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Expression of c-erbB proto-oncogene during dimethylbenzanthracene-induced tumorigenesis in hamster cheek pouch.

Repeated local applications of dimethylbenzanthracene (DMBA) induce epidermoid carcinomas in 14 weeks in the cheek pouch of Syrian hamsters. Characteristic histopathological changes similar to the ones observed in human oral cancers can be detected during the development of these tumors in the hamster cheek pouch. Results presented in this report demonstrate that the cellular proto-oncogene c-erbB is amplified and expressed in an epidermoid carcinoma cell line (HCPC-1), derived from one such cheek pouch tumor. The expression of the gene cannot be detected in the untreated cheek pouch tissue whereas the level of expression of the gene is significantly high in the tumor cell line. The expression of c-erbB gene can also be detected in cheek pouch tissue at an early stage (8-9 weeks) of tumor development and in all tumor-bearing tissue of subsequent stages. The stage of expression of c-erbB gene does not coincide with the stage in which extensive hyperplasia of the epithelial cells (5 weeks) is observed. Rather, this coincides with the onset of the early invasion of the connective tissue by the dysplastic epithelium. The expression of c-erbB gene increases in parallel with the increased tumor burden. These results implicate the possible role of c-erbB gene in the genesis of DMBA-induced oral epithelial carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

The role of the cheek pouch in effecting transplantation immunity in the hamster.

The cheek pouch of the hamster is alymphatic. Molecules, too large to penetrate the vascular endothelium, reach general circulation by slowly diffusing through the cheek pouch membrane to vessels found in the connective tissues in the neck and these vessels drain primarily into the superficial cervical node. The tissues of the cheek pouch membrane limit the diffusion of large particles and it is this "barrier" which explains, in part, the "privilege" conferred by the cheek pouch.

Animals↗

The lip-cheek groove: a new analysis with treatment options.

OBJECTIVE: To present a clinical classification of the lip-cheek groove. DESIGN: The clinical classification, which is based on years of analysis, will provide optimal management options for achieving the greatest degree of correction and rejuvenation of the lip-cheek groove. RESULTS: The use of the clinical classification of the lip-cheek groove will guide the surgeon to the management option(s) that will attain the best aesthetic outcome. CONCLUSION: The classification of the lip-cheek groove enables the surgeon to choose the optimal approach for improvement of the groove.

Cheek↗

Closure of large nose-cheek groove defects.

Reconstruction of large defects involving the nose-cheek groove area present technical and cosmetic problems. A combination of a cheek falp with a dorsal-nasal rotation flap gives excellent survival and cosmesis for the nose as well as the cheek. The techniques of the dorsal-nasal flap alone and in combination with a cheek advancement flap are demonstrated.

Aged↗

Relative cheek-tooth size in Australopithecus.

Until the discovery of Australopithecus afarensis, cheek-tooth megadontia was unequivocally one of the defining characteristics of the australopithecine grade in human evolution along with bipedalism and small brains. This species, however, has an average postcanine area of 757 mm2, which is more like Homo habilis (759 mm2) than A. africanus (856 mm2). But what is its relative cheek-tooth size in comparison to body size? One approach to this question is to compare postcanine tooth area to estimated body weight. By this method all Australopithecus species are megadont: they have cheek teeth 1.7 to 2.3 times larger than modern hominoids of similar body size. The series from A. afarensis to A. africanus to A. robustus to A. boisei shows strong positive allometry indicating increasing megadontia through time. The series from H. habilis to H. erectus to H. sapiens shows strong negative allometry which implies a sharp reduction in the relative size of the posterior teeth. Postcanine megadontia in Australopithecus species can also be demonstrated by comparing tooth size and body size in associated skeletons: A. afarensis (represented by A.L. 288-1) has a cheek-tooth size 2.8 times larger than expected from modern hominoids; A. africanus (Sts 7) and A. robustus (TM 1517) are over twice the expected size. The evolutionary transition from the megadont condition of Australopithecus to the trend of decreasing megadontia seen in the Homo lineage may have occurred between 3.0 and 2.5 m.y. from A. afarensis to H.habilis but other evidence indicates that it is more likely to have occurred between 2.5 to 2.0 m.y. from an A. africanus-like form to H. habilis.

Body Weight↗

The development of the Syrian hamster cheek pouch.

