Role of a corrugated Dion-Jacobson 2D perovskite as an additive in 3D MAPbBr3 perovskite-based light emitting diodes.

Metal halide perovskites represent an intriguing class of materials, and a very promising approach to tune the properties of optoelectronic devices and improve their performance involves the implementation of architectures based on mixed 3D and 2D perovskites. In this work, we investigated the use of a corrugated 2D Dion-Jacobson perovskite as an additive to a classical 3D MAPbBr3 perovskite for applications in light-emitting diodes. Taking advantage of the properties of this emerging class of materials, we studied the effect of a 2D 2-(dimethylamino)ethylamine (DMEN)-based perovskite on the morphological, photophysical, and optoelectronic properties of 3D perovskite thin films. We used α-DMEN perovskite both in a mixture with MAPbBr3 creating mixed 2D/3D phases and as a passivating thin layer deposited on the top of a 3D perovskite polycrystalline film. We observed a beneficial modulation of the thin film surface, a blue shift in the emission spectrum, and enhanced device performance.

Amino-terminal fragment of pro-brain natriuretic hormone identifies functional impairment and right ventricular overload in operated tetralogy of Fallot patients.

To evaluate the relationship between plasma concentration of amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), functional capacity, and right ventricular overload in survivors of tetralogy of Fallot (TOF) repair, we prospectively studied 70 operated TOF patients (44 males, 21 +/- 1 years old; mean +/- SEM) who underwent, during the same day, echocardiography, cardiac magnetic resonance imaging, neurohormonal characterization (plasma NT-proBNP, catecholamines, plasma renin activity, and aldosterone assay), and cardiopulmonary exercise testing. Forty-eight age- and sex-matched healthy volunteers served as the control group. Compared to controls, maximal workload and peak oxygen consumption (VO2/kg) were lower in operated TOF patients (p < 0.001), whereas NT-proBNP concentration was elevated (p < 0.001). No difference was found among the other neurohormones. In operated TOF patients, NT-proBNP showed a significant positive correlation with right ventricular (RV) end systolic and end diastolic volumes and RV systolic pressure, and it showed a negative correlation with peak VO2/kg and RV ejection fraction. From multivariable analysis, NT-proBNP concentration was found to be an independent predictor of peak VO2/kg, RV end systolic volume, and RV systolic pressure. These results show an association among RV overload, decrease in functional capacity, and cardiac natriuretic peptide expression in operated TOF patients. NT-proBNP plasma assay may be a useful tool for diagnostic purposes and for decision making in this setting.

Vasoactive biomarkers and oxidative stress in healthy recently postmenopausal women treated with hormone replacement therapy.

BACKGROUND: Despite biologically plausible mechanisms for cardiac protection from estrogen therapy, recent clinical trials have suggested possible cardiovascular risk rather than benefit. However, it has been speculated that cardioprotective benefits from hormone replacement therapy (HRT) may be more evident in the early postmenopausal period. We have previously reported early beneficial effects on biochemical markers of endothelial function in healthy women after short-term estradiol replacement therapy. In this study we aimed to evaluate the effect of long-term HRT on different vasoactive factors and oxidative stress in healthy recently postmenopausal women. METHODS: Fifteen women (age 50 +/- 1 years, time since menopause 1.6 +/- 0.1 years) were randomized to a sequential oral and transdermal estradiol regimen (2 mg oral micronized 17beta-estradiol/day or 1.5 mg 17beta-estradiol gel/day). Oral dydrogesterone (10 mg/day, 12 days/month) was then cyclically combined with either of the estrogen therapies for 1 year. Blood samples were collected at baseline and after 1, 2, 6 and 12 months of therapy to evaluate levels of follicle stimulating hormone (FSH), estradiol, 6-keto PGF1alpha (prostacyclin metabolite), nitrite/nitrate, epinephrine, norepinephrine, 8-isoprostane (8-epi PGF2alpha) and lipid profile values. RESULTS: FSH levels decreased (p < 0.001) while estradiol levels increased (p < 0.001) during HRT. Levels of epinephrine (p < 0.001), norepinephrine (p < 0.01), mean blood pressure (p < 0.01) and low density lipoprotein (LDL) cholesterol (p < 0.01) decreased, and nitrite/nitrate levels increased (p < 0.01) during HRT, which did not significantly affect 8-epi PGF2alpha levels. CONCLUSIONS: One-year HRT significantly reduced the levels of catecholamines, mean blood pressure and LDL cholesterol while it increased levels of nitrite/nitrate, indicating cardiovascular benefit in healthy recent postmenopausal women. Levels of 8-epi PGF2alpha did not change, suggesting no evident relationship between HRT and oxidative stress.

Increase in circulating levels of cardiac natriuretic peptides after hormone replacement therapy in postmenopausal women.

The mechanisms that mediate the cardioprotective action of steroid hormones in postmenopausal women are poorly understood. To study the inter-relationship between female steroid hormones and cardiac natriuretic peptides, plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in postmenopausal women, both before and after oestrogen replacement therapy. A total of 22 healthy postmenopausal women (mean age 51.9+/-4.6 years) were enrolled in the study; all had been postmenopausal for at least 1 year and all reported climacteric symptoms accompanied by increased levels of follicle-stimulating hormone (>30 m-i.u./ml) and luteinizing hormone (>20 m-i.u./ml), and a reduction in oestradiol (<25 pg/ml). All women were given hormone replacement therapy with transdermal oestradiol, either patch (50 microg/24 h) or gel (1 mg/day), cyclically combined with oral dihydrogesterone (10 mg/day for 12 days/month, on days 19-30 of the month). ANP and BNP were measured directly in plasma samples with specific and sensitive immunoradiometric assays before and after hormone replacement therapy (transdermal oestradiol combined with oral dihydrogesterone). Body weight, arterial blood pressure and echocardiographic examination values did not change after hormone replacement therapy. As expected, serum oestradiol increased significantly and gonadotropins decreased as an effect of the hormone replacement therapy. On average, both ANP and BNP had increased significantly after 3 months of hormone replacement therapy [ANP: before treatment, 17.6+/-9.6 pg/ml; after, 23.6+/-5.6 pg/ml (P=0.0173); BNP: before treatment, 12.6+/-10.2 pg/ml; after, 19.8+/-14.0 pg/ml (P<0.0001)]. Our study indicates that hormone replacement therapy for a period of 3 months induces a rise in the circulating levels of cardiac natriuretic hormones in postmenopausal women. Our data also suggest the working hypothesis that cardiac natriuretic peptides may play an important role in mediating the cardioprotective effects of female steroid sex hormones in women throughout life.

Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability.

BACKGROUND: Studies have implicated a role for prostaglandin (PG) E(2)-dependent matrix metalloproteinase (MMP) biosynthesis in the rupture of atherosclerotic plaque. Cyclooxygenase-2 (COX-2) and PGE synthase (PGES) are coregulated in nucleated cells by inflammatory stimuli. The aim of this study was to characterize the expression of COX-2 and PGES in carotid plaques and to correlate it with the extent of inflammatory infiltration and MMP activity and with clinical features of patients' presentation. METHODS AND RESULTS: Plaques were obtained from 50 patients undergoing carotid endarterectomy and divided into 2 groups (symptomatic and asymptomatic) according to clinical evidence of recent transient ischemic attack or stroke. Plaques were analyzed for COX-2, PGES, MMP-2, and MMP-9 by immunocytochemistry and Western blot, whereas zymography was used to detect MMP activity. Immunocytochemistry was used to identify CD68+ macrophages, CD3+ T lymphocytes, and HLA-DR+ cells. The percentage of macrophage-rich areas was larger (P<0.0001) in symptomatic plaques. COX-2, PGES, and MMPs were detected in all specimens; enzyme concentration, however, was significantly higher in symptomatic plaques. COX-2, PGES, and MMPs were especially noted in shoulders of symptomatic plaques, colocalizing with HLA-DR+ macrophages. All symptomatic plaques contained activated forms of MMPs. Finally, inhibition of COX-2 by NS-398 was accompanied by decreased production of MMPs that was reversed by PGE(2). CONCLUSIONS: This study demonstrates the colocalization of COX-2 and PGES in symptomatic lesions and provides evidence that synthesis of COX-2 and PGES by activated macrophages is associated with acute ischemic syndromes, possibly through metalloproteinase-induced plaque rupture.

