Psycho-Neuro-EndocrinE-Immunology Therapy of Cancer, Autoimmunity, Geriatric Disorders, Covid-19, and Hypertension.

Despite the great number of experimental investigations in the area of psycho-neuro-endocrine-immunology showing that endocrine, nervous, and immune systems cannot be in vivo physiologically separated, the diagnosis and therapies of the pathologies of these three functional biological systems continue to be separately performed from a clinical practice point of view. The separation between experimental and clinical medicine became dramatic after the discovery of more than 10 human molecules provided by anti-inflammatory and antitumor activity, completely devoid of any toxicity, which may be subdivided into three fundamental classes, consisting of the pineal indole, beta-carboline, and methoxy-kynuramine hormones. Moreover, human systemic diseases, including cancer, autoimmunity, and cardiovascular pathologies, despite their different pathogenesis and symptomatology, are commonly characterized by a progressive decline in the endogenous production of pineal hormones, endocannabinoids, and Ang 1-7, with a consequent inflammatory status and diminished natural resistance against cancer.

How to Monitor the Neuroimmune Biological Response in Patients Affected by Immune Alteration-Related Systemic Diseases.

The clinical management of patients affected by systemic diseases, including cancer and autoimmune diseases, is generally founded on the evaluation of the only markers related to the single disease rather than the biological immuno-inflammatory response of patients, despite the fundamental role of cytokine network in the pathogenesis of cancer and autoimmunity is well known. Cancer progression has appeared to be associated with a progressive decline in the blood levels of the main antitumor cytokines, including IL-2 and IL-12, in association with an increase in those of inflammatory cytokines, including IL-6, TNF-alpha, and IL-1-beta, and immunosuppressive cytokines, namely TGF-beta and IL-10. On the other hand, the severity of the autoimmune diseases has been proven to be greater in the presence of high blood levels of IL-17, TNF-alpha, IL-6, IL-1-beta, IFN-gamma, and IL-18, in association with low levels of TGF-beta and IL-10.

The psychoneuroendocrine-immunotherapy of cancer: Historical evolution and clinical results.

The prognosis of the neoplastic diseases depends not only on the biogenetic characteristics of cancer cells but also on the immunological response of patients, which may influence the biological features of cancer cells themselves as well as the angiogenic processes. Moreover, the immune system is under a physiological psychoneuroendocrine (PNE) regulation, mainly mediated by the brain opioid system and the pineal gland. In more detail, the anticancer immunity is stimulated by the pineal hormone melatonin (MLT) and inhibited by the opioid system, namely, through a mu-opioid receptor.

Cancer as the main aging factor for humans: the fundamental role of 5-methoxy-tryptamine in reversal of cancer-induced aging processes in metabolic and immune reactions by non-melatonin pineal hormones.

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.

Psychoimmunological analysis of cancer patients: correlation with the prognosis.

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.

Principles of psychoneuroendocrinoimmunotherapy of cancer.

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.

Psychoneuroendocrine modulation of regulatory T lymphocyte system: in vivo and in vitro effects of the pineal immunomodulating hormone melatonin.

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.

Synchronization of cortisol circadian rhythm by the pineal hormone melatonin in untreatable metastatic solid tumor patients and its possible prognostic significance on tumor progression.

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.

HER2 expression in breast cancer: correlation with endocrine function and psychological status in operable and metastatic breast cancer.

Background: 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.

A randomized study of chemotherapy versus biochemotherapy with chemotherapy plus Aloe arborescens in patients with metastatic cancer.

Background: 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.

Neuroimmunomodulation in medical oncology: application of psychoneuroimmunology with subcutaneous low-dose IL-2 and the pineal hormone melatonin in patients with untreatable metastatic solid tumors.

Background: 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).

Patients And Methods: 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.

Endocrine effects of erythropoietin in cancer patients.

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.

IGF-1 and IGF-1BP3 in gastric adenocarcinoma. Preliminary study.

Background/aims: 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.

Effects of IL-2 preoperative immunotherapy on surgery-induced changes in angiogenic regulation and its prevention of VEGF increase and IL-12 decline.

Background/aims: 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.

Oncostatic activity of pineal neuroendocrine treatment with the pineal indoles melatonin and 5-methoxytryptamine in untreatable metastatic cancer patients progressing on melatonin alone.

OBJECTIVE: The recent advances in psycho-neuro-endocrino-immunology have demonstrated the existence of several endogenous neuroendocrine substances, capable of affecting both tumor growth and host anticancer immune defenses. The pineal gland would represent one of the most important organs releasing antiproliferative and immunostimulating substances, the most known of them is melatonin (MLT). However, MLT would not be the only pineal indole provided by antitumor activity.

Evidence of pineal endocrine hypofunction in autistic children.

OBJECTIVE: The pineal hormone melatonin (MLT) has been proven to play a fundamental physiological regulatory role on both biological and psychic functions and alterations of the light/dark circadian rhythm of MLT have been described in several chronic immunoinflammatory diseases and in psychic disorders. Aim of the present biological explanatory study was the evaluation of MLT circadian rhythm in autistic children, in order to preliminary assess the pineal endocrine function in the autistic syndrome. METHODS: The study included 14 children suffering from classical infantile autism, who were investigated for the whole 24-hour circadian rhythm by collecting venous blood samples at 4-hour intervals.

Malignancy: Changes in Circulating Immature and Mature Dendritic Cells During IL-2 Cancer Immunotherapy and Their Relation with Lymphocyte Increase and Clinical Response.

Lymphocytosis is the main biomarker predicting the efficacy of subcutaneous IL-2 anticancer immunotherapy. In addition, it has been demonstrated the fundamental role of dendritic cells (DC) in the generation of an effective anticancer immunity. However, the relation between IL-2 and DC system needs to be further understood.