Buccal Pouch Research Articles

Efficacy of Nutrients in Reducing the Symptoms of Radiation Induced Oral Mucositis in a Hamster Model

Radiation-induced oral mucositis (RIOM) is a painful, dose-limiting toxicity in cancer therapy. RIOM was induced by radiation on the left buccal pouch mucosa of Golden Syrian hamsters (n = 8/group). Animals were treated topically with polyphenols (Curcumin or Quercetin) or amino acids/metabolite mixtures (Alanyl-Glutamine or Arginine + Glutamine + β-Hydroxy β-methylbutyric acid (Arg/Gln/HMB)) for over 20 day. Progression of RIOM was assessed using a standard visual scoring six-point scale, for differences in severity of mucositis (score ≥3) (Chi-square analysis) and in the daily group scores (Mann-Whitney rank sum test). Compared to the controls, there was a significant reduction in number of days with severe RIOM (score ≥3) in the treatment groups: Curcumin (50 μg/ml) = 17%; Control = 38.5%, p < 0.001; Quercetin (50 μg/ml) = 27.6% and Quercetin (100 μg/ml) = 25%; Control = 41.3%, p = 0.007 and p = 0.001, respectively; Arg/Gln/HMB (50 mg/ml) = 31.9%; Control = 50.0%, p = 0.040. In addition, Curcumin (50 μg/ml), Quercetin (100 μg/ml) and Arg/Gln/HMB (100 mg/ml) groups had lower mucositis scores (≥3) on at least two consecutive time points over the course of the study than their respective controls. There were no significant group differences in deaths or body weight. This study demonstrates the potential benefits of topical application of either plant polyphenols or amino acid/metabolite mixtures in addressing severity and progression of RIOM.

Modulator effect of mangiferin on biochemical characterization in 7,12-dimethylbenz[a]anthracene induced oral cancer in experimental hamsters.

BackgroundNewly, chemo‐preventive technique might be a hopeful advancement in developing countries for treating cancers with the aid of toxic less natural based constituents. Malignancy urges to augment effectual chemo‐preventive agents that are look forward to suppress the tumours which may be stimulated by chewing and smoking of tobacco and over alcohol consumption related with the high prevalence of human oral cancer (OC) patients.MethodsIn the present research, we examined to assess antioxidants, lipid peroxidation (LPO) and detoxification enzymes levels of anticancer activity of mangiferin on 0.5% 7.12‐dimethylbenz[a]anthracene (DMBA) provoked hamster cheek pouch carcinoma (HCPC). OC on hamster buccal pouch (HBP) was incited by DMBA treatment for thrice per week for over 14 weeks.Results100% well defined OC establishment with body weight (bw), tumour burden (TB), antioxidant, LPO and liver marker enzymes and also histological changes were observed on DMBA‐challenged buccal pouch carcinoma (BPC) in hamsters. Orally treated mangiferin at an effective dosage of 50 mg/kg bw, to DMBA painted hamsters were significantly averted the body weight, succession of tumour, the biochemical as well as histopathological changes.ConclusionFindings of this work clearly suggest that the anti‐carcinoma effect of mangiferin possesses the modulator effects on potent antioxidant, anti‐LPO and detoxification agents to expel the metabolites of malignant cells, on DMBA‐provoked BPC in hamsters.

The Effect of Laser Bio-modulation on Dysplastic Lesions, an Animal Study.

Potentially malignant disorders are one of the clinical challenges. Dysplasia in these lesions can be a predictor of more potential for malignant changes. Photo-bio-modulation in benign lesions has advantages, but there is doubt on its safety in potentially malignant lesions. This study aims to assess if low-level laser can promote dysplastic changes while the method can play an important role in management of dysplastic lesions. Dysplasia was induced on anterior wall of the buccal pouch of 80 young Syrian male hamsters. Then, hamsters were divided to four groups to receive 4 and 12 sessions irradiation of 660 and 810 nanometers low-level lasers. For histopathologic study of the tissue, we used light microscopes. Using SPSS, data were analyzed via Wilcoxon signed rank test and Mann-Whitney U-test. In all of our four groups, the severity of dysplasia had no statistical difference in study sides comparing with their own controls. Wavelength and numbers of laser irradiation sessions had no statistically meaningful effect on the severity of dysplasia either. Low-level lasers appear to show no relevant or significant effect over the aggravation of the dysplasia's severity. Neither the wavelength nor the number of sessions appear to have any impact in the results.

