Impact of e-cigarettes as cancer risk: A protocol for systematic review and meta-analysis.

BACKGROUND: The use of electronic cigarettes is one of the current public health problems on increasing alert, has been growing at an accelerating rate, and has become a public health emergency. Its importance is explained by the continuous growth and acceleration of oncological rates among all ages versus the absence of high-quality evidence, correlated to the use of nicotine derived products, being at their regular versions or the new ones. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms, which results can significantly reduce life's quality. This systematic review and meta-analysis protocol aims to clarify the connection between the use of electronic cigarettes by adults over the age of 18 and the development of malignant neoplastic diseases. METHOD: The proposed systematic review and meta-analysis will be reported conforming to the preferred reporting items for systematic reviews and meta-analyses guidelines. Will include the following studies: case-control or cohort studies showing adults (18 years old age) using e-cigarettes. There will be no language or publication period restrictions. Articles published, but not peer-reviewed, will not be included in the review. Data will be entered in the Review Manager software (RevMan5.2.3). For dichotomous outcomes, we extracted or calculated the OR and 95% CI for each study. In case of heterogeneity (I²>50%), the random-effects model will be used to combine the studies to calculate the OR and 95% CI.

TWIST1 regulates proliferation, migration, and invasion and is a prognostic marker for oral tongue squamous cell carcinoma.

BACKGROUND: Epithelial-mesenchymal transition is one of the main mechanisms for tumor progression and metastasis. Transcription factors such as TWIST1 are key regulators of the epithelial-mesenchymal transition and are regarded as potential therapeutic targets for the treatment of cancer. The purpose of this study was to examine TWIST1 as a possible epithelial-mesenchymal transition-related prognostic biomarker in oral epithelial dysplasia and oral tongue squamous cell carcinomas, as well as the biological behavior of TWIST1-silencing in oral tongue squamous cell carcinomas cell lines. METHODS: Immunohistochemical analysis of TWIST1, E-cadherin, and N-cadherin was carried out in 47 samples representing oral epithelial dysplasia and 41 oral tongue squamous cell carcinomas. The suppression of TWIST1 expression was performed using shRNA-expression vectors in HSC-3 and SCC-9 cells to investigate in vitro the impact of TWIST1 on proliferation, apoptosis, viability, migration, and invasion of SCC-9 and HSC-3 cells. RESULTS: The expression of nuclear TWIST1 was significantly higher in oral tongue squamous cell carcinomas than in oral epithelial dysplasis (p < 0.0001), whereas TWIST1 in the cytoplasm was more expressed in oral epithelial dysplasis (p = 0.012). The high cytoplasmic expression of TWIST1 was significantly associated with shortened overall survival (p < 0.05), and increased nuclear TWIST1 expression was significantly related to high risk of recurrence (p = 0.03). Knockdown of TWIST1 in oral tongue squamous cell carcinomas cells induced the expression of E-cadherin and inhibited N-cadherin, which were followed by decreased proliferation, migration, and invasion. CONCLUSIONS: Our research suggests that TWIST1 is linked to the development of oral tongue carcinogenesis and may be used as a prognostic indicator and therapeutic target for oral tongue squamous cell carcinomas patients.

Five-year survival and prognostic factors for oropharyngeal squamous cell carcinoma: retrospective cohort of a cancer center.

INTRODUCTION: Oropharyngeal cancer is characterized by high morbidity and mortality. Prognostic factors for this cancer are therefore useful to predict overall survival and may provide additional therapeutic targets. OBJECTIVE: To evaluate the 5-year overall survival and prognostic factors for oropharyngeal squamous cell carcinoma. METHODS: Retrospective cohort (2008-2018) of a cancer referral center. The population of the study was a hospital-based cohort consisting of patients diagnosed with oropharyngeal cancer who underwent surgery and/or adjuvant therapy (radio- and/or chemotherapy). RESULTS: A total of 253 patients with oropharyngeal squamous cell carcinoma were analyzed. The mean age was 59.8 ± 11.9 years and there was a male predominance (81.8%). Smoking and alcohol consumption were found in 88.0% and 84.2% of the sample, respectively. The combination of radiotherapy and chemotherapy was the treatment modality in 42.7% of the sample, followed by surgery combined with radio- and chemotherapy in 15.8%. There were 143 deaths (events), the mean survival was 11.55 ± 9.69 months, and the 5-year overall survival rate was 1.1%. Overall survival was lower for clinical stage III/IV (p < 0.001), HPV p16-negative status (p = 0.019), and an interval > 4 weeks between diagnosis and the beginning of treatment (p < 0.007). CONCLUSION: Among the prognostic factors analyzed in this cohort, p16-negative status as a poor prognostic indicator and tumor stage III/IV and an interval longer than 4 weeks between diagnosis and the beginning of treatment were significantly associated with lower overall survival.

