Immunohistochemical expression of matrix metalloproteinase-9 and 13 in oral squamous cell carcinoma and their role in predicting lymph node metastasis

BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remo-deling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.The authors wish to thank Jadhav KB for his valuable opinion during the preparation of the manuscript.

Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma

AIM： To investigate the role of cytochrome P450 （CYP） in the carcinogenesis of squamous-cell carcinoma （SCC） in human esophagus by determining expression patterns and protein levels of representative CYPs in esophageal tissue of patients with SCC and controls. METHODS： mRNA expression of CYP2E1, CYP2C, CYP3A4, and CYP3A5 was determined using RT-PCR in both normal and malignant esophageal tissues of patients with untreated esophageal SCC （/7 = 21） and in controls （n = 10）. Protein levels of CYP2E1, CYP2CS, CYP3A4, and CYP3A5 were measured by Western blot. RESULTS： Within the group of SCC patients, mRNA expression of CYP 3A4 and CYP2C was significantly lower in malignant tissue （-39% and -74%, respectively, P 〈 0.05） than in normal tissue. Similar results were found in CYP3A4 protein levels. Between groups, CYP3A4, CYP3A5, and CYP2C8 protein concentration was significantly higher in non-malignant tissue of SCC patients （4.8-, 2.9-, and 1.9-fold elevation, P 〈 0.05） than in controls. In contrast, CYP2E1 protein levels were significantly higher in controls than in SCC patients （＋46%, P 〈 0.05）. CONCLUSION： Significant differences exist in protein levels of certain CYPs in non-malignant esophageal tissue （e.g. CYP2CB, CYP3A4, CYP3A5, and CYP2E1） between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Argon plasma coagulation for superficial esophageal squamous-cell carcinoma in high-risk patients

AIM: To evaluate the usefulness and safety of argon plasma coagulation (APC) for superficial esophageal squamous-cell carcinoma (SESC) in high-risk patients. METHODS: We studied 17 patients (15 men and 2 women, 21 lesions) with SESC in whom endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and open surgery were contraindicated from March 1999 through February 2009. None of the patients could tolerate prolonged EMR/ESD or open surgery because of severe concomitant disease (e.g., liver cirrhosis, cerebral infarction, or ischemic heart disease) or scar formation after EMR/ESD and chemoradiotherapy. After conventional endoscopy, an iodine stain was sprayed on the esophageal mucosa to determine the lesion margins. The lesion was then ablated by APC. We retrospectively studied the treatment time, number of APC sessions per site, complications, presence or absence of recurrence, and time to recurrence.RESULTS: The median duration of follow-up was 36 mo (range: 6-120 mo). All of the tumors were macroscopically classified as superficial and slightly depressed type (0-Ⅱc). The preoperative depth of invasion was clinical T1a (mucosal cancer) for 19 lesions and clinical T1b (submucosal cancer) for 2. The median treatment time was 15 min (range: 10-36 min). The median number of treatment sessions per site was 2 (range: 1-4). The median hospital stay was 14 d (range: 5-68 d). Among the 17 patients (21 lesions), 2 (9.5%) had recurrence and underwent additional APC with no subsequent evidence of recurrence. There were no treatment-related complications, such as bleeding or perforation. CONCLUSION: APC is considered to be safe and effective for the management of SESC that cannot be resected endoscopically because of underlying disease, as well as for the control of recurrence after EMR and local recurrence after chemoradiotherapy.

Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

TCGA-based analysis of oncogenic signaling pathways underlying oral squamous cell carcinoma

Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.

Galectin 2 regulates JAK/STAT3 signaling activity to modulate oral squamous cell carcinoma proliferation and migration in vitro

Background:Galectin 2(LGALS2)is a protein previously reported to serve as a mediator of disease progression in a range of cancers.The function of LGALS2 in oral squamous cell carcinoma(OSCC),however,has yet to be explored,prompting the present study to address this literature gap.Methods:Overall,144 paired malignant tumor tissues and paracancerous OSCC patient samples were harvested and the LGALS2 expression levels were examined through qPCR and western immunoblotting.The LGALS2 coding sequence was introduced into the pcDNA3.0 vector,to enable the overexpression of this gene,while an LGALS2-specific shRNA and corresponding controls were also obtained.The functionality of LGALS2 as a regulator of the ability of OSCC cells to grow and undergo apoptotic death in vitro was assessed through EdU uptake and CCK-8 assays,and flow cytometer,whereas a Transwell system was used to assess migratory activity and invasivity.An agonist of the Janus Kinase 2(JAK2)/Signal Transducer and Activator of Transcription 3(STAT3)pathway was also used to assess the role of this pathway in the context of LGALS2 signaling.Results:Here,we found that lower LGALS2 protein and mRNA expression were evident in OSCC tumor tissue samples,and these expression levels were associated with clinicopathological characteristics and patient survival outcomes.Silencing LGALS2 enhanced proliferation in OSCC cells while rendering these cells better able to resist apoptosis.The opposite was instead observed after LGALS2 was overexpressed.Mechanistically,the ability of LGALS2 to suppress the progression of OSCC was related to its ability to activate the JAK/STAT3 signaling axis.Conclusion:Those results suggest a role for LGALS2 as a suppressor of OSCC progression through its ability to modulate JAK/STAT3 signaling,supporting the potential utility of LGALS2 as a target for efforts aimed at treating OSCC patients.

