Myelomas

Mycotrienols Mycrox Myelography Myeloma cell Myfungar Myk Mykrox Mylanta Mylar... 

In 1975, the first successful production of MAbs was reported (44). By fusing normal antibody-producing cells with a B-ceU tumor (myeloma), hybridoma cell lines resulted which produced antibodies having a specificity to only one deterrninant on an antigen ie, all the antibodies produced from the cell line are identical. These studies resulted in a standard approach to MAb production. In this approach, the hybridoma cells are produced in large quantities in culture and screened to select specific clones producing the desired MAb using an appropriate assay. The selected clones are then expanded in culture (or in animals), the cells are collected, and the MAbs are extracted and purified. 

Mammalian Cells Unlike microbial cells, mammalian cells do not continue to reproduce forever. Cancerous cells have lost this natural timing that leads to death after a few dozen generations and continue to multiply indefinitely. Hybridoma cells from the fusion of two mammalian lymphoid cells, one cancerous and the other normal, are important for mammalian cell culture. They produce monoclonal antibodies for research, for affinity methods for biological separations, and for analyses used in the diagnosis and treatment of some diseases. However, the frequency of fusion is low. If the unfused cells are not killed, the myelomas 1 overgrow the hybrid cells. The myelomas can be isolated when there is a defect in their production of enzymes involved in nucleotide synthesis. Mammahan cells can produce the necessary enzymes and thus so can the fused cells. When the cells are placed in a medium in which the enzymes are necessaiy for survival, the myelomas will not survive. The unfused normal cells will die because of their limited life span. Thus, after a period of time, the hybridomas will be the only cells left ahve. 

The majority of promising drug candidates emerging from marine natural products research to date are potential cancer treatments. Six anti-cancer compounds that are either marine natural products or synthetic analogs of marine natural products have made it to clinical trials. The first of these compounds to enter clinical trials was didemnin B (43), one of a family of cyclic depsipetides isolated from the Caribbean tunicate Trididemnum solidum Didemnin B was advanced to Phase II clinical trials for treatment of small cell lung cancer, myeloma, prostate cancer, and melanoma. Unfortunately, no favorable responses were found so the compound has been withdrawn. Crude extracts of another Caribbean tunicate, Ecteinascidia turbinata, showed extremely... 

Carmustine is a bicyclohexylnitrosourea (BCNU, Fig. 3) with broad spectrum of antineoplastic activity (e.g., lymphomas, multiple myeloma, sarcomas, brain tumors, gastrointestinal tumors, melanomas). At doses of 80-200 mg/m2 it is given i.v. at 6 week s intervals. 

Bendamustine is a useful antineoplastic drug for the treatment of non-Hodgkin s lymphomas, multiple myeloma and as a partner drug in the combination therapy of some solid tumors. The cross-resistance with other alkylating drugs is not complete. Myelosuppression and lymphocytopenia is its main dose-limiting toxicity. 

Liposomal encapsulation of DOX or DNR Preferred anthracycline delivery to the tumor Breast cancer, ovarian cancer, AIDS-related Kaposi s sarcoma, multiple myeloma (pegylated liposomal DOX). Breast cancer (uncoated liposomal DOX). AIDS-related Kaposi s sarcoma, acute mye-loblastic leukemia, multiple myeloma, non-Hodgkin s lymphomas (uncoated liposomal DNR)... 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

Bisphosphonates have been shown to be highly effective in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget s disease of bone. While generally very well tolerated, these drugs do have potential adverse effects. Recently, the association of long-term high dose bisphosphonate treatment with osteonecrosis of the jaw has been described. This is a potentially serious side effect seen mostly in patients with multiple myeloma or... 

Monoclonal antibodies are derived from a single, monospecific B cell clone. Monoclonal antibodies can be obtained from hybridoma cells that result from the fusion of antibody-producing B cells with immortal cells of a myeloma cell line. 

Proteasomal inhibition represents a novel strategy in cancer treatment and the small molecule Bortezomid (PS-341, Velcade ) has been approved for the treatment of refractory and relapsed multiple myeloma, a proliferative disease of plasma cells. Bortezomid inhibits an active site in a proteasome subunit and remarkably shows selective cytotoxicity to cancer cells. Although the underlying mechanisms are not completely understood bortezomid apparently induces a cell stress response in these tumor cells followed by caspase-dependent apoptosis. Whether bortezomid is beneficial for the treatment of other proliferative disease is currently being tested in clinical trials. 

Lung (Fz9) Multiple myeloma Colorectal cancer Skin cancer Leukemia... 

Grown In presence of HAT medium Hybridoma multiplies myeloma and B cells die... 

Interferon does not only inhibit vims replicahon, it also has mulhple effects on cell metabolism and slows down the growth and mulhplicahon of treated cells. This is probably responsible for its widely reported anhtumour effect Encouraging results have been reported from clinical trials of interferon against several human tumours such as osteogenic sarcoma, myeloma, lymphoma and breast cancer. 

The cell fusion mixture is transferred to a culture medium containing hypoxanthine, aminopterin and thymidine (HAT medium). Unflised myeloma cells are unable to grow as they lack HGPRT. Unflised normal spleen cells can grow but their proliferahon is limited and they eventually die out. The hybridoma cell can proliferate in the HAT medium as the normal spleen cell supplies the enzyme which enables the hybridoma to utilize extracellular hypoxanthine. 

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