Biomedical subjects

L Fumagalli

Publications and source records attributed to L Fumagalli.

149 records · Page 9Linked to original sources

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

Anticancer neuroimmunomodulation by pineal hormones other than melatonin: preliminary phase II study of the pineal indole 5-methoxytryptophol in association with low-dose IL-2 and melatonin.

Despite several years of experimental observations, the clinical application of the neuroimmunomodulation is still at the beginning. The pineal gland plays a main role in mediating the link between psychoneuroendocrine and immune systems. Melatonin (MLT), which is the main pineal hormone produced during the night, has appeared to amplify IL-2 anticancer activity. Other pineal hormones, however, would have immunomodulatory activity, in particular 5-methoxytryptophol (5-MTT), which is mainly produced during the light phase of the day. Previous clinical studies have shown that low-dose IL-2 plus MLT may have therapeutic efficacy in advanced cancer patients with neoplasms generally resistant to IL-2 alone, with a tumor regression rate generally less than 20% and an acceptable toxicity. The present study was carried out to evaluate the efficacy of low-dose IL-2 in association with both MLT and 5-MTT. The study included 14 untreatable advanced solid tumor patients (lung cancer: 4; gastric cancer: 3; mesothelioma: 2; hepatocarcinoma: 2; pancreatic cancer: 1; melanoma: 1; colon cancer: 1). IL-2 was injected subcutaneously at 3 MIU/day for 6 days/week for 4 weeks, by repeating a second cycle after a 21- day rest period. Both MLT and 5-MTT were given orally at 40 mg/day in the evening and at 1 mg/day at noon. The clinical results, as evaluated by WHO criteria after each cycle, consisted of partial response (PR) in 4/14 (29%) (lung cancer: 2; hepatocarcinoma: 1; mesothelioma: 1), stable disease (SD) in 6 and progressive disease in the last 4 patients. The treatment was extremely well tolerated in all patients, and in particular no fever greater than 38 degrees C occurred. These preliminary results show that the neuroimmunotherapy with low-dose IL-2 plus two pineal hormones, MLT and 5-MTT, is a well tolerated and potentially effective cancer therapy of untreatable advanced solid tumor patients, with results apparently superior with respect to those previously described with IL-2 plus MLT alone.

Adjuvants, Immunologic↗

PubMedDate not supplied

Melatonin as a new possible anti-inflammatory agent.

Several experiments have suggested that the pineal hormone melatonin (MLT) may regulate cancer growth by exerting both oncostatic and immunomodulating effects. In particular, MLT would stimulate the anticancer immunity induced by interleukin-2 (IL-2). Recent studies seem to suggest that the activation of the inflammatory response may counteract the anticancer efficacy of IL-2 immunotherapy because of the immunosuppressive action of inflammatory-related cytokines, mainly IL-6. At present, it is still unknown whether MLT may influence host immune antitumor defences by modulating the inflammatory response. To analyze this hypothesis, we have evaluated the effects of a chronic administration of MLT on some of the commonly used markers of inflammation, including erythrosedimentation rate (ESR), IL-6, neopterin and SIL-2R, in patients with evidence of activation of the inflammatory response due to advanced solid neoplasms or auto-immune diseases. The study included 14 patients (solid tumors: 9; autoimmune diseases: 5). MLT was given orally at 20 mg/day during the dark phase of the day for 7 consecutive days. Mean serum levels of IL-6, neopterin and SIL-2R significantly decreased in both groups of patients. ESR values also decreased on therapy, without, however, significant differences. This preliminary study shows that the pineal hormone MLT may inhibit the acute inflammatory reaction. Therefore, because of the immunosuppressive section of inflammation-related cytokines, this study could suggest that MLT may contribute to the generation of the immune reaction against cancer at least in part by removing the immunosuppression related to the activation of the inflammatory response.

Adjuvants, Immunologic↗

PubMedDate not supplied

Correlation between IL-12 and IL-2 blood levels in the metastatic neoplastic disease: a possible inhibitory feedback system regulating their secretion.

Despite the great importance of IL-2 and IL-12 in activating the anticancer immune response in humans, cancer-related physiopathology of their secretion needs to be better investigated. IL-2 blood levels have been proven to decrease in the advanced neoplastic disease, whereas preliminary data would suggest an enhanced secretion of IL-12 in metastatic cancer patients. This study was performed to analyze IL-2 levels in relation to those of IL-12 in metastatic solid neoplasms. The study included 40 untreated metastatic cancer patients. Serum levels of both IL-2 and IL-12 were measured by ELISA. Abnormally low blood levels of IL-2 and elevated values of IL-12 were observed in 16/40 and in 18/40 patients, respectively. Moreover, patients with IL-2 deficiency showed significantly higher mean levels of IL-12 than patients with normal values of IL-2. This preliminary result, by showing an increased secretion of IL-12 in advanced cancer patients with IL-2 endogenous deficiency, would suggest the existance of a possible feedback mechanism operating between macrophage release of IL-12 and T lymphocyte secretion of IL-2.

Adult↗

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↗