Hep Par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma

To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Comparative cross-sectional study. Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma [83%]. Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma [HCC]. It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver

Anti-tumor immunostimulatory effect of heat-killed tumor cells

As a part of our ongoing search for a safe and efficient anti-tumor vaccine, we attempted to determine whether the molecular nature of certain tumor antigens would influence immune responses against tumor cells. As compared with freeze-thawed or formaldehyde-fixed tumor antigens, heat-denatured tumor antigens elicited profound anti-tumor immune responses and greatly inhibited the growth of live tumor cells. The heat-denatured tumor antigens induced a substantial increase in the anti-tumor CTL response in the absence of any adjuvant material. This response appears to be initiated by strong activation of the antigen-presenting cells, which may recognize heat-denatured protein antigens. Upon recognition of the heat-denatured tumor antigens, macrophages and dendritic cells were found to acutely upregulate the expression of co-stimulatory molecules such as B7.2, as well as the secretion of inflammatory cytokines such as IL-12 and TNF-alpha. The results of this study indicate that heat-denatured tumor extracts might elicit protective anti-tumor adaptive immune responses and also raise the possibility that a safe and efficient adjuvant-free tumor vaccine might be developed in conjunction with a dendritic cell-based tumor vaccine.

Morphometric evaluation of NB84, synaptophysin and AgNOR is useful for the histological diagnosis and prognosis in peripheral neuroblastic tumors (pNTs)

OBJECTIVE: To study the importance of NB84, synaptophysin and AgNOR and explore the quantitative association of these factors with diagnosis and outcome as well as the association between NB84 and AgNOR and other tumor and stromal factors in twenty-eight peripheral neuroblastic tumors. METHODS: We assessed AgNORs, NB84, synaptophysin and several other markers in tumor tissues from 28 patients with primary neuroblastic tumors. The treatment included: surgery for stage 1, chemotherapy and bone marrow transplantation for most of stages 3 and 4. Histochemistry, immunohistochemistry and morphometry were used to evaluate the amount of tumor staining for AgNOR, NB84 and synaptophysin; the outcome for our study was survival time until death due to recurrent neuroblastic tumors. RESULTS: Only stage (p<0.01), AgNOR (p<0.01), NB84 (p<0.01) and synaptophysin (p=0.01) reached statistical significance as prognostic indicators. CONCLUSIONS: Determination of NB84 and synaptophysin are useful tools for the diagnosis of peripheral neuroblastic tumors The association of the evaluation of AgNOR expression by the tumor cells may provide an important contribution to the prognostic evaluation and management approach of the patients.

OBJETIVO: Estudar a importância dos marcadores NB84 e AgNOR e explorar as relações quantitativas entre esses marcadores com o diagnóstico e prognóstico assim como as relações entre NB84 e AgNOR e outros marcadores tumorais e estromais em 28 tumores neuroblásticos periféricos. MÉTODOS: Examinamos AgNOR, NB84 e sinaptofisina e vários outros marcadores em tecidos tumorais de vinte e oito pacientes com tumors neuroblásticos primários. Tratamento dos pacientes incluiu: cirurgia para o estágio 1, quimioterapia e transplante de medula óssea para a maioria dos pacientes nos estágios 3 e 4. Utilizamos histoquímica, imunohistoquímica e morfometria para avaliar a intensidade e extensão de expressão do AgNOR, NB84 e sinaptofisina, tendo o prognóstico dos pacientes incluído o tempo de sobrevida até a morte por recurrência dos tumores neuroblásticos. RESULTADOS: Estadiamento (p<0.01), AgNOR (p<0.01), NB84 (p<0.01) e sinaptofisina (p=0.01) foram marcadores independents de sobrevida. CONCLUSÕES: A determinação dos marcadores NB84 e sinaptofisina mostrou-se como uma ferramenta útil no diagnóstico dos tumors neuroblásticos periféricos; a associação desses marcadores à expressão de AgNOR pelas células tumorais contribuiu à determinação do prognóstico e estabelecimento do protocolo terapêutico para os pacientes.

Presence of autocrine hepatocyte growth factor-Met signaling and its role in proliferation and migration of SNU-484 gastric cancer cell line

Autocrine stimulation via coexpression of hepatocyte growth factor (HGF) and its receptor (Met) has been reported in many human sarcomas, but few in carcinomas. In this report, we found that one gastric cancer cell line, SNU-484, among 11 gastric cell lines tested has an autocrine HGF- Met stimulation. RT-PCR, ELISA and scattering assay using MDCK cells revealed that SNU-484 cells secreted a significant amount of active HGF (about 1.25 +/- 0.41 ng/24 h/106 cells) into conditioned medium. Resultantly, Met in this cell line was constitutively phosphorylated. Neutralizing antibodies against HGF reduced the tyrosine phosphorylation of Met, resulting in the inhibition of cell proliferation and migration (P <0.005). To the best of our knowledge, this is the first report on autocrine HGF-Met signaling in a gastric cancer cell line. Our observations with SNU-484 cells suggest that HGF is involved in the development and/or progression of some gastric carcinoma through an autocrine mechanism.

The level of cancer markers in relation to certain biological characteristics of the gastrointestinal tumors

Niveis de marcadores de cancer circulantes sao considerados dependentes da natureza biologica das celulas neoplasicas. A producao de CEA em resposta a uma lesao gastrointestinal maligna variou de acordo com a localizacao e estadiamento patologico do tumor primario, enquanto que o grau histologico nao interferiu com os niveis do antigeno. Carcinomas do estomago pareceram sintetizar menos CEA do que aqueles do intestino grosso. A atividade enzimatica dos tumores malignos do colon e do reto, determinada pelos ensaios da gama-GT e PHI revelou estar associada com a progressao tumoral, enquanto que o grau histologico nao foi um fator importante na determinacao dos niveis destes mercadores...

Respuesta inmune en conejos a extractos de tejidos tumoral de colón humano / Immune response in rabbits to tumoral tissue extracts of human colon

Se aisló y purificó antígeno carcinoembriónico (CEA) a partir de tumores de colon humano; se obtuvieron antisueros al extracto perclórico de glicoproteínas de colon normal y de colon tumoral, y al CEA puro en conejos. Se comprobó por electroforesis en gel de poliacrilamida que, al inmunizar en forma prolongada con el extracto tumoral, hubo aumento de proteínas de movilidad alfa2. Los antisueros obtenidos rinden por imnunodifusión bajos títulos al enfrentarlos a los distintos antígenos examinados. En general se obtienen los mayores títulos con la fracción obtenida por focalización isoeléctrica del extracto perclórico de glico proteínas de colon tumoral, y este fenómeno se repite al titular los antisueros por radioinmunoensayo (RIE). Al efectuar el análisis estadístico de los resultados obtenidos al medir la concentración de CEA en muestras de sueros de pacientes, no se obtuvieron diferencias significativas al usar sueros provenientes de distintas sangrías. Se concluye que para cubrir un amplio rango de concentraciones en la medición de CEA por RIE es suficiente purificar al antígeno que se usará, como "standard" y trazador hasta la etapa de focalización, y utilizar de anti-sueros obtenidos de animales inyectados con extracto perclórico de glicoproteínas de colon tumoral con esquemas de inmunización largos o con CEA puro con un esquema corto