Combined Photothermal and Nanochemotherapy in Treatment of Induced Oral Squamous Cell Carcinoma in Hamsters

Introduction: Oral squamous cell carcinoma (OSCC) shows unsatisfied survival rate which remains not changed over the last years. Thymoquinone (TQ) is a phyto­chemical, and many studies proved its promising therapeutic effect against OSCC. Gold nanorod (GNR) is a photothermal agent, has an efficient near-infrared heat conversion and induces ablation of solid tumors. The combination of photothermal therapy (PTT) and chemotherapy can enhance synergistic effects that markedly exceed the sum of individual treatments alone. Aim: this study aimed to evaluate the effect of combined photothermal and nano chemotherapy in treatment of induced oral squamous cell carcinoma in hamsters. Material and Methods: In the present study, the combined drug GNR/NTQ loaded on (poly) (lactic-co-glycolic acid) (PLGA) was prepared. The targeting agent, folate or folic acid (FA), was conjugated to the prepared nanoparticles. The therapeutic ac­tivity of the drug against chemically-induced OSCC in hamster buccal pouches was evaluated by clinical observations, tumor volume analysis, histopathological alterations and blood analysis. Results: The combined drug (GNR/NTQ/PLGA/FA/laser) had the highest therapeutic activity compared to individual treatments. It significantly ablated and regressed tumor size in chemically-induced OSCC in the hamster model as com­pared to the other preparations; GNR/NTQ/PLGA/FA without laser, GNR/ PLGA/FA/ laser and NTQ/PLGA/FA/laser. Conclusion: Compared to the single PTT or nanoche­motherapy, the combined PTT/nanochemotherapy with laser provides better therapeu­tic effects against OSCC

Radiation-induced oral mucositis hamster model using a linear accelerator enhances clinical relevance of preclinical studies for treatment strategy investigation.

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory‐initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation‐induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, as well as the progression of injury, pro‐inflammatory marker, histological, and elasticity analyses of the buccal pouch were conducted to verify replicability and reproducibility of the injury model. The findings from this model demonstrated its ability to consistently induce injury and resolution over 28 days using an acute dose of 60 Gy. This model was developed to enhance clinical relevance when evaluating potential efficacious treatments and can now be utilized in efficacy studies to better evaluate developed therapeutics in a preclinical model that is easy to translate to clinical studies..

Therapeutic efficacy of intraperitoneally injected curcumin on experimentally induced hamster buccal pouch carcinoma

Abstract: The aim of the present study was directed to investigate the therapeutic efficacy of intraperitoneally injected curcumin as anticarcinogenic treatment modality on 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch(s) (HBP(s)) carcinoma. Subjects and methods: Thirty Syrian male hamsters, five weeks old, weighing 90-130g were divided into three group(s) (G(s)): A, B, and C. G-A (negative control): HBP mucosa of 10 animals were painted with liquid paraffin alone three times a week for 14 weeks. G-B (positive control): 10 animals were painted with 0.5% DMBA in paraffin oil 3 times a week for 14 weeks. Then animals were left untreated for 6 weeks after DMBA painting. G-C (curcumin treated group): 10 animals were injected intraperitoneally with curcumin 80 mg/kg body weight every day for 6 weeks following DMBA-treatment. The assessment was based on the gross observation, histological and immunohistochemical examination utilizing anti-apoptotic Bcl-2 antibody. Results: Gross observation revealed variation in reduction of the tumor size in the treated group (G-C) compared to that observed in group G-B. Histopathological findings revealed variations between G-B and G-C groups. Immunohistochemical results revealed that Bcl-2 expression has a variability in the area % throughout the groups used. Groups G-A, G-B, and G-C were 7.78%, 75.51%, and 41.65% respectively. Conclusion: The therapeutic effect of intraperitoneally injected curcumin resulted in promising outcome in regression of DMBA induced HBP carcinoma.

Inhibitory effect of mosinone-A on immunohistochemical expression of inflammatory and angiogenic markers in 7, 12-dimethylbenz (a) anthracene induced hamster buccal pouch carcinogenesis

Inhibitory effect of mosinone-A on immunohistochemical expression of inflammatory and angiogenic markers in 7, 12-dimethylbenz (a) anthracene induced hamster buccal pouch carcinogenesis

Oral cancer preventive potential of Polydatin: A nanoencapsulation approach

Over the period, several medicinal plants are recognized as attractive sources of anti-cancer molecules. About 35,000 plant organisms have been tested for possible anticancer activities by the National Cancer Center (NCI). Among them, reproducible anticancer behavior has been shown by around 3,000 plant organisms. Based on this information, we aimed to investigate the cancer preventive efficiency of Polydatin encapsulated PLGA nanoparticles (POL-PLGA-NPs) against 7,12 dimethylbenz (a) anthracene (DMBA) induced buccal pouch carcinogenesis by modulating the antioxidants process in male Syrian hamsters. Oral cancer was initiated on left side buccal pouches by applying DMBA (0.5%), (a known potent chemical carcinogen) on alternative days in a week (thrice a week) for a period of 14 weeks to provoke oral cancer. Sequences of oral squamous cell carcinoma are noted to be manifested exhibiting the formation of incidence, size, mass and development of tumor presented as preneoplastic and neoplastic lesions in hamsters oral buccal pouch tissues. At the same time, oral administration of POL-PLGA-NPs (30mg/kg.b.wt.) considerably increased glutathione peroxidase (GPx) and glutathione (GSH) levels in the buccal tissue thereby decreasing lipid peroxidation activity which resulted in neoplasms incidence in buccal tissue of DMBA painted animals. Thus, POL-PLGA-NPs activity seemed to be a potent cancer preventive agent.

6]-Gingerol impedes 7,12-dimethylbenz(a)anthracene-induced inflammation and cell proliferation-associated hamster buccal pouch carcinogenesis through modulating Nrf2 signaling events.

The present study examines the chemopreventive role of [6]-gingerol, an active component of ginger, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis models. The HBP has been developed with an addition of 0.5% of DMBA to the HBP area three times per week, up to the end of the 16th experimental week. At the end of the experiment, we noticed 100% tumor incidence and precancerous lesions, such as dysplasia, hyperplasia, keratosis, and well-differentiated squamous cell carcinoma, in DMBA-induced HBP. Furthermore, we observed that [6]-gingerol inhibited the increased thiobarbituric acid-reactive substancesand decreased antioxidant levels in DMBA-induced hamsters. Moreover, [6]-gingerol inhibits DMBA-exposed over expression of inflammatory markers (inducible nitric oxide synthase, interleukin [IL]-1β, IL-6, cyclooxygenase-2, and tumor necrosis factor-α) and cell proliferation markers (cyclin D1, proliferating cell nuclear antigen); induces proapoptotic markers in HBP. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a major antioxidant transcription factor, which regulates the antioxidant gene-dependent scavenge of tumor proliferation and apoptosis. Overexpression of Nrf2 signaling plays a pivotal role and can be a novel target in preventing carcinogenesis. In this study, [6]-gingerol restores the DMBA-induced depletion of Nrf2 signaling and thereby prevents buccal pouch carcinogenesis in hamsters. These results point out that [6]-gingerol impedes the responses of inflammatory and cell proliferation-associated progression of cancer through the action of Nrf2 signaling.

Anticancer activity of Vicenin-2 against 7,12 dimethylbenz[a]anthracene-induced buccal pouch carcinoma in hamsters.

