• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.54-54
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• 2003

Prostate gland contains neuroendocrine cells (PNECs) are playing important roles in physiological and pathophysiological processes of the prostate gland. Here, we investigated the role of purinoceptors in PNECs freshly isolated from rat ventral prostate (RPNECs) that show immunoreactivity to chromogranin A. Fura-2 ratiometry revealed that ATP evokes both fast Ca$\^$2+/ influx and store Ca$\^$2+/ release in RPNECs. A whole-cell patch clamp study demonstrated fast inactivating cationic current activated by ATP or by ${\alpha}$,${\beta}$-MeATP, which was blocked by ATP-TNP. The activation of P2X inward current was tightly associated with a sharp increase in [Ca$\^$2+/]$\sub$c/. The presence of P2X1/3 subtypes were proved by RT-PCR analysis. For the stored Ca$\^$2+/ release, ATP and UTP showed similar effects, suggesting the dominant role or P2Y2 subtypes, also confirmed by RT-PCR. Both P2X (${\alpha}$,${\beta}$-MeATP) and P2Y (UTP) stimulation induced changes in the cell morphology (initial shrinkage and blob formation on the surface) reversibly. Exocytotic membrane trafficking events were monitored with the membrane-bound fluorescent dye, FM1-43 using confocal microscopy. In spite of the similar Ca$\^$2+/ responses, UTP was far less effective in triggering exocytosis than ${\alpha}$,${\beta}$ -MeATP. Since serotonin is reportedly stored in the secretory granule of PNECs, we directly examined whether the aforementioned agonists elicit release of serotonin using carbon fiber electrode-amperometry. In accordance with the results of FM1 -43 experiments, ${\alpha}$,${\beta}$-MeATP efficiently evoke serotonin secretion while not with UTP. In summary, the P2X-mediated Ca$\^$2+/ influx plays crucial roles in the exocytosis of RPNECs. Although a global increase in [Ca$\^$2+]$\sub$c/ might be related with the morphological changes, a sharp rise of [Ca$\^$2+/]$\sub$c/ in the putative sub-plasmalemmal ‘microdomains’ might be a decisive factor for the exocytosis.

• Journal of Gastric Cancer
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• v.19 no.1
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• pp.121-131
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• 2019

Purpose: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. Materials and Methods: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED ($P_{NED}$) and demographic and clinicopathological parameters. Results: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. $P_{NED}$, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff $P_{NED}$ was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher $P_{NED}$. Tumors with ${\geq}10%$ NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. Conclusions: GC with ${\geq}10%$ NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.