Overview of glottic laryngeal cancer treatment recommendation changes in the NCCN guidelines from 2011 to 2022.

BACKGROUND: The treatment of glottic cancer remains challenging, especially with regard to morbidity reduction and larynx preservation rates. The National Comprehensive Cancer Network (NCCN) has published guidelines to aid decision-making about this treatment according to the tumor site, clinical stage, and patient medical status. AIM: The present review was conducted to identify changes in the NCCN guidelines for glottic cancer treatment made between 2011 and 2022 and to describe the published evidence concerning glottic cancer treatment and oncological outcomes in the same time period. METHODS AND RESULTS: Clinical practice guidelines for head and neck cancer published from 2011 up to 2022 were obtained from the NCCN website (www.NCCN.org). Data on glottic cancer treatment recommendations were extracted, and descriptive analysis was performed. In addition, a review of literature registered in the PubMed database was performed to obtain data on glottic cancer management protocols and treatment outcomes from randomized controlled trials, systematic reviews, and meta-analyses published from 2011 to 2022. In total, 24 NCCN guidelines and updates and 68 relevant studies included in the PubMed database were identified. The main guideline changes made pertained to surgical and systemic therapies, the consideration of adverse features, and new options for the treatment of metastatic disease at initial presentation. Early-stage glottic cancer received the most research attention, with transoral endoscopic laser surgery and radiotherapy assessed and compared as the main treatment modalities. Reported associations between treatment types and survival rates for this stage of glottic cancer appear to be similar, but functional outcomes can be highly compromised. CONCLUSION: NCCN panel members provide updated recommendations based on currently accepted treatment approaches for glottic cancer, constantly reviewing new surgical and non-surgical techniques. The guidelines support decision-making about glottic cancer treatment that should be individualized and prioritize patients' quality of life, functionality, and preferences.

Cancer chemo-preventive role of grape seed oil and cisplatin as a combination adjuvant therapy in the treatment of tongue squamous cell carcinoma: A biological in-vitro study.

OBJECTIVES: Grape seed oil (GSO) has recently gained popularity due to its anticancer properties. This study aimed to investigate the efficacy of combining cisplatin (CP) and GSO in tongue squamous cell carcinoma (TSCC) treatment. METHODS: In this study, human tongue carcinoma cell line (HNO-97) was treated with CP and GSO alone or in combination. The effects of CP and GSO on cytotoxicity and cell cycle arrest were studied using the MTT assay and flowcytometry, respectively. The apoptotic markers, including p53 and caspase 8, were assessed using reverse-transcription polymerase chain reaction (RT-PCR), caspase 3 using immunohistochemistry, and the angiogenic marker vascular endothelial growth factor (VEGF) using enzyme-linked immunosorbent assay (ELISA). RESULTS: The IC50 drug concentrations were found to be 16.4 ug/mL of GSO and 2.18 ug/mL of CP. When compared to the untreated control group, the percentage of S phase cells and apoptotic cells was significantly higher in the GSO, CP, and GSO/CP combination therapy groups. Furthermore, p53, caspase 8, caspase 3 expression were significantly upregulated in the GSO-and CP-treated groups, with evident upregulation with GSO/CP combination therapy. However, VEGF levels were significantly lower in the GSO-, CP-, and combined GSO/CP-treated groups. CONCLUSIONS: GSO has both an apoptotic and antiangiogenic effect in the treatment of TSCC, suggesting a new strategy for phytochemical-based combination therapy.

[Influencing factors of nutritional status and change in 50 patients with oral squamous cell carcinoma during treatment].

PURPOSE: To investigate the changes of nutritional status in patients with oral squamous cell carcinoma(OSCC) and analyze the influencing factors during treatment. METHODS: Anthropometry (weight, BMI, waistline, middle circumference of left and right upper arms) and laboratory index(serum prealbumin, serum albumin, transferrins, 25-hydroxyvitamin D) were measured to represent the nutritional status of 50 patients with OSCC before operation, two days, one month and three months after operation. SPSS 24.0 software package was used for statistical analysis of the data, and influencing factors of nutrition risk in OSCC patient were analyzed with binary logistic regression model. RESULTS: Univariate and multivariate analysis showed that advanced age(OR=1.127,95%CI: 1.053-1.207), low educational level (OR=5.250, 95%CI: 1.147-21.796), smoking(OR=6.182, 95%CI: 1.631-23.433), alcohol use(OR=5.227, 95%CI: 1.336-20.450), chemoradiotherapy (OR=3.984, 95%CI: 1.199-13.242), free flap surgery (OR=8.000, 95%CI: 2.060-31.068), tracheostomy(OR=3.960, 95%CI: 1.069-14.671), cervical lymph node metastasis(OR=4.821, 95%CI: 1.418-16.399), buccal carcinoma(OR=9.000, 95%CI:1.140-71.038), tongue cancer(OR=7.200, 95%CI: 1.081-47.962), tumor stage T3-4(OR=3.542, 95%CI: 1.066-11.771) were independent influencing factors of the nutritional status of patients with OSCC. CONCLUSIONS: Aging, low educational level, smoking history and drinking history in the general demographic characteristics of patients, and chemoradiotherapy, free flap surgery, tracheostomy during treatment, as well as buccal carcinoma, tongue cancer, advanced stage and cervical lymph node metastasis are clinical characteristics, which affect the nutrition level during the treatment for OSCC patients.

Ganoderma lucidum polysaccharides inhibit in vitro tumorigenesis, cancer stem cell properties and epithelial-mesenchymal transition in oral squamous cell carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The polysaccharides of the millenary mushroom Ganoderma lucidum (GL) have been shown for decades to present anti-tumor activities, but few studies evaluated its importance on cancer stem cells and EMT process. Cancer stem cells (CSC) drive the development of carcinoma and are also involved in cancer treatment failure, being a good target for treatment success. Also, the process of epithelial-mesenchymal transition (EMT) is involved in metastasis and cancer relapse. Besides that, the increasing incidence worldwide of oral squamous cell carcinoma (OSCC) became a public health issue with a high rate of metastasis and poor quality of life for patients during and after treatment. AIM OF THE STUDY: to evaluate G. lucidum polysaccharides (GLPS) in vitro effects on OSCC, focusing on hallmarks associated with tumorigenesis using the SCC-9, a squamous cells carcinoma lineage from the tongue. MATERIALS AND METHODS: SCC-9 cells were treated in vitro for 72h with different GLPS concentrations. The controls cells were maintained with culture media only and cisplatin was used as treatment control. After the treatment period, the cells were evaluated. RESULTS: GLPS treatment changed cell morphology and granularity, delayed migration, decreased colony, and impaired sphere formation, thereby leading to a non-invasive and less proliferative behavior of tumoral cells. Additionally, GLPS downregulated CSC, EMT, and drug sensitivity (ABC) markers. CONCLUSIONS: These results show that the natural product GLPS has the potential to be an important ally for tongue squamous cell carcinoma treatment, bringing the millenary compound to modern therapy, providing a basis for future studies and the improvement of life quality for OSCC patients.

Impact on patients with oral squamous cell carcinoma in different anatomical subsites: a single-center study in Taiwan.

The incidence of oral cavity squamous cell carcinoma (OSCC) is particularly high in South Asia. According to the National Comprehensive Cancer Network, OSCC can arise in several subsites. We investigated survival rates and the clinical and pathological characteristics of OSCC in different anatomical subsites in the Taiwanese population. We retrospectively analyzed data for 3010 patients with OSCC treated at the Changhua Christian Hospital. Subsequently, we compared clinical and pathological features of OSCC in different subsites. Pathological T4 stage OSCCs occurred in the alveolar ridge and retromolar trigone in 56.4% and 43.7% of cases, respectively. More than 25% of patients with tongue OSCC and 23.4% of those with retromolar OSCC had lymph node metastasis. The prognosis was worst for hard palate OSCC (hazard ratio 1.848; p < 0.001) and alveolar ridge OSCC (hazard ratio 1.220; p = 0.017). Retromolar OSCC recurred most often and tongue OSCC second most often. The risk for cancer-related mortality was highest for hard palate OSCC, followed by alveolar ridge and retromolar OSCC. We found distinct differences in survival among the different subsites of OSCC. Our findings may also help prompt future investigations of OSCC in different subsites in Taiwanese patients.

Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma.

OBJECTIVES: To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance. METHODS: TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo. KEY FINDINGS: The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo. CONCLUSIONS: PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.

Radiological approach for the newly incorporated T staging factor, depth of invasion (DOI), of the oral tongue cancer in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual: assessment of the necessity for elective neck dissection.

The 8th edition of American Joint Committee on Cancer's (AJCC) Cancer Staging Manual was modified by incorporating depth of invasion (DOI) in the T categorization of oral cavity cancer. This is because DOI is strongly associated with cervical lymph node metastasis, which is the most important negative prognostic factor of oral cavity cancer. This major change in the AJCC Cancer Staging Manual caused re-staging of T category in several cases. Although, the DOI on MRI and CT (radiological DOI; r-DOI) strongly correlated with pathological DOI (p-DOI), it is often 2-3 mm larger than p-DOI. Due to this variance, estimation of p-DOI based on r-DOI may not be accurate. However, when a lesion is undetectable on MRI, p-DOI was often smaller than 4 mm. On the other hand, when MRI depicts lesions with styloglossus and hyoglossus muscle invasion, p-DOI was always larger than 4 mm. These correlations between MRI findings and p-DOI are important when assessing the need for elective neck dissection, as the National Comprehensive Cancer Network (NCCN) recommends elective neck dissection in cases with DOI greater than 4 mm.

Polish Propolis-Chemical Composition and Biological Effects in Tongue Cancer Cells and Macrophages.

The purpose of this study was to compare the chemical composition and biological properties of Polish propolis. Ethanol, ethanol-hexane, hexane and hexane-ethanol extracts of propolis from three different regions of Poland were prepared. On the basis of the evaluation of their chemical composition as well as the extraction yield and free radical scavenging activity, the ethanol and hexane-ethanol extractions were proposed as the most effective methods. Subsequently, the biological properties of the extracts were evaluated to investigate the selectivity of an anticancer effect on tongue cancer cells in comparison to normal gingival fibroblasts. The obtained products demonstrated anticancer activity against tongue cancer cells. Additionally, when the lowest extract concentration (100 µg/mL) was applied, they were not cytotoxic to gingival fibroblasts. Finally, a possible anti-inflammatory potential of the prepared products was revealed, as reduced mitochondrial activity and proliferation of macrophages exposed to the extracts were observed. The results obtained indicate a potential of Polish propolis as a natural product with cancer-selective toxicity and anti-inflammatory effect. However, further studies are still needed to thoroughly explain the molecular mechanisms of its action and to obtain the promising health benefits of this versatile natural product.

Magnetic resonance imaging findings of styloglossus and hyoglossus muscle invasion: Relationship to depth of invasion and clinical significance as a predictor of advisability of elective neck dissection in node negative oral tongue cancer.

PURPOSE: By comparing styloglossus and hyoglossus muscle invasion (SHMI) of oral tongue squamous cell cancer (OTSCC) on MR imaging to pathological depth of invasion (DOI) and prognosis, we aimed to evaluate the clinical significance of MR imaging findings of SHMI. METHOD: Forty-five, early stages and clinically N0 OTSCCs were retrospectively reviewed. Data included pathological DOI, DOI on MR imagings, two-year potential cervical lymph node positive, locoregional control, disease-free survival, and overall survival. Data were statistically compared between the groups with MR evidence of SHMI (SHMI+) and without MR evidence of SHMI (SHMI-). RESULTS: There were 17 SHMI + and 28 SHMI-. Elective neck dissections performed on 13 cases revealed five node positive cases, all of which were SHMI + . Pathological DOI in SHMI + was significantly larger than SHMI- (average 9.0 vs 4.6 mm, p < 0.001). All SHMI + revealed pathological DOI larger than 4 mm. The two-year potential cervical lymph node positive rate of SHMI + was significantly higher than SHMI- (p =  0.01). Locoregional control rate and disease-free survival of SHMI+ were significantly lower than in SHMI- (p =  0.02). There was no significant difference in overall survival. Interobserver agreement in evaluation of SHMI on MR imaging was good (kappa value = 0.72, p <  0.001). CONCLUSIONS: Pathological DOIs of SHMI + were all larger than 4 mm, which is the cut-off point that National Comprehensive Cancer Network recommends for neck dissection, and SHMI + had a worse prognosis than SHMI-. SHMI + can be used as a criterion for elective neck dissection.

TORS excision of lingual thyroid carcinoma: Technique and systematic review.

