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1.
Cancer Immunol Immunother ; 73(4): 70, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430375

RESUMO

BACKGROUND: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR). METHODS: Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective response rates (ORRs) were evaluated based on prespecified cut-offs for PD-L1 (tumor cell [TC] ≥ 50%/immune cell ≥ 25% or TC ≥ 25%), bTMB (≥ 16 mutations [mut] per megabase [Mb]), and NLR (≤ 7). Ad hoc analyses of exploratory cut-offs were performed. RESULTS: Prespecified or exploratory cut-offs for PD-L1 did not enrich for ORR or OS for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME. In the bTMB ≥ 16 mut/Mb subgroup, OS hazard ratios (95% confidence interval) for durvalumab monotherapy and durvalumab plus tremelimumab versus EXTREME were 0.90 (0.48-1.72) and 0.69 (0.39-1.25), respectively. Complete response rates were 8.6% with durvalumab plus tremelimumab and 4.3% with EXTREME (≥ 16 mut/Mb subgroup). No improvement in OS was observed for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME at prespecified or exploratory NLR cut-offs. CONCLUSIONS: bTMB demonstrated potential utility for selecting patients with R/M HNSCC who benefited from durvalumab with or without tremelimumab versus EXTREME. Trial registration ClinicalTrials.gov identifier NCT02551159.


Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Antígeno B7-H1 , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Antígeno B7-H1/metabolismo , Resultado do Tratamento , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Biomarcadores Tumorais/metabolismo
2.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 285-290, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38431838

RESUMO

Cerebral aneurysm can rupture a blood vessel and cause bleeding in the brain. Microsurgical clipping of the tumor neck has been reported to be effective in treating cerebral aneurysm rupture and bleeding. This research attempted to clarify the clinical efficacy of early microsurgical clipping of tumor neck for treating cerebral aneurysm rupture and bleeding, and its impact on the prognosis of patients. One hundred patients with cerebral aneurysm rupture and bleeding patients were treated. They were selected and divided into experimental group (n=25) and control group (n=25) according to surgical time. All patients underwent microsurgical clipping of tumor neck for therapy. The control group chose to undergo surgery 72 hours after the onset of cerebral aneurysm rupture and bleeding, while the experimental group chose to undergo complete surgery within 72 hours after the onset of cerebral aneurysm rupture and bleeding. Primary outcome measures were incidence of complications, cognitive function scores, prognosis, surgical indicators, oxidative stress response and quality of life. Results showed that compared to the control group, the incidence of complications in experimental group exhibited depletion (P<0.05), the prognosis in experimental group exhibited elevation (P<0.05), the hospitalization time in experimental group exhibited depletion (P<0.05), the nomination, abstraction, language, orientation, attention, delayed recall and visual and executive function scores and total scores in experimental group exhibited elevation (P<0.05), serum levels of oxidative stress-related indicators in experimental group exhibited depletion (P<0.05) and the quality of life in experimental group exhibited elevation (P<0.05). In conclusion, early microsurgical clipping of the tumor neck can reduce the risk of complications and cognitive impairment in patients with cerebral aneurysm rupture and bleeding.


Assuntos
Neoplasias de Cabeça e Pescoço , Aneurisma Intracraniano , Acidente Vascular Cerebral , Humanos , Aneurisma Intracraniano/cirurgia , Qualidade de Vida , Resultado do Tratamento , Hemorragia
3.
Lancet Healthy Longev ; 5(3): e182-e193, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38432247

