RESUMEN
This study was performed to determine the prevalence, antimicrobial susceptibility, and genetic relatedness of Salmonella enterica subsp. enterica and Campylobacter spp. in poultry meat, and to analyze the association of genetic types of these bacteria with their geographical distribution and antimicrobial resistance profiles. Salmonella and Campylobacter isolates have been detected, respectively, in 54 and 71 samples out of 100 samples tested. Nine Salmonella serotypes were found, including S. enterica subsp. enterica serovar Infantis (33%), Schwarzengrund (12%), Manhattan (9%), and others. Campylobacter jejuni and C. coli were detected in 64 (64%) and 14 (14%) samples, respectively. S. enterica subsp. enterica isolates were very frequently resistant to tetracycline (78.3%) and streptomycin (68.3%). Many C. jejuni and C. coli isolates were resistant to sulfamethoxazole/trimethoprim (90.5%), nalidixic acid (47.3%), ampicillin (45.9%), and ciprofloxacin (40.5%). Cluster analysis was performed for the Salmonella isolates using pulsed-field gel electrophoresis (PFGE) data. For Campylobacter isolates, the cluster analysis was based on both PFGE and comparative genomic fingerprinting. The molecular typing results were compared with the information about antimicrobial resistance and geographical locations in which the poultry meat was produced. This analysis revealed that C. jejuni strains with a particular genotype and antimicrobial resistance profile are spreading in specific areas of Japan.
Asunto(s)
Campylobacter jejuni/aislamiento & purificación , Contaminación de Alimentos , Carne/microbiología , Aves de Corral/microbiología , Salmonella/aislamiento & purificación , Animales , Antibacterianos/farmacología , Campylobacter jejuni/clasificación , Campylobacter jejuni/efectos de los fármacos , Campylobacter jejuni/genética , Análisis por Conglomerados , Farmacorresistencia Bacteriana , Electroforesis en Gel de Campo Pulsado , Japón , Tipificación Molecular , Filogeografía , Prevalencia , Salmonella/clasificación , Salmonella/efectos de los fármacos , Salmonella/genéticaRESUMEN
OBJECTIVES: Experimental data based on cell line-derived xenograft models (cell xenograft) seldom reproduce the clinical situation, and therefore we demonstrated here the superiority of a murine model involving transplantation of human pancreatic cancer tissue fragments (tumor graft), focusing on the histological features and drug delivery characteristics. METHODS: Tumor pieces from 10 pancreatic cancer patients were transplanted into SCID (severe combined immunodeficient) mice. Histological characteristics of tumor grafts, including morphology, desmoplastic reaction, and vascularization, were compared with those of cell xenografts. Drug delivery was evaluated by quantifying the concentrations of injected drug, and the results were compared with its histological features. RESULTS: Eight of the 10 transplanted tumors successfully engrafted. Histological comparisons between tumor grafts and cell xenografts revealed the following: the amount of stroma was more (22.9% ± 11.8% vs 10.8% ± 5.4%; P < 0.05), vessel-cancer cell distance was longer (35.3 ± 39.0 vs 3.9 ± 3.1 µm; P < 0.001), and microvessel density was lower (6.8 ± 1.9 vs 10.8 ± 2.1 vessels/0.4 mm(2); P < 0.05) in tumor grafts. Drug concentrations in tumor grafts were lower than those in cell xenografts (3.3 ± 1.2 vs 6.0±0.2 µg/mL; P = 0.003), and the differences were correlated with the histological differences. CONCLUSIONS: Pancreatic tumor grafts better reproduce the histological nature of clinical cancer and thus provide a more realistic model that is applicable for pharmacokinetic studies.
