Cancer lineage

The argument against any given cell lineage can be made for hepatocytes and/or human cancer cell lines, both of which are a major part of the drug development process. There is also an emphasis on the pharmacodynamic mechanisms of the drug effect, because of the absence of CYP/transport members. Because a drug s pharmacokinetics are usually adequately characterized as part of the preclinical and early clinical development, pharmacodynamics remains an area of needed research. Specific steps have been taken to try to understand how relevant the CEPH cell lines are to other cancer cell line systems. 

Moreover gene-expression analysis of leukemia cells from B-lineage acute lymphoblastic leukemia pediatric patients has identified sets of differentially expressed genes that are associated specifically with sensitivity or resistance to chemotherapy. Such information can also be used in diagnostic assay to stratify the patients in sub-categories, to develop new drugs and later on to personalize the anti-cancer therapy. 

Schreurs, M.W., de Boer, A.J., Figdor, C.G. and Adema, G.J. (1998) Genetic vaccination against the melanocyte lineage-specific antigen gplOO induces cytotoxic T lymphocyte-mediated tumor protection. Cancer Res., 58, 2509-2514. 

Interleukin-11 is the first growth factor to gain FDA approval for treatment of thrombocytopenia. It is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by patients who experienced severe thrombocytopenia after a previous cycle of chemotherapy. Although IL-11 has broad stimulatory effects on hematopoietic cell lineages in vitro, it does not appear to have significant effects on the leukopenia or neutropenia caused by myelosuppressive chemotherapy. Interleukin-11 is given by subcutaneous injection at a dose of 50 g/kg/d. It is started 6-24 hours after completion of chemotherapy and continued for 14-21 days or until the platelet count passes the nadir and rises to > 50,000 cells/ L. 

C21. Chiang, A. K., Chan, A. C., Srivastava, G., and Ho, F. C., Nasal T/natural killer (NK)-cell lymphomas are derived from Epstein-Barr virus-infected cytotoxic lymphocytes of both NK-and T-cell lineage. Int. J. Cancer 73, 332-338 (1997). 

In eastern Europe. Letoozim , a mixture of the papaya proteinases, is used for the treatment of eye burns [115] as well as for some cases of cataract [1161. Recently, a new application for chymopapain has been reported, Chymodiactin has been used in the process of removal of tumor cells from autologous marrow grafts in a positive selection system [117,118], This process clears the way for the use of autologous bone marrow transplants in the treatment of several types of cancer, since the authors showed tlst hemopoietic stem cells, the nrecyr ors of al lymphohemopoietic lineages, are present in cell mixtures purified in this way [119],... 

Cytotoxic chemotherapy is the cornerstone of therapy for metastatic testicular cancer. This type of cancer (known as a type of germ cell tumour as it is thought to be derived from cells in the germ cell lineage that are blocked in maturation) has been found to be extremely responsive to chemotherapeutic agents, in particular cisplatin and etoposide. There is no role for radiotherapy at this stage due to the advanced nature of the disease. 

The basic principle of hybridoma technology is shown in Fig. 2.23. B cells obtained from the spleens of mice immunized with the antigen of interest are fused with estabhshed mouse myeloma cells. Myeloma cells are transformed cancerous cells of the B lymphocyte lineage with infinite growth capacity. While many myeloma cell hnes continue to secrete their antibody, others lose the ability to produce antibodies. Spleen cells from immunized animals are fused with non-antibody-producing myeloma cells, resulting in a hybrid cell which inherits the properties of both the fusion partners. Thus the hybrids are capable of continued growth in culture like the myeloma cell and also maintain the antibody production of the spleen B cell. 

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