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Biomedical subjects

M Gion

Publications and source records attributed to M Gion.

At least 55 records · Page 3Linked to original sources

Relationship between prostatic acid phosphatase and prostate-specific antigen serum levels and prostatic volume in benign prostate hyperplasia. Pitfall on tumor markers assessment in primary prostatic cancer?

Serum levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were measured in 78 patients with benign prostate hyperplasia and compared with both the gland weight and the glandular component of prostatic tissue. Both PAP and PSA were significantly higher where prostate was heavier; however, we could not find a consistent factor which could correlate weight increase to marker levels. PSA tended to be higher when glandular component was more expressed. From the present findings we conclude that in patients with prostate cancer, PAP and PSA serum levels should be investigated considering also the benign components of prostate gland.

Acid Phosphatase↗

Comparison between single saturating dose ligand binding assay and enzyme immunoassay for low-salt extractable oestrogen and progesterone receptors in breast cancer: a multicentre study.

An excellent correlation between ligand binding assay (LBA) and enzyme immunoassay (EIA) for both oestrogen (ER) and progesterone (PR) receptors has been reported. Nevertheless, considering that the clinical value of any discrepancy between LBA and EIA probably varies with the receptor level, we undertook a collaborative study in which a single saturating dose (SSD) LBA and EIA were compared in different ER and PR dose ranges. The values of ER measured by EIA were higher in tumours with low or intermediate receptor content, causing a misclassification of ER status in 9% of cases (ER+: 77.5%, EIA, 68.8% SSD). In the case of ER, EIA values tended to be higher than SSD in all centres. For PR, EIA and SSD were generally more comparable (PR+: 66.0% EIA, 72.0% SSD, discordance rate 6%), with EIA showing, however, different trends in different centres. PR concentration was not significantly different in ER SSD-/EIA+ and in ER SSD+/EIA+ cases, suggesting that EIA detects at least in part integer ER. We conclude that although EIA may be a reliable methodological alternative to SSD, the two methods are not interchangeable until effective cut-off levels for clinical decisions are assessed for EIA.

Adult↗

The tumour associated antigen CA15.3 in primary breast cancer. Evaluation of 667 cases.

CA15.3 preoperatory serum levels have been determined in 667 patients with primary untreated breast cancer and in 193 controls. The relationships between CA15.3 and several clinical and pathological parameters were evaluated. CA15.3 levels showed a highly significant direct relationship with stage, T, pT, N and the number of positive lymph nodes. The close relationship between CA15.3 and the number of positive lymph nodes was also demonstrated in a subgroup of 406 patients in which more than ten lymph nodes had been examined. CA15.3 levels were correlated with tumour size in patients without axillary metastasis as well as with the number of positive lymph nodes in pT1 tumours. CA15.3 was significantly higher in medullary than in ductal carcinoma. No relationships were found between serum CA15.3 and receptor status. We conclude from the present findings that CA15.3 in primary untreated breast cancer is a marker of tumour burden as well as of the tendency of local invasiveness (relationship between CA15.3 and nodal status in pT1 tumours).

Adult↗

Epidermal growth factor receptor in lung malignancies. Comparison between cancer and normal tissue.

Epidermal growth factor receptors (EGFr) were measured using a radioligand binding assay, in membrane preparations from 51 human non-small cell lung cancers and in normal tissue of the same patients. The binding characteristics of EGFr were similar in tumour and normal lung membranes (range of dissociation constant of high affinity sites: 0.1-0.6 nM). However, the concentrations in tumours (median, 16.4 fmol mg-1 of protein; range, 1.5-176) were significantly higher than in normal tissues (median, 7.4 fmol mg-1 of protein; range, 1.9-13.4). The receptor levels in normal tissue were normally distributed. It was therefore possible to define a normal/pathologic cut-off level (12.9 fmol mg-1 of protein). In 57% of cases EGFr in cancer was higher than the cut-off. No relationships were found between receptor concentrations and positivity rates of EGFr and histology, stage, lymph node positivity and pT. A trend for a direct relation between receptor positivity and grading was found.