Buccal mucosa carcinoma is a significant cause of death in developing nations. Vicenin-2 is a significant bioactive compound found in Ocimum sanctum Linn or Tulsi that possesses several pharmacologic properties. Our focus is to understand the possible impact of Vicenin-2 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters. Buccal carcinoma was induced by treatment with carcinogenic DMBA, three times a week for 14 weeks. We determined 100% tumor incidence, abnormal tumor volume, inclined tumor burden, and deduced body weight in DMBA-induced oral squamous cell carcinoma (OSCC) hamsters. The upregulation of cytokine levels (interleukin [IL]-6, IL-1β, and tumor necrosis factor-alpha [TNF-α]) was observed in DMBA-induced OSCC hamsters. Moreover, dysplastic, hyperplastic, and squamous cell carcinoma was identified in the DMBA-induced OSCC hamsters. The diminished activities of lipid peroxidation andenzymatic/nonenzymatic antioxidants were observed in DMBA-induced hamsters. Furthermore, the high expression of proliferating cell nuclear antigen (PCNA), Cyclin-D1, and Bcl-2, and attenuated Bax expression were observed in DMBA-induced hamsters. Our study results explored that Vicenin-2 (30 mg/kg) treated with DMBA-brushed hamsters averted tumor incidence, improved the antioxidant status, and inhibited lipid peroxidation. Moreover, Vicenin-2 inhibited the immunohistochemical expression of PCNA, Cyclin-D1, and Bcl-2, and significantly restored apoptotic Bax levels. The Vicenin-2 treatment prevents the lesion formation in the oral epithelium of the DMBA-induced hamsters. The Vicenin-2 treatment potentially halts the proinflammatory cytokines (IL-6, IL-1β, and TNF-α) production in OSCC hamsters. Thus, we proved that Vicenin-2 prevents DMBA-induced buccal carcinogenesis in hamsters via improving antioxidants by modulating apoptotic and cytokines signaling pathways.

Reserpine inhibits DNA repair, cell proliferation, invasion and induces apoptosis in oral carcinogenesis via modulation of TGF-β signaling

Reserpine is a natural indole alkaloid isolated from Rauwolfia serpentina and has potent antioxidant, antimicrobial, and anti-mutagenic properties. Accordingly, this study aimed to investigate the effect of reserpine on DNA repair, cell proliferation, invasion and apoptosis in 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Transforming growth factor-β (TGF-β) was found to induce Smad2, 3 and 4 phosphorylation triggering Smad3/Snail mediated DNA repair proteins and Smad2/4 nuclear translocation. In contrast, reserpine inhibits TGF-β dependent Smad2/3/4 phosphorylation, thereby blockage Smad3/Snail activation and Smad2/4 nuclear translocation. Interruption of these oncogenic signaling pathways leads to downregulating ERCC1, XPF, Ku70, DNA-PKcs, PCNA, cyclin D1, HIF-1α, IL-6, Mcl-1 and stimulates Bax, cytochrome C, Apaf-1, caspase-9, caspase-3 and PARP protein expressions. This study provides therapeutic potential of reserpine in inhibiting DNA repair, cell proliferation, and invasion while simultaneously inducing apoptosis via modulation TGF-β signals.

Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12-dimethylbenz[a]anthracene-induced hamster oral cancer via the down-regulation of PI3K/AKT/mTOR signaling pathways.

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

Effect of nano-thymoquinone on tumor necrosis factor-α in DMBA-induced hamster buccal pouch carcinogenesis

This study aimed to evaluate the anti-inflammatory effect of TQ-PLGA/PVA in treatment of oral carcinogenesis. Nanoparticles were fabricated via emulsification-solvent technique. Their characterization including the morphological analysis and size distribution on NPs performed using TEM and the structure composition was carried out via the FTIR. The charge determined via the DLS and ZP analysis. This study was carried out on 24 hamsters and divided into: group A served as negative control, group B was painted with DMBA for 6 weeks then subdivided into three subgroups: B1 served as positive control, B2 was injected with TQ, B3 was injected with TQ-PLGA. Assessment of the blood cells counts, histologically, immunohistochemically through detection of TNF-α protein were performed. Comparisons between groups were performed using ANOVA. The results showed proper encapsulation for TQ-PLGA, significant regression in tumors histologically, marked improvement in blood cells and expression levels of TNF-α protein. Conclusion: systemic application of TQ-PLGA was considered a promising chemo-therapeutic agent in tumors regression.