RESUMO

BACKGROUND: At present, there is no established standard treatment for frail older patients with recurrent or metastatic head and neck squamous cell carcinoma. We aimed to compare the efficacy and safety of cetuximab to those of methotrexate (the reference regimen) in this population. METHODS: This randomised, open-label, phase 3 trial was done at 20 hospitals in France. Patients aged 70 years or older, assessed as frail by the ELAN Geriatric Evaluation, with recurrent or metastatic head and neck squamous cell carcinoma in the first-line setting and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were eligible for inclusion. Patients were randomly assigned (1:1) to receive cetuximab 500 mg/m2 intravenously every 2 weeks or methotrexate 40 mg/m2 intravenously every week, with minimisation by ECOG performance status, type of disease evolution, Charlson Comorbidity Index score, serum albumin concentration, and geriatrician consultation. To avoid deterministic minimisation and assure allocation concealment, patients were allocated with a probability of 0·80 to the treatment that most reduced the imbalance. Treatment was continued until disease progression or unacceptable toxicity, whichever occurred first. The primary endpoint was failure-free survival (defined as the time from randomisation to disease progression, death, discontinuation of treatment, or loss of 2 or more points on the Activities in Daily Living scale, whichever occurred first) and was analysed in the intention-to-treat population. 151 failures expected out of 164 patients were required to detect a hazard ratio (HR) of 0·625 with 0·05 alpha error, with 80% power. A futility interim analysis was planned when approximately 80 failures were observed, based on failure-free survival. Safety analyses included all patients who received at least one dose of the study drug. This study is registered on ClinicalTrials.gov (NCT01884623) and was stopped for futility after the interim analysis. FINDINGS: Between Nov 7, 2013, and April 23, 2018, 82 patients were enrolled (41 to the cetuximab group and 41 to the methotrexate group); 60 (73%) were male, 37 (45%) were aged 80 years or older, 35 (43%) had an ECOG performance status of 2, and 36 (44%) had metastatic disease. Enrolment was stopped for futility at the interim analysis. At the final analysis, median follow-up was 43·3 months (IQR 30·8-52·1). At data cutoff, all 82 patients had failure; failure-free survival did not differ significantly between the groups (median 1·4 months [95% CI 1·0-2·1] in the cetuximab group vs 1·9 months [1·1-2·6] in the methotrexate group; adjusted HR 1·03 [95% CI 0·66-1·61], p=0·89). The frequency of patients who had grade 3 or worse adverse events was 63% (26 of 41) in the cetuximab group and 73% (30 of 41) in the methotrexate group. The most common grade 3-4 adverse events in the cetuximab group were fatigue (four [10%] of 41 patients), lung infection (four [10%]), and rash acneiform (four [10%]), and those in the methotrexate group were fatigue (nine [22%] of 41), increased gamma-glutamyltransferase (seven [17%]), natraemia disorder (four [10%]), anaemia (four [10%]), leukopenia (four [10%]), and neutropenia (four [10%]). The frequency of patients who had serious adverse events was 44% (18 of 41) in the cetuximab group and 39% (16 of 41) in the methotrexate group. Four patients presented with a fatal adverse event in the cetuximab group (sepsis, decreased level of consciousness, pulmonary oedema, and death of unknown cause) as did two patients in the methotrexate group (dyspnoea and death of unknown cause). INTERPRETATION: The study showed no improvement in failure-free survival with cetuximab versus methotrexate. Patients with an ECOG performance status of 2 did not benefit from these systemic therapies. New treatment options including immunotherapy should be explored in frail older patients with recurrent or metastatic head and neck squamous cell carcinoma, after an initial geriatric evaluation, such as the ELAN Geriatric Evaluation. FUNDING: French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC and the Ligue Contre le Cancer), GEMLUC, GEFLUC, and Merck Santé. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.


Assuntos
Neoplasias de Cabeça e Pescoço , Metotrexato , Humanos , Masculino , Idoso , Feminino , Metotrexato/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Cetuximab/efeitos adversos , Idoso Fragilizado , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Progressão da Doença , Fadiga
4.
Artigo em Chinês | MEDLINE | ID: mdl-38433692

RESUMO

Objective:This study aims to provide a comprehensive summary of the pathogenesis, screening modalities, treatment strategies, repair modalities and preliminary results associated with facial nerve tumors. Methods:A retrospective analysis was conducted on the clinical data of 12 patients with facial nerve tumors who were admitted to our department between May 2018 and February 2023. The study population consisted of 5 males and 7 females, with ages ranging from 35 to 90 years. Clinical symptoms observed in these patients included facial nerve palsy, hearing loss, tinnitus, headache, and otalgia, etc. The severity of facial nerve dysfunction was assessed using the House-Brackmann(H-B) facial nerve function classification, with 3 cases classified as grade Ⅰ, 4 cases as grade Ⅲ, 2 cases as grade Ⅳ, and 3 cases as grade Ⅴ. There was a total of 11 patients who presented with hearing loss. Among these patients, 7 cases were diagnosed with conductive hearing loss, 2 cases with sensorineural hearing loss, and 2 cases with mixed hearing loss. The selection of the observation or surgical route for tumor localization was based on clinical symptoms, facial nerve function grading, and imaging examination results including temporal bone CT and enhanced MRI. Specifically, the location of the tumor was selected for observation or the best surgical route: 2 cases were followed up for observation, 1 case underwent biopsy, and 9 cases underwent tumor resection(7 cases of trans-mastoid approach, 2 cases of combined parotid-mastoidal approach), concurrent repair of the facial nerve(4 cases of auricular nerve grafting, 3 cases of facial nerve diversion anastomosis, 2 cases of peroneal nerve grafting). (4 cases of auricular nerve graft, 3 cases of facial nerve diversion anastomosis and 2 cases of peroneal nerve grafting). Periodic postoperative evaluation of facial nerve function was conducted. Results:1-year follow-up was available. Intraoperatively, it was observed that 66.7%(6 out of 9) of the facial nerve tumors were present in multiple segments. Among these segments, the vertical segment had the highest proportion, accounting for 77.8%(7 out of 9), followed by the labyrinthine segment/geniculate ganglion with 66.7%(6 out of 9) and the horizontal segment with 55.6%(5 out of 9). Postoperative pathology confirmed 8 cases with nerve sheath meningioma, Ⅰ with seminal fibroma and 1 with hemangioma. Postoperative facial nerve function was graded as H-B grade I in one patient), grade Ⅲ in three, grade Ⅳ in four, grade Ⅴ in 2, and grade Ⅵ in 2 patients. The auditory outcomes following surgery are as follows: 8 individuals experienced postoperative hearing loss, while 2 individuals demonstrated postoperative hearing preservation. Conclusion:In the case of patients presenting with facial nerve palsy as their initial symptom, it is imperative to consider the potential presence of a facial nerve tumor. To determine the appropriate course of action, it is necessary to ascertain the size and location of the tumors through imaging examinations. This information will aid in the decision making process regarding whether surgical intervention is warranted, and so, the most suitable approach. Additionally, the choice of repair method during the operation should be guided by the extent of facial nerve defect.


Assuntos
Neoplasias dos Nervos Cranianos , Surdez , Paralisia Facial , Neoplasias de Cabeça e Pescoço , Feminino , Masculino , Humanos , Nervo Facial , Estudos Retrospectivos , Paralisia Facial/cirurgia
5.
Sultan Qaboos Univ Med J ; 24(1): 52-57, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38434449

RESUMO

Objectives: This study aimed to analyse the association of tumour budding (TB) and tumour-stroma ratio (TSR) with clinicopathological parameters that can be easily viewed on routine haematoxylin and eosin (H&E)-stained slides to provide an easy and cost-effective method for prognosticating oral squamous cell carcinoma (OSCC). Methods: This study was conducted at the ESIC Medical College and Hospital in Faridabad, India, from July 2022 to October 2022. In patients with histologically diagnosed OSCC, TB and TSR were evaluated via routine H&E-stained sections and correlated with clinicopathological parameters. Statistical analysis was performed using Chi-squared test. Results: A total of 50 patients were included. The mean age of participants was 61 ± 12.72, and the male-to-female ratio was 7.1:1. Most of the tumours were located on the tongue (46%), followed by the buccal mucosa (26%), gingivobuccal sulcus (12%) and retromolar trigone (8%). The palate and alveolus were the other sites involved, constituting 4% each. TB and TSR were both found to be significantly associated with the tumour grade, lymph node metastasis and tumour size. A highly significant correlation was also found between TB and TSR (P = 0.001). Conclusions: Both TB and TSR can be easily evaluated on routine H&E sections; they are highly reproducible and were found to be reliable independent prognostic markers in OSCC. Therefore, this simple and cost-effective method of prognostication, which is currently lacking in clinical practice, will help clinicians to identify patients with poor prognosis and thus individualise their treatment plan.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Feminino , Masculino , Carcinoma de Células Escamosas de Cabeça e Pescoço , Hospitais
6.
Cancer Med ; 13(3): e6986, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38426619

RESUMO

BACKGROUND: PTGS2 encodes cyclooxygenase-2 (COX-2), which catalyses the committed step in prostaglandin synthesis. Various in vivo and in vitro data suggest that COX-2 mediates the VEGF signalling pathway. In silico analysis performed in TCGA, PanCancer Atlas for head and neck cancers, demonstrated significant expression and co-expression of PTGS2 and genes that regulate VEGF signalling. This study was designed to elucidate the expression pattern of PTGS2 and genes regulating VEGF signalling in patients with locally advanced oral squamous cell carcinoma (OSCC). METHODOLOGY: Tumour and normal tissue samples were collected from patients with locally advanced OSCC. RNA was isolated from tissue samples, followed by cDNA synthesis. The cDNA was used for gene expression analysis (RT-PCR) using target-specific primers. The results obtained were compared with the in silico gene expression of the target genes in the TCGA datasets. Co-expression analysis was performed to establish an association between PTGS2 and VEGF signalling genes. RESULTS: Tumour and normal tissue samples were collected from 24 OSCC patients. Significant upregulation of PTGS2 expression was observed. Furthermore, VEGFA, KDR, CXCR1 and CXCR2 were significantly upregulated in tumour samples compared with paired normal samples, except for VEGFB, whose expression was not statistically significant. A similar expression pattern was observed in silico, except for CXCR2 which was highly expressed in the normal samples. Co-expression analysis showed a significant positive correlation between PTGS2 and VEGF signalling genes, except for VEGFB which showed a negative correlation. CONCLUSION: PTGS2 and VEGF signalling genes are upregulated in OSCC, which has a profound impact on clinical outcomes.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Ciclo-Oxigenase 2/genética , Fator A de Crescimento do Endotélio Vascular/genética , DNA Complementar
7.
Medicine (Baltimore) ; 103(9): e37387, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428879

RESUMO

Squamous cell carcinoma is seen as principal malignancy of head and neck. Tumor immune microenvironment plays a vital role in the occurrence, development and treatment of head and neck squamous cell carcinoma (HNSCC). The effect of immunotherapy, in particular, is closely related to tumor immune microenvironment. This review searched for high-quality literature included within PubMed, Web of Science, and Scopus using the keywords "head and neck cancers," "tumor microenvironment" and "immunotherapy," with the view to summarizing the characteristics of HNSCC immune microenvironment and how various subsets of immune cells promote tumorigenesis. At the same time, based on the favorable prospects of immunotherapy having been shown currently, the study is committed to pinpointing the latest progress of HNSCC immunotherapy, which is of great significance in not only further guiding the diagnosis and treatment of HNSCC, but also conducting its prognostic judgement.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Microambiente Tumoral , Carcinoma de Células Escamosas/terapia , Imunoterapia , Neoplasias de Cabeça e Pescoço/terapia , Prognóstico
8.
Cancer Med ; 13(5): e7094, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468595

