RESUMEN
Treatment of patients with chylous or non-chylous lymphatic leakage can be difficult. An approach using therapeutic lymphangiography can reduce the lymphatic leakage, but it seldom stops the leakage immediately and subsequent conservative treatment is necessary. We report three cases in which intranodal lymphangiography was performed multiple times to inhibit lymphatic leakage. In each case, the lymph node was punctured under ultrasound guidance using a 23-gauge needle and lipiodol was injected manually at a rate of 1 ml/3 min. The procedure was repeated twice in two cases of gastrointestinal carcinoma and four times in one case of lymphoma. In all three cases, the postoperative lymphatic leakage stopped after the repeated intranodal lymphangiography.
Asunto(s)
Aceite Etiodizado/administración & dosificación , Ganglios Linfáticos/diagnóstico por imagen , Linfocele/terapia , Linfografía/métodos , Anciano , Quilo/metabolismo , Drenaje , Femenino , Humanos , Inyecciones , Ganglios Linfáticos/metabolismo , Linfocele/diagnóstico por imagen , Linfocele/fisiopatología , Masculino , Persona de Mediana Edad , Punciones , Retratamiento , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
Mouse monocyte/macrophage major histocompatibility complex (MHC) receptor 1 (MMR1; or MMR2) specific for H-2D(d) (or H-2K(d) ) molecules is expressed on monocytes from non-H-2D(d) (or non-H-2K(d) ), but not those from H-2D(d) (or H-2K(d) ), inbred mice. The MMR1 and/or MMR2 is essential for the rejection of H-2D(d) - and/or H-2K(d) -transgenic mouse skin onto C57BL/6 (H-2D(b) K(b) ) mice. Recently, we found that human leucocyte antigen (HLA)-B44 was the sole ligand of human MMR1 using microbeads that had been conjugated with 80 types of HLA class I molecules covering 94·2% (or 99·4%) and 92·4% (or 96·2%) of HLA-A and B molecules of Native Americans (or Japanese), respectively. In the present study, we also explored the ligand specificity of human MMR2 using microbeads. Microbeads coated with HLA-A32, HLA-B13 or HLA-B62 antigens bound specifically to human embryonic kidney (HEK)293T or EL-4 cells expressing human MMR2 and to the solubilized MMR2-green fluorescent protein (GFP) fusion protein; and MMR2(+) monocytes from a volunteer bound HLA-B62 molecules with a Kd of 8·7 × 10(-9) M, implying a three times down-regulation of MMR2 expression by the ligand expression. H-2K(d) (or H-2D(d) ) transgene into C57BL/6 mice down-regulated not only MMR2 (or MMR1) but also MMR1 (or MMR2) expression, leading to further down-regulation of MMR expression. In fact, monocytes from two (i.e. MMR1(+) /MMR2(+) and MMR1(-) /MMR2(-) ) volunteers bound seven to nine types of microbeads among 80, indicating ≤ 10 types of MMR expression on monocytes. The physiological role of constitutive MMRs on monocytes possibly towards allogeneic (e.g. fetal) cells in the blood appears to be distinct from that of inducible MMRs on macrophages toward allografts in tissue.