Effect of rosmarinic acid as a chemopreventive modality on experimentally induced hamster buccal pouch carcinogenesis

Abstract: The aim of the present study was directed to investigate the effect of rosmarinic acid (RA) as a chemopreventive modality on experimentally induced hamster buccal pouch (HBP) carcinogenesis. Material and methods: Forty Syrian male hamsters five weeks old, weighing 80-120g, were divided into four groups of ten animals in each as follows, GI: Topical application of liquid paraffin alone (three times a week for 14 weeks), GII: Topical application of 7, 12 dimethyl benz[a]anthracene (DMBA) alone (0.5% in liquid paraffin, three times a week for 14 weeks), GIII: Topical application of DMBA (0.5% in liquid paraffin, three times a week for 14 weeks) + Oral administration of RA (100mg/kg b.w in 1ml distilled water by oral gavage, three times a week for 14 weeks on alternate days of DMBA application), GIV : Oral administration of RA alone (100mg/kg b.w in 1ml distilled water by oral gavage, three times a week for 14 weeks). Results: Gross observation and histopathological findings revealed a-GI: normal stratified squamous epithelium b- GII: well and moderately differentiated SCC c-: GIII: revealed considerably reversed tumor incidence d: GIV: normal similar to GI. Immunohistochemical results revealed, oral administration of RA to DMBA treated hamsters restored the normal expression of bcl-2 and Bax indicating that RA may have chemopreventive mechanism and/or pro-apoptotic effects. Conclusion: RA may act through various mechanisms, such as exerting anti-inflammatory, antioxidant effects as well as inhibiting cell proliferation, migration, and selectively inducing cancer cells apoptosis.

XRCC1 immunohistochemical expression in DMBA – induced oral squamous cell carcinoma treated with different thymoquinone preparations

The X-ray repair cross-complementing 1 (XRCC1) enzyme plays an important role in the DNA repair pathway. XRCC1 polymorphism increased the risk of human oral squamous cell carcinoma. Loading of thymoquinone on gold nanoparticles as a drug carrier, had revealed a superior anti-cancer effect as a chemotherapeutic agent in DMBA-induced OSCC. This study aimed to evaluate the expression of DNA repair enzyme X-ray repair cross-complementing 1 (XRCC1) following treatment of induced oral cancer in hamster buccal pouch with thymoquinone (TQ) only and loaded on gold nanoparticles (AuNps). Sixty male Syrian golden hamsters were divided into 4 groups: Group A: (negative control). The left pouches of the rest of animals were painted with the carcinogen DMBA (3times / week/ 12 weeks), then: Group B: (positive control), Group C: painted and injected intraperitoneally (i.p) with TQ only (3 times/week for 6 and 12 weeks). Group D: painted with TQ loaded on AuNps (3 times/week for 6 and 12 weeks). After euthanization, all pouches were surgically excised, fixed and processed for H&E and XRCC1 immunohistochemical stains. Groups B, C1, C2, and D1 showed well-differentiated squamous cell carcinoma with low intensity of immune staining. Groups D2 showed remarkable regression of tumors both clinically and histologically with high intensity of IHC staining. Loading of TQ at low concentration (0.001 mg/kg) on AuNps /12 weeks was a promising chemotherapeutic combination, through enhancing XRCC1 expression to regress the carcinogenesis process. This effect could be due to the anti-oxidant, free-radicle scavenging effect and enhancing apoptosis by TQ.