Aged↗

Tumor-associated trypsin inhibitor (TATI) in primary esophageal carcinoma.

Esophageal carcinoma has a catastrophic clinical course with a very low 5 year survival rate of 5%. A circulating tumor marker with good specificity and sensitivity would be useful in the management strategy of the disease. So far, no tumor marker effective in esophageal carcinoma has been identified. Preliminary reports suggest satisfactory positivity rates of tumor-associated trypsin inhibitor (TATI) in esophageal carcinoma. We measured TATI levels in 71 patients with primary squamous cell esophageal carcinoma as well as in 30 tissue samples from both carcinoma and normal esophageal mucosa. Detectable TATI levels were not found in tumor tissue samples. The marker showed significantly higher serum levels in patients than in controls, with an overall positivity rate of 28%. TATI levels were significantly lower in patients with a high number of tumor-positive lymph nodes. No relationship was found between TATI and several other clinical and pathological parameters. High TATI levels correlated with a lower probability of overall survival as well as in cases without clinical evidence of lymph node metastases. TATI did not show any relationship with CEA, TPA, ferritin or SCC. The results of the present study suggest that TATI shows a satisfactory positivity rate in esophageal carcinoma, and TATI levels are related to local disease spread and prognosis.

Biomarkers, Tumor↗

Is tissue polypeptide antigen still a useful tumor marker in breast carcinoma? Comparison with CA15.3 and MCA.

Serum levels of tissue polypeptide antigen (TPA) are related to the proliferative activity and to the mass of the malignancy, differently from any other available tumor marker. We therefore evaluated TPA in comparison with CA15.3 and MCA (mucinous-like carcinoma-associated antigen) in patients with primary breast cancer. TPA was measured in tumor cytosol and in serum. Cytosol and serum TPA levels were not significantly correlated. Serum TPA was higher in patients with locally more advanced disease and in receptor-negative cases. The relation between TPA and disease spread was not directly dependent on tumor bulk, whereas CA15.3 and MCA were highly correlated to the number of positive lymph nodes and tumor size. No correlations were found between TPA and CA15.3 or MCA, and the positivity concordance rate between TPA and CA15.3 or MCA was very low. Patients with higher TPA serum levels showed a worse prognosis in cases with and in those without axillary metastases. From our data we conclude that TPA provides information different from that obtained with breast-specific tumor markers and could therefore be useful in association with CA15.3 and/or MCA in the management of patients with breast cancer.

Adult↗

Tissue polypeptide antigen in tumor cytosol: a new prognostic indicator in primary breast cancer.

The assessment of the risk of relapse is a critical need in the management strategy of breast cancer patients. To date, the most reliable prognostic factor is axillary nodal status. Several other pathological and biological parameters are currently under evaluation. Since 1982 we have been studying the prognostic role of several tumor markers in breast cancer cytosol. Elevated cytosol concentrations of tissue polypeptide antigen (TPA) have been found to have a highly significant direct correlation with both prolonged relapse-free interval (RFI) and higher survival rate. The information provided by cytosol TPA was independent of both axillary nodal status and steroid receptor content. In patients with a low risk of relapse (no axillary metastases, estrogen and progesterone receptor positive), cytosol TPA was still a significant prognostic indicator.

Adult↗

Radioligand binding assay of epidermal growth factor receptor: causes of variability and standardization of the assay.

Although experimental evidence indicates a probable role of epidermal growth factor receptor (EGFr) in clinical oncology, no standardized method for its determination has been yet described, and discrepant results have been reported in clinical studies. In standardizing a radioligand binding assay for EGFr, we evaluated the causes of variability in each step of the assay. Entrapment of EGFr in the nuclear fraction and contamination of the crude membrane fraction by cytosol protein were eliminated through preliminary purification steps. Both Scatchard and Rosenthal analysis of the saturation reaction of the membrane fraction with a wide range of concentrations of 125I-labeled EGF revealed a double class of binding sites. Study of the saturation reaction showed a partial exchange of 125I-labeled EGF with endogenous EGF within 20 h. The present method--incubation of partly purified membrane fraction with 125I-labeled EGF, 0.5 nmol/L, with and without 100-fold excess of cold EGF, for 20 h at 26 degrees C, followed by centrifugation at 5000 x g for 30 min to separate membrane-bound 125I-labeled EGF--shows good sensitivity, precision, and accuracy; is reasonably simple; and may be suitable for routine clinical use.

