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[Clinical use of a rotation cheek flap].

The inverse triangular skin defect between lower eyelid and up lip can be repaired by cheek rotation flap. In order to preventing lower eyelid eversion, the author designed a triangular flap in the lateral canthal area which can change force bearing direction in this area. The flap can repair the defect as wide as 8 X 5 cm when the combination of bilobate flap of the posterior auricular flap and cheek flap was used. This technique was performed in 23 cases in last three years.

Adolescent↗

Sequential analysis of experimental oral carcinogenesis in hamster cheek pouch using 9,10-dimethyl-1-2-benzanthracene.

The utility of hamster cheek pouch model for studies on oral carcinogenesis has been explored using 9,10-dimethyl-1-2-benzanthracene as a carcinogen. Based on the morphological, histopathological and electron microscopic observations the hamster cheek pouch carcinogenesis can be separated into different stages starting from the normal to the fully grown carcinomas. This system is reliable, precise, consistent and can be used for the evaluation of different agents for initiating or promoting effects and as well as for the studies on mechanism of oral carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Periarteriolar localization of mast cells promotes oriented interstitial migration of leukocytes in the hamster cheek pouch.

As studied by intravital microscopy, mast cell-dependent inflammatory reactions evoked by antigen or compound 48/80 in the hamster cheek pouch involved leakage of plasma and emigration of leukocytes exclusively from the venules. The leukocyte diapedesis and subsequent tissue migration induced by antigen or compound 48/80 were oriented from the venules towards adjacent arterioles. In contrast, leukocyte emigration induced by a mast cell-independent stimulus, leukotriene B4, did not show preferential orientation towards arterioles. Moreover, mast cells were abundant in the hamster cheek pouch, and they were localized predominantly along arterioles, rather than along venules. Because mast cells are considered to be the source of the chemotactic mediators causing the leukocyte emigration, the periarteriolar mast cell localization may be of functional significance by creating chemotactic gradients between arterioles and venules, thereby promoting oriented and effective interstitial migration of leukocytes. Whether or not a similar mechanism is operative in other species and tissues remains to be established, however, arteriolar predominance of mast cells was observed also in rat calvarial periosteum and in mouse skin.

Animals↗

Low level X-radiation effects on carcinogenesis by 7,12-dimethylbenz(a)anthracene in Syrian hamster cheek pouch epithelium: acute vs fractionated radiation dose studies.

Studies examined the effects of acute and fractionated low to moderate level X-ray exposures on hamster cheek pouch carcinogenesis in vivo by 7,12-dimethylbenz(a)anthracene (DMBA). Animals were grouped by treatment as follows: acute doses of 0.85-3.40 Gy X rays; 17 once weekly doses of 0.01-0.20 Gy X rays (fractionated radiation); topical DMBA for 10 weeks; DMBA plus fractionated radiation starting together; DMBA plus acute radiation in Week 1 or 10 of DMBA treatments; and sham irradiation, DMBA vehicle, or anesthesia controls. After 44 weeks, hamsters were sacrificed, and their cheek pouches were excised, serially sectioned, and examined by light microscopy for histopathology. No histologic changes were observed in radiation-only hamsters. Carcinoma incidences in DMBA-only groups ranged from 45 to 60%. Carcinoma incidences were greater in groups receiving DMBA plus fractionated radiation than in groups receiving either acute radiation + DMBA or DMBA alone. Carcinoma incidences in acute radiation plus DMBA groups were lower than those in DMBA-only groups. These results suggest complex interactions between radiation and DMBA, perhaps with radiogenic cell killing being a principal factor in acute radiation + DMBA groups, and reciprocal additive or synergistic effects of radiation and DMBA on cancer induction and manifestation in fractionated radiation + DMBA groups.

9,10-Dimethyl-1,2-benzanthracene↗

Macromolecular permeability increase following incomplete ischemia in the hamster cheek pouch and its inhibition by terbutaline.

The microvascular permeability increase during the reperfusion after incomplete ischemia in the everted hamster cheek pouch preparation was measured by intravital microscopy. FITC-dextran 1500,000 was given i.v. as tracer of macromolecular leakage. Incomplete ischemia of the left cheek pouch was obtained by occlusion of the ipsilateral carotid artery, its external branch and the contralateral external carotid artery. Reperfusion after thirty minutes of incomplete ischemia resulted in a fully reversible increase in the number of FITC-dextran leakage sites (leaks) from 0 to 68 +/- 18 in 7 hamsters. The response to a second period of ischemia, starting one hour after the first ischemia period, was significantly smaller (9 +/- 5 leaks). Local treatment with terbutaline (10(-6) M), a beta 2-receptor agonist, abolished the permeability response to ischemia almost completely (0.5 +/- 0.3 leaks, n = 6). Local application of histamine (2 X 10(-6) M) at the end of the experiments gave a response that was in accordance with that seen in hamsters not subjected to ischemia. These results were compared with those obtained from previous studies in our laboratory with a complete ischemia model and it appears as these two methods, incomplete and complete ischemia, give similar results.

