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1.
Microsurgery ; 44(6): e31238, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39289853

RESUMO

INTRODUCTION: Facial artery perforator (FAP) flap is a versatile and reliable one-step facial reconstruction technique. However, its full potential remains underutilized due to a lack of clear guidelines and rigorous technique requirements. This study report the use of FAP flaps in our centre for the management of perioral and nasal oncologic defects, focusing on surgical technique performed and post-operative management. METHODS: We conducted a retrospective review of all patients who underwent reconstruction with a perioral or perinasal FAP flap only following tumor resection over a 4-year period (n = 29). Parameters measured included flap survival, complication rates, surgical technique performed, and the need for touch-up procedures. Patients were grouped based on age, defect size, and location and outcomes were compared across these groups. RESULTS: The mean histological tumor defect area was 331 mm2. During at least 6 months of follow-up, no local recurrence was observed. Twenty-seven (93.1%) flaps survived completely. Major postsurgical complications occurred in seven (23.8%) patients, including complete flap necrosis (1), partial flap necrosis (1), flap collapse (1), venous congestion (1), wound dehiscence (1), and local infection (2). A higher complication rate was associated with nose tip defects (80.0% vs. 12.5%, p = 0.007). Touch-up procedures were more frequently required for reconstructions involving the nasal sidewall and dorsum (53.8% vs. 13.3%, p = 0.04). CONCLUSION: Based on our experience, the FAP flap is highly effective for the reconstruction of the upper lip, nasolabial fold, and certain oncologic nasal defects. However, specific defect locations, such as the nose tip, may be associated with higher complication rates, necessitating careful patient selection and surgical planning.


Assuntos
Neoplasias Nasais , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/transplante , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Idoso , Adulto , Neoplasias Nasais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Neoplasias Bucais/cirurgia , Face/cirurgia , Idoso de 80 Anos ou mais , Sobrevivência de Enxerto , Artérias/cirurgia , Seguimentos
2.
Artigo em Chinês | MEDLINE | ID: mdl-39289961

RESUMO

Objective: To investigate the effect of anatomical unit resection on the overall survival rate of patients with T4 stage posterior buccal carcinoma. Methods: We conducted a retrospective study on 79 patients with T4 stage posterior buccal squamous cell carcinoma underwent radical surgery for buccal mucosa cancer and reconstruction with free anterolateral thigh flap in the Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University from March 2014 to December 2019. The 74 patients were males and the 5 patients were females, aged from 28 to 72 years old. The 40 patients in control group underwent traditional extended resection (1.5-2.0 cm safe margin), and 39 patients in the experimental group underwent anatomical unit resection. The clinicopathological parameters of patients were collected and followed up regularly. The overall survival rate was assessed by Log-rank and Cox proportional risk regression model. Multivariate analysis was performed by linear regression model. Results: There were significant differences between experimental group and control group in overall survival rates (61.53% vs 27.50%, χ2=6.624, P=0.010) and local disease control rates (74.36% vs 27.50%, χ2=17.350, P<0.001). Multiple linear regression analysis showed that local disease control rate was significantly correlated with anatomical unit resection (t=3.880, P<0.001) and lymph node metastasis (t=2.619, P=0.011), and also Cox proportional hazards regression model analysis identified that overall survival rate was significantly correlated with anatomical unit resection (Z=2.421, P=0.016) and lymph node metastasis (Z=2.793, P=0.005). Conclusion: For posterior buccal carcinoma with multiple anatomical units involved, anatomical unit resection can significantly reduce local recurrence and improve overall survival rate of patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Taxa de Sobrevida , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Procedimentos de Cirurgia Plástica/métodos , Mucosa Bucal/cirurgia , Estadiamento de Neoplasias
3.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(9): 942-949, 2024 Sep 09.
Artigo em Chinês | MEDLINE | ID: mdl-39289983

