RESUMEN
Squamous cell carcinoma (SCC) of the head and neck region is the sixth most frequent malignancy with high mortality rate. Due to its poor prognosis it is considered a growing public health problem worldwide inspite of existing treatment modalities. Thus, early diagnosis of new diseases and recurrences is emerging on one hand, but on the other hand troublesome in the lack of reliable tumor markers in this field. The rapid development of proteomics has opened new perspectives in tumor marker discovery. Liquid chromatography/mass spectrometry (LC/MS) as the gold standard in proteomics enables the semi-quantitative analysis of proteins within various tissues. Abundance differences between tumor and normal tissue also can be interpreted as tumor specific changes. The aim of this study was to identify potential tumor markers of laryngeal/hypopharyngeal SCC by revealing abundance changes between cancerous and the surrounding phenotypically healthy tissue. After separating the phenotypically cancerous and healthy parts of formalin-fixed paraffin-embedded tissues, each sample underwent protein recovery process and tryptic digestion for label-free semi-quantitative LC/MS analysis. Eight proteins showed significantly higher abundance in tumor including tenascin, transmembrane emp24 domain-containing protein 2, cytoplasmic dynein light chain 1, coactosin-like protein, small proline-rich protein 2D, nucleolin, U5 small nuclear RNP 200-kDa helicase and fatty aldehyde dehydrogenase. Desmoglein-1 and keratin type I cytoskeletal 9 were down-regulated in tumor. Using Ingenuity Pathway Analysis we mapped the signaling pathways these proteins play role in regarding other tumors. Based on these findings these proteins may serve as promising biomarkers in the fight against laryngeal/hypopharyngeal SCCs.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Formaldehído/química , Neoplasias Hipofaríngeas/patología , Neoplasias Laríngeas/patología , Adhesión en Parafina/métodos , Proteoma/análisis , Anciano , Carcinoma de Células Escamosas/metabolismo , Cromatografía Liquida/métodos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Laríngeas/metabolismo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Proteoma/metabolismo , Espectrometría de Masas en Tándem/métodosRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
The aim of this study was to visualize the tumor propagation and surrounding mucosal field in radiography-based 3D model for advanced stage HNSCC and combine it with HPV genotyping and miRNA expression characterization of the visualized area. 25 patients with T1-3 clinical stage HNSCC were enrolled in mapping biopsy sampling. Biopsy samples were evaluated for HPV positivity and miR-21-5p, miR-143, miR-155, miR-221-5p expression in Digital Droplet PCR system. Significant miRNA expression differences of HPV positive tumor tissue biopsies were found for miR-21-5p, miR-143 and miR-221-5p compared to the HPV negative tumor biopsy series. Peritumoral mucosa showed patchy pattern alterations of miR-21-5p and miR-155 in HPV positive cases, while gradual change of miR-21-5p and miR-221-5p was seen in HPV negative tumors. In our study we found differences of the miRNA expression patterns among the HPV positive and negative tumorous tissues as well as the surrounding mucosal fields. The CT based 3D models of the cancer field and surrounding mucosal surface can be utilized to improve proper preoperative planning. Complex evaluation of HNSCC tissue organization field can elucidate the clinical and molecular differentiation of HPV positive and negative cases, and enhance effective organ saving therapeutic strategies.
Asunto(s)
Imagenología Tridimensional/métodos , MicroARNs/genética , Neoplasias de la Boca/patología , Membrana Mucosa/patología , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/complicaciones , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Genómica/métodos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/genética , Neoplasias de la Boca/virología , Membrana Mucosa/diagnóstico por imagen , Membrana Mucosa/metabolismo , Membrana Mucosa/virología , Neoplasias Orofaríngeas/diagnóstico por imagen , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
The prognosis for recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) remains dismal and its treatment poses a challenge for oncologists. Nivolumab belongs to the class of immune checkpoint inhibitors (ICI) and is an antibody developed to target the programmed cell death protein 1 (PD-1) receptor. The CheckMate 141 randomized phase 3 trial proved the efficacy of nivolumab in the treatment of R/M HNSCC as it was shown to significantly increase overall survival and quality of life. We present the case of a 53-year-old woman with R/M HNSCC who was given nivolumab monotherapy, as third-line treatment due the progression of her tumor. After treatment with nivolumab, the size of her tumor decreased, then was stable, while she did not experience any adverse events or notable side effects. Our case report is the first to demonstrate the application of nivolumab in R/M HNSCC in Hungary.
Asunto(s)
Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Femenino , Humanos , Hungría , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: The role of microRNAs (miRNA) in carcinogenesis is related to their genome-regulatory function. The aim of the present study was to identify and compare miRNA expression signatures of meso- and hypopharynx squamous cell cancers in consideration of the cancer field hypothesis. PATIENTS AND METHODS: Thirteen snap-frozen biopsy series of tumors and peritumoral tissues from the meso- and hypopharynx were analyzed regarding their miRNA expression with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Significant miRNA expression changes of miR-21, -27a, -34a, -143 and -146a were found in peritumoral tissues that were dependent from the tumor location and the distance from the primary tumor site. CONCLUSION: miRNA expression analysis was found to be appropriate for molecular segregation of tumor location and peritumoral tissue segments, and appears to be a promising marker for cancer field characterization.
Asunto(s)
Carcinoma de Células Escamosas/genética , Perfilación de la Expresión Génica , Neoplasias Hipofaríngeas/genética , MicroARNs/genética , Membrana Mucosa/metabolismo , Humanos , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
INTRODUCTION: MicroRNAs play a role in carcinogenesis through their genome regulatory function. AIM: The aim of the authors was to identify and compare microRNA expression signatures of meso- and hypopharynx squamous cell cancers on the basis of the cancer field hypothesis. METHOD: Using standard mapping biopsy (tumour tissue and macroscopically normal tissues obtained 1, 2 and 3 cm from margin) 13 snap frozen sample series were analysed for microRNA expression with quantitative real-time polymerase chain reaction. RESULTS: MiR-221 was significantly overexpressed in mesopharynx cancers, whole miR-21, miR-143 and miR-155 showed significant overexpression in hypopharynx cancers. CONCLUSIONS: Using microRNA expression profiles the authors were able to distinguish peritumoural tissues according to distance from the primary tumour site. Future application of the method may prove to be useful in early detection of the altered epigenetic regulation in tissue fields representing normal phenotype. This may be helpful in cancer risk assessment and prevention.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , MicroARNs/metabolismo , Neoplasias Faríngeas/metabolismo , Neoplasias Faríngeas/patología , Transcriptoma , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patología , Neoplasias Faríngeas/genéticaRESUMEN
This article presents data on health care spending for 30 OECD countries from OECD Health Data 2003, the latest edition of OECD's annual data collection on health systems across industrialized countries. OECD data show health care expenditures as a proportion of gross domestic product at an all-time high, due to both increased expenditures and overall economic slow-down. The article discusses similarities and differences across countries in how health care expenditures are funded and how the health care dollar is spent among types of services.