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A Ardizzoia

Publications and source records attributed to A Ardizzoia.

17 recordsLinked to original sources
PubMed1992

Neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma.

On the basis of our previous preliminary data which showed that the pineal hormone melatonin (MLT) may potentiate IL-2 activity and reduce the dose of IL-2 required to determine an effective host antitumor response, we performed a clinical study with low-dose IL-2 given once/day subcutaneously (3 million IU/day for 6 days/week for 4 weeks) in association with MLT (50 mg/day orally at 8.00 p.m. every day) as a second-line therapy in metastatic colorectal cancer patients pretreated with 5-fluorouracil. Evaluable patients were 13/14, and most of them showed disseminated liver metastases. No objective tumor regression was seen. A stabilization of disease was achieved in 4/13 patients (median duration 5+ months), and the other 9 patients progressed. Mean number of lymphocytes and eosinophils significantly increased during the treatment. Moreover, the mean increase in lymphocyte number was significantly higher in patients with stable disease than in those with progressive disease, whereas there was no difference as regards eosinophils. Serum levels of neopterin and tumor necrosis factor (TNF) significantly increased during therapy, and TNF increase was correlated to the side effects rather than to the control of cancer development. This study shows that neuroimmunotherapy with low-dose interleukin-2 and MLT, even though capable of determining an evident expansion of immune cells involved in host antitumor response, does not seem to be effective in terms of tumor regression in metastatic colon cancer patients pretreated with 5-fluorouracil.

Adult↗
PubMed1992

Weekly doxorubicin chemotherapy for breast cancer in pregnancy. A case report.

The simultaneous occurrence of breast cancer and pregnancy is rare. Little data are available about cytostatic treatment in patients with breast cancer during pregnancy. We report on a 31-year-old woman with a 28-week pregnancy and a T3 N+ Mx breast cancer treated with weekly doxorubicin chemotherapy. This was a well tolerated treatment without toxicity or complications for the mother. A partial response of the tumor was observed after 4 treatment courses. A normal baby was delivered. Doxorubicin and its metabolites were not detected in amniotic fluid collected through amniocentesis. Macroscopic and pathologic examinations of the placenta were normal. Although larger experiences are needed, weekly doxorubicin seems to yield satisfactory results without additional risks of fetal distress or malformations when given in women during the second and third trimester of pregnancy.

Adult↗
PubMed1992

Intracavitary administration of interleukin-2 as palliative therapy for neoplastic effusions.

Cytokines have recently appeared to be effective in the palliative therapy of neoplastic effusions. The present study was carried out to evaluate the efficacy and the tolerability of an intracavitary injection of IL-2 in patients with neoplastic effusion due to solid tumors. The study included 14 patients with cytologically positive effusion (pleura, 11; peritoneum, 2; pericardium, 1). Tumor histotypes were: mesothelioma, 5; non-small cell lung cancer, 3; breast cancer, 2; ovarian cancer, 2; cervix carcinoma, 1; unknown primary tumor, 1. The efficacy was evaluated according to the criteria of Paladine et al. (Cancer 38: 1903, 1976). An objective response was achieved in 10/14 (71%) patients (4 CR, 6 PR), with a median duration of 4 months (range, 2-8). No important toxicity was seen. This preliminary study showed that low dose IL-2 given intracavitarily is an effective and well-tolerated therapy in patients with neoplastic effusions.

Adult↗
PubMed1992

Second line therapy with low-dose subcutaneous interleukin-2 alone in advanced renal cancer patients resistant to interferon-alpha.

Interleukin-2 (IL-2), given subcutaneously with interferon-alpha, induces clinical results similar to those achieved with intravenous administration in advanced renal cancer but with lower toxicity. This study was performed to investigate the efficacy of IL-2 subcutaneous therapy alone in advanced renal cancer patients pretreated with interferon-2 alpha. The study included 13 evaluable patients, 6 of whom had visceral metastasis sites. The cycle consisted of IL-2 at 9 x 10(6) IU/m2 twice daily for 2 days, followed by 1.8 x 10(6) IU/m2 every 12 h for 5 days/week for 6 weeks. Clinical responses were: partial response: 4(31%); stable disease: 7(54%), progressive disease: 2(15%). The median duration of response was 9+ months (range 6(+)-12+). Toxicity was low in all patients, and in particular no important cardiovascular side-effect was seen. The results of this study show that IL-2 subcutaneous therapy alone is an effective and well tolerated treatment in advanced renal cancer patients progressed under interferon-alpha therapy.

Adenocarcinoma↗
PubMed1992

Biological and clinical results of a neuroimmunotherapy with interleukin-2 and the pineal hormone melatonin as a first line treatment in advanced non-small cell lung cancer.

The metastatic non-small cell lung cancer (NSCLC) still remains an untreatable disease, and the role played by chemotherapy has yet to be defined. The new immunotherapeutic strategies, such as interferon and IL-2, seem to be also less effective, since they generally determine only a stabilisation of disease. On the basis of previous experimental results suggesting a synergistic action between IL-2 and the pineal neurohormone melatonin (MLT), a study was started to evaluate the clinical efficacy and toxicity of a neuroimmunotherapeutic combination consisting of IL-2 plus MLT as a first line therapy in metastatic NSCLC. The study included 20 patients (adenocarcinoma: 10; epidermoid cell carcinoma: 7; large cell carcinoma: 3). MLT was given orally at a dose of 10 mg day-1 at 8.00 pm every day, starting 7 days before the onset of IL-2 administration. IL-2 was given subcutaneously at a dose of 3 x 10(6) IU m-2 every 12 h for 5 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In responder patients or in those with stable disease, a second cycle was given after a rest-period of 21 days. A partial response was achieved in 4/20 (20%) patients. Ten other patients had a stable disease (50%), whereas the last six patients progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapeutic therapy with IL-2 and the pineal hormone MLT may represent a new effective and well tolerated treatment in metastatic NSCLC, with results comparable to those obtained with chemotherapy, but with an apparent lower biological toxicity.

Biopterins↗
PubMed1992

Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin.

At present, there is no effective medical therapy in metastatic nonsmall cell (NSC) lung cancer patients who progressed under a first-line chemotherapy containing cisplatin. Since recent data have demonstrated the antineoplastic properties and the lack of toxicity of the pineal hormone melatonin (MLT), a randomized study was designed to evaluate the influence of an MLT treatment (10 mg/day orally at 7.00 p.m.) on the survival time at 1 year from the progression under chemotherapy in respect to supportive care alone in a group of metastatic NSC lung cancer patients, who did not respond to a first-line chemotherapy containing cisplatin. The study includes 63 consecutive metastatic NSC lung cancer patients, who were randomized to receive MLT (n = 31) or supportive care alone (n = 32). The percentage of both stabilizations of disease and survival at 1 year was significantly higher in patients treated with MLT than in those treated only with supportive care. No drug-related toxicity was seen in patients treated with MLT, who, on the contrary, showed a significant improvement in performance status. This randomized study shows that the pineal hormone MLT may be successfully administered to prolong the survival time in metastatic NSC lung cancer patients who progressed under a first-line chemotherapy with cisplatin, for whom no other effective therapy is available up to now.

Adult↗
PubMed1992

Modulation of macrophage response to interleukin-2 immunotherapy by interleukin-3 in cancer patients.

It has been observed that neopterin, a specific marker of macrophage activation, increases during cancer immunotherapy with IL-2, and this effect is mediated by interferons produced by IL-2-stimulated lymphocytes. Moreover, our previous studies have shown that neopterin rise during IL-2 immunotherapy is associated with an enhanced release of soluble IL-2 receptor (SIL-2R), which may suppress IL-2-dependent immune functions. This finding would suggest that neopterin increase may be related to the generation of suppressive events, which occur during IL-2 immunotherapy. On the basis of the documented modulatory effect of IL-3 on macrophage functions, we have evaluated the influence of IL-3 on neopterin secretion during IL-2 immunotherapy. The study was performed in advanced lung cancer patients. We have investigated 9 immunotherapeutic courses consisting of IL-2 (6M IU/day s.c. for 5 days/week for 3 weeks) plus IL-3 (1 microgram/(kg x day) i.v. for 14 days, starting 7 days before IL-2). The results were compared to those found during 18 courses with IL-2 alone. Mean neopterin levels increased significantly during IL-2 alone, but not in response to IL-3 plus IL-2. SIL-2R rise was significantly higher during IL-2 than during IL-3 plus IL-2. Mean numbers of NK cells and activated lymphocytes increased significantly in both groups of patients, but were significantly lower at the end of the treatment in patients receiving IL-2 alone than in those treated with IL-3 plus IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

A clinical study of the pineal hormone melatonin in patients with growth hormone or prolactin secreting pituitary tumours.

