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Biomedical subjects

S Barni

Publications and source records attributed to S Barni.

304 records · Page 17Linked to original sources
PubMedDate not supplied

Effects of granulocyte-macrophage colony stimulating factor on soluble interleukin-2 receptor serum levels and their relation to neopterin and tumor necrosis factor-alpha in cancer patients.

SIL-2R levels mainly depend on a T lymphocyte production. The mechanisms responsible for the elevated blood concentrations of SIL-2R in advanced solid tumors are still unknown. To investigate the role played by the monocyte-macrophage system on SIL-2R release, we have evaluated serum levels of SIL-2R in 10 head and neck cancer patients during GM-CSF subcutaneous administration (3 mcg/kg/day for 11 consecutive days). Serum levels of TNF and neopterin, both produced by macrophages, were also measured. SIL-2R mean concentration significantly enhanced in response to GM-CSF, and their rise positively correlated to that in TNF and neopterin values, while lymphocyte mean number did not increase during the study. The present results represent the first in vivo demonstration that SIL-2R release is related to macrophage activation, rather than to depend only on lymphocyte proliferation.

Adult↗
PubMedDate not supplied

Inhibition of tumor necrosis factor-alpha secretion by pentoxifylline in advanced cancer patients with abnormally high blood levels of tumor necrosis factor-alpha.

TNF, in addition to its antitumor activity, would play an important role in the pathogenesis of cancer-related severe complications, including ARDS and DIC. Therefore, the modulation of TNF secretion could be important in the supportive care of advanced cancer patients. At present, PTX is the only drug which has been proven to be able to inhibit in vitro the release of TNF. The present study was performed to evaluate the effect of PTX on TNF blood concentrations in disseminated cancer patients with abnormally high TNF values. The study included 14 cancer patients, with initial or conclamate signs of ARDS (n = 8) or DIC (n = 6). PTX was given intravenously at a dose of 300 mg/day for 7 days. Mean serum levels of TNF significantly decreased in response to PTX therapy, and they returned to normal range in 5/14 patients. These preliminary data would suggest that PTX may be considered as a biological response modifier, capable of inhibiting TNF secretion in humans, with a following potential use in the treatment of cancer-related severe complications.

Adult↗
PubMedDate not supplied

Cytokine regulation of iron metabolism: effect of low-dose interleukin-2 subcutaneous therapy on ferritin, transferrin and iron blood concentrations in cancer patients.

It is known that the anemias of chronic diseases, which often occur in neoplastic and in systemic inflammatory disorders, are characterized by high levels of ferritin associated with generally low iron concentrations, by suggesting an iron transfer defect due to unknown factors. Since both chronic inflammatory diseases and advanced neoplasms are characterized by alterations in the endogenous production of cytokines, a possible involvement of interleukins in chronic disease-related anomalies of iron metabolism cannot at present be excluded. The present study was carried out to investigate the effect of low-dose IL-2 subcutaneous immunotherapy (3 million IU/day for 6 days/week for 4 weeks) on ferritin, transferring and iron serum levels in cancer patients. Six patients with metastatic gastrointestinal carcinomas were evaluated. Ferritin mean levels significantly decreased during IL-2 treatment, and this finding was associated with a significant increase in transferrin values. Iron mean levels increased in response to IL-2, without, however, significant differences in respect to the pretreatment concentrations. These preliminary data, by showing changes in ferritin, transferrin and iron in cancer patients during the immunotherapy with IL-2, would suggest the existence of a cytokine regulation of iron transfer from tissues to blood, perhaps by modulating the macrophage function.

Adult↗
PubMedDate not supplied

Amplification of eosinophilia by melatonin during the immunotherapy of cancer with interleukin-2.

Eosinophilia, which occurs during IL-2 immunotherapy, has appeared to be due to an enhanced secretion of IL-5 and to be associated with a clinical response. Since our previous experimental studies showed that the pineal hormone MLT potentiates IL-2 efficacy, a study was started to evaluate the influence of a concomitant MLT administration on IL-2-induced eosinophilia. The study included 30 advanced solid tumor patients, 16 of whom received IL-2 alone (6 million IU/day) and the other 14 IL-2 plus MLT (10 mg/day orally at 8.00 P.M.). Eosinophil mean number was significantly enhanced during both treatments, but its increase in patients receiving IL-2 plus MLT was significantly higher than that seen in patients treated with IL-2 alone. These results show that MLT may enhance IL-2-induced eosinophilia, by suggesting that T helper lymphocyte- type 2, which is the source of IL-5, may be the target cell for MLT action.

