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Biomedical subjects

F Battaglia

Publications and source records attributed to F Battaglia.

At least 73 records · Page 4Linked to original sources

Type-II estrogen binding sites in a lymphoblastoid cell line and growth-inhibitory effect of estrogen, anti-estrogen and bioflavonoids.

Type-II estrogen-binding sites (type-II EBS) have been demonstrated in the human lymphoblastoid cell line IM-9 using a whole-cell assay with (6,7-3H) estradiol (3H-E2) as tracer. Competition analysis showed that the anti-estrogen tamoxifen and the flavonoids quercetin and rutin competed for (3H)-E2 binding to type-II EBS. Growth experiments demonstrated that diethylstilbestrol (DES) tamoxifen (TAM), quercetin and rutin exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM. The relative binding affinity of quercetin, rutin, DES and TAM for type-II EBS correlated well with their potency as cell growth inhibitors. Moreover, hesperidin, a flavonoid which does not bind to type-II EBS, was ineffective in inhibiting cell growth. Cell-cycle analysis showed that the growth-inhibitory effect of DES, TAM or quercetin was due to a blocking effect in the G0-G1 phases. Our results suggest that high estrogen and anti-estrogen concentrations and flavonoids may regulate IM-9 cell growth through a common mechanism involving a binding interaction with type-II EBS.

Binding, Competitive↗

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↗

Steroid hormone receptors in carcinoma of the cervix: lack of response to an antiestrogen.

Levels of estrogen (ER) and progesterone (PR) receptors were measured in 81 patients with primary cervical cancer. In 10 patients, receptor levels were evaluated before and after a short course of tamoxifen treatment. Fifty-six percent of cervical tumors contained ER, and 58%, PR. Receptor level and expression were not related to any clinical and histological characteristic. Moreover, both survival time and response to neoadjuvant chemotherapy did not correlate with the presence of ER and PR. Tamoxifen treatment did not influence ER and PR levels. Our results suggest that steroid hormone receptors are of little value in the management of cervical cancer, and that in this neoplasia, ER is probably not functional.

Antineoplastic Agents↗

Circulating tumor markers in cervical cancer.

Serum levels of CA 19-9, CA 125 and CA 15-3 were measured in 91 patients with cervical cancer (16 with intraepithelial neoplasia and 75 with invasive cancer). In 35 patients with locally advanced cervical cancer, serum marker levels were measured at monthly intervals during neo-adjuvant chemotherapy. CA 19-9 was found to be abnormally high only in advanced stages with an overall sensitivity of 7.3%. CA 125 and CA 15-3 were elevated in 31.9 and 23.1% of the patients, respectively, with a combined sensitivity of about 40%. The mean values of CA 125 and CA 15-3 were positively related to clinical stage and tumor differentiation. CA 125 and CA 15-3 values were correlated with response to chemotherapy in more than 80% of the cases. These findings suggest that CA 125 and CA 15-3 could be usefully employed in the management of cervical cancer.

Adult↗

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↗

Multiple serum markers in patients with endometrial cancer.

Serum levels of carcinoembryonic antigen (CEA), CA 125 and CA 15-3 were measured in 47 patients with endometrial cancer and 20 with endometrial hyperplasia. Before treatment elevated serum levels of CEA, CA 125 and CA 15-3 were found in 14, 43 and 32% of cancer patients, respectively. In the 20 patients with endometrial hyperplasia, CEA and CA 15-3 values were normal, while elevated CA-125 titers were detected in 1 case. There was an increasing incidence of abnormal levels of all markers in relation to a higher tumor stage (stage I: 36%; II: 66%; III: 100%). The percentage of positive marker values increased in case of deep myometrial infiltration (greater than M1) and/or poorer tumor differentiation (greater than G1). However, only percent increase in CA 15-3 positivity was significantly higher in more infiltrating (greater than M1, 7 vs. 65%, p less than 0.01) and less differentiated (greater than G1, 0 vs. 47%, p = 0.01) tumors. These findings suggest that CA 15-3 is in some way associated with the prognostic factors of the disease. All patients except 2 with no evidence of disease after surgery had normal serum marker values. Moreover, CA 125 and CA 15-3 levels reflected the clinical course of the disease during chemotherapy and seemed to be useful for monitoring response to treatment.

