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The effect of vitamin C on the hamster cheek pouch treated with the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO).

Vitamin C is an essential nutrient whose protective influence is carcinogenesis has been reported frequently, suggesting that vitamin C inhibits the formation of some carcinogens and decreases the incidence and delays of the neoplastic lesions. However, the mechanisms by which this occurs are unknown. In this study, the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) has been used to induce a high yield of tumours in the oral cavity either singly or in combination with tobacco. Since the mucosa of rats is less susceptible to carcinogens than the hamster cheek pouch, the hamster cheek pouch has been used to study the influence of vitamin C on 4NQO-induced oral malignancy. The aim of this study was to determine whether topically applied vitamin C had an effect on the oral carcinogenesis induced by application of 4NQO. Similarly, an attempt was made to study the modulating effect of vitamin C on the histopathological and ultrastructural changes during the neoplastic process in the hamster. Vitamin C appeared to delay tumour induction and had other protective effects against neoplasia.

4-Nitroquinoline-1-oxide↗

The supernumerary cheek tooth in tabby/EDA mice-a reminiscence of the premolar in mouse ancestors.

OBJECTIVE: A supernumerary cheek tooth occurs mesially to the first molar in tabby/EDA (Ta) mice affected by hypohidrotic ectodermal dysplasia. The supernumerary tooth (S) has been hypothetically homologized to the premolar, which has disappeared during mouse evolution. DESIGN: This hypothesis was tested using available morphological data on the lower cheek teeth in wild type (WT) and Ta mice. RESULTS: The presence of S is accompanied by a reduction in the mesial portion of the M(1) in mutant mice. 3D reconstructions suggest that the S in Ta homo/hemizygous embryos originates from a split off the mesial portion of the first molar (M(1)) cap. In WT embryos, two vestigial tooth primordia are transiently distinct in front of the M(1). The distal vestige has the form of a wide bud and participates during the development of the mesial portion of the M(1). This bud has been homologized with the vestigial primordium of the fourth premolar of mouse ancestors. The premolar disappearance coincided with a mesial lengthening of the M(1) during mouse evolution. The incorporation of the distal premolar vestige into the mesial part of the M(1) in WT embryos can be regarded as a repetition of the premolar disappearance during evolution. CONCLUSION: : Ontogenetic and phylogenetic data support that the S in Ta mice arises due to the segregation of the distal premolar vestige from the molar dentition and thus represents an evolutionary throwback (atavism).

Animals↗

Facial emphysema caused by cheek bite.

Biting of the buccal mucosa is very frequent injury, whereas facial emphysema caused by cheek bite is rare. We report a case of facial emphysema causing puffing of the cheek through a self-inflicted bite of the buccal mucosa.

Bites, Human↗

Double-skin paddle perforator flap from the lateral lower leg for reconstruction of through-and-through cheek defect - a report of two cases.

Extensive defects after ablative surgery of oral cancer, involving exterior skin of the cheek, demand for complex reconstruction. It often requires two free flaps, or double-skin paddle scapular-, radial forearm- or fibular-flap to reconstruct through-and-through cheek defects. The outcome is mostly described as successful and functional. Nevertheless donor site morbidity and functional impairment should not be neglected. This report describes the use of double-skin paddle perforator flaps from the lateral lower leg for combined intra and extraoral reconstruction after tumour resection. This kind of flap first avoids the need of an additional free flap, secondly it produces minimal donor site morbidity because of consequent preservation of the peroneal artery and primary wound closure. Thirdly it enables a good aesthetic outcome possible because of the primarily thin, pliable and variable skin paddles.

Adenoma, Pleomorphic↗

Longchain n-3 polyunsaturated fatty acids and microvascular reactivity: observation in the hamster cheek pouch.

