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1.
Sci Rep ; 14(1): 14092, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890401

RESUMO

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumours, warranting novel treatments. Here, we examined the therapeutic efficacy of inhibiting p21 activated kinase 4 (PAK4) in OSCC and determined its immunomodulatory effect by focusing on the enhancement of anti-tumour effects. We examined PAK4 expression in OSCC cells and human clinical samples and analysed the proliferation and apoptosis of OSCC cells following PAK4 inhibition in vitro. We also investigated the effects of in vivo administration of a PAK4 inhibitor on immune cell distribution and T-cell immune responses in OSCC tumour-bearing mice. PAK4 was detected in all OSCC cells and OSCC tissue samples. PAK4 inhibitor reduced the proliferation of OSCC cells and induced apoptosis. PAK4 inhibitor significantly attenuated tumour growth in mouse and was associated with increased proportions of IFN-γ-producing CD8+ T-cells. Furthermore, PAK4 inhibitor increased the number of dendritic cells (DCs) and up-regulated the surface expression of various lymphocyte co-stimulatory molecules, including MHC-class I molecules, CD80, CD83, CD86, and CD40. These DCs augmented CD8+ T-cell activation upon co-culture. Our results suggest that PAK4 inhibition in OSCC can have direct anti-tumour and immunomodulatory effects, which might benefit the treatment of this malignancy.


Assuntos
Carcinoma de Células Escamosas , Proliferação de Células , Imunomodulação , Neoplasias Bucais , Quinases Ativadas por p21 , Quinases Ativadas por p21/metabolismo , Quinases Ativadas por p21/antagonistas & inibidores , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Imunomodulação/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Feminino , Masculino
2.
Head Face Med ; 20(1): 37, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890650

RESUMO

BACKGROUND: The treatment of oral squamous cell carcinoma (OSCC) remains challenging and survival rates have not been improved significantly over the past decades. Integrins have been recognized driving the cancer progression and high expression levels cause poor outcomes in patients afflicted with OSCC. Integrin αvß6 and its subunit integrin beta 6 (ITGB6) were discovered to enhance the invasiveness by providing beneficial effects on downstream pathways promoting the cancer progression. The objective of this study was to establish a CRISPR/Cas9-mediated knock out of ITGB6 in the human OSCC cell line HN and investigate the effects on the migration and proliferation ability. METHODS: ITGB6 knock out was performed using the CRISPR/Cas9-system, RNPs, and lipofection. Monoclonal cell clones were achieved by limiting dilution and knock out verification was carried out by sanger sequencing and FACS on protein level. The effects of the knock out on the proliferation and migration ability were evaluated by using MTT and scratch assays. In addition, in silico TCGA analysis was utilized regarding the effects of ITGB6 on overall survival and perineural invasion. RESULTS: In silico analysis revealed a significant impact of ITGB6 mRNA expression levels on the overall survival of patients afflicted with OSCC. Additionally, a significantly higher rate of perineural invasion was discovered. CRISPR/Cas9-mediated knock out of ITGB6 was performed in the OSCC cell line HN, resulting in the generation of a monoclonal knock out clone. The knock out clone exhibited a significantly reduced migration and proliferation ability when compared to the wildtype. CONCLUSIONS: ITGB6 is a relevant factor in the progression of OSCC and can be used for the development of novel treatment strategies. The present study is the first to establish a monoclonal CRISPR/Cas9-mediated ITGB6 knockout cell clone derived from an OSCC cell line. It suggests that ITGB6 has a significant impact on the proliferative and migratory capacity in vitro.


Assuntos
Sistemas CRISPR-Cas , Carcinoma de Células Escamosas , Movimento Celular , Proliferação de Células , Cadeias beta de Integrinas , Neoplasias Bucais , Humanos , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Cadeias beta de Integrinas/genética , Técnicas de Inativação de Genes , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Invasividade Neoplásica/genética , Regulação Neoplásica da Expressão Gênica
3.
J Nanobiotechnology ; 22(1): 344, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890730

RESUMO

BACKGROUND: Functional drug testing (FDT) with patient-derived tumor cells in microfluidic devices is gaining popularity. However, the majority of previously reported microfluidic devices for FDT were limited by at least one of these factors: lengthy fabrication procedures, absence of tumor progenitor cells, lack of clinical correlation, and mono-drug therapy testing. Furthermore, personalized microfluidic models based on spheroids derived from oral cancer patients remain to be thoroughly validated. Overcoming the limitations, we develop 3D printed mold-based, dynamic, and personalized oral stem-like spheroids-on-a-chip, featuring unique serpentine loops and flat-bottom microwells arrangement. RESULTS: This unique arrangement enables the screening of seven combinations of three drugs on chemoresistive cancer stem-like cells. Oral cancer patients-derived stem-like spheroids (CD 44+) remains highly viable (> 90%) for 5 days. Treatment with a well-known oral cancer chemotherapy regimen (paclitaxel, 5 fluorouracil, and cisplatin) at clinically relevant dosages results in heterogeneous drug responses in spheroids. These spheroids are derived from three oral cancer patients, each diagnosed with either well-differentiated or moderately-differentiated squamous cell carcinoma. Oral spheroids exhibit dissimilar morphology, size, and oral tumor-relevant oxygen levels (< 5% O2). These features correlate with the drug responses and clinical diagnosis from each patient's histopathological report. CONCLUSIONS: Overall, we demonstrate the influence of tumor differentiation status on treatment responses, which has been rarely carried out in the previous reports. To the best of our knowledge, this is the first report demonstrating extensive work on development of microfluidic based oral cancer spheroid model for personalized combinatorial drug screening. Furthermore, the obtained clinical correlation of drug screening data represents a significant advancement over previously reported personalized spheroid-based microfluidic devices. Finally, the maintenance of patient-derived spheroids with high viability under oral cancer relevant oxygen levels of less than 5% O2 is a more realistic representation of solid tumor microenvironment in our developed device.


Assuntos
Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Dispositivos Lab-On-A-Chip , Neoplasias Bucais , Células-Tronco Neoplásicas , Medicina de Precisão , Esferoides Celulares , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Esferoides Celulares/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Antineoplásicos/farmacologia , Medicina de Precisão/métodos , Impressão Tridimensional , Fluoruracila/farmacologia , Paclitaxel/farmacologia
4.
Front Cell Infect Microbiol ; 14: 1356907, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863832

RESUMO

Introduction: Microbial community composition is closely associated with host disease onset and progression, underscoring the importance of understanding host-microbiota dynamics in various health contexts. Methods: In this study, we utilized full-length 16S rRNA gene sequencing to conduct species-level identification of the microorganisms in the oral cavity of a giant panda (Ailuropoda melanoleuca) with oral malignant fibroma. Results: We observed a significant difference between the microbial community of the tumor side and non-tumor side of the oral cavity of the giant panda, with the latter exhibiting higher microbial diversity. The tumor side was dominated by specific microorganisms, such as Fusobacterium simiae, Porphyromonas sp. feline oral taxon 110, Campylobacter sp. feline oral taxon 100, and Neisseria sp. feline oral taxon 078, that have been reported to be associated with tumorigenic processes and periodontal diseases in other organisms. According to the linear discriminant analysis effect size analysis, more than 9 distinct biomarkers were obtained between the tumor side and non-tumor side samples. Furthermore, the Kyoto Encyclopedia of Genes and Genomes analysis revealed that the oral microbiota of the giant panda was significantly associated with genetic information processing and metabolism, particularly cofactor and vitamin, amino acid, and carbohydrate metabolism. Furthermore, a significant bacterial invasion of epithelial cells was predicted in the tumor side. Discussion: This study provides crucial insights into the association between oral microbiota and oral tumors in giant pandas and offers potential biomarkers that may guide future health assessments and preventive strategies for captive and aging giant pandas.