Prognostic Factors and Survival in Adenoid Cystic Carcinoma of the Head and Neck: A Retrospective Clinical and Histopathological Analysis of Patients Seen at a Cancer Center.

Adenoid cystic carcinoma (AdCC) is a rare malignancy that accounts for approximately 1% of all head and neck cancers. This neoplasm is characterized by slow but often relentless growth and dissemination. Our aim was to retrospectively evaluate the clinical-pathological features of patients diagnosed with head and neck AdCC and to identify possible prognostic factors. This retrospective observational study analyzed 87 cases of AdCC of the head and neck. Clinical parameters (tumor size, lymph node and distant metastasis, clinical stage, and survival) were obtained from the records. Survival curves were constructed using the Kaplan-Meier method. A p value ≤ 0.05 was considered significant. There was a slight predominance of cases diagnosed in female patients (54%). The mean age at diagnosis was 51.5 years. Analysis using Cox's proportional hazards model considering 10-year disease-specific survival identified histologic pattern and presence of perineural invasion as independent prognostic variables. Primary tumor size and distant metastasis were prognostic predictors of 5- and 10-year disease-free survival. Detailed analysis of the association between clinical-pathological parameters and prognosis can assist professionals with cancer treatment planning and adequate patient management. Considering the long-term aggressive behavior of AdCC, rigorous patient follow-up is important to identify possible locoregional or distant recurrences.

The occurrence and pattern of head and neck sarcomas: a comprehensive cancer center experience.

PURPOSE: This study aimed to analyze the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas diagnosed in a reference center in the Brazilian Northeast. MATERIALS AND METHODS: This retrospective cohort study reviewed the clinical records of patients with head and neck sarcomas. Epidemiologic data consisted in clinical location, age, gender, histopathological diagnosis, clinical TNM staging and treatment. Outcome variables were local recurrence and survival. The statistical analyses were performed by a binary logistic regression analysis. The survival analysis was assessed through the Kaplan-Meier curve. RESULTS: Sixty-nine patients with head and neck sarcomas (male 39; female 30) were analyzed. The most common histologic subtypes were rhabdomyosarcoma, dermatofibrosarcoma, and pleomorphic sarcoma. The mean age of the patients at the time of diagnosis was 38.1 years old. A total of 31 patient died (sarcoma-related death) up to the end of the follow-up, with a mean follow-up rate of 1.63 years. A multivariate analysis revealed that anatomical site, treatment modality, histopathological diagnosis, and clinical stage of the disease were associated with specific survival, reaching statistical significance. CONCLUSION: This study demonstrates the impact of important clinical-pathological parameters on the overall prognosis of head and neck sarcomas.

Immunohistochemical expression of TFIIH and XPF in oral tongue squamous cell carcinoma.

PURPOSE: The query for biomarkers that indicate tumor aggressiveness and the host's response to treatment is still one of the leading aims of cancer research. To investigate a possible role for DNA nucleotide repair proteins in oral cancer behavior, this study evaluated the immunoexpression of the proteins TFIIH and XPF and its association with clinical, histological, and survival parameters in oral tongue squamous-cell carcinoma (OTSCC). METHODS: TFIIH and XPF immunoexpressions were evaluated in 82 cases of oral tongue squamous-cell carcinoma. Tumor budding and depth of invasion were assessed for histopathological grading (BD model). RESULTS: Tumor cells exhibited high expression of TFIIH and XPF, which was associated to nodal status; both proteins were not associated with other clinical parameters, histopathological grading or survival. Tumor size, nodal status, tumor staging, and depth of invasion > 4 mm were significantly associated to disease-specific survival. CONCLUSIONS: We have demonstrated that the overexpression of TFIIH correlates positively with node metastasis, while XPF correlates negatively with node metastasis; therefore, the expression of XPF and TFIIH had a potential value for predicting the progression of OTSCC patients.

Polymorphisms associated with oral clefts as potential susceptibility markers for oral and breast cancer.

