T-lymphoma cells

Combinations of drugs displaying distinct effects on cell proliferation/ differentiation and immunomodula-tion (e.g., retinoids and chemotherapy in advanced cutaneous T cell lymphoma). 

The multidrug resistance (mdr) reversing effect of the new phenothiazine complexes were tested on mouse T cell lymphoma cell lines. Trifluoperazine (TFP) was much more effective at the same concentration than verapamil. The efficacy of some metal coordination complexes [TFP-Cu(ll) and TFP-V(IV)] exceeded the action of TFP alone. Chlorpromazine (CPZ) or CPZ-Pt(ll) complex had the same or less effect than verapamil or promethazine (Pz) used as a control. 

Denileukin diftitox is a combination of the active sections of interleukin 2 and diphtheria toxin. It binds to high-affinity interleukin 2 receptors on the cancer cell (and other cells), and the toxin portion of the molecule inhibits protein synthesis to result in cell death. The pharmacokinetics of denileukin diftitox are best described by a two-compartment model, with an a half-life of 2 to 5 minutes and a terminal half-life of 70 to 80 minutes. Denileukin diftitox is used for the treatment of persistent or recurrent cutaneous T-cell lymphoma whose cells express the CD25 receptor. Side effects include vascular leak syndrome, fevers/chills, hypersensitivity reactions, hypotension, anorexia, diarrhea, and nausea and vomiting. 

Extranodal NK/T-cell lymphoma, nasal type Enteropathy-type T-cell lymphoma Hepatosplenic gamma-delta T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides/sezary syndrome... 

Peripheral T-Cell lymphoma, not otherwise characterized AngioimmunoblasticT-cell lymphoma... 

Ishida T, Inagaki H, Utsunomiya A, et al. CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified. Clin Cancer Res 2004 10 5494-5500. 

Protein kinase B, or Akt, was discovered as the product of an oncogene of the acutely transforming retrovirus AKT8, causing T-cell lymphomas in mice. It encodes a fusion product of a cellular serine/threonine protein kinase and the viral structural protein Gag. This kinase is similar to both protein kinase Ce (PKCe 73% identity to the catalytic domain) and protein kinase A (PKA 68%). It differs from other protein kinases in that it contains a pleckstrin homology (PH) domain, which allows it to bind to polyphosphoinositide head groups (and also to G-protein fly subunits). To date, three subtypes have been identified a, (3, and y, all of which show a broad tissue distribution. It... 

Denileukin -for use in refractory CD25 positive cutaneous T-cell lymphomas diftitox (Ontak) Ontak 9-18pg/kg IV(oveM5min) days 1-5... 

In the oxygen-independent Type III reactions the excited/sensi-tized psoralen donates its excitation energy directly to, or reacts with, the target compound. This occurs if the substrate and the target compound (e.g., DNA) are already in close proximity or intercalated. The reactions will proceed very rapidly via the excited singlet state, and are, typically, cyclization reactions or electron-transfer between the sensitizer and the target. In addition, the psoralen can be ionized, either directly or via the excited state, and react with the target compound in the form of a radical cation. Furocoumarins are also employed in treatment of cutaneous T-cell lymphoma and some infections connected with AIDS, by so-called photopheresis processes [71, 74-76]. In this case, peripheral blood is exposed to, e.g., photoactivated (sensitized) 8-methoxypsoralen (8-MOP) in an extracorporeal flow system. This... 

Chemotherapy-induced neutropenia Neutropenia during bone marrow transplant Severe chronic neutropenia Autologous or allogeneic bone marrow transplantation Mobilization of autologous PBPCs after chemotherapy Persistent or recurrent cutaneous T cell lymphoma Feb. 1991 June 1994 Dec. 1994 Dec. 1995 April 1998 Feb. 1994... 

UV and/or laser activation of oxsoralen for psoriasis or cutaneous T-Cell lymphoma. 

Proleukin is a recombinant form of IL-2. It is approved for the treatment of malignant melanoma and renal cell cancer. Ontak (denileukin diftitox) is a fusion protein for the treatment of persistent or recurrent T-cell lymphoma. Activated T cells express lL-2 receptors. Ontak has a fragment that binds to the IL-2 receptor while the other part presents a diphtheria toxin to kill the activated T cell. 

IL-2 promotes the growth of B cells for antibody production and induces the release of IFN-yand TNF (see below). It has been approved by the FDA for the treatment of different types of cancer, including metastatic melanoma and metastatic renal carcinoma. Examples of IL-2 for the treatment of malignant melanoma and a protein that targets IL-2 receptor in T-cell lymphoma are given in Exhibit 4.9. 

Like MOZ, the HBOl coding region has been identified as a common retroviral integration site leading to myeloid leukemia and B/T cell lymphoma in mice (Suzuki et al., 2002). This observation suggests that its loss may lead to development of human cancer. 

Piekarz RL, Robey R, Sandor V, Bakke S, Wilson WH, Dahmoush L, Kingma DM, Turner ML, Altemus R, Bates SE (2001) Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma a case report. Blood 98 2865-2868 Pierson T, McArthur J, Siliciano RF (2000) Reservoirs for HlV-1 mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu Rev Immunol 18 665-708... 

Krenacs, L., Harris, C. A., Raffeld, M., andJaffe, E. S. (1996) Immunohistochemi-cal diagnosis of T-cell lymphomas in paraffin sections. J. Cell. Pathol. 1,125-136. 

Table 11 lists the reactivity of antibodies to various lymphoreticular neoplasms in formalin- or B5-fixed tissues. Many of the monoclonal antibodies available to B- or T-cell lymphomas are not strictly lineage specific (MBl, MB2, LNl, MTl). CD20 (L26) (45) for B-cells and CD45RO (UCHL-1) (46) for T-cells has been shown to be fairly specific. UCHL-1 is not present on all T-cells, therefore one may want to include another T-cell marker to detect T-cell lymphomas. (3-FI (47), which recognizes a framework epitope on the T-cell P chain antigen receptor, and anti-CD3 (48) may be particularly promising in specifically detecting T-cell lymphomas. 

Anderson, C., Rezuke, W. N., Kosciol, C. M., Pasmszak, W. T., and Caitun, R. W. (1991) Identification of T-cell lymphomas in paraffn-embedded tissues using polyclonal anti-CD3 antibody comparison with frozen section immunopheno-typing and genotypic analysis. Mod. Pathol. 4, 358-362. 

Prestidge RL, Watson JD, Urdal DL et al. Biochemical comparison of murine colony stimulating factors secreted by a T cell lymphoma and a myelomonoc34ic leukemia. J Immunol. 1984 133 293-298. 

Prassolov, V., Ivanov, D., Hein, S., Rutter, G., Miink, C., Lohler, J. and Stocking, C. (2001b) The Mus cervicolor MuLV isolate M813 is highly fusogenic and induces a T-cell lymphoma associated with large multinucleated cells. Virologyl Q, 39-49. 

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