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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↗
PubMed1992

In vivo and in vitro growth-inhibitory effect of bovine seminal ribonuclease on a system of rat thyroid epithelial transformed cells and tumors.

We investigated the antitumoral effect of bovine seminal RNase (BS-RNase) in vivo and in vitro on a model system of epithelial tumor- and metastasis-derived cells as well as on epithelial tumors derived from the same system. We found that while BS-RNase significantly inhibited the growth in vitro of the epithelial tumor-derived cells, its inhibitory effect was even more dramatic on the growth of metastasis-derived cells. BS-RNase exerted no appreciable growth inhibition on normal thyroid epithelial cells. When administered in vivo to rats bearing solid carcinomas, having the same thyroid origin, BS-RNase induced a drastic reduction in the tumor weight, with no detectable toxic effects on the treated animals. These data show, for the first time on a system of neoplastically transformed epithelial cells, that BS-RNase has a potent specific antitumoral activity.

Animals↗
PubMed1992

Histopathologic classification of breast cancer in Sweden and Italy: a comparison between two pathologists.

Two large series of breast cancers (BC), identified in the Pathology Departments of Malmö (Sweden) and Florence (Italy), were independently reviewed by two experienced pathologists, one from each department. Overall, comparison of diagnoses of 372 BCs according to a simplified WHO histologic classification system (in four combined categories) revealed agreement for 74% of the cases. Concordance, as measured by the kappa statistic, was relatively good (0.53 overall). Kappa values for specific categories were also acceptable, being highest for "invasive lobular" BC (0.63) and lowest for "other types" (0.45). The kappa value for "noninvasive" versus all other categories of invasive BC was 0.53. Some BCs were systematically classified as "noninvasive" by one pathologist and as "invasive ductal with a predominant intraductal component" by the other. Invasive lobular BCs were also diagnosed more frequently by one pathologist. These findings suggest that when planning geographical or temporal comparisons of distribution for BC histologic categories, standardization of classification and a centralized review may play an important role.

Aged↗
PubMed1992

Oxoammonium cation intermediate in the nitroxide-catalyzed dismutation of superoxide.

Dismutation of superoxide has been shown previously to be catalyzed by stable nitroxide compounds. In the present study, the mechanism of superoxide (.O2-) dismutation by various five-membered ring and six-membered ring nitroxides was studied by electron paramagnetic resonance spectrometry, UV-visible spectrophotometry, cyclic voltammetry, and bulk electrolysis. Electron paramagnetic resonance signals from the carbocyclic nitroxide derivatives (piperidinyl, pyrrolidinyl, and pyrrolinyl) were unchanged when exposed to enzymatically generated .O2-, whereas, in the presence of .O2- and reducing agents such as NADH and NADPH, the nitroxides underwent reduction to their respective hydroxylamines. The reaction of 4-hydroxy-2,2,6,6-tetramethyl-1-hydroxypiperidine (Tempol-H) with .O2- was measured and, in agreement with earlier reports on related compounds, the rate was found to be too slow to be consistent with a mechanism of .O2- dismutation involving the hydroxylamine as an intermediate. Voltammetric analyses of the carbocyclic nitroxide derivatives revealed a reversible one-electron redox couple at positive potentials. In contrast, oxazolidine derivatives were irreversibly oxidized. At negative potentials, all of the nitroxides studied exhibited a broad, irreversible reductive wave. The rate of .O2- dismutation correlated with the reversible midpoint redox potential. Bulk electrolysis at positive potentials was found to generate a metastable oxidized form of the nitroxide. The results indicate that the dismutation of .O2- is catalyzed by the oxoammonium/nitroxide redox couple for carbocyclic nitroxide derivatives. In addition to the one-electron mitochondrial reduction pathway, the present results suggest the possibility that cellular bioreduction by a two-electron pathway may occur subsequent to oxidation of stable nitroxides. Furthermore, the cellular destruction of persistent spin adduct nitroxides might also be facilitated by a primary univalent oxidation.

Cyclic N-Oxides↗
PubMed1992

New modified heterocyclic phenylalanine derivatives. Incorporation into potent inhibitors of human renin.

Modified heterocyclic phenylalanine analogues designed as replacements for the P3-P4 region were synthesized and incorporated into renin inhibitors. These inhibitors were found to have significant activity versus human recombinant renin, as well as in vivo activity. The compounds proved to be very resistant to chymotrypsin degradation, as exemplified by compound 8, which remained greater than 60% intact after a 24-h exposure to chymotrypsin. In contrast, the Boc-Phe analogue was nearly completely degraded after 1 h. Compound 6 proved to be the most potent renin inhibitor with an IC50 = 8.9 nM. These stable cyclized phenylalanines should prove to be generally useful as a substitute for Boc-Phe in protease inhibitors.

