Primary peritoneal adenocarcinoma as content of an incarcerated umbilical hernia: A case-report and review of the literature.

INTRODUCTION: Umbilical hernia is a common finding in many cases, posing potentially life-threatening complications, such as incarceration or strangulation. The presence of malignancy in hernia sacs is, however, rather rare. PRESENTATION OF CASE: Here we report on a case of primary peritoneal adenocarcinoma found through histological examination of omental tissue, resected due to an incarcerated umbilical hernia of an 84-years-old woman. There was no macroscopic sign of malignancy during operation; only after routine examination of histological sections the diagnosis was found. DISCUSSION: To our knowledge this is the first report of primary peritoneal cancer as content of an umbilical hernia. This is a rare neoplasm and histologically identical to epithelial ovarian carcinoma. For this reason, the diagnosis is usually based on the histological finding and exclusion of a primary ovarian tumor. Primary peritoneal cancer has a poor outcome in general. Early diagnosis is, therefore, essential for effective treatment. CONCLUSION: Histological analysis of resected hernia sac or content should be performed routinely to discover malignant diseases in the background of a hernia.

Defective diacylglycerol-induced Ca2+ entry but normal agonist-induced activation responses in TRPC6-deficient mouse platelets.

BACKGROUND: Platelet adhesion, activation and aggregation at sites of vascular injury are essential processes for primary hemostasis. Elevation of the intracellular Ca(2+) concentration is a central event in platelet activation but the underlying mechanisms are not fully understood. Store-operated calcium entry (SOCE) through Orai1 was shown to be the main Ca(2+) influx pathway in murine platelets, but there are additional non-store-operated Ca(2+) (non-SOC) and receptor operated Ca(2+) (ROC) channels expressed in the platelet plasma membrane. OBJECTIVE: Canonical transient receptor potential (TRPC) channel 6 is found both in human and murine platelets and has been proposed to mediate diacylglycerol (DAG) activated ROCE but also a role in the regulation of SOCE has been suggested. METHODS: To investigate the function of TRPC6 in platelet Ca(2+) signaling and activation, we analyzed platelets from mice deficient in TRPC6 using a wide range of in vitro and in vivo assays. RESULTS: In the mutant platelets, DAG activated Ca(2+) influx was found to be abolished. However, this did not significantly affect SOCE or agonist induced Ca(2+) responses. Platelet function in vitro and in vivo was also unaltered in the absence of TRPC6. CONCLUSION: Our results indicate that DAG activated ROCE is mediated exclusively by TRPC6 in murine platelets, but this Ca(2+) influx has no major functional relevance for hemostasis and thrombosis. Further, in contrast to previous suggestions, based on studies with human platelets, TRPC6 appears to play an insignificant role in the regulation of SOCE in murine platelets.

Integrins in platelet activation.

Heterodimeric receptors of the beta1 and beta3 integrin families mediate platelet adhesion and aggregation in hemostasis and thrombosis. In resting platelets, integrins are expressed in a low-affinity state but they shift to a high-affinity state and efficiently bind their ligands in response to cellular activation. This review summarizes recent advances in understanding the functional regulation and (patho-) physiological significance of individual platelet integrins with a special focus on studies in genetically modified mice. It is now recognized that beta1 and beta3 integrins have partially redundant roles in the adhesion process and that their activation is regulated by similar mechanisms, involving Ca2+-dependent and -independent signaling events and essential functions of talin-1 and kindlin-3 in the terminal activation step.

Calcium signaling in platelets.

Agonist-induced elevation in cytosolic Ca2+ concentrations is essential for platelet activation in hemostasis and thrombosis. It occurs through Ca2+ release from intracellular stores and Ca2+ entry through the plasma membrane (PM). Ca2+ store release is a well-established process involving phospholipase (PL)C-mediated production of inositol-1,4,5-trisphosphate (IP3), which in turn releases Ca2+ from the intracellular stores through IP3 receptor channels. In contrast, the mechanisms controlling Ca2+ entry and the significance of this process for platelet activation have been elucidated only very recently. In platelets, as in other non-excitable cells, the major way of Ca2+ entry involves the agonist-induced release of cytosolic sequestered Ca2+ followed by Ca2+ influx through the PM, a process referred to as store-operated calcium entry (SOCE). It is now clear that stromal interaction molecule 1 (STIM1), a Ca2+ sensor molecule in intracellular stores, and the four transmembrane channel protein Orai1 are the key players in platelet SOCE. The other major Ca2+ entry mechanism is mediated by the direct receptor-operated calcium (ROC) channel, P2X1. Besides these, canonical transient receptor potential channel (TRPC) 6 mediates Ca2+ entry through the PM. This review summarizes the current knowledge of platelet Ca2+ homeostasis with a focus on the newly identified Ca2+ entry mechanisms.