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Biomedical subjects

S Barni

Publications and source records attributed to S Barni.

At least 163 records · Page 9Linked to original sources

Correlation of serum interleukin-2 levels, soluble interleukin-2 receptors and T lymphocyte subsets in cancer patients.

An interleukin-2 (IL-2) in vitro reduced production has been observed in most metastatic cancer patients. At present, however, there are no data on blood IL-2 levels in vivo, because of the too low sensitivity of previous biological and enzyme immunoassay methods. The recent development of a sensitive RIA method allowed us to start a preliminary investigation of IL-2 production in basal conditions in human solid tumors. The study included 42 cancer patients. Breast and lung cancer were the two commonest neoplasms. Serum levels of IL-2 and soluble IL-2 receptors (SIL-2R), and CD4/CD8 ratio were measured in each patient. The control group consisted of 58 healthy subjects. Mean serum levels of IL-2 were significantly lower in metastatic patients (n = 23) than in those without metastases (n = 19). Patients with low CD4/CD8 ratio (n = 16) had significantly lower mean values of IL-2 than those with normal ratio (n = 26). Finally, mean IL-2 concentrations were significantly lower in patients with elevated levels of SIL-2R than in those with normal values. These results would suggest that metastatic dissemination is associated with a decreased IL-2 production in vivo, and that reduced IL-2 production is more frequent in patients with low CD4/CD8 ratio.

Antigens, Differentiation, T-Lymphocyte↗

A study of the pineal hormone melatonin as a second line therapy in metastatic colorectal cancer resistant to fluorouracil plus folates.

Since there is no effective second line chemotherapy in colorectal cancer resistant to fluorouracil, this study was carried out to evaluate the therapeutic activity of the pineal hormone melatonin, which has appeared to have antineoplastic activity in some experimental conditions, in patients with metastatic colorectal carcinoma who did not respond to fluorouracil. The study included 14 patients (8 men, 6 women; mean age 58 years). Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; after that, melatonin therapy was continued at 10 mg/day orally in responder patients, in those with stable disease and/or an evident improvement in PS. One patient had a minor response; 3 other patients had a stable disease, whereas the other 10 cases progressed. An evident improvement in PS was seen in 5/14 (36%) patients. These preliminary results show that melatonin does not have important antitumor activity in metastatic colorectal cancer patients resistant to fluorouracil. However, the pineal hormone could be usefully employed as supportive care to improve the quality of life in these patients for whom no standard treatment is yet available.

Adult↗

A study of pineal-prolactin interaction: prolactin response to an acute melatonin injection in patients with hyperprolactinemia.

Several studies demonstrated that the pineal gland plays a regulatory role in PRL secretion. At present, however, there are few clinical data only about the pineal function in PRL secretion disorders. To further clarify which is the pineal importance in the dysfunctions of PRL release, we have evaluated the effect of an acute injection of the pineal hormone melatonin in 19 patients with hyperprolactinemia, 8 of whom had idiopathic hyperprolactinemia, while the other 11 had a prolactinoma. Melatonin was given im at a dose of 20 mg at 09:00 h, and venous blood samples were collected at -20, 0, 20, 60, 120, 180 min. A normalization of PRL levels was achieved after melatonin injection in 3/8 patients with idiopathic hyperprolactinemia, while no effect was seen in patients with prolactinoma. Further studies, by evaluating the effect of a chronic treatment, will be required to define which is the action of melatonin on PRL release in PRL secretion disorders, and to evaluate its possible therapeutic role.

Adult↗

The biological significance of soluble interleukin-2 receptors in solid tumors.

In an attempt to further understand the biological significance of soluble IL-2 receptors (sIL-2R) in solid tumors, we have evaluated 160 cancer patients (breast: 40; lung: 66; colon: 18; stomach: 22; uterine cervix: 14) and 58 healthy subjects, as controls. Serum mean levels of sIL-2R, measured with an enzyme immunoassay, were significantly higher in cancer patients than in controls. Metastatic cancer patients showed significantly higher values than the non-metastatic ones; this difference was significant in all tumor histotypes, except small cell lung carcinoma. Moreover, in 15 patients in whom sIL-2R were evaluated either before or after radical surgery, a significant surgery-induced increase in sIL-R mean values was seen. Finally, the chemotherapy-induced rise in sIL-2R appeared to be associated with a lack of clinical response. These results seem to suggest that sIL-2R may be a marker of host biological response in patients with solid tumors, the significance of which needs further investigation.

Adult↗

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↗

Pineal gland and tumor cell kinetics: serum levels of melatonin in relation to Ki-67 labeling rate in breast cancer.

