Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.074
Filtrar
1.
Adv Exp Med Biol ; 1287: 105-122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034029

RESUMO

The NOTCH pathway is critical for the development of many cell types including the squamous epithelium lining of cutaneous and mucosal surfaces. In genetically engineered mouse models, Notch1 acts as one of the first steps to commit basal keratinocytes to terminally differentiate. Similarly, in human head and neck squamous cell cancers (HNSCCs), NOTCH1 is often lost consistent with its essential tumor-suppressive role for initiating keratinocyte differentiation. However, constitutive NOTCH1 activity in the epithelium results in expansion of the spinous keratinocyte layers and impaired terminal differentiation is consistent with the role of NOTCH1 as an oncogene in other cancers, especially in T-cell acute lymphoblastic leukemia. We have previously observed that NOTCH1 plays a dual role as both a tumor suppressor and oncogene, depending on the mutational context of the tumor. Namely, gain or loss or NOTCH1 activity promotes the development of human papillomavirus (HPV)-associated cancers. The additional HPV oncogenes likely disrupt the tumor-suppressive activities of NOTCH and enable the oncogenic pathways activated by NOTCH to promote tumor growth. In this review, we detail the role of NOTCH pathway in head and neck cancers with a focus on HPV-associated cancers.


Assuntos
Carcinogênese , Neoplasias Bucais/metabolismo , Neoplasias Bucais/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Humanos , Infecções por Papillomavirus/virologia
2.
PLoS One ; 15(8): e0237465, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785290

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear. METHODS: We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⁺ T-cells and CTLA-4⁺ cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC. RESULTS: Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⁺ T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⁺ cells in the parenchyma of the invasive front. CONCLUSIONS: The presence of FoxP3⁺ T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⁺ T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4+ cells suppress the function of FoxP3+ T-cells and promote anti-tumor immunity in OSCC.


Assuntos
Antígeno CTLA-4/metabolismo , Carcinoma de Células Escamosas/patologia , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/mortalidade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo
3.
Anticancer Res ; 40(7): 3685-3696, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620607

RESUMO

BACKGROUND/AIM: Although chemotherapy agents, such as oxaliplatin, cisplatin, paclitaxel and bortezomib frequently cause severe peripheral neuropathy, very few studies have reported the effective strategy to prevent this side effect. In this study, we first investigated whether these drugs show higher neuropathy compared to a set of 15 other anticancer drugs, and then whether antioxidants, such as sodium ascorbate, N-acetyl-L-cysteine, and vitamin B12 have any protective effect against them. MATERIALS AND METHODS: Rat PC12 cells were induced to differentiate into neuronal cells by repeated overlay of serum-free medium supplemented with nerve growth factor. The cytotoxic levels of anticancer drugs against four human oral squamous cell carcinoma cell lines, three normal oral cells, and undifferentiated and differentiated PC12 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cells were sorted for apoptotic cells (distributed into subG1 phase) and cells at different stages of cell cycle (G1, S and G2/M). RESULTS: All 19 anticancer drugs showed higher cytotoxicity against PC12 compared to oral normal cells. Among them, bortezomib showed the highest cytotoxicity against both undifferentiated and differentiated PC12 cell and, committed them to undergo apoptosis. Sodium ascorbate and N-acetyl-L-cysteine, but not vitamin B12, completely reversed the cytotoxicity of bortezomib. CONCLUSION: Bortezomib-induced neuropathy might be ameliorated by antioxidants.


Assuntos
Antioxidantes/farmacologia , Bortezomib/efeitos adversos , Síndromes Neurotóxicas/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Bortezomib/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Fator de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Síndromes Neurotóxicas/metabolismo , Células PC12 , Doenças do Sistema Nervoso Periférico/metabolismo , Ratos
4.
Gene ; 757: 144936, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32640301

RESUMO

Oral squamous cell carcinoma (OSCC) accounts for nearly 90 percent of oral cavity malignancies and is one of the most widespread oral cancers in the world. The microRNAs (miRNAs or miRs) have an important role in cellular processes comprising cell cycle, differentiation, and also apoptosis. MiRNAs are also implicated in the progression of cancers, including OSCC, through a variety of signaling pathways. One of the most significant signaling pathways in OSCC is the PI3K / Akt pathway that has been illustrated to be under the tight regulation of miRNAs. Deregulation or activation of the PI3K / Akt pathway due to mutations has been revealed to be implicated in the development of oral cancer. According to studies, more than 47% of HNSCC and around 38% of OSCC samples indicate at least one molecular alteration in this signaling pathway. The potential of miRNAs for their use as therapeutic tools in the diagnosis as well as treatment of numerous diseases have been confirmed. In the current review, we summarize miRNAs and their possible mechanisms as well as their functions in OSCC advancement and progression.


