Pterostilbene downregulates BCR/ABL and induces apoptosis of T315I-mutated BCR/ABL-positive leukemic cells.

In this study, we examined the antileukemic effects of pterostilbene, a natural methylated polyphenol analog of resveratrol that is predominantly found in berries and nuts, using various human and murine leukemic cells, as well as bone marrow samples obtained from patients with leukemia. Pterostilbene administration significantly induced apoptosis of leukemic cells, but not of non-malignant hematopoietic stem/progenitor cells. Interestingly, pterostilbene was highly effective in inducing apoptosis of leukemic cells harboring the BCR/ABL fusion gene, including ABL tyrosine kinase inhibitor (TKI)-resistant cells with the T315I mutation.

Comprehensive Genetic Search to Clarify the Molecular Mechanism of Drug Resistance Identifies ASCL2-LEF1/TSPAN8 Axis in Colorectal Cancer.

Background: Treatment-resistance genes limiting anticancer therapy have not been well clarified in colorectal cancer (CRC). We explored gene expression profiles to identify biomarkers for predicting treatment resistance to an anticancer drug in CRC.

Methods: Six CRC cell lines were treated with phenylbutyrate (PB).

Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells.

Although vitamin C (VC) has recently garnered interest as an alternative cancer therapy, its clinical effects remain controversial. It was recently reported using in vitro prostate cancer cell lines that excess extracellular iron (EEI) diminishes anti-cancer effects of VC, promoting the decomposition of hydrogen peroxide (HO) generated by VC. Here we demonstrated that EEI diminished the inhibitory effect of VC on the survival of K562 human leukemic cells in vitro, by reducing the amount of HO and abrogating the apoptosis pathways induced by VC.

Epigenetic regulation of ZEB1-RAB25/ESRP1 axis plays a critical role in phenylbutyrate treatment-resistant breast cancer.

Phenylbutyrate (PB) is a histone deacetylase antagonist that also exhibits antitumor activity. In this study, we used 7 breast cancer cell lines to identify biomarker candidates that predict PB sensitivity in breast cancer.Comprehensive gene expression profiles were compared using microarrays, and the importance of the identified genes to PB sensitivity was confirmed in gene transfection experiments.

Phase I Clinical Trial of Intravenous L-ascorbic Acid Following Salvage Chemotherapy for Relapsed B-cell non-Hodgkin's Lymphoma.

Purpose: To determine the safety and the appropriate dose of intravenous l-ascorbic acid (AA) in conjunction with chemotherapy for patients with relapsed lymphoma.

Patients And Methods: Patients with relapsed CD20-positive B-cell non-Hodgkin's lymphoma, who were going to receive the CHASER regimen as salvage therapy, were enrolled and treated with escalating doses of AA administered by drip infusion after the 2nd course of the CHASER regimen. The target plasma concentration immediately after AA administration was >15 mM (264 mg/dl).

High concentrations of L-ascorbic acid specifically inhibit the growth of human leukemic cells via downregulation of HIF-1α transcription.

We examined the antileukemic effects of high concentrations of L-ascorbic acid (high AA) on human leukemic cells. In vitro, high AA markedly induced apoptosis in various leukemic cell lines by generating hydrogen peroxide (H2O2) but not in normal hematopoietic stem/progenitor cells. High AA significantly repressed leukemic cell proliferation as well as neoangiogenesis in immunodeficient mice.

Reactive hemophagocytic syndrome in a case of systemic lupus erythematosus that was diagnosed by detection of hemophagocytosing macrophages in peripheral blood smears.

A 38-year-old woman with pancytopenia and liver dysfunction was diagnosed with active systemic lupus erythematosus (SLE). On days 9 and 10 of admission, peripheral blood smears showed macrophages phagocytosing platelets, and reactive hemophagocytic syndrome (HPS) was diagnosed. Hemophagocytic syndrome was successfully treated with high-dose prednisolone therapy and one course of methylprednisolone pulse therapy.

[Close correlations between CD20 expression, a small mature plasma cell morphology and t(11 ; 14) in multiple myeloma].

Stratification of patients with multiple myeloma (MM) may be important. We investigated 138 MM patients, focusing on correlations between CD20 expression, 11 ; 14 translocation, morphology of MM cells, cyclin D1 immunostaining, and the prognosis. About 15% of patients (7/47cases) were CD20-positive, small mature MM cells, with positive cyclin D1 in the nucleus and 11; 14 translocation.

Clinical implications of abnormalities of chromosomes 1 and 13 in multiple myeloma.

Stratification of patients with multiple myeloma according to clinical severity was attempted by chromosomal analysis of 180 bone marrow specimens from 79 patients. The 79 patients were hospitalized and treated between 1994 and 1999. Abnormalities of chromosome 1 were detected at the initial medical examination in 8 (10%) of the 79 patients and were found during follow-up in additional 3 patients.

Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are characterized by peripheral blood cytopenias despite hypercellularity of the bone marrow regarded as the result of ineffective hematopoiesis mainly caused by apoptosis. In this study, we examined the role of tumor necrosis factor (TNF)-induced apoptosis in the bone marrow cells of MDS patients. The constitutive expression of mRNA for TNF receptors (TNFR), including TNFRI and TNFRII, and the adapter molecules, such as the TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor interacting protein (RIP) and TNF receptor-associated factor 2 (TRAF-2) were analyzed by reverse transcriptase (RT)-PCR in bone marrow samples from control, MDS and AML cases.

Aplastic anaemia with 13q-: a benign subset of bone marrow failure responsive to immunosuppressive therapy.

In an attempt to determine the pathological significance of a long arm deletion of chromosome 13 (13q-) in bone marrow failure syndrome, we reviewed the clinical records of nine patients who were initially diagnosed with aplastic anaemia due to bone marrow hypoplasia without dysplasia. Six patients responded to immunosuppressive therapy and the other three improved with steroids. None of the patients developed acute leukaemia (follow up: 54-129 months) and the estimated 5-year survival was 78%.