Analysis of Variance↗

Tumor markers in serum of patients with primary squamous cell carcinoma of the esophagus.

Serum levels of several tumor markers were studied in 96 patients with untreated primary squamous cell carcinoma of the esophagus. Three markers specific for digestive tract malignancies--CEA, CA19.9 and CA50--and two non organ specific indicators of malignancy--ferritin and TPA--were evaluated. Positivity rates of CA19.9 and CA50 were very low (4.4% and 8.6% respectively); the markers were therefore considered ineffective in the disease. CEA, TPA and ferritin showed a fair positivity rate (27.1%, 28.1%, 33.7% respectively); CEA and TPA were directly related to clinical stage, CEA levels being significantly higher in stage IV than in stage III cases (p = 0.016). TPA preoperatory levels were also directly related to a lower survival probability (p = 0.004). CEA showed significantly lower levels in tumors of lower than in those of middle (p = 0.03) and upper esophagus (p = 0.004). TPA showed a similar behaviour with lower levels in tumors of lower than of middle esophagus (p = 0.03). These findings could be due to a bulky metabolism of tumor markers drained via portail vein in the liver. From our data the following conclusions may be drawn: 1) CEA and TPA may be useful in the staging of esophageal cancer as an ancillary tool to assess the extent of the disease; 2) tumor location is an important variable when evaluating blood levels of tumor markers in patients with esophageal cancer.

Adult↗

A mucinous-like carcinoma-associated antigen (MCA) in the tissue and blood of patients with primary breast cancer.

The monoclonal antibody (MAb) b12 raised against human breast cancer cell lines was found to identify an epitope of a mucinous-like carcinoma associated antigen (MCA) that is strongly represented on breast tumor cells. The b12 MAb was used to develop an enzyme immunoassay (EIA) kit. MCA levels were measured with the EIA method in the cytosol of both breast cancer and normal breast tissue as well as in the blood of 147 patients with primary breast cancer and 92 healthy subjects. MCA cytosol levels were significantly higher in carcinoma than in normal breast tissue cytosol samples. Higher MCA levels were found in the cytosol of tumor without lymph nodal involvement. The 95th percentile of the MCA value distribution in the healthy control group (11.0 U/ml) was chosen as negative/positive cut-off level. The overall positivity rate in breast cancer group was 26.5% with MCA showing a trend toward higher levels in patients with more advanced disease. Significantly higher levels were found in patients with a higher number of positive lymph nodes.

Adult↗

Tumor marker radioimmunoassays in gastric juice. Methodologic drawbacks due to pH variations.

Conflicting data have been reported on tumor marker determination in gastric juice. In the present study the effect of pH variations on both antibody-antigen binding and the immunologic stability of the antigen were evaluated for the radioimmunoassay of carcinoembryonic antigen, CA19-9, tissue polypeptide antigen, and ferritin. A significant inhibition of antibody-antigen binding was constantly found in acidic conditions. Antigen concentration was lower in acidified than in untreated samples, possibly due to the carryover of acidity in the incubation mixture. Neutralization of acidified samples partly improved recovery of carcinoembryonic antigen and CA19-9. Tissue polypeptide antigen and ferritin were not recovered by neutralization in samples with pH less than 4.5, suggesting an irreversible damage of the immunologic characteristics of the two antigens. From the present data we conclude that an accurate validation of methods and a rigorous standardization of sample collection are mandatory for tumor marker determination by radioimmunoassay in gastric juice.