Assuntos
Campylobacter , Fusobacterium , Microbiota , Boca , Porphyromonas , RNA Ribossômico 16S , Ursidae , Ursidae/microbiologia , Animais , RNA Ribossômico 16S/genética , Porphyromonas/genética , Porphyromonas/isolamento & purificação , Porphyromonas/classificação , Campylobacter/genética , Campylobacter/isolamento & purificação , Campylobacter/classificação , Boca/microbiologia , Fusobacterium/genética , Fusobacterium/isolamento & purificação , Fibroma/microbiologia , Fibroma/veterinária , Neisseria/isolamento & purificação , Neisseria/genética , Neisseria/classificação , Neoplasias Bucais/microbiologia , Neoplasias Bucais/veterinária , Neoplasias Bucais/patologia , Filogenia , Análise de Sequência de DNA
5.
SLAS Discov ; 29(4): 100158, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38852983

RESUMO

3D in vitro systems offer advantages over the shortcomings of two-dimensional models by simulating the morphological and functional features of in vivo-like environments, such as cell-cell and cell-extracellular matrix interactions, as well as the co-culture of different cell types. Nevertheless, these systems present technical challenges that limit their potential in cancer research requiring cell line- and culture-dependent standardization. This protocol details the use of a magnetic 3D bioprinting method and other associated techniques (cytotoxicity assay and histological analysis) using oral squamous cell carcinoma cell line, HSC3, which offer advantages compared to existing widely used approaches. This protocol is particularly timely, as it validates magnetic bioprinting as a method for the rapid deployment of 3D cultures as a tool for compound screening and development of heterotypic cultures such as co-culture of oral squamous cell carcinoma cells with cancer-associated fibroblasts (HSC3/CAFs).


Assuntos
Bioimpressão , Carcinoma de Células Escamosas , Técnicas de Cocultura , Neoplasias Bucais , Impressão Tridimensional , Esferoides Celulares , Humanos , Neoplasias Bucais/patologia , Bioimpressão/métodos , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/patologia , Técnicas de Cocultura/métodos , Esferoides Celulares/patologia , Técnicas de Cultura de Células em Três Dimensões/métodos
6.
J Med Primatol ; 53(3): e12717, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38853391

RESUMO

BACKGROUND: Oral cavity squamous cell carcinomas (OCSCCs) are relatively common in multiple non-human primate species but are poorly documented in Goeldi's monkeys. METHODS: Four Goeldi's monkeys with OCSCC, from three zoological collections, underwent necropsy with cytology, histopathology, immunohistochemistry, and pan-herpesvirus PCR analysis. RESULTS: All animals were euthanised and exhibited poor-to-emaciated body condition. Three OCSCCs arose from the maxillary oral mucosa and a single OCSCC was primarily mandibular, with bone invasion evident in three cases. Histologically, one OCSCC in situ was diagnosed, whilst the rest were typically invasive OCSCCs. Neoplastic cells were immunopositive for pancytokeratin and E-cadherin. All examined cases were negative for regional lymph node (RLN) and/or distant metastases, cyclooxygenase-2 (COX-2) immunoexpression, and panherpesvirus PCR expression. CONCLUSIONS: OCSCCs in Goeldi's monkeys may be deeply invasive, but not readily metastatic. No herpesvirus-association or COX-2 expression was evident; the latter suggesting that NSAIDs are unlikely to be a viable chemotherapeutic treatment.


Assuntos
Animais de Zoológico , Carcinoma de Células Escamosas , Doenças dos Macacos , Neoplasias Bucais , Animais , Carcinoma de Células Escamosas/veterinária , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/virologia , Neoplasias Bucais/veterinária , Neoplasias Bucais/patologia , Neoplasias Bucais/etiologia , Doenças dos Macacos/patologia , Doenças dos Macacos/virologia , Masculino , Feminino
7.
Cell Biochem Funct ; 42(4): e4074, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38874340

RESUMO

Usnic acid (UA) is a unique bioactive substance in lichen with potential anticancer properties. Recently, we have reported that UA can reduce 7,12-dimethylbenz[a] anthracene-induced oral carcinogenesis by inhibiting oxidative stress, inflammation, and cell proliferation in a male golden Syrian hamster in vivo model. The present study aims to explore the relevant mechanism of cell death induced by UA on human oral carcinoma (KB) cell line in an in vitro model. We found that UA can induce apoptosis (cell death) in KB cells by decreasing cell viability, increasing the production of reactive oxygen species (ROS), depolarizing mitochondrial membrane potential (MMP) levels, causing nuclear fragmentation, altering apoptotic morphology, and causing excessive DNA damage. Additionally, UA inhibits the expression of Bcl-2, a protein that promotes cell survival, while increasing the expression of p53, Bax, Cytochrome-c, Caspase-9, and 3 proteins in KB cells. UA also inhibits the expression of nuclear factor-κB (NF-κB), a protein that mediates the activation of pro-inflammatory cytokines such as TNF-α and IL-6, in KB cells. Furthermore, UA promotes apoptosis by enhancing the mitochondrial-mediated apoptotic mechanism through oxidative stress, depletion of cellular antioxidants, and an inflammatory response. Ultimately, the findings of this study suggest that UA may have potential as an anticancer therapeutic agent for oral cancer treatments.


Assuntos
Apoptose , Benzofuranos , Inflamação , Neoplasias Bucais , NF-kappa B , Transdução de Sinais , Humanos , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Benzofuranos/farmacologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos
8.
Sultan Qaboos Univ Med J ; 24(2): 152-160, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38828241

RESUMO

Objectives: This study aimed to quantify the vascularity in histological grades of oral submucous fibrosis (OSMF) and to determine if there is any connection between vasculogenesis and malignisation. Recent studies show no significant change in vascularity as the stage advances as opposed to the conventional concept. Methods: A comprehensive database search until December 2022 was conducted for published articles on vascularity in OSMF following preferred reporting items for systematic reviews and meta-analyses guidelines. Results: A total of 98 articles were screened of which 13 were included for systematic evaluation. The study included 607 cases, with a definite predilection for the male gender. Of the 13 studies, 11 evaluated mean vascular density. In more than half of the studies, the vascularity decreased as the stage advanced. Similar results were obtained for endothelial cells/µm2, mean vascular area percentage and mean vascular area. Conclusion: The present review supports the prevailing concept that vascularity decreases with the advancement of the OSMF stage. This denies the systemic absorption of carcinogens into the circulation with resultant longer exposure of compromised epithelium and malignisation.


Assuntos
Fibrose Oral Submucosa , Humanos , Fibrose Oral Submucosa/patologia , Fibrose Oral Submucosa/fisiopatologia , Masculino , Feminino , Neoplasias Bucais/patologia , Neoplasias Bucais/fisiopatologia
9.
Cells ; 13(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38891124

