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Biomedical subjects

C Natoli

Publications and source records attributed to C Natoli.

At least 73 records · Page 4Linked to original sources

Two new estrogen-supersensitive variants of the MCF-7 human breast cancer cell line.

Two new estrogen-sensitive variants of MCF-7 human breast cancer cells, CG-4 and CG-5, are described in this report. These cells were derived from a casual contamination by MCF-7 cells of primary cultures from a human adenocarcinoma of the breast and a pleural effusion of a patient with advanced breast cancer, respectively. Careful characterization of these variants revealed chromosomal properties highly similar to and alloenzyme phenotypes identical to those of MCF-7 cells which were simultaneously cultured in the laboratory. MCF-7, CG-4 and CG-5 cells were tested for estrogen responsiveness under identical growth conditions, that is in the presence of culture medium supplemented with 5% charcoal-treated serum. While the number of MCF-7 cells increases by about 40% over the controls in the presence of physiological concentrations of estradiol, the number of CG-4 cells doubles and the number of CG-5 cells triples. All these cell lines have approximately the same number of estrogen, androgen, glucocorticoid, and progesterone receptor sites/cell. Since several difficulties arise in demonstrating the estrogen responsive growth stimulation of currently available human breast cancer cells, these two new variants, characterized by a high and reproducible estrogen responsiveness, afford a new model for studying the mechanisms by which estrogen regulates cell proliferation. The problems related to the careful characterization of every established cell line are discussed.

Adenocarcinoma↗

Glucocorticoids inhibit the stimulatory effect of epidermal growth factor on the initiation of DNA synthesis.

Confluent, quiescent Swiss 3T3 cells in culture can be stimulated to initiate DNA synthesis and divide by addition of growth factors to the culture medium. Here we show that hydrocortisone and other steroids which have glucocorticoid activity inhibit the stimulation of these cells by epidermal growth factor (EGF) in contrast to their reported enhancement of stimulation by fibroblast growth factor (FGF). Binding studies using [3H]-triamcinolone acetonide show that Swiss 3T3 cells contain a single class of glucocorticoid receptor of uniform affinity (KD = 2.0 nM), and about 34,000 receptor sites per cell. Those steroids which displace bound [3H]-triamcinolone acetonide are also effective in inhibiting the stimulation of DNA synthesis by EGF in the presence or absence of insulin, and the concentration of triamcinolone acetonide required for one-half maximal biological effect is in the same range as the KD. A similar concentration is required for one-half maximal enhancement of the effect of FGF. These results suggest that both the inhibitory and stimulatory effects of glucocorticoids may be mediated via these receptors, the different effects thus being due to differences in the intracellular events triggered by each growth factor.

Animals↗

[The insulinomas].

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Adenoma, Islet Cell↗

Gastric carcinoma associated with severe hypoglycemia sensitive to diazoxide.

A case of carcinoma of the stomach associated with severe hypoglycemia is reported. Diagnosis of insulinoma was excluded on the basis of history as well as laboratory tests. Postmortem examination revealed widespread small metastases to various organs; no metastasis was found in the pancreas; the histology of this gland did not show any pathological finding. No impairment in pituitary, thyroid, adrenal and liver function was detected. Fasting blood sugar ranged from 18 to 56 mg/100 ml. An oral glucose tolerance test showed a diabetic pattern with low insulin. Tolbutamide, glucagon and glucose injected i.v. gave only a moderate rise in plasma insulin levels; plasma glucagon response to arginine was subnormal. The determination of NSILA-s and gastrin in the serum of this patient gave normal values. Diazoxide infusion induced an increase in blood glucose and subsequent treatment with diazoxide relieved hypoglycemia for some months. The occasional detection of an islet cell antibody by immunofluorescence in this case is not easily understandable, but it might partly account for the carbohydrate intolerance. An impairment in gluconeogenesis dependent upon some substrate deficiency might account for the hypoglycemia in this patient.

Adenocarcinoma↗

Vesicocolonic fistulas in diverticulitis.

Diverticulitis is a disease affecting patients in the fifth to sixth decades. The charts of 12 patients with cesicocolonic fistulas secondary to diverticulitis were reviewed. Their presentation was primarily urological with pneumaturia present in 10 of 12 patients and fecaluria present in 5 of 12. The process of fistulization occurs in stages. If the incipient stage can be identified early fistulization can be prevented and the morbidity and mortality rates will be reduced significantly. In older patients with bladder irritation (with or without positive urine cultures) a high degree of suspicion for diverticular disease will ensure an accurate diagnosis earlier. Patients with penumaturia or fecaluria present less of a diagnostic challenge. Cystoscopy is a reliable procedure and we recommend its use in discovering a vesicocolonic fistula. Surgical therapy should be individualized for each patient and good results were obtained with primary resection as well as staged repair.

Aged↗

Chronomodulated infusion of cisplatin, 5-fluorouracil and folinic acid: lack of activity in advanced colorectal cancer.

BACKGROUND: The chronomodulated infusion of 5-FU, FA and oxaliplatin allows a significant increase in dose intensity and antitumor efficacy in patients with metastatic colorectal cancer. Here we investigated if substitution of oxaliplatin with cisplatin produced a similar antitumor activity in previously untreated patients with advanced colorectal cancer. METHODS: We enrolled 21 consecutively evaluated ambulatory patients with metastatic colorectal cancer. Each treatment cycle consisted of a 5-day course of continuous chronomodulated venous infusion of drugs. Daily doses were 600 mg/m2 5-FU, 150 mg/m2 FA (L-form), and 12 mg/m2 cisplatin. The cycles were repeated every 21 days. RESULTS: All patients completed at least 3 cycles. Overall a total number of 105 cycles were administered. One partial response (lasting 3 months) and 13 stable disease (lasting from 3 to 12 months) were observed. The remaining 7 patients had progression of the disease. Hematologic and gastrointestinal toxicity was always < or = G2 in all cycles. CONCLUSIONS: The results of this study discourage the substitution of cisplatin for the more active compound, oxaliplatin, in a chronomodulated schedule of infusion with 5-FU and FA in patients with metastatic colorectal cancer.

Adult↗

Peritoneal mesothelial cells as a significant source of ascitic immunostimulatory protein 90K.

The tumor associated antigen 90K is known to possess cytokine-like modulatory properties on the cellular immune system, whereby accessory cells are the primary target of this molecule. In 67 ovarian cancer patients presenting with significant amounts of ascites, immunostimulatory protein 90K was detected in all ascitic fluid samples examined. Furthermore, 90K levels correlated to ascitic s-IL-2R content. To elucidate the source of protein 90K in ascitic fluid; its in vitro release was investigated in primary cultured normal human peritoneal mesothelial cells (HPMC). Peritoneal mesothelium was found to produce five-fold more 90K than ovarian cancer cells. Release of protein 90K was significantly increased by treatment with IFN-gamma in both mesothelial and ovarian cancer cells. In contrast neither IL-1 beta nor TNF-alpha treatment consistently influenced the secretion of 90K in either cell type.

Adult↗

Advanced breast cancer: response to somatostatin.

It has previously been reported that a somatostatin analogue has a direct antiproliferative effect on human breast cancer cells in vitro. Here we report preliminary data on the effects of the in vivo administration of SMS in patients with advanced breast cancer. The regimen consisted of iv infusion of 750 micrograms SMS t.i.d. for 10 days followed by 5 days at 500 micrograms im b.i.d. A partial response was observed in 3 out of 10 patients treated. Moreover, a marked reduction of oedema, cyanosis and bleeding from ulcerated tumor lesions was noted in most of the treated patients. Administration of SMS was devoid of toxic side effects. It is suggested that SMS may be of potential value in the therapeutic approach to advanced breast cancer.

Breast Neoplasms↗

Bone marrow micrometastases detected by a monoclonal antibody in patients with breast cancer.

One major problem in primary breast cancer is the identification of new parameters able to select patients at high risk of recurrence. Our study was aimed at detecting mammary tumor cells in the bone marrow of breast cancer patients using a single bone marrow sampling and the monoclonal antibody AB/3. This antibody recognizes a membrane carbohydrate epitope present in human breast cancer cells but not in normal tissues. Only 2 out of 45 breast cancer patients were found to have a bone marrow positive AB/3 staining reaction. Our data confirm and extend previous reports that single bone marrow sampling coupled with immunocytochemistry is not sensitive enough to be used as a routine procedure to acquire prognostic information in breast cancer.

Antibodies, Monoclonal↗

An antiestrogenic action of interferons in human breast cancer cells.

The antiproliferative and antiestrogenic effects of human interferon on estrogen-dependent CG-5 human breast cancer cells in vitro are reported. Fibroblast beta - interferon as well as recombinant alpha - and gamma -interferon inhibited proliferation of CG-5 cells in a dose and time - dependent fashion. In addition, they completely suppressed the two-fold increase in cell number induced by estradiol and showed an additive antiproliferative effect when used in combination with the antiestrogen tamoxifen. These antiestrogenic effects of interferons were accompanied by a reduced receptor binding of estradiol to the cells.

Breast Neoplasms↗

Elevated serum levels of a 90,000 daltons tumor-associated antigen in cancer and in infection by human immunodeficiency virus (HIV).

Levels of a 90,000 daltons monoclonal antibody-defined tumor-associated antigen, termed 90K, were measured in the serum from 649 patients with various types of cancer and 1215 patients infected by the human immunodeficiency virus (HIV). Significantly increased 90K serum levels (12.1 +/- 0.5 U/ml) were found in cancer patients with respect to healthy controls (5.7 +/- 0.3 U/ml), with the highest levels in neoplasms of the breast, lung and gastrointestinal tract. In 355 patients with breast cancer, the elevation of serum 90K levels was more pronounced at advanced stages of disease. Mean levels of 90K for 1215 HIV-infected subjects (21.2 +/- 0.8 U/ml) were significantly higher than controls and cancer patients, and the levels progressively increased with disease worsening from asymptomatic infection to full blown AIDS. These data suggest that 90K is not merely a tumor-associated antigen and lead us to postulate it to be a signalling molecule whose production might be related to the immune deficit caused by pathogenetic events such as neoplastic progression and virus infection.

Antigens, Neoplasm↗

Chronomodulated infusion of 5-fluorouracil, folinic acid and carboplatin in colorectal cancer: a pilot study.

We investigated if chronomodulated infusion of fluorouracil, folinic acid in combination with carboplatin shows antitumor efficacy in patients advanced metastatic colorectal cancer. Thirteen patients entered into the study. Each treatment cycle consisted of a 5 day course of continuous venous infusion of 5-fluorouracil (5-FU; 500 mg/m2/die), folinic acid (FA; L-form, 150 mg/m2/die) and carboplatin (CBDCA; the dose being calculated according to the Calvert's formula). Patients received the drugs according to the circadian-modified infusion schedule with a sinusoidally modulated delivery with peak flow rate at 4.00 AM for 5-FU and FA and 4.00 PM for CBDCA. Overall a total number of 54 cycles were administered. Two partial responses and one minor response were observed among the 5 untreated patients. Five patients had progression of disease. Stabilization of previously progressive disease was obtained in the 5 remaining patients. These preliminary results show that the combination of 5-FU, FA and CBCDA infused at circadian-modulated rate has moderate activity in colorectal cancer, specially in previously untreated patients, with a mild and acceptable toxicity.

Adult↗