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Biomedical subjects

P Lissoni

Publications and source records attributed to P Lissoni.

At least 109 records · Page 6Linked to original sources
PubMed1991

Clinical results with the pineal hormone melatonin in advanced cancer resistant to standard antitumor therapies.

The pineal hormone melatonin (MLT) is able to exert an oncostatic action. Its possible use in the treatment of human tumors, however, has not yet been investigated. The present study was carried out to evaluate the effects of MLT in patients with metastatic solid tumors resistant to conventional therapies. The study included 54 patients, most of them were affected by lung cancer or colorectal carcinoma. MLT was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; this induction phase was followed by a maintenance period at a dose of 10 mg orally in responder patients or in those with an improvement in performance status (PS). The clinical response was as follows: 1 partial response (cancer of pancreas), 2 minor responses (colon cancer and hepatocarcinoma) and 21 with stable disease. The remaining 30 patients rapidly progressed within the first 2 months of therapy. An evident improvement in PS was achieved in 18 of 54 (33%) cases. These results, by showing an apparent control of the neoplastic growth and an improvement in the quality of life in a reasonable number of cancer patients for whom no other standard therapy is available, would justify further clinical trials to better define the impact of MLT therapy on the survival and quality of life of untreatable advanced cancer patients.

Adult↗
PubMed1991

[Cardioangioimmunology: the immune implications in the principle cardiovascular pathologies].

At present, it is known that the immune system acts through the release of protein factors, so-called cytokines. In addition to their immunomodulating and endocrinometabolic effects, cytokines have appeared to be able to have an influence on the cardiovascular system by inducing important haemodynamic changes. Cytokines cause hypotension, particularly IL-2 and TNF, due at least in part to a production of nitric oxide by endothelial cells. Cytokines, such as IL-1, IL-6 and TNF, stimulate myocardial infiltration by activating leukocytes and inducing the release of cytotoxic factors during myocardial infarction; that would extend the area of necrosis. Finally, cytokines would be involved in the pathogenesis of the atherosclerosis, and cholesterol metabolism itself would be under a cytokine control. On these bases, it is possible to suggest in the near future the elaboration of new therapeutic strategies and prognostic indications, according to the bioimmunological response of patients with cardiovascular diseases.

Arteriosclerosis↗
PubMed1990

Evaluation of the cardiovascular toxicity related to cancer immunotherapy with interleukin-2 by monitoring atrial natriuretic peptide secretion: a case report.

Increased capillary permeability and severe hypotension represent the two major cardiovascular complications of IL-2 immunotherapy. The mechanisms responsible for IL-2 cardiovascular toxicity are still obscure. Since increased vascular permeability and vasodilatation may be also induced by the cardiac hormone atrial natriuretic peptide (ANP), we have evaluated ANP concentrations in relation to mean arterial pressure in one patient with metastatic renal carcinoma, treated with a 24-h intravenous infusion of IL-2 at a dose of 3 x 10(6) Cetus U/m2/day for 5 days. The results showed that episodes of important hypotension were associated with abnormally high plasma levels of ANP. Owing to its vasodilator activity, exaggerated ANP secretion, perhaps due to an inappropriate cardiac endocrine function in response to hemodynamic changes induced by IL-2, may play a role in hypotension, which occurs during IL-2 immunotherapy for cancer.

Atrial Natriuretic Factor↗
PubMed1990

Severe hypotension in disseminated colon cancer due to a possible decreased dopamine brain content: a case report.

The case of a patient with advanced colon carcinoma is reported. She was hospitalized for severe hypotension, which was probably due to systemic vasodilatation. The patient was responsive only to continuous intravenous infusion of dopamine and was then successfully treated with an oral combination, consisting of L-dopa plus benserazide. Since benserazide blocks the peripheral production of dopamine, the effectiveness of this schedule in the treatment of severe hypotension would suggest the existence of a dopaminergic deficiency of the central nervous system rather than the peripheral vascular system. The present case report might represent a useful model to better understand the biochemical basis of hemodynamic dysfunction, which may occur in disseminated neoplasms or during immunotherapy of cancer with cytokines.

