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Biomedical subjects

S Barni

Publications and source records attributed to S Barni.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

Endocrine effects of a 24-hour intravenous infusion of interleukin-2 in the immunotherapy of cancer.

Several experiments have demonstrated that there is a relationship between neuroendocrine and immune systems. Despite these interesting findings, only few studies have been performed up to now to evaluate the possible importance of neuroimmune interactions in influencing the biological efficacy and toxicity of cancer immunotherapy with IL-2. To analyze the effects of IL-2 on endocrine secretions, we have measured by RIA serum levels of cortisol, beta-endorphin, GH, PRL and of the pineal hormone melatonin in metastatic renal cancer patients, treated with 5-day courses of IL-2 at a daily dose of 3 x 10(6) U/m2, given through a 24-hour intravenous infusion. Six IL-2 courses were evaluated, by collecting blood samples at 4-hour intervals for 24 hours and by comparing the hormonal values with those observed in baseline conditions. Both cortisol and beta-endorphin mean values significantly increased during IL-2 infusion. GH and PRL also increased, but not in a significant manner. Finally, melatonin mean levels significantly decreased during the infusion. The IL-2-induced effects on cortisol, beta-endorphin and melatonin resulted in a complete abolition of their physiological circadian rhythm. These results show that IL-2 infusion induces important changes in endocrine secretions. Because of the immunosuppressive effect of cortisol and the stimulatory one of melatonin, their changes during IL-2 infusion might influence the biological activity of immunotherapy itself. Further studies will be required to define better the clinical importance of IL-2 induced hormonal changes.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Neuroimmunotherapy of human cancer with interleukin-2 and the neurohormone melatonin: its efficacy in preventing hypotension.

The pineal hormone melatonin (MLT) has been shown to influence many biological functions, including immune response, cancer growth and brain neurotransmitter contents. On the basis of its biological properties, a study was started to evaluate the influence of MLT on IL-2 immunotherapy toxicity. The study was carried out in metastatic renal cancer patients. Thirty-three 5-day courses of IL-2 at a daily dose of 3 x 10(6) Cetus U/m2 were randomized to consist of IL-2 alone or IL-2 plus MLT (10 mg/day orally at 8.00 p.m.). The frequency of episodes of severe hypotension was significantly greater during IL-2 alone than during IL-2 + MLT. Moreover, the depressive symptomatology occurred more frequently during IL-2 alone. No other toxicity, including capillary leak syndrome, vomiting and fever, were significantly influenced by the concomitant treatment with MLT. These preliminary results would suggest that the pineal hormone MLT may be successfully associated with IL-2 in the immunotherapy of human tumors.

Circadian Rhythm↗
PubMedDate not supplied

The action of cisplatinum (cis-DDP) on the postnatal growth of the rat liver. Cytokinetics and ultrastructural studies.

The early and late effects of cis-DDP treatment on liver cell kinetics were analyzed after its intraperitoneal injection into 17-day old rats. Frequency of binucleate hepatocytes, cellular DNA content distribution, 3H-thymidine labelling and ultrastructure of the nuclei were analyzed. Two days after treatment, a block of mononucleate hepatocytes in the S phase and in the G2 phase was demonstrated by the increase of intermediate 2c-4c and 4c DNA values in the absence of changes in 3H-thymidine labelling; 8c binucleate cells, which are essential for the formation of tetraploid mononucleate cells, were not found. In cell nuclei, large areas of more condensed chromatin appeared, perhaps providing further evidence for a G2 block. Seven days after treatment, there was a tendency to catch up with the normal situation, as shown by the unblocking of the S phase in mononucleate cells indicated by both cytophotometry and autoradiography. The presence of 8c binucleate cells and 4c-8c mononucleate cells indicates that 4c mononucleate hepatocytes are either diploid cells in the G2 phase or true tetraploid G1 cells. The decrease in the heterochromatin areas and the appearance of hypertrophic nucleoli demonstrate an increase in the metabolic activity of the nuclei. Thirty six days after treatment, the incidence of different DNA hepatocyte classes and the 3H-thymidine labelling were already similar in control and in treated rats.

Aging↗
PubMedDate not supplied

Alterations of pineal gland and of T lymphocyte subsets in metastatic cancer patients: preliminary results.

Melatonin (MLT), the main hormone produced by the pineal gland, has been seen to play a role in antineoplastic activity either by exerting a direct inhibitory effect on cancer cell growth, or by stimulating the immune system. Moreover, MLT blood levels have been shown to be often increased in cancer patients. On the basis of these data, a study was started to evaluate what relation exists between MLT levels and T lymphocyte subsets in patients with metastatic solid neoplasm. The study included 28 patients (breast: 10; non-small cell lung: 18). None of the patients was previously treated for their metastatic disease. Abnormally high MLT levels and a low T helper/suppressor ratio (CD4/CD8) were seen in 10/28 and in 11/28 patients, respectively. Serum mean levels of MLT were significantly higher in patients with low CD4/CD8 ratio than in those with a normal ratio. These results would suggest that immune dysfunctions may represent a signal for MLT release from the pineal in patients with metastatic solid neoplasm.

Adult↗
PubMedDate not supplied

Effects of cancer chemotherapy on the relation between serum levels of soluble interleukin-2 receptors and CD4/CD8 ratio in patients with solid neoplasms.

The clinical significance of sIL-2R in solid tumors has still to be clarified. To further define the biological role of sIL-2R in cancer and their relation to chemotherapy, we have measured serum levels of sIL-2R and CD4/CD8 ratio in 45 patients with limited or metastatic solid tumor, 28 of whom had never received chemotherapy, whereas the other 17 had been previously treated with chemotherapy. sIL-2R were significantly higher in metastatic cancer patients than in the non-metastatic ones, while no difference was seen between patients treated and untreated with chemotherapy. Within the untreated group, sIL-2R mean values were significantly higher in patients with low CD4/CD8 ratio than in those with the normal one, while an opposite behavior was seen in patients previously treated with chemotherapy. The present study shows that cancer chemotherapy influences the release of sIL-2R and its relation to T lymphocyte subpopulations.

Adult↗
PubMedDate not supplied

[Contents of nuclear Feulgen-DNA in carcinoma of the breast. Cytophotometric analysis].

The frequency distributions of the nuclear Feulgen-DNA, obtained with cytophotometric technique, in different types of female mammary carcinomas (invasive ductal carcinoma, papillary and mucinous ductal carcinomas and invasive lobular carcinoma) were correlated with the histological diagnoses and with the age of the patients. The highest and broadly scattered values of nuclear Feulgen-DNA content, in agreement with the cytomorphologic pictures, were observed in the invasive ductal carcinomas, above all in the youngest subjects (values from 2c to 16c). Papillary and mucinous ductal carcinomas from subjects of the same age, showed lower values; the cases of invasive lobular carcinomas exhibited more homogeneous values with a higher number of cells in the 2c region. The tissue with histological normal patterns showed 2c values of Feulgen-DNA contents with some values near 4c. The general situation point out a different complexity of the tumor population which can be related to a mosaic composition and/or to a multifocal origin with presence of cycling, non-cycling, euploid, aneuploid and polyploid fractions. Then, the Feulgen-DNA content can be correlated to the tumor type and the patient age; it is useful for diagnostic and prognostic problems in the oncological field.

Adult↗
PubMedDate not supplied

[Changes in the sialomucin content of cells of the Yoshida ascites hepatoma after radiotherapy. Cytophotometric analysis].

The X-ray (400 R) action on the membrane glycoproteins, glycolipids and sialic acid residues was studied in Yoshida ascites tumour cells. Some cells were pretreated with neuraminidase and then all were submitted to the Hale's reaction; the stain intensity was determined by integrating microdensitometer at a wave length of 660 nm. A significant decrease of the Hale-positivity (P less than 0,05) has been observed in cells submitted either to radiation or to enzyme treatment.

Animals↗
PubMedDate not supplied

DNA-protein cell content of lymphokine activated killer (LAK) and target cells in coculture.

