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2.
J Med Case Rep ; 18(1): 311, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970133

RESUMO

BACKGROUNDS: Manifestation of cystic hygroma in adulthood is very rare. The rarity of cystic hygroma in adults has caused problems in its diagnosis and management and few studies have reported cystic hygroma in adults. CASE PRESENTATION: In this study, we reported a rare case with cervical cystic hygroma in adults. We report a 20-year-old Iranian male (Iranian ethnicity) with a diagnosis of right-side neck cystic hygroma and discuss the presentation, diagnosis, and clinical, radiological, and operative aspects of it. CONCLUSION: Cystic hygromas are a rare occurrence in adults. They are typically asymptomatic, rarely complicated, and can be mistaken for a cystic neck mass. This study showed that in our case, surgical resection may be a safe and effective treatment for cystic hygroma, with minimal risk of complications during the procedure.


Assuntos
Linfangioma Cístico , Humanos , Linfangioma Cístico/cirurgia , Linfangioma Cístico/diagnóstico , Linfangioma Cístico/diagnóstico por imagem , Masculino , Adulto Jovem , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Pescoço/diagnóstico por imagem , Pescoço/cirurgia , Pescoço/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
3.
Int J Surg Oncol ; 2024: 5339292, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966634

RESUMO

Objective: Determine the histopathologic features that correlate with head and neck cancer (HNC) cachexia. Methods: A single-institution, retrospective study was performed on adults with HPV-negative, mucosal squamous cell carcinoma of the aerodigestive tract undergoing resection and free flap reconstruction from 2014 to 2019. Patients with distant metastases were excluded. Demographics, comorbidities, preoperative nutrition, and surgical pathology reports were collected. Comparisons of histopathologic features and cachexia severity were made. Results: The study included 222 predominantly male (64.9%) patients aged 61.3 ± 11.8 years. Cachexia was identified in 57.2% patients, and 18.5% were severe (≥15% weight loss). No differences in demographics were identified between the groups. Compared to control, patients with severe cachexia had lower serum hemoglobin (p=0.048) and albumin (p < 0.001), larger tumor diameter (p < 0.001), greater depth of invasion (p < 0.001), and elevated proportions of pT4 disease (p < 0.001), pN2-N3 disease (p=0.001), lymphovascular invasion (p=0.009), and extranodal extension (p=0.014). Multivariate logistic regression identified tumor size (OR [95% CI] = 1.36 [1.08-1.73]), oral cavity tumor (OR [95% CI] = 0.30 [0.11-0.84]), and nodal burden (OR [95% CI] = 1.16 [0.98-1.38]) as significant histopathologic contributors of cancer cachexia. Conclusions: Larger, more invasive tumors with nodal metastases and aggressive histologic features are associated with greater cachexia severity in mucosal HNC.


Assuntos
Caquexia , Neoplasias de Cabeça e Pescoço , Humanos , Caquexia/patologia , Caquexia/etiologia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/complicações , Idoso , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Prognóstico , Invasividade Neoplásica , Retalhos de Tecido Biológico
4.
FASEB J ; 38(13): e23759, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38949635

RESUMO

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.


Assuntos
ADP Ribose Transferases , Receptores ErbB , Exotoxinas , Neoplasias de Cabeça e Pescoço , Imunoglobulina G , Imunotoxinas , Exotoxina A de Pseudomonas aeruginosa , Fatores de Virulência , Humanos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Receptores ErbB/imunologia , Animais , Imunotoxinas/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/metabolismo , Camundongos , Imunoglobulina G/farmacologia , Linhagem Celular Tumoral , Exotoxinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Cetuximab/farmacologia , Camundongos Nus , Toxinas Bacterianas , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Feminino , Movimento Celular/efeitos dos fármacos , Antineoplásicos/farmacologia
5.
Sci Rep ; 14(1): 15006, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951583

RESUMO

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case-control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58-88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.


Assuntos
Neoplasias de Cabeça e Pescoço , Hipersensibilidade , Humanos , Masculino , Feminino , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , Hipersensibilidade/epidemiologia , Hipersensibilidade/complicações , Fatores de Risco , Idoso , Adulto , Razão de Chances
6.
FASEB J ; 38(13): e23803, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38963404

RESUMO

Cancer neuroscience is an emerging field of cancer biology focused on defining the interactions and relationships between the nervous system, developing malignancies, and their environments. Our previous work demonstrates that small extracellular vesicles (sEVs) released by head and neck squamous cell carcinomas (HNSCCs) recruit loco-regional nerves to the tumor. sEVs contain a diverse collection of biological cargo, including microRNAs (miRNAs). Here, we asked whether two genes commonly amplified in HNSCC, CCND1, and PIK3CA, impact the sEV miRNA cargo and, subsequently, sEV-mediated tumor innervation. To test this, we individually overexpressed these genes in a syngeneic murine HNSCC cell line, purified their sEVs, and tested their neurite outgrowth activity on dorsal root ganglia (DRG) neurons in vitro. sEVs purified from Ccnd1-overexpressing cells significantly increased neurite outgrowth of DRG compared to sEVs from parental or Pik3ca over-expressing cells. When implanted into C57BL/6 mice, Ccnd1 over-expressing tumor cells promoted significantly more tumor innervation in vivo. qPCR analysis of sEVs shows that increased expression of Ccnd1 altered the packaging of miRNAs (miR-15-5p, miR-17-5p, and miR-21-5p), many of which target transcripts important in regulating axonogenesis. These data indicate that genetic amplifications harbored by malignancies impose changes in sEV miRNA cargo, which can influence tumorc innervation.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Camundongos Endogâmicos C57BL , MicroRNAs , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Camundongos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Ciclina D1/genética , Ciclina D1/metabolismo , Gânglios Espinais/metabolismo , Humanos , Amplificação de Genes , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
7.
Curr Opin Otolaryngol Head Neck Surg ; 32(4): 278-281, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38963437

RESUMO

PURPOSE OF REVIEW: Surgery, radiation, and chemotherapy are often utilized in the treatment of head and neck cancer. These treatments can cause extensive scarring within the neck and can limit the viability of recipient vessels for further microvascular reconstruction. Patients with vessel-depleted necks provide a significant challenge for microvascular surgeons and are a topic of much discussion in the field. RECENT FINDINGS: While reconstruction in the vessel-depleted neck is an active area of interest, the patient population is rare. Therefore, single institution series with small numbers comprise the majority of published literature. Recent publications describe techniques for identifying adequate recipient vessel options outside of the field of treatment with excellent free flap outcomes. Further, recent summary articles describe techniques for addressing issues with pedicle length that can arise when using vessels that are far from the defect to be reconstructed. SUMMARY: When viable vessel options are available within the treatment field, these recipient vessels can be used with good reliability and free flap success. If in-field recipient vessels are not available, minimal access incisions can be used to identify superficial temporal, angular, contralateral facial, or transverse cervical vessels. Further away from the treatment field, internal mammary vessels can be harvested through open or robotic approaches. If the use of these distant vessels creates issues with pedicle length, interposition vein grafts, arteriovenous (AV) loops, or flow-through flaps can be used to augment vessel length.


Assuntos
Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Humanos , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Pescoço/irrigação sanguínea , Pescoço/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos de Tecido Biológico/irrigação sanguínea
8.
Psychooncology ; 33(7): e6375, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38987936

RESUMO

BACKGROUND: Head and neck cancers (HNC) are associated with high rates of anxiety. Anxiety has been linked to biological pathways implicated in cancer progression, though little is known about its effects on overall survival. We hypothesized that higher pretreatment anxiety levels in patients with HNC would predict poorer 2-year overall survival and expected this relationship to be mediated by both systemic inflammation and tumor response to treatment. METHODS: Patients (N = 394) reported anxiety symptomatology via the GAD-7 at treatment planning. Pre-treatment hematology workup provided an index of systemic inflammation (SII; N = 292). Clinical data review yielded tumor response and overall survival. Logistic and multiple regressions and Cox proportional hazard models tested hypothesized relationships. RESULTS: Higher pretreatment anxiety levels were significantly associated with poorer 2-year survival (hazard ratio [HR], 1.039; 95% confidence interval [CI], 1.014-1.066, p = 0.002). The association between anxiety and SII was not significant, though anxiety was associated with poorer tumor response (odds ratio [OR], 1.033; 95% CI, 1.001-1.066, p = 0.043). Tumor response fully mediated the relationship between anxiety symptoms and 2-year survival (HR, 9.290, 95% CI, 6.152-14.031, p < 0.001). CONCLUSIONS: Anxiety was associated with overall survival. Tumor response, but not systemic inflammation, emerged as a potential biological pathway mediating this effect. Screening for anxiety may be beneficial to help prospectively address these concerns and ameliorate potentially detrimental impact on clinically meaningful cancer outcomes.


