PurposeAcute pancreatitis in pregnancy (APIP) is a rare condition; however, it markedly affects maternal and fetal health. This study aimed to describe the types, clinical characteristics, mortality, and the safety and necessity of gestation termination of acute pancreatitis in pregnancy (APIP).MethodsWe retrospectively reviewed 121 APIP cases in the Gastroenterology Department of The First Affiliated Hospital of Nanchang University. APIP diagnosis were based on 2012 Atlanta Criteria. The correlation between APIP types, severity, biochemical parameters and mortality was analyzed.ResultsThe most common symptoms for APIP were abdominal pain (86.8%) and vomiting (73.6%). The most common causes for APIP were gallstone (36.4%) and hypertriglyceridemia (32.2%) and hypertriglyceridemic APIP was correlated with a higher rate for local complication (P = 0.012). Serum calcium level was negatively correlated with the severity of APIP (P < 0.01). The overall maternal and fetal mortality rate were 3.3% (4/121) and 11.6% (14/121), respectively. The severity of APIP was significantly correlated with higher risks for maternal and fetal death (P < 0.01). 72.7% of moderate-to-severe APIP patients underwent Cesarean section to terminate gestation safely.ConclusionThe most common causes of APIP were gallstone and hypertriglyceridemia. Lower level of serum calcium could be used as an indicator for the severity of the APIP. The severity of APIP was associated with higher risk for neonate asphyxia, and maternal and fetal death.

IntroductionTobacco smoke is known to be the main cause of lung, head and neck tumors. Recently, evidence for an increasing breast cancer risk associated with tobacco smoke exposure has been emerging. We and other groups have shown that nicotine, as a non-conventional carcinogen, has the potential to facilitate cancer genesis and progression. However, the underlying mechanisms by which the smoke affects the breast, rather than the lung, remain unclear. Here, we examine possible downstream signaling pathways of the nicotinic acetylcholine receptor (nAChR) and their role in breast cancer promotion.MethodsUsing human benign MCF10A and malignant MDA-MB-231 breast cells and specific inhibitors of possible downstream kinases, we identified nAChR effectors that were activated by treatment with nicotine. We further tested the effects of these effector pathways on the regulation of E2F1 activation, cell cycle progression and on Bcl-2 expression and long-term cell survival.ResultsIn this study, we demonstrated a novel signaling mechanism by which nicotine exposure activated Src to sensitize epidermal growth factor receptor (EGFR)-mediated pathways for breast cancer cell growth promotion. After the ligation of nAChR with nicotine, EGFR was shown to be activated and then internalized in both MCF10A and MDA-MB-231 breast cancer cells. Subsequently, Src, Akt and ERK1/2 were phosphorylated at different time points following nicotine treatment. We further demonstrated that through Src, the ligation of nicotine with nAChR stimulated the EGFR/ERK1/2 pathway for the activation of E2F1 and further cell progression. Our data also showed that Akt functioned directly downstream of Src and was responsible for the increase of Bcl-2 expression and long-term cell survival.ConclusionsOur study reveals the existence of a potential, regulatory network governed by the interaction of nicotine and nAChR that integrates the conventional, mitogenic Src and EGFR signals for breast cancer development.

Nicotine, one of major components in tobacco, has been shown to be at high concentrations in the blood stream of cigarette smokers. However, the mechanisms of how nicotine affects tumor development and whether nicotine is a potential carcinogen for malignancies induced by second-hand smoking are not fully understood yet. Here, we investigate the signaling pathways by which nicotine potentiates tumorigenesis in human mammary epithelial-like MCF10A or cancerous MCF7 cells. We demonstrate that human MCF10A and MCF7 cells both express four subunits of nAChR. The treatment of these cells with nicotine enhances the activity of protein kinase C (PKC) α without altering the expression level of this kinase. Nicotine also stimulates [3H]thymidine incorporation into the genome of these cells as well as forces serum-starved cells to enter S phase of the cell cycle, resulting of growth promotion. Importantly, upon nicotine treatment, the mobility of MCF10A and MCF7 cells are enhanced, which can be blocked by the addition of nAChR or PKC inhibitor. Experiments using siRNA knockdown or ectopic expression of cdc42 demonstrated that cdc42 functions as a downstream effector of PKC and is crucial in the regulation of nicotine-mediated migratory activity in the cells. Together, our findings suggest that nicotine, through interacting with its receptor, initiates a signaling cascade that involves PKC and cdc42, and consequently promotes migration in mammary epithelial or tumor cells.

It is known that Ras mutations, together with loss of PKC, are apoptotic in various types of mammalian cells. The mechanism of how aberrant Ras transmits this apoptotic signaling remains unclear. Using three V12-Ha-ras loop mutants that preferentially bind to and activate one of Ras effectors, we tested the role of Ras downstream pathways in the induction of apoptosis in rat lung epithelia, human lung or prostate cancer cells. After PKC inhibition, the activation of PI3K/Akt renders the susceptibility of cells to apoptosis. We also demonstrate that the amount of ROS is moderately increased in the cells ectopically expressing V12C40 and dramatically elevated by suppression of PKC, which leads to apoptosis through the activation of UPR. Thus, our study suggests that after PKC abrogation, PI3K functions downstream of Ras to perturb the state of cellular redox and signals to ER stress-regulated apoptotic machinery.