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Composite (Adenocarcinoid) tumors of the gastrointestinal tract 总被引:2,自引:0,他引:2
Dr. Hulya Levendoglu MD FACG Conrad A. Cox MD Venkat Nadimpalli MD 《Digestive diseases and sciences》1990,35(4):519-525
Tumors of the gut with composite features of both adenocarcinoma and carcinoid have been recognized mainly in the appendix. There also have been isolated reports of similar tumors arising from other parts of the gastrointestinal tract. It is generally concluded that these tumors have better prognosis than adenocarcinomas of the gastrointestinal tract. We reported six patients with composite tumors arising from the stomach in one, small intestine in two, cecum in two, and rectum in one patient. Clinical presentations in each was suggestive of malignancy with extension to either serosa and/or lymph nodes. Metastasis to liver was present in two patients. Histologically, the tumor showed glands with surface microvilli resembling adenocarcinoma and also organoid pattern with neurosecretory granules in cells resembling carcinoid. Two patients died three and nine months after surgery. The clinical presentation, findings at operation, and the postsurgical course of these six patients reveal that these tumors behave more like an adenocarcinoma than carcinoid and do not appear to have a better prognosis than ordinary adenocarcinoma. 相似文献
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H Rollema A Shrikhande KM Ward FD Tingley III JW Coe BT O'Neill E Tseng EQ Wang RJ Mather RS Hurst KE Williams M de Vries T Cremers S Bertrand D Bertrand 《British journal of pharmacology》2010,160(2):334-345
Background and purpose:
Smoking cessation trials with three high-affinity partial agonists of α4β2 neuronal nicotinic acetylcholine receptors (nAChRs) have demonstrated differences in their clinical efficacy. This work examines the origin of the differences by taking into account brain exposure and pharmacological effects at human α4β2 nAChRs.Experimental approach:
Rat plasma and brain pharmacokinetics were characterized and used to predict human steady-state plasma and brain concentrations following recommended doses of each of the three compounds. The pharmacological characterization included in vitro affinities at different nAChR subtypes, functional efficacies and potencies at the human α4β2 nAChR, as well as in vivo effects on rat mesolimbic dopamine turn-over.Key results:
A comparison of predicted human brain concentrations following therapeutic doses demonstrated that varenicline and nicotine, but not dianicline and cytisine, can extensively desensitize and, to a lesser extent, activate α4β2 nAChRs. The limited clinical efficacy of dianicline may be accounted for by a combination of weak functional potency at α4β2 nAChRs and moderate brain penetration, while recommended doses of cytisine, despite its high in vitro potency, are predicted to result in brain concentrations that are insufficient to affect α4β2 nAChRs.Conclusions and implications:
The data provide a plausible explanation for the higher abstinence rate in smoking cessation trials following treatment with varenicline than with the two other α4β2 nAChR partial agonists. In addition, this retrospective analysis demonstrates the usefulness of combining in vitro and in vivo parameters with estimated therapeutic human brain concentrations for translation to clinical efficacy. 相似文献119.
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