RESUMO

Objective: To establish a human buccal mucosa squamous cell carcinoma (BMSCC) cell line SCC117 in China, analyze and identify its basic biological characteristics. Methods: A 59-year-old Chinese male patient with BMSCC in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology in January 2011 was included in this study, his surgical specimens were primary cultured in vitro by improved tissue block culture method. The BMSCC cell line SCC117 was established after continuous passage and stable growth. The morphological characteristics of the cells were observed by light and electron microscope, and their basic biological characteristics were analyzed by growth curve, chromosome karyotype and xenotransplantation tumorigenicity in nude mice experiment. The expressions of cytokeratin (CK14), tumor-related proteins retinoblastoma tumor suppressor protein (RB), P53, E-cadherin, P21, phosphatase and tensin homolog deleted on chromosome ten (PTEN) were detected by immunohistochemical and human papilloma virus (HPV) were tested by PCR. SCC117 was identified by short tandem repeat (STR) analysis of genomic DNA. Results: SCC117, a human BMSCC cell line, had been continuously subcultured in vitro for more than 150 generations. The cells grew in polygonal mosaic and lost contact inhibition, the typical desmosomes and tensional fibrils were observed by electron microscope, and CK14 was positive by immunohistochemistry. The doubling time was 40.16 h, the chromosome mode of the cell line was concentrated between 67 and 69, hypo-triploid. All 4 nude mice inoculated with SCC117 cells developed tumors, indicating that the SCC117 cell line had the ability of xenogeneic tumorigenesis. The histopathological type of the transplanted tumor in nude mice was consistent with that of the primary tumor tissue, both of which were squamous cell carcinoma. The immunohistochemical results showed that in both human primary tumor and the transplanted tumor tissue in nude mice, RB, P53, and E-cadherin were all positive, P21 was weakly positive, while PTEN was negative. SCC117 was tested negative for the presence of HPV. STR sequence analysis showed that SCC117 cell line originated from primary tumor tissue and was not cross-contaminated by other cell lines. Conclusions: The human BMSCC cell line SCC117 was successfully established in China, which could provide a new experimental model for the study of oral SCC without HPV infection, especially BMSCC.


Assuntos
Carcinoma de Células Escamosas , Camundongos Nus , Mucosa Bucal , Humanos , Carcinoma de Células Escamosas/patologia , Animais , Linhagem Celular Tumoral , Camundongos , Mucosa Bucal/patologia , Mucosa Bucal/citologia , Masculino , Caderinas/metabolismo , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Proteína Supressora de Tumor p53/metabolismo , Transplante de Neoplasias , Queratina-14/metabolismo , Papillomaviridae , PTEN Fosfo-Hidrolase
4.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39273239

RESUMO

5-fluorouracil (5-FU), a chemotherapeutic agent against oral squamous cell carcinoma (OSCC), is limited by poor pharmacokinetics and toxicity. The pH-sensitive zeolite imidazolate framework-8 (ZIF-8) may increase the selectivity and length of 5-FU released into the acidic tumor microenvironment. This study examined the in vitro 5-FU absorption and release profiles of ZIF-8, and then progressed to cytotoxicity assays using the OSCC primary cell line SCC7. The 5-FU loading capacity of ZIF-8 was calculated with UV-vis spectroscopy (λ = 260 nm). 5-FU release was quantified by submerging 5-FU@ZIF-8 in pH 7.4 and 5.5 acetate buffer over 48 h. For the cytotoxicity assays, 5-FU, ZIF-8, and 5-FU@ZIF-8 were added to SCC7 cultures at 25, 50, and 100 µg/mL. Cell viability was assessed through toluidine blue staining and further quantified through transcriptomic RNA sequencing. ZIF-8 stabilized at a maximum absorption of 2.71 ± 0.22 mg 5-FU, and released 0.66 mg more 5-FU at pH 5.5 than 7.4 for at least 72 h. The cytotoxicity assays showed that 5-FU@ZIF-8 had a synergistic inhibitory effect at 50 µg/mL. The RNA sequencing analysis further revealed the molecular targets of 5-FU@ZIF-8 in SCC7. 5-FU@ZIF-8 may release 5-FU based on the pH of the surrounding microenvironments and synergistically inhibit OSCC.


