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1.
Oral Dis ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38380784

RESUMO

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

2.
J Oral Pathol Med ; 52(7): 601-609, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247331

RESUMO

BACKGROUND: The expression of heat-shock protein 47 (HSP47) has been linked to collagen synthesis control and implicated in fibrotic disorders, but more recent studies have demonstrated its role in solid tumors. In this study, we explored the prognostic impact of HSP47 in oral squamous cell carcinomas (OSCC) and determined the in vitro effects of its loss-of-function on viability, proliferation, migration, invasion, and resistance to cisplatin of OSCC cells. METHODS: The HSP47 expression in tumor samples was assessed by immunohistochemistry in two independent cohorts totaling 339 patients with OSCC, and protein levels were associated with clinicopathological features and survival outcomes. The OSCC cell lines HSC3 and SCC9 were transduced with lentivirus expressing short hairpin RNA to stably silence HSP47 and used in assays to measure cellular viability, proliferation, migration, and invasion. RESULTS: HSP47 was overexpressed in OSCC samples, and its overexpression was significantly and independently associated with poor disease-specific survival and shortened disease-free survival in both OSCC cohorts. The knockdown of HSP47 showed no effects on cell viability or cisplatin sensitivity, but impaired significantly proliferation, migration, and invasion of OSCC cells, with stronger effects on SCC9 cells. CONCLUSION: Our results show a significant prognostic impact of HSP47 overexpression in OSCC and reveal that HSP47 inhibition impairs the proliferation, migration, and invasion of OSCC cells. HSP47 may represent a potential therapeutic target for OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteínas de Choque Térmico HSP47/genética , Proteínas de Choque Térmico HSP47/metabolismo , Neoplasias Bucais/patologia , Cisplatino/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética
3.
Oral Dis ; 28(4): 1085-1093, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33615627

RESUMO

BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) has unclear clinical role in oral squamous cell carcinomas (OSCC). Here, we investigated the association of TROP2 immunoexpression with clinicopathological parameters and survival of OSCC patients. SUBJECTS AND METHODS: Cancer-specific survival (CSS) and disease-free survival (DFS) were assessed in a cohort composed of 266 OSCC. An independent cohort with 88 OSCC samples matched with the normal oral tissue, as well as 17 metastatic lymph nodes, was used for validation. RESULTS: Multivariate analysis showed TROP2 as an independent marker of favorable prognosis for both CSS (HR: 0.60, 95% CI: 0.40-0.90, p = .01) and DFS (HR: 0.57, 95% CI: 0.36-0.89, p = .01). Furthermore, TROP2 protein expression was significantly higher in morphologically normal tissues compared to primary tumors (p < .0001) and lymph node metastases (p = .001), and it was significantly associated with CSS (HR: 0.26, 95% CI: 0.09-0.74, p = .008) in the validation cohort. A pooled mRNA analysis performed on the Oncomine™ database confirmed the underexpression in OSCC compared with normal tissues (p = .014). CONCLUSIONS: In summary, our results point to a favorable prognostic significance of TROP2 overexpression in a large cohort of oral cancer patients, suggesting it as an attractive clinical marker.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Carcinoma de Células Escamosas/patologia , Moléculas de Adesão Celular/genética , Humanos , Neoplasias Bucais/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Trofoblastos/metabolismo , Trofoblastos/patologia
4.
Oral Dis ; 28(6): 1561-1572, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34263964

RESUMO

OBJECTIVE: To report the clinicopathologic features of acquired oral syphilis cases in South American countries. MATERIALS AND METHODS: Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. RESULTS: The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3 years. Individuals aged 20-29 years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. CONCLUSION: This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries.


Assuntos
Doenças da Boca , Sífilis , Adulto , Brasil/epidemiologia , Humanos , Masculino , Doenças da Boca/diagnóstico , Doenças da Boca/tratamento farmacológico , Doenças da Boca/epidemiologia , Palato Duro , Estudos Retrospectivos , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sífilis/epidemiologia , Adulto Jovem
5.
Int J Mol Sci ; 24(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36613922

RESUMO

The interaction between malignant cells and the tumor microenvironment is critical for tumor progression, and the chemokine ligand/receptor axes play a crucial role in this process. The CXCR4/CXCL12 and CCR5/CCL5 axes, both related to HIV, have been associated with the early (epithelial-mesenchymal transition and invasion) and late events (migration and metastasis) of cancer progression. In addition, these axes can also modulate the immune response against tumors. Thus, antagonists against the receptors of these axes have been proposed in cancer therapy. Although preclinical studies have shown promising results, clinical trials are needed to include these drugs in the oncological treatment protocols. New alternatives for these antagonists, such as dual CXCR4/CCR5 antagonists or combined therapy in association with immunotherapy, need to be studied in cancer therapy.