Asunto(s)
Regulación hacia Abajo/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Macrófagos/inmunología , Monocitos/inmunología , Animales , Células HEK293 , Humanos , Ligandos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos/inmunología , Receptores Inmunológicos/inmunologíaRESUMEN
AIM: To demonstrate that carbon dioxide (CO2) microbubble contrast enhancement depicts blood vessels when used for x-ray examinations. MATERIALS AND METHODS: Microbubbles were generated by cavitation of physiological saline to which CO2 gas had been added using an ejector-type microbubble generator. The input pressure values for CO2 gas and physiological saline that produced a large quantity of CO2 microbubbles were obtained in a phantom. In an animal study, angiography was performed in three swine using three types of contrast: CO2 microbubbles, conventional CO2 gas, and iodinated contrast medium. For CO2 microbubble contrast enhancement, physiological saline, and CO2 gas were supplied at the input pressures calculated in the phantom experiment. Regions of interest were set in the abdominal aorta, external iliac arteries, and background. The difference in digital values between each artery and the background was calculated. RESULTS: The input pressures obtained in the phantom experiment were 0.16 MPa for physiological saline and 0.5 MPa for CO2 gas, with physiological saline input volume being 8.1 ml/s. Three interventional radiologists all evaluated the depictions of all arteries as "present" in the CO2 microbubble contrast enhancement, conventional CO2 contrast enhancement, and iodinated contrast enhancement performed in three swine. Digital values for all vessels with microbubble CO2 contrast enhancement were higher than background values. CONCLUSIONS: In x-ray angiography, blood vessels can be depicted by CO2 microbubble contrast enhancement, in which a large quantity of CO2 microbubbles is generated within blood vessels.
Asunto(s)
Angiografía de Substracción Digital/métodos , Aorta Abdominal/diagnóstico por imagen , Dióxido de Carbono , Medios de Contraste , Arteria Ilíaca/diagnóstico por imagen , Microburbujas , Intensificación de Imagen Radiográfica/métodos , Animales , Yopamidol/administración & dosificación , Variaciones Dependientes del Observador , Fantasmas de Imagen , Cloruro de Sodio , PorcinosRESUMEN
BACKGROUND AND STUDY AIMS: Pyloric stenosis is currently managed using open or laparoscopic pyloromyotomy. However, with recent improvements in flexible endoscopic instrumentation and techniques, totally peroral endoscopic approaches could reduce the invasiveness of myotomic procedures. The aim of the study was to establish the feasibility and efficacy of endoscopic submucosal pyloromyotomy in a porcine model. METHODS: Four pigs were included in a preliminary study and a 2-week survival study was performed in another four pigs. An esophagogastroduodenoscope was inserted perorally into the stomach. Saline solution was injected into the submucosal space proximal to the pylorus. The gastric mucosa was incised and a 5-cm submucosal tunnel was created. After exposure of the muscular layer in a submucosal tunnel, myotomy of the circular muscle layer was performed until the longitudinal muscular layer was reached. Once myotomy was completed, endoscopic clips were used to re-approximate the mucosal incision. RESULTS: Submucosal dissection, identification of the circular muscular layer, and pyloromyotomy were achieved in all animals. Acute complications such as bleeding and perforation were not observed in any cases. Median pyloric resting pressure was reduced from 16.5 mmHg to 6.1 mmHg immediately after myotomy and 8.4 mmHg at 14 days after myotomy. CONCLUSION: Peroral endoscopic submucosal pyloromyotomy appears to be technically feasible and effective. Potential clinical applications, such as for infantile hypertrophic pyloric stenosis or delayed gastric emptying after esophagectomy, could be considered after confirmation of safety in additional survival studies.
Asunto(s)
Gastroscopía/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Estenosis Pilórica/cirugía , Píloro/cirugía , Animales , Modelos Animales de Enfermedad , Estudios de Factibilidad , Mucosa Gástrica/cirugía , Manometría , Píloro/patología , Porcinos , Resultado del TratamientoRESUMEN
BACKGROUND: This study compared postoperative pain following four-port laparoscopic cholecystectomy (LC) and single-port cholecystectomy (SPC). METHOD: This prospective, quasi-randomized, single-centre trial focusing on postoperative pain included 49 patients undergoing elective surgery with either a conventional LC, or SPC using a surgical glove port. Postoperative pain was evaluated using a visual analogue scale (VAS) and postoperative analgesic use as primary outcome measures. Total duration of operation, length of hospital stay, blood test results on the day after surgery and total port cost were secondary outcome measures. RESULTS: Twenty-five LCs and 24 SPCs were undertaken. The VAS score on day 1 after surgery was significantly less in the SPC group than in the LC group: median (range) 24 (12-38) versus 45 (33-57) mm (P = 0·002). Significantly fewer patients in the SPC group required analgesia (9 of 24 versus 19 of 25 in the LC group; P = 0·007). There were no significant differences in total duration of operation, length of hospital stay, and blood test results on the day after surgery. CONCLUSION: Single-port surgery using a surgical glove port reduces postoperative pain compared with conventional LC.
