ResearchPad - head-and-neck-cancers https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Precision and reliability of tape measurements in the assessment of head and neck lymphedema]]> https://www.researchpad.co/article/elastic_article_15733 Tape measurement is a commonly used method in the clinical assessment of lymphedema. However, few studies have assessed the precision and reliability of tape measurement in assessing head and neck lymphedema. This study aimed to evaluate the reliability and precision of using tape measurement, performed by different evaluators, for the assessment of head and neck lymphedema.MethodsThis study was conducted at a tertiary care cancer hospital. Between January and December 2019, 50 patients with head and neck cancers and 50 normal subjects were enrolled. Each subject was examined using tape measurements for 7 point-to-point distances of facial landmarks, 3 circumferences of the neck (upper, middle, and lower), and 2 circumferences of the face (vertical and oblique) by 3 random examiners. Test precision and reliability were assessed with the within-subject standard deviation (Sw) and intra-class correlation coefficient (ICC), respectively.ResultsOverall, the standard deviation of the tape measurements varied in the range of 4.6 mm to 18.3 mm. The measurement of distance between the tragus and mouth angle (Sw: 4.6 mm) yielded the highest precision, but the reliability (ICC: 0.66) was moderate. The reliabilities of neck circumference measurements (ICC: 0.90–0.95) were good to excellent, but the precisions (Sw: 8.3–12.3 mm) were lower than those of point-to-point facial measurements (Sw: 4.6–8.8 mm).ConclusionsThe different methods of tape measurements varied in precision and reliability. Thus, clinicians should not rely on a single measurement when evaluating head and neck lymphedema. ]]> <![CDATA[Reference values of physiological 18F-FET uptake: Implications for brain tumor discrimination]]> https://www.researchpad.co/article/N80bdbd58-ef10-47b0-8bc3-8bde8c3b2b52

Purpose

The aim of this study was to derive reference values of 18F-fluoro-ethyl-L-tyrosine positron emission tomography (18F-FET-PET) uptake in normal brain and head structures to allow for differentiation from tumor tissue.

Materials and methods

We examined the datasets of 70 patients (median age 53 years, range 15–79), whose dynamic 18F-FET-PET was acquired between January 2016 and October 2017. Maximum standardized uptake value (SUVmax), target-to-background standardized uptake value ratio (TBR), and time activity curve (TAC) of the 18F-FET-PET were assessed in tumor tissue and in eight normal anatomic structures and compared using the t-test and Mann-Whitney U-test. Correlation analyses were performed using Pearson or Spearman coefficients, and comparisons between several variables with Pearson’s chi-squared tests and Kruskal-Wallis tests as well as the Benjamini-Hochberg correction.

Results

All analyzed structures showed an 18F-FET uptake higher than background (threshold: TBR > 1.5). The venous sinuses and cranial muscles exhibited a TBR of 2.03±0.46 (confidence interval (CI) 1.92–2.14), higher than the uptake of caudate nucleus, pineal gland, putamen, and thalamus (TBR 1.42±0.17, CI 1.38–1.47). SUVmax, TBR, and TAC showed no difference in the analyzed structures between subjects with high-grade gliomas and subjects with low-grade gliomas, except the SUVmax of the pineal gland (t-tests of the pineal gland: SUVmax: p = 0.022; TBR: p = 0.411). No significant differences were found for gender and age.

Conclusion

Normal brain tissue demonstrates increased 18F-FET uptake compared to background tissue. Two distinct clusters have been identified, comprising venous structures and gray matter with a reference uptake of up to SUVmax of 2.99 and 2.33, respectively.

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<![CDATA[Adequacy of surgical margins in oral cancer patients with respect to various types of reconstruction]]> https://www.researchpad.co/article/N23e64ed3-4652-44e7-9e87-be541bf33c9b

Background:

Surgical margin is an important prognostic factor for oral cancers (oral squamous cell carcinoma [OSCC]). The correlation of margin with the type of reconstruction has never been studied.

Aim:

This study aimed to correlate surgical margins with the type of reconstruction.

