Tongue squamous cell carcinoma (TSCC) has been well-known for its high metastasis and poor prognosis, but the molecular mechanisms of TSCC pathogenesis and chemoresistance are still largely unknown. ...Thus, the present study aimed to identify the involvement of a classic Hippo/Yes-associated protein 1 (YAP1) pathway in regulating TSCC progression and cisplatin (DDP) resistance. DDP-resistant TSCC cell lines were established by gradual exposure to DDP. Through western blot analysis, the protein expression of Hippo/YAP1 axis in TSCC tissues and cell lines was detected separately. Then, YAP1 was inhibited or overexpressed in TSCC cells. Cell viability and drug resistance were evaluated by cell counting kit-8 method, colony formation assay and Trypan blue staining assay. Cell migration ability was measured by Transwell assay. The Hippo pathway was dysregulated, and YAP1 was upregulated and dephosphorylated in the TSCC tissues or DDP-resistant cell lines, compared with normal tissues or DDP-sensitive cells. YAP1 knockdown inhibited cell proliferation, colony formation ability and migration, whereas overexpression of YAP1 exacerbated these malignant characteristics. YAP1 knockdown increased DDP-sensitivity by reducing the RAD51-mediated DNA damage repair behavior under DDP intervention in the DDP-resistant TSCC cells. Conversely, YAP1 overexpression significantly increased DDP-resistance by enhancing the RAD51-mediated DNA damage repair behavior under DDP intervention in the DDP-sensitive TSCC cells. In a word, upregulation and dephosphorylation of YAP1 caused dysregulation of the tumor-inhibiting Hippo pathway, resulting in the aggressiveness and DDP resistance in TSCC.
Fluorescence visualization devices (FVs) are useful for detecting malignant lesions because of their simple and noninvasive application. However, their quantitative application has been challenging. ...This study aimed to quantitatively and statistically evaluate the change in fluorescence intensity (FI) during the progression from normal epithelium to squamous cell carcinoma using a reproducible animal tongue carcinogenesis model. To establish this model, rats were treated with 50 ppm 4-Nitroquinoline 1-oxide (4NQO) in their drinking water for 10, 15, and 20 weeks. After 4NQO administration, each rat tongue was evaluated by gross observation, histology, and FI measurements. Fluorescence images were captured by FV, and ImageJ was used to measure FI, which was analyzed quantitatively and statistically. The establishment of a reproducible tumor progression model was confirmed, showing precancerous lesions (low-grade dysplasia LGD), early cancers (high-grade dysplasia/carcinoma in situ HGD/CIS), and advanced cancers (Cancer). This carcinogenesis model was quantitatively evaluated by FI. The FI of LGD stage was 54.6, which was highest intensity of all groups. Subsequently, the HGD/CIS and Cancer stages showed decreased FI (HGD/CIS: 46.1, Cancer: 49.1) and manifested as dark spots. This result indicates that FI had more variation and a wider range with increasing tumor progression. We demonstrated that FI migration and an uneven distribution are consistent with tumor progression. Since each step of tumor progression occurs reproducibly in this animal model, statistical evaluation was possible. In addition, tumor progression can be monitored by this new FI analysis method in humans.
•Depth of invasion is significantly associated with nodal metastasis.•There is not a critical depth that predicts regional recurrence.•The relative hazard increases progressively at increasing depth ...of invasion.•Cumulative incidence of recurrence increases sharply after 2 mm depth of invasion.•The risk of regional metastasis increases continuously with increasing depth.
To determine if there is a critical depth of invasion that predicts micrometastasis in early oral tongue cancer.
Retrospective series identifying patients undergoing primary surgical resection of T1 or T2 oral tongue cancer who elected against neck treatment between 2000 and 2015. Cox proportional-hazard model compared the relative hazard and cumulative incidence of recurrence to depth of invasion. The model used a 2 parameter quadratic effect for depth that was chosen based on Akaike's information criterion.
Ninety-three patients were identified with T1 or T2 oral tongue squamous cell carcinoma and clinically N0 neck undergoing glossectomy without elective neck treatment. 61% were male and median age was 60 years. Median follow up was 45 months, and 76 patients had at least two years of follow up. Thirty-six of 76 patients recurred (47.4%), with 15 recurring in the oral cavity (19.7%) and 21 developing nodal metastasis (27.6%). Cox proportional-hazards quadratic polynomial showed increasing hazard of recurrence with depth of invasion and the cumulative incidence increased sharply within the range of data from 2 to 6 mm depth of invasion.
Depth of invasion is significantly associated with nodal metastasis and has been added to the 8th AJCC staging guidelines. Variable depths of invasion have been associated with regional metastasis; however, there is likely not a critical depth that predicts neck recurrence due to progressive hazards and cumulative risk of occult metastasis. The risk of regional metastasis is likely much greater than previously believed and increases progressively with increasing depth.
Abstract Aim To investigate whether the rise during the past decades in the incidence of tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and the proportion of human ...papillomavirus (HPV) positive cancer has continued in Stockholm. Patients and methods Pre-treatment biopsies ( n = 252) available from 280 patients diagnosed with TSCC and BOTSCC during 2008–2012 in the County of Stockholm were tested for HPV DNA by a multiplex bead-based assay. Incidence records were acquired from the Swedish Cancer Registry. The data obtained were evaluated together with previous figures from 1970 to 2007. Results HPV DNA was present in 186/252 (74%) of TSCC and BOTSCC biopsies obtained during 2008–2012 in Stockholm. In this region the age-standardised incidence, including the prevalence of HPV-positive and HPV-negative TSCC stabilised 2007–2012 compared to 2000–2006, while for BOTSCC throughout 1998–2012 the same parameters increased moderately ( p < 0.05, for all). In parallel, from 2000 to 2006 through 2007–2012 in Sweden, the age-standardised incidence of both TSCC and BOTSCC continued to rise ( p = 0.012 and p = 0.001 respectively). Conclusion During 2000–2012 the age-standardised incidence and the proportion of HPV-positive TSCC have stabilised at a high level, while the proportion of HPV-negative cancer has remained at a low level in Stockholm, whereas for BOTSCC all parameters are increasing moderately. In contrast, in Sweden the incidence of both TSCC and BOTSCC is still increasing. We hypothesise that the HPV epidemic could be stabilising, first for TSCC, but so far not for BOTSCC, in e.g. some urban areas, while previous trends for both tumours persist at other geographic locations.
The new AJCC staging system (8th edition) incorporates depth of invasion to stage oral cancers. It is a recognized predictor for neck nodal metastasis and local recurrence, the associated risk is not ...well defined. The aim of this study was to explore the risk of occult neck nodal metastasis and local recurrence in relation to depth in early stage squamous cell carcinoma of oral tongue.
We have evaluated records of 179 patients with early tongue cancer treated in our unit from 2006-2015 with a mean age of 57.92 ± 11.93 years. Treatment modalities used were surgery (26%), surgery followed by radiotherapy (64%) and chemo-radiation (10%). Neck dissection was ipsilateral in 94% and bilateral in 6% of the patients. Patients were grouped according to the AJCC cut off points in 8th edition for depth; group A: 1-5 mm (35%), group B: 6-10 mm (47%) and group C: > 10 mm (18%).
Risk of local recurrence and nodal metastasis for Group A was 15% (10/63) and 23% (15/63), group B 20% (17/84) and 34% (29/84), and group C 40% (13/32) and 53% (17/32).
Depth more than 10 mm is associated with significantly increased risk of recurrence and nodal metastasis. Elective neck dissection should be a consideration for tumors having depth less than 5mm.
Numerous findings have demonstrated that long noncoding RNA (lncRNA) dysregulation plays a key role in many human neoplasms, including tongue squamous cell carcinoma (TSCC), yet the potential ...mechanisms of lncRNAs in chemo-resistance remain elusive. Our research showed that the lncRNA KCNQ1OT1 was upregulated in chemo-insensitive TSCC tissues compared with chemo-sensitive TSCC specimens. Meanwhile, high KCNQ1OT1 expression was closely correlated with poor prognosis. Furthermore, KCNQ1OT1 promoted TSCC proliferation and conferred TSCC resistance to cisplatin-induced apoptosis in vitro and in vivo. Using online database analysis, we predicted that the lncRNA KCNQ1OT1 facilitates tumor growth and chemo-resistance by acting as a competing endogenous RNA (ceRNA) to modulate the expression of miR-211-5p. And miR-211-5p upregulation significantly impaired TSCC proliferation and resumed TSCC chemo-sensitivity, which is contrary to the function of lncRNA KCNQ1OT1. Luciferase experiments confirmed that miR-211-5p harbor binding sites for the 3'-UTRof Ezrin mRNA, and Ezrin/Fak/Src signaling was activated in cisplatin-resistant TSCC cells. Finally, miR-211-5p inhibition in sh-KCNQ1OT1-expressing TSCC cells rescued the suppressed cell proliferation and cisplatin resistance induced by KCNQ1OT1 knockdown. In summary, our study has elucidated the role of the oncogenic lncRNA KCNQ1OT1 in TSCC growth and chemo-resistance, which may serve as a new target for TSCC therapy.
Abstract Background This study characterized the infiltration of primary tumors along the intrinsic and extrinsic muscles of the tongue in oral tongue squamous cell carcinoma (OTSCC), to create a new ...surgical strategy that is suitable for most stages. A preliminary evaluation of this novel surgical approach was also conducted. Methods An anatomic study of macroscopic specimens from 10 human cadavers and 100 OTSCC patients was conducted. The anatomic characteristics of the primary tumors and the origin and distribution of fibers of the intrinsic and extrinsic tongue muscles were observed and measured. After initial treatment with curative intent, the 100 patients were regularly followed-up with clinical examination and imaging. Result Based on the anatomic characteristics of the primary tumors and tongue muscles, a new surgical approach was developed, and was described as muscle anatomy tongue surgery (MATS). MATS proved suitable for almost all stages of OTSCC. According to the morphology of the invasive tumor front, the 100 cases were divided into four types. The rate of 2-year local disease control was 98%, locoregional control 86%, disease-free survival 85%, and overall survival 89%. Tongue functions were perfectly recovered in more than 60% of the patients. Conclusion Application of the principles of MATS to the treatment of OTSCC proved suitable for almost all stages of the disease. MATS is a novel surgical technique that may improve outcomes in tongue cancer surgery.
Objective
To investigate the association of social determinants of health (SDoH) in squamous cell carcinoma of the tongue in the United States and to evaluate the real‐world contribution of specific ...disparities.
Study Design
Retrospective cohort study.
Setting
United States.
Methods
The Centers for Disease Control and Prevention‐Social Vulnerability Index (SVI) and National Cancer Institute‐Surveillance, Epidemiology, and End Results Program database were used to study 62,103 adult tongue squamous cell carcinoma patients from 1975 to 2017. Regression analysis assessed trends in months of follow‐up and survival across social vulnerability and 4 subcategories of social vulnerability.
Results
As overall SVI score increases (increased social vulnerability), there is a significant decrease in the average length of follow‐up (22.95% decrease from 63.99 to 49.31 months; P < .001) across patients from the lowest and highest social vulnerability groups. As overall SVI score increases, there is a significant decrease in the average months of survival (28.00% decrease from 49.20 to 35.43 months; P < .001). There is also a significantly greater odds ratio (OR = 1.05; P < .001) of advanced cancer staging upon presentation at higher SVI scores. Patients with higher SVI scores have a lower OR (0.93; P < .001) of receiving surgery as their primary treatment when compared to patients with lower SVI scores. Patients with higher SVI scores also have a significantly greater OR (OR = 1.05; P < .001) of receiving chemotherapy as their primary treatment when compared to patients with lower SVI scores.
Conclusion
Increased social vulnerability is shown to have a detrimental impact on the treatment and prognosis of patients with squamous cell carcinoma of the tongue.
Black hairy tongue (BHT) is a rare condition that is conventionally managed by discontinuing associated medications or habits and practicing good oral hygiene, including tongue brushing. Previous ...studies have indicated that black tongue coating is often associated with gastrointestinal discomfort, which traditional Chinese medicine (TCM) could be a potentially effective option for treating this condition with minimal side effects. We present a case of BHT diagnosed and treated within 2 weeks by using TCM methods.
A 73-year-old woman presented with a chief concern of a black tongue that had persisted for 2 weeks and was accompanied by thirst and diarrhea. These symptoms were initially observed during her hospitalization for the treatment of staghorn calculi, xanthogranulomatous pyelonephritis, and urosepsis. Using the "four diagnostic methods" of TCM, we observed that her tongue had a thick black coating surrounded by a thick white coating; her tongue was of medium size with tooth marks, and its body color was light red.
On the basis of TCM theory, we made a clinical diagnosis of BHT and "spleen Qi deficiency with turbid dampness," which may have been caused by the antibiotic treatment during hospitalization. Subsequently, we administered a Chinese herbal medicine (CHM) formula comprising a combination of Wu-Ling-San () and a modification of Da-Yuan-Yin (). After 2 weeks of CHM treatment, the patient's BHT was nearly eliminated, and the thick white coating and the corresponding symptoms were ameliorated. After 4 weeks of CHM treatment, the BHT was completely resolved.
We present a case of BHT, a benign condition that may be caused by antibiotics. The literature does not contain reports on TCM-based diagnosis and treatment strategies for BHT. Using the 4 diagnostic methods of TCM, we observed that BHT was associated with gastrointestinal symptoms, which is consistent with the TCM theory. Moreover, CHM treatment rapidly relieved BHT and related symptoms without adverse events.
PDF
