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Biomedical subjects

M Ferdeghini

Publications and source records attributed to M Ferdeghini.

At least 73 records · Page 4Linked to original sources

[Growth factors and oncogenes in development and carcinogenesis. Role of the epidermal growth factor system].

The processes of cellular proliferation and progressive acquisition of a specialized phenotype show a remarkable degree of coordination that involves both intracellular programming and intercellular communication. One of the major incentives for studying factors that regulate the processes of cellular proliferation and differentiation is the recognition of their potential contribution to tumorigenesis. In normal cells, stimulatory and inhibitory events are believed to be under the control of growth factors and growth inhibitory factors, which are known to be protooncogene products. Growth regulatory mechanisms usually involve the binding of a growth factor to a specific receptor on the cell surface, which then through an intracellular biochemical cascade leads to cell division. The cell regulation pathways initiated by growth factors may be subverted at several distinct levels in cancer cells. Studies of oncogenes have shown that they may function as abnormal growth factors or abnormal receptors, induce expression of potential signal regulators or encode proteins which modulate gene transcription. The purpose of the present paper is to examine the role of growth factors, growth factor receptors and intracellular proteins involved in signal transduction (with particular regard to the epidermal growth factor receptor system) in the control of normal growth and differentiation, and their contribution to transformation and tumorigenesis. We also review the classical theories of neoplasia and various other models. Chemical carcinogenesis and Vogelstein-Lane model are presented.

Amino Acid Sequence↗

Plasma parameters of the prothrombotic state in chronic uremia.

We measured plasma parameters of the prothrombotic state, namely thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA). D-dimer (DD), von Willebrand factor (vWF), tissue-type plasminogen activator (tPA), beta-thromboglobulin (beta TG), platelet factor 4 (PF4) and serotonin (5HT) in a series of 51 adult patients with chronic uremia: 22 were on maintenance hemodialysis (MHD) and 29 on conservative dietary treatment. Serum tumor necrosis factor alpha (TNF) was determined as well. Uremics presented significantly higher levels of TAT, FPA, DD, vWF, TNF, beta TG and 5HT than normal controls. Patients on conservative treatment showed lower levels of TAT, DD, TNF and beta TG than patients on MHD. Our results provide evidence that a prothrombotic state exists in chronic uremia and that MHD patients have a higher degree of hypercoagulation. Both hemodialysis procedure and uremia-related factors are likely to contribute to the hemostatic derangement.

Adult↗

Serum soluble interleukin-2 receptor assay in epithelial ovarian cancer.

Preoperative serum soluble interleukin-2 receptor (sIL-2R) and CA 125 levels were measured in 183 patients with ovarian masses undergoing laparotomy. Serum sIL-2R levels were higher in the 54 patients with epithelial ovarian cancer than in the 129 patients with benign ovarian diseases (p < 0.0001). Elevated serum levels of sIL-2R (> or = 71 U/ml) and CA 125 (> or = 83 U/ml) were found in 79.6 and 77.8% of patients with epithelial ovarian cancer, respectively. Serum sIL-2R and CA 125 positivity rates correlated with the FIGO stage (p = 0.0033 and p = 0.0001, respectively). Raised serum levels of sIL-2R and CA 125 were detected in 11.6 and 7.0% of patients with benign ovarian diseases, respectively. The combination sIL-2R or CA 125 had a sensitivity of 88.9%, and the association sIL-2R and CA 125 had a specificity of 98.4% for epithelial ovarian cancer. As for the 16 patients with this malignancy who were serially monitored during and after chemotherapy, changes in sIL-2R and CA 125 levels correlated with the clinical course of disease in 62.3 and 94.3% of 53 instances, respectively. In conclusion, the serum sIL-2R assay could represent a useful adjunctive tool for the differential diagnosis of ovarian masses, while it seems to be of limited benefit for monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer.

Adolescent↗

Evaluation of CEA, TPA, CA 15-3, CA 549 and TPS in the monitoring of metastatic breast cancer.