Assuntos
Antagonistas dos Receptores CCR5 , Carcinoma , Receptores CXCR4 , Humanos , Carcinoma/tratamento farmacológico , Quimiocina CXCL12 , Receptores CCR5 , Receptores CXCR4/antagonistas & inibidores , Transdução de Sinais , Microambiente Tumoral , Antagonistas dos Receptores CCR5/uso terapêutico
6.
J Prosthet Dent ; 128(5): 886-896, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33715834

RESUMO

STATEMENT OF PROBLEM: Established restorative protocols for patients after head and neck radiotherapy are lacking, increasing the failure rates of dental adhesive restorations. PURPOSE: The purpose of this systematic review and meta-analysis was to analyze the evidence regarding the impact of head and neck radiotherapy on the longevity of dental adhesive restorations. MATERIAL AND METHODS: A search was performed using PubMed, Scopus, and Embase in May 2018 (updated in November 2020). Data extraction was performed regarding the percentage of restoration failure among dental adhesive materials, including glass ionomer cements, resin-modified glass ionomer cements, and composite resins. Risk of bias was assessed by the meta-analysis of statistics assessment and review instrument (MAStARI). Confidence in cumulative evidence was evaluated by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. RESULTS: Four studies met the inclusion criteria. All included studies were classified as having a moderate risk of bias and reported results regarding class V restorations. Overall, composite resins presented lower failure rates at 2 years (30%) when compared with resin-modified glass ionomer (41%) and glass ionomer cements (57%). Meta-analysis showed that the risk of failure with glass ionomer cements was greater than with resin-modified glass ionomer cements (RR: 1.71, P<.001). Composite resins presented lower risk of failure when compared with glass ionomer (RR: 2.29, P<.001) and resin-modified glass ionomer cements (RR: 1.30, P=.03). Three studies reported results regarding fluoride compliance, which had a negative effect on the survival rates of glass ionomer and resin-modified glass ionomer cements and a positive effect on composite resin restorations. CONCLUSIONS: The results suggest that composite resin restorations associated with fluoride gel compliance seems to be the best alternative for restoring class V lesions in patients after head and neck radiotherapy. However, the results showed moderate certainty of evidence, which justifies the need for more randomized clinical trials regarding this subject.


Assuntos
Adaptação Marginal Dentária , Restauração Dentária Permanente , Humanos , Restauração Dentária Permanente/métodos , Fluoretos , Falha de Restauração Dentária , Cimentos de Ionômeros de Vidro/uso terapêutico , Resinas Compostas/uso terapêutico , Cimentos de Resina
7.
Int J Exp Pathol ; 102(6): 242-248, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34791724

RESUMO

Optogenetics is a molecular biological technique involving transfection of cells with photosensitive proteins and the subsequent study of their biological effects. The aim of this study was to evaluate the effect of blue light on the survival of HeLa cells, transfected with channelrhodopsin-2 (ChR2). HeLa wild-type cells were transfected with a plasmid that contained the gene for ChR2. Transfection and channel function were evaluated by real-time polymerase chain reaction (RT-PCR), fluorescence imaging using green fluorescent protein (GFP) and flow cytometry for intracellular calcium changes using a Fura Red probe. We developed a platform for optogenetic stimulation for use within the cell culture incubator. Different stimulation procedures using blue light (467 nm) were applied for up to 24 h. Cell survival was determined by flow cytometry using propidium iodide and rhodamine probes. Change in cell survival showed a statistically significant (p < 0.05) inverse association with the frequency and time of application of the light stimulus. This change seemed to be associated with the ChR2 cis-trans-isomerization cycle. Cell death was associated with high concentrations of calcium in the cytoplasm and stimulation intervals less than the period of isomerization. It is possible to transfect HeLa cells with ChR2 and control their survival under blue light stimulation. We suggest that this practice should be considered in the future development of optogenetic systems in biological or biomedical research.


Assuntos
Sobrevivência Celular/fisiologia , Cálcio/metabolismo , Ciclo Celular/fisiologia , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Células HeLa , Humanos , Optogenética , Transfecção
8.
J Oral Pathol Med ; 50(6): 613-621, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34089204

RESUMO

BACKGROUND: Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a single lesion (plasmacytoma) or as multiple lesions (multiple myeloma). METHODS: Paraffin-embedded tissue blocks of patients microscopically diagnosed with plasma cell neoplasms in the jaws were retrieved from five pathology files. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed and follow-up status were retrieved from the pathology reports. RESULTS: Fifty-two cases were retrieved (mean age: 59.4 years) without sex predilection. The mandible was the most affected site (67.3%), usually associated with pain and/or paresthesia (53.8%). Lesions in other bones besides the jaws were reported for 24 patients (46.2%). Radiographically, tumours usually presented as poorly defined osteolytic lesions with unilocular or multilocular images, while microscopy revealed diffuse proliferation of neoplastic plasma cells with nuclear displacement and abundant eosinophilic cytoplasm. Two cases were classified as anaplastic, and amyloid deposits were found in two other cases. Immunohistochemistry was positive for plasma cell markers and negative for CD20 and CD3, and monoclonality for kappa light chain predominated. The overall survival rate after 5 years of follow-up was 26.6%. CONCLUSION: Plasma cell neoplasms are aggressive tumours with a poor prognosis and involvement of the jaws may be the first complaint of the patient. Thus, oral pathologists, head and neck surgeons and dentists should be aware of their clinical, radiographic and microscopic manifestations.


Assuntos
Mieloma Múltiplo , Neoplasias de Plasmócitos , Plasmocitoma , Humanos , Imuno-Histoquímica , Arcada Osseodentária/diagnóstico por imagem , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico por imagem , Neoplasias de Plasmócitos/diagnóstico por imagem , Plasmocitoma/diagnóstico por imagem
9.
Gen Dent ; 68(5): 66-68, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857052

RESUMO

Cannabis, a psychoactive drug widely used for medicinal, recreational, and religious purposes, can have detrimental effects on several body systems, including the respiratory, cardiovascular, and central nervous systems. The use of cannabis in cigarette form can produce a series of oral alterations, including periodontitis, caries, xerostomia, a decreased salivary pH, and an increase in the density of Candida albicans. However, the occurrence of oral candidal lesions related to cannabis use is little reported in the literature. This article reports 2 cases of oral candidiasis associated with cannabis use. The adult male patients, both of whom were systemically healthy, had white and red spots consistent with oral candidiasis on the dorsal surface of the tongue. One of the patients also had a red lesion on an area of the hard palate that was in contact with the affected area of the tongue. Neither patient was currently undergoing antibiotic or corticosteroid treatment, and both reported frequent smoking of cannabis. One patient was initially treated with an oral suspension of nystatin without clinical improvement. Miconazole gel therapy was then prescribed, and clinical improvement was observed after 2 weeks. The patient did not stop smoking cannabis, and a recurrence of oral candidiasis was observed 6 months posttreatment. Treatment with miconazole gel was repeated, resulting in resolution of the infection. The second patient declined treatment. The reported cases demonstrate that, although it is infrequently reported, oral candidiasis may occur in cannabis smokers.


Assuntos
Candidíase Bucal , Cannabis , Adulto , Candida albicans , Humanos , Masculino , Fumar , Língua
10.
Br J Cancer ; 118(12): 1628-1638, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29872149

RESUMO

BACKGROUND: The extracellular matrix modulates the hallmarks of cancer. Here we examined the role of agrin-a member of this matrix-in progression of oral squamous cell carcinoma (OSCC). METHODS: We evaluated the immunohistochemical expression of agrin in OSCC and dysplasias. Benign lesions were used as control. In subsequent experiments, we investigated whether the silencing of agrin interferes with tumour expansion both in vitro as well as in vivo. To gain insights into the role of agrin, we identified its protein network (interactome) using mass spectrometry-based proteomics and bioinformatics. Finally, we evaluated the clinical relevance of agrin interactome. RESULTS: Agrin was elevated in malignant and premalignant lesions. Further, we show that agrin silencing interferes with cancer cell motility, proliferation, invasion, colony and tumour spheroid formation, and it also reduces the phosphorylation of FAK, ERK and cyclin D1 proteins in OSCC cells. In orthotopic model, agrin silencing reduces tumour aggressiveness, like vascular and neural invasion. From a clinical perspective, agrin contextual hubs predict a poor clinical prognosis related with overall survival. CONCLUSIONS: Altogether, our results demonstrate that agrin is a histological marker for the progression of oral cancer and is a strong therapeutic target candidate for both premalignant and OSCC lesions.


