Synergism between rViscumin and cisplatin is not dependent on ERCC-1 expression.

Interactions between recombinant mistletoe lectin (rViscumin) and anticancer drugs were investigated in vitro. rViscumin enhanced the cytotoxic effects of vincristine, mafosfamide, idarubicin and cisplatin in the human leukemia cell lines K562 and KG1a. In human marrow progenitor cells, rViscumin inhibited colony formation and did not exert any protective activity against cisplatin-induced inhibition of clonogenicity. Quantitative real-time reverse transcription polymerase chain reaction analysis revealed that cisplatin treatment of K562 cells resulted in a 1.9-fold increase in mRNA expression of the nucleotide excision repair gene ERCC-1. This upregulation was not prevented when cells were post-incubated with rViscumin. Our study provides evidence that rViscumin is capable of enhancing cytotoxicity of anticancer agents in vitro. This synergism appears to be independent of transcriptional activity of DNA repair relevant genes.

Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells.

In addition to signaling proliferation, growth factors may contribute to the persistence of hematopoietic tumors upon chemotherapeutical challenge. In multiple myeloma, malignant growth is mediated either by paracrine interleukin-6 (IL-6) elaborated by bone marrow stromal cells or via autocrine loops by malignant myeloma cells themselves. Although melphalan is one of the most active drugs in this tumor entity, the development of drug resistance frequently impedes cure of patients by attenuating melphalan-induced DNA-damage. We analyzed whether IL-6 protects XG-1 cells and plasma cells of a patient suffering from end-stage multiple myeloma (plasma cell leukemia) from melphalan with respect to DNA damage and DNA repair. Investigating the housekeeping gene glucose-6-phosphate dehydrogenase (G6PD) by using a PCR-stop assay, we found that there was more DNA damage in the G6PD gene of IL-6 deprived XG-1 and the patient's plasma cells, respectively, than in those with IL-6 supplementation. After cessation of melphalan exposure and 24 hours post-incubation in melphalan-free medium, DNA repair was observed in the patient's plasma cells but not in XG-1 cells. There was more DNA repair with IL-6 addition than without IL-6 addition. Similarly, the apoptotic cell fractions, as measured by flow cytometry, were lower if IL-6 was added to the medium. These results indicate that IL-6 may contribute to drug resistance in multiple myeloma.

[HbH disease--a rare differential diagnosis in a patient with anemia and abdominal pain]. / HbH-Krankheit--eine seltene Differentialdiagnose bei Anämie und Oberbauchschmerzen.

CASE REPORT: A 45-year-old Vietnamese male was admitted to hospital with severe hypochromic anemia and acute abdominal pain. The peripheral blood smear showed extreme anisocytosis and poikilocytosis as well as teardrops and target cells. Hemoglobin electrophoresis and brilliant cresyl blue staining revealed hemoglobin H (HbH) disease with an infection-associated hemolytic crisis. CONCLUSION: In the diagnostic workup of hemolytic and hypochromic anemia, HbH disease as a special type of alpha-thalassemia should be considered early. In patients from Eastern Asia with a mean corpuscular hemoglobin (MCH) < 25 pg, hemoglobin analysis should be performed in order to avoid unnecessary diagnostic procedures. The prognosis of HbH disease is generally favorable, and symptomatic treatment is only recommended during hemolytic crises in association with, e.g., infections or pregnancy.