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Biomedical subjects

S Iacobelli

Publications and source records attributed to S Iacobelli.

At least 91 records · Page 5Linked to original sources
PubMed1989

Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma. A multicentre phase II study.

Twenty-four evaluable patients with metastatic melanoma have been entered in a multicentre Phase II study of two induction cycles of human recombinant interleukin-2 (rIL-2) 18 x 10(6) IU/m2/day continuous i.v. bolus on days 1-5 and days 12-17. Dacarbazine (DTIC) 850 mg/m2 i.v. bolus was given on day 26. The cycle was repeated at five weeks. Maintenance therapy was scheduled three weeks after the completion of the induction treatment, consisting of rIL-2 18 x 10(6) IU/m2/day for five days alternating with DTIC 850 mg/m2 i.v., every three weeks, for a total of 18 weeks. Median age was 44 years (range 23-80), and Karnofsky index was 100 (range 80-100). One patient had received prior chemotherapy with hydroxyurea and one patient had prior radiotherapy. Six patients responded (25%): two had complete responses (CR) and four had partial responses (PR). Stable disease (SD) was seen in five patients. Responses occurred in the following sites: liver 2/9 (22%), lung 3/14 (21%), skin 2/11 (18%), and lymph nodes 3/12 (25%). Duration of CR was 11+ and 13 months. PRs lasted 2, 5, 7, and 11+ months. Of note, time to progression in patients with SD was similar to that of responders: 4, 4, 11+, 11+, and 14+ months. Toxicity included fever, skin rash, fatigue, anorexia, and diarrhoea in most patients. Two patients had a weight gain of more than 10%. Hypotension requiring vasoactive agents or interruption of rIL-2 occurred in four patients, creatinine elevations WHO grade 1-2 in seven patients, and bilirubin elevations WHO grade 1-3 in six patients. One patient developed transient ventricular tachycardia. It appears that rIL-2 and DTIC in this schedule is feasible and effective, but not clearly superior to rIL-2 alone.

Adult↗
PubMed1988

Recombinant human leukocyte interferon-alpha 2b stimulates the synthesis and release of a 90K tumor-associated antigen in human breast cancer cells.

We have previously reported the production of a new monoclonal antibody (MAb) (SP-2) recognizing a 90-kDa tumor-associated antigen, termed 90K, which is increased in the serum of many cancer patients. Treatment of CG5 human breast cancer cells with recombinant interferon-alpha 2b (rIFN-alpha 2b) can increase the synthesis and release, in culture medium, of the 90K. The effect of rIFN-alpha 2b was dose-related and occurred at concentrations which did not affect cell proliferation. The increase of 90K expression was due to de novo protein synthesis since cycloheximide, added within 3 hr of the beginning of rIFN-alpha 2b stimulation treatment, completely abolished the effect of rIFN-alpha 2b. The stimulatory effect of rIFN-alpha 2b was already evident after 24 hr treatment. Finally, an increase in serum 90K levels was observed in 3 patients with advanced breast cancer receiving a short course of rIFN-alpha 2b (Intron A). No effect of rIFN-alpha 2b was seen in 3 normal women. The ability of rIFN-alpha 2b to increase the synthesis and release of 90K both in vitro and in vivo may be of clinical importance in the early detection of tumors.

Antibodies, Monoclonal↗
PubMed1988

Effects of antiestrogen and progestin on immune functions in breast cancer patients.

Several immunologic variables were evaluated in 14 patients with untreated primary breast cancer and 20 postmastectomized patients undergoing tamoxifen (TAM) or high-dose medroxyprogesterone acetate (MPA) treatment. Immunologic evaluation in the peripheral blood included lymphocyte count, definition of T-lymphocyte subsets by monoclonal antibodies (OKT3, OKT11, OKT4, and OKT8), and lymphocyte blastogenic response to phytohemagglutinin (PHA) and Concanavalin A (Con A). Moreover, the in vitro effect of TAM and MPA on the blastogenic response of peripheral lymphocytes from normal female subjects was tested. Primary breast cancer patients did not differ from controls in any of the variables tested. Similarly, the immunologic variables of the group treated with TAM were normal, with the exception of a slight reduction of the OKT4+/OKT8+ ratio. In MPA-treated patients, a reduction of the percentage of OKT4+ cells and a decrease of the OKT4+/OKT8+ ratio were observed. Moreover, response to PHA was reduced sharply. However, the addition of interleukin-2 (IL-2) to the culture medium restored PHA response. Likewise, the in vitro addition of MPA to peripheral blood lymphocytes from normal female subjects resulted in a sharp dose-dependent depression of PHA response while TAM was ineffective completely. The inhibitory effect of MPA was not evident when IL-2 was added simultaneously to the culture medium. These results show that the administration of high-dose MPA may alter immunocompetence as defined by T-lymphocyte subsets and response to mitogens. The latter effect may be related to a diminished production of IL-2. In contrast, TAM does not appear to have a significant immunodepressant action either in vitro or in vivo.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Immunohistochemical localization of creatine kinase BB in primary breast cancer: correlation with estrogen receptor content.

