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Biomedical subjects

S Barni

Publications and source records attributed to S Barni.

At least 271 records · Page 15Linked to original sources
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

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

Blood concentrations of tumor necrosis factor-alpha in malignant lymphomas and their decrease as a predictor of disease control in response to low-dose subcutaneous immunotherapy with interleukin-2.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-alpha secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-alpha secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-alpha serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-alpha levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-alpha concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-alpha levels in seven evaluable lymphoma patients (NHL: 6; HD: 1)--who did not respond to conventional therapies--during subcutaneous low-dose IL-2 (3 MIU/day, 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-alpha concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-alpha secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-alpha levels in malignant lymphomas.

Adolescent↗
PubMedDate not supplied

Interleukin-2 induces the growth of human glioblastoma cells in culture.

The ability of the T cell growth factor interleukin-2 (IL-2) to support the proliferation of human glioblastoma cells in short-term cultures was evaluated. A morphological, cytochemical and immunocytochemical analysis was carried out at different times of treatment. In the presence of IL-2 growth of tumor cells was observed. On the contrary, in the absence of IL-2 only few colonies derived from tumor fragments were obtained and these were so after a long time. The immunocytochemical study revealed that IL-2 induces the expression of the IL-2 receptor on human glioblastoma cells. In the presence of IL-2 proliferation of infiltrating lymphoid cells inside the tumor fragments was also observed. Morphological and cytochemical analysis of these cells revealed positivity for acid phosphatase (AP), dihydrofolate reductase (DHFR), dipeptydilaminopeptidase (DAP IV) and negativity for serine esterase. These data are in agreement with our previous study on activated lymphoid subsets. On the other hand, an absence of infiltrating lymphocytes was observed in cultures without IL-2. These results indicate that local treatment of human glioblastoma using IL-2 might produce tumor cell proliferation.

Brain Neoplasms↗
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Circulating dendritic cells in early and advanced cancer patients: diminished percent in the metastatic disease.

Despite the well demonstrated fundamental role of dendritic cells (DC) in generating antitumor immunity in experimental conditions, to date there are only few preliminary studies which investigate the percent of DC in the peripheral blood of cancer patients. Several cell surface markers have now been described which are specific to cultured DC, however their expression in vivo is still controversial. Recently, however, two DC subsets, consisting of immature and mature DC, have been shown to be present in peripheral blood, which can be recognized as CD123+ and CD11c+ cells, respectively. On this basis, we decided to investigate the presence of both mature and immature DC in the peripheral blood of early or advanced cancer patients. The study included 40 solid tumor patients, 18 of whom had a locally limited disease, while the other 22 showed distant organ metastases. CD123+ and CD11c+ cells were detected by FACS using monoclonal antibodies, and expressed as the percent of total leukocytes. The control group consisted of 50 healthy subjects. The mean percent of both CD123+ and CD11c+ cells was significantly lower in cancer patients than in controls. Moreover, the mean percent of both DC subsets was significantly lower in metastatic patients than in the non-metastatic ones. This study, demonstrating significantly lower percents of both immature and mature DC in the peripheral blood of cancer patients, particularly in those with distant organ metastases, suggests that DC deficiency may play a role in inducing cancer-related immunosuppression. Therefore, the demonstration of a diminished percent of DC in peripheral blood may represent a new interesting biological marker predicting a poor prognosis in human neoplasms, as with lymphocytopenia, the unfavourable prognostic significance of which has been well demonstrated.

Adult↗
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

Induction of karyological damage by bleomycin in polyploidizating rabbit hepatocytes.

The effects of the antitumor drug bleomycin on polyploidizating hepatocytes of immature rabbits were investigated by combining cytochemical (static microfluorometry) and morphological (fluorescence and electron microscopy) approaches. In addition to a decelerating effect of the drug on the cell kinetics, there were several types of karyological damage (micronuclei, internuclear chromatin bridges, mitotic chromosome bridges), thus demonstrating a clastogenic activity of bleomycin on the DNA, Moreover, anomalous nuclear and cytoplasmic divisions suggest interference of the drug with other cellular structures (mainly the microtubule network) responsible for the cell kinetics.

Animals↗
PubMedDate not supplied

[Antiproliferative activity of cimetidine and a copper-cimetidine complex on rat fibroblasts cultured in vitro].

Cimetidine is an active H2-receptor antagonist which, combined with other drugs, has antitumor effect. It has been recently shown that some drugs complexed with copper increase their inhibitory effect on tumor growth and promote cell differentiation. In the present investigation we analysed the modifications of some cell proliferation parameters (mitotic, labelling and apoptotic indices and DNA synthesis) by microfluorometry and autoradiography in 2-day low and high cell density fibroblast cultures in presence of 20 microM cimetidine or copper-cimetidine complex. In low density cultures, a more intense proliferation activity was found while in the high density ones there was accumulation of 4c and 8c polyploid cells. The highest antiproliferative effect was found in low density cultures in presence of copper cimetidine complex, which caused mitotic anomalies and increased chromocenters. Simultaneous evaluation of nuclear DNA content and 3H-T labelling indicated the extension of G1 and G2 phases, followed by a lower cell proliferation and degeneration.

Animals↗
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↗
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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

Histochemical probes for the detection of hypoxic tumour cells.

Hypoxia is thought to be a major cause of failure in cancer treatment. In this paper, we report methods transposable to clinical practice, for identifying hypoxic tumour cells. They consist of histochemical tests for revealing lactate dehydrogenase activity, endogenous lactate and accumulation of neutral fat. An ascites tumour (Yoshida hepatoma) and a solid tumour (Ehrlich carcinoma) were used as the experimental models. A gel film technique was used for visualizing lactate dehydrogenase and "nothing dehydrogenase" (or endogenous lactate). The fluorescent dyes Nile Red and Acridine Orange were used to demonstrate lipid accumulation and to visualize the tumour morphology, respectively. Tumour cells at the edge of areas of necrosis and at a distance of about 130 microns from a blood vessel were presumed to be hypoxic and showed the following features: 1) a dark blue granular pattern of lactate dehydrogenase (LDH) activity, ascribed to intense activity of the LDH5 and/or LDHk isoenzymes bound to membranous structures; 2) an intense granular positivity of "Nothing Dehydrogenase" due to high concentrations of endogenous lactate; 3) neutral lipid droplets emitting an intense yellow fluorescence in Nile Red-stained preparations; 4) a yellow cytoplasmic fluorescence in Acridine Orange-stained sections, attributable to a low cellular RNA content. Electron microscopy revealed moderately osmiophilic lipid globules in close association with damaged mitochondria. Better oxygenated cells showed: (a) a reddish-blue diffuse pattern of LDH, ascribed to moderately active soluble LDH isoenzymes containing H subunits; (b) almost no "Nothing Dehydrogenase" positivity; (c) no cytoplasmic lipid droplets; and (d) an intense orange-red fluorescence in the cytoplasm of Acridine Orange-stained specimens, due to high concentrations of cellular RNA. Nile Red fluorescence showed that the lipids of the solid tumour membranes were more hydrophobic than in the normal surrounding tissue. This suggests that there are abnormal domains of neutral lipids in the tumour cell membranes. In solid tumours, cells with the characteristics attributable to hypoxia were usually observed on the edge of necrosis of cuff-like formations. In very advanced growth stages, however, they were also seen surrounding (and occasionally clogging) blood vessels, or in tentacular formations coming from a necrosis border and polarized towards the vessels. Lipid-loaded cells were also seen in blood vessels distant from the tumour. These observations point towards a chemotactic process of hypoxic cells towards better environments.

Animals↗
PubMedDate not supplied

Possible patterns of nuclear rotation in binucleate hepatocytes in vivo: static examination with fluorescence and electron microscopy.

To demonstrate nuclear rotation in the intact organism, we induced the formation in vivo of internuclear chromatin bridges in binucleate hepatocytes and examined their morphological arrangement in static conditions. Fixed isolated hepatocytes were observed by fluorescence microscopy and solid liver tissue by electron microscopy. The morphological patterns provided information about different modalities of nuclear rotation, related to equatorial (stationary nuclei), peripheral (nuclei rotating in opposite direction) or oblique (nuclei rotating in the same direction) dispositions of chromatin bridges. Moreover, data indicate that the entire nucleus can rotate. The independence of the bridge arrangements from the cell cycle phases (G1, S, G2) suggests that the nuclear rotation is probably not due to exchange of substances between the active chromatin and the cytoplasm.

Animals↗
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↗
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Effect of mastectomy versus mastectomy plus adjuvant ovariectomy on prolactin response to TRH in breast cancer.

The endocrine effects of ovariectomy need to be further investigated. The present study was carried out to evaluate the influence of the adjuvant ovariectomy on the mastectomy-induced changes in PRL response to TRH in breast cancer. The study included 34 patients with locally limited breast carcinoma, 18 of whom were treated with radical mastectomy, whereas the other 16 underwent mastectomy plus adjuvant ovariectomy. PRL secretion in response to TRH (200 mcg I.V. as bolus) was evaluated one day before and 7 days after surgery. In patients treated with mastectomy only, PRL increase after TRH was significantly higher after surgery than before. On the contrary, no difference was seen in patients treated with mastectomy plus ovariectomy. This study shows that the adjuvant ovariectomy may block the increase in PRL response to TRH induced by mastectomy in breast cancer.

Adult↗