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R Santi

Publications and source records attributed to R Santi.

At least 19 recordsLinked to original sources
PubMed2001

Long-term immunotherapy with low-dose interleukin-2 and interferon-alpha in the treatment of patients with advanced renal cell carcinoma.

BACKGROUND: The objective of this study was to evaluate response, toxicity, and immunologic effects of an original immunotherapy schedule based on repeated cycles of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFNalpha) in patients with metastatic renal cell carcinoma (mRCC). METHODS: Fifty patients who underwent nephrectomy received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFNalpha twice weekly for 4 consecutive weeks. The cycle was regularly repeated indefinitely at 4-month intervals in all patients, irrespective of their response. rIL-2 (1 x 10(6) IU/m(2)) was administered every 12 hours on Days 1 and 2 and once per day on Days 3-5 of each week; rIFNalpha (1.8 x 10(6) IU/m(2)) was given on Days 3 and 5. Toxicity was graded according to the World Health Organization (WHO) criteria. Forty percent of the patients had only one metastatic disease site at the time of treatment. The Kaplan-Meier method was used to estimate survival, and an analysis of variance was used to evaluate the effects on leukocytes and lymphocyte subsets over time. RESULTS: A total of 241 cycles were administered. One patient achieved a complete response, and five patients achieved a partial response. Five patients had stable disease, and 30 patients had progressive disease. Nine patients were not evaluable for response. The overall response rate was 12% (95% confidence interval, 3-21%) on the basis of an intent-to-treat analysis. The 36-month survival probability for all 50 patients was 47%. Treatment-related toxicity was limited to WHO Grades 1 and 2. Both lymphocyte and eosinophil levels significantly increased after all cycles (by 42% and 353%, respectively). The treatment also induced significant increases in the CD25 positive (24%), CD56 positive (28%), and CD3 negative/CD56 positive (54%) lymphocyte subsets. CONCLUSIONS: Long-term, repeated treatment with low doses of rIL-2 and rIFNalpha is feasible in patients with mRCC. The schedule induces clinical response rates and survival probabilities are similar to those obtained using higher doses.

Aged↗
PubMed2001

Long-term treatment with low doses of interleukin-2 and interferon-alpha: immunological effects in advanced renal cell cancer.

PURPOSE: We aimed to determine the immunological effects of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) in patients bearing advanced renal cell carcinoma. METHODS: Twenty-seven patients received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFN-alpha twice weekly, for 4 consecutive weeks. The cycle was repeated indefinitely at regular 4-month intervals, for all patients. rIL-2 (1 x 10(6) IU/m2) was administered every 12 h on days 1 and 2 and once a day on days 3-5 of each week; rIFN-alpha (1.8 x 10(6) IU/m2) was given on days 3 and 5. In the enrolled patients, total and differential white blood cell counts, phenotypic analysis of some lymphocyte subsets, and soluble IL-2 receptor (sIL-2R), were investigated before and after each of the first six cycles of therapy (about 24 months of follow-up). RESULTS: The cycles of immunotherapy induced a significant increase of total lymphocytes (37%, P < 0.001), eosinophils (222%, P < 0.001), CD25+ cells (27%, P=0.004), sIL-2R (174%, P < 0.001) and natural killer (NK) cells (CD3-CD56+) (61%, P < 0.001); the subset that expresses CD56 with high density (CD56+ bright) expanded more (233%, P < 0.001) than the subset expressing the same marker with low density (CD56+ dimmer) (15%, P = 0.043). Unlike the previous subsets, the treatment decreased significantly T-lymphocytes with NK cell marker (CD3+ CD56+) (28%, P = 0.011). No significant differences of effectiveness were found among the subsequent treatment cycles, except for CD25+ cells and sIL-2R (P = 0.036 and P = 0.005, respectively): the increase induced by immunotherapy was maximum after the first cycle and decreased progressively thereafter. CONCLUSIONS: Long-term repeated cycles of low-dose immunotherapy induced repeated and significant expansion of one of the most important lymphocyte subsets for the non-MHC-restricted immune response to the tumour mass: CD3-CD56+ cells.