The brain-type (BB) isoenzyme of creatine kinase (CK) has recently been shown to be estrogen-regulated in human breast cancer cells in vitro. In this study we have correlated the presence of CK-BB, evaluated by immunoperoxidase procedures, with the estrogen receptor (ER) content in 35 primary breast cancers. Of 35 tumors examined, 66% revealed moderate to strong CK-BB immunoreactivity. Staining was exclusively located in the cytoplasm of neoplastic cells. A positive relationship was observed between CK-BB positivity and ER content with ER-rich tumors (greater than 50 fmoles/mg protein) showing a more intense immunoreactivity than ER-poor ones. The results indicate that CK-BB is estrogen-regulated in human breast cancer and suggest that evaluation of this enzyme may be of potential value for the detection of hormone responsive tumors.

Biomarkers, Tumor↗
PubMed1988

Antiproliferative effects of somatostatin and the somatostatin analog SMS 201-995 on three human breast cancer cell lines.

The antiproliferative effect of somatostatin and the somatostatin analog SMS 201-995 on three human breast cancer cell lines (CG5, T 47 D, and ZR 75-1) is reported. Both peptides markedly inhibited CG5 cell growth with a maximal inhibition of about 40% as compared with control cells. The antiproliferative effect of somatostatin on T 47 D and ZR 75-1 cells was much less evident. These results suggest that somatostatin is a peptide inhibitory factor for human breast cancer cells. Possible therapeutic implications of these findings are still to be investigated.

Breast Neoplasms↗
PubMed1988

Measurement of a breast cancer associated antigen detected by monoclonal antibody SP-2 in sera of cancer patients.

An enzyme-linked immuno-absorbent assay has been developed for the detection of a circulating tumor-associated antigen, 90K, recognized by murine monoclonal antibody SP-2 (Iacobelli et al., Cancer Res 46: 3005-3010, 1986). This assay was found to be simple and reproducible. Using this method, 6% of 165 apparently healthy individuals and 15% of 91 patients with benign breast disease showed 90K levels above 1.7 units/ml. Approximately 50% of 129 patients with advanced breast cancer demonstrated serum antigen levels above 1.7 units/ml. All histological types of breast cancer were positive, and no association between the incidence of elevated 90K levels and other prognostic variables could be detected. The titers of 90K were significantly higher in sera from advanced-stage (3 and 4) patients than in those from patients with limited-stage (1 and 2) disease. Elevated 90K levels were also observed in patients with carcinomas of other sites, including gastrointestinal, gynecological, and lung tumors. By means of the immune blotting technique, the antigenic components carrying the determinants in serum and extracts of breast cancer cells have been identified. The levels of 90K did not correlate with those of CA 15-3 or CEA. The measurement of 90K in sera appears to be a useful adjunct to other available assays for the detection and monitoring of breast cancer and other malignant tumors.

Antibodies, Monoclonal↗
PubMed1988

Epidermal growth factor receptor in human breast cancer: correlation with steroid hormone receptors and axillary lymph node involvement.

Epidermal growth factor (EGF-R) estrogen (ER) and progesterone (PR) receptors were evaluated in 89 primary breast cancers and 23 axillary lymph node metastases. About 57% of primary and 72.2% of metastatic tumors were EGF-R positive and median EGF-R levels were higher in metastatic deposits than in primary breast tumors (P less than 0.05). An inverse distribution of EGF-R and steroid hormone receptor positive tumors was found (chi 2 = 10.87; P less than 0.001 for PR and chi 2 = 5.01; P less than 0.05 for ER) and an interesting correlation between EGF-R expression in primary tumor and axillary lymph node involvement was demonstrated (chi 2 = 21.4; P less than 0.001). Immunohistochemical studies with a monoclonal antibody against EGF-R revealed the presence of EGF-R only in malignant cells. Our data suggest that EGF-R could identify a class of more aggressive breast tumors endowed with a higher metastatic potential and may therefore represent an unfavorable prognostic parameter in breast cancer.

Adult↗
PubMed1988

Receptors for epidermal growth factor and steroid hormones in human breast cancer.

Epidermal growth factor (EGF) seems to play an important role in regulating the proliferation of human breast cancer. Fifty-five primary breast tumors and 7 lymph node metastases were simultaneously assayed for the presence of EGF receptors (EGFR), estrogen receptors (ER), and progesterone receptors (PR). Overall, 42% (23/55) of the tumors were EGFR positive. EGFR were more frequently present in ER- and PR-negative than in ER- and PR-positive tumors. In particular, a negative correlation between EGFR and PR (chi 2 = 6.8; p greater than 0.01) was observed. All metastatic tumors were EGFR negative, and in all cases but 1 the levels of EGFR were higher in metastatic than in primary tumors. Our results suggest the presence of a subclass of breast tumors, the growth of which is primarily regulated by EGF or EGF-like substances rather than by steroid hormones. In this group, not amenable to endocrine therapy, EGF receptors should represent a target for therapeutic intervention.

Breast Neoplasms↗
PubMed1987

Glucocorticoid receptors predict response to combination chemotherapy in patients with acute lymphoblastic leukemia.

Glucocorticoid receptor levels were quantified in leukemic blasts from peripheral blood of 86 patients with acute lymphoblastic leukemia. Subsequent achievement of complete remission correlated with high receptor levels. Forty-seven of 50 patients with leukemic cells containing more than 6,000 receptor sites and 22 of 36 patients with cells containing less than 6,000 receptor sites achieved remission. The study of glucocorticoid receptors in leukemic cells may predict response to combination chemotherapy in acute lymphoblastic leukemia patients.

Acute Disease↗
PubMed1986

Effect of tamoxifen on steroid hormone receptors and creatine kinase activity in human endometrial carcinoma.

Estrogen receptor (ER), progesterone receptor (PR) and creatine kinase (CK) were measured in cancerous tissue from 29 post-menopausal patients with endometrial carcinoma under basal conditions and after a short course of tamoxifen treatment. ER and PR were detected in nearly all tumors. CK was detected in all of the tumors examined. After tamoxifen, PR and CK increased simultaneously in 26% of cases, while they were either enhanced, decreased or unmodified in the remainder. No correlation could be found between increase of PR and tumor differentiation. CK, however, was enhanced only in the more differentiated cancers. These results indicate that only a percentage of endometrial cancers are responsive to tamoxifen. It is hypothesized that patients bearing these tumors are those likely to benefit from endocrine therapy.

Cell Transformation, Neoplastic↗
PubMed1986

Detection of antigens recognized by a novel monoclonal antibody in tissue and serum from patients with breast cancer.

Monoclonal antibodies were produced in mice immunized with proteins released into tissue culture fluid of human breast cancer cells maintained in vitro. One monoclonal antibody (SP-2) identified a Mr 90,000 antigen which appears to be a proteolipid. In immunoperoxidase assays, SP-2 reacted with 81 of 90 specimens of human breast cancer. It also reacted with 12 of 23 cancers of nonbreast origin but was unreactive with all normal tissues tested. The Mr 90,000 antigen, purified by immunoaffinity chromatography using SP-2, was used in an indirect binding inhibition assay for the detection of antigen in human serum. With this assay, 35 of 69 patients with breast cancer and 11 of 37 patients with benign breast lesions showed serum antigen levels above 6 units/ml. Patients with nonbreast cancers also demonstrated elevated levels of antigen in 32% of cases. The SP-2 defined Mr 90,000 antigen appeared to be distinct from carcinoembryonic antigen and other monoclonal antibody-defined breast cancer antigens of similar molecular weight. SP-2 may prove useful as a serum and/or tissue marker in breast pathology.

Animals↗
PubMed1985

Sex steroid receptors in normal and malignant human vulvar tissue.

Receptors for estrogens, progesterone and androgens were assayed in 6 specimens of normal vulvar tissue and in 9 specimens of carcinomatous vulvar tissue. These receptors were not always present in all specimens examined. In both normal and carcinomatous tissues receptor concentration was highly variable. Malignant tissues did not show significant changes in values compared to normal tissue.

Aged↗
PubMed1985

Effects of intra-amniotic isoxsuprine on amino acid placental transfer in rats.

Direct administration of isoxsuprine to the rat fetus increases placental transfer of 35S-methionine and this increase is statistically significant on day 17 as compared with intraperitoneal administration and controls (p less than 0.01; p less than 0.05). In contrast, no statistically significant differences were found between the groups on day 16.

Amino Acids↗
PubMed1985

[Glucocorticoid receptors and response to polychemotherapy in acute lymphatic leukemia].

Glucocorticoid receptor (GR) levels were quantified in leukemic blasts from peripheral blood of 86 patients with acute lymphoblastic leukemia. The subsequent achievement of complete remission after combination chemotherapy was correlated with high receptor levels. Forty-seven of 50 patients with leukemic cells containing more than 6,000 receptor sites and 22 of 36 patients with cells containing less than 6,000 receptor sites achieved remission. The study of glucocorticoid receptors in leukemic cells may predict response to combination chemotherapy in patients with acute lymphoblastic leukemia.

Adolescent↗
PubMed1985

A monoclonal antibody (AB/3) reactive with human breast cancer.

Monoclonal antibody AB/3 was produced from a fusion of spleen cells of a human breast cancer cell-primed BALB/c mouse with the murine myeloma cell line P3-NS1-Ag4-1. The antibody reacted strongly with the plasma membrane of human breast cancer cells. Tissue sections of both malignant and benign human mammary carcinomas and tumors of non-breast origin as well as apparently normal tissues were tested with immunoperoxidase. Ninety-six of 124 (77%) primary human breast cancers, 12 of 14 (86%) metastatic breast lesions, and 12 of 44 (27%) benign breast lesions reacted positively. Little or no appreciable reactivity was observed with apparently normal human tissues and carcinomas of non-breast origin, with the exception of colon carcinoma. Antibody AB/3 did not immunoprecipitate any identifiable protein from radiolabeled extracts of the immunizing cell line.

Animals↗