Abstract 10: Sclareol induces apoptosis and inhibits notch signaling in hamster oral carcinogenesis

Abstract The Notch signaling pathway is an evolutionarily conserved cell signaling pathway. It plays a central role in cell fate decisions and differentiation. The bioavailability of sclareol has been widely studied due to its anti-carcinogenic and antioxidant effects. However, chemo preventive effects of sclareol on notch signaling in 7, 12-dimethylbenz [a] anthracene (DMBA) induced hamster buccal pouch(HBP) carcinogenesis remain to be fully elucidated. In the present study, tumors were induced by applying 0.5% DMBA topically to HBP thrice a week for 14 weeks and sclareol was orally administered at a dose of 20mg/kg body weight on alternate days of DMBA painting. We analyzed expression of Notch signaling in DMBA induced oral squamous cell carcinoma (OSCC) in experimental oral carcinogenesis and inhibition of notch signaling by sclareol. This study thus observed up regulation of Notch1, Notch2, Jagged1, Hes1 and Hey1 in DMBA alone induced hamsters. Furthermore, oral administration of sclareol led to reduced Notch1, Notch2 activation and expression of Jagged-1 and its downstream targets of Hes-1 and Hey-1 in tumor bearing hamsters. In addition, sclareol treatment increased pro-apoptotic and decreased anti-apoptotic proteins survival indicating apoptosis through activation of caspase 3, and promoting cell death by dysregulation of cyclin D1 levels in tumor bearing hamsters. Immunohistochemical examination showed that Notch intracellular domain accumulates in the nucleus of cells in DMBA induced hamster buccal pouch carcinogenesis, and Jagged1 was found to be dysregulated in sclareol treated tumor animals. In conclusion, the results provide an important new insight of Notch signaling pathway for a potential therapeutic target for oral cancer. Citation Format: Aiyavu Chinnaiyan, Anandhi Nallu, Suresh Kathiresan. Sclareol induces apoptosis and inhibits notch signaling in hamster oral carcinogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 10.

Abstract 129: Apoptosis &amp; anti-proliferative nature of Aescin on 7,12 dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis via downregulating Notch signaling

Abstract Worldwide, oral squamous cell carcinoma (OSCC) is the sixth most common cancer &amp; ranked as second most common cancer in India. The most implicated etiologic factors in the development of oral cancer is the use of tobacco, alcohol &amp; also HPV infection. Aescin, a pentacyclic triterpenoid saponin mixtures derived from Aesculus hippocastanum L (horse chestnut) that has been used as traditional herbal medicine, exists the pharmacodynamic properties, anti- edematous, anti-inflammatory &amp; antitumor. The present study, Tumors were induced by applying 0.5% DMBA topically to hamster buccal pouch (HBP) thrice a week for 14 weeks &amp; Aescin was orally administered at a various dose of 40 mg/kg body weight on alternate days of DMBA painting. We observed, reduced the tumor incidence, diminished lipid peroxidation, &amp; elevation of antioxidants, liver marker enzymes by Aescin. Furthermore, aescin induced apoptosis in DMBA induced tumor bearing animals significantly inhibited cell to cell communication of Notch-1, Notch-2 &amp; its ligand &amp; Jagged-1 leads to inhibited expression of the Notch downstream signaling target Hes-1 &amp; Hey-1 analyzed by immunohistochemical analysis. These results clearly suggest that Aescin prevents lipid peroxidation, protects the antioxidant defense system, prohibit the dysplasia &amp; anti-carcinogenic potential. we concluded; the results provide an important new insight of Notch signaling pathway &amp; aescin might be developed as a potential chemo preventive agent for oral cancer. Key words: Oral cancer, aescin, antioxidant, apoptosis, chemopreventive, Notch signaling Citation Format: Hemavardhini Ramadoss, Suresh Kathiresan, Sanjay Gupta. Apoptosis &amp; anti-proliferative nature of Aescin on 7,12 dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis via downregulating Notch signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 129.