Aged↗

Ultrasonic and endocrinologic relationships in spontaneous and induced follicular phase.

To correlate ovarian growth and follicular size with 17 beta-estradiol (E2) and androstenedione (A) peripheral levels, 20 induced cycles, 6 spontaneous ovulatory cycles and 6 spontaneous anovulatory cycles from 32 women during follicular phase were examined in order to obtain a better insight in the events involved in multiple folliculogenesis. In spontaneous ovulatory cycles, a significant correlation was obtained between E2 plasma levels and volume of the dominant follicle (p less than 0.05) as well as total follicular volume (p less than 0.01). Plasma A was significantly related with sonographic features likely related to ovarian stroma as well as preantral and antral subordinated follicles, which usually fail to ovulate. Significant correlation between E2/A peripheral ratio and volume of the dominant follicle(s) was also found (p less than 0.01). In anovulatory cycles, inverse significant correlation between E2 and sonographic aspects of degenerating antral follicles (p less than 0.001) was found, whereas a positive significant correlation between E2 and ovarian stroma was obtained (p less than 0.001). No correlation between peripheral A and any ovarian sonographic compartment was evident. However in the anovulatory cycles group a significant correlation between A v E2 peripheral levels was found, too. During HMG regimen, all the ovarian compartments seemed to be responsible for E2 peripheral levels. Ovarian stroma as well as preantral and multiple antral follicles were related to A levels. E2/A peripheral ratio did not result to be a good indicator of the large follicles. During "pure" FSH therapy, exclusive correlations between estrogen and large follicles as well as total follicular volume were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

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↗

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↗

Prolyl derivatives of enalapril as potential angiotensin converting enzyme inhibitors.

The synthesis of a new class of potential angiotensin converting enzyme (ACE) inhibitors, analogs of enalapril, is reported. In these molecules the C-terminal amino acidic sequence Ala-Pro of enalapril was replaced by the sequence Pro-Pro. The compounds were tested both in vitro and in vivo. They showed no in vivo activity but only a week in vitro inhibitory activity.

Angiotensin-Converting Enzyme Inhibitors↗

Characteristics of the effect of S-100 proteins on the assembly-disassembly of brain microtubule proteins at alkaline pH in vitro.

The ability of S-100 proteins to inhibit the assembly of brain microtubule proteins (MTPs) in the presence of microM levels of Ca2+ increases as a function of pH. This seems to be due to an increasingly larger inhibitory effect of S-100 on the nucleation and, probably, on the elongation of microtubules (MTs) as the pH raises. In the presence of microM Ca2+ levels, the ability of S-100 to disassemble MTs also increases linearly with the pH, suggesting that the larger inhibitory effect of S-100 on MTP assembly at alkaline than at acidic pH may depend on both a decrease in the assembly rate and an increase in the disassembly rate. Also, S-100 inhibits the assembly of phosphocellulose-purified tubulin to a larger and larger extent as the pH raises. S-100 brings about its effect on MT assembly-disassembly probably by sequestering soluble tubulin, though additional mechanisms cannot be excluded. The present data are briefly discussed in relation to the role attributed to changes in intracellular pH in the regulation of the state of assembly of cytoplasmic MTs.

Animals↗

Plasma levels of vitamin D metabolites in fetal and pregnant ewes.

The plasma concentrations of calcium; inorganic phosphorus; 25-hydroxyvitamin D; 24,25-dihydroxyvitamin D; and 1,25-dihydroxyvitamin D were determined in sheep maternal and fetal arterial circulations. In addition, plasma concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were determined simultaneously across the uterine and umbilical circulations. Fetal arterial levels of calcium (r = 0.560); inorganic phosphorus (r = -0.095); and 1,25-dihydroxyvitamin D (r = 0.040) were significantly higher than and did not correlate with maternal arterial levels. Maternal levels of 25-hydroxyvitamin D were significantly higher than and correlated (r = 0.693) with fetal 25-hydroxyvitamin D levels. No significant difference existed between maternal and fetal arterial levels of 24,25-dihydroxyvitamin D. No significant difference was detected in the concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D across the uterine or umbilical circulations.