Assuntos
Ansiedade , Neoplasias de Cabeça e Pescoço , Inflamação , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ansiedade/psicologia , Neoplasias de Cabeça e Pescoço/psicologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Idoso , Adulto , Modelos de Riscos Proporcionais , Resultado do Tratamento
9.
BMC Cancer ; 24(1): 832, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992600

RESUMO

Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.


Assuntos
Neoplasias de Cabeça e Pescoço , Mitocôndrias , Glândulas Salivares , Xerostomia , Xerostomia/etiologia , Xerostomia/prevenção & controle , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Glândulas Salivares/efeitos da radiação , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/patologia , Lesões por Radiação/prevenção & controle , Lesões por Radiação/etiologia , Animais , Radioterapia/efeitos adversos , Radioterapia/métodos , Qualidade de Vida
10.
Cells ; 13(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38994960

RESUMO

Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/genética , Papillomaviridae/genética , Regulação Neoplásica da Expressão Gênica
11.
J Extracell Vesicles ; 13(7): e12480, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978304

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is a global cancer burden with a 5-year overall survival rate of around 50%, stagnant for decades. A tumour-induced immunosuppressive microenvironment contributes to HNSCC progression, with the adenosine (ADO) pathway and an upregulated expression of inhibitory immune checkpoint regulators playing a key role in this context. The correlation between high neutrophil-to-lymphocyte ratio (NLR) with advanced tumour staging suggests involvement of neutrophils (NØ) in cancer progression. Interestingly, we associated a high NLR with an increased intracellular PD-L1 localization in primary HNSCC samples, potentially mediating more aggressive tumour characteristics and therefore synergistically favouring tumour progression. Still, further research is needed to harness this knowledge for effective treatments and overcome resistance. Since it is hypothesized that the tumour microenvironment (TME) may be influenced by small extracellular vesicles (sEVs) secreted by tumours (TEX), this study aims to investigate the impact of HNSCC-derived TEX on NØ and blockade of ADO receptors as a potential strategy to reverse the pro-tumour phenotype of NØ. UMSCC47-TEX exhibited CD73 enzymatic activity involved in ADO signalling, as well as the immune checkpoint inhibitor PD-L1. Data revealed that TEX induce chemotaxis of NØ and the sustained interaction promotes a shift into a pro-tumour phenotype, dependent on ADO receptors (P1R), increasing CD170high subpopulation, CD73 and PD-L1 expression, followed by an immunosuppressive secretome. Blocking A3R reduced CD73 and PD-L1 expression. Co-culture experiments with HNSCC cells demonstrated that TEX-modulated NØ increase the CD73/PD-L1 axis, through Cyclin D-CDK4/6 signalling. To support these findings, the CAM model with primary tumour was treated with NØ supernatant. Moreover, these NØ promoted an increase in migration, invasion, and reduced cell death. Targeting P1R on NØ, particularly A3R, exhibited potential therapeutic strategy to counteract immunosuppression in HNSCC. Understanding the TEX-mediated crosstalk between tumours and NØ offers insights into immunomodulation for improving cancer therapies.


Assuntos
5'-Nucleotidase , Antígeno B7-H1 , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Neutrófilos , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Antígeno B7-H1/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/imunologia , Neutrófilos/metabolismo , Neutrófilos/imunologia , Microambiente Tumoral/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , 5'-Nucleotidase/metabolismo , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Linhagem Celular Tumoral , Imunomodulação , Adenosina/metabolismo , Proteínas Ligadas por GPI
12.
Phys Med ; 123: 103427, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38959576

RESUMO

BACKGROUND: Reirradiation of head and neck cancer (HNC) became more accessible in the last decade, owing to modern irradiation techniques which offer a reduction in treatment related toxicities. The aim of this paper was to comparatively evaluate the dosimetric aspects derived from intensity modulated photon vs. proton treatment planning in reirradiated HNC patients. METHODS: Six recurrent HNC patients were enrolled in this retrospective study. For each patient two treatment plans were created: one IMRT/VMAT and one IMPT plan. The prescribed dose for the second irradiation was between 50 and 70 Gy RBE. The study comparatively analyzed the CTV coverage, doses to organs at risk (OARs) and low doses received by the healthy tissue (other than OAR). RESULTS: Similar CTV coverage was achieved for photon vs proton plans, with the latter presenting better homogeneity in four cases. Maximum dose to CTV was generally higher for photon plans, with differences ranging from 0.3 to 1.9%. For parotid glands and body, the mean dose was lower for proton plans. A notable reduction of low dose to healthy tissue (other than OARs) could be achieved with protons, with an average of 60% and 64% for D10% and Dmean, respectively. CONCLUSION: The dosimetric comparison between photon and proton reirradiation of HNC showed a great need for treatment individualization, concluding that protons should be considered for reirradiation on an individual basis.


