RESUMEN
The present paper shows methods to suppress radon emanation from artificial porous materials such as phosphorous fertiliser or diatomaceous earth with a small amount of radium. The basic concept of suppression is making the radon emanation mechanism 'null', which comes from the fact that recoil is the main mechanism of radon emanation at room temperature. Nullifying may be done through removal of water in the pore volume by heating and through removal of pores by melting or filling with sulphur. These radon emanation suppression methods were tried for phosphorous fertiliser and diatomaceous earth with a small amount of radium. The melting method was the most effective of all. Sustainability of these methods was also studied. The melting method was the most sustainable. The heating method was also sustainable for diatomaceous earth in spite of a long-term immersion in water.
Asunto(s)
Tierra de Diatomeas/química , Fertilizantes , Compuestos de Fósforo/química , Protección Radiológica/métodos , Radio (Elemento)/química , Radón/química , Radón/aislamiento & purificación , Desecación/métodos , Calor , Dosis de Radiación , Radiometría , Azufre/químicaRESUMEN
Emergence in a system appears through the interaction of its components, giving rise to higher order or complexity in the system. We tested for the presence of emergent properties in a biological system using the simplest biological entity of a unicellular organism; the plasmodium of Physarum polycephalum, a giant unicellular amoeboid organism that forms a network-like tubular structure connecting its food sources. We let two plasmodium networks within a single cell interact with each other, and observed how the intracellular interaction affected the morphologenesis of the plasmodium networks. We found that the two networks developed homologous morphology. We further discuss the presence of autonomous and emergent properties in homologous network formation.
Asunto(s)
Physarum polycephalum/citología , Physarum polycephalum/fisiología , Animales , Transporte Biológico , Modelos BiológicosRESUMEN
Neoadjuvant chemoradiotherapy (CRT) was expected to improve surgical curability and prognosis for advanced esophageal cancer. However, the clinical efficacy of neoadjuvant CRT followed by esophagectomy with three-field lymphadenectomy (3FL) for initially resectable esophageal squamous cell carcinoma (SCC) remains unclear. Since 1998, we have defined the status of metastases to five or more nodes, or nodal metastases present in all three fields as multiple lymph node metastasis, which was previously shown to be associated with poor prognosis. Between 1998 and 2002, 83 patients with initially resectable esophageal SCC were prospectively allocated into two groups, according to the clinical status of nodal metastasis. Nineteen patients clinically accompanied by multiple lymph node metastasis initially underwent neoadjuvant CRT followed by curative esophagectomy with 3FL (CRT group). The other 64 patients clinically without multiple lymph node metastasis immediately received curative esophagectomy with 3FL (control group). Although the overall morbidity rate was significantly higher in the CRT group, no in-hospital death occurred in either group. Patients without pathologic multiple lymph node metastasis in the CRT group showed a significantly better disease-free survival rate than either patients pathologically with multiple lymph node metastasis in the control group or those in the CRT group. However, the differences in the overall survival rate among the groups were not significant. Thus, the significant survival benefit by neoadjuvant CRT in addition to esophagectomy with 3FL was not confirmed, although it may have been advantageous, without increase in mortality, to at least some patients who responded well to neoadjuvant CRT. Therefore, neoadjuvant CRT can be an initial treatment of choice for resectable esophageal SCC clinically with multiple lymph node metastasis. The prediction of response to CRT and the development of alternative treatment for hematogenous recurrence could achieve a further survival benefit of this trimodality treatment.
Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Esofagectomía , Ganglios Linfáticos/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Cisplatino/administración & dosificación , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Fluorouracilo/administración & dosificación , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Laparoscopy-assisted surgery with extraperigastric lymph node dissection for gastric cancers has been described, but the clinical benefits of these surgeries still are unclear. Short-term clinical outcomes were compared between laparoscopy-assisted distal gastrectomy (LADG) and conventional open distal gastrectomy (ODG) for early gastric cancer in a prospective randomized fashion. METHODS: For this study, 28 patients with early gastric cancers in the lower half of the stomach were randomly assigned to either LADG (n = 4) or ODG (n = 14). Postoperative pain, levels of acute inflammatory responses, and pathologic evaluation of the operative specimens were compared. RESULTS: The LADG group required a significantly shorter period of postoperative epidural anesthesia, showed significantly lower levels of serum interleukin-6 and C-reactive protein, and had no major postsurgery complications. Pathologic examinations showed that surgery was equally radical in the two groups. CONCLUSION: The findings show that LADG with extraperigastric lymph node dissection is a safe and less invasive alternative to the open procedure.
