F Rovelli

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Lombardy, Italy

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Publications (237)500.54 Total impact

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    ABSTRACT: Thanks to the discoveries of psychoneuroendocrinoimmunology, we now know that every psychological state is mediated by a specific neurochemical condition and every neurochemical change in turn influences psychological status. We can now identify three different levels of neurochemical mediation of the psychological states: neurotransmission, neuromodulation, and the psychoneuromodulation. Neurotransmission is composed of five main neural pathways, noradrenaline, acetylcholine, dopamine, serotonin, and histamine; neuromodulation; and the psychoneuromodulation. We have performed several clinical studies in an attempt to correlate the psychological status of cancer patients with the immune alterations characteristic of the clinical history of neoplastic disease. We have studied the immunologic status by evaluating cytokine blood levels and the lymphocyte subpopulation; the psychological status was assessed by the Rorschach's test; and spiritual status was evaluated by a previously published test to explore spiritual faith. These preliminary psychological studies seem to suggest that a pre-treatment analysis of psychological and spiritual status may predict the efficacy of both chemotherapy and immunotherapy in advanced cancer patients.
    Current Aging Science 01/2013;
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    ABSTRACT: Aging and advanced cancer are characterized by similar neuroendocrine and immune deficiencies; the most important of them consist of diminished nocturnal production of the pineal hormone melatonin (MLT) and decreased production of IL-2. At present, however, it is known that the pineal gland may produce indole hormones other than MLT. The most investigated of them is represented by 5-methoxy-tryptamine (5-MTT), which may exert antitumor, anticachectic, and immunomodulating effects under experimental conditions, in addition to those effects produced by MLT itself. In an attempt to obtain some preliminary data in human subjects about the potential therapeutic properties of 5-MTT, three different studies of 5-MTT have been carried out in advanced solid tumor patients. The first study of MLT plus 5-MTT included 14 thrombocytopenic cancer patients who did not respond to MLT alone. In the second study we have compared the clinical efficacy of MLT plus 5-MTT in a group of 25 untreatable metastatic cancer patients to the results obtained in a control group of 25 cancer patients receiving MLT alone. Finally, the third study of MLT plus 5-MTT included 14 untreatable metastatic cancer patients who did not respond to MLT alone. In all of these studies, MLT and 5-MTT were given orally at the level of 20 mg/day in the evening and at 5 mg/day during the period of maximum light. A normalization of platelet number was achieved by MLT plus 5-MTT in 5 of 14 (36%) thrombocytopenic cancer patients who did not respond to MLT alone. The percentage of disease control obtained by MLT plus 5-MTT in untreatable metastatic cancer patients was significantly higher than that achieved by MLT alone (15/25 [60%] vs. 8/25 [32%], P < 0.05). Finally, the association of 5-MTT with MLT induced disease stabilization in 4 of 14 (29%) untreatable metastatic cancer patients who did not respond to MLT alone.
    Current Aging Science 12/2012; 5(3):231-5.
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    Paolo Lissoni, Franco Rovelli
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    ABSTRACT: Recent advances in the knowledge of the mechanisms responsible for antitumor immunity have stimulated the elaboration of new cancer immunotherapeutic strategies. Moreover, more recent discoveries have demonstrated that immune responses are under a physiological modulatory control played by several neuroendocrine pathways, which explain the differences between the in vivo and in vitro immune responses. While until a few years ago the evaluation of the immune status of cancer patients was substantially established on the basis of clinical empirical criteria, recent discoveries of the antitumor cytokine network have allowed the biochemical bases of anticancer immunity to be defined, leading to new anticancer immunotherapeutic strategies, on the basis of patient neuroendocrine and neuroimmune status, in an attempt to correct the great number of cancer-related alterations on the basis of knowledge of the physiopathology of anticancer immunity. The rationale for cancer neuroimmunotherapy consists of the possibility to enhance the efficacy of the various immunotherapeutic strategies by a concomitant administration of antitumor cytokines (namely IL-2), in addition to neuroendocrine endogenous molecules (namely the pineal indole hormones), able to stimulate the anticancer immunoresponse by amplifying the anticancer reaction and/or by counteracting the generation of immunosuppressive events.
