RESUMO
Background: Exercise-induced vasospastic angina (VSA) is a relatively uncommon clinical scenario and is difficult to diagnose in the catheterization laboratory. Case summary: A 61-year-old Japanese man presented to our hospital with complaints of angina upon exertion in the morning. Neither a 12-lead electrocardiogram nor an echocardiogram showed any abnormal findings. Invasive coronary angiogram revealed moderate stenosis in the left anterior descending coronary artery. A hand grip test was performed, during which the patient experienced chest pain, and coronary angiogram showed coronary spasm at the site of organic stenosis with delayed coronary flow. Intracoronary nitrates (300â ug) were administered, resulting in the release of coronary spasm. Conclusion: The hand grip test may serve as a useful method for diagnosing exercise-induced VSA in the catheterization laboratory.
RESUMO
BACKGROUND & AIMS: Regenerating (Reg) gene IV is predominantly expressed in gastrointestinal cells and highly up-regulated in many gastrointestinal malignancies, including colorectal cancer (CRC). Human CRC cells expressing higher levels of Reg IV gene and its protein product (Reg IV) are resistant to conventional therapies, including irradiation (IR). However, the underlying mechanism is not well defined. METHODS: A murine model of IR-induced intestinal injury and in vitro and in vivo models of human CRC were used to determine the role of Reg IV in regulation of normal intestinal and colorectal cancer cell susceptibility to IR-induced apoptosis. RESULTS: Treatments of recombinant human Reg IV (rhR4) protein protected normal intestinal crypt cells from IR-induced apoptosis by increasing the expression of antiapoptotic genes Bcl-2, Bcl-XL, and survivin. However, overexpression of Reg IV in human CRC cells was associated with increased resistance to IR-induced apoptosis. Therefore, we used antagonism of Reg IV as a tool to increase CRC cell susceptibility to IR-induced cell death. Two complementary approaches using specific monoclonal antibodies and small interfering RNAs were tested in both in vitro and in vivo models of human CRC. Both approaches resulted in increased apoptosis and decreased cell proliferation, leading to decreased tumor growth and increased animal survival. Furthermore, these approaches increased CRC cell susceptibility to IR-induced apoptosis. CONCLUSIONS: These results implicate Reg IV as an important modulator of gastrointestinal cell susceptibility to IR; hence, it is a potential target for adjunctive treatments for human CRC and other gastrointestinal malignancies.
