Relationship between psychoncology and psychoneuroendocrinoimmunology (PNEI): enhanced T-regulatory lymphocyte activity in cancer patients with self-punishement, evaluated by Rorschach test.

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/mm(3) and >4mm(3), 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+/-0.2 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.

Enhancement of the efficacy of cancer chemotherapy by the pineal hormone melatonin and its relation with the psychospiritual status of cancer patients.

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.

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. 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Psychooncology and cancer progression-related alterations of pleasure-associated neurochemical system: Abnormal neuroendocrine response to apomorphine in advanced cancer patients.

OBJECTIVES: The clinical approach of the Psychooncology is generally limited to the investigation of the only psychological status of cancer patients, without taking into consideration the well demonstrated cancer progression-related psychoneuroendocrine alterations, namely consisting of a progressive decline in the pineal endocrine function and an anomalous activity of brain opioid system. The endocrine response to apomorphine, a dopaminergic agent, has been proven to reflect the dopaminergic sensitivity, which would be involved at least in part in pleasure-related neurochemical mechanisms. The present study was performed to analyze the endocrine response to apomorphine in metastatic cancer patients, as a preliminary approach to the investigation of pleasure-related neuroendocrine mechanisms in human neoplasms. MATERIALS & METHODS: The study included 10 metastatic cancer male patients and 6 male volunteers as a control group. Apomorphine was given orally at 0.01 mg/kg body weight in the morning, and venous blood samples were collected before, and at 20, 60 and 120 minutes after apomorphine administration. The endocrine analysis consisted of the measurement of serum levels of GH, PRL and cortisol. RESULTS: All cancer patients presented alterations involving one or more endocrine responses to apomorphine. GH and cortisol mean levels after apomorphine were significantly higher in controls than in cancer patients, whereas no substantial difference occurred in those of PRL. CONCLUSIONS: This preliminary study, by showing an altered endocrine response to apomorphine in metastatic cancer patients, would suggest that cancer progression may be associated with an altered dopaminergic sensitivity. Because of the involvement of the dopaminergic system in pleasure-related neurochemical mechanisms, this finding would demonstrated that the decline in the perception of pleasure with cancer progression may depend not only on psychological factors, but also, at least in part, on psychochemical alterations occurring during the clinical course of the neoplastic disease.