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Biomedical subjects

J J W M Janssen

Publications and source records attributed to J J W M Janssen.

8 recordsLinked to original sources

[Stem cells: hype and hope].

There is increasing interest in the use of stem cells for therapeutic purposes. The use of embryonic stem cells carries ethical and legal restrictions that limit their role in tissue regeneration. These restrictions do not apply to somatic stem cells, such as haematopoietic stem cells, which normally reside in the bone marrow. Preclinical studies have produced very promising results using these cells in experimental models of myocardial infarction. Bone-marrow cells have also been used to generate several different types of tissue. However, experimental data suggest that bone marrow also houses other non-haematopoietic stem cells, which could account for the alleged plasticity of haematopoietic stem cells. So far, the results of randomised clinical trials in patients with myocardial infarction or heart failure have been disappointing. It is clear that further research in this field is needed.

Animals↗

Identification of genes potentially involved in disease transformation of CML.

In patients with chronic myeloid leukemia (CML) who do not reach a (near) complete cytogenetic response, the disease progresses over several years from an indolent, chronic phase into a rapidly fatal blast crisis. Events that are responsible for this transformation process are largely unknown. To identify changes in gene expression that occurred during the course of the disease, we performed cDNA subtraction on sequentially stored peripheral blood mononuclear cell pellets, collected throughout the course of disease of a single CML patient. In total, 32 differentially expressed sequences were identified, of which 27 corresponded to known genes. On quantitative PCR, eight of these genes, YWHAZ, GAS2, IL8, IL6, PBEF1, CCL4, SAT and MMRN, showed comparable differential expression in additional CML patient samples. This set of genes can be considered as a starting point for further research on causes of disease transformation in CML and may lead to new targets in the treatment of resistant CML.

Apoptosis↗

Reduced-intensity conditioning regimens in malignant haematological diseases.

Allogeneic stem cell transplantation is a potentially curative procedure for patients with haematological malignancies. Conventional, myeloablative conditioning is, however, poorly tolerated by patients of advanced age, those receiving second transplants and those with concomitant diseases. Based on recognition of the importance of a graft-versus-disease (GVD) effect in curing malignant haematological disease, reduced intensity conditioning (RIC) as preparation for allogeneic stem cell transplantation has been developed for these patients. Although large prospective randomised clinical trials with significant follow-up are lacking, transplant-related morbidity and mortality of RIC transplants seem to compare favourably with conventional conditioning in this group of patients.

Antineoplastic Combined Chemotherapy Protocols↗

CD40-targeted adenoviral GM-CSF gene transfer enhances and prolongs the maturation of human CML-derived dendritic cells upon cytokine deprivation.

Vaccination with autologous leukaemia-derived dendritic cells (DC) presents an adjuvant treatment option for chronic myeloid leukaemia (CML). Here, we show that high-efficiency CD40-targeted adenoviral gene transfer of GM-CSF to CML-derived DC induces long-lived maturation in the absence of exogenous cytokines and may thus ensure protracted stimulation of CML-specific T cells upon vaccination.

Adenoviridae↗

Successful treatment of subcutaneously disseminated aspergillosis with caspofungin acetate in an allogeneic peripheral blood stem cell transplantation patient.

We present a patient with acute myeloid leukaemia who developed subcutaneously disseminated aspergillosis after allogeneic peripheral stem cell transplantation (PSCT). Disseminated aspergillosis after stem cell transplantation has a high mortality despite treatment with amphotericin B or one of the azoles. Aspergillosis in our patient was refractory to amphotericin B and itraconazole but was successfully treated with caspofungin acetate.

Antifungal Agents↗