404 research outputs found
Somatostatin receptor scintigraphy in cutaneous malignant lymphomas
Background: Lymphoid cells may express somatostatin receptors (SS-Rs) on their cell surface.
Therefore radiolabeled somatostalin analogues may be used to visualize SS-R-positive
lymphoid neoplasms in vivo. Exact staging is the basis for treatment decisions in cutaneous
malignant lymphoma. We considered the possibility that SS-R scintigraphy might offer a
clinically useful method of diagnostic imaging in patients with cutaneous malignant
lymphoma.
Objective: We evaluated SS-R scintigraphy in comparison with conventional staging methods
in the staging of cutaneous malignant lymphoma.
Methods: We conducted a prospective study in 14 consecutive patients with histologically
proven cutaneous malignant lymphoma. SS-R scintigraphy was compared with physical, radiologic,
and bone marrow examinations. Lymph node excisions were performed in patients
with palpable lymph nodes.
Results: SS-R scintigraphy was positive in the lymph nodes in all four patients with malignant
lymph node infiltration and negative in the three patients with dermatopathic lymphadenopathy.
In two patients, previously unsuspected lymphoma localizations were visualized by
SS-R scintigraphy. In only three patients all skin lesions were visualized by SS-R scintigraphy;
these three patients had not been treated with topical corticosteroids. SS-R scintigraphy
failed to detect an adrenal mass in one patient and bone marrow infiltration in two patients.
Conclusion: SS-R scintigraphy may help distinguish dermatopathic lymphadenopathy from
malignant lymph node infiltration in patients with cutaneous malignant lymphoma
Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells
Stem cell factor (SCF) has an important role in the proliferation,
differentiation, survival, and migration of hematopoietic cells. SCF
exerts its effects by binding to cKit, a receptor with intrinsic tyrosine
kinase activity. Activation of phosphatidylinositol 3'-kinase (PI3-K) by
cKit was previously shown to contribute to many SCF-induced cellular
responses. Therefore, PI3-K-dependent signaling pathways activated by SCF
were investigated. The PI3-K-dependent activation and phosphorylation of
the tyrosine kinase Tec and the adapter molecule p62Dok-1 are reported.
The study shows that Tec and Dok-1 form a stable complex with Lyn and 2
unidentified phosphoproteins of 56 and 140 kd. Both the Tec homology and
the SH2 domain of Tec were identified as being required for the
interaction with Dok-1, whereas 2 domains in Dok-1 appeared to mediate the
association with Tec. In addition, Tec and Lyn were shown to phosphorylate
Dok-1, whereas phosphorylated Dok-1 was demonstrated to bind to the SH2
domains of several signaling molecules activated by SCF, including Abl,
CrkL, SHIP, and PLCgamma-1, but not those of Vav and Shc. These findings
suggest that p62Dok-1 may function as an important scaffold molecule in
cKit-mediated signaling
Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia
BACKGROUND: Sensitization of leukemic cells with hematopoietic growth
factors may enhance the cytotoxicity of chemotherapy in acute myeloid
leukemia (AML). METHODS: In a multicenter randomized trial, we assigned
patients (age range, 18 to 60 years) with newly diagnosed AML to receive
cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle
2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or
without G-CSF (319). G-CSF was given concurrently with chemotherapy only.
Idarubicin and amsacrin were given at the end of a cycle to allow the
cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to
have a greater effect. The effect of G-CSF on disease-free survival was
assessed in all patients and in cytogenetically distinct prognostic
subgroups. RESULTS: After induction chemotherapy, the rates of response
were not significantly different in the two groups. After a median
follow-up of 55 months, patients in complete remission after induction
chemotherapy plus G-CSF had a higher rate of disease-free survival than
patients who did not receive G-CSF (42 percent vs. 33 percent at four
years, P=0.02), owing to a reduced probability of relapse (relative risk,
0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not
significantly improve overall survival (P=0.16). Although G-CSF did not
improve the outcome in the subgroup with an unfavorable prognosis, the 72
percent of patients with standard-risk AML benefited from G-CSF therapy
(overall survival at four years, 45 percent, as compared with 35 percent
in the group that did not receive G-CSF [relative risk of death, 0.75; 95
percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival,
45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence
interval, 0.55 to 0.90; P=0.006). CONCLUSIONS: Sensitization of leukemic
cells with growth factors is a clinically applicable means of enhancing
the efficacy of chemotherapy in patients with AML
Commentaire
Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch–Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (‘primary refractoriness’). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML
Density fluctuations and single-particle dynamics in liquid lithium
The single-particle and collective dynamical properties of liquid lithium
have been evaluated at several thermodynamic states near the triple point. This
is performed within the framework of mode-coupling theory, using a
self-consistent scheme which, starting from the known static structure of the
liquid, allows the theoretical calculation of several dynamical properties.
Special attention is devoted to several aspects of the single-particle
dynamics, which are discussed as a function of the thermodynamic state. The
results are compared with those of Molecular Dynamics simulations and other
theoretical approaches.Comment: 31 pages (in preprint format), 14 figures. Submitted to Phys. Rev.
Aberrant DNA hypermethylation of the ITIH5 tumor suppressor gene in acute myeloid leukemia
Epigenetic mechanisms such as DNA hypermethylation and modifications of histone amino acids are known to play an important role in the control of gene expression both in normal human development and tumorigenesis. Hypermethylation of CpG islands within promoter regions of tumor suppressor genes is associated with transcriptional inactivation and represents, in addition to genetic aberrations, an important mechanism of gene silencing in the pathogenesis of human cancer. Inter-α-trypsine inhibitors (ITIs) are a family of serine protease inhibitors consisting of one light chain (bikunin) and two heavy chains (ITI heavy chains, ITIHs). ITIHs stabilize the extracellular matrix (ECM) by interacting with hyaluronic acid, which is a major ECM component. Hypermethylation in the upstream region of the promoter-associated CpG island of ITIH5, the most recently described member of the ITIH family, has been previously detected in breast cancer and was associated with an adverse outcome. In this study, we determined the DNA methylation status of the promoter region near the transcription start site of the ITIH5 tumor suppressor gene in leukemia cell lines and primary samples from patients with acute myeloid leukemia (AML) as well as the potential use of demethylating agents to restore a demethylated state of the promoter. Aberrant ITIH5 promoter hypermethylation occurred in 15 of 104 (14.4%) diagnostic AML samples. There were no statistically significant correlations between the ITIH5 methylation status and clinical prognostic parameters. Our results indicate that aberrant ITIH5 promoter hypermethylation is a novel epigenetic event in AML
Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells
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