The impact of high-dose sodium selenite therapy on Bcl-2 expression in adult non-Hodgkin's lymphoma patients: correlation with response and survival.

The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the expression of Bcl-2 in patients with non-Hodgkin's lymphoma (NHL). Fifty patients with newly diagnosed NHL were randomly divided into two groups. Group A-I received standard chemotherapy whereas group A-II received adjuvant sodium selenite 0.2 mg kg-1 day-1 for 30 days in addition to chemotherapy. Enzyme-linked immunosorbent assay was used to assess Bcl-2 at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant decline of Bcl-2 level after therapy in group A-II (8.6 +/- 6.9 ng/ml vs 3 6.9 +/- 7.9 ng/ml, P < 0.05). Also, complete response reached 60% in group A-II compared to 40% in group A-I. Significant increase in CD4/CD8 ratio was noticed in group A-II compared to group A-I after therapy (1.45 +/- 0.36 vs 1.10 +/- 0.28 p 0.04). Overall survival time in months was significantly longer in complete remission patients in group A-II (21.87 +/- 1.41) compared to group A-I (19.70 +/- 1.95) (p = 0.01). It is concluded that sodium selenite administration at the dosage and duration chosen acts as a down regulator of Bcl-2 and improves clinical outcome.

Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients.

The present study was undertaken to explore the effect of the administration of high doses of sodium selenite on apoptosis in polymorphonuclear leukocytes in patients with non-Hodgkin's lymphoma. Thirty patients with newly diagnosed non-Hodgkin's lymphoma were randomly divided into two groups. Group I was treated with chemotherapy and group II received 0.2 mg/kg/d sodium selenite in addition to chemotherapy. Flow cytometry was used for the monitoring of apoptosis on peripheral blood neutrophils at the time of diagnosis and after treatment in both groups of patients. Sodium selenite administration resulted in a significant reduction in neutrophils apoptosis (82+/-10% vs 32+/-18%, p<0.05) and this was associated with significant reduction in infection rate following chemotherapy (67% vs 20%, p<0.05). Also, significant improvement in cardiac ejection fraction was observed (62+/-4% vs 69+/-5% p<0.05). It is concluded that sodium selenite administration at the dosage chosen acts as a cytoprotective agent, alleviating side effects and immunosuppressive effects of cytotoxic chemotherapeutic agents.

Expression of indoleamine 2,3-dioxygenase in acute myeloid leukemia and the effect of its inhibition on cultured leukemia blast cells.

Indoleamine 2,3-dioxygenase (IDO), a catabolizing enzyme of tryptophan, is a novel immunosuppressive agent blocking T-cell activation in neoplastic cells, including acute myeloid leukemia (AML) cells. IDO inhibitors as 1-methyl tryptophan (1MT) can abrogate IDO enzymatic activity and may result in an effective immune response. Mononuclear cells (MNCs) were separated from peripheral blood of 25 AML patients and 25 normal adults. IDO expression was detected by RT-PCR and its enzymatic activity by a colorimetric method. MNCs were cultured and the effects of Adriamycin, 1MT and a mixture of both on blast and lymphocyte cell counts after 24 and 72 h were detected. IDO mRNA and activity were detected in 52% of patients and absent in normal subjects. There was a significant correlation between IDO mRNA expression and its enzymatic activity in AML. IDO activity was correlated positively with patient's ages and negatively with hemoglobin levels. There was a significant inhibition of blast cells proliferation with Adriamycin and more inhibition when combined with 1MT. The inhibition was more after 72 h more than 24 h of culture. However, using 1MT alone showed no significant inhibitory effect on blast cells, with a significant increase in lymphocyte counts. Our study confirms the role of indoleamine 2,3-dioxygenase in tumor-induced immune tolerance and points to the possible benefit of 1-methyl tryptophan as immunotherapeutic enhancing the anticancer effects of traditional chemotherapeutics.

Changing therapy from Glivecto a "copy" imatinib results in a worsening of chronic myeloid leukemia disease status: two case reports.

