The potential preventive effect of dietary phytochemicals In Vivo.

INTRODUCTION: Chemoprevention refers to using specific substances during oncogenesis. Curcumin and catechins are both polyphenol types of phytochemicals present in curcuma longa and green tea. The effect of curcumin is synergistic with epigallocatechin gallate, the most abundant polyphenol in tea. AIM: To evaluate and compares the chemopreventive effect of both green tea and curcumin (each individually and in combination) through induction of hamster buccal pouch carcinoma. MATERIALS AND METHODS: Squamous cell carcinoma was chemically induced in fifty Syrian golden hamsters divided into 5 groups (10 each). The first group was used as a normal control group. The second group received the carcinogenic agent only. The other three groups received green tea, curcumin, and a combination of both, respectively. Flow cytometry, immunofluorescence, and immunohistochemical assays were used to evaluate apoptosis, proliferation, and angiogenesis. ANOVA test was used to analyze the results between the study groups. RESULTS: The cells of the positive control group (B) resulted in 11.57% apoptosis. In the study groups, treatment of the cells with green tea (C), and curcumin (D) and both of them (E) showed increased apoptosis. The fluorescent image in group B showed an increase of the red fluorescence in the nucleus and cytoplasm of the squamous cell carcinoma cells while groups C, D, and E showed a decrease of the red fluorescence in the nuclei of the squamous cell carcinoma cells. The microvessel density was higher in the positive control group as compared to the treated groups. CONCLUSIONS: The combination of green tea and curcumin has a significant chemopreventive effect against oral carcinogenesis.

Exploiting Vitamin D Receptor and Its Ligands to Target Squamous Cell Carcinomas of the Head and Neck.

Vitamin D (VitD) and its receptor (VDR) have been intensively investigated in many cancers. As knowledge for head and neck cancer (HNC) is limited, we investigated the (pre)clinical and therapeutic relevance of the VDR/VitD-axis. We found that VDR was differentially expressed in HNC tumors, correlating to the patients' clinical parameters. Poorly differentiated tumors showed high VDR and Ki67 expression, whereas the VDR and Ki67 levels decreased from moderate to well-differentiated tumors. The VitD serum levels were lowest in patients with poorly differentiated cancers (4.1 ± 0.5 ng/mL), increasing from moderate (7.3 ± 4.3 ng/mL) to well-differentiated (13.2 ± 3.4 ng/mL) tumors. Notably, females showed higher VitD insufficiency compared to males, correlating with poor differentiation of the tumor. To mechanistically uncover VDR/VitD's pathophysiological relevance, we demonstrated that VitD induced VDR nuclear-translocation (VitD < 100 nM) in HNC cells. RNA sequencing and heat map analysis showed that various nuclear receptors were differentially expressed in cisplatin-resistant versus sensitive HNC cells including VDR and the VDR interaction partner retinoic acid receptor (RXR). However, RXR expression was not significantly correlated with the clinical parameters, and cotreatment with its ligand, retinoic acid, did not enhance the killing by cisplatin. Moreover, the Chou-Talalay algorithm uncovered that VitD/cisplatin combinations synergistically killed tumor cells (VitD < 100 nM) and also inhibited the PI3K/Akt/mTOR pathway. Importantly, these findings were confirmed in 3D-tumor-spheroid models mimicking the patients' tumor microarchitecture. Here, VitD already affected the 3D-tumor-spheroid formation, which was not seen in the 2D-cultures. We conclude that novel VDR/VitD-targeted drug combinations and nuclear receptors should also be intensely explored for HNC. Gender-specific VDR/VitD-effects may be correlated to socioeconomic differences and need to be considered during VitD (supplementation)-therapies.

Regeneration of critical-sized grade II furcation using a novel injectable melatonin-loaded scaffold.