Asunto(s)
Colecistectomía Laparoscópica/métodos , Enfermedades de la Vesícula Biliar/cirugía , Dolor Postoperatorio/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/etiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The safety and efficacy of percutaneous vertebroplasty (PVP), a new treatment modality for painful malignant vertebral compression fractures (PMVCF) using interventional radiology techniques, were evaluated prospectively. MATERIALS AND METHODS: After confirming the absence of safety issues in phase 1, a total of 33 cases were registered up to and including phase 2. Safety and efficacy were evaluated by National Cancer Institute-Common Toxicity Criteria version 2 and Visual Analogue Scale (VAS) at 1 week after PVP. Based on VAS score decreases, efficacy was classified into significantly effective (SE; > or = 5 or reached 0-2), moderately effective (ME; 2-4), or ineffective (NE; <2 or increase). RESULTS: Procedures were completed in all 33 patients (42 vertebrae). Thirty days after PVP, two patients died of primary disease progression, but no major adverse reactions (>grade 2) were observed. Response rate was 70% (95% confidence interval 54% to 83%) [61% (n = 20) with SE, 9% (n = 3) with ME, and 30% (n = 10) with NE] and increased to 83% at week 4. Median time to response was 1 day (mean 2.4). Median pain-mitigated survival period was 73 days. CONCLUSION: For PMVCF, PVP is a safe and effective treatment modality with immediate onset of action.
Asunto(s)
Neoplasias Óseas/complicaciones , Fracturas por Compresión/terapia , Cuidados Paliativos , Fracturas de la Columna Vertebral/terapia , Vertebroplastia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fracturas por Compresión/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Fracturas de la Columna Vertebral/complicaciones , Vertebroplastia/efectos adversosRESUMEN
Detection of early gastric tube cancers (GTCs) has increased with more detailed surveillance endoscopy using indigo carmine dye following esophagectomy. This retrospective study clarified the clinicopathological features and application of endoscopic submucosal dissection (ESD) for GTCs. Data collected for eight GTCs treated by ESD included clinical and pathological features and outcomes following ESD. Overall, eight GTCs were identified in seven (6.3 %) of 112 patients who underwent esophagectomy and gastric tube reconstruction. Almost all lesions were macroscopically type 0-IIa with mucosal to submucosal invasion, and seven GTCs were successfully resected en bloc by ESD. Submucosal invasion to > 500 microm was observed in one case with associated delayed perforation that was treated conservatively. No local recurrences of GTCs were observed. Detailed surveillance endoscopy using indigo carmine dye appears useful for diagnosing early-stage GTC. Furthermore ESD represents a feasible alternative to conventional endoscopic mucosal resection as a minimally invasive therapy for early-stage GTC.