Angiotensin I↗
PubMed1992

Antimutagenicity of a low molecular weight superoxide dismutase mimic against oxidative mutagens.

A set of stable nitroxide free radicals that are used as spin labels have been shown to possess metal-independent superoxide dismutase-like activity. Unlike superoxide dismutase (SOD), these compounds are low molecular weight, and readily penetrate into the cell. A representative nitroxide, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (Tempol), was investigated for antimutagenic activity in the XPRT forward mutation assay in CHO AS52 cells. AS52 cells were exposed to hydrogen peroxide, or the hypoxanthine/xanthine oxidase superoxide generating system, in the presence or absence of 10 mM Tempol. Tempol itself was not mutagenic or toxic to AS52 cells. Tempol protected cells nearly completely from the cytotoxic and mutagenic effects of hydrogen peroxide and hypoxanthine/xanthine oxidase. We have previously shown that nitroxides do not alter the extracellular concentration of hydrogen peroxide, and that they are taken up by mammalian cells, suggesting that the antimutagenic activity of Tempol is an intracellular phenomenon.

Animals↗
PubMed1992

Further evidence for the aneuploidogenic properties of chelating agents: induction of micronuclei in mouse male germ cells by EDTA.

A micronucleus assay based on cytogenetic analysis of early spermatids (Tates et al.; Mutation Research 121:131-138, 1983) was applied to determine if the chelating agent ethylenedinitrilotetraacetic acid (EDTA) may induce aneuploidy in mouse meiotic cells. Previous results indicated aneuploidogenic activity of EDTA in Drosophila female germ cells (induction of chromosome loss; Zordan et al.: Environ Mol Mutagen 15:205-213, 1990). In the same study, a standard aneuploidy test based on chromosome counting in mouse secondary spermatocytes failed however to show aneuploidogenic properties of EDTA in mouse somatic and germ cells. In the present study the effects of two clastogens, adriamycin (ADM) and mitomycin C (MMC), and of the aneuploidogenic agent chloral hydrate (CH) were also evaluated. All compounds were tested at a single dose level and at two time intervals corresponding to the treatment of diakinesis/metaphase I/metaphase II spermatocytes. The clastogenic potential of the compounds under study was also evaluated, by chromosomal aberration analysis in mouse spermatogonia, in an independent set of experiments. The results obtained indicate that ADM, CH and EDTA are able to induce micronuclei at meiosis. On the contrary, only ADM and MMC induced chromosomal aberrations in mouse spermatogonia. Therefore, the most probable origin of micronuclei produced by CH and EDTA is whole chromosome lagging. These results provide further evidence for the aneuploidogenic properties of these chelating agents.

Aneuploidy↗
PubMed1992

Flow cytometric DNA analysis of hepatic tumours on ultrasound-guided fine-needle aspirates.

A study was performed on a nonconsecutive series of 51 patients in order to assess the feasibility, reliability, and usefulness of flow cytometric (FCM) DNA analysis of samples obtained from benign and malignant hepatic tumours by means of ultrasound-guided fine-needle aspiration (UG-FNA). Cytological and often histological confirmation of the nature of the lesion was obtained in all cases from an expert pathologist. For FCM DNA analysis in 32 cases, it was also possible to use samples obtained at surgery from the actual tumours. There were no post UG-FNA complications, either early or late. It was possible to perform FCM DNA analysis on 6/7 (85.7%) of the benign tumour aspirates and all 44 (100%) coming from the malignant tumours. All the benign tumours showed a DNA-diploid pattern, while the DNA content was aneuploid in 91% of the malignant tumours. Apart from one case, the results of the FCM DNA analysis of the samples removed at surgery were the same as those obtained from the aspirates (97%). FCM DNA analysis on UG-FNA samples from hepatic tumours is a fairly simple, reproducible, well-tolerated technique; it does not involve risks if performed by skilled operators and, since it can be easily repeated even on small tumours, it is a suitable method for monitoring hepatic metastases during chemotherapy.

Adult↗
PubMed1992

Transglutaminase activity in primary and subcultured rat astroglial cells.

