Regresión tumoral espontánea. A propósito de dos casos

Two cases of spontaneous tumor regression (STR) occurring in a patient with non Hodgkin lymphoma and in another patient with squamous carcinoma of the lung are presented. Both cases fulfill the criteria of STR defined by Everson and Cole. Recent results obtained in basic and clinical studies have indicated that immunological mechanisms could play an important role in STR. The mediator effects more frequently referred are: 1) generation of antineoplastic cytotoxic cells; 2) production of immunoregulatory cytokines by lymphocytes and monocytes, and 3) possible cross reaction between tumor and bacterial antigens. These mechanisms of action are discussed in relation to the presented case

Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an increase of cytotoxicity against HT-29 cells. It was found that the active peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether

Depresión del sistema mononuclear-fagocítico provocada por altas dosis de morfínico

We evaluated in human monocytes the effect of high doses of alfentanyl on the expression of vimentin filaments, the phagocytic activity and the membrane display of HLA-DR molecules in the subjects undergoing surgery. The study was performed on 30 patients, ASAI-II. The patients received 100 mcg/kg i.v. of Alfentanil and the maintenance of anaesthesia was made with Alfentanil (2-3 mcg/kg/min.). The patients were randomized in two groups. The patients were ventilated with N2O:O2 (1:1) (Group I) or air: O2 (1:1) (Group II). After surgery, all patients of the Group II received Naloxone (0.2-0.4 mg). Central venous blood samples were obtained before induction, one and two hours after induction of anaesthesia and at the end of surgery. Separation of monocytes was performed according to Boyum technique. CD35 and HLA-DR molecules and vimentin filaments were studied by indirect immunofluorescence method using monoclonal antibodies. Percentage of positive cells were read with a cytofluorometer. The phagocytic function of monocytes was determined by ingestion of latex particles. Cortisol and ACTH plasma levels were determined by RIA. High doses of Alfentanyl depress phagocytic function and membrane display of CD35 and HLA-DR molecules in monocyte and induce marked changes in the organization of vimentin filaments in these cells in patients undergoing surgery. This monocytic depression was more marked in the patients ventilated with N2O. In our results there was uninhibition of ACTH and cortisol plasma levels responses to surgical stress by Alfentanil administration. Since the effects of Alfentanil were reversed by Naloxone, an opioid receptor mechanism seems to mediate these event

Co-expression of inducible nitric oxide synthase and arginases in different human monocyte subsets. Apoptosis regulated by endogenous NO

Human monocyte subsets, isolated from cultures of mononuclear cells, or freshly obtained from patients with multiple sclerosis, Graves' disease or pemphigus vulgaris, differed in phenotype, apoptotic features, mRNA levels of arginase II (A-II) and the inducible form of nitric oxide synthase (iNOS). Liver-type arginase I mRNA was present in all subsets. Apoptosis was followed by the expression of T cell intracellular antigen (TIA) and the simultaneous detection of DNA stainability by propidium iodine and annexin V binding. Apoptosis was practically absent both in activated CD14(++)CD33(++)DR(++)CD25(++)CD69(++)CD71(++/+) CD16(-) cells, expressing A-II mRNA and having arginase activity, but not iNOS mRNA, and in not fully mature large CD14(++)CD16(+)CD23(+)DR(++) monocytes, expressing simultaneously both mRNAs and having both enzyme activities. However, differentiated small CD14(+/++)CD16(+)CD69(+)CD25(+/-)CD71(++)CD23(+) DR(++) monocytes, expressing high levels of iNOS mRNA, exhibited apoptotic signs. Amounts of NO synthesised by monocytes co-expressing iNOS and arginase changed with the addition of arginine or an iNOS inhibitor; in that case a correlation of NO production and apoptotic features was observed. Data suggest a regulatory role for endogenous NO in apoptosis of stimulated and differentiated monocytes, and also that iNOS and A-II, when simultaneously present, could control the production of NO as a consequence of their competition for arginine

Regresión tumoral espontánea. A propósito de dos casos

Two cases of spontaneous tumor regression (STR) occurring in a patient with non Hodgkin lymphoma and in another patient with squamous carcinoma of the lung are presented. Both cases fulfill the criteria of STR defined by Everson and Cole. Recent results obtained in basic and clinical studies have indicated that immunological mechanisms could play an important role in STR. The mediator effects more frequently referred are: 1) generation of antineoplastic cytotoxic cells; 2) production of immunoregulatory cytokines by lymphocytes and monocytes, and 3) possible cross reaction between tumor and bacterial antigens. These mechanisms of action are discussed in relation to the presented case

