Search PubMed⌕ Search

Biomedical subjects

G Tancini

Publications and source records attributed to G Tancini.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

Clinical and biological effects of interleukin-2 with or without a concomitant administration of granulocyte-macrophage colony-stimulating factor in metastatic cancer patients.

GM-CSF has been shown to modulate the anticancer activity of IL-2 with, however, controversial results depending on the great variety of biological effects induced by GM-CSF itself. The activation of dendritic cells and the generation of suppressive cells would constitute the main favourable and unfavourable biological effects of GM-CSF, respectively. The present study was performed in an attempt to evaluate the clinical and biological effects of a concomitant GM-CSF administration of the immunotherapy of metastatic renal cell carcinoma with IL-2. The study included 25 patients, who were randomized to be treated with IL-2 alone or IL-2 plus GM-CSF. IL-2 was injected subcutaneously at 6 MIU/day for 6 days/week for 4 consecutive weeks, coressponding to one complete cycle. GM-CSF was injected subcutaneously at 0.3 micrograms/kg b.w. for 3 consecutive days for the first 3 days of each week of IL-2 administration. Two immunotherapeutic cycles at 21-day intervals were planned. No significant difference was observed in the percent of non-progressive disease between the two groups of patients. The increase in leukocyte mean number was significantly higher in patients concomitantly treated with GM-CSF, whereas no difference was observed in that of lymphocytes. This preliminary study suggests that the concomitant administration of GM-CSF does not enhance the therapeutic efficacy of IL-2 immunotherapy of metastatic renal cell cancer.

Aged↗
PubMedDate not supplied

Antiprolactinemic approach in the treatment of metastatic breast cancer: a phase II study of polyneuroendocrine therapy with LHRH-analogue, tamoxifen and the long-acting antiprolactinemic drug cabergoline.

Despite the well-demonstrated stimulatory role of prolactin (PRL) on breast cancer cell growth and the possible existence of a PRL-dependency in estrogen-independent mammary tumors, the therapeutic role of the antiprolactinemic drugs in the treatment of human breast cancer has still to be investigated and defined. Previous preliminary studies have already shown that the concomitant administration of antiprolactinemic agents may enhance the efficacy of cancer chemotherapy for breast carcinoma, whereas their impact on the efficacy of the endocrine therapy is still unknown. At present, the classic endocrine therapy for breast cancer consists of anti-estrogens plus LHRH-analogue. The concomitant administration of antiprolactinemic drugs could enhance the efficacy of treatment by blocking not only the action of estrogens, but also that of another growth factor for breast cancer, such as PRL. The present phase II study was performed to evaluate the efficacy and tolerability of a polyneuroendocrine approach for breast cancer, consisting of LHRH-analogue plus the anti-estrogen tamoxifen plus a long-acting antiprolactinemic agent, cabergoline. The study included 14 consecutive metastatic breast cancer women, heavily pretreated with the standard anticancer therapies and for whom no other conventional treatment was available. The LHRH-analogue, triptorelin, was given intramuscularly at a dose of 3.75 mg every 28 days, tamoxifen was given orally at 20 mg/day and cabergoline was given orally at 0.5 mg once/week. The clinical response consisted of partial response (PR) in 4 out of 14 (29%) patients, including one who had progressed on a previous treatment with triptorelin plus tamoxifen alone. A stable disease (SD) was achieved in another 5 patients, whereas the other 5 patients had a progressive disease (PD). Mean serum levels of PRL significantly decreased on treatment within the first month of therapy, and its decline was significantly more evident in patients with PR or SD than in those with PD. The treatment was well-tolerated in all patients, and in particular no cabergoline-related toxicity occurred. This preliminary study would suggest that the association of the long-acting antiprolactinemic drug cabergoline may further enhance the efficacy of the classical endocrine therapy for advanced breast cancer with anti-estrogens plus LHRH-analogues.

Adult↗
PubMedDate not supplied

Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations.