Adult↗
PubMedDate not supplied

Correlation between pretreatment serum levels of neopterin and response to interleukin-2 immunotherapy in cancer patients.

IL-6 levels have been proven to correlate with resistance to IL-2 immunotherapy. Since IL-6 may be produced by both macrophages and TH2 lymphocytes, it is not possible to establish whether the negative prognostic significance of IL-6 levels may primarily depend on an enhanced macrophage or TH2 activation. Macrophage activation may be documented by the increase in its specific marker neopterin. In an attempt to establish whether the negative significance of IL-6 high levels prior to IL-2 immunotherapy may reflect an enhanced macrophage activation, we have investigated the relation existing between pretreatment concentrations of neopterin and response to IL-2 immunotherapy in cancer patients. The study included 20 metastatic renal cell cancer patients, who were treated with IL-2 subcutaneously at 6 million IU/day for 5 days/week for 6 weeks. Before the onset of IL-2 therapy, abnormally high serum levels of neopterin were seen in 11/20 patients. Moreover, neopterin concentrations were significantly correlated with those of IL-6. Tumor regression rate was significantly higher in patients with normal than in those with elevated levels of neopterin prior to therapy (5/9 vs 1/11, P < 0.05), as well as the percent of the survival at 1 year (9/9 vs 4/11, P < 0.01). This preliminary study would suggest that pretreatment values of the macrophage marker neopterin correlate with resistance to IL-2 cancer immunotherapy.

Adult↗
PubMedDate not supplied

Cell activation and death (apoptosis) induced by IL-2: ultrastructural evidence.

Peripheral blood cells of cancer patients with advanced renal carcinoma and treated with interleukin-2 by intravenous application were studied by electron microscopy at different intervals from the beginning of rIL-2 administration. Morphofunctional modifications of lymphocytes, circulating hystiocytes containing phagocitated bodies and polimorphonucleated cells undergoing phagocytosis were observed with a time dependent increase of altered cells. The analysis of blood cells cultured in the presence of recombinant IL-2 confirmed the in vivo results. Our data suggest that IL-2 induces apoptotic phenomena in the peripheral blood cells of treated patients.

Apoptosis↗
PubMedDate not supplied

Relation between macrophage and T helper-2 lymphocyte functions in human neoplasms: neopterin, interleukin-10 and interleukin-6 blood levels in early or advanced solid tumors.

At present, it is known that there are two main mechanisms responsible for cancer-related immunosuppression, mediated by macrophages and by TH2 lymphocytes. The relation existing between macrophage- and TH2-mediated immunosuppression still remains to be understood. The present study was performed in an attempt to establish which is the correlation existing in cancer patients between IL-10 and neopterin levels, which reflect TH2- and macrophage-mediated suppressive events, respectively. The study included 40 solid tumor patients and 60 healthy subjects as controls. Serum concentrations of neopterin and IL-10 were measured by the RIA method and by an immuno-enzymetric assay, respectively. Because of its possible production both by TH2 and macrophages, serum levels of IL-6 were also determined. Neopterin, IL-10 IL-6 mean concentrations were significantly higher in cancer patients than in controls. Mean values of both neopterin and IL-6 were significantly higher in metastatic patients than in those with locally limited disease. IL-10 mean levels were also significantly higher in patients with metastatic disease. IL-6 levels were significantly correlated with those of neopterin, whereas no correlation was found between neopterin and IL-10 values. This preliminary study would suggest that macrophage- and TH2-mediated immunosuppression may occur independently in solid tumors, and that it becomes more evident with disease progression.

Adult↗
PubMedDate not supplied

Neuroimmunotherapy with low-dose subcutaneous interleukin-2 plus melatonin in AIDS patients with CD4 cell number below 200/mm3: a biological phase-II study.