Monitoring the response to treatment in relapsed breast cancer patients is one of the chief uses of tumor markers. Thus far the carcinoembryonic antigen (CEA)-tissue polypeptide antigen (TPA)-breast cancer associated antigen 115 D8/DF3 (CA 15-3) association has been routinely used to follow-up breast cancer patients. We have found that TPA reflects the response to treatment much better than CEA and slightly better than CA 15-3. Recently carcinoma associated antigen 549 (CA 549) and tissue polypeptide specific antigen (TPS) have been reported to be highly sensitive tumor markers for breast cancer. TPS is claimed to be particularly suitable for monitoring the response to treatment because of its more specific assessment of proliferation activity. Therefore, in 13 relapsed patients with prolonged follow-up and detailed clinical-instrumental information, the mean percentage of samples with high CEA, TPA, and CA 15-3 values and their expressions were compared with those of CA 549 and TPS. All markers were also evaluated in terms of their correspondence with the evolution of disease. The correspondence with clinical-instrumental behaviour was scored absent (0), poor (1), good (2) and very good (3) by three different observers. Other more suitable associations than those already used were also investigated. It was found that CA 15-3 and CA 549 were expressed more often (92%) than TPS (85%), TPA (60%) and CEA (46%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Chromatographic identification in serum of endogenously radioiodinated thyroid hormones after iodine-131 whole-body scintigraphy in the follow-up of patients with differentiated thyroid carcinoma.

Patients with differentiated thyroid cancer (DTC) are conventionally followed with serial 131I whole-body scintigraphy (WBS) and serum thyroglobulin (hTg) assay. Given the 15%-20% incidence of discordant results, we developed a sensitive and specific procedure for monitoring such patients, based on the assumption that 131I uptake, even if too low to be detected by 131I WBS, could be assayed in serum as thyroid products (hTg, T3 and T4) endogenously labeled with 131I. Our study included 125 patients routinely monitored for tumor recurrence or for the persistence of functioning thyroid tissue after complete primary treatment for DTC (surgery and 131I ablation of remnants). A plasma sample, taken 72 hr after administering 131I for WBS was fractionated on a Sephadex-G25 superfine column by first eluting all of the radioactive species except the thyroid hormones and then the radioiodothyronines. The sensitivity and specificity of chromatography in detecting functioning thyroid tissue after primary treatment for DTC were 98.4% and 100% (accuracy 99.2%), respectively, versus 90.6% and 95.1% for 131I WBS (accuracy 92.8%) and 60.9% and 100% for hTg (accuracy 80%). Combining chromatography with serum hTg gave the highest gains in diagnostic performance (100% for all parameters). This chromatographic method can be used in addition to conventional procedures in the follow-up of patients with DTC and represents a highly sensitive test for assessing the results of 131I ablation of postsurgical remnants.

Adolescent↗

Clinical use of prostaglandin F2 alpha to induce early abortion in bitches: serum progesterone, treatment outcome and interval to subsequent oestrus.

Records of elective abortion in 27 bitches presented to the Veterinary Surgery and Reproduction Clinic of the University of Pisa were reviewed. Treatment consisted of twice-daily subcutaneous injections of 150-270 micrograms natural prostaglandin F2 alpha kg-1 for 4 consecutive days starting between cytological dioestrous days 5 and 19. None of the treated bitches whelped. Luteolysis appeared to be complete (serum progesterone < 3.2 nmol l-1) at the end of treatment in 22 of 25 bitches in which progesterone was assayed in serum obtained daily during therapy. Serum progesterone rose after treatment to a concentration consistent with pregnancy in four of 17 bitches in which progesterone was measured once between dioestrous days 23 and 51. The mean intercycle interval (pro-oestrus-pro-oestrus) of the cycle in which abortion was induced was 134 +/- 45 days for 15 dogs for which the interval could be determined, and was significantly shorter than the average preceding interoestrous intervals (210 +/- 40.0 days) for the same dogs (P < 0.001).

Abortifacient Agents↗

The concomitant determination of different tumor markers in patients with epithelial ovarian cancer and benign ovarian masses: relevance for differential diagnosis.

The serum levels of CA 125 (cutoff limit, 65 U/ml), CA19.9 (cutoff, 40 U/ml), CA 15.3 (cutoff, 32 U/ml), CA72.4 (cutoff, 3.8 U/ml), and TATI (cutoff, 22 ng/ml) were preoperatively measured in 90 patients with epithelial ovarian cancer and in 254 patients with benign ovarian pathology. CA125 had a sensitivity of 75.6%, a specificity of 86.6%, and a diagnostic accuracy of 83.7% for epithelial ovarian cancer; CA19.9 had a sensitivity of 35.6%, a specificity of 81.1%, and a diagnostic accuracy of 69.2%; CA15.3 had a sensitivity of 57.1%, a specificity of 93.9%, and a diagnostic accuracy of 84.6%; CA72.4 had a sensitivity of 70.7%, a specificity of 91.8%, and a diagnostic accuracy of 86.2%; and TATI had a sensitivity of 47.3%, a specificity of 95.3%, and a diagnostic accuracy of 82.9%. CA 125 was the most sensitive marker for nonmucinous tumors, while CA19.9 and CA72.4 were the antigens more frequently expressed by mucinous malignancies. The sensitivities of serum CA 125 (81.1% vs 50.0%; P = 0.01) and TATI (55.2% vs 18.8%; P = 0.02) were higher in patients above 50 years of age than in younger patients while specificities were quite similar in both age groups. The association of serum CA125 and CA19.9 had a significantly higher sensitivity (93.2% vs 81.1%; P = 0.03) and a slightly lowered specificity (78.9% vs 86.0%; P = 0.46) than CA125 assay alone in the differential diagnosis of ovarian masses in patients above 50 years of age.

Adenocarcinoma↗

The concomitant determination of different serum tumor markers in epithelial ovarian cancer: relevance for monitoring the response to chemotherapy and follow-up of patients.

The levels of CA125, CA19.9, CA15.3 CA72.4, and TATI were serially measured during and after chemotherapy in 43 patients with epithelial ovarian cancer having elevated concentrations of one or more of the antigens before initial surgery. The value of 35 U/ml was chosen as cutoff level of CA125 for the monitoring of disease. Changes in the serum levels of CA125, CA19.9, CA15.3, CA72.4, and TATI correlated with the clinical course of disease in 87.4% of 215, 76.3% of 80, 71.3% of 122, 76.0% of 167, and 48.5% of 101 instances, respectively. After the sixth course of monthly primary chemotherapy, elevated antigen levels were strong predictors of persistent disease, while normal antigen values were associated with both positive and negative second-look findings. It is worth noting that antigen levels above the cut-off limits before the third course, but still in the normal range after the sixth course, seemed to be predictive of positive second-look findings. Among patients with elevated antigen levels at diagnosis, clinical detection of neoplastic progression after treatment was stopped was preceded by an elevation of serum CA125 in 93.3% of 15 patients, of serum CA19.9 in 80.0% of 5 patients, of serum CA15.3 in 66.7% of 9 patients, of serum CA72.4 in 81.8% of 11 patients, and of serum TATI in 40% of 10 patients. In patients with positive CA125 assay at diagnosis, the concomitant evaluation of the other antigens did not seem to be of additional benefit for monitoring epithelial ovarian cancer. However, the measurement of the other tumor markers could represent an interesting biochemical tool for the management of patients with negative CA125 assay. In particular the evaluation of serum CA19.9 or CA72.4 could be very useful in the monitoring of patients with mucinous ovarian cancer, which often fails to express CA125 antigen.

Antigens, Tumor-Associated, Carbohydrate↗

Percutaneous ethanol injection treatment of autonomous thyroid adenoma: hormonal and clinical evaluation.

