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1.
PLoS One ; 15(9): e0239586, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991600

RESUMO

In this study, we sought to identify the potential impacts of disease characteristics on the prognosis of cutaneous squamous cell carcinoma (cSCC). We searched the PubMed, EmBase, and Cochrane Library databases from their inception until February 2020 to identify studies that investigated the prognosis of cSCC. The pooled effect estimates were applied using odds ratios (OR) and 95% confidence intervals (CI) and were calculated using the random-effects model. Forty-three studies including a total of 21,530 patients and reporting 28,627 cases of cSCC were selected for the final meta-analysis. Poor differentiation (OR, 3.54; 95% CI, 2.30-5.46; P < 0.001), perineural invasion (OR, 3.27; 95% CI, 1.60-6.67; P = 0.001), Breslow greater than 2 mm (OR, 5.47; 95% CI, 2.63-11.37; P < 0.001), diameter greater than 20 mm (OR, 4.62; 95% CI, 2.95-7.23; P < 0.001), and location on temple (OR, 3.20; 95% CI, 1.12-9.15; P = 0.030) were associated with an increased risk of recurrence, whereas immunosuppression status and location on cheek, ear, or lip were not associated with the risk of recurrence. Poor differentiation (OR, 6.82; 95% CI, 4.66-9.99; P < 0.001); perineural invasion (OR, 7.15; 95% CI, 4.73-10.83; P < 0.001); Breslow greater than 2 mm (OR, 6.11; 95% CI, 4.05-9.21; P < 0.001); diameter greater than 20 mm (OR, 5.01; 95% CI, 2.56-9.80; P < 0.001); and location on ear (OR, 2.38; 95% CI, 1.39-4.09; P = 0.002), lip (OR, 2.15; 95% CI, 1.26-3.68; P = 0.005), and temple (OR, 2.77; 95% CI, 1.20-6.40; P = 0.017) were associated with an increased risk of metastasis, whereas immunosuppression status and location on cheek did not affect the risk of metastasis. Finally, poor differentiation (OR, 5.97; 95% CI, 1.82-19.62; P = 0.003), perineural invasion (OR, 6.64; 95% CI, 3.63-12.12; P < 0.001), and Breslow greater than 2 mm (OR, 3.42; 95% CI, 1.76-6.66; P < 0.001) were associated with an increased risk of disease-specific death, whereas diameter; immunosuppression status; and location on ear, lip, and temple did not affect the risk of disease-specific death. We found that differentiation, perineural invasion, depth, diameter, and location could affect the prognosis of cSCC. The potential role of other patient characteristics on the prognosis of cSCC should be identified in further large-scale prospective studies.


Assuntos
Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Humanos , Imunossupressão/métodos , Prognóstico , Fatores de Risco
2.
Nucleic Acids Res ; 48(17): 9505-9520, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32870263

RESUMO

Rapid growth of single-cell transcriptomic data provides unprecedented opportunities for close scrutinizing of dynamical cellular processes. Through investigating epithelial-to-mesenchymal transition (EMT), we develop an integrative tool that combines unsupervised learning of single-cell transcriptomic data and multiscale mathematical modeling to analyze transitions during cell fate decision. Our approach allows identification of individual cells making transition between all cell states, and inference of genes that drive transitions. Multiscale extractions of single-cell scale outputs naturally reveal intermediate cell states (ICS) and ICS-regulated transition trajectories, producing emergent population-scale models to be explored for design principles. Testing on the newly designed single-cell gene regulatory network model and applying to twelve published single-cell EMT datasets in cancer and embryogenesis, we uncover the roles of ICS on adaptation, noise attenuation, and transition efficiency in EMT, and reveal their trade-off relations. Overall, our unsupervised learning method is applicable to general single-cell transcriptomic datasets, and our integrative approach at single-cell resolution may be adopted for other cell fate transition systems beyond EMT.


