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PubMed2000

Postoperative delirium in patients with chronic lower limb ischaemia: what are the specific markers?

OBJECTIVES: we determined the incidence and specific markers of postoperative delirium in elderly patients with chronic lower limb ischaemia. PATIENTS AND METHODS: since April, 1995, 110 patients aged 60 years or older (mean: 71.6+/-6.6 years) who underwent bypass surgery were assessed regarding aetiological factors of delirium: age, sex, dementia, body-mass index, hypertension, diabetes, cerebral disease, laboratory test results, severity of limb ischaemia, type of arterial occlusion, operative time, and blood transfusion. RESULTS: discriminant analysis showed statistical significance in the following five variables: age >/=70 years; critical limb ischaemia (and/or ankle pressure <40 mmHg); dementia; duration of operation >/=7 hours; low serum albumin. The overall percentage of cases correctly classified was 78.2% (Wilks>> Lambda=0.695, p<0.001); the standardized regression coefficients of the five variables were 0.648, 0.500, 0.329, 0.218, and 0.200, respectively. In logistic regression, the regression coefficients for old age and critical limb ischaemia were 2.646 (14.1 of odds ratio; 95% confidence interval, 2.7-72.0) and 1.337 (3.8; 1.3-10.9), respectively. CONCLUSIONS: the incidence of postoperative delirium in elderly patients with chronic lower-limb ischaemia was as high as 42.3%, and an age of over 70 years and critical limb ischaemia were identified as specific markers, with 14.1 times and 3.8 times the odds of suffering from delirium after bypass surgery.

Age Distribution↗
PubMed2006

Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma.

BACKGROUND AND AIMS: Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein-3 alpha (MIP-3alpha), correlates with metastasis of hepatocellular carcinoma (HCC). METHODS: To observe the reaction of CCR6 expressed cancer cells to MIP-3alpha stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF-7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real-time polymerase chain reaction. Patients were classified into two groups, high (>or= 20 copies; n=10) CCR6 and low (<20 copies; n=20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features. RESULTS: When HepG2 cells (CCR6 high) were stimulated with MIP-3alpha, they migrated in a dose-dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P<0.05). Disease-free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P<0.05). CONCLUSIONS: It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.

Aged↗
PubMed2003

Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis.

BACKGROUND: Increased expression of the beta2 integrin Mac-1 (CD11b/CD18, alphaMbeta2), which is responsible for firm leukocyte adhesion to platelets and fibrinogen at injured vessels, is found in association with neointimal hyperplasia after coronary interventions. The role of Mac-1 in the pathophysiology of restenosis is incompletely defined. To clarify further the role of Mac-1, we determined whether coronary stenting induced activation of Mac-1, which is required for high-affinity receptor-ligand interactions. METHODS AND RESULTS: Expression of CD11b (alpha-subunit of Mac-1) and binding of 8B2 (monoclonal antibody against an activation-dependent neoepitope of Mac-1) on the surface of polymorphonuclear leukocytes were analyzed in 62 patients undergoing coronary stenting using flow cytometric analysis of whole blood obtained from the coronary sinus and femoral vein. Transcardiac CD11b expression increased significantly at 24 hours and maximally at 48 hours after stenting; 8B2 began to increase at 10 minutes and was maximally increased at 48 hours after stenting. These changes were more prominent in patients with subsequent restenosis. Multiple regression analysis showed that the late lumen loss by quantitative coronary angiographic analysis was independently correlated with the CD11b increase (R=0.42, P<0.01) and the 8B2 increase (R=0.55, P<0.001) 48 hours after the procedure. Mac-1 activation, as assessed by 8B2 binding, was the most powerful predictor of late lumen loss. CONCLUSIONS: Coronary stenting produced upregulation and early activation of the leukocyte integrin Mac-1, which is associated with late lumen loss and restenosis. These data support a role for inflammation in neointimal thickening and suggest the validity of targeting leukocyte recruitment for preventing clinical restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2004

Safety of AT-1015, a novel 5-HT2A antagonist, in combination with high-dose aspirin: an open-label study.