OBJECTIVE: Clinically significant lingual thyroid tissue has a prevalence of 1/3000-10,000, and in 70% of these individuals, the lingual thyroid is their only thyroid tissue. Malignant transformation is exceedingly rare. Herein, we present a case of lingual thyroid carcinoma with a systematic literature review and description of our treatment technique. DATA SOURCES: PubMed, Ovid. REVIEW METHOD: The primary author performed a search of the literature for reports of lingual thyroid carcinoma or ectopic thyroid carcinoma associated with the tongue. Articles that did not present novel data, presented cases of ectopic thyroid carcinoma outside the tongue, non-malignant cases, non-thyroid carcinomas, or were non-English articles were excluded. Studies were limited to those published in the last 60 years. RESULTS: There are 39 cases reported in the literature. 23 cases occurred in females. Age at diagnosis ranged from 12 to 86; cases were more commonly diagnosed in the second decade of life, then in the 5th and 6th decades of life. Dysphagia, globus sensation, episodes of bleeding, voice changes, and presence of a neck mass were common symptoms at initial presentation. Nearly all patients underwent some form of pre-operative imaging, but practices varied as to the type of imaging. Treatment included surgical excision of the tumor in all but one case that was successfully treated with radioactive iodine therapy alone. CONCLUSIONS: Surgeons should be aware of lingual thyroid, its presentation, workup, and carcinoma treatment. Tumors are amenable to surgical excision, possibly followed by radioactive iodine therapy. Advances in robotic and endoscopic surgery over the past decade now allow for less morbid excisions of lingual thyroid tumors.

[A Case of Consciousness Disorder Induced by the Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Cisplatin and 5-Fluorouracil Chemotherapy in a Patient with Tongue Cancer].

We herein report a case of a consciousness disorder that was induced by the syndrome of inappropriate antidiuretic hormone secretion following cisplatin (CDDP) and 5 -fluorouracil (5-FU) chemotherapy in a patient with tongue cancer. A 72- year-old woman complained of tongue pain and was admitted to our hospital for neoadjuvant chemotherapy, under a diagnosis of tongue squamous cell carcinoma (T4aN2bM0). She was treated with CDDP and 5-FU. On the second day after administration, she complained of nausea and anorexia, and on the third day, she showed impaired consciousness. Laboratory studies revealed that the patient had a serum sodium concentration 112mEq/L, and no dehydration was noted. The patient was diagnosed with SIADH, using the appropriate diagnostic criteria based on serum and urine hypoosmolality. We subsequently discontinued chemotherapy and initiated fluid restriction and sodium supplements. Two days after this treatment, her consciousness level improved, and on the fifth day of treatment, laboratory studies revealed a serum sodium level of 134mEq/ L.

Anticancer activity of chlorhexidine and cranberry extract: an in-vitro study.

INTRODUCTION: Oral cancer is considered to be a global pandemic. The study was conducted to assess the anti-cancer activities of Chlorhexidine (CHX) and Cranberry against oral cancer cell lines. MATERIAL AND METHODS: Anticancer activity of CHX and Cranberry extract (CE) was assessed against AW13516 (poorly to moderately differentiated squamous cell carcinoma of tongue) and KB (Nasopharyngeal carcinoma) using Sulforhodamine B (SRB) assay at the Advanced Centre for Treatment Research and Education in Cancer (ACTREC) Mumbai, India. Three dose related parameters GI50, TGI and LC50 were calculated for each drug. RESULTS: CE (80µg/ml) showed no anti-cancer property against AW13516 cell line; however it showed 70.6% growth inhibition against KB cell line. CHX demonstrated 80.15% & 95.7% of growth inhibition against AW13516 & KB cell line respectively. Both the drugs were less potential than positive control drug Adriamycin, as reflected by their GI50, TGI and LC50 values. CONCLUSION: CHX exhibited better anti-cancer properties than CE for both the oral cancer cell lines.

Thymol inhibits oral squamous cell carcinoma growth via mitochondria-mediated apoptosis.

BACKGROUND: Thymol is a transient receptor potential ankyrin subtype 1 channel, (TRPA1) agonist found in thyme and oregano. Thymol has antioxidant, anti-inflammatory, and antimicrobial properties; thus, thymol is added to many commercially available products including Listerine mouthwash. Thymol is also cytotoxic to HL-60 (acute promyelocytic leukemia) cells in vitro. Therefore, we evaluated the effects of thymol against oral squamous cell carcinoma (OSCC) and its anticancer mechanism-of-action. METHODS: The antiproliferative effects of thymol in OSCC Cal27 cells were determined by MTS assays. Antitumor effects were evaluated in Cal27- and HeLa-derived mouse xenografts. Calcium imaging, mitochondrial transmembrane potential (ΔΨm) studies, and Western blot analysis of cleaved PARP (c-PARP) evaluated thymol's mechanism-of-action. RESULTS: Thymol had significant, long-lasting antiproliferative effects in vitro. In vivo, thymol displayed significant antitumor effects in Cal27-derived tumors. Thymol's anticancer effects were confirmed in HeLa-derived xenografts demonstrating that thymol effects are not tumor-type specific. Calcium imaging verified calcium influx in Cal27 cells that were reversed with the TRPA1 antagonist, HC030031. However, no calcium influx was seen in HeLa cells indicating that TRP channels do not regulate thymol cytotoxicity. This was confirmed using cell viability assays in which pre-treatment with HC030031 had no effect on thymol cytotoxicity. Instead, ΔΨm studies revealed that thymol induces significant ΔΨm depolarization and apoptosis. CONCLUSION: Our findings provide the first evidence of thymol's novel antitumor effects against OSCC in vivo, which do not rely on TRPA1 activity. Instead, we show that thymol induces mitochondrial dysfunction and apoptosis and may be efficacious against multiple cancers.

Effects of Curcumin on Squamous Cell Carcinoma of Tongue: An In Vitro Study.

BACKGROUND: The Squamous Cell Carcinoma of the Tongue (TSCC) is the most frequent cancer of oral cavity often characterized by poor prognosis. Conventional therapies are not very efficient and often may cause serious side effects. In this context, introduction of natural substances as possible adjuvant in the treatment and prevention of cancer is becoming a relevant topic. In fact, curcumin has been used for decades in Chinese traditional medicine for its beneficial effects. Curcumin has anticancer properties in many tumors however, its action on the tongue carcinoma is not entirely clear and many other investigations are necessary. OBJECTIVE: Curcumin seems to be a good adjuvant in the treatment of head and neck tumors. However, these studies are generic and there are not many specific studies on TSCC, the most frequent and most aggressive cancer of the head-neck region. Our goal is to demonstrate its effectiveness also for TSCC. METHODS: In this study, we evaluated the effects of curcumin on TSCC cells using different concentrations (1, 5, 10, 20 and 50 µM) and 3 different treatment times (24, 48 and 72 hours). The inhibition of adhesion, proliferation, viability, migration and apoptosis was studied. RESULTS: IC50 value of curcumin is about 10 µM and there have been inhibitory effects even for treatments at low concentrations. Curcumin reduces migration and progression of TSCC cells and it promotes apoptosis and inhibits tumorigenesis. CONCLUSIONS: These results suggest the possible use of curcumin as an anti-cancer agent in TSCC. However, in vivo studies are needed to confirm these effects and overcome its low bioavailability.

Protective effects of purple carrot extract (Daucus carota) against rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

The aim of this study was to evaluate the chemopreventive potential of purple carrot extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). For this purpose, histopathological analysis, proliferative status, antioxidant activity and inflammatory status were investigated in this setting. A total of 20 male rats were distributed into four groups as follows (n = 5 per group): Group 1-free access to water and commercial diet for 12 weeks; Group 2-received 4NQO at 50 ppm dose in drinking water daily and commercial diet for 12 weeks; Group 3-free access to water and received diet supplemented with purple carrot extract (0.1 g/kg) for 12 weeks; and Group 4-received 4NQO at 50 ppm dose in drinking water daily and diet supplemented with purple carrot extract (0.1 g/kg) for 12 weeks. Histopathological analysis revealed that animals treated with purple carrot extract reduced the oral lesions such as dysplasia and squamous cell carcinoma. Animals with oral pre-neoplastic lesions and treated with purple carrot extract decreased ki-67 and 8-OHdG immunoexpression. Moreover, pNFκBp50 and MyD88 protein expressions were decreased after purple carrot treatment associated or not with 4NQO exposure. SOD-Mn mRNA levels increased with treatment with purple carrot extract as well. In conclusion, our results demonstrated that purple carrot extract was able to protect oral lesions induced by 4NQO in Wistar rats as a result of antioxidant activity, anti-inflammatory potential and antiproliferative and antimutagenic actions.

Effectiveness of radiotherapy+ozone on tumoral tissue and survival in tongue cancer rat model.

OBJECTIVE: The objective of this study is to examine therapeutic effect of the combination of radiotherapy and ozone which features increasing of the destruction of cancer cells by increasing oxygen level of the body on advanced tongue cancer induced in rats. METHODS: A total of 36 female rats were included in this study as 4 groups. Group 1 (Cancer, n=8): 4NQO. Group 2 (Cancer+Radiotherapy, n=10): 4NQO+Radiotherapy. Group 3 (Cancer+Ozone+Radiotherapy, n=10): 4NQO+Ozone+Radiotherapy. Group 4 (Cancer+Ozone, n=10): 4NQO+Ozone. Group 5 (Control, n=8): Physiological saline solution. At the end of the week 20, rats in Groups 1 and 5 were sacrified. The rats in Groups 2,3 and 4 were waited until oral food intake was disrupted. The necessary applicatione were then carried out and survivals were evaluated. Each rat was sacrified after death. Tongues of the rats were excised, stained with hematoxylin & eosin and histopathologically evaluated. RESULTS: Histopathologic evaluation: The model that we applied was seen to achieve success in Group 1 in which 7 of the rats developed squamous cell carcinoma and one rat developed dysplasia at the end of the week 20. In Group 2 squamous cell cancer was seen in 6 and dysplasia in 4 rats. Six rats presented normal tongue tissues and 4 rats developed hyperplasia in Group 3. In Group 4; 3 rats had squamous cell cancer, 2 rats dysplasia, 3 rats hyperplasia and 2 rats had normal tissue. In Group 5, normal tongue tissues were observed in all rats. A significant histopathological improvement was observed in Group 3 compared to Group 2 (p<0.05). Histopathologic scorings were similar in Groups 3 and 5 (p>0.05). No statistically significant difference was found in histopathologic scorings between Group 1 and Group 2 (p>0.05). A significant improvement was observed in Group 4 compared to Group 1 (p<0.05). Group 3 showed a significant histologic improvement compared to Group 4 (p<0.05). Evaluation of survival: Survival times were found as 3.4±1.3 days, 76.4±14.9days and 76.4±14.9 days in the Groups 2, 3 and 4; respectively. Survival was significantly longer in Group 3 than in Groups 2 and 4 (p<0.05). Survival was significantly longer in Group 4 compared to Group 2 (p<0.05). CONCLUSION: In this study, demonstrated that radiotherapy plus ozone application both provided histopathological improvement and prolonged survival in advanced tongue cancer rat model.

Grape seed proanthocyanidins inhibit the proliferation, migration and invasion of tongue squamous cell carcinoma cells through suppressing the protein kinase B/nuclear factor-κB signaling pathway.

Tongue squamous cell carcinoma (TSCC) is the most common oral squamous cell carcinoma. Despite significant advances in combined therapies, the 5-year survival rate of patients with TSCC has not notably improved; this is due to regional recurrences and lymph node metastasis. Grape seed proanthocyanidins (GSPs) are consumed as dietary supplements worldwide and possess anticancer activity against several different types of cancer. However, their effect on TSCC and the underlying mechanisms by which they function remain unclear. In the present study, it was identified that GSPs significantly inhibited the viability and induced the apoptosis of Tca8113 cells in a dose-dependent manner. This was associated with a significantly increased expression of the pro-apoptosis regulator BAX protein and a significantly decreased expression of the anti-apoptosis regulator Bcl-2 protein at 100 µg/ml GSPs. In addition, at non-toxic concentrations GSPs significantly inhibited the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9 from Tca8113 cells, as well as their migration and invasion. Furthermore, it was demonstrated that GSPs significantly inhibited the phosphorylation of protein kinase B (Akt) and IκB kinase, as well as the translocation of nuclear factor-κB (NF-κB) into the nucleus of Tca8113 cells. Taken together, these results suggest that GSPs inhibit the proliferation, migration and invasion of Tca8113 cells through suppression of the Akt/NF-κB signaling pathway. This indicates that GSPs may be developed as a novel potential chemopreventive agent against TSCC.

High-dose ascorbic acid induces carcinostatic effects through hydrogen peroxide and superoxide anion radical generation-induced cell death and growth arrest in human tongue carcinoma cells.