    Immunotherapy 01/2012; 4(1):77-86. · 2.39 Impact Factor
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    ABSTRACT: IntroductionNeuroanathomy, neurochemistry and neurophysiology of the sexual orientation are still an enigma.The topical problem is to draw a systemic theory of the psycho-sexual status of people based on the great and often contradictory experimental data.
    Lancet. 01/2010; 29(2):73-77.
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    ABSTRACT: Several clinical studies have clearly demonstrated that the immune status is one a major prognostic factor for the survival time in cancer patients. However the main clinical problem is to identify the most prognostically important index within the great number of immune parameters. Recently the evaluation of regulatory T (T-reg) (CD4CD25) lymphocyte count and function with respect to the T helper (TH) (CD4) number has been shown to represent the main immune parameters capable of representing the functional status of the anticancer immunity in cancer patients. This study evaluated the influence of the four main conventional anticancer therapies (surgery, chemotherapy, radiotherapy, immunotherapy) on the CD4/CD4CD25 ratio. The study included 70 patients. The oncological treatments consisted of surgery in 14, chemotherapy in 36, radiotherapy in 12 and immunotherapy (subcutaneous low-dose, S.C.-low, interleukin, IL-2) in 8 patients. The normal value of the CD4/CD4CD25 ratio was greater then 4.0. Surgery induced a significant decline in the CD4/CD4CD25 mean ratio. Radiotherapy also induced also a dramatic significant decrease in the CD4/CD4CD25 ratio, whereas the effect of both chemotherapy and immunotherapy reflected the clinical response to the treatments. The CD4/CD4CD25 mean ratio was significantly enhanced in the patients who obtained control of the neoplastic growth, whereas it diminished in progressing patients. The commonly used anticancer therapies profoundly modify the levels of amounts of T-reg lymphocytes. Because of the fundamental role of T-reg cells in suppressing the anticancer immunity, thus diminishing survival, the monitoring of the CD4/CD4CD25 ratio could constitute an important clinical index during conventional anticancer therapies to predict the prognosis of cancer patients.
    Anticancer research 06/2009; 29(5):1847-52. · 1.71 Impact Factor
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    ABSTRACT: The recent advances in the psychoneuroendocrinology have suggested the possibility to modulate tumor hormone dependency through a neuroendocrine approach. In particular, it has been proven that the pineal neurohormone melatonin (MLT) may stimulate estrogen receptor (ER) expression in breast cancer cells and inhibit the aromatase activity. On this basis, a study was planned to evacuate the efficacy of a concomitant treatment with the aromatase inhibitor anastrozole plus MLT in metastatic breast cancer. The study included 14 metastatic breast cancer women of poor clinical conditions with ER positive or unknown. Both anastrozole and MLT were given orally at a dose of 1 mg at noon and of 20 mg in the evening, respectively. The clinical response consisted of complete response in 2 and partial response in 6 patients. Then, an objective tumor regression was achieved in 8/14 (57%) patients, with a median duration of 26 months. No neoplastic cachexia occurred on treatment. This preliminary study shows that a neuroendocrine strategy with anastrozole plus the pineal hormone MLT may represent a new effective and well tolerated regimen in the treatment of metastatic breast cancer women, including those with poor clinical status, with therapeutic results apparently superior to those reported in the literature with the only aromatase inhibitor. Then, these results would justify further randomized studies of aromatase inhibitors with or without a concomitant administration of MLT, in an attempt to establish whether the pineal hormone may enhance the efficacy of the aromatase inibibitors in the treatment of human advanced breast cancer.
    Cancer Therapy Vol. 01/2009; 7:302-304.
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    ABSTRACT: Abbreviations: Melatonin (MLT), complete response (CR), partial response (PR), stable disease (SD), disease control (DC), progressive disease (PD), T helper lymphocytes (TH, CD4 +), T regulatory lymphocytes (T reg, CD4 + CD25 +) Summary Background: The recent advances in understanding the immunobiological interactions responsible for cancer progression have allowed us to define the mechanisms of action of some plants, whose antitumor properties were already known by the popular Medicine, in particular Aloe and Myrrha, whose mixture was already therapeutically utilized more than 2000 years ago by the Essence medicine. Moreover, some endogenous natural substances, namely the main hormone produced by the pineal gland melatonin (MLT) may also play anticancer activity. On this basis, a study was performed with a biological regimen consisting of MLT, Aloe and Myrrha in untreatable metastatic cancer patients with life expectancy lower than 1 year. Methods: The study included 35 patients. MLT was given orally at 20 mg/day in the evening and a mixed Aloe and Myrrha tincture was administered at a dose of 5 ml/thrice daily. Results: The clinical response consisted of complete response (CR) in 1, partial response (PR) in 2, stable disease (SD) in 19 patients, whereas the remaining 13 patients had a progressive disease (PD). Thus, a disease control (CR + PR + SD) was achieved in 22/35 (63%)patients. Moreover, a survival longer than 1 year was achieved in 17/35 (49%) patients. Finally, DC was associated with an evident improvement in the immune status, namely consisting of a decrease in the number of T regulatory lymphocytes, which are the main cells responsible for the suppression of the anticancer immunity. Conclusion: This preliminary study shows that a biological anticancer regimen consisting of the pineal hormone MLT in association with Aloe and Myrrha mixture, already known at the times of the Essence medical tradition, may induce a control of the neoplastic disease by stimulating the anticancer immunity, in a relevant percentage metastatic cancer patients, who did not respond to the conventional anticancer treatments and for whom no other standard therapy was available.
    Cancer Therapy Vol Cancer Therapy. 01/2009; 7(7):397-401.
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    ABSTRACT: The evaluation of the immune status of cancer patients is not routinely included in clinical oncological practice mainly because of the great number of candidate immune parameters that could potentially be the best index of the status of anticancer immunity. Until recently, the T-helper/T-suppressor lymphocyte ratio (CD4/CD8) was considered to be an index of immunosuppression in cancer patients. Successive studies documented the existence of several subtypes of CD4+ lymphocytes, as well as showing that CD8+ cells were not in fact suppressive, but cytotoxic lymphocytes. More recently, the existence of a subtype of T-helper lymphocytes has been demonstrated provided by an evident suppressive activity on anticancer immunity. These are the so-called T-regulator (T-reg) lymphocytes, which may be detected as CD4+CD25+ cells. A study was carried out to evaluate CD4+/CD4+CD25+ ratio, corresponding to the T-helper/T-reg cell ratio (TH/TR), in a group of 50 cancer patients in relation to their disease extension and in 20 healthy controls. The mean TH/TR ratio observed in patients with metasytases was significantly lower with respect to that found in both patients without metastases and controls. On the contrary, the absolute mean number of T-reg cells was higher in patients with metastases than in those without, but the difference was not statistically significant. The evaluation of T-reg cells in terms of their proportion with respect to T-helper cell total number seems to be more appropriate than the simple measurement of their absolute count, in order to quantify cancer-related immunosuppression. Thus, the TH/TR ratio could represent a useful biological marker to explore the immune status of cancer patients.
    In vivo (Athens, Greece) 01/2008; 22(5):647-50. · 1.15 Impact Factor
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    ABSTRACT: Lymphocytopenia represents one of the most evident side-effects of radiotherapy (RT), particularly in the case of irradiation of pelvis, since it is the main location of bone-marrow proliferating cells in adults. Because of the fundamental role of lymphocytes in suppressing anticancer immunity, RT-induced lymphocytopenia could negatively influence the prognosis of cancer patients and the therapeutic efficacy of RT itself. In experimental conditions, the biological toxicity of irradiation appeared to be reduced by antioxidant agents, such as pineal hormones melatonin. A preliminary study was conducted to evaluate the influence of different immunobiological strategies with pineal indoles melatonin (MLT), 5 methoxytriptamine (5-MTT) or low-dose IL-2, the lymphocyte growth factor, on pelvic irradiation-induced lymphocytopenia in cancer patients suffering from rectal cancer or uterine cervix carcinoma. The study included 20 consecutive patients, who underwent pelvic irradiation for a total dose of 50.4 Gy. The patients were randomized to be concomitantly treated with MLT alone, with MLT plus 5-MTT or with s.c. low-dose IL-2 . RT induced a significant decline in the mean number of lymphocytes while neither MLT alone, nor MLT plus 5-MTT were able to significantly reduce this decline. Conversely, IL-2 caused a statistically significant reduction of the RT-induced effect, so that the mean number of lymphocytes was significantly higher in patients concomitantly treated by IL-2 than in the other groups. This preliminary study showed that low-dose IL-2 was sufficient to reduce, even though not to completely abrogate, RT-induced lymphocytopenia. Further studies with different schedules and doses of IL-2 will be required to optimize the protective effect of IL-2 on irradiation-induced lymphocytopenia in humans.
    In vivo (Athens, Greece) 01/2008; 22(3):397-400. · 1.15 Impact Factor
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    ABSTRACT: The recent advances in the psychooncological and psychoneuroimmunological investigations of cancer patients has allowed the rediscovery of the importance of spiritual faith in influencing the clinical course of neoplastic disease, not only in terms of supportive care but also as a potential prognostic variable. Clinical criteria were worked out to explore the existence of a real status of faith, in an attempt to correlate the degree of faith with the clinical response to chemotherapy, consisting of cisplatin plus gemcitabine, and the overall survival time in a group of 50 metastatic nonsmall cell lung cancer patients. The tumor response rate achieved in patients with a high degree of faith was significantly higher than in the other group of patients. Moreover, the mean postchemotherapeutic lymphocyte number was significantly higher in the patients with evident spiritual faith than in the other patients. Finally, the percent age of 3-year survival observed in the patients with a high degree of faith was significantly higher than that in the patients with a low faith score. This preliminary study suggests that spiritual faith may positively influence the efficacy of chemotherapy and the clinical course of neoplastic disease, at least in lung cancer, by improving the lymphocyte-mediated anticancer immune response.
    In vivo (Athens, Greece) 01/2008; 22(5):577-81. · 1.15 Impact Factor
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    ABSTRACT: Cancer progression depend on the immune and endocrine status of the patients. In particular, it has been observed that abnormally high levels of cortisol and/or an altered circadian secretion are associated with a poor prognosis in advanced cancer patients. The present study was performed to establish whether cancer-induced hypercortisolemia depends on an activation of the hypothalamic-pituitary axis or on a direct adrenal stimulation by inflammatory cytokines, such as IL-6, which have been proven to induce cortisol secretion. The study included 50 metastatic solid tumor patients, who were evaluated before the onset of chemotherapy. Venous blood samples were collected in the morning to measure IL-10, IL-6, ACTH and cortisol serum levels. Moreover, to analyze its circadian secretion, cortisol levels were also evaluated on venous blood samples collected at 4.00 p.m. Abnormally high morning levels of cortisol were observed in 19/50 (38%) patients. Moreover, a lack of a normal circadian rhythm of cortisol was seen in 8/50 (16%) patients. None of the patients showed high levels of ACTH. Abnormally high concentrations of IL-6 and IL-10 were present in 21/50 (42%) and in 14/50 (28%) patients, respectively. Mean serum levels of both IL-6 and IL-10 were significantly higher in patients with hypercortisolemia than in those with normal cortisol values (p<0.005 and p<0.001, respectively). According to previous clinical studies, these results confirm that the advanced neoplastic disease may be associated with enhanced cortisol levels and alterations of its circadian secretion. The lack of enhanced ACTH secretion excludes the possibility that the abnormal cortisol production is due to the activation of the hypothalamic-pituitary axis. On the contrary, the evidence of significantly higher concentrations of IL-6 in hypercortisolemic patients would suggest that cancer-related enhanced cortisol production may depend on a direct adrenal stimulation by IL-6 itself The well-demonstrated stimulatory role of cortisol on IL-10 production would explain the enhanced IL-10 secretion in hypercortisolemic patients. Cancer-related hypercortisolemia would seem to depend on alterations of the feedback mechanisms between endocrine and cytokine secretions, occurring in the neoplastic disease.
    In vivo (Athens, Greece) 01/2007; 21(4):647-50. · 1.15 Impact Factor
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    ABSTRACT: The recent advances in the investigation of tumor immunobiology have suggested that cancer chemotherapy, in addition to its well known cytotoxic activity, may play modulatory effects on the endogenous production of cytokines involved in the control of both tumor angiogenesis and antitumor immunity. Cancer chemotherapy constantly acts with inhibitory effects on anti-bacterial, anti-viral and anti- mycotic immune responses, whereas its action on anticancer immunity, which is mainly mediated by lymphocytes, has still to be better investigated and defined. The present study was carried out to evaluate the influence of chemotherapy on lymphocyte count and its relation to the clinical response in cancer patients suffering from the most commonly frequent tumor histotypes, including lung, colorectal, breast and prostate carcinomas. The study included 144 consecutive metastatic solid tumor patients. Lung cancer patients were treated with cisplatin plus gemcitabine, colorectal cancer patients received oxaliplatin plus 5-fluorouracil, while those affected by breast cancer or prostate carcinoma were treated with taxotere alone. An objective tumor regression was achieved in 66 out of 144 (46 percent) patients, whereas the remaining 78 patients had only a stable disease (SD)or a progressive disease. Independently of tumor histotype and chemotherapeutic regimen, a lymphocytosis occurred in patients who achieved an objective tumor regression in response to chemotherapy, and lymphocyte mean count observed at the end of the chemotherapeutic treatment was significantly higher with respect to the values seen before the onset of treatment. On the contrary, lymphocyte mean number decreased on chemotherapy in patients with SD or PD, even though the decline was statistically significant with respect to the pretreatment values in the only patients who had a PD in response to chemotherapy. This study would suggest that chemotherapy itself may paradoxically act, at least in part, as a cancer immunotherapy by inducing lymphocytosis, as well as previously demonstrated for the only immunotherapy with IL-2, probably by modulating the cytokine network and correcting the altered endogenous production of cytokines, responsible for cancer-related immunodeficiency.
    Journal of biological regulators and homeostatic agents 01/2006; 20(1-2):29-35. · 5.18 Impact Factor
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    ABSTRACT: The recent advances in the knowledge of the psychoneuroimmunological pathogenesis of human neoplasms have demonstrated the existence of feed-back mechanisms operating between interleukins and endocrine secretions, which play an important role in the regulation of the immune responses, including the anticancer immunity. In contrast, few studies only have been performed to investigate the possible relation between endocrine activities and hematopoietic growth factors. The present study was performed to analyze the acute endocrine effects of erythropoietin-alpha (EPO) on the main endocrine secretions. The study was carried out in 10 advanced solid tumor patients. EPO was injected subcutaneously at a dose of 10,000 U, and venous blood samples were collected before and 2, 4 and 6 h after EPO administration. No significant changes in mean serum levels of FSH, LH and TSH were seen in response to EPO. Cortisol and DHEAS concentrations increased after EPO injection, whereas those of PRL decreased, but none of these differences was statistically significant. Finally, mean serum levels of both growth hormone (GH) and somatomedin-C (IGF-1) significantly decreased after EPO administration. This preliminary study shows that EPO may inhibit GH secretion from the pituitary gland and IGF-1 production. Since GH would stimulate EPO release, the results of this study may suggest the existence of feedback mechanism operating between GH secretion and EPO production, with inhibitory effect of EPO on GH secretion, and stimulatory action of GH on EPO production. Therefore, this study would describe the first example of hemato-endocrine feedback mechanisms. Moreover, this study, by showing an inhibitory effect of EPO on IGF-1 secretion, would suggest a possible use of EPO in the medical oncology not only for the treatment of cancer related anemia, but also to counteract tumor growth by blocking IGF-1 production, which has been proven to be a growth factor for several tumor histotypes. Obviously, IGF-1 is not the only tumor growth factor, but it could play a fundamental role in the regulation of production and activity of several other tumor growth factors. In any case, this study describes the only acute endocrine effects of EPO. Therefore, further studies, by evaluating the endocrine effects of a chronic treatment with EPO, will be required to establish which may be its effect on IGF-1 endogenous production, and its consequence on survival time.
    Hematology 01/2004; 9(5-6):363-7. · 1.39 Impact Factor
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    ABSTRACT: In addition to the occurrence of pain, the evidence of a diminished capacity to feel pleasure is one of the most common cancer-related symptoms. Recent advances in psychoneuroendocrinological knowledge has shown that the perception of pleasure is mainly mediated by the dopaminergic pathways in the brain. Moreover, it has also been demonstrated that the brain dopaminergic sensitivity may be clinically explored by evaluating the endocrine response to the administration of dopaminergic agents, such as apomorphine, which consists of a decline in PRL concentrations and an increase in GH and cortisol levels. The present study was performed to evaluate dopaminergic sensitivity by the administration of apomorphine in cancer patients in an attempt to document possible cancer-related neuroendocrine anomalies, which could explain the psychological status of the patients. The study included 24 cancer patients (breast cancer: 12; colorectal cancer: 7; non-small cell lung cancer: 5), 12 of whom showed distant organ metastases. Apomorphine was given orally at 0.01 mg/kg b.w., by collecting venous blood samples before and after 20 and 60 minutes. A normal decline in PRL levels was seen in both non-metastatic and metastatic cancer patients. No cortisol increase in response to apomorphine was achieved and the lack of cortisol response was particularly evident in metastatic patients. No GH rise occurred in either metastatic or non-metastatic cancer patients. Finally, no significant difference in the endocrine response to apomorphine was seen in relation to the histotype of tumor. The results of this study show that the neoplastic disease is characterized by neurochemical alterations involving pleasure-related dopaminergic pathways, which are more evident in the metastatic disease, without particular differences in relation to tumor histotype. Therefore, the psychological condition of cancer patients would not depend only on psychological factors, but it could be due at least in part to cancer-related neuroendocrine alterations involving the dopaminergic system.
    In vivo (Athens, Greece) 01/2003; 17(6):647-50. · 1.15 Impact Factor
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    ABSTRACT: Abnormally high blood levels of vascular endothelial growth factor (VEGF) appear to be associated with a poor prognosis in advanced cancer, probably as a consequence of its angiogenic and immunosuppressive effects. The prognostic significance of changes in VEGF secretion during cancer chemotherapy is still unknown. This study aimed to investigate the relation between VEGF variations and therapeutic results during chemotherapy in advanced malignancies. The study included 90 metastatic cancer patients, 59 with non-small cell lung cancer and 31 with colorectal carcinoma. Chemotherapy consisted of cisplatin plus etoposide for NSCLC and camptothecin for colorectal cancer. Abnormally high (> 2 SD with respect to values in healthy controls) pretreatment VEGF levels were found in 38/90 (42%) patients. The percentage of non-progressive disease in response to chemotherapy was significantly higher in patients with normal levels of VEGF prior to therapy than in those with elevated pretreatment values of VEGF (10/32 vs 4/27; p < 0.05). Moreover, the percentage of VEGF level normalization during chemotherapy was significantly higher in patients with objective tumor response or stable disease than in progressing patients (10/18 vs 0/20; p < 0.001). Finally, among patients with tumor response or disease stabilization, the one-year survival rate was significantly higher in patients with chemotherapy-induced normalization of VEGF than in those with persistently high VEGF blood levels (9/10 vs 3/8; p < 0.05). These results suggest that changes in VEGF levels during chemotherapy may represent a useful biomarker to predict the effect of chemotherapy in terms of tumor response and survival in patients with metastatic solid neoplasms.