RESUMO

Canine oral melanoma is the most prevalent malignant tumor in dogs and has a poor prognosis due to its high aggressiveness and high metastasis and recurrence rates. More research is needed into its treatment and to understand its pathogenic factors. In this study, we isolated a canine oral mucosal melanoma (COMM) cell line designated as COMM6605, which has now been stably passaged for more than 100 generations, with a successful monoclonal assay and a cell multiplication time of 22.2 h. G-banded karyotype analysis of the COMM6605 cell line revealed an abnormal chromosome count ranging from 45 to 74, with the identification of a double-armed chromosome as the characteristic marker chromosome of this cell line. The oral intralingual and dorsal subcutaneous implantation models of BALB/c-nu mice were successfully established; Melan-A (MLANA), S100 beta protein (S100ß), PNL2, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2) were stably expressed positively in the canine oral tumor sections, tumor cell lines, and tumor sections of tumor-bearing mice. Sublines COMM6605-Luc-EGFP and COMM6605-Cherry were established through lentiviral transfection, with COMM6605-Luc-EGFP co-expressing firefly luciferase (Luc) and enhanced green fluorescent protein (EGFP) and COMM6605-Cherry expressing the Cherry fluorescent protein gene. The COMM6605-Luc-EGFP fluorescent cell subline was injected via the tail vein and caused lung and lymph node metastasis, as detected by mouse live imaging, which can be used as an animal model to simulate the latter steps of hematogenous spread during tumor metastasis. The canine oral melanoma cell line COMM6605 and two sublines isolated and characterized in this study can offer a valuable model for studying mucosal melanoma.


Assuntos
Melanoma , Mucosa Bucal , Neoplasias Bucais , Animais , Cães , Melanoma/patologia , Melanoma/genética , Melanoma/veterinária , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/veterinária , Linhagem Celular Tumoral , Mucosa Bucal/patologia , Mucosa Bucal/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Camundongos Nus
10.
Cancer Med ; 13(12): e7213, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888352

RESUMO

BACKGROUND: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC. METHODS: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis. RESULTS: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001). CONCLUSIONS: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays.


Assuntos
Procedimentos Cirúrgicos Eletivos , Tempo de Internação , Neoplasias Bucais , Traqueotomia , Humanos , Traqueotomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Prognóstico , Idoso , Procedimentos Cirúrgicos Eletivos/métodos , Tempo de Internação/estatística & dados numéricos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Adulto
11.
Oral Oncol ; 154: 106870, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823171

RESUMO

OBJECTIVE(S): To assess the influence of treatment package time (TPT) on overall survival (OS) and event free survival (EFS) in oral cavity cancer (OCC) patients treated with surgery and adjuvant radiation therapy (RT) with or without concurrent chemotherapy (CHT). MATERIALS/METHODS: 354 adult OCC patients treated at a single, high-volume center between 2012-2022 with various pathologic risk features were included. TPT was defined as days from surgery to RT completion. Kaplan-Meier estimates, log-rank p-values, univariable (UVA) and multivariable (MVA) Cox regression analyses were performed to determine the impact of TPT on OS and EFS, and the optimal TPT cutoff. RESULTS: The optimal TPT cutoff was 105 days. TPT < 105 days was significantly associated with improved OS and EFS (p = 0.002 and p = 0.027, respectively) compared to TPT ≥ 105 days. On UVA, factors significantly associated with OS were TPT < 105 days, former/current smoker status, pathologic stage IV, positive perineural invasion (PNI), and extranodal extension (ENE) (all p < 0.05). On MVA for OS, TPT < 105 days, former/current smoker status, pathologic stage IV, and positive PNI (all p < 0.05) remained significant. Factors significantly associated with EFS on UVA were TPT < 105 days, former/current smoker status, pathologic stage IV, positive PNI or ENE, and concurrent CHT (all p < 0.05). On MVA, TPT < 105 days, pathologic stage IV, and positive PNI (all p < 0.05) remained significant. CONCLUSIONS: In a large, homogenous cohort of OCCs, optimal TPT was <105 days, with TPT ≥ 105 days significantly associated with worse OS and EFS. Multidisciplinary coordination should analyze factors potentially contributing to treatment delay.


Assuntos
Neoplasias Bucais , Humanos , Neoplasias Bucais/terapia , Neoplasias Bucais/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/radioterapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Radioterapia Adjuvante
12.
Oral Oncol ; 154: 106808, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823172

RESUMO

BACKGROUND: An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC. METHODS: PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact. RESULTS: Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis. CONCLUSION: The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.