Animals↗

Diagnostic significance of steroid hormones in patients with ovarian cancer.

One hundred and fourteen pre- and postmenopausal patients with nonendocrine tumors or simple cysts of the ovary were studied. These patients had androstenedione (A) plasma levels determined preoperatively. Some of these subjects had estrone (E1) and 17 beta-estradiol (E2) determinations also. Of the tumor patients, 58 had also measured the postoperative steroid levels. The results were compared with the hormone levels found in 188 normal women, who were of similar weight and reproductive status. Significantly increased (p less than 0.001) A, E1 and E2 plasma concentrations were found in postmenopausal patients with nonfunctioning tumors. In the tumor patients before the menopause, the levels of A were significantly elevated (p less than 0.001). In the patients with simple cysts, these steroid levels were within the normal range. Following ovariectomy, the decrease of plasma A suggested that the origin of the high levels of this steroid was the ovary where the neoplasm resided. For possible diagnostic purposes, both A and E1 abnormal test results showed adequate sensitivity and good specificity to permit detection of ovarian carcinoma after the menopause. Plasma levels of A were partially related to the histological types and FIGO Stages of the tumor.

Adult↗

Angiotensin converting enzyme inhibitors as antihypertensive agents: 1-[(2-mercaptocycloalkyl)carbonyl]-L-prolines.

The synthesis of 1-[(2-mercaptocyclopentyl)carbonyl]-L-prolines, 1-[(2-mercaptocyclobutyl)carbonyl]-L-prolines and related benzoyl derivatives as pure isomers is described. The abilities of all the compounds to inhibit angiotensin converting enzyme (ACE) in vitro and in vivo and to lower the systolic blood pressure in renal hypertensive dogs were determined. Three of them, namely 1-[[2-(benzoylthio)cyclopentyl]carbonyl]-L-proline (10f(R,S], 1-[(2-mercaptocyclopentyl)carbonyl]-L-proline (10g(R,S], and 1-[[2-(benzoylthio)cyclobutyl]carbonyl]-L-proline (16f(R,S], were found to be as potent as captopril in reducing blood pressure. The influence of chirality and ring size on the ACE inhibition is described.

Angiotensin-Converting Enzyme Inhibitors↗

Structure-activity studies of 16-methoxy-16-methyl prostaglandins.

The synthesis of the pure diastereoisomer of 16-methoxy-16-methyl-PGF2 alpha, -PGE2, and -PGE1 is described. The absolute configuration of C-16 was established by chemical methods, while the absolute C-15 configurations of the diastereoisomers were assigned tentatively on the basis of their chromatographic behavior and NMR spectra. The synthetic prostaglandin analogues were evaluated for antisecretory, antifertility, and diarrheogenic effects. Both the C-15 and C-16 configurations were found to be critical for the biological activities. These studies indicate that the introduction of the methyl and methoxy groups at C-16 into the prostaglandin analogues markedly increases the ratio of antisecretory to diarrheogenic action. One of the PGE1 derivatives, 9f(15 alpha, 16R) (MDL 646, mexiprostil), was selected for further pharmacological evaluation and is currently under clinical investigation.

Alprostadil↗

Effects of S-100 proteins on assembly of brain microtubule proteins: correlation between kinetic and ultrastructural data.

Microtubules formed in vitro in the presence of S-100 proteins and micromolar Ca2+ concentrations are fewer in number and longer than those formed in the presence of Ca2+ alone. Moreover, microtubules growing after addition of microtubule fragments to a microtubule protein solution in the presence of S-100 are shorter than those growing in its absence. These data lend support to previous results of kinetic studies indicating that S-100 interferes with both the nucleation and the elongation of microtubules in vitro.

Animals↗