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Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 37 records · Page 2Linked to original sources

DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study.

PURPOSE: The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis. METHODS: TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. RESULTS: The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P<0.05) and DNA aneuploid tumors (P<0.05) tumors. DNA-aneuploidy was associated with distal tumors (P<0.01), histological grade (G3) (P<0.05), advanced Dukes' stage (C and D) (P<0.01), lymph node metastases (P<0.01) and high SPF (>18.3%) (P<0.01). The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA-aneuploidy, and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death. CONCLUSIONS: Our results indicate that DNA aneuploidy and high SPF are associated in CRC with a poor clinical 5-year outcome, while in contrast the prognostic role of TP53 and NM23-H1 expression is still to be clarified.

Adenocarcinoma↗

Ras family genes: an interesting link between cell cycle and cancer.

Ras genes are evolutionary conserved and codify for a monomeric G protein binding GTP (active form) or GDP (inactive form). The ras genes are ubiquitously expressed although mRNA analysis suggests different level expression in tissue. Mutations in each ras gene frequently were found in different tumors, suggesting their involvement in the development of specific neoplasia. These mutations lead to a constitutive active and potentially oncogenic protein that could cause a deregulation of cell cycle. Ras protein moderates cellular responses at several mitogens and/or differentiation factors and at external stimuli. These stimuli activate a series of signal transduction pathways that either can be independent or interconnected at different points. Recent observations begin to clarify the complex relationship between Ras activation, apoptosis, and cellular proliferation. A greater understanding of these processes would help to identify the factors directly responsible for cell cycle deregulation in several tumors, moreover it would help the design of specific therapeutic strategies, for the control on the proliferation of neoplastic cells. We summarize here current knowledge of ras genes family: structural and functional characteristics of Ras proteins and their links with cell cycle and cancer.

Animals↗

Umbilical cord blood collection in Cesarean section: a comparison before and after placental delivery.

Fetal stem cells transplants depend on nucleated cells from fetal blood. This study was a prospective randomized trials to compare the collection of fetal blood by gravity into a bag containing anticoagulant, before and after delivery of the placenta. The obstetric and the newborn characteristics in the two group were not significantly different. The mean volume of fetal blood collected while the placental was still in utero was 74.93+/-7.1 ml as against 35.78+/-3.6 ml for collection of fetal blood after delivery of the placenta.

Cesarean Section↗

Comparison of dexa and ultrasonometry in the measurement of bone density.

The aim of our study was to evaluate the diagnostic agreement between quantitative sonography of the calcaneum (QUS) and dual energy X-ray absorptiometry (DEXA) of the spine and femur. 153 women enrolled in our study and were divided in three groups. Group A was composed of women aged between 45 and 55, Group B of women of 56-66 and Group C of women 67-77. Mean height cm 164+/-2.8; mean weight kg 68+/-3.2. The most concordant results were obtained in group B. This suggests that QUS screening for osteoporosis may be suitable for the "younger" perimenopausal patient.

Absorptiometry, Photon↗

DNA damage in human fibroblasts exposed to fumonisin B(1).

Fumonisins are mycotoxins produced by several Fusarium species (Fusarium verticilloides and F. proliferatum) that infest corn and other cereals. Fumonisin B(1) (FB(1)), structurally resembling sphingoid bases, is an inhibitor of ceramide synthetase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover. This inhibitory effect leads to accumulation of free sphinganine and sphingosine and subsequent induction of cell death. However, the downstream effectors activated by these sphingolipids in the cell death-signalling pathway are little known. The aim of this study was to evaluate, in FB(1)-exposed human fibroblasts, the involvement of oxygen free radicals and of some other biochemical pathways, caspase-3 activity, poly(ADP-ribose)polymerase (PARP) cleavage and DNA damage evaluated by comet assay. Our results indicate that FB(1) treatment (48, 72 h and 10, 50, 100 microM) does not affect cellular viability. Conversely, after 72 h of treatment, FB(1) (50 and 100 microM) induced DNA damage, an enhancement of caspase-3-activity and cleavage of PARP compared to controls. In addition, FB(1) increased the expression of HSP70 in a concentration and time-dependent manner. Our results indicate that DNA damage of apoptotic type in human fibroblasts is caused by exposure to FB(1) at high concentrations and for a prolonged time and that the genotoxic potential of FB(1) has probably been underestimated and should be reconsidered.