The objective of this study was to provide a detailed account of the morphogenesis and early cytodifferentiation of the hamster cheek pouch. Although the newborn "cheek pouch" is used for in vitro studies of the effects of retinoids and carcinogens, its rudimentary structure has not been adequately described. Complete paraffin serial sections of the heads of 14- and 15-day fetuses were cut in three planes to determine the location and shape of the earliest pouch rudiments. Complete paraffin serial sections were prepared from pouch rudiments dissected from hamsters at birth and at daily intervals from 3 to 12 days postnatal. Semithin Epon sections were examined by light microscopy and ultrathin sections by transmission electron microscopy. The pouch can appear in the fetus as two solid epithelial ingrowths from the lining of the oral cavity. They are the margins of an ingrowing sheet of oral epithelium which becomes leaflike at about the time of birth, as it grows caudad into the tissue of the cheek. The central cells of the ingrowth accumulate large quantities of glycogen before differentiating as a stratum spinosum 5 days after birth. Within the stratum spinosum, groups of cells containing keratohyalin granules initiate the stratum granulosum. Keratinized cells appear within the stratum granulosum areas. Spaces appear between keratinized cells, and the spaces coalesce to form the pouch cavity between 7 and 12 days postnatal. Soon afterward, this cavity opens to the oral cavity to make a pouch, and the ultrastructure of the cheek pouch epithelium closely resembles that of the adult.

Age Factors↗

Folded free radial forearm flap for reconstruction of full-thickness defects of the cheek.

BACKGROUND: Full thickness defects of the cheek have been conventionally reconstructed using the folded forehead flap, cervical flap, pectoralis major myocutaneous flap, or deltopectoral flap in various combinations. We report a modified technique of folding the radial forearm flap for reconstruction of full-thickness defects of the cheek. METHODS: The free radial forearm flap is a type C fasciocutaneous flap based on the radial artery along with its vena commitans and superficial forearm vein. The size and shape of the flap are determined according to the dimensions of the surgical defect. The flap is then lifted off with the fascia of the forearm making it a fasciocutaneous flap, in which the radial artery lies deep to the fascia and gives numerous branches. The flap is disconnected from the donor site only after the recipient vessels have been prepared for anastomosis. Vascular anastomosis is then performed using the operating microscope. This technique was used in 13 patients with carcinoma of the buccal mucosa who underwent fill-thickness excision of the cheek. RESULTS: Flap edema was observed in 4 patients in the immediate post-operative period. Necrosis of the outer paddle was seen in 1 patient. Donor site morbidity was seen in 4 patients who required dressings on an outpatient basis for up to 3 weeks. CONCLUSION: Single-stage reconstruction of full-thickness defects of the cheek with the folded free radial forearm flap is reliable and produces excellent cosmesis with minimal donor site morbidity.

Adult↗

Comparative morphology and evolution of cheek pouches in rodents.

There are two types of cheek pouches in extant rodents. Internal cheek pouches are evaginations of the oral cavity deep to M. platysma and M. sphincter colli profundus, and have evolved independently in some species of the superfamilies Sciuroidea and Muroidea. External, furlined cheek pouches open lateral to and separate from the oral cavity, (also deep to M. platysma and M. sphincter colli profundus), and occur in all species of the families Geomyidae and Heteromyidae. The presence of external, furlined cheek pouches is a synapomorphy for the superfamily Geomyoidea. The posterior retractor muscle of the pouch is derived from facial musculature in sciurids, from trapezius musculature in cricetids, and from both facial and trapezius muscle groups in the Geomyoidea. Differences also exist in the musculature associated with the pouch opening. In the Sciuridae and Cricetidae, the M. buccinatorius muscle group acts as a sphincter to control the size of the pouch opening. In the Geomyoidea, the size of the opening is controlled by the M. orbicularis sacculi in concert with a slip of the M. platysma myoides. Thin sections and scanning electron micrographs of the pouch tissue reveal the presence of dermal papillae in Phodopus sungorus but not in a close relative, Mesocricetus auratus. All members of the subfamily Cricetinae have a peninsula of highly folded tissue projecting anteriorly from the posteromedial pouch wall. This folding allows for expansion of the pouch walls when food is stored in the pouch.

Animals↗

Structure and composition of the oral mucous membrane on the lips and cheeks of the monkey, Macaca fascicularis.

In seven monkeys (6 Macaca fascicularis, 1 M. mulatta; 2.4 +/- 0.6 kg in weight) the labial and buccal mucosae were studied morphologically and quantitatively. Following fixation by perfusion, the upper and lower lips and entire cheeks were dissected free and processed for light-, scanning and transmission electron microscopy. Established programs (HISTOMEP, MUMANA II) and appropriate morphometric techniques were used to estimate, at the light-microscopic level, the epithelial thickness, the width of the combined lamina propria/submucosa, and the volumetric composition of the gland-containing portions of lip and cheek mucosae. The cheek epithelium was more than twofold thicker than the lip epithelium, on the average 0.46 +/- 0.04 and 0.21 +/- 0.02 mm, respectively, with no differences related to sex or topographical sites. The combined lamina propria/submucosa was 1.32 +/- 0.19 and 1.50 +/- 0.26 mm in width in cheeks and lips, respectively. The main mucosal constituents at both sites were glandular and connective tissue, and lymph follicles associated with secretory ducts. In lips, the volume of plasma cells around gland acini correlated positively with the amount of lymphoid tissue present around topographically related ducts. It is suggested that the duct/lymph follicle assembly may serve as a local antigen-recognition system.

Animals↗

Stimulation of human cheek cell Na+/H+ antiporter activity by saliva and salivary electrolytes: amplification by nigericin.

Proton-dependent, ethylisopropylamiloride (EIPA)-sensitive Na+ uptake (Na+/H+ antiporter) studies were performed to examine if saliva, and ionophores which alter cellular electrolyte balance, could influence the activity of the cheek cell Na+/H+ antiporter. Using the standard conditions of 1 mmol/l Na+, and a 65:1 (inside:outside) proton gradient in the assay, the uniport ionophores valinomycin (K+) and gramicidin (Na+) increased EIPA-sensitive Na+ uptake by 177% (p < 0.01) and 227% (p < 0.01), respectively. The dual antiporter ionophore nigericin (K(+)-H+) increased EIPA-sensitive Na+ uptake by 654% (p < 0.01), with maximal Na+ uptake achieved by 1 min and at an ionophore concentration of 50 mumol/l, with an EC50 value 6.4 mumol/l. Pre-incubation of cheek cells with saliva or the low molecular weight (MW) components of saliva (saliva activating factors, SAF) for 2 h at 37 degrees C, also significantly stimulated EIPA-sensitive Na+ uptake. This stimulation could be mimicked by pre-incubation with 25 mmol/l KCl or K(+)-phosphate buffer. Pre-incubating cheek cells with SAF and the inclusion of 20 mumol/l nigericin in the assay, produced maximum EIPA-sensitive Na+ uptake. After pre-incubation with water, 25 mmol/l K(+)-phosphate or SAF, with nigericin in all assays, the initial rate of proton-gradient dependent, EIPA-sensitive Na+ uptake was saturable with respect to external Na+, with Km values of 0.9, 1.7, and 1.8 mmol/l, and Vmax values of 13.4, 25.8, and 31.1 nmol/mg protein/30 sec, respectively. With 20 mumol/l nigericin in the assay, Na+ uptake was inhibited by either increasing the [K+]o in the assay, with an ID50 of 3 mmol/l. These results indicate that nigericin can facilitate K+i exchange for H+o and the attending re-acidification of the cheek cell amplifies 22Na+ uptake via the Na+/H+ antiporter. The degree of stimulation of proton-dependent, EIPA-sensitive Na+ uptake is therefore dependent, in part, on the intracellular [K+]i.

Adult↗

Role of nitric oxide in modulating permeability of hamster cheek pouch in response to adenosine 5'-diphosphate and bradykinin.

