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Biomedical subjects

A Luini

Publications and source records attributed to A Luini.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Microcalcifications in non-palpable breast carcinoma. Analysis of 427 cases].

Of 836 nonpalpable breast lesions histologically assessed between 1985 and 1991 at the Milan Cancer Institute, 427 were malignant (51%). Microcalcifications were present in 283 tumors (66%), alone in 200 cases or associated with a mass (72 cases) or within a focal distortion (11 cases). Several mammographic, clinical and histological features were analyzed, comparing the 283 lesions with microcalcifications with the 144 tumors represented only by nodular opacities or distortions. This was done to assess the existence of morphologic and prognostic characters differentiating the two subsets and to investigate the reliability of mammography in estimating lesion size. On the average, in our series of cases, the patients with microcalcifications were younger, had a higher rate of dense breasts and a large number of partially or totally intraductal carcinomas. In situ carcinomas were frequent and minimal lesions (< 5 mm) accounted for 43% of the whole at pathologic examination. However, the lesions with microcalcifications were associated with more positive nodes (32% vs 18%). Therefore, microcalcifications, although generally representing an early sign of cancer, appear to suggest a less favorable prognosis.

Adult↗
PubMed1992

Tetanus toxin potently stimulates tissue transglutaminase. A possible mechanism of neurotoxicity.

The observation that tetanus toxin (TT) contains two sequences that show homology to known transglutaminase (TGase) substrate sites suggested that the toxin and TGase might interact. This prediction was confirmed by two pieces of evidence. First, TT potently stimulated the enzymatic activity of TGase. The effect was maximal at physiological (micromolar) concentrations of the endogenous TGase regulators calcium and GTP. Second, TT and TGase displayed marked variations of their intrinsic fluorescence properties when they were coincubated, indicating the occurrence of binding between them. TT-TGase binding and TGase activation occurred at similar concentrations of TT and are probably causally related. The activation of TGase, an enzyme present in nerve endings that, when activated, can irreversibly cross-link cellular proteins, might mediate the neurotoxic action of TT.

Amino Acid Sequence↗
PubMed1992

Glucocorticoid stabilization of actin filaments: a possible mechanism for inhibition of corticotropin release.

The mechanism by which glucocorticoids induce various cellular responses in different tissues is only partially understood. Here we demonstrate that glucocorticoids stabilize the actin cytoskeleton of several cell types, as revealed by increased resistance of actin filaments to the disrupting effect of cytochalasin and by visible thickening of actin filament bundles. These effects require several hours to develop, require protein synthesis, and are accompanied by increased expression of the actin-binding protein caldesmon. These data may help to explain why glucocorticoids inhibit corticotropin release from pituitary cells, if interpreted in terms of the current idea that an actin filament "barrier" modulates exocytotic secretion in various cell types. In support of this idea, we find that in "model" corticotrophs (AtT-20 cells), glucocorticoids stabilize actin filaments and inhibit corticotropin release with similar potencies. Furthermore, we show here that glucocorticoid inhibition is overcome by exposing AtT-20 cells to concentrations of cytochalasin B or D that disrupt their stabilized actin filaments. On the other hand, our freeze-etch electron microscopy of AtT-20 cells has shown that actin filaments do not, in fact, create a dense submembranous barrier that might prevent corticotropin secretory droplets from discharging; instead, they form open networks near the membrane that appear to hold secretory droplets in their interstices. We propose that the delicate physical crosslinks maintaining this actin-mediated membrane "docking" of secretory droplets may need to disconnect in order to permit corticotropin discharge and that these crosslinks may be stabilized along with the actin filaments in dexamethasone-treated cells.

Actin Cytoskeleton↗
PubMed1992

Adenosine receptors in rat basophilic leukaemia cells: transductional mechanisms and effects on 5-hydroxytryptamine release.

