LINC01308 accelerates the malignant progression of ovarian cancer by binding to miRNA-506.

OBJECTIVE: To detect the expression pattern of LINC01308 in ovarian cancer (OC), and further clarify whether LINC01308 could promote the malignant progression of OC by mediating microRNA-506 (miRNA-506). PATIENTS AND METHODS: Relative level of LINC01308 in 28 pairs of OC tissues and paracancerous tissues was determined by quantitative Real-time polymerase chain reaction (qRT-PCR). We analyzed the correlation between LINC01308 level and the prognosis of OC patients. Subsequently, LINC01308 level in OC cell lines was determined as well. By transfection of sh-LINC01308 in 3AO and CAOV3 cell lines, we evaluated the influence of LINC01308 on cellular behaviors of OC through cell counting kit-8 (CCK-8), transwell and wound healing assay. Target downstream of LINC01308 was verified by dual-luciferase reporter gene assay. Finally, the regulatory effect of LINC01308/miRNA-506 on OC cell behaviors was examined through a series of rescue experiments. RESULTS: LINC01308 was highly expressed in OC tissues relative to controls. OC patients with high-level LINC01308 had higher rates of lymph node metastasis and distant metastasis, and lower survival rate compared with those with low level. By transfection of sh-LINC01308 in OC cells, the migratory and invasive abilities were markedly weakened. MiRNA-506 was found to be the target gene of LINC01308, and its level was negatively regulated by LINC01308 in OC tissues. Finally, we found that miRNA-506 knockdown reversed the regulatory effect of LINC01308 on the migratory and invasive abilities of OC cells. CONCLUSIONS: LINC01308 is highly expressed in OC and correlated to metastasis and poor prognosis. LINC01308 enhances OC cells to migrate and invade by targeting miRNA-506.

Renal haemodynamics and oxygenation during and after cardiac surgery and cardiopulmonary bypass.

Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac surgery-associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra-operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi-disciplinary pathway for translation comprising three components. Firstly, large-animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non-invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts.

Ropinirole alters gene expression profiles in SH-SY5Y cells: a whole genome microarray study.

Ropinirole (ROP) is a dopamine agonist that has been used as therapy for Parkinson's disease. In the present study, we aimed to detect whether gene expression was modulated by ROP in SH-SY5Y cells. SH-SY5Y cell lines were treated with 10 µM ROP for 2 h, after which total RNA was extracted for whole genome analysis. Gene expression profiling revealed that 113 genes were differentially expressed after ROP treatment compared with control cells. Further pathway analysis revealed modulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, with prominent upregulation of PIK3C2B. Moreover, batches of regulated genes, including PIK3C2B, were found to be located on chromosome 1. These findings were validated by quantitative RT-PCR and Western blot analysis. Our study, therefore, revealed that ROP altered gene expression in SH-SY5Y cells, and future investigation of PIK3C2B and other loci on chromosome 1 may provide long-term implications for identifying novel target genes of Parkinson's disease.

Natriuretic peptide resistance of mesenteric arteries in spontaneous hypertensive rat is alleviated by exercise.

Proximal resistance vessels, such as the mesenteric arteries, contribute substantially to the peripheral resistance. The reactivity of resistance vessels to vasoactive substance like natriuretic peptides plays an important role in the regulation of blood pressure. In current study, we investigated the reactivity of mesenteric arteries to atrial natriuretic peptide (ANP), a well known vasodilating factor, in spontaneously hypertensive rats (SHR), as well as the effects of exercise training on it. As a result, ANP-induced vasorelaxation was attenuated in SHR with significantly increased phosphodiesterase type 5 (PDE5), and decreased cGMP/ANP ratio, compared with WKY rats as control. Intriguingly, the decreased reactivity to ANP in SHR was markedly reversed by exercise training. In addition, ANP resistance of in vitro mesenteric arteries was diminished by sildenafil a potent selective inhibitor of PDE5. In conclusion, ANP resistance occurs in resistance vessels of SHR, suggesting predisposition to hypertension, which can be reversed by exercise.