Previous experiments in our laboratory, using the hamster cheek pouch microcirculation, have shown that precapillary vessels exhibit spontaneous rhythmic luminal variations, termed vasomotion, a myogenic activity sustained by a balance between membrane currents among which polarizing K(+) currents play an important role. In these microvessels, endothelium-derived relaxing factors (EDRFs) seem to regulate arteriolar diameter [via nitric oxide (NO) and cyclic GMP] and vasomotion [probably via endothelium-derived hyperpolarizing factor (EDHF)]. Fish or fish oil diet can decrease the risk of cardiovascular diseases, probably by modifying the conductance of selective ion channels, such as K(+) and/or Ca(++), and/or increasing the production of vasodilators, such as NO. To investigate its effect on microvascular reactivity, using the same preparation and an intravital microscope coupled to a closed circuit TV system, male hamsters were treated for 14 days, twice a day, with 0.4 mL/100 g body weight with fish or olive oil. An attempt was also undertaken to record in arterioles, in vivo, the membrane potential of smooth muscle cells during their vasomotor activity combining conventional microelectrode and intravital microscopy techniques. The effects of topical application of two vasodilators, acetylcholine [endothelium-dependent one, NO release and membrane hyperpolarization via Ca(++)-activated K(+) channels (K(Ca))] and sodium nitroprusside (endothelium-independent, NO donor and no change on membrane potential) and two vasoconstrictors which elicited membrane depolarization via Ca(++) channels, phenylephrine (alpha(1)-adrenergic receptor agonist) and serotonin (5-hydroxi-tryptamine) on mean internal diameter of arterioles and venules, arteriolar blood flows, spontaneous arteriolar vasomotion frequency and amplitude and functional capillary density (FCD, number of capillaries with flowing red blood cells per unit area of tissue) were determined. Anesthesia was induced by sodium pentobarbital (i.p.) and maintained with alpha-chloralose through the femoral vein. In the presence of vasomotion, the membrane potentials are slowly oscillating by about 20 mV around values of approximately -50 mV in perfect synchrony with vasomotor movements and depolarizing phases coincide with vasoconstrictions while polarizing ones with vasodilatations. Comparing all parameters, in control conditions, only the spontaneous vasomotion frequency was significantly higher (2.37 times higher) on the group treated with fish oil and persisted as such throughout all experiments. With topical application of the drugs mentioned above, the group treated with fish oil showed, for each drug concentration, a balance towards vasodilatation with consequent increase on arteriolar blood flow and on FCD, compared with the olive oil treated one. No significant changes on mean arterial pressure, spontaneous arteriolar vasomotion amplitude or venular diameter could be detected in the two groups. Our results support the concept that, in the hamster cheek pouch microcirculation, fish oil supplementation activates K(+) channels which act as the EDHF and might also increase the production of vasodilators, probably NO.

Acetylcholine↗

Hamsters chewing betel quid or areca nut directly show a decrease in body weight and survival rates with concomitant epithelial hyperplasia of cheek pouch.

Betel quid (BQ) chewing is strongly associated with the occurrence of oral leukoplakia, oral submucous fibrosis, and oral cancer. There are about 200-600 million BQ chewers in the world. Previous animal studies support the potential carcinogenicity of BQ in different test systems. However, little animal experiment has let hamsters or rats to chew BQ directly, similar to that in humans. In the present study, we established a hamster model of chewing BQ or areca nut (AN). A total of 81 2-week-old hamsters were randomly divided into three groups: 25 for control group, 28 for BQ-chewing group, and 28 for AN-chewing group. These animals were fed with powdered diet with/without BQ or AN for 18 months. Although the consumption of BQ or AN showed some variations, hamsters fed with powdered diet could chew and grind AN or BQ into small pieces of coarse fibers during the entire experimental period. The survival rate of AN-chewing hamsters decreased significantly after 6 months of exposure. The mean survival time was 15.6 +/- 0.9 months for control animals, 13.6 +/- 0.98 months for AN-chewing animals, and 15.7 +/- 0.55 months for BQ-chewing animals. The body weight of BQ- or AN-chewing animals also decreased after 4-13 months. Hamsters fed with AN for 18 months showed hyperkeratosis in 80% and acanthosis in 50% of cheek pouches. Animals fed with BQ for 18 months also showed hyperkeratosis in 93% and acanthosis in 14% of cheek pouches. These results indicate that AN and BQ components may induce alterations in proliferation and differentiation of oral epithelial cells. Animal model of chewing BQ or AN can be useful for future tumor initiation, promotion and chemoprevention experiments simulating the condition of BQ chewing in humans.

Animals↗

A modified method of carcinogenesis induction in the DMBA hamster cheek pouch model of squamous neoplasia.