Assuntos
Células-Tronco Embrionárias/patologia , Transição Epitelial-Mesenquimal/fisiologia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Modelos Biológicos , Animais , Diferenciação Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Camundongos , Análise de Célula Única , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
3.
J Exp Clin Cancer Res ; 39(1): 200, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967703

RESUMO

BACKGROUND: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas. METHODS: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC. RESULTS: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation. CONCLUSIONS: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Neoplasias de Cabeça e Pescoço/patologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Pneumonia Viral/complicações , Serina Endopeptidases/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estudos de Casos e Controles , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pandemias , Infecções por Papillomavirus/virologia , Pneumonia Viral/virologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Taxa de Sobrevida
4.
Nat Commun ; 11(1): 4788, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963234

RESUMO

Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the skin and oral mucosa. VAV2 is also required to maintain those traits in hnSCC patient-derived cells. This function, which is both catalysis- and RHO GTPase-dependent, is mediated by c-Myc- and YAP/TAZ-dependent transcriptomal programs associated with regenerative proliferation and cell undifferentiation, respectively. High levels of VAV2 transcripts and VAV2-regulated gene signatures are both associated with poor hnSCC patient prognosis. These results unveil a druggable pathway linked to the malignancy of specific SCC subtypes.


Assuntos
Proliferação de Células , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas Proto-Oncogênicas c-vav/genética , Proteínas Proto-Oncogênicas c-vav/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Animais , Diferenciação Celular , Modelos Animais de Doenças , Epiderme/metabolismo , Epiderme/patologia , GTP Fosfo-Hidrolases , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hiperplasia/patologia , Queratinócitos/patologia , Camundongos , Camundongos Knockout , Membrana Mucosa/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transcriptoma
5.
Anticancer Res ; 40(10): 5621-5630, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988886

RESUMO

BACKGROUND: Targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) are subject to extensive research. Different mutations of genes belonging to the fibroblast growth factor (FGF) family have been detected in HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus (HPV)-positive and -negative SCC lines. MATERIALS AND METHODS: Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 µmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those for untreated HPV-negative SCC cells. RESULTS: FGF1 and FGF2 were detected in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was stronger in the HPV-positive cell line. CONCLUSION: Alterations in FGF signalling are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our results show that the expression of FGF1 and -2 can be influenced effectively by small-molecule TKIs and everolimus. Based on our data, future research should include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms.


Assuntos
Everolimo/farmacologia , Fatores de Crescimento de Fibroblastos/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Serina-Treonina Quinases TOR/genética , Linhagem Celular Tumoral , Dasatinibe/farmacologia , Cloridrato de Erlotinib/farmacologia , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Gefitinibe/farmacologia , Papillomavirus Humano 16/efeitos dos fármacos , Papillomavirus Humano 16/patogenicidade , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/patogenicidade , Inibidores de Proteínas Quinases/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Serina-Treonina Quinases TOR/antagonistas & inibidores
6.
Jpn J Clin Oncol ; 50(10): 1089-1096, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32776100

RESUMO

Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and complicated in the new era of individualized medicine. Ongoing trials are investigating immunotherapeutic approaches in the curative setting for locoregionally advanced disease. This review article summarizes knowledge of the role of the immune system in the development and progression of squamous cell carcinoma of the head and neck, and provides a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases.


Assuntos
Imunoterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
7.
Cancer Imaging ; 20(1): 56, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32771060

