Screening and chemoprevention in lung cancer

Lung cancer is a major health problem due to its incidence and mortality. The risk factors, the existence of a preclinical phase, and the relationship between stage at diagnosis and survival are known. A number of strategies that aim to diagnose lung cancer in its earliest stages, based principally on imaging studies, are therefore being tested. Several drugs aimed at reducing the probability of developing lung cancer in the at-risk population are also under study. At the present time, the results obtained have not been encouraging and we do not have a clear strategy either for early diagnosis or for the use of chemopreventive agents.     

Myeloperoxidase Activity Imaging Using <Superscript>67</Superscript>Ga Labeled Substrate

Purpose The aim of the study is to assess the feasibility of imaging specific activity of myeloperoxidase (MPO), a leukocyte enzyme with important roles in inflammation and atherosclerosis, by single photon emission computed tomography (SPECT) using a novel ⁶⁷Ga-labeled radiotracer obtained by conjugating desferrioxamine (DF) and hydroxyindolyl acetic acid in vivo. Materials and Methods A reducing substrate of MPO (I) was synthesized by reacting commercially available DF with 2-(5-hydroxy-1H-indol-3-yl) acetic acid in the presence of a coupling agent [dicyclohexyl carbodiimide (DCC)]. The chelating unit was labeled with ⁶⁷Ga, and its interaction with MPO was characterized using MALDI-TOF and UV–vis. Mice with Matrigel implants containing human MPO were used to model diseased tissues rich in MPO. Three hours after the injection of ⁶⁷Ga–I, SPECT/computed tomography (CT) imaging was performed on a high-resolution Gamma Medica X-SPECT system. Biodistribution studies were performed six hours after the injection of the radiotracer. Results The feasibility of compound I oligomerization in the presence of MPO and MPO-mediated cross-linking with proteins was initially confirmed in vitro. In vivo, a 2.7-fold increase in target-to-muscle ratio could be measured in MPO-containing Matrigel implants in mice. Biodistribution experiments demonstrated a 60% increase of radioactivity in MPO-containing vs. control (contralateral) Matrigel implants. Conclusion ⁶⁷Ga–I can be used to image MPO activity in a model system. The accumulation mechanism is based on a differential pharmacokinetics because of the size increase resulting from ⁶⁷Ga–I interaction with the target enzyme. M. Querol and J. W. Chen contributed equally to this work.     

Androgen receptors in hepatocellular carcinoma and surrounding liver: relationship with tumor size and recurrence rate after surgical resection

Background/Aims: This study aimed to evaluate the parameters associated with the presence of androgen receptors in hepatocellular carcinoma and surrounding non-tumoral liver. Furthermore, we have assessed whether androgen receptor positively influences disease recurrence after surgical resection.Methods: Androgen receptor concentration was calculated by receptor binding assay in tumoral and non-tumoral liver in 43 patients (40 of them with cirrhosis) with hepatocellular carcinoma who underwent surgical resection.Results: Androgen receptors were found in 28 of the tumoral and in 30 of the non-tumoral samples, at concentrations ranging between 5 and 211 fmol/mg protein. The presence of androgen receptors within the tumor was significantly related to a smaller tumor size. Thereby, 22 of the 29 nodules ≤3 cm contained androgen receptors, while this occurred in only six of the 14 tumors larger than 3 cm (p<0.05). In contrast, the only parameter associated with the presence of androgen receptors in the non-tumoral liver was a lower gamma-glutamyltranspeptidase concentration. Disease recurrence after surgical resection was not only related to some tumor characteristics (increased alfa-fetoprotein concentration, presence of satellites, differentiation degree), but also to the presence of androgen receptors in the surrounding liver. Thus, the probability of recurrence after 1- and 2-year follow up in patients with androgen-positive livers was 33% and 50%, respectively, while it was 0% and 20% in those with androgen-negative livers (p<0.05). In contrast, the presence of androgen receptors within the tumor was not associated with a higher recurrence rate.Conclusions: These results show that only two thirds of hepatocellular carcinomas contained androgen receptors and that this feature was more frequent in small tumors. In addition, our data indicate that the presence of androgen receptors within the tumor does not imply a different outcome after surgical resection. In contrast, the presence of these receptors in the surrounding non-tumoral liver may be considered a risk factor for a higher incidence of disease recurrence.     

Acute stent thrombosis after early withdrawal of platelet glycoprotein IIb/IIIa antagonists: Potential rebound prothrombotic effect?

We report on two cases of acute coronary stent thrombosis after early withdrawal of different competitive inhibitors of the platelet glycoprotein IIb/IIIa receptor, eptifibatide and tirofiban. Differences in pharmacokinetics between different types of glycoprotein IIb/IIIa receptor blockers and a potential rebound prothrombotic effect with the use of these antiplatelet drugs are reviewed.