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Biomedical subjects

A Piffanelli

Publications and source records attributed to A Piffanelli.

At least 55 records · Page 3Linked to original sources

Relationship between epidermal growth factor receptor and other prognostic factors in gynecological cancers.

In 62 cases of gynecological malignancies, 16 of the ovarian, 31 of the endometrium and 15 of the cervix, the EGF-R status was evaluated in order to establish its prognostic value and its correlation with other classical prognostic factors. We have failed to demonstrate any correlation between EGF-R status and stage, grade and hormonal receptors, ER/PgR, in ovarian and cervical cancer. In contrast, in endometrial cancer, we observed significantly lower levels of EGF-R in poorly differentiated tumors. Moreover, a weak negative relationship between EGF-R and PgR status was found. Regarding survival, we noticed a better prognosis in patients with ovarian cancer EGF-R positive, but without statistical significance.

Adult↗

[Nuclear medicine in the integrated diagnosis of fatigue fractures].

Nuclear medicine applications deal with the functional and dynamic study of organs and apparatuses in each diagnostic protocol. Bone scintigraphy (diagnostic accuracy: 80%) plays an important role in the differential diagnosis of the various musculoskeletal conditions in sports, mainly in the so-called "stress syndrome". The method is rather simple, including three steps: 1) study of radioactivity in the ROI; 2) capillary phase, with early imaging; 3) bone phase, with a static image 5 hours after injection. Slight differences in marker uptake, with fusiform and elongated marker accumulation areas, can be seen in the tibial stress syndrome, which exhibits no increase in the vascular phase, while in stress fractures, mainly in the late stages, increased activity can be seen in the arteriolar and capillary phases. Stress fractures are divided into 5 stages, from stage 1 = < 20% skeletal involvement to stage 5 = complete fracture, with > 80% bone involvement. The advantages of 3-phase bone scintigraphy can be summarized as follows: 1) it yields objective information, where clinics and radiology are often negative; 2) it allows the differential diagnosis between soft tissue lesions and bone fractures even in an early stage; 3) it allows prognosis to be made and the resumption of sport activity to be planned.

Athletic Injuries↗

Cytosol cathepsin-D content and proliferative activity of human breast cancer. The Comitato Italiano per il Controllo di Qualita del Laboratorio in Oncologia.

Mitogenic properties have been demonstrated in vitro for the lysosomal acidic protease cathepsin-D (cath-D). We investigated possible relationships between cath-D cytosol cell content and tumor proliferative activity in a series of 129 operable breast cancer patients. For total cytosol cath-D evaluation, a solid phase two-site immunoradiometric assay was utilized on tumor cell cytosol obtained for hormone receptor assay (DCC method). The percentage of S-phase cells was analyzed by 3H-thymidine autoradiographic assay. Median 3H-thymidine Labeling Index (3H-Tdr-LI) of the series was 2.7%; median cath-D content resulted 57 pmol/mg of protein cytosol and was significantly higher in node-positive with respect to the node-negative subgroup (p < 0.03). When classified in low, intermediate or high tumor cath-D content and slow or fast proliferative activity (cut-off: median values of the series), no significant agreement was found between the two variables. Statistical analysis, however, showed that a significant inverse correlation existed in node positive tumors between cath-D and 3H-Tdr-LI values which was even more evident in N-positive high estrogen receptor-positive (ER+) cases (coefficient of correlation = 0.6828; p = 0.0001). Cytosol cath-D content cannot be generally proposed as a direct marker of proliferative activity for operable breast cancer.

Breast Neoplasms↗

Quality control of cathepsin-D measurement by the EORTC Receptor Study Group.

Cathepsin-D is a lysosomal protease that can serve as an important prognostic cytosolic factor in breast cancer. To evaluate the performance of a commercially available immunoradiometric assay kit, 15 lyophilised cytosol participating EORTC laboratories for preparations containing various levels of cathepsin-D have been sent to 13 participating EORTC laboratories for quality control purposes. The between-laboratory variation, when expressed as coefficient of variation, did not exceed 24%. The within-laboratory variation was assessed by analysing five samples of the 15 specimens containing lyophilised material from a homogeneous cytosol pool. The mean within-laboratory coefficient of variation was 7%. Analysis of human breast tumour cytosols in one of the participating EORTC laboratories resulted in a median within-assay variation between duplicate measurements of 2.1% (n = 408), with a between-assay variation of a pooled human breast tumour cytosol of 4.6% (n = 11).

Breast Neoplasms↗

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen-receptor positive breast cancer patients. An update at 7 years of the 1st GROCTA (Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group) trial.

504 evaluable node positive oestrogen receptor (ER) positive breast cancer patients were randomly allocated to receive either 5 years tamoxifen treatment or chemotherapy [six courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 4 courses of epirubicin] or a combination of both treatments. At a median follow-up of 5 years tamoxifen appeared to be more effective than chemotherapy, the difference being highly significant in postmenopausal women. The addition of chemotherapy to tamoxifen was not able to significantly improve the results achieved by tamoxifen alone, irrespective of menopausal status. Trends were similar even after stratification for the number of involved nodes. The protective effect of tamoxifen in terms of reduction of the odds of death increased with time and no rebound phenomena on recurrence or death has occurred so far after the completion of tamoxifen treatment. Overall, the prognostic value of number of involved nodes and of progesterone receptor (PgR) status was confirmed by multivariate analysis. However, the predictive value of PgR was lost in patients receiving tamoxifen alone. Similarly, the degree of ER positivity was not predictive of the response to tamoxifen. Tamoxifen treatment should still be regarded as the gold standard for postmenopausal ER positive patients. In younger women the antioestrogen proved to be safe and at least as effective as chemotherapy. However, the analysis of the annual risks suggests that the concurrent or the sequential use of chemotherapy and tamoxifen might represent a more appropriate treatment for this patient subset, particularly for those with four or more involved nodes. Different cut-offs of ER and PgR assays from those we have arbitrarily employed in the present analysis should probably be used to select more properly the patients who can benefit from endocrine therapy.

Adult↗

Steroid receptor assays: an Italian quality assessment program.

An Italian Committee for the quality assessment of steroid receptor assay was instituted in 1979; the number of laboratories participating in this program increased from 7 in 1979 to 43 in 1989. The Italian program in collaboration with EORTC (European Organization Research and Treatment of Cancer) initiatives, utilizes as working standards lyophilized samples that tolerate prolonged storage at 4 degrees C. The national representatives agreed, according to EORTC, that all laboratories would perform, for measurement of steroid receptors, the dextran coated charcoal (DCC) method using the same concentration of radioactive ligands (3-H-estradiol, 3-H-ORG-2058) and would determine the non-specific binding with the same compounds (diethylstilbestrol and ORG-2058). The computation method is a potential source of interlaboratory variation; the multipoint Scatchard analysis, though difficult to apply for receptor problems, is the most widely used approach at present. The standardized DCC method is the most common and recognized (Food and Drug Administration) procedure for quantifying hormone receptor in human cancer. Since new technologies are being introduced (receptor enzyme immunoassay, EIA), adequate programs of quality assessment are required; in general, it has demonstrated an excellent correlation between radioligand binding assay (DCC) and immunochemical assay (EIA). Other prognostic factors, such as proteins produced by oncogenes and growth factors of the malignant cells have become more important. Some of these factors, as well as estrogen receptor status, seem the major determinants of recurrence after the first treatment.

Antibodies, Monoclonal↗

Regulation of progesterone receptor gene expression.

The levels of progesterone receptor (PR) mRNA, PR protein, and [3H]R5020 binding activity were measured in parallel experiments conducted on a T47D subline expressing the estrogen receptor. A significant increase of PR mRNA levels could be detected within 6 h of exposure of the cells to estradiol (10(-8) M). The changes in mRNA, however, did not lead to any variation of PR protein levels of [3H]R5020 binding activity. A parallel analysis of PR mRNA and [3H]R5020 binding was then performed in a series of tumor biopsies. In estrogen receptor-positive and PR-positive tissues a correlation among the two values was found. It is postulated that the above mentioned data could reflect the existence of a difference in the mechanisms controlling the numerous steps of the PR synthesis in the various hormone-responsive tissues. This variability could allow an organ-specific response to the cyclic changes of circulating hormone.

Blotting, Northern↗

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.

Between November 1, 1983 and June 30, 1987, 510 node-positive, estrogen receptor (ER)-positive breast cancer patients have been randomly allocated to receive either chemotherapy (six intravenous [IV] cyclophosphamide, methotrexate, and fluorouracil [CMF] courses followed by four IV epirubicin courses) or 5 years of tamoxifen treatment or a combination of both therapies. After a median follow-up of 40 months, patients receiving the combined treatment achieved the best results, and those treated with chemotherapy alone achieved the worst, the difference being particularly evident in postmenopausal women. However, while the concurrent use of chemotherapy and tamoxifen did improve the results achieved by chemotherapy alone, particularly in postmenopausal women and in those with four or more involved nodes, it did not significantly improve the results achieved by tamoxifen alone, particularly in patients with higher ER tumor concentrations. Side effects were more numerous and more severe in patients receiving chemotherapy (with or without tamoxifen). Our findings, although still preliminary, confirm that tamoxifen should be the treatment of choice for postmenopausal breast cancer patients with node-positive, ER-positive tumors. In addition, the findings suggest that tamoxifen may represent a safe alternative to chemotherapy (at least to the cytotoxic regimen we used) for younger women, provided they have ER-positive tumors. In patients with ER-positive tumors, the addition of chemotherapy to tamoxifen does not seem to improve significantly the effectiveness of tamoxifen alone.

Adult↗

Characterization of laboratory working standard for quality control of immunometric and radiometric estrogen receptor assays. Clinical evaluation on breast cancer biopsies. Italian Committee for Hormone Receptor Assays Standardization.

The objective of the study was to characterize a low-cost and reliable working standard material for quality control of estrogen receptor (ER) determination with dextran-coated charcoal (DCC) and enzyme immunoassay (EIA) methods. Human fibromatous uterine lyophilized cytosol demonstrated good characteristics of stability and applicability for this purpose. Eleven laboratories participated in the intralaboratory and interlaboratory quality control study, and they achieved slightly higher coefficients of variation for ER-EIA (interlaboratory, 37.7%; intralaboratory, 22.9%) than for ER-DCC (interlaboratory, 24.2%; intralaboratory, 15.7%). There was an excellent correlation between ER results with ER-EIA and ER-DCC for 268 breast cancer biopsies. Quality assurance for ER assays using DCC techniques and immunometric methods with monoclonal antibodies (ER-EIA) can be set up with this available material of human origin to satisfy the characteristics of both techniques and the species specificity of monoclonal antibodies.

Breast Neoplasms↗

Selection of high-risk groups for breast cancer screening. Evidence from an Italian multicentric case control study.

In recent years techniques for the selection of risk groups for high priority breast screening have been evaluated. We used data from a large multicentric case control study in Italy, recently published, to fit a reduced logistic model for predictive purposes, using variables which are easily collected. The predicted probability of being a case obtained through the logistic analysis was then used to classify the same set of data by calculating values of sensitivity and specificity at different cutoff points of the predicted probability. The results showed the low predictive power of the model. The selection of higher risk groups in a screening population program is discussed.

Adult↗

Amiodarone and thyroid status in refractory arrhythmias.

Out of 20 subjects selected for refractory arrhythmias, amiodarone therapy (200 mg/day) was efficacious in 85%. No statistically significant variations in electrocardiographic parameters (QTc) were observed; similarly, there was little evidence of side effects 1 year after initiation of treatment. These results were most likely due to the low daily dosage administered. We observed: 1) a significant increase in rT3 levels; 2) a decrease in TT3; 3) a uniform homeostasis of free fraction (FT3;FT4) These effects are all characteristic patterns of a "Low T3 Syndrome". The dosage of circulating amiodarone in 6 patients with borderline hormonal status (3 hyper- and 3 hypothyroidism) was not found to be an efficacious test for therapeutic monitoring. Identification of a statistically significant linear regression relationship between cumulative dose of amiodarone and rT3 levels may be a useful test in clinical practise for establishing more appropriate therapeutic dosages. Furthermore, it provides a guideline for threshold levels (maximum rT3 = 100-110 ng/dl) which are in close association with several side effects.

Adult↗

A new approach to the quality control of steroid receptor assays.

Lyophilized cytosols prepared from calf uterus and human breast tumor tissue are commonly used to assess the reliability of routine steroid receptor assays. However, preanalytical error (sample preparation, storage, homogenization) cannot be detected in this way. Participating laboratories were asked to mail us all their receptor results obtained over a four-month interval, and to include some information about the patients involved (age, menopausal status, nodal status). After verifying the homogeneity of the populations investigated, we computed consensus means for the percentages of positive samples and for their absolute value. Despite the homogeneity of the characteristics of the populations studied, results from some laboratories systematically differed from the consensus mean. This approach to the quality control of steroid receptors allows evaluation of the whole procedure, from sample preparation to analysis, and thus may be helpful as an addition to the usual practice of distribution of cytosols and tissue powders for assay.

Age Factors↗

Testis cytological structure, plasma sex steroids, and gonad cytosol free steroid receptors of heterologous gonadotropin (hCG)-stimulated silver eel, Anguilla anguilla L.

Complete testicular maturation was induced in silver eels, kept at 24 degrees in fresh water, by a single injection of 1000 I.U. of heterologous gonadotropin (hCG). Each week, for 4 weeks, some eels were examined for testis structural pattern, plasma sex steroids, and gonad cytosol steroid receptors. The first effect of the hCG was on the tubular organization of the testis, followed by spermatogenesis. Plasma androgens were not detectable in the untreated eels, whereas a peak was detected a week after in those treated with the injection and afterward a decline. Plasma progesterone and estradiol showed a peak 2 weeks after treatment. Untreated eel gonads showed a high content of cytosolic free estradiol receptors which disappeared in the hCG-treated ones, a peak of free progesterone receptors was found 1 week after injection. The results are discussed in relation to the differentiation and maturation of eels testes.

Anguilla↗