Assuntos
Metástase Linfática , Neoplasias Bucais , Micrometástase de Neoplasia , Neoplasias Orofaríngeas , Humanos , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Bucais/patologia , Neoplasias Bucais/mortalidade , Prognóstico , Micrometástase de Neoplasia/patologia , Linfonodos/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade
13.
Int Immunopharmacol ; 136: 112377, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38838554

RESUMO

The tumor microenvironment (TME) concept has been proposed and is currently being actively studied. The development of extracellular matrix (ECM) in the TME is known as desmoplasia and is observed in many solid tumors. It has also been strongly associated with poor prognosis and resistance to drug therapy. Recently, cellular senescence has gained attention as an effect of drug therapy on cancer cells. Cellular senescence is a phenomenon wherein proliferating cells become resistant to growth-promoting stimuli, secrete the SASP (senescence-associated phenotypic) factors, and stably arrest the cell cycle. These proteins are rich in pro-inflammatory factors, such as interleukin (IL)-6, IL-8, C-X-C motif chemokine ligand 1, C-C motif chemokine ligand (CCL)2, CCL5, and matrix metalloproteinase 3. This study aimed to investigate the desmoplasia-like changes in the TME before and after cancer drug therapy in oral squamous cell carcinomas, evaluate the effect of anticancer drugs on the TME, and the potential involvement of cancer cell senescence. Using a syngeneic oral cancer transplant mouse model, we confirmed that cis-diamminedichloroplatinum (II) (CDDP) administration caused desmoplasia-like changes in cancer tissues. Furthermore, CDDP treatment-induced senescence in tumor-bearing mouse tumor tissues and cultured cancer cells. These results suggest CDDP administration-induced desmoplasia-like structural changes in the TME are related to cellular senescence. Our findings suggest that the administration of anticancer drugs alters the TME of oral cancer cells. Additionally, oral cancer cells undergo senescence, which may influence the TME through the production of SASP factors.


Assuntos
Antineoplásicos , Senescência Celular , Cisplatino , Neoplasias Bucais , Fenótipo Secretor Associado à Senescência , Microambiente Tumoral , Animais , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Cisplatino/farmacologia , Humanos , Senescência Celular/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Citocinas/metabolismo , Masculino , Feminino
14.
BMC Oral Health ; 24(1): 689, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872175

RESUMO

BACKGROUND: Alveolar soft part sarcoma (ASPS) occurs most often in the deep muscles or fascia of the extremities in adults, with only 3.4% of these tumours originating from the head, face and neck. To date, only 17 cases of buccal ASPS have been reported, including the case presented here. Only one case of ASPS recurrence at the primary site, similar to our case, has been reported thus far. Immune checkpoint inhibitors (ICPis)-associated diabetes, with an estimated incidence of 0.43%, is usually seen in older cancer patients and has not been reported in younger people or in patients with ASPS. CASE PRESENTATION: A 24-year-old male patient presented with a slowly progressing right cheek mass with a clinical history of approximately 28 months. Sonographic imaging revealed a hypoechoic mass, which was considered a benign tumour. However, a pathological diagnosis of ASPS was made after excision of the mass. Five days later, functional right cervical lymph node dissection was performed. No other adjuvant therapy was administered after surgery. In a periodic follow-up of the patient six months later, blood-rich tumour growth was noted at the primary site, and Positron emission tomography-computedtomography (PET-CT) ruled out distant metastasis in other areas. The patient was referred to the Ninth People's Hospital of Shanghai Jiaotong University. Due to the large extent of the mass, the patient received a combination of a Programmed Cell Death Ligand 1(PD-L1) inhibitor and a targeted drug. Unfortunately, the patient developed three episodes of severe diabetic ketoacidosis after the administration of the drugs. A confirmed diagnosis of ICPis-associated diabetes was confirmed. After the second operation, the postoperative pathological diagnosis was ASPS, and the margins were all negative. Therefore, we made a final clinical diagnosis of ASPS recurrence at the primary site. Currently in the follow-up, the patient is alive, has no distant metastases, and undergoes multiple imaging examinations every 3 months for the monitoring of their condition. CONCLUSIONS: In analysing the characteristics of all previously reported cases of buccal ASPS, it was found that the clinical history ranged from 1 to 24 months, with a mean of approximately 3 to 9 months. Tumour recurrence at the primary site has been reported in only one patient with buccal ASPS, and the short-term recurrence in our patient may be related to the extraordinarily long 28-month history. ICPis-associated diabetes may be noted in young patients with rare tumours, and regular insulin level monitoring after use is necessary.