OBJECTIVE: We have evaluated the efficacy of percutaneous ethanol injection as an alternative to surgery and iodine-131 treatment in solitary autonomous thyroid adenoma. DESIGN: Percutaneous ethanol injection (0.5-2.8 ml ethanol/ml nodular tissue) was performed under sonographic guidance in 3-5 (1-2 weekly) sessions; a 7.5 MHz linear real-time scanner (Toshiba, mod. 32B) was used for sonographic studies. The thyroid hormone profile was assessed during treatment and for the next 6 months. PATIENTS: Fifty-six patients (40 females, 16 males, mean age 46 +/- SD 9 years; 30 pretoxic, 26 toxic) were included in the study: their pretreatment technetium-99 m thyroid scan showed a single hot nodule with total suppression of extranodular tissue in 45 and near-total suppression in 11. MEASUREMENTS: Thyroid hormones, antithyroglobulin and antiperoxidase antibodies were measured by specific radioimmunoassay, while thyrotrophin was evaluated by ultrasensitive immunoradiometric assay. RESULTS: Apart from a case of transient pyrexia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following a treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 18 out of 22 toxic patients (81.8%); a significant increase of TSH levels was seen in both groups (P less than 0.01). With follow-up, significant volume shrinkage (P less than 0.001) as well as structural alterations of the nodule were consistently recorded at sonography; a linear relationship (r = 0.98; P less than 0.0001) between pretreatment volume and volume reduction was found. At scintiscan, functional activity of extranodular parenchyma was found in 40 out of 56 patients (71.4%), 16/26 (61.5%) in the hyperthyroid group, 24/30 (80.0%) in the pretoxic group. CONCLUSIONS: These data confirm that percutaneous ethanol injection is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; adverse effects seem infrequent.

Adenoma↗

Combined evaluation of serum CA 125 and CAM 29 in patients with epithelial ovarian cancer.

We examined 92 patients with epithelial ovarian cancer and 262 patients with benign ovarian diseases undergoing laparotomy. On the basis of a nonparametric method, antigen levels corresponding to prefixed 95% specificity values in a group of 674 women with benign gynecologic diseases were taken as cutoff limits (88.8 U/ml for CA 125 and 13.7 U/ml for CAM 29). Moreover, CA 125 and CAM 29 levels were measured serially during and after chemotherapy in 26 women selected from the patients with advanced epithelial ovarian cancer. At diagnosis, serum CA 125 was as sensitive as serum CAM 29 for nonmucinous tumors, but more sensitive than serum CAM 29 for mucinous tumors. The association of the two markers seemed to give no advantage over the CA 125 assay alone in the diagnosis of epithelial ovarian cancer. In monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer, changes in CA 125 levels correlated with the clinical course of disease better than changes in CAM 29 levels, and the serum CA 125 assay was more reliable than the serum CAM 29 assay in the early detection of tumor progression. In conclusion, serum CAM 29 did not seem to represent a complementary assay to serum CA 125 in the management of patients with epithelial ovarian cancer.

Adolescent↗

Comparison between serum CA 125 and CA 19-9 assays and tissular OC 125 and 1116NS 19-9 reactivity in malignant and benign ovarian tumors.

This preliminary study included 25 patients with primary epithelial ovarian cancer (EOC) (18 serous, 3 serous-mucinous, 1 endometrioid, 2 undifferentiated carcinomas and 1 malignant Brenner carcinoma); 2 patients with borderline ovarian tumors and 20 patients with benign ovarian tumors (9 benign cystic teratomas, 6 serous cystoadenomas and 5 mucinous cystoadenomas). Blood samples for the measurement of CA 125 and CA 19-9 were drawn from all patients before surgery. Serum CA 125 (Reference Value-RV = 65 U/ml) and CA 19-9 (RV = 40 U/ml) were measured with IRMAs using the monoclonal antibodies (MoAbs) OC 125 and 1116NS 19-9. The same antigens were detected on paraffin-embedded tissue sections by immunocytochemistry with the avidin-biotin complex method employing the same MoAbs used for serum IRMAs. Among the 25 patients with EOC serum CA 125 levels were elevated in 20: tissular OC 125 reactivity was observed in 15 (75%) of them. Of the 5 EOC patients with normal CA 125 levels, 4 showed OC 125 reactivity. Only 2 of the 25 EOC patients had elevated serum CA 19-9 levels: one of them had tissular 1116 NS 19-9 reactivity. Among the 23 patients with normal serum CA 19-9 levels only 5 had immunocytochemical reactivity for this antigen. The 2 patients with borderline ovarian tumors had negative serum CA 125 and CA 19-9 assay: tissular OC 125 reactivity was observed in both patients, while 1116 NS 19-9 reactivity was detected in only one.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Blockade of cholinergic muscarinic receptors by pirenzepine and GHRH-induced GH secretion in the acute and recovery phase of anorexia nervosa and atypical eating disorders.

In view of the important role played by the cholinergic system in the neural regulation of growth hormone (GH) secretion, the ability of pirenzepine, a selective antagonist of muscarinic cholinergic receptors, to blunt the GH response to GH-releasing hormone (GHRH) was studied in adolescent females with anorexia nervosa in the acute (AN-AP) five AN-AP patients, administration of GHRH 1-40 (1 microgram/kg IV) evoked a significantly higher GH response than in controls at established intervals, whereas in eight AN-RP and seven AED patients it was higher than in controls at only one (150-min) and two (150-min, 180-min) time intervals, respectively. In the AN-AP patients, pretreatment with pirenzepine (0.6 mg/kg IV) only partially blocked the GH response to GHRH, whereas in the same AN-AP patients tested during recovery, and in AN-RP and AED patients, the drug completely suppressed the GH response to GHRH, as it did in controls. In view of pirenzepine's mechanism of action, these findings are best explained by the existence in the hypothalamus of AN-AP patients of a cholinergic hypertone and/or a diminished somatostatinergic function. Evaluation of the clinical and hormonal characteristics of the anorectic patients studied would indicate that factors other than undernutrition and its biological consequences, which subside in the recovery stage of the disease and are not present in AED patients, contribute to the anomalous GH response pattern of AN-AP patients.

Adolescent↗

Comparison of tumor-associated trypsin inhibitor (TATI) with CA125 as a marker for diagnosis and monitoring of epithelial ovarian cancer.

Preoperative serum levels of CA125 and tumor-associated trypsin inhibitor (TATI) were measured in 220 patients undergoing laparotomy for adnexal masses. Of the 57 patients with epithelial ovarian cancer. 86% had serum CA125 higher than 35 kU/l and 81% higher than 65 kU/l while 51% had serum TATI above 22 micrograms/l. In eight patients with mucinous ovarian malignancies, serum levels of CA125 were above 65 kU/l in 6 cases while serum TATI was above 22 micrograms/l in 4 cases. Of the 163 patients with benign ovarian masses, 41% had serum CA125 levels above 65 kU/l and 17% above 65 kU/l whereas serum TATI was above 22 micrograms/l in 6%. In 11 cancer patients having elevated levels of both CA125 and TATI at diagnosis, the serum concentrations of these antigens were periodically measured during and after treatment. Changes in CA125 and TATI levels correlated with the clinical course in 84% and 37% of the instances, respectively. After the sixth course of chemotherapy, the diagnostic accuracy of the markers in the evaluation of the disease status at second-look laparotomy was 55% for CA125 with a cut-off level of 35 kU/l, 36% for a cut-off level of 65 kU/l, 55% for TATI, and 66% for the combination of CA125 and TATI with cut-off levels of 65 kU/l and 22 micrograms/l. CA125 is the most sensitive marker for epithelial ovarian cancer, but the concomitant measurement of TATI could be of benefit in both differential diagnosis of adnexal masses and monitoring of response of epithelial ovarian cancer to treatment.

Antigens, Tumor-Associated, Carbohydrate↗

Failure of glucose infusion to suppress the exaggerated GH response to GHRH in patients with anorexia nervosa.