OBJECTIVE: To assess the safety of AT-1015 in combination with high-dose aspirin (300 mg daily). Study subjects were 17 healthy male volunteers. METHODS: This was an open-label, single-center study. Subjects received aspirin 300 mg once daily, alone on days 1-4, and together with AT-1015 40 mg twice daily on days 5-11. A follow-up assessment was performed on day 18. The primary outcome measure was bleeding time; secondary outcome measures were vital signs, adverse events, physical examinations, 12-lead electrocardiograms (ECG) and laboratory safety tests. RESULTS: There was a significant increase in bleeding time between screening and the end of the aspirin-only period (mean bleeding time 4.8 vs 7.6 min, p = 0.01), but there were no further significant increases during the combination treatment period. The most common adverse events were dry mouth, epistaxis, gingival bleeding and abdominal pain. All treatment-related adverse events were mild in severity and no major bleeding episodes occurred. There were no clinically significant changes in vital signs, physical examinations, 12-lead ECGs or laboratory safety tests. CONCLUSIONS: AT-1015 was safe and well-tolerated in healthy male volunteers when taken in combination with high-dose aspirin, and did not significantly prolong bleeding time compared with aspirin alone.

Administration, Oral↗
PubMed2005

[Usefulness of diffusion-weighted MRI in differentiating benign from malignant musculoskeletal tumors].

PURPOSE: To evaluate the usefulness of diffusion-weighted MRI in distinguishing different components and in differentiating benign from malignant musculoskeletal tumors. MATERIALS AND METHODS: Fifty-seven patients with musculoskeletal tumors underwent MR at our institution from October 1999 to April 2002. We evaluated 57 tumors (9 bone tumors and 48 soft tissue tumors). All tumors were classified into 8 groups (myxomatous, fibrous, cystic, cartilaginous, fatty components, hematomas, other benign tumors, and other malignant tumors). MR examinations were performed with a 1.5-Tesla system. Diffusion-weighted single-shot EPI images were obtained in all patients. Apparent diffusion coefficients (ADCs) were calculated by using b factors of 0 and 1,000 sec/mm2. RESULTS: ADC values of myxomatous, cystic, and cartilaginous components were significantly higher than those of other tumors. In cartilaginous tumors, malignant tumor ADC values (2.33 +/- 0.44) were higher than those of benign tumors (2.13 +/- 0.13). However, there was no significant difference between benign and malignant tumors. Except for high-intensity components on T1-weighted imaging and low or homogeneously very high intensity components on T2-weighted imaging, there was a significant difference in ADC between malignant (1.35 +/- 0.40) and benign (1.97 +/- 0.50) tumors. CONCLUSION: Within the limited number of cases, there was a significant difference in ADC between malignant and benign tumors.

Adolescent↗
PubMed2004

Antecedent hypertension interacts with adverse ventricular remodeling after myocardial infarction.

BACKGROUND: Ventricular remodeling is an independent predictor of left ventricular function in patients with myocardial infarction (MI). Accelerated ventricular remodeling is a probable contributor to the increased mortality observed after MI in hypertensive patients. The purpose of this study is to assess the relationship of antecedent hypertension to ventricular remodeling after MI. METHODS: Seventy-nine patients presenting with a first acute MI (AMI) who were treated and attained Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 with re-perfusion therapy within 12 hours of their symptom onset were enrolled in this study. All of them underwent left ventriculography (LVG) immediately after re-perfusion therapy and again at 6 months after the occurrence of MI. Patients were divided into two groups; hypertensive group and normotensive group. End-diastolic volume index (EDVI), end-systolic volume index (ESVI), and EF were compared between acute phase and 6 months after AMI in each group. RESULTS: The hypertensive group showed a significant increase in both EDVI and ESVI after 6 months, whereas the normotensive group did not. In addition, there was no change in EF in the hypertensive group, whereas EF increased significantly after 6 months in the normotensive group. As a result, percent change in ESVI and EF showed significantly differences between the hypertensive group and normotensive group, whereas percent change in EDVI showed no significant difference between the two groups. CONCLUSIONS: Antecedent hypertension interacts with ventricular remodeling after MI.

Aged↗
PubMedDate not supplied

Synergy of the combination of nedaplatin with etoposide in murine and human lung carcinoma.

BACKGROUND: The combination of cisplatin (CDDP) and etoposide (ETP) has been shown to be an effective treatment for lung cancer. Nedaplatin (NDP) has been developed as a second generation plainum complex. Because of its superior antitumor activity and lower nephrotoxicity in comparison with CDDP, the antitumor effects of NDP in combination with ETP against murine and human lung cancer was investigated. MATERIALS AND METHODS: Lewis murine lung carcinoma, RERF-LC-AI, and Ma44 human lung cancer were used in this study. NDP (1/4 to 1 maximum to related dose; MTD) and CDDP (1/4 to 1 MTD) were administered once and ETP (1/32MTD) was administered daily for five days via the tail vein of mice. RESULTS: In the mice bearing Lewis lung carcinoma, a combination of NDP and ETP resulted in synergistically enhanced inhibition of tumor growth (Treated/Control ratio; T/C = 0.001) in comparison with either NDP or ETP alone (T/C = 0.12 for NDP, T/C = 0.13 for ETP), and prolonged survival (Increased Life Span; ILS% > or = 172) in comparison with either NDP or ETP alone (ILS% = 65 for NDP, ILS% = 54 for ETP). NDP showed a more potent combination effect with ETP than CDDP did for both growth inhibition and survival. This effect was confirmed in human lung cancer. Although body weight loss was enhanced by the combined treatment, it was tolerable. With regards to myelosuppression, no significant difference between NDP plus ETP and CDDP plus ETP was observed. CONCLUSION: These results suggest the superiority of a combination of NDP with ETP against CDDP with ETP as a clinical therapy for lung cancer.

Animals↗
PubMed2000

Clinical evaluation of 99mTc-Technegas SPECT in thoracoscopic lung volume reduction surgery in patients with pulmonary emphysema.

UNLABELLED: 99mTc-Technegas (Tcgas) SPECT is useful for evaluating the patency of the airway and highly sensitive in detecting regional pulmonary function in pulmonary emphysema. The aim of this study is to evaluate regional ventilation impairment by this method pre and post thoracoscopic lung volume reduction surgery (LVRS) in patients with pulmonary emphysema. METHODS: There were 11 patients with pulmonary emphysema. The mean age of patients was 64.1 years. All patients were males. LVRS was performed bilaterally in 8 patients and unilaterally in 3 patients. Post inhalation of Tcgas in the sitting position, the subjects were placed in the supine position and SPECT was performed. Distribution of Tcgas on axial images was classified into 4 types, A: homogeneous, B: inhomogeneous, C: hot spot, D: defect. Three slices of axial SPECT images, the upper, middle and lower fields were selected, and changes in deposition patterns post LVRS were scored (Tcgas score). RESULTS: Post LVRS, dyspnea on exertion and pulmonary function tests were improved. Pre LVRS, inhomogeneous distribution, hot spots and defects were observed in all patients. Post LVRS, improvement in distribution was obtained not only in the surgical field and other fields, but also in the contralateral lung of unilaterally operated patients. In 5 patients some fields showed deterioration. The Tcgas score correlated with improvements in FEV1.0, FEV1.0% and %FEV1.0. CONCLUSION: Tcgas SPECT is useful for evaluating changes in regional pulmonary function post LVRS.

Aged↗
PubMed2005

Simplifying psychotropic medication regimen into a single night dosage and reducing the dose for patients with chronic schizophrenia.