Animals↗

Reconstruction of full-thickness defects of the cheek in cancer surgery.

Two techniques are presented that can be used for reconstruction of full-thickness defects of the cheek. Defects involving a small area of mucosa can be reconstructed with an anteriorly based neck-pectoral skin flap in combination with primary closure of the mucosa. Defects involving a large part of the mucosa can be managed with a deltopectoral flap in combination with a pectoralis major myocutaneous flap. The two techniques have been applied with satisfactory results in a group of patients with neoplasms of the cheek.

Carcinoma, Squamous Cell↗

Low-level X-radiation effects on functional vascular changes in Syrian hamster cheek pouch epithelium during hydrocarbon carcinogenesis.

Effects of repeated low-level X radiation on functional microvascular changes in hamster cheek pouch epithelium during and following carcinogenesis by 7,12-dimethylbenz[a]anthracene (DMBA) were studied. Prior studies showed enhancement of such carcinogenesis by repeated 20 rad head and neck X-radiation exposures, and it was proposed that one possible mechanism was radiogenic alteration of the functional microvasculature in a manner which favored subsequent tumor development. Hamsters were treated with either radiation, DMBA, radiation + DMBA, or no treatment. Animals were sacrificed at 3-week intervals from 0 to 39 weeks after treatments began. Pouch vascular volume and permeability changes were studied by fractional distributions of radiotracers and were analyzed by a variety of statistical methods which explored the vascular parameters, treatment types, elapsed time, presence of the carcinogen, and histopathologic changes. All treatments resulted in significant changes in vascular volume with time, while only DMBA treatments alone resulted in significant changes in vascular permeability with time. Prior to the appearances of frank neoplasms, volumetric changes in DMBA only and radiation only groups were similar, while volume changes in DMBA + radiation groups increased slowly to a peak later than in other groups and then declined steadily to levels similar to the radiation only group. As in prior studies, there were significant vascular volume differences between DMBA and DMBA + radiation groups of tumor-bearing cheek pouches. DMBA maxima were significantly higher than those of DMBA + radiation. Radiation significantly affected DMBA-associated vascular volume and permeability changes during carcinogenesis. Several possible explanations for the relationship of these changes to the enhancement of DMBA carcinogenesis include: radiation blocking normal capillary proliferative and/or dilatory responses to inflammation secondary to neoplastic changes; radiation-induced focal increases in the pericapillary connective tissue histohematic barrier, stimulating angiogenesis but reducing nutrient diffusion; radiation exposures sensitizing vascular endothelium to subsequent angiogenic stimulation from premalignant tissues; DMBA vascular and epithelial effects partially or completely blocking radiation effects on epithelial and/or endothelial cells; and radiation damage to vessel walls partially or fully inhibiting normal physiologic mechanisms of repairing DMBA damage to the vessels.

9,10-Dimethyl-1,2-benzanthracene↗

Histidine-rich and cystine-rich keratohyalin granules in hamster cheek pouch epidermis. 1. Histochemical examination with a fluorescent thiol reagent (DACM).

Hamster cheek pouch epidermis was examined with a thiol-specific fluorescent reagent [7-(N-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM)], with the Pauly reagent and by electron microscopy. There were many keratohyalin granules in the cells of the stratum granulosum where they were positively stained with the Pauly reagent, and were fluorescent as a whole, rather than partially, with DACM with or without reduction of disulfide bonds. These data indicate that the whole of a keratohyalin granule was rich in both histidine and cystine. Besides keratohyalin granules, the cellular envelope of the lower half of the stratum corneum showed fluorescence before reduction of disulfide bonds and following reduction of disulfide bonds, the cellular envelope of all stratum corneum cells showed fluorescence. Electron microscopically, keratohyalin granules in hamster cheek pouch epidermis were electron-dense and had a homogeneous structure which was identical to small keratohyalin granules in newborn rat epidermis. Structures corresponding to the single granule of Jessen or to dense homogeneous deposits were not seen. When the specimen was fixed in glutaraldehyde alone, keratohyalin granules consisted of electron-dense and electron-translucent parts. However, the profile was different from that of composite granules seen in both rat tongue epithelium and newborn rat epidermis. Several membrane coating granules were seen in stratum granulosum cells, and marginal band formation also occurred.

Animals↗

[Effect of epidermal chalones on the development and growth of cheek pouch tumors in the hamster].