High-dose ascorbic acid (AsA) treatment, known as pharmacological AsA, has been shown to exert carcinostatic effects in many types of cancer cells and in vivo tumour models. Although pharmacological AsA has potential as a complementary and alternative medicine for anticancer treatment, its effects on human tongue carcinoma have not yet been elucidated. In this study, we investigated the effect of AsA treatment on human tongue carcinoma HSC-4 cells compared with non-tumourigenic tongue epithelial dysplastic oral keratinocyte (DOK) cells. Our results show that treatment with 1 and 3 mM of AsA for 60 min preferentially inhibits the growth of human tongue carcinoma HSC-4 over DOK cells. Furthermore, AsA-induced effects were accompanied by increased intracellular oxidative stress and were repressed by treatment with a hydrogen peroxide (H2O2) scavenger catalase and a superoxide anion radical (O2-) scavenger, tempol. Time-lapse observation and thymidine analog EdU incorporation revealed that AsA treatment induces not only cell death but also suppression of DNA synthesis and cell growth. Moreover, the growth arrest was accompanied by abnormal cellular morphologies whereby cells extended dendrite-like pseudopodia. Taken together, our results demonstrate that AsA treatment can induce carcinostatic effects through induction of cell death, growth arrest, and morphological changes mediated by H2O2 and O2- generation. These findings suggest that high-dose AsA treatment represents an effective treatment for tongue cancer as well as for other types of cancer cells.

Near-Infrared Fluorescent Ag2 Se-Cetuximab Nanoprobes for Targeted Imaging and Therapy of Cancer.

Theranostic nanoprobes integrated with diagnostic imaging and therapy capabilities have shown great potential for highly effective tumor therapy by realizing imaging-guided drug delivery and tumor treatment. Developing novel high-performance nanoprobes is an important basis for tumor theranostic application. Here, near-infrared (NIR) fluorescent and low-biotoxicity Ag2 Se quantum dots (QDs) have been coupled with cetuximab, a clinical antiepidermal growth factor receptor antibody drug for tumor therapy, via a facile bioconjugation strategy to prepare multifunctional Ag2 Se-cetuximab nanoprobes. Compared with the Ag2 Se QDs alone, the Ag2 Se-cetuximab nanoprobes display faster and more enrichment at the site of orthotopic tongue cancer, and thus present better NIR fluorescence contrast between the tumor and the surrounding regions. At 24 h postinjection, the NIR fluorescence of Ag2 Se-cetuximab nanoprobes at the tumor site is still easily detectable, whereas no fluorescence is observed for the Ag2 Se QDs. Moreover, the Ag2 Se-cetuximab nanoprobes have also significantly inhibited the tumor growth and improved the survival rate of orthotopic tongue cancer-bearing nude mice from 0% to 57.1%. Taken together, the constructed multifunctional Ag2 Se-cetuximab nanoprobes have achieved combined targeted imaging and therapy of orthotopic tongue cancer, which may greatly contribute to the development of nanotheranostics.

Radiosensitization of oral tongue squamous cell carcinoma by nanosecond pulsed electric fields (nsPEFs).

Nanosecond pulsed electric fields (nsPEFs) are a non-thermal and non-toxic technology that induce a myriad of biological effects. They have been proven to be effective in tumor shrinkage, but few studies focus on its radiosensitization in oral tongue squamous cell carcinoma. The purpose of this research was to study the radiosensitization effect of nsPEFs on a human oral tongue cancer cell line Tca8113 and to investigate the potential antitumor mechanism. A Tca8113 cell line was tested respectively by MTT assay, clonogenic assay, flow cytometry assay, annexin V-FITC/PI assay, mitochondrial potential assay and total nitric oxide assay. Our results showed that nsPEFs had a time and field strength dependent inhibition effect on Tca8113 cells. The sensitization enhancement ratio (SER) of nsPEFs was 1.453±0.038. Furthermore, radiation induced G2/M arrest was augmented by treatment with nsPEFs. We observed many more Tca8113 cells showing early apoptosis after nsPEFs combined with radiotherapy. Additionally, the NO concentration was significantly increased after nsPEFs treatment. These findings indicate that combination of nsPEFs with radiotherapy can enhance the radiosensitivity of Tca8113 cells and nsPEFs could be a potential radiosensitizer for oral tongue squamous cell carcinoma.