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Biomedical subjects

F Brivio

Publications and source records attributed to F Brivio.

At least 37 records · Page 2Linked to original sources
PubMed1993

Subcutaneous therapy with low-dose interleukin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status.

AIMS AND BACKGROUND: Patients with disseminated gastric cancer are generally in very bad clinical conditions, which make them not eligible for potentially active polychemotherapies. This justifies the development of less toxic therapies such as the use of biological response modifiers. Unfortunately, IL-2, one of the most promising cytokines, does not seem to be effective in gastric cancer. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify IL-2 activity, which becomes biologically effective also at very low doses. Based on these considerations, a pilot study was performed with low-dose subcutaneous IL-2 in combination with MLT in metastatic gastric cancer patients with low performance status. METHODS: The study included 14 patients with metastatic gastric cancer who received IL-2 at a dose of 3 million IU/day at 8.00 p.m. subcutaneously for 6 days/week for 4 weeks. MLT was given orally at a dose of 50 mg/day at 8.00 p.m. every day starting 7 days before IL-2. In patients in whom the disease did not progress, a second cycle was given after a rest period of 21 days. RESULTS: A tumor regression was obtained in 3/14 (21%) patients, complete response in 1 and partial in 2, with a median duration of 13 + months. The disease stabilized in 6/14 (43%) patients and progressed in the remaining 5 (36%). Survival was significantly longer in patients with response or stable disease than in those with progression. Toxicity was low in all cases. CONCLUSIONS: These preliminary results show that the combination on of low-dose subcutaneous IL-2 and the pineal hormone MLT may represent a new well tolerated biotherapy, capable of inducing objective tumor regression also in patients with metastatic gastric cancer and low performance status.

Aged↗
PubMed1993

Immunoendocrine therapy with interleukin-2 (IL-2) and medroxyprogesterone acetate (MPA): a randomized study with or without MPA in metastatic renal cancer patients during IL-2 maintenance treatment after response or stable disease to IL-2 subcutaneous therapy.

AIMS AND BACKGROUND: It is known that interleukin-2 (IL-2) activated cytotoxic lymphocytes require a cell-cell contact to exert their anticancer action. Therefore, the pronounced fibrosis that generally characterizes the neoplastic mass could counteract the action of cytotoxic lymphocytes. Some preliminary studies have shown that progesterone and its analogs may inhibit fibroblast proliferation. On the basis of such evidence, we have designed a clinical study with or without the progestational agent medroxyprogesterone acetate (MPA) in metastatic renal cancer patients in maintenance therapy with IL-2 following response or stable disease (SD) after two cycles of IL-2 subcutaneous immunotherapy, in an attempt to evaluate the influence of MPA on free-from progression (FPP) period. METHODS: The study included 30 consecutive patients who were randomized to receive IL-2 alone (3 million IU twice/day for 5 days/month subcutaneously) or IL-2 plus low-dose MPA (500 mg orally one day/week) without interruption until disease progression. RESULTS: A FPP period longer than 1 year was obtained in 8/14 patients treated with IL-2 plus MPA and in only 3/16 patients treated with IL-2 alone. The difference was statistically significant. On the contrary, no significant difference was seen in the mean number of lymphocytes and eosinophils, which was evaluated monthly. Finally, no hyperglycemic or thromboembolic complications occurred in patients concomitantly treated with MPA. CONCLUSIONS: This preliminary study would suggest that the concomitant administration of low-dose MPA may prolong the FFP period in metastatic renal cancer patients under maintenance therapy with IL-2. A longer follow-up will be required to evaluate the influence of MPA on overall survival.

Adult↗
PubMed1993

Influence of blood transfusions on surgery-induced immune changes in colorectal carcinoma.

Perioperative blood transfusions have been shown to enhance recurrence rates in patients with operable solid tumors, perhaps by inducing immunosuppression through unknown mechanisms. Since the surgical treatment per se has been proven to induce immune alterations, the present study was carried out to evaluate the immune effect of blood transfusions on surgery-induced immune variations. The study included 27 patients with resectable colorectal carcinoma, 18 of whom received no transfusion, while the other 9 received blood transfusions in the perioperative period. Total lymphocytes, total T lymphocytes (CD3) and soluble IL-2 receptor serum levels (SIL-2R) were measured on venous blood samples collected from each patient either before or 7 days after surgery. Both in non transfused and in transfused patients, SIL-2R mean levels were significantly higher after than before surgery. Their increase was associated with a significant decrease in both lymphocytes and CD3 cells in non-transfused patients, while in the transfused ones lymphocytes and CD3 cells did not show significant changes with surgery. This study shows that blood transfusions modify the relation between changes in SIL-2R and those in lymphocyte number induced by major surgery. It remains to be understood which relation exist between these immune effects and the promoting action of blood transfusion on relapse frequency in cancer.

Adult↗
PubMed1993

In vitro modulatory effects of interleukin-3 on macrophage activation induced by interleukin-2.

BACKGROUND: The concomitant activation of macrophage-mediated immunosuppressive events might represent one of the most important biologic factors responsible for the decreased efficacy of cancer immunotherapies, including that of interleukin (IL)-2. In previous studies, the authors observed that the increase in the soluble IL-2 receptor (SIL-2R) and neopterin levels was related to the generation of macrophage-mediated immunosuppression and associated with a reduced clinical efficacy during IL-2 cancer immunotherapy. Because both cytokines and neurohormones may influence the macrophage system, the current study was done to evaluate the effects of IL-3 and of the pineal hormone melatonin (MLT) on monocyte response to IL-2 administration. METHODS: Peripheral blood monocytes were incubated with different concentrations of IL-2, IL-3, and MLT, either alone or in association. RESULTS: SIL-2R, neopterin, and tumor necrosis factor-alpha mean concentrations in the medium significantly increased during incubation with IL-2 at a concentration of 100 Cetus units/ml. IL-3 alone, at a dose of 10 ng/ml, also stimulated tumor necrosis factor release; no effect was found on SIL-2R and neopterin. The IL-2-induced neopterin rise was blocked by a concomitant incubation with IL-3 at a dose of 10 ng/ml. Finally, the concomitant incubation with IL-3 and MLT further inhibited neopterin release and significantly decreased IL-2-induced SIL-2R secretion. CONCLUSIONS: These results suggest that IL-3 alone or in association with MLT may modulate macrophage functions during cancer immunotherapy with IL-2 and decrease the IL-2-induced macrophage activation.

Biopterins↗
PubMed1993

Neuroimmunotherapy of advanced solid neoplasms with single evening subcutaneous injection of low-dose interleukin-2 and melatonin: preliminary results.

On the basis of the demonstrated existence of immunoneuroendocrine interactions and on the previously observed synergistic action between the pineal hormone melatonin (MLT) and interleukin-2 (IL-2), we have designed a neuroimmunotherapeutic combination consisting of low-dose IL-2 and MLT in the treatment of advanced solid neoplasms. The study included 24 patients with advanced solid tumours (non-small cell lung cancer 9; colorectal cancer 7; gastric cancer 3; breast cancer 2; cancer of pancreas 1; hepatocarcinoma 1; unknown primary tumour 1), 21 of whom showed distant organ metastases. Not all patients responded to previous chemotherapies, or had tumours for which no standard therapy was available. Moreover, not all patients were able to tolerate IL-2 immunotherapy at the conventional doses. IL-2 was given subcutaneously at a dose of 3 x 10(6) U/day at 8:00 p.m. for 6 days/week for 4 weeks. MLT was given orally at a dose of 50 mg at 8:00 p.m. every day, starting 7 days before IL-2 injection. In non-progressed patients, a second cycle was given after a 21-day rest period. A partial response was seen in 3/24 patients (lung 2; stomach 1; duration: 11, 4, 4 months, respectively). Moreover, a minimal response (duration: 8+ months) was seen in 1 lung cancer patient. Stable disease was obtained in 14/24 patients (median duration: 6+ months), while the remaining 6 patients progressed. An improvement in performance status was seen in 7/24 patients. No important toxicity was observed. Mean eosinophil and lymphocyte levels significantly increased during the immunotherapy, and their rise was significantly higher in patients with response or stable disease than in those with progressive disease. These preliminary results show that neuroimmunotherapy with low-dose IL-2 and the pineal hormone MLT is a biologically active and well tolerated strategy, capable of determining an apparent control of tumour growth in patients with advanced solid neoplasms, for whom no standard effective therapy is available.