Methods:

This was a retrospective study of 410 treatment-naïve OSCC patients. As per the methods of reconstruction, three groups were made when reconstruction was performed using pedicled flap (PF) or local flap, free flap, and primary closure (PC).

Statistical Analysis:

Chi-square test was used for comparison of margin status as per the method of reconstruction. Mann–Whitney test was used to find the difference between the mean margin width with respect to the type of reconstruction.

Results:

The overall incidence of close/positive margins was 7.8%. The incidence of close/positive margins was not significantly different in free flap group compared to PF (P = 0.06) or PC (P = 0.835) group. However, there was a significant difference in the incidence of close/positive margins between PC and PF groups (P = 0.021). Whether the reconstruction is performed by the primary surgeon or by a another surgeon, it did not have an impact on adequacy of margins (P = 0.334). Margins were wider when the reconstruction is performed by a different team (P = 0.015) or when reconstruction is performed as compared to PC.

Conclusion:

Margins are not affected by the type of reconstruction (pedicled vs. free flap) and the team doing reconstruction (same vs. another team). Margins are significantly compromised when a surgeon performs PC himself/herself compared to PF.

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<![CDATA[Nimotuzumab with intensity-modulated radiation therapy in unresectable and platinum-ineligible locally advanced head-and-neck cancer]]> https://www.researchpad.co/article/Nef7302e5-39f1-4348-9c5c-d57bc65635ae

Background:

Outcomes with conventional treatment are poor in patients with squamous cell carcinoma of head and neck (SCCHN). Treatment options are further limited for patients ineligible to receive platinum-based chemotherapy due to various factors such as geriatric age, comorbidity, and organ dysfunctions. The present study retrospectively evaluated the effectiveness of nimotuzumab when added to radiation therapy in unresectable, locally advanced SCCHN patients who were ineligible for platinum-based chemotherapy.

Materials and Methods:

The medical records of 21 patients with unresectable, locally advanced head-and-neck cancer and histologically confirmed squamous cell carcinoma who were ineligible for platinum-based chemotherapy treated with nimotuzumab and intensity-modulated radiation therapy (IMRT) from 2012 to 2017 were retrospectively analyzed. The tumor response rate and overall survival (OS) were analyzed. Patients were assessed for toxicity and adverse events (AEs) as per CTCAE version 4. Statistical analysis was performed using SPSS software.

Results:

The median number of doses of nimotuzumab received was 6, and median dose of radiotherapy was 60 Gy. The tumor response rate was calculated at 24 weeks after the completion of radiotherapy and was as follows: 76.2% (16) of patients showed complete response, 9.5% (2) of patients showed partial response, 4.8% (1) of patients showed stable disease, and 9.5% (2) of patients showed progression of disease. Median OS was 21 months, whereas 1-year survival rate was 63.7%. No Grade 3 or Grade 4 AEs were observed.

Conclusion:

Nimotuzumab with IMRT has achieved promising clinical outcomes in unresectable locally advanced SCCHN patients who are ineligible for platinum-based chemotherapy, without accumulation of toxicity.

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<![CDATA[Demography and treatment pattern of patients with head and neck carcinoma presenting to a tertiary care center in India: Need for urgent decentralization of cancer care]]> https://www.researchpad.co/article/N3753b3b5-1d85-4656-9102-d2c3da061da6

Aims:

This study aims to report on the demographic profile and treatment pattern of head and neck cancer patients and impact of an early treatment decision on treatment. This study also aims to suggest recommendations to improve treatment compliance.

Methods:

All new patients registered under the head and neck disease management group (DMG) over a period of 3 months at a single center were included. Their demographic details, time to treatment decision, and treatment compliance were determined. The findings were presented to head and neck DMG, and changes were implemented to patient workup with an aim to improve compliance. A reaudit was performed over a period of 3 months and results were compared.