Asunto(s)
Neoplasias Esofágicas/patología , Esofagostomía/métodos , Gastrostomía/métodos , Neoplasias de Células Escamosas/patología , Neoplasias Gástricas/patología , Adenocarcinoma/patología , Adenocarcinoma Papilar/patología , Anciano , Anciano de 80 o más Años , Colorantes , Disección/métodos , Endoscopía Gastrointestinal , Neoplasias Esofágicas/cirugía , Esofagectomía , Femenino , Gastrectomía , Mucosa Gástrica/patología , Humanos , Carmin de Índigo , Persona de Mediana Edad , Neoplasias de Células Escamosas/cirugía , Procedimientos de Cirugía Plástica/métodosRESUMEN
BACKGROUND: Although metallic stents are characterized by strong expanse of force, thin walls, and easy stent deployment, their removal from the body is usually difficult or impossible due to the difficulty of unraveling their mesh structure. A stent built of a composite material comprising a metallic wire and a polylactic acid (PLA) fiber, in which the metallic wire component could be unraveled after PLA fiber degradation in the body, should allow easy stent removal. PURPOSE: To evaluate the mechanical strength and retrievability of a composite material stent comprising a metallic wire and a PLA fiber. MATERIAL AND METHODS: We produced a composite material stent comprising a metallic wire and a biodegradable fiber (hybrid stent). As the metallic wire is not cross-linked with itself, but with the PLA fibers only, the hybrid stent can be easily unraveled after PLA fiber degradation. This stent was built with a 0.2-mm stainless-steel wire and a 0.23-mm PLA fiber knitted in the same textile as an Ultraflex stent. For comparison, an identical stent was built using PLA fiber only (PLA stent). The mechanical strength of these stents was tested by the radial expansive force response against circumferential shrinkage stress load. Change in radial force due to PLA fiber degradation was estimated by adding an artificial PLA degeneration process, by immersing each stent in a water bath at 80 degrees C for 48 hours. Retrievability of the hybrid stent after PLA degeneration was examined by hooking and pulling out the residual stainless-steel wire from a silicon tube. RESULTS: The hybrid stent exhibited a linear response in radial expansive force within the range of 15% diameter reduction. The PLA stent did not exhibit linear response at over 15% diameter reduction. Decrease of radial expansive force after PLA degradation was within 5% of the original force in the hybrid stent, but the PLA stent did not create effective radial expansive force. Hybrid stents, even after PLA degradation, exhibited a linear response in radial expansive force, within the range of 15% diameter reduction. The metallic component of the heat-processed hybrid stent was easily unraveled by pulling out the wire. CONCLUSION: The hybrid stent comprising a stainless-steel wire and a PLA fiber appears to provide effective radial expansive force and retrievability.
Asunto(s)
Remoción de Dispositivos , Ácido Láctico , Ensayo de Materiales , Polímeros , Acero Inoxidable , Stents , Implantes Absorbibles , Materiales Biocompatibles , Poliésteres , Estrés MecánicoRESUMEN
BACKGROUND: Drainage of large amounts of shunt blood into deep veins via collaterals reduces resistance to venous outflow and decreases blood flow to the artery distal to the arterial anastomotic site, potentially resulting in steal syndrome. PURPOSE: To evaluate the effectiveness of transcatheter coil embolization for collateral veins of hemodialysis access in the treatment of steal syndrome. MATERIALS AND METHODS: Five hemodialysis patients (four male, one female; mean age 58.8 years, range 40-71 years) with symptomatic steal syndrome were treated. Steal syndrome was diagnosed based on decreased or absent distal pulse, coolness, pain, abnormal skin color, ischemic ulceration of digits, numbness, sensory impairment, or motor impairment. Coil embolization was performed to block collaterals communicating with deep veins, with conscious sedation and local anesthesia. Fistulography was performed before, immediately after, and 1 month after embolization. Ultrasonography was performed 2 days after embolization. Symptoms and signs were assessed 2 days after embolization. Clinical findings related to steal syndrome and access failure were observed at each hemodialysis. RESULTS: Blood flow in the collaterals was successfully blocked by coil embolization in all patients. Distal pulse, coolness, pain, and skin color improved in all patients. Numbness, sensory impairment, and motor impairment were unimproved in two patients. In all patients, hemodialysis following embolization was performed normally. The mean observation period after embolization was 33 months (range 9-75 months). CONCLUSION: Coil embolization of collaterals that drain shunt blood into deep veins is effective for steal syndrome for hemodialysis access originating in the brachial artery.
Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Embolización Terapéutica/métodos , Diálisis Renal , Síndrome del Robo de la Subclavia/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía Intervencional , Síndrome del Robo de la Subclavia/diagnóstico por imagen , Síndrome del Robo de la Subclavia/etiologíaRESUMEN
BACKGROUND: Percutaneous vertebroplasty (PVP) improves back pain and corrects spinal misalignment to some extent, and thus may improve respiratory function. PURPOSE: To retrospectively investigate changes in respiratory function after PVP. MATERIAL AND METHODS: 41 patients (mean age 72.0 years, range 59-86 years; 39 women, two men) who had undergone PVP for vertebral compression fractures (37 thoracic vertebral bodies [Th6-Th12] and 50 lumbar vertebral bodies [L1-L5]) caused by osteoporosis visited our hospital for follow-up consultation between January and June 2005. At this follow-up consultation, respiratory function testing, including percent forced vital capacity (FVC%) and percent forced expiratory volume in 1 s (FEV(1)%), was performed. We retrospectively compared these values with those taken before PVP using a Wilcoxon signed-rank test. RESULTS: FVC% was 85.2+/-30.3% before PVP and 91.5+/-16.8% at follow-up (mean 10 months after PVP), which represented a significant difference (P<0.003). No significant difference in FEV(1)% was detected. Regarding the number of treatment levels, that is, single vertebroplasty versus multiple vertebroplasty, no significant difference in improvement of FVC% was confirmed (P=0.1). FVC% was abnormally low (Asunto(s)
Fracturas por Compresión/cirugía
, Vértebras Lumbares/cirugía
, Enfermedades Pulmonares/prevención & control
, Vértebras Torácicas/cirugía
, Vertebroplastia/métodos
, Anciano
, Anciano de 80 o más Años
, Femenino
, Estudios de Seguimiento
, Fijación Interna de Fracturas/métodos
, Fracturas por Compresión/etiología
, Humanos
, Masculino
, Persona de Mediana Edad
, Osteoporosis/complicaciones
, Pruebas de Función Respiratoria
, Estudios Retrospectivos
, Resultado del Tratamiento
RESUMEN
BACKGROUND: Percutaneous vertebroplasty (PVP) is a technique that structurally stabilizes a fractured vertebral body. However, some patients return to the hospital due to recurrent back pain following PVP, and such pain is sometimes caused by new compression fractures. PURPOSE: To investigate whether the apparent diffusion coefficient (ADC) of adjacent vertebral bodies as assessed by diffusion-weighted imaging before PVP could predict the onset of new compression fractures following PVP. MATERIAL AND METHODS: 25 patients with osteoporotic compression fractures who underwent PVP were enrolled in this study. ADC was measured for 49 vertebral bodies immediately above and below each vertebral body injected with bone cement before and after PVP. By measuring ADC for each adjacent vertebral body, ADC was compared between vertebral bodies with a new compression fracture within 1 month and those without new compression fractures. In addition, the mean ADC of adjacent vertebral bodies per patient was calculated. RESULTS: Mean preoperative ADC for the six adjacent vertebral bodies with new compression fractures was 0.55 x 10(-3) mm(2)/s (range 0.36-1.01 x 10(-3) mm(2)/s), and for the 43 adjacent vertebral bodies without new compression fractures 0.20 x 10(-3) mm(2)/s (range 0-0.98 x 10(-3) mm(2)/s) (P < 0.001). Mean preoperative ADC for the six patients with new compression fractures was 0.55 x 10(-3) mm(2)/s (range 0.21-1.01 x 10(-3) mm(2)/s), and that for the 19 patients without new compression fractures 0.17 x 10(-3) mm(2)/s (range 0.01-0.43 x 10(-3) mm(2)/s) (P < 0.001). CONCLUSION: The ADC of adjacent vertebral bodies as assessed by diffusion-weighted imaging before PVP might be one of the predictors for new compression fractures following PVP.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Fijación Interna de Fracturas/métodos , Fracturas por Compresión/cirugía , Fracturas Espontáneas/cirugía , Osteoporosis/complicaciones , Fracturas de la Columna Vertebral/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del TratamientoRESUMEN