RESUMO

BACKGROUND: Estimation of prognosis of oral squamous cell carcinoma (OSCC) is inaccurate prior to surgery, only being effected following subsequent pathological analysis of the primary tumour and excised lymph nodes. Consequently, a proportion of patients are overtreated, with an increase in morbidity, or undertreated, with inadequate margins and risk of recurrence. We hypothesise that it is possible to accurately characterise clinical outcomes from infrared spectra arising from diagnostic biopsies. In this first step, we correlate survival with IR spectra derived from the primary tumour. METHODS: Infrared spectra were collected from tumour tissue from 29 patients with OSCC and subject to classification modelling. RESULTS: The model had a median AUROC of 0.89 with regard to prognosis, a median specificity of 0.83, and a hazard ratio of 6.29 in univariate Cox proportional hazard modelling. CONCLUSION: The data suggest that FTIR spectra may be a useful early biomarker of prognosis in OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Prognóstico
9.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(1): 46-55, 2024 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38475950

RESUMO

OBJECTIVES: This study aimed to explore the effect of pituitary tumor-transforming gene 1 (PTT-G1) on the invasion and proliferation of oral squamous cell carcinoma (OSCC) cell lines under the action of miR-362-3p. METHODS: The bioinformatics online database was used to query the expression of PTTG1 in head and neck squamous cell carcinoma (HNSCC). The expression of PTTG1 in the Cal-27, HN-30, and HOK cell lines was detected by Western blot. A wound-healing assay was used to determine the effect of PTTG1 on the migration ability of the OSCC cells. The Transwell assay was used to examine the changes in cell-invasion ability. 5-ethynyl-2'-deoxyuridine (EdU) cell-proliferation assay was used to detect changes in cell-proliferation ability. Bioinformatics approach predicted the upstream miRNA of PTTG1. The targeting relationship between miR-362-3p and PTTG1 was examined by the dual luciferase assay, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of miRNA in OSCC tissues. RESULTS: The ENCORI database showed that PTTG1 expression was up-regulated in OSCC tissues. Western blot confirmed that PTTG1 expression was up-regulated in Cal-27 and HN-30 cells than HOK cells. PTTG1 knockout can inhibit the migration, invasion, and proliferation of Cal-27 and HN-30 cells (P<0.05). Bioinformatics prediction websites predicted that the upstream miRNA of PTTG1 was miR-362-3p, and PTTG1 can bind to miR-362-3p. Results of qRT-PCR showed that miR-362-3p expression was downregulated in OSCC tissues compared with normal tissue (P<0.05). Transwell and EdU experiments confirmed that miR-362-3p knockdown can promote the invasion and proliferation of Cal-27 and HN-30 after PTTG1 knockdown. CONCLUSIONS: miR-362-3p can inhibit the invasion and proliferation of Cal-27 and HN-30 cells by targeting PTTG1.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Neoplasias Hipofisárias , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Neoplasias Hipofisárias/genética , Invasividade Neoplásica/genética , Movimento Celular/genética , MicroRNAs/genética , Proliferação de Células , Oncogenes , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
10.
PLoS One ; 19(3): e0297387, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38470874

RESUMO

Head and neck cancer treatment often consists of surgical resection of the tumor followed by ionizing radiation (IR), which can damage surrounding tissues and cause adverse side effects. The underlying mechanisms of radiation-induced salivary gland dysfunction are not fully understood, and treatment options are scarce and ineffective. The wound healing process is a necessary response to tissue injury, and broadly consists of inflammatory, proliferative, and redifferentiation phases with immune cells playing key roles in all three phases. In this study, select immune cells were phenotyped and quantified, and certain cytokine and chemokine concentrations were measured in mouse parotid glands after IR. Further, we used a model where glandular function is restored to assess the immune phenotype in a regenerative response. These data suggest that irradiated parotid tissue does not progress through a typical inflammatory response observed in wounds that heal. Specifically, total immune cells (CD45+) decrease at days 2 and 5 following IR, macrophages (F4/80+CD11b+) decrease at day 2 and 5 and increase at day 30, while neutrophils (Ly6G+CD11b+) significantly increase at day 30 following IR. Additionally, radiation treatment reduces CD3- cells at all time points, significantly increases CD3+/CD4+CD8+ double positive cells, and significantly reduces CD3+/CD4-CD8- double negative cells at day 30 after IR. Previous data indicate that post-IR treatment with IGF-1 restores salivary gland function at day 30, and IGF-1 injections attenuate the increase in macrophages, neutrophils, and CD4+CD8+ T cells observed at day 30 following IR. Taken together, these data indicate that parotid salivary tissue exhibits a dysregulated immune response following radiation treatment which may contribute to chronic loss of function phenotype in head and neck cancer survivors.


Assuntos
Neoplasias de Cabeça e Pescoço , Glândula Parótida , Camundongos , Animais , Glândula Parótida/efeitos da radiação , Fator de Crescimento Insulin-Like I , Glândulas Salivares , Imunidade
11.
Clin Exp Dent Res ; 10(2): e877, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38481355

RESUMO

OBJECTIVES: Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long-term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR-3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oral potentially malignant disorder (OLP) and malignant (OSCC) lesions for miR-3928 expression. MATERIALS AND METHODS: In this cross-sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patients with OSCC were collected. The evaluation of miR-3928 expression by q-PCR and its correlation with clinicopathological indices were analyzed by Shapiro-Wilk, Kruskal-Wallis, Pearson's χ2 , and Mann-Whitney tests. The p-value less than .05 indicated statistically significant results. RESULTS: Based on nonparametric Kruskal-Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR-3928 expression in three study groups (p < .05). The result of the χ2  test showed a statistically significant difference in miR-3928 expression between patients with OLP (p = .01) and also patients with OSCC (p < .0001) in comparison to the control group. CONCLUSIONS: The salivary miR-3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR-3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Líquen Plano Bucal , MicroRNAs , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Líquen Plano Bucal/diagnóstico , Líquen Plano Bucal/genética , Estudos Transversais , Regulação para Baixo , Biomarcadores/análise , MicroRNAs/genética
12.
Immunity ; 57(3): 406-408, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38479356

RESUMO

Combined anti-PD-L1+anti-CTLA-4 therapy has shown benefits over anti-PD-L1 monotherapy as a neoadjuvant treatment in head and neck cancer. In this issue of Immunity, Franken et al. report that CD4+ T cell trafficking from lymph nodes to tumors and expansion toward T helper 1 cells are features specific to combination therapy.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Antígeno CTLA-4 , Terapia Combinada , Antígeno B7-H1
13.
Front Cell Infect Microbiol ; 14: 1329057, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481661

RESUMO

Head and neck squamous cell carcinoma (HNSCC) exhibits significant genetic heterogeneity and primarily concerns the oral cavity and oropharynx. These cancers occur more frequently in men with a 5-year survival rate below 50%. Major risk factors include human papilloma virus (HPV) (notably type 16), Epstein-Barr virus, tobacco, alcohol, and poor oral hygiene with approximately 4.5% of global cancers linked to HPV. Notably, differences in the microbiome between healthy individuals and patients with head and neck cancers (HNCs) have been identified. Recent studies highlight the significance of certain oral microbes in risk assessment and the potential of the microbiome as a biomarker for HNCs. Additionally, role of the microbiome in metastasis has been acknowledged. Treatment for HNCs includes local methods, such as surgery and radiotherapy, and systemic approaches, such as immunotherapy. Numerous side effects accompany these treatments. Emerging research suggests the beneficial role of preoperative immunonutrition and probiotics in patient outcomes, emphasizing the influence of the microbiome on treatment efficacy. This review explores the reciprocal effects of HNC treatment and the gut microbiome using radiotherapy, brachytherapy, surgery, immunotherapy, and chemotherapy.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias de Cabeça e Pescoço , Microbiota , Infecções por Papillomavirus , Masculino , Humanos , Herpesvirus Humano 4 , Neoplasias de Cabeça e Pescoço/terapia
15.
J Exp Clin Cancer Res ; 43(1): 76, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38468260

RESUMO

BACKGROUND: While T cell-activating immunotherapies against recurrent head and neck squamous cell carcinoma (HNSCC) have shown impressive results in clinical trials, they are often ineffective in the majority of patients. NK cells are potential targets for immunotherapeutic intervention; however, the setback in monalizumab-based therapy in HNSCC highlights the need for an alternative treatment to enhance their antitumor activity. METHODS: Single-cell RNA sequencing (scRNA-seq) and TCGA HNSCC datasets were used to identify key molecular alterations in NK cells. Representative HPV-positive ( +) and HPV-negative ( -) HNSCC cell lines and orthotopic mouse models were used to validate the bioinformatic findings. Changes in immune cells were examined by flow cytometry and immunofluorescence. RESULTS: Through integration of scRNA-seq data with TCGA data, we found that the impact of IL6/IL6R and CCL2/CCR2 signaling pathways on evasion of immune attack by NK cells is more pronounced in the HPV - HNSCC cohort compared to the HPV + HNSCC cohort. In orthotopic mouse models, blocking IL6 with a neutralizing antibody suppressed HPV - but not HPV + tumors, which was accompanied by increased tumor infiltration and proliferation of CD161+ NK cells. Notably, combining the CCR2 chemokine receptor antagonist RS504393 with IL6 blockade resulted in a more pronounced antitumor effect that was associated with more activated intratumoral NK cells in HPV - HNSCC compared to either agent alone. CONCLUSIONS: These findings demonstrate that dual blockade of IL6 and CCR2 pathways effectively enhances the antitumor activity of NK cells in HPV-negative HNSCC, providing a novel strategy for treating this type of cancer.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Animais , Camundongos , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Interleucina-6/metabolismo , Infecções por Papillomavirus/complicações , Recidiva Local de Neoplasia/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Células Matadoras Naturais , Receptores CCR2/genética , Receptores CCR2/metabolismo
16.
Int J Mol Sci ; 25(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38473807

RESUMO

The high incidence of, and mortality from, head and neck cancers (HNCs), including those related to Epstein-Barr virus (EBV), constitute a major challenge for modern medicine, both in terms of diagnosis and treatment. Therefore, many researchers have made efforts to identify diagnostic and prognostic factors. The aim of this study was to evaluate the diagnostic usefulness of matrix metalloproteinase 3 (MMP 3) and matrix metalloproteinase 9 (MMP 9) in EBV positive oropharyngeal squamous cell carcinoma (OPSCC) patients. For this purpose, the level of these MMPs in the serum of patients with EBV-positive OPSCC was analyzed in relation to the degree of histological differentiation and TNM classification. Our research team's results indicate that the level of both MMPs is much higher in the EBV positive OPSCC patients compared to the EBV negative and control groups. Moreover, their levels were higher in more advanced clinical stages. Considering the possible correlation between the level of MMP 3, MMP 9 and anti-EBV antibodies, and also viral load, after statistical analysis using multiple linear regression, their high correlation was demonstrated. The obtained results confirm the diagnostic accuracy for MMP 3 and MMP 9. Both MMPs may be useful in the diagnosis of EBV positive OPSCC patients.


Assuntos
Carcinoma de Células Escamosas , Infecções por Vírus Epstein-Barr , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Humanos , Herpesvirus Humano 4 , Metaloproteinase 3 da Matriz , Metaloproteinase 9 da Matriz , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Biomarcadores , Neoplasias Orofaríngeas/patologia
17.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473853

