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Biomedical subjects

F Paolorossi

Publications and source records attributed to F Paolorossi.

At least 37 records · Page 2Linked to original sources
PubMed1990

Postoperative hyperprolactinaemia and early recurrence rate in breast cancer.

Serum levels of prolactin before and after surgery were measured in 90 women with breast cancer until the 5th postoperative month. Surgery-induced hyperprolactinaemia occurred in 51 patients, without significant correlation to any other clinical variable. After a median follow-up of 39 months, irrespective of each other variable (i.e. nodal involvement, oestrogen receptor status, adjuvant therapies), patients with postoperative hyperprolactinaemia had a significantly lower recurrence rate than those in whom surgery was not followed by an abnormal increase in prolactin secretion (3/51 vs. 13/39, P less than 0.001). These results suggest that, despite the stimulatory role of prolactin on mammary tumours, the lack of postoperative hyperprolactinaemia is an unfavourable prognostic factor because of its association with a higher relapse rate.

Adult↗
PubMed1989

Ki-67 labeling index in breast cancer.

Measurements of cell cycle kinetics have been found to correlate with the clinical course of patients with breast cancer. However, the thymidine labeling index and more rapid methods like flow cytometry remain complicated and costly. We assessed cell proliferation of 67 breast carcinomas by an immunoperoxidase procedure using a monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The percentage of Ki-67 positive cells ranged from 2% to 70%. Tumors with high mitotic rate, high nuclear grade, high histologic grade, and negative estrogen receptors had statistically higher Ki-67 labeling rates. We found no significant differences between the Ki-67 labeling rate and other clinical (age at diagnosis, menopausal status) or pathologic (necrosis, fibrosis, vascular invasion, lymphatic invasion, cellular reaction, tumor size, lymph node metastases) features assessed. These results parallel previously reported data, and confirm that this immunohistochemical staining of breast carcinoma by Ki-67 monoclonal antibody can be considered a rapid and convenient method for assessing cell cycle kinetics. However, further studies, evaluating the correlation between Ki-67 labeling rate and prognosis are needed to better define the real usefulness of this analysis in clinical practice.

Antibodies, Monoclonal↗
PubMed1989

A study of thyroid function in cancer cachexia.

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.

Adult↗
PubMed1988

Increased level of soluble interleukin-2 receptor in advanced solid tumors: a preliminary study.

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.

Adult↗
PubMed1988

A study on the relationship between the pineal gland and the opioid system in patients with cancer. Preliminary considerations.

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.

Adult↗
PubMed1988

Melatonin increase as predictor for tumor objective response to chemotherapy in advanced cancer patients.

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Alteration of opioid peptide circadian rhythm in cancer patients.

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.

Adult↗
PubMed1988

Relation between lymphocyte subpopulations and pineal function in patients with early or metastatic cancer.

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.

Adult↗
PubMed1987

Clinical study of melatonin in untreatable advanced cancer patients.

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.

Adult↗
PubMed1987

Correlation between changes in prolactin and melatonin serum levels after radical mastectomy.

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.

Adult↗
PubMed1987

Acute effects of various chemotherapeutic combinations on hypophyseal and pineal hormone secretions in cancer patients.

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.

Adult↗
PubMed1987

Effects of radical mastectomy on prolactin blood levels in patients with breast cancer.

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.

Adult↗
PubMed1987

Evidence for altered opioid activity in patients with cancer.

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.

Adult↗
PubMed1987

[Concomitant therapy with cisplatin and radiotherapy in locally advanced tumors of the cervico-facial area].

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.

Adult↗
PubMed1986

Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer.

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.

Adult↗
PubMedDate not supplied

Prognostic factors of the clinical response to subcutaneous immunotherapy with interleukin-2 alone in patients with metastatic renal cell carcinoma.

The intravenous immunotherapy with interleukin 2 (IL-2) represents one of the most active therapies of metastatic renal cell carcinoma (RCC). Recently, it has been demonstrated that IL-2 given subcutaneously in association with interferon alpha (IFN) may determine a response rate in RCC comparable to that obtained with an intravenous route of administration, but with a lower toxicity. Moreover, our previous data have suggested that IFN is not essential for IL-2 efficacy. On the basis of these data, we have designed a protocol of immunotherapy with IL-2 alone given subcutaneously in the treatment of metastatic RCC. The study included 48 consecutive evaluable patients. IL-2 was given at a daily dose of 6 million IU for 5 days/week for 6 consecutive weeks, corresponding to one IL-2 cycle. The overall response rate was 14/48 (29%; CR:1; PR:13). Response rate was significantly higher in nephrectomized than in nonnephrectomized patients, and in patients with a good compared to those with a low performance status. Patients with an interval between the diagnosis of primary renal tumor and of its metastases longer than 1 year did better than those with a lower interval, as did patients with a single metastasis compared to those with multiple metastases, while no significant difference was seen in relation to sex, age and previous IFN therapy. As far as dominant metastasis sites are concerned, patients with liver metastases showed a response rate significantly lower than that seen in patients with metastases in sites other than liver. Toxicity was low in all patients. This study shows that the subcutaneous immunotherapy with IL-2 alone is a well tolerated and effective therapy of metastatic RCC. The evidence of a low PS, disseminated tumor and liver metastases represents the most important negative prognostic factor for the response to therapy.

Adult↗