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BACKGROUND: LEM domain containing 1 (LEMD1) is a novel factor involved in the development of oral squamous cell carcinoma (OSCC). We previously performed a microarray analysis and found that serpin peptidase inhibitor, clade E, member 2 (SERPINE2) is an LEMD1-related signal. SERPINE2 is an extracellular serine proteinase inhibitor with secretory capacity. Although SERPINE2 displays tumor-promoting properties in many cancers, some reports indicate that SRPINE2 also has a tumor-suppressing function. Therefore, there are many unclear points about its role in cancer. In this study, we investigated SERPINE2 expression in OSCC. METHODS: The gene expression and secretion levels of SERPINE2 were examined in 42 frozen specimens of OSCC, and SERPINE2 immunostaining was investigated in 167 cases of OSCC. Furthermore, the effect of SERPINE2 on angiogenesis and lymphangiogenesis was analyzed using OSCC cells and endothelial cells. RESULTS: In the frozen specimens, the gene expression (P < 0.0001) and secretion levels (P < 0.0001) of SERPINE2 were higher in OSCC than in the normal oral mucosa. According to the immunohistochemical analysis, SERPINE2 expression was correlated with the depth of invasion (P = 0.0163), nodal metastasis (P = 0.0085), microvessel density (P < 0.0001), and lymphovessel density (P < 0.0001). Additionally, univariate and multivariate analyses indicated that the SERPINE2 expression level was an independent poor prognostic factor for OSCC. In vitro studies using OSCC cells revealed that SERPINE2 promotes angiogenesis and lymphangiogenesis. CONCLUSION: These results suggest that SRPX2 might be a useful tumor marker for OSCC.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Boca , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Células Endoteliales , Humanos , Linfangiogénesis , Neoplasias de la Boca/genética , Pronóstico , Serpina E2/genéticaRESUMEN
PURPOSE: Transport and Golgi organization protein 1 (TANGO) promotes angiogenesis and lymphangiogenesis in oral squamous cell carcinoma (OSCC). To elucidate the underlying mechanisms, this study aims to identify and characterize elements downstream of TANGO that mediate its involvement in OSCC. METHODS: In this study, microarray analysis compared gene expression between control and TANGO-repressed HSC3 cells. Protein expression in 213 OSCC tissue samples was analyzed immunohistochemically. RESULTS: TANGO repression decreased or increased expression of Mucin 20 (MUC20) and small proline-rich protein 1B (SPRR1B), respectively. MUC20 increased the growth and invasiveness of OSCC cells via altered matrix metalloproteinase (MMP)-2 and E-cadherin expression and c-met phosphorylation. MUC20 induced angiogenesis and lymphangiogenesis by activating vascular endothelial growth factors A and C. In well-differentiated OSCC, SPRR1B expression was high (P = 0.0091) and correlated with keratinization markers and promoted proliferation by inducing mitogen-activated protein kinase p38 phosphorylation. MUC20 expression correlated significantly with clinical stage (P = 0.0024), lymph node metastasis (P = 0.0036), and number of blood and lymph vessels (P < 0.0001). MUC20-expressing cases had a significantly worse prognosis than non-expressing cases (P < 0.0001). CONCLUSION: MUC20 and SPRR1B located downstream of TANGO may be useful molecular markers for OSCC.
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Translocador Nuclear del Receptor de Aril Hidrocarburo/fisiología , Biomarcadores de Tumor/aislamiento & purificación , Proteínas Ricas en Prolina del Estrato Córneo , Mucinas , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas , Células Cultivadas , Proteínas Ricas en Prolina del Estrato Córneo/genética , Proteínas Ricas en Prolina del Estrato Córneo/aislamiento & purificación , Proteínas Ricas en Prolina del Estrato Córneo/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inmunohistoquímica , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , Neoplasias de la Boca , Mucina 2/genética , Mucina 2/aislamiento & purificación , Mucina 2/metabolismo , Mucinas/genética , Mucinas/aislamiento & purificación , Mucinas/metabolismo , Transducción de Señal/genéticaRESUMEN
Despite dramatic progress in cancer diagnosis and treatment, the five-year survival rate of oral squamous cell carcinoma (OSCC) is still only about 50%. Thus, the need for elucidating the molecular mechanisms underlying OSCC is urgent. We previously identified the peroxidasin gene (PXDN) as one of several novel genes associated with OSCC. Although the PXDN protein is known to act as a tumor-promoting factor associated with the Warburg effect, its function and role in OSCC are poorly understood. In this study, we investigated the expression, function, and relationship with the Warburg effect of PXDN in OSCC. In immunohistochemical analysis of OSCC specimens, we observed that elevated PXDN expression correlated with lymph node metastasis and a diffuse invasion pattern. High PXDN expression was confirmed as an independent predictor of poor prognosis by multivariate analysis. The PXDN expression level correlated positively with that of pyruvate kinase (PKM2) and heme oxygenase-1 (HMOX1) and with lactate and ATP production. No relationship between PXDN expression and mitochondrial activation was observed, and PXDN expression correlated inversely with reactive oxygen species (ROS) production. These results suggest that PXDN might be a tumor progression factor causing a Warburg-like effect in OSCC.
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Neoplasias de la Boca/metabolismo , Peroxidasas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Efecto Warburg en Oncología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Because oral squamous cell carcinomas (OSCCs) have a high potential for locoregional invasion and nodal metastasis, early detection and treatment are essential. A LAP2, emerin, MAN1 (LEM) domain containing 1 (LEMD1) is associated with local progression, clinical stage, nodal metastasis, poor prognosis, angiogenesis, and lymphangiogenesis in OSCC. Although LEMD is a cancer-testis antigen, the cancer-related signals related to LEMD1 remain unknown. In this study, we used a microarray analysis of OSCC cells to identify sushi repeat containing protein X-linked 2 (SRPX2) as a LEMD1-related downstream signal. LEMD1 expression was correlated with lymph node metastasis of OSCC according to the immunohistochemistry analysis. Furthermore, patients expressing SRPX2 had a significantly worse prognosis than those without SRPX2 expression. The concentration of SRPX2 in OSCC was positively correlated with the concentrations of LEMD1, urokinase plasminogen activator receptor (uPAR), and hepatocyte growth factor (HGF). In OSCC cells, SRPX2 secretion levels were elevated by interactions with uPAR and HGF. We also found that SRPX2 promotes endothelial cell proliferation and adhesion between endothelial cells and OSCC cells. These results suggest that SRPX2 might be a useful tumor marker for OSCC.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Metástasis Linfática , Proteínas de la Membrana/metabolismo , Neoplasias de la Boca/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Proteínas de Neoplasias/genética , Neovascularización Patológica/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , ARN Interferente Pequeño , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genéticaRESUMEN
Mast cells (MCs) are present in the tumor stroma, and MCs that express the mast cellspecific proteases tryptase and chymase (MCTC) exhibit several tumorrelated functions. It was previously reported that melanoma inhibitory activity (MIA) gene family members, including MIA, MIA2, and transport and Golgi organization protein 1 (TANGO), possess oncogenic functions in oral squamous cell carcinoma (OSCC). However, the relationships between MCTC, and clinicopathological characteristics and activation of the MIA gene family in OSCC remain unknown. In the present study, the functional roles of MCTC in patients with OSCC were investigated using immunohistochemistry and reverse transcriptionquantitative PCR. In addition, the effects of extracellular chymase on oral cancer cells were examined. In patients with OSCC, MCTC density was significantly affected by tumor progression and nodal metastasis, and was correlated with vessel density. MCTC density was also correlated with MIA and MIA2 expression. In OSCC cells, extracellular chymase promoted the secretion of vascular endothelial growth factor family proteins, and the transmigration and adhesion of HSC3 cells to endothelial cells; knockdown of MIA, MIA2 and TANGO attenuated these effects. The present findings indicated that MCTC act as tumorprogressive factors in OSCC via the activation and secretion of MIA and MIA2, and the induction of angiogenesis and lymphangiogenesis.
Asunto(s)
Antígenos de Neoplasias/metabolismo , Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Carcinoma de Células Escamosas/metabolismo , Quimasas/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Neoplasias de la Boca/metabolismo , Proteínas de Neoplasias/metabolismo , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/genética , Translocador Nuclear del Receptor de Aril Hidrocarburo/genética , Carcinoma de Células Escamosas/genética , Adhesión Celular , Línea Celular Tumoral , Quimasas/genética , Progresión de la Enfermedad , Proteínas de la Matriz Extracelular/genética , Femenino , Técnicas de Silenciamiento del Gen , Células Endoteliales de la Vena Umbilical Humana , Humanos , Metástasis Linfática , Masculino , Mastocitos/metabolismo , Persona de Mediana Edad , Neoplasias de la Boca/genética , Clasificación del Tumor , Proteínas de Neoplasias/genética , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. METHODS: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Further, we determined the effects of miR-29b-1-5p on the phenotypes of OSCC cell lines. RESULTS: The expression levels of miR-29b-1-5p in most patients with OSCC were higher than those of the normal oral epithelium. In OSCC, upregulation of miR-29b-1-5p significantly correlated with histological grade, the EMT, and the immunohistochemical grade, indicated by c-Met expression. The prognosis was poor for patients with miR-29b-1-5p expression and coexpression of miR-29b-1-5p and c-Met. In OSCC cells exhibiting the EMT phenotype, knockdown of miR-29b-1-5p suppressed the EMT, which was recovered by enforced expression of c-Met. Further, the mRNA encoding cadherin 1 (CDH1) was a direct target of miR-29b-1-5p. CONCLUSIONS: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells.
RESUMEN
BACKGROUND: Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common malignancy. OSCC has strong invasive ability, and its malignant potential is closely associated with local expansion and lymph node metastasis. Furthermore, local or nodal recurrence worsens OSCC prognosis. In our previous cDNA microarray analysis, non-structural maintenance of chromosome (SMC) condensin I complex subunit H (NCAPH) was identified as an upregulated gene in recurrent OSCC. Although NCAPH has several functions in tumors, its role in OSCC is unknown. METHODS: In this study, we examined NCAPH expression in OSCC and performed a functional analysis of human OSCC cells. RESULTS: NCAPH expression was higher in OSCC than in normal oral mucosa. In immunohistochemistry using 142 OSCC specimens, the immunostaining of NCAPH was strongly associated with nodal metastasis and lymphatic infiltration. In multivariate analysis using the Cox proportional hazards model, NCAPH expression was an independent poor prognostic indicator for OSCC. Moreover, NCAPH promoted the migration and adhesion of endothelial cells to OSCC cells and promoted the resistance to platinum anticancer drugs. CONCLUSIONS: Our present findings suggest that NCAPH is a novel diagnostic and therapeutic target in OSCC.
RESUMEN
Head and neck cancers, including oral squamous cell carcinoma (OSCC), are the sixth most common malignancies worldwide. OSCC frequently leads to oral dysfunction, which worsens a patient's quality of life. Moreover, its prognosis remains poor. Unlike normal cells, tumor cells preferentially metabolize glucose by aerobic glycolysis. Pyruvate kinase (PK) catalyzes the final step in glycolysis, and the transition from PKM1 to PKM2 is observed in many cancer cells. However, little is known about PKM expression and function in OSCC. In this study, we investigated the expression of PKM in OSCC specimens and performed a functional analysis of human OSCC cells. We found that the PKM2/PKM1 ratio was higher in OSCC cells than in adjacent normal mucosal cells and in samples obtained from dysplasia patients. Furthermore, PKM2 expression was strongly correlated with OSCC tumor progression on immunohistochemistry. PKM2 expression was higher during cell growth, invasion, and apoptosis in HSC3 cells, which show a high energy flow and whose metabolism depends on aerobic glycolysis and oxidative phosphorylation. PKM2 expression was also associated with the production of reactive oxygen species (ROS) and integration of glutamine into lactate. Our results suggested that PKM2 has a variety of tumor progressive functions in OSCC cells.
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Carcinogénesis/genética , Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca/genética , Piruvato Quinasa/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Proliferación Celular , Metabolismo Energético , Femenino , Humanos , Masculino , Ratones Endogámicos BALB C , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Piruvato Quinasa/análisis , Piruvato Quinasa/metabolismoRESUMEN
Oral squamous cell carcinoma (OSCC) has a high potential for local invasion and nodal metastasis. Therefore, early detection and elucidation of the detailed molecular mechanisms underlying OSCC are essential. Dehydrogenase/reductase member 9 (DHRS9) is downregulated in recurrent OSCC. Although DHRS9 is reported to act as a tumour suppressor in several malignancies, its expression in OSCC cells is unknown. In this study, we examined DHRS9 expression immunohistochemically in specimens from a sample of 98 OSCC patients. Reduced DHRS9 expression was observed in 68 of 98 patients (69.4%) with OSCC. A significant association was found between low DHRS9 expression and local progression (T factor) (p = 0.0135). Furthermore, patients with low DHRS9 expression had a significantly poorer prognosis than those with high DHRS9 expression (p = 0.0443). In multivariate analysis using the Cox proportional hazards model, decreased DHRS9 expression strongly correlated with worse prognosis. The study findings suggest that DHRS9 might be a useful diagnostic and prognostic marker for OSCC.
Asunto(s)
3-Hidroxiesteroide Deshidrogenasas/biosíntesis , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de la Boca/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Regulación hacia Abajo , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
BACKGROUND: [(18)F]fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) is widely used to evaluate tumor metabolic activity. The aim of this study was to evaluate the usefulness of FDG-PET in assessing the histopathological response to preoperative concurrent chemoradiotherapy (CRT) in patients with oral squamous cell carcinoma (OSCC). METHODS: Forty-five patients with resectable advanced OSCC who had received preoperative CRT followed by tumor ablative surgery between January 2004 and December 2011 were included in the study. All patients underwent FDG-PET before and after preoperative CRT. The maximum standardized uptake value (SUVmax) before (pre-SUV) and after preoperative CRT (post-SUV) and the SUVmax reduction rate (ΔSUV %) were used to evaluate the response to preoperative CRT. Correlations among SUVmax, histopathological response, and expression of cancer antigen Ki-67 and hypoxia-inducible factor-1α (HIF-1α) were analyzed. RESULTS: Preoperative CRT significantly reduced intratumoral FDG uptake (P < 0.001). The pre-SUV and post-SUV were significantly lower in patients with a pathological complete response (pCR) than in those with a non-pCR (pre-SUV P = 0.037; post-SUV P = 0.001). ΔSUV % was higher in patients with pCR than in those with non-pCR (P = 0.029). The pre-SUV was significantly correlated with Ki-67 and HIF-1α expression in pretreatment biopsy specimens (Ki-67 P = 0.046, R = 0.292; HIF-1α P = 0.007, R = 0.385). The expression of both Ki-67 and HIF-1α was significantly lower in patients with pCR than in those with non-pCR (Ki-67 P < 0.001; HIF-1α P < 0.001). CONCLUSIONS: Low pre-SUV and post-SUV and high ΔSUV % may predict a good histopathological response to preoperative CRT. Ki-67 and HIF-1α expression in pretreatment biopsy specimens were predictors of histopathological response to preoperative CRT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/terapia , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/terapia , Tomografía de Emisión de Positrones , Adulto , Anciano , Carboplatino/administración & dosificación , Carcinoma de Células Escamosas/patología , Quimioradioterapia Adyuvante , Fraccionamiento de la Dosis de Radiación , Femenino , Fluorodesoxiglucosa F18 , Fluorouracilo/administración & dosificación , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Terapia Neoadyuvante , Cuidados Preoperatorios , RadiofármacosRESUMEN
BACKGROUND & AIMS: We evaluated whether spleen stiffness (SS), measured by acoustic radiation force impulse imaging, can identify patients who have esophageal varices (EVs); those without EVs would not require endoscopic examination. METHODS: In a prospective study, we measured SS and liver stiffness (LS) in 340 patients with cirrhosis undergoing endoscopic screening for EVs and 16 healthy volunteers (controls) at the Kurashiki Central Hospital in Okayama, Japan. The diagnostic accuracy of SS for the presence of EVs was compared with that of other noninvasive parameters (LS, spleen diameter, and platelet count). Optimal cutoff values of SS were chosen to confidently rule out the presence of varices. RESULTS: Patients with cirrhosis had significantly higher SS and LS values than controls (P < .0001 and P < .0001, respectively). Levels of SS were higher among patients with EVs (n = 132) than controls, and values were highest among patients with high-risk EVs (n = 87). SS had the greatest diagnostic accuracy for the identification of patients with EVs or high-risk EVs compared with other noninvasive parameters, independent of the etiology of cirrhosis. An SS cutoff value of 3.18 m/s identified patients with EVs with a 98.4% negative predictive value, 98.5% sensitivity, 75.0% accuracy, and 0.025 negative likelihood ratio. An SS cutoff value of 3.30 m/s identified patients with high-risk EVs with a 99.4% negative predictive value, 98.9% sensitivity, 72.1% accuracy, and 0.018 negative likelihood ratio. SS values less than 3.3 m/s ruled out the presence of high-risk varices in patients with compensated or decompensated cirrhosis. SS could not be measured in 16 patients (4.5%). CONCLUSIONS: Measurements of SS can be used to identify patients with cirrhosis with EVs or high-risk EVs. A cutoff SS was identified that could rule out the presence of varices and could be used as an initial noninvasive screening test; UMIN Clinical Trials Registry number, UMIN000004363.
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Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas/diagnóstico , Cirrosis Hepática/diagnóstico por imagen , Bazo/diagnóstico por imagen , Bazo/patología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Várices Esofágicas y Gástricas/sangre , Várices Esofágicas y Gástricas/etiología , Femenino , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Tamaño de los Órganos , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Curva ROC , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Adulto JovenRESUMEN
We describe a case of autoimmune hepatitis diagnosed after acute hepatitis B. The patient was a 65-year-old man admitted because of markedly elevated transaminase level. Laboratory tests showed positive IgM-HBc antibody and a short prothorombin time. He was diagnosed as severe acute hepatitis B due to sexual transmission. He received lamivudine and steroid pulse therapy. Transaminase level increased again after steroid pulse therapy and liver atrophy progressed, so cyclosporine was induced. Liver biopsy was done because of prolonged liver function disorder. Biopsy specimens showed not only centrizonal inflammation but also interface hepatitis and bridging fibrosis, which were characteristic of autoimmune hepatitis. We diagnosed autoimmune hepatitis which became clinically evident after acute hepatitis B. Lamivudine was discontinued 7 months after diagnosis and he is now receiving 3mg prednisolone.
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Hepatitis B/complicaciones , Hepatitis Autoinmune/etiología , Enfermedad Aguda , Anciano , Humanos , MasculinoRESUMEN
BACKGROUND AND AIM: The prognosis of cryptogenic cirrhosis-associated hepatocellular carcinoma (CC-HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC-HCC. METHODS: Consecutive 36 curatively treated CC-HCC patients satisfying the Milan Criteria were compared with corresponding 211 HCV-associated HCC (HCV-HCC) patients. The clinical background, tumor recurrence rate, overall survival rate, and prognostic values of the patients were assessed. RESULTS: The size of CC-HCCs was larger than that of HCV-HCCs (P = 0.01). The respective tumor recurrence rates at 1, 3, and 5 years were 11%, 32%, and 46% in the CC-HCC, and 21%, 59%, and 81% in the HCV-HCC. The respective overall survival rates at 1, 3, and 5 years were 94%, 85%, and 80% in the CC-HCC, and 98%, 81%, and 61% in the HCV-HCC. CC-HCC patients had a lower tumor recurrence rate and a higher survival rate compared to the HCV-HCC patients (P = 0.001 and P = 0.02, respectively). Via multivariate analysis, significant factors for high recurrence rate were number of HCCs (P = 0.02) and serum alpha fetoprotein levels (P = 0.03) in CC-HCC, whereas multiple tumors (P < 0.001), large tumor size (P = 0.01), and high alanine aminotransferase (P = 0.04) in HCV-HCC. The factor for survival was albumin in both groups. CONCLUSION: The size of CC-HCC was larger than that of HCV-HCC even in patients who received curative treatment; however, the risk for recurrence and the mortality of the patients with CC-HCC was lower than those with HCV-HCC.
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Carcinoma Hepatocelular/terapia , Ablación por Catéter , Hígado Graso/complicaciones , Hepatectomía , Hepatitis C/complicaciones , Cirrosis Hepática/etiología , Neoplasias Hepáticas/terapia , Anciano , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Femenino , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Humanos , Japón , Estimación de Kaplan-Meier , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Recurrencia Local de Neoplasia , Enfermedad del Hígado Graso no Alcohólico , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Survival predictors in patients with ruptured hepatocellular carcinoma (HCC) treated by transarterial embolization (TAE), have not been fully investigated. METHODOLOGY: Predictors of short-term (< or = 30 days) and long-term (>30 days) survival were evaluated by using the logistic regression model and the Cox proportional hazard model, respectively. RESULTS: Forty-eight patients treated by emergency TAE were enrolled. The median survival time was 231 days. Although hemostasis was attained by TAE in 44 patients (91.7%), 15 patients (31.3%) died within 30 days. In a multivariate analysis, low serum creatinine level (p=0.018) was the only significant predictor of increased short-term survival. Of the 33 patients who survived more than 30 days after TAE, he patic resection was performed in 8, transarterial chemoembolization or chemotherapy in 8, and conservative treatment in 17. In a multivariate analysis, among the 33 who survived, unilateral location of tumors (p=0.041) and low a-fetoprotein level (p=0.004) were significant predictors of increased long-term survival. CONCLUSIONS: Short-term survival of patients with ruptured HCC who were treated by TAE depended on serum creatinine level on arrival. Long-term survival of patients who survived more than 30 days after TAE, was influenced by tumor location and a-fetoprotein level.
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Carcinoma Hepatocelular/terapia , Embolización Terapéutica , Neoplasias Hepáticas/terapia , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
We report a case of advanced upper gingival carcinoma with a contralateral metastatic lymph node invading the maxillary sinus (T4aN2cM0). An 83-year-old man was treated concurrently with chemoradiotherapy and S-1. S-1 (80 mg/body/day) was administered for 2 weeks followed by a 1-week rest period as one course. Radiation therapy involved a total of 60 Gy (2 Gy/day; 5 days/week). There were side effects of mild leucopenia and a grade 2 stomatitis. After the completion of 2 courses and radiation therapy, the primary tumor disappeared, and the patient achieved a pathologically complete response. The metastatic lymph node also completely disappeared. S-1 was then administered in the same regimen for 1 year. Neither local recurrence nor distant metastasis has been detected 2 years after the completion of the concurrent chemoradiotherapy with S-1.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gingivales/tratamiento farmacológico , Ácido Oxónico/uso terapéutico , Tegafur/uso terapéutico , Anciano de 80 o más Años , Biopsia , Terapia Combinada , Combinación de Medicamentos , Neoplasias Gingivales/diagnóstico por imagen , Neoplasias Gingivales/patología , Neoplasias Gingivales/radioterapia , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Expression of ligands of natural killer group 2D (NKG2D) immunoreceptors, such as major histocompatibility complex class I-related chain A/B (MICA/B), has been proposed to play an important role in tumour immunosurveillance. Soluble forms of MICA/B are increased in sera of cancer patients and are postulated to impair antitumour immune response by downregulating expression of NKG2D immunoreceptors. Serum levels of soluble MICA have been shown to be of diagnostic significance in malignant diseases. AIMS: The potential of soluble MICB (sMICB) as a marker for oral squamous cell carcinoma (OSCC) was investigated. RESULTS: sMICB levels did not differ significantly from those in normal control individuals. However, the findings indicate that sMICB levels are significantly increased in stage IV OSCC and high sMICB levels are significantly associated with decreased survival rates in patients.
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Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Antígenos de Histocompatibilidad Clase I/sangre , Neoplasias de la Boca/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Antígenos de Histocompatibilidad Clase I/biosíntesis , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Estadificación de NeoplasiasAsunto(s)
Trasplante Óseo/métodos , Peroné/trasplante , Mandíbula/cirugía , Modelos Anatómicos , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/irrigación sanguínea , Peroné/irrigación sanguínea , Humanos , Imagenología Tridimensional , Osteotomía , Tomografía Computarizada por Rayos XRESUMEN
NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Polymorphisms in MICA may influence its binding to the NKG2D. The soluble form of MICA is released from the surface of tumor cells of epithelial origin. Whereas MICA expressed on the cell surface stimulates the immunoreceptor natural killer group 2, member D (NKG2D), the secreted form down-regulates NKG2D activity, thus allowing the tumor to escape immunosurveillance by NKG2D-expressing cells. In this study, we examined the association between MICA gene microsatellite polymorphisms and serum levels of soluble MICA in patients with oral squamous cell carcinoma (OSCC). We found that patients with OSCC were more likely to have the A5.1 allele when compared to healthy subjects and also more likely to be homozygous for this allele (p=0.041). Patients with the homozygous A5.1 genotype had higher levels of soluble MICA (p=0.031) and a lower survival rate (p=0.026).
Asunto(s)
Carcinoma de Células Escamosas/fisiopatología , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/metabolismo , Neoplasias de la Boca/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Estadificación de Neoplasias , Polimorfismo Genético , SolubilidadRESUMEN
OBJECTIVE: The aim of this study was to determine the association between pretreatment intrahepatic mRNA levels of interferon receptor and interferon-stimulated genes and response to interferon therapy for genotype 1b chronic hepatitis C. METHODS: Forty-four patients with genotype 1b chronic hepatitis C who underwent liver biopsy and then received interferon therapy participated in this study. Pretreatment intrahepatic mRNA levels of interferon receptor genes (IFNAR1, IFNAR2b, and IFNAR2c) and interferon-stimulated genes (OAS1 and PKR) were quantified by competitive polymerase chain reaction. RESULTS: In the genes examined, only IFNAR1 mRNA level was significantly higher in patients with sustained virological and biochemical response to interferon therapy versus those with nonsustained response (p < 0.01). Moreover, mRNA expression ratios of IFNAR1 to IFNAR2 were also significantly higher in patients with sustained virological and biochemical response to IFN therapy (p < 0.01 and p < 0.05, respectively). On the other hand, mRNA levels of IFNAR2b, IFNAR2c, and PKR were significantly higher in patients with histologically active or advanced liver rather than patients with mild or less advanced liver. CONCLUSIONS: High intrahepatic mRNA levels of IFNAR1 and mRNA ratio of IFNAR1 to IFNAR2 before treatment may be associated with a favorable response to interferon therapy.
Asunto(s)
2',5'-Oligoadenilato Sintetasa/metabolismo , Hepatitis C Crónica/tratamiento farmacológico , Hígado/metabolismo , ARN Mensajero/metabolismo , Receptor de Interferón alfa y beta/metabolismo , eIF-2 Quinasa/metabolismo , 2',5'-Oligoadenilato Sintetasa/genética , Adulto , Antivirales/farmacología , Antivirales/uso terapéutico , Femenino , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/farmacología , Interferón-alfa/uso terapéutico , Interferón beta/farmacología , Interferón beta/uso terapéutico , Hígado/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Viral/sangre , Receptor de Interferón alfa y beta/genética , Resultado del Tratamiento , eIF-2 Quinasa/genéticaRESUMEN
BACKGROUND: Platelet count has been shown to correlate with the hepatic fibrosis stage in chronic hepatitis C (CHC). The aim of the present study was to assess hepatic fibrosis progression or regression of CHC patients by long-term monitoring of the platelet count. METHODS: A total of 429 interferon (IFN)-treated CHC patients were studied. Follow-up data on the platelet count were collected every 6 months after IFN therapy. The IFN response was defined as follows: complete responders (CR, n = 121) demonstrating persistent clearance of serum hepatitis C virus (HCV) RNA; biochemical responders (BR, n = 94) demonstrating alanine aminotransferase (ALT) normalization for >/=6 months without eradication of HCV-RNA; and non-responder (NR, n = 214) demonstrating all other patterns. RESULTS: In comparison with the baseline level, mean platelet count increased in the CR group from 0.5 years after IFN therapy (for each point, P < 0.01), but significantly decreased in the NR group from 1 year after IFN therapy (for each point, P < 0.01). In the BR group, an increase in mean platelet count was observed from 0.5 to 3.5 years following IFN therapy (for each point, P < 0.01), followed by a gradual decrease. CONCLUSION: An increase from baseline values in platelet count was observed, regardless of the presence of HCV-RNA, in both the CR and BR groups, suggesting the importance of ALT normalization in preventing hepatic fibrosis progression in IFN-treated CHC patients.