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Biomedical subjects

S Iacobelli

Publications and source records attributed to S Iacobelli.

At least 73 records · Page 4Linked to original sources

90K protein: a new predictor marker of disease progression in human immunodeficiency virus infection.

A 90,000-Da molecular mass tumor-associated protein has recently been identified in the sera of patients infected by HIV. In this study, we have evaluated the serum levels of 90K for its ability to predict the progression to ARC or AIDS retrospectively in 49 HIV-seropositive subjects who were initially symptom-free. 90K levels were higher in those HIV-seropositive subjects who progressed to ARC or AIDS than in those who had not progressed both at entry into the study and at the latest visit. CD4+ cell number was not different in the two groups at entry but was lower in the progressors at the latest visit. Evaluation of the patterns of change over time showed that 90K increased and CD4+ cells decreased more in progressors than in nonprogressors. During the 3 years preceding the onset of ARC or AIDS, 90K increased regularly while CD4+ cell decrease was later. Elevated levels of 90K (p = 0.007) and lower numbers of CD4+ cells (p = 0.001) were significantly associated with a higher cumulative incidence of ARC or AIDS. These findings suggest that 90K is an early indicator of progression to ARC and AIDS.

AIDS-Related Complex↗

Neoadjuvant chemotherapy with cisplatin, epirubicin and VP-16 for stage IIIA-IIIB non-small-cell lung cancer: a pilot study.

Twenty patients with stage IIIA-IIIB non-small-cell lung cancer were treated with cisplatin, epirubicin and VP-16 (PEV) neoadjuvant chemotherapy (CDDP, 70 mg/m2, i.v., d 1; EDX, 60 mg/m2, i.v., d 1; VP-16, 100 mg/m2, i.v., d 1-2-3; every 3 weeks). A partial response was obtained in 11 cases (55%), stable disease in 3 cases (15%), and progressive disease in 6 cases (30%). After chemotherapy, 8 (40%) patients, all achieving a partial response, were elegible for surgery: 5 (25%) had a complete resection (4 IIIA and 1 IIIB) and 3 (15%) an incomplete resection. The treatment was well tolerated. These data show that PEV is an active regimen for neoadjuvant chemotherapy in NSCLC and recommend this therapeutic approach for stage IIIA patients.

Adult↗

Recombinant alpha-2b-interferon dynamic test as a potential tool in predicting disease status during second look in ovarian cancer. A preliminary report.

The circulating levels of a 90-kilodalton (KD) tumor-associated antigen were measured in the blood of 26 patients with ovarian cancer in clinical remission who received a short course of recombinant alpha-2b-interferon (rIFN-alpha-2b, 3 million U/m2/d intramuscularly for 3 days) before second-look procedures. The administration of rIFN-alpha-2b to 90-KD antigen-positive patients produced a slight increase of the marker. However, in patients without the marker but with evidence of disease, a remarkable increase above the cutoff level was observed. Less pronounced modifications of 90-KD antigen serum levels were found in patients with no disease at second look. Moreover, considering the 90-KD antigen mean percentage increase, the dynamic test with rIFN-alpha-2b was able to eliminate five of six false-negative results obtained with the 90-KD antigen basal assay alone. The sensitivity of the assay increased to 92% after IFN compared with 54% for the 90-KD antigen assay alone. An increase (greater than 100% above pretreatment titer) of 90-KD antigen levels during the test also was observed in four patients with no evidence of disease at second look. In two of these false-positive cases, recurrence of disease was observed 13 and 24 months later. At the time of this analysis, none of the patients with a negative second look and negative dynamic test had relapsed. These results suggest that the dynamic test with rIFN-alpha-2b might be a new tool to assess disease status in patients with ovarian cancer before second-look procedures.

Adult↗

Upregulation of epidermal growth factor receptor induced by alpha-interferon in human epidermoid cancer cells.

Unregulated or increased expression of epidermal growth factor receptor (EGF-R) is a common event in neoplastic transformation; modulation of such a receptor by physiological agents could be, therefore, of clinical interest. We have studied the binding ability, the availability at cell surface, and the synthesis of EGF-R in the A431 and KB human epidermoid cancer cell lines after treatment with recombinant alpha-interferon (IFN-alpha). After 48 h of treatment, IFN-alpha induces, in both cell lines, growth inhibition and enhances class I major histocompatibility HLA complex expression, which is a common marker of IFN action. [125I]EGF total binding assessed after 48 h of treatment with IFN-alpha shows a dose-dependent upregulation of EGF-R binding capacity. Saturation plots of the binding data show that IFN-alpha treatment does not dramatically alter the affinity of the EGF-R and indicate that IFN-alpha only increases the number of low affinity receptors. We show that this effect is due to a specific increase in the synthesis of the receptor protein, as assessed by immunoprecipitation of [35S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed an increase of EGF-R proteins at cell surface without major changes in the morphology of the cells. Taken together, these results indicate that IFN-alpha consistently induces both the binding capacity and the synthesis of EGF-R in human epidermoid cancer cells and suggest the use of such a mechanism for new anticancer therapies.