Adenocarcinoma↗
PubMed1990

Correlation of serum interleukin-2 levels, soluble interleukin-2 receptors and T lymphocyte subsets in cancer patients.

An interleukin-2 (IL-2) in vitro reduced production has been observed in most metastatic cancer patients. At present, however, there are no data on blood IL-2 levels in vivo, because of the too low sensitivity of previous biological and enzyme immunoassay methods. The recent development of a sensitive RIA method allowed us to start a preliminary investigation of IL-2 production in basal conditions in human solid tumors. The study included 42 cancer patients. Breast and lung cancer were the two commonest neoplasms. Serum levels of IL-2 and soluble IL-2 receptors (SIL-2R), and CD4/CD8 ratio were measured in each patient. The control group consisted of 58 healthy subjects. Mean serum levels of IL-2 were significantly lower in metastatic patients (n = 23) than in those without metastases (n = 19). Patients with low CD4/CD8 ratio (n = 16) had significantly lower mean values of IL-2 than those with normal ratio (n = 26). Finally, mean IL-2 concentrations were significantly lower in patients with elevated levels of SIL-2R than in those with normal values. These results would suggest that metastatic dissemination is associated with a decreased IL-2 production in vivo, and that reduced IL-2 production is more frequent in patients with low CD4/CD8 ratio.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

A study of the pineal hormone melatonin as a second line therapy in metastatic colorectal cancer resistant to fluorouracil plus folates.

Since there is no effective second line chemotherapy in colorectal cancer resistant to fluorouracil, this study was carried out to evaluate the therapeutic activity of the pineal hormone melatonin, which has appeared to have antineoplastic activity in some experimental conditions, in patients with metastatic colorectal carcinoma who did not respond to fluorouracil. The study included 14 patients (8 men, 6 women; mean age 58 years). Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; after that, melatonin therapy was continued at 10 mg/day orally in responder patients, in those with stable disease and/or an evident improvement in PS. One patient had a minor response; 3 other patients had a stable disease, whereas the other 10 cases progressed. An evident improvement in PS was seen in 5/14 (36%) patients. These preliminary results show that melatonin does not have important antitumor activity in metastatic colorectal cancer patients resistant to fluorouracil. However, the pineal hormone could be usefully employed as supportive care to improve the quality of life in these patients for whom no standard treatment is yet available.

Adult↗
PubMed1990

A study of pineal-prolactin interaction: prolactin response to an acute melatonin injection in patients with hyperprolactinemia.

Several studies demonstrated that the pineal gland plays a regulatory role in PRL secretion. At present, however, there are few clinical data only about the pineal function in PRL secretion disorders. To further clarify which is the pineal importance in the dysfunctions of PRL release, we have evaluated the effect of an acute injection of the pineal hormone melatonin in 19 patients with hyperprolactinemia, 8 of whom had idiopathic hyperprolactinemia, while the other 11 had a prolactinoma. Melatonin was given im at a dose of 20 mg at 09:00 h, and venous blood samples were collected at -20, 0, 20, 60, 120, 180 min. A normalization of PRL levels was achieved after melatonin injection in 3/8 patients with idiopathic hyperprolactinemia, while no effect was seen in patients with prolactinoma. Further studies, by evaluating the effect of a chronic treatment, will be required to define which is the action of melatonin on PRL release in PRL secretion disorders, and to evaluate its possible therapeutic role.

Adult↗
PubMed1990

The biological significance of soluble interleukin-2 receptors in solid tumors.