Assuntos
Carcinoma de Células Escamosas , Fluoruracila , Neoplasias Bucais , Fluoruracila/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Sobrevivência Celular/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Zeolitas/química , Microambiente Tumoral/efeitos dos fármacos , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Imidazóis
5.
Front Cell Infect Microbiol ; 14: 1417946, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39286811

RESUMO

Fusobacterium nucleatum is an anaerobic commensal of the oral cavity recently reported to be associated with cancers of the gastrointestinal tract and oral squamous cell carcinoma (OSCC). In this study, we investigate the impact on oral keratinocytes of infection with a genetically diverse set of strains of F. nucleatum subsp. polymorphum recovered from patients with oral dysplasia (n=6). We employed H357 oral keratinocytes derived from a stage 1 OSCC and H376 cells derived from a stage 3 OSCC. Adhesion phenotypes were strain specific, with 3/6 clinical isolates examined exhibiting higher adherence to the stage 3 H376 cell line. Conversely, intracellular invasion was greatest in the H357 cells and was associated with specific transcriptional responses including autophagy and keratinization. Infection of both H357 and H376 cell lines induced transcriptional and cytokine responses linked to cancer cell migration and angiogenesis. F. nucleatum infection induced greater levels of MMP9 secretion in the H376 cell line which was associated with enhanced motility and invasion phenotypes. Additionally, the degree of F. nucleatum induced invasive growth by H376 cells varied between different clinical isolates of F. nucleatum subsp. polymorphum. Blockage of CCL5 signalling using the inhibitor metCCL5 resulted in reduced keratinocyte invasion. F. nucleatum infection also induced expression of the pro-angiogenic chemokine MCP-1 and the angiogenic growth factor VEGF-A resulting in increased capillary-like tube formation in HUVEC cells, most significantly in H376 cells. Treatment of HUVEC cells with resveratrol, a VEGF-A signalling inhibitor, significantly attenuated F. nucleatum induced tube formation. Our data indicate that the outcomes of F. nucleatum-oral cell interactions can vary greatly depending on the bacterial genotype and the malignant phenotype of the host cell.


Assuntos
Infecções por Fusobacterium , Fusobacterium nucleatum , Queratinócitos , Neoplasias Bucais , Humanos , Fusobacterium nucleatum/patogenicidade , Queratinócitos/microbiologia , Neoplasias Bucais/microbiologia , Neoplasias Bucais/patologia , Infecções por Fusobacterium/microbiologia , Linhagem Celular Tumoral , Movimento Celular , Aderência Bacteriana , Carcinoma de Células Escamosas/microbiologia , Carcinoma de Células Escamosas/patologia , Neovascularização Patológica/microbiologia , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Citocinas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Boca/microbiologia
6.
Int J Mol Sci ; 25(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39273384

RESUMO

The fatty acid receptor CD36 is expressed on various malignant cells and is suggested to contribute to tumor progression. CD36 is also expressed by several immune cells and involved in immune responses and may be a potential target in cancer immunotherapy. In this study, we investigated whether the selective inhibition of CD36 can inhibit tumor progression and facilitate an antitumor immune response in oral squamous carcinoma cells (OSCCs). We assessed the effects of sulfosuccinimidyl oleate sodium (SSO), a CD36 inhibitor, on the proliferation apoptosis and alteration in tumor cell surface expression levels of immune accessory molecules in vitro. We also assessed whether SSO-treated OSCCs could promote a T cell response via a Mixed Lymphocyte Reaction (MLR) assay. We also investigated the direct antitumor effects and immunomodulatory effects of SSO using a mouse oral cancer OSCC model. SSO treatment significantly inhibited OSCC proliferation, increased apoptotic cell death, and upregulated the cell surface expression of several immune accessory molecules, including CD83, MHC-Class II, and PD-L1. SSO-treated OSCCs augmented T cell proliferation following MLR. In vivo SSO administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T, CD8+ T, and dendritic cells; it also decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor and regulatory T cells. These results suggest that the selective inhibition of CD36 can induce direct and indirect antitumor effects by facilitating host antitumor immune responses in OSCCs.