Apoptosis↗

Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin.

Propolis, a natural product produced by the honeybee, has been used for thousands of years in folk medicine for several purposes. The extract contains amino acids, phenolic acids, phenolic acid esters, flavonoids, cinnamic acid, terpenes and caffeic acid. It possesses several biological activities such as antiinflammatory, immunostimulatory, antiviral and antibacterial. The exact mode of physiological or biochemical mechanisms responsible for the medical effects, however, is yet to be determined. In this work, we have investigated the antioxidant activity of a propolis extract deprived of caffeic acid phenethyl ester (CAPE). In addition, the activity of CAPE and galangin was also examined. Propolis extract (with and without CAPE) and its active components showed a dose-dependent free radical scavenging effect, a significant inhibition of xanthine oxidase activity, and an antilipoperoxidative capacity. Propolis extract with CAPE was more active than propolis extract without CAPE. CAPE, used alone, exhibited a strong antioxidant activity, higher than galangin. The experimental evidence, therefore, suggests that CAPE plays an important role in the antioxidant activity of propolis.

Antioxidants↗

Effect of a propolis extract and caffeic acid phenethyl ester on formation of aberrant crypt foci and tumors in the rat colon.

We have studied the effect of propolis and its main active ingredient caffeic acid phenetyl ester (CAPE) on formation of aberrant crypt foci (ACF) and tumors in the rat colon in vivo. CAPE (50 mg/kg i.p.) reduced the formation of ACF and tumor induced by azoxymethane, while propolis ethanolic extract was without effect. These results suggest a potential anti-carcinogenesis of CAPE but not propolis.

Animals↗

Phytochemical compounds involved in the anti-inflammatory effect of propolis extract.

Two ethanolic propolis extracts (EPE) with and without the caffeic acid phenethyl ester (CAPE), CAPE and galangin (major components of propolis) were investigated for anti-inflammatory activity in rats using carrageenin foot oedema, carrageenin pleurisy and adjuvant arthritis. In our experiments, EPE with CAPE and CAPE alone significantly inhibited carrageenin oedema, carrageenin pleurisy and adjuvant arthritis. In contrast EPE without CAPE and galangin did not exhibit anti-inflammatory effects in acute and chronic inflammation. These results suggest that the anti-inflammatory activity of propolis is due to CAPE.

Acute Disease↗

DNA damage in astrocytes exposed to fumonisin B1.

Fumonisins are a group of toxic metabolites mainly produced by Fusarium moniliforme and Fusarium proliferatum, fungi that commonly occur on corn throughout the world. Fumonisin B1 (FB1), structurally resembling sphingoid bases, is an inhibitor of ceramide synthase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover. This inhibitory effect leads to accumulation of free sphinganine (SA) and sphingosine (SO), inducing cell death. However, little is known on the down stream effectors activated by these sphingolipids in the cell death signaling pathway. We exposed rat astrocytes to FB1 with the aim of evaluating the involvement of oxygen free radicals and of some other biochemical pathways such as caspase-3 activity and DNA damage. Our results indicate that FB1 treatment (48, 72 h and 6 days in vitro, DIV, and 10, 50, 100 microM) does not affect cell viability. Conversely, after 72 h of treatment, FB1 (50 and 100 microM) induced DNA damage and an enhancement of caspase-3 activity compared to controls. In addition, FB1 increased the expression of HSP70 at 10 and 50 microM at 48, 72 h, and 6 DIV of treatment. We conclude that DNA damage of apoptotic type in rat astrocytes is caused by FB1 and that the genotoxic potential of FB1 has probably been underestimated and should be reconsidered.

Animals↗

The inhibitory effect of propolis and caffeic acid phenethyl ester on cyclooxygenase activity in J774 macrophages.