Antibodies, Monoclonal↗

Carcinoembryonic antigen, ferritin, and tissue polypeptide antigen in serum and tissue. Relationship with the receptor content in breast carcinoma.

In 225 primary breast carcinomas the concentrations of carcinoembryonic antigen (CEA), ferritin, and tissue polypeptide antigen (TPA) were determined by radioimmunometric assays both in serum and in cytosol. The relationship of the three markers with the receptor content of the tumor was evaluated. No relationships were found between the serum level of each marker and the receptor status. In the cytosol, ferritin was higher in receptor-negative than in receptor-positive cases, whereas CEA and TPA showed significantly higher values in receptor-positive than in receptor-negative patients. Moreover, a direct relationship was found between estrogen receptor and both CEA and TPA and between progesterone receptor and TPA. Even if the significance of these findings is still unclear, from our data it can be concluded that there exists a noncasual relationship between the receptor status and the cytosol content of CEA and, particularly, TPA.

Antigens, Neoplasm↗

Estrogen and progesterone receptors in breast carcinoma and in nonmalignant breast tissue.

Since 1983 we have studied the relationship, in the same patient, between receptor status in breast carcinoma and in nonmalignant breast tissue. Fifty patients have been evaluated to date. The total unoccupied cytosol estrogen and progesterone receptors were determined by a dextran-coated charcoal method. In nonmalignant breast tissue we found a measurable receptor concentration above the sensitivity of the method in 62% of cases for estrogen receptors and in 44% of cases for progesterone receptors. No relationships were found between the receptor level of each tumor and that of the corresponding benign tissue. The data suggest that the levels of the receptors in the tumor and in the nonmalignant tissue are totally independent.

Breast↗

Aldosterone regulation in primary aldosteronism: differences between adenoma and bilateral hyperplasia.

1. The diurnal patterns of plasma aldosterone, plasma renin activity (PRA), cortisol and adrenocorticotrophic hormone (ACTH) in the supine and in the upright position have been studied in fourteen patients with primary aldosteronism, five with adenoma and nine with bilateral hyperplasia. Blood samples were drawn at intervals from 6 h to 30 min. 2. Supine patients with an adenoma showed marked diurnal variations of aldosterone, with maximal values at 08.00 hours and minimal values of 18.00 hours and secretory spurts beginning after 02.00 hours. Plasma cortisol paralleled aldosterone, and ACTH seemed to anticipate aldosterone and cortisol variations; PRA remained unchanged. In patients with hyperplasia, aldosterone was significantly lower than in the adenoma group at 08.00 hours, and its decline during the day was less marked; fluctuations rather than secretory episodes were seen. 3. After patients assumed the upright posture, aldosterone remained unchanged or decreased in patients with adenoma, whereas it significantly increased in hyperplasia; PRA remained low, although a slight increment was seen in the latter group. The different response of aldosterone in the two groups was not modified by the administration of propranolol, apparently excluding a renin-dependent mechanism. On the other hand, dexamethasone seemed to affect the response of aldosterone to the upright posture in both groups; in adenoma there was a slight but significant increase, and in hyperplasia the usual rise was partially suppressed. 4. It is concluded that ACTH has a predominant role in regulating aldosterone secretion in primary aldosteronism due to adenoma, whereas its action in bilateral hyperplasia is only permissive.

Adenoma↗

[Effect of diazoxide on blood pressure, PRA and plasma aldosterone in hypertensive patients (author's transl)].

