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Biomedical subjects

F Brivio

Publications and source records attributed to F Brivio.

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

Effects of a preoperative therapy with interleukin-2 on surgery-induced lymphocytopenia in cancer patients.

It is known that major surgery may determine immunosuppression. This side effect might have a prognostic significance particularly in cancer patients, in whom the decrease in host defenses during the postoperative period could promote the proliferation of possible micrometastases. Since antitumor immune response is an IL-2-dependent phenomenon, a study was started to evaluate the effects of a preoperative injection of IL-2 on surgery-induced immune changes in cancer patients. The study included 12 colon cancer patients, treated subcutaneously with IL-2 at a dose of 9 x 10(6) IU/m2 twice daily for 3 consecutive days before surgery. Patients underwent surgery within 36 h from IL-2 interruption. The results were compared to those found in a control group of 18 colon cancer patients. Mean number of lymphocytes, T lymphocytes and NK cells significantly decreased after surgery in control patients; on the contrary, no postoperative decrease in immune cells was seen in IL-2 group. No anesthesiologic or surgical complication was seen in patients pretreated with IL-2 before surgery. This preliminary study would suggest that a preoperative therapy with IL-2 is an effective and well tolerated medical approach to neutralize surgery-induced immunosuppression in cancer patients.

Adult↗
PubMed1991

Effect of antitumor surgery on soluble interleukin-2 receptor serum levels.

Surgically induced immunosuppression may play a role in cancer, because of the possible existence of micrometastases at the time of surgical removal of tumors. Antitumor immune reactions are mediated by interleukin-2 (IL-2). IL-2 acts on a specific IL-2 cell surface receptor; moreover, a soluble form of IL-2 receptor (sIL-2R) can be released in the blood. This study was carried out to evaluate the effect of surgery on sIL-2R serum levels in patients with operable solid tumors. A total of 48 patients with cancer and 11 controls who underwent major surgery for non-neoplastic disease were evaluated before and 7 days after surgery. Serum mean levels of sIL-2R were significantly higher after than before surgery in both the cancer and control groups. No correlation was seen between surgery-induced changes in sIL-2R and in T lymphocyte subsets. Because of its capacity of binding to IL-2, the increased blood concentrations of sIL-2R could reduce the IL-2 availability and negatively affect antitumor immune reactions.

Breast Neoplasms↗
PubMed1991

Increase in soluble interleukin-2 receptor and neopterin serum levels during immunotherapy of cancer with interleukin-2.

Both immunostimulatory and immunosuppressive events would occur during the immunotherapies of cancer, including interleukin 2 (IL-2) therapy. The marked increase in soluble IL-2 receptor (SIL-2R) levels during IL-2 therapy could represent a potentially negative biological effect, because of the receptor's capacity to bind IL-2 and compete for it with IL-2 cell surface receptor. Since it has been observed that macrophages stimulate in vitro the release of SIL-2R, a study was started to evaluate in vivo the role of macrophages in IL-2-induced SIL-2R rise by measuring neopterin, which is a marker of macrophage activity. The study included 9 advanced renal cancer patients, treated subcutaneously with IL-2 at 1.8 x 10(6) IU/m2 twice daily for 5 days/week for 6 weeks. Both SIL-2R and neopterin serum mean levels significantly increased during IL-2 treatment, and the highest concentrations were reached on the second week of therapy. SIL-2R rise was significantly correlated to that of neopterin. This study, by showing a positive correlation between SIL-2R and neopterin rise, would suggest a macrophage involvement in the stimulation of SIL-2R release during IL-2 immunotherapy of cancer.

Adenocarcinoma↗
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↗
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

[Choice of technique in "difficult" inguinal hernias. Personal experience].

The authors refer on their positive results in the treatment of so-called difficult inguinal hernias (relapsing or multiple hernias) with the use of prosthetic prolene mesh according to Stoppa's procedure (partly modified) through a preperitoneal approach after a Pfannenstiel's incision. On the other hand recurrent hernias in risky patients as well as gross hernias are treated by Rives' method which consists in a prolene mesh placement through the inguinal approach.

Hernia, Inguinal↗
PubMed1990

A proposal for intraoperative washout of colon for the endoscopic diagnosis of the lower gastrointestinal tract haemorrhage.

The authors refer about a proposal for an intraoperative wash-out of colon in order to improve the endoscopic diagnosis of the bleeding's precise site in case of lower gastrointestinal tract haemorrhage. The colonic wash-out is obtained by the transanal insertion of a Baker type silicone tube this is guided by the surgeon up to the caecum followed by the insertion of the colonoscope. This method turned out useful in one case of haemorrhagic shock.

Colon↗
PubMedDate not supplied

The pineal gland and breast cancer: serum levels of melatonin in patients with mammary tumors and their relation to clinical characteristics.

Several studies have suggested that the pineal gland hormone melatonin may influence the growth of breast cancer. The importance of melatonin blood concentrations in the clinical history of human breast cancer, however, has still to be defined. To further investigate this problem, we used a RIA method to assay serum levels of the pineal hormone in 74 untreated breast cancer patients, clinical stage T1-3 NO-2 MO, and in 46 age-matched healthy women as controls. Mean serum melatonin levels were significantly higher in patients than in controls. Melatonin concentrations were highest in breast cancer patients with the best prognosis (i.e. estrogen receptor-positive/node-negative cases). Mean levels of melatonin were significantly higher in estrogen receptor-positive patients than in the negative ones. They were also higher in node-negative than in node-positive cases, and in progesterone receptor-positive patients than negative ones, but none of these differences was statistically significant. No difference was observed in relation to menopausal status and to tumor histotype. These results suggest that melatonin plays a role in the hormone-dependency of human breast cancer.

Adult↗
PubMedDate not supplied

Lack of changes in soluble interleukin-2 receptor serum levels during chemotherapy-induced lymphocyte damage.

The biological significance of soluble IL-2 receptors (sIL-2R) is still unknown; in particular, it is not yet clear whether their increase in the blood may reflect activation of immune cells, or whether it is related to an immune dysfunction. To investigate this problem, we evaluated serum levels of sIL-2R before and after administration of a highly lymphocytolitic chemotherapy (FEC: fluorouracil, epirubicin, cyclophosphamide) in a group of 6 patients with advanced breast cancer. SIL-2R were analyzed in relation to lymphocyte number. Absolute mean number of lymphocytes was significantly lower after than before chemotherapy. On the contrary, no significant difference was seen in sIL-2R mean levels, and no significant correlation was observed between changes in sIL-2R and in lymphocyte number following chemotherapy. These results would exclude that sIL-2R may simply be due to a passive release following lymphocytic damage.

Adult↗
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

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↗
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↗