The goal of this study was to determine the role of the synthesis and release of nitric oxide in modulating alterations in microvascular permeability of the hamster cheek pouch in response to adenosine 5'-diphosphate and bradykinin. We used intra-vital fluorescent microscopy to examine the permeability of the hamster cheek pouch to agonists before and following application of enzymatic inhibitors of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 0.01, 0.1, and 1.0 microM) and NW-nitro-L-arginine methyl ester (L-NAME; 0.01, 0.1, and 1.0 microM). Increases in permeability of the hamster cheek pouch were quantitated by the formation of microvascular leaky sites. ADP and bradykinin produced an increase in the number of venular leaky sites, and superfusion of L-NMMA and L-NAME significantly decreased ADP- and bradykinin-induced increases in microvascular permeability. To determine the specificity of nitric oxide blockade on microvascular permeability, we examined changes in permeability in response to adenosine, and examined the effects of D-NMMA on microvascular permeability. Adenosine-induced increases in permeability were not altered by treatment with L-NMMA, and D-NMMA did not inhibit ADP-induced increases in microvascular permeability. Thus, these findings suggest that production of nitric oxide, in response to application of ADP and bradykinin, has a role in modulating macromolecular permeability of the hamster cheek pouch in vivo.

Adenosine Diphosphate↗

Differential effect of submandibular gland resection on the growth of pancreatic cancer in cheek pouch and subcutaneous tissue.

Exogenous administration of epidermal growth factor (EGF) enhances tumor growth of H2T, a hamster pancreatic cancer that is inoculated in the cheek pouch. The effect of endogenous EGF on tumor growth, however, is not known. The main source of EGF in the body is the submandibular glands. This study examined the influence of submandibular gland resection (SMx) on H2T tumor growth in the cheek pouch and compared it to the growth in SC tissue. Bilateral SMx or sham operation was performed on male Syrian golden hamsters. In 30 hamsters (n = 15 for each operation group), 5 x 10(4) and 5 x 10(5) H2T cells were inoculated in the bilateral cheek pouches and intrascapular SC tissue, respectively (Exp. 1). In another 30 hamsters (n = 15 for each operation group), 5 x 10(5) and 1 x 10(6) H2T cells were inoculated at the same sites (Exp. 2). Two longest perpendicular diameters of the tumor were measured once a week for 12 wk (Exp. 1) or 8 wk (Exp. 2), and the tumor area was calculated. The tumor area in the cheek pouch became significantly smaller in the SMx group than the sham-operated group after the 8th wk (Exp. 1) or the 7th wk (Exp. 2). On the other hand, the tumor area in the SC tissue did not show any difference between groups through the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased microvascular permeability in the hamster cheek pouch induced by oxidized low density lipoprotein (oxLDL) and some fragmented apolipoprotein B proteins.

OBJECTIVE AND DESIGN: Oxidized low-density lipoproteins (oxLDL) and protein fractions obtained by size exclusion chromatography of oxLDL were tested for vascular permeability effects on topical application to the hamster cheek pouch. MATERIALS: The hamster cheek pouch was prepared for intravital microscopy observations of macromolecular leakage at post capillary venules (=leaks) with FITC-dextran as tracer. TREATMENT: OxLDL (0.1 mg/ml), PAF (platelet activation factor, 50-100 nM) and protein fractions of oxLDL (10 microg/ml) were applied topically to hamster cheek pouches. RESULTS: Application of oxLDL and PAF resulted in reversible increases in the number of leaks. The PAF-antagonist WEB 2170, L-NAME and a beta(2)-adrenoceptor agonist inhibited (P<0.01) almost completely the macromolecular leakage induced with oxLDL or PAF. Protein fractions were found to be more effective than unfractionated oxLDL in inducing plasma leakage as calculated on mg/ml-basis. CONCLUSION: Hamster oxLDL is a potent inducer of macromolecular leakage increase in the hamster cheek pouch microcirculation. The principal effect is mediated by PAF-like structures produced by the oxidation of the LDL-particle but oxLDL also contains low molecular weight proteins that could contribute to the overall vascular permeability increasing effect of ox LDL.

Adrenergic beta-2 Receptor Agonists↗

Histologic evaluation of effect of thiocyanate topical application on hamster cheek pouch.

The present study was conducted to investigate the effect of topical thiocyanate (SCN(-)) application on hamster cheek pouch mucosa. Sixty-six hamsters were divided into two groups. The test substance containing potassium thiocyanate was applied on the hamsters' cheek pouches at 55 mg/kg dosages. Cheek pouches were grossly examined after 12 weeks. Histometric evaluation included height measurements from the epithelium without stratum corneum, stratum corneum, and full epithelium. Clear cells frequency was compared between groups. Results were analyzed using Student's t test. The experimental group showed a lower height of the stratum corneum (p=0.035) and higher frequency of clear cells (p<0.001). There was no height difference for the epithelium without stratum corneum (p=0.677) and full epithelium (p=0.904) between groups. SCN(-) promotes no gross alterations on hamsters' cheek pouch and does not induce dysplastic features at the epithelium or inflammation at the connective tissue. The ion promotes histologic alterations on mucosa that need to be investigated in further studies.

