BACKGROUND Human chorionic gonadotropin (hCG)‐producing large or giant cell carcinoma of the lung is not uncommon, but primary pulmonary choriocarcinoma is an extremely rare entity. Even rarer are cases occurring in males; to date the authors have found only 12 reported cases in the English literature. METHODS The clinical record of a 61‐year‐old man who presented with hemoptysis is described. A review of the literature regarding patients with primary pulmonary choriocarcinoma also is reported. RESULTS Computed tomography scan of the chest demonstrated an expanding thickness of the bullous wall within areas of emphysematous change in the lower lobe of the right lung. Moreover, a new, round tumor near the thickness appeared and rapidly expanded evenly into the surrounding lung tissue. Exploratory thoracotomy revealed the previous tumor to be adenocarcinoma with a small foci of choriocarcinoma, and the new tumor to be a hemorrhage with choriocarcinoma. Because of the pleural dissemination, the patient was treated with chemotherapy. At last follow‐up he was alive and well with a gradually increasing serum hCG‐β level in spite of chemotherapy. CONCLUSIONS Primary pulmonary choriocarcinoma occurring in men is an extremely rare entity with a fatal prognosis. Of the 12 cases reported to date in the English literature, 3 cases of choriocarcinoma with the coexistence of another type of pulmonary carcinoma were reported. To the authors' knowledge the clinical relation between these two types of carcinoma are unknown because all cases to date have been detected at the time of autopsy. Only in the current study case could the clinical course of the disease be followed and pathologic confirmation achieved, although the pathogenesis of the two types of carcinoma could not be determined. Cancer 2001;91:123–9. © 2001 American Cancer Society.
Human serum albumin (HSA) has two major ligand-binding sites, sites I and II, and also hydrolyzes some compounds at both sites. In the present study, we investigated differences in esterase activity among HSA preparations, and also the effects of warfarin, indomethacin, and naproxen on the hydrolytic activities of HSA to aspirin and p-nitrophenyl acetate. The esterase activities of HSA to aspirin or p-nitrophenyl acetate were measured from the pseudo-first-order formation rate constant (k obs ) of salicylic acid or p-nitrophenol by HSA. Inter-lot variations were observed in the esterase activities of HSA to aspirin and p-nitrophenyl acetate; however, the esterase activity of HSA to aspirin did not correlate with that to p-nitrophenyl acetate. The inhibitory effects of warfarin and indomethacin on the esterase activity of HSA to aspirin were stronger than that of naproxen. In contrast, the inhibitory effect of naproxen on the esterase activity of HSA to p-nitrophenyl acetate was stronger than those of warfarin and indomethacin. These results suggest that the administration of different commercial HSA preparations and the co-administration with site I or II high-affinity binding drugs may change the pharmacokinetic profiles of drugs that are hydrolyzed by HSA.
Warfarin, which consists of a racemic mixture of S-and Renantiomer, has been used as an anticoagulant agent. The anticoagulant activity of S-warfarin is 3-5 times greater than that of R-warfarin.1) This drug has a narrow therapeutic index and shows marked drug-drug interactions when coadministered with other agents that alter warfarin metabolism.2,3) The stereoselective metabolism of warfarin enantiomers in humans has been shown to be catalyzed by cytochrome P450 (CYP) such as CYP1A1/2, 2C9, and 3A4. 4,5) The 7-hydroxylation of S-warfarin is exclusively catalyzed by CYP2C9. RWarfarin is metabolized primarily by CYP1A2 to 6-and 8-hydroxywarfarin, and by CYP3A4 to 10-hydroxywarfarin. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), is also metabolized to 4Ј-hydroxydiclofenac by CYP2C9. 6,7)Ethanol is widely used as a pharmaceutical excipient for the solubilization of many hydrophobic drugs. Various drugs can pharmacokinetically or pharmacodynamically interact with alcohol. 8) Our previous study suggested that ethanol changes the binding of warfarin enantiomer to human serum albumin stereoselectively. 9) Acute intoxication by alcohol reduces the metabolism of warfarin by CYPs, causing increased anticoagulant effects, and leading to a risk of hemorrhage.10) Conversely, chronic alcohol ingestion might enhance metabolic enzyme activity, leading to a decrease in the anticoagulant effects of warfarin. Hamitouche et al. 11) showed that CYP2C9, as well as other CYPs such as CYP2E1, CYP1A2, and CYP3A4, is also able to metabolize ethanol, and indicated that these CYPs have a low affinity for ethanol for its metabolization. The apparent K m value determined for ethanol oxidation by various CYPs was around 10 mM. 11)Therefore, it is possible that ethanol affects the metabolism of other substrates by CYP2C9. Few studies on the effect of ethanol on warfarin metabolism by human CYP2C9 in vitro have been reported. The non-significant metabolic interaction of diclofenac (15 mM) with ethanol by CYP2C9 has been reported. 12) However, the effect of ethanol on the metabolism of diclofenac at lower concentrations by CYP2C9 has not been examined. In this paper, we have examined the effect of ethanol on the metabolism of S-warfarin and diclofenac by recombinant CYP2C9.1 microsomes (CYP2C9.1). MATERIALS AND METHODS Materials S-(Ϫ)-Warfarin, diclofenac sodium, ethanol, naproxen, NADPϩ , glucose-6-phosphate, MgCl 2 · 6H 2 O, and glucose-6-phosphate dehydrogenase were purchased from Wako Pure Chemical Ind. (Osaka, Japan). 4Ј-Hydroxydiclofenac was purchased from Sigma-Aldrich (MO, U.S.A.). 7-Hydroxywarfarin and human CYP2C9.1ϩP450 reductase microsomes derived from baculovirus expression systems were purchased from BD Gentest (MA, U.S.A.). All other chemicals and solvents were of analytical grade or higher.Inhibition Study According to the method of Iwakawa et al., 13) a metabolic inhibition study was performed. The time of incubation and concentration of microsomal protein in the study were determined to be in a linear range for ...
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