A phase-II pilot clinical study was performed to evaluate the effects of low-dose subcutaneous IL-2 with the pineal hormone melatonin (MLT) in AIDS patients with CD4 counts below 200/mm3. The study included 11 patients. IL-2 was given subcutaneously at 3 million IU/ day in the evening for 6 days/week for 3 weeks. MLT was given orally at 40 mg/day in the evening every day, starting 7 days prior to IL-2. The treatment was substantially well tolerated, and in particular no cardiovascular or pulmonary complication occurred. An increase in CD4 cell number greater than 30% occurred in 4/11 (36%) patients, and CD4 cell mean values observed during the study were significantly higher with respect to those found before. In addition, the treatment induced a significant increase in mean number of lymphocytes, eosinophils, T lymphocytes, NK cells, CD25- and DR-positive lymphocytes. Finally, CD4/CD8 mean ratio significantly increased during the study. This preliminary clinical study suggests that the combined neuroimmunotherapy with low-dose subcutaneous IL-2 and MLT may improve the immune status also in AIDS patients with CD4 cell counts below 200/mm3, who generally do not respond to IL-2 alone.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Treatment of cancer-related thrombocytopenia by low-dose subcutaneous interleukin-2 plus the pineal hormone melatonin: a biological phase II study.

Despite the platelet production in response to IL-2, cancer immunotherapy with IL-2 tends to induce thrombocytopenia, which probably depends on an enhanced peripheral destruction. On the basis of our previous studies, this effect may be neutralized by a concomitant administration of the pineal hormone melatonin (MLT). This study was performed to investigate the influence of an immunotherapeutic combination with low-dose IL-2 and MLT on platelet number in advanced cancer patients showing persistent thrombocytopenia. The study included 14 advanced solid tumor patients, affected by thrombocytopenia due to different causes (portal hypertension: 9; previous chemotherapies: 3; DIC: 2). IL-2 was injected at 3 million IU/day subcutaneously for 6 days/week for 4 weeks, in association with MLT (40 mg/day orally). A normalization of platelet number occurred in 10/14 (71%) patients, and platelet mean number significantly increased on treatment. No important therapy-related toxicity was observed. This preliminary study would suggest that the concomitant administration of MLT is able not only to neutralize IL-2-induced thrombocytopenia, but also to increase platelet number in thrombocytopenic cancer patients.

Adult↗
PubMedDate not supplied

Clinical significance of erythrosedimentation rate in cancer in relation to cytokine production: correlation with high IL-6 and low IL-2 blood concentrations.

Despite its well documented unfavourable prognostic significance in several human diseases, including cancer, the cytokinic mechanisms responsible for an increased erythrosedimentation rate (ESR) still remain to be better analyzed and defined. The recent possibility to measure cytokine concentrations in the blood of patients has allowed us to explore the possible relation between ESR values and endogenous cytokine secretions. This preliminary study was performed to evaluate the relationship between ESR values and serum levels of IL-2 and IL-6, which represent the most important cytokines responsible for the activation and the suppression, respectively, of host anticancer immune reaction. The study included 33 consecutive solid tumor patients, 22 of whom showed distant organ metastases. Abnormally high values of ESR were present in 21 patients, including 18/22 metastatic patients and 3/11 nonmetastatic patients. Patients with elevated values of ESR showed significantly higher mean levels of IL-6 and significantly lower mean concentrations of IL-2 with respect to those found in patients with normal ESR values. These results would show that cancer-related increase in ESR values is associated with low levels of IL-2 and high levels of IL-6. Since IL-2 plays an essential role in the anticancer immunity and IL-6 may suppress the antitumor immune defenses, the evidence of low levels of IL-2 and high values of IL-6 in cancer patients with increased ESR values would explain the unfavourable prognostic significance of high ESR values in human neoplasms.

Adult↗
PubMedDate not supplied

Hyperthermic effects on the human metastatic liver: a TEM study.

Using ultrastructural analysis, we studied the effects of hyperthermic treatment of one case of human liver metastasis from colon carcinoma. The results indicate that the main hyperthermic response involves the neoplastic and the histiocytic cell population. The drastic decrease in metastatic cells was accompanied by the appearance of cell fragments and apoptotic bodies. Consequently, the histiocytic component (Kupffer cells) showed increased frequency, indicating an activated state. The data are consistent with a direct action of the heat on tumor cells with subsequent activation of Kupffer cells.