To the cheek pouch mucosa of 118 male Syrian golden hamsters 0.5% acetone solution of 7,12-dimethylbenz (a) anthracene was applied 3 times a week during 2 months. Two months after beginning of the experiments all the hamsters developed tumors. Since that time a mixture of epidermal G1 and G2 chalones was applied to the cheek pouch mucosa of the experimental animals 5 times a week. The control hamsters received saline alone. As compared to the control, the experimental hamsters demonstrated an increase in the life-span, tumor growth retardation and regression of part of the tumors. The data obtained attest to the anti-neoplastic action of chalones.

9,10-Dimethyl-1,2-benzanthracene↗

[Cytomorphological study of the mucosa of the hamster cheek pouch in the process of carcinogenesis].

An 0.5% acetone solution of 7,12-dimethylbenz(a) anthracene was applied to the mucosa of the cheek pouch of 68 Syrian male hamsters. Cytological examination of mucosa samples obtained from the cheek pouch was carried out, and the bioptates and tissues of dead animals were studied histologically. Squamous cell carcinoma of the pouch was identified in 100%. Cytologically-confirmed hyperplasia and dysplasia of the epithelium were found to precede cancer development.

9,10-Dimethyl-1,2-benzanthracene↗

Diurnal variation of DNA synthesis in premalignant hamster cheek pouch.

The right cheek pouch of hamsters was painted twice a week with DMBA for 4 and 7 weeks in different groups. It was found that there were diurnal rhythms and non-random distributions of DNA synthesis and mitotic events in DMBA-treated hamster-cheek-pouch epithelium. The degree of these changes was markedly greater than the changes in non-treated control pouches. The finding of cluster formation was described as 'symphokinesis', the non-random grouping of basal cells with synchronous DNA cycles during tissue growth.

9,10-Dimethyl-1,2-benzanthracene↗

Anatomical and functional vascular changes in hamster cheek pouch during carcinogenesis induced by 7, 12-dimethylbenz(a)anthracene.

Anatomical and functional vascular changes during hamster cheek pouch carcinogenesis were studied by light microscopy; scanning electron microscopy of vascular casts; transmission electron microscopy of cheek pouch capillaries; and fractional distributions of 51Cr-erythrocytes, 125I-human serum albumin, and 86RbCI which were used to determine vascular volume, permeability, and perfusion. Histopathological changes and focal capillary changes in vascular casts were measured quantitatively by an image analyzer. Male Syrian hamsters received 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil for 11 weeks and were sacrificed at periodic intervals from 2 to 20 weeks after initial treatment. Simple hyperplasia was first seen at Week 1. The area of hyperplastic epithelium, expressed as percentage, increased to about 60% by Week 8 and then decreased to 30% at Week 20. Dysplastic foci were first seen at Week 2. The percentage of the area of dysplasia increased with time to 41% at Week 20. Squamous cell carcinomas occurred from Week 10, increased with time, and were found in all animals at Week 20. Vascular cast diameters of normal-looking capillaries were larger during than after DMBA treatment. Type 3 vascular proliferations were found beneath dysplasia and cancer. Capillaries beneath simple hyperplasia and type 3 capillaries beneath dysplasia and cancers were dilated but not fenestrated. Changes in vascular volume were independent of changes in permeability and perfusion and also occurred in contralateral untreated pouches of treated animals. While 86Rb values initially correlated with 125I values, the 86Rb values were unstable in intermediate and later time periods. Changes of vascular volume were accompanied initially by the presence of DMBA and were coincident with increased areas of dilated capillaries beneath simple hyperplasia and later with areas of type 3 capillary proliferation beneath dysplasia and cancer. Changes of vascular permeability were related to inflammation indices throughout the study. DMBA may lastingly alter capillary endothelium in a manner which allows or aids in its subsequent dilatory and proliferative responses to angiogenic stimulation from malignant tumors, and possibly from premalignant or malignantly transformed cells.

9,10-Dimethyl-1,2-benzanthracene↗

[Comparison of 2 chemosensitivity tests by grafting a polyoma tumor in the cheek pouch of syngeneic hamsters and under the renal capsule of syngeneic mice].

The immunocompetent subrenal capsule assay tumour graft is a good chemosensitivity test. We have compared it to immunocompetent white hamster cheek pouch tumour graft. These two assays are both easy to perform. Each has specific advantages and disadvantages. However the six days immunocompetent mouse subrenal capsule assay tumour graft is the most practicable and reproducible. The hamster cheek pouch assay would be used when mouse subrenal capsule assay would not be efficient for the molecules under study.