Depresión del sistema mononuclear-fagocítico provocada por altas dosis de morfínico

We evaluated in human monocytes the effect of high doses of alfentanyl on the expression of vimentin filaments, the phagocytic activity and the membrane display of HLA-DR molecules in the subjects undergoing surgery. The study was performed on 30 patients, ASAI-II. The patients received 100 mcg/kg i.v. of Alfentanil and the maintenance of anaesthesia was made with Alfentanil (2-3 mcg/kg/min.). The patients were randomized in two groups. The patients were ventilated with N2O:O2 (1:1) (Group I) or air: O2 (1:1) (Group II). After surgery, all patients of the Group II received Naloxone (0.2-0.4 mg). Central venous blood samples were obtained before induction, one and two hours after induction of anaesthesia and at the end of surgery. Separation of monocytes was performed according to Boyum technique. CD35 and HLA-DR molecules and vimentin filaments were studied by indirect immunofluorescence method using monoclonal antibodies. Percentage of positive cells were read with a cytofluorometer. The phagocytic function of monocytes was determined by ingestion of latex particles. Cortisol and ACTH plasma levels were determined by RIA. High doses of Alfentanyl depress phagocytic function and membrane display of CD35 and HLA-DR molecules in monocyte and induce marked changes in the organization of vimentin filaments in these cells in patients undergoing surgery. This monocytic depression was more marked in the patients ventilated with N2O. In our results there was uninhibition of ACTH and cortisol plasma levels responses to surgical stress by Alfentanil administration. Since the effects of Alfentanil were reversed by Naloxone, an opioid receptor mechanism seems to mediate these event

Co-expression of inducible nitric oxide synthase and arginases in different human monocyte subsets. Apoptosis regulated by endogenous NO

Human monocyte subsets, isolated from cultures of mononuclear cells, or freshly obtained from patients with multiple sclerosis, Graves' disease or pemphigus vulgaris, differed in phenotype, apoptotic features, mRNA levels of arginase II (A-II) and the inducible form of nitric oxide synthase (iNOS). Liver-type arginase I mRNA was present in all subsets. Apoptosis was followed by the expression of T cell intracellular antigen (TIA) and the simultaneous detection of DNA stainability by propidium iodine and annexin V binding. Apoptosis was practically absent both in activated CD14(++)CD33(++)DR(++)CD25(++)CD69(++)CD71(++/+) CD16(-) cells, expressing A-II mRNA and having arginase activity, but not iNOS mRNA, and in not fully mature large CD14(++)CD16(+)CD23(+)DR(++) monocytes, expressing simultaneously both mRNAs and having both enzyme activities. However, differentiated small CD14(+/++)CD16(+)CD69(+)CD25(+/-)CD71(++)CD23(+) DR(++) monocytes, expressing high levels of iNOS mRNA, exhibited apoptotic signs. Amounts of NO synthesised by monocytes co-expressing iNOS and arginase changed with the addition of arginine or an iNOS inhibitor; in that case a correlation of NO production and apoptotic features was observed. Data suggest a regulatory role for endogenous NO in apoptosis of stimulated and differentiated monocytes, and also that iNOS and A-II, when simultaneously present, could control the production of NO as a consequence of their competition for arginine

High-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients

A phase II study of postoperative high-dose carmustine (HDBCNU), intracarotid cisplatin (CDDP), and radical radiotherapy in patients with high-grade glioma was performed. Patients underwent 4-6 consecutive days of blood hematopoietic progenitor cell (HPC) apheresis without prior mobilization. Chemotherapy included intracarotid CDDP, 60 mg/m2, and BCNU, 900 mg/m2. HPC were infused 48 h after HDBCNU. Whole brain irradiation, up to 50 Gy, was started on the 8th day after HPC infusion. With a median follow-up time of 44 months, median overall survival was 15.5 months. Eight patients (23.5%) are alive free of disease 2-6 years after treatment (seven out of 25 patients with glioblastoma multiforme and one out of nine patients with anaplastic astrocytoma). Survival was influenced by young age, good performance and complete surgical resection. Two patients (5.8%) died of therapy-related complications. Acute hematological toxicity of HDBCNU was moderate, with a full recovery on day 26. No acute pulmonary or hepatic toxicity was found. Late severe neurological toxicity was observed in one third of patients surviving beyond 2 years. We conclude that HDBCNU, 900 mg/m2, intracarotid CDDP and radical radiotherapy appear to benefit some patients with high-grade gliomas, and phase III studies should preferentially select young patients with resectable tumors