Ropinirole alters gene expression profiles in SH-SY5Y cells: a whole genome microarray study

Ropinirole (ROP) is a dopamine agonist that has been used as therapy for Parkinson's disease. In the present study, we aimed to detect whether gene expression was modulated by ROP in SH-SY5Y cells. SH-SY5Y cell lines were treated with 10 µM ROP for 2 h, after which total RNA was extracted for whole genome analysis. Gene expression profiling revealed that 113 genes were differentially expressed after ROP treatment compared with control cells. Further pathway analysis revealed modulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, with prominent upregulation of PIK3C2B. Moreover, batches of regulated genes, including PIK3C2B, were found to be located on chromosome 1. These findings were validated by quantitative RT-PCR and Western blot analysis. Our study, therefore, revealed that ROP altered gene expression in SH-SY5Y cells, and future investigation of PIK3C2B and other loci on chromosome 1 may provide long-term implications for identifying novel target genes of Parkinson's disease.

Angiotensin II type 1 receptor gene A1166C polymorphism and breast cancer susceptibility.

Numerous studies have evaluated the association between the angiotensin II type-1 receptor (AGTR1) gene A1166C polymorphism and breast cancer risk. However, the specific association is controversial. The aim of the present study was to derive a more precise estimation of the relationship. A comprehensive research was conducted of the PubMed and the Google Scholar databases through February 2015. Data were assessed using STATA version 12.0. Pooled odds ratios with 95%CIs were derived from the fixed-effect or random-effect models. A total of 911 patients with breast cancer and 1284 controls from 5 case-control studies were included in this meta-analysis. The meta-analysis results showed no significant association between the AGTR1 gene A1166C polymorphism and breast cancer risk. Similarly, in the subgroup analysis regarding ethnicity, no associations were observed. Heterogeneity and publication bias were not observed in this meta-analysis. The A1166C polymorphism in the AGTR1 gene may not be a risk factor for breast cancer. Further, large, and well-designed studies are needed to confirm this conclusion.

Clinicopathological features of invasive lobular carcinoma of the breast: A nationwide multicenter study in China.

OBJECTIVE: To analyze the clinicopathological features of invasive lobular carcinoma (ILC) and compare them with invasive ductal carcinoma (IDC), hoping to find the fact of ILC in China and assist the decision makers with proper individualized treatment. MATERIALS AND METHODS: A nationwide multicenter retrospective study was performed. A total of 4211 primary breast cancer cases were randomly selected from 1999 to 2008 in seven regions of China. ILC cases were compared with IDC by clinicopathological features and molecular subtypes. RESULTS: A total of 135 (3.2%) ILC and 3471 (82.4%) IDC cases were included for analysis. The age, tumor size, menopausal state, family history, nodal status, and stage of ILC were similar to that of IDC. ILC was more likely to be positive for estrogen receptor (65.5% vs. 57.7%) and progesterone receptor (64.7% vs. 58.5%), and less likely to overexpress human epidermal growth factor receptor-2 (17.3% vs. 23.6%). Even though, these differences are not significant, the proportion of luminal A type of ILC is significantly larger than that of IDC (54.8% vs. 42.7%; P < 0.05). CONCLUSION: ILC has a larger proportion of luminal A type compared with IDC. Larger sample size study for better known of molecular subtypes of ILC is needed in future to individualize the treatment decision.

Vasonatrin peptide, a new regulator of adiponectin and interleukin-6 production in adipocytes.

BACKGROUND: In addition to lipolytic function, ANP plays regulatory roles in the production of various adipokines including adiponectin, leptin, and interleukins. However, the adipose effects of vasonatrin peptide (VNP), a new manmade natriuretic peptide, are largely unknown. AIM: The aim of the present study was to identify the roles of VNP on adipokines production, as well as signaling pathways involved. MATERIAL, SUBJECTS, AND METHODS: 3T3-L1 cells were differentiated into adipocytes and exposed to various concentrations of VNP. Quantitative PCR and immunoassays were performed to determine the mRNA and protein levels of adiponectin and interleukin-6 (IL-6), respectively. The involved signaling pathway was identified by radioimmunoassay to detect the levels of intracellular cyclic GMP (cGMP), mimicking experiments using 8-brcGMP (a membrane-permeable cGMP analog). Also, blocking experiments were performed using HS-142-1, an antagonist of particulate guanylyl cyclase-coupled natriuretic peptide receptor (NPR), or KT-5823, the cGMP-dependent protein kinase (PKG) inhibitor. RESULTS: VNP markedly enhanced adiponectin mRNA expression, as well as protein secretion, however, suppressed IL-6 production in mature adipocytes. In addition, VNP significantly increased the intracellular levels of cGMP. The effects of VNP were mimicked by 8-br-cGMP, whereas inhibited by HS-142-1, or KT-5823. CONCLUSIONS: Taken together, VNP regulates adiponectin and IL-6 production in adipocytes via guanylyl cyclase-coupled NPR/cGMP/PKG pathway.

Oligomycins A and C, major secondary metabolites isolated from the newly isolated strain Streptomyces diastaticus.

During the screening program for fungicides, one actinomycete strain ECO 00047 was isolated with the potential activity against fungus. According to the morphology and analysis of the nucleotide sequence of the 16S rRNA gene (1500 bp) this isolate was identified as Streptomyces diastaticus. The active compounds were separated by silica gel column chromatography, Sephadex LH-20 gel filtration and then purified by flash chromatography on C18 (20-45 microm). The chemical structure of the bioactive compounds I and II were elucidated, based on the spectroscopic data of MS, IR, UV, 1H-NMR, 13C-NMR and X-ray single crystal diffraction analysis. Compounds I and II were identical with oligomycins A and C, the macrolide antibiotics which have been known to be produced by Streptomyces diastatochromogenes, S. libani and S. avermitilis. The two compounds exhibited a strong activity against Aspergillus niger, Alternaria alternata, Botrytis cinerea and Phytophthora capsici but no activity toward bacteria. Although the two above antibiotics were known, their isolation has so far not been reported from S. diastaticus.

Proteases from Bacillus: a new insight into the mechanism of action for rhizobacterial suppression of nematode populations.

AIMS: The aim of this study was to investigate the role of proteases in Bacillus spp. of rhizobacteria in suppressing nematode populations and to understand their mechanism of action. METHODS AND RESULTS: Rhizobacteria with nematicidal activity were isolated from soil samples of five root knot nematode-infested farms. Among these strains, nematotoxicities of Bacillus strains were intensively analysed. Further assays of nematicidal toxins from Bacillus sp. strain RH219 indicated an extracellular cuticle-degrading protease Apr219 was an important pathogenic factor. The Apr219 shared high similarity with previously reported cuticle-degrading proteases from Brevibacillus laterosporus strain G4 and Bacillus sp. B16 (Bacillus nematocida). The cuticle-degrading protease genes were also amplified from four other nematicidal Bacillus strains isolated from the rhizosphere. In addition to Apr219, a neutral protease Npr219 from Bacillus sp. RH219 was also investigated for activity against nematodes. CONCLUSIONS: The wide distribution of cuticle-degrading proteases in Bacillus strains with nematicidal activity suggested that these enzymes likely play an important role in bacteria-nematode-plant-environment interactions and that they may serve as important nematicidal factors in balancing nematode populations in the soil. SIGNIFICANCE AND IMPACT OF THE STUDY: Increased understanding of the mechanism of action of Bacillus spp. against nematodes could potentially enhance the value of these species as effective nematicidal agents and develop new biological control strategies.

Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine.

In Europe, swainsonine has been studied widely for prevention of metastasis and cancer therapy. In order to investigate the effects and mechanisms of swainsonine on the human gastric carcinoma SGC-7901 cell, we carried out in vivo and in vitro experiments. After treatment with swainsonine, an effective dose and IC50 value of swainsonine for SGC-7901 cells were examined by MTT assay. Cell-cycle distribution and apoptotic rates were analyzed using FCM, and [Ca2+]i was measured using LSCM. The expression of p53, c-myc and Bcl-2 were determined using an immunocytochemical method. Simultaneously, 50 mice were divided randomly into five groups. Three groups were administrated swainsonine at dose of 3, 6 and 12 mg/kg body wt., two control groups were administrated N.S. 20 ml/kg body wt. and 5-Fu 20 mg/kg body wt., respectively, by intraperitoneal injection. The inhibition rate was calculated and pathological sections were observed. The growth of SGC-7901 cell is inhibited by swainsonine in vitro, with an IC50 value at 24 h of 0.84 microg/ml, and complete inhibition concentration is 6.2 microg/ml. After treatment with swainsonine at the concentrations of 0.5, 1.5 and 4.5 microg/ml for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreases, and the apoptotic trigger gene c-myc increases markedly (p<0.05), as well as [Ca2+]i overloading, SGC-7901 cell is induced to apoptosis in the end. It is also found that the percentages of S phase are 38.8%, 39.7% and 29.6%, respectively (20.0% in control group and 23.2% in 5-Fu group). The rates of inhibition were 13.2%, 28.9%, 27.3%, respectively, when the nude mice were administered swainsonine (p<0.05 or 0.01). The structure of the tumor showed hemorrhage, necrosis and inflammatory cell infiltration. We therefore conclude that swainsonine could inhibit cell proliferation in vitro and the growth of human gastric carcinoma in vivo. The mechanisms of swainsonine-induced apoptosis may relate to [Ca2+]i overloading and the expression of apoptosis-related genes.

