F Rovelli

University of Milan, Milano, Lombardy, Italy

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Publications (254)550.4 Total impact

  • Giuseppina Messina · Paolo Lissoni · Franco Rovelli
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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.
    No preview · Article · Jan 2013 · Current Aging Science
  • Paolo Lissoni · Giuseppina Messina · Franco Rovelli
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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.
    No preview · Article · Dec 2012 · Current Aging Science
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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.
    Full-text · Article · Jan 2012 · Immunotherapy
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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.
    No preview · Article · Jun 2010 · Quaderni Italiani di Psychiatria
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    ABSTRACT: 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. The study included 14 untreatable metastatic cancer patients showing alterations of cortisol rhythm. They were treated by MLT at 20 mg/day orally, in the evening, for 3 consecutive months. 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. 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.
    No preview · Article · Mar 2010 · In vivo (Athens, Greece)
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    ABSTRACT: 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. 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. 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. 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.
    No preview · Article · Nov 2009 · In vivo (Athens, Greece)
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    ABSTRACT: Node involvement, negative estrogen receptor (ER) and HER2 expression are the main negative prognostic factors for breast cancer. Prolactin (PRL) is involved in the control of breast cancer growth and differentiation. Surgery-induced hyperprolactinemia seems to be a positive prognostic factor for operable breast cancer, whereas high PRL levels may predict a poor prognosis in women with metastatic breast cancer. In this study, we evaluated the relation between HER2 expression and PRL blood concentrations in women with metastatic breast cancer women and those whit operable breast cancer patients prior to before and 7 days after surgery. The study included 50 women with breast cancer, 22 of whom had metastatic disease. HER 2 expression and serum levels of PRL were evaluated by fluorescence in situ hybridization (FISH) method and immunoradiometric assay (IRMA) method, respectively. HER2 expression occurred in 11/28 operable cases and in 8/22 metastatic cases. The percentage of surgery-induced hyperprolactinemia was significantly higher in HER2-negative patients than in those with its expression. Moreover, HER2-positive metastatic cases showed significantly higher mean serum PRL levels than in the negative group. These preliminary results show that metastatic cancer-related hyperprolactinemia and lack of surgery-induced hyperprolactinemia are statistically more frequent in HER2-positive patients, thus suggesting a link between PRL endogenous secretion and HER2 expression in breast cancer.
    No preview · Article · Nov 2009 · In vivo (Athens, Greece)
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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.
    No preview · Article · Jun 2009 · Anticancer research
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    ABSTRACT: Desmoid tumour is a rare neoplasm locally invasive characterized from a high incidence of recurrence after surgical removal. Recently has been proven tumour growth pathological mechanism due to abnormal secretion of TGF β from fibroblasts and TNF from monocytes. This is the first detection of an endocrine immunological alteration involved in tumour development and progression. Probably, it can be considered a paradigm of tumour connective growth also for other solid tumour. We report our successful experience of combined surgical and hormone therapy with toremifene plus melatonin in a casistic of 10 patients observed in the last ten years. Anti-estrogens are able to counteract TGF β production (Locci et al, 2001) and melatonin is proven to reduce TNF secretion (Sacco et al, 1998). In order to the pathological mechanism and the experience reported, we consider hormone combined therapy and surgery the first line no toxic treatment of this rare disease.
    No preview · Article · Jan 2009
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    ABSTRACT: The recent advances in the analysis of tumor immunobiology suggest the possibility of biologically manipulating the efficacy and toxicity of cancer chemotherapy by endogenous or exogenous immunomodulating substances. Aloe is one of the of the most important plants exhibiting anticancer activity and its antineoplastic property is due to at least three different mechanisms, based on antiproliferative, immunostimulatory and antioxidant effects. The antiproliferative action is determined by anthracenic and antraquinonic molecules, while the immunostimulating activity is mainly due to acemannan. A study was planned to include 240 patients with metastatic solid tumor who were randomized to receive chemotherapy with or without Aloe. According to tumor histotype and clinical status, lung cancer patients were treated with cisplatin and etoposide or weekly vinorelbine, colorectal cancer patients received oxaliplatin plus 5-fluorouracil (5-FU), gastric cancer patients were treated with weekly 5-FU and pancreatic cancer patients received weekly gemcitabine. Aloe was given orally at 10 ml thrice/daily. The percentage of both objective tumor regressions and disease control was significantly higher in patients concomitantly treated with Aloe than with chemotherapy alone, as well as the percent of 3-year survival patients. This study seems to suggest that Aloe may be successfully associated with chemotherapy to increase its efficacy in terms of both tumor regression rate and survival time.
    Preview · Article · Jan 2009 · In vivo (Athens, Greece)
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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.
    Full-text · Article · Jan 2009
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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.
    Full-text · Article · Jan 2009
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    ABSTRACT: The pituitary hormone prolactin (PRL) may be a potential growth factor for breast cancer. High blood levels of PRL are associated with a poor prognosis in metastatic breast cancer whereas hyperprolactinemia after breast surgery may predict a better prognosis in women with operable breast cancer. The lack of postoperative hyperprolactinemia would represent the consequence of an alteration in the neuroendocrine control of breast cell proliferation. On this basis, a study was planned to establish the relation which exists between changes in PRL perioperative secretion and the psychological maternal behaviour in women with operable breast cancer. The study included 20 patients with operable breast cancer. Serum levels of PRL were measured before and 7 days after breast surgery. The maternal behaviour was investigated by the Rorschach test. Surgery-induced hyperprolactinemia occurred in 7/20 patients. The Rorschach test documented an absence of a maternal profile in 13/20 patients. The proportion of surgery-induced hyperprolactinemia was significantly higher in patients presenting a normal maternal profile than in those who lacked a maternal behaviour. The results, by showing a higher proportion of postoperative hyperprolactinemia in women with breast cancer who maintained a maternal behaviour, would suggest that the poor prognosis associated with the absence of surgery-induced hyperprolactinemia in patients with operable breast cancer may, at least in part, be the consequence of a suppression of maternal psychological behaviour.
    Full-text · Article · Nov 2008 · In vivo (Athens, Greece)
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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.
    Preview · Article · Sep 2008 · In vivo (Athens, Greece)
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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.
    Preview · Article · Sep 2008 · In vivo (Athens, Greece)
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    P Lissoni · F Rovelli · F Brivio · L Fumagalli · G Brera
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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.
    Full-text · Article · May 2008 · In vivo (Athens, Greece)
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    ABSTRACT: Anticancer immunity is under psychoneuroendocrine regulation, mainly via the pineal gland and brain opioid system, which may stimulate and inhibit antitumor immunity respectively. Cancer-related immuno-suppression does not depend only on functional damage of immune cells, but also on alterations of systems responsible for the neuroimmunomodulation, the most frequent of wich is a decline in blood levels of the pineal hormone melatonin (MLT). A study was performed to evaluate the influence of an exogenous administration of MLT alone or MLT plus subcutaneous (SC) low-dose interleukin-2 on tumor progression and survival time in patients with untreatable metastatic solid tumors. The study included 846 patients with metastatic solid tumor (non-small cell lung cancer or gastrointestinal tract tumors) randomized to receive the best supportive care only, supportive care plus MLT (20 mg/day, orally in the evening), or MLT plus SC low-dose IL-2 (3 MIU/day for 5 days/week, for 4 consecutive weeks). The MLT alone was able to induce a significant increase of disease stabilization and survival time with respect to supportive care alone. The association of lL-2 with MLT provided a further improvement in the percentage of tumor regressions and of 3-year survival with respect to MLT alone. The administration of IL-2 and the pineal hormone MLT may induce control of neolplastic growth and a prolonged survival time in patients with metastatic solid tumors, for whom no other conventional anticancer therapy is available.
    Preview · Article · Mar 2008 · Anticancer research

  • No preview · Article · Nov 2007 · The International journal of biological markers
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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.
    Preview · Article · Jul 2007 · In vivo (Athens, Greece)
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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.
    No preview · Article · Jan 2006 · Journal of biological regulators and homeostatic agents

Publication Stats

2k Citations
550.40 Total Impact Points

Institutions

  • 2009-2012
    • University of Milan
      Milano, Lombardy, Italy
  • 1988-2012
    • Azienda Ospedaliera San Gerardo
      Monza, Lombardy, Italy
  • 1987-1996
    • Mario Negri Institute for Pharmacological Research
      Milano, Lombardy, Italy
    • Azienda Ospedaliera Niguarda Ca' Granda
      • Department of Cardiology
      Milano, Lombardy, Italy
  • 1990
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy