Biomedical subjects
Publications and source records attributed to S Crispino.
This is the eighteenth case of testicular tumor in a father and son reported in the literature. The father had a seminoma and the son an embryonal carcinoma. The trend favoring more malignant tumors occurring at younger ages in the sons is confirmed by this report.
The mechanisms responsible for cancer cachexia have not yet been clarified. To further investigate the role played by the hypothalamic-pituitary-thyroid axis in cancer cachexia, we evaluated serum levels of T3, FT3, T4, FT4, TSH and TBG in a group of 26 cancer patients, 14 of whom showed cachexia, whereas the other 12 had a body weight within the normal range despite their advanced diseases. As controls, 58 healthy subjects and 11 patients with benign weight loss were included in the study. Low levels of both T3 and FT3 were observed in all patients with benign weight loss and in 9/12 advanced cancer patients who had no cancer cachexia. On the contrary, only 4/14 cachectic cancer patients presented decreased values of T3 and FT3. Moreover, the mean serum levels of T3 and FT3 in cachectic oncologic patients were significantly higher than those seen both in non-cachectic cancer patients and in patients with benign weight loss. Since T3 is the biologically active thyroid hormone, the lack of a decrease in its production might play a role in the pathogenesis of cancer cachexia.
Melatonin, the most important indole hormone produced by the pineal gland, appears to inhibit tumor growth; moreover, altered melatonin secretion has been reported in cancer patients. Despite these data, the possible use of melatonin in human neoplasms remains to be established. The aim of this clinical trial was to evaluate the therapeutic, immunological and endocrine effects of melatonin in patients with metastatic solid tumor, who did not respond to standard therapies. The study was carried out on 14 cancer patients (colon, six; lung, three; pancreas, two; liver, two; stomach, one). Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m., followed by a maintenance period in an oral dose of 10 mg daily in patients who had a remission, stable disease or an improvement in PS. Before and after the first 2 months of therapy, GH, somatomedin-C, beta-endorphin, melatonin blood levels and lymphocyte subpopulations were evaluated. A partial response was achieved in one case with cancer of the pancreas, with a duration of 18+ months; moreover, six patients had stable disease, while the other eight progressed. An evident improvement in PS was obtained in 8/14 patients. In patients who did not progress, T4/T8 mean ratio was significantly higher after than before melatonin therapy, while it decreased in patients who progressed. On the contrary, hormonal levels were not affected by melatonin administration. This study would suggest that melatonin may be of value in untreatable metastatic cancer patients, particularly in improving their PS and quality of life; moreover, based on its effects on the immune system, melatonin could be tested in association with other antitumor treatments.
Both activated normal and transformed lymphocytes produce not only cell-associated but also cell-free IL-2R. Evidence of high serum concentrations of IL-2R appears to serve as a tumor marker in patients with lymphomas On the contrary, the role of soluble IL-2R in solid neoplasms has still to be defined. This investigation was carried out to analyze soluble IL-2R production in human solid tumors. The study included 35 patients with solid tumors (12 without and 23 with metastases), 58 healthy subjects and 6 lymphoma patients. Among cancer patients, lung and breast carcinoma were the two most frequent neoplasms. In each subject or patient, serum levels of IL-2R were measured by using an enzyme immunoassay. Moreover, in 14/23 patients with metastatic solid tumors, lymphocyte subpopulations were also evaluated. Serum levels of IL-2R were significantly higher in the cancer patients than in the normal subjects. The patients with metastatic solid tumors showed significantly higher mean levels than those without metastases, and similar to those observed in the lymphoma patients. Finally, there was no correlation between serum levels of IL-2R and the T4/T8 ratio, which was reduced in 5/14 cancer patients. Further studies will be needed to establish if elevated concentrations of IL-2R in the serum can contribute to the immunoincompetence of patients with disseminated solid neoplasms.
Recent studies showed that both the pineal gland and the endogenous opioid system are involved in the modulation of the immune system and in the regulation of tumor growth. Moreover, a relationship between pineal and opioid system has been demonstrated. In order get an overall view of the psychoneuroendocrine interactions in cancer patients, the levels of melatonin, the most important pineal hormone, and of beta-endorphin have been measured on blood samples collected during the morning. The study was carried out on 54 patients, 42 healthy subjects, and in 34 patients having illnesses other than cancer. Breast cancer, lung carcinoma, and colorectum cancer were the three neoplasms detected in the patients investigated. Growth hormone (GH), somatomedin-C and prolactin (PRL) levels were also determined. beta-endorphin levels were found to be substantially within the normal range in patients with cancer, whereas those of melatonin were raised in several cases. The beta-endorphin/melatonin ratio was higher than 2 in normal subjects, in non-neoplastic patients and in most cancer patients without metastases, whereas this ratio was lower than 2 in almost all patients in a metastatic stage of the disease. Neither melatonin levels nor those of beta-endorphin appeared to be significantly correlated with GH, somatomedin-C, and PRL concentrations. The low beta-endorphin/melatonin ratio observed in metastatic patients suggests the presence of an unbalanced relation between the pineal and the opioid system in those subjects. Therefore, an anomalous relationship between pineal function and opioid activity might play a role in the clinical course of neoplastic disease.
Buserelin represents one of the main LHRH analogues. It appears to be effective in untreated metastatic breast cancer, whereas its activity in pretreated advanced patients remains to be established. To evaluate endocrine and clinical effects of buserelin in pretreated advanced mammary carcinoma, 14 postmenopausal women with metastatic breast cancer, which had been previously treated with hormones and/or chemotherapy, entered the study. Buserelin was subcutaneously injected at a daily dose of 1.5 mg for 7 days, then intranasally at a daily dose of 1.2 mg until progression. Before and after the 7 days of subcutaneous administration of the LHRH analogue, FSH, LH, estradiol, testosterone basal serum levels, and PRL response to TRH were examined. After the 7 days of buserelin subcutaneous injection, a significant decrease in FSH, LH and estradiol values was observed, whereas testosterone was not affected. PRL response to TRH did not change after buserelin subcutaneous treatment in 8 patients, it decreased in one and was completely abolished in the last 5 cases. All patients whose PRL response to TRH did not decrease had a progression within the first month of therapy, whereas only 1 of 6 patients whose PRL response to TRH was reduced or abolished following buserelin administration showed a progression. Among the other 5 cases, 2 minor responses and 3 stable diseases were achieved. These preliminary results suggest that buserelin has only a limited effectiveness in metastatic breast cancer patients who have been previously treated with hormones and/or chemotherapy, and that its activity in the control of tumor growth is associated with a reduction in PRL secretion.
Clinical studies have demonstrated an altered pineal function in cancer patients. Owing to the documented antineoplastic activity of the pineal gland, these anomalies could have a prognostic significance. This study was carried out to monitor changes in blood levels of melatonin, the most important pineal hormone, in relation to the clinical response to chemotherapy in human neoplasms. The study included 42 cancer patients of both sexes (breast cancer, 10; lung cancer, 13; colon cancer, 11; soft tissue sarcoma, 4; testicular cancer, 1; Hodgkin's disease, 1; peritoneal mesothelioma, 2). Melatonin serum levels were measured by radioimmunoassay before and 28 days after each cycle of chemotherapy. The results showed that, irrespectively of the type of tumor and chemotherapeutic regimen, 12/16 patients (75%) whose melatonin markedly enhanced after chemotherapy had an objective regression. In contrast, 2/26 patients only (8%) whose melatonin did not enhance after chemotherapy had a clinical response. The percentage of objective responses was statistically significantly higher in patients with a chemotherapy-induced melatonin increase than in those with no melatonin increase (p less than 0.001). This study seems to demonstrate that melatonin determination can be used as a predictor of the objective response to chemotherapy in cancer patients. Moreover, it suggests that the antineoplastic effect of cytotoxic drugs may require participation of the pineal gland.
Endogenous opioid peptides have been seen to play a role in regulating immunity and tumor growth. This study was carried out to investigate opioid activity in human cancer. We evaluated by radioimmunoassay beta-endorphin plasma levels on blood samples collected at 9.00 a.m. from 121 cancer patients and 42 healthy subjects. In 22 cancer patients and in 12 controls, beta-endorphin circadian rhythm was also investigated. Finally, in 14 cancer patients and in 10 controls GH, PRL, FSH, LH and cortisol serum levels were measured after the administration of a metenkephalin analogue, FK 33-824 (0.3 mg i.v.). No significant differences were seen in beta-endorphin mean levels between cancer patients and normal subjects. Moreover, no differences were found between patients with or without metastases, nor between those with or without chronic pain. beta-Endorphin circadian rhythm appeared to be altered in 16/22 cancer patients, and anomalous hormonal responses to FK 33-824 were seen in 13/14 patients. This study shows an altered opioid activity in human neoplasms, whose clinical significance remains to be determined.
It has been demonstrated that melatonin and other pineal hormones play a role in the neuroendocrine control of immunity. Anomalies of both pineal and immune functions have been reported in cancer. Pineal and lymphocyte functions, however, have never been simultaneously evaluated in oncologic patients. This preliminary study was carried out in order to analyze the melatonin-lymphocyte relationship in human neoplasms. In a first investigation, we evaluated melatonin serum levels and lymphocyte subpopulations on venous blood samples collected during the morning from 46 healthy controls and from 27 cancer patients, 13 of whom had metastases, while the other 14 were without metastases. Moreover, melatonin levels were high in 10 oncological patients and within the normal range in the other 17 cases. B lymphocyte (B), total T lymphocyte (T3), T helper/inducer (T4) and T suppressor/cytotoxic (T8) mean percentages and T4/T8 mean ratios did not significantly differ, either between patients with high and normal melatonin levels, or between metastatic and nonmetastatic cancer patients. In a second study, we evaluated the effects of a prolonged treatment with melatonin (20 mg/daily intramuscularly at 3:00 p.m. for 2 months) on 8 patients with advanced cancer, in whom conventional antitumor therapies had failed. Mean percentages of B, T3, T4, T8 lymphocytes and T4/T8 mean ratios were not significantly different before or after melatonin treatment. In only one patient did the T4/T8 ratio decrease after therapy; in this case only, a stabilization of the disease was obtained, while in all 7 other patients the neoplastic disease progressed also during melatonin treatment, even if an evident improvement of the performance status was seen as it was in most cases. These results seem to exclude that melatonin may influence lymphocyte functions in cancer. Longitudinal studies and further data, however, will be needed to clarify this question.
It is known that the pineal gland has some antitumor activity. Melatonin, its most important hormone, has been shown to inhibit tumor growth in vivo and in vitro. Moreover, some investigations have demonstrated an altered melatonin secretion in cancer patients. Despite these interesting data, clinical trials have never been carried out to evaluate the effects of melatonin on human neoplasms. The aim of this study was to draw some preliminary conclusions on melatonin therapy in advanced human neoplasms. Nineteen patients suffering from advanced solid tumors, which did not respond to standard therapies, entered the study. Performance status (PS) was 20 or less in 9 cases, and more than 20 in the other 10. Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m., followed by a maintenance period with lower doses in patients who had a remission, a stabilization of disease or an improvement in PS. Among patients with a PS higher than 20, a partial response was achieved in one case with cancer of the pancreas; moreover, 5 of 10 had stable disease, but the other 4 cases had a progression; an evident improvement of PS was obtained in 6 of the 10 cases. In contrast, among patients with a very poor PS, 7 of 9 died within the first 2 months of therapy. This preliminary study would suggest that melatonin may be of some value in treating cancer patients in whom standard antitumor therapies have failed, particularly in improving their PS and quality of life.
A squamous cell carcinoma of the anal canal appeared 10 years and 6 months after ionizing radiation therapy (58 Gy) for a previous squamous cell carcinoma in the same region. The patient was treated with chemotherapy alone, which produced a complete remission for 17+ months without relevant acute toxicity.
Both prolactin (PRL) and melatonin (MLT) (the most important pineal hormone) have been shown to play a role in regulating breast cancer growth. The present study was carried out to investigate the relationship between PRL and MLT secretions in human breast cancer. Twenty-four women with breast cancer, at clinical stage T1-2 N0-2 M0, were evaluated before and after radical mastectomy. As controls, 14 women who underwent surgery for reasons other than neoplastic disease were included in the study. PRL and MLT serum levels were measured by RIA before and 15 days after surgery. There were no significant differences in mean PRL serum levels between patients and controls; mean MLT serum values were significantly higher in patients than in controls. In no control subject was PRL affected by surgery. In contrast, 13/24 breast cancer women showed high PRL levels after mastectomy; the PRL rise induced by surgery was significantly higher in patients without axillary node involvement. MLT was not affected by mastectomy in 13 patients, whereas it was enhanced in 5 women and decreased in the last 6 cases. No significant correlation was seen between PRL and MLT changes induced by mastectomy. The present study shows that radical mastectomy influences PRL and MLT secretions, however, its clinical significance remains to be established.
It is known that prolonged therapy with cytotoxic drugs may affect the endocrine system. The present study was carried out to establish whether administration of chemotherapeutic drugs acutely influences hypophyseal and pineal activities. Nineteen patients affected by solid tumors were included in the study, 5 of whom were treated with CMF, 4 with FEC, 4 with CEV, and 6 with CDDP. Cytotoxic drugs were intravenously administered. Venous blood samples were collected at zero time and at 30, 60, 120 and 180 min after drug administration. On a separate occasion, venous blood samples were drawn during a saline infusion only. In each sample FSH, LH, GH, PRL, TSH, cortisol, melatonin and beta-endorphin were determined by the RIA method. The only significant changes observed in this study were a rise in PRL and a decrease in beta-endorphin after CDDP administration. Melatonin was enhanced after CDDP and CMF, and cortisol decreased after CMF and FEC, but their variations were not statistically significant with respect to those seen during saline infusion.
The role played by PRL in human breast cancer is still obscure. Several observations, however, demonstrated that antitumor therapies for breast cancer are associated with changes in PRL secretion, clinical significance of which remains to be determined. The present investigation was carried out to further clarify the effects of mastectomy on PRL levels in breast cancer women. The study included 34 patients at clinical stage T1-2N0-2M0 treated with radical mastectomy. In each patient, venous blood samples were drawn before, and 15 days, 1 month, 45 days, 2 months and 3 months after surgery to determine PRL serum levels. As controls, 14 women surgically treated for reasons other than neoplastic disease were included in the study. Mastectomy was followed by hyperprolactinemia in 18 of the 34 cases (52.9%). PRL remained elevated for at least 1 month, and it became normal within 2 months. On the contrary, no PRL increase was seen in controls. Among breast cancer women, PRL increase was irrespective of the type of surgery, the histology of the tumor and the menopausal status. In contrast, PRL increase was significantly higher in patients without node involvement and with negative hormonal receptors, with respect to that observed in cases with node involvement and positive receptors, respectively. The mechanisms by which mastectomy induces enhanced PRL secretion are still obscure. They might depend, however, on changes in feed-back systems operating in the regulation of PRL secretion, due to the removal of a target organ for PRL itself. Longitudinal studies, by evaluating the percentage of relapse either in patients with surgery-induced hyperprolactinemia or in those with normal hormonal values, will be needed to clarify the prognostic significance of the enhanced PRL secretion induced by mastectomy.
Endogenous opioid peptides have been shown to be involved in the regulation of tumour growth. At present, however, no data are available about the secretion of opioid peptides in cancer patients. To draw some preliminary conclusions on opioid brain function in human neoplasms, we evaluated hypophyseal hormone responses to the administration of a met-enkephalin analogue, FK 33-824. The study included 14 patients affected by early or advanced neoplastic disease, 12 healthy subjects and 7 patients with a chronic medical illness other than cancer. FK 33-824 was given intravenously at a dose of 0.3 mg. Venous blood samples were collected at zero time, and 30, 60 and 120 min after drug administration. In each sample, PRL, GH, LH, cortisol and beta-endorphin levels were measured by RIA. In all normal subjects and in patients with non-neoplastic chronic illness, FK 33-824 induced a rise in PRL and GH levels, and a decrease in LH, cortisol and beta-endorphin. A normal endocrine response to FK 33-824 was seen in our cancer patient only, while in the other cases with tumour no hormonal changes or a paradoxical response were seen after FK 33-824. Based on the fact that an abnormal endocrine response to FK 33-824 has been described in hypothalamic-pituitary disorders, in which anomalous brain opioid activity has been demonstrated, these results suggest the existence of an altered function of the opioid system in cancer patients, the clinical importance of which remains to be determined.
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Nineteen patients with locally advanced head and neck cancer were treated from November 1983 to January 1986 with standard loco-regional Radiotherapy: 2 Gy for 5 days/week up to a total dose of 70 Gy and simultaneous Cisplatinum 20 mg/m2 weekly. All patients achieved a response: 10 (52%) obtained a complete remission (CR) and 9 (48%) a partial remission (PR). Four of 9 patients in PR after chemoradiotherapy were disease-free after radical resection of the residual masses, while another patient was completely cured after second-line chemotherapy. The overall CR was then 79% (15/19). The results were analyzed according to the nodal status and showed that: 92% (11/12) of patients with initial nodal involvement (N1-2) achieved a CR and 75% of them were disease-free after a median follow-up of 23+ months, while only 57% (4/7) of patients with advanced nodal involvement (N3) obtained a CR (p greater than 0.05; NS) and 28% (2/7) of them were alive without evidence of disease (p less than 0.05) after 4+ and 30+ months. Toxicity was moderate: nausea and vomiting (grade 2-3) occurred in about 50% of patients, mucosal toxicity (grade 1-2) in 58%. Myelosuppression was negligible. No patient developed renal failure. Weekly cisplatinum administration during radiotherapy deserves further study especially in the management of patients with advanced primary tumor and minimal lymph node involvement.
While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demonstrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation.