days of incubation, there was a noted decrease in tumor proliferation. The plating efficiency for 24 hours was observed to produce a 54-89% inhibition in plating density. The results indicated here provide in vitro evidence of the inhibitory and cytotoxic activity on an oral carcinoma cell line.

Allium↗

Prevention by vitamin E of experimental oral carcinogenesis.

In the standard model for hamster buccal pouch, using a 0.5% solution of 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6], it was shown that vitamin E (alpha-tocopherol) inhibited carcinogenesis. With a less potent carcinogen (0.1% DMBA), vitamin E was shown to prevent tumor development. Eighty (total) male and female Syrian hamsters (Mesocricetus auratus) were divided into 4 equal groups. After 28 weeks, animals in group 2 that had left buccal pouches painted with 0.1% DMBA (in heavy mineral oil) three times/week and that had been given 10 mg DL-alpha-tocopherol on alternate days (i.e., two times/wk) showed no tumors there. However, the pouches of group 1 animals that had been similarly painted with DMBA but that had received no vitamin E demonstrated grossly and microscopically the presence of epidermoid carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

Regression by vitamin E of experimental oral cancer.

Vitamin E was shown to regress established epidermoid carcinomas of Syrian hamster buccal pouch in 20 experimental animals following tumor induction by applications three times a week of 0.5% 7,12-dimethylbenz[a]anthracene (CAS: 57-97-6) in mineral oil for 13 weeks. The vitamin E was injected into the tumor-bearing buccal pouch twice weekly for 4 weeks in a dose of 250 micrograms in minimum essential medium. Twenty animals were maintained as untreated controls, and another 20 animals were sham-inoculated vehicle controls. Microscopic examination of buccal pouches with regressed tumor showed small epidermoid carcinomas with degeneration of tumor cells and a dense infiltrate of leukocytes, lymphocytes, and histiocytes. Buccal pouches of control animals showed large well-differentiated or moderately differentiated epidermoid carcinomas. The hamster buccal pouch cancer model presents many similarities to human oral cancer, including expression of the same oncogene, and these results offer hope for the chemotherapy of human oral cancer with the use of a relatively nontoxic agent injected locally.

Animals↗

The effect of chemotherapeutic agents on human oral squamous cell carcinoma transplanted to nude mice: a histologic study.

Clearly differentiated squamous cell carcinomas were transplanted to the backs of nude mice; tumor cells of a human tongue carcinoma cell line were used. Animals bearing tumors that measured at least 4 mm in diameter were treated with either methotrexate (MTX), cis-diamminedichloroplatinum II (CDDP) or bleomycin intraperitoneally for 5 days. Histologic evaluation of tumors obtained 24 hours after the last injection revealed degenerative and necrotic morphology in all treatment groups. The histologic alterations were observed prior to any clinical evidence of tumor shrinkage. The most impressive changes were found in CDDP-treated tumors, with creation of large pseudocysts containing necrotic material and cell debris. Pseudocyst formation was less obvious in MTX-treated animals and was absent in bleomycin-treated tumors. Drug treatment had no obvious influence on the keratinization in tumors. The findings suggest that the nude mouse model may be useful for the histologic determination of drug-induced effects on tumors in human beings.

Animals↗

Significance of the head and neck in late infection in renal transplant recipients.

The present study was undertaken to evaluate the overall significance of the mouth and contiguous structures as sites of late opportunistic infection in renal transplant recipients, to define the flora of such infections, and to determine factors that place patients at risk of infection. Of 323 patients who underwent renal transplants, 57% developed infection at least 1 month postoperatively. Sex, donor source, or age did not influence the risk of infection. Of the posttransplant infections, 30.6% occurred in the head and neck, 21.9% in the respiratory tract, 23.7% in the urinary tract, and 10% at sites of trauma. Of head and neck infections, 16.4% were bacterial, 20.5% were viral, and 21.9% were fungal. In the remainder a definitive causative organism could not be identified. These results emphasize that the head and neck area is a major site of late opportunistic infection in renal transplant recipients.

Adult↗

Vitamin E stimulates proliferation of experimental oral carcinoma cells in vitro.

Vitamin E was found to have a stimulatory effect on the growth in culture of an epidermoid carcinoma cell line derived from chemically induced tumors of hamster buccal pouch. This effect was found to be dose related, with a maximum stimulatory effect at 10 microM. At a concentration of 100 microM, there was an inhibitory effect on both cell turnover and colony formation.