Assuntos
Antígenos CD36 , Metabolismo dos Lipídeos , Neoplasias Bucais , Animais , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/imunologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Camundongos , Antígenos CD36/metabolismo , Humanos , Linhagem Celular Tumoral , Metabolismo dos Lipídeos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Succinimidas/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
7.
Int J Mol Sci ; 25(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39273519

RESUMO

The epithelial-mesenchymal transition (EMT) phenotype, identified as a significant clinical indicator in regard to cancer, manifests as a biological process wherein cells transition from having epithelial to mesenchymal characteristics. Physiologically, EMT plays a crucial role in tissue remodeling, promoting healing, repair, and responses to various types of tissue damage. This study investigated the impact of BNE-RRC on oral cancer cells (KB) and revealed its significant effects on cancer cell growth, migration, invasion, and the EMT. BNE-RRC induces the epithelial-like morphology in KB cells, effectively reversing the EMT to a mesenchymal-epithelial transition (MET). Extraordinarily, sustained culturing of cancer cells with BNE-RRC for 14 days maintains an epithelial status even after treatment withdrawal, suggesting that BNE-RRC is a potential therapeutic agent for cancer. These findings highlight the promise of BNE-RRC as a comprehensive therapeutic agent for cancer treatment that acts by inhibiting cancer cell growth, migration, and invasion while also orchestrating a reversal of the EMT process. In this study, we propose that BNE-RRC could be an effective agent for cancer treatment.


Assuntos
Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Extratos Vegetais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Extratos Vegetais/farmacologia , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo
8.
Clinics (Sao Paulo) ; 79: 100477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39217675

RESUMO

OBJECTIVES: To determine the prevalence and association of HPV and Herpesviruses in saliva and tissue samples of patients with orofacial tumors. METHODS: Biopsies of tumors were done, and saliva samples were collected from patients with orofacial tumors for the determination of viruses using nested multiplex PCR. Independent variables were sex, age, comorbidities, tumor stage, and length of stay. Outcome variables were the presence or absence of herpesviruses and HPV. Descriptive summaries and inferential statistics were done. RESULTS: A hundred patients were included in the study. Prevalence of herpesviruses and HPV were 17.6 % and 57.0 % in tumors, and 48.3 % and 60.0 % in the saliva of patients respectively. Herpesviruses detected included EBV (21.3 %), HHV-7 (11.2 %), CMV (6.7 %), HSV-1 (5.1 %), HSV-2 (1.1 %), VZV (1.1 %), and Kaposi sarcoma virus (0.6 %). The most prevalent HPV genotypes were HPV-42 (29 %), HPV-43 (22.7 %), HPV-52 (22.2 %), HPV-39 (18.8 %), and HPV-18 (9.1 %). The odds of EBV being detected in malignant orofacial tumors were 2 times that of benign orofacial tumors. HPV DNA in the saliva of patients with orofacial tumors was 69.7 %, compared to 18.2 % of the control sample (p < 0.001). The median length of stay for all participants was 6.5 days, those associated with viruses stayed longer. CONCLUSION: There was a high prevalence of Herpesviruses and HPV in saliva and tumor samples of patients with orofacial tumors, signalling some potential for more work to be done in this area.


Assuntos
Herpesviridae , Papillomaviridae , Saliva , Humanos , Feminino , Saliva/virologia , Masculino , Pessoa de Meia-Idade , Herpesviridae/isolamento & purificação , Herpesviridae/genética , Adulto , Papillomaviridae/isolamento & purificação , Papillomaviridae/genética , Idoso , Biópsia , Adulto Jovem , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/epidemiologia , Prevalência , DNA Viral/análise , Neoplasias Bucais/virologia , Neoplasias Bucais/patologia , Adolescente , Brasil/epidemiologia , Idoso de 80 Anos ou mais , Reação em Cadeia da Polimerase Multiplex , Papillomavirus Humano
9.
Anal Chem ; 96(37): 14980-14988, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39235216

RESUMO

PD-L1-positive extracellular vesicles (PD-L1+ EVs) play a pivotal role as predictive biomarkers in cancer immunotherapy. These vesicles, originating from immune cells (I-PD-L1+ EVs) and tumor cells (T-PD-L1+ EVs), hold distinct clinical predictive values, emphasizing the importance of deeply differentiating the PD-L1+ EV subtypes for effective liquid biopsy analyses. However, current methods such as ELISA lack the ability to differentiate their cellular sources. In this study, a novel step-wedge microfluidic chip that combines magnetic microsphere separation with single-layer fluorescence counting is developed. This chip integrates magnetic microspheres modified with anti-PD-L1 antibodies and fluorescent nanoparticles targeting EpCAM (tumor cell marker) or CD45 (immunocyte marker), enabling simultaneous quantification and sensitive analysis of PD-L1+ EV subpopulations in oral squamous cell carcinoma (OSCC) patients' saliva without background interference. Analysis results indicate reduced levels of I-PD-L1+ EVs in OSCC patients compared to those in healthy individuals, with varying levels of heterogeneous PD-L1+ EVs observed among different patient groups. During immunotherapy, responders exhibit decreased levels of total PD-L1+ EVs and T-PD-L1+ EVs, accompanied by reduced levels of I-PD-L1+ EVs. Conversely, nonresponders show increased levels of I-PD-L1+ EVs. Utilizing the step-wedge microfluidic chip allows for simultaneous detection of PD-L1+ EV subtypes, facilitating the precise prediction of oral cancer immunotherapy outcomes.


