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P Porcu

Publications and source records attributed to P Porcu.

44 records · Page 3Linked to original sources
PubMed1991

The protooncogene c-myb increases the expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor messenger RNAs by a transcriptional mechanism.

The protooncogene c-myb is the cellular equivalent of the viral transforming oncogene v-myb. When human c-myb is constitutively expressed in Balb/c3T3 cells it abrogates their absolute requirement for insulin-like growth factor 1 (IGF-1). We show now, in two different cell lines, that the constitutive expression of the protooncogene c-myb causes an increase in both IGF-1 and IGF = 1 receptor mRNA levels. This increase in mRNA levels is due, at least in part, to an increase in the rate of transcription since, by run-on assay, cells carrying the human c-myb cDNA show a 3-fold increase in transcriptional rates in comparison to the control parent cell lines. The increased expression of IGF-1 receptor mRNA also results in an increased number of IGF-1 binding sites per cell. Although some oncogenes have been described that are homologous to growth factors, or growth factor receptors, c-myb seems to represent a novel way of oncogene action inasmuch as it increases the expression of both a growth factor receptor and its ligand, thus establishing a quasi-autocrine mechanism which modifies the growth factor requirements of the cell and its growth regulation.

3T3 Cells↗
PubMed1991

Interleukin 3-dependent proliferation of the human Mo-7e cell line is supported by discrete activation of late G1 genes.

The hemopoietic growth factor interleukin 3 (IL-3) supports the survival and proliferation of multipotent and committed progenitor cells in vitro. To elucidate the molecular mechanisms triggered by IL-3 we studied the expression of cell cycle-related genes in a recently established human IL-3-dependent clone (M-07e). No changes in the level of expression of early (c-myc), mid (ornithine decarboxylase), or mid-late G1 (p53, c-myb) cell cycle genes were detected after restoration of IL-3 in deprived cells. The fact that only late G1-S-phase genes [proliferating cell nuclear antigen (PCNA) thymidine kinase (TK), histone H3] are modulated by IL-3 suggests that this factor may control human cell proliferation by acting at the G1-S boundary.

Cell Division↗
PubMed1989

Lymphokine-activated killer (LAK) cells inhibit the clonogenic growth of human leukemic stem cells.

The effect of lymphokine-activated killer (LAK) cells on the in vitro clonogenic capacity of acute myeloid leukemia (AML) blasts was investigated in a semisolid medium assay. The leukemic clonogenic capacity of 11 AML cases, selected on the basis of their ability to grow in vitro, was highly reduced following overnight preincubation with LAK effectors. The degree of colony inhibition, which ranged between 66% and 98% (mean 83.8% +/- 11.4 SD), was quantitatively greater than by 51Cr release, which gave rise to lytic values between 5% and 65% (mean 43.2% +/- 19.2 SD). The demonstration that the clonogenic inhibition was still induced following a shorter pre-incubation period (4 hours) suggests that the effect is unlikely to be due only to the generation of cytotoxic activity during the incubation time. The possibility that LAK cells may be employed in the management of residual disease is strengthened by the evidence that the clonogenic potential of samples containing as few as 20% and 14.3% leukemic cells could be almost completely abolished by LAK effectors. These findings further point the possible role of adoptive immunotherapy with interleukin 2/LAK cells in the treatment of patients with acute leukemia.

Adult↗
PubMed1988

Interleukin 3 enhances the cytotoxic activity of 1-beta-D-arabinofuranosylcytosine (ara-C) on acute myeloblastic leukaemia (AML) cells.

We have evaluated the possibility of enhancing the cell killing effect of ara-C on AML blasts by increasing their proliferative activity with haemopoietic growth factors. Leukaemic cells from 10 AML patients were incubated for 3 d in liquid culture in the presence or in the absence of the human recombinant growth factors IL-1 beta (5 U/ml) and IL-3 (3 U/ml), and subsequently exposed to ara-C (3 micrograms/ml) for the last 24 h. The number of residual leukaemic stem cells was evaluated by a clonogenic assay in semisolid medium. The results showed that ara-C exposure inhibits the proliferation of a higher proportion of clonogenic cells in cultures pretreated with growth factors than in the controls (mean inhibitory values: in the absence of growth factors = 49.8%; with IL-1 beta = 58.3%; with IL-3 78.9%). The effect was statistically significant only when IL-3 was used as a growth factor. The results suggest that haemopoietic growth factors may help to improve the therapeutic index of cytostatic agents.

Cell Survival↗
PubMedDate not supplied

Evaluation and management of the "new" lymphoma entities: mantle cell lymphoma, lymphoma of mucosa-associated lymphoid tissue, anaplastic large-cell lymphoma, and primary mediastinal B-cell lymphoma.

Non-Hodgkin's lymphomas (NHL) represent a major health problem worldwide, and incidence has been on the rise continuously for the last few decades. It is estimated that approximately 55,000 new cases of NHL will be diagnosed in the United States in 1998 and that slightly fewer than 25,000 patients will die of treatment failure or recurrent disease. The rising incidence of NHL is related not only to the acquired immunodeficiency syndrome epidemic but to also a steady increase in the number of cases diagnosed in older patients without immunosuppression. The new pathologic classification of NHL (revised European-American lymphoma classification, REAL) developed by the International Lymphoma Study Group (ILSG) is already resulting in more accurate disease-specific epidemiologic and clinical investigations. These studies have brought a new awareness of the existence and the relative prevalence of discrete NHL subtypes that appear to predominate among patients in different populations according to age, sex, geographic distribution, and predisposing conditions. This developing database has also the potential to result in the discovery of specific environmental causes, predisposing genetic factors, and therapeutic approaches. Some of the entities defined in the REAL classification, such as follicular lymphomas, diffuse B large-cell lymphomas, and T-cell lymphoblastic lymphomas, were already well described in the older classification systems (Kiel and Working Formulation). Others, such as mantle cell lymphoma, (MCL) anaplastic large-cell lymphoma (ALCL), lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), and primary mediastinal B-cell lymphoma (PMBCL) are relatively new members of the family, and accurate data on their clinicopathologic features and natural histories have only recently begun to emerge. This review presents in detail the most recent data on the clinical presentation of, diagnostic evaluation of, and treatment options for the most common of the new NHL entities: MCL, MALT lymphoma, CD30+ (Ki-1+) ALCL, and PMBCL. These four entities combined represent approximately 20% of all cases of NHL and exemplify well the broad clinicopathologic spectrum of NHL and the diagnostic and therapeutic challenges facing those who care for patients affected by these conditions.

Adult↗
PubMedDate not supplied

Haematologic abnormalities in the acquired immunodeficiency syndrome.

During the clinical history of HIV infection, haematological abnormalities represent a common finding which not only contributes to worsening the clinical condition but also limit the use of antibacterial as well as antiviral agents. On the basis of the regulatory role played by the immune system on haemopoiesis, in the present review the foremost derangements of the immunoregulatory circuits are first discussed. The main functional and quantitative defects of peripheral blood erythrocytes, granulocytes, platelets and monocytes are then analysed, and the different bone marrow pictures observed during the progression of the disease are described. To elucidate the physiophatogenetic mechanisms responsible for bone marrow and peripheral cytopenia, the most relevant in vitro studies are reported and discussed. These studies suggest that both a direct cytopathic effect of HIV on haemopoietic progenitors and an immune system mediated mechanism are involved. In view of the HIV selective tropism for lymphocytes and macrophages, which are a major source of haemopoietic growth factors, the new therapeutical strategies for the treatment of cytopenias based on exogenous administration of these cytokines, alone or in combination with antiviral drugs, are briefly reported.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[Renal artery aneurysms. Our experience].

A retrospective study concerned 8 aneurysms of the renal artery. There were 6 females and 2 males with a mean age of 50.7 years. Diagnosis was obtained angiographically in all cases, in 7 during a reno-vascular work-up for hypertension and fortuitously in 1 after angiography for arteriopathy of the lower limbs. The aneurysm was due to fibromuscular dysplasia in 5 cases and to atheromatous lesions in 3. Reconstruction techniques and their indications were analyzed on the basis of a review of the literature. Outcome for hypertensive patients are the same for the different techniques.

Anastomosis, Surgical↗