This retrospective study evaluated the safety and efficacy of combination chemotherapy using docetaxel and nedaplatin in an outpatient setting compared with those of chemotherapy using cisplatin (CDDP) and 5-Fu under hospitalization. Subjects comprised 21 patients who had been diagnosed with recurrent esophageal squamous cell carcinoma (ESCC), with 10 patients receiving combination chemotherapy comprising CDDP and 5-fluorouracil (5-Fu) under hospitalization (FP group; n = 10), and 11 patients receiving combination chemotherapy comprising docetaxel and nedaplatin in an outpatient setting (Doc/Ned group; n = 11). In the Doc/Ned group, patients received 30 mg/m(2) of docetaxel over a 1-h infusion on day 1, followed by 40 mg/m(2) of nedaplatin over a 2-h infusion on day 1 in an outpatient setting. In the Doc/Ned group, complete response was observed in two patients (18.1%), one with liver metastasis and one with abdominal lymph node metastasis, and two (18.1%) achieved partial response. In contrast, no complete responses were obtained in the FP group, and partial response was observed in only one patient (10.0%) with local recurrence. Response rates were thus 36.3% for the Doc/Ned group and 10.0% for the FP group. With a median follow-up of 234 days in the Doc/Ned group and 279 days in the FP group, median survival time (MST) was 234 days in the Doc/Ned group and 378 days in the FP group. No significant differences in MST were identified between groups. Thus regimen based on docetaxel and nedaplatin allows administration on an outpatient basis and appears feasible for recurrent ESCC as a second-line chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Docetaxel , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Compuestos Organoplatinos/administración & dosificación , Probabilidad , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Taxoides/administración & dosificación , Resultado del TratamientoAsunto(s)
Neoplasias de la Mama/patología , Carcinoma de Células Acinares/patología , Carcinoma Ductal de Mama/patología , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/cirugía , Colorantes Azulados , Biopsia con Aguja Fina , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/cirugía , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/cirugía , Citodiagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Invasividad Neoplásica/patología , Prueba de PapanicolaouRESUMEN
Increasing evidence from experimental studies indicates that apoptosis may be related to angiogenesis in tumor progression. To explore how spontaneous apoptosis correlates with tumor angiogenesis, we measured the apoptotic index (AI) using the ApopTag kit (Oncor) and intratumoral microvessel density using an anti-CD34 monoclonal antibody in 101 cases of gastric carcinoma. Immunohistochemical staining for Ki-67 labeling index and the expression of p53 were conducted simultaneously. Statistical analysis revealed an inverse correlation between AIs and intratumoral microvessel densities (r = -0.4066, P < 0.0001) and failed to find significant correlations between AI and Ki-67 labeling index, as well as the expression of p53. The results of this study demonstrated for the first time that the incidence of apoptosis in gastric carcinoma is significantly influenced by the extent of neovascularization and suggests that tumor angiogenesis may contribute to a reduction of apoptosis in tumor cells.