An extensive study of the interactions between LAK-target cells in cocultures was performed by means of cytometric (relative DNA and protein content) and morphological parameters. The aim was to obtain new information about the cell cycle stage of tumor target cells (Chang line) during the attack of LAK cells. Specimens obtained from cocultures at 0, 24, 48 hours were processed for electron microscopy, flow cytometry, immunocytochemistry (anti-BrdU reaction) and light microscopy (L.I., M.I., cell-cell interaction). The most intense activity of LAK cells against the target was found at 24 hours of coculture independently of the proliferative stage of the tumor cells. These results suggest that the high affinity between killer and target cells was not affected by the molecular changes of the Chang cell surface during the cell cycle.

Cell Communication↗
PubMedDate not supplied

Role of the pineal gland in the control of macrophage functions and its possible implication in cancer: a study of interactions between tumor necrosis factor-alpha and the pineal hormone melatonin.

Recent studies have shown the existence of reciprocal links between cytokine activity and immunomodulating neurohormones or neuropeptides. In particular, the pineal hormone melatonin (MLT) appears to influence IL-2 activity in cancer. The present study was performed to evaluate which interaction exists between MLT and another important cytokine, tumor necrosis factor-alpha (TNF), which is responsible for both antitumor cytolytic activity and cancer-related cachexia. In a first study, we analyzed MLT circadian rhythm under TNF administration (0.75 mg/day i.v. for 5 days) in 10 metastatic solid tumor patients. In a second study, we evaluated TNF serum levels in 10 metastatic solid tumor patients under therapy with MLT alone (20 mg/day orally in the evening for at least 1 month). In a third study, we have measured concomitantly daily serum levels of MLT and TNF in 30 patients with metastatic solid neoplasms. Nocturnal mean serum concentrations significantly increased in response to TNF injection. MLT therapy induced a significant decline in TNF mean values. Finally, patients with abnormally high MLT diurnal levels showed significantly lower TNF mean concentrations with respect to those with normal levels of the pineal hormone. This study, by showing the stimulatory effect of TNF on MLT secretion and the inhibitory action of MLT on TNF release, would suggest the existence of feed-back mechanisms operating between the pineal gland and TNF released from macrophages in human neoplasms.

Adult↗
PubMedDate not supplied

Preliminary study on modulation of the biological effects of tumor necrosis factor-alpha in advanced cancer patients by the pineal hormone melatonin.

Previous experimental studies have suggested the possibility to modulate the biological activity and toxicity of cytokines by immunomodulating neurohormones. In particular, the pineal hormone melatonin (MLT) has been proven to amplify the immune effects of IL-2 and to reduce its toxicity. On this basis, we decided to investigate the effect of MLT on biological activity and toxicity of another important antitumor cytokine, TNF. The study was performed in 14 metastatic solid tumor patients, for whom no effective standard antitumor therapy was available. Informed consent was previously obtained from each patient. Patients were randomized to be treated with TNF or TNF plus MLT. Recombinant human TNF was given at a daily dose of 0.75 mg intravenously for 5 consecutive days. MLT was given orally at a daily dose of 40 mg, starting 7 days before TNF. Lymphocyte mean number observed at the end of TNF infusion was significantly higher in patients treated with TNF plus MLT than in those receiving TNF alone. On the contrary, no significant difference occurred in hemoglobin, platelet and neutrophil mean values. Asthenia and hypotension were significantly less frequent in patients treated with TNF plus MLT, whereas no difference occurred in the frequency of fever and chills. Even though limited to a small number of patients, this preliminary study would suggest the possibility to modulate TNF toxicity and biological activity by a concomitant treatment with the pineal hormone MLT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Weekly epirubicin plus low-dose interleukin-2 subcutaneous therapy in breast cancer: preliminary immunobiological results.

Experimental studies have shown that IL-2 may antagonize chemotherapy-induced lymphocytopenia. On this basis, we have evaluated the influence of low-dose IL-2 on lymphocyte and NK cell numbers in cancer patients treated with the anthracycline drug, epirubicin. The study included 7 metastatic breast cancer women treated with epirubicin at a dose of 25 mg/m2 i.v. weekly. IL-2 was given subcutaneously at 3 million IU/day for 6 days/week. Venous blood samples were drawn at weekly intervals, and the results were compared to those seen in 14 patients treated with epirubicin alone. Lymphocyte mean number observed on treatment was higher in patients concomitantly treated with IL-2 than in those receiving epirubicin alone, without, however, significant differences. In addition, NK cell mean number was significantly higher in patients receiving IL-2 than in those treated with epirubicin alone. These preliminary results would suggest that IL-2 may antagonize lymphocyte and NK cell declines during cancer chemotherapy with anthacyclines. Further studies will be required to confirm these results and to establish their possible influence on chemotherapy-induced tumor regressions.