Recent observations showed that host may regulate either endocrinologically or immunologically tumor growth and differentiation, perhaps by modulating oncogene expression. Within the endocrine system, the pineal hormone, melatonin, seems to play an important antineoplastic role. To investigate its secretion in relation to tumor growth, we have evaluated the daily serum levels of melatonin in a group of 25 untreated breast cancer patients with a locally limited disease. Tumor cell proliferation was established by measuring Ki-67 labeling rate. As controls, 46 healthy women were considered. Breast cancer patients showed significantly higher mean values of melatonin than controls. Moreover, patients with negative Ki-67 labeling rate had significantly higher levels of the pineal hormone than those with a positive Ki-67 rate. Since tumors with high growth fraction present a worse prognosis, this study would suggest that the relief of an increased melatonin secretion represents a favorable prognostic sign, because of its association with less proliferating breast cancers.

Adult↗

Analysis of T helper and suppressor lymphocyte subsets in relation to the clinical stage of solid neoplasms.

Neoplastic disease affect the immunity in cancer patients. The immune alterations in human neoplasms, however, need to be further defined. The present study was carried out to analyze T lymphocyte subsets in patients with solid tumors. The study included 93 patients suffering from early or metastatic solid neoplasms. T helper and T suppressor subsets were measured on venous blood samples by using flow cytometry and monoclonal antibodies. As controls, 58 healthy subjects were included in the study. The T mean helper/suppressor ratio (CD4/CD8) was significantly lower in metastatic cancer patients with respect to that observed either in controls or in patients without metastases. A low CD4/CD8 ratio was seen in 25 of 93 cancer patients (26.9%), 8 of whom had no metastases, while the other 17 showed a metastatic disease. Within the nonmetastatic group, the decline in the CD4/CD8 ratio was due to increases in the T suppressor subset alone in 7. On the contrary, the percentage of cases with decreased T helper subset was significantly higher in metastatic than in the nonmetastatic patients. The results of this study suggest that the decrease in the CD4/CD8 ratio mainly depends on an increase in T suppressor cells in patients without metastases whereas it is due to a decrease in the T helper subset in most patients with metastatic diseases.

Adult↗

[Effect of dimethyladipimidate and dimethylsuberimidate on cell-cell adhesion in rat fibroblasts].

In a study performed to identify the molecular mechanisms which regulate cell to cell adhesion and contact inhibition in neoplastic and syngeneic normal cells of the rat we have observed that the adhesive capacity depends on the reagents used, either EDTA or trypsin, to release the cells from monolayer. Taking profit of this last property and of the possibility of blocking free -NH2 groups on membrane proteins with specific cross-linking reagents "in vitro", we have studied in this work the behaviour of the proteins of the cell coat involved in cell to cell adhesion of rat fibroblasts FG/2. The cross-linking reagents used were dimethyladipimidate (DMA) and dimethylsuberimidate (DMS). The cells were exposed to the reagents at 0 degrees C for 30'. Cell to cell adhesion was measured by determining the percentage of single cells labeled with 3H-leucine, adhering to a confluent monolayer at different incubation times. The inhibitory effect on cell to cell adhesion brought about by cross-linking reagents indicates that a) EDTA-released cells are more sensitive to both imides than those released with trypsin, b) DMA is more effective on trypsin-released cells and c) DMS is more effective on EDTA-released cells. Therefore, we conclude that the inhibition of adhesion by reaction with the two cross-linking reagents is more likely due to a stiffening of the molecules of the cell coat involved in the adhesion, rather than to the modification of -NH2 residues which should specifically participate to adhesive process.

Animals↗

[Radiotherapy plus a combination of cisplatin and 5-fluorouracil for locally advanced head and neck neoplasms. Study of feasibility and preliminary results].