Asunto(s)
Apoptosis , Neovascularización Patológica/patología , Neoplasias Gástricas/irrigación sanguínea , Neoplasias Gástricas/patología , Humanos , Antígeno Ki-67/metabolismo , Microcirculación , Proteínas de Neoplasias/metabolismo , Neovascularización Patológica/inmunología , Neovascularización Patológica/metabolismo , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
A novel inhibitor of apoptosis designated survivin has recently been found in many common human cancers but not in normal tissues. A potential distribution of survivin in gastric cancer and its implication for apoptosis inhibition have been investigated. Recombinant survivin expressed in Escherichia coli as a glutathione S-transferase fusion protein was used to raise a novel panel of mouse monoclonal antibodies. In an immunohistochemical analysis of 174 cases of gastric carcinomas (stages I-III), anti-survivin monoclonal antibody 8E2 (IgG1) reacted with 34.5% of cases (60 of 174 cases) with a variable number of tumor cells stained (20-100%). In contrast, no expression of survivin in neighboring normal tissues was observed. When stratified for p53 and bcl-2 expression and apoptotic index, the expression of survivin significantly segregated with p53- and bcl-2-positive cases [56.1 versus 15.2% (P = 0.001) and 69.2 versus 31.6% (P = 0.006), respectively] and with a decreased apoptotic index as compared with that of survivin-negative tumors (0.97 +/- 0.64 versus 0.62 +/- 0.39%, P < 0.001). These data identify a role for survivin in promoting aberrantly increased cell viability in gastric cancer and suggest a potential correlation between accumulated p53 and survivin expression in neoplasia.
Asunto(s)
Apoptosis , Proteínas Asociadas a Microtúbulos , Proteínas/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Monoclonales , Femenino , Humanos , Técnicas para Inmunoenzimas , Proteínas Inhibidoras de la Apoptosis , Masculino , Ratones , Persona de Mediana Edad , Proteínas de Neoplasias , Estadificación de Neoplasias , Proteínas/inmunología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Recombinantes/metabolismo , SurvivinRESUMEN
Cellular interaction and in vitro antitumor activity of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), were studied in relation to its physicochemical characteristics. MMC-D with cationic and anionic charges were examined. The cationic MMC-D was synthesized using a spacer, epsilon-aminocaproic acid and dextrans with molecular weights of 10,000, 70,000, or 500,000 [MMC(C6)Dcat]. The anionic MMC-D was synthesized using 6-bromohexanoic acid as a spacer and dextran with a molecular weight of 70,000 [MMC(C6)Dan]. Cellular adsorption was determined by measuring the concentration of the drug in the medium after incubation with three tumor cell lines, Ehrlich ascites carcinoma, L1210 leukemia, and AH66 ascites hepatoma cells. MMC(C6)Dcat was adsorbed more readily than MMC or MMC(C6)Dan on the tumor cell surface by an electrostatic force. The percentage of adsorption remained almost constant during the course of incubation and no significant difference was observed between the incubation at 4 degrees C and that at 37 degrees C. A corresponding increase in the amounts of MMC(C6)Dcat adsorbed on with higher molecular weights was noted, which conformed to Langmuir's adsorption isotherm. In vitro antitumor activity was evaluated using L1210 and EAC cell culture systems and human tumor colony forming assay. MMC(C6)Dcat showed growth inhibition essentially equal to that of MMC in continuous drug exposure experiments. In a 1-h drug exposure experiment, MMC(C6)Dcat with a molecular weight of 70,000 or 500,000 was more active than MMC, and a good correlation was observed between the effects of MMC(C6)Dcat and the extent of cellular interaction. These results show that cellular interaction played an important role in the manifestation of the antitumor effect of MMC-D and that these phenomena are governed by the physicochemical properties of macromolecular prodrugs, such as electric charge and molecular weight.
Asunto(s)
Mitomicinas/administración & dosificación , Neoplasias Experimentales/tratamiento farmacológico , Adsorción , Animales , Transporte Biológico , Compartimento Celular , Ciclo Celular/efectos de los fármacos , Membrana Celular/metabolismo , Medios de Cultivo , Dextranos/administración & dosificación , Inhibidores de Crecimiento/administración & dosificación , Punto Isoeléctrico , Ratones , Mitomicina , Peso Molecular , Ratas , Ácidos Siálicos/fisiología , Relación Estructura-Actividad , Factores de TiempoRESUMEN
Neovascularization promotes tumor growth by facilitating nutrient exchange and by the paracrine effect. To investigate the relationship between tumor angiogenesis and patient outcome in colorectal cancer, 133 primary tumors were immunostained for CD34 antigen. Blood vessels within five microscopic fields at x200 were counted, and the mean was assigned. Mean patient age was 62.9 years, mean follow-up was 56.4 months, and mean vessel count was 112 (range, 23-298). Cox proportional hazards model and multivariate logistic regression analyses showed that the vessel count was the most important prognostic factor and correlated significantly with hematogenous, but not peritoneal or lymph node, metastasis.