Adult↗
PubMed1993

Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract.

The advanced tumours of the digestive tract are generally less responsive to conventional chemotherapies. Moreover, preliminary results with IL-2 immunotherapy also seem to show a low efficacy. On the basis of our previous studies suggesting s synergistic action between IL-2 and some neurohormones, such as the pineal indole MLT, a clinical trial was performed to investigate the clinical efficacy and tolerability of an immunotherapy with IL-2 plus MLT in patients with advanced neoplasms of the digestive tract. The study included 35 patients (colorectal cancer: 14; gastric cancer: 8; hepatocarcinoma: 6; pancreas adenocarcinoma: 7). Distant organ metastases were present in 31/35 patients. MLT was given orally at a daily dose of 50 mg at 8.00 p.m., starting 7 days before IL-2, which was given subcutaneously at a dose of 3 million IU/day at 8.00 p.m. for 6 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In nonprogressed patients, a second cycle was given after a 21-day rest period. A complete response was achieved in two patients (gastric cancer: 1; hepatocarcinoma: 1). Six other patients obtained a partial response: (gastric cancer: 2; hepatocarcinoma: 2; colon cancer: 1; pancreas cancer: 1). Therefore, the overall response rate was 8/35 (23%). Stable disease was obtained in 11/35 (31%) patients, whereas the remaining 16 patients (46%) progressed. The response rate was significantly higher in untreated patients than in those previously treated with chemotherapy. Toxicity was low in all patients, who received the treatment as a home therapy. This study shows that the immunotherapy with low-dose IL-2 plus the pineal hormone MLT is a new well tolerated and effective therapy of advanced tumours of the digestive tract, mainly in gastric cancer and hepatocarcinoma.

Adult↗
PubMed1993

Effects of a preoperative course of interleukin-2 on surgical and immunobiological variables in patients with colorectal cancer: a phase 2 study.

OBJECTIVE: A phase 2 study to evaluate the effects of a short preoperative course of interleukin-2 (IL-2) on the postoperative course of patients with cancer. DESIGN: Open study. SETTING: San Gerardo Hospital, Monza, Italy. SUBJECTS: 16 Consecutive patients with locally advanced colorectal cancer, with or without metastases. INTERVENTION: IL-2 in a dose of 9 x 10(6) IU/m2 twice daily for three days; patients were operated on within 36 hours of the cessation of IL-2 treatment. MAIN OUTCOME MEASURES: Morbidity, mortality, and changes in numbers of lymphocytes, T lymphocytes, natural killer (NK) cells, and CD25 (cluster of determination) positive cells. RESULTS: There was no morbidity or mortality--in particular, there were no infections even in the patients who were at highest risk. The mean numbers of lymphocytes, T lymphocytes, NK cells, and CD25 positive cells increased significantly during the postoperative period. All patients showed evidence of infiltration of lymphocytes or eosinophils (or both) into the tumour tissue. CONCLUSIONS: The results suggest that a three day course of IL-2 preoperatively is well tolerated, stimulates would repair, neutralizes the lymphocytopenia induced by major operation, and induces immune cells to infiltrate the tumour. Randomised studies are needed to confirm these results.

Adult↗
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↗