Recent advances in immunobiological knowledge have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones. In particular, the pineal neurohormone melatonin (MLT), which is able to exert both antioxidant and immunomodulating effects, has been proven to enhance the efficacy of various chemotherapeutic drugs, namely cisplatin, anthracyclines and 5-fluorouracil, whereas at present there are no data about its possible influence on cytotoxic drugs effective in the treatment of colon cancer other than 5-fluorouracil, such as irinotecan (CPT-11). The present study was performed to evaluate the influence of a concomitant administration of MLT on CPT-11 therapeutic activity in metastatic colorectal cancer. The study included 30 metastatic colorectal cancer patients progressing after at least one previous chemotherapeutic line containing 5-fluorouracil, who were randomized to be treated with CPT-11 alone or CPT-11 plus MLT. According to a weekly low-dose schedule, CPT-11 was given i.v. at 125 mg/m2/week for 9 consecutive weeks. MLT was administered orally at 20 mg/day during the dark period of the day. No complete response was observed. A partial response (PR) was achieved in 2 out of 16 patients treated with CPT-11 alone and in 5 out of 14 patients concomitantly treated with MLT. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with CPT-11 alone and in 7 out of 14 patients treated with CPT-11 plus MLT. Therefore, the percent of disease-control achieved in patients concomitantly treated with MLT was significantly higher than that observed in those treated with chemotherapy alone (12 out of 14 vs 7 out of 16, p < 0.05). The only important toxicity was diarrhoea grade 3-4, which occurred in 6 out of 16 patients treated with CPT-11 alone and in 4 out of 14 patients treated with CPT-11 plus MLT, which required a 50% dose reduction. However, taken together, patients treated with CPT-11 at 50% of the planned dose showed a percent of disease control comparable to that achieved in patients who had no dose reduction (6 out of 10 vs 13 out of 20). This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone MLT, according to the results previously reported for other chemotherapeutic agents. Moreover, since the dose reduction of CPT-11 does not influence its efficacy, the dose of CPT-11 for successive studies might be not greater than 70 mg/m2.

Adjuvants, Immunologic↗
PubMedDate not supplied

Immunological effects of a single evening subcutaneous injection of low-dose interleukin-2 in association with the pineal hormone melatonin in advanced cancer patients.

Recent experiments have shown that a great variety of neurohormones can interact with IL-2 in the modulation of host antitumor immune response. On the basis of these data, a study was started to evaluate the effect of the pineal hormone melatonin (MLT) on IL-2-induced immune changes in cancer. The study included 30 advanced cancer patients. They were randomized to be treated with IL-2 at a dose of 3 million IU subcutaneously twice/daily (8.00 a.m. and 8.00 p.m.) for 6 days/week for 4 weeks, with IL-2 once/daily in the evening, with IL-2 once/daily plus MLT at 10 or at 50 mg/day. MLT was given orally at 8.00 p.m. Both IL-2 given twice daily and IL-2 given once daily and IL-2 given once daily in association with MTL induced a significant increase in mean number of lymphocytes, T lymphocytes, NK cells, CD25-positive cells and eosinophils, whereas the single administration of IL-2 alone was unable to determine a significant rise in the mean number of immune cells. Soluble IL-2 receptor and neopterin increase was significantly higher during IL-2 given twice/daily than during IL-2 plus MLT, while no difference was seen in TNF rise. This study would suggest that a single daily injection of low-dose IL-2 is able to efficiently activate the lymphocyte proliferation in cancer patients when it is given in association with the pineal hormone MLT.

Adult↗
PubMedDate not supplied

Effects of granulocyte-macrophage colony stimulating factor on cortisol, growth hormone, prolactin and melatonin in cancer patients (short communication).