INTRODUCTION: Imatinib mesylate (Glivec((R))/Gleevec((R))) is the standard first-line therapy for the treatment of chronic myeloid leukemia due to its high hematologic, cytogenetic, and molecular response rates and favorable long-term safety profile. A copy version of imatinib is currently available in several countries. We report on two cases of CML who were originally treated with Glivec in Egypt and subsequently switched to the copy drug CASE PRESENTATION: Case one was a 35-year old female with chronic myeloid leukemia in blast crisis who began treatment with combination chemotherapy and Glivec. The patient achieved and maintained a complete hematologic response and continued on Glivec 400 mg/day. In March 2007, she was switched to the copy drug In September 2007, the patient presented in hematologic relapse. At this time, treatment with chemotherapy in combination with Glivec 400 mg/day was resumed. The patient quickly achieved, and maintained, complete hematologic response on Glivec 400 mg/day. The second patient was a 64-year old male with chronic myeloid leukemia in blast crisis who began treatment with truncated chemotherapy in combination with Glivec 400 mg/day. After 6 months, the patient achieved a partial hematologic response and continued on alternating cycles of chemotherapy with continuous administration of Glivec 400 mg/day. The patient received Glivec from January 2006 to February 2007, after which time he was switched to the copy drug. In November 2007, he presented with upper gastrointestinal bleeding and multiple gastric erosions and died the same day. CONCLUSION: The safety and efficacy of the copy drug has not been established in randomized clinical trials. It is unknown whether patients, who respond to Glivec and then switch to copy versions of imatinib, will tolerate the copy drug and maintain their response.

Selenium and glutathione peroxidase status in adult Egyptian patients with acute myeloid leukemia.

This study was undertaken to evaluate selenium (Se) and glutathione peroxidase (GPX) status in patients with newly diagnosed acute myeloid leukemia (AML) before and after induction therapy. Twenty-five patients with newly diagnosed AML and 15 healthy age- and sex-matched control subjects were included in this study. Serum Se level by the graphite furnace atomic absorption spectrometric technique and GPX activity by an adaptation of Beutler method was performed for the patients before and after receiving the induction therapy. Serum Se level was significantly lower in patients with AML versus control subjects (63.1 ± 8.8 versus 77 ± 8.8 µg/L before therapy with a P value <0.01 and 69 ± 6.8 versus 77 ± 8.8 µg/L after therapy with a P value <0.01).GPX activity was significantly lower in patients with AML versus control subjects (1.6 ± 0.4 versus 3.4 ± 0.7 µ/g protein pretreatment with a P value <0.01 and 1.9 ± 0.6 versus 3.4 ± 0.7 µ/g protein post induction treatment with P value <0.01).Se level and GPX activity significantly increased in AML patients after treatment. Patients who accomplished complete remission after induction harbored significantly higher Se levels than resistant patients before and after treatment. There was no significant correlation between serum Se level and GPX activity. Decreased Se level and reduced GPX activity in AML patients support the association of carcinogenesis and subnormal Se states.

High-dose sodium selenite can induce apoptosis of lymphoma cells in adult patients with non-Hodgkin's lymphoma.

The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the apoptosis of lymphoma cells in patients with non-Hodgkin's lymphoma (NHL). Forty patients with newly diagnosed NHL were randomly divided into two groups. Group I received standard chemotherapy, whereas group II received adjuvant sodium selenite 0.2 mg kg(-1) day(-1) for 7 days in addition to chemotherapy. Flow cytometry was used for monitoring of lymphoma cells apoptosis at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant increase in percentage of apoptotic lymphoma cells after therapy in group II (78.9 +/- 13.3% versus 58.9 +/- 18.9%, p < 0.05). In addition, patients who received sodium selenite treatment demonstrated statistically significant increase in percentage of reduction of cervical and axillary lymphadenopathy, decrease in splenic size, and decreased percentage of bone marrow infiltration. Also, we found a statistically significant decrease in cardiac ejection fraction (CEF) in group I and no reduction in CEF in patients who received sodium selenite 'group II', denoting the cardioprotective effect of selenium. It is concluded that sodium selenite administration at the dosage and duration chosen has synergistic effect to chemotherapy in inducing apoptosis and, consequently, could improve clinical outcome.