Asunto(s)
Xenoinjertos/patología , Trasplante de Páncreas/métodos , Páncreas/patología , Neoplasias Pancreáticas/patología , Anciano , Anciano de 80 o más Años , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacocinética , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Femenino , Xenoinjertos/irrigación sanguínea , Xenoinjertos/metabolismo , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones SCID , Persona de Mediana Edad , Páncreas/irrigación sanguínea , Páncreas/metabolismo , Neoplasias Pancreáticas/irrigación sanguínea , Neoplasias Pancreáticas/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Trasplante Heterólogo , Carga TumoralRESUMEN
CD44(+) /CD24(+) /EpCAM(+) cells have been reported to be cancer stem cells in pancreatic cancer; however, the histological and clinical importance of these cells has not yet been investigated. Here we clarified the characteristics of CD44(+) /CD24(+) /EpCAM(+) cells in clinical specimens of pancreatic cancer using immunohistochemical assay. We used surgical specimens of pancreatic ductal adenocarcinoma from 101 patients. In view of tumor heterogeneity, we randomly selected 10 high-power fields per case, and triple-positive CD44(+) /CD24(+) /EpCAM(+) expression was identified using our scoring system. The distribution, histological characteristics, and prognostic importance of CD44(+) /CD24(+) /EpCAM(+) cells were then analyzed. As a result, the distribution of CD44(+) /CD24(+) /EpCAM(+) cells varied widely among the 101 cases examined, and CD44(+) /CD24(+) /EpCAM(+) expression was correlated with poor glandular differentiation and high proliferation. Survival analysis showed that CD44(+) /CD24(+) /EpCAM(+) expression was not correlated with patient outcome; however, CD44(+) /CD24(+) expression appeared to be correlated with poor prognosis. In conclusion, CD44(+) /CD24(+) /EpCAM(+) expression overlapped with poorly differentiated cells and possessed high proliferative potential in clinical pancreatic cancer. In particular, the presence of double-positive CD44(+) /CD24(+) expression seemed to have clinical relevance, associating with poor prognosis.
Asunto(s)
Antígenos de Neoplasias/biosíntesis , Antígeno CD24/biosíntesis , Moléculas de Adhesión Celular/biosíntesis , Receptores de Hialuranos/biosíntesis , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Antígeno CD24/genética , Antígeno CD24/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Diferenciación Celular/genética , Procesos de Crecimiento Celular/genética , Molécula de Adhesión Celular Epitelial , Femenino , Humanos , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Pronóstico , Análisis de SupervivenciaRESUMEN
A rectoseminal vesicle fistula is a rare complication after a low anterior resection for rectal cancer, usually developing in the outpatient postoperative period with pneumaturia, fever, scrotal swelling or testicular pain. A diagnostic water-soluble contrast enema, cystography and computed tomography reveal a tract from the rectum to the seminal vesicle. Anastomotic leakage is thought to be partially responsible for the formation of such tracts. This report presents three cases of rectoseminal vesicle fistula, and the presumed course of the disease and optimal treatment options are discussed.
Asunto(s)
Adenocarcinoma/cirugía , Enfermedades de los Genitales Masculinos , Complicaciones Posoperatorias , Fístula Rectal , Neoplasias del Recto/cirugía , Vesículas Seminales , Anciano , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Enfermedades de los Genitales Masculinos/diagnóstico , Enfermedades de los Genitales Masculinos/terapia , Humanos , Masculino , Persona de Mediana Edad , Fístula Rectal/diagnóstico , Fístula Rectal/terapia , Neoplasias del Recto/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
IgG4-associated sclerosing cholangitis (IAC) was recently defined as biliary involvement of IgG4-related systemic disease. It is frequently associated with autoimmune pancreatitis, characterized by pancreatic enlargement and irregular narrowing of the pancreatic duct. However, a few cases of IAC with no apparent pancreatic involvement have been described, the characteristics of which may mimic those of cholangiocarcinoma. We report two rare cases of IgG4-associated sclerosing cholangitis at the hepatic hilum, mimicking hilar cholangiocarcinoma. When trying to establish the diagnosis, we should consider other organs that could be involved, such as the pancreas, salivary glands, retroperitoneum, lymph nodes, and kidneys, as well as chronic inflammatory changes. By recognizing these lesions and measuring serum IgG4, IAC can be diagnosed correctly, thereby avoiding unnecessary major surgery for a condition that is treated effectively by steroid therapy.
Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Colangitis Esclerosante/diagnóstico , Inmunoglobulina G/inmunología , Pancreatitis Crónica/diagnóstico , Corticoesteroides/uso terapéutico , Anciano , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangitis Esclerosante/patología , Colangitis Esclerosante/terapia , Terapia Combinada , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Inmunoglobulina G/metabolismo , Imagen por Resonancia Magnética/métodos , Masculino , Pancreatitis Crónica/patología , Pancreatitis Crónica/terapia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Although chemotherapeutic nanoparticles would confer various advantages, the majority of administrated nanoparticles are known to be spoiled by the reticuloendothelial system (RES). Intending to more effectively deliver therapeutic nanoparticles to target regions in vivo, host RES, especially Kupffer cells in the liver, have been depleted ahead of drug administration. To demonstrate this hypothesis, clodronate liposomes were preinjected into BALB/c nude mice for depletion of Kupffer cells 2 days before, and pegylated liposomal doxorubicin (Doxil) at the doses of 1.25, 2.5 and 5.0 mg/kg was administered. As a result, doxorubicin accumulation in the liver was decreased from 36 to 26% injected dose/organ by the Kupffer cells depletion, and consequently, the plasma concentration of doxorubicin was significantly enhanced threefold (from 11 to 33 µg/mL) on day 1 at 1.25 mg/kg-dose group. Doxorubicin accumulation in the tumor was increased from 0.78 to 3.0 µg/g-tissue on day 3, and tumor growth inhibition by Doxil was significantly boosted (tumor volumes from 751 to 482 mm(3) on day 24) by the Kupffer cells depletion. In conclusion, Kupffer cells depletion by clodronate liposomes enhanced the plasma concentration and antitumor effects of Doxil, and would be widely applicable for various clinical cancer chemotherapies using nanoparticles.
Asunto(s)
Doxorrubicina/análogos & derivados , Macrófagos del Hígado/efectos de los fármacos , Nanoconjugados/administración & dosificación , Polietilenglicoles/farmacología , Animales , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Polietilenglicoles/administración & dosificación , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Recent studies have demonstrated that natural antisense transcripts, which are complementary sequences to messenger RNA, have important cellular functions such as the stabilization and silencing of mRNA. However, the possible contribution of antisense transcripts in hepatocellular carcinoma (HCC) development has not been described. Therefore, we simultaneously investigated the sense and antisense transcripts of HCC and non-cancerous tissues to explore the possible contribution of antisense transcripts to HCC progression. RNA was prepared from 15 HCV-associated HCCs and from 6 corresponding non-cancerous tissues and was subjected to expression profile analysis of sense and antisense transcripts using a human custom microarray. Differential expression of 161 sense and 25 antisense transcripts was observed with more than 2-fold between HCC and non-cancerous tissue (p<0.001). The expression of the sense and antisense transcripts was used to cluster cancer and non-cancerous tissues, and the cancer and non-cancerous tissues were found to be clearly separated into different clusters. Additionally, the sense and antisense expression profiles were analyzed with regard to HCC differentiation (p<0.001), resulting in 71 sense and 43 antisense transcripts. These unique transcripts did not overlap with those found in the discrimination of HCC from non-cancerous tissues. When the HCC tissues were clustered by transcript expression, the antisense transcripts resulted in clustering of HCC that was consistent with grouping based on histology. These findings strongly indicate that the antisense transcripts together with the sense transcripts are involved in liver tumorigenesis.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Hepatitis C/complicaciones , Neoplasias Hepáticas/metabolismo , Hígado/metabolismo , Transcripción Genética , Anciano , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Análisis por Conglomerados , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis de Componente Principal , ARN sin Sentido/genética , ARN sin Sentido/metabolismoRESUMEN
BACKGROUND: In the present study we undertook a retrospective analysis of gallbladder carcinoma to assess whether histologically determined hepatic artery (HA) invasion and portal vein (PV) invasion can be considered prognostic factors. METHODS: Seventy-one patients who had undergone radical resection for gallbladder carcinoma between 1995 and 2008 at University of Tsukuba were selected from the database for analysis. Patients who required extended surgery for para-aortic lymph node metastasis were also included. Correlation between invasion of the HA and the PV and prognosis and other clinicopathologic factors were analyzed. RESULTS: There were two postoperative deaths among the 71 patients. Pathological invasion of the HA was confirmed in 16 (22.5%) cases and PV invasion was confirmed in 15 patients. Patients with invasion of the HA had a significantly poorer prognosis than those without HA invasion (P < 0.0001). Additionally, in univariate analysis, gender (male), positive para-aortic lymph node metastasis, PV invasion, and HA invasion were identified as significant poor prognostic factors. In multivariate analysis, only HA invasion was an independent prognostic factor (Odds Ratio 0.323; P = 0.029). CONCLUSIONS: Invasion of the HA is a crucial prognostic factor in patients with gallbladder carcinoma.
