Biomedical subjects

F Barbera

Publications and source records attributed to F Barbera.

13 recordsLinked to original sources

PubMed2006

Y179C, F486L and N550H are BRCA1 variants that may be associated with breast cancer in a Sicilian family: results of a 5-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Over 600 different pathogenic mutations have been identified in the BRCA1 gene. Nevertheless, numerous missense mutations of unknown biological function still exist. Understanding of biological significance of these mutations should help in genetic counselling to carriers and their families. PATIENTS AND METHODS: A total of 104 patients with breast and/or ovarian cancer whose genetic counselling answered the criteria of the American Society of Clinical Oncology (ASCO 2003), were prospectively screened for mutations in all coding exons of the BRCA1 gene by automatic direct sequencing. RESULTS: During these mutational screening procedures one case presented three mutations classified in the Breast Cancer Information Core Database as unknown variants. These were 655A/G found in exon 8 of BRCA1, 1575T/C and 1767A/C found in exon 11 of the same gene. The identification of the three unknown variants in the proband (16SIRIO) and in her mother and sister indicates that such alterations exist in cis. CONCLUSIONS: Our results suggest that the charge and stechiometry variations determined by the changes in the amino acids Y179C, F486L and N550H might produce an effect on the conformation of the protein and, consequently, on its function.

Adult↗

PubMed2003

Stage I seminoma of the testis: a bi-institutional retrospective analysis of patients treated with radiation therapy only.

OBJECTIVE: To analyse relapse patterns, toxicity and second malignancy in patients with stage I pure germ cell testicular tumours, treated in 1970-1999. PATIENTS AND METHODS: In all, 487 patients received irradiation after surgery to the infra- (407, 83.5%) or infra- and supra-diaphragmatic volumes (80, 16.5%). Treatment-related toxicity was classified according to previous criteria and fertility investigated in 246 men. Second malignancies were identified by retrospective analysis of clinical records or telephone interviews in men who no longer needed a long-term follow-up. RESULTS: The 10-year overall survival was 97% (98% and 96%, respectively, for the aortic nodes only, or aortic and iliac nodes, i.e. the 'dog leg' field) and disease-free survival was 94%. Twenty-one patients relapsed (five with a true 'in-field' recurrence, nine progressed to the mediastinum, and seven had disseminated disease). Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade II. In all, 73 men achieved paternity after irradiation; nine did not but had normal sperm. Second malignancies were diagnosed in 16 (3.3%) men. CONCLUSION: Para-aortic irradiation may be used safely in patients with stage I seminoma and undisturbed testicular drainage, with equivalent results to the 'dog-leg' group; these unrandomized data confirm the lower toxicity and equivalent survival rates of this treatment.

Adolescent↗

PubMed1999

Prothrombin activation in rabbits.

The suitability of rabbit prothrombin activation fragment F 1.2 as a marker for the activation of the coagulation system was tested. Monoclonal antibodies to rabbit F 1.2 were raised, and a competitive F 1.2 ELISA was developed. Within the detection limit of the ELISA, no increase in rabbit F 1.2 was detected upon recalcification of plasma, whereas human F 1.2 increased 1500-fold. The apparent lack of F 1.2 formation in rabbit serum was confirmed by immunoblotting analysis of endogenous and biotin-labeled prothrombin. Meizothrombin and the B-chain of thrombin were the only prothrombin fragments detectable. In contrast, labeled human prothrombin formed, in addition, prethrombin 2 and F 1.2 in both human and rabbit serum. In contrast, rabbit F 1.2 formation could be demonstrated using purified rabbit prothrombin and factor Xa. These observations raise the possibility that rabbit prothrombin is less susceptible than the human counterpart to factor Xa cleavage at the 271/272 peptide bond. Thus, the primary structure of rabbit prothrombin was deduced by cDNA sequencing. While the 320/321 Xa cleavage site giving rise to meizothrombin was identical in rabbit and human prothrombin, the flanking region of the 271/272 Xa sensitive site contained a six amino acid deletion in the rabbit sequence. Taken together, these observations suggest that the observed differences between human and rabbit prothrombin activation may be due to different susceptibilities of the two Xa cleavage sites rather than plasma or serum cofactor(s).

Amino Acid Sequence↗

PubMed1998

A novel angiotensin II binding site in murine tissues.

A novel binding site for angiotensin II has been identified in certain murine tissues. This site, denoted ATm, is distinct from both the AT1 and AT2 sites, as well as the various atypical sites that have been described. The site has a low affinity for angiotensin II (100 nM) and is not blocked by losartan, PD123177 or saralasin. The site shows structural specificity for angiotensin II since both angiotensin III and angiotensin II (1-7) failed to inhibit the binding. Numerous standard drugs, including various receptor blockers, enzyme inhibitors and therapeutic agents, showed no affinity for the site. In murine tissues the site is associated with active tissue generation, as found in spleen, placenta and growing tumors, but its occurrence appears to be rare outside of the mouse.

Amino Acid Sequence↗

PubMed1996

Accelerated radiation therapy for locally advanced squamous cell carcinomas of the oral cavity and oropharynx selected according to tumor cell kinetics--a phase II multicenter study.

PURPOSE: A Phase II multicenter trial testing an accelerated regimen of radiotherapy in locally advanced and inoperable cancers of the head and neck, in patients selected on the basis of 5-bromo-2-deoxyuridine/DNA flow cytometry-derived tumor potential doubling time (Tpot). METHODS AND MATERIALS: From September 1992 to September 1993, 23 patients consecutively diagnosed to have locally advanced, inoperable carcinomas of the oral cavity and the oropharynx, with Tpot of < or = 5 days, received an accelerated radiotherapy regimen (AF) based on a modification of the concomitant boost technique: 2 Gy/fraction once a day, delivered 5 days a week up to 26 Gy, followed by 2 Gy/fraction twice a day, with a 6-h interval, one of the two fractions being delivered as a concomitant boost to reduced fields, up to 66 Gy total dose (off-cord reduction at 46 Gy), shortening the overall treatment time to 4.5 weeks. A contemporary control group of 46 patients with Tpot of >5 days or unknown was treated with conventional fractionation (CF): 2 Gy/fraction once a day, 5 days a week, up to 66 Gy in 6.5 weeks, with fields shrinkage after 46 Gy. RESULTS: All patients completed the accelerated regimen according to protocol and in the prescribed overall treatment time. Immediate tolerance was fairly good: 65% of the patients in the AF group experienced Grade 3 mucositis vs. 45% in the CF group (p = n.s.). Symptoms related to mucosal reactions seemed to persist longer in AF than in CF patients. The crude proportion of mild (Grades 1 and 2) late effects on skin (p < 0.01) and salivary glands (p < 0.05) was higher in AF than in CF patients, although these reactions did not exceed the limits of tolerance. Three patients in the AF and 1 in the CF arm experienced a late Grade 4 bone complication. Actuarial estimates of severe (Grades 3 and 4) late complications showed a 2-year hazard of 33.3% in the AF arm and 49.7% in CF (p = NS). The actuarial 2-year local control rate of the AF patients was 49.4%, while actuarial 2-year overall survival for the same patients was 43.5%. CONCLUSION: The results suggested that this accelerated regimen is worth testing in a controlled randomized trial to compare different accelerated schedules. Our findings also confirmed the 5-bromo-2-deoxyuridine/DNA flow cytometry technique as a suitable method of evaluating tumor cell kinetics in multicenter clinical studies, on condition that all measurements are carried out by one most experienced laboratory.

Adult↗

PubMed1996

[Conservative surgery in the environment of a screening program for breast carcinoma: evaluation of the results in terms of local recurrence].

This report evaluates the results of conservative surgery plus radiotherapy (QUART) in a group of 123 patients from the screening programme of the District Health Board USSL 41 in Brescia, Italy (over 250 tumours diagnosed in two screening rounds, between 1987 and 1993). To date no recurrence of neoplasms in the operated breast have been diagnosed in either of the two QUART groups (64 patients from the first round, average follow-up 28 months, median 66 months; 59 patients from the second round, average follow-up 28 months, median 30 months). A new carcinoma in the contralateral breast occurred in 3 patients (2 from the first and 1 from the second round), while in 3 cases there was a recurrence in another site (2 from the first and 1 from the second round). These results confirm both the proven effectiveness of conservative treatment in the local control of breast tumours, and the importance of the correct choice of conservative treatment in optimising aesthetic and therapeutic results.

Breast Neoplasms↗

PubMed1996

[Is radiotherapy still the first choice treatment in spinal metastases from breast cancer?].

