OBJECTIVE: To evaluate the inhibitory effect of cordycepin on oral cancer xenograft in nude mice and explore the underlying mechanisms. METHODS: Sixteen BALB/c mice bearing subcutaneous human tongue squamous cell carcinoma (TSCC) TCA-8113 cell xenografts were randomized into model group and cordycepin treatment group for daily treatment with saline and cordycepin for 4 weeks. After the treatment, the tumor xenografts were dissected and weighed to assess the tumor inhibition rate. Histological changes in the heart, spleen, liver, kidney, and lung of the mice were evaluated with HE staining, and tumor cell apoptosis was examined using TUNEL staining; The expressions of Bax, Bcl-2, GRP78, CHOP, and caspase-12 in the xenografts were detected using RT-qPCR and Western blotting. RESULTS: Cordycepin treatment resulted in a tumor inhibition rate of 56.09% in the nude mouse models, induced obvious changes in tumor cell morphology and significantly enhanced apoptotic death of the tumor cells without causing pathological changes in the vital organs. Cordycepin treatment also significantly reduced Bcl-2 expression (P < 0.05) and increased Bax, GRP78, CHOP, and caspase-12 expressions at both the RNA and protein levels in the tumor tissues. CONCLUSION Cordycepin treatment can induce apoptotic death of TCA-8113 cell xenografts in nude mice via the endogenous mitochondrial pathway and endoplasmic reticulum stress pathways.
Humans ; Animals ; Mice ; Carcinoma, Squamous Cell/drug therapy* ; Heterografts ; Mice, Nude ; Tongue Neoplasms/drug therapy* ; Cordyceps ; Caspase 12 ; Endoplasmic Reticulum Chaperone BiP ; bcl-2-Associated X Protein ; Tongue

PURPOSE: There is sparse literature on treatment outcomes research on resectable oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to measure the treatment outcomes, explore the failure patterns, and identify the potential clinicopathological prognostic factors affecting treatment outcomes for resectable OTSCC. MATERIALS AND METHODS: It is a retrospective analysis of 202 patients with resectable OTSCC who underwent upfront primary surgical resection followed by adjuvant radiotherapy with or without concurrent chemotherapy if indicated. RESULTS: The median follow-up was 35.2 months (range, 1.2 to 99.9 months). The median duration of locoregional control (LRC) was 84.9 months (95% confidence interval, 67.3–102.4). The 3- and 5-year LRC rate was 68.5% and 58.3%, respectively. Multivariate analysis showed that increasing pT stage, increasing pN stage, and the presence of extracapsular extension (ECE) were significantly associated with poorer LRC. The median duration of overall survival (OS) was not reached at the time of analysis. The 3- and 5-year OS rate was 70.5% and 66.6%, respectively. Multivariate analysis showed that increasing pT stage and the presence of ECE were significantly associated with a poorer OS. CONCLUSION: Locoregional failure remains the main cause of treatment failure in resectable OTSCC. There is scope to further improve prognosis considering modest LRC and OS. Pathological T-stage, N-stage, and ECE are strong prognostic factors. Further research is required to confirm whether adjuvant therapy adds to treatment outcomes in cases with lymphovascular invasion, perineural invasion, and depth of invasion, and help clinicians tailoring adjuvant therapy.
Carcinoma, Squamous Cell ; Drug Therapy ; Epithelial Cells ; Follow-Up Studies ; Humans ; Mouth Neoplasms ; Multivariate Analysis ; Outcome Assessment (Health Care) ; Prognosis ; Radiotherapy ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Tongue ; Treatment Failure ; Treatment Outcome

