RESUMEN

OBJECTIVE: Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells. METHODS: Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies. RESULTS: Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53. CONCLUSIONS: This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions.

Asunto(s)

Carcinoma de Células Escamosas , Metformina , Neoplasias de la Boca , Fármacos Sensibilizantes a Radiaciones , Humanos , Metformina/farmacología , Metformina/uso terapéutico , Neoplasias de la Boca/radioterapia , Fármacos Sensibilizantes a Radiaciones/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Tolerancia a Radiación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proteómica , Gliceraldehído-3-Fosfato Deshidrogenasas , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante) , Hipoxia de la Célula/efectos de los fármacos , Hipoxia Tumoral/efectos de los fármacos

RESUMEN

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. The current study aimed to identify potential biomarkers associated with OSCC survival. MATERIALS AND METHODS: Differentially expressed genes (DEGs) in atypical OSCC cases were identified using two public datasets: The Cancer Genome Atlas and the Gene Expression Omnibus database. Receiver operating characteristic (ROC) analysis was performed to identify the cutoff, and the candidate DEGs related to survival. Kaplan-Meier and Cox regression analysis using the categorized genes were employed to identify genes that impact the overall survival in OSCC. RESULTS: A total of 263 OSCC samples and 105 healthy tissues were used to identify 295 upregulated and 131 downregulated genes expressed only in non-smokers. ROC analyses identified 25 candidate genes associated with death. Survival analyses demonstrated that the following DEGs, namely CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5, are potential OSCC prognostic factors. CONCLUSION: We found that CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5 are associated with a low survival rate in OSCC. However, further studies are needed to validate our findings and facilitate the development of these factors as potential biomarkers for OSCC survival.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas/patología , Transcriptoma , Neoplasias de la Boca/metabolismo , Regulación Neoplásica de la Expresión Génica , Análisis de Supervivencia , Biomarcadores de Tumor/genética , Neoplasias de Cabeza y Cuello/genética , Pronóstico

RESUMEN

Differences in the features of aggressiveness of non-melanoma skin cancer (NMSC) subtypes, between basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are relevant characteristics. Comparing the characteristics between NMSC subtypes might help identify molecules associated with cancer metastasis and invasion. Considering these facts, the current study aimed to identify a molecular target for inhibiting skin cancer metastasis and invasion. Proteomic analysis suggested that heat shock protein 90 kDa, alpha, class B member 1 (HSP90AB1), pentaxin (PTX3), caspase-14 (CASP14), S100, actin-1, and profilin were the primary targets related to metastasis and invasion. However, after a differential expression comparison between BCC and SCC, HSP90AB1 was identified as the best target to repress metastasis and invasion. Based on molecular docking results, gallic acid (GA) was selected to inhibit HSP90AB1. A specific Hsp90ab1 siRNA targeting was designed and compared to GA. Interestingly, GA was more efficient in silencing HSP90AB1 than siRNAhsp90ab1. Hence, our data suggest that HSP90AB1 is a crucial biomarker for identifying invasion and metastasis and that its inhibition may be a viable strategy for treating skin cancer.

Asunto(s)

Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Proteínas de Choque Térmico , Ácido Gálico/farmacología , Proteómica , Simulación del Acoplamiento Molecular , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Proteínas HSP90 de Choque Térmico/genética

RESUMEN

The aim of this study is to investigate the antineoplastic potential of photodynamic therapy (PDT) mediated by an aluminum-phthalocyanine chloride nanoemulsion (AlPc-NE), against an oral squamous cell carcinoma (OSCC) cell line in vitro. Both OSCC (SCC9) and A431 cell lines were studied in vitro. Four study groups were used: Group 1 (phosphate-buffered saline [PBS]), Group 2 (PBS + 28.3 J/cm2 irradiation), Group 3 (AlPc-NE alone), and Group 4 (AlPc-NE + 28.3 J/cm2 irradiation). To test the effect of PDT with AlPc-NE, cell viability, migration, and cell death assays were performed. Moreover, the expressions of Ki-67 and TP53 were evaluated using immunoassays. The results showed that PDT mediated by all AlPc-NE concentrations evaluated (i.e., 0.7, 0.35, and 0.17 nM AlPc) significantly reduced the viability of SCC9 cells. Migration and cell death assays also revealed that PDT with AlPc-NE significantly reduced the rate of migration and increased cell death compared to the control groups. In addition, it was found that PDT with AlPc-NE reduced Ki-67 and mutated TP53 immunoexpression. PDT with AlPc-NE is effective in reducing the viability and migration of SCC9. Moreover, PDT with AlPc-NE nanoemulsions reduces the cell proliferation and expression of mutant TP53.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de la Boca , Nanopartículas , Compuestos Organometálicos , Fotoquimioterapia , Aluminio , Carcinoma de Células Escamosas/tratamiento farmacológico , Humanos , Isoindoles , Antígeno Ki-67 , Neoplasias de la Boca/tratamiento farmacológico , Compuestos Organometálicos/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico

RESUMEN

BACKGROUND: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases. OBJECTIVE: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells. METHODS: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards. RESULTS: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation. CONCLUSION: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts.

Asunto(s)

Anticarcinógenos/farmacología , Antineoplásicos Fitogénicos/farmacología , Carcinogénesis/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Proteínas de Neoplasias/genética , Anticarcinógenos/química , Anticarcinógenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Brasil , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Proliferación Celular/efectos de los fármacos , Biología Computacional/métodos , Etopósido/química , Etopósido/aislamiento & purificación , Etopósido/farmacología , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Irinotecán/química , Irinotecán/aislamiento & purificación , Irinotecán/farmacología , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Paclitaxel/química , Paclitaxel/aislamiento & purificación , Paclitaxel/farmacología , Extractos Vegetales/química , Plantas Medicinales , Vinblastina/química , Vinblastina/aislamiento & purificación , Vinblastina/farmacología

RESUMEN

Cancer patients present a higher risk of experiencing anxiety disorders (AD). However, it is not clear if AD might be associated with cancer development. Thus, our study aimed to evaluate if AD might be related to head and neck squamous cell carcinoma (HNSCC) development. The combination of an applied animal basic study and a retrospective diagnostic case and control study in patients was performed. As a result, we obtained that stress reduced the locomotor activity of the animals in the group stress and stress + 4NqO (p < 0.0001). The stress showed no influence on the progression of neoplasia in mice. In the same way, the case group did not present differences in anxiety scores in comparison to control. Moreover, no association between HNSCC staging and anxiety scores was observed. In conclusion, our in vivo findings in humans and animals have shown that there is no relationship between AD and oral squamous cell carcinoma.

RESUMEN

Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.

Asunto(s)

Hipoxia de la Célula/efectos de la radiación , Subunidad alfa del Factor 1 Inducible por Hipoxia/efectos de la radiación , L-Lactato Deshidrogenasa/efectos de la radiación , MicroARNs/efectos de la radiación , Radioterapia/efectos adversos , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , L-Lactato Deshidrogenasa/sangre , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Tolerancia a Radiación , Adulto Joven

RESUMEN

OBJECTIVE: Malignant salivary gland tumors (MSGTs) present different phenotypic characteristics and various clinical outcomes, which proved to be a diagnostic challenge. Considering the heterogeneity of MSGT, this study aims to identify molecule related to the nature of MSGT. METHODS: For screening, proteomic analysis comparing MSGT with pleomorphic adenoma (PA) and salivary gland was performed. The MSGT-associated protein which presented in the higher number in the Gene Expression Omnibus (GEO) database was selected. To validate the data, immunohistochemistry (IHC) was performed in 14 patients with PA, 22 patients with MSGT, and 14 controls. RESULTS: 16 proteins were associated with MSGT. ANXA2 was the primary protein, according to GEO database analyses. ANXA2 was most expressed in the cell membrane. However, some ANXA2 staining was also observed in the cytoplasm and nucleus. ANXA2 was highly expressed in MSGT in comparison with control. Also, ANXA2 has a higher expression in adenocarcinoma not otherwise specified (ANOS) and myoepithelial carcinoma (MC) in comparison with PA. CONCLUSION: In conclusion, this study demonstrated that MSGT presented higher levels of ANXA2 in comparison with normal salivary glands. Also, ANXA2 might be interesting as a molecular marker of ANOS and MS.

