Biomedical subjects
Publications and source records attributed to G Martelli.
The synthesis of an orthogonally protected constrained analogue of dipeptide DG (Asp-Gly) is reported exploiting alkylation of a chiral lactam. The versatility of this analogue was proven by removal of t-Boc protecting group, followed by coupling under homogeneous conditions with t-Boc-Arg(Z(2))-Gly, to give a conformationally restricted analogue of RGDG tetrapeptide.
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Ninety-six laying hens were allocated to 4 groups and fed diets (control diet (0-0), diet supplemented with 2.5 ppm aflatoxin B1 (0-AF); diet supplemented with 0.11% mannanoligosaccharide (MOS-0); diet supplemented with 0.11% MOS and 2.5 ppm aflatoxin B1 (MOS-AF) for 4 wk to evaluate the effect of aflatoxin B1 (AFB1), mannanoligosaccharide (MOS), or both on egg quality and the in vivo efficacy of MOS to interact with an oral administration of AFB1. After 2 and 3 wk, egg weight decreased (P < 0.05) in the group fed MOS-0 versus groups on 0-0 and 0-AF. Egg shell weight was lower (P < 0.05) in the group fed 0-AF. Aflatoxin influenced color parameters, which were probably related to interference of AFB1 with lipid metabolism and pigmentary substances deposition in yolk. MOS appeared to increase protein percentage in albumen. No AFB1 or aflatoxin M1 (AFM1; a polar metabolite of AFB1) residues were found in eggs of the experimental groups. Livers from groups 0-0 and MOS-0 always tested negative for AFB1 and AFM1. Differences (P < 0.01) were found between AFB1 hepatic levels of group 0-AF (mean +/- SD: 4.13 +/- 1.95 ppb) and group MOS-AF (mean +/- SD: 2.21 +/- 1.37 ppb). The data demonstrated the ability of MOS to adsorb and degrade AFB1, reducing gastrointestinal absorption of AFB1 and its levels in tissues.
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[formula: see text] Conrotatory ring closure of 1-halo-3-aza-4-alkyl-1,3-dienes in refluxing toluene gives rise to 3-halo-4-aryl-2-azetidinones in satisfactory yields. Dehalogenation of the resulting beta-lactams by tris(trimethylsilyl)silane furnished 3-unsubstituted azetidinones, valuable intermediates in the synthesis of biologically active compounds.
The predictive role of tumour proliferative rate and expression of p53, bcl-2 and bax proteins, alone and in association with tumour size, nodal involvement and oestrogen receptors (ER), was analysed on 145 elderly patients (> or =70 years of age) with histologically assessed node-positive breast cancers treated with radical or conservative surgery plus radiotherapy followed by adjuvant tamoxifen for at least 1 year. The 7-year probability of relapse was significantly higher for patients with tumours rapidly proliferating (hazard ratio (HR) = 2.0, P = 0.01), overexpressing p53 (HR = 4.4, P = 0.0001), weakly or not exhibiting bcl-2 (HR = 1.9, P = 0.02), without ERs (HR = 3.4, P = 0.0001) or with > or = 4 positive lymph nodes (HR = 2.3, P = 0.003) than for patients with tumours expressing the opposite patho-biological profile. Conversely, tumour size and bax expression failed to influence relapse-free survival. Adjustment for the duration of tamoxifen treatment did not change these findings. Oestrogen receptors, cell proliferation, p53 accumulation and bcl-2 expression were also predictive for overall survival. Within ER-positive tumours, cell proliferation, p53 accumulation, bcl-2 expression and lymph node involvement provided significant and independent information for relapse and, in association, identified subgroups of patients with relapse probabilities of 20% (low-risk group, exhibiting only one unfavourable factor) to 90% (high-risk group, exhibiting three unfavourable factors). Such data could represent the initial framework for a biologically tailored therapy even for elderly patients and highlight the importance of a patho-biological characterization of their breast cancers.
In 83 elderly breast cancer patients, oestrogen and progesterone receptors (ER, PgR), pS2 and cathepsin D (CathD) were evaluated for their possible prognostic role on disease-free survival (DFS). The biomarkers were determined on the same cytosol by using immunoradiometric assays, and the variables were considered on a continuous scale. Univariate analysis indicated a linear relationship between logarithmic hazard ratio (log(HR)) and the log(ER) and log(PgR) concentration, but a non-linear relationship between log(HR) and CathD. As regards pS2, there was no evidence of a relationship with log(HR). In multivariate analysis, log(ER) content did not have a significant prognostic role, whereas log(PgR) retained a significant prognostic role. As regards the predictive ability, log(PgR) was the best discriminator of outcome followed by CathD, whereas the contribution of log(ER) was negligible. In multivariate analysis, 2 models were considered: one with log(ER), pS2, CathD and the interaction between pS2 and CathD, and another with log(PgR), pS2, CathD and the interaction between pS2 and CathD. In the first model, log(ER) content did not have a significant prognostic role, whereas in the second model log(PgR) retained a significant prognostic role. Our findings indicate that the quantitative determination of pS2 and CathD, in addition to steroid receptors, on the same cytosolic fraction could be a complementary tool to describe all breast cancer patients rather than just the elderly and that the use of a continuous scale, instead of a simple dichotomous "status", may improve the biological information supplied by the variables.