PURPOSE: The purpose of this study was to compare the clinical and functional outcomes in patients with primary base of tongue (BOT) cancer who received definitive radiotherapy (RT) or surgery followed by radiotherapy (SRT). MATERIALS AND METHODS: Between January 2002 and December 2016, 102 patients with stage I-IVB primary BOT cancer underwent either definitive RT (n=46) or SRT (n=56), and treatment outcomes were compared between two groups. The expression of p16 was also analyzed. RESULTS: The RT group had more patients with advanced T stage (T3-4) disease (58.7% vs. 35.7%, p=0.021) and who received chemotherapy (91.3% vs. 37.5%, p < 0.001) than the SRT group. At a median follow up of 36.9 months (range, 3.3 to 181.5 months), the 5-year overall survival (OS) and disease-free survival (DFS) were 75.5% and 68.7%, respectively. With respect to treatment group, the 5-year OS and DFS in the RT and SRT groups did not differ significantly (OS, 68.7% vs. 80.5%, p=0.601; DFS, 63.1% vs. 73.1%, p=0.653). In multivariate analysis, OS differed significantly according to p16 expression (p16-negative vs. p16-positive; hazard ratio [HR], 0.145; 95% confidence interval [CI], 0.025 to 0.853; p=0.033). Regarding DFS, p16 expression (p16-negative vs. p16-positive; HR, 0.164; 95% CI, 0.045 to 0.598; p=0.006) showed a significant effect in multivariate analysis. Functional defects (late grade ≥ 3 dysphagia or voice alteration) were more frequently reported in the SRT than in the RT group (16.1% vs. 2.2%, p=0.021). CONCLUSION: Despite advanced disease, patients in the RT group showed comparable survival outcomes and better functional preservation than those in the SRT group.
Chemoradiotherapy* ; Deglutition Disorders ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Organ Preservation ; Radiotherapy ; Radiotherapy, Adjuvant* ; Tongue Neoplasms* ; Tongue* ; Treatment Outcome ; Voice

OBJECTIVETo explore the effect of MSH3 knock-down on sensitivity of tongue cancer cells to cisplatin.

METHODSThree small interfering RNA (siRNA) fragments targeting MSH3 CDS region were synthesized and transfected into CAL27 cells via Lipofectamine. Real-time PCR and Western blotting were used to assess the efficiency of MSH3 silencing. MTS, apoptosis staining and cell immunofluorescence assay were used to examine the cisplatin sensitivity, apoptosis and DNA repair of transfected CAL27 cells.

RESULTSs One of the 3 siRNAs was found to significantly reduce the expression of MSH3 protein in CAL27 cells (P<0.05). MTS assay showed that MSH3 silencing resulted in an significant reduction of IC50 of cisplatin from 21.32 to 13.95 µmol/L (P<0.05) and increased the apoptotic index of the exposed cells from 4.23∓1.27 to 11.32∓1.82 (P<0.05). Immunofluorescence assay demonstrated that silencing MSH3 markedly reduced the number of γ-H2AX foci.

CONCLUSIONSilencing MSH3 can significantly increase cisplatin sensitivity of tongue cancer cells, the mechanism of which involves mainly attenuation of repair of DNA double-strand damage in the cells.

Apoptosis ; Cell Line, Tumor ; Cisplatin ; pharmacology ; DNA-Binding Proteins ; genetics ; metabolism ; Gene Silencing ; Humans ; MutS Homolog 3 Protein ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Tongue Neoplasms ; drug therapy ; genetics ; Transfection

Metastases to skeletal muscle and paraneoplastic syndromes involving beta-human chorionic gonadotropin (HCG) production are an extremely rare manifestation of head and neck squamous cell carcinoma. We report a patient with a beta-HCG-secreting squamous cell carcinoma of the tongue with diffuse metastases involving skeletal muscle. A 47 year old female, who was being treated heavily with palliative chemotherapy for metastatic tongue cancer, was admitted with a palpable thigh mass and pain. A magnetic resonance image showed an intramuscular metastasis in the thigh. Ultrasound-guided biopsy of the thigh mass confirmed metastatic squamous cell carcinoma. She was scheduled for enrollment into a clinical trial; however, a positive serum beta-HCG test was noticed. There was no evidence of pregnancy or a trophoblastic or non-trophoblastic tumor secreting beta-HCG. Finally, she was revealed to have a paraneoplastic syndrome with diffuse metastases and was ultimately referred for palliative care. We review the literature of previously reported cases of an increase of beta-HCG in patients with head and neck cancer.
Biopsy ; Carcinoma, Squamous Cell ; Chorionic Gonadotropin ; Chorionic Gonadotropin, beta Subunit, Human ; Drug Therapy ; Female ; Head ; Head and Neck Neoplasms ; Humans ; Muscle, Skeletal* ; Neck ; Neoplasm Metastasis* ; Palliative Care ; Paraneoplastic Syndromes ; Pregnancy ; Thigh ; Tongue Neoplasms* ; Tongue* ; Trophoblasts