Animals↗

The effects of intermittent and continuous stimulation of microvessels in the cheek pouch of hamsters with histamine and bradykinin on the development of venular leaky sites.

Continuous and intermittent stimulation of the hamster cheek pouch with either histamine or bradykinin was studied to evaluate microvascular permeability. Microscopy was accomplished by placing a chamber in the cheek pouch, suffusing the membrane with Ringer's bicarbonate (pH 7.4, 35 degrees C) and observing the microvessels with a Zeiss epistage microscope. Using FITC-dextran (MW 70,000) as the intravascular tracer, the number of leaky sites per cm2 tissue was quantitated before, during and after exposure to histamine (10(-5) M) or bradykinin (10(-7) M). Continuous superfusion with histamine or bradykinin for 60-90 minutes produced an increase in leaky sites which returned toward control during the superfusion. Intermittent stimulation with either histamine or bradykinin produced a maximal response which was not reduced by subsequent 30 minute pulses; whereas reducing the stimulus interval to 15 minutes led to a reduction in leaky sites on subsequent applications. After termination of continuous stimulation with either agent, the application of the other agent produced a response which was similar to the original. There was a minor reduction of responsiveness to intermittent applications of either histamine or bradykinin when the stimulus interval was greater than 15 minutes. These results support the concept of a receptor-mediated modulation of venular leaky sites.

Animals↗

Comparative reactivity of hamster cheek pouch microvessels to arginine vasopressin and angiotensin II.

Experiments were carried out to determine the relative sensitivity of hamster cheek pouch vessels to arginine vasopressin (AVP) and angiotensin II (AII). Hamsters were anesthetized with pentobarbital sodium (6 mg/100 g, ip), a plastic chamber inserted into the cheek pouch and the membrane exposed. The membrane was suffused continuously with bicarbonate-buffered Ringer's solution at 36 degrees C while constantly monitoring blood pressure. After stabilization (30 min) of the membrane, arterioles (30-80 microM diam) were selected for application of AVP or AII in a random fashion. The peptides were applied to the vessels through a micropipette (10-15 mM tip diam) over two minutes using a pump. Total volume delivered was always 20 microliters irrespective of the total amount of peptide (10(0)-10(-4) ng) applied. Vessel diameter was monitored continuously with a shearing device before, during and after the administration of the peptide. The following results were obtained tachyphylaxis was noted to AII but to AVP; the dose response curve for AVP was shifted to the left of that for AII with the threshold dose for AII one hundred times more than that of AVP and AVP had little effect on venules whereas AII produced venoconstriction. These results indicate that AVP is a more potent vasoconstrictor than AII, whereas AII is a more potent venoconstrictor.

Angiotensin II↗

Regional differences in the distribution of dividing cells in hamster cheek pouch epithelium.

Examination of vinblastine-arrested metaphase figures in sections from the medial wall of 15 hamster cheek pouches showed that: (1) the distribution of dividing cells was non-random and (2) mitotic activity declined in an anteroposterior direction. Although there was some variation between different pouches these features were statistically significant (P less than 0.05) in individual pouches from half the animals and highly significant (P less than 0.005) when the data from all pouches were pooled. The average sample size required to determine a mitotic index representative of the whole length of the pouch was equivalent to approximately 32 mm of surface length of epithelium or 4562 basal cells. This estimate exceeds the sample size generally examined and it is suggested that inadequate sampling could account for some of the inconsistencies in the literature on hamster cheek pouch cell kinetic data.

Animals↗

Reconstruction of cheek and buccal mucosa with latissimus dorsi musculocutaneous flap.

This paper reports the experience of the author in the use of the latissimus dorsi musculocutaneous flap in the reconstruction of the cheek defect following tumour ablation. The advantages of this flap are its improved vascularity, bulk, and greater length which enable resurfacing of both surfaces of the cheek with the use of a single flap.

Aged↗

Optical and ultrastructural pathology of vitamin A pretreated hamster cheek pouch--exposed to lime (Ca(OH)2) and tobacco over total life span.

A close correlation is postulated between tobacco chewing and the high incidence of oral cancer and precancer in many South East Asian nations. However, attempts to induce malignancy in laboratory animals by exposure to ingredients of betel quid are unsuccessful. This is another attempt to induce malignancy in the hamster cheek pouch epithelium by exposure to the ingredients of betel quid - lime and tobacco, for the total life span of the animals - 100 to 110 weeks. Parallel conditioning by exposure to vitamin A is also included. The cheek pouch epithelium of animals exposed to the test substances for total life span shows only epithelial dysplasia of a marked degree, but no evidence of malignancy. It is concluded that it is not possible to simulate the time-dose relationship in human addiction to tobacco or to betel chew in experimental animals due to their comparatively small life span.

Animals↗