In March 1989 we started a feasibility study of combined radio-chemotherapy in patients with locally-advanced head and neck cancer. The first phase of treatment consisted of conventional radiotherapy (2 Gy/day, 5 days/week for a total dose of 70 Gy to primary tumor and +/- 50 Gy to nodes) and cisplatinum (20 mg/m2, i.v., for 4 days) +5FU (200 mg/m2, i.v., for 4 days) every 4th week, during radiant sessions. The second phase of treatment was started about one month after the end of simultaneous chemotherapy and radiotherapy: patients in complete remission received 1 more cycle of chemotherapy, as consolidation, while patients in partial remission received two more cycles of chemotherapy. Non-responding patients received no more chemotherapy. During the second phase the days of cisplatinum and 5FU were 5. Up to April 1990, 17 patients have been included in the study. They were stage III (64%) and IV (36%). The mean administered dose of radiotherapy was 66 Gy (range: 60-70 Gy) to primary tumor and 60 Gy (range: 40-70 Gy) to nodes. The total number of chemotherapy cycles administered during radiant sessions was 37, the mean number of cycles was 2 (range: 1-3), with 100% dose percentage. The interval between cycles was 3 weeks in 84% of patients. The relationship between number of cycles administered and planned cycle was 37/39 (feasibility: 95%). Acceptability was 100% (no patient refused the treatment). Feasibility of the second phase was 77% and acceptability 90% (1 patient refused the treatment). Toxicity was moderate during the first and the second phases. After the first phase 14/15 evaluable patients (92%) had major response (complete remission: 46%). After the second phase 10/10 evaluable patients had a complete remission. In conclusion, this combined treatment is very easy to administer, and very well accepted. Moreover, it yields a high number of objective responses.

Aged↗

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↗

Evidence for altered hypothalamic-hypophyseal-gonadal axis in untreated patients with testicular germ-cell tumor.

To investigate the function of the hypothalamic-hypophyseal-gonadal axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (GnRH) in 12 untreated patients with testicular cancer (5 seminomas and 7 non-seminomas). GnRH was given i.v. at a dose of 100 micrograms as a bolus, and venous blood samples were collected at 0, 20, 60, and 120 min. As controls, 14 healthy males were studied. Basal levels of testosterone, estradiol and prolactin were also detected in each patient. Hormonal serum concentrations were measured by the radioimmunoassay. Mean basal testosterone, estradiol and prolactin levels were not significantly different from those of controls. Patients had a lower FSH and LH peak after GnRH than controls, without, however, any significant difference. As regards histology, non-seminoma patients lacked an FSH response to GnRH and had statistically lower mean peak levels than controls. Moreover, non-seminoma patients had statistically lower mean peak values of LH after GnRH than controls. These data show that patients with testicular germ cell tumor, and more particularly those with non-seminomas, have an altered function of the hypothalamic-hypophyseal-gonadal axis, which is already present prior to therapy. Further studies, particularly in stage I patients treated only with orchiectomy, should be performed to confirm and better define the physiopathologic significance of the altered hypothalamic-hypophyseal-gonadal axis in testicular cancer and to clarify the alteration of fertility, which is frequently present before treatment.

Adult↗

A radiologic study by CT scan of pineal size in cancer patients: correlation to melatonin blood levels.

Alterations in size of the pineal body and melatonin secretion have been observed in cancer patients. The present study was carried out to evaluate pineal dimensions in a group of cancer patients and their relation to melatonin blood levels. The study included 70 oncologic patients. As controls, 41 patients with acute or chronic disease other than cancer entered the study. Melatonin serum levels were measured by radioimmunoassay on venous blood samples collected at 9:00 a.m. Pineal size was determined by brain CT scan, by considering the product of the two longest perpendicular diameters, multiplied by the thickness of the stratum. The volume of the pineal body was found to be enlarged in 12/70 (17%) cancer patients, and its mean value was significantly higher than that observed in controls. Melatonin levels were also significantly higher in oncologic patients than in controls. However, there was no correlation between melatonin levels and pineal size in cancer patients. Finally, cancer patients did not show a higher degree of pineal calcifications than controls. The clinical significance of pineal enlargement in cancer patients remains to be understood.

Adult↗

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↗

DNA double staining for a fluorescence energy transfer study of chromatin in liver cells.

Methodological aspects related to the application of techniques based on fluorescence energy transfer in the study of chromatin structure, were first examined. Fluorochromes specific for DNA with different interaction mechanisms were employed, both in single and double stainings. The following dye pairs were considered as donor/acceptor couples: Hoechst 33342 or DAPI/Mithramycin A or Chromomycin A3, Hoechst 33342 or DAPI/Propidium Iodide, and Mithramycin A or Chromomycin A3/Propidium Iodide. Spectrofluorometric analysis showed that the spectral distribution of the dye pair Ho/PI is more suitable for the evaluation of energy transfer efficiency. This dye pair was used in the study of the chromatin microstructure in rat hepatocytes isolated from livers at two different growth stages. In particular, diploid mono- and binucleated cells from young and adult rats were considered. The results indicated the existence of a more homogeneous situation in young than in adult rats. In the latter case, the statistical analysis indicates the presence of two groups of energy transfer values. The different efficiency values in energy transfer can be considered a consequence of chromatin structure rearrangement and are tentatively interpreted according to the functional role of the diploid cells in the two stages of liver growth.

Animals↗