Adult↗
PubMed1999

Primary dural leiomyosarcoma in a patient infected with human immunodeficiency virus: case report.

INTRODUCTION: We report the magnetic resonance imaging, angiographic, and immunohistochemical characteristics of a dural leiomyosarcoma in a patient infected with human immunodeficiency virus. METHODS AND RESULTS: A 38-year-old homosexual man presented with a recent history of headaches. Magnetic resonance imaging of the brain revealed an enhancing dural based right lateral wing mass that was thought to be a meningioma. The tumor had a signal intensity similar to the adjacent gray matter on T1-, T2-, and proton-weighted images. Angiography revealed that the tumor was vascular, supplied by the middle meningeal artery, but with contrast puddling as if there were small vascular lakes within the tumor. This evoked the possibility of a cavernous hemangioma. A craniotomy was performed, and the mass was resected. The pathological finding was consistent with a leiomyosarcoma. Immunohistochemistry revealed that the tumor was positive for alpha smooth muscle actin. Repeat testing for human immunodeficiency virus 2 months postoperatively was positive. Dural leiomyosarcomas are thought to take origin from the smooth muscles of the blood vessel walls. Another possible source is pluripotential mesenchymal cells. There may be an association with immunosuppression. CONCLUSION: Primary dural leiomyosarcomas simulate meningiomas on preoperative magnetic resonance images. They should be included in the differential diagnosis of dural based enhancing lesions.

Adult↗
PubMed1984

Sexual behavior of male rats: influence of short- and long-term adrenalectomy.

Adult male rats (3 months old) were tested for their copulatory behavior: those satisfying the criterion of sexual vigor in the last three out of five weekly tests were randomly divided into two groups and adrenalectomized or sham operated, and their copulatory activity was retested 35 and 420 days after surgery. Short-term adrenalectomy did not modify any of the parameters of sexual behavior. On the other hand, a higher percentage of adrenalectomized than of sham-operated rats still had successful sexual performance when 18 months old (420 days after surgery); moreover, blood levels of testosterone were higher in adrenalectomized than in sham-operated old rats. The possibility that adrenal steroids may play a role in the age-linked decline in male sexual activity in mammals is discussed.

Adrenal Glands↗
PubMed1981

Metabolism of succinonitrile in liver: studies on the systems involved in cyanide release.

The liberation of cyanide from succinonitrile has been studied to obtain information on the cellular systems responsible for the release of this metabolite. 1) Using isolated endoplasmic reticulum preparations a complex between succinonitrile and cyt. P 450 has been detected. This finding together with the inhibition of cyanide liberation by SKF-525A in liver slices indicates that the endoplasmic reticulum is involved in the early stages of succinonitrile metabolism. 2) The decreased metabolism of succinonitrile which was observed after addition of inhibitors of oxidative phosphorylation indicates that an energy-dependent mitochondrial step might be involved in the subsequent steps. 3) It is concluded that cyanide liberation from succinonitrile is a multistep process in which the mitochondrial membrane and the endoplasmic reticulum are involved. The requirement for cellular integrity in order to accomplish the process of succinonitrile metabolism suggests other components or equilibria that are difficult to reproduce in in vitro experiments.

Animals↗
PubMed1980

[The behaviour of gamma-glutamyltranspeptidase in the diagnosis of secondary hepatic malignancy: its relationship to other serum enzymes (author's transl)].

In order to determine the value of serum Gamma-glutamyltranspeptidase in the diagnosis of secondary hepatic malignancy, the variations of the serum measurement of different hepatic enzymes have been studied in 160 patients, 80 of which have hepatic metastases gamma GT showed an increase in 95% of the patients with metastases even if there has been a high percentage of false-positive results in the control patients and in those who were carriers of cancer without hepatic metastases. The Authors, after having briefly discussed the meaning of the false positivity rate, conclude that such an enzyme proves once to be a simple and sensitive test of secondary hepatic malignancy and that further studies will help to make it more specific.

Adult↗