1. The presence of adenosine receptors linked to adenylate cyclase activity and their functional role in calcium-evoked 5-hydroxytryptamine (5-HT) release was investigated in rat basophilic leukaemia (RBL) cells, a widely used model for studying the molecular mechanisms responsible for stimulus-secretion coupling. 2. In [3H]-5-HT-loaded cells triggered to release by the calcium ionophore A23187, a biphasic modulation of 5-HT secretion was induced by adenosine analogues, with inhibition of stimulated release at nM and potentiation at microM concentrations, suggesting the presence of adenosine receptor subtypes mediating opposite effects on calcium-dependent release. This was also confirmed by results obtained with other agents interfering with adenosine pharmacology, such as adenosine deaminase and the non-selective A1/A2 antagonist 8-phenyl-theophylline. 3. Similar biphasic dose-response curves were obtained with a variety of adenosine analogues on basal adenylate cyclase activity in RBL cells, with inhibition and stimulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) production at nM and microM concentrations, respectively. The rank order of potency of adenosine analogues for inhibition and stimulation of adenylate cyclase activity and the involvement of G-proteins in modulation of cyclic AMP levels suggested the presence of cyclase-linked A1 high-affinity and A2-like low-affinity adenosine receptor subtypes. However, the atypical antagonism profile displayed by adenosine receptor xanthine antagonists on cyclase stimulation suggested that the A2-like receptor expressed by RBL cells might represent a novel cyclase-coupled A2 receptor subtype.4. Micromolar concentrations of adenosine analogues could also increase inositol phospholipid hydrolysis and inositol tris-phosphate formation in both unstimulated cells and in cells triggered to release by the calcium ionophore. The stimulation was constant, small and additive to that exerted by the calcium ionophore.5. It is concluded that RBL cells express both A1 and A2-like adenosine receptors which exert opposite effects on 5-HT release and intracellular cyclic AMP levels. However, besides modulation of cyclic AMP levels, additional transduction pathways, such as modulation of phospholipase C activity, may contribute to the release response evoked by adenosine analogues in this cell-line.

Adenylyl Cyclases↗
PubMed1992

[Nonpalpable breast lesions. General considerations and a review of the literature in the light of the authors' own experience with 344 cases located preoperatively].

The widespread use of mammography in breast cancer screening has increased the number of non-palpable breast lesions being detected in which the differential diagnosis between benign and malignant cases requires surgical biopsy. In order to remove these mammographically identified lesions the surgeon must be guided, which is why the techniques guiding the surgeon during lesions ablation have become most important. Accurate preoperative lesion localization must be done so that the excision can be complete and with the best cosmetic result. In this report we discuss localization methods, from the simplest to the most complicated ones. The commonest method has the advantage of employing no special instruments, and it is very simple, safe and fast. It requires a skilled hand and a little training. Instrumental methods are then discussed, from the simple dedicated compressor to the stereotactic techniques and, finally, the role of ultrasonography both in preoperative localization and in cytologic biopsy. The importance of mammographic examination of the surgical specimen is also stressed.

Adult↗
PubMed1992

The preservation of minor pectoralis muscle in axillary dissection for breast cancer: functional and cosmetic evaluation.

We have evaluated, in two groups of 50 patients each submitted to axillary dissection for breast cancer (10 mastectomies and 90 conservative procedures), the advantage of the preservation of the minor pectoralis muscle. This muscle was preserved in one group and removed in the other. Whereas in the immediate postoperative period complications (shoulder pain, functional impairment, quantity or duration of serum drainage from the axilla) were the same in the two groups, at longer follow-up (more than 6 months after surgery) the patients whose pectoralis minor muscle was preserved showed a reduction in the incidence of partial atrophy and fibrosis of the pectoralis major muscle. Patients treated with conservation of the pectoralis minor muscle showed this atrophy in 6% of cases vs 54% observed in the other patients. This fact may be related to disruption of the pectoral nerves, which are in close contact with the pectoralis minor during their course from the brachial plexus to the pectoralis major muscle.

Axilla↗
PubMed1991

Characterization of calcium-triggered secretion in permeabilized rat basophilic leukemia cells. Possible role of vectorially acting G proteins.

Strong, albeit indirect, evidence suggests that a GTP-binding (G) protein(s) can act directly on the secretory machinery by a post-second messenger mechanism. The type and function of this putative Ge (exocytosis) protein were investigated in streptolysin-O-permeabilized rat basophilic leukemia (RBL) cells. The exocytotic response to calcium was first characterized both morphologically and biochemically using the release of preloaded [3H]serotonin as an index of exocytosis. Calcium-induced secretion (EC50 about 3 microM) in RBL cells requires ATP (EC50 about 2.5 mM) and is modulated by pH, the optimal value being 7.2. Another requirement for calcium-induced secretion is an activated G protein, since inactivators of G proteins such as GDP beta S (EC50 about 800 microM) inhibit the secretagogue effect of 10 microM free calcium. Conversely, GTP gamma S (EC50 about 1 microM) and other nonhydrolyzable analogs of GTP, which keep G proteins in a permanently active conformation, potentiate the effect of calcium. GTP gamma S alone is without effect. The effect of GTP gamma S on exocytosis is apparently not mediated by known second messengers, suggesting that a Ge protein is involved. Electron microscopic images show that in resting cells, secretory granules are clustered in the perinuclear area, whereas they become scattered upon calcium stimulation. A paradoxical effect of GTP gamma S is observed when applied during permeabilization; under these conditions, in fact, the nucleotide inhibits the subsequent secretory response to calcium. The scattering of granules is also inhibited. This effect of GTP gamma S is counteracted by coadministration of GTP. These responses to guanine nucleotides are typical of vectorially acting G proteins involved in protein synthesis and in intracellular vesicle transport. Taken together, the data presented suggest that calcium-dependent release requires a vectorially acting G protein controlling the movement of secretory granules. This and alternative models are discussed.

Alkaloids↗
PubMed1991

Quantitative and qualitative cosmetic evaluation after conservative treatment for breast cancer.

148 consecutive patients treated by two different types of conservative surgery were objectively and subjectively evaluated for cosmetic outcome. In 73 patients, tumorectomy, axillary dissection, external radiotherapy (45 Gy) plus iridium implant (15 Gy) were performed, while in the other group of 73 patients a more extensive surgical approach was carried out: quadrantectomy, axillary dissection plus external radiotherapy (50 + 10 Gy). The appearance of the patients' breasts was analysed for symmetry by computer, and differences in symmetry were correlated with tumour location and breast size. A subjective assessment was given by a 3-member panel and the results were correlated with objective measurements. In addition, patients were asked to fill out a self-assessment questionnaire on the aesthetic result of the operated breast. Better results were generally noted in the group of patients treated by more conservative surgery. Substantial differences in the aesthetic outcome were noted between the patient's own evaluation, the computer's measurement of symmetry and the assessment of the panel of observers.

Adult↗
PubMed1991

Evaluation of resection margins after breast conservative surgery with monoclonal antibodies.

An immunocytochemical method for the detection of cancer cells, in the cell suspension obtained by scraping the surface of the surgical resection margins is described and its sensitivity compared to the conventional histology performed on random biopsies from the same margins. The reactivity of the cells with a pool of monoclonal antibodies (Mab) directed against epithelial markers indicated that in 80% of the 42 cases tested, the scraping method was adequate for the gathering of cells from the margins. The analysis of the samples using B72.3 Mab specific for tumor cells revealed that, among B72.3-positive tumor cases, 31% of breast margins contained tumor cells, whereas only 12% were histologically positive. Our results indicate that the immunocytological methodology is therefore more sensitive and should be used alongside histological examination to detect the tumor contamination in the surgical resection margins.

Antibodies, Monoclonal↗
PubMed1991

Preoperative localization and surgical approach in 344 cases of non-palpable breast lesions.

From June 1985 to August 1989, 344 cases of mammographic non-palpable breast lesions were operated on at the National Cancer Institute in Milan. The mammographic findings consisted of clusters of microcalcifications in 162 cases (42.1%), suspicious opacities with irregular borders in 116 cases (37.7%) and opacities containing microcalcifications in 66 cases (19.2%). The mean age of the patients was 51 years (range 31-77 years). In all patients localization was performed 1 day before the operation, introducing a self-retaining anchor wire into the mammary parenchyma. The histological findings showed benign breast disease in 184 cases (53.4%); proliferative dysplasia without atypia in 150 cases (81.5%); proliferative dysplasia with atypia in 22 cases (12%); fibroadenoma in nine and papilloma in three cases. Of 160 patients with carcinoma, 37 had non-infiltrating carcinoma: 28 of these cases (17.5%) had non-infiltrating ductal carcinoma and nine cases (5.6%) had lobular carcinoma in situ. In the 123 cases with infiltrating breast cancer the histological types were ductal infiltrating carcinoma (32.5%), lobular infiltrating carcinoma (9.8%), and 34.1% of the cases an associated or prevalent intraductal carcinoma was found. In 138 cases (85.6%) a conservative surgical procedure (quadrantectomy or more limited excision) was done, and in 22 (14.4%) cases a total mastectomy was necessary because of the extent of the disease. Axillary dissection was performed in 116 of the 123 patients with histological invasive carcinoma. Nodal metastases were found in 24 cases (20.7%), and only one node was involved in nine of the cases (37.5%), two to three nodes in nine cases (37.5%) and four to ten nodes in six cases (25%).

Adult↗
PubMed1990

Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more.

