Mucinous adenocarcinoma (MC) has attracted much attention as a distinct histologic subtype of colorectal cancer in recent years. However, data about its epidemiologic and prognostic characteristics are limited. Therefore, patient data extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program were collected to analyze the epidemiologic and clinicopathological characteristics of MC.To determine the epidemiologic and clinicopathological characteristics of MC.The incidence trend of MC was calculated through the Joinpoint Regression Program. Cox regression analyses were performed to identify prognostic factors associated with overall survival (OS). A nomogram was established to predict the survival probability of individual patients with MC.We found that rates of MC decreased from 4.50/100000 in 2000 to 1.54/100000 in 2018. Rates of MCs in patients aged ≤ 50 years decreased 2.27%/year during 2000-2018. The incidence of appendiceal MCs increased from 0.14/100000 in 2000 to 0.24/100000 in 2018, while the incidence in other anatomic subsites continued to decrease. On multivariable Cox analyses, age, race, tumor site, T stage, N stage, M stage, surgery, and chemotherapy were associated with OS. A nomogram was developed based on these factors, and the area under the curve for 1-year, 3-year, and 5-year OS in the training cohort was 0.778, 0.778, and 0.768, respectively.Our results demonstrated that MC incidence decreased in almost all anatomic subgroups except for the appendix. A nomogram predicting the survival probability of patients with MCs showed good performance.
Abstract Phosphodiesterase 4 (PDE4) has four isoforms (PDE4A-D) with at least 25 splice variants. PDE4 subtype nonselective inhibitors produce potent antidepressant-like and cognition-enhancing effects via increased intracellular cyclic AMP (cAMP) signaling in the brain. Our previous data have demonstrated that long-form PDE4Ds appear to be involved in these pharmacological properties of PDE4 inhibitors in the normal animals. However, it is not clear whether long-form PDE4Ds are critical for the behaviors and related cellular signaling/neuronal plasticity/neuroendocrine alterations in the depressed animals. In the present study, animals exposed to the chronic unpredictable stress (CUS), a rodent model of depression, exhibited elevated corticosterone, depressive-like behavior, memory deficits, accompanied with decreased cAMP-PKA-CREB and cAMP-ERK1/2-CREB signaling and neuroplasticity. These alterations induced by CUS were reversed by RNA interference (RNAi)-mediated prefrontal cortex long-form PDE4Ds (especially PDE4D4 and PDE4D5) knock-down, similar to the effects of the PDE4 subtype nonselective inhibitor rolipram. Furthermore, these effects of RNAi were not enhanced by rolipram. These data indicate a predominant role of long-form PDE4Ds in the pharmacotherapies of PDE4 inhibitors for depression and concomitant memory deficits. Long-form PDE4Ds, especially PDE4D4 and PDE4D5, appear to be the promising targets for the development of antidepressants with high therapeutic indices.
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