There is considerable evidence that, when recalling past events, Westerners exhibit greater episodic specificity than East Asians and women exhibit greater episodic specificity than men. Yet it is unknown whether the same cultural and gender differences are true for future events. In the present study 209 European American and Chinese young adults were asked to recall past personal events and imagine future personal events occurring in varied time periods (i.e., 1 week, 1 year, 10-15 years). Regardless of time period, European Americans consistently produced more specific details than Chinese for future events than they did for past events, and women produced more specific details than men for both past and future events. These findings provide additional support for the constructive-episodic-simulation hypothesis, and shed new light on the influence of culture and gender on episodic thinking.
The tumor suppressor p53, nuclear factor-κB (NF-κB) and reactive oxygen species (ROS) have crucial roles in tumorigenesis, although the mechanisms of cross talk between these factors remain largely unknown. Here we report that miR-506 upregulation occurs in 83% of lung cancer patients (156 cases), and its expression highly correlates with ROS. Ectopic expression of miR-506 inhibits NF-κB p65 expression, induces ROS accumulation and then activates p53 to suppress lung cancer cell viability, but not in normal cells. Interestingly, p53 promotes miR-506 expression level, indicating that miR-506 mediates cross talk between p53, NF-κB p65 and ROS. Furthermore, we demonstrated that miR-506 mimics inhibited tumorigenesis in vivo, implicating that miR-506 might be a potential therapeutic molecule for selective killing of lung cancer cells.
The heat shock protein 90 (HSP90) is overexpressed and highly associated with poor prognosis in many malignancies. However, the role of HSP90 in gastric cancer has not been thoroughly elucidated. The aim of this study is to investigate the relationship of HSP90 expression with clinicopathological parameters and prognosis in advanced gastric cancer, and estimate the alteration of HSP90 expression after neoadjuvant chemotherapy. HSP90 and matrix metallopeptidase 9 (MMP-9) antigen expression was evaluated by immunohistochemistry in 322 advanced gastric carcinoma samples. The relationships between HSP90 and clinicopathological parameters and prognosis were analyzed. The response of HSP90 level was assessed in chemotherapeutic effect in 54 patients received 1–2 cycles of neoadjuvant chemotherapy. The positive expression of HSP90 was found to be 69.6% in 322 advanced gastric carcinoma samples. HSP90 protein expression was significantly associated with depth invasion (P<0.001), lymph node metastasis (P<0.001) and stage of disease (P<0.001). The positive rates of HSP90 expression were higher in both prominent serosal invasion group (P<0.001) and lymph node metastasis group (P<0.001). Moreover, HSP90 was significantly correlated with MMP-9 among 322 gastric cancer tissues (P<0.001). In univariate and multivariate analyses, HSP90 was an independent prognostic factor for both recurrence-free survival (RFS) and overall survival (OS). These results suggested that HSP90 may play an important role on tumor invasion, metastasis and prognosis, and might act as a promising target for prognostic prediction.
The chemoresistance of colon cancer cells limits the efficacy of chemotherapy. miR-409-3p has been shown to be downregulated in various types of cancer. In the present study, we examined the role of miR-409-3p in colon cancer as well as the effects of miR‑409-3p on the sensitivity of colon cancer cells to oxaliplatin. The expression of miR-409 was significantly downregulated in the human colon cancer cell lines compared with the normal colon epithelial cells. Importantly, the miR-409-3p expression levels were lower in human colon cancer patient samples than in normal colon tissues. Moreover, we observed a negative correlation between the miR‑409-3p levels and resistance to oxaliplatin: the oxaliplatin-resistant colon cancer cells exhibited significantly downregulated miR‑409-3p levels, but higher autophagic activity than the oxaliplatin-sensitive cells. Using bioinformatics analysis, we predicted that miR‑409-3p miRNA binds to the key autophagy gene encoding Beclin-1. Our findings indicated that the overexpression of miR‑409-3p inhibited Beclin-1 expression and autophagic activity by binding to the 3'-untranslated region of Beclin-1 mRNA. In addition, the overexpression of miR‑409-3p enhanced the chemosensitivity of the oxaliplatin-sensitive and oxaliplatin-resistant colon cancer cells. The restoration of Beclin-1 abrogated these effects of miR‑409-3p. In a xenograft model using nude mice, we examined the effects of miR‑409-3p on tumor growth during chemotherapy. miR‑409-3p overexpression sensitized the tumor to chemotherapy, while inhibiting chemotherapy-induced autophagy in a manner dependent on Beclin-1. The findings of our study suggest that miR-409-3p is capable of enhancing the chemosensitivity of colon cancer cells by inhibiting Beclin-1-mediated autophagy.
Abstract. Colon cancer is one of the most common and lethal malignancies worldwide. Despite major advances in the treatment of colon cancer, the prognosis remains very poor. Thus, novel and effective therapies for colon cancer are urgently needed. In the present study, the expression status of miR-218 and the role of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were investigated in colon cancer samples. Firstly, we observed that miR-218 expression was significantly reduced, while PI3K/Akt/mTOR pathway activity was enhanced. The overexpression of miR-218 suppressed the proliferation, migration and invasion of LoVo colon cancer cells, whereas the inhibition of miR-218 promoted these processes. Furthermore, the PI3K/Akt/mTOR signaling pathway was identified as a direct target of miR-218. The upregulation of miR-218 inhibited the activation of the PI3K/Akt/mTOR signaling pathway, as well as the expression of matrix metalloproteinase (MMP)9. The downregulation of miR-218 activated the PI3K/Akt/mTOR signaling pathway and promoted MMP9 expression. Taken together, our results demonstrate that miR-218 suppresses the proliferation, migration and invasion of LoVo colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway and MMP9. Our data indicate that miR-218 is a potential target in the treatment of colon cancer.
Key Points
Question
Is the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to primary cytoreductive surgery (PCS) associated with better outcomes for patients with stage III epithelial ovarian cancer?
Findings
In this multicenter retrospective cohort study of 584 patients with stage III epithelial ovarian cancer, for patients undergoing PCS with HIPEC and those undergoing PCS alone, the median overall survival was 49.8 and 34.0 months, respectively, and the 3-year overall survival rates were 60.3% and 49.5%, respectively. Complete PCS with HIPEC was associated with the best survival outcomes, with a median overall survival of 53.9 months and a 3-year overall survival rate of 65.9%.
Meaning
In this study, the addition of HIPEC to PCS was associated with better survival outcomes for patients with stage III epithelial ovarian cancer.
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