Apoptosis↗
PubMedDate not supplied

Acute endocrine effects of interleukin-12 in cancer patients.

IL-12, which play a fundamental antitumor role, would be also involved in the physiological regulation of neuroendocrine and immune interactions. At present, however, there are no data about the endocrine effects of IL-12. This preliminary study was performed to investigate the acute endocrine effects of IL-12 in metastatic renal cell cancer patients. Each IL-12 injection consisted of 0.5 micrograms/kg/bw subcutaneously in the morning. The study has evaluated the effects of 6 different injection cycles. Serum samples were collected before, and 4, 8 and 12 hours from IL-12 injection. In each sample, we have measured by the RIA method serum levels of GH, PRL, TSH, FSH, LH, T3, T4, cortisol, testoterone, estradiol and the pineal hormone melatonin. No significant change occurred in TSH, FSH, LH, T3, T4, testoterone and melatonin mean serum levels in response to IL-12 administration. In contrast, cortisol, PRL and estradiol significantly increased after Il-12 injection. GH also increased in response to IL-12, without however, significant differences with respect to the baseline values. This preliminary study shows that the acute subcutaneous injection of IL-12 may influence the endocrine secretions in humans. In particular, IL-12 would stimulate the secretions of cortisol, PRL and estradiol. Therefore, this study would further confirm that IL-12 may act as biological response modifier in humans, not only on the immune system, but also on the neuroendocrine functions.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Reactivation of a normal endogenous secretion of interleukin-2 in metastatic cancer patients by a chronic subcutaneous injection of interleukin-2.

It is known that advanced cancer patients may show abnormally low levels of IL-2. The immunotherapy with IL-2 can induce objective tumor regressions, but at present there are no data about the influence of a chronic exogenous IL-2 administration on endogenous secretion of IL-2. This preliminary study was performed to evaluate whether a prolonged IL-2 injection may be able to correct an eventual IL-2 endogenous deficiency in cancer patients. The study included 10 metastatic renal cancer patients, who underwent an immunotherapeutic cycle consisting of IL-2 at 6 million IU/day subcutaneously for 6 days/week for 4 weeks. Serum levels of IL-2 evaluated on venous blood samples collected before and 21 days after the end of IL-2 injection. Before the onset of treatment, abonormally low levels of IL-2 were seen in 6/10 patients. In patients with response or stable disease, mean levels of IL-2 observed 21 days after IL-2 cycle were significantly higher than those seen before therapy, whereas no difference occurred in those who progressed. This preliminary study would suggest that a prolonged subcutaneous injection of low-dose IL-2 may correct an eventual IL-2 endogenous deficiency in advanced cancer patients.

Adult↗
PubMedDate not supplied

Physiopathology of IL-12 in human solid neoplasms: blood levels of IL-12 in early or advanced cancer patients, and their variations with surgery and immunotherapy.

Experimental studies have shown that IL-12 plays an important role in the activation of the anticancer immune defenses. Unfortunately, at present the behavior of IL-12 secretion in human neoplasms remain to be established. In an attempt to draw some preliminary data about IL-12 secretion in human cancer, in the present study we have evaluated serum levels of IL-12 in a group of non-metastatic and metastatic solid tumor patients in relation to the survival time, and their changes in surgically treated cancer patients and in metastatic patients undergoing immunotherapy with IL-2. Mean serum levels of IL-12 were significantly higher metastatic patients (n = 40) than in those with locally limited solid neoplasm (n = 16). Moreover, within the metastatic group, the percent of 1-year survival was significantly higher in patients with abnormally elevated blood concentrations of IL-12 than in those with normal values. In the group of 10 patients surgically treated for gastrointestinal tract tumors, the surgical operation induced a significant decline in IL-12 mean serum levels. Finally, in a group of 23 metastatic renal cell cancer patients treated with IL-12 immunotherapy (6 million IU/day S.C. for 6 days/week for 4 weeks), the treatment was associated with a significant and progressive increase in IL-12 mean values. Moreover, serum mean levels of IL-12 observed in therapy in patients with response or stable disease were significantly higher than those found in progressing patients. This preliminary study seems to suggest that the evidence of high levels of IL-12 may have a favourable prognostic significance in solid tumor patients, either in baseline conditions or in response to IL-2 cancer immunotherapy.

Adult↗