RATIONALE: Taking psychotropic medications is frequently problematic from both consumers' and caregivers' perspective. Occasionally missed doses may lead to pervasive non-adherence with relapse a likely outcome. OBJECTIVE: To evaluate the simple medication regimen, all psychotropics were given at night for patients with chronic schizophrenia, who had been taking them at least twice a day for more than 12 weeks before the entry. METHODS: Switching of agents took place in two ways: converting only antipsychotic medications followed by other psychotropics, and changing all psychotropics simultaneously. Any psychotropics of little clinical significance were then cautiously minimized. Final evaluation was made 12 weeks after the competed dose consolidation. Patients finally rated their subjective impression on this intervention. RESULTS: Twenty-five patients were recruited in each treatment arm (50 in total). After switching, 11 got better, 29 remained stable whereas seven got worse, according to the Global Improvement. Three were not assessable. Overall, there were no relevant changes in clinical ratings including adverse effects. However, the chlorpromazine equivalent dose of antipsychotics and the number of total psychotropics were significantly reduced from 957 to 722 mg/day (p<0.0001) and from 4.0 to 3.2 (p<0.0001), respectively. Dose deflation of psychotropics was feasible in 35 subjects (74.5%). Twenty-six (of 40 successful) patients indicated that they favored the night-time regimen mainly because it was less complicated. Sedation in the morning was identified as an important adverse event, which should be addressed by reducing the dose. CONCLUSIONS: The procedure may be of value to counteract a recent trend of psychotropic polypharmacy in schizophrenia.

Adult↗
PubMed2004

The decrease of plaque volume during percutaneous coronary intervention has a negative impact on coronary flow in acute myocardial infarction: a major role of percutaneous coronary intervention-induced embolization.

OBJECTIVES: The aim of this study was to evaluate how decreased plaque volume during percutaneous coronary intervention (PCI) affects coronary flow in patients with acute myocardial infarction (AMI). BACKGROUND: Coronary flow after reperfusion therapy is a major determinant of clinical outcomes in patients with AMI. However, little is still known about the changes in coronary flow that appear after PCI in response to the decreased plaque during the procedure. METHODS: The study group comprised 60 patients with AMI who underwent pre- and post-PCI intravascular ultrasound (IVUS). Qualitative and quantitative analyses were performed on all IVUS procedures. External elastic membrane volume (EEMV), lumen volume (LV), and plaque volume (PV) were measured every 1.0 mm to include the lesion and reference segments 3.0 mm proximal and distal to the lesion. The difference between pre- and post-PCI PV was defined as the index of the decrease in plaque volume (DeltaPV). The corrected TIMI frame count (CTFC) was used to evaluate coronary flow after PCI. RESULTS: Plaque volume was decreased at post-PCI IVUS in all 60 patients. Inadequate reflow (CTFC >40) was observed in 13 patients (21.7%). The decrease in PV was significantly larger in patients with inadequate reflow than in those with reflow (49.4 +/- 18.9 vs. 31.7 +/- 15.5 mm(3), p = 0.0010). Also, DeltaPV was significantly correlated with CTFC after PCI (r = 0.415, p = 0.0012). CONCLUSIONS: The decrease in PV during PCI has a negative impact on coronary flow after PCI in patients with AMI. Embolization induced by PCI may occur in all patients with AMI.

Angioplasty, Balloon, Coronary↗
PubMed2005

Efficacy of Seprafilm for reducing reoperative risk in pediatric surgical patients undergoing abdominal surgery.

BACKGROUND: The safety and efficacy of Seprafilm (Genzyme Corporation, Cambridge, Mass) in adult surgery patients have been established. The aim of this study was to evaluate the safety and efficacy of Seprafilm in pediatric surgical patients. METHODS: One hundred twenty-two pediatric abdominal surgery patients were enrolled. Sixty-seven patients received Seprafilm application. Of these patients, 18 again received Seprafilm at abdominal closure during a second surgery, and of the 18, 4 received Seprafilm at closure after a third surgery. Of the 55 control patients who did not receive Seprafilm, 14 had a second surgery, and of these 14 patients, 4 had a third surgery. Adverse events, operation time, and blood loss were compared with assessed Seprafilm safety. Seprafilm efficacy evaluations included incidence and severity of adhesions in those patients who required relaparotomy. RESULTS: The incidence (Seprafilm, 40.9%; control, 82.4%) and severity (Seprafilm: 59.1%, grade 0; control: 17.6%, grade 0) of adhesions under the abdominal incision site were significantly reduced in the Seprafilm group (P = .007 and P = .0009, respectively). In addition, mean relaparotomy operation time was significantly shorter for Seprafilm patients (P = .004). At relaparotomy, blood loss/body weight ratio for Seprafilm patients compared with control patients showed a trend toward but did not reach significance (P = .09). CONCLUSIONS: Decreased incidence and severity of postsurgical adhesions with Seprafilm in pediatric patients may lead to reduction of the risks associated with subsequent operation.

Abdomen↗
PubMed1998

Microencapsulation of hepatitis B core antigen for vaccine preparation.

PURPOSE: To prepare poly(lactide-co-glycolide)(PLGA) microspheres containing recombinant hepatitis B core antigen (HBcAg; Mw = 3,600,000) by a w/o/w emulsion/solvent evaporation method and evaluate the possibility of this system as a potent long-acting carrier for hepatitis B core antigen in mice. METHODS: Various additives had been incorporated in the internal aqueous phase during the process of microencapsulating HBcAg, HBcAg antigenicity in the medium extracted from the prepared microspheres were measured by ELISA. Shape confirmation of the HBcAg antigen was performed by a sucrose gradient velocity centrifugal technique. For in vivo study, prepared microspheres were administered subcutaneously to Balb/C mice, and the serum IgG level was determined by ELISA. RESULTS: The inactivation of HBcAg by methylene chloride was dramatically reduced by the addition of gelatin (4-8% (w/v)) to the internal aqueous phase during the preparation. Further improvement of the loading efficiency to almost 61% resulted with cooling (4 degrees C). The prepared microspheres (4.27 microm+/-1.23 microm) containing 0.15% HBcAg displayed burst release (50-60% within 2 days). In subcutaneous inoculation, the adjuvant effect of PLGA microspheres was almost the same as that of the complete Freund's adjuvant. Whereas oral inoculation using the microspheres was not effective. CONCLUSIONS: The pH of the added gelatin seemed to be the key to the stabilization of HBcAg from various stability tests and CD spectrum study. Finally, the possibility of using this system as a potent long-acting hepatitis B vaccine was demonstrated.

Animals↗
PubMed2002

Increases in collagen type I synthesis in asthma: the role of eosinophils and transforming growth factor-beta.

BACKGROUND: Collagen type I is one of the major deposits in thickening of the reticular basement membrane of asthma. OBJECTIVE AND METHODS: In this study, we assessed turnover of collagen type I in asthma by measuring procollagen type I C-terminal peptide (PICP) and collagen type I C-terminal telopeptide (ICTP) in induced sputum. RESULTS: PICP but not ICTP was found to be significantly higher in asthma subjects than in normal volunteers (P < 0.05). In asthma, PICP was inversely correlated with %FEV(1.0) (r = -0.539), and its levels significantly increased upon exacerbation (P < 0.05), indicating that collagen synthesis increases during asthma exacerbation. Additionally, PICP was found to significantly correlate with eosinophil counts in sputum (r = 0.539), indicating that eosinophils stimulate collagen turnover. Because eosinophils can produce TGF-beta, a potent stimulator of collagen synthesis, we immunocytochemically examined TGF-beta-positive cells in sputum. TGF-beta-positive cells significantly correlated with eosinophil counts (r = 0.811) and PICP (r = 0.569), suggesting that TGF-beta released from eosinophils is involved in collagen synthesis. CONCLUSIONS: The results of the present study suggest that collagen synthesis is stimulated in asthmatic airways by eosinophils through TGF-beta, while collagen degradation is not, and that PICP in sputum can act as a new marker for airway inflammation in asthma.

Asthma↗
PubMedDate not supplied

Pathogenesis of calcium crystal deposition in the ligamentum flavum correlates with lumbar spinal canal stenosis.

OBJECTIVE: To investigate the histological and immunohistochemical properties of degenerative changes and calcium crystal deposition in the lumbar ligamentum favum. METHODS: We examined the ligamentum flavum harvested from 119 surgical cases with symptomatic lumbar spinal stenosis. Sections of the ligament were examined by scanning electron microscopy (SEM), energy dispersive X-ray micro-analysis, and were immunostained for S-100 protein, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and CD34. The results were compared with those of ligament tissue harvested from 10 cases of lumbar disc herniation. RESULT: The elastic fibres of the ligamentum favum showed regular, or sometimes irregular, and fragmented fibre bundles. Large areas of fibrosis with reduced elastic component and increased collagenous tissue were frequently seen in the degenerated ligaments. Calcium crystal deposits were observed in these fibrous ligaments, associated with many hypertrophic chondrocytes, and with small blood vessel formation. These chondrocytes stained positively for S-100 protein, VEGF and bFGF Calcium pyrophosphate dihydrate crystals were identified in the calcium deposit area. CONCLUSION: We believe that rupture of elastic fibre bundles is the first change to occur in degeneration of the ligamentum favum. Calcium crystal deposition was seen within these fibrous and chondrometaplastic areas. Hypertrophic chondrocytes regulate crystal formation and tissue reconstruction by secreting cytokines.

Adult↗
PubMed1991

[Pharmacokinetic study of adriamycin in the emulsion mixed with lipiodol-difference resulting from composition and methods of preparation, and behavior after mesenteric arterial injection in rat].

We experimentally investigated the pharmacokinetics of adriamycin (ADM) in a similar of transcatheter arterial chemoembolization therapy (TAE) of hepatocellular carcinoma using emulsion of lipiodol (Lp) mixed with ADM followed by gelatin sponge, and the difference resulting from composition and method of preparation of the emulsion as well as behavior after mesenteric arterial injection in rat. In in vitro study, the emulsion with iopamidol (iopamiron 300 : IP) was more stable than with amidotrizoic acid (60% Urografin : UG). The highest stability was found in the mixing ratio of Lp. IP and distilled water at 1 : 0.42 : 0.08. Frequent pumping also made the emulsion more stable. But in optimally composed emulsion, pumping 20 or 50 times made no difference in the stability during 30 min. which may be longer than the time from preparation to injection time of the emulsion in clinical application. After injection of the emulsion into the mesenteric artery which may simulate injection into the hepatic artery in hepatocellular carcinoma, the arterial blood flow was suspended. In the peripheral arteries the emulsion separated into two phases of Lp and ADM solution, forming striped pattern, and Lp embolization of the peripheral artery persisted for over 45 min. while ADM extravasated. These findings suggest that after Lp-TAE, Lp maintains an embolizing effect while ADM penetrates into the surrounding tumor tissue, and that this is an underlying mechanism for the anti-cancer effect of Lp-TAE.

Animals↗
PubMed2005

Multivariate analysis of the neurological outcome of surgery for cervical compressive myelopathy.

BACKGROUND: The neurological outcome of decompressive surgery for cervical myelopathy is influenced by several factors. Although each factor may have an independent effect, it is more likely that the outcome is influenced by more than one factor. We examined the results of multivariate analysis and multiple regression analysis of the neurological outcome of patients treated by cervical cord decompression. METHODS: A total of 77 patients with cervical spondylotic myelopathy (43 men, 34 women) and 58 with ossification of the posterior longitudinal ligament (OPLL) (39 men, 19 women) were studied with an average follow-up interval of 8.3 years. The clinical data, neurological and radiological findings, and results of spinal cord evoked potentials (SCEPs) were retrieved from the medical records and included in the analysis. RESULTS: Multivariate analysis indicated that the outcome for patients with spondylosis was positively influenced, in order of importance, by increased transverse area of the cord >or=60%, presence of single-level anterior fusion, a high preoperative neurological score, normal epidural SCEPs, and clinical features of brachialgia and cord type. In patients with OPLL, multivariate analysis showed that the long-term outcome was positively influenced, in order of importance, by the presence of mixed or localized OPLL, normal epidural SCEPs, high preoperative neurological score, a single-vertebra spondylectomy with anterior fusion, laminoplasty, widening of the transverse area of the cord >or=40%, and an expansion rate of the spinal canal after laminoplasty >or=40%. CONCLUSIONS: We suggest that multivariate analysis is useful for assessing the neurosurgical outcome in patients with cervical compressive myelopathy.

Adult↗
PubMed2002

The prognostic significance of overexpression of the decoy receptor for Fas ligand (DcR3) in patients with gastric carcinomas.

BACKGROUND: The FasL-Fas system has an important role in mediating immune-cytotoxic killing of cells such as virus-infected or tumor cells. It was recently reported that there is a soluble decoy receptor (DcR3), which binds to FasL and inhibits FasL-induced apoptosis, and certain tumors may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL. We evaluated whether DcR3 has clinical relevance in actual human gastric cancers. METHODS: : The expression of DcR3 was investigated by Northern blot analysis in a series of 84 primary gastric carcinomas and compared with clinicopathological features and prognosis. The DcR3 expression level was analyzed and quantified densitometrically. The location of DcR3 mRNA in gastric carcinoma tissue was detected by in situ hybridization. RESULTS: The frequency of DcR3 overexpression was 26% (22 of 84 surgical specimens). The DcR3 expression level was significantly associated with lymph node metastasis and pathological stage, but did not correlate with tumor size, metastatic status, or histological type. In situ hybridization demonstrated that DcR3 mRNA was expressed in tumor cells. When the patients were followed up for 63 months, DcR3 overexpression was found to be associated with a significantly shortened duration of overall survival compared with findings in patients having normal DcR3 expression. CONCLUSION: The DcR3 decoy receptor for FasL may be involved in the progression of gastric cancer. Further evaluation of these possible roles of DcR3 and the regulation of DcR3 expression in malignant cells will be critically important for the development of new strategies for controlling the growth of malignant cells that escape host immune surveillance.

Adenocarcinoma↗
PubMed1986

Vascular changes associated with growth of primary and transplantable pancreatic adenocarcinomas induced in Syrian golden hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP).

Microangiographic and histological methods were used to characterize vascular structure of primary and transplantable pancreatic adenocarcinomas induced by propylnitrosamines in Syrian golden hamsters. Originally of well-differentiated tubular morphology, serial transplantation subcutaneously to the back region was not associated with change in histopathological pattern or increase in invasive or metastatic potential. In contrast, pancreatic subserosal grafts displayed prominent invasion of surrounding tissues. Whereas primary tumors induced by N-nitrosobis(2-oxopropyl)amine (BOP) and those transplanted subserosally were characterized by hypovascularity, subcutaneous transplantation resulted in hypervascular tumors. Encasement, which is defined as invasion of normal arteries by the tumor, showing uneven caliber, irregular outline, appeared on earlier microangiographic findings rather than luminal irregularity, which is change of tumor vessels in neovascularization and occurs in tumor blood vessels subsequent to transplantation. The vascular component of subcutaneously transplanted tumors had a total vessel length ranging from 9.2 +/- 0.7 mm to 18.1 +/- 1.1 mm, a total vessel surface from 2.5 +/- 0.4 mm2 to 9.3 +/- 0.6 mm2 and a total vessel volume from 0.07 +/- 0.02 mm3 to 0.49 +/- 0.04 mm3, indicating that the vessels were of relatively large diameter and short length.

Adenocarcinoma↗