Asunto(s)
Neoplasias de la Vesícula Biliar/patología , Arteria Hepática/patología , Vena Porta/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias de la Vesícula Biliar/cirugía , Hepatectomía , Arteria Hepática/cirugía , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Pronóstico , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
INTRODUCTION: Reactive lymphoid hyperplasia, also known as pseudolymphoma or nodular lymphoid lesion of the liver, is a rare benign lesion. It is mainly detected in the lung, stomach, small intestine, orbit, pancreas, skin, and breast. It remains difficult to distinguish reactive lymphoid hyperplasia from malignant disease clinically when it develops in the liver. CASE REPORT: We have recently encountered a patient with liver reactive lymphoid hyperplasia who had undergone colon cancer surgery. CONCLUSION: Preoperative MR imaging showed some useful findings indicating reactive lymphoid hyperplasia.
Asunto(s)
Hepatopatías/diagnóstico , Imagen por Resonancia Magnética/métodos , Seudolinfoma/diagnóstico , Anciano , Diagnóstico Diferencial , Femenino , HumanosRESUMEN
Natural antisense transcripts (NATs) constitute a class of non-coding RNAs that have emerged as important regulators of gene expression. However, involvement of NATs in colorectal cancer (CRC) development has not been reported to date. In the present study, the up- and down-regulation of NATs were investigated in human CRC for their possible involvement in CRC development. Total RNAs isolated from 51 CRC tissues, 9 corresponding non-cancerous tissues and 19 liver metastatic tissues from surgically resected samples were subjected to expression analysis using a custom-microarray containing human sense/antisense probes for ca. 21,000 genes. Comparing CRC tissues with non-cancerous tissues, we identified 415 NATs differentially expressed in CRC and non-cancerous tissues to a significant degree (p<0.001, fold change >4.0 or ≤4.0). When a hierarchical clustering was performed on CRC and non-cancerous samples using these 415 NATs, the samples were separately clustered. Principal component analysis with the same NATs showed clear separation of CRC and non-cancerous samples using the first two principal components (PC1, 80%; PC2, 10%). To validate the expression results obtained from the microarray, the expressions of the 3 selected NATs were examined by strand-specific RT-qPCR, revealing that these expression profiles were consistent with those obtained from microarray analysis. In addition, the NAT expression patterns were found to be different between primary tumors with liver metastasis and those without liver metastasis. In conclusion, these findings taken together indicated that NATs identified in the present study would be involved in CRC development as well as possibly in its metastasis.
Asunto(s)
Carcinoma/genética , Neoplasias Colorrectales/genética , ARN sin Sentido/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , Metástasis de la Neoplasia , ARN sin Sentido/genética , ARN no Traducido/genética , ARN no Traducido/fisiologíaRESUMEN
Fatty acid synthase (FAS) is highly expressed in many kinds of human cancers, including colorectal cancer (CRC), and we have investigated the potential use of FAS inhibitors for chemoprevention of liver metastasis of CRC in mice. Expression of FAS was evaluated in murine CRC cell lines Colon 26 and CMT 93. Cerulenin, a natural inhibitor of FAS, induced apoptosis in these cell lines. The ability of cerulenin to prevent development of liver metastatic lesions in Colon 26 was evaluated. The numbers and sizes of liver metastatic CRC tumors were significantly reduced by treating mice with cerulenin. Cerulenin treatment was associated with reduced levels of phosphorylated Akt in Colon 26 cells, suggesting that inhibition of this signal transduction pathway might be involved in the chemopreventive activity of this compound. Based on studies in mouse models, inhibiting FAS would be an effective strategy to prevent and retard growth of liver metastatic tumors of CRC that have high expression of this enzyme.
Asunto(s)
Cerulenina/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Ácido Graso Sintasas/antagonistas & inhibidores , Neoplasias Hepáticas Experimentales/prevención & control , Neoplasias Hepáticas Experimentales/secundario , Animales , Caspasas/fisiología , Línea Celular Tumoral , Neoplasias del Colon/patología , Relación Dosis-Respuesta a Droga , Lipogénesis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Accidental ingestion of foreign objects by teenagers or young adults without mental impairment is a rare event. We present a case of a patient who unintentionally swallowed a ballpoint pen several days before seeking medical attention. She concealed the event until abdominal radiographs revealed the foreign object. Because swallowed foreign objects can be potentially harmful, they should be removed endoscopically as soon as possible to prevent development of complications. At times, they need to be removed operatively. This report describes the laparoscopic removal of a ballpoint pen that perforated the duodenum.
Asunto(s)
Enfermedades Duodenales/etiología , Duodeno , Cuerpos Extraños/complicaciones , Perforación Intestinal/etiología , Adolescente , Enfermedades Duodenales/cirugía , Duodeno/diagnóstico por imagen , Endoscopía Gastrointestinal , Femenino , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Humanos , Perforación Intestinal/cirugía , Laparoscopía , Intensificación de Imagen RadiográficaRESUMEN
One of the major challenges in the treatment of solid cancers by allogenic hematopoietic stem cell transfer (alloHSCT) is the specific enhancement of antitumor immunity. Interferon (IFN) is a cytokine with pleiotropic biological functions including an immunomoduration, and our preclinical studies have shown that an intratumoral IFN-alpha gene transfer induced strong local tumor control and systemic tumor-specific immunity. In the present study, we examined whether the IFN-alpha gene transfer could enhance recognition of tumor-associated antigens by donor T cells and augment the antitumor activity of alloHSCT. First, when a mouse IFN-alpha adenovirus vector (Ad-mIFN) was injected into subcutaneous xenografts of syngeneic renal and colon cancer cells, tumor growth was significantly suppressed in a dose-dependent manner. A significant tumor cell death and infiltration of immune cells was recognized in the Ad-mIFN-injected tumors, and the dendritic cells isolated from the tumors showed a strong Th1-oriented response. The antitumor effect of Ad-mIFN was then examined in a murine model of minor histocompatibility antigen-mismatched alloHSCT. The intratumoral IFN-alpha gene transfer caused significant tumor suppression in the alloHSCT recipients, and this suppression was evident not only in the gene-transduced tumors but also in simultaneously inoculated distant tumors which did not receive the vector injection. A cytotoxicity assay showed specific tumor cell lysis by donor T cells responding to IFN-alpha. Graft-versus-host disease was not exacerbated serologically or clinically in the mice treated with IFN-alpha. This combination strategy deserves evaluation in future clinical trials for human solid cancers.
Asunto(s)
Neoplasias del Colon/inmunología , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/inmunología , Interferón-alfa/genética , Neoplasias Renales/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/terapia , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Técnicas de Transferencia de Gen , Terapia Genética , Vectores Genéticos , Enfermedad Injerto contra Huésped/inmunología , Neoplasias Renales/terapia , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Linfoma/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos DBARESUMEN
PURPOSE: In autologous hematopoietic stem cell transplantation (HSCT), lymphopenia-induced homeostatic proliferation of T cells is driven by the recognition of self-antigens, and there is an opportunity to skew the T-cell repertoire during the T-cell recovery by engaging tumor-associated antigens, leading to a break of tolerance against tumors. However, the homeostatic proliferation-driven antitumor responses seem to decline rapidly in association with tumor growth. We hypothesized that a tumor-specific immune response induced by an immune gene therapy could enhance and sustain homeostatic proliferation-induced antitumor immunity. EXPERIMENTAL DESIGN: The antitumor effect of allogeneic MHC (alloMHC) gene transfer was examined at the early phase of the immune reconstitution after syngeneic HSCT. RESULTS: Syngeneic HSCT showed significant tumor growth inhibition of syngeneic colon cancer cells within a period of 30 days; however, the tumor then resumed rapid growth and the survival of the mice was not prolonged. In contrast, when the alloMHC plasmid was intratumorally injected at the early phase after syngeneic HSCT, the established tumors were markedly regressed and the survival of recipient mice was prolonged without significant toxicities, whereas no survival advantage was recognized in recipient mice injected with a control plasmid. This tumor suppression was evident even in the other tumors that were not injected with the alloMHC plasmid. The antitumor response was characterized by the development of tumor-specific T cell- and natural killer cell-mediated cytotoxicities. CONCLUSION: The results suggest the efficacy and safety of integrating intratumoral alloMHC gene transfer with an autologous HSCT for the treatment of solid cancers.
Asunto(s)
Técnicas de Transferencia de Gen , Terapia Genética/métodos , Antígenos H-2/genética , Antígenos H-2/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasias Experimentales/terapia , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Complejo Mayor de Histocompatibilidad/genética , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción Genética , Trasplante Autólogo , Trasplante HomólogoRESUMEN
PURPOSE: We investigated the predictors of successful resection of recurrent tumors and improved survival in patients with local pelvic recurrence of rectosigmoid colon and rectal cancer. METHODS: We analyzed the clinicopathological factors of 94 patients who underwent treatment between 1993 and 2002 for the local pelvic recurrence of curatively resected primary rectosigmoid colon and rectal adenocarcinoma. RESULTS: Of the 94 patients, 48 underwent salvage surgery and 46 were treated conservatively. The survival rate of the patients who underwent salvage surgery was significantly higher than that of those treated conservatively (P < 0.0001). Logistic regression analysis revealed that the following factors were significantly associated with successful salvage surgery: tumor differentiation (well or moderately; P < 0.04), a long interval between the initial operation and the detection of recurrence (P < 0.03), and negative lymph node status at the initial operation (P < 0.02). The Cox proportional hazard model revealed the following predictors of better survival after surgery: tumor differentiation (well and moderate), negative lymph node status at the initial operation (pN0), and a perianastomotic pattern of recurrence. CONCLUSION: The predictors of successful salvage surgery are the tumor differentiation and nodal status of the primary tumor, the interval between the initial operation and the detection of recurrence, and the pattern of tumor recurrence.
Asunto(s)
Colon/cirugía , Neoplasias Colorrectales/cirugía , Recto/cirugía , Terapia Recuperativa , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios ProspectivosRESUMEN
The interferon (IFN) protein is a cytokine with pleiotropic biological functions that include induction of apoptosis, inhibition of angiogenesis and immunomodulation. We previously examined the two antitumor mechanisms, taking advantage of the fact that IFN-alpha did not show cross-species activity in its in vivo effect. In a nude mouse subcutaneous xenograft model using human pancreatic cancer cells, the expression of human IFN-alpha effectively induced cell death of human pancreatic cancer cells, whereas mouse IFN-alpha augmented antitumor immunity by stimulation of natural killer cells. Here, we extended our investigation to a syngeneic pancreatic cancer model, so that the integrated antitumor activity of local IFN-alpha gene therapy, including the antiproliferative, proapoptotic, antiangiogeneic and immunomodulatory effects, can be evaluated rigorously. When a recombinant hamster IFN-alpha adenovirus was injected into syngeneic subcutaneous tumors of hamster pancreatic cancer (PGHAM-1) cells in Syrian hamster, tumor growth was significantly suppressed due to cell death and T cell- and natural killer cell-mediated antitumor immunity. Moreover, in this case, tumor regression was observed not only for the injected subcutaneous tumors but also for the untreated tumors both in the peritoneal cavity and at distant sites. No significant systemic toxicity was observed in the treated hamsters. Moreover, the subcutaneous rechallenge of PGHAM-1 cells was rejected in three of four cured hamsters from the initial tumor challenge. This study further demonstrated that local IFN-alpha gene therapy is a promising therapeutic strategy for pancreatic cancer, due to its multiple mechanisms of antitumor activity and its lack of significant toxicity.
Asunto(s)
Modelos Animales de Enfermedad , Terapia Genética , Interferón-alfa/genética , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/terapia , Adenoviridae/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Cricetinae , Femenino , Técnicas de Transferencia de Gen , Vectores Genéticos , Interferón-alfa/uso terapéutico , Mesocricetus , Trasplante de Neoplasias , Neoplasias Pancreáticas/patología , Trasplante IsogénicoRESUMEN
BACKGROUND/AIM: Indications for local resection for tumors of the ampulla of Vater have not been established. The present study evaluated suitable treatments for tumors of the papilla of Vater. PATIENTS AND METHODS: Clinicopathological factors were reviewed for 53 patients with tumors of the ampulla of Vater treated between February 1993 and August 2003. RESULTS: Of 53 patients, 41 were treated surgically. Local resection was performed in 7 of these 41 patients, with a histologically involved margin evident in 4 patients. Lymph node metastasis was identified in 20 patients who received radical resection, including 1 patient with pT1 cancer. CONCLUSION: Given the presence of some positive surgical margins, local resection is indicated as a therapeutic approach to tumors of the papilla of Vater only for benign tumors or some malignant tumors that cannot undergo pancreaticoduodenectomy (PD).