Assuntos
Carcinoma de Células Escamosas/genética , MicroRNAs/genética , Neoplasias Bucais/genética , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo
5.
Proc Natl Acad Sci U S A ; 117(28): 16167-16173, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601197

RESUMO

Saliva is a noninvasive biofluid that can contain metabolite signatures of oral squamous cell carcinoma (OSCC). Conductive polymer spray ionization mass spectrometry (CPSI-MS) is employed to record a wide range of metabolite species within a few seconds, making this technique appealing as a point-of-care method for the early detection of OSCC. Saliva samples from 373 volunteers, 124 who are healthy, 124 who have premalignant lesions, and 125 who are OSCC patients, were collected for discovering and validating dysregulated metabolites and determining altered metabolic pathways. Metabolite markers were reconfirmed at the primary tissue level by desorption electrospray ionization MS imaging (DESI-MSI), demonstrating the reliability of diagnoses based on saliva metabolomics. With the aid of machine learning (ML), OSCC and premalignant lesions can be distinguished from the normal physical condition in real time with an accuracy of 86.7%, on a person by person basis. These results suggest that the combination of CPSI-MS and ML is a feasible tool for accurate, automated diagnosis of OSCC in clinical practice.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Metabolômica , Neoplasias Bucais/diagnóstico , Saliva/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Testes Imediatos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
6.
PLoS One ; 15(7): e0236101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32678829

RESUMO

Dysregulation of histone demethylase Jumonji-C domain-containing protein 5 (JMJD5) has been identified as a great effect on tumorigenesis. Silibinin is a commonly used anti-hepatotoxic drug and exhibits anticancer effect in various cancers. However, the antitumor mechanism between silibinin and JMJD5 in oral squamous cell carcinoma (OSCC) remains unclear. In this study, the clinical significance of JMJD5 on OSCC patients was assessed through tissue microarray. Furthermore, mice bearing patient-derived tumor xenografts (PDTXs) and tongue cancer cell lines were treated with silibinin and evaluated for tumor growth and JMJD5 expression. High expression of JMJD5 in oral cancer was significantly associated with tumor size (P = 0.0241), cervical node metastasis (P = 0.0001) and clinical stage (P = 0.0002), was associated with worse survival rate compared with that of the total cohort (P = 0.0002). Collectively the data indicate that JMJD5 expression may be suitable for detection of unfavorable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. In addition, silibinin inhibits cancer growth in vitro and in PDTX models. Furthermore, metastasis-associated protein 1 (MTA1) could regulate the expression for JMJD5 and had a positive correlation with JMJD5. Moreover, silibinin could downregulate JMJD5 and MTA1 in oral cancer. Present study thus identifies that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression. In addition, silibinin is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating JMJD5 in OSCC, through a mechanism likely involving MTA1/JMJD5 axis.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Histona Desmetilases/metabolismo , Neoplasias Bucais/patologia , Proteínas Repressoras/metabolismo , Silibina/farmacologia , Transativadores/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/genética , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Prognóstico , Proteínas Repressoras/genética , Taxa de Sobrevida , Transativadores/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Med Hypotheses ; 143: 110089, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32673940

RESUMO

Extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, is a cell surface glycoprotein that belongs to the immunoglobulin superfamily and plays a significant role in intercellular recognition in immunology, cellular differentiation and development. Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. In the present paper, it is proposed that OSCC, by the virtue of upregulation of EMMPRIN expression, increases the susceptibility to coronavirus disease (COVID-19). In turn, COVID-19 in OSCC patients causes exhaustion of EMMPRIN receptor due to binding with 'S' receptor leading to a downregulation of related carcinogenesis events. We proposed that in the ACE-2 depleted situation in OSCC, EMMPRIN receptor might get high jacked by the COVID-19 virus for the entry into the host cells. Apart from the anti-monoclonal antibody, it is recommended to explore the use of grape seed and skin containing mouthwash as an adjunct, which could also have anti EMMPRIN effects in patients with OSCC and OPMDs.


