Die Diels‐Alder‐Reaktion von trans‐ Pentadien‐1,3 (I) mit Acrylnitril (II) liefert in Abhängigkeit von der Polarität des verwendeten Lösungsmittels die vier isomeren Cycloaddukte (III)‐(VI).

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Pancreatic cancer is one of the leading causes of cancer-related mortality and has the lowest 5-year survival rate. Therefore, novel strategies are urgently required to treat pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) cells rely on enhanced lysosomal function for survival and proliferation to facilitate the degradation of contents accumulated via autophagy and macropinocytosis. Previously, we have reported that the combination of epidermal growth factor receptor/HER2 inhibitor lapatinib and sphingosine analog fingolimod (FTY720) confers a significant cytostatic effect in lung cancer cells. In the present study, the combined effects of these drugs on PDAC cell lines, BxPC-3, KP-4, PANC-1 and MIA PaCa-2, were examined. It was observed that FTY720 enhanced the lapatinib-induced cytotoxic effect and caused non-canonical and lysosome-dependent death in PDAC cells. Lapatinib and FTY720 induced lysosomal swelling and inhibited lysosomal acidification. Combination treatment with lapatinib and FTY720 increased lysosomal membrane permeability, induced mitochondrial depolarization, induced endoplasmic reticulum stress and disturbed intracellular calcium homeostasis. Additionally, the cytotoxic effect of lapatinib was enhanced by hydroxychloroquine or the CDK4/6 inhibitor abemaciclib, both of which induce lysosomal dysfunction. Collectively, these results indicated that the lysosome-targeted drug combination induces multiple organelle dysfunction and exerts a marked cytotoxic effect in PDAC cells.

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An 86-year-old woman was admitted for emergency treatment of increasing dyspnea. Transthoracic echocardiography revealed decreased left ventricular systolic function with dyskinesis at the apex, and severe aortic stenosis. The apex of the left ventricle showed a huge mobile thrombus. Coronary angiography revealed total occlusion at the middle portion of the left anterior descending coronary artery. Emergency operation was successful, and a partially calcified thrombus was observed at the site of the old myocardial infarction area. In this case, myocardial infarction and elevated intraventricular pressure due to aortic stenosis likely contributed to the wall motion abnormality and thrombus formation.