Asunto(s)

Adenoma Pleomórfico/metabolismo , Anexina A2/metabolismo , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Neoplasias de las Glándulas Salivales/metabolismo , Adenoma Pleomórfico/patología , Biomarcadores de Tumor/metabolismo , Carcinoma Adenoide Quístico/patología , Carcinoma Mucoepidermoide/patología , Estudios de Casos y Controles , Humanos , Proteoma , Proteómica , Neoplasias de las Glándulas Salivales/patología

RESUMEN

BACKGROUND: There is significant controversy in the literature regarding the relationship between hypoxia and salivary gland neoplasms (SGNs). OBJECTIVE: The current study aims to investigate levels of hypoxia markers in both benign and malignant salivary neoplasms. PATIENTS AND METHODS: The current study sample is comprised of a total of 62 samples. HIF-1α expression was evaluated by immunohistochemistry. Additionally, HIF-1α mRNA and miR-210 levels were assessed using qRT-PCR. RESULTS: No differences in HIF-1α expression were observed among the control group, benign and malignant SGNs. Similarly, HIF-1α mRNA levels were similar between benign and malignant SGNs. Also, there was no difference in miR-210 expression between case and control groups. CONCLUSION: The angiogenic markers, miR-210 and HIF-1α, do not appear to distinguish malignancy in salivary glands.

Asunto(s)

Biomarcadores de Tumor/biosíntesis , Regulación Neoplásica de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neovascularización Patológica/metabolismo , Neoplasias de las Glándulas Salivales , Estudios Transversales , Femenino , Humanos , Masculino , MicroARNs/biosíntesis , Neovascularización Patológica/patología , ARN Neoplásico/biosíntesis , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/irrigación sanguínea , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología

RESUMEN

BACKGROUND: Metformin is a biguanide, belonging to the oral hypoglycemic agents and is a widely used in the treatment of type 2 diabetes. Evidence indicate that Metformin inhibits cell proliferation in several human cancers and inhibits the Warburg phenomenon in tumor cells. RESULTS: Low PDH levels were observed in OSCC, and Metformin promotes an increase in PDH levels in hypoxic conditions. Metformin also reduced HIF-1α mRNA and protein levels. Metformin demonstrated antiproliferative effects, inhibited migration, increased the number of apoptotic cells and increased the transcription of caspase 3. OBJECTIVE: The present study aims to explore the effects of Metformin in hypoxic conditions. Specifically, we focused on pyruvate dehydrogenase (PDH), (hypoxia-inducible factor 1α) HIF-1α levels and the oral squamous cell carcinoma (OSCC) cell phenotype. Additionally, we also investigated a theoretical consequence of Metformin treatment. METHODS: PDH levels in patients with OSCC and oral dysplasia were evaluated. Metformin was administered in vitro to test the effect of Metformin under hypoxic conditions. The results were complemented by Bioinformatics analyses. CONCLUSIONS: In conclusion, our current findings show that Metformin reduces HIF-1α gene expression and increases PDH expression. Metformin inhibits cell proliferation and migration in the OSCC cell line model. Additionally, Metformin enhances the number of apoptotic cells and caspase 3 levels. Interestingly enough, Metformin did not increase the mutant p53 levels under hypoxic conditions.

Asunto(s)

Carcinoma de Células Escamosas/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Metformina/farmacología , Neoplasias de la Boca/genética , Complejo Piruvato Deshidrogenasa/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Hipoxia de la Célula , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Complejo Piruvato Deshidrogenasa/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is considered a serious public health problem in many countries. Recently, genetic variations have been considered as important factors to cancer susceptibility and prognosis. More specifically, genetic polymorphisms have been associated with the development and prognosis of HNSCC. The purpose of the current study was to investigate an association among p16 (CDKN2A) gene polymorphism at rs11515, age, and HNSCC aggressiveness. PCR-RFLP analysis was used to investigate the p16 (CDKN2A) gene in 96 patients with HNSCC and in 100 individuals without HNSCC. A case group was categorized by age in younger (<60 years) and older (≥ 60 years) patients. Differences between the case and control groups were determined using Fisher and chi-squared tests. Time of survival was calculated from the date of diagnosis to the date of last follow-up visit or to the date of death using the Kaplan-Meier estimator and comparing this to the log-rank test. Statistical significance was set at p<0.05. In the present study, no association was established between HNSCC and rs11515 polymorphism, as indicated in a previous study. We found that HNSCC individuals with large-sized tumors and with metastatic disease presented worse overall survival, consistent with fundamental concepts that establish the effects of tumor size and lymph node metastasis to HNSCC outcomes. This study identified that there is no difference in the distribution of rs11515 between the control and HNSCC groups. In addition, no differences between rs11515 genotypes and clinicopathological parameters were observed.

Asunto(s)

Carcinoma de Células Escamosas/genética , Neoplasias de Cabeza y Cuello/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello