Biomedical subjects

R Giardini

Publications and source records attributed to R Giardini.

At least 55 records · Page 3Linked to original sources

PubMed1993

Combined modality treatment for primary gastrointestinal non-Hodgkin's lymphoma: the Milan Cancer Institute experience.

BACKGROUND: The study analyzes clinical-pathologic features, treatment and outcome of all patients with primary lymphoma of the gastrointestinal tract (GI-NHL) seen during the past two decades at the Milan Cancer Institute. SUBJECTS AND METHODS: Clinical and histopathological data from 135 patients presenting with GI-NHL and disease localized within the abdomen were reviewed. Of these, 114 (84%) presented with limited disease (stage I and II), while 21 patients were found to have disease involvement of other abdominal organs (i.e., liver, pancreas, peritoneum) or more than one gastrointestinal site and were therefore classified as stage IV. Seventy-three percent presented with lymphoma in the stomach, 15% in the small intestine and 9% in the large bowel, while in 5 cases multiple localizations of the gastrointestinal tract were documented. Median age was 50 years, with one-fourth of patients older than 60 years. According to the revised Kiel classification for GI-NHL, 61% of patients presented with pure high-grade lymphoma, 9% high-grade NHL associated with residual low-grade lymphoma, and 30% had low-grade NHL. Nine percent presented with bulky disease, 5% with elevated LDH and 21% with a Karnofsky performance status (PS) < or = 80. RESULTS: Laparotomy with radical (108 patients) or palliative (15 patients) intent was performed in all patients who were not deemed at high risk of complication from major surgery. Complete removal of all measurable tumor was feasible in 101 patients, with no difference relative to primary site. Surgical morbidity and mortality were 11% and 2%, respectively. Overall, 83% of patients were treated with chemotherapy. Patients who did not receive systemic chemotherapy included 12 managed with surgery alone and 10 who received only postoperative irradiation mainly because of low-grade lymphoma with superficial disease. Of patients with limited disease, 99% achieved complete tumor remission. After a median follow-up of 73 months, 13 of 113 patients have relapsed, mostly (70%) outside the gastrointestinal tract. The actuarial 10-yr. freedom from progression (FFP) and overall survival (OS) were 84% and 86%, respectively. Aside from age, no other factor revealed a statistically significant impact on outcome. There was only a trend in favor of low-grade histology (FFP 97% vs. 79%), that failed to reach statistical significance. Of patients with advanced abdominal disease, 48% achieved complete remission with chemotherapy with or without prior surgical debulking. Actuarial 10-yr. FFP and OS were 44% and 42%, respectively. In this subset, tumor burden and LDH levels represented the most important prognostic factors affecting outcome. CONCLUSIONS: This retrospective study underscores the good results obtained in a wide and unselected population of patients with limited-stage primary GI-NHL following a combined-modality approach that included surgical debulking and systemic chemotherapy for most patients. Surgery alone can be considered adequate treatment for patients with low-grade NHL disease that does not infiltrate beyond the submucosa. Patients with advanced GI-NHL show a long-term outcome similar to that of patients with advanced NHL arising outside the gastrointestinal tract.

Aged↗

PubMed1993

Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas.

PURPOSE: A single-center, prospective, nonrandomized trial was conducted to evaluate therapeutic results of a short-term program of chemotherapy followed by locoregional radiotherapy in stage I or II intermediate/aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1985 to 1990, 183 consecutive patients with a diagnosis of NHL (Working Formulation [WF] E through J excluding Burkitt's type), Ann Arbor stage I or II, and no more than three sites of disease involvement were treated with four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (six cycles in partial responders). Radiation therapy to initial sites of disease involvement (40 to 44 Gy) and to proximal uninvolved nodal region (36 Gy) was delivered shortly after completion of the chemotherapy program. RESULTS: The complete remission (CR) rate was 98% at the end of combined therapy. Diagnostic excision of all measurable disease was performed in 33% of patients. In the remaining patients, 87% achieved CR with chemotherapy and 11% with radiation therapy, while three patients failed to achieve CR. After a median follow-up of 51 months, 26 patients have relapsed and 25 have died. The 5-year relapse-free and total survival rates were 83%. Aside from age older than 60 years, no other factor such as histology, stage, extranodal disease, bulky lymphoma, or abnormal lactic dehydrogenase (LDH) could predict for treatment outcome. There was a trend toward higher relapse rate for patients achieving CR at the time of radiation therapy (31%) as opposed to patients achieving CR with chemotherapy (15%) or with initial surgery (10%). Treatment was well tolerated and no deaths due to acute toxicity were observed. CONCLUSION: For patients who present with limited-stage, aggressive NHL, a short course of CHOP chemotherapy followed by locoregional irradiation is safe, highly effective, and curative for most. Therefore, at the present time this approach can be regarded as standard therapy for these patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Primary non-Hodgkin's lymphomas of the female breast.

The charts of 35 women with primary malignant non-Hodgkin's lymphomas (NHL) of the breast were retrieved from the files of the Istituto Nazionale Tumori, Milan, over a 30-year period (1957 to 1986). These cases represented 0.1% of the more than 25,000 primary malignant tumors of the breast treated during the same period. The median age of these patients was 57 years (range, 28 to 81 years). In most cases, the clinical diagnosis was carcinoma. The tumors were either Stage IE(48%) or IIE(52%) at presentation, and only two patients had B symptoms. The right breast was involved in 17 patients, the left breast in 14, and both breasts in two. According to the updated Kiel classification and the Working Formulation (WF) for Clinical Usage, three cases were lymphoplasmacytoid (immunocytoma) NHL (WF, A); three, centroblastic-centrocytic, follicular NHL (WF, B); four, centroblastic-centrocytic, diffuse NHL (WF, F); 17 centroblastic NHL (WF, G); three immunoblastic NHL (WF, H); two B-lymphoblastic NHL (WF, I); and one, a Burkitt-like NHL (WF, J). Treatment consisted either of a combination of surgery, radiation therapy, and chemotherapy or radiation therapy and chemotherapy. The follow-up period for 32 patients ranged from 6 to 161 months (mean, 45 months); 17 patients died of their disease. The prognosis appeared to be related to the histologic type and stage of the disease. Median survival periods were 63, 52, 42, and 47 months for centroblastic-centrocytic follicular, centroblastic-centrocytic diffuse, centroblastic, and immunoblastic NHL, respectively. The overall 5-year survival rate was 43%; the 5-year survival rate and the probability of freedom from progression at 5 years were, respectively, 61% and 50% for Stage I and 27% and 26% for Stage II disease.

Breast Neoplasms↗

PubMed1992

Flow cytometric detection of the mitochondrial BCL-2 protein in normal and neoplastic human lymphoid cells.

The bcl-2 proto-oncogene, rearranged and deregulated in B-cell lymphomas bearing the t(14;18) translocation, encodes an inner mitochondrial membrane protein that blocks apoptotic cell death. We have developed a sensitive immunofluorescence assay for the single- and multicolor flow cytometric analysis of bcl-2 protein in relation to other markers and cell cycle, based on a fixation-permeation step of cells with paraformaldehyde and Triton X100 and the use of a bcl-2 specific monoclonal antibody (MoAb). As an application of this method, we have examined the expression of bcl-2 in normal and neoplastic lymphoid cells. We have found that greater than 80% of normal T-and B-cells are bcl-2 positive; following in vitro mitogen activation, the bcl-2 reactivity decreased slightly in the former but markedly in latter cells. In both cases the bcl-2 expression was not restricted to a specific phase of the cell cycle, as evidenced by two-color analysis. On lymphoblastoid cell lines, the bcl-2 staining intensity was variable and not necessarily correlated to molecular rearrangements of the bcl-2 gene. Among fresh B-cell non-Hodgkin's lymphomas (B-NHL), most sporadic Burkitt's cases were bcl-2 negative. Of four centroblastic-centrocytic cases with rearrangements of the bcl-2 gene, only two presented elevated amounts of bcl-2 protein, indicating that the levels of bcl-2 are not diagnostic of the translocation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1992

Contribution of 3H-thymidine labelling index and flow cytometric S-phase in predicting survival of patients with non-Hodgkin's lymphoma.

The 3H-thymidine labelling index (3H-dT LI) of cell suspensions from fresh material and the flow cytometric S-phase (FCM-S) of nuclei recovered from paraffin blocks were determined on the same pathologic lymph node specimen for 190 non-Hodgkin's lymphomas (NHLs). FCM-S was defined by a planimetric method and by an optimization procedure. Poor correlation coefficients were observed among the three cell kinetic variables. All three cell kinetic variables were significant indicators of 8-year survival and median survival time. The life-regression procedure evidenced a significant relative contribution of 3H-dT LI and FCM-S, thus suggesting a different biologic meaning of the two cell kinetic variables. This finding was further supported by evidence that simultaneous use of 3H-dT LI and FCM-S can identify groups of patients with different survival better than when either modality is used alone. Multivariate analysis indicated that the risk groups as defined by cell kinetic variables are predictors of survival even in the presence of established factors such as histology and stage.

Autoradiography↗

PubMed1992

Thymoma in childhood: a clinicopathological study of five cases.

The histological and clinical findings in five cases of thymoma arising in paediatric patients have been studied. The age range was 11-15 years and no patient was affected by myasthenia gravis. All tumours were macroscopically encapsulated, but two of them displayed evidence of microscopic capsular invasion. Histologically, four cases were of the predominantly cortical type (organoid thymoma) with prominent areas of medullary differentiation and Hassall's bodies; one case was of the cortical type. All patients are alive and disease-free 3 months to 9 years after surgery. These findings suggest that thymoma in the paediatric age group may be characterized by fairly uniform clinicopathological features, with a low rate of association with myasthenia gravis and a favourable prognosis.

Adolescent↗

PubMed1990

Purification and properties of carnitine acetyltransferase from human liver.

Carnitine acetyltransferase was purified from the supernatant obtained after centrifugation of human liver homogenate to a final specific activity of 78.75 unit.mg-1 with acetyl-CoA as a substrate. Human carnitine acetyltransferase is a monomer of 60.5 kDa with maximum activity in the presence of propionyl-CoA and a pH optimum of 8.7. Apparent Km values for acetyl-CoA are three times lower than for decanoyl-CoA. Km values for L-carnitine in the presence of acetyl-CoA are six times lower than in the presence of decanoyl-CoA. Km values for acetylcarnitine are three times lower than for octanoylcarnitine. The polyclonal antibodies against human carnitine acetyltransferase recognize a 60.5-kDa peptide in the purified preparation of human liver and brain homogenates and in immunoblots of mitochondrial and peroxisomal fractions from human liver. Immunoprecipitation and SDS/PAGE analysis of 35S-labelled proteins produced by human fibroblasts indicate that mitochondrial carnitine acetyltransferase is synthesized as a precursor of 65 kDa. We also purified carnitine acetyltransferase from the pellet obtained after centrifugation of liver homogenate. The pellet was extracted by sonication in the presence of 0.5% Tween 20. The chromatographic procedures for the purification and the kinetic, physical and immunological properties of pellet-extracted carnitine acetyltransferase are similar to those of carnitine acetyltransferase purified from the supernatant of human liver homogenate.

Acetyltransferases↗

PubMed1990

Follicular non Hodgkin's lymphoma in adenolymphoma: report of a case.

A case of centroblastic centrocytic follicular lymphoma arising within a bilateral adenolymphoma of the parotid glands with involvement of the adjacent lymph nodes is reported. The patient was treated with combination chemotherapy and three years after the first cycle of therapy there was no evidence of disease. The occurrence of primary malignant lymphomas in the lymphoid stroma of an adenolymphoma has seldom been discussed in literature. All cases reported of follicular centre cell type were characterized by an indolent clinical course.

Adenolymphoma↗

PubMed1990

Correlation between disc potency and zone size in temafloxacin activity in vitro.

A multi-test disc potency evaluation of a new fluoroquinolone, temafloxacin, has been prepared in order to evaluate the variation of the zone dimension with the disc antibiotic concentration. A direct correlation between these parameters has been demonstrated. All pathogens have been isolated in hospitalized patients.

4-Quinolones↗

PubMed1990

Malignant histiocytosis. A phenotypic and genotypic investigation.

Ten cases of malignant histiocytosis (MH) were evaluated for clinical and histopathologic features, phenotype, and rearrangement of T cell receptor (TCR) beta, gamma, and alpha and immunoglobulin (Ig) genes (7/10). All cases were HLA-DR+ and CD30-positive. Four cases had molecular evidence of T cell lineage such as TCR beta, gamma, and alpha rearrangements, and one additional case synthesized the cytoplasmic TCR beta chain. The remaining five cases did not show unequivocal T, B, natural killer (NK) cell, or macrophagic origin, and three of them had germline TCR and Ig genes. Ultrastructural analysis was not helpful for the definition of the cell lineage. Most myelomonocytic markers (MAC387, CD13, CD14, CD64, CD68) were either negative on the MH cells or were expressed on cells with rearranged TCR gene. Precursor (CD34, CD7) and NK (CD16, CD56, and CD57) cell markers were not found. The lineage of a number of cases of MH remains unresolved.

Adolescent↗

PubMed1988

Leiomyoma of the kidney.

This is the report of a 27-year old woman with a symptomatic leiomyoma of the left kidney. Symptoms consisted of a mild discomfort at the left flank and a walking difficulty. A left radical nephrectomy was performed. The tumor measured 15 cm in its largest diameter and was composed of elongated cells which demonstrated positive reactivity with anti-desmin and anti-actin antisera and negative reactivity for S-100 protein and cytokeratins. Histologic differential diagnosis is with other spindle cell renal tumors such as leiomyosarcoma, mesoblastic nephroma, angiomyolipoma, fibroma, schwannoma and sarcomatoid renal cell carcinoma.

Actins↗

PubMed1988

Specificity of the rearrangements of the T-cell receptor gamma gene in human lymphomas.

The structure and function of the human T-cell rearranging gamma gene are not completely understood. Several reports have suggested that this gene rearranges specifically in normal T cells, but the pattern of rearrangement in human lymphoid neoplasms is not clear. Some authors have described the rearrangements of this gene in unmanipulated leukemias as relatively specific for T-derived tumors, whereas others were unable to observe such specificity in malignant lymphomas. The present paper reports the analysis of the structure of the gamma gene in 32 lymphoid samples of different origin, with emphasis on non-T lymphomas. Four out of four T-cell lymphomas had this gene rearranged, whereas none of the 17 cases of B-cell lymphomas, 5 of Hodgkin's disease or 6 of nonneoplastic lesions showed any alterations of the gamma gene. Therefore, our data support the relative specificity of the gamma gene rearrangements in human T-cell malignant proliferations.

Genes, Immunoglobulin↗

PubMed1988

CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset.

The CD1 cluster of monoclonal antibodies (MoAbs) CD1a, CD1b, and CD1c, identifies molecules that are differentially expressed on hematopoietic and nonhematopoietic tissues. Our earlier finding that the mantle zone (MZ) but not the germinal center (GC) of normal lymph nodes (LN) is CD1c+, CD1a-, and CD1b- prompted us to further investigate the expression of these molecules on normal, activated, and malignant B cells. We report that blood and spleen contain CD1c+ B cells that account for 49% +/- 20.4% (mean +/- SD) and 50.9% +/- 4.4% of the total B cell population, respectively. CD1a- and CD1b-specific MoAbs are unreactive with both B and T cells; these latter are CD1c- as well. When CD1c+ and CD1c- B cells are activated in vitro, the CD1c molecule is upregulated in the former subset and induced de novo in the latter. Conversely, activated blood T cells remain CD1c-. Neither CD1a nor CD1b molecules are detected on activated T and B lymphocytes. At ultrastructural level, the CD1c+ B cells exhibit distinctive features, namely, condensed chromatin with or without a nucleolus and a unique cluster of cytoplasmic vesicles and organelles; the number of nucleolated cells is higher in the spleen (95%) than in the tonsil (40%) or blood (5%). These findings further confirm the similarity between blood and MZ B cells. The CD1c expression assessed on 27 B-cell chronic lymphocytic leukemias (B-CLL) and 46 B non-Hodgkin's lymphomas (B-NHL) was detected on 41% and 32% of cases, respectively; the latter comprised four follicular and 11 diffuse histotypes. The Burkitt's lymphomas were CD1c-negative. The B-cell neoplasms were all CD1a- and, except for four with a weak cytoplasmic staining, all CD1b- as well. The clear-cut CD1c distribution in normal LN (MZ+, GC-) contrasted with the evidence that some B-NHL cells of GC origin (eg, follicular with predominantly small cleaved cells) were CD1c+. Overall, the finding that CD1c expression is restricted to a fraction of B cells present in lymphoid organs and in peripheral blood indicates that CD1c is a powerful marker for the identification and dissection of B-cell subsets whose functional properties can now be evaluated.

Antigens, Differentiation, B-Lymphocyte↗

PubMed1987

A cytogenetic, phenotypic, and molecular study of an immunoblastic lymphoma with a 14q + translocation.

An uncultured immunoblastic lymphoma, obtained from an untreated patient, was examined from a cytogenetic, immunophenotypic, and molecular viewpoint. The B-cell lineage, immunoglobulin light-chain type, and percentage of neoplastic cells were determined immunologically. Karyotyping showed the presence of a 14q + marker and suggested that the donor chromosome was chromosome 8. Southern-blot analysis of DNA from normal and lymphoma cells, using a molecular probes sequences related to the IGHJ and IGK immunoglobulin genes, confirmed the immunophenotype. A similar analysis, using probes homologous to IGHAC and MYC genes, showed that the t(8;14) detected by cytogenetic analysis resulted in a IGHAC-MYC rearrangement.