The skeletal system is a frequent site of metastatic involvement from breast cancer, whose pattern of spread is such that cure becomes practically impossible. The best palliation with the minimum discomfort for the patient must therefore be the major objective. With an increasing number of reports about major surgical procedures for spinal metastases, we reviewed our series of patients submitted to radiotherapy. Of 2,189 breast cancer patients, we selected 28 who might have been potential candidates for surgical resection (with lesions only in the spine, only one or no more than three contiguous bodies involved and no other metastases). All these patients had been treated with 20 or 30 Gy plus systemic (chemo, hormone, or both) therapy. Follow-up revealed that all of them had developed new metastases outside the treated field within one year. Local control was achieved in 68% of patients and 75% of them had stable or better performance status at 3 months. Median survival was 36 months. From our analysis, even patients with a so called "solitary lesion" seem not to have a better prognosis than others. We conclude that radiotherapy is still the method of choice to treat vertebral metastases from breast cancer. The role of surgery should be limited to patients with neurologic compression or severe mechanical instability.

Breast Neoplasms↗

PubMed1993

[Biliary surgery and cholescintigraphy with iminodiacetic acid (IDA) analogs. An evaluation of the results and the complications].

Hepatobiliary scintigraphy with analogs of iminodiacetic acid (IDA) has become one of the primary tools in the diagnosis of biliary tract diseases, especially in the evaluation of surgical results and detection of complications that may arise from biliary operative procedures. We have performed cholescintigraphy in 19 patients. Of them, 9 underwent choledochojejunostomy with Roux-en-Y reconstruction for recurrent choledocholithiasis, 1 underwent right hepatic resection for metastasis extirpation, 8 were post cholecystectomy patients effected with upper abdominal pain located either in the epigastric region or right upper quadrant referable to post cholecystectomy syndrome and the last exhibited chronic pancreatitis ans suspicious sphincter of Oddi stenosis. The scintigraphy data were compared with the information yielded by sonography, intravenous cholangiogram (IVC) and, when possible, by endoscopic retrograde cholangiopancreatography (ERCP). Scans were considered pathologic when one or more of the following criteria were present: a) delayed biliary to bowel transit (greater than 1 hr), b) abnormal time-activity dynamic, c) no intestinal activity (obstruction), d) apparent ductal dilatation. In the group of biliary-enteric anastomosed patients, cholescintigraphic findings have shown 3 normal cases, 3 cases of biliary-intestinal obstruction confirmed by surgery, and 3 with abnormal activity retention in the jejunum loop due, in 2 patients, to hypokinesia since the quick emptying following the administration of 10 mg i.v. of metoclopramide, while in the other one, the surgery reexploration exhibited the presence of adhesions producing intestinal stricture. in the last patient of this group, the cholescintigraphy was performed to detect possible biliary leaks. In the post cholecystectomy patients, the cholescintigraphy exhibited in 3 cases dilated common duct with functional patency since the normal biliary-bowel transit time (less than 1 hr); this was confirmed by sonogram and IVC.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Synthesis of carboxyalkylthio-triazoles and bicyclic derivatives with antiinflammatory and analgesic activity.

3-Carboxyalkylthio derivatives of 5-alkoxyphenyl-1,2,4-triazole were prepared, performing some substitutions both on carboxyalkyl chain, by lengthening it or introducing substituents with increasing molecular weight in alpha- at the carboxy group, and on N-4 atom in the triazole ring, by introducing an amino or methyl group, so that to vary steric conformation along with the lipophilicity of molecules. The corresponding bicyclic thiazolo-triazolone and triazolo-thiazinone derivatives, which represent the rigid models of carboxymethylthio- and carboxyethylthio- open structures, were also obtained. All the compounds show "in vivo" antiinflammatory activity, while only carboxyalkylthio derivatives of 4-amino- and 4-methyltriazole display an appreciable analgesic one. From the relief of some data on substituent present in the synthesized compounds, a structure-activity relationship is also suggested.

Animals↗

PubMed1991

[Hormone profile of hypothyroidism in an area of the Central African Republic with endemic goiter].

In the Ouham region of Centro African Republic, one of the present Authors (B.P.) described a severe goiter endemia due to marked iodine deficiency and high daily intake of manioc as staple food. In the present study serum TSH, T3 and T4 of 233 subjects were determined; 150 of them lived in rural villages (Group 1) and 83 lived in Bocaranga, chief town of the province (Group 2). The blood samples done contemporaneously to the epidemiological survey, were strictly randomized in the population examined. The subjects of each group were divided in 4 sub-groups: A) with TSH, T3 and T4 in normal range; B) with elevated TSH; C) with elevated TSH and sub-normal T4; D) with elevated TSH and sub-normal T3 and T4. An apparently euthyroid pattern of TSH, T3 and T4 was evident in only 60 subjects (19.3% from group 1; 37.35% from group 2); the remaining 173 (80.67% from group 1; 62.65% from group 2) were hypothyroid (subclinical in the sub-group B; mild in the sub-group C; overt in the sub-group D). The mean hormonal values of the apparently euthyroid subjects (sub-group A) in the villages and in the chief town, were significantly different (p less than 0.05) from the control values of our laboratory. More significant differences were clearly evident between the control values and the mean values of sub-groups B, C and D in each of the two groups (1 villages; 2 chief town).(ABSTRACT TRUNCATED AT 250 WORDS)

Central African Republic↗

PubMed1991

[Thyroid hormone profiles in goitrous and non-goitrous subjects seen in an endemic goiter area of the Central African Republic].

In the present study T3, T4, TSH serum concentrations were measured in 166 subjects whose goiter grading was ascertained according to WHO classification; 39 of them had no goiter (grading 0), 127 were goitrous with a grading comprised between 1a and 4. The two samples were composed by Males and Females of various ages whose choice was strictly predetermined by random numbers. The median ages of 127 goitrous and 39 non goitrous subjects were respectively 23.5 years and 33.5 years; 30 Males and 5 Females were in the first group; 58 Males and 69 Females in the second. They lived in the Ouham region of Centro African Republic where some of the Authors ascertained a severe goiter endemia due to iodine deficiency and manioc consumption as staple food. All the values of T4 and TSH of the two group of subjects, were significantly different from the control values (p less than 0.01) excepting T3. Goitrous subjects had T4 value lower than non goitrous subjects (p less than 0.05). The subjects of each group were distributed in the four subsequent subgroups: A) with T3, T4, TSH in the normal range; B) with elevated TSH and T3 and T4 in normal range; C) with elevated TSH, subnormal T4, and T3 in normal range; D) with elevated TSH and subnormal T3 and T4. From fig. 1 it can be seen that the 79.5% of goitrous subjects had a supranormal TSH (subgroups B + C + D) and 40.7% of them had a subnormal T4 (subgroups C + D).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

[Evaluation of the accuracy of the study on diverse techniques of planning radiotherapy of breast tumors].

The authors report the results of the analysis of several factors contributing to the accuracy of treatment planning in the radiation therapy of breast cancer. Different techniques (non-radiological vs CT-based) were used for the acquisition of patients' data; different methods (manual vs computerized) were employed for dose calculation. As for geometric parameters describing the external outline and target volume, mean differences were lower than 4%. Switching from a completely manual method to a CT-based one with computerized calculation, a 3.56% mean decrease in the value of reference isodose (p less than 0.01) was observed, together with a 3.87% mean increase in the estimated inhomogeneity (p less than 0.001). The non-CT-based outline of target volume exhibited geographic missing of inner portions of the target in 8/16 patients. Our results demonstrate that treatment planning procedures can be a significant source of clinically relevant inaccuracy, which may affect treatment outcome and tumor control.

Breast Neoplasms↗

PubMedDate not supplied

Radiotherapy and spinal brace: still first-choice treatment for vertebral metastases from breast cancer.

In metastatic breast cancer the goal to reach must be the best possible palliation with minimum discomfort for the patient. We reviewed our experience with radiotherapy (20 or 30 Gy), systemic therapy and brace. Among 2200 breast cancer patients, we extracted 28 potential candidates for resection. All of them developed new metastases outside the treated field within one year. Local control was achieved in 68%, and 80% of them had stable or better performance status at 3 months. From our analysis, even patients with a so called "solitary lesion" do not seem to have a better prognosis than others. We conclude that radiotherapy (with systemic therapy and a brace) is still first-choice treatment for vertebral metastases; CT-guided percutaneous biopsy can avoid worthless major operations. The role of surgery should be limited to neurological compression, severe mechanical instability and to salvage the failures of conservative treatment.

Antibiotics, Antineoplastic↗