In 165 women with breast cancer who were candidates for mastectomy because the largest diameter of the tumor was 3 cm or more, we administered primary chemotherapy in the attempt to substitute conservative for mutilating surgery. We then systematically quantitated tumor reduction by clinical, radiologic, and histopathologic evaluations. Five consecutive groups of 33 patients received cyclophosphamide, methotrexate, and fluorouracil (CMF); fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC); or fluorouracil, epirubicin, and cyclophosphamide (FEC). The regimens for the five groups were as follows: group 1, three cycles of CMF; group 2, four cycles of CMF; group 3, three cycles of FAC; group 4, four cycles of FAC; and group 5, three cycles of FEC. In response to primary chemotherapy, 157 of the 161 assessable patients showed measurable tumor shrinkage; progressive disease was documented in four. Tumor shrinkage to less than 3 cm was documented in 127 (81%) of the 157 women subjected to surgery, thus allowing a breast-saving procedure, rather than modified radical mastectomy, in these 127 women. Histopathologic complete remission was documented in seven patients. Tumor response was unrelated to age, menopausal status, DNA content (ploidy), [3H]thymidine-labeling index, drug combination used, or number of treatment cycles in excess of three. The degree of response was inversely proportional to the initial tumor size, and the frequency of response was greater in receptor-negative tumors. Severe vomiting and hair loss were less frequent with CMF than with anthracycline-containing regimens, and the frequency of severe leukopenia and thrombocytopenia was minimal. Our results challenge the classical indication for primary mastectomy by showing that use of full-dose primary chemotherapy, sequentially combined with conservative surgery and radiation, can offer an effective and safe alternative to women concerned about the preservation of body integrity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Breast conservation is the treatment of choice in small breast cancer: long-term results of a randomized trial.

From 1973 to 1980, 701 women with small breast cancer (less than 2 cm in diameter) were randomized into two different treatments. 349 patients received classic Halsted mastectomy and 352 patients received quadrantectomy, axillary dissection and radiotherapy on the ipsilateral breast. 24.6% of the patients in the mastectomy group and 27.0% of the patients in the conservation group had axillary metastases. Overall 10 year survival was 76% in the Halsted patients and 79% in the quadrantectomy patients; 13 year survival was 69% and 71%, respectively. No differences were observed after analysis by site and size of the primary tumour and age of the patients. Patients with positive axillary nodes had consistently better survival curves in the quadrantectomy group compared with the Halsted group (not significant). Among the quadrantectomy patients there were 11 local recurrences (with 4 deaths) while among the Halsted patients, 7 had local recurrences (5 deaths). There were 19 cases of contralateral breast carcinomas in the quadrantectomy group and 20 in the Halsted group. At 16 years from the beginning of the trial no evidence of oncogenic radiation risk was observed. In patients with small size carcinomas total mastectomy should have no role.

Breast Neoplasms↗
PubMed1990

Quadrantectomy versus lumpectomy for small size breast cancer.

Between 1985 and 1987 quadrantectomy plus external radiotherapy and lumpectomy plus external and interstitial radiotherapy were compared in a randomized trial of patients with small carcinomas of the breast. Quadrantectomy involves excision of 2-3 cm of normal tissue around the tumour plus the removal of a sufficiently large portion of overlying skin and underlying fascia whilst lumpectomy removes only the tumour mass with a narrow margin of normal tissue. Patients in both groups also received total axillary dissection. 705 cases were evaluable, 360 quadrantectomies and 345 lumpectomies. No differences in distant metastases and survival were observed in the two groups. However, lumpectomy patients had a much higher frequency of local recurrences (7.0 vs. 2.2%). Since a local recurrence needs a second operation and creates severe psychological distress to the patient, conservative surgical procedures should include generous excision of normal tissue around the primary carcinoma plus intensive postoperative radiotherapy.

Breast Neoplasms↗
PubMed1990

Evidence that receptor-linked G protein inhibits exocytosis by a post-second-messenger mechanism in AtT-20 cells.

In AtT-20 cells somatostatin inhibits the secretion of adrenocorticotropic hormone (ACTH) through the activation of GTP binding proteins (G proteins) linked to second messengers such as calcium and cyclic AMP (cAMP). Recently, it has been proposed that there may be G proteins that regulate directly the exocytotic machinery. We have investigated whether somatostatin could inhibit secretion at a step distal to second messengers through a GTP binding protein. For these studies two experimental paradigms were used: (1) intact cells stimulated by calcium ionophores and (2) digitonin-permeabilized cells exposed to buffers of increasing Ca2+ concentrations. Somatostatin inhibited by 70% the ACTH release caused by the calcium ionophore ionomycin without modifying the ionophore-induced elevation in cytosolic [Ca2+]. This effect was cAMP independent because (1) it was observed in the presence of high concentrations of membrane-permeant cAMP analogues, and (2) it was not accompanied by a change in cAMP levels. The effect was also independent of the levels of activators of protein kinase C because it could be produced in the presence of high concentrations of phorbol esters. The action of somatostatin was prevented by pertussis toxin. In digitonin-permeabilized AtT-20 cells somatostatin inhibited release induced by calcium buffers in a GTP-dependent manner. These two observations indicate the involvement of a G protein. It is proposed that a G protein coupled to somatostatin receptors inhibits the intracellular machinery of secretion at a step distal to second messengers, perhaps at the exocytotic site.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Conservative treatment of early breast cancer. Long-term results of 1232 cases treated with quadrantectomy, axillary dissection, and radiotherapy.

One thousand two hundred and thirty-two women with invasive breast cancer lesions measuring less than 2 cm in diameter, clinically assessed as T1N0-1M0, were treated from 1970 to 1983 at the National Cancer Institute of Milan with quadrantectomy, axillary dissection, and radiotherapy (QUART). Pathologic evidence of lymph-nodes metastases was found in 32% of the patients. Overall survival at 5 and 10 years from surgery was 91% and 78%, respectively. The cumulative probability of survival tends to decrease with increasing tumor size: the 7-year survival rate was 84% in cases in which lesions measured from 1.6 to 2.0 cm, and 94% in cases in which the lesions were less than 0.5 cm. Tumor site in the treated breast did not affect distant outcome. No difference was found between the patients without node metastases and patients with one node involved, whereas the patients with more than one node showed a lower probability of survival. The survival curves of 352 cases treated inside a randomized trial and that of 880 cases routinely treated appear to be superimposable. Local recurrences and new primary ipsilateral tumors were, respectively, 35 (2.8%) and 19 (1.6%); 56 women with local recurrences or second tumors underwent second surgery (total mastectomy, 43; wide resection, 11). Five of them died from distant spread of breast cancer, while 49 are alive and well. In the contralateral breasts 45 carcinomas were recorded during the follow-up time. The results of the present analysis of a large number of T1 cases reconfirm the safety of integrated radiosurgical conservative treatments.

Adult↗
PubMed1990

Extent of metastatic axillary involvement in 1446 cases of breast cancer.

One thousand, four hundred and forty-six patients with carcinoma of the breast treated with Halsted mastectomy (167), Patey mastectomy (732), and conservative surgery with axillary dissection, either at the same time (340), or separately (207), were evaluated with regard to the number and distribution of axillary lymph nodes. A total of 29,378 were removed and examined, on average 20.3 per patient. The average number of nodes was 13.5 at the first level, 4.5 at the second and 2.3 at the third. The same number of nodes were removed in patients treated with extensive surgery, such as Halsted mastectomy and limited surgery such as lumpectomy and in independent axillary dissection. In 839 cases metastases were found in the axilla. The average number of involved nodes was 6.4. Out of 839 patients, the first level was the site of metastases in 828, the second level in 364 and the third in 187. When a single lymph node was involved, it was nearly always at the first level. In only 11 cases, were the second and/or third levels invaded without metastases at the first level. Therefore, the percentage of cases with skipping metastases was very low (1.3%). It appears from the present data that the spread of breast cancer to the axilla follows a regular pattern; the first level is invaded first, whilst in most cases, the second and third levels are involved only when the first is substantially affected.

Adult↗
PubMed1989

G protein-linked receptors in the thyroid.

The FRTL5 cell line has the advantage that its hormonal activation leads to important and measurable thyroid function such as the transport of iodide and the iodination of thyroglobulin. Secondly, the coexistence in the plasma membrane of these cells of several physiologically relevant receptors (TSH, alpha 1-adrenergic, M1 and M2 muscarinic, insulin, IGF1) coupled to at least three transducing enzymes (adenylyl cyclase, PLC, PLA2) gives the possibility to analyze the interaction among second messengers in the cell activation process. This has allowed us and others to show that in the case of the iodide efflux regulation at least two second messengers (Ca++ and arachidonic acid) mediate the adrenergic stimulation, whereas the TSH activation of the same phenomenon probably uses other signals in addition to Ca++ and arachidonic acid. Growth is mostly regulated by TSH, that activates the adenylyl cyclase by a mechanism that may involve the modulation of the availability of Gi. TSH is also able to regulate an endogenous ADP ribosyl transferase in FRTL5. This could be a novel mechanism of cell regulation by this hormone, but the role of this phenomenon in the physiological action of TSH is still unclear.

Adenylyl Cyclases↗