Antigens, Surface↗

PubMed1986

Growth characteristics of human colorectal and non-small cell lung tumors xenografted into nude mice: possible correlation with prognosis.

Specimens from human colorectal tumors and from non-small-cell lung tumors obtained at surgery were subcutaneously implanted as xenografts in athymic Swiss mice of both sexes to investigate to what extent the properties of the original tumors were maintained. A successful take was obtained in 5 of 9 colorectal tumor and 6 of 11 non-small-cell lung tumor xenografts. Moreover, 44% and 45% of the respective tumors could be established as tumor lines. Neither metastases nor local tumor invasion was observed in tumor-bearing mice. Seven of 9 serially transplantable tumors had a short latency period (14-30.5 days) when first xenografted. No significant changes in tumor histopathology were noted after growth into nude mice. Tumor take was partially related to clinical stage and prognosis of patients. In fact, 8 of 12 specimens from N0 patients failed to grow, whereas 7 of 8 tumors from patients with nodal invasion and/or metastasis grew in nude mice. Moreover, for the group of patients whose tumor was "take - ", the one-year survival was 85%, compared to 40% for the "take + " group (p less than 0.05).

Adult↗

PubMed1986

Alkaline phosphatase and gamma glutamyltranspeptidase in human lymphomas.

Alkaline phosphatase (AP) and gamma glutamyltranspeptidase (GGT) were studied in normal lymphoid cells and in 28 cases of human lymphomas (23 of non-Hodgkin's and 5 of Hodgkin's disease). The expression of AP was enhanced in several samples with a high proportion of mature B cells, particularly in centroblastic-centrocytic lymphoma, whereas tissues mainly composed of T cells always showed low levels of this enzyme. GGT levels were high in thymus, as well as in centroblastic-centrocytic lymphoma and other NHL, thus demonstrating no restriction to a particular cell lineage. Some B-cell neoplasms with cellular origin different from that of centroblastic-centrocytic lymphoma, such as chronic lymphocytic leukemia and centrocytic lymphoma, had low levels of both enzymes. The role of investigation with specific antibodies against these two enzymatic activities in the physiology of lymphoma cell membrane is discussed.

Alkaline Phosphatase↗

PubMed1986

The contribution of molecular biology in the diagnosis of human lymphomas.

The relationship between T cell receptor (TCR) beta and gene immunoglobulin heavy chain locus was investigated in 25 cases of unselected human lymphomas as well as in normal and non-neoplastic lymphoid tissues. Hybridizing our blots with Jurkat 2, a clone specific for the beta chain gene of TCR, did not demonstrate extra bands in non-neoplastic tissues composed of 50-95% T-cells. On the contrary, rearranged bands were detected in six out of six cases of T-cell lymphomas. No TCR beta gene rearrangements were detected in 11 B-cell lymphomas, which in turn presented modification of the immunoglobulin heavy chain gene germline configuration. Our results suggest that TCR beta chain gene rearrangements are a good marker for human T-cell neoplasias in humans and complement the analysis with immunoglobulin genes probes. Eighth samples were devoid of any rearrangements: this group comprises cases of Hodgkin's disease T-lymphoblastic lymphomas in clinical remission and malignancies of unknown origin, as discussed in the text. We conclude that the analysis using DNA probes specific for TCR beta and IgH genes can be of aid to the pathologist in the diagnosis and classification of human lymphomas.

DNA, Neoplasm↗

PubMed1986

Morphological and clinical significance of cell kinetics in non-Hodgkin's lymphomas.

The relation between the proliferative activity and morphologic features according to Rappaport and Kiel classifications and the Working Formulation (WF) was analyzed in a series of 123 adult patients with non-Hodgkin lymphomas. Cell kinetics was determined as in vitro 3H-thymidine labelling index (LI). A significant association was observed between low LI and follicular histology or low grade of the WF, as well as between high LI and high-grade of malignancy of the Kiel and WF. The analysis of the clinical relevance of cell kinetics on objective response to treatment showed a higher frequency (91%) of complete remission in the tumors with low proliferative activity versus tumors with high proliferative activity (48%) (p = 0.00003). Moreover, cell kinetics proved to be and important indicator of 6-year survival on the whole population of patients (66% for slowly vs 18% for fast-proliferating tumors; p less than 10(-9)) and a further discriminant within diffuse histology (68% vs 9%; p less than 0.0001), low-grade malignancy according to the Kiel (64% vs 15%; p less than 10(-8)) and low (64% vs 28%; p less than 0.005) and intermediate grades of the WF (68% vs 9%; p less than 0.0001).

Adolescent↗