Assuntos
Bochecha , Recidiva Local de Neoplasia , Sarcoma Alveolar de Partes Moles , Humanos , Masculino , Sarcoma Alveolar de Partes Moles/patologia , Sarcoma Alveolar de Partes Moles/diagnóstico por imagem , Sarcoma Alveolar de Partes Moles/cirurgia , Bochecha/patologia , Adulto Jovem , Recidiva Local de Neoplasia/patologia , Neoplasias Bucais/patologia , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/cirurgia
16.
Sci Rep ; 14(1): 12921, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839809

RESUMO

We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma (OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan-Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p < 0.001). A preoperative mGNRI below 73.3 was independently associated with unfavorable DFS and OS. A mGNRI-based nomogram was constructed to provide accurate OS predictions (concordance index, 0.781). Hence, preoperative mGNRI is a valuable and cost-effective prognostic biomarker in patients with OCSCC. Our nomogram facilitates the practical use of mGNRI and offers individualized predictions of OS.


Assuntos
Neoplasias Bucais , Avaliação Nutricional , Humanos , Feminino , Masculino , Neoplasias Bucais/cirurgia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Idoso , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Avaliação Geriátrica/métodos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Estado Nutricional , Idoso de 80 Anos ou mais , Estimativa de Kaplan-Meier , Intervalo Livre de Doença , Curva ROC , Fatores de Risco , Modelos de Riscos Proporcionais , Medição de Risco/métodos
17.
Head Neck Pathol ; 18(1): 47, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884825

RESUMO

PURPOSE: The aim of the study is to investigate the immunohistochemical expression of both Alpha smooth muscle actin and Transforming Growth Factor beta and compare their expression in oral papillary squamous cell carcinoma with their expression in different histological grades of oral squamous cell carcinoma. A correlation between these immuno-histochemical expressions and histological findings will then be performed. The research question is "Do the percentages of α-SMA and TGF-ß immune-expression in OPSCC differ from that in the conventional OSCC?". METHODS: This will be achieved by collecting archival blocks of oral papillary squamous cell carcinoma and different grades of oral squamous cell carcinoma, staining the specimens with Transforming Growth Factor beta and alpha smooth muscle actin, then measuring the mean staining index of expression in each group and the area percent of both markers. RESULTS: Results revealed that transforming growth factor beta expression in the epithelium was high in all cases of well-differentiated squamous cell carcinoma, most oral papillary squamous cell carcinoma, and poorly differentiated oral squamous cell carcinoma. On the other hand, different grades of oral squamous cell carcinoma showed a high staining index of alpha smooth muscle actin expression in the stroma. While cases of oral papillary squamous cell carcinoma were either moderate or low-staining. CONCLUSIONS: Oral papillary squamous cell carcinoma has a favourable prognosis compared to different histological grades, and the prognosis does not depend only on histological grade but also on other prognostic factors.


Assuntos
Actinas , Biomarcadores Tumorais , Imuno-Histoquímica , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Actinas/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/análise , Masculino , Feminino
18.
BMC Cancer ; 24(1): 730, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877437

RESUMO

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. METHODS: A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. RESULTS: 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. CONCLUSION: The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.