Transglutaminases, calcium-dependent thiol enzymes, may be involved in cellular growth control and differentiation, having an intracellular regulatory role in some post-translational modifications found in various classes of proteins. In order to elucidate the involvement of this class of enzymes in cellular differentiation processes, we have assayed transglutaminase activity in primary and subcultured rat glial cells. Reduced activity was found from 3rd to 5th passage. In the 5th passage the activity was some 50% of that found in the primary cultures and was not restored by addition of 10 microM retinoic acid. The decrease of TGase activity, observed during serial passages, could represent an early metabolic alteration related to cell dedifferentiation and loss of growth control. In fact, the subcultured cells may have undergone a "disarranged" state, as confirmed by a decrease in GFAP-stained cells and glutamine synthetase activity, respectively, immunocytochemical and biochemical markers of astroglial cells.

Animals↗
PubMed1992

Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age.

In the present study, we have assayed the enzymatic activity of Cu,Zn-SOD, Mn-SOD, GSH-Px, GSH-Red, Cat, and G6PD in rat retina as a function of age. Conjugated diene levels and MDA formation were also determined. The conjugated diene levels in rat retina were found to increase significantly with age, accompanied by a marked decrease in GSH-Px and Cat activities. No age-related change in MDA levels and in GSH-Red and G6PD activity was found, whereas a significant increase in SOD activity was observed between 1 and 4 months. Decreased GSH-Px and Cat activity is related to increased lipid peroxidation with age.

Aging↗
PubMed1992

High-dose folinic acid and 5-fluorouracil plus cisplatin on a weekly schedule in the treatment of advanced cancer of the head and neck.

A group of 60 patients with advanced head/neck cancer were treated with high-dose folinic acid (500 mg/m-2/week-1) plus 5-fluorouracil (400 mg/m-2/week-1 on day 1, and cisplatin (20 mg/m-2/week-1) 24 h after folinic acid infusion was completed. Out of 55 evaluable patients, 10 patients (18%) experienced a complete response with a mean duration of 11.4+ months, 25 patients had a partial response (45%) of 6.7+ months, 6 patients (11%) showed a stabilization of 4.8+ months, and 14 (25%) progressed. The overall response rate was 63.6% (95% confidence limits 56.5%-69.5%). Patients pretreated with radiotherapy had a 67% overall response rate, while those pretreated with chemotherapy showed a 54% overall response rate. All patients with cancer of the oropharynx had a major response, while patients with cancer of the oral cavity had the lowest response rate. The mean survival of patients who attained a complete response was 14.5+ months. Partial responders had a mean survival of 10.6+ months, while patients who progresses survived a mean of 3.6+ months. The treatment has been very well tolerated with few cases of grade 3 gastrointestinal toxicity. Grade 1-2 leukopenia was recorded in 64% of cases, grade 1-2 nausea/vomiting in 85%. In one case therapy was stopped because of persistent diarrhoea.

Adenocarcinoma↗
PubMed1992

The catecholic metal sequestering agent 1,2-dihydroxybenzene-3,5-disulfonate confers protection against oxidative cell damage.

Tiron (1,2-dihydroxybenzene-3,5-disulfonate), a nontoxic chelator of a variety of metals, is used to alleviate acute metal overload in animals. It is also oxidized to the EPR-detectable semiquinone radical by various biologically relevant oxidants, such as .OH, O2-., alkyl, and alkoxyl radicals. Since Tiron reacts with potentially toxic intracellular species and is also a metal chelator, we evaluated its protective effects in V79 cells subjected to various types of oxidative damage and attempted to distinguish the protection due to direct detoxification of intracellular radicals from that resulting from chelation of redox-active transition metals. We found that Tiron protects Chinese hamster V79 cells against both O2.(-)-induced (and H2O2 via dismutation of O2.-) and H2O2-induced cytotoxicity as measured by clonogenic assays. In experiments where Tiron was incubated with V79 cells and rinsed prior to exposure to HX/XO or H2O2, cytoprotection was observed, indicating that it protects against intracellular oxidative damage. On the other hand, Tiron did not protect V79 cells against the damage caused by ionizing radiation under aerobic conditions, which is predominantly mediated by H., .OH, and hydrated electrons in a metal-independent fashion. We demonstrate also that in in vitro studies, Tiron protects supercoiled DNA from metal-mediated superoxide-dependent strand breaks. We conclude that Tiron is a potentially useful protecting agent against the lethal effects of oxidative stress and suggest that it offers protection by chelating redox-active transition metal ions, in contrast to earlier reports where the protection by this compound in cellular systems subjected to oxidative damage has been interpreted as due to radical scavenging alone.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1992

Persistence of chromosomal lesions induced in actively proliferating bone marrow cells of the mouse.