Assuntos
Neoplasias de Cabeça e Pescoço , Órgãos em Risco , Fótons , Terapia com Prótons , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Reirradiação , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Fótons/uso terapêutico , Radioterapia de Intensidade Modulada/métodos , Reirradiação/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Órgãos em Risco/efeitos da radiação , Estudos Retrospectivos
13.
Sci Rep ; 14(1): 15962, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987626

RESUMO

The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Células-Tronco Neoplásicas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Prognóstico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
14.
Mol Cancer ; 23(1): 141, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982480

RESUMO

BACKGROUND: The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. METHODS: We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. RESULTS: Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. CONCLUSION: Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.


Assuntos
Progressão da Doença , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Proteínas Proto-Oncogênicas c-myc , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Camundongos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Linhagem Celular Tumoral , Fosfofrutoquinase-1 Tipo C/metabolismo , Fosfofrutoquinase-1 Tipo C/genética , Proliferação de Células , Prognóstico , Feminino , Masculino , Ensaios Antitumorais Modelo de Xenoenxerto , Biomarcadores Tumorais/metabolismo
15.
J Transl Med ; 22(1): 645, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982511

RESUMO

BACKGROUND: Cancer-associated fibroblast (CAF)-cancer cell crosstalk (CCCT) plays an important role in tumor microenvironment shaping and immunotherapy response. Current prognostic indexes are insufficient to accurately assess immunotherapy response in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to develop a CCCT-related gene prognostic index (CCRGPI) for assessing the prognosis and response to immune checkpoint inhibitor (ICI) therapy of HNSCC patients. METHODS: Two cellular models, the fibroblast-cancer cell indirect coculture (FCICC) model, and the fibroblast-cancer cell organoid (FC-organoid) model, were constructed to visualize the crosstalk between fibroblasts and cancer cells. Based on a HNSCC scRNA-seq dataset, the R package CellChat was used to perform cell communication analysis to identify gene pairs involved in CCCT. Least absolute shrinkage and selection operator (LASSO) regression was then applied to further refine the selection of these gene pairs. The selected gene pairs were subsequently subjected to stepwise regression to develop CCRGPI. We further performed a comprehensive analysis to determine the molecular and immune characteristics, and prognosis associated with ICI therapy in different CCRGPI subgroups. Finally, the connectivity map (CMap) analysis and molecular docking were used to screen potential therapeutic drugs. RESULTS: FCICC and FC-organoid models showed that cancer cells promoted the activation of fibroblasts into CAFs, that CAFs enhanced the invasion of cancer cells, and that CCCT was somewhat heterogeneous. The CCRGPI was developed based on 4 gene pairs: IGF1-IGF1R, LGALS9-CD44, SEMA5A-PLXNA1, and TNXB-SDC1. Furthermore, a high CCRGPI score was identified as an adverse prognostic factor for overall survival (OS). Additionally, a high CCRGPI was positively correlated with the activation of the P53 pathway, a high TP53 mutation rate, and decreased benefit from ICI therapy but was inversely associated with the abundance of various immune cells, such as CD4+ T cells, CD8+ T cells, and B cells. Moreover, Ganetespib was identified as a potential drug for HNSCC combination therapy. CONCLUSIONS: The CCRGPI is reliable for predicting the prognosis and immunotherapy response of HSNCC patients and may be useful for guiding the individualized treatment of HNSCC patients.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias de Cabeça e Pescoço , Aprendizado de Máquina , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Prognóstico , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/genética , Comunicação Celular/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Resultado do Tratamento , Linhagem Celular Tumoral , Feminino
16.
Oncotarget ; 15: 444-458, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985143

RESUMO

OBJECTIVE: Patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) after primary local therapy have low response rates with cetuximab, systemic chemotherapy or check point inhibitor therapy. Novel combination therapies with the potential to improve outcomes for patients with HNSCC is an area of high unmet need. METHODS: This is a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment. The primary endpoints were safety and tolerability and the primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were evaluated for outcome. RESULTS: Twenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 - 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 45%) with 2 of these patients achieving a complete response (CR). The median PFS in HPV-negative/EphrinB2 positive patients was 3.2 months (95% CI 1.1, 7.3). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7). Hypertension, transaminitis and fatigue were the most common toxicities. DISCUSSION: The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.