OBJECTIVE: To identify risk factors for dysphagia in tongue cancer patients. Dysphagia is a common complication of surgery, radiotherapy, and chemotherapy in tongue cancer patients. Previous studies have attempted to identify risk factors for dysphagia in patients with head and neck cancer, but no studies have focused specifically on tongue cancer patients. METHODS: This study was conducted on 133 patients who were diagnosed with tongue cancer and who underwent a videofluoroscopy swallowing study (VFSS) between January 2007 and June 2012 at the Asan Medical Center. Data collected from the VFSS were analyzed retrospectively. Patients with aspiration were identified. RESULTS: Patients showed a higher incidence of inadequate tongue control, inadequate chewing, delayed oral transit time, aspiration or penetration, vallecular pouch and pyriform residue, and inadequate laryngeal elevation after surgery. Moreover, male gender, extensive tumor resection, a higher node stage, and more extensive lymph node dissection were major risk factors for aspiration in tongue cancer patients. CONCLUSION: Tongue cancer patients have difficulties in the pharyngeal phase as well as the oral phase of swallowing. These difficulties can worsen after tongue cancer surgery. Gender, the extent of tumor resection, and lymph node metastasis affect swallowing in tongue cancer patients. Physicians should take these risk factors into account when administering swallowing therapy to tongue cancer patients.
Chungcheongnam-do ; Deglutition ; Deglutition Disorders* ; Drug Therapy ; Head and Neck Neoplasms ; Humans ; Incidence ; Lymph Node Excision ; Lymph Nodes ; Male ; Mastication ; Neoplasm Metastasis ; Radiotherapy ; Retrospective Studies ; Risk Factors ; Tongue ; Tongue Neoplasms*

OBJECTIVETo establish the diagnosis evidence of objective tongue inspection for liver cancer (LC) patients with damp-heat syndrome (DHS) by dynamically observing their tongue figures using modern tongue image analytic apparatus, and to explore the effect of intervention on the tongue figures.

METHODSTongue figures were collected from 142 LC patients with DHS by tongue image analytic apparatus. Red (R), green (G) and blue (B) values were analyzed. The r and g values were calculated requesting r=R/(R+G+B), g=G/(R+G+B), and b=1-r-g, and scored in combination with Chinese medical symptoms scale. The tongue figure and correlated scores were collected from 59 of them 3 days after transcatheter arterial chemoembolization intervention.

RESULTSThe range of objective tongue inspection of LC patients with DHS was as follows: as for tongue fur, 0.360tongue proper, 0.404tongue figures and the average scores of quality of life, DHS, poor appetite, aggravated pain, decreased sleep quality and aggravated fever were obviously changed in the 59 LC patients with DHS after intervention, showing statistical difference when compared with before intervention (P<0.05 or P<0.01).

CONCLUSIONThe range of objective tongue inspection of LC patients with DHS could be known by collecting and analyzing objective indicator of tongue figures, thus laying foundation for further studies with analysis of correlation between intervention and Chinese medicine based on tongue figures.

Hot Temperature ; Humans ; Image Processing, Computer-Assisted ; Liver Neoplasms ; diagnosis ; drug therapy ; Middle Aged ; Observation ; Syndrome ; Tongue ; pathology

OBJECTIVETo investigate the effects of survivin short hairpin RNA (shRNA) on survivin expression, cell apoptosis, and chemosensitivity of human tongue cancer cell Tca8113 to cisplatin.

METHODSSurvivin-directed shRNA plasmid vector was delivered into Tca8113 cells with lipofectamine(TM) 2000 reagent. Survivin expression was detected with the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Flow cytometry was used to examine cell apoptosis, and the sensitivity to anticancer agents was evaluated by methyl thiazolyl tetrazolium (MTT) assay.