BACKGROUND: Periodontal regenerative therapy using bone-substituting materials has gained favorable clinical significance in enhancing osseous regeneration. These materials should be biocompatible, osteogenic, malleable, and biodegradable. This study assessed the periodontal regenerative capacity of a novel biodegradable bioactive hydrogel template of organic-inorganic composite loaded with melatonin. MATERIALS AND METHODS: A melatonin-loaded alginate-chitosan/beta-tricalcium phosphate composite hydrogel was successfully prepared and characterized. Thirty-six critical-sized bilateral class II furcation defects were created in six Mongrel dogs, and were randomly divided and allocated to three cohorts; sham, unloaded composite, and melatonin-loaded. Periodontal regenerative capacity was evaluated via histologic and histomorphometric analysis. RESULTS: Melatonin-treated group showed accelerated bone formation and advanced maturity, with a significant twofold increase in newly formed inter-radicular bone compared with the unloaded composite. The short-term regenerative efficacy was evident 4 weeks postoperatively as a significant increase in cementum length concurrent with reduction of entrapped epithelium. After 8 weeks, the scaffold produced a quality of newly synthesized bone similar to normal compact bone, with potent periodontal ligament attachment. CONCLUSIONS: Melatonin-loaded hydrogel template accelerated formation and enhanced quality of newly formed bone, allowing complete periodontal regeneration. Furthermore, the scaffold prevented overgrowth and entrapment of epithelial cells in furcation defects.

The theranostic potentialities of bioavailable nanocurcumin in oral cancer management.

BACKGROUND: Oral cancer, one of the most common cancers, has unimproved 5-years survival rate in the last 30 years and the chemo/radiotherapy-associated morbidity. Therefore, intervention strategies that evade harmful side effects of the conventional treatment modalities are of need. Herbal therapy as a complementary preventive/therapeutic modality has gained attention. Curcumin is one of the herbal compounds possessing unique anticancer activity and luminescent optical properties. However, its low water solubility limits its efficacy. In contrast, curcumin at the nanoscale shows altered physical properties with enhancing bioavailability. METHODS: The current study evaluated the impact of nanocurcumin as an anti-oral cancer herbal remedy, comparing its efficacy against the native curcumin complement and conventional chemotherapeutic. An optimized polymeric-stabilized nanocurcumin was synthesized using the solvent-antisolvent precipitation technique. After assuring the solubility and biocompatibility of nanocurcumin, we determined its cytotoxic dose in treating the squamous cell carcinoma cell line. We then evaluated the anti-tumorigenic activity of the nano-herb in inhibiting wound closure and the cytological alterations of the treated cancer cells. Furthermore, the cellular uptake of the nanocurcumin was assessed depending on its autofluorescence. RESULTS: The hydrophilic optimized nanocurcumin has a potent cancerous cytotoxicity at a lower dose (60.8 µg/mL) than the native curcumin particles (212.4 µg/mL) that precipitated on high doses hindering their cellular uptake. Moreover, the nanocurcumin showed differential targeting of the cancer cells over the normal fibroblasts with a selectivity index of 4.5. With the confocal microscopy, the luminescent nanoparticles showed gradual nuclear and cytoplasmic uptake with apparent apoptotic cell death, over the fluorescent doxorubicin with its necrotic effect. Furthermore, the nanocurcumin superiorly inhibited the migration of cancer cells by -25%. CONCLUSIONS: The bioavailable nanocurcumin has better apoptotic cytotoxicity. Moreover, its superior luminescence promotes the theranostic potentialities of the nano-herb combating oral cancer.

Central Odontogenic Fibroma with Giant Cell Granuloma-Like Lesion: A Report of an Additional Case and Review of Literature.

Central odontogenic fibroma is a rare benign odontogenic tumor that relies on clinical-radiographic-histological correlation to reach its diagnosis, especially its rare variants. Of these rare types is the coexistence of giant cell granuloma-like lesion, with the characteristic odontogenic epithelial rests. The presented case is a 33 years old female complaining of asymptomatic mandibular bony swelling. Radiographically, the lesion is unilocular radiolucent, without root resorption. Histological examination revealed the presence of multinucleated giant cells within the diagnosed central odontogenic fibroma. Immunohistochemical staining highlighted the presence of both components.