Resistance antineoplastics

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. 

As described in several monographs [4], bryostatin 1 exhibits significant in vitro and in vivo antineoplastic activity against a range of tumor cell lines including murine leukemia, B-cell lymphoma, reticulum cell sarcoma, ovarian carcinoma, and melanoma. It is also effective in the modulation of apoptotic function [5], the reversal of multidrug resistance [6], and stimulation of the immune system [7]. These unique features displayed by bryostatin 1 are attributed to its high affinity for protein kinase C (PKC) isozymes and its ability to selectively modulate their functions [8]. PKCs are a type of intracellular serine and threonine kinase that... 

Heavy Metals. Some heavy metals such as gold and platinum are used pharmacologically as immunomodulators to treat rheumatoid arthritis and as antineoplastic drugs, respectively. Most heavy metals inhibit mitogenicity, antibody responses, and host resistance to bacterial or viral challenge, and tumor growth. Platinum has been shown to suppress humoral immunity, lymphocyte proliferation, and macrophage function (Lawrence, 1985). Clinically, mild to moderate myelosuppression may also be evident with transient leukopenia and thrombocytopenia. 

Cyclophosphamide is an antineoplastic agent that causes DNA cross-linking and abnormal base-pairing through a mechanism called alkylation, hence the name alkylating agent. Cyclophosphamide may also be used in resistant rheumatoid arthritis. 

There is no evidence that 5-fluorouracil becomes unable to penetrate tumor cells. There may be an increase in P-glycoprotein, but this is not usually associated with 5-fluorouracil. There may be an induction in the drug metabolism for some antineoplastic drugs, but this does not appear to be the case for 5-fluorouracil. Increased metallothionein content has been associated with resistance in the case of cisplatin but not 5-fluorouracil. 

Pentostatin is an adenosine deaminase inhibitor primarily used as an antineoplastic agent for lymphoid malignancies, and produces a profound lymphopenia. It is now frequently used for steroid-resistant graft-versus-host disease after allogeneic stem cell transplantation, as well as in preparative regimens prior to those transplants to provide severe immunosuppression to prevent allograft rejection. 

Another observation that underlines the importance of drug-membrane interactions in tumor therapy is the increase in antineoplastic activity against resistant cell lines with increasing lipophilicity of the cytotoxic drugs at constant degree of ionization (pit, -8.4). Independently of the anthracycline used to induce resistance, cross-... 

Deazaaminopterin derivatives (folate analogues) are potent antineoplastics <88USP4725687, 91USP5077404) particularly in treating tumors resistant to methotrexate or aminopterin <90MIP9000172>. Some derivatives are equipotent with methotrexate, both as inhibitors of bovine liver dihydrofolate reductase and of L1210 murine leukemia cells. 

Thbulin-polymerizing chemotherapeutic agents, such as taxanes, have been shown to be one of the most effective drug classes in the treatment of ovarian cancer. The clinical success of paclitaxel has stimulated research into compounds with similar modes of activity in an effort to emulate its antineoplastic efficacy while minimizing its less desirable aspects, which include non-water solubility, difficult synthesis, and emerging resistance. 

Table 3 IC50 ( xM) for Entry P2 and existing antineoplastic agents in a line panel representing defined forms of cytotoxic drug resistance...

Gemcitabine is a clinically active antineoplastic drug in platinum-refractory ovarian cancer. The efficacy and tolerability of the particular drug in combination with liposomal DXR were investigated in athymic mice bearing cisplatin-resistant human ovarian carcinoma [458]. 

Pseudomembranous colitis was known before the introduction of antimicrobial agents and can still occur without previous antibiotic use, for example after antineoplastic chemotherapy (125) or even spontaneously. However, the number of cases has increased dramatically since antibiotics began to be used (126). Patients treated with lincomycin or clindamycin, cephalosporins, penicillinase-resistant penicillins, or combinations of several antibiotics... 

Berbamine was shown to have a similar but weaker effect than isotetrandrine or tetrandrine on overcoming resistance in the multidrug-resistant subline, ChR-24, derived from human KB carcinoma cells to various antineoplastic drugs. Berbamine partially overcomes the resistance of CHR24 cells to daunomycin [183]. 

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