Results:

Two thousand two hundred and forty patients were included in the analysis. Patients with a treatment decision at 1–4 weeks stood at 28.32%, 63.88%, 80.8%, and 89.87%, respectively. Dropout rate was 26%. About 50% of patients planned for surgical intervention could be treated within the institution. After implementation of changes as recommended by DMG, 2418 patients were analyzed and findings were compared to the previous audit. The dropout rate reduced to 17.57%. The number of patients with a treatment decision at 1–4 weeks were 51.26%, 77.42%, 89.46%, and 94.31%, respectively.

Conclusion:

Early treatment decision and referral could significantly improve patient dropout and possibly compliance to treatment. Decentralization of cancer care is urgently needed to manage the high numbers of patients presenting to tertiary care centers. Setting up of new regional cancer centers and increasing infrastructure in the existing centers should be the long-term goals.

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<![CDATA[HPV-driven oropharyngeal squamous cell cancer in Croatia — Demography and survival]]> https://www.researchpad.co/article/5c5df339d5eed0c484580f3c

Objectives

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Main HNSCC risk factors are tobacco, alcohol, and high-risk human papillomavirus (HPV). HPV+ oropharyngeal squamous cell cancer (OPSCC) usually have different etiology, increasing incidence and often show an improved survival when compared to HPV-negative cases. The objective of the current study was to retrospectively examine the influence of HPV on the survival of OPSCC patients in a non-Western population setting.

Materials and methods

We determined the presence of HPV DNA and/or RNA in 99 formalin-fixed paraffin embedded (FFPE) tissue samples of OPSCC patients treated between 2002 and 2015. Patients were compared based on laboratory, demographic, clinical, life style characteristics and survival.

Results

HPV RNA was found in 29.3% cases. However, groups based on HPV data (either RNA, DNA or retrospectively collected p16 staining) did not show significant differences. Overall, 5-year survival was 30% with minimal influence of the HPV positivity.

Conclusions

The HPV influence on survival of OPSCC patients is not identical between populations probably due to other factors overshadowing the HPV effect. This should be taken into account when treatment or policy decisions are made in each particular setting.

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<![CDATA[A microRNA signature for the differential diagnosis of salivary gland tumors]]> https://www.researchpad.co/article/5c57e6b8d5eed0c484ef3c33

Salivary gland tumors (SGTs) are rare tumors of the head and neck with different clinical behavior. Preoperative diagnosis, based on instrumental and cytologic examinations, is crucial for their correct management. The identification of molecular markers might improve the accuracy of pre-surgical diagnosis helping to plan the proper treatment especially when a definitive diagnosis based only on cytomorphology cannot be achieved. miRNAs appear to be new promising biomarkers in the diagnosis and prognosis of cancer. Studies concerning the useful of miRNA expression in clinical decision-making regarding SGTs remain limited and controversial.The expression of a panel of 798 miRNAs was investigated using Nanostring technology in 14 patients with malignant SGTs (6 mucoepidermoid carcinomas, 4 adenoid cystic carcinomas, 1 acinic cell carcinoma, 1 ductal carcinoma, 1 cystadenocarcinoma and 1 adenocarcinoma) and in 10 patients with benign SGTs (pleomorphic adenomas). The DNA Intelligent Analysis (DIANA)-miRPath v3.0 software was used to determinate the miRNA regulatory roles and to identify the controlled significant Kyoto Encyclopedia of Genes and Genomes (KEGG) molecular pathways. Forty six miRNAs were differentially expressed (False Discovery Rate—FDR<0.05) between malignant and benign SGTs. DIANA miRPath software revealed enriched pathways involved in cancer processes as well as tumorigenesis, cell proliferation, cell growth and survival, tumor suppressor expression, angiogenesis and tumor progression. Interestingly, clustering analysis showed that this signature of 46 miRNAs is able to differentiate the two analyzed groups. We found a correlation between histological diagnosis (benign or malignant) and miRNA expression profile.The molecular signature identified in this study might become an important preoperative diagnostic tool.