Several interleukins and interferons have been proven to induce endocrine effects. On the contrary, only few data are available about the possible hormonal activity of hemopoietic growth factors. This study was carried out to evaluate the endocrine influence of GM-CSF in humans. The study included nine head and neck cancer patients, evaluated in basal conditions and after an acute subcutaneous injection of GM-CSF at a dose of 3 mcg/kg b.w., by determining serum levels of cortisol, growth hormone (GH), prolactin (PRL) and melatonin. Both cortisol and GH significantly increased in response to GM-CSF, while PRL, and melatonin were not influenced. This preliminary study shows that hemopoietic growth factors, as well as interleukins, may also play endocrine effects in humans.

Adult↗
PubMedDate not supplied

Inhibitory effect of interleukin-3 on interleukin-2-induced cortisol release in the immunotherapy of cancer.

The stimulatory effect of IL-2 on cortisol rise represents an undesirable biological event during IL-2 cancer immunotherapy. At present, no cytokine has been proven to be able to counteract IL-2-induced cortisol increase. This study was carried out to evaluate the influence of IL-3 on IL-2 stimulation of cortisol secretion. Five lung cancer patients were investigated after IL-2 (3 x 10(6) IU s.c.), after IL-3 (1 mcg/kg b.w. i.v.) and after IL-3 plus IL-2, by administering IL-3 two hours before IL-2 injection. IL-2 significantly stimulated cortisol secretion. IL-3 alone had no effect on cortisol levels. The pretreatment with IL-3 completely neutralizes IL-2-induced cortisol release. These preliminary results would suggest that IL-3 may be associated with IL-2 during cancer immunotherapy to modulate the effect of IL-2 on the endocrine system.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

A psychoneuroendocrine study of brain dopaminergic sensitivity in locally limited or metastatic cancer patients.

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.

Adult↗
PubMedDate not supplied

Tumor necrosis factor in solid tumors: increased blood levels in the metastatic disease.

TNF, a cytokine produced by macrophages, is able either to exert an antitumor activity, or to determine severe clinical complications, such as cachexia and septic shock. Increased blood levels of TNF have been described in cancer patients. The present study was performed to better define TNF secretion in patients with solid tumors. The study included 48 cancer patients (lung cancer: 22; colon cancer: 11; breast cancer: 10; renal cancer: 5), and among them 27 showed distant organ metastases. TNF serum levels were measured by IRMA method. The control group comprised 40 healthy subjects. TNF levels were also evaluated in relation to those of SIL-2R, whose increase seems to be associated with an unfavorable prognosis in cancer. High levels of TNF were seen in 27/48 (56%) patients. Mean levels of TNF were significantly higher in cancer patients than in controls. Moreover, within the cancer group, TNF mean values were significantly higher in metastatic patients than in those without metastases; the highest levels were observed in patients with visceral lesions as dominant metastasis sites. Finally, patients with high TNF concentrations showed significantly higher mean levels of SIL-2R than those with normal values. This study shows that the neoplastic metastatic disease is associated with an exaggerated TNF secretion.

Adult↗
PubMedDate not supplied

A psychoncological study of lymphocyte subpopulations in relation to pleasure-related neurobiochemistry and sexual and spiritual profile to Rorschach's test in early or advanced cancer patients.

