Lymphoma. Hodgkinlymfomen and non-Hodgkin's disease

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PDT - photodynamic therapy lymfklierkankercellen kills T cells and leave intact.

September 8, 2004: Source: Contact Hodgkin.

More information about PDT = Photodynamic Therapy in what is PDT

[4643] Preferential Induction of B Cell Apoptosis Using Photodynamic Therapy. Session Type: Publication Only

Gorazd Krosl, Pascale Dubé, Nancy Dallaire, Marc Vaillancourt, Denis-Claude Roy. Hematology-Immunology, Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, Canada, Celmed BioSciences, Montreal, QC, Canada Apoptotic cell death in cancer cells promotes antigen presentation and Favors the Development of an anti-tumor vaccination effect. While lymphoma cells can-be Easily Obtained from peripheral blood or lymph nodes, malignant cell hypothesis Usually co-localize with normal hematopoietic T lymphocytes, rendering the selective induction of apoptosis in malignant B cells Particularly Difficult.

We have found That photodynamic therapy (PDT) Using the photosensitizer 4-5 dibromorhodamine methyl ester (TH9402) and visible light (514 nm) Can Be Used To Eliminate preferentially malignant B-lineage non-Hodgkin's lymphoma cells (mean of 4.3 logs ) on T lymphocytes.

Axis a rhodamine derivative, TH9402 cellular efflux is mediated through the P-glycoprotein (Pgp) pump. However, the preferential elimination of B cells to resting T cells could-not be ascribed to Pgp and inactivation we found no difference in intracellular retention of TH9402 Between B and T cells.

In order to understand the molecular events leading to B cell Such high susceptibility to PDT, then we Investigated the nature of death pathways Involved. To whethere determining apoptosis was the preponderant mechanism leading to the rapid elimination of B cells, we Measured the bond or Annexin V (AnnV) in 7-aminoactinomycin D (7AAD) negative (ie live) B and T cells Using flow cytometry, and Quantified DNA fragmentation and caspase 3 and 9 activity in isolated CD3 + and CD19 + PDT Treated and untreated cells.

That we found B cells demonstrated high levels of apoptosis after PDT with 53? 1.3% (mean? SE) AnnexinV + / 7AAD-cells compared to 30? 1.9% in T cells (p <0.05). The Extent of DNA fragmentation, as Determined by the TUNEL reaction was extensification in B cells (33.7? 9.8%) (mean? SE) but not T cells (2.3? 0.1%) When Measured at 4 hours post-PDT (p <0.01 ).

After PDT, catalytic caspase 3 levels Were Also 4-fold higher in CD19 + cells Than CD3 + cells (p <0.01). In contrast, caspase 9 levels remained low for Both cell types. The induction of apoptosis translated Into the elimination of More Than 90% of B cells within-four hours after PDT, while the Majority or T cells Were not Affected. Importantly, similar elimination of B-lineage cell lines and patient cells was observed, Using a limiting dilution assay, whethere cells overexpressed the anti-apoptotic protein Bcl-2 or not. Galanthus, theses results Indicating That the predominant caspase 3 apoptotic pathway is specifically implicated in PDT-induced B cell death, and Its Early activation Explains the rapid and profound sensitivity to PDT or B lymphocytes. This strategy could-PromoteLimit tumor cell vaccination in the context of autologous TH9402-PURGED Stem Cell Transplantation for Patients with B-lineage malignancies. In Addition, preferential B cell targeting could-take advantage of the immunomodulatory Crucial Role of apoptosis for the Treatment of Patients with B cell autoimmune disorders. Abstract # 4643 Appears in Blood, Volume 104, Issue 11, November 1916, 2004