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Biomedical subjects

F Rovelli

Publications and source records attributed to F Rovelli.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Changes in circulating VEGF levels in relation to clinical response during chemotherapy for metastatic cancer.

Abnormally high blood levels of vascular endothelial growth factor (VEGF) appear to be associated with a poor prognosis in advanced cancer, probably as a consequence of its angiogenic and immunosuppressive effects. The prognostic significance of changes in VEGF secretion during cancer chemotherapy is still unknown. This study aimed to investigate the relation between VEGF variations and therapeutic results during chemotherapy in advanced malignancies. The study included 90 metastatic cancer patients, 59 with non-small cell lung cancer and 31 with colorectal carcinoma. Chemotherapy consisted of cisplatin plus etoposide for NSCLC and camptothecin for colorectal cancer. Abnormally high (> 2 SD with respect to values in healthy controls) pretreatment VEGF levels were found in 38/90 (42%) patients. The percentage of non-progressive disease in response to chemotherapy was significantly higher in patients with normal levels of VEGF prior to therapy than in those with elevated pretreatment values of VEGF (10/32 vs 4/27; p < 0.05). Moreover, the percentage of VEGF level normalization during chemotherapy was significantly higher in patients with objective tumor response or stable disease than in progressing patients (10/18 vs 0/20; p < 0.001). Finally, among patients with tumor response or disease stabilization, the one-year survival rate was significantly higher in patients with chemotherapy-induced normalization of VEGF than in those with persistently high VEGF blood levels (9/10 vs 3/8; p < 0.05). These results suggest that changes in VEGF levels during chemotherapy may represent a useful biomarker to predict the effect of chemotherapy in terms of tumor response and survival in patients with metastatic solid neoplasms.

Adult↗
PubMedDate not supplied

Neuroimmunomodulation in cancer patients: correlations between melatonin and beta-endorphin blood levels and T helper/suppressor ratio.

The pineal gland and opioid peptides play roles in the neuroendocrine control of immunity. Both neuroendocrine and immune dysfunctions have been observed in cancer but the importance of the altered secretion of neurohormones in the immunoincompetence of cancer patients has never been investigated. This study concomitantly evaluated neuroendocrine and immune functions in 40 patients with early or advanced neoplastic disease. In each patient, melatonin and beta-endorphin blood levels and lymphocyte subtypes were determined on venous blood samples collected during the morning. Metastatic patients had lower melatonin levels and a lower T4/T8 ratio than patients without metastases but no significant correlation was found between melatonin and the T4/T8 ratio. beta-endorphin levels appeared to be normal in all patients. These results suggest that melatonin and beta-endorphin secretion have no role in determining immune dysfunctions in cancer.

Adult↗
PubMedDate not supplied

Serum levels of melatonin in cancer patients and their relation to body sizes.

Melatonin secretion is often enhanced in patients with cancer. In the light of a reported correlation between melatonin levels and body size, we investigated blood levels of this pineal hormone in a group of 72 patients affected by cancer, 30 of whom had body weight within the normal range, 30 were obese and the last 12 cases had body weight below the normal range, in order to establish whether in fact melatonin blood concentrations were related to body size. Melatonin levels were high in 19/72 patients (26%). The mean levels of the pineal hormone were similar in patients with normal, low and high body weight. Finally, there was no significant correlation between melatonin values and body weight, height or surface. Melatonin secretion thus does not appear to be influenced by body size in cancer patients.

Body Constitution↗
PubMedDate not supplied

Interleukin-2 receptor positive cells and circulating soluble interleukin-2 receptors in patients with solid tumors are not correlated.

Activated lymphocytes can release a soluble form of IL-2 receptor (sIL-2R), which retains the capacity to bind IL-2. Abnormally high values of sIL-2R have been observed in patients with advanced solid tumors. In an attempt to further understand the biological significance of sIL-2R in solid tumors, this study investigated the relation between sIL-2R and Tac-positive cells. sIL-2R serum levels and Tac-positive cells were determined in 18 patients with solid tumors metastatic, 108 non-metastatic. Tumor types were: breast 7; lung 6; colon 2; stomach 1; testis 1; larynx 1. No correlation was found between circulating sIL-2R values and Tac-positive cells, and there was no difference between Tac-positive cell mean number in patients with high and normal sIL-2R levels. These preliminary results suggest that different mechanisms are responsible for sIL-2R release in the blood and IL-2 receptor expression on the immune cell surface.

Adult↗
PubMedDate not supplied

Lack of changes in soluble interleukin-2 receptor serum levels during chemotherapy-induced lymphocyte damage.

The biological significance of soluble IL-2 receptors (sIL-2R) is still unknown; in particular, it is not yet clear whether their increase in the blood may reflect activation of immune cells, or whether it is related to an immune dysfunction. To investigate this problem, we evaluated serum levels of sIL-2R before and after administration of a highly lymphocytolitic chemotherapy (FEC: fluorouracil, epirubicin, cyclophosphamide) in a group of 6 patients with advanced breast cancer. SIL-2R were analyzed in relation to lymphocyte number. Absolute mean number of lymphocytes was significantly lower after than before chemotherapy. On the contrary, no significant difference was seen in sIL-2R mean levels, and no significant correlation was observed between changes in sIL-2R and in lymphocyte number following chemotherapy. These results would exclude that sIL-2R may simply be due to a passive release following lymphocytic damage.

Adult↗
PubMedDate not supplied

Endocrine effects of human recombinant interleukin-3 in cancer patients.

It is known that several cytokines can exert hormonal effects. At present, no data are available about the possible influence of IL-3 on the endocrine system. In order to investigate the endocrine effects of IL-3 in humans, we have evaluated serum levels of cortisol, beta-endorphin, GH, PRL, FSH, LH, TSH and melatonin in response to intravenous injection of IL-3 at a dose of 1 mcg/kg b.w. at 6.00 p.m. The study was performed in 5 non-small cell lung cancer patients. GH increased significantly in response to IL-3. PRL showed a progressive decrease after IL-3 injection, but its variations were not statistically significant. All other hormones, including cortisol, were not affected by IL-3. This preliminary study shows that IL-3 may exert endocrine effects in humans, which would seem at variance with previously reported results on most other cytokines.

Biomarkers, Tumor↗
PubMedDate not supplied

Increased blood concentrations of interleukin-12 are associated with a longer survival in untreatable metastatic solid tumor patients: preliminary observations.

IL-2 and IL-12 are the main antitumor cytokines in humans. Endogenous IL-2 production is generally low in metastatic cancer patients. In contrast, preliminary data suggest a possible increased secretion of IL-12 in a subgroup of metastatic cancer patients, of which the prognostic significance is still to be established. This preliminary study was performed to investigate the survival time in relation to IL-12 blood levels in patients with untreatable metastatic solid tumors. The study included 40 patients (lung cancer: 16; gastrointestinal tumors: 24). Abnormally elevated serum levels of IL-12 were observed in 15/40 (37%) patients, without any apparent relation with tumor histotype. The 1-year survival rate was significantly higher in patients with elevated IL-12 baseline values than in those with normal concentrations (8/15 vs 3/25, p < 0.01). The results of this preliminary study, which need to be confirmed in a greater number of patients by monitoring the clinical course of the neoplastic disease, seem to suggest that abnormally high baseline serum levels of the antitumor cytokine IL-12 may have a favorable prognostic significance, as they appear to be associated with a longer survival time.

Biomarkers, Tumor↗
PubMedDate not supplied

Vascular endothelial growth factor (VEGF) serum levels during cancer immunotherapy with IL-2: preliminary considerations.

Neoangiogenesis has been proven to play a fundamental role in promoting cancer spread, and vascular endothelial growth factor (VEGF) is known to represent one of the most important angiogenic factors. The present study was planned to investigate changes in VEGF secretion in cancer patients undergoing immunotherapy with IL-2, with the aim of establishing whether VEGF variations play a role in mediating the IL-2-induced control of neoplastic diseases. The study involved 14 metastatic renal cell cancer patients treated with IL-2 immunotherapy (6 million IU/day subcutaneously for 6 days/week for 4 weeks). The clinical response consisted of partial response (PR) in 3, stable disease (SD) in 6 and progressive disease (PD) in the remaining 5 patients. VEGF serum levels were measured by an enzyme immunoassay designed to determine both bound and unbound VEGF. No significant changes in VEGF mean levels occurred during IL-2 therapy. Moreover, neither in patients with PR or SD nor in those with PD did the mean serum levels of VEGF change significantly in response to IL-2. This preliminary study seems to exclude that changes in the angiogenic factor VEGF may play a role in mediating the therapeutic efficacy of IL-2 cancer immunotherapy. However, since the method of measurement used in our study was designed to detect the total amount of VEGF, it cannot be excluded that changes in the free fraction of the molecule may occur during IL-2 cancer immunotherapy.

Adult↗
PubMedDate not supplied

Dehydroepiandrosterone sulfate (DHEAS) secretion in early and advanced solid neoplasms: selective deficiency in metastatic disease.

Several endogenous hormones have been proven to stimulate cancer growth, whereas at present very few hormones are known to display oncostatic activity. The most widely investigated antitumor hormone is the pineal indole melatonin (MLT), and cancer progression has been shown to be associated with a decline in MLT secretion. Recently, another hormone, the adrenal steroid dehydroepiandrosterone-sulfate (DHEAS), has appeared to exert antitumor effects similar to those previously described for MLT. In addition, experimental studies suggest a diminished DHEAS production with neoplastic progression. This preliminary study was performed to evaluate the daily secretion of DHEAS in a group of early and advanced cancer patients. The study included 70 patients with solid tumors (gastrointestinal tract tumors: 28; breast cancer: 24; non-small cell lung cancer: 18), 28 without and 42 with distant metastases. The serum levels of DHEAS were measured by RIA in blood samples collected in the morning. The control group consisted of 100 age- and sex-matched healthy subjects. No significant difference in mean serum levels of DHEAS was observed between controls and non-metastatic patients. In contrast, metastatic patients, irrespectively of tumor histotype, showed significantly lower mean levels of DHEAS with respect to either controls or non-metastatic patients. Moreover, metastatic patients with visceral locations showed significantly lower values of DHEAS than those with bone or soft-tissue metastases. This preliminary study would suggest there to be a deficiency in the daily DHEA secretion in patients with disseminated cancer. Further studies evaluating circadian DHEAS secretion in relation in that of the pineal hormone MLT will be required to better define the biological significance of the advanced cancer-related decline in endogenous DHEAS production.

Adult↗
PubMedDate not supplied

Blood concentrations of interleukin-15 in cancer patients and their variations during interleukin-2 immunotherapy: preliminary considerations.

In addition to the better known cytokines IL-2 and IL-12, IL-15, which is mainly produced by macrophages, is a new antitumor cytokine with a mechanism of action similar to that of IL-2. At present, however, there are no data about IL-15 secretion in cancer patients. This study was carried out to evaluate IL-15 blood concentrations in patients with early or advanced cancer and their possible variations in response to IL-2 cancer immunotherapy. The study included 40 patients with solid tumors, 24 of whom had metastatic disease. In addition, IL-15 secretion was evaluated during subcutaneous low-dose IL-2 therapy (6 million IU/day for 6 days/week for 4 weeks) in 14 metastatic renal cell cancer patients by collecting blood samples at weekly intervals. The control group consisted of 40 age-matched healthy subjects. Serum levels of IL-15 were measured by an enzyme immunoassay. No significant difference in mean serum levels of IL-15 was observed between cancer patients and controls. Moreover, the mean serum levels of IL-15 found in metastatic cancer patients were not significantly different from those found in patients with limited disease. Finally, no significant changes in mean levels of IL-15 occurred during IL-2 cancer immunotherapy. This preliminary study would suggest that IL-15 secretion is substantially within the normal range in cancer patients, both in early and advanced disease, and no variation seems to occur in response to IL-2 administration.

Adult↗
PubMedDate not supplied

Serum concentrations of interleukin-18 in early and advanced cancer patients: enhanced secretion in metastatic disease.

The recent availability of adequate methods for cytokine measurement could contribute to better understanding the immunophysiopathology of neoplastic disease. Unfortunately, very little data is available about cytokine secretion in cancer patients. At present, IL-2, IL-12 and IL-15 represent the major antitumor cytokines in humans. Preliminary clinical studies have shown a progressive decline in IL-2 levels with cancer progression, whereas IL-12 seems to increase in the advanced disease. IL-18 is the latest cytokine discovered by potential anticancer and anti-angiogenetic activity, and it has effects similar to those of IL-12. This preliminary study was carried out to analyze IL-18 secretion in early or advanced cancer patients. The study included 40 cancer patients (lung cancer, 21; gastrointestinal tumors, 19), 17 of whom had metastatic disease, and 50 healthy controls. Serum levels of IL-18 were measured by ELISA. No significant difference in IL-18 mean levels was seen between controls and non-metastatic patients. In contrast, metastatic patients showed significantly higher IL-18 mean values with respect to both healthy controls and non-metastatic patients. This preliminary study seems to suggest that metastatic disease may be characterized by enhanced IL-18 secretion the biological and prognostic significance to be established by successive clinical investigation.

Adult↗
PubMedDate not supplied

A phase II study of subcutaneous low-dose interleukin-2 plus erythropoietin in metastatic renal cell carcinoma progressing on interleukin-2 alone.

OBJECTIVE: The activation of angiogenesis has been proven to suppress the anti-cancer immunity. The evidence of abnormally high pretreatment blood levels of vascular endothelial growth factor (VEGF), which is the main angiogenic factor, has appeared to predict resistance to IL-2 immunotherapy of metastatic renal cell carcinoma (RCC). Therefore, the control of VEGF secretion could influence the efficacy of IL-2. Recent data suggest that erythropoietin (EPO) may modulate VEGF secretion and IL-2 biological activity. On this basis, a study was planned with subcutaneous (s.c.) low-dose IL-2 plus EPO in metastatic RCC, which had progressed on IL-2 alone (6 million IU/day for 6 days/week for 4 weeks). METHODS: Patients received IL-2 at the same dose as the previous cycle, plus EPO (10,000 3 times/week until the end of IL-2 therapy. Serum levels of VEGF were measured by enzyme immunoassay on venous blood samples collected at weekly intervals. The study included 12 evaluable metastatic RCC patients. RESULTS: The treatment was well-tolerated and most patients referred a relief of IL-2-induced asthenia. A partial response (PR) and 4 stable diseases (SD) were achieved on IL-2 plus EPO, whereas the other 7 patients had a progressive disease (PD). Hemoglobin mean levels were significantly higher on IL-2 plus EPO than during the previous therapy with IL-2 alone in the same patients. In the same way, mean lymphocyte increase was higher on IL-2 plus EPO than on IL-2 alone, even though this difference was not significant. Finally, VEGF increase was significantly lower on IL-2 plus EPO than during IL-2 alone. CONCLUSION: This preliminary study shows that the concomitant administration of EPO may allow a control of the neoplastic growth in advanced cancer patients progressing on IL-2 alone, reduce the subjective toxicity, prevent hemoglobin decrease and counteract IL-2-related VEGF increase.

Aged↗