Binding Sites↗

Phase II study of mitomycin C, etoposide and vindesine in metastatic stage IV non-small-cell lung cancer.

A total of 72 patients with metastatic stage IV non-small-cell lung cancer (NSCLC) were treated with combination chemotherapy comprising the MEV regimen (mitomycin C, 8 mg/m2 given i.v. on day 1; etoposide, 100 mg/m2 given i.v. on days 1-3; and vindesine, 3 mg/m2 given i.v. on day 1; treatment repeated every 3 weeks). In 65 evaluable patients, the objective response rate was 37% (complete responses, 4.7%; partial responses, 32.3%). The median survival was 7.6 months for all patients. The treatment was very well tolerated. MEV proved to be an active and non-toxic regimen for the treatment of metastatic NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study.

Twenty-five assessable patients with metastatic melanoma have been entered in a multicenter phase II study of two induction cycles of human recombinant interleukin-2(IL2), 18 x 10(6) IU/m2/d continuous intravenous (IV) infusion on days 1 to 5 and days 12 to 17. Dacarbazine (DTIC), 850 mg/m2 IV bolus was given on day 26. The cycle was repeated at 5 weeks. Maintenance therapy was scheduled 3 weeks after the completion of induction treatment, consisting of IL2, 18 x 10(6) IU/m2/d for 5 days alternating with DTIC, 850 mg/m2 IV every 3 weeks, for a total of 18 weeks. Six patients responded (24%); two complete and four partial. Stable disease was seen in five patients. None of the six patients with more than two sites of metastases responded. Maximum response was observed in the first 3 months of treatment. Progression-free periods of 6 months and longer were seen in the two complete responders (8 and 17+ months), in two of the four partial responders (7 and 12+ months), and in three of the five patients with stable disease (9+, 15, and 17+ months). Toxicity included fever, skin rash, fatigue, anorexia, and diarrhea in most patients. Two patients had a weight gain of more than 10%. Eight patients needed intensive care for the observation and treatment of a myocardial injury (one patient), ventricular tachycardia (one), hypotension and oliguria (four), and sepsis (two). Sequential treatment with IL2 and DTIC appears to be effective but not clearly better than could be expected of IL2 alone.

Adult↗

Immunohistochemical expression of c-erbB-2 in human breast cancer by monoclonal antibody: correlation with lymph node and ER status.

c-erbB-2 Protein expression was investigated in a series of fifty primary breast cancers by means of a specific monoclonal antibody and immunocytochemistry. Specific staining was observed at the plasma membrane level of neoplastic cells, according to the reported localization of c-erbB-2 protein. Sixty-four percent of tumors scored positive, with a variable amount of stained cells. The rate of protein expression was found to exceed the reported gene amplification. No relationship was observed between c-erbB-2 protein staining and age, menopausal status or histologic subtypes. An inverse association was found between c'erbB-2 protein staining and estrogen receptor content of tumors, assayed by immunocytochemistry. A positive relationship was observed between c-erbB-2 protein expression and presence of axillary node metastasis. These findings suggest that c-erbB-2 protein expression is a marker of tumor aggressiveness and that its prognostic power deserves further investigation both in node-positive and node-negative patients.

Adult↗

Recombinant alpha-2b-interferon enhances the circulating levels of a 90-kilodalton (K) tumor-associated antigen in patients with gynecologic and breast malignancies.

The circulating levels of a 90-kilodalton (K) tumor-associated antigen were measured in the blood of 43 patients with gynecologic and breast malignancies who underwent a short course of recombinant alpha-2b-interferon (rIFN alpha-2b) (3 million U/m2/d intramuscularly [IM] for 3 days). Of the 43 patients, 23 showed abnormal 90-K levels (greater than 1.7 U/ml). A significant increase of antigen levels was already observed 24 hours after the first administration and persisted throughout the investigation period. Of 20 patients with 90-K levels below the normal limit, 12 went over the normal cutoff value after two rIFN alpha-2b injections. No significant modifications of 90-K levels were detected in nine women receiving rIFN alpha-2b for the treatment of genital condylomata. The serum levels of two other tumor-associated antigens, CA 125 and CA 15-3, were not modified by rIFN alpha-2b administration. The ability of rIFN alpha-2b to increase the circulating levels of 90-K might have important clinical implications for the serodetection of cancer.

Antigens, Neoplasm↗

Hormone receptors and enzymatic activities in human endometrial adenocarcinoma.