RESULTSAfter survivin shRNA vector transfection in Tca8113 cells, the expression of mRNA/protein declined significantly, and the apoptotic rate increased in time-dependent manner up to 37.9% at 48 hours. RNAi-mediated survivin reduction selectively inhibited growth and enhanced chemosensitivity of cisplatin but not of 5-fluorouracil.

CONCLUSIONSSurvivin shRNA could inhibit the expression of survivin mRNA and it's protein and enhance the chemosensitivity of cisplatin.

Apoptosis ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; pathology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Genetic Vectors ; Humans ; Liposomes ; Microtubule-Associated Proteins ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; Tongue Neoplasms ; drug therapy ; genetics ; pathology ; Transfection

OBJECTIVETo evaluate the effect of induction chemotherapy on the patients with moderate tongue squamous cell carcinoma and to investigate the factors that influence prognosis of these patients.

METHODSOne hundred and twenty two patients with moderate tongue squamous cell carcinoma (stage II-III, T2-3 N0/T1-3N1), treated from Jan. 1990 to Dec. 1999 were retrospectively reviewed. Among them, 69 and 53 patients were received operation alone and operation after induction chemotherapy respectively [cisplatin + 5-fluorouracil + bleomycin-A5 (PBF), 17 cases; bleomycin-A5, 36 cases]. Survival rate was estimated by Kaplan-Meier method. Multivariate analysis by the Cox proportional hazard model.

RESULTSThe mean follow-time of all patients were (79.9 +/- 49.8) (x +/- s) months (range: 7 to 177 months), and 45 patients died (including 5 lost to follow up) , 66 of 77 patients alive followed more than 5 years. The overall 3-year and 5-year survival rate were 79.4% and 69. 0% respectively. The overall 3-year and 5-year free-disease survival rate were 71.7% and 66. 3% respectively. The survival rate of 3-year and 5-year was 82.5% and 73.1% respectively for the group of operation alone; 82.4% and 70.1% respectively for the group of operation after induction chemotherapy with PBF, 72.2% and 61.1% respectively for the group of operation after induction chemotherapy with bleomycin-A5; and there were no significant difference between the above three groups (chi2 = 0.42, P = 0.8106). The locoregional recurrence rate were 30.4%, 41.2% and 38.9% for the operation alone group, operation after PBF induction chemotherapy group and operation after bleomycin-A5 induction chemotherapy group respectively. No significant benefit on decreasing locoregional recurrence (chi2 = 1.148, P = 0.563) or distant metastasis rate (chi2 = 2.305, P = 0.316) were found by induction chemotherapy by univariate analysis. Using multivariate analysis, risk factor that independently influence survival was the recurrence.

CONCLUSIONSRisk factors that independently influence survival of moderate tongue squamous cell carcinoma was the locoregional recurrence. No significant benefit on improving survival rate or decreasing locoregional recurrence or metastasis rate were found by induction chemotherapy, there was no difference between the two induction chemotherapy schemes on the survival rate or locoregional recurrence or metastasis rate of these patients.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; drug therapy ; mortality ; pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate ; Tongue Neoplasms ; drug therapy ; mortality ; pathology ; Young Adult

OBJECTIVEMicrocapsule chemoembolism is a promising treatment of tumors. We describe a deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum.

METHODSLingual artery cast specimens from cadavers were microscopically examined, and 78 patients with tongue cancer were recruited and treated with the deep lingual arterial embolization therapy.

RESULTSMicrocapsule embolism occurred approximately at the fifth or sixth level of the deep lingual artery branches. The five-year survival rate was 88.5% (69 out of 78), and the ten-year survival rate 52.6% (41 out of 78).

CONCLUSIONThe deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum is an effective therapy to treat carcinoma in mid-margin or mid-body of the tongue.

Antineoplastic Agents ; administration & dosage ; Capsules ; Carboplatin ; administration & dosage ; Chemoembolization, Therapeutic ; methods ; Drug Carriers ; administration & dosage ; Humans ; Injections, Intra-Arterial ; Tongue ; drug effects ; Tongue Neoplasms ; therapy