Inhibition of the proliferation of smooth muscle cells from human coronary bypass vessels by vasonatrin peptide.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is known to be a key event in the development of atherosclerosis and restenosis. The present study examined the effect of a novel synthetic natriuretic peptide, vasonatrin peptide (VNP), on norepinephrine (NE)-induced proliferation of VSMCs from coronary bypass vessels. Human VSMCs were isolated from an internal mammary artery (IMA) and saphenous vein (SV) by explant culture and stimulated with NE. MTT assay and [3H] thymidine-incorporation were undertaken to analyze cell proliferation and radioimmunoassay was used to determine the level of intracellular cyclic 3',5'-guanosine monophosphate (cyclic GMP). NE (10(-8) - 10(-7) mol/l) had a mitogenic effect in human VSMCs from both SV and IMA. However, NE-stimulated proliferation of VSMCs from SV was greater than that from IMA. Furthermore, low concentration of NE (10(-10) mol/l) promoted cell growth in SV-derived cells but not in IMA-derived cells. VNP (10(-8) - 10(-6) mol/l) reduced NE-induced cell proliferation and increased intracellular cyclic GMP, which were abrogated by HS-142-1. In addition, the growth inhibition of VNP was mimicked by 8-bromo-cGMP. These results indicate that VNP has a significant inhibitory effect on NE-stimulated proliferation of human VSMCs from both IMA and SV, which is mediated by guanylate cyclase-linked receptors by increasing cyclic GMP.

QTLs for Na+ and K+ uptake of the shoots and roots controlling rice salt tolerance.

An F2 and an equivalent F3 population derived from a cross between a high salt-tolerance indica variety, Nona Bokra, and a susceptible elite japonica variety, Koshihikari, were produced. We performed QTL mapping for physiological traits related to rice salt-tolerance. Three QTLs for survival days of seedlings (SDSs) under salt stress were detected on chromosomes 1, 6 and 7, respectively, and explained 13.9% to 18.0% of the total phenotypic variance. Based on the correlations between SDSs and other physiological traits, it was considered that damage of leaves was attributed to accumulation of Na+ in the shoot by transport of Na+ from the root to the shoot in external high concentration. We found eight QTLs including three for three traits of the shoots, and five for four traits of the roots at five chromosomal regions, controlled complex physiological traits related to rice salt-tolerance under salt stress. Of these QTLs, the two major QTLs with the very large effect, qSNC-7 for shoot Na+ concentration and qSKC-1 for shoot K+ concentration, explained 48.5% and 40.1% of the total phenotypic variance, respectively. The QTLs detected between the shoots and the roots almost did not share the same map locations, suggesting that the genes controlling the transport of Na+ and K+ between the shoots and the roots may be different.

[Vasonatrin peptide attenuates hypoxia-induced increase in [Ca(2+)] (i) of culured rat cardiac fibroblasts].

The purpose of this work was to test the hypothesis that vasonatrin peptide (VNP) can attenuate the growth-promoting effect by hypoxia in cardiac fibroblasts of cultured neonatal rats. Cultured fibroblasts were divided into four groups: control group, hypoxia group, VNP group and VNP+hypoxia group. The growth of cardiac fibroblasts was observed using MTT method and the incorporation of (3)H-TdR, and the effect of VNP on the intracellular level of Ca(2+) was measured by means of interactive laser cytometry. It was found that hypoxia (2% - 3%) increased significantly the MTT optical density (OD) of cardiac fibroblasts (P<0.05 vs control group), but the increase was greatly attenuated in the VNP (10(- 6)mol/L) group and also the incorporation of (3)H-TdR in cardiac fibroblasts (P<0.05 vs hypoxia group). VNP (10(- 6)mol/L) also decreased the intracellular level of Ca(2+) which was increased by hypoxia (P<0.05) as compared with control and hypoxia group. These findings demonstrate that VNP can attenuate the hypoxia-induced growth-promoting effect in cardiac fibroblasts, which may be associated with the elevation of intracellular Ca(2+).

[The vasodilation and its mechanism of C-type natriuretic peptide].

AIM AND METHODS: With routine blood vessel perfusion in vitro, the vasodilation and its mechanism of C-type natriuretic peptide, a new member of natriuretic peptide family were observed in rabbits. RESULTS: CNP had the dose-dependent vasodilation effects on abdominal artery and celiac vein at the range of 10(-10)-10(-6) mol/L, its action on vein was just like nitroglycerin, its action on artery was weaker than that of ANP. Atropine (10(-7) mol/L), Regitine (20 microg), and indomethacin (20 microg) had nothing effect on the vasodilation of CNP on abdominal artery. But glibenclamide (10(-6) mol/L) and propranolol (10(-6) mol/L) could decrease the vasodilation of CNP obviously, in addition, CNP couldn't inhibit the vasoconstriction of NE. CONCLUSION: (1) CNP might be kind of venous systemic vasodilator, and it was also a arterial selective peptide controlling the vessel tone. (2) CNP dilated the vessel at least through two ways: (a) ATP-sensitive K+ channel, (b) beta-receptor.

Specific cytolytic T-cell responses to human CEA from patients immunized with recombinant avipox-CEA vaccine.

Avipox viruses are replication-defective members of the poxvirus family. Avipox-derived vectors such as ALVAC (canarypox) and fowlpox have the ability to infect mammalian cells, including human cells, but do not replicate. The first clinical trial of an avipox recombinant vaccine for patients with advanced carcinomas has recently been conducted using the ALVAC vector and the human carcinoembryonic antigen (CEA) transgene (designated ALVAC-CEA; J. L. Marshall et al, J. Clin. Oncol., 17: 332-337, 1999). The T-cell responses elicited by patients before and after vaccination with the ALVAC-CEA recombinants are characterized in this report. Pre- and postvaccination peripheral blood mononuclear cells (PMBCs) of the eight patients positive for HLA-class I A2 allele, were incubated with the HLA-A2-CEA peptide CAP-1 and interleukin 2. In no cases using prevaccination PMBCs could cultures be established that had the ability to lyse C1R-A2 target cells pulsed with the CAP-1 peptide. However, T-cell cultures from seven of eight of these same patients, obtained from PBMCs after ALVAC-CEA vaccination, were shown to lyse C1R-A2 cells only when pulsed with CAP-1. Moreover, all seven of these T-cell cultures were shown to lyse allogeneic human carcinoma cell lines (SW1463 and SW480) that were both A2+ and expressed CEA; an allogeneic tumor cell line (LS174T) expressing CEA that was negative for A2 expression was not lysed. HLA-A2+ and CEA+ autologous tumor cells were also capable of being lysed by CEA-specific T cells from this patient. Analysis of this CTL line also revealed the expression of several homing and adhesion-associated molecules. Fluorescence-activated cell sorter analysis of the T-cell lines established from patients after ALVAC-CEA vaccination revealed that most were CD8+/CD4-, but many also had a CD8+/CD4+ component. Analyses of T-cell receptor Vbeta usage of several of the CEA-specific CTL lines showed a relatively diverse Vbeta pattern. These studies demonstrate for the first time the ability to vaccinate cancer patients with an avipox recombinant and derive T cells that are capable of lysing allogeneic and autologous tumor cells in a MHC-restricted manner. These studies thus form the rationale to use such replication-deficient recombinant vaccines in future cancer vaccine trials.

[The blocking effects of extracellular Mn2+ on the inward rectifier potassium channel (IRK1)].

AIM AND METHODS: Two-microelectrode voltage clamp (TEV) method was used to study the blocking effects of extracellular Mn2+ on the inward rectifier potassium channel (IRK1) expressed in the Xenopus oocytes. RESULTS: Mn2+ can concentration-, time- and vol-tage dependently block IRK1 instantaneous currents (2 ms after voltage applied). Mn2+ has almost no effect on the gating property of IRK1. IRK1 can not permeate Mn2+ because reverse potential did not changed. External Mn2+ can inhibit IRK1 macroscopic currents more powerfully when external Mn2+ concentration is lower and external Mn2+ can increases standard chord conductance of IRK1. CONCLUSION: External Mn2+ works through surface potential mechanism. Ba2+ is considered as one fast open channel blocker of IRK1 and three exponential fitting results indicates that external Mn2+ can compete with Ba2+ in the same binding site in IRK1 when external Ba2+ concentration is 30 mumol/L. These mean two different mechanisms about external Mn2+ blocking exist.