Assuntos
Antígeno B7-H1 , Vesículas Extracelulares , Imunoterapia , Dispositivos Lab-On-A-Chip , Neoplasias Bucais , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/análise , Neoplasias Bucais/terapia , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Saliva/química , Saliva/metabolismo
10.
Sci Rep ; 14(1): 20802, 2024 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-39242879

RESUMO

Currently, surgical resection remains the primary approach for treating oral squamous cell carcinoma (OSCC), with limited options for effective drug therapy. Cardamonin, a principal compound derived from Myristica fragrans of the Zingiberaceae family, has garnered attention for its potential to suppress the onset and progression of various malignancies encompassing breast cancer, hepatocellular carcinoma, and ovarian cancers. Nevertheless, the involvement of cardamonin in the treatment of OSCC and its underlying mechanisms are yet to be elucidated. This research explored the possible target of cardamonin in treating OSCC via network pharmacological analysis. Subsequently, this research investigated the impact of cardamonin on OSCC cells via in vitro experiments, revealing its capacity to impede the migration, proliferation, and invasion of OSCC cells. Additionally, western blotting analysis demonstrated that cardamonin facilitates apoptosis by regulating the PI3K/AKT pathway. The findings suggest that MMP9 and the PI3K/AKT signaling pathway may serve as the target and pathway of cardamonin in treating OSCC. To summarize, the research findings suggest that cardamonin may facilitate apoptosis in OSCC cells by inhibition of PI3K/AKT pathway activation. These outcomes offer a theoretical basis for the utilization of cardamonin as a natural drug for treating OSCC.


Assuntos
Apoptose , Carcinoma de Células Escamosas , Movimento Celular , Proliferação de Células , Chalconas , Neoplasias Bucais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Chalconas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Metaloproteinase 9 da Matriz/metabolismo
12.
Theranostics ; 14(12): 4787-4805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239507

RESUMO

Rationale: Immunosuppressive tumor microenvironment (iTME) plays an important role in carcinogenesis, and some macrophage subsets are associated with iTME generation. However, the sub-population characterization of macrophages in oral carcinogenesis remains largely unclear. Here, we investigated the immunosuppressive status with focus on function of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in oral carcinogenesis. Methods: We built a single cell transcriptome atlas from 3 patients simultaneously containing oral squamous cell carcinoma (OSCC), precancerous oral leukoplakia (preca-OLK) and paracancerous tissue (PCA). Through single-cell RNA sequencing and further validation using multicolor immunofluorescence staining and the in vitro/in vivo experiments, the immunosuppressive cell profiles were built and the role of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in the malignant transformation of oral leukoplakia was evaluated. Results: The iTME formed at preca-OLK stage, as evidenced by increased exhausted T cells, Tregs and some special subsets of macrophages and fibroblasts. Macro-IDO1 was predominantly enriched in preca-OLK and OSCC, distributed near exhausted T cells and possessed tumor associated macrophage transformation potentials. Functional analysis revealed the established immunosuppressive role of Macro-IDO1 in preca-OLK and OSCC: enriching the immunosuppression related genes; having an established level of immune checkpoint score; exerting strong immunosuppressive interaction with T cells; positively correlating with the CD8-exhausted. The immunosuppression related gene expression of macrophages also increased in preca-OLK/OSCC compared to PCA. The use of the IDO1 inhibitor reduced 4NQO induced oral carcinogenesis in mice. Mechanistically, IFN-γ-JAK-STAT pathway was associated with IDO1 upregulation in OLK and OSCC. Conclusions: These results highlight that Macro-IDO1-enriched in preca-OLK possesses a strong immunosuppressive role and contributes to oral carcinogenesis, providing a potential target for preventing precancerous legions from transformation into OSCC.


Assuntos
Transformação Celular Neoplásica , Indolamina-Pirrol 2,3,-Dioxigenase , Leucoplasia Oral , Macrófagos , Neoplasias Bucais , Análise de Célula Única , Microambiente Tumoral , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Leucoplasia Oral/imunologia , Leucoplasia Oral/genética , Leucoplasia Oral/patologia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Camundongos , Microambiente Tumoral/imunologia , Transformação Celular Neoplásica/genética , Neoplasias Bucais/imunologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Análise de Célula Única/métodos , Análise de Sequência de RNA , Masculino , Tolerância Imunológica , Feminino , Carcinogênese/imunologia , Carcinogênese/genética
13.
BMC Oral Health ; 24(1): 1080, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39272161

RESUMO

BACKGROUND: The microvascular free fibula (MFF) flap is a reliable treatment modality for mandibular reconstruction and is suitable for dental implant placement after oncologic surgery. The most common issue with the MFF flap is its limited bone height, which typically results in excessive interarch space and complicates prosthodontic therapy. Overcoming the physical limitations from tumor excision and reducing the treatment time for prosthodontic rehabilitation to improve quality of life are critical clinical challenges. CASE PRESENTATION: A 64-year-old male with lower left gum and bilateral buccal cancer received a single-layer microvascular MFF flap to reconstruct a mandibular defect post-tumor excision. He underwent a bilateral modiolus Z-plasty combined with a skin flap debulking procedure to relieve oral contracture, achieving adequate mouth opening for prosthodontic rehabilitation. Scar tissue bands on the bilateral cheeks significantly affected retention and stability, hampering dental impression performance. The patient sought prosthodontic rehabilitation to enhance his chewing function and quality of life promptly. Prosthodontic rehabilitation with all-on-4 implant therapy, utilizing computer-aided design and computer-assisted manufacturing (CAD/CAM), was completed within one month. CONCLUSION: This case utilized the all-on-4 implant system to address the insufficient fibular height for conventional dental implant placements. Dental CAD/CAM was employed to mill custom prosthetic abutments and a large titanium framework for the implant bar overdenture, compensating for the excessive interarch space between the grafted fibula and maxilla. This treatment approach successfully shortened the prosthodontic rehabilitation time and overcame anatomical limitations.


Assuntos
Desenho Assistido por Computador , Prótese Dentária Fixada por Implante , Humanos , Masculino , Pessoa de Meia-Idade , Reconstrução Mandibular/métodos , Fíbula/transplante , Neoplasias Bucais/cirurgia , Neoplasias Bucais/reabilitação , Implantes Dentários , Retalhos de Tecido Biológico , Implantação Dentária Endóssea/métodos
14.
Int J Mol Sci ; 25(17)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39273139

RESUMO

CD44 regulates cell adhesion, proliferation, survival, and stemness and has been considered a tumor therapy target. CD44 possesses the shortest CD44 standard (CD44s) and a variety of CD44 variant (CD44v) isoforms. Since the expression of CD44v is restricted in epithelial cells and carcinomas compared to CD44s, CD44v has been considered a promising target for monoclonal antibody (mAb) therapy. We previously developed an anti-CD44v10 mAb, C44Mab-18 (IgM, kappa), to recognize the variant exon 10-encoded region. In the present study, a mouse IgG2a version of C44Mab-18 (C44Mab-18-mG2a) was generated to evaluate the antitumor activities against CD44-positive cells compared with the previously established anti-pan CD44 mAb, C44Mab-46-mG2a. C44Mab-18-mG2a exhibited higher reactivity compared with C44Mab-46-mG2a to CD44v3-10-overexpressed CHO-K1 (CHO/CD44v3-10) and oral squamous cell carcinoma cell lines (HSC-2 and SAS) in flow cytometry. C44Mab-18-mG2a exerted a superior antibody-dependent cellular cytotoxicity (ADCC) against CHO/CD44v3-10. In contrast, C44Mab-46-mG2a showed a superior complement-dependent cytotoxicity (CDC) against CHO/CD44v3-10. A similar tendency was observed in ADCC and CDC against HSC-2 and SAS. Furthermore, administering C44Mab-18-mG2a or C44Mab-46-mG2a significantly suppressed CHO/CD44v3-10, HSC-2, and SAS xenograft tumor growth compared with the control mouse IgG2a. These results indicate that C44Mab-18-mG2a could be a promising therapeutic regimen for CD44v10-positive tumors.