Asunto(s)
Gastrectomía/métodos , Laparoscopía , Escisión del Ganglio Linfático/métodos , Neoplasias Gástricas/cirugía , Anciano , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias Gástricas/patologíaRESUMEN
Incineration of infectious waste is considered to be biologically safe. We performed basic experiments to confirm that bacillus spores are killed by incineration in a muffle furnace. Biological samples containing 10(6) spores of Bacillus stearothermophilus were placed in stainless steel Petri dishes and then into hot furnaces. The furnace temperature and duration of incineration were 300 degrees C for 15 min, 300 degrees C for 30 min, 500 degrees C for 15 min, 500 degrees C for 30 min and 1100 degrees C for 3 min. We confirmed that all spores of B. stearothermophilus were killed at each of these settings. The effect of incineration seems to be equivalent to that of sterilization, based on the satisfactory sterilization assurance level of 10(-6).
Asunto(s)
Incineración , Eliminación de Residuos Sanitarios/métodos , Geobacillus stearothermophilus/crecimiento & desarrollo , Calor , Esporas Bacterianas , Esterilización , Temperatura , Factores de TiempoRESUMEN
Immunosuppressive acidic protein (IAP) is a potent biological marker of immunological surveillance in patients with malignant tumors. The aim of this study was to analyze the clinicopathologic significance of IAP in patients with esophageal carcinoma. Preoperative serum IAP concentration was measured by enzyme-linked immunosorbent assay in 115 patients with primary esophageal squamous cell carcinomas. The associations between clinicopathologic factors, C-reactive protein (CRP) values and IAP concentration were determined. Prognostic values were determined by multivariate analysis using Cox's proportional hazards model. The IAP concentration is significantly higher in patients with stage II-IV cancers than in those with stage I cancer. Significant differences in IAP concentration were observed depending upon tumor size, tumor depth, lymph node status and CRP values. A high IAP concentration, more than 500 micro g/mL, was an independent prognostic factor. Thus, a high IAP concentration is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Neoplasias Esofágicas/sangre , Proteínas de Neoplasias/sangre , Anciano , Proteína C-Reactiva/análisis , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/mortalidad , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Cuidados Preoperatorios , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: The prognostic value of the number of metastatic lymph nodes in early gastric cancer has not been evaluated much, although the significance of metastatic lymph nodes is defined by the location of positive nodes, according to the JRSGC for gastric cancer. METHODS: The postoperative courses of 305 early gastric cancer patients who had undergone D2-extended lymphadenectomy were followed up for a median of 108 months to evaluate the significance of the number of metastatic lymph nodes on recurrence of the disease. RESULTS: Recurrence of gastric cancer was more frequently observed in submucosal cancer than in mucosal cancer. All patients but one who revealed recurrence had nodal metastasis at the time of surgery. In cases with 1-3 metastatic lymph nodes, no patient had revealed any sign of recurrence; however, in cases with 4 or more metastatic lymph nodes, 6 of 7 patients died of recurrent disease. There were 3 cases of bone metastases, 2 of peritoneal dissemination, and 1 each of both recurrent diseases. CONCLUSIONS: These data suggest that in n-positive cases, in which there are 4 or more metastatic lymph nodes, there is a high probability of recurrence of early gastric cancer, and especially of hematogenic metastasis.
Asunto(s)
Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Causas de Muerte , Ganglios Linfáticos/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Biopsia con Aguja , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Gastrectomía/métodos , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Probabilidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Neoplasias Gástricas/cirugía , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Electroporation facilitates transfer of chemicals or plasmid DNA from extracellular milieu into cells by increasing the permeability of the cell membrane. Delivery of electric pulses to established tumors thereby can improve the susceptibility of tumors to an anti-cancer agent administered. We examined whether electroporation-mediated transfer of cytokine genes into solid tumors could produce anti-tumor effects in the tumor-bearing mice. Plasmid DNA containing cytokine genes were injected into human esophageal T.Tn tumors developed in nude mice and electric pulses were then delivered. Administration of murine GM-CSF or human IL-2 gene followed by electroporation significantly suppressed the subsequent growth of T.Tn tumors and prolonged the survival of the inoculated mice. In contrast, electroporation-mediated introduction of a control gene, human GM-CSF gene, whose products do not bind to murine GM-CSF receptors, did not achieve any anti-tumor effects. In vivo transfection of cytokine genes with electroporation could be a possible therapeutic strategy for established solid tumors.
Asunto(s)
Electroporación , Neoplasias Esofágicas/terapia , Terapia Genética/métodos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Interleucina-2/genética , Animales , Neoplasias Esofágicas/genética , Femenino , Técnicas de Transferencia de Gen , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Plásmidos/administración & dosificación , Plásmidos/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
There is a genetic problem in living donor liver transplantation, involving Wilson's disease, because the majority of donors have a kinship relationship. Recently, it was reported that the serum ceruloplasmin level is insufficient in some persons with one allele mutation. The recipient was a 13-year-old male child, and the donor was a 22-year-old woman, who was his sister by a different father. The gene analysis for Wilson's disease (ATP7B gene) was preoperatively carried out by the amplification refractory mutation system-PCR. Homozygous and heterozygous deletion of 2871 cytosine (C) were detected in the recipient and donor, respectively, in the ATP7B gene. Serum ceruloplasmin level was sufficient in the donor. The right hepatic lobe graft was transplanted to the recipient. Immediately after the liver transplantation, the copper metabolism improved to increase the serum ceruloplasmin levels up to the normal range, and decrease the urinary copper excretion. However, the serum ceruloplasmin levels gradually decreased below the normal base line, although the urine copper levels continued to be low without any clinical symptoms. We should perform gene analyses and confirm the serum ceruloplasmin levels in donors before living donor liver transplantation for Wilson's disease, to screen for their impairment of copper metabolism. After living donor liver transplantation for Wilson's disease, we should carefully follow-up the transition of serum ceruloplasmin levels in the recipient.
Asunto(s)
Adenosina Trifosfatasas/genética , Proteínas de Transporte de Catión/genética , Cobre/sangre , Degeneración Hepatolenticular/cirugía , Fallo Hepático/cirugía , Trasplante de Hígado/fisiología , Donadores Vivos , Mutación/genética , Adolescente , Adulto , Ceruloplasmina/metabolismo , ATPasas Transportadoras de Cobre , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Degeneración Hepatolenticular/sangre , Degeneración Hepatolenticular/genética , Humanos , Fallo Hepático/sangre , Fallo Hepático/genética , Pruebas de Función Hepática , MasculinoRESUMEN
BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis in malignant tumors. An increased in the serum VEGF concentration (S-VEGF) has been found in patients with various solid tumors and appears to be correlated with tumor burden. The objective of the current study was to determine the correlation between pretreatment S-VEGF and clinicopathologic features in patients with esophageal squamous cell carcinoma. METHODS: Pretreatment S-VEGF was measured by enzyme-linked immunoadsorbent assay in 24 healthy controls and 96 patients with esophageal squamous cell carcinoma (82 patients with primary tumors and 14 with recurrent tumors). Chemoradiotherapy was performed in 35 patients followed by response evaluation. RESULTS: S-VEGF was found to be significantly elevated in patients with primary esophageal carcinoma (P = 0.0011). Significant differences were observed when S-VEGF was categorized by tumor size (P = 0.0002), tumor depth (P = 0.0082), lymph node metastasis (P = 0.0002), distant metastasis (P = 0.028), and International Union Against Cancer TNM stage (P < 0.0001). The patients who achieved a partial or complete response to chemoradiotherapy showed significantly less S-VEGF than those patients who were nonresponders (P = 0.018). A high (> 451 pg/mL) S-VEGF level was associated with poor survival (P < 0.001). Multivariate analysis found S-VEGF to be a significant and independent prognostic factor (P < 0.001). CONCLUSIONS: In the current study, a high S-VEGF was found to be associated with tumor progression, poor treatment response, and poor survival in patients with squamous cell carcinoma of the esophagus.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Factores de Crecimiento Endotelial/sangre , Neoplasias Esofágicas/sangre , Linfocinas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Progresión de la Enfermedad , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estadística como Asunto , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
Resistance to chemotherapy remains a serious problem inhibiting the successful treatment of advanced esophageal cancer. A number of studies have revealed that p53 genetic alteration and protein overexpression can predict chemosensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conducted to examine whether analysis of serum p53 Abs could predict the chemosensitivity of esophageal cancer. Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 19 patients with esophageal squamous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues were also analyzed for chemosensitivity by the histoculture drug response assay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5-FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 protein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibition index of patients positive for p53-Abs was significantly lower than that of patients negative for p53-Abs (P < 0.001). This tendency was also observed in the inhibition index to 5-FU. The presence of serum p53-Abs was associated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, the detection of serum p53-Abs is suggested to be useful for predicting chemosensitivity in patients with esophageal cancer.
Asunto(s)
Anticuerpos/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/inmunología , Resistencia a Medicamentos/inmunología , Neoplasias Esofágicas/inmunología , Proteína p53 Supresora de Tumor/inmunología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/tratamiento farmacológico , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%-80% at 100 plaque-forming units (PFU)/cell and 80%-100% at 300PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer.
Asunto(s)
Adenovirus Humanos/genética , Neoplasias Esofágicas/terapia , Genes p53 , Terapia Genética/métodos , Animales , Apoptosis , Supervivencia Celular , Células Cultivadas , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/metabolismo , Neoplasias Esofágicas/patología , Esófago/citología , Vectores Genéticos , Humanos , Técnicas In Vitro , Ratones , Ratones Desnudos , Recombinación Genética , Transducción Genética , Células Tumorales CultivadasRESUMEN
This study analyzes ten cases of malignancy in a cohort of 183 renal transplant recipients, examining surgical management, postoperative immunosuppressive therapy, and long-term outcome. One of these ten patients, who had malignant lymphoma of the jejunum, died of the neoplasm, but the other nine patients did not show any signs of tumor recurrence after removal. All of these nine patients, except for one who had transplant renal cell carcinoma (RCC), received the same dose of immunosuppressive agents after surgery for the malignant disease. Seven patients were still alive at the time of this report, six of whom had good transplant renal function. The findings of this study indicate that even if immunosuppressive agents predispose to the development of cancer, it is not necessary to reduce their dose after removal of the tumor.
Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Neoplasias/inmunología , Complicaciones Posoperatorias/inmunología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The Bmx gene, a member of the Tec tyrosine kinase gene family, is known to be expressed in subsets of hematopoietic and endothelial cells. In this study, mice were generated in which the first coding exon of the Bmx gene was replaced with the lacZ reporter gene by a knock-in strategy. The homozygous mice lacking Bmx activity were fertile and had a normal life span without an obvious phenotype. Staining of their tissues using beta-galactosidase substrate to assess the sites of Bmx expression revealed strong signals in the endothelial cells of large arteries and in the endocardium starting between days 10.5 and 12.5 of embryogenesis and continuing in adult mice, while the venular endothelium showed a weak signal only in the superior and inferior venae cavae. Of the five known endothelial receptor tyrosine kinases tested, activated Tie-2 induced tyrosyl phosphorylation of the Bmx protein and both Tie-2 and vascular endothelial growth factor receptor 1 (VEGFR-1) stimulated Bmx tyrosine kinase activity. Thus, the Bmx tyrosine kinase has a redundant role in arterial endothelial signal transduction downstream of the Tie-2 and VEGFR-1 growth factor receptors.
Asunto(s)
Endotelio Vascular/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinasas/fisiología , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transducción de Señal/fisiología , Angiopoyetina 1 , Animales , Línea Celular , Línea Celular Transformada , Endotelio Vascular/citología , Perfilación de la Expresión Génica , Humanos , Operón Lac , Ratones , Ratones Endogámicos DBA , Ratones Noqueados , Regiones Promotoras Genéticas , Proteínas Tirosina Quinasas/genética , Receptor TIE-2 , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
Posttransplant renal cell carcinoma (RCC) usually arises in the native kidneys of renal transplant recipients rather than in the transplanted kidney. This report describes a case of RCC that developed in the transplanted cadaveric kidney in a 37-year-old male recipient 9 months after transplantation. An en bloc radical transplant nephrectomy was performed, and he has subsequently remained stable on hemodialysis for 3 years without any sign of recurrence.
Asunto(s)
Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Trasplante de Riñón , Complicaciones Posoperatorias/cirugía , Adenocarcinoma/patología , Adulto , Cadáver , Carcinoma de Células Renales/patología , Carcinoma de Células en Anillo de Sello/patología , Humanos , Riñón/patología , Neoplasias Renales/patología , Masculino , Siembra Neoplásica , Nefrectomía , Neoplasias Gástricas/patología , Donantes de TejidosRESUMEN
Environmental electromagnetic fields have been implicated in human cancers. We examined whether high extremely low frequency (ELF) AC magnetic fields could affect DNA synthesis, transcription or repair, using in vitro model systems with defined sequences. The rate and fidelity of DNA polymerase catalyzed DNA synthesis, as well as of RNA polymerase catalyzed RNA synthesis, were not statistically significantly affected by 60 Hz 0.25-0.5 Tesla magnetic fields. The efficiency of mutS dependent mismatch repair with human cell extracts was also not affected by the magnetic field exposure. The results suggest that the core processes related to the transmission of genetic information are stable under high ELF magnetic fields.
Asunto(s)
Disparidad de Par Base , Reparación del ADN , ADN Polimerasa Dirigida por ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/metabolismo , Campos Electromagnéticos , Animales , Sistema Libre de Células , ADN/biosíntesis , Reparación del ADN/efectos de la radiación , ADN Polimerasa Dirigida por ADN/efectos de la radiación , ARN Polimerasas Dirigidas por ADN/efectos de la radiación , Escherichia coli/genética , Escherichia coli/efectos de la radiación , Células HeLa , Humanos , Cinética , ARN/biosíntesisRESUMEN
Delivery of electric pulses to an established solid tumor augments the permeability of cell membrane and increases the susceptibility of tumors to an anti-cancer agent that is administered in the vicinity of tumors. Forced expression of the wild-type p53 gene in tumor cells that have non-functional p53 gene(s) can also enhance their sensitivity to a DNA-damaging agent. To investigate the feasibility of electroporation-mediated therapy for cancer, electric pulses were delivered to human esophageal tumors developed in nude mice after they received an anti-cancer agent and/or plasmid DNA containing the wild-type p53 gene. The growth of esophageal tumors was suppressed with electroporation-mediated chemotherapy compared with the treatment with an anti-cancer agent or electroporation alone. Intratumoral injection of the wild-type p53 gene into p53-mutated esophageal tumors followed by electroporation also inhibited tumor growth. When mice were administered with the wild-type p53 gene and an anti-cancer agent, subsequent electroporation produced a synergistic therapeutic effect. Combinatory transfer of plasmid DNA and a pharmacological agent by electroporation is thereby a possible therapeutic strategy for the treatment of solid tumors.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Electroporación/métodos , Neoplasias Esofágicas/terapia , Genes p53/genética , Terapia Genética/métodos , Transfección , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Bleomicina/administración & dosificación , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Compuestos Organoplatinos/administración & dosificación , Proteína p53 Supresora de Tumor/metabolismoAsunto(s)
Linfoma de Células B Grandes Difuso/patología , Neoplasias Pancreáticas/patología , Adenocarcinoma/diagnóstico , Anciano , Antígenos CD20/análisis , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Humanos , Periodo Intraoperatorio , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/cirugía , Masculino , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugíaRESUMEN
The basic strategies for gene therapy that have been explored include immunogene therapy such as cytokine gene transfer, selective prodrug activation, so-called suicide genes, transfer of a tumor suppressor gene, and inhibition of activated oncogenes by antisense mechanisms. Many therapeutic protocols have so far been registered in the office of the Recombinant DNA Advisory Committee, NIH, as of June 1999. Regarding the basic research in gene therapy, we planned a clinical application of gene therapy for an esophageal cancer patient at our institution. We review herein the present status of gene therapy for cancer overseas, and describe a protocol of clinical trials for gene therapy for esophageal cancer at our institution.