RESUMO

Laser-induced breakdown spectroscopy (LIBS) was recently introduced as a rapid bone analysis technique in bone-infiltrating head and neck cancers. Research efforts on laser surgery systems with controlled tissue feedback are currently limited to animal specimens and the use of nontumorous tissues. Accordingly, this study aimed to characterize the electrolyte composition of tissues in human mandibular bone-infiltrating head and neck cancer. Mandible cross-sections from 12 patients with bone-invasive head and neck cancers were natively investigated with LIBS. Representative LIBS spectra (n = 3049) of the inferior alveolar nerve, fibrosis, tumor stroma, and cell-rich tumor areas were acquired and histologically validated. Tissue-specific differences in the LIBS spectra were determined by receiver operating characteristics analysis and visualized by principal component analysis. The electrolyte emission values of calcium (Ca) and potassium (K) significantly (p < 0.0001) differed in fibrosis, nerve tissue, tumor stroma, and cell-rich tumor areas. Based on the intracellular detection of Ca and K, LIBS ensures the discrimination between the inferior alveolar nerve and cell-rich tumor tissue with a sensitivity of ≥95.2% and a specificity of ≥87.2%. The heterogeneity of electrolyte emission values within tumorous and nontumorous tissue areas enables LIBS-based tissue recognition in mandibular bone-infiltrating head and neck cancer.


Assuntos
Neoplasias de Cabeça e Pescoço , Lasers , Animais , Humanos , Análise Espectral/métodos , Eletrólitos , Mandíbula , Fibrose
18.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473882

RESUMO

Different efforts have been made to find better and less invasive methods for the diagnosis and prediction of oral cancer, such as the study of saliva as a source of biomarkers. The aim of this study was to perform a scoping review about salivary molecules that have been assessed as possible biomarkers for the diagnosis of oral squamous cell carcinoma (OSCC). A search was conducted using EBSCO, PubMed (MEDLINE), Scopus, and Web of Science. The research question was as follows: which molecules present in saliva have utility to be used as biomarkers for the early detection of oral cancer? Sixty-two studies were included. Over 100 molecules were assessed. Most of the markers were oriented towards the early diagnosis of OSCC and were classified based on their ability for detecting OSCC and oral potentially malignant disorders (OPMDs), OSCC outcome prediction, and the prediction of the malignant transformation of OPMDs. TNF-α, IL-1ß, IL-6 IL-8, LDH, and MMP-9 were the most studied, with almost all studies reporting high sensitivity and specificity values. TNF-α, IL-1ß, IL-6 IL-8, LDH, and MMP-9 are the most promising salivary biomarkers. However, more studies with larger cohorts are needed before translating the use of these biomarkers to clinical settings.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Neoplasias Bucais/patologia , Metaloproteinase 9 da Matriz , Biomarcadores Tumorais , Interleucina-8 , Fator de Necrose Tumoral alfa , Interleucina-6 , Carcinoma de Células Escamosas/patologia , Biomarcadores , Carcinoma de Células Escamosas de Cabeça e Pescoço , Saliva , Interleucina-1beta
19.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474047

RESUMO

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV+OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV+OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV+OPSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Orofaríngeas/patologia , Sistema Imunitário/patologia , Papillomavirus Humano , Imunoterapia , Papillomaviridae
20.
Cells ; 13(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38474377

RESUMO

Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature and limited treatment options. Conventional therapies such as surgery, radiation, and chemotherapy often have limited success rates and can have significant side effects. Immunotherapy harnesses the power of the immune system to recognize and eliminate cancer cells, and thus represents a novel approach with the potential to improve patient outcomes. In the management of head and neck squamous cell carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy. In this review, we are focusing on the latter. Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells. The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC. Thus, immune checkpoint inhibitor therapy holds promise in overcoming the limitations of conventional therapies. However, further research is needed to optimize treatment regimens, identify predictive biomarkers, and overcome potential resistance mechanisms. With ongoing advancements in immunotherapy, the future holds great potential for transforming the landscape of oral tumor treatment and providing new hope for patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Inibidores de Checkpoint Imunológico , Imunoterapia/efeitos adversos , Carcinoma de Células Escamosas/etiologia
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