The persistence of chromosomal lesions induced in vivo by mitomycin C (MMC) was evaluated by cytogenetic analysis of mouse bone marrow cells. Chromosome aberration (CA) and micronucleus (MN) frequencies were estimated at different times after treatment, up to 42 days. The frequency of CA per cell decreased in the first 3 days after treatment, but a secondary peak appeared on the 4th day, followed by a stabilization around 0.03 CA per cell (significantly different from the control value), which persisted up to 17 days. At the next time intervals tested (28 and 42 days), the CA frequency returned to the control level. In disagreement with these data obtained directly on metaphases, the MN frequency, as evaluated in polychromatic erythrocytes, decreased quickly after treatment, reaching the control value on the 5th day. We attempted to enhance the sensitivity of the MN test by using CREST antibodies and indirect immunofluorescence. However, higher proportions of CREST- MN in treated than in control animals were observed only at short time intervals, confirming the results obtained with the conventional MN assay.

Animals↗
PubMed1992

Detection of aneuploidy in male germ cells of mice by means of a meiotic micronucleus assay.

The possibility of using a micronucleus (MN) assay in mouse germ cells for the identification of aneuploidogenic agents was evaluated by comparing the pattern of effects induced by 4 chemicals with different mechanisms of action (adriamycin, ADM; mitomycin C, MMC; chloral hydrate, CH; ethylenedinitrilotetraacetic acid, EDTA). The results obtained after treatment of spermatocytes at the premeiotic S-phase (preleptotene) indicated that only clastogenic agents (ADM and MMC) were able to induce MN at this cell stage. Previous data obtained with the same compounds demonstrated by contrast that the micronucleus spermatid assay may detect both clastogenic and aneuploidogenic effects after treatment of diakinesis/MI/MII cells. Analysis of MN size distributions, in the present and previous spermatid samples, revealed that the clastogens ADM and MMC produced relatively more small MN than CH and EDTA. These data are in agreement with the proposed mechanism of action of the chemicals tested.

Aneuploidy↗
PubMed1992

Lipid peroxidation in rat cerebral cortex during post-ischemic reperfusion: effect of exogenous antioxidants and Ca(++)-antagonist drugs.

Although the role of oxidant-antioxidant metabolism in total ischemia and reperfusion in the central nervous system and cardiac myocardium have been well studied, less is known about the consequences of partial ischemic episodes. Here we show that reperfusion contributes to free radical formation as judged by conjugated diene formation. Also, antioxidants and Ca++ antagonists were able to reduce free radical formation. These results would suggest that free radical generation following ischemia and reperfusion may result from more than one injury process in cerebral cortex.

Animals↗
PubMed1992

Surgery of the 'only hearing ear' with chronic ear disease.

The management of chronic ear disease affecting the only hearing ear is a controversial subject. The relative scarcity of literature on the subject prompted us to prepare a questionnaire which was sent to European and American otologists and to review 19 cases operated at the ENT Clinic of the University of Parma, Italy, and 16 cases operated at The Baptist Memorial Hospital, Memphis, U.S.A. Surgery of cholesteatoma involving the only hearing ear is advised by all the interviewed otologists without exception, even in the presence of a labyrinthine fistula. The cases from the University of Parma were managed as follows: a classic modified radical mastoidectomy was performed in 10 cases, a staged intact canal wall tympanoplasty was done in four cases, an open tympanoplasty in three and a radical mastoidectomy in the remaining two cases. The cases from The Baptist Memorial Hospital were managed with an intact canal wall tympanoplasty (ICWT) in nine and with an open procedure in seven cases. All the otologists interviewed agreed that surgery of the only hearing ear requires particular attention and experience, and should be performed with extreme care by a very experienced surgeon.

Attitude of Health Personnel↗
PubMed1992

A case-control study of cancers of the gastric cardia in Italy.

In a case-control study of gastric cancer (GC) in high-risk and low-risk areas in Italy, 923 GCs were reviewed by one pathologist and classified according to anatomic site. There were 68 (7.4%) cancers occurring in the gastric cardia. Compared to other GCs, cardia cancer tended to occur more often in males (sex ratio 2.8 vs 1.7) and as intestinal or unclassified histologic types. Nutritional factors for cardia tumours resembled those of other GCs, showing inverse associations with the consumption of raw vegetables, citrus and other fresh fruit, and ascorbic acid, and positive associations with the intake of traditional soups and meat, protein and cholesterol, and preference for salty foods. Cigarette smoking and wine consumption were unrelated to cardia cancer risk, and there was only a weak association with total alcohol intake. Cardia tumours showed a greater familial occurrence of GC than did other sites, with a 7-fold increase in risk for those reporting two first-degree relatives with GC. The authors discuss these findings in view of the rising incidence of adenocarcinomas of the cardia and lower oesophagus that has been reported in some western countries.

Adult↗