RESUMEN
We previously reported significant relationships between sialyl Lewis antigen expression on gastric cancer cells and both hepatic metastasis and clinical prognosis. The purpose of this study was to compare the expression of sialyl Lewis antigens on gastric cancer cells to elucidate the possible role of sialyl Lewis antigens in predicting the spread of a tumor with regard to histological findings. Subjects consisted of 38 patients with gastric cancer. For comparison we measured the values for sialyl Lewisa (sLea) and sialyl Lewisx (sLex) expression on the surface of about 10,000-30,000 cancer cells. Monoclonal antibodies CA19-9 and KM-93 were used to determine the frequency (%) and quantity (channel) of the expression by flow cytometry. We assessed the correlation of sLea and sLex expression with histological findings (depth of tumor invasion (pT), lymphatic invasion (ly), venous invasion (v), and lymph node metastasis (pN)), by comparing sLea and sLex expression in relation to the grade of histological findings. A significant relationship was found between lymphatic invasion and the frequency of sLea expression (r = 0.40, p<0.05). The mean values of sLea frequency in cases categorized as ly 2 (36.30) and ly 3 (31.81) were statistically higher than those in ly 1 cases (12.74) (p<0.05). A significant relationship was also observed between lymph node metastasis and the frequency of sLea expression (r = 0.46, p<0.01). The mean value of sLea frequency in pN 3 cases (44.14) was statistically higher than those in pN 0 (17.11) and pN 1 (19.03) cases (p<0.05). Neither the depth of tumor invasion nor venous invasion showed any correlation with the expression of sialyl Lewis antigens. In conclusion the frequency of sLea expression on the surface of gastric cancer cells was greater in those patients who developed lymphatic invasion and lymph node metastasis. However, the mechanism by which sialyl Lewisa expression is upregulated remains unclear.
Asunto(s)
ADN de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica , Antígenos del Grupo Sanguíneo de Lewis/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Citometría de Flujo , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Estudios RetrospectivosRESUMEN
The patient was a 46-year-old women who was treated for axillary lymph node recurrence of breast cancer by a variety of methods, including surgery, chemotherapy, and radiotherapy, but who experienced recurrences in the cervical and mediastinal lymph nodes and skin, and developed hydrothorax and ascites. Although the recurrent foci responded to 4 cycles of CAF chemotherapy, there was concern that the foci would become refractory or resistant to chemotherapy. The administration of paclitaxel was therefore initiated. The patient received a dose of paclitaxel once a week for 5 consecutive weeks followed by a 1-week recovery period (one cycle). After two cycles of the paclitaxel treatment, a marked shrinkage of the lymph nodes and complete resolution of the hydrothorax and ascites were observed. Even though the patient exhibited bone marrow suppression and G-CSF was administered twice for neutropenia, there were no adverse effects except mild alopecia, again suggesting the possibility that paclitaxel is effective chemotherapy for recurrent breast cancer.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Ganglios Linfáticos/patología , Paclitaxel/administración & dosificación , Axila , Neoplasias de la Mama/patología , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Humanos , Hidrotórax/tratamiento farmacológico , Hidrotórax/etiología , Metástasis Linfática , Persona de Mediana Edad , Derrame Pleural Maligno/tratamiento farmacológico , Derrame Pleural Maligno/etiologíaRESUMEN
Ten patients with liver metastases from advanced gastric cancer received percutaneous ethanol injection therapy (PEI) and chemotherapy by hepatic arterial infusion (HAI) via implantable reservoir. A 90% ethanol solution including 10%. Lipiodol was injected in the liver as PEI.5-FU, EPIR and MMC were used as the regimen for HAI chemotherapy. We have performed this therapy (PEI + HAI) for ten patients with liver metastases since February, 1997. These patients have received this therapy for 4-36 months and three patients died within 16 months. However, three patients did not develop any liver failure after this therapy. The median survival rate was 25.2 months. There are statistically significant differences between upto ss and over se of invasion, and between INF alpha and gamma (p = 0.005).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Etanol/administración & dosificación , Bombas de Infusión Implantables , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Gástricas/patología , Anciano , Epirrubicina/administración & dosificación , Fluorouracilo/administración & dosificación , Arteria Hepática , Humanos , Infusiones Intraarteriales , Inyecciones Intralesiones , Aceite Yodado/administración & dosificación , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Tasa de SupervivenciaRESUMEN
We reported that a cell surface thrombin receptor, thrombomodulin (TM), was regulated by cyclic AMP in fibroblasts and in parietal endoderm-like cells derived from F9 embryonal carcinoma cells. In this paper, the genetic basis for augmentation of TM expression by cyclic AMP was studied in F9 and BALB/3T3 cells. Transient expression assays were performed with plasmid constructs containing various 5' flanking sequences of the TM gene and a reporter gene, chloramphenicol acetyltransferase (CAT). Two regulatory DNA regions, the proximal (-411 to -50) and the distal (-1026 to -850), were located. Interplay of the two regions was suggested using a heterologous thymidine kinase promoter in differentiated F9 cells. Both proximal and distal regions contributed to cyclic AMP-dependent augmentation of CAT expression in differentiated F9 cells, whereas only the proximal region was functional in BALB/3T3 cells. The two cell types responded differently also to a protein synthesis inhibitor, cycloheximide, with respect to TM message accumulation. In BALB/3T3 cells TM message accumulation was refractory to the inhibitor in contrast to that of differentiated F9 cells, which was only partially so. We propose that there are at least two separate genomic DNA regions that regulate cyclic AMP-dependent TM gene expression and that their functions are cell type dependent.
Asunto(s)
Bucladesina/farmacología , Expresión Génica/efectos de los fármacos , Receptores de Superficie Celular/genética , Células 3T3 , Animales , Secuencia de Bases , Clonación Molecular , Cicloheximida/farmacología , Análisis Mutacional de ADN , Elementos de Facilitación Genéticos , Genes , Ratones , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , ARN Mensajero/genética , Receptores de Trombina , Mapeo Restrictivo , Teratoma/patología , Timidina Quinasa/genéticaRESUMEN
Fetomodulin (FM) was previously shown to be a surface marker protein of parietal endoderm by in vitro differentiation of F9 embryonal carcinoma cells and by immunohistochemistry of in vivo embryos. BALB/3T3 and sarcoma S180 cells of the mouse were also shown to possess a protein which was indistinguishable from FM by immunological and structural criteria. We now show by protein and DNA sequencing and by functional assays that FM is identical to thrombomodulin, an anticoagulant endothelial thrombin receptor. Partial amino acid sequences of FM from S180 cells suggested homology between FM and thrombomodulin. An FM cDNA fragment was obtained by screening an expression library, which was constructed with restricted BALB/3T3 cDNA, with polyclonal anti-FM antibody. Several longer cDNA clones were than isolated using this fragment as a probe. They elucidated a 3369-bp partial sequence which encompassed 93% of the coding sequence. The remaining structure was determined from a genomic DNA clone. The deduced FM structure proved to be identical to that of thrombomodulin of mouse lung. Affinity-purified FM of BALB/3T3 and differentiated F9 cells was as active as thrombomodulin of the lung in binding thrombin and also as an anticoagulant. Structural and functional identity of the two proteins was thus confirmed. During embryonic development, FM immunoreactivity is localized not only in vasculatures but also at sites of cell-to-cell contact, including lung bud and neural epithelium, which were not expected a priori to possess this endothelial surface protein. FM may be a multifunctional protein with unique roles in embryonic development.