Assuntos
Anticorpos Monoclonais , Carcinoma de Células Escamosas , Receptores de Hialuronatos , Neoplasias Bucais , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/imunologia , Camundongos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Humanos , Anticorpos Monoclonais/farmacologia , Linhagem Celular Tumoral , Células CHO , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Cricetulus , Antineoplásicos Imunológicos/farmacologia , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C
15.
Colloids Surf B Biointerfaces ; 244: 114179, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39217727

RESUMO

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and aggressive, but therapies based on single-targeted nanoparticles frequently address these tumors as a single illness. To achieve more efficient drug transport, it is crucial to develop nanodrug-carrying systems that simultaneously target two or more cancer biomarkers. In addition, combining chemotherapy with near-infrared (NIR) light-mediated thermotherapy allows the thermal ablation of local malignancies via photothermal therapy (PTT), and triggers drug release to improve chemosensitivity. Thus, a novel dual-targeted nano-loading system, DOX@GO-HA-HN-1 (GHHD), was created for synergistic chemotherapy and PTT by the co-modification of carboxylated graphene oxide (GO) with hyaluronic acid (HA) and HN-1 peptide and loading with the anticancer drug doxorubicin (DOX). Targeted delivery using GHHD was shown to be superior to single-targeted nanoparticle delivery. NIR radiation will encourage the absorption of GHHD by tumor cells and cause the site-specific release of DOX in conjunction with the acidic microenvironment of the tumor. In addition, chemo-photothermal combination therapy for cancer treatment was realized by causing cell apoptosis under the irradiation of 808-nm laser. In summary, the application of GHHD to chemotherapy combined with photothermal therapy for OSCC is shown to have important potential as a means of combatting the low accumulation of single chemotherapeutic agents in tumors and drug resistance generated by single therapeutic means, enhancing therapeutic efficacy.


Assuntos
Carcinoma de Células Escamosas , Doxorrubicina , Sistemas de Liberação de Medicamentos , Grafite , Raios Infravermelhos , Neoplasias Bucais , Doxorrubicina/farmacologia , Doxorrubicina/química , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Grafite/química , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química , Nanopartículas/química , Liberação Controlada de Fármacos , Animais , Apoptose/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Terapia Fototérmica , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Hialurônico/química , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Tamanho da Partícula , Propriedades de Superfície
16.
BMC Cancer ; 24(1): 1136, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261756

RESUMO

BACKGROUND: A variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis. METHODS: Data on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed. RESULTS: Hypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage. CONCLUSIONS: Preoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker.


Assuntos
Carcinoma de Células Escamosas , Metástase Linfática , Neoplasias Bucais , Estadiamento de Neoplasias , Tromboelastografia , Humanos , Tromboelastografia/métodos , Masculino , Feminino , Neoplasias Bucais/patologia , Neoplasias Bucais/sangue , Neoplasias Bucais/cirurgia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Prognóstico , Período Pré-Operatório
17.
BMC Oral Health ; 24(1): 1062, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261828

RESUMO

BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Queratina-19 , Leucoplasia Oral , Neoplasias Bucais , Fibrose Oral Submucosa , RNA Mensageiro , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Neoplasias Bucais/sangue , Neoplasias Bucais/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnóstico , Masculino , RNA Mensageiro/sangue , Fibrose Oral Submucosa/sangue , Fibrose Oral Submucosa/genética , Feminino , Leucoplasia Oral/sangue , Leucoplasia Oral/genética , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Queratina-19/sangue , Adulto , Líquen Plano Bucal/sangue , Líquen Plano Bucal/genética , Estudos de Casos e Controles , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Detecção Precoce de Câncer/métodos , Idoso , Reação em Cadeia da Polimerase em Tempo Real , Curva ROC
18.
BMC Oral Health ; 24(1): 1060, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261854