RESUMO

BACKGROUND: To determine the usefulness of Diffusion Weighted Imaging (DWI) derived from PET/MRI in discriminating normal from metastatic lymph nodes and the correlation between the metastatic lymph nodes with the grade and the localization of the primary tumor. METHODS: Retrospective study of 90 lymph nodes from 90 subjects; 65 patients who had proven histopathological metastatic lymph nodes from (HNSCC) who had undergone 18F- PET/MRI for clinical staging and assessment and twenty-five lymph nodes were chosen from 25 healthy subjects. Apparent Diffusion Coefficient (ADC) map was generated from DWI with b values (0 and 800 s/mm2). ADC values of the metastatic lymph nodes were calculated and compared to the normal lymph nodes ADC values, ROC was used to determine the best cut-off values to differentiate between the two group. Metastatic lymph nodes ADC mean values were compared to primary tumor grade and localization. RESULTS: ADCmean value of the metastatic lymph nodes in the overall sample (0.899 ± 0.98*10- 3 mm2/sec) was significantly lower than the normal lymph nodes' ADCmean value (1.267 ± 0.88*10- 3 mm2/sec); (P = 0.001). The area under the curve (AUC) was 98.3%, sensitivity and specificity were 92.3 and 98.6%, respectively, when using a threshold value of (1.138 ± 0.75*10- 3 mm2/sec) to differentiate between both groups. Significant difference was found between metastatic lymph nodes (short-axis diameter < 10 mm), ADCmean (0.898 ± 0.72*10- 3 mm2/sec), and the benign lymph nodes ADCmean, (P = 0.001). No significant difference was found between ADCmean of the metastatic lymph nodes < 10 mm and the metastatic lymph nodes > 10 mm, ADCmean (0.899 ± 0.89*10- 3 mm2/sec), (P = 0.967). No significant differences were found between metastatic lymph nodes ADCmean values and different primary tumor grades or different primary tumor localization, (P > 0.05). CONCLUSION: DWI-ADC is an effective and efficient imaging technique in differentiating between normal and malignant lymph nodes, and might be helpful to discriminate sub-centimeters lymph nodes. TRIAL REGISTRATION: The trial is registered in clinical trials under ID: NCT04360993 , registration date: 17/04/2020.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Adulto , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
8.
Lancet Oncol ; 21(9): 1173-1187, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32758455

RESUMO

BACKGROUND: Debio 1143 is an orally available antagonist of inhibitor of apoptosis proteins with the potential to enhance the antitumour activity of cisplatin and radiotherapy. The radiosensitising effect of Debio 1143 is mediated through caspase activation and TNF, IFNγ, CD8 T cell-dependent pathways. We aimed to investigate the efficacy and safety of Debio 1143 in combination with standard chemoradiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. METHODS: This double-blind, multicentre, randomised, phase 2 study by the French Head and Neck Radiotherapy Oncology Group (GORTEC) was run at 19 hospitals in France and Switzerland. Eligible patients were aged 18-75 years with locoregionally advanced, squamous cell carcinoma of the head and neck (characterised as non-metastatic, measurable stage III, IVa, or IVb [limited to T ≥2, N0-3, and M0] disease), Eastern Cooperative Oncology Group performance status of 0 or 1, a history of heavy tobacco smoking (>10 pack-years) with no previous or current treatment for invasive head and neck cancer, and no previous treatment with inhibitor of apoptosis protein antagonists. Patients were randomly assigned (1:1) to receive oral Debio 1143 (200 mg per day on days 1-14 of 21-day cycles, for three cycles) or oral placebo (20 mg/mL, administered at the same dosing schedule) using a stochastic minimisation technique according to node involvement and primary tumour site, and HPV-16 status in patients with an oropharyngeal primary tumour site. All patients received standard high-dose cisplatin chemoradiotherapy. The primary endpoint was the proportion of patients with locoregional control 18 months after chemoradiotherapy, analysed in the intention-to-treat population (primary analysis), and repeated in the per-protocol population. Responses were assessed according to Response Evaluation Criteria in Solid Tumors (version 1.1). This trial is registered with ClinicalTrials.gov, NCT02022098, and is still active but not recruiting. FINDINGS: Between Jan 25, 2016, and April 24, 2017, 48 patients were randomly assigned to the Debio 1143 group and 48 to the placebo group (one patient in the placebo group did not receive the study drug and was not included in the safety analysis). Median duration of follow-up was 25·0 months (IQR 19·6-29·4) in the Debio 1143 group and 24·2 months (6·6-26·8) in the placebo group. Locoregional control 18 months after chemoradiotherapy was achieved in 26 (54%; 95% CI 39-69) of 48 patients in the Debio 1143 group versus 16 (33%; 20-48) of 48 patients in the placebo group (odds ratio 2·69 [95% CI 1·13-6·42], p=0·026). Grade 3 or worse adverse events were reported in 41 (85%) of 48 patients in the Debio 1143 group and in 41 (87%) of 47 patients in the placebo group. The most common grade 3-4 adverse events were dysphagia (in 24 [50%] patients in the Debio 1143 group vs ten [21%] in the placebo group), mucositis (in 15 [31%] vs ten [21%]), and anaemia (in 17 [35%] vs 11 [23%]). Serious treatment-emergent adverse events were recorded in 30 (63%) of 48 patients in the Debio 1143 group and 28 (60%) of 47 in the placebo group. In the placebo group, two (4%) deaths were due to adverse events (one multiple organ failure and one asphyxia; neither was considered to be related to treatment). No deaths due to adverse events occurred in the Debio 1143 group. INTERPRETATION: To our knowledge, this is the first treatment regimen to achieve superior efficacy in this disease setting against a high-dose cisplatin chemoradiotherapy comparator in a randomised trial. These findings suggest that inhibition of inhibitor of apoptosis proteins is a novel and promising approach in this poor prognostic population and warrant confirmation in a phase 3 study with the aim of expanding the therapeutic options for these patients. FUNDING: Debiopharm.


