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Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 19 recordsLinked to original sources
PubMed2026

Liquid biopsy: a new window on the BRCA genes.

The Breast Cancer Susceptibility Gene (BRCA)-associated tumors represent a constantly evolving and intriguing scenario in oncology, in which the availability of novel systemic treatment, mainly including the poly (ADP-ribose) polymerase (PARP) inhibitors, has enabled an improved survival benefit in clinical subgroups. The expanding regulatory approvals of PARP inhibitors have inevitably reshaped the clinical indications for BRCA testing, moving the BRCA1/2 profiling from the traditional and preventive workflows to therapeutic paths. Despite advances in technology and treatment, substantial limitations remain in current genetic and genomic tools for the detection of deleterious BRCA1/2 variants. Germline and tumor tissue testing provide only a snapshot of a patient's disease, failing to capture the dynamic and longitudinal aspects of tumor clonal evolution. In this scenario, liquid biopsy (LB) profiling of BRCA1/2 genes, primarily as circulating tumor DNA, represents a highly active area of research potentially affecting many aspects of cancer screening, diagnosis, and monitoring in individuals who are carriers of BRCA1/2 deleterious variants. Beyond the attractive potential to surrogate the tumor tissue testing, to overcome the cancer spatial and temporal heterogeneity, and to monitor the tumor mutational profile over time, accurately detecting all clinically relevant BRCA genetic variants and epigenetic modifications using LB remains technically challenging.

BRCA1/2↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

Influence of the kind of delivery on umbilical cord blood collection.

From December 1999 to February 2001, the Microbiological and Gynaecological Science Department of the University of Catania has been involved in the collection of umbilical cord blood samples. Eight hundred and sixty-three cord blood units were collected and sent to Sciacca's UCB bank. Among them, 429 were collected from newborns delivered vaginally, while the remaining were collected from Caesarean sections. The aim of this study was to evaluate the difference between umbilical cord blood samples collected during a vaginal delivery and those from a Caesarean section. In particular, the blood volume collected and cord blood CD34+ stem cell count were considered. The method of blood collection consisted of puncturing the umbilical cord vein with an 18-gauge needle and withdrawing the blood into a sterile bag immediately after clamping and newborn assistance. The blood was collected when the placenta was still in utero and the indication to the kind of delivery was, independently of the study, according to obstetrical good practice. The results of the analysis showed that the cord blood volume and the number of CD34+ cells collected were similar for the two groups. The higher median volume of blood collected from infants delivered by Caesarean section seems mainly due to the different clamping time, rather than to the kind of delivery.

Blood Specimen Collection↗
PubMed2002

[The evolution of viscerosynthesis and its methodological implications: from manual sutures to biocompatible materials].

This study aims to provide an overview of the different suturing techniques used in surgery, paying special attention to cancer surgery which, compared to general surgery, has precise requirements correlated to the type of patient and form of exeresis used, which often tends to be extensive. In this panorama which manages to avoid any form of superficiality, the discussion ranges from mechanical automatic suturing devices to recent advances in so-called biological repair, without omitting an analysis of the gold standard of tissue repair, namely suture thread, which appears to have been overwhelmed by the enthusiasm for technological innovation, even in the literature.

Biocompatible Materials↗
PubMed2002

[Malignant carcinoid of the last ileal ansa. Report on 2 consecutive clinical cases].

Carcinoid tumors are very rare neoplasms, arising from enterochromaffin cells, classified in Apud system, exhibiting an intermediate malignancy, because of their long lasting clinical silence and low evolution to advanced stage. At the same time, these features unfortunately cause a high incidence of lymphatic and liver metastases, visible at first diagnostic approach, which are also determined by aspecific symptoms and signs, especially involving jejunal and ileal carcinoids, as the two cases described, and by very frequent absence, in current clinical practice, of pathognomonic carcinoid syndrome. Two carcinoids located into the distal ileal ansa, strictly adjacent to the ileocecal valve, are reported; the first tumor, accompanied by lymphonodal positivity, the second by a solitary hepatic metastasis, requiring segmentectomy of the liver, in addition to right hemicolectomy.

Aged↗
PubMed2002

Influence of sport and low animal saturated fats intake diet on lipid dismetabolisms in postmenopausal women.

BACKGROUND: An important aetiopathogenetic factor leading to menopausal age pathologies (such as hypertension, diabetes, cardiovascular diseases and so on) is certainly represented by the worsening of lipid dismetabolism. This condition is generally characterized by an increase in total mean cholesterol levels, LDL-cholesterol (low density lipoprotein-cholesterol), VLDL-cholesterol (very low density lipoprotein-cholesterol), triglycerides, with reduction of HDL-cholesterol (high density lipoprotein-cholesterol) mean levels. All these metabolic modifications are triggered or increased by the hypoestrogenemia typical of postmenopausal age. The aim of our study was to evaluate the influence on postmenopausal women's lipid metabolism of a low contribution of animal saturated fat diets, associated with physical training. METHODS: We enrolled in our study 36 mild hypercholesterolemic postmenopausal women (non smokers and not complaining of hypertension and diabetes) and we put them through aerobic training, consisting of 1 hour of a light continuous run, repeated 4 times per week. The final control of their metabolic status and of their lipid order was executed after 6 months, but during this period, all the women were observed bi-weekly or monthly, to assure a high uniform compliance in the group. None of the women enrolled took specific drugs for the lipid metabolism during the study. RESULTS: After 6 months from the beginning of the diet, with associated physical training, an important weight loss was observed. Increases of HDL-cholesterol mean levels (p<0.05) associated with a decrease of total cholesterol mean levels (p<0.05) were reported in all the subject examined. A statistically non-significant decrease in LDL and VLDL cholesterol mean levels was also noticed. CONCLUSIONS: A mild lipid dysmetabolism in postmenopause may be corrected advantageously by an opportune diet associated with moderate, but constant, physical training.

Cholesterol↗
PubMed2002

[Preoperative imaging in chronic otitis surgery].

High resolution computed tomography (CT) is presently the most accurate technique to study the temporal bone. Nevertheless, there is no general agreement about its usefulness in pre-operative evaluation of chronic otitis media. Indeed, if we rule out some exceptions, CT is not fundamental for diagnosis which can often be obtained through an accurate otomicroscopy. The Otology Group in Piacenza applies the following absolute indications for pre-operative CT in chronic otitis media: 1) difficult otomicroscopy evaluation; 2) suspected petrous bone cholesteatoma; 3) dubious diagnosis; 4) suspect of malformations; 5) review of cases that had previously undergone mastoidectomy; 6) suspected intracranial complications and/or meningoencephalic herniation (in this case also a magnetic resonance imaging must be performed). With the exception of these specific conditions, pre-operative CT is useless in cases of simple chronic otitis. However, when a cholesteatoma is suspected, CT can provide the surgeon, particularly when inexperienced, useful, but not indispensable, informations. Pre-operative knowledge of these informations can allow a more accurate evaluation of the case, with a better planning of the surgical procedure, in order to ensure a more specific informed consent. Finally, the Authors point out the fact that surgeon must be able to interpret by his own the CT data to have a real advantage by this examination.

Ear↗