Diagnostic Role of Computerised Tomography in Mandibular Invasion among Patients with Oral Squamous Cell Carcinoma

Background: Oral cavity malignancy can result from surface epithelium, salivary glands, or submucosal soft tissue. Common symptoms may include non-healing ulcers, slurred speech, dysphagia, neck mass and pain which may indicate cortical invasion. Morbidity and quality of life have been seen to rise with mandibular excision in oral cavity squamous cell carcinoma. Therefore, in order to design the surgery appropriately, it is vital to be aware of the mandibular invasion prior to the procedure. Various researches have been focused on the accuracy of clinical examination and imaging technique in predicting tumour invasion of the mandible in oral malignancy. The goal of this study was to find a correlation between histological assessment, clinical examination, and computed tomography results in patients with mandibular involvement and oral cavity squamous cell carcinoma. Objectives: To determine the sensitivity, specificity, NPV and PPV of CECT and clinical diagnosis in patients with oral squamous cell carcinoma with mandibular invasion. Methods: A cross-sectional observational study was set out to review preoperative clinical and radiological assessment;and post operative histopathological finding of mandibular resection specimen in clinically evaluated and diagnosed cases of oral cavity squamous cell carcinoma (SCC) with mandibular invasion. Results: 43 individuals of oral cavity SCC with mandibular involvement were examined. 12 out of 28 mandibular resections had bone invasion, with numerous tumour entry sites being the most frequent mechanism of invasion, according to post-operative HPE. The positive predictive value (PPV) of contrast enhanced computerised tomography (CECT) scans was 42.8%, as 28 individuals had invasions revealed;sensitivity is almost 100%;specificity is 48.3. Conclusion: Prioritizing the identification of mandibular invasion is essential to enhance the prognosis of patients with oral SCC. There is an urgent necessity to review the usefulness of radiology in the treatment of mandibulectomy. Combination of clinical and radiological examination increases sensitivity and specificity.

COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma

Objective: To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer. Methods: The immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC. Results: The expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) ( P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) ( P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM ( P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP ( P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM ( P<0.01). The COX-2 expression was associated with clinical stage ( P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis ( P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC. Conclusions: The abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.

Honokiol:a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells

Honokiol （HNK） is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma （OSCC） cells is unknown. We investigated the antitumor activities of HNK on OSCC ceils in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-（4,5-dimethyl thiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and propidium iodide （PI） assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling （TUNEL）, and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 μg.mL-1 or 20 μg.mL-1 of HNK were more stronger compared with those of 20 μg-mL-1 5-fluorouracil （5-Fu, the control） applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.

A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma

Oral squamous cell carcinoma （OSCC） has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases （CLNM） in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy （aRT） and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.

In vitro effect of iASPP on cell growth of oral tongue squamous cell carcinoma

iASPP is an inhibitory member of the apoptosis-stimulating proteins of P53 （ASPP） family. iASPP is over expressed in several malignant tumors and potentially affects cancer progression. However, the expression and potential role of iASPP in oral tongue squamous cell carcinoma （OTSCC） have not been addressed. In our study, we detected iASPP expression in OTSCC by immunohistochemistry, iASPP expression is up-regulated in OTSCC tissues. Moreover, in clinical pathology specimens, we found that increased iASPP expression correlates with poor differentiation and lymph node metastasis. Using multicellular tumor spheroids （MTS） and flow cytometry, we demonstrated that iASPP down-regulation arrests OTSCC cells at the G0/G1 phase, induces OTSCC cell apoptosis and inhibits OTSCC cell proliferation. These results indicate that iASPP plays a significant role in the progression of OTSCC and may serve as a biomarker or therapeutic target for OTSCC patients.