Assuntos
Cisplatino/administração & dosagem , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto Jovem
9.
Cancer Radiother ; 24(6-7): 559-566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32753240

RESUMO

PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. MATERIAL AND METHODS: We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. RESULTS: Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. CONCLUSION: Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.


Assuntos
Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Algoritmos , Humanos , Metástase Neoplásica/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
10.
Mol Carcinog ; 59(10): 1147-1158, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32805066

RESUMO

Acquired resistance is a barrier to cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Secreted phosphoprotein 1 (SPP1) is involved in various biological processes, including immune responses, cancer progression, and prognosis in many cancers, while little is known in HNSCC. Bioinformatics methods were used to identify candidate genes and further in vivo and in vitro experiments were performed to examine and validate the function of SPP1. We found that SPP1 was upregulated and has been found to have an oncogenic role in HNSCC. We further confirmed that overexpression of SPP1 affected proliferation, migration, invasion, and survival, and inhibited apoptosis, whereas silencing of SPP1 yielded opposite results to those of SPP1 overexpression. In addition, activation of the KRAS/MEK pathway contributed to the SPP1-induced malignant progression of HNSCC and resistance to cetuximab. Furthermore, SPP1 knockdown or an MEK inhibitor overcame this cetuximab-resistance pattern. Taken together, our findings for the first time identify the role of SPP1 in tumor promotion, prognostic prediction, and potential therapeutic targeting, as well as resistance to cetuximab in HNSCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Cetuximab/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Cabeça e Pescoço/patologia , MAP Quinase Quinase 1/metabolismo , Osteopontina/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Animais , Antineoplásicos Imunológicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , MAP Quinase Quinase 1/genética , Camundongos , Camundongos Nus , Invasividade Neoplásica , Osteopontina/genética , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Oncology ; 98(11): 763-770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32629446