[Comparison of inhibitory effects of three natriuretic peptides on the proliferation of pulmonary artery smooth muscle cells of rats].

The inhibitory effects of atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) and vasonatrin peptide (VNP) on the proliferation of pulmonary artery smooth muscle cells (PASMCs) were compared in rats. Total protein and OD value of MTT were detected in cultured rat PASMCs to examine the influence of the three peptides on PASMC proliforation induced by phorbol 12-myristate 13-acetate (PMA). The results show that PMA (10( 9) 10( 7) mol/L) increased and VNP (10( 8) 10( 6) mol/L), ANP and CNP (10( 7) 10( 6) mol/L) decreased the total protein and OD value in a dose-dependent manner (P<0.05). The data above suggest that PMA stimulates the proliferation of PASMCs while the three peptides inhibit the proliferation induced by PMA. Of the three peptides VNP has the strongest inhibitory effect.

Phase I study in cancer patients of a replication-defective avipox recombinant vaccine that expresses human carcinoembryonic antigen.

PURPOSE: A phase I clinical trial in patients with advanced carcinoma was conducted, using a replication-defective avipox vaccine containing the gene for the human carcinoembryonic antigen (CEA). The canarypox vector, designated ALVAC, has the ability to infect human cells but cannot replicate. PATIENTS AND METHODS: The recombinant vaccine, designated ALVAC-CEA, was administered intramuscularly three times at 28-day intervals. Each cohort of six patients received three doses of either 2.5 x 10(5), 2.5 x 10(6), or 2.5 x 10(7) plaque-forming units of vaccine. RESULTS: The vaccine was well tolerated at all dose levels and no significant toxicity was attributed to the treatment. No objective antitumor response was observed during the trial in patients with measurable disease. Studies were conducted to assess whether ALVAC-CEA had the ability to induce cytolytic T-lymphocyte (CTL) responses in patients with advanced cancer. Peripheral blood mononuclear cells (PBMCs) from patients with the MHC class I A2 allele were obtained before vaccine administration and 1 month after the third vaccination. Peripheral blood mononuclear cells were incubated with the CEA immunodominant CTL epitope carcinoembryonic antigen peptide-1 and interleukin 2 and quantitated using CTL precursor frequency analysis. In seven of nine patients evaluated, statistically significant increases in CTL precursors specific for CEA were observed in PBMCs after vaccination, compared with before vaccination. CONCLUSION: These studies constitute the first phase I trial of an avipox recombinant in cancer patients. The recombinant vaccine ALVAC-CEA seems to be safe and has been demonstrated to elicit CEA-specific CTL responses. These studies thus form the basis for the further clinical exploration of the ALVAC-CEA recombinant vaccine in phase I/II studies in protocols designed to enhance the generation of human T-cell responses to CEA.

[Comparison of vasorelaxing actions of vasonatrin peptide, C-type natriuretic peptide and atrial natriuretic peptide].

The vasorelaxing effects of vasonatrin peptide (VNP), C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP) on isolated rat pulmonary artery, abdominal aorta and celiac vein were measured by in vitro perfusion. The results showed that VNP, CNP and ANP caused concentration-dependent relaxation in isolated rat pulmonary artery, abdominal aorta and celiac vein with endothelium or without endothelium. The maximal responses (Rmax) of VNP were (76 +/- 17)%, (51 +/- 14)% and (62 +/- 14)% in pulmonary artery, abdominal aorta and celiac vein with endothelium respectively, whereas those of CNP were (31 +/- 8)%, (22 +/- 7)% and (41 +/- 8)%, and ANP (38 +/- 10)%, (41 +/- 10)% and (11 +/- 4)%. The median effective concentration (EC50) of VNP were 16 +/- 11, 35 +/- 18 and 12 +/- 8 nmol/L in pulmonary artery, abdominal aorta and celiac vein with endothelium respectively, while those of CNP were 148 +/- 112, 299 +/- 84 and 14 +/- 12 nmol/L, and ANP 66 +/- 47, 16 +/- 15 and 909 +/- 445 nmol/L. VNP were more effective than CNP and ANP, and the differences were statistically significant (P < 0.05-0.01). The potency of these peptides for relaxing the blood vessels can be summarized as: VNP > ANP > or = CNP for pulmonary artery; VNP > ANP > CNP for abdominal aorta; VNP > CNP > ANP for celiac vein. There was no significant difference between vessels with intact endothelium and those denuded of endothelium (P > 0.05).