Anti-Cancer Effects of Cordycepin on Oral Squamous Cell Carcinoma Proliferation and Apoptosis in Vitro

Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of human solid tumors. We sought to determine the effects of Cordycepin on oral squamous cell carcinoma in vitro and in vivo. Two oral squamous cell carcinoma cell lines, KB and HSC3, were used in this study. Cells were treated with Cordycepin or diluent, followed by determinations of proliferation by sulforhodamine method and apoptosis by TUNEL assay in vitro. For in vivo experiments, tumor cells were transplanted into nude mice, followed by treatment with Cordycepin or control diluent. In addition, cells were examined for expression of adenosine receptor isotypes, and tested whether cordycepin-induced effects were mediated through adenosine receptors by combinatorial treatment of cordycepin and antagonists specific to each isotype of adenosine receptors. Two cell lines expressed protein of all types of adenosine receptors stronger than normal oral keratinocytes. Cordycepin showed anti-proliferating effect and apoptotic effect on both cell lines in vitro in a dose dependent manner. However, any adenosine receptors did not reverse the effect of cordycepin. In our in vivo experiments, cordycepin failed to decrease the tumor volume significantly, and failed to induce more apoptosis of tumor cells. Cordycepin has anti-proliferating effect and induces apoptosis not mediated by adenosine receptor on oral squamous cell carcinoma cells in vitro. However, in vivo results suggest that cordycepin in itself has a limited value as a novel chemotherapeutic agent for oral squamous cell carcinoma.

Diagnostic delay in oral squamous cell carcinoma: the role of cognitive and psychological variables

This retrospective study investigated, in two cohorts of subjects living in Southern Italy and awaiting treatment for oral squamous cell carcinoma （OSCC）, the variables related to diagnostic delay ascribable to the patient, with particular reference to the cognitive and psychological ones. A total of 156 patients with OSCC （mean age： 62 years, M/F： 2.39 ： 1） were recruited at the Universities of Palermo and Naples. Risk factors related to patient delay included： sociodemographic, health-related, cognitive and psychological variables. The analysis was conducted by considering two different delay ranges： dichotomous （≤1 month vs. 〉 1 month） and polytomous （〈1 month, 1-3 months, 〉3 months） delay. Data were investigated by univariate and multivariate analyses and a Pvalue≤0.05 was considered statistically significant. For both delay measurements, the most relevant variables were： ＇Personal experience of cancer＇ （dichotomous delay： P=0.05, odds ratio （0R）=0.33, 95% confidence interval （CI）=0. 11-0.99; polytomous delay： P=0.006, Chi-square= 10.224） and ＇Unawareness＇ （dichotomous delay： P〈0.01, 0R=4.96, 95% CI--2.16-11.37; polytomous delay： P=0.087, Chi-square=4.77）. Also ＇Denial＇ （P〈0.01, 0R=6.84, 95% CI=2.31-20.24） and ＇Knowledge of cancer＇ （P=0.079, Chi-square=8.359） were found to be statistically significant both for dichotomous and for polytomous categorization of delay, respectively. The findings of this study indicated that, in the investigated cohorts, the knowledge about cancer issues is strongly linked to the patient delay. Educational interventions on the Mediterranean population are necessary in order to increase the patient awareness and to emphasize his/her key role in early diagnosis of OSCC.

Differential mRNA expression profiling of oral squamous cell carcinoma by high-throughput RNA sequencing

Differentially expressed genes are thought to regulate the development and progression of oral squamous cell carcinomas （OSCC）. The purpose of this study was to screen differentially expressed mRNAs in OSCC and matched paraneoplastic normal tissues, and to explore the intrinsic mechanism of OSCC development and progres- sion. We obtained the differentially expressed mRNA expression profiles in 10 pairs of fresh-frozen OSCC tissue specimens and matched paraneoplastic normal tissue specimens by high-throughput RNA sequencing. By using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses, the functional significance of the differentially expressed genes were analyzed. We identified 1,120 sig- nificantly up-regulated mRNAs and 178 significantly down-regulated mRNAs in OSCC, compared to normal tissue. The differentially expressed mRNAs were involved in 20 biological processes and 68 signal pathways. Compared to adjacent normal tissue, the expression of MAGEAll was up-regulated; TCHH was down-regulated. These find- ings were verified by real-time PCR. These differentially expressed mRNAs may function as oncogenes or tumor suppressors in the development and progression of OSCC. This study provides novel insights into OSCC. However, further work is needed to determine if these differentially expressed mRNAs have potential roles as diagnostic bio- markers and candidate therapeutic targets for OSCC.