RESUMO

OBJECTIVES: Induction chemotherapy followed by cetuximab and RT (IBRT) (Arm A) was compared to cisplatin/RT (CRT) (Arm B) in a randomized phase III study. PATIENTS AND METHODS: Naïve patients with stage III-IVa, histologically proven locally advanced head and neck cancer (LASCCHN) were eligible. Arm A (IBRT): 3 TPF induction followed by cetuximab-RT (equivalent daily dose 2 Gy up to 70 Gy); Arm B: 3 cisplatin concurrent with the same RT scheduling. Due to slow accrual and incomplete data collection a futility analysis was performed. RESULTS: 236/282 patients were evaluable. Therefore, no formal analyses can be made between the two arms. OS was 45.2/53.6 months in Arm A/B. Complete responses were achieved in 64% of patients in both arms. Neutropenia and skin toxicity were significantly worse in Arm A and body weight loss was significantly worse in Arm B. Compliance with the planned drug administration was higher in Arm B (p = 0.0008). CONCLUSION: The study suggests that IBRT and CRT have similar efficacy, activity and toxicity.


Assuntos
Cetuximab/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/efeitos adversos , Quimiorradioterapia , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução , Masculino , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
12.
J Cancer Res Clin Oncol ; 146(10): 2497-2507, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32620987

RESUMO

PURPOSE: Tumor explant culture systems can mimic the in vivo tumor microenvironment, proposing as a substitute for preclinical studies for prediction of individual treatment response. Therefore, our study evaluated the potential usefulness of ex vivo tumor explants culture assembled into the cell sheets by anticancer drug screening in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Our model included tumor explants incorporated into cell sheet composing of epithelium and subepithelial stroma using tumor and mucosal samples obtained from the HNSCC patients who underwent surgery. Cell growth, viability, and hypoxia were measured by cell counting kit-8, live/dead assay, propidium iodide, and LOX-1 staining, and were compared among the different treatment groups with vehicle, cisplatin or docetaxel. RESULTS: Tumor explants stably survived in the cell sheet over 10 days after explantation, whereas most of the explants in non-matrix culture became nonviable within 5-8 days with the significant daily decrease of viability. The live tissue areas of tumor explants in the cell sheet maintained over 30 days without significant changes although hypoxic cell areas gradually increased up to 5 days. Tissue viability and live cancer tissue areas significantly decreased after the treatment of cisplatin or docetaxel in the dose and time-dependent manners. CONCLUSION: Our cell sheet-based tumor explants model might be applied to the reliable ex vivo screening for anticancer chemotherapeutics for HNSCC.


Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Hipóxia Celular/fisiologia , Sobrevivência Celular/fisiologia , Cisplatino/farmacologia , Docetaxel/farmacologia , Relação Dose-Resposta a Droga , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Técnicas de Cultura de Órgãos/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Células Tumorais Cultivadas
13.
J Cancer Res Ther ; 16(3): 434-439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719247

RESUMO

Objective: The aim of this study was to review the published literature and investigate whether sex determining region Y-box 2 (SOX2) is a prognostic factor in head and neck squamous cell carcinoma (HNSCC) by conduct a meta-analysis. Materials and Methods: Trials were identified from the major electronic databases (MEDLINE, EMBASE, and Cochrane Library) using the key words "HNSCC" and "SOX2." The overall survival (OS), disease-specific survival (DPS), and disease-free survival (DFS) were the primary outcome measures. Results: We identified 371 articles, 9 articles 11 studies with a total number of 1334 cases were eligible for inclusion of this meta-analysis. The results showed that OS (DPS) in low-expression group was higher than that in high-expression group. However, the difference between the two groups was not significant (hazard ratio [HR] = 1.30, 95% confidence interval [95% CI] = [0.88, 1.91]; P = 0.18), and there was great statistical heterogeneity (I2 = 66%, P = 0.002). After subgroup analysis, the HR for OS of the patients with reduced expression of SOX2 was 1.34 (95% CI = [1.04, 1.74], P = 0.03), and the heterogeneity became acceptable (I2 = 32%, P = 0.16). The HR for DFS of the patients with reduced expression of SOX2 was 1.39 (95% CI = [1.00, 1.93]; P = 0.05). Conclusion: The findings of this meta-analysis are indicative of that high SOX2 expression is a negative prognostic factor of HNSCC and exhibit both worse OS and DFS. However, the small sample size available for this systematic review limited the power of this quantitative meta-analysis. It may therefore be too early to place complete confidence in these results.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Fatores de Transcrição SOXB1/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Taxa de Sobrevida
14.
J Cancer Res Ther ; 16(3): 530-533, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719262