In an attempt to further understand the biological significance of soluble IL-2 receptors (sIL-2R) in solid tumors, we have evaluated 160 cancer patients (breast: 40; lung: 66; colon: 18; stomach: 22; uterine cervix: 14) and 58 healthy subjects, as controls. Serum mean levels of sIL-2R, measured with an enzyme immunoassay, were significantly higher in cancer patients than in controls. Metastatic cancer patients showed significantly higher values than the non-metastatic ones; this difference was significant in all tumor histotypes, except small cell lung carcinoma. Moreover, in 15 patients in whom sIL-2R were evaluated either before or after radical surgery, a significant surgery-induced increase in sIL-R mean values was seen. Finally, the chemotherapy-induced rise in sIL-2R appeared to be associated with a lack of clinical response. These results seem to suggest that sIL-2R may be a marker of host biological response in patients with solid tumors, the significance of which needs further investigation.

Adult↗
PubMed1990

Postoperative hyperprolactinaemia and early recurrence rate in breast cancer.

Serum levels of prolactin before and after surgery were measured in 90 women with breast cancer until the 5th postoperative month. Surgery-induced hyperprolactinaemia occurred in 51 patients, without significant correlation to any other clinical variable. After a median follow-up of 39 months, irrespective of each other variable (i.e. nodal involvement, oestrogen receptor status, adjuvant therapies), patients with postoperative hyperprolactinaemia had a significantly lower recurrence rate than those in whom surgery was not followed by an abnormal increase in prolactin secretion (3/51 vs. 13/39, P less than 0.001). These results suggest that, despite the stimulatory role of prolactin on mammary tumours, the lack of postoperative hyperprolactinaemia is an unfavourable prognostic factor because of its association with a higher relapse rate.

Adult↗
PubMed1990

Melatonin response to atrial natriuretic peptide administration in healthy volunteers.

Recent observations have demonstrated that the pineal hormone melatonin (MLT) plays a role in the neuroendocrine control of the cardiovascular system. On the other hand, it has been observed that the cardiac hormone alpha-atrial natriuretic peptide (ANP) may regulate the neuroendocrine functions. The present study was carried out to investigate the possible relationship between cardiac and pineal endocrine functions. Six healthy volunteers were treated on two different occasions with placebo or ANP at a dose of 0.1 mg i.v. as a bolus. An increase of greater than 100% in MLT serum levels was seen in 2/6 subjects. These preliminary results would suggest that ANP may play a role in the regulation of MLT secretion. Further studies will be needed to define better the cardiac-pineal interactions.

Adolescent↗
PubMed1990

A study of heart-pineal interactions: atrial natriuretic peptide response to melatonin administration in healthy humans.

It is known that the pineal hormone melatonin plays a role in the regulation of several biological functions. In an attempt to investigate interactions between the pineal and the cardiac endocrine activity, in this preliminary study we have evaluated the effect of melatonin on the secretion of the cardiac hormone, atrial natriuretic peptide (ANP). The study included five healthy volunteers, and melatonin was given orally at a dose of 30 mg at 17:00. The results of the study show that the administration of melatonin does not influence ANP plasma concentrations. Further studies will be required to better define the cardiac-pineal interaction.

Administration, Oral↗
PubMed1990

Preliminary studies on melatonin in the treatment of myelodysplastic syndromes following cancer chemotherapy.

Experimental studies have suggested that the pineal hormone melatonin, in addition to its documented antineoplastic action, plays a role in the physiological regulation of blood cell proliferation. Based on these data, we evaluated the clinical effects of melatonin therapy in patients with myelodysplastic syndrome (MDS) secondary to cancer chemotherapy for primary neoplasms. The study was carried out on six patients, and melatonin was given orally at a dose of 20 mg/daily, following a schedule prepared to reproduce the circadian rhythm of the pineal hormone. A transient improvement in platelet and neutrophil count was achieved in two of five patients with thrombocytopenia and in two of four patients with neutropenia before therapy, respectively, while no effect was seen on hemoglobin concentration. Mean survival time was 12.5 months, and a long survival, greater than 30 months, was achieved in two of six patients. These preliminary results seem to suggest that melatonin may have a role in the treatment of MDS induced by previous cancer chemotherapy.

Aged↗
PubMed1990

Pineal gland and tumor cell kinetics: serum levels of melatonin in relation to Ki-67 labeling rate in breast cancer.

Recent observations showed that host may regulate either endocrinologically or immunologically tumor growth and differentiation, perhaps by modulating oncogene expression. Within the endocrine system, the pineal hormone, melatonin, seems to play an important antineoplastic role. To investigate its secretion in relation to tumor growth, we have evaluated the daily serum levels of melatonin in a group of 25 untreated breast cancer patients with a locally limited disease. Tumor cell proliferation was established by measuring Ki-67 labeling rate. As controls, 46 healthy women were considered. Breast cancer patients showed significantly higher mean values of melatonin than controls. Moreover, patients with negative Ki-67 labeling rate had significantly higher levels of the pineal hormone than those with a positive Ki-67 rate. Since tumors with high growth fraction present a worse prognosis, this study would suggest that the relief of an increased melatonin secretion represents a favorable prognostic sign, because of its association with less proliferating breast cancers.

Adult↗
PubMed1990

Analysis of T helper and suppressor lymphocyte subsets in relation to the clinical stage of solid neoplasms.

Neoplastic disease affect the immunity in cancer patients. The immune alterations in human neoplasms, however, need to be further defined. The present study was carried out to analyze T lymphocyte subsets in patients with solid tumors. The study included 93 patients suffering from early or metastatic solid neoplasms. T helper and T suppressor subsets were measured on venous blood samples by using flow cytometry and monoclonal antibodies. As controls, 58 healthy subjects were included in the study. The T mean helper/suppressor ratio (CD4/CD8) was significantly lower in metastatic cancer patients with respect to that observed either in controls or in patients without metastases. A low CD4/CD8 ratio was seen in 25 of 93 cancer patients (26.9%), 8 of whom had no metastases, while the other 17 showed a metastatic disease. Within the nonmetastatic group, the decline in the CD4/CD8 ratio was due to increases in the T suppressor subset alone in 7. On the contrary, the percentage of cases with decreased T helper subset was significantly higher in metastatic than in the nonmetastatic patients. The results of this study suggest that the decrease in the CD4/CD8 ratio mainly depends on an increase in T suppressor cells in patients without metastases whereas it is due to a decrease in the T helper subset in most patients with metastatic diseases.

Adult↗
PubMed1990

[Radiotherapy plus a combination of cisplatin and 5-fluorouracil for locally advanced head and neck neoplasms. Study of feasibility and preliminary results].

In March 1989 we started a feasibility study of combined radio-chemotherapy in patients with locally-advanced head and neck cancer. The first phase of treatment consisted of conventional radiotherapy (2 Gy/day, 5 days/week for a total dose of 70 Gy to primary tumor and +/- 50 Gy to nodes) and cisplatinum (20 mg/m2, i.v., for 4 days) +5FU (200 mg/m2, i.v., for 4 days) every 4th week, during radiant sessions. The second phase of treatment was started about one month after the end of simultaneous chemotherapy and radiotherapy: patients in complete remission received 1 more cycle of chemotherapy, as consolidation, while patients in partial remission received two more cycles of chemotherapy. Non-responding patients received no more chemotherapy. During the second phase the days of cisplatinum and 5FU were 5. Up to April 1990, 17 patients have been included in the study. They were stage III (64%) and IV (36%). The mean administered dose of radiotherapy was 66 Gy (range: 60-70 Gy) to primary tumor and 60 Gy (range: 40-70 Gy) to nodes. The total number of chemotherapy cycles administered during radiant sessions was 37, the mean number of cycles was 2 (range: 1-3), with 100% dose percentage. The interval between cycles was 3 weeks in 84% of patients. The relationship between number of cycles administered and planned cycle was 37/39 (feasibility: 95%). Acceptability was 100% (no patient refused the treatment). Feasibility of the second phase was 77% and acceptability 90% (1 patient refused the treatment). Toxicity was moderate during the first and the second phases. After the first phase 14/15 evaluable patients (92%) had major response (complete remission: 46%). After the second phase 10/10 evaluable patients had a complete remission. In conclusion, this combined treatment is very easy to administer, and very well accepted. Moreover, it yields a high number of objective responses.

Aged↗