Function of gold nanoparticles in oral cancer beyond drug delivery: Implications in cell apoptosis

Gold nanoparticles (AuNPs) are used to deliver drugs and therapeutic small molecule inhibitors to cancer cells. Evidence shows that AuNPs coated with nuclear localization sequence can cross the nuclear membrane and induce cellular apoptosis. To determine the therapeutic role of AuNPs, we compared two nanoconstructs conjugated to doxorubicin (DOX) through pH-sensitive and pH-resistant linkers. We tested DOX nanoconjugates' cytotoxicity, cellular and nuclear uptake in oral squamous cell carcinoma cell line. Furthermore, we evaluated the therapeutic effect of pH-sensitive and pH-resistant DOX bioconjugates in hamster buccal pouch carcinoma model. Our data indicate that pH-resistant and pH-sensitive DOX-nanoconjugates were equally localized in cancer cells, but the pH-resistant DOX nanoparticles were more localized in the nuclei inducing a 2-fold increase in the apoptotic effect compared with the pH-sensitive DOX nanoparticles. Our in vivo results show significantly higher tumor shrinkage and survival rates in animals treated with DOX pH-resistant AuNPs compared with pH-sensitive ones. Our findings suggest that AuNPs enhance the cytotoxic effect against cancer cells in addition to acting as drug carriers. DOX pH-resistant AuNPs enhanced accumulation of AuNPs in cancer cells' nuclei inducing a significant cellular apoptosis which was confirmed using in vitro and in vivo experiments without deleterious effects on blood cell count.

Chewing Khat and periodontal health status in Dhamar - Yemen

The clinical examination involves eighty one males Yemenis, in Dhamar of age 15-45 years old and of similar and regular daily habit of chewing Khat unilaterally at the left side of the oral cavity to enjoy the amphetamin - like effect of Khat as a stimulant in a company with their friends under special environment & social rules in Yemen since a lot of years ago. The sample was divided equally into three age groups, (15-24 years), (25-34 years) and (35-45 years). The periodontal health status examined clinically to measure the plaque index, gingival index and periodontal pocket depth. Measurements divided into three groups, non - chewing right site of the mandible, and chewing left buccal site and chewing left lingual site of the mandible in the same individual. The periodontal health status according to the three parameters, revealed that the scores at the chewing site were higher than that at the non - chewing site, and higher buccally than lingually at the same chewing site. With the age and prolong abuse of Khat chewing, the scores increased and the periodontal pocket depth significantly differed in the age group (35-45 years) than the (15-24 years) and (25-34 years), age group. The periodontal pockets were significantly higher buccally than lingually at the same chewing site, may be due to the manner of Khat chewing, where the leaves of Khat accumulate gradually and held in the lower buccal pouch unilaterally in a bolus for several hours daily.

Ionic liquid-mediated delivery of insulin to buccal mucosa

Buccal drug delivery offers a potential non-invasive means of delivering therapeutics to patients. Despite the promise, the feasibility of transporting proteins and peptides into systemic circulation from buccal administration remains a daunting challenge. Here, we report the fabrication of a biodegradable polymeric patch for buccal delivery of insulin using chitosan as the mucoadhesive matrix and ionic liquids (ILs)/deep eutectic solvent (DES) as the transport facilitator. Insulin is mixed with ILs/DES made from Choline and Geranic acid (CAGE) to form a viscoelastic CAGE gel and sandwiched between two layers of a biodegradable polymer. The rheological properties of the CAGE gel were dominated by the elastic modulus and suggested a solid-like viscoelastic behavior. CAGE induced a 7-fold increase in the cumulative insulin transport across the ex vivo porcine buccal tissue (~26% of loaded insulin) which was also confirmed by confocal microscopy. The CAGE/insulin patches placed in the rat buccal pouch in vivo lowered blood glucose levels in a dose-dependent manner (up to 50% drop recorded) with no obvious tissue damage at the application site. The pharmacokinetic performance of the delivered insulin indicated a sustained profile as serum insulin levels plateaued after 3 h for the duration of study. The safety and efficacy of the polymeric patch using insulin as a model drug holds significant promise as a platform technology to deliver injectables through the buccal route.