Animals↗

Inhibition of experimental oral carcinogenesis by topical beta carotene.

beta-Carotene was found to significantly inhibit the formation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced squamous cell carcinoma of hamster buccal pouch when applied topically on days alternate to the application of 0.25% DMBA in heavy mineral oil thrice weekly for 22 weeks. An initial experiment utilized 40 male young adult Syrian hamsters divided into four equal groups. Group 1 had DMBA applied to left buccal pouches thrice weekly. Group 2 had DMBA applied as in group 1 but also beta-carotene thrice weekly on days alternate to the DMBA application. Group 3 animals were painted with only beta-carotene and group 4 animals were untreated controls. In a second experiment with 80 animals, beta-carotene was found to inhibit oral carcinogenesis in an initiation--promotion hamster buccal pouch system using 0.1% DMBA as initiator and 40% benzoyl peroxide as promoter. beta-Carotene inhibited both initiation and promotion.

9,10-Dimethyl-1,2-benzanthracene↗

Effects of hydrogen peroxide on oral carcinogenesis in hamsters.

The effects of twice weekly topical applications of hydrogen peroxide on the buccal epithelium of Syrian hamsters were studied. Animals were treated either with hydrogen peroxide alone, with hydrogen peroxide and the carcinogen 9, 10-dimethyl-1,2-benzanthracene (DMBA), or with DMBA alone. In animals treated with 30% H2O2 alone, histopathologic examination after 22 weeks revealed hyperkeratosis and hyperplasia in all animals with hyperchromatic cells and mild dysplasia in four of nine: no tumors were seen. In animals treated with DMBA alone, three of seven (43%) developed epidermoid carcinoma, while six of 11 (55%) of animals treated with DMBA plus 3% hydrogen peroxide and five of five (100%) of animals treated with DMBA plus 30% hydrogen peroxide (P = 0.054) developed carcinoma. Thus, hydrogen peroxide can, by itself, induce pathologic changes frequently associated with preneoplastic lesions; it may also augment carcinogenesis associated with DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

Inhibition of oral carcinogenesis by a protease inhibitor.

The effect of the Bowman-Birk inhibitor (BBI) and soybean trypsin inhibitor (SBTI) on experimental 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]-induced oral carcinogenesis in Syrian male hamsters was examined. All treatments were applied topically on both cheek pouches for 20 weeks, and the animals were then sacrificed. Gross and microscopic evaluations revealed a statistically significant reduction in the number of invasive carcinomas, the total number of tumors, and the tumor mass for the DMBA + BBI treatment group compared to animals treated with DMBA alone, DMBA and autoclaved BBI (a preparation in which protease inhibitor activity is destroyed), or DMBA + SBTI. A protease activity (with the use of Boc-Val-Pro-Arg-MCA as substrate) was measured and found to be elevated about tenfold in tumorous and nontumorous tissue from DMBA-treated cheek pouches. This protease activity was found to be decreased in the DMBA and BBI treatment group but not in the DMBA + SBTI or DMBA and autoclaved BBI treatment groups, as compared to the protease activity in the DMBA treatment group. Partial characterization of the Boc-Val-Pro-Arg-MCA hydrolyzing activity with diisopropyl fluorophosphate suggests that the proteolytic activity is a serine protease. Iodoacetamide and diethyl pyrocarbonate also inhibit enzyme activity, suggesting that other residues may be necessary for catalysis, possibly including cysteine and histidine. Our results suggest that this protease activity may play a role in DMBA-induced cheek pouch carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Combined effect of herpes simplex virus and tobacco on the histopathologic changes in lips of mice.

In the present study we have examined the combined effect of HSV-1 inoculation and tobacco application (snuff water extract or smoking tar condensate) on the histopathologic changes of mouse labial mucosa. Two months' exposure to tobacco or HSV-1 inoculation alone did not induce dysplasia in the epithelium of labial mucosa, while HSV-1 inoculation combined with snuff water extract or smoking tar condensate produced epithelial dysplasia and other histomorphologic changes (that is, hyperkeratosis, increased granular cell layer thickness, acanthosis, and increased inflammatory cell infiltration in a significant number of animals). This result indicates that HSV-1 and tobacco could possibly act synergistically in the development of precancerous oral lesions and oral cancer.

Animals↗

The effect of radiation on the response of dental pulp to operative and endodontic procedures: an experimental study.

Thirty-six 56-day-old male Sprague-Dawley albino rats served as two groups of experimental animals. Group 1 was irradiated with 400 rads delivered as total-body radiation from a cesium source. Group 2 served as the control group and was not irradiated. Three weeks later, the dental microscope was used to facilitate various dental procedures in both groups of animals (cavity preparation filled with zinc oxide-eugenol, pulp exposure capped with zinc oxide-eugenol, and pulp exposure left open). Two animals for each procedure from Groups 1 and 2 were killed at time intervals of 2, 4, and 8 weeks. The results showed that (1) radiation at this dose resulted in a depression of the normal response of the dental pulp to the trauma and infection induced by pulpal exposure, (2) there were no pathologic changes in the untreated molars of the irradiated animals, and (3) the use of the dental microscope greatly facilitated cavity preparation in the molars of rats.

Animals↗