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<![CDATA[Safety and efficacy of nimotuzumab with concurrent chemoradiotherapy in unresectable locally advanced squamous cell carcinoma of head and neck: An Indian rural hospital experience]]> https://www.researchpad.co/article/5c7561e7d5eed0c484cb4c3f

Context:

Nimotuzumab is the only anti-epidermal growth factor receptor monoclonal antibody which can be safely added to concurrent chemoradiotherapy (CRT) to improve efficacy in the management of unresectable, locally advanced squamous cell carcinoma of head and neck (LA-SCCHN). However, the evidence available on this is limited.

Aims:

We retrospectively investigated efficacy and safety of nimotuzumab when combined with chemoradiation for LA-SCCHN.

Settings and Design:

Hospital records of 39 patients from January 2012 to December 2016 diagnosed with locally advanced (Stage III-IVb), unresectable SCCHN, and treated with concurrent CRT with weekly nimotuzumab were reviewed retrospectively after fulfilling the inclusion/exclusion criteria.

Subjects and Methods:

Tumor response was calculated as per response evaluation criteria in solid tumors criteria 1.1. Association of tumor response with independent variables was assessed. Overall survival (OS) and progression-free survival (PFS) were calculated. All patients were assessed for toxicity as per common terminology criteria for adverse events Common Terminology Criteria for Adverse Events v 4.0 (U.S. Department of health and human services, National Institutes of Health, National Cancer Institute).

Results:

At 6 months after completion of treatment, objective response rate was 97.44% with 26 (66.67%) patients attaining Complete response (CR), 12 (30.77%) patients with Partial response (PR), and one patient (2.56%) had stable disease. Subgroup analysis did not show a significant association of tumor response with independent factors. OS at 1 and 2-year was 100% and 72.9%, while PFS at 1 and 2-year was 87% and 54.40%. The incidence of Grade I, II, III, and IV toxicity was 30%, 18.18%, 41.82%, and 10%, respectively. No grade V toxicity was observed. Common adverse events observed were mucositis (33.64%), skin reaction (24.55%), neutropenia (20.91%), vomiting (18.18%), and diarrhea (2.73%).

Conclusions:

Nimotuzumab is an efficacious and safe option when added to concurrent CRT in unresectable, LA-SCCHN.

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<![CDATA[Squamous cell carcinoma of upper alveolus: An experience of a tertiary care center of Northeast India]]> https://www.researchpad.co/article/5c7561d1d5eed0c484cb4b3f

Objective:

The main objective of this study was to analyze the clinical behavior and the impact of nodal metastasis on the prognosis of upper alveolus squamous cell carcinoma (SCC).

Materials and Methods:

The medical records of 110 patients with SCC of the upper alveolus (International Classification of Diseases-10-C03.0) diagnosed during 2010–2015 were reviewed. Survival analysis was done using the Kaplan–Meier method and was compared using log rank-test. P < 0.05 was considered statistically significant.

Results:

Of the 110 patients, 59 were males and 51 were females. Forty-six (41.8%) patients presented with lymph node metastasis. Fifty-three (51.8%) patients presented in Stage IVA, thirty (27.3%) patients in Stage IVB, ten (9.1%) patients in Stage III, 12 (10.9%) patients in Stage II. The 5-year overall survival (OS) was 71.1% in Stage II, in Stage III it was 65.6%, in Stage it was IVA 56.7%, and in Stage IVB it was 19.4% (P = 0.02). The 5-year OS for node negative compared with node positive was 66.3% versus 37.3%, respectively (P = 0.019).

Conclusion:

Presence of lymph node metastasis is associated with lower survival rates. Adequate surgical resection with adjuvant treatment, where necessary, offers the best chance of disease control.

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<![CDATA[A comparative study of treatment outcome in younger and older patients with locally advanced oral cavity and oropharyngeal cancers treated by chemoradiation]]> https://www.researchpad.co/article/5c7561d9d5eed0c484cb4b83

Background:

Evidence suggests that older patients with oral cavity and oropharyngeal cancers may behave differently from their younger peers.

Aim:

The aim of this study is to determine if there is difference in responses, survival, and toxicities between young patients (≤40 years of age) with oral cavity and oropharyngeal cancers and older patients (>40 years of age) treated with concurrent chemoradiation.