BACKGROUND: The classic hamster cheek pouch model of squamous cell neoplasia requires triweekly application of 9,10-dimethyl-1,2-benzanthracene (DMBA) on tissues for 20 weeks. This study describes a new methodology for induction of neoplasia using a sustained-release delivery of carcinogen that is less labor intensive with decreased risk to personnel. METHODS: Cotton sutures were impregnated with DMBA and coated with silicone elastomer. These sutures were then placed in the cheek pouch of animals, were harvested at weekly intervals, and residual DMBA was measured confirming sustained release. Carcinogenesis was compared in Syrian hamsters grouped into classic triweekly painted model (n = 10), sustained-release DMBA (n = 19), sustained-release with weekly painting (n = 17), and control (n = 10). RESULTS: The sustained-release implants resulted in a 90% yield of squamous neoplasia at 20 weeks, similar to the classic painted model but with less handling of the carcinogen and the animals. CONCLUSIONS: This model is safer for personnel, time efficient, and effective for inducing carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Biodistribution of a carborane-containing porphyrin as a targeting agent for Boron Neutron Capture Therapy of oral cancer in the hamster cheek pouch.

Boron Neutron Capture Therapy (BNCT) is a bimodal cancer treatment based on the selective accumulation of 10B in tumors and concurrent irradiation with thermalized neutrons. The short-range, high-LET radiation produced by the capture of neutrons by 10B could potentially control tumor while sparing normal tissue if the boron compound targets tumor selectively within the treatment volume. In previous studies, we proposed and validated the hamster cheek pouch model of oral cancer for BNCT studies, proved that absolute and relative uptake of the clinically employed boron compound boronophenylalanine (BPA) would be potentially therapeutic in this model and provided evidence of the efficacy of in vivo BPA-mediated BNCT to control hamster oral mucosa tumors with virtually no damage to normal tissue. We herein present the biodistribution and pharmacokinetics of a lipophilic, carborane-containing tetraphenylporphyrin (CuTCPH) in the hamster oral cancer model. CuTCPH is a novel, non-toxic compound that may be advantageous in terms of selective and absolute delivery of boron to tumor tissues. For potentially effective BNCT, tumor boron concentrations from a new agent should be greater than 30 ppm and tumor/blood and tumor/normal tissue boron concentration ratios should be greater than 5/1 without causing significant toxicity. We administered CuTCPH intraperitoneally (i.p.) as a single dose of 32 microg/g body weight (b.w.) (10 microg B/g b.w.) or as four doses of 32 microg/g b.w. over 2 days. Blood (Bl) and tissues were sampled at 3, 6, 12, 24, 48, and 72 h in the single-dose protocol and at 1-4 days after the last injection in the multidose protocol. The tissues sampled were tumor (T), precancerous tissue surrounding tumor, normal pouch (N), skin, tongue, cheek and palate mucosa, liver, spleen, parotid gland and brain. The maximum mean B ratios for the single-dose protocol were T/N: 9.2/1 (12h) and T/Bl: 18.1/1 (72 h). The B value peaked to 20.7+/-18.5 ppm in tumor at 24h. The multidose protocol maximum mean ratios were T/N: 11.9/1 (3 days) and T/Bl: 235/1 (4 days). Absolute boron concentration in tumor reached a maximum value of 116 ppm and a mean value of 71.5+/-48.3 ppm at 3 days. The fact that absolute and relative B values markedly exceeded the BNCT therapeutic threshold with no apparent toxicity may confer on this compound a therapeutic advantage. CuTCPH-mediated BNCT would be potentially useful for the treatment of oral cancer in an experimental model.

Animals↗

High-voltage pulsed current: its influence on diameters of histamine-dilated arterioles in hamster cheek pouches.

Results from five independent studies from our laboratory indicate that cathodal high-voltage pulsed current (HVPC) significantly curbs posttraumatic edema formation in several animal models. Conversely, anodal HVPC did not curb edema formation. The mechanism by which HVPC reduces edema formation is unknown. We hypothesize that HVPC causes a decrease in local blood flow by active vasoconstriction of arterioles. Because we had previously observed positive effects with cathodal HVPC but not anodal HVPC, we further hypothesized that cathodal but not anodal HVPC would reduce diameters of histamine-dilated arterioles. Changes in diameters of resistance arterioles (5 to 30 microns internal diameter) were measured directly in cheek pouches of anesthetized hamsters, using in vivo video microscopy. Three minutes after superfusion with the inflammatory mediator (histamine) was begun, sensory-level HVPC at 120pps was applied concurrently for 30 minutes. Five animals received cathodal HVPC and five received anodal HVPC. Four other animals received 30-minute treatments of both cathodal and anodal HVPC in random order. Three control animals received histamine without HVPC for 30 minutes. Diameter changes of one arteriole from each cheek pouch was measured every 20 seconds throughout the treatment period. One-way analysis of variance (ANOVA) with repeated measures showed that diameters of histamine-dilated controls varied little over 30 minutes, and that adding cathodal HVPC did not significantly alter diameters of arterioles superfused with histamine. However, applying anodal HVPC to histamine-dilated arterioles significantly reduced arteriolar diameters. These results do not support the hypothesis that cathodal HVPC curbs edema formation by increasing arteriolar tone in the injured area.

Animals↗

Subunits of the cheek: an algorithm for the reconstruction of partial-thickness defects.

Reconstruction of partial-thickness defects of the cheek can be challenging. In addition to maintaining function, the repair must restore contour, minimise donor-site deformity and not distort the eyelid, mouth or jaw line. Since the demands for repair differ according to the site, so do the reconstructive options. To aid in selecting the best method, we classify the cheek into five subunits based on vascular anatomy and relevant landmarks. Based on our experience with 160 patients over a 12 year period, we present an algorithm that helps to select the best reconstructive option for each site. This algorithm is easy to follow and conforms to anatomical principles.

Algorithms↗

Capillary-based fully integrated and automated system for nanoliter polymerase chain reaction analysis directly from cheek cells.

A miniaturized, integrated and automated system based on capillary fluidics has been developed for nanoliter DNA analysis directly from cheek cells. All steps for DNA analysis, including injecting aqueous reagents and DNA samples, mixing the solutions together, thermal cell lysis, polymerase chain reaction (PCR), transfer and injection of PCR product, separation, sizing and detection of those products are performed in a capillary-based integrated system. A small amount of cheek cells collected by a plastic toothpick is directly dissolved in the PCR cocktail in a plastic vial or mixed on-line with a small volume of PCR cocktail (125 nl) in the capillary. After thermal cell lysis and PCR in a microthermal cycler, the DNA fragments are mixed with DNA size standards and transferred to a micro-cross for injection and separation by capillary gel electrophoresis. Programmable syringe pumps, switching valves, multiposition and freeze-thaw valves are used for microfluidic control in the entire system. This work establishes the feasibility of performing all the steps of DNA analysis from real samples in a capillary-based nanoliter integrated system.

Automation↗

Permeation of several drugs through keratinized epithelial-free membrane of hamster cheek pouch.

The hamster cheek pouch mucosa was selected as a substitute for the human buccal mucosa in an in vitro permeation study. Considering that a keratinized layer is not present in the human buccal mucosa, keratinized epithelial-free hamster cheek pouch (KEF-membrane) was prepared by chemical splitting. To confirm the usefulness of the KEF-membrane, a permeation study was conducted using several drugs with different lipophilicities. The permeability coefficient of hydrophilic drugs through the KEF-membrane (Pkef) was significantly greater than that through a viable KEF-membrane (Pkef-viable), which was estimated by using the permeability coefficient of the viable full-thickness membrane and that of the keratinized layer. On the other hand, the Pkef values of lipophilic drugs were comparable with the Pkef-viable values. Furthermore, the ratio of these P values (Pkef/Pkef-viable) decreased with increasing lipophilicity of drugs. These findings indicate that the KEF-membrane may be useful for buccal permeation studies of lipophilic drugs.

Animals↗

Recovery of infraorbital nerve function after zygomaticomaxillary cheek pedicled flap.

