Biology of Oral Mucosa and Esophagus

Squier, Christopher A.; Kremer, Mary

doi:10.1093/oxfordjournals.jncimonographs.a003443

Cited by 477 publications

(407 citation statements)

References 45 publications

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“…S3A, arrowheads). Furthermore, iASPP and loricrin or iASPP and filaggrin expression were mutually exclusive as loricrin and filaggrin are expressed in differentiated suprabasal cells (29) (Fig. S3A).…”

Section: Resultsmentioning

confidence: 99%

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) prevents senescence and is required for epithelial stratification

Notari

Koch

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is the most ancient member of the ASPP family of proteins and an evolutionarily conserved inhibitor of p53. iASPP is also a binding partner and negative regulator of p65RelA. Because p65RelA and the p53 family members often have opposite effects in controlling cell fate, it is important to understand the cellular context in which iASPP can regulate their activities. To address this question and to study the biological importance of iASPP in vivo, we generated a transgenic mouse in which iASPP expression is controlled by the Cre/loxP recombination system. We observed that iASPP is able to prevent premature cellular senescence in mouse embryonic fibroblasts. iASPP loss resulted in increased differentiation of primary keratinocytes both in vitro and in vivo. In stratified epithelia, nuclear iASPP often colocalized with p63 in the nuclei of basal keratinocytes. Consistent with this, iASPP bound p63 and inhibited the transcriptional activity of both TAp63α and ΔNp63α in vitro and influenced the expression level of p63-regulated genes such as loricrin and involucrin in vivo. In contrast, under the same conditions, p65RelA was frequently expressed as a cytoplasmic protein in the suprabasal layers of stratified epithelia and rarely colocalized with nuclear iASPP. Thus, iASPP is likely to control epithelial stratification by regulating p63's transcriptional activity, rather than p65RelA's. This study identifies iASPP as an inhibitor of senescence and a key player in controlling epithelial stratification.

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Section: Resultsmentioning

confidence: 99%

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) prevents senescence and is required for epithelial stratification

Notari

Koch

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Most recent chemotherapy was defined as any systemic therapy given within the last 60 days excluding agents such as hydroxyurea, IFN or intrathecal therapy. As epithelial cell-turnover time has been reported to range from a median of 14 days in the buccal mucosa to 24 days in the hard palate, 15 60 days was considered a sufficient time frame to allow for variability among patients. Recent exposure to MTX and VP16 was documented.…”

Section: Data Collected and Definitionsmentioning

confidence: 99%

Etoposide induces more severe mucositis than CY when added to TBI as conditioning in allograft recipients receiving CsA and MTX

Hoyt

Ritchie

Wirth

et al. 2010

Bone Marrow Transplant

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Fractionated TBI and etoposide (FTBI-VP16) conditioning is effective therapy for patients receiving allogeneic stem cell transplants for ALL. One of the major doselimiting toxicities with this regimen is mucositis although its effect on patients and hospital resources is not well described. To determine the severity of mucositis (WHO grade 3-4) experienced and assess resource utilisation, we compared the non-haematological toxicities of 38 patients receiving FTBI-VP16 with 104 patients receiving CY and TBI (CYTBI). FTBI-VP16 patients were more likely to develop severe mucositis (odds ratio (OR) 6.0 (95% confidence interval (CI) 1.36, 54.42), Po0.01) and its duration was longer (11.5 vs 8 days, Po0.01). Resource utilisation was considerably higher especially in the use and duration of i.v. narcotics and parenteral nutrition, nursing care requirements and plt-transfusion support. Patients receiving FTBI-VP16 conditioning are ideal candidates for new therapies to prevent or reduce the severity of mucositis.

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“…It is smooth and intact and consists of stratified, squamous, epithelium supported on a connective-tissue layer (Squier & Kremer, 2001). In addition, its low cost for in vivo studies and ready availability in local 105 butcheries for ex vivo experiments, makes the porcine buccal mucosa an ideal model for drug permeation studies.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, its low cost for in vivo studies and ready availability in local 105 butcheries for ex vivo experiments, makes the porcine buccal mucosa an ideal model for drug permeation studies. The porcine oesophageal mucosa is smooth and intact and consists of stratified, squamous, non-keratinised epithelium supported on a connective-tissue layer (Squier & Kremer., 2001). Various studies have reported on permeation through pig buccal mucosa for different drugs including fentanyl citrate (del Consuelo et al, 2005), beta blockers (Amores et 110 al., 2014), propofol (Tsagogiorgas et al, 2013) and galantamine (De Caro et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Functional physico-chemical, ex vivo permeation and cell viability characterization of omeprazole loaded buccal films for paediatric drug delivery

Khan

Trivedi

Boateng

2016

International Journal of Pharmaceutics

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25Buccal films were prepared from aqueous and ethanolic Metolose gels using the solvent casting approach (40°C). The hydration (PBS and simulated saliva), mucoadhesion, physical stability (20°C, 40°C), in vitro drug (omeprazole) dissolution (PBS and simulated saliva), ex vivo permeation (pig buccal mucosa) in presence of simulated saliva, ex vivo bioadhesion and cell viability using MTT of drug loaded (DL) films were investigated. Hydration and mucoadhesion 30 results showed that swelling capacity and adhesion was higher in the presence of PBS than simulated saliva (SS) due to differences in ionic strength. Omeprazole was more stable at 20°C than 40°C whilst omeprazole release reached a plateau within 1 hour and faster in PBS than in SS. Fitting release data to kinetic models showed that Korsmeyer-Peppas equation best fit the dissolution data. Drug release in PBS was best described by zero order via non-Fickian 35 diffusion but followed super case II transport in SS attributed to drug diffusion and polymer erosion. The amount of omeprazole permeating over 2 hours was 275ug/cm 2 whilst the formulations and starting materials showed cell viability values greater than 95%, confirming their safety for potential use in paediatric buccal delivery.

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Biology of Oral Mucosa and Esophagus

Cited by 477 publications

References 45 publications

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) prevents senescence and is required for epithelial stratification

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) prevents senescence and is required for epithelial stratification

Etoposide induces more severe mucositis than CY when added to TBI as conditioning in allograft recipients receiving CsA and MTX

Functional physico-chemical, ex vivo permeation and cell viability characterization of omeprazole loaded buccal films for paediatric drug delivery

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