Assuntos
Basigina/metabolismo , Infecções por Coronavirus/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais/metabolismo , Pneumonia Viral/metabolismo , Anticorpos Monoclonais , Betacoronavirus , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/metabolismo , Infecções por Coronavirus/complicações , Suscetibilidade a Doenças , Extrato de Sementes de Uva , Humanos , Neoplasias Bucais/complicações , Antissépticos Bucais , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Ligação Proteica
8.
J Cancer Res Ther ; 16(3): 546-550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719265

RESUMO

Background: The objective of this study was to evaluate the serum and salivary L-fucose in oral potentially malignant disorders (OPMDs) and oral cancer (OC) in order to investigate the possibility of using this as biomarker for early diagnosis. Materials and Methods: The study included 85 participants, who were grouped as control (30), OPMDs patients (25), and OC patients (30). Serum and unstimulated whole saliva were collected from participants of all groups and fucose estimation was done using spectrophotometry. The results were tabulated and analyzed statistically. Results: The mean serum L-fucose levels in normal, OPMDs, and OC group were 3.49, 19.18, and 35.75 mg/dl, respectively, while the levels of salivary L-fucose were 3.18, 7.02, and 11.66 mg/dl, respectively. A highly significant rise (P < 0.001) in serum and salivary L-fucose was observed in the study participants compared to control. Conclusions: The present study showed a significant and gradual increase in serum and salivary L-fucose from control to OPMDs to OC. From this study, we suggest that L-fucose can be used as a reliable biomarker and saliva can be used as a diagnostic fluid for screening and early detection of OC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/sangue , Fucose/metabolismo , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/sangue , Saliva/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Fucose/sangue , Fucose/química , Humanos , Masculino , Neoplasias Bucais/sangue , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Saliva/química
9.
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
10.
J Cancer Res Ther ; 16(3): 605-611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719275

RESUMO

Aim: This study aims to assess the usefulness of salivary sialic acid (SA) as a tumor marker in the detection of oral squamous cell carcinoma (OSCC) among tobacco chewers. Materials and Methods: After the approval of study protocol by the Institutional Ethics Committee and informed voluntary consent, salivary samples were collected from 96 participants in each group of tobacco chewers with OSCC, tobacco chewers without precancerous or cancerous lesion, and healthy controls. Salivary protein-bound SA (PBSA) and salivary-free SA (FSA) were measured by Yao et al.'s method of acid ninhydrin reaction, and the data were subjected to appropriate statistical analysis. Results: The salivary PBSA and FSA levels in the Groups 1, 2, and 3 participants were 31.17 ± 7.6 mg/dL and 63.45 ± 9.8 mg/dL, 25.45 ± 16.61 mg/dL and 33.18 ± 11.38 mg/dL, and 22.73 ± 3.01 mg/dL and 21.62 ± 8.86 mg/dL, respectively. Salivary FSA levels were significantly increased among the tobacco chewers with OSCC patients (Group 1) and tobacco chewers with no premalignant lesions of the oral cavity (Group 2) compared to the healthy controls (Group 3) with P < 0.05 being statistically significant. Salivary FSA levels were significantly increased in Group 1 as compared with Group 2. The salivary PBSA was high among Group 1 as compared to the control Group 3; there was however no significant difference in the levels of salivary PBSA between Group 1 and Group 2. There was no significant difference in the PBSA levels between OSCC patients of Group 1 and the tobacco chewers without precancerous or cancerous lesion in the oral cavity of Group 2. Conclusion: Salivary PBSA and FSA are significantly raised in both tobacco chewers with OSCC and in tobacco chewers with no precancerous or cancerous lesions in the oral cavity. SA should therefore be used cautiously while considering it as a marker for the early detection of oral cancer. Tobacco can be a crucial confounding factor when SA is used as a biomarker in OSCC since their levels are elevated to some extent even in tobacco chewers without any clinically obvious precancerous or cancerous lesions in the oral cavity.