The zygomaticomaxillary cheek pedicled flap (ZMCF) involves the intentional section of the infraorbital nerve to reflect the flap laterally in order to give access to the rhinopharynx, clivus and upper cervical spine. The aim of this trial was to examine the recovery of sensation of the infraorbital nerve, both quantitatively (touch sensation, localisation test, two-point discrimination) and qualitatively (sharp/blunt test, temperature sensation, pain sensitivity, dental sensitivity) in 7 patients, at least 12 months after surgery. In each patient, four cutaneous areas (lower eyelid, nose ala, upper lip, cheek) and the upper vestibulum were tested. Results of each test in all the examined areas were evaluated and compared with the data obtained on the nonoperated side (control side). Results of neurosensory tests indicated good recovery of sensation with little difference in comparison with the control side, showing that the functional consequence of ZMCF should actually be considered only as a transitory event.

Adolescent↗

Tuberculoma of the cheek: a case report.

Tuberculoma of the cheek in the absence of tuberculosis elsewhere in the body is rarely seen and hence rarely thought of as a differential diagnosis when such a patient presents. In the following case, the patient was provisionally diagnosed as carcinoma of the cheek because of the exophytic nature of the growth and its presentation. However, histopathology of a biopsy revealed tuberculoma and the response to antituberculous therapy was rapid and curative.

Cheek↗

Schistosoma mansoni: cellular reactions to challenge infections in the cheek pouch skin of chronically infected Chinese hamsters.

The cellular reactions to the migration of challenge schistosomula of Schistosoma mansoni through the cheek pouch skin in Chinese hamsters immunized 20 weeks previously via the abdomen has been investigated at the ultrastructural level. The composition of the leucocytic infiltrate into the dermis and epidermis changed with time after infection. At 24 and 48 h the infiltrate was composed mainly of neutrophils and mononuclear cells. At 72 h fewer neutrophils but more eosinophils were present. The interaction of the leucocytes with the challenge schistosomula is described. Degranulation of eosinophils at the cell-parasite interface has been observed. Despite the fact that approximately 30% of 48 h schistosomula and 50% of 72 h schistosomula examined had adherent leucocytes only a few of the parasites exhibited signs of damage, consisting of tegumental vacuolation and changes in the electron opacity of the tegumental cytoplasm. There was no strong evidence of increased attrition of challenge schistosomula in the cheek pouch skin relative to the primary infection, although some dead challenge parasites were observed. It is concluded that a substantial proportion of the attrition of challenge infections in the Chinese hamster occurs at a post-dermal location.

Animals↗

The primary implantation of human tumours to the hamster cheek pouch.

The hamster cheek pouch is an immunologically privileged site. The present study is of simple implantation of human tumours direct from operative specimen to cheek pouch, in particular to determine whether tumour type influences the rate of successful implant. All implants were studied 10 or 20 days later. The use of cortisone significantly improved the number of implants growing.Carcinomas of the cervix were found to show growth in 55% of implants, in animals conditioned with cortisone. Growth from tumours of the uterine body, or from colorectal carcinomas, occurred in 25-30% of implants. Breast cancer gave poor results.

Animals↗

Selectivity of the photosensitiser Tookad for photodynamic therapy evaluated in the Syrian golden hamster cheek pouch tumour model.

The response to photodynamic therapy (PDT) with the photosensitiser (PS) Tookad was measured in the Syrian hamster cheek pouch model on normal mucosae and chemically induced squamous cell carcinoma. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 538 and 762 nm. The light dose, drug dose and drug injection-light irradiation times (DLI), ranging between 100 and 300 J cm(-2), 1-5 mg kg(-1) and 10-240 min respectively, were varied and the response to PDT was analysed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. A fast time decay of the tissular response with drug dose of 1-5 mg kg(-1) was observed for DLI ranging from 10 to 240 min and for light doses of 100-300 J cm(-2) delivered at a light dose rate of 150 mW cm(-2). A significantly higher level of tissular response was observed for squamous cell carcinoma compared to normal tissue. Nevertheless, the threshold level of the drug-light dose for a detectable response was not significantly different in the tumoral vs normal tissue. The highest response at the shortest DLIs and the absence of measurable response at DLI larger than 240 min at light dose of 300 J cm(-2) and drug dose of 5 mg kg(-1) reveals the predominantly vascular effect of Tookad. This observation suggests that Tookad could be effective in PDT of vascularised lesions.

9,10-Dimethyl-1,2-benzanthracene↗