Antineoplastic agents resistance

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. 

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. 

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

Introduction - Research on antineoplastic agents follows an orderly sequence. Drugs which exhibit antitumor activity in animals bearing transplanted neoplasms or cytotoxicity in cell cultures are considered for further study. These chemicals are examined with respect to toxicology, effects upon resistant tumors, and biochemical mechanism of action. 

In a nut shell, irrespective of the actual cause, the prevailing resistance invariably negates the usefulness of an antineoplastic agent to an appreciable extent. 

In general, hospital patients have an increased susceptibility to infection [7]. Common chemotherapeutic treatments (e.g., corticosteroids, antineoplastic agents, and antibiotics) individually and synergistically contribute to increased susceptibility [8]. This is due mainly to immune system suppression and/or altering the patient s normal flora, often with replacement by antibiotic-resistant hospital microorganisms, as previously discussed. 

Schwope AD, Costas PP, Mond CR, Nolen RL, Conoley M, Garcia DB, Walters DB, Prokopetz AT (1988) Gloves for protection from aqueous formaldehyde permeation resistance and human factors analysis. Appl Ind Hyg 3 167-176 Sessink PJM, van de Kerkhof, MC A, Anzion RB, Bos RP (1994) Environmental contamination and assessment of exposure to antineoplastic agents by determination of Cyclophosphamide in urine of exposed pharmacy technicians Is skin absorption an important exposure route Arch Environ Health 4 165-169 Van Ketle WG, Tan-Lim HN (1975) Contact dermatitis from ethanol. Contact Dermatitis 1 7-10... 

Teicher BA, Lazo JS, Sartorelli AC (1981) Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res 41 73-81 Tr dan O, Galmarini CM, Patel K, Tannock IF (2007) Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst 99 1441-1454... 

Metallothionein is also induced by a variety of nonmetals, and exposure to these agents often can cause tesistance to anticancer drugs such as cisplatin (Basu and Lazo 1991). Expression of v mos can attenuate the glucocorticoid-induced metallothionein expression and cisplatin resistance. Transcriptional activation of c-Ha-ras oncogene expression in murine NIH 3T3 cells with dexamethasone produces an increase in metallothionein content and a decrease in cisplatin accumulation (Isonishi et al. 1991). The ability of dexamethasone to affect the sensitivity of cells to electrophilic antineoplastic agents could be of some clinical interest because of its frequent usage as an antiemetic. 

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. 

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... 

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