Assuntos
Neoplasias Bucais/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Lesões Pré-Cancerosas/metabolismo , Saliva/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Uso de Tabaco/efeitos adversos , Uso de Tabaco/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Saliva/química , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Uso de Tabaco/patologia
11.
J Cancer Res Ther ; 16(3): 401-404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719243

RESUMO

To review the relevance of sialic acid as a tumour marker in oral cancer. Tumour marker are useful in the screening for early malignancy. Sialic acids are important in determining the surface properties of cells and has been implicated in cellular invasiveness, adhesiveness, and immunogenicity. Sialic acids are commonly found at the outermost end of glycan chains of all cell types. Increase in the levels of sialic acid in oral cancer indicates its importance as a tumour marker.Both serum and salivary sialic acid levels can be used as a screening tool and a diagnostic aid for oral cancer. Salivary sialic acid can be used as a non-invasive, cost effective and reliable diagnostic methods for screening and monitoring of oral cancer. In patients with oral cancer, glycoprotein metabolism is altered. Increase in the levels of sialic acid in oral cancer indicate its importance as a tumour marker. Changes in the serum is reflected in saliva. Salivary sialic acid can be used as non-invasive, cost effective and reliable diagnostic methods for screening and monitoring of oral cancer. Early the diagnosis, better the prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Bucais/diagnóstico , Ácido N-Acetilneuramínico/análise , Lesões Pré-Cancerosas/diagnóstico , Saliva/metabolismo , Carcinoma de Células Escamosas/metabolismo , Humanos , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/metabolismo , Prognóstico , Saliva/química
12.
J Cancer Res Ther ; 16(3): 452-457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719250

RESUMO

Introduction: Cytokeratin fragment 21-1 (CYFRA21-1), a constituent of the intermediate filament protein is known to be elevated in cancer. In vitro cleavage of cytokeratin 19 (CK19) protein results in the release of it's fragments into the supernatants of premalignant cell lines. This study was designed with the aim to investigate the concentrations of CYFRA21-1 in serum and saliva of oral potentially malignant disorders (OPMD), to evaluate CK19 expression in tissues of the same patients and to correlate the levels of CYFRA21-1 concentration in serum and saliva with CK19 expression in OPMDs, and to compare it with oral squamous cell carcinoma (OSCC), which was taken as positive control. Materials and Methods: Concentration of CYFRA21-1 was measured in saliva and serum of 30 OPMD cases with five patients having OSCC using ELISA technique and analysis of CK19 protein expression in the tissue of same patients using immunohistochemical technique was done. Results: Concentration of CYFRA21-1 in saliva and serum with regard to CK19 protein expression in tissues was significantly higher in control group than in study groups. Conclusion: CYFRA21-1 can be used as a promising diagnostic molecule and as an adjunctive marker for early detection, disease staging, and monitoring.


Assuntos
Antígenos de Neoplasias/análise , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Queratina-19/análise , Queratina-19/metabolismo , Neoplasias Bucais/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Saliva/metabolismo , Adulto , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/metabolismo
13.
J Cancer Res Ther ; 16(3): 494-499, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719256

RESUMO

Introduction: Conventional oral squamous cell carcinoma (OSCC) is relatively easy to diagnose on histopathology, as it comprises dysplastic epithelial cells with variable degrees of squamous differentiation. Different grading systems have been employed in grading OSCC based on its dysplastic features and host response. Some unusual features such as clear cell change, epithelial-mesenchymal transition (EMT), stromal hyalinization, stromal desmoplasia, perineural invasion, vascular invasion, tissue eosinophilia, giant cells, and tertiary lymphoid follicle formation are evident in OSCC histologically but have not yet been accounted in any grading systems of OSCC except perineural and vascular invasion. Aim: The aim of the present study was to identify these uncommon features and to correlate them with different grades of OSCC.Materials and Methods:This study was conducted on 100 histopathologically confirmed OSCC cases retrieved from the archives of our department. They were graded on the basis of Broder's grading system and were reviewed for the features mentioned above. Data collected were subjected to statistical analysis. Results: Clear cell change, EMT, foreign body giant cells, and tumor giant cells were observed in 13%, 20%, 1%, and 3% of cases, respectively. We found stromal desmoplasia in 15% and stromal hyalinization in 9% of cases. Tissue eosinophilia, tertiary lymphoid follicle formation, and perineural invasion were observed in 12%, 3%, and 2% of cases, respectively. Vascular invasion was not evident in any of the cases examined. Conclusion: The incidence of the unusual features was 7.8% in our study.