RESUMO

Context: An objective conformal radiotherapy treatment planning criteria that can predict severity of early effects of radiotherapy would be quite useful in reducing the side effects of radiotherapy thereby improving quality of life for head and neck cancer patients. Aim of Study: Retrospective study aimed at correlating the maximum dose in planning target volume (PTV) with early effects of radiation. Materials and Methods: Patients with squamous cell carcinoma of H and N region who received radical radiotherapy and concomitant chemotherapy were retrospectively analyzed for maximum dose in PTV and the requirement of gap during radiotherapy or else hospitalization for supportive care during or up to 1 month after completion of radical radiotherapy. Results: Of a total of 23 patients, 8 patients (34.7%) required a gap of 2-14 days during their treatment. Twelve patients (52.1%) required hospitalization for 1-4 days and 4 patients (17.3%) required hospitalization for supportive care after completion of radiotherapy. The maximum dose in PTV ranged from 105.1% to 132.8% with an average of 112.68%. Subgroup analysis revealed a nonsignificant highest maximum dose of 114.72% in subset of patients requiring gap during radiotherapy (n= 8). Conclusion: It was concluded that maximum dose in PTV is a useful predictor of need for inhospital supportive care.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Determinação de Necessidades de Cuidados de Saúde/estatística & dados numéricos , Cuidados Paliativos/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Segurança do Paciente , Qualidade de Vida , Dosagem Radioterapêutica , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Resultado do Tratamento
15.
Anticancer Res ; 40(8): 4207-4214, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727746

RESUMO

BACKGROUND/AIM: To assess factors that predict detection of tumors and oncologic outcomes in head and neck squamous cell carcinoma of unknown primary (SCCUP). PATIENTS AND METHODS: This was a retrospective cohort study at a single tertiary care institution. RESULTS: The primary site was detected at examination under anesthesia (EUA) in 92 (51.1%) patients. The primary site was detected by directed biopsies in 60 (65%), palatine tonsillectomy in 28 (30.4%), and lingual tonsillectomy in 4 patients (4.3%). Four of eight lingual tonsillectomies were positive (50%). Primary locations included: palatine tonsils (51, 28.3%), base of tongue (37, 20.6%), larynx (4, 2.2%), oral cavity (3, 1.67%) and nasopharynx (1, 0.6%). Human papillomavirus (HPV) positive status (HR=0.26, p=0.004) and treatment with chemoradiation (CRT) (HR=0.38, p=0.004) were associated with better disease free survival (DFS). CONCLUSION: A primary site was located after aggressive investigation in approximately half of the patients. More research is warranted towards the use of lingual tonsillectomy. Predictors of favorable prognosis included HPV positive status and treatment with CRT.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias Primárias Desconhecidas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Idoso , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
16.
PLoS One ; 15(7): e0236678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716971

RESUMO

Head and neck squamous cell carcinoma (HNSCC), a tumor included oral cavity, lips, larynx, oropharynx, and the nasopharynx et al. The cell division cycle-associated (CDCA) protein family (CDCA1-8) critical for normal cell function and cancer cell proliferation. We explored the mutation signatures and expression levels of various CDCAs in detail in HNSCC. A comprehensive bioinformatics analysis pipeline based on copy number and gene expressions data from patients with HNSCC in order to given new insights into the possible functions and distinct prognostics that underlie CDCAs regulation. We compared the transcriptional expression of CDCAs in HNSCC and found significantly elevated mRNA expression of CDCA1-8 in HNSCC tissues across multiple datasets. We also found CDCA5/6/8 are over-expressed both transcriptionally and translationally in patients with HNSCC. Our results suggested that that mRNA levels of CDCA1/2/4/7 related to the prognosis and can be used as a new useful biomarker for predicting the survival of HNSCC patients. The top 5 CDCAs neighboring gene alterations in HNSCCs were found in MYC, STAG1, RAD21, KLHL9 and NDC80. Multivariable Cox proportional hazard model also showed that CD8+ T cells were higher (P<0.05) in HNSCC-HPV-pos patients and that this was related to CDCA1/2/3/4/5/7. This study utilizes online tools to conduct specific gene analyses from free open databases, but our study requires more large-scale genomics research and basic research.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Bases de Dados Factuais , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade
17.
J Cancer Res Ther ; 16(3): 551-558, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719266

RESUMO

Background: Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common cancers that contribute to 20%-40% of all cancer incidences in India. Indian patients with HNSCC are mostly associated with tobacco usage and may have different genetic alterations compared with Western patients who are mostly associated with human papillomavirus infection. Polymorphisms in DNA repair genes are correlated to individuals' susceptibility and progression of cancer. XRCC1 is a DNA repair enzyme. Materials and Methods: In the present prospective study, Indian population of HNSCC patients (n = 45) were screened for Arg399Gln variant of XRCC1 using polymerase chain reaction-restriction fragment length polymorphism technique, prospective evaluation of the patients was done after treatment, and the single-nucleotide polymorphism results were correlated to survival functions. Results: Out of 45 patients, 28 patients were Arg/Arg, 12 patients were Arg/Gln, and 5 patients were Gln/Gln. Overall survival for the entire cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 36.3 (95% confidence interval [CI]: 33-39.5), 38.6 (95% CI: 35.3-41.9), 35.8 (95% CI: 28.6-42.9), and 26.4 (95% CI: 13.7-39.1) months (P = 0.097), respectively. Progression-free survival (PFS) of the entire patient cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 35.2 (95% CI: 31.4-39.1), 38.2 (95% CI: 34.3-42.1), 32.7 (95% CI: 26.2-39.1), and 22.3 (95% CI: 9.4-35.3) (P = 0.061), respectively. Conclusions: This study suggests that HNSCC patients with Gln substitution in place of Arg at position 399 (both homozygous and heterozygous) in XRCC1 protein have significantly inferior survival functions, higher recurrence rate, and events after radical treatment.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Polimorfismo de Nucleotídeo Único , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Adulto , Estudos de Casos e Controles , Reparo do DNA , Feminino , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida
18.
J Cancer Res Ther ; 16(3): 559-564, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719267

RESUMO

Background: Head-and-neck cancer is the most common cancer in developing countries of Southeast Asia. Most of the patients present to the hospital in advanced stage and have a poor prognosis. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of methotrexate and celecoxib in locally advanced, recurrent and metastatic head-and-neck cancers. Materials and Methods: This was a single-arm retrospective observational study that included posttreatment patients with locally advanced, recurrent and metastatic disease in the year 2016 (January 1, to December 31, 2016). A total of 84 patients warranting palliative chemotherapy but not willing to take intravenous chemotherapy were included in the study. The oral MCT schedule consisted of oral celecoxib (200 mg twice daily) and oral methotrexate (15 mg/m2/week). Response evaluation was done using the Response Evaluation Criteria in Solid Tumors criteria version 1.1, and toxicity profile was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Descriptive statistics and Kaplan-Meier analysis were performed. Results: Eighty-four patients, 68 males and 16 females, with a median age of 62 years (range: 35-80 years), were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group performance status was 0-1 in 62 patients and 2-3 in 22 patients. The primary sites of disease were buccal mucosa (18), tongue (22), tonsil (24), lower alveolus (7), hypopharynx (10), and soft palate (3). The best clinical response rate in post oral MCT was seen in the first 4 months (120 days). Objective response was observed in 67% of patients in the form of stable disease (56%) and partial response (11%). Disease progression was observed in 27% of patients. The median follow-up was 192 (6.4 months) days. The median estimated overall survival was 195 (6.5 months) days. The median estimated progression-free survival was 110 (3.6 months) days. Symptomatic relief with respect to pain was reported in about 75% of patients. Eighteen (21%) patients had Grade I-II mucosal reactions. Grade III-IV mucosal reactions were observed in five (6%) patients. Seventy-eight (93%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (18%) patients. Conclusion: Oral MCT using celecoxib and methotrexate is an effective, economical, and well-tolerated regimen with good pain control and low toxicity profile in patients with locally advanced, recurrent and metastatic head-and-neck cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Cuidados Paliativos/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Administração Metronômica , Adulto , Idoso , Idoso de 80 Anos ou mais , Celecoxib/administração & dosagem , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Índia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida
19.
J Cancer Res Ther ; 16(3): 565-568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719268