Asunto(s)
Adenocarcinoma/patología , Neoplasias Colorrectales/patología , Metástasis de la Neoplasia/fisiopatología , Neovascularización Patológica/fisiopatología , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Anciano , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/secundario , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
Deregulated inhibition of apoptosis (programmed cell death) may facilitate the insurgence of neoplasia, but whether it also influences the outcome of common cancers has remained controversial. In this study, we investigated the expression of a novel inhibitor of apoptosis, survivin, in colorectal cancer and its relationship with tumor cell apoptosis and overall prognosis. By immunohistochemistry, survivin was expressed in 91 of 171 (53.2%) cases of colorectal carcinomas of histological stages 0 to IV. In contrast, normal colon epithelium did not express survivin. Although survivin expression did not correlate with p53 abnormalities (46.5% versus 58.0%; P = 0.18), survivin-positive cases were strongly associated with bcl-2 expression (72.5% versus 27.4%; P < 0.0001) and reduced apoptotic index (0.76% +/- 0.39% versus 1.17% +/- 0.62%; P < 0.0001). Expression of survivin alone in bcl-2-negative (discordant) cases also resulted in reduced apoptotic index (0.82% +/- 0.57% versus 1.16% +/- 0.66%; P = 0.0046). When analyzed for prognostic significance, patients with low apoptotic index (< 0.97%) had worse survival rates than the group with high apoptosis (P < 0.001), and a multivariate Cox proportional hazard model identified reduced apoptosis as an independent predictive factor for overall survival (P < 0.0001). These data demonstrate that apoptosis inhibition by survivin, alone or in cooperation with bcl-2, is an important predictive/prognostic parameter of poor outcome in colorectal carcinoma and identify survivin as a new diagnostic/therapeutic target in cancer.
Asunto(s)
Apoptosis/fisiología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Proteínas Asociadas a Microtúbulos , Proteínas de Neoplasias/fisiología , Proteínas/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/fisiopatología , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Tasa de Supervivencia , Survivin , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
To determine whether tumor angiogenesis correlates with prognosis and metastasis of patients with gastric carcinoma, we counted the microvessels within the primary carcinoma and compared their numbers with the patient's prognosis and mode of metastasis. Tumor specimens from 110 patients with gastric carcinoma, who had undergone curative resection more than 24 months before, were investigated. Intratumoral microvessels were stained with anti-CD34 and anti-von Willebrand factor monoclonal antibodies before being quantitated by light microscopy (x200). The antibody against von Willebrand factor often showed variability and stromal background staining, providing misleading low vessel counts. The data from three patients who died from nongastric carcinoma within 24 months after surgery were deleted. A total of 107 patients took part in the analysis examining the association between intratumoral microvessels and clinical outcomes. Vessel counts derived from CD34 expression were significantly higher in patients who experienced hematogenous or peritoneal metastasis after surgery than in patients with nonmetastatic tumors. No correlation between vessel counts and lymph node metastasis was found. The prevalence of hematogenous metastasis. but not peritoneal metastasis, increased as the vessel counts increased. Multivariate logistic regression and Cox hazards model analyses showed that the vessel counts obtained with CD34 staining correlated with the development of hematogenous recurrence but not peritoneal recurrence. It was the most important factor for predicting overall survival. These findings support the hypothesis that tumor angiogenesis is closely related to the development of hematogenous metastasis in human gastric carcinomas. Assessment of tumor vascularization may, therefore, prove valuable in identifying patients with gastric carcinoma at high risk for recurrence who would benefit from adjuvant therapy.