Assuntos
Carcinoma de Células Escamosas/patologia , Eosinófilos/patologia , Transição Epitelial-Mesenquimal , Neoplasias Bucais/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
14.
Immunol Med ; 43(3): 121-129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32546118

RESUMO

The roles of interleukin-22 (IL-22) in carcinogenesis have been proposed in various neoplasms. Increased expression of IL-22 has been observed in oral squamous cell carcinoma (OSCC) lesions as well as in other cancers. OSCC is still associated with poor prognosis and a high mortality rate because of its invasiveness and frequent lymph node metastasis. In the present study, we investigated the effects of IL-22 on OSCC cells. The human OSCC cell lines Ca9-22 and SAS were stimulated with IL-22 (1-10 ng/mL), and their migration abilities were examined using a cell scratch assay. A Matrigel invasion assay was performed to evaluate the invasion abilities of OSCC cells. Signal transducer and activator of transcription 3 (STAT3) phosphorylation, matrix metalloproteinase (MMP) and epithelial-mesenchymal transition (EMT)-related genes and proteins were also examined. IL-22 treatment promoted the migration and invasion abilities of OSCC cells without increasing their viability. IL-22 stimulation also induced STAT3 phosphorylation, MMP-9 activity and EMT-related genes and proteins. Our findings suggest that IL-22 has possible roles in the development of OSCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Movimento Celular/efeitos dos fármacos , Interleucinas/efeitos adversos , Interleucinas/fisiologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Invasividade Neoplásica/genética , Fosforilação/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
15.
Anticancer Res ; 40(5): 2467-2474, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366390

RESUMO

BACKGROUND/AIM: The hormonally-active form of vitamin D, 1,25(OH)2D3, demonstrated activity against oral squamous cell carcinoma (OSCC). Cytochrome P450scc (CYP11A1)-derived vitamin D hydroxyderivatives, such as 20(OH)D3 and 1,20(OH)2D3, have overlapping beneficial effects with 1,25(OH)2D3 without causing hypercalcemia. This study sought to determine (i) whether 20(OH)D3 and 1,20(OH)2D3 exhibit antitumor effects against OSCC comparable to those of 1,25(OH)2D3 and (ii) whether these effects may stem from down-regulation of sonic hedgehog (SHH) or WNT/ß-catenin signaling pathways. MATERIALS AND METHODS: Effects on CAL-27 cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt and spheroid assays. Signaling pathways were assessed by immunofluorescence and western blotting. RESULTS: 20(OH)D3 and 1,20(OH)2D3 inhibited the growth of CAL-27 and demonstrated inhibition of WNT/ß-catenin and the SHH signaling as evidenced by down-regulation of nuclear translocation of glioma-associated oncogene 1(GLI1) and ß-catenin. CONCLUSION: Noncalcemic vitamin D hydroxyderivatives demonstrated antitumor activities against OSCC comparable to those of 1,25(OH)2D3 Their activities against SHH and the WNT/ß-catenin pathways provide insight for a possible target for OSCC treatment.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Proteínas Hedgehog/metabolismo , Neoplasias Bucais/metabolismo , Vitamina D/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Biomarcadores , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Núcleo Celular , Imunofluorescência , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/etiologia , Neoplasias Bucais/patologia , Transporte Proteico , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico , beta Catenina/metabolismo
16.
Life Sci ; 254: 117695, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407849

RESUMO

AIMS: To investigate the therapeutic potential of itraconazole in oral squamous cell carcinoma (OSCC) and its molecular mechanism. MATERIALS AND METHODS: The in vitro anti-cancer effects of itraconazole was determined by CCK-8 assay and colony formation assay. Transwell and wound healing assays were used to examine cell invasion and migration. The in vivo therapeutic efficacy of itraconazole was assessed by OSCC patient-derived xenograft (PDX) model. Western blot was performed to explore the anti-cancer mechanism. KEY FINDINGS: Itraconazole inhibited cell proliferation and colony formation of OSCC cells in a time and concentration dependent manner; induced cell cycle arrest and apoptosis, as well as inhibited cell invasion and migration. In the OSCC PDX model, itraconazole impeded tumor growth, reduced Ki-67 expression and induced apoptosis. Itraconazole downregulated the protein expression of Hedgehog pathway to inhibit proliferation and migration of oral squamous cell carcinoma cells, which can be revised by recombinant human sonic hedgehog protein (rSHH). SIGNIFICANCE: Itraconazole showed anti-cancer effects on OSCC via inhibiting the Hedgehog pathway.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/patologia , Proteínas Hedgehog/antagonistas & inibidores , Itraconazol/farmacologia , Neoplasias Bucais/patologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Humanos , Neoplasias Bucais/metabolismo
17.
Cancer Sci ; 111(7): 2385-2399, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32385953

RESUMO

The tumor microenvironment (TME) consists of various components including cancer cells, tumor vessels, cancer-associated fibroblasts (CAFs), and inflammatory cells. These components interact with each other via various cytokines, which often induce tumor progression. Thus, a greater understanding of TME networks is crucial for the development of novel cancer therapies. Many cancer types express high levels of TGF-ß, which induces endothelial-to-mesenchymal transition (EndMT), leading to formation of CAFs. Although we previously reported that CAFs derived from EndMT promoted tumor formation, the molecular mechanisms underlying these interactions remain to be elucidated. Furthermore, tumor-infiltrating inflammatory cells secrete various cytokines, including TNF-α. However, the role of TNF-α in TGF-ß-induced EndMT has not been fully elucidated. Therefore, this study examined the effect of TNF-α on TGF-ß-induced EndMT in human endothelial cells (ECs). Various types of human ECs underwent EndMT in response to TGF-ß and TNF-α, which was accompanied by increased and decreased expression of mesenchymal cell and EC markers, respectively. In addition, treatment of ECs with TGF-ß and TNF-α exhibited sustained activation of Smad2/3 signals, which was presumably induced by elevated expression of TGF-ß type I receptor, TGF-ß2, activin A, and integrin αv, suggesting that TNF-α enhanced TGF-ß-induced EndMT by augmenting TGF-ß family signals. Furthermore, oral squamous cell carcinoma-derived cells underwent epithelial-to-mesenchymal transition (EMT) in response to humoral factors produced by TGF-ß and TNF-α-cultured ECs. This EndMT-driven EMT was blocked by inhibiting the action of TGF-ßs. Collectively, our findings suggest that TNF-α enhances TGF-ß-dependent EndMT, which contributes to tumor progression.


Assuntos
Transição Epitelial-Mesenquimal , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Biomarcadores , Fibroblastos Associados a Câncer/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Células Cultivadas , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , NF-kappa B/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Microambiente Tumoral/genética , Fator de Necrose Tumoral alfa/farmacologia
18.
Res Vet Sci ; 131: 7-14, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32278962

RESUMO

Melanoma progression is associated with the epithelial-mesenchymal transition (EMT) when tumor cells reduce E-cadherin and increase N-cadherin expression resulting in an escape from the microenvironment via loss of cellular adhesion and gain of motility. Transcription factor proteins Snail and ZEB trigger EMT by repression of epithelial markers and activation of mesenchymal properties. This study evaluated E-cadherin, N-cadherin, Snail, ZEB1 and ZEB2 expression by IHC and investigated their relationship with morphological characteristics in cutaneous and oral canine melanoma. Results from melanoma cases demonstrated E-cadherin expression in 45% (9/20) of oral and 58% (22/38) of cutaneous tumors, while N-cadherin expression was observed in 95% (18/19) of oral and 92% (34/37) of cutaneous melanoma. Cytoplasmic and nuclear N-cadherin expression was positively correlated with ZEB1 expression, while the cell membrane N-cadherin expression was positively correlated with ZEB2. In addition, an increase in nuclear N-cadherin expression was associated with reduced Snail expression in cutaneous melanoma and an increase in Snail expression in oral melanoma, indicating that the correlation between N-cadherin and Snail expression is coincident with tumor location. Our data suggest that ZEB family protein is associated with N-cadherin translocation from cell membrane to the cytoplasm and nuclei, and may act as important transcription factors of EMT regulation in canine melanoma.