Oral Squamous Cell Carcinoma: Epidemiology, Clinical Presentation and Treatment

Squamous cell carcinoma accounts for 90% of all oral cancers. It may affect any anatomical site in the mouth, but most commonly the tongue and the floor of the mouth. It usually arises from a pre-existing potentially malignant lesion, and occasionally de novo;but in either case from within a field of precancerized epithelium. The use of tobacco and betel quid, heavy drinking of alcoholic beverages and a diet low in fresh fruits and vegetables are well known risk factors for oral squamous cell carcinoma. Important risk factors related to the carcinoma itself that are associated with a poor prognosis include large size of the tumour at the time of diagnosis, the presence of metastases in regional lymphnodes, and a deep invasive front of the tumour. Squamous cell carcinoma is managed by surgery, radiation, and chemotherapy singularly or in combination;but regardless of the treatment modality, the five-year survival rate is poor at about 50%. This can be attributed to the fact that about two-thirds of persons with oral squamous cell carcinoma already have a large lesion at the time of diagnosis.

Lactate Promotes Cancer Stem-like Property of Oral Sequamous Cell Carcinoma

Accumulation of lactate in tumor has been linked to poor prognosis of oral squamous cell carcinoma (OSCC), but the underlying mechanism remained largely uncertain. Previous studies have suggested that presence of cancer stem cells (CSCs) closely correlated with cellular malignancy of OSCC. Here, using 3D organoid culture model, we investigated whether lactate promoted CSCs phenotype in primary OSCC cells. We generated organoids using fresh OSCC specimens and verified that organoids recapitulated histopathology and cellular heterogeneity of parental tumor;Organoids were then transfected with a Wnt reporter to visualize Wnt activity. The sphere forming assay demonstrated that high Wnt activity functionally designated CSCs population in OSCC cells. Further investigations indicated that lactate treatment promoted Wnt activity and increased the expression of CSCs (i.e. CD133^+ cells) in organoids. Moreover, silencing monocarboxylate transporter 1 (MCT1), the prominent path for lactate uptake in human tumor with siRNA significantly impaired organoid forming capacity of OSCC cells. Together, our study demonstrated that lactate can promote CSCs phenotype of OSCC,and MCT1 may be a therapeutic target against OSCC growth.

Neck observation versus elective neck dissection in management of clinical T1/2N0 oral squamous cell carcinoma: a retrospective study of 232 patients

Objective: The management of early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation (OBS) and elective neck dissection (END) in treating patients with cT1/2N0 OSCC. Methods: A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test. Results: There was no significant difference in 5-year OS and DSS rates between END and OBS groups (OS: 89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group (90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group (7/51) had similar 5-year OS rate (57.1% vs. 64.1%, P=0.839) and DSS rate (71.4% vs. 74.4%, P=0.982) to those in END group (39/181). In the regional recurrence patients, the 5-year OS rate (57.1% vs. 11.1%, P=0.011) and DSS rate (71.4% vs. 22.2%, P=0.022) in OBS group (7/51) were higher than those in END group (9/181). Conclusions: The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.

Levels of biological markers of nitric oxide in serum of patients with squamous cell carcinoma of the oral cavity

The aim of the study was a determination of the levels of nitric oxide（NO）and its biological markers such as malonyldialdehyde（MDA）and nitrotyrosine in the serum of patients with squamous cell carcinoma（SCC）of the oral cavity and identification of the relationships between NO and those markers.These studies were performed on patients with SCC of the oral cavity before and after treatment.Griess reaction was used for the estimation of the total concentration of NO in serum.The nitrotyrosine level in serum was assessed with an enzyme-linked immunosorbent assay（ELISA）kit,and MDA level using a spectrophotometric assay.Higher concentrations of NO in blood serum were determined in patients with stage IV of the disease before treatment in comparison to the control group and patients with stages II and III of the disease.Moreover,higher concentrations of MDA and nitrotyrosine were determined in the serum of patients in all stages of the disease in comparison to healthy people.After treatment,lower concentrations of NO in the serum of patients with stage IV of the disease were observed in comparison to the amounts obtained prior to treatment.In addition,lower levels of nitrotyrosine in the serum of patients with all stages of the disease were recorded,whereas higher concentrations of MDA were determined in these patients in comparison to results obtained before treatment.The compounds formed with the contribution of NO,such as MDA and nitrotyrosine,may lead to cancer progression in patients with SCC of the oral cavity,and contribute to formation of resistance to therapy in these patients as well.Moreover,the lack of a relationship between concentrations of NO and MDA,and between NO and nitrotyrosine in serum suggests that the process of lipid peroxidation and nitration in patients with SCC does not just depend on NO.

Squamous cell carcinoma of the oral cavity and circulating tumour cells

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.