The effect of an ethanolic extract of propolis, with and without CAPE, and some of its components on cyclooxygenase (COX-1 and COX-2) activity in J774 macrophages has been investigated. COX-1 and COX-2 activity, measaured as prostaglandin E2 (PGE2) production, were concentration-dependently inhibited by propolis (3 x 10(-3) - 3 x 10(2) microgml(-1)) with an IC50 of 2.7 microgml(-1) and 4.8 x 10(-2) microgml(-1), respectively. Among the compounds tested pinocembrin and caffeic, ferulic, cinnamic and chlorogenic acids did not affect the activity of COX isoforms. Conversely, CAPE (2.8 x 10(-4) - 28 microgml(-1); 10(-9) - 10(-4) M) and galangin (2.7 x 10(-4) - 27 microgml(-1); 10(-9) - 10(-4) M) were effective, the last being about ten-twenty times less potent. In fact the IC50 of CAPE for COX-1 and COX-2 were 4.4 x 10(-1) microgml(-1) (1.5 x 10(-6) M) and 2 x 10(-3) microgml(-1) (6.3 x 10(-9) M), respectively. The IC50 of galangin were 3.7 microgml(-1) (15 x 10(-6) M) and 3 x 10(-2) microgml(-1) (120 x 10(-9) M), for COX-1 and COX-2 respectively. To better investigate the role of CAPE, we tested the action of the ethanolic extract of propolis deprived of CAPE, which resulted about ten times less potent than the extract with CAPE in the inhibition of both COX-1 and COX-2, with an IC50 of 30 microgml(-1) and 5.3 x 10(-1) microgml(-1), respectively. Moreover the comparison of the inhibition curves showed a significant difference (p < 0.001). These results suggest that both CAPE and galangin contribute to the overall activity of propolis, CAPE being more effective.

Animals↗

Two CD34+ stem cells from umbilical cord blood enrichment methods.

The authors describe the relation between clamping time and blood volume collected, and two enrichment systems of CD34+ stem cells from umbilical cord blood, to determine an excellent recovery with high proliferate ability and bone marrow reconstitution. After an obstetrician-based cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies (negative selections) using the Stem Sep method, or with a positive cells selection thanks to their surface CD34 antigens, using the Mini Macs system. An excellent recovery of hematopoietic progenitors, burst-forming unit erythroid, colony-forming unit granulocyte and macrophage, and colony-forming unit granulocyte, erythroid, monocyte, and macrophage, inversely related to the rising of clamping time, was performed with the Mini Macs system (54% of colonies, with a 90% purity), while with Stem Sep method, hematopoietic progenitor recovery was 35% (with an 80% purity). By applying early clamping of the umbilical cord blood a greater number of CD34+ cells was obtained and their clonogenic activity increased with enrichment. This is particularly useful, considering that the number of CD34+ stem cells contained in a unit of placental blood is enough for transplanting to a child, but not for an adult engraftment. Thus, using this method, a larger number of CD34+ stem cells can be obtained, which increases the possibility to reduce graft versus host disease also in adult patients, producing survival rates similar to the ones obtained with transplantation of bone marrow from unrelated donors.

Antibodies, Monoclonal↗

Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype.

BACKGROUND: K-ras mutations, one of the earliest events observed in colorectal carcinogenesis, are mostly found in codons 12 and 13, and less frequently in codon 61, all three of which are estimated to be critical for the biological activity of the protein. Nevertheless the prognostic significance of such mutations remains controversial. Our purpose was to assess whether any or specific K-ras mutations in primary colorectal cancer had prognostic significance and were linked to clinico-pathological parameters. PATIENTS AND METHODS: Paired tumor and normal tissue samples from a consecutive series of 160 untreated patients (median of follow up 71 months), undergoing resective surgery for primary colorectal carcinoma, were prospectively studied for K-ras mutations by PCR/single strand conformation polymorphism sequencing. RESULTS: Seventy-four of the 160 (46%) primary colorectal carcinomas presented mutations in K-ras: 54% in codon 12, 42% in codon 13 (particularly G-->A transition) and 4% in both. Codon 12 K-ras mutations were associated with mucinous histotype (P <0.01), while codon 13 K-ras mutations were associated with advanced Dukes' stage (P <0.05), lymph-node metastasis (P <0.05) and high S-phase fraction (P <0.05). Multivariate analysis showed that codon 13 K-ras mutations, but not any mutation, were independently related to risk of relapse or death. CONCLUSIONS: Our results suggest that codon 12 K-ras mutations may have a role in the mucinous differentiation pathway, while codon 13 mutations have biological relevance in terms of colorectal cancer clinical outcome.

Adenocarcinoma↗

The vascularity of internal fistulae in Crohn's disease: an in vivo power Doppler ultrasonography assessment.

AIM: To evaluate the efficacy of power Doppler sonography (US) in depicting internal fistulae and their vascularity, and to study the characteristics of blood flow within the fistula wall. PATIENTS AND METHODS: The study involved 45 consecutive patients with Crohn's disease and suspected internal fistulae detected by grey scale US. The fistulae were subsequently evaluated using power Doppler US to reveal any areas of increased vascularity, and the results were compared with radiographic, endoscopic, or intraoperative findings. Whenever feasible, we also performed spectral analysis of blood flow revealed by power Doppler US, calculated its resistance index (RI), and analysed its characteristics, reproducibility, and relationship with biochemical and clinical variables (Crohn's disease activity index, disease duration, location, and abdominal complications). RESULTS: Power Doppler US revealed vascularity in all of the internal fistulae that where subsequently confirmed by diagnostic procedures. In the case of intra-abdominal abscesses in the vicinity of the fistula, vascular signals were detected mostly around and not within the lesions. The intensity and distribution of the signals differed within the fistulae tracks and had only slight day to day reproducibility; furthermore, there was no significant correlation with clinical or biochemical variables. Spectral analyses of blood flow within the fistulae revealed arterial flow in 96.7% of patients (median RI 0.715). RI was a more reproducible parameter and significantly correlated with clinical (r= 0.54) and biochemical activity (r= 0.56) of CD. It was also higher in fistulae complicated by abscesses. CONCLUSION: Power Doppler US can reveal the presence of vasculature within the wall of internal fistulae and therefore enhance grey scale US performance. The RI characteristics of blood flow within the fistulae are reproducible and correlate with biochemical and clinical disease activity.

Adult↗

Estimate of population coverage with the prostate specific antigen (PSA) test to screen for prostate cancer in a metropolitan area of northern Italy.

The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was examined. Data were drawn from the outpatient database of the local health information system. A total of 139 350 PSA tests were used in 83 943 subjects. Overall, 26.9% of the male population aged 40 or older, with no history of prostate cancer, received a PSA test in the 2 year study period. For subjects older than 50 the rate rose to 34%. Results show a high coverage of the male population in northern Italy with screening using the PSA test for prostate cancer.

Adult↗

VLA-2 and VLA-5 cell adhesion molecules expression in CD34+ cells from umbilical cord blood and from bone marrow.

BACKGROUND/AIMS: Umbilical cord blood contains a large number of early hematopoietic cells with high proliferating capacity, that has been used as an alternative to bone marrow transplantation. The aim of this study is to investigate the number of two cell adhesion molecules in cord blood and in bone marrow. METHODS: We investigated two integrins, named VLA-2 and VLA-5 (Very Late Appearing Antigen), expressed in the surface of CD34+ cells. The CD34+ cells, isolated with MACS CD34+ isolation kit, were labelled with the appropriate monoclonal antibodies. RESULTS: Cell adhesion molecules showed highly expressed in both cord blood and bone marrow CD34+ cells. CONCLUSION: There are no significant differences between the two sources of CD34+ populations.

Antigens, CD34↗

Differences in umbilical cord blood units collected during cesarean section, before or after the delivery of the placenta.

Umbilical cord blood is largely employed as an alternative source of stem cells in the treatment of hemato-oncological diseases. Current results show that the success rate of purified umbilical cord blood engraftment is comparable to that obtained using bone marrow, and it is directly related to the number of pluripotent stem cells transplanted. The technique of fetal blood collection varies among different umbilical cord blood banks. Many authors collect umbilical cord blood during vaginal delivery, after placental detachment, while others collect it while the placenta is still within the uterus. In a previous randomized trial, we showed a greater collection of umbilical cord blood before placental detachment during vaginal delivery. The present study was performed to determine whether umbilical cord blood collection before placental detachment (group A) during cesarean section is superior to that after placental delivery (group B) puncturing the umbilical vein once and using a closed bag system. To accomplish this, 47 pregnant women subjected to cesarean section were enrolled in the study. Twenty-one of them were allocated to group A, while the remaining 26 formed group B. The volume of umbilical cord blood collected from the patients of group A was greater than that collected from patients of group B. The cord blood volume collected was 90.7 +/- 6.0 versus 60.9 +/- 13.7 ml; the cord blood nucleated cell number was 10.1 +/- 1.2 x 10(8) vs. 7.1 +/- 0.8 x 10(8); and the mean cord blood CD34+ cell number was 20.0 +/- 6.0 x 10(5) vs. 16.4 +/- 2.4 x 10(5), respectively.

Adult↗