Assuntos
Doenças do Cão/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Melanoma/veterinária , Neoplasias Cutâneas/veterinária , Fatores de Transcrição da Família Snail/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Animais , Caderinas/metabolismo , Adesão Celular , Movimento Celular , Doenças do Cão/genética , Cães , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/veterinária , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
19.
Cancer Sci ; 111(5): 1774-1784, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32112605

RESUMO

The signal transducer and activator of transcription 3 (STAT3) signaling pathway is a key mediator of cancer cell proliferation, survival and invasion. Aberrant STAT3 has been demonstrated in various malignant cancers. YHO-1701 is a novel quinolinecarboxamide derivative generated from STX-0119. Here, we examined the effect of YHO-1701 on STAT3 and evaluated antitumor activity of YHO-1701 as a single agent and in combination. YHO-1701 inhibited STAT3-SH2 binding to phospho-Tyr peptide selectively and more potently than STX-0119 in biochemical assays. Molecular docking studies with STAT3 suggested more stable interaction of YHO-1701 with the SH2 domain. YHO-1701 exhibited approximately 10-fold stronger activity than STX-0119 in abrogating the STAT3 signaling pathway of human oral cancer cell line SAS. YHO-1701 also blocked multi-step events by inhibiting STAT3 dimerization and suppressed STAT3 promoter activity. As expected, YHO-1701 exerted strong antiproliferative activity against human cancer cell lines addicted to STAT3 signaling. Orally administered YHO-1701 showed statistically significant antitumor effects with long exposure to high levels of YHO-1701 at tumor sites in SAS xenograft models. Moreover, combination regimen with sorafenib led to significantly stronger antitumor activity. In addition, the suppression level of survivin (a downstream target) was superior for the combination as compared with monotherapy groups within tumor tissues. Thus, YHO-1701 had a favorable specificity for STAT3 and pharmacokinetics after oral treatment; it also contributed to the enhanced antitumor activity of sorafenib. The evidence presented here provides justification using for this approach in future clinical settings.


Assuntos
Antineoplásicos/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Interleucina-6/sangue , Camundongos , Simulação de Acoplamento Molecular , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Oxidiazóis/química , Oxidiazóis/farmacologia , Multimerização Proteica/efeitos dos fármacos , Quinolinas/química , Quinolinas/farmacologia , Fator de Transcrição STAT3/química , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Survivina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Domínios de Homologia de src
20.
Cancer Sci ; 111(5): 1491-1499, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32167621

RESUMO

Human leukocyte antigen (HLA) class Ⅰ molecules play a central role in anticancer immunity, but their prognostic value in oral squamous cell carcinoma (OSCC) remains unclear. We examined HLA class I expression in 2 distinct tumor compartments, namely, the tumor center and invasive front, and evaluated the association between its expression pattern and histopathological status in 137 cases with OSCC. Human leukocyte antigen class Ⅰ expression was graded semiquantitatively as high, low, and negative. At the invasive front of the tumor, HLA class I expression was high in 72 cases (52.6%), low in 44 cases (32.1%), and negative in 21 cases (15.3%). The HLA class I expression in the tumor center was high in 48 cases (35.0%), low in 58 cases (42.4%), and negative in 31 cases (22.6%). The 5-year overall survival and disease-specific survival rates were good in cases with high HLA class I expression at the invasive front; however, there was no significant difference in survival based on HLA class I expression in the tumor center. In addition, high HLA class I expression was correlated with high CD8+ T cell density, whereas negative HLA class I expression was correlated with low CD8+ T cell density at the invasive front. These results suggest that it is easier for CD8+ T cells to recognize presented peptides in the case of high HLA class Ⅰ expression at the tumor invasive front and could be a prognostic factor for OSCC.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/metabolismo , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA