155)

A 12 year old male with acute lymphoblastic leukemia is treated with 6-mercaptopurine for maintenance of remission. The drug used in this patient is mostly inactivated by which of the following enzymes? A) P450 mixed function oxidases B) Xanthine oxidase C) Dihydrofolate reductase D) Hypoxanthine-guanine phosphoribosyl transferase E) Adenosine deaminase F) Topoisomerase II G) Monoamine oxidase 6MP blocks de novo purine synthesis. They are converted by HGRPT. Active metabolite is metabolized by xanthine oxidase, which furthermore could see toxic effects increased by allopurinol. 156) A certain antineoplastic drug used in a patient with a rare hematological malignancy is an analog of adenosine. This drug reaches high intracellular concentrations due to its resistance to adenosine deaminase. The drug described in this scenario is most likely which of the following? A) Cyclophosphamide B) Lomustine C) Dacarbazine D) Cisplatin E) Methotrexate F) Mercaptopurine G) Cladribine Cladribine is a purine analog resistance to degradation by adenosine deaminase. Adenosine deaminase serves in the purine disposal pathway and this enzyme typically degrades chemotherapeutic purine analogs as well as adenosine. 157) Cancer cells from a 23 year old male with testicular cancer demonstrate high sensitivity to etoposide. The etoposide-killed cancer cells show a high number of double-stranded DNA fractures. These fractures are due to dysfunction of which of the following? A) Thymidylate synthase B) Topoisomerase I C) Topoisomerase II D) Microtubules E) Dihydrofolate reductase Etoposide is an antineoplastic which inhibits topoisomerase II during DNA synthesis which leads to DNA degradation. Its clinical use is for small cell carcinoma of the lung, prostate, or testicular carcinoma. 158) A 34 year old male diagnosed with acute myelogenous leukemia recently underwent successfully induction chemotherapy with doxorubicin. Several weeks later, he presents to your office complaining of progressive exertional dyspnea and orthopnea. Which of the following is most likely responsible for this patients symptoms? A) Right ventricular overload B) Focal myocardial scarring C) Restrictive cardiomyopathy D) Hypertrophic cardiomyopathy E) Dilated cardiomyopathy F) Pericardial fibrosis

Doxorubicin generates free radicals and noncovalently intercalate in DNA, which breaks in DNA, and decreases replication. Its clinical use is hodgkins lymphoma, myeloma, and sarcomas. Toxicity includes cardiotoxicity (dilated cardiomyopathy), myelosuppression, and alopecia. Dexrazoxane (iron chelator) is used to prevent cardiomyopathy. 159) A 56 year old female with lymph node positive breast cancer is treated with systemic chemotherapy. One month later, she develops frequent urination, suprapubic pain, dysuria, and hematuria. Which of the following could have prevented this patients condition? A) N-acetylcysteine B) Folinic acid C) Ondasetron D) Filgrastim E) Mesna F) Dexrazoxane G) Amifostine Cyclophosphamide and ifosfamide work by covalently x-linking DNA at guanine N-7. Its clinical use is non-hodgkins lymphoma , breast and ovarian carcinomas. Toxicity includes myelosuppression, and hemorrhagic cystitis (seen here) which is treated by Mesna which binds toxic metabolites. 160) A 34 year old Caucasian male receives a kidney transplant. His T-lymphocytes quickly recognize the foreign HLA molecules of the renal transplant cells. Inhibition of which of the following substances would specifically reduce the proliferation and differentiation of these T-lymphocytes? A) E-cadherin B) Neurofibromin C) Calcineurin D) Bcl-2 E) p53 Cyclosporine binds to cyclophilins. Complex blocks differentiation and activation of T cells by inhibiting calcineurin, thus preventing the production of IL-2. Clinical use includes suppressing organ rejection following transplant.