Materials and Methods:

Sixty-one patients with unresectable, locally advanced oral cavity and oropharyngeal cancers received concomitant chemoradiation to a dose of 70 Gray in 35 fractions over 7 weeks with concomitant weekly cisplatin (40 mg/m2). These patients were then distributed in two arms. Arm-A patients having age ≤40 years and Arm-B patients having age >40 years, and the two arms were assessed for treatment outcome.

Results:

The overall response rate (complete responders + partial responders) evaluated using response evaluation criteria in solid tumors criteria version 1.1 was equivalent in both groups (80.76% in Arm-A and 74.28% in Arm-B; P = 0.93). Older patients (>40 years) experienced more acute mucositis and xerostomia (P < 0.5); although not statistically significant, more acute skin and pharynx toxicities were also observed in this group. Higher late salivary gland toxicity (P < 0.5) was also seen in older patients; however, disease-free survival and progression-free survival were found to be similar in both groups.

Conclusions:

Older patients with locally advanced oral cavity and oropharyngeal cancers have similar response rates and survival as compared to their younger counterparts but may experience higher treatment-related toxicities.

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<![CDATA[Decomposing the subclonal structure of tumors with two-way mixture models on copy number aberrations]]> https://www.researchpad.co/article/5c1ab82fd5eed0c4840270cf

Multistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Most of the methods focused on single-nucleotide variants (SNVs). However, somatic copy number aberrations (CNAs) also play critical roles in carcinogenesis. Therefore, further modeling subclonal CNAs composition would hold the promise to improve the analysis of tumor heterogeneity and cancer evolution. To address this issue, we developed a two-way mixture Poisson model, named CloneDeMix for the deconvolution of read-depth information. It can infer the subclonal copy number, mutational cellular prevalence (MCP), subclone composition, and the order in which mutations occurred in the evolutionary hierarchy. The performance of CloneDeMix was systematically assessed in simulations. As a result, the accuracy of CNA inference was nearly 93% and the MCP was also accurately restored. Furthermore, we also demonstrated its applicability using head and neck cancer samples from TCGA. Our results inform about the extent of subclonal CNA diversity, and a group of candidate genes that probably initiate lymph node metastasis during tumor evolution was also discovered. Most importantly, these driver genes are located at 11q13.3 which is highly susceptible to copy number change in head and neck cancer genomes. This study successfully estimates subclonal CNAs and exhibit the evolutionary relationships of mutation events. By doing so, we can track tumor heterogeneity and identify crucial mutations during evolution process. Hence, it facilitates not only understanding the cancer development but finding potential therapeutic targets. Briefly, this framework has implications for improved modeling of tumor evolution and the importance of inclusion of subclonal CNAs.

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<![CDATA[Development of a Non-Invasive Method, Multiplex Methylation Specific PCR (MMSP), for Early Diagnosis of Nasopharyngeal Carcinoma]]> https://www.researchpad.co/article/5989daadab0ee8fa60baa22f

Increasing evidence demonstrated that inactivation of tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event during carcinogenesis. Aiming at developing early diagnostic or prognostic tools for various tumors, we took an EBV-associated tumor, nasopharyngeal carcinoma (NPC), as a model and developed a powerful assay based on “multiplex methylation specific-PCR (MMSP)”. The MMSP assay was designed to detect tumor-specific methylation status of several NPC-related genes and was capable of acquiring multiplex information simultaneously through a single PCR reaction with the tiny tumor DNA derived from the direct body fluid close to the primary tumor. In this study, we collected paired nasopharyngeal (NP) swabs and NPC biopsies from 49 NPC patients and twenty noncancerous controls. A panel of markers including two EBV, and two cellular TSG markers were applied in this NPC-specific-MMSP assay. We optimized the working condition of MMSP so that it provides information equal to that from the corresponding separate PCRs. The results showed that MMSP patterns of NPC swab were largely consistent with those of corresponding biopsies and significantly distinguished themselves from those of 20 noncancerous volunteers. Among the 69 samples (49 NPCs and 20 normal controls), the sensitivity of detecting NPC from NP swabs is 98%. The specificity is as high as 100%. In conclusion, being characterized by its noninvasiveness, high reproducibility and informativeness, MMSP assay is a reliable and potential diagnostic tool for NPC. It paves the way for the development of population screening and early diagnosis approaches for various tumor types.