RESUMO

Context: Head-and-neck cancer patients undergoing chemoradiation. Aims: The aim of the study was to see if there is any correlation between the planning target volume (PTV) and mucositis. Settings and Design: This was a single-arm prospective study. Subjects and Methods: A total of forty head-and-neck cancer patients undergoing chemoradiation were assessed for mucositis at the 5th week. The grades of mucositis were correlated with PTVs of low risk (54 Gy) and high risk (60-66 Gy). Statistical Analysis Used: The data were analyzed using the statistical software, SPSS Inc. Release 2009, predictive analytics software statistics for windows version 20.0, Chicago. Log transformation was done as the data were skewed. Independent t-test was used to compare between the two grades of toxicity. P <0.01 was considered for statistical significance. Results: The mean PTVlow risk was 522cc (228-771) and PTVhigh risk was 254cc (20-780). Grade II mucositis was seen in 27 (67%) patients and Grade III in 11 (28%) patients. The mean PTVlow risk was higher for patients, who had Grade III compared to Grade II mucositis (571 vs. 517 cc, P = 0.052). Conclusions: The same was seen for PTVhigh risk(367 vs. 222 cc, P = 0.017). PTV is a better predictor of mucositis, and those patients with larger PTV require close monitoring and early intervention of mucositis.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Mucosite/etiologia , Lesões por Radiação/etiologia , Planejamento da Radioterapia Assistida por Computador/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/diagnóstico , Mucosite/patologia , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estomatite/diagnóstico , Estomatite/etiologia , Estomatite/patologia
20.
J Cancer Res Ther ; 16(3): 569-574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719269

RESUMO

Background: Screening for oral squamous cell carcinomas (OSCCs) and oral premalignant lesions may decrease the devastating morbidity and mortality associated with the disease. This has led to widespread research for the identification of molecular-based biomarkers. Among them, survivin is a recently characterized protein which is a member of the inhibitor of apoptosis family. The aim of this study is evaluating the expression of survivin in oral leukoplakia, oral lichen planus, and OSCC compared with normal mucosa. Materials and Methods: The retrospective study consisted of twenty cases of oral leukoplakia, oral lichen planus, and OSCC in the age group of 20-70 years. Twenty cases of normal mucosa made up the control group. Immunohistochemical staining was performed with the use of survivin polyclonal antibody. Grades of expression of survivin were evaluated. Kruskal-Wallis test was used for statistical analysis. Results: The expression of survivin was higher in OSCC (80%) when compared to oral leukoplakia (70%), oral lichen planus (45%), and normal mucosa (35%). The variation in the expression of survivin between the samples was statistically significant with P = 0.015 (Kruskal-Wallis test significant at 0.01 level). Conclusion: It is concluded that survivin can be identified as a useful tool for the identification of potentially malignant disorders at higher risk for progression into invasive carcinoma.


Assuntos
Leucoplasia Oral/metabolismo , Líquen Plano Bucal/metabolismo , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Survivina/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Leucoplasia Oral/patologia , Líquen Plano Bucal/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto Jovem
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