Assuntos
Neoplasias Bucais , Nomogramas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Neoplasias Bucais/cirurgia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Prognóstico , Idoso , Período Pós-Operatório , Adulto , Intervalo Livre de Doença , Estimativa de Kaplan-Meier , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estadiamento de Neoplasias
19.
BMC Cancer ; 24(1): 731, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877482

RESUMO

BACKGROUND: This study sought to investigate the prognostic value of basement membrane (BM)-associated gene expressions in oral cancer. METHODS: We harvested and integrated data on BM-associated genes (BMGs), the oral cancer transcriptome, and clinical information from public repositories. After identifying differentially expressed BMGs, we used Cox and Lasso regression analyses to create a BMG-based risk score for overall survival at various intervals. We then validated this score using the GSE42743 cohort as a validation set. The prognostic potential of the risk scores and their relations to clinical features were assessed. Further, we conducted functional pathway enrichment, immune cell infiltration, and immune checkpoint analyses to elucidate the immunological implications and therapeutic potential of the BMG-based risk score and constituent genes. To confirm the expression levels of the BMG LAMA3 in clinical samples of oral cancer tissue, we performed quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. RESULTS: The BMGs LAMA3, MMP14, and GPC2 demonstrated notable prognostic significance, facilitating the construction of a BMG-based risk score. A higher risk score derived from BMGs correlated with a poorer survival prognosis for oral cancer patients. Moreover, the risk-associated BMGs exhibited a significant relationship with immune function variability (P < 0.05), discrepancies in infiltrating immune cell fractions, and immune checkpoint expressions (P < 0.05). The upregulated expression levels of LAMA3 in oral cancer tissues were substantiated through qRT-PCR and immunohistochemical staining. CONCLUSION: The BMG-based risk score emerged as a reliable prognostic tool for oral cancer, meriting further research for validation and potential clinical application.


Assuntos
Membrana Basal , Biomarcadores Tumorais , Neoplasias Bucais , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Prognóstico , Membrana Basal/metabolismo , Membrana Basal/patologia , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Feminino , Perfilação da Expressão Gênica , Masculino , Laminina/genética
20.
Med Oncol ; 41(7): 167, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831079

RESUMO

Cancer stem cells (CSCs) are mainly responsible for tumorigenesis, chemoresistance, and cancer recurrence. CSCs growth and progression are regulated by multiple signaling cascades including Wnt/ß-catenin and Hh/GLI-1, which acts independently or via crosstalk. Targeting the crosstalk of signaling pathways would be an effective approach to control the CSC population. Both Wnt/ß-catenin and Hh/GLI-1 signaling cascades are known to be regulated by p53/p21-dependent mechanism. However, it is interesting to delineate whether p21 can induce apoptosis in a p53-independent manner. Therefore, utilizing various subtypes of oral CSCs (SCC9-PEMT p53+/+p21+/+, SCC9-PEMT p53-/-p21+/+, SCC9-PEMT p53+/+p21-/- and SCC9-PEMT p53-/-p21-/-), we have examined the distinct roles of p53 and p21 in Resveratrol nanoparticle (Res-Nano)-mediated apoptosis. It is interesting to see that, besides the p53/p21-mediated mechanism, Res-Nano exposure also significantly induced apoptosis in oral CSCs through a p53-independent activation of p21. Additionally, Res-Nano-induced p21-activation deregulated the ß-catenin-GLI-1 complex and consequently reduced the TCF/LEF and GLI-1 reporter activities. In agreement with in vitro data, similar experimental results were obtained in in vivo mice xenograft model.


Assuntos
Apoptose , Inibidor de Quinase Dependente de Ciclina p21 , Neoplasias Bucais , Nanopartículas , Células-Tronco Neoplásicas , Resveratrol , Proteína Supressora de Tumor p53 , Proteína GLI1 em Dedos de Zinco , beta Catenina , Apoptose/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Resveratrol/farmacologia , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , beta Catenina/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Animais , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Camundongos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
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