The growth hormone (GH) response to GH-releasing hormone (GHRH) is characteristically exaggerated in anorexia nervosa (AN). Hyperglycemia suppresses the GH response to GHRH in normal subjects. To test whether this inhibitory action of hyperglycemia is preserved in AN, we performed a GHRH (GHRH 1-40, 1 micrograms/kg) test under basal conditions (saline infusion) and during steady-state hyperglycemia (200 mg/dl, induced by the intravenous administration of 8 mg/min.kg of glucose) in 6 adolescent girls with acute-stage AN (as diagnosed by psychopathological, hormonal, and nutritional criteria) and in 5 age-matched female controls. In control subjects, GHRH stimulated GH release during saline, but not glucose, infusion. In the anorectic patients, the GH response to GHRH was exaggerated during both saline infusion (2.97 +/- 0.79 versus 0.52 +/- 0.22 micrograms.120 min.ml-1, p less than 0.02) and under hyperglycemic conditions (4.61 +/- 0.56 versus 0.33 +/- 0.10, p less than 0.001). We conclude that the inhibitory action of hyperglycemia on GHRH-induced GH release is lost in the acute phase of AN.

Acute Disease↗

Thyroidal and peripheral production of 3,5,3'-triiodothyronine in humans by multicompartmental analysis.

Multicompartmental analysis of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) kinetics based on the plasma disappearance curves of the two tracer hormones (J. J. DiStefano III, M. Jang, T. K. Malone, and M. Broutman. Endocrinology 110: 198-213, 1982 and J. J. DiStefano III, T. K. Malone, and M. Jang. Endocrinology 111: 108-117, 1982) was extended to include additional experimental data, namely, the appearance curve in plasma of labeled T3 generated in vivo from precursor T4. Kinetic analysis of data obtained in 14 studies carried out in normal subjects by using a composite six-pool model made it possible to quantify the contributions of the thyroid (3.3 micrograms.day-1.m-2) and the periphery (12.7 micrograms.day-1.m-2) to T3 production. T4 monodeiodination occurred mainly in peripheral tissues rapidly exchanging with plasma (10.7 micrograms T3.day-1.m-2), whereas only 2.0 micrograms T3.day-1.m-2 arose in slowly exchanging tissues. In contrast, if plasma disappearance curves only were analyzed, a value of 10.9 micrograms T3.day-1.m-2 was calculated for peripheral conversion in slowly exchanging tissues; this underscores the need for additional data, such as the [125I]T3 plasma appearance curve for the partition of central and peripheral production of T3.

Adult↗

CAM26, CAM29 and mucin-like carcinoma associated antigen in epithelial ovarian cancer.

The levels of CA125 (reference values [RVs] 35 U/mL and 65 U/mL), CA15.3 (RV = 32 U/mL), Mucin-like carcinoma associated antigen (MCA; RV = 15 U/mL), CAM26 (RV = 75 U/mL) and CAM29 (RV = 15 U/mL) were preoperatively assayed in blood samples drawn from 42 patients with ovarian carcinoma and 101 patients with benign ovarian pathology undergoing laparotomy at the Department of Gynecology and Obstetrics of the University of Pisa. With 65 U/mL as RV, CA125 had a sensitivity (SE) of 80.9% and a specificity (SP) of 89.1% for ovarian carcinoma; with 35 U/mL as RV, CA125 had a SE of 85.7% and a SP of 66.3%; CA15.3 had a SE of 57.1% and a SP of 96.0%; MCA had a SE of 59.5% and a SP 86.1%; CAM26 had a SE of 21.4% and a SP of 96.0%, CAM29 had a SE of 64.3% and a SP of 97.0%. The association of CA125 with each of other antigens did not improve the SE of CA125 assay alone in the detection of patients with ovarian carcinoma. In conclusion, the present data showed that the measurement of CA15.3, MCA and CAM26 did not give any additional information with respect to CA125 assay in the diagnosis of ovarian carcinoma. The good SE and the very good SP and diagnostic accuracy of CAM29 could suggest further investigation in order to evaluate the role of this antigen in the management of patients with this malignancy.

Adenocarcinoma↗