    The International journal of biological markers 01/2003; 18(2):152-5. · 1.59 Impact Factor
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    ABSTRACT: Insulin-like growth factor-1 (IGF-1) is a mitogenic and anti-apoptotic factor, mainly produced by the liver, which regulates cell proliferation. Most serum IGF-1s are bound with IGF-1BP3. Plasma IGF-1 values are positively related to cancer risk (breast, colon, and lung cancer) and seem to have a prognostic significance in prostatic cancer. The aim of this study is to investigate the relationship between IGF-1, IGF-1BP3 and gastric cancer. IGF-1 and IGF-1BP3 serum levels were measured in 26 consecutive patients (M/F = 15/11, mean age 65 yrs) with histologically proven gastric adenocarcinoma from January 1999 to December 2000. Blood samples were collected at baseline, before surgery with radical intent (total and subtotal gastrectomies + D2 lymphadenectomy), and then at 14th and 50th postoperative days. These values were compared to a control group of healthy people. At baseline was observed a significant increase of IGF-1 serum levels in cancer patients versus control group (p < 0.001). All gastric cancer patients showed IGF-1 over normal limits. After surgery there was a significant decrease of IGF-1 levels (14th day vs. baseline, p = 0.001) that was still present in late postoperative period (50th day). At baseline IGF-1 values were not related to tumor extension or nodal involvement status. Otherwise in postoperative period IGF-1 significantly decreased in earlier stages (N0; T < or = 2) but not in more advanced ones (N+; T > 2). At baseline, IGF-1BP3 values were increased compared to control group but did not significantly decrease after surgery. IGF-1 values in gastric cancer patients are increased compared to control group, without stratification for stage and nodal status. Moreover radical surgery, with complete tumor ablation, induces a significant decrease in IGF-1 levels, without reach normal limits. Besides at baseline abnormally higher IGF-1BP3 values were observed, suggesting an alteration in IGF-1 and IGF-1BP3 system.
    Hepato-gastroenterology 01/2003; 50(49):297-300. · 0.77 Impact Factor
  • Hepato-gastroenterology 01/2002; 49(45):857-9. · 0.77 Impact Factor
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    ABSTRACT: IL-2 preoperative immunotherapy has been proven to abrogate surgery-induced immunosuppression in cancer patients. In contrast, at present there are no data about the possible influence of IL-2 on angiogenesis-related molecular changes determined by the surgical operation. At present, it is known that VEGF (vascular endothelial growth factor) is the main endogenous angiogenic factor, whereas the antitumor cytokine IL-12 has appeared to play an anti-angiogenetic role. On this basis, a study was planned to evaluate the influence of IL-2 presurgical immunotherapy on the perioperative changes in VEGF and IL-12 secretions. The study was performed on 30 colorectal cancer patients undergoing radical surgery, who were randomly chosen to be treated with or without preoperative immunotherapy of IL-2 (12 million IU/day subcutaneously for 3 consecutive days prior to surgery). Serum levels of VEGF and IL-12 were measured by ELISA for blood samples collected before surgery, and at days 3, 7 and 10 of the postoperative period. VEGF mean concentrations progressively and significantly increased during the postoperative period in patients treated with surgery alone. Mean values of VEGF were enhanced also in patients pretreated with IL-2, but VEGF increase observed in the IL-2 group was delayed, more transient and significantly lower with respect to that found in controls. IL-12 mean concentrations significantly decreased during the postoperative period only in the control patients, whereas in the IL-2-treated patients IL-12 postoperative mean values were not significantly lower than those found before surgery. This preliminary study would suggest that IL-2 preoperative immunotherapy may abrogate surgery decline in IL-12 levels and reduce, although not completely prevent, VEGF increase during the postoperative period in surgically treated cancer patients. These results would suggest that IL-2 presurgical immunotherapy may counteract surgery-induced stimulation of the angiogenesis, by either opposing the decline in blood levels of the anti-angiogenetic cytokine IL-12, or reducing the increase in those of the angiogenic factor VEGF.
    Hepato-gastroenterology 01/2002; 49(44):385-7. · 0.77 Impact Factor
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    ABSTRACT: With the advances in the knowledge of neuroimmunomodulation, a new era of investigations about the chemical basis of the state of mind has been initiated. Both emotions and states of spiritual consciousness may influence immune functions and cancer growth. Stress, anxiety and depressive states are associated with immunosuppression and enhanced frequency of tumors. On the other hand, the states of sexual pleasure and spiritual joy enhance the immune efficacy, by counteracting tumor onset and dissemination. The biochemistry of pleasure and immunostimulation is mainly mediated by pineal indoles and cannabinergic substances, whereas that of stress, anxiety and depression is associated with enhanced production of adrenal steroids, opioids and catecholamines. The sexual repression would allow a progressive immunosuppression through a profound damage in the biochemistry of pleasure. Therefore, a better definition of psychospiritual status-associated neuroimmunochemistry could allow us to improve the immune dysfunction by acting on the same neuroendocrine secretions which are involved in mediating the psychic influence on the immunity, including that against cancer.
    Neuro endocrinology letters 07/2001; 22(3):175-80. · 0.93 Impact Factor
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    ABSTRACT: Recent studies have suggested the involvement of the pineal gland and its main hormone melatonin (MLT) in the pathogenesis of psychiatric disturbances, namely the depressive syndrome. In contrast, the behavior of MLT secretion in schizophrenia is still controversial. The present study was carried out to analyze light/dark rhythm of MLT secretion in relation to that of cortisol and prolactin (PRL) in schizophrenic patients. The study included 13 schizophrenic patients, 8 of whom were untreated, while the other 5 patients were on neuroleptic therapy. Serum levels of MLT, PRL and cortisol were measured by RIA on venous blood samples collected at 8 A.M., 12 A.M., 8 P.M. and 1 A.M. The control group consisted of 20 age-matched healthy subjects. A physiological nocturnal increase in MLT levels occurred in 6/13 patients, whereas the other 7 patients showed an abnormally low MLT peak during the night. Moreover, both light and night mean levels of MLT were significantly lower in patients than in controls. In addition, mean nocturnal levels of MLT were significantly lower in chronic patients than in those evaluated at the onset of disease. Cortisol rhythm was normal in 11/13 patients, whereas PRL levels were abnormally high in 10/13 patients. This preliminary study would suggest that schizophrenia may be associated with a diminished secretion of MLT from the pineal gland, and pineal deficiency would be more evident in the chronic disease. Finally, pineal alterations have appeared to be associated with an altered secretion of PRL and cortisol, by suggesting that the schizophrenic disease may be characterized by marked neuroendocrine disturbances, whose physio-pathological and prognostic significance needs to be established by successive clinical investigations.
    Neuro endocrinology letters 05/2001; 22(2):137-41. · 0.93 Impact Factor

Publication Stats

1k Citations
500.54 Total Impact Points

Institutions

  • 2013
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      Milano, Lombardy, Italy
  • 1988–2012
    • Azienda Ospedaliera San Gerardo
      Monza, Lombardy, Italy
  • 1987–1999
    • Azienda Ospedaliera Niguarda Ca' Granda
      • Department of Cardiology
      Milano, Lombardy, Italy
  • 1991–1995
    • University of Milan
      • Institute of Medical Statistics and Biometry "G. A. Maccacaro" IBSUM
      Milano, Lombardy, Italy
  • 1987–1990
    • Mario Negri Institute for Pharmacological Research
      Milano, Lombardy, Italy