Liver colonization by human colon cancer cells is reduced by antisense inhibition of MUC2 mucin synthesis.

BACKGROUND & AIMS: Alterations in the production of epithelial mucins have been correlated with advanced tumor stage in the colon, but direct evidence for a role of specific mucin genes in liver metastasis is lacking. The current study was designed to establish more directly the role of MUC2 in colon cancer metastasis. METHODS: MUC2 levels were manipulated in highly metastatic human colon cancer cells using eukaryotic expression constructs designed to express a portion of MUC2 complementary DNA in antisense orientation. To assess the effect of MUC2 levels on metastatic potential, liver colonization was assessed in athymic mice after splenic-portal inoculation. RESULTS: Stable integration of the MUC2 antisense construct into metastatic colon cancer cells (LS LiM6) resulted in an 80% reduction in MUC2-specific messenger RNA and a concomitant decrease in MUC2 apomucin protein. This reduction was associated with a 50% reduction in synthesis of mature glucosamine-labeled mucin, almost complete inhibition of secretion of sialyl-LeX and sialyl-Tn antigens, and a 40% decrease in binding of colon cancer cells to E-selectin. Reduction in MUC2 levels was associated with a marked decrease in liver colonization. CONCLUSIONS: This study provides direct evidence that MUC2 plays an important role in colon cancer metastasis.

Clinical differentiation of narrow QRS complex tachycardias.

Supraventricular tachycardias generally present with narrow QRS complexes and are quite commonly seen in the emergency department. Regular narrow QRS complex tachycardias occur in all age groups and may be associated with minimal symptoms, such as palpitations, or, present with hemodynamic compromise resulting in syncope. While history and physical examination are indispensable, they usually do not lead to a definitive diagnosis. The diagnosis is made by careful analysis of the 12-lead ECG. Therapy is based on hemodynamic assessment and understanding of the tachycardia mechanism.

Clinical approach to wide QRS complex tachycardias.

Wide QRS complex tachycardia is a frequently encountered arrhythmia in the emergency department and presents a diagnostic challenge to the emergency physician. The history, physical examination, chest radiograph, and electrocardiogram analysis are important in making the correct diagnosis. The diagnosis of ventricular tachycardia is supported by, 1) a history of prior myocardial infarction or congestive heart failure; 2) a physical examination showing cannon A-waves in the jugular venous pulsation or variable heart sounds; 3) a chest radiograph showing cardiomegaly or evidence of prior cardiac surgery; and 4) characteristic ECG features that include AV dissociation, fusion-capture beats, QRS concordance, or, typical morphologic features in leads V1 and V6. This article presents the diagnostic and therapeutic approaches to wide QRS tachycardias.

Permanent cardiac pacing.

Implantation of a permanent pacemaker is the most commonly performed surgical operation involving the heart. The modern cardiac pacemaker is a complex device that can sense and pace in both the atrium and ventricle. It also modulates the pacing rate based on sensed physiologic parameters. This article reviews the fundamental principles of pacemaker technology and provides the emergency physician with approaches to common pacemaker problems.

Implantable cardioverter defibrillators.

Implantable cardioverter defibrillators have proven to be an effective therapy for life-threatening ventricular arrhythmias. Given the ever-increasing number of patients who have these devices, increasing numbers of patients are likely to present to emergency departments with defibrillator-related problems. This article discusses normal device function, indications for implantation, and technique of implantation. It also focuses on the evaluation and management of patients with these devices presenting to the emergency department.