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P(a) Pulmonary toxicity: Bleomycin (b) Hepatotoxicity L-Asparaginase 0Cyclophosphamide (c) Renal toxicityCyclophosphamide (d) NeurotoxicityVincristine0Cisplatin (e) Allergic responseL-Asparaginase0Bleomycin0Paclitaxel :0ff1ffGff           8XH X 0޽h ? 3333y___PPT10Y+D='  = @B +0 \D(  \8 \ Z9m? ??"6?@`NNN?N%  p(2) Long term toxicity(0fg f @` \  f>m? ??"6?@`NNN?N"*H H@8___PPT9  : Treatment-induced tumors Infertility and deformability <911;g8XH \ 0޽h ? 3333 0 <(  ^  6A?Z  vWGn$H!fjJ?Thank you[SOm H  0޽h ? 33___PPT10i.s +D='  = @B +m  0  | `  (       F\Jm0e0e     ? A@  A5% 8c8c     ?A)BCD|Ec " ?@  `    @ABC DEEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN E5%  N E5%  N F   5%    !"?N@ABC DEFFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `ab{ /  m x   c $JmT  m \   C &Aline12"v<J   C "A b059TH   0޽h ? 33___PPT10i.u x+D='  = @B +  0 p$0(  $J $ C "A b059T $  F^m0e0e     ? A@  A5% 8c8c     ?A)BCD|E||c " ?@  `    @ABC DEEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN E5%  N E5%  N F   5%    !"?N@ABC DEFFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `ab T/  m H $ 0޽h ? 33___PPT10i.u x+D='  = @B +0 p(  pX p C     p S #  0   CBoth normal cells and tumor cells go through a growth cycle (Figure 38.4). However, normal and neoplastic tissue may differ in the number of cells that are in the various stages of the cycle. Chemotherapeutic agents that are effective only in replicating cells, that is those cell- "at are cycling, are said to be cell-cycle specific (see Figure, +), whereas other agents are cell-cycle nonspecific. The nonspe- cific drugs such as the alkylating agents, although generally more toxic in cycling cells, are also useful against tumors with a low percentage of replicating cells. P_ , H p 0޽h ? 3380___PPT10.u@A0 1)t(  tX t C    ) t S X* 0   !Bifunctional alkylating agents,such as the nitrogen mustards, may form covalent bonds with each of two adjacent guanine residues. Such interstrand cross-linkages will inhibit DNA replication and transcription. Intrastrand cross-links also may be produced between DNA and a nearby protein. $"+PZ   d @ EH t 0޽h ? 3380___PPT10.ue10 x*(  xX x C     x S H  0   ,Chemotherapy may result in the destruction of actively proliferating hematopoietic precursor cells. White blood cell and platelet counts may in turn be decreased, resulting in an increased incidence of life-threatening infections and hemorrhage.Maximum toxicity usually is observed 10 to 14 days after initiation of drug treatment, with recovery by 21 to 28 days. The nausea and vomiting frequently observed after anticancer drug administration are actually thought to be caused by a stimulation of the vomiting center or chemoreceptor trigger zone in the central nervous system (CNS) rather than by a direct gastrointestinal effect. Most anticancer drugs damage hair follicles and produce partial or complete alopecia. Hair usually regrows normally after completion of chemotherapy. The duration of the side effects varies widely. For example, alopecia is transient, but the cardiac, pulmonary, and bladder toxicities are irreversible.  >E H x 0޽h ? 3380___PPT10.u030  |(  |X | C      | S O  0   Since most antineoplastic agents are mutagens, neoplasms (for example, acute nonlymphocytic leukemia) may arise 10 or more years after the original cancer was cured. Treatment-induced neoplasms are especially a prob- lem after therapy with alkylating agents   ]   H | 0޽h ? 3380___PPT10. upߒ50 @(  X  C      S \u  0   !Many patients undergoing chemotherapy fail to respond to treatment from the outset; their cancers are resistant to the available agents. Some neoplastic cells, for example, melanoma, are inherently resistant to most anticancer drugs. Other tumor types may be selected for or acquire resistance to the cytotoxic effects of the medication, particularly after prolonged administration of low drug doses. The development of drug resistance is minimized by short-term, intensive, intermittent therapy with combinations of drugs. Drug combinations are also effective against a broader range of resistant cell lines in the tumor population. A variety of mechanisms are responsible for drug resistance; each is considered separately under the particular drug. Tumor cells may become generally resistant to a variety of cytotoxic drugs on the basis of decreased uptake or retention of the drugs. This form of resistance is termed multidrug, resistance, Stepwise selection of an amplified gene that codes for a transmembrane protein (P-glycoprotein for "permeabil- ity" glycoprotein, is responsible for multidrug resistance (MDR). The resistance is due to ATP-dependent pumping of the drug out of the cell, associated with the presence of P-glyco-protein. 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