Treatment of elderly patients with AML: results of an individualized approach.

Background And Objective: AML treatment in elderly patients must be individualized according to their characteristics. We report the results of a tailored treatment approach in all consecutive AML patients older than 60 years diagnosed at our institution during the last 2 years.

Design And Methods: Between December 1994 and December 1996, 43 AML patients over 60 years of age (median, 72; range 61-89) were managed according to their performance status (PS) and associated diseases.

Hematopoietic stem cell transplantation in chronic lymphocytic leukemia: a report of 12 patients from a single institution.

Background: Stem-cell transplantation is a reasonable therapeutic approach for younger patients with high-risk CLL.

Patients And Methods: Twelve patients (seven males; median age 47 years, range 29-51) with high-risk CLL underwent transplantation (allo, n = 7; auto, n = 5). The conditioning regimen consisted of cyclophosphamide and total body irradiation in 11 patients, and BEAC in the remaining one.

sst2 somatostatin receptor mediates negative regulation of insulin receptor signaling through the tyrosine phosphatase SHP-1.

We have previously reported in Chinese hamster ovary (CHO) cells expressing sst2 that activation of the sst2 somatostatin receptor inhibits insulin-induced cell proliferation by a mechanism involving stimulation of a tyrosine phosphatase activity. Here we show that the tyrosine phosphatase SHP-1 was associated with the insulin receptor (IR) at the basal level. Activation of IR by insulin resulted in a rapid and transient increase of tyrosine phosphorylation of IR, its substrates IRS-1 and Shc, and also of SHP-1.

The changing profile of idiopathic myelofibrosis: a comparison of the presenting features of patients diagnosed in two different decades.

In an attempt to ascertain whether the presenting features of idiopathic myelofibrosis (IM) have changed in recent years, 2 groups of patients diagnosed with IM in a single institution in different time periods were compared. The first group included 53 patients diagnosed from 1975 to 1986, and the second included 56 patients diagnosed from 1987 to 1997. No significant differences were observed between the two groups with regard to age, gender, delay from first symptoms to disease diagnosis, peripheral blood hematological values and serum biochemical parameters.

[Idiopathic myelofibrosis: initial features, evolutive patterns and survival in a series of 106 patients].

Background: Idiopathic myelofibrosis (IM) is an infrequent myeloproliferative disorder with few large series published in the medical literature. Information on the characteristics of more recently diagnosed patients with IM is scarce.

Patients And Methods: The initial features, evolutive patterns and survival from 106 patients diagnosed with IM in a single institution between 1975 and 1996 were analyzed.

'Lymphoid' blast crisis of chronic myeloid leukaemia is associated with distinct clinicohaematological features.

It has been suggested that in blast crisis (BC) of chronic myeloid leukaemia (CML) the clinical and laboratory features of patients with 'lymphoid' phenotype differ from those of patients with non-lymphoid BC. In order to assess any differences, 97 patients consecutively diagnosed with BC that followed a known chronic phase of CML were analysed. 19 patients had 'lymphoid' BC: in 17 the blasts expressed a B-lineage phenotype: in the remaining two they corresponded to T lymphoblasts.

Simultaneous occurrence of B-cell chronic lymphocytic leukemia and chronic myeloid leukemia with further evolution to lymphoid blast crisis.

The coexistence of chronic myeloid leukemia (CML) and B-cell chronic lymphocytic leukemia (CLL) in the same patient is rare. A 71-year-old woman developed a B-lineage lymphoid blast crisis at 18 months after diagnosis of Ph-positive CML. At this time, a lymphoid cell population with morphologic and immunophenotypic features of CLL was demonstrated.

Expression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy.

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma, successful treatment with the somatostatin analog octreotide was conducted during the first month and the second half of pregnancy without side-effects on placental and fetal development. As observed in normal pregnancy, both serum placental GH and IGF-I levels increased throughout pregnancy and dropped sharply after delivery.

The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling.

Activation of the somatostatin receptor sst2, a member of the Gi protein-coupled receptor family, results in the stimulation of a protein-tyrosine phosphatase activity involved in the sst2-mediated growth inhibitory signal. Here, we report that SHP-1, a cytoplasmic protein-tyrosine phosphatase containing two Src homology 2 domains constitutively associated with sst2 as evidence by coprecipitation of SHP-1 protein with sst2, in Chinese hamster ovary cells coexpressing sst2 and SHP-1. Activation of sst2 by somatostatin resulted in a rapid dissociation of SHP-1 from sst2 accompanied by an increase of SHP-1 activity.

Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5.

We investigated cell proliferation modulated by cholecystokinin (CCK) and somatostatin analogue RC-160 in CHO cells bearing endogenous CCKA receptors and stably transfected by human subtype sst5 somatostatin receptor. CCK stimulated cell proliferation of CHO cells. This effect was suppressed by inhibitor of the soluble guanylate cyclase, LY 83583, the inhibitor of the cGMP dependent kinases, KT 5823, and the inhibitor of mitogen-activated protein (MAP) kinase kinase, PD 98059.

Differential effect of a low-molecular-weight heparin (dalteparin) and unfractionated heparin on platelet interaction with the subendothelium under flow conditions.

Effects of heparins on platelet function are controversial, but perfusion studies, that simulate physiological conditions, might help to explain their clinical behaviour. We used a perfusion system to test the effect unfractionated heparin and a low-molecular-weight heparin (dalteparin, Fragmin) on platelet adhesion promoted by a damaged vascular surface. Normal blood samples containing increasing concentrations of unfractionated heparin and dalteparin were perfused through annular chambers containing enzymatically denuded rabbit aorta segments (5 min at 800 sec-1).

Identification of 'short-lived' and 'long-lived' patients at presentation of idiopathic myelofibrosis.

To contribute to a better knowledge of the prognosis of idiopathic myelofibrosis (IM), the prognostic value of the presenting features in 106 patients diagnosed with IM at a single institution during a 21-year period was retrospectively analysed. Median survival was 59.4 months (95% CI 40.

Atypical central neurocytoma.

The proliferative potential of central neurocytomas was determined in a biopsy series of 36 cases and compared with clinical outcome. The mean size of the growth fraction, as determined by MIB-1 labeling index (MIB-1 LI) at first biopsy, was 2.8 +/- 2.

sst2 somatostatin receptor expression reverses tumorigenicity of human pancreatic cancer cells.

Among the five cloned somatostatin receptor subtypes (sst1 to sst5), sst2 mediates the antiproliferative effect of somatostatin analogues in vitro. Somatostatin analogues have been shown to inhibit cell growth in vitro and in vivo in pancreatic cancer models that expressed sst2. We recently demonstrated the loss of sst2 gene expression in human pancreatic adenocarcinomas and most of the derived pancreatic cancer cell lines.

Screening for neuroblastoma in France: methodological aspects and preliminary observations.

A pilot study of neuroblastoma mass screening was initiated in January 1990 in the Rhône French district. The expected number of births per year is 26,000. The study is designed for a 5-year period with three major goals: 1) measurement of the compliance rate of a voluntary test at 4 months of age; 2) evaluation of the technical value of high-pressure liquid chromatography (HPLC) as a screening method; and 3) detailed biological characterization of all detected tumors.

Tumors associated with p53 germline mutations: a synopsis of 91 families.

Although inherited p53 mutations are present in all somatic cells, malignant transformation is limited to certain organs and target cells. The analysis of 475 tumors in 91 families with p53 germline mutations reported since 1990 shows that breast carcinomas are most frequent (24.0%), followed by bone sarcomas (12.

[Chronic myeloid leukemia after renal transplantation: report of a new case and review of the bibliography].

The increase in cancer incidence in renal transplant recipients is a well recognized fact, which has been related to post-transplant immunosuppressive therapy. Solid tumors, skin cancer and non-Hodgkin's lymphomas account for most of the neoplasms in these patients, whereas chronic myeloproliferative disorders are infrequent. A patient is reported who developed chronic myelogenous leukemia (CML) six years after renal transplantation, which was followed by immunosuppressive with azathioprine, and the published data on such an association are reviewed.

A 5-year (1990-1994) neuroblastoma screening feasibility study in France. Methodology and preliminary observations.

Introduction: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990-1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhône district (1.5 M inhabitants, 26,000 births per year).

Comparison of the diagnostic and prognostic value of biological markers in neuroblastoma. Proposal for a common methodology of analysis. SENSE group.

Background: The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. Screening programs have been initiated in infants of less than one year of age, based on the hypothesis that neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. However, recent analyses suggest that most cases discovered by screening are low stage tumors considered as dysembryogenetic residues devoid from major abnormalities and that high-grade tumors with molecular abnormalities are unrelated diseases.

Molecular mechanisms of antiproliferative effect of somatostatin: involvement of a tyrosine phosphatase.

A protein of 66 kd immunoreactive to anti-tyrosine phosphatase (PTP1C) antibodies coeluted with, and so may be associated with, somatostatin receptors (ssts) from rat pancreatic membranes. Also, anti-PTP1C antibodies immunoprecipitated functional ssts from pancreatic membranes, suggesting a PTP1C protein can associate with ssts at the membrane level. Somatostatin analog RC 160 had good affinity for sst2,3 and sst5 (IC50 = 0.

[Treatment with fludarabine of lymphoid neoplasms with low grade malignity resistant to treatment or in relapse].

Background: In the last years the treatment of patients with chronic lymphocytic leukemia (CLL) and low-grade lymphomas (NHL) has changed because of the introduction of new agents, mainly the purine analogs. We report our experience with fludarabine in patients with indolent lymphoid malignancies that were previously treated with conventional agents.

Patients And Methods: Twenty patients were studied.

Induction of a negative autocrine loop by expression of sst2 somatostatin receptor in NIH 3T3 cells.

The somatostatin receptor subtype sst2 mediates both activation of a tyrosine phosphatase activity and inhibition of cell proliferation induced by somatostatin analogues. In the absence of exogenous ligand, expression of sst2 in NIH 3T3 cells resulted in inhibition of cell growth. Polymerase chain reaction coupled to reverse transcription demonstrated that expression of sst2 in NIH 3T3 cells stimulated the expression of preprosomatostatin mRNA accompanied by a production of immunoreactive somatostatin-like peptide which corresponded predominantly to somatostatin 14.

Multiple primary cancers and estimation of the incidence rates and trends.

The use of different registration rules from one registry to another, both generally and also for paired organs, leads to variations in the proportion of multiple primary cancers: in men, from 0.4 to 4.9% for the colon, 0.