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Biomedical subjects

F Y Lin

Publications and source records attributed to F Y Lin.

At least 19 recordsLinked to original sources
PubMed2001

Level of maternal antibody required to protect neonates against early-onset disease caused by group B Streptococcus type Ia: a multicenter, seroepidemiology study.

Because of the difficulty of conducting efficacy trials of vaccines against group B streptococcus (GBS), the licensure of these vaccines may have to rely on studies that measure vaccine-induced antibody levels that correlate with protection. This study estimates the level of maternal antibody required to protect neonates against early-onset disease (EOD) caused by GBS type Ia. Levels of maternal serum IgG GBS Ia antibodies, measured by ELISAs in 45 case patients (neonates with EOD caused by GBS Ia) and in 319 control subjects (neonates colonized by GBS Ia but without EOD) born at > or =34 weeks gestation were compared. The probability of developing EOD declined with increasing maternal levels of IgG GBS Ia antibody (P = .03). Neonates whose mothers had levels of IgG GBS Ia antibody > or =5 microg/mL had an 88% lower risk (95% confidence interval, 7%-98%) of developing type-specific EOD, compared with those whose mothers had levels < 0.5 microg/mL. A vaccine that induces IgG GBS Ia antibody levels > or =5 microg/mL in mothers can be predicted to confer a high degree of type-specific immunity to EOD to their infants.

Age of Onset↗
PubMed2001

Microcalorimetric studies on the interaction mechanism between proteins and hydrophobic solid surfaces in hydrophobic interaction chromatography: effects of salts, hydrophobicity of the sorbent, and structure of the protein.

This study examines the effects of different salts as well as the influence of the relative hydrophobicities of different sorbents on the adsorption processes of proteins in hydrophobic interaction chromatography (HIC). Comparative data acquired by the equilibrium binding analysis and by isothermal titration microcalorimetry (ITC) are presented. In particular, thermodynamic parameters, including the enthalpy changes, related to the interactions between several globular proteins and various Toyopearl 650 M sorbents under solvent conditions containing either 2.0 M ammonium sulfate or 2.0 M sodium sulfate at pH 7.0 and 298.15 K have been evaluated in terms of the molecular properties of these systems. The results reveal that the dependence of the free energy change, deltaGads, for protein adsorption to HIC sorbents on the salt composition can be mainly attributed to the enthalpy changes associated with protein and sorbent dehydration and hydrophobic interactions. Differences in binding mechanisms between the n-butyl- and phenyl-HIC sorbents were evident. In the latter case, the participation of pi-pi hydrophobic interactions leads to significant differences in the associated enthalpy and entropy changes. Furthermore, an increase in the hydrophobicity of either the sorbent or the protein resulted in more negative values for the free energy change, which arose mostly from dehydration processes. Entropic effects favoring HIC adsorption increased with an increase in the exposed nonpolar surface area of the protein. Consequently, an increased contribution from the entropy change to the respective change in free energy occurs when HIC sorbents or proteins of higher hydrophobicity are employed, with these larger entropy changes consistent with a change in the interaction mechanism from a binding event dominated by adsorption to a partitioning-like process. Data extracted from the ITC measurements also provided insight into the interaction mechanisms that occur between proteins and hydrophobic solid surfaces, yielding information that can be applied to the HIC purification of proteins according to the concept of critical hydrophobicity of the system and its thermodynamic consequences.

Calorimetry↗
PubMed2001

Molecular recognition in imprinted polymers: thermodynamic investigation of analyte binding using microcalorimetry.

This study aimed at elucidating the interaction mechanism between an imprinted polymer and its template in aqueous environment with thermodynamic aspects. The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was chosen as a model template to imprint a co-polymer of 4-vinylpyridine (4-VP) and ethyleneglycol dimethacrylate. Equilibrium binding isotherm analysis and isothermal titration microcalorimetry were used to quantify the contribution of enthalpy and entropy to the binding process, identify the nature of the interactions involved and confirm the existence of binding pockets with shape-complementarity to the template. For the binding process of 2,4-D to the imprinted polymer, we postulate three subprocesses: (1) dehydration of the binding pocket and of the 2,4-D, (2) adsorption of 2,4-D, and (3) rearrangement of the water molecules from the dehydration process. We found that binding in aqueous environment was due to the cumulative effect of pi-stacking and electrostatic interactions between the template and the functional monomers. At pH<6, entropy is the dominating driving force, while at pH>6 where the highest difference in binding between the imprinted and a non-imprinted reference polymer was observed, the enthalpy change accounts for most of the binding free energy. The developed microcalorimetric method sheds light on the binding mechanism of analyte molecules with imprinted polymers, in particular if the polymers are used in aqueous solvents.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children.

BACKGROUND: Typhoid fever is common in developing countries. The licensed typhoid vaccines confer only about 70 percent immunity, do not protect young children, and are not used for routine vaccination. A newly devised conjugate of the capsular polysaccharide of Salmonella typhi, Vi, bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA), has enhanced immunogenicity in adults and in children 5 to 14 years old and has elicited a booster response in children 2 to 4 years old. METHODS: In a double-blind, randomized trial, we evaluated the safety, immunogenicity, and efficacy of the Vi-rEPA vaccine in children two to five years old in 16 communes in Dong Thap Province, Vietnam. Each of the 11,091 children received two injections six weeks apart of either Vi-rEPA or a saline placebo. Cases of typhoid, diagnosed by the isolation of S. typhi from blood cultures after 3 or more days of fever (a temperature of 37.5 degrees C or higher), were identified by active surveillance over a period of 27 months. We estimated efficacy by comparing the attack rate of typhoid in the vaccine group with that in the placebo group. RESULTS: S. typhi was isolated from 4 of the 5525 children who were fully vaccinated with Vi-rEPA and from 47 of the 5566 children who received both injections of placebo (efficacy, 91.5 percent; 95 percent confidence interval, 77.1 to 96.6; P<0.001). Among the 771 children who received only one injection, there was 1 case of typhoid in the vaccine group and 8 cases in the placebo group. Cases were distributed evenly among all age groups and throughout the study period. No serious adverse reactions were observed. In all 36 children studied four weeks after the second injection of the vaccine, levels of serum IgG Vi antibodies had increased by a factor of 10 or more. CONCLUSIONS: The Vi-rEPA conjugate typhoid vaccine is safe and immunogenic and has more than 90 percent efficacy in children two to five years old. The antibody responses and the efficacy suggest that this vaccine should be at least as protective in persons who are more than five years old.

ADP Ribose Transferases↗
PubMed2001

Microcalorimetric studies of the interaction mechanisms between proteins and Q-sepharose at pH near the isoelectric point (pI) effects of NaCl concentration, pH value, and temperature.

This study examined the interaction mechanisms of beta-lactoglobulins A and B (Lg A, Lg B) with an anion exchanger, Q-Sepharose at pH near the isoelectric point at which the proteins are expected to be electrically neutralized under various NaCl concentrations and temperatures by the equilibrium binding analysis and the adsorption enthalpy directly measured by isothermal titration calorimetry. The data evaluated from isotherms fitted by the Langmuirean model reveal that the addition of NaCl considerably reduced the binding affinities and capacities of both the proteins with Q-Sepharose at pH 5.2, indicating that electrostatic forces are dominant during the adsorption. However, the hydrophobic interaction seems to be involved in adsorption as well at a higher NaCl concentration, and the adsorption enthalpies confirm this suggestion. In addition, the effects of temperature on the equilibrium binding behaviors for Lg A or Lg B with Q-Sepharose were found to be salt concentration-dependent, probably due to their different binding mechanisms at 0.03 M and 0.3 M NaCl. Where, at 0.3 M NaCl, the hydrophobic interaction plays a more pronounced role. This implication was again supported by the adsorption enthalpies. The presented data provide further insight to the interaction mechanisms between proteins and ion exchangers, facilitating the optimization of protein separations.

Calorimetry↗
PubMed2001

Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer.

PURPOSE: The purpose of this study was to evaluate the correlation between the expression of four different vascular endothelial growth factor (VEGF) mRNA isoforms (VEGF121, VEGF165, VEGF 189, and VEGF206) and the clinicopathologic characteristics, tumor angiogenesis, and outcome of patients with non-small-cell lung cancer. PATIENTS AND METHODS: We examined the expression of four different VEGF mRNA isoforms in 57 non-small-cell lung cancers using reverse transcriptase polymerase chain reaction and the tumor angiogenesis using immunohistochemical staining. RESULTS: All 57 lung cancer samples expressed the VEGF121, VEGF165, and VEGF189 mRNA isoforms, and three expressed the VEGF206 mRNA isoform. A high tumoral VEGF189 mRNA isoform expression ratio was associated with a high intratumoral microvessel count (P = .013), short survival (< 24 months; P = .001), and early postoperative relapse (< 12 months; P = .001). Survival and postoperative relapse time were significantly shorter in patients with a high compared with a low tumor VEGF189 mRNA isoform expression ratio (P = .0001 and P = .0086, respectively, log-rank test). In contrast, the VEGF165 and VEGF 206 mRNA isoform expression ratios showed no statistical correlation with tumor angiogenesis, postoperative relapse time, or survival. A high VEGF121 mRNA isoform expression ratio was associated with short survival (< 24 months) and early relapse (< 12 months). Multivariate analysis showed that VEGF 189 mRNA isoform expression, microvessel count, and nodal status were the most important independent prognostic factors for patient survival and postoperation recurrence. CONCLUSION: The VEGF189 mRNA isoform expression ratio shows a greater correlation with tumor angiogenesis, postoperative relapse time, and survival than do the expression ratios for the VEGF121, VEGF165, and VEGF206 mRNA isoforms and can be used as a prognostic indicator for patients with non-small-cell lung cancers.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Value of chest sonography in the diagnosis and management of acute chest disease.

PURPOSE: The aim of this study was to investigate the value of chest sonography in the diagnosis and management of patients with chest radiograph opacities in an emergency department. METHODS: Seventy-eight patients with acute chest complaints whose chest radiographs showed opacities underwent chest sonography. The initial diagnosis (based on clinical manifestations and the chest radiograph), the sonographic diagnosis (before any invasive procedures), and the final diagnosis were compared. The impact of chest sonography on the management of patients with chest opacities was also analyzed. RESULTS: The initial diagnosis was in concordance with the final diagnosis in 60 (77%) of the 78 patients, while the sonographic diagnosis was in concordance with the final diagnosis in 75 (96%) of the patients. Chest sonography therefore significantly increased the rate of correct diagnoses from 77% (95% confidence interval, 67-87%) to 96% (95% confidence interval, 92-100%; p < 0.0001). Sonography provided new information in 52 patients (67%): a different diagnosis from the initial diagnosis in 18 patients and additional diagnostic information in 34 patients. New information gained from sonography affected the management of 35 patients. Sonography also provided help in guiding 42 (70%) of 60 invasive diagnostic procedures and 22 (73%) of 30 invasive therapeutic procedures for which chest radiography and physical examination had failed to or were unsuitable to provide guidance. Overall, sonography assisted in the management of 64 (82%) of 78 patients. Sonography was of no benefit in 14 patients (18%). CONCLUSIONS: We conclude that chest sonography can complement chest radiography and is of value in the diagnosis and management of emergency department patients with acute chest diseases presenting as opacities on chest radiographs.

Acute Disease↗
PubMed2001

Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF-alpha-treated human aortic endothelial cells.

Attachment to, and migration of leukocytes into the vessel wall is an early event in atherogenesis. Expression of cell adhesion molecules by the arterial endothelium may play a major role in atherosclerosis. It has been suggested that antioxidants inhibit the expression of adhesion molecules and may thus attenuate the processes leading to atherosclerosis. In the present study, the effects of a potent water-soluble antioxidant, salvianolic acid B (Sal B), and an aqueous ethanolic extract (SME), both derived from a Chinese herb, Salvia miltiorrhiza, on the expression of endothelial-leukocyte adhesion molecules by tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs) were investigated. When pretreated with SME (50 and 100 microg/ml), the TNF-alpha-induced expression of vascular adhesion molecule-1 (VCAM-1) was notably attenuated (77.2 +/- 3.2% and 80.0 +/- 2.2%, respectively); and with Sal B (1, 2.5, 5, 10, and 20 microg/ml), 84.5 +/- 1.9%, 78.8 +/- 1.2%, 58.9 +/- 0.4%, 58.7 +/- 0.9%, and 57.4 +/- 0.3%, respectively. Dose-dependent lowering of expression of intercellular cell adhesion molecule-1 (ICAM-1) was also seen with SME or Sal B. In contrast, the expression of endothelial cell selectin (E-selectin) was not affected. SME (50 microg/ml) or Sal B (5 microg/ml) significantly reduced the binding of the human monocytic cell line, U937, to TNF-alpha-stimulated HAECs (45.7 +/- 2.5% and 55.8 +/- 1.2%, respectively). SME or Sal B significantly inhibited TNF-alpha-induced activation of nuclear factor kappa B (NF-kappaB) in HAECs (0.36- and 0.48-fold, respectively). These results demonstrate that SME and Sal B have anti-inflammatory properties and may explain their anti-atherosclerotic properties. This new mechanism of action of Sal B and SME, in addition to their previously reported inhibition of LDL, may help explain their efficacy in the treatment of atherosclerosis.

Antioxidants↗
PubMed2001

New method of coronary artery occlusion for beating-heart coronary artery bypass surgery.

Temporary occlusion of the coronary artery is an essential step in beating-heart coronary artery bypass surgery. The traditional method of occlusion of the coronary artery, by looping and suspension with thread or elastic slings, carries some potential risk for damage to the vessels. We report another method for temporary coronary artery occlusion involving parallel placement of stitches with pledgets along the coronary artery distal and proximal to the target area. This offers a clean operative field by gentle occlusion of the target coronary artery.

Coronary Artery Bypass↗
PubMed2001

Preliminary result of an algorithm to select proper ventricular assist devices for high-risk patients with extracorporeal membrane oxygenation support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is not suitable for long-term support because of its high incidence of complications. Conversion from ECMO to ventricular assist device (VAD) is reasonable, and we have developed a simple algorithm for selecting proper VADs for these ECMO-supported patients. METHODS: We converted 12 patients who were receiving ECMO support to VAD for bridge to transplantation. Group I (n = 6) was converted directly from ECMO to VAD. Group II (n = 6) underwent stage conversion. We added left atrial drainage to ECMO because of lung edema or marked left heart distension. We discontinued drainage after recovery of right heart function. Group II had more unfavorable risk factors for VAD before ECMO. RESULTS: Three patients (50%) in Group I received biventricular VADs. The other 3 patients were converted to left ventricular assist device (LVAD), but only 1 (16.7%) experienced successful conversion. We successfully converted 5 patients (83.3%) in Group II to LVAD without right VAD, and 4 of them could be weaned from the ventilator. The multiple-organ dysfunction score gradually improved in Group II despite additional surgery. Two patients in each group received heart transplantation and survived long term. CONCLUSION: Using a conversion protocol provides a good guideline for making decisions. According to the protocol, right heart and pulmonary function can be clearly assured before shifting to LVAD in these critical ECMO-supported patients.

Algorithms↗
PubMed2001

Application of extracorporeal membrane oxygenation in adult burn patients.

Adult respiratory distress syndrome (ARDS) has been the major cause of mortality in burn injury. The authors reported the experience of using extracorporeal membrane oxygenation (ECMO) to treat adult burn patient with ARDS. Three patients with burn or electric injury, around 48.9% of body surface area over second-degree burns, developed ARDS after resuscitation. All had positive blood culture and depended on a ventilator more than 5 days before ECMO. Venovenous (VV) ECMO was started at the beginning of severe respiratory failure with an oxygen index of 61.6 +/- 15.5 cm H2O/mm Hg (> or =40 cm H2O/mm Hg), partial arterial oxygen tension to inspired oxygen fraction (Pa(O2)/Fi(O2)) of 46.1 +/- 7.0 mm Hg (< or =200 mm Hg), positive end expiratory pressure (PEEP) of 15.7 +/- 1.6 cm H2O (> or =10 cm H2O), alveolar-arterial difference in oxygen concentration (A-a D(O2)) of 618.9 +/- 19.3 mm Hg (> or =300 mm Hg), and lung compliance of 17.3 +/- 4.6 ml/cm H2O (< or =30 ml/cm H2O). The VV type had to be converted to the newly designed veno-venoarterial (V-VA) ECMO due to the myocardial dysfunction. Two of three patients survived. The duration of ECMO was 160.2 +/- 51.1 h. Two patients received debridement of escar during ECMO support and desmopressin infusion, and no increased bleeding or coagulopathy was found. The respiratory parameters were significantly improved after ECMO, especially in the survivors. ECMO is also suitable for ARDS in adult burn injury.

Adult↗
PubMed2001

New application of heparin-bonded extracorporeal membrane oxygenation in difficult neurosurgery.

We wished to evaluate the safety and the advantages of using heparin-bonded extracorporeal membrane oxygenation (ECMO) to replace conventional cardiopulmonary bypass (CPB) in deep hypothermic circulation for complex cerebral aneurysm surgery.Heparin-bonded ECMO without the bridging tube and the cardiotomy reservoir was set up through the femoral vessels. Limited heparin was infused. In deep hypothermia, the ECMO blood flow was temporarily decreased as low as the neurosurgeons' request. It was applied to 4 patients with difficult intracranial aneurysms who were selected for the procedure. Clipping, wrapping, or vascular bypass was implemented to manage the aneurysms under deep hypothermia. The total heparin dosage used in the whole procedure was 9,875 +/- 1,625 U, and the mean ECMO time was 270 +/- 105 min. The blood consumption was packed red blood cell 3.0 +/- 0.5 U and fresh frozen plasma 3.8 +/- 2.3 U. Compared with our previous experiences using conventional CPB, ECMO did need less heparin and blood transfusions. Clipping was applied in 2 patients, wrapping in 1, and venous graft interposition was performed in 1. Mortality occurred in 1 patient (25%) due to brain herniation. This preliminary study suggested that the heparin-bonded ECMO without reservoir in deep hypothermia could be safe in cerebral aneurysm surgery under a low flow circuit.

Adult↗
PubMed2001

The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease.

OBJECTIVE: Our purpose was to evaluate the effectiveness of a risk-based intrapartum antibiotic prophylaxis strategy for the prevention of early-onset neonatal group B streptococcal disease. STUDY DESIGN: Cases and controls were selected from infants born to women with one or more risk factors: preterm labor or rupture of membranes, prolonged rupture of membranes (>18 hours), fever during labor, or previous child with group B streptococcal disease. Cases were matched with controls by birth hospital and gestational age. Data abstracted from medical records were analyzed to estimate the effectiveness of intrapartum antibiotic prophylaxis. RESULTS: We analyzed data from 109 cases and 207 controls. Nineteen (17%) case versus 69 (33%) control mothers received an acceptable regimen of intrapartum antibiotic prophylaxis. In adjusted analyses, the effectiveness of intrapartum antibiotic prophylaxis was 86% (95% confidence interval, 66%-94%). When the first dose of antibiotics was given > or =2 hours before delivery, the effectiveness increased to 89% (95% confidence interval, 70%-96%); when it was given within 2 hours of delivery, the effectiveness was 71% (95% confidence interval, -8%-92%). Effectiveness was lowest in mothers with intrapartum fever (72%, 95% confidence interval, -9%-93%). On the basis of a 70% prevalence of maternal risk factors expected among cases in the absence of intrapartum antibiotic prophylaxis, we estimate that the risk-based strategy could reduce early-onset group B streptococcal disease by 60%. CONCLUSIONS: The risk-based approach to intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease. To achieve the maximum preventive effect, the first dose of antibiotics should be administered at least 2 hours before delivery.

Adult↗
PubMed2001

Recurrent cardiac myxoma with multiple distant metastasis and malignant change.

A 37 year-old female underwent open heart surgery for a left atrial myxoma. The post-operative course was uneventful and she was discharged two weeks later. She had regular monthly follow-up in the outpatient department until 10 months postoperatively when she was readmitted to the orthopedic ward for excision of a left ankle tumor. Two days after admission, she developed severe orthopnea. The initial diagnosis was heart failure, and she was transferred to the medical ward for treatment. Transthoracic and transesophageal echocardiography revealed a recurrent left atrial tumor. Because of acute obstruction of the mitral valve and deterioration of her condition, she underwent emergent open heart surgery. The recurrent atrial tumor was excised; histopathologic examination revealed a myxoid sarcoma. Multiple tumors were found on this admission, including a mass in the neck and in the left forearm; computed tomography revealed a brain tumor in the left posterior frontal lobe and a chest wall tumor. She died two months later. Recurrent cardiac myxoma with multiple distant metastasis may have a malignant potential. Because of the potential for tumor recurrence, long-term and regular follow-up is mandatory.

Adult↗
PubMed2001

[Bovine alpha-sl-casein gene sequences direct expression of a variant of human tissue plasminogen activator in the milk of transgenic mice].

The fusion gene containing the promoter of casein gene, LAtPA minigene and 3' flanking sequences of casein gene was introduced into the fertilized eggs of mice by microinjection. Five positive transgenic mice were obtained. The concentration of LAtPA in the milk of one female transgenic mouse is 0.18 microgram/ml. This result showed that the LAtPA minigene could correctly express the bioactive LAtPA in the milk of the transgenic mouse under the control of the regulatory elements of the casein gene.

Animals↗
PubMed2001

Conversion of extracorporeal membrane oxygenation to non-pulsatile left ventricular assist device. Is it out-of-date for non-pulsatile LVAD?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides an immediate support for acute deterioration of hemodynamic and pulmonary status, but what is the best decision for these critical patients? Biventricular assist device (BVAD) or left ventricular assist device (LVAD)? We proposed a protocol of step-by-step conversion from ECMO to LVAD after assurance of the reversibility of right ventricle and pulmonary function. METHODS: After femoral venoarterial ECMO was inserted for the critical patients, the left atrial drainage was added to the ECMO firstly and the femoral arterial inflow was shifted to the ascending aorta for preventing possible peripheral vascular complications. Temporary clamp of right heart drainage was tried to test right heart function 24 to 48 hours later. The sweep gas flow of oxygenator could be reduced gradually to test the pulmonary function. Therefore, the right heart drain and the oxygenator could be withdrawn to become a non-pulsatile LVAD or shift to pneumatic LVAD directly. There were four clinical experiences with successful conversion without temporary right ventricular assist device. RESULTS: All of them were able to convert their ECMO to LVAD smoothly in 8.0+/-2.5 days. Three of them were shifted to non-pulsatile LVAD, and one was converted to HeartMate. All but one could be weaned from the ventilator. No BVAD was needed in these patients. Due to the shortage of donor hearts, only one had the chance to undergo heart transplantation. CONCLUSIONS: The protocol did provide a good guideline for decision-making for those under ECMO support necessitating bridge to transplantation.

Cardiotonic Agents↗
PubMed2000

Correlation of total VEGF mRNA and protein expression with histologic type, tumor angiogenesis, patient survival and timing of relapse in non-small-cell lung cancer.

We have quantified the expression of all 4 isoforms of vascular endothelial growth factor (VEGF) mRNA in non-small-cell lung cancer (NSCLC) using a new kinetic quantitative PCR method, real-time quantitative (RTQ) RT-PCR, and investigated the association between VEGF expression at the mRNA and protein levels and the clinicopathologic variables, tumor angiogenesis, patient survival and timing of relapse. Surgical tumor specimens from 72 NCSLC patients (37 squamous-cell carcinomas, 35 adenocarcinomas) were examined. Twenty-eight patients had stage I, 10 stage II and 34 stage IIIA or IIIB disease. Total VEGF mRNA (all 4 isoforms) was quantified by RTQ RT-PCR, while VEGF protein expression and microvessel number in tumors were assessed immunohistochemically. VEGF mRNA was detected in all 72 tumor samples at significantly higher levels than in adjacent normal tissue. Tumoral VEGF mRNA levels correlated strongly with the VEGF protein staining score and microvessel count. Adenocarcinomas showed significantly higher VEGF mRNA expression and a higher protein staining score than squamous-cell carcinomas. High tumoral VEGF mRNA expression was associated with advanced (IIIA or IIIB) tumor stage, lymph node metastasis, high tumoral microvessel counts, short patient survival (<24 months) and early relapse (<12 months), while a high VEGF protein staining score was associated with high tumoral microvessel counts, short patient survival and early relapse. Patients with high tumoral levels of both VEGF mRNA and protein had significantly shorter survival and earlier relapse. In multivariate analysis, the VEGF protein staining score and nodal status were the most important independent predictors of survival and recurrence. We conclude that RTQ RT-PCR is a sensitive method for detecting and quantifying VEGF mRNA expression in NSCLC and that the expression levels of total VEGF mRNA and protein in NSCLC are strongly associated with histologic type, tumor angiogenesis, survival and timing of relapse. High VEGF expression in adenocarcinomas may contribute to their greater metastatic potential.

Analysis of Variance↗