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Lissoni P.,Institute of Biological Medicine
Methods in Molecular Biology | Year: 2012

The recent discoveries in the oncological researches have demonstrated that the prognosis of the neoplastic diseases depends on not only the biological characteristics of tumors, including oncogene expression and growth factor receptor activity, but also on the immune status of cancer patients. This is because the well-documented importance of the anticancer immunity in the initiation of the tumor that is mainly modulated by lymphocytes. In addition, the knowledge on the interactions between the immune and neuroendocrine systems has demonstrated that the immune responses are physiologically under a psychoneuroendocrine control. In particular, it has been confirmed that the activation of the brain opioid tone may suppress the generation of an effective anticancer immunity, whereas it is stimulated by other neuroendocrine structure, namely the pineal gland, through the release of at least two indole hormones with anticancer activity, melatonin and 5-methoxytryptamine, exerting both antiproliferative and immunostimulatory effects. By investigating the immune and neuroendocrine functions in cancer patients, it has been observed that cancer progression is associated with a progressive decline in the pineal function, which would constitute the main cancer-related endocrine deficiency, and the occurrence of the irreversible immune alterations. The most prognostically important factors would consist of a diminished endogenous production of anticancer cytokines, such as IL-2 and IL-12, as well as an abnormally enhanced secretion of cytokines provided by suppressive effect on the anticancer immunity, namely IL-14, TGF-beta, and IL-6. The psychoneuroimmunotherapeutic approach in the treatment of cancer would simply consist of the corrections of the various endocrine and immune cancer-related alterations in an attempt to re-establish the neuroimmune condition of the health status. © 2012 Springer Science+Business Media, LLC.

Messina G.,Psychological Service | Lissoni P.,Institute of Biological Medicine | Marchiori P.,Natur Spiritual | Bartolacelli E.,Psychological Service | And 2 more authors.
Journal of Research in Medical Sciences | Year: 2010

BACKGROUND: The anti-oxidant and immunomodulating natural agents may enhance the efficacy of cancer chemotherapy. One of the most important agents is the pineal hormone melatonin (MLT) which may exert both anti-oxidant and antiproliferative immunostimulating anticancer effects. This study was performed to evaluate the efficacy of a biochemotherapeutic regimen in metastatic cancer patients, and its therapeutic activity in relation to the psychospiritual status of patients. METHODS: The study included 50 metastatic non-small cell lung cancer (NSCLC) patients and a control group of 100 patients. Chemotherapy consisted of cisplatin plus gemcitabine. MLT was given orally at 20 mg/day in the evening. Patients were subdivided into 5 psychic profiles, as follows: spiritual faith, rationale faith, anxiety, apathy, and accusation behavior. RESULTS: Tumor response rate was significantly higher in patients treated by chemotherapy plus MLT than in those treated by chemotherapy alone (21/50 vs. 24/100, p < 0.001). However, the percentage of objective tumor regressions obtained in patients with spiritual faith was significantly higher than that found in the overall other patients concomitantly treated by chemotherapy plus MLT (6/8 vs. 15/42, p < 0.01). CONCLUSIONS: In conclusion, the efficacy of chemotherapy may be enhanced by the pineal hormone MLT, by representing a new promising biochemotherapeutic combination; also despite its objective ability to enhance chemotherapy efficacy, the activity of MLT is depending at least in part on the psychospiritual status of cancer patients, and it is maximal in the presence of a real spiritual faith.

Brivio F.,Bassini Hospital | Fumagalli L.,Bassini Hospital | Fumagalli G.,S.Gerardo Hospital | Pescia S.,S.Gerardo Hospital | And 4 more authors.
In Vivo | Year: 2010

Background: Cancer progression has been associated with neuroendocrine alterations involved in the control of the circadian rhythms, particularly those of cortisol. Moreover, the evidence of an altered cortisol rhythm may predict a poor prognosis in cancer patients. Finally, cancer progression has been proven to be associated with alterations in the pineal gland, which plays a fundamental role in the control of circadian biological rhythms. On this basis, a study was planned to evaluate the effects of a chronic treatment with the pineal hormone melatonin (MLT) in advanced cancer patients with altered cortisol circadian rhythm. Patients and Methods: The study included 14 untreatable metastatic cancer patients showing alterations of cortisol rhythm. They were treated by MLT at 20 mglday orally, in the evening, for 3 consecutive months. Results: a normalization of cortisol rhythm was achieved in 4/14 (29%) patients. Moreover, stable disease (SD) was obtained in 6/14 (43%) patients under MLT therapy, whereas the other 8 patients had progressive disease (PD). Finally, the percentage of cortisol rhythm normalization achieved in patients with SD was significantly higher than that observed in patients with PD. Conclusion: These results show that MLT may normalize cortisol rhythm in advanced cancer patients and this effect appears to be associated with SD, thus confirming the negative prognostic significance of cortisol rhythm alterations in cancer.

Vigore L.,Laboratory of Immunomicrobiology | Messina G.,Polyclinic Hospital | Brivio F.,Bassini Hospital | Fumagalli L.,Bassini Hospital | And 3 more authors.
In Vivo | Year: 2010

Background: At present, it is known that cancer-related immunosuppression would mainly depend on an immunosuppressive action mediated by a subtype of CD4+ lymphocytes, the so-called regulatory T lymphocytes (T-reg), which are identified as CD4+CD25+ cells. Moreover, it has been shown that anticancer immunity is under psychoneuroendocrine regulation, mainly mediated by the pineal hormone melatonin (MLT). This study was performed to investigate the in vivo and in vitro effects of MLT on T-reg generation. Materials and Methods: We evaluated the in vivo effects of MLT (20 mg/daily orally in the evening) in 20 patients with untreatable metastatic solid tumor and the in vitro effects of MLT incubation (at 10 and 100 pg/ml) of pure lymphocyte cultures on T-reg cell count. Results: MLT induced a statistically significant decline in mean T-reg cell numbers in patients who achieved disease control, whereas no effect was seen in those who had progressed. In contrast, no in vitro effect of MLT incubation was apparent. Conclusion: This preliminary study would suggest that MLT may exert in vivo an inhibitory action on T-reg cell generation in cancer patients which is associated with a control of the neoplastic progression, whereas no direct effect was seen in vitro on lymphocyte differentiation. This finding would suggest that MLT may counteract T-reg cell generation in vivo by inhibiting macrophage activity which is involved in stimulating T-reg cell production.

Messina G.,Psychological Service | Lissoni P.,Institute of Biological Medicine | Bartolacelli E.,Psychological Service | Magotti L.,ARS Legrenzi Cazzullo Foundation | And 3 more authors.
In Vivo | Year: 2010

Background: Psychological studies have documented the presence of a self-punishment profile in cancer patients. Recent immuno-oncological studies have shown that within the group of CD4+ cells, which play a fundamental role in the generation of anticancer immunity, there is a subtype of cells that in contrast mediates the suppression of the anticancer immunity, the so-called T-regulatory cells (T-reg), which may be identified as CD4 +CD25+ cells. Patients and Methods: On this basis, we performed a psychoncological study to evaluate CD4+CD25+ cell numbers in relation to the response to Rorschach's test in a group of 30 cancer patients suffering from the most frequent tumor histotypes. Results: Normal values obtained in our laboratory (95% confidence limits) of T-reg lymphocytes and CD4+/CD4+CD25+ were <240/mm3 and >4mm3, respectively. The psychological profile of self-punishment was found in 18/30 patients (60%). The percentage of patients with abnormally high CD4+CD25+ values observed in the group with self-punishment was significantly higher than that found in patients without self punishment (11/18 vs. 3/12 (25%), p<0.05). In the same way, the percentage of patients with abnormally low CD4+/CD4 +CD25+ ratios was significantly higher in the group with self-punishment (16/18 vs. 4/12, p<0.01). The mean numbers of T-reg lymphocytes observed in the group with self-punishment was significantly higher than that found in patients who had no self-punishment (314±39 vs. 173±27, p<0.05). In addition, the mean CD4+/ CD4 +CD25+ ratio was significantly lower in patients with self-punishment than in the other group (2.6±02 vs. 5.2±0.8, p<0.025). On the contrary, no significant difference was seen in the mean number of CD4+ lymphocytes. Conclusion: The study suggests that self-punishment may inhibit the generation of an effective anticancer immune response by stimulating the activation and proliferation of T-reg lymphocytes, which in turn stimulate tumor dissemination by suppressing anticancer immunity. The abnormally high number of T-reg lymphocytes in patients with self-punishment would suggest a specific immune alteration, as suggested by the evidence of a normal profile for other immune parameters, such as total CD4+ lymphocytes.

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