Adult↗
PubMedDate not supplied

Normalization of idiopathic arterial hypertension following cancer immunotherapy with interleukin-2.

It is known that IL-2 cancer immunotherapy is associated with hypotension. The present study was performed to evaluate the influence of low-dose IL-2 subcutaneous therapy on blood pressure in cancer patients with idiopathic hypertension requiring hypotensive therapy. The study included 12 patients, who received IL-2 at 6 million IU/day for at least 4 weeks. Mean values of both systolic and diastolic pressure significantly decreased under IL-2 therapy, and the hypotensive agents were interrupted within 2 weeks in 10/12 patients. Moreover, 6 of them still showed normal blood pressure values without hypotensive therapy after a median follow-up of 6 months. This preliminary study would suggest that low-dose IL-2 subcutaneous therapy may normalize blood pressure values in cancer patients with idiopathic hypertension.

Aged↗
PubMedDate not supplied

A study of interactions among markers of macrophage functions in metastatic solid tumors: neopterin levels in relation to those of tumor necrosis factor-alpha and of soluble interleukin-2 receptors.

High levels of the macrophage activation marker neopterin have been described in metastatic cancer patients. Since macrophages may either counteract or stimulate tumor development, it is important to establish which macrophage activity is mainly related to neopterin release. The present study was carried out to evaluate neopterin levels in metastatic solid tumor patients in respect with the antitumor macrophage cytokine TNF and with soluble IL-2 receptor (SIL-2R), whose secretion is stimulated by macrophages and it is associated with the immunosuppressive status of cancer patients. The study included 35 patients with metastatic solid neoplasms. Serum levels of neopterin, TNF and SIL-2R were measured in blood samples collected during the morning. Abnormally high concentrations of neopterin were seen in 18/35 (51%) patients. Patients with high levels of neopterin showed significantly higher concentrations of SIL-2R than those with normal neopterin values, whereas no difference was found in TNF levels. This study would suggest that the increased secretion of neopterin may reflect macrophage-mediated immunosuppression in metastatic solid neoplasms, rather than to be associated with the antitumor activity of macrophages.

Adult↗
PubMedDate not supplied

Cancer immunotherapy with low-dose interleukin-2 subcutaneous administration: potential efficacy in most solid tumor histotypes by a concomitant treatment with the pineal hormone melatonin.

The antitumor efficacy of IL-2 is limited to renal cancer and melanoma. Several cytokines have been associated with IL-2 in an attempt to improve its activity, without, however, any clear benefit. Recent experimental and clinical studies have suggested the possibility to manipulate the host biological response by immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). On the bases of these considerations, we have designed a neuroimmunotherapeutic protocol with low-dose IL-2 subcutaneous therapy (3 million IU/day for 6 days/week for 4 weeks) plus MLT (40 mg/day orally, starting 7 days before IL-2) in advanced solid neoplasms other than renal cancer and melanoma, which are generally resistant to IL-2 alone. The study included 82 patients, 72 of whom showed distant organ metastases. Tumor histotypes were, as follows: non-small cell lung cancer: 19; hepatocarcinoma: 16; colon cancer: 15; gastric cancer: 11; cancer of pancreas: 11; breast cancer: 6; miscellaneous: 4. Objective tumor regression were achieved in 17/82 (21%) patients, consisting of CR in 4 (liver: 2; pancreas: 1; stomach: 1) and PR in 13 (lung: 4; liver: 4; stomach: 2; pancreas: 1; breast: 1; colon: 1). The median duration of response was 8+ months. A stabilization of disease was obtained in 30 patients, while the other 35 patients progressed. The lack of progression was associated with a significantly higher increase in lymphocyte and eosinophil mean number and with a significantly lower increase in neopterin mean levels. The treatment was well tolerated in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