RESUMO

BACKGROUND: The Surgical Tool for Auditing Records scoring system [STAR] focuses on surgical record auditing with promising outcomes. It offers a structured approach to evaluating the quality of surgical notes. AIMS AND OBJECTIVES: This study aimed to assess the effectiveness of the STAR in evaluating oral surgical records and identifying areas for improvement in documentation practices. MATERIALS AND METHODS: The data was obtained from the Dental Information Archival Software (DIAS) of our institution. The sample size was determined using G*Power 3.1.9.4 software. Fifty consecutive oral surgery clinical records of oral squamous cell carcinoma patients were evaluated using STAR. Each record was reviewed for adherence to documentation standards including Initial Assessment (10 points), Follow-up Entries (8 points), Consent Documentation (7 points), Anesthesia Report (7 points), Surgical Log (9 points), and Discharge Synopsis (9 points). compiling a total STAR score (50 points). The data was tabulated in Google Sheets. The descriptive statistics with inter-observer agreement and the mean score were recorded. RESULTS: We observed that each of the 50 records received a score of 49/50 points on the STAR. Deductions were necessary in the Operative record section due to the lack of information regarding the sutures used. CONCLUSION: To summarize, this study emphasizes the effectiveness of the STAR scoring system in evaluating the quality of oral surgical records. Identifying deficiencies, particularly in documenting operative details, can improve the completeness and accuracy of patient records. It can ultimately enhance patient care and facilitate better communication among healthcare professionals.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Documentação/normas , Procedimentos Cirúrgicos Bucais/normas , Registros Odontológicos/normas
19.
Int J Nanomedicine ; 19: 9227-9253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267724

RESUMO

Purpose: Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy. Methods: We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved. Results: The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the ß-catenin signaling pathway and other downstream genes without inducing acute toxicity. Conclusion: Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the ß-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.


Assuntos
Nanopartículas Metálicas , MicroRNAs , Neoplasias Bucais , Prata , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , MicroRNAs/administração & dosagem , MicroRNAs/genética , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Humanos , Linhagem Celular Tumoral , Nanopartículas Metálicas/química , Camundongos , Prata/química , Prata/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Movimento Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética
20.
Microsurgery ; 44(6): e31235, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39268866

RESUMO

Bilateral trismus associated with oral cancer was commonly occurred in those who had received surgical intervention and radiotherapy. Complete release of bilateral fibrotic tissues followed by free flaps reconstruction was the main current surgical intervention. However, reconstructions of both defects mostly needed to harvest two flaps from different donor sites were time-consuming and increasing morbidities. Herein, we presented three cases who undergone modified reconstructive method by harvesting the anterolateral thigh (ALT) flap and tensor fascia latae (TFL) flap simultaneously from the same donor site. Trismus release was performed including resection of the buccal part and fibrotic tissue, myotomy of the masticatory and medial pterygoid muscles, and bilateral coronoidectomy. Case 1, a 52 years-old man, with severe trismus as the interincisal distance (IID) was about 0 mm. He undergone a combined 12 × 7.5 cm ALT and 11 × 6 cm TFL flap reconstruction from a single-donor thigh. The IID apparently increased to 37 mm after 1-year follow-up. Case 2, a 64 years-old man, went through a combination of 6 × 7 cm ALT and 6 × 6 cm TFL flap reconstruction from unilateral thigh for severe trismus. The IID significantly improved from 10 mm to 30 mm after one and a half-year follow-up. Case 3, a 53 years-old woman, with IID was around 0 mm before the surgery. A combined 9 × 3 cm ALT and 9 × 3 cm TFL flap reconstruction was performed as the IID enhanced to 20 mm after 6 months follow-up. This reconstruction method using ALT and TFL flaps harvested from a single-donor thigh simultaneously could be suitable for patients with bilateral severe trismus.


Assuntos
Fascia Lata , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Coxa da Perna , Trismo , Humanos , Masculino , Pessoa de Meia-Idade , Coxa da Perna/cirurgia , Retalhos de Tecido Biológico/transplante , Procedimentos de Cirurgia Plástica/métodos , Trismo/cirurgia , Trismo/etiologia , Fascia Lata/transplante , Neoplasias Bucais/cirurgia , Neoplasias Bucais/complicações
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