Assuntos
Agrina/biossíntese , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Progressão da Doença , Células HEK293 , Xenoenxertos , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mucosa Bucal/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
11.
J Cosmet Laser Ther ; 20(2): 117-122, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29020483

RESUMO

INTRODUCTION: Head and neck radiotherapy (HNRT) is associated with acute and chronic side effects, some of which result in great morbidity. The aim of this study was to determine the efficacy of low-level laser therapy (LLLT) as an oral care tool for the management of these effects. MATERIALS AND METHODS: Clinical information was collected from 216 patients undergoing HNRT; these individuals were divided into a control group without laser therapy (n = 108) and a laser group (n = 108). The intervention of the laser group was performed in a different period to the control group and was applied three times weekly. All data were analyzed by a descriptive statistical analysis. RESULTS: The presence and severity of mucositis were similar between the groups. However, the laser group showed a lower frequency of interruption of oncologic therapy related to mucositis (p = 0.030) and the need of nasogastric tube nutrition during the HNRT (p = 0.027). In addition, trismus was less intense in the laser group (p = 0.023). CONCLUSIONS: The introduction of laser therapy in the supportive care for patients undergoing HNRT showed benefits for the patient and the medical system, reducing morbidity and costs associated with side-effects.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Masculino , Pessoa de Meia-Idade
12.
Front Oral Health ; 5: 1363052, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450102

RESUMO

Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38760287

RESUMO

OBJECTIVE: We aimed to describe the association between CX3CR1, CX3CL1, and ITGAV immunoexpression with PNI and adverse oncologic outcomes in patients with OSCC. STUDY DESIGN: Expression CX3CR1, CX3CL1, and ITGAV was assessed by immunohistochemistry in a cohort of 50 paraffin-embedded resections of OSCC. Survival analysis, Cox, and binary logistic regressions were undertaken to determine the impact on patient survival and predictive value for PNI. RESULTS: CX3CL1 positive nerves exhibited a significant association with tumor budding (TB) (P = .043), whereas nerves positive for ITGAV were associated with PNI (P = .021), T3-T4 tumor size (P = .029), and III-IV stage (P = .044). Cases with ITGAV-positive nerves exhibited an odds ratio of 9.603 (P = .008) for PNI, whereas cases with CX3CL1-positive nerves exhibited and odds ratio of 4.682 (P = .033) for TB. A trend toward decreased 5-year overall survival (P = .078) and 5-year disease-specific survival (P = .09) was observed in relation to ITGAV-positive nerves. However, no independent predictors for poor survival were identified. CONCLUSIONS: The expression of ITGAV was associated with PNI and advanced disease, whereas the expression of CX3CL1 was related to TB, suggesting that ITGAV and CX3CL1 are involved in their respective developments. Therefore, further investigations are encouraged to assess the potential utility of targeted therapies against CX3CL1 receptors in OSCC.


Assuntos
Biomarcadores Tumorais , Receptor 1 de Quimiocina CX3C , Carcinoma de Células Escamosas , Quimiocina CX3CL1 , Imuno-Histoquímica , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Feminino , Masculino , Quimiocina CX3CL1/metabolismo , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo , Adulto , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais , Prognóstico , Invasividade Neoplásica , Análise de Sobrevida , Valor Preditivo dos Testes
14.
Support Care Cancer ; 21(7): 2007-15, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23430007