Transient autonomic nervous system dysfunction during hyperacute stroke.

Forty-four patients suffering a stroke for the first time were examined within 10 h of the onset of symptoms; the tests performed on their admission to hospital, and thereafter on the third and seventh day, were 24-h Holter EKG with spectral analysis of heart rate variability, evaluation of arterial blood pressure and the levels of catecholamine in the blood and 24-h urine. The dynamic EKG on admission revealed that 31 (70.5%) out of the 44 patients already had arrhythmia. These alterations were observed in 9 (75%) out of 12 haemorrhagic patients with a significant (P < 0.05) prevalence compared to 22 (68.8%) of the 32 ischaemic ones. Arrhythmia showed up in 16 (76.2%) out of 21 cases with right hemisphere lesions and in 12 (63.2%) out of 19 cases of left hemisphere lesions; this difference was also significant (P<0.05). Arrhythmia was still present in 19 (43.2%) patients after 3 days and only in 2 (6.5%) patients after 7 days. The spectral analysis parameters on admission and after 3 days were significantly (P < 0.05) modified in patients with stroke plus arrhythmia, compared to patients with stroke alone and to control subjects, whereas no further differences were observed on the seventh day. Moreover, the percentage of patients with arterial hypertension and high levels of catecholamine greatly decreased from the third day onwards. A transient autonomic nervous system imbalance with prevalent sympathetic activity may justify this cardiovascular impairment during the hyperacute phase of stroke.

Endogenous digitalislike factors in obstructive sleep apnea.

Recent studies have provided evidence that hypoxia may stimulate the release of endogenous digitalislike factors (EDLF). Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia during sleep and may be associated with sympathetic activation and a high risk of developing hypertension. This study was designed to measure EDLF in the plasma of patients with OSA diagnosed by polysomnography, with patients being classified by the number of apneic-hypopneic episodes/h sleep (apnea-hypopnea index, AHI). Plasma was obtained in the morning from 8 male normotensive OSA patients (OSA-N) (AHI 70+/-6), 2 untreated hypertensive OSA patients (OSA-HT), and 11 age-matched healthy male controls (C). EDLFs of different hydrophobicities were separated from the same plasma sample by solid-state C18-cartridges with 25% acetonitrile (ACN) (EDLF-1) followed by 40% ACN (EDLF-2). This procedure recovered ouabain in the first fraction and digoxin and digoxigenin in the second. EDLF was quantified in pM ouabain-equivalents by a human placenta radioreceptor assay. EDLF-1 levels were similar for OSA-N and C (231+/-55 vs. 258+/-58), whereas EDLF-2 levels were increased in OSA-N (244+/-51 vs. 110+/-25 in C, p=0.02). Norepinephrine was increased in apneics. The two OSA-HT had EDLF and norepinephrine levels similar to OSA-N. These preliminary results suggest that OSA is associated with an increase in the more hydrophobic EDLF levels in both normotensive and hypertensive states. No significant increase was found for the less hydrophobic ouabain-like EDLF.

Effects of aerobic training on lactate and catecholaminergic exercise responses in mitochondrial myopathies.

The aim of this study was to evaluate the effects of an aerobic training program on the metabolic and sympathetic responses to exercise in 12 patients with mitochondrial myopathies. A 10-week course of aerobic training, consisting of supervised exercise every other day on an electrically braked pedal-rate bicycle ergometer was prescribed to each patient and four healthy controls. Venous lactate, epinephrine (EP) and norepinephrine (NEP) levels were assessed at baseline and after the aerobic training by means of constant-workload exercise performed at near lactate threshold (LT). In patients, a decrease in exercise peak values, significant for lactate (-38.6%, P < 0.01) but not for catecholamines (EP: -26.0%, NEP: -22.1%) was observed after training, findings confirmed by the lactate/EP and lactate/NEP area ratios. The results show that lactate accumulation during exercise is decreased after aerobic training in mitochondrial myopathies and that the effect is partially dissociated from the catecholaminergic response. This in turn suggests that the lactate decrease can be explained, at least in part, by the improved muscle oxidative metabolism consequent to the proposed training program.

The relationship of plasma catecholamine and lactate during anaerobic threshold exercise in mitochondrial myopathies.

Sympathetic system activation is considered one of the main factors influencing lactate production during exercise in normal individuals. In order to assess the role of such activation in mitochondrial myopathies, we compared blood catecholamine levels to those of lactate during an intermittent exercise performed at workloads near anaerobic lactate threshold. Following an initial increment, the patients (n = 10) exhibited a steady-state blood lactate shifted right relative to controls (n = 7), the peaks being respectively 665 +/- 29% and 322 +/- 11% of baseline. Plasma catecholamine increase in mitochondrial myopathies was 272 +/- 21% for norepinephrine and 261 +/- 18% for epinephrine, not statistically different from controls. Lactate/norepinephrine and lactate/epinephrine area ratios were significantly higher in the subjects than in controls (2.36 versus 1.48 and 2.40 versus 1.57, respectively). The study shows that the abnormal lactate production in mitochondrial myopathies is independent of the catecholaminergic response at the transition from aerobic to anaerobic exercise.

Serum preoperative vascular endothelial growth factor (VEGF) in epithelial ovarian cancer: relationship with prognostic variables and clinical outcome.

Substantial experimental and clinical evidence links tumor growth, progression and metastatic potential with neoangiogenesis. This process is modulated by several angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Little data are currently available on serum VEGF levels in cancer patients. In the present retrospective investigation preoperative serum VEGF was higher in 53 patients with epithelial ovarian cancer than in 25 patients with benign ovarian disease as controls (median, range: 229.7, 23.5-1807.5 pg/ml versus 140.3, 14.7-1038.7 pg/ml, p = 0.034). With regard to FIGO stage, antigen values were significantly elevated in stage III-IV (p = 0.027) but not in stage I-II ovarian cancer patients when compared to controls. In patients with advanced disease preoperative serum VEGE was significantly related to the presence of ascites (p = 0.013), but not to common prognostic variables, response to chemotherapy and survival. In conclusion, preoperative serum VEGF assay reflects tumor progression and ascites generation in epithelial ovarian cancer, but it seems to have a limited predictive and prognostic value in patients with advanced disease.

Inhibition of gelatinase A (MMP-2) by batimastat and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma.

We have examined the effects of the synthetic matrix metalloproteinase inhibitor, batimastat (BB-94) and the angiotensin-converting enzyme inhibitor, captopril, on metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice. The effect of BB-94 and captopril on the survival of the 3LL-tumor-bearing mice was also examined. Here we report that captopril treatment resulted in decreased transcription and protein levels of gelatinase A by 3LL cells. Both BB-94 and captopril also prevented substrate degradation by gelatinase A and B released in conditioned medium by cultured cells. Treatment of tumor-bearing animals with BB-94 (i.p.) or captopril (in drinking water) resulted in significant inhibition of the mean tumor volume (25 and 33% respectively) and of the mean lung metastasis number (26 and 29% respectively). When both agents were given, they acted in synergy, resulting in 51 and 80% inhibition of tumor growth and metastasis. The survival time of the mice treated with both BB-94 and captopril was also significantly longer compared with the groups treated with each agent alone or with the vehicle. Our data support the hypothesis of an essential role of metalloproteinase(s) in the metastatic process. Moreover, blockade of invasion, angiogenesis and other processes mediated by metalloproteinases may underlie the anti-tumor and anti-metastatic effect of BB-94 and captopril and their combination. It is conceivable that this combination could be tested in selected clinical conditions as an adjuvant modality to cytotoxic therapy.

Serum macrophage colony-stimulating factor (M-CSF) levels in patients with epithelial ovarian cancer.

The preoperative macrophage colony-stimulating factor (M-CSF) levels were measured in serum samples from 56 patients with epithelial ovarian cancer and 68 patients with benign ovarian disease who had undergone laparotomy. M-CSF values were significantly higher in the former (median, range: 2.18, 0.70-10.00 ng/ml versus 1.19, 0.17-5.54 ng/ml, P < 0.0001), and were not significantly related to stage, histology, grade of differentiation, age, and residual disease after first surgery. M-CSF concentrations were also measured in 163 serum samples drawn from patients with stage III-IV epithelial ovarian cancer at different times since the first surgery. M-CSF values were higher in the 81 samples from patients with clinically evident disease than in the 82 samples from patients with no clinical evidence of disease (median, range: 2.13, 0.60-10.00 ng/ml versus 1.05, 0.40-10.00 ng/ml, P < 0.0001). M-CSF levels before second-look laparotomy were similar in the 18 patients who showed persistent disease at surgical reevaluation and in the 11 patients who achieved pathological complete response (median, range: 1.26, 0.70-3.27 ng/ml versus 0.94, 0.46-4.23 ng/ml, P = NS). M-CSF concentrations were raised (> or = 1.70 ng/ml) only in 1 (14.3%) of the 7 samples from patients with clinically evident disease and serum CA125 < 35 U/ml, and only in 5 (38.5%) of the 13 samples from patients with positive second-look findings and serum CA125 < 35 U/ml. In conclusion, serum M-CSF levels correlated with the clinical status of disease in patients with epithelial ovarian cancer. However, the concomitant determination of serum M-CSF seems to add little to the CA125 assay alone in the monitoring of patients with this malignancy.

The serum assay of soluble CD44 standard (sCD44-st), CD44 splice variant 5 (sCD44-v5), and CD44 splice variant 6 (sCD44-v6) in patients with cervical cancer.

The pretreatment serum levels of soluble CD44 standard (sCD44st), CD44 splice variant 5 (sCD44-v5), and CD44 splice variant 6 (sCD44-v6) were retrospectively measured in 37 patients with untreated cervical cancer and in 36 patients with benign gynecological diseases as controls. Median sCD44-st levels were significantly higher in patients with cervical cancer than in controls (547 ng/ml, range 244-880 ng/ml versus 400.5 ng/ml, range 217-723 ng/ml, p = 0.004), whereas sCD44-v5 and sCD44-v6 concentrations were significantly lower in the former (34 ng/ml, range 0-140 ng/ml versus 44 ng/ml, range 11-109 ng/ml, p = 0.038; and 37 ng/ml, range 1-191 ng/ml versus 52.5 ng/ml, range 11-173 ng/ml, p = 0.007, respectively). sCD44-st, sCD44-v5, and sCD44-v6 levels were not related to FIGO stage and histologic type. Moreover, among patients with stage Ib-IIa cervical cancer, the preoperative levels of these glycoproteins correlated with neither the common prognostic variables nor the clinical outcome. Therefore, the serum assay of sCD44-st, sCD44-v5, and sCD44-v6 seems to have no clinical relevance for the management of patients with cervical cancer.

cAMP involvement in the expression of MMP-2 and MT-MMP1 metalloproteinases in human endothelial cells.

Matrix metalloproteinases (MMPs) are a multigene family of enzymes secreted by a variety of cells, including human umbilical vein endothelial cells (HUVECs). Because metalloproteinases are potentially destructive agents, their production is tightly controlled at several levels. Rather little is known about the presence and regulation of MMPs in endothelial cells. In this study, we investigated the expression and regulation of MMP-2 and membrane type-matrix metalloproteinase (MT-MMP1), a membrane metalloproteinase strictly related to MMP-2 activation. Zymographic analysis of conditioned medium (CM) of HUVECs showed the presence of gelatinolytic activity mainly at 72 and 64 and 62 kD. The 64- and 62-kD bands, respectively, represent the intermediate and the completely active forms of MMP-2. When HUVECs were treated with forskolin (FK) (100 and 25 mumol/l), there was a decrease in the appearance of the 64 to 62 kDa doublet, suggesting an inhibition of the fully activated form of MMP-2. FK raises intracellular cAMP in HUVECs. The same data were obtained using dibutyryl-cAMP. Northern analysis revealed that the expression of MMP-2 increased slightly after treatment with FK, in contrast with gelatin zymography results. Taking into consideration the mechanism of activation of MMP-2, we tested the hypothesis that this compound could modulate MT-MMP1. As expected, FK was able to decrease MT-MMP1 expression. These data correlate with experiments using membranes of FK-treated HUVECs and incubated with control CM. Zymography revealed that when CM was incubated with membranes prepared from FK-treated HUVECs, there was a decrease in the appearance of the 64-kDa band, suggesting that the expression of MT-MMP1 was negatively modified. These results correlate with the MT-MMP1 protein level, negatively modified after FK treatment.

Plasma cholesterol regulates soluble cell adhesion molecule expression in familial hypercholesterolemia.

BACKGROUND: Hypercholesterolemia is associated with endothelial dysfunction. On the basis of the hypothesis that high plasma cholesterol per se may be a sufficient stimulus to upregulate endothelial adhesiveness and that this phenomenon might be reversible, soluble endothelial leukocyte adhesion molecules (sELAMs) were studied in patients with familial hypercholesterolemia undergoing LDL apheresis. METHODS AND RESULTS: Selective LDL absorption by dextran sulfate columns was used to treat plasma volumes of 6.5 to 9.2 L; after LDL apheresis, total cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a) levels were reduced by 74%, 82%, 79%, 56%, and 86%, respectively. Soluble intercellular adhesion molecule-1 (sICAM-1) and sELAM- were measured before, immediately after, and 2 and 6 days after LDL apheresis. Basal sICAM-1 and sELAM-1 values were higher than in healthy control subjects. After LDL apheresis, they decreased (P<.0001 and P<.0004, respectively); their removal by extracorporeal circulation components was excluded. Individual pretreatment and posttreatment values of sICAM-1 and sELAM-1 were positively correlated (P<.0001 and P<.001, respectively) with total cholesterol; their rebound curves showed patterns similar to the total cholesterol rebound curve but not to the triglyceride and lipoprotein(a) curves. CONCLUSIONS: In the absence of changes in clinical chemical parameters, tumor necrosis factor-alpha, interleukin-6, and acute-phase reactant proteins, these results confirm in a clinical setting the upregulation of endothelial adhesiveness observed in experimental hypercholesterolemia and suggest a direct role for cholesterol in regulating this phenomenon, at least in familial hypercholesterolemia.

Blood markers of early and late airway responses to allergen in asthmatic subjects. Relationship with functional findings.

We evaluated the relationship between blood markers of mast-cell (plasma histamine and serum level of heat-stable neutrophil chemotactic activity [NCA]) and eosinophil (serum eosinophil cationic protein [ECP]) activation during early airway response (EAR) and late airway response (LAR) to allergen inhalation in 24 asthmatic subjects. After EAR, 14 subjects showed significant LAR (FEV1 fall: > or = 25%), while 10 subjects showed equivocal LAR (FEV1 fall: 15-20%). A significant increase from baseline value was observed in plasma histamine and in serum NCA during both EAR and LAR, while serum ECP significantly increased only during LAR. The sensitivity of different markers to detect significant FEV1 fall during EAR and LAR was low, except for NCA. Changes in blood mediators were similar in both groups with significant and equivocal LAR. There was a significant relationship between the increase in NCA during EAR and the severity of LAR. Stepwise regression between changes in different blood markers showed a significant relationship between histamine increase during EAR and ECP increase during LAR. Thus, serum NCA is a more sensitive marker of EAR and LAR than plasma histamine and serum ECP, and its increase during EAR seems predictive of the severity of the subsequent LAR.

Serum assay of soluble CD44 standard (sCD44-st), CD44 splice variant v5 (sCD44-v5), and CD44 splice variant v6 (sCD44-v6) in patients with epithelial ovarian cancer.

Different variants of the cell adhesion molecule CD44 have been involved in malignant transformation and cancer metastasis. In the present investigation we assessed the preoperative serum levels of soluble CD44 standard (sCD44-st), sCD44 splice variant 5 (sCD44-v5), and sCD44 splice variant 6 (sCD44-v6) in 51 patients with ovarian cancer. Median preoperative sCD44-st, sCD44v5, and sCD44-v6 levels were 417 ng/ml (range, 240- > 602 ng/ml), 78 ng/ml (range, 5-314 ng/ml), and 86 ng/ml (range, 1-243 ng/ml), respectively. No significant relationship was detected between sCD44-st concentrations and the common clinicopathological variables. Conversely, sCD44-v5 and sCD44-v6 levels were significantly lower in FIGO stage III-IV than in stage I disease (p < 0.0001 and p = 0.001, respectively). Moreover, with regard to advanced ovarian cancer, sCD44-v5 levels were lower in patients with poorly differentiated (G3) than in those with moderately (G2) or well (G1) differentiated tumors (p = 0.038), as well as in patients whose residual disease was > 2 cm than in those with smaller residuum (p = 0.025). Similarly, sCD44-v6 levels were lower in patients with large residual disease (p = 0.05). The median value of serum sCD44-v6 was lower in patients with G3 than in those with G1-G2 tumor, but the difference was not significant. In conclusion, sCD44-st, sCD44-v5, and sCD44-v6 are detectable in sera from patients with epithelial ovarian cancer. A reduction in preoperative sCD44-v5 and sCD44-v6 levels seems to be associated with advanced, poorly differentiated tumors and with large residual disease after first surgery, and it might reflect an increased biological aggressiveness of the malignancy.

Preoperative serum antibodies against the p53 protein in patients with ovarian and endometrial cancer.

Antibodies against the p53 protein were measured with a sandwich-type enzyme-linked immunosorbent assay in blood samples preoperatively collected from 30 patients with ovarian cancer and 30 patients with endometrial cancer. Anti-p53 antibodies were detected in 33.3% of patients with ovarian cancer, comprising 22.2% of the 9 patients with stage I-II disease, 30.8% of the 13 patients with stage III disease, and 50.0% of the 8 patients with stage IV disease. Anti-p53 antibodies were found in none of the 4 patients with well differentiated tumors and in 38.5% of the 26 patients with moderately or poorly differentiated tumors. Among the 21 patients with stage III-IV disease, a complete clinical response to front-line platinum-based chemotherapy was obtained by 46.2% of the 13 patients without anti-p53 antibodies and 25.0% of the 8 patients with anti-p53 antibodies. Antibodies against the p53 protein were detected in only 6.7% of patients with endometrial cancer. The low incidence of anti-p53 antibodies in patients with endometrial cancer seems to suggest that the serum assay of these autoantibodies has a limited clinical relevance in the management of this malignancy. On the other hand in patients with ovarian cancer the incidence of serum anti-p53 antibodies is relatively high, and, moreover, it seems to increase with tumor stage and grade and seems to be associated with a lower response rate to chemotherapy. However, the small number of patients did not allow us to obtain statistically significant differences.

Serum levels of soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) in endometrial cancer.

The pretreatment serum levels of the soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) were retrospectively measured in 38 patients with endometrial cancer and 55 patients with benign uterine diseases as controls. Serum p55 and p75 sTNFr levels were significantly higher in patients with endometrial cancer (median = 2.4 ng/ml, range = 1.4-6.8 ng/ml, and median = 7.1 ng/ml, range = 2.5-19.5 ng/ml, respectively) than in controls (median = 1.7 ng/ml, range = 0.5-4.0 ng/ml, p < 0.0001, and median = 5.2 ng/ml, range = 2.6-21.9 ng/ml, p = 0.03, respectively). In the former, serum p55 and p75 sTNFr values correlated with the extent of disease (stage III-IV versus I-II: p = 0.04 and p = 0.03, respectively). Among the 23 patients with stage I endometrial cancer who underwent initial surgery, the preoperative serum levels of both receptors correlated with the histologic grade and myometrial invasion but not with the clinical outcome. In conclusion, a stage-dependent release of the soluble receptors for TNF into the bloodstream occurs in patients with endometrial cancer.