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The aim of the present study was to evaluate the response of adrenocorticotropin ([ACTH]) and growth hormone ([GH]) concentrations to a typical aerobic swimming set during a training season. Nine top-level male endurance swimmers (age range 17-23 years) were tested during three training sessions occurring 6, 12 and 18 weeks after the beginning of the season. During each session, after a standard warm-up, the swimmers performed a training set of 15 x 200-m freestyle, with 20 s of rest between repetitions, at a predetermined individual speed. Blood samples were collected before warm-up and at the end of the training set. A few days before each session, the individual swimming velocity corresponding to the 4 mmol x 1(-1) blood lactate concentration (nu4) was assessed as a standard of aerobic performance. Aerobic training affected nu4 levels, which were highest 18 weeks after the beginning of the season; at the same time, while [ACTH] response was attenuated, [GH] response was enhanced. These results could be considered as adaptations to the exercise intensity. In our training programme, these adaptations seemed to have occurred between the 12th and 18th weeks of the training season.
A total of 606 consecutive patients with palpable breast lesions underwent physical examination, mammography, and fine-needle aspiration for cytologic and flow-cytometric (FCM) DNA analyses. FCM determinations included DNA ploidy and the fraction of cells in S + G2 + M phases. Aneuploid clones were considered indicative of malignancy; diploid, rapidly proliferating (S+G2+M>12%) clones were considered suggestive of malignancy; and diploid, slowly proliferating clones were considered indicative of benignancy. Sensitivity, specificity, and the predictive accuracy for positive or negative results of FCM information were 82%, 90%, 93.1% and 69.8%, respectively. These values were lower than those observed for the three conventional diagnostic assays owing to the presence of false-positive results (in 23 cases) or unassessable DNA plots (in 90 cases). FCM information alone detected five cases in which the other tests gave inconclusive results and in association to the conventional diagnostic triple test, increased the incidence of positive conclusive cases from 97.9% to 99.2%. However, further refinements are needed before this approach can be used as a routine diagnostic tool.
In eight top-level male endurance swimmers the aerobic performance and the response to exercise of total testosterone (T), free testosterone (fT), sex hormone binding globulin (SHBG), non-SHBG-bound testosterone (NST) and cortisol (C) were evaluated during a training season. The swimmers participated in three test sessions which occurred 6, 12 and 24 weeks after the beginning of the season. During each session, after a standard warm-up, the swimmers performed a set of 15 x 200-m freestyle, with a 20-s rest between repititions, at a predetermined individual speed. Three blood samples were collected: before warm-up, at the end of the set, and after 1 h of recovery. A few days before each session, the individual swimming velocity associated with a 4 mmol.l-1 blood lactate concentration (v4) was assessed as a standard of aerobic performance. The values of v4 were lower in the second session than in the third one. The concentrations of C. which increased after the exercise, showed the highest values in the second session. The values of T and the T:SHBG ratio increased after the exercise but returned to their initial concentrations during the recovery period. The values of fT and NST increased after the exercise in the first and third sessions. In the initial two sessions, when the aerobic performance was still low, the concentrations of NST decreased to below the initial values after recovery. In session III, when the adaptation to the training workload was complete, NST returned to resting concentrations after recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
Between 1982 and 1990, 321 elderly patients (range 70-92 years, median age 77) with operable breast cancer (T1 in 219, T2 in 77, T3 in one and T4b in 24 patients) and clinically uninvolved axillary nodes underwent surgery without axillary dissection and received adjuvant tamoxifen. All patients had surgery performed under local anaesthesia. Tamoxifen was given after surgery at the dose of 20 mg daily, indefinitely. With a median follow-up of 67 months (range 42-141), 17 patients developed local relapse, 14 ipsilateral axillary recurrence, five ipsilateral breast cancer, five contralateral breast cancer, 13 second primary and 23 developed distant metastases. The cumulative probability of developing a local, axillary and distant recurrence at 72 months was estimated to be 5.4%, 4.3% and 6.2%, respectively. Out of 244 patients who did not develop any relapse, 83 (25.8%) died from intercurrent disease. The 72 month relapse-free survival rate was 76%. This experience suggests that elderly patients with small tumours without clinical axillary involvement may be satisfactorily treated with conservative surgery and tamoxifen. The importance of axillary dissection is controversial owing to a high response rate to hormonal therapy and an increased death rate due to concomitant diseases.
The plasma hormonal response following a swimming competition in the sea (18 km) was evaluated in 12 top level male endurance swimmers. At the end of the effort, while plasma renin activity (PRA) and aldosterone concentration (ALDO) were unchanged, a significant increase in plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) concentrations were recorded. These changes were associated with a decrease in haematocrit and an increase in Na+ and Cl- plasma concentrations. The individual variations of ANP (difference between the final and initial concentrations) were inversely correlated with the corresponding individual variations of PRA and ADH. The results suggest that, during prolonged swimming, ANP may exert an inhibitory effect on the PRA-ALDO axis and have a modulatory role with regard to ADH secretion.
Pilomatrix carcinomas are malignant uncommon tumors of hair matrix origin. The clinicopathologic features of a case of pilomatrix carcinoma are described and compared with those of the previously reported cases. Because these tumors behave similarly to a basal cell carcinoma, a complete excision is necessary in order to minimize the likelihood of relapse.
BACKGROUND: The diagnosis of second malignant tumors, the incidence of which is increased because of the increased duration of survival for many tumor types in patients treated for cancer, represents one of the most important aspects of application of fine-needle aspiration (FNA). METHODS: Forty patients who had been treated for a malignant tumor and who developed a second primary tumor detected by FNA and subsequently confirmed by histologic examination were studied. The primary tumors were malignant lymphoma (15 cases); breast carcinoma (10 cases); cutaneous melanoma (3 cases); carcinoma of the larynx and of the uterine cervix (2 cases each); and dysgerminoma of the ovary, chronic myeloid leukemia, and carcinoma of the nose, floor of the mouth, tonsil, anus, kidney, and skin (one case each). The interval between the diagnosis of the first and second malignant tumors ranged from 1 month to 22 years. RESULTS: Carcinoma of the lung, mainly represented by adenocarcinoma, was the most frequent second malignant tumor that occurred in this series (15 cases). It was followed by carcinoma of the breast (5 cases); soft tissue sarcoma (3 cases); and carcinoma of the liver, kidneys, ovaries, thyroid gland (2 cases each), parotid gland, and skin. Five cases of non-Hodgkin lymphoma and one of Hodgkin disease developed in patients with a previous carcinoma at various sites. Four non-Hodgkin lymphomas occurred as the second primary malignant tumor in patients treated with radiation therapy for a mammary carcinoma. One case of multiple myeloma occurred. CONCLUSION: The accuracy of FNA in diagnosing second primary tumors (100%) and in classifying them by histologic type (62.5%) was demonstrated.
BACKGROUND: DNA ploidy and cell kinetics determined by flow-cytometric (FCM) analysis have provided relevant information on the natural history of breast cancer. These highly feasible and evaluable assays are particularly appropriate for small samples from fine-needle aspirates (FNA) to complement cytologic information for diagnosis of breast lesions. METHODS: DNA content and the percentage of cells in the cell cycle phases were evaluated on FCM DNA histograms from 281 consecutive FNA of benign and malignant breast lesions. RESULTS: FCM analysis was possible in 93% of FNA. Qualitative concordance in DNA content between FNA and surgical specimens was observed in 82% of the patients. Of the 145 aneuploid FNA, 144 (99%) were histologically diagnosed as carcinomas. The presence of only diploid clones was observed in 115 FNA: rapidly proliferating (S+G2M > 12%) diploid lesions proved to be histologically malignant in 67% of patients, and slowly proliferating diploid lesions were histologically benign in 79% of patients. False-positive results of ploidy and cell kinetics were observed in 1 and 10 patients, respectively. Of the 163 cancers evaluable for cytology and FCM, 158 were positive at cytology. The presence of aneuploid or of diploid rapidly proliferating clones in cytologically false-negative aspirates resulted in the detection of four additional cancers. CONCLUSIONS: Flow cytometric analysis of ploidy and cell kinetics on FNA could be a valuable tool complementary to cytology for breast cancer diagnosis.
Between March 1982 and May 1989, 151 women with primary breast cancer ranging in age from 70 to 91 years (median 79), were treated with conservative surgical procedure followed by adjuvant tamoxifen. Surgery was performed under local anaesthesia without axillary node dissection. The median duration of follow-up was 60 months (range 36-124). There were six local, six ipsilateral axillary node and six distant relapses. Local recurrences were successfully managed with further surgery whereas axillary node relapses required radiotherapy in 3 cases, surgery in 2 cases and hormonal treatment in 1 case. 2 patients died of progression of disease and one of unrelated conditions. The 5-year relapse-free survival rate was 0.82. This treatment option in elderly patients yields an acceptable local control and reduces the risks of major surgery.