The hormone sensitivity of endometrial carcinoma is related to the presence of steroid hormone receptors. The determination of progesterone receptors has been proposed in order to predict clinical prognosis and to aid treatment selection. The integrity of the hormone receptor system and postreceptoral events in tumors is essential to endocrine therapy response. Nevertheless, although hormone receptors are present in a large number of endometrial carcinomas, only 30% of cases respond to hormone therapy. In some neoplasms the receptors can be present, but not functioning, or else neoplastic transformation could have induced alterations in processes after hormone-receptor interaction.

17-Hydroxysteroid Dehydrogenases↗

Hormone receptor status in human endometrial adenocarcinoma.

Steroid receptor levels were determined in 196 samples of endometrial adenocarcinoma: cytosol estradiol receptors (ERc) were measured in 171 samples, cytosol progesterone receptors (PRc) in all samples; nuclear estradiol receptors (ERn) and nuclear progesterone receptors (PRn) in 68 samples; total estradiol receptors (ERt = ERc plus ERn) and total progesterone receptors (PRt = PRc plus PRn) were measured in 68 samples. The ERc levels were 88.2 +/- 8.9 (mean +/- SEM) and ERn were 94.4 +/- 15.6 fmol/mg protein; PRc levels were 197.9 +/- 25.9 and PRn 178.3 +/- 55.9 fmol/mg protein. The ERt levels were 162.6 +/- 23.2 and PRt 249.8 +/- 75.7 fmol/mg protein. The presence of PRc was related to the ERc levels according to the cut-off used. Estradiol receptors (ER) and progesterone receptors (PR) were present in the cytoplasmic and nuclear fractions in 60.2% and 36.8% of cases, respectively. The simultaneous presence of both ERt and PRt was observed only in 27.9% of cases. In the normal endometrium ERc and PRc were negatively correlated (r = -0.525, P less than 0.005), whereas in endometrial adenocarcinoma the correlation was positive (r = 0.491, P less than 0.001). In contrast with the normal endometrium the correlation between ERc and ERn was positive (r = 0.582, P less than 0.001) in tumor tissue. In neoplastic tissue Scatchard analysis showed a single class of specific ERc sites with a dissociation constant (Kd) of 1.39 +/- 0.8 X 10(-9) mol/l, one tenth of that found in the normal premenopausal endometrium. Qualitative and quantitative analysis of the receptor status showed that in 30% to 40% of cases studied the behavior of the neoplastic cell was similar to that found in the normal endometrial cell. In a 4-year follow-up of patients affected by endometrial adenocarcinoma there is better survival in the groups of patients with a simultaneous presence of ERt and PRt than in the group with their absence.

Adenocarcinoma↗

Predictive value of multiple tumor marker assays in second-look procedures for ovarian cancer.

Sera from 51 ovarian cancer patients in clinical remission undergoing a second-look operation were studied. CA 125, CA 15-3, and 90K assays were performed in the week preceding surgery. Twenty-seven patients (53%) had no evidence of disease; 3 (6%) and 21 (41%) had microscopic and macroscopic disease. All patients but two with no evidence of disease had normal CA 125 serum levels, as did the three cases with microscopic disease and 6 patients with macroscopically detectable tumor. Of 17 patients with high CA 125 values, 15 (88%) were found to have persistent disease. Hence, the sensitivity and specificity of a CA 125 assay were 62 and 93%, respectively. CA 15-3 levels were low in all patients with no evidence of disease, in 2 cases with microscopic disease, and in 2 cases with residual tumor greater than 1 cm. All patients with high CA 15-3 titers had a positive second-look. The sensitivity and specificity of assay were 69 and 100%, respectively. With the 90K assay, 4 false-positive and 4 false-negative results were found and the sensitivity and specificity were 69 and 67%, respectively. However, 3 of 4 cases with a false-positive 90K assay had recurrence of disease with 7, 9, and 20 months later. Combination of the three markers increased sensitivity to 79%. These data suggest that more effective surveillance of disease status at second-look is obtained by using a combination of tumor marker assays.

Antigens, Tumor-Associated, Carbohydrate↗

Epidermal growth factor receptor expression in gynecological malignancies.

Epidermal growth factor receptor (IEGF-R) levels were analyzed in 72 gynecological tumor specimens. Measurable EGR-R levels were found in a significant percentage of ovarian and uterine tumors. Moreover, all vulvar epidermoid carcinomas and uterine sarcomas analyzed were EGF-R positive. In all tumor types examined, scattered EGF-R levels were observed. Higher EGF-R levels were found in metastatic than in primary ovarian tumors. Moreover, EGF-R were found to be more expressed in less differentiated than in well-moderately differentiated endometrial tumors. Our results suggest a role of EGF or EGF-like substances in regulating the growth of gynecological malignancies, and indicate EGF-R expression as a possible prognostic factor.

ErbB Receptors↗