OBJECTIVE: To evaluate the association of single nucleotide polymorphisms (SNPs) in genes/loci consistently altered in nonsyndromic oral clefts in patients with oral and breast cancer in a Brazilian population. DESIGN: This case-control study evaluated the association of SNPs in IRF6 (rs642961), WNT3A (rs708111), GSK3ß (rs9879992), 8q24 (rs987525) and WNT11 (rs1533767), representing regions consistently identified as of susceptibility for oral clefts, with oral cancer (oral squamous cell carcinoma) and breast cancer. Logistic regression analyses were used for confounding adjustments, and p values ≤0.01 were considered statistically significant (Bonferroni correction = 0.05/5 polymorphic markers). RESULTS: The minor G allele of rs9879992 in GSK3ß was associated with oral cancer risk (p = 0.02), whereas rs1533767 in WNT11 showed a protective effect against it (p = 0.04). Several SNP-SNP interactions containing GSK3ß rs9879992 were significantly associated with oral cancer after 1000 permutation test. To breast cancer, the A allele of rs987525 was associated with increase risk in early stage (p = 0.02) and SNP-SNP interactions involving the 5 SNPs were significantly observed, with the most significant interaction among rs708111, rs1533767, rs9879992 and rs642961 (p1000permutation<0.001). CONCLUSION: Our results reveal associations of SNPs consistently altered in oral cleft with oral and breast cancer risk, raising interesting possibilities to identify risk markers for those tumors.

DNA base excision repair proteins APE-1 and XRCC-1 are overexpressed in oral tongue squamous cell carcinoma.

BACKGROUND: DNA repair systems play a critical role in protecting the human genome from damage caused by carcinogens. Modifications in DNA repair genes may be responsible for tumor development and resistance of malignant cells to chemotherapeutic agents. The major pathway for oxidative DNA damage repair is the base excision repair pathway. This study aimed to assess the immunoexpression of DNA repair proteins APE-1 and XRCC-1 and its association with clinical, histologic, and survival parameters in oral tongue squamous cell carcinoma, to investigate a possible role for those proteins in tumor behavior. METHODS: The expression of APE-1 and XRCC-1 was evaluated by immunohistochemistry in 82 cases of oral tongue squamous cell carcinoma. Histopathological grading was performed for each case. Pearson's chi-square and Fisher's exact tests were used to determine the association between protein expressions and clinicopathological features of tumors, whereas Kaplan-Meier curves and Cox regression were used to analyze disease-specific and disease-free survival. Statistical significance was set at P ≤ 0.05. RESULTS: APE-1 was highly expressed in the nucleus and cytoplasm in 64.6% of cases, and XRCC-1 showed overexpression only in the nucleus in 61% of cases. High expression of XRCC-1 was significantly associated with tumors at early clinical stages (I and II, P < 0.01) and nodal status (P = 0.03). Both proteins were not associated with other clinical parameters, histopathological grading, or survival. CONCLUSIONS: DNA base excision repair proteins APE-1 and XRCC-1 are upregulated in oral tongue squamous cell carcinoma, and XRCC-1 expression is associated with better clinical staging and nodal status.

Distribution of Hypoxia-Inducible Factor-1α and Glucose Transporter-1 in Human Tongue Cancers.

PURPOSE: Oral squamous cell carcinomas have the potential for rapid and unlimited growth. Therefore, hypoxic tissue areas are common in these malignant tumors and contribute to cancer progression, therapy resistance, and poor outcomes. The aim of the present study was to analyze the gene product distribution of hypoxia-inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) in cases of tongue squamous cell carcinoma (TSCC) and to identify a preliminary correlation between these proteins and clinical staging and Brynes's histologic grading system (HGS). MATERIALS AND METHODS: The sample included 57 cases of TSCC. Histologic sections of 3 µm were submitted to the immunoperoxidase method and semiquantitative analysis. The association between HIF-1α and GLUT-1 expression in TSCC and the clinical stage and the HGS of Bryne (1998) was evaluated using the χ(2) test, with the significance level set at 0.05 (α = 0.05). RESULTS: HIF-1α was mainly expressed in the nucleus/cytoplasm of neoplastic cells, most specimens exhibited diffuse staining in neoplastic cells (84.2%), and focal staining was only observed in perinecrotic areas (15.8%). GLUT-1 was expressed in the cytoplasm and membrane of malignant cells, and diffuse staining was observed in all cases. The intensity of HIF-1α expression correlated significantly with clinical stage (P = .011) and HGS (P = .002). A significant association was observed between the distribution of HIF-1α expression and metastasis (P = .040). Immunoexpression of GLUT-1 correlated significantly with clinical stage (P = .002) and HGS (P = .000). GLUT-1 expression in the peripheral island was predominant in most low-grade tumors (78.6%); in the high-grade cases, the expression prevailed in the location center/periphery (55.8%). Comparison of the location of the tumor island in the different histologic grades showed a statistically significant difference (P = .025). CONCLUSION: The expression of HIF and GLUT proteins within TSCC appears to be associated with disease stage, grade, and the presence of metastases. Additional studies are needed to evaluate the diagnostic and prognostic uses of these proteins in the treatment of TSCC.