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<![CDATA[Genetic Variations in Key MicroRNA Processing Genes and Risk of Head and Neck Cancer: A Case-Control Study in Chinese Population]]> https://www.researchpad.co/article/5989da71ab0ee8fa60b94ca6

MicroRNAs (miRNAs) have been reported to play a key role in oncogenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the miRNA-mRNA interactions, hence promoting tumorigenesis. In the present study, we hypothesized that potentially functional polymorphisms in miRNA processing genes may contribute to head and neck cancer (HNC) susceptibility. To test this hypothesis, we genotyped three SNPs at miRNA binding sites of miRNA processing genes (rs1057035 in 3′UTR of DICER, rs3803012 in 3′UTR of RAN and rs10773771 in 3′UTR of HIWI) with a case-control study including 397 HNC cases and 900 controls matched by age and sex in Chinese. Although none of three SNPs was significantly associated with overall risk of HNC, rs1057035 in 3′UTR of DICER was associated with a significantly decreased risk of oral cancer (TC/CC vs. TT: adjusted OR  = 0.65, 95% CI  = 0.46–0.92). Furthermore, luciferase activity assay showed that rs1057035 variant C allele led to significantly lower expression levels as compared to the T allele, which may be due to the relatively high inhibition of hsa-miR-574-3p on DICER mRNA. These findings indicated that rs1057035 located at 3′UTR of DICER may contribute to the risk of oral cancer by affecting the binding of miRNAs to DICER. Large-scale and well-designed studies are warranted to validate our findings.

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<![CDATA[Network Modeling Identifies Molecular Functions Targeted by miR-204 to Suppress Head and Neck Tumor Metastasis]]> https://www.researchpad.co/article/5989d9faab0ee8fa60b71821

Due to the large number of putative microRNA gene targets predicted by sequence-alignment databases and the relative low accuracy of such predictions which are conducted independently of biological context by design, systematic experimental identification and validation of every functional microRNA target is currently challenging. Consequently, biological studies have yet to identify, on a genome scale, key regulatory networks perturbed by altered microRNA functions in the context of cancer. In this report, we demonstrate for the first time how phenotypic knowledge of inheritable cancer traits and of risk factor loci can be utilized jointly with gene expression analysis to efficiently prioritize deregulated microRNAs for biological characterization. Using this approach we characterize miR-204 as a tumor suppressor microRNA and uncover previously unknown connections between microRNA regulation, network topology, and expression dynamics. Specifically, we validate 18 gene targets of miR-204 that show elevated mRNA expression and are enriched in biological processes associated with tumor progression in squamous cell carcinoma of the head and neck (HNSCC). We further demonstrate the enrichment of bottleneckness, a key molecular network topology, among miR-204 gene targets. Restoration of miR-204 function in HNSCC cell lines inhibits the expression of its functionally related gene targets, leads to the reduced adhesion, migration and invasion in vitro and attenuates experimental lung metastasis in vivo. As importantly, our investigation also provides experimental evidence linking the function of microRNAs that are located in the cancer-associated genomic regions (CAGRs) to the observed predisposition to human cancers. Specifically, we show miR-204 may serve as a tumor suppressor gene at the 9q21.1–22.3 CAGR locus, a well established risk factor locus in head and neck cancers for which tumor suppressor genes have not been identified. This new strategy that integrates expression profiling, genetics and novel computational biology approaches provides for improved efficiency in characterization and modeling of microRNA functions in cancer as compared to the state of art and is applicable to the investigation of microRNA functions in other biological processes and diseases.

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<![CDATA[MicroRNA-193b Enhances Tumor Progression via Down Regulation of Neurofibromin 1]]> https://www.researchpad.co/article/5989db2cab0ee8fa60bd1749

Despite improvements in therapeutic approaches for head and neck squamous cell carcinomas (HNSCC), clinical outcome has remained disappointing, with 5-year overall survival rates hovering around 40–50%, underscoring an urgent need to better understand the biological bases of this disease. We chose to address this challenge by studying the role of micro-RNAs (miRNAs) in HNSCC. MiR-193b was identified as an over-expressed miRNA from global miRNA profiling studies previously conducted in our lab, and confirmed in HNSCC cell lines. In vitro knockdown of miR-193b in FaDu cancer cells substantially reduced cell proliferation, migration and invasion, along with suppressed tumour formation in vivo. By integrating in silico prediction algorithms with in vitro experimental mRNA profilings, plus mRNA expression data of clinical specimens, neurofibromin 1 (NF1) was identified to be a target of miR-193b. Concordantly, miR-193b knockdown decreased NF1 transcript and protein levels significantly. Luciferase reporter assays confirmed the direct interaction of miR-193b with NF1. Moreover, p-ERK, a downstream target of NF1 was also suppressed after miR-193b knockdown. FaDu cells treated with a p-ERK inhibitor (U0126) phenocopied the reduced cell proliferation, migration and invasion observed with miR-193b knockdown. Finally, HNSCC patients whose tumours expressed high levels of miR-193b experienced a lower disease-free survival compared to patients with low miR-193b expression. Our findings identified miR-193b as a potentially novel prognostic marker in HNSCC that drives tumour progression via down-regulating NF1, in turn leading to activation of ERK, resulting in proliferation, migration, invasion, and tumour formation.

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<![CDATA[Upregulation of MiR-155 in Nasopharyngeal Carcinoma is Partly Driven by LMP1 and LMP2A and Downregulates a Negative Prognostic Marker JMJD1A]]> https://www.researchpad.co/article/5989d9d1ab0ee8fa60b64638

The role of microRNA-155 (miR-155) has been associated with oncogenesis of several human tumors. However the expression pattern of miR-155 has not been investigated in nasopharyngeal carcinoma (NPC). The present study was to assess miR-155 expression pattern and its possible function in NPC, to identify its targets and evaluate their clinical applications in NPC. MiR-155 was found to be upregulated in two Epstein-Barr virus (EBV) negative NPC derived cell lines CNE1 and TW03, as well as in NPC clinical samples by quantitative Real-time PCR and in situ hybridization detection. EBV encoded LMP1 and LMP2A could further enhance the expression of miR-155 in NPC CNE1 and TW03 cells. JMJD1A and BACH1 were identified as putative targets of miR-155 in a bioinformatics screen. Overexpression of miR-155 downregulated a luciferase transcript fused to the 3′UTR of JMJD1A and BACH1. MiR-155 mimic could downregulate the expression of JMJD1A and BACH1, while miR-155 inhibitor could upregulate JMJD1A expression in NPC cell lines. Moreover, downregulation of JMJD1A was significantly correlated with N stage in TNM classification (p = 0.023), a lower five-year survival rate (p = 0.021), and a lower five-year disease-free survival rate (p = 0.049) of NPC patients. Taken together, up-regulation of miR-155 in NPC is partly driven by LMP1 and LMP2A, and results in downregulation of JMJD1A, which is associated with N stage and poor prognosis of NPC patients. The potential of miR-155 and JMJD1A as therapeutic targets in NPC should be further investigated.

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<![CDATA[Identifying Factors to Improve Oral Cancer Screening Uptake: A Qualitative Study]]> https://www.researchpad.co/article/5989db0aab0ee8fa60bc9d10

Aims

To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake.

Methods

Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week), irregular dental attenders living in economically deprived areas of Teesside.

Results

There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is ‘inaccessible’ on a physical and psychological level, costly, a ‘tooth specialist’ not a ‘mouth specialist’, and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer.

Conclusions

The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a “health” screening setting as opposed to a “dental” setting for such checks.

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<![CDATA[Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf6fc

Calcium signal plays an important role in a variety of cancer cell metabolism, but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is limited. Store-operated calcium entry (SOCE) is the principal Ca2+ entry mechanism that maintains calcium concentration and produces calcium signal in non-excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1), which is located in endoplasmic reticulum (ER) as Ca2+ sensor. Although, many studies demonstrated that STIM1 and SOCE play important functions in the regulation of many cancer progressions, their clinical relevance in HNSCC remains unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC tissues compared with those in adjacent normal tissues. Meanwhile, this overexpression was close associated with tumor size but not with neck lymph node metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2 (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer cell line) with STIM1 expression level lower than previous two cell lines, were selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER stress was amplified when STIM1 expression was downregulated but was attenuated as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study provides new insight into HNSCC molecular mechanism and potential therapeutic target through targeting SOCE-dependent process. However, whether STIM1 participates in HNSCC metastasis requires further study.

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<![CDATA[Gender Difference in the Prognostic Role of Interleukin 6 in Oral Squamous Cell Carcinoma]]> https://www.researchpad.co/article/5989da2dab0ee8fa60b83299

Background

Interleukin 6 (IL6) plays an important role in immunoregulation and tumorigenesis in human cancers. Oral squamous cell carcinoma (OSCC) is a malignant tumor of the oral cavity with a male predominant tendency and a poor clinical prognosis. Due to the relatively few cases in females, the gender difference of prognostic markers for OSCC is seldom discussed.

Methods

In this study, we used immunohistochemical staining methods to investigate the associations between IL6 expression and the clinicopathological characteristics of OSCC. In addition, we collected 74 female and 263 male OSCC patients for evaluation.

Results

High IL6 expression in tumor cells was significantly associated OSCC patient characteristics including female gender (P<0.001), high lymph node metastatic rate (P = 0.007), and poor tumor differentiation (P = 0.008). Tumor-expressed IL6 had prognostic role in male OSCC patients as defined by the log-rank test (P = 0.014), but not in female patients (P = 0.959). In male OSCC patients, high IL6 expression in tumor cells was associated with poor prognosis (P = 0.025) and a 1.454-fold higher death risk, as determined by Cox regression.

Conclusions

High IL6 expression in tumor cells was therefore significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in male OSCC patients.

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<![CDATA[Epithelial Cell Transforming Sequence 2 in Human Oral Cancer]]> https://www.researchpad.co/article/5989da09ab0ee8fa60b76d73

Background

Epithelial cell transforming sequence 2 (ECT2) is a guanine nucleotide exchange factor for Rho family GTPase, which has been implicated in the malignant phenotype of human cancers. Little is known about the effect of a high level of ECT2 in regulating oral cancer cell behavior. In this study, we investigated the involvement of ECT2 in oral squamous cell carcinoma (OSCC).

Methodology/Principal Findings

We analyzed ECT2 expression in OSCC-derived cell lines and primary OSCCs compared with matched normal tissue (n = 96) by quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. We then evaluated the correlation between the ECT2 expression status in primary OSCCs and the clinicopathological features. ECT2 expression was significantly up-regulated in OSCCs in vitro and in vivo (p<0.05). Among the clinical variables analyzed, higher ECT2 expression also was associated with the TNM stage grading (p<0.05). When we performed functional analyses of ECT2 in OSCC-derived cells using the shRNA system, the cellular proliferation of the ECT2 knockdown cells decreased significantly compared with the control cells (p<0.05). Cell cycle analysis by flow cytometry showed arrest of cell cycle progression at the G1 phase in the ECT2 knockdown cells. We also found up-regulation of the Cip/Kip family of the cyclin-dependent kinase inhibitors, p21cip1 and p27kip1, and down-regulation of cyclin D1, cyclin E, and CDK4. These data suggested that the elevated Cip/Kip family induced inhibition of the cyclin D1-CDK complex activity leading to cell cycle arrest at the G1 phase.

Conclusions/Significance

Our results proposed for the first time that ECT2 is an indicator of cellular proliferation in OSCCs and that ECT2 might be a potential therapeutic target for the development of new treatments for OSCCs.

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