RESUMO

PURPOSE: Side effects of head and neck radiotherapy are common and can interfere with treatment. However, scientific information on a patient's understanding of these complications is scarce and confusing. Therefore, the aim of this study was to assess the effect of an educational video on improving the understanding of head and neck cancer patients undergoing radiotherapy about treatment complications. METHODS: A 6-min video about head and neck radiotherapy side effects was produced by a multidisciplinary oncology team. A controlled clinical study was performed with two groups: the control group (N = 19), which received verbal information, and the video group (N = 19), which received verbal information and watched the video. Two questionnaires were given to both groups, one before the beginning of radiotherapy and the other after finishing radiotherapy. RESULTS: Thirty-eight patients were included in the study (mean age of 59.7 years in the video group and 57.9 in the control group). Thirty-one patients had an education level less than high school education. All patients of the video group answered correctly why they were undergoing radiotherapy. On the other hand, three patients of the control group did not know the reason for the treatment. More patients of the video group demonstrated better knowledge about radiotherapy side effects than patients of the control group. Only one patient of the video group had doubts about the treatment, compared to seven of the control group. CONCLUSIONS: The present study showed that an educational video may improve patient understanding of head and neck radiotherapy and its side effects despite their education level.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Educação de Pacientes como Assunto/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Radioterapia/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Inquéritos e Questionários , Gravação em Vídeo
15.
Gen Dent ; 61(4): e15-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23823354

RESUMO

Amiodarone is one of the most commonly used drugs for treatment of cardiac arrhythmia. Several undesirable effects are associated with its long-term use. This report describes the case of a 71-year-old female patient, with a diagnosis of cardiac arrhythmia, who presented with a stigmatizing blue-gray facial pigmentation and altered serum values of thyroid hormones associated with the intake of amiodarone. The patient was referred to her cardiologist. The aim of this report is to increase clinicians' awareness about the potential adverse effects of this drug.


Assuntos
Amiodarona , Transtornos da Pigmentação , Face , Humanos , Pigmentação , Transtornos da Pigmentação/induzido quimicamente
16.
Biomed Mater ; 18(4)2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37167997

RESUMO

Although there have been many advances in injectable hydrogels as scaffolds for tissue engineering or as payload-containing vehicles, the lack of adequate microporosity for the desired cell behavior, tissue integration, and successful tissue generation remains an important drawback. Herein, we describe an effective porous injectable system that allowsin vivoformation of pores through conventional syringe injection at room temperature. This system is based on the differential melting profiles of photocrosslinkable salmon gelatin and physically crosslinked porogens of porcine gelatin (PG), in which PG porogens are solid beads, while salmon methacrylamide gelatin remains liquid during the injection procedure. After injection and photocrosslinking, the porogens were degraded in response to the physiological temperature, enabling the generation of a homogeneous porous structure within the hydrogel. The resultant porogen-containing formulations exhibited controlled gelation kinetics within a broad temperature window (18.5 ± 0.5-28.8 ± 0.8 °C), low viscosity (133 ± 1.4-188 ± 16 cP), low force requirements for injectability (17 ± 0.3-39 ± 1 N), robust mechanical properties after photo-crosslinking (100.9 ± 3.4-332 ± 13.2 kPa), and favorable cytocompatibility (>70% cell viability). Remarkably,in vivosubcutaneous injection demonstrated the suitability of the system with appropriate viscosity and swift crosslinking to generate porous hydrogels. The resulting injected porous constructs showed favorable biocompatibility and facilitated cell infiltration for desirable potential tissue remodeling. Finally, the porogen-containing formulations exhibited favorable handling, easy deposition, and good shape fidelity when used as bioinks in 3D bioprinting technology. This injectable porous system serves as a platform for various biomedical applications, thereby inspiring future advances in cell therapy and tissue engineering.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Gelatina/química , Porosidade , Materiais Biocompatíveis/química , Hidrogéis/química , Impressão Tridimensional
17.
J Cancer Res Clin Oncol ; 149(19): 17335-17346, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37831273

