PubMed Health⌕ Search

Biomedical subjects

M Petrini

Publications and source records attributed to M Petrini.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

[Adjuvant adoptive immunotherapy in patients with stage III and resected stage IV melanoma: a pilot study].

Adoptive immunotherapy trials with tumor infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) were carried out in the treatment of advanced melanoma with a 34% of overall responses (OR). However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stages (stage III and resected stage IV). In a pilot study, 22 patients (aged 23-72 years) with stage III-IV melanoma who underwent radical metastasectomy were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 10(6) IU/m2) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) in the remaining 14 patients were 44% and 37% and 52% and 45% at 2 and 3 years, respectively. The CNS was the only site of disease recurrence in 57% of patients who relapsed. DF patients received a higher median dose of IL-2 than those who progressed (total dose 110 x 10(6) vs 86 x 10(6) IU/m2, respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. The effects of tumor immunosuppression in lymphocytes inside the tumor (TCR z and e chains, p56lck, FAS and FAS-ligand) confirmed that the potential function of TIL, immunodepressed at the time of metastasectomy, was significantly restored after in vitro, culture with IL-2. Adjuvant adoptive immunotherapy with TIL and IL-2 seems to improve DFS and OS, in comparison with literature data. Further studies are required to determine its role in the adjuvant treatment of patients with high-risk melanoma.

Adult↗
PubMedDate not supplied

High efficacy of Rituximab in indolent HCV-related lymphoproliferative disorders associated with systemic autoimmune diseases.

OBJECTIVE: The evidence of an increased frequency of B-non Hodgkin's lymphomas (NHL) in patients with HCV and systemic autoimmune diseases suggests a close relationship between infection, autoimmunity and cancer. Choosing the best therapy for patients affected either by HCV-related lymphoma or autoimmune disorders is not easy; in fact, some treatments may be accompanied by an excessive hepatic toxicity and may be followed by a reactivation of hepatitis. There is growing interest in the search for an ideal therapy for this kind of patient. Thanks to its mechanism of action and good toxicity profile, Rituximab could prove to be an attractive therapeutic option: it has been reported to be highly active in low-grade NHLs and has been proposed for the management of autoimmune diseases. RESULTS: In this paper we evaluate the role of anti-CD20 monoclonal antibody in mono-therapy in 10 patients with either indolent HCV-related lymphoma or autoimmune disease. A very high rate of response, of both NHL and of the associated autoimmune disease, was observed (100% of clinical response), with no significant hepatic and extra-hepatic toxicity. CONCLUSION: Thus, although the number of patients was small, our data strongly support the use of anti-CD20 in this patient setting.

Adult↗
PubMedDate not supplied

Low-dose ARA-C and 1(OH) D3 administration in acute non lymphoid leukemia: pilot study.

BACKGROUND AND METHODS: Vitamin D3 metabolites have been shown to be able to induce monocytic differentiation both in vitro and in vivo. In this paper we report the preliminary results of an uncontrolled clinical trial where low doses of ARA-C and 1(OH)D3 were administered to patients affected by acute non lymphoid leukemia. The achievement of complete or partial remission was recorded. Morphological and cytochemical studies were performed in order to control the blastic populations under therapy. Immunocytochemical studies were also performed in some patients in order to detect the presence of 1,25(OH)2D3 receptors in the blast population. Seventeen percent reached complete remission and 45% reached only a partial remission. RESULTS AND CONCLUSIONS: The results are in line with those showing that low doses of ARA-C are an effective treatment in this type of leukemia. In some cases (7/11), a monocytic/monoblastic shift was detected. The demonstration of 1,25(OH)2D3 receptors in some blasts is also reported. Thus it is possible to suggest that the vitamin D metabolite displays "in vivo" the differentiating activity already shown "in vitro".

Adult↗
PubMedDate not supplied

Synergistic effects of alpha interferon and 1,25 dihydroxyvitamin D3: preliminary evidence suggesting that interferon induces expression of the vitamin receptor.

BACKGROUND: To active metabolite of vitamin D3-1,25(OH)2D3-is a well-known differentiation inducer. The addition of this metabolite to sensitive cell cultures inhibits proliferation and induces monocytic-macrophagic differentiation. Alpha interferon may also inhibit proliferation and increase the expression of some surface antigens in some neoplastic cells. In the present report, we describe the synergistic activity of these two drugs on U-937 and on cultured cells from a leukemic patient. METHODS: Proliferation was studied by 3H-thymidine incorporation; differentiation markers were evaluated immunologically by monoclonal antibodies and by cytochemical tests. Phagocytosis and NBT reduction test were also performed in order to confirm the differentiating properties of these drugs. Finally, the expression of the 1,25(OH)2D3 receptor was evaluated by immunochemical methods. RESULTS: After culturing these cells for 72 hours in the presence of 1,25(OH)2D3, cell proliferation was reduced and the expression of some phenotypic and functional markers suggested monocytic-macrophagic differentiation. Alpha interferon and 1,25(OH)2D3 synergistically inhibit the proliferation of U-937 cells. Alpha interferon increased the expression of the 1,25(OH)2D3 receptor in U-937 cells. CONCLUSIONS: The reported results confirm the synergistic activity of INF and 1,25(OH)2D3 on cell proliferation in monoblastic cells. The possible role of the increased expression of the vitamin receptor in cells cultured in the presence of INF is discussed.

Calcitriol↗
PubMedDate not supplied

IL-6/BSF-2 selectively stimulates the GO----S progression of CD8+ lymphocytes.

IL-6 preferentially promotes the DNA synthesis of human peripheral blood CD8+, rather than CD4+, lymphocytes in presence of PHA: this effect is observed in serum-free cultures of greater than 99% purified CD8+ lymphocytes. However, IL-6 is able to stimulate DNA synthesis of CD8+ lymphocytes triggered by a mitogenic anti-CD2 mAb, but not by anti-CD3 mAb: these results suggest that IL-6 selectively induces activation of CD8+ lymphocytes through the CD2 rather than the CD3 pathway. Limiting dilution analysis indicates that accessory cells are not required to mediate the action of IL-6 on CD8+ cells. Furthermore, this action is not blocked by addition of mAb neutralizing either IL-2 or IL2R, thus suggesting that IL-6 does not act via IL-2. CD8+ lymphocytes grown in the presence of PHA + IL-6 incorporate (3H)-thymidine to the same extent as those stimulated with PHA + IL-2, but do not increase in number until day 6 of culture. It is hence apparent that the stimulating activity of IL-6 on CD8+ lymphocytes is restricted to the GO----S phase progression, but does not lead to mitosis. IL-6 receptors are expressed on resting CD4+ and CD8+ lymphocytes: their expression is significantly enhanced on both activated CD4+ and CD8+ cells. Scatchard analysis of (125I)-IL-6 binding data showed the presence of high (Kd, 3 x 10(-10) M) and low (Kd, 6 x 10(-8) M) affinity IL6R on both lymphocyte populations. Similarly, mRNA encoding IL6R was detected in both CD4+ and CD8+ lymphocytes. Thus, our studies indicate that IL-6 directly and selectively stimulates the GO----S progression of CD8+ lymphocytes in the presence of mitogen and absence of IL-2: this phenomenon may be of interest for the elucidation of mechanisms activating cytotoxic T lymphocytes.

Antibodies, Monoclonal↗
PubMedDate not supplied

A case of B-CLL expressing P-glycoprotein in peripheral leukocytes. Methodological considerations.

P-glycoprotein, the molecular marker of multidrug resistance, was investigated by means of the specific monoclonal antibody C219 in circulating lymphocytes obtained from a patient affected by B-CLL, who had undergone chemotherapy with chlorambucil and CVP. Dot-immunobinding and immunoblotting revealed the presence of P-glycoprotein in the cell lysate, but the immunoperoxidase method and indirect immunofluorescence carried out with a fluorescence microscope and a cytofluorimeter failed to detect the protein. Some methodologic problems are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

P-glycoprotein expression in multiple myeloma.

P-glycoprotein expression was investigated in ten drug resistant patients suffering from multiple myeloma. The immunoperoxidase method on bone marrow plasma cells and immunoblotting were performed by using the monoclonal antibody C219. Five patients resistant to protocols including vincristine, melphalan and doxorubicin were found to express P-glycoprotein. The immunoperoxidase method appeared to be sensitive and suitable for P-glycoprotein detection in bone marrow samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Multidrug resistance: focus in hematology.

The appearance of chemoresistance is the most relevant limitation of chemotherapy. It has been shown that multidrug resistance (MDR) is frequently related to the expression of a membrane glycoprotein (P-170). This protein is able to bind ATP and leads to decreased accumulation of structurally unrelated antineoplastic drugs extensively used in the management of hematological patients. The availability of monoclonal antibodies and probes allowed extensive studies both "in vitro" and "in vivo" of the protein structure and of its mechanism of action. The P 170 activity may be antagonized by drugs able to compete with chemotherapic agents for the binding or by calcium antagonists that inhibit the expulsion activity of the protein. P 170 has been found in variable percentages of several hematological malignancies such as leukemia, myelodysplastic syndromes, myeloma and lymphoma. The reported data seem to indicate that the patients carrying P 170-positive neoplastic cells should be treated with drugs that are not bound by the protein. However, the possibility of inhibiting the protein function and the recent reports suggesting the use of P 170 as a target for immunotoxins could be the basis for new therapeutic protocols.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

P-glycoprotein and drug resistance in acute leukemias and in the blastic crisis of chronic myeloid leukemia.

The aim of this work is to evaluate the relationship between P-glycoprotein expression in circulating blasts and clinical response in patients suffering from acute lymphoblastic leukemia, acute non-lymphoblastic leukemia, and chronic myeloid leukemia in either lymphoid or myeloid blastic crisis. The results obtained show that: a) patients whose blasts express P-glycoprotein are resistant towards protocols including Doxorubicin, Daunorubicin, Etoposide, Mithramycin, Vincristine; b) P-glycoprotein can be expressed constitutively in some cases; c) P-glycoprotein does not appear to be the only mechanism responsible for resistance towards anthracyclines and Etoposide.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Automatic differential blood counting in plasma cell leukemia.

The authors report a case of primary plasma cell leukemia and two cases of multiple myeloma with a large number of circulating plasma cells. The display of Technicon H-1 shows a very high "cloud" in the area of large unstained cells. A massive invasion of the basophil area was not found. Differences between these results and those found in different lymphoid leukemias are discussed.

Aged↗
PubMedDate not supplied

Rubidium is a possible supporting element for bone marrow leukocyte differentiation.

In the present paper the possible role of rubidium (Rb) on leukocyte differentiation is evaluated. When the metal was added to human mononuclear bone marrow cells cultured for 14 days in soft agar, it was able to increase the number of clusters and to reduce the number of colonies. This activity depended upon the presence of conditioned medium. Rb induced a faster differentiation of HL 60 cells cultured in a medium able to promote granulocyte differentiation. The metal did not show any activity on continuously cultured HL 60. These data suggest that Rb is a supporting element for cell differentiation. Toxicity tests on rats are also reported.

Animals↗