Administration, Topical↗

Initial lymphatics are present in the loose areolar connective tissue of the golden hamster's cheek pouch.

The immunologically privileged status of the hamster cheek pouch has been attributed to both the loose, areolar connective tissue that lines the pouch and to the lack of lymphatics in it. Although early reports described an absence of demonstrable lymphatics by classical histologic and lymphangiographic methods, issue has been taken recently as to whether the cheek pouch is alymphatic. We became interested in this issue accidentally during a study of microembolic microvascular injury. Our results, which were obtained by coordinated use of intravital, light, and transmission electron microscopy, showed that a small population of initial lymphatics are present in the loose, areolar connective tissue. The areal density of initial lymphatics in 12 cheek pouches averaged 1.5 lymphatics/cm2 of pouch connective tissue. We conclude that the hamster cheek pouch is drained by a small population of initial lymphatics, the general paucity of which probably contributes to the delayed egress of antigens to regional lymph nodes.

Animals↗

Nasal reconstruction with the cheek island pedicle flap.

BACKGROUND: Reconstruction of the lower third of the nose can be challenging. Maintaining the nasal subunit symmetry and providing good tissue match with regard to color, sebaceous quality, and thickness is essential. For extensive defects in this area, paramedian forehead flaps are often considered. OBJECTIVE: Our purpose was to develop the technique of preparing and executing the cheek island pedicle flap, as well as to define the limitations and "pitfalls" of the flap. METHODS: The cheek island pedicle flap is described. RESULTS: The cheek island pedicle flap can provide excellent cosmetic results in reconstructing defects of the lower third of the nose. The flap dynamics are predictable, and anticipated complications are described. CONCLUSION: The cheek island pedicle flap provides an excellent alternative to the paramedian forehead flap for reconstruction of extensive defects of the lower third of the nose.

Aged↗

Release of mandibular ankylosis due to gross tissue loss in the cheek.

Experience with mandibular ankylosis due to the loss of variable amounts of cheek tissue as a result of cancrum oris is reviewed. Where enough cheek has been lost to cause an ankylosis, replacement tissue in the form of a graft is necessary to prevent recurrence and to reconstruct the cheek. A number of methods are reviewed, including free grafts, local flaps and pedicled skin from the neck and abdomen. The best functional and cosmetic result was obtained by using a tubed pedicle of abdominal skin based on the superior epigastric artery and attached to the wrist as a carrier. This can be raised under local anaesthesia prior to the release of the ankylosis so it is available to cover the raw surfaces and to reform the cheek at the time of operation. Blind intubation was found to be feasible and desirable when compared with administering the anaesthetic through a trachesotomy. The importance of close supervision of post-operative exercises is emphasized, but was not able to be carried out under the conditions of treatment.

Ankylosis↗

Carrier-mediated absorption of salicylic acid from hamster cheek pouch mucosa.

Previously, we found that monocarboxylic acids undergo carrier-mediated transport in primary cultures of oral mucosal epithelial cells.1 In this study, we investigated whether carrier-mediated absorption of a monocarboxylic acid from the oral mucosa occurs in vivo. Salicylic acid was administered to hamster cheek pouch. At predetermined intervals, the concentration of salicylic acid in the fluid remaining in the cheek pouch lumen and the blood salicylic acid concentration were determined. The absorption of salicylic acid was saturable at high salicylic acid concentrations. Sodium azide, a metabolic inhibitor, and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), a protonophore, significantly inhibited the absorption of salicylic acid but not the absorption of salicylamide from the oral mucosa. Various monocarboxylic acids inhibited the absorption of salicylic acid, whereas dicarboxylic acids had no such effect. Transfer of [14C]salicylic acid from the cheek pouch mucosa to the systemic circulation was observed, and the blood [14C]salicylic acid concentration in the case of coadministration with propionic acid was significantly lower than that in the case of no propionic acid coadministration. These results show that monocarboxylic acids undergo carrier-mediated absorption from the hamster cheek pouch mucosa.

Absorption↗