OBJECTIVES: Despite the well documented influence of the pineal gland on pituitary function, the evaluation of pineal activity is not generally included in the clinical investigation of patients with pituitary tumours. The present study analyzed the circadian secretion of melatonin, the main pineal hormone, in patients with pituitary adenomas. METHODS: The study included 36 patients with pituitary tumours (acromegaly: 11; prolactinoma: 25), by comparing the results with those seen in 42 healthy controls. Moreover, patients were endocrinologically investigated after oral administration of 10 mg of melatonin. RESULTS: Abnormally high serum levels of melatonin during the period of maximum light and abnormally low increases during the night were seen in 7/36 and 16/36 patients, respectively, without any relation to tumour histotype. Moreover, night serum mean levels of melatonin were significantly lower in patients than in controls. Finally, the exogenous administration of melatonin did not influence growth hormone and prolactin secretions in patients with acromegaly and prolactinomas, respectively. CONCLUSION: This study demonstrates the existence of an altered pineal function in patients with pituitary tumours. Further studies will be required to establish the pathogenetic and prognostic significance of pineal disorders in neoplastic disease of the pituitary gland.

Acromegaly↗
PubMed1991

Decrease in cholesterol levels during the immunotherapy of cancer with interleukin-2.

IL-2, in addition to its immunomodulating and antitumour properties, induces important systemic actions, including cardiovascular, neuroendocrine and metabolic effects. The present study was carried out to evaluate IL-2 effects on cholesterol metabolism. The study included 14 advanced cancer patients (renal carcinoma: ten; colon carcinoma: four), who received IL-2 subcutaneously at a dose of 1.8 x 10(6) IU ml-2 twice daily for 5 days/week for 6 weeks. Venous blood samples were collected 7 days before, on days 0, 3, 7, 14, 21, 42 of IL-2 therapy, and on days 14 and 28 of the rest-period. IL-2 induced a rapid and evident decrease in cholesterol levels, with a normalisation of its concentrations within 7 days in 10/10 hypercholesterolemic patients. The lowest mean levels of cholesterol were reached within the first 2 weeks; after that they still slowly increased. LDL-/HDL-cholesterol ratio was significantly reduced by IL-2 therapy. Cholesterol fall was associated with a marked increase in conjugated biliary acid levels. Finally, triglyceride values increased during IL-2 therapy, but not in a significant manner. These results, by showing that IL-2 exerts an evident and very rapid cholesterol-lowering activity, would represent a further demonstration of the physiological importance of cytokines in the control of cholesterol metabolism.

Adenocarcinoma↗
PubMedDate not supplied

Endocrine effects of human recombinant interleukin-3 in cancer patients.

It is known that several cytokines can exert hormonal effects. At present, no data are available about the possible influence of IL-3 on the endocrine system. In order to investigate the endocrine effects of IL-3 in humans, we have evaluated serum levels of cortisol, beta-endorphin, GH, PRL, FSH, LH, TSH and melatonin in response to intravenous injection of IL-3 at a dose of 1 mcg/kg b.w. at 6.00 p.m. The study was performed in 5 non-small cell lung cancer patients. GH increased significantly in response to IL-3. PRL showed a progressive decrease after IL-3 injection, but its variations were not statistically significant. All other hormones, including cortisol, were not affected by IL-3. This preliminary study shows that IL-3 may exert endocrine effects in humans, which would seem at variance with previously reported results on most other cytokines.

Biomarkers, Tumor↗
PubMedDate not supplied

Immunological effects of a single evening subcutaneous injection of low-dose interleukin-2 in association with the pineal hormone melatonin in advanced cancer patients.

Recent experiments have shown that a great variety of neurohormones can interact with IL-2 in the modulation of host antitumor immune response. On the basis of these data, a study was started to evaluate the effect of the pineal hormone melatonin (MLT) on IL-2-induced immune changes in cancer. The study included 30 advanced cancer patients. They were randomized to be treated with IL-2 at a dose of 3 million IU subcutaneously twice/daily (8.00 a.m. and 8.00 p.m.) for 6 days/week for 4 weeks, with IL-2 once/daily in the evening, with IL-2 once/daily plus MLT at 10 or at 50 mg/day. MLT was given orally at 8.00 p.m. Both IL-2 given twice daily and IL-2 given once daily and IL-2 given once daily in association with MTL induced a significant increase in mean number of lymphocytes, T lymphocytes, NK cells, CD25-positive cells and eosinophils, whereas the single administration of IL-2 alone was unable to determine a significant rise in the mean number of immune cells. Soluble IL-2 receptor and neopterin increase was significantly higher during IL-2 given twice/daily than during IL-2 plus MLT, while no difference was seen in TNF rise. This study would suggest that a single daily injection of low-dose IL-2 is able to efficiently activate the lymphocyte proliferation in cancer patients when it is given in association with the pineal hormone MLT.

Adult↗
PubMedDate not supplied

Effects of granulocyte-macrophage colony stimulating factor on cortisol, growth hormone, prolactin and melatonin in cancer patients (short communication).

Several interleukins and interferons have been proven to induce endocrine effects. On the contrary, only few data are available about the possible hormonal activity of hemopoietic growth factors. This study was carried out to evaluate the endocrine influence of GM-CSF in humans. The study included nine head and neck cancer patients, evaluated in basal conditions and after an acute subcutaneous injection of GM-CSF at a dose of 3 mcg/kg b.w., by determining serum levels of cortisol, growth hormone (GH), prolactin (PRL) and melatonin. Both cortisol and GH significantly increased in response to GM-CSF, while PRL, and melatonin were not influenced. This preliminary study shows that hemopoietic growth factors, as well as interleukins, may also play endocrine effects in humans.

Adult↗
PubMedDate not supplied

Inhibitory effect of interleukin-3 on interleukin-2-induced cortisol release in the immunotherapy of cancer.

The stimulatory effect of IL-2 on cortisol rise represents an undesirable biological event during IL-2 cancer immunotherapy. At present, no cytokine has been proven to be able to counteract IL-2-induced cortisol increase. This study was carried out to evaluate the influence of IL-3 on IL-2 stimulation of cortisol secretion. Five lung cancer patients were investigated after IL-2 (3 x 10(6) IU s.c.), after IL-3 (1 mcg/kg b.w. i.v.) and after IL-3 plus IL-2, by administering IL-3 two hours before IL-2 injection. IL-2 significantly stimulated cortisol secretion. IL-3 alone had no effect on cortisol levels. The pretreatment with IL-3 completely neutralizes IL-2-induced cortisol release. These preliminary results would suggest that IL-3 may be associated with IL-2 during cancer immunotherapy to modulate the effect of IL-2 on the endocrine system.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

Tumor necrosis factor in solid tumors: increased blood levels in the metastatic disease.

TNF, a cytokine produced by macrophages, is able either to exert an antitumor activity, or to determine severe clinical complications, such as cachexia and septic shock. Increased blood levels of TNF have been described in cancer patients. The present study was performed to better define TNF secretion in patients with solid tumors. The study included 48 cancer patients (lung cancer: 22; colon cancer: 11; breast cancer: 10; renal cancer: 5), and among them 27 showed distant organ metastases. TNF serum levels were measured by IRMA method. The control group comprised 40 healthy subjects. TNF levels were also evaluated in relation to those of SIL-2R, whose increase seems to be associated with an unfavorable prognosis in cancer. High levels of TNF were seen in 27/48 (56%) patients. Mean levels of TNF were significantly higher in cancer patients than in controls. Moreover, within the cancer group, TNF mean values were significantly higher in metastatic patients than in those without metastases; the highest levels were observed in patients with visceral lesions as dominant metastasis sites. Finally, patients with high TNF concentrations showed significantly higher mean levels of SIL-2R than those with normal values. This study shows that the neoplastic metastatic disease is associated with an exaggerated TNF secretion.

Adult↗
PubMedDate not supplied

Modulation of interleukin-2-induced macrophage activation in cancer patients by the pineal hormone melatonin.

The concomitant induction of immunosuppressive events, at least in part mediated by macrophages, would represent one of the mechanisms responsible for the lower activity of IL-2 in vivo than in vitro. Since macrophages have recently appeared to be under neuroendocrine control, the present study was carried out to evaluate the effect of the pineal neurohormone MLT on IL-2-induced macrophage activation during cancer immunotherapy, by determining serum levels of neopterin, which is a specific marker of macrophage activity. The study included 21 advanced cancer patients (lung cancer: 12; renal cancer: 9), 10 of whom received IL-2 subcutaneous therapy alone (1.8 x 10(6) IU/m2 twice daily), or IL-2 plus MLT (10 mg/day orally at 8.00 P.M.). Neopterin levels increased in all patients during IL-2 immunotherapy, but neopterin mean peak was significantly higher in patients treated with IL-2 alone than in those who received IL-2 plus MLT. This preliminary study would suggest the possible use of neurohormones to modulate host antitumor immune response during cancer immunotherapy with IL-2.

Adult↗