Assuntos
Anticorpos Monoclonais Humanizados , Efrina-B2 , Neoplasias de Cabeça e Pescoço , Receptor EphB4 , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Idoso , Efrina-B2/metabolismo , Adulto , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Receptor EphB4/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso de 80 Anos ou mais
17.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000120

RESUMO

Head and neck squamous cell carcinoma (HNSCC) affects squamous cells in the head and neck region and is currently ranked as the sixth most common cancer worldwide. NF-E2-related factor 2 (NRF2) plays a crucial role in cellular protection and defence mechanisms and NRF2 over-expression has been linked to various cancers; however, its role in the response of HNSCC cells remains elusive. We investigated the effects of ML385, a selective NRF2 inhibitor, on HNSCC to understand the underlying molecular mechanisms, and to assess the potential of ML385 as a therapeutic agent. We treated HNSCC cell lines with ML385 and observed a significant reduction in the expression of NRF2 and its downstream target, heme oxygenase-1 (HO-1), using Western blotting. We evaluated its effects on various cellular processes, including cell proliferation, cloning, migration, and wound healing, in HNSCC cell lines. ML385 treatment substantially reduced NRF2 expression, promoting a decrease in the investigated cellular activities. Additionally, we examined changes in the expression of cell-cycle-related proteins and found that ML385 induced cell cycle arrest at the G1/S phase in HNSCC cell lines. Our findings suggest that ML385 can regulate cell cycle progression, inhibit HNSCC growth, and have potential as a therapeutic agent for HNSCC.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias de Cabeça e Pescoço , Fator 2 Relacionado a NF-E2 , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Movimento Celular/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antineoplásicos/farmacologia , Acetamidas , Benzodioxóis
18.
Br J Nurs ; 33(14): 656-662, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023020

RESUMO

The number of urgent '2-week-wait' referrals to hospital for people with suspected head and neck cancer being sent by primary care is constantly growing and it is becoming increasingly difficult for head and neck cancer services to meet this demand. In order for trusts to meet their Faster Diagnosis Standards, there needs to be an effective and efficient way to ensure there is capacity for patients to receive the appropriate assessments and diagnostic investigations without compromising the quality of care delivered. This article presents the proposal of introducing a nurse-led 2-week-wait clinic to meet the ever-growing demands on the service. There is discussion of the consultant-led training programme used to upskill an advanced nurse practitioner in a single-centre study, as well as explanation of the processes followed to maintain patient safety throughout the pilot project. There will also be consideration of clinical governance and discussion of how patient satisfaction with the novel service will be measured.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/enfermagem , Neoplasias de Cabeça e Pescoço/diagnóstico , Reino Unido , Encaminhamento e Consulta , Medicina Estatal , Listas de Espera , Padrões de Prática em Enfermagem , Projetos Piloto
19.
Sci Rep ; 14(1): 16300, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009605

RESUMO

Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the ACC exhibited diverse levels of species richness. We identified two main microbial subtypes within the ACC: oral-like and gut-like. Oral-like microbiomes, characterized by increased diversity and abundance of Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with a less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with a more diverse microbiome, less aggressive tumor phenotype, and better survival that reveal the genera as potential pancancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. Conversely, gut-like intratumoral microbiomes, which feature low diversity and colonization by gut mucus layer-degrading species, such as Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival and positively correlated with tumor cell biosynthesis of glycan-based cell membrane components.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Microbiota , RNA Ribossômico 16S , Humanos , Carcinoma Adenoide Cístico/microbiologia , Carcinoma Adenoide Cístico/patologia , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/patologia , Feminino , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Idoso , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação
20.
Mol Biomed ; 5(1): 27, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39009906

RESUMO

miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.


Assuntos
Adenosina , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , MicroRNAs , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Linhagem Celular Tumoral , Adenosina/análogos & derivados , Adenosina/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Movimento Celular/genética , Regiões 3' não Traduzidas/genética , Metiltransferases/genética , Metiltransferases/metabolismo
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