Intravenous diazoxide (300 mg) was administered to 29 hypertensive patients previously classified in subgroups according to their plasma renin and urinary aldosterone levels. The blood pressure was measured before and periodically after injection and plasma renin activity (PRA) and plasma aldosterone before and after 2 hours. The mean systolic and diastolic blood pressure fell notably from 193/118 to 155 93 mmHg; whereas PRA increased from 7.51 to 13.21 ng/ml/3 hrs and plasma aldosterone did not change significantly (71.3 and 102.8 ng%). Examining the individual sub-groups, a significant decrease in blood pressure was observed in 15 patients with low, posture unresponsive PRA, both in subjects with normal urinary aldosterone and those with surgically proven primary aldosteronism. In the former only the mean PRA showed a slight but sigificant increase, while in the latter the changes for both PRA and aldosterone were not significant. In the subgroups of patients with normal renin and urinary aldosterone the arterial pressure also significantly and promptly decreased. However, in this group the mean PRA substantially increased whereas the plasma aldosterone levels remained constant. The same blood pressure decline was observed in those patients with high PRA and aldosterone, including 1 case of pheocromocytoma. The mean PRA showed a further modest increase while the plasma aldosterone did not change significantly. These results indicate that the antihypertensive action of diazoxide is similar in the different types of hypertension (volume, vasoconstrictor or mixed form according to Laragh's classification), being independent of the basal plasma renin and aldosterone levels. Furthermore, the response of the blood pressure to diazoxide is not related in any way to the induced changes in PRA and plasma aldosterone values.

Adrenal Gland Neoplasms↗

Comparison of immunoassays for tumor markers CA 19-9, CA 15-3 and CA 125: data from an international quality assessment scheme.

Data collected in the 1993 and 1994 cycles of an international external quality assessment (EQA) program and in a national multicenter collaborative study were cumulatively analyzed to evaluate the standardization of the methods currently in use for the assay of mucinous tumor markers CA 19-9, CA 15-3 and CA 125. On average the between-laboratory variability was 15.2 and 16.0 CV% for CA 15-3 and CA 125 respectively; the between-laboratory variability found for CA 19-9 was markedly worse (mean 28.3 CV%). The variability component attributable to systematic differences between different methods/kits was relatively small for CA 15-3 and CA 125 (18% and 24% of the total variability) but markedly larger for CA 19-9 (48% of the total variability). The agreement of CA 19-9 results worsened in the last few years when new nonisotopic techniques became available. The precision of the methods/kits most used in the survey ranged from 9.9 to 13.3 CV% for CA 125 and from 11.6 to 13.9 CV% for CA 15-3. For these two tumor markers the precision of the traditional IRMAs does not appear different from that of the new fully automated nonisotopic techniques. The precision of CA 19-9 methods was on average worse (from 11.7 to 19.6 CV%) although two automated systems exhibited a precision better than that of IRMAs. In conclusion, the results of this study indicate that CA 15-3 and CA 125 are satisfactorily assayed whereas CA 19-9 assay appears affected by larger differences between methods and by poorer precision of laboratories and kits.

Antigens, Tumor-Associated, Carbohydrate↗

Preliminary results of clinical evaluation of the free/total prostate-specific antigen ratio in a multicentric study.

AIMS AND BACKGROUND: The free/total (F/T) prostate-specific antigen (PSA) ratio is probably the most promising tool proposed to increase the specificity of PSA in the diagnosis of prostate cancer. The aim of the present study was to evaluate the clinical value of the F/T ratio in 138 patients with benign hyperplasia, 101 with untreated prostate cancer, and 176 apparently healthy men. METHODS: We used a new immunometric assay of free PSA (FPSA-RIACT, CIS Diagnostici, Italy) which has shown good analytical performance; sample handling and storage under routine conditions did not affect the antigen stability. RESULTS: The diagnostic efficiency of the F/T ratio was significantly better than that of total PSA. In patients with total PSA ranging from 4 to 10 ng/ml, at a specificity level of 95% total PSA showed a sensitivity of 7%, whereas the sensitivity of F/T increased to 70%. Using the F/T ratio as a decision tool in association with total PSA and considering all cases candidate to biopsy (total PSA greater than 3.79 ng/ml corresponding to the 95% level), we demonstrated a 35% reduction of total biopsies that would have been required on the basis of total PSA alone. CONCLUSIONS: The determination of the percentage of F/T serum PSA significantly improves the specificity of the marker, particularly in the 4-10 ng/ml dose range where unnecessary prostate biopsies can be reduced.

Analysis of Variance↗