RESUMO

PURPOSE: The CCR5/CCL5 axis is essential for interactions between malignant cells and microenvironment components, promoting tumor progression in oral squamous cell carcinoma (OSCC). This study aims to evaluate the association of CCL5 and CCR5 with the behavior of oral cancer and assess the therapeutic potential of a CCR5 antagonist. METHODS: A retrospective study to analyze CCR5 and CCL5 expression on paraffin-embedded tissues was performed. In cell lines, rhCCL5 was added to induce CCR5-related pathways, and Maraviroc and shRNA against CCR5 were used to neutralize the receptor. Finally, an in vivo murine orthotopic xenograft model of tongue cancer was used to evaluate Maraviroc as an oncologic therapy. After 15 days, the mice were killed, and the primary tumors and cervical lymph nodes were analyzed. RESULTS: The expression of CCR5 was associated with clinical stage and metastasis, and CCL5 was related to overall survival. Adding rhCCL5 induced cell proliferation, while shRNA and Maraviroc reduced it in a dose-dependent manner. Maraviroc treatment also increased apoptosis and modified cytoskeletal organization. In vivo, Maraviroc reduced neck metastasis. CONCLUSIONS: The effects of CCR5 antagonists in OSCC have been poorly studied, and this study reports in vitro and in vivo evidence for the effects of Maraviroc in OSCC. Our results suggest that the CCR5/CCL5 axis plays a role in oral cancer behavior, and that its inhibition is a promising new therapy alternative.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Animais , Camundongos , Maraviroc/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Retrospectivos , Linhagem Celular Tumoral , Neoplasias Bucais/tratamento farmacológico , RNA Interferente Pequeno/metabolismo , Microambiente Tumoral , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo
18.
Front Oncol ; 12: 1085917, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713524

RESUMO

Objective: Although there have been remarkable achievements in the molecular landscape of oral squamous cell carcinoma (OSCC) in recent years, bringing advances in the understanding of its pathogenesis, development and progression, little has been applied in the prognosis and choosing the optimal treatment. In this study, we explored the influence of the stress induced phosphoprotein 1 (STIP1), which is frequently reported to be highly expressed in many cancers, in OSCCs. Methods: STIP1 expression was assessed in the TCGA database and in two independent cohorts by immunohistochemistry. Knockdown strategy was applied in OSCC cell lines to determine the impact of STIP1 on viability, proliferation, migration and invasion. The zebrafish model was applied for studying tumor formation and metastasis in vivo. The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection. Results: STIP1 was highly expressed in OSCCs and significantly associated with shortened survival and higher risk of recurrence. STIP1 down-regulation decreased proliferation, migration and invasion of tumor cells, and reduced the number of metastases in the Zebrafish model. STIP1 and miR-218-5p were inversely expressed, and the transfection of miR-218-5p mimics into OSCC cells decreased STIP1 levels as well as proliferation, migration and invasion. Conclusion: Our findings show that STIP1 overexpression, which is inversely associated with miR-218-5p levels, contributes to OSCC aggressiveness by controlling proliferation, migration and invasion and is a determinant of poor prognosis.

19.
Nat Commun ; 13(1): 6725, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344512

RESUMO

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.


Assuntos
Neoplasias de Cabeça e Pescoço , Proteoma , Humanos , Metástase Linfática/patologia , Proteômica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/patologia , Microambiente Tumoral
20.
Front Oral Health ; 2: 614045, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35047990

RESUMO

Oral leukoplakia is the most prevalent potentially malignant disorder of the oral cavity. To evaluate its potential for malignancy, appropriate documentation of the biological parameters is crucial, allowing the patients' progression to be assessed. We hypothesized a lack of standardization in the parameters employed for the prognostic study of oral leukoplakia; our aims were to determine the different parameters used for follow-up according to definition, importance, and frequency of use, and to provide a standardization proposal of follow-up research. We made a scoping review to identify papers with the keywords "leukoplakia," "oral," and "follow-up" published until June 2019 in English, Spanish and Portuguese literature through an online search in PUBMED, SCIELO, and SCOPUS databases. In total, 514 articles were initially identified, and fifty-nine publications were selected, of which 37 were retrospective. The reports included a total of 18,660 patients between 13 and 98 years old, with a mean age of 57.6 years. Tobacco and alcohol habits were positive for 77 and 37% of the patients, respectively. Our results showed that reported leukoplakias were predominantly located on buccal mucosa (40.4%), were homogeneous (60.8%), multiple (59.9%), smaller than 2 cm (74.4%) and histopathologically non-dysplastic (71%). The mean follow-up time was 55 months, with a 13% malignant transformation rate. The categorization and definition of multiple variables were notably diverse. Age, sex, habits (tobacco and alcohol), site, size, distribution, morphology, degree of dysplasia, and evolution were the chosen parameters for our proposal. The current study reflected the lack of consensus found in the literature regarding parameters for diagnosis or follow-up, impacting negatively on clinical and research results. standardization comprises an efficient way to facilitate the prognosis assessment of oral leukoplakia, being beneficial for clinical practice, and enabling better quality information to apply in research.

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