According to recent advances in psychoneuroimmunology concerning the neurobiochemistry of emotions, the pshychological status of cancer patients should be investigated in relation to the function of the psychoneurodocrine system, in an attempt to put into evidence possible cancer progression-related alterations, particularly those involving the dopaminergic pathways, which play a fundamental role in the perception of pleasure. In fact, the decreased capacity of feeling pleasure is one of the most frequent psychic symptoms occurring in cancer patients. Rorschach's test has been proven to be an appropriate psychological tool to investigate psychic condition including sexual and spiritual profiles. On this basis, a study was planned to evaluate if a relation exists between psychological response to Rorschach's test and immunoneuroendocrine status of cancer patients. The immune status was investigated by measuring lymphocyte subsets and serum levels of IL-2 and IL-10. The neuroendocrine status was analyzed by evaluating the endocrine response of PRL, GH and cortisol to an oral administration of apomorphine (0.01 mg/kg b.w.), a dopaminergic agent able to explore dopaminergic sensitivity. The study included 40 cancer patients (breast cancer: 15; colorectal cancer: 14; lung cancer: 11), 21 of whom showed distant organ metastases. Rorschach's test demonstrated a simultaneous suppression of sexual and spiritual profiles in 31/40 (78%) patients, without significant differences in relation to either tumor histotype or disease state. A normal decline in PRL levels and a normal increase in those of GH and cortisol was observed in 29/40 (73%), 5/40 (13%) and 9/40 (23%) patients. The percent of normal responses of PRL, GH and cortisol was higher in patients with normal than in those with altered response to Rorschach's test, even though only the difference in PRL and cortisol response was statistically significant. Patients with normal sexual and spiritual expression at Rorschach's test showed a significantly higher number of total lymphocytes, T lymphocytes, T helper lymphocytes and NK cells with respect to the patients with altered psychological response, whereas no difference was found in T cytotoxic lymphocyte mean number. IL-2 and IL-10 mean serum concentrations were lower and higher, respectively, in patients with altered than in those with normal response to Rorschach's test, even though only the difference in IL-10 values was statitistically significant. This preliminary study, carried out to analyze the psychological status of cancer patients in relation to neuroendocrine and immune conditions, would suggest that neoplastic disease is characterized by a simultaneous suppression of sexual and spiritual profiles, and that this is associated with neuroendocrine alterations and immunosuppression.

Administration, Oral↗
PubMedDate not supplied

Biological response modifiers of cancer-related neuroendocrine disorders: efficacy of the long-term dopaminergic agonist cabergoline in the treatment of breast cancer-induced hyperprolactinemia.

The evaluation of the biological status of cancer patients should not be limited only to investigation of immune reactivity, but should also include analysis of the endocrine condition, namely concerning those hormones which have appeared to be tumor growth factors, such as prolactin (PRL) for breast and prostate carcinomas. This statement is justified by the fact that the evidence of abnormally high serum concentrations of PRL has been proven to be associated with poor prognosis in breast and prostate cancer patients. Moreover, since hyperprolactinemia negatively influences the efficacy of anticancer therapies in breast cancer, it could be fundamental to achieve a normalization of PRL levels by long-acting dopaminergic agents, such as cabergoline. On this basis, a study was planned to evaluate the effect of cabergoline on PRL levels in hyperprolactinemic metastatic breast cancer subjects. The study included 20 hyperprolactinemic metastatic breast cancer subjects, who were randomized to receive no therapy or cabergoline at 0.5 mg/week orally for 4 consecutive weeks. Cabergoline therapy induced a normalization in all patients, whereas no spontaneous normalization of PRL levels occured in the control group. These results show that a weekly oral administration of the long-acting dopaminergic agent cabergoline is a well tolerated and effective treatment of metastatic breast cancer-related hyperprolactinemia. The possible prognostic impact of PRL normalization needs to be established by successive studies.

Aged↗
PubMedDate not supplied

Blood levels of IGF-I in non-small cell lung cancer: relation to clinical data.

Recent observations have demonstrated that somatomedins, mainly insulin-like growth factor-I (IGF-I), are growth factors for non-small cell lung cancer (NSCLC). On the basis of this evidence, a study was started to evaluate serum levels of IGF-I in a group of untreated NSCLC patients. The study included 46 patients, 25 of whom had an operable tumor, while the other 21 showed distant organ metastases. IGF-I and GH serum levels were measured by RIA in each patient; moreover, in operable patients, hormonal detections were made either before, or 7 days after surgery. The control group comprised 38 age-matched healthy subjects. Mean serum levels of IGF-I were significantly higher in cancer patients with respect to controls, while no difference was seen in mean GH values. Moreover, patients with metastases showed significantly higher levels of IGF-I than the patients without. Within the operable group, patients with lung adenocarcinoma had higher levels of IGF-I than those with epidermoid cell carcinoma, but this difference was not significant. Finally, no significant difference in IGF-I mean values was seen before and after surgical removal of tumors. This preliminary study shows that NSCLC patients may present abnormally high levels of IGF-I. Because of the stimulating role of IGF-I on NSCLC growth, this evidence could play a role in the clinical course of neoplastic lung disease.

Adult↗
PubMedDate not supplied

Modulation of interleukin-2-induced macrophage activation in cancer patients by the pineal hormone melatonin.

The concomitant induction of immunosuppressive events, at least in part mediated by macrophages, would represent one of the mechanisms responsible for the lower activity of IL-2 in vivo than in vitro. Since macrophages have recently appeared to be under neuroendocrine control, the present study was carried out to evaluate the effect of the pineal neurohormone MLT on IL-2-induced macrophage activation during cancer immunotherapy, by determining serum levels of neopterin, which is a specific marker of macrophage activity. The study included 21 advanced cancer patients (lung cancer: 12; renal cancer: 9), 10 of whom received IL-2 subcutaneous therapy alone (1.8 x 10(6) IU/m2 twice daily), or IL-2 plus MLT (10 mg/day orally at 8.00 P.M.). Neopterin levels increased in all patients during IL-2 immunotherapy, but neopterin mean peak was significantly higher in patients treated with IL-2 alone than in those who received IL-2 plus MLT. This preliminary study would suggest the possible use of neurohormones to modulate host antitumor immune response during cancer immunotherapy with IL-2.

Adult↗
PubMedDate not supplied

Endocrine effects of a 24-hour intravenous infusion of interleukin-2 in the immunotherapy of cancer.

Several experiments have demonstrated that there is a relationship between neuroendocrine and immune systems. Despite these interesting findings, only few studies have been performed up to now to evaluate the possible importance of neuroimmune interactions in influencing the biological efficacy and toxicity of cancer immunotherapy with IL-2. To analyze the effects of IL-2 on endocrine secretions, we have measured by RIA serum levels of cortisol, beta-endorphin, GH, PRL and of the pineal hormone melatonin in metastatic renal cancer patients, treated with 5-day courses of IL-2 at a daily dose of 3 x 10(6) U/m2, given through a 24-hour intravenous infusion. Six IL-2 courses were evaluated, by collecting blood samples at 4-hour intervals for 24 hours and by comparing the hormonal values with those observed in baseline conditions. Both cortisol and beta-endorphin mean values significantly increased during IL-2 infusion. GH and PRL also increased, but not in a significant manner. Finally, melatonin mean levels significantly decreased during the infusion. The IL-2-induced effects on cortisol, beta-endorphin and melatonin resulted in a complete abolition of their physiological circadian rhythm. These results show that IL-2 infusion induces important changes in endocrine secretions. Because of the immunosuppressive effect of cortisol and the stimulatory one of melatonin, their changes during IL-2 infusion might influence the biological activity of immunotherapy itself. Further studies will be required to define better the clinical importance of IL-2 induced hormonal changes.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Neuroimmunotherapy of human cancer with interleukin-2 and the neurohormone melatonin: its efficacy in preventing hypotension.

The pineal hormone melatonin (MLT) has been shown to influence many biological functions, including immune response, cancer growth and brain neurotransmitter contents. On the basis of its biological properties, a study was started to evaluate the influence of MLT on IL-2 immunotherapy toxicity. The study was carried out in metastatic renal cancer patients. Thirty-three 5-day courses of IL-2 at a daily dose of 3 x 10(6) Cetus U/m2 were randomized to consist of IL-2 alone or IL-2 plus MLT (10 mg/day orally at 8.00 p.m.). The frequency of episodes of severe hypotension was significantly greater during IL-2 alone than during IL-2 + MLT. Moreover, the depressive symptomatology occurred more frequently during IL-2 alone. No other toxicity, including capillary leak syndrome, vomiting and fever, were significantly influenced by the concomitant treatment with MLT. These preliminary results would suggest that the pineal hormone MLT may be successfully associated with IL-2 in the immunotherapy of human tumors.

Circadian Rhythm↗
PubMedDate not supplied

Alterations of pineal gland and of T lymphocyte subsets in metastatic cancer patients: preliminary results.

Melatonin (MLT), the main hormone produced by the pineal gland, has been seen to play a role in antineoplastic activity either by exerting a direct inhibitory effect on cancer cell growth, or by stimulating the immune system. Moreover, MLT blood levels have been shown to be often increased in cancer patients. On the basis of these data, a study was started to evaluate what relation exists between MLT levels and T lymphocyte subsets in patients with metastatic solid neoplasm. The study included 28 patients (breast: 10; non-small cell lung: 18). None of the patients was previously treated for their metastatic disease. Abnormally high MLT levels and a low T helper/suppressor ratio (CD4/CD8) were seen in 10/28 and in 11/28 patients, respectively. Serum mean levels of MLT were significantly higher in patients with low CD4/CD8 ratio than in those with a normal ratio. These results would suggest that immune dysfunctions may represent a signal for MLT release from the pineal in patients with metastatic solid neoplasm.

Adult↗
PubMedDate not supplied

Effects of cancer chemotherapy on the relation between serum levels of soluble interleukin-2 receptors and CD4/CD8 ratio in patients with solid neoplasms.

The clinical significance of sIL-2R in solid tumors has still to be clarified. To further define the biological role of sIL-2R in cancer and their relation to chemotherapy, we have measured serum levels of sIL-2R and CD4/CD8 ratio in 45 patients with limited or metastatic solid tumor, 28 of whom had never received chemotherapy, whereas the other 17 had been previously treated with chemotherapy. sIL-2R were significantly higher in metastatic cancer patients than in the non-metastatic ones, while no difference was seen between patients treated and untreated with chemotherapy. Within the untreated group, sIL-2R mean values were significantly higher in patients with low CD4/CD8 ratio than in those with the normal one, while an opposite behavior was seen in patients previously treated with chemotherapy. The present study shows that cancer chemotherapy influences the release of sIL-2R and its relation to T lymphocyte subpopulations.

Adult↗
PubMedDate not supplied

Role of the pineal gland in the control of macrophage functions and its possible implication in cancer: a study of interactions between tumor necrosis factor-alpha and the pineal hormone melatonin.

Recent studies have shown the existence of reciprocal links between cytokine activity and immunomodulating neurohormones or neuropeptides. In particular, the pineal hormone melatonin (MLT) appears to influence IL-2 activity in cancer. The present study was performed to evaluate which interaction exists between MLT and another important cytokine, tumor necrosis factor-alpha (TNF), which is responsible for both antitumor cytolytic activity and cancer-related cachexia. In a first study, we analyzed MLT circadian rhythm under TNF administration (0.75 mg/day i.v. for 5 days) in 10 metastatic solid tumor patients. In a second study, we evaluated TNF serum levels in 10 metastatic solid tumor patients under therapy with MLT alone (20 mg/day orally in the evening for at least 1 month). In a third study, we have measured concomitantly daily serum levels of MLT and TNF in 30 patients with metastatic solid neoplasms. Nocturnal mean serum concentrations significantly increased in response to TNF injection. MLT therapy induced a significant decline in TNF mean values. Finally, patients with abnormally high MLT diurnal levels showed significantly lower TNF mean concentrations with respect to those with normal levels of the pineal hormone. This study, by showing the stimulatory effect of TNF on MLT secretion and the inhibitory action of MLT on TNF release, would suggest the existence of feed-back mechanisms operating between the pineal gland and TNF released from macrophages in human neoplasms.

Adult↗