Tanshinone IIA inhibits endometrial carcinoma growth through the MAPK/ERK/TRIB3 pathway.

Endometrial carcinoma is the most common gynecological tumor in developed countries. Tanshinone IIA is a traditional herbal medicine which is to treat cardiovascular disease and has been shown to have various biological effects, such as anti-inflammatory, antioxidative and antitumor activities. However, there has been no study about the effect of tanshinone IIA on endometrial carcinoma. Thus, the aim of this study was to determine the antitumor activity of tanshinone IIA against endometrial carcinoma and investigate the associated molecular mechanism. We demonstrated that tanshinone IIA induced cell apoptosis and inhibited migration. We further demonstrated that tanshinone IIA activated the intrinsic (mitochondrial) apoptotic pathway. Mechanistically, tanshinone IIA induced apoptosis by upregulating TRIB3 expression and inhibiting the MAPK/ERK signaling pathway. In addition, knockdown of TRIB3 with an shRNA lentivirus accelerated proliferation and attenuated inhibition mediated by tanshinone IIA. Finally, we further demonstrated that tanshinone IIA inhibited tumor growth by inducing TRIB3 expression in vivo. In conclusion, these findings suggest that tanshinone IIA has a significant antitumor effect by inducing apoptosis and may be used as a drug for the treatment of endometrial carcinoma.

Clinical presentation, treatment, and outcomes associated with vaginal intraepithelial neoplasia: A retrospective study of 118 patients.

The incidence of vaginal intraepithelial neoplasia (VAIN) is increasing annually; however, the reported values are likely underestimated. Risk factors for VAIN include advanced age, human papillomavirus (HPV) infection, history of hysterectomy, and simultaneous or previous cervical intraepithelial neoplasia (CIN) or cervical cancer cervical cancer. The most common presentation is abnormal cytology without clinical symptoms. Despite various treatment modalities available, the rate of disease recurrence is high, and its malignant potential has been documented. This study aimed to examine demographic and clinical characteristics and associated treatment outcomes of patients with VAIN. We retrospectively reviewed clinicopathologic data and clinical outcomes of patients diagnosed with VAIN at a single center between January 2010 and December 2017. Overall, 118 patients were included (average age 49.81 ± 9.77 years; range, 26-70 years). The distribution of the histologic grade was as follows: VAIN1, 30.5%; VAIN2, 41.5%; and VAIN3, 28.0%. In total, 97 (82.2%) patients had either prior or simultaneous cervical lesions, CIN (35.6%), or cervical cancer (55, 46.6%). A total of 100 cases (84.7%) were diagnosed using colposcopy and 18 (15.3%) were diagnosed by pathological accident after hysterectomy. Thin-prep cytology test (TCT) results were available for 112 (94.9%) patients, and 111 (94.1%) patients had abnormal cytology findings. Most patients were confirmed as HPV positive (115, 97.5%), and 84 (71.2%) patients were confirmed as positive for high-risk HPV types. Forty-two (35.6%) patients underwent hysterectomy before VAIN diagnosis, and the median interval between hysterectomy and VAIN diagnosis was 26.5 (range: 3-68) months. Most surgical indications were HPV-related diseases (34, 80.9%), such as CIN (8, 19.0%) or cervical cancer (26, 61.9%). Eight patients had no history of cervical lesions. A total of 100 patients underwent initial treatment. During the median follow-up period of 29 (range: 9-96) months, 78 (78%) patients experienced disease remission after initial treatment, 7 (7%) experienced disease recurrence, 10 (10%) had persistent disease, and 5 (5%) had progressive disease. Finally, two patients developed vaginal cancer without death. Colposcopy should be performed before vaginal hysterectomy for VAIN, particularly HPV-related cases. The incidence of VAIN was 20% after hysterectomy owing to non-HPV-related lesions; thus, this part of the screening should not be discontinued. VAIN grade 2,3 and VAIN associated with CIN or cervical cancer are disease types more likely to recur and progress to invasive cancer; active medical intervention is recommended.

Key factors mediated by PI3K signaling pathway and related genes in endometrial carcinoma.

By analyzing the gene expression of endometrial carcinoma (EC) patients, the key factors in PI3K signaling pathway and its related genes mediating EC were explored. The EC samples and normal endometrial samples were downloaded from TCGA database and GTEx database. The R language "limma" package was used for differential analysis, and the expression level of genes in each tissue was analyzed by "gganatogram" package. Functional enrichment analysis of differential genes was carried out by KOBAS, an online bioinformatics website. The correlation between key genes and differential genes was evaluated using TCGA data and GTEx combined gene expression data. The corresponding clinical data were downloaded from TCGA database and GTEx database, and the R language "survival" package was used to assess the potential of candidate differential genes as a key factor of EC. Based on the combined differential analysis of TCGA and GTEx databases, 299 genes with significant differential in expression were finally got. Functional enrichment analysis revealed that genes were predominantly enriched in the entry of "Pathways in cancer", including RAC2 and PIK3R3 genes which were related with the abnormal PI3K pathway in cancer. PIK3R3, a key gene in the PI3K signaling pathway, was highly-expressed in EC. SPDEF, GCNT2, KIAA1324, C9orf152, MARVELD3, and APEX2 genes were found to be positively correlated with PIK3R3 in EC, all of which were highly expressed in EC. KM survival analysis showed that SPDEF, GCNT2, KIAA1324 and C9orf152 were significantly correlated with patients' survival. ROC analysis showed that SPDEF, GCNT2, KIAA1324 and C9orf152 gene could be used as potential markers for prognosis and survival of EC patients. It was found that PIK3R3, a key gene in the PI3K signaling pathway, was highly expressed in EC. The SPDEF, GCNT2, KIAA1324 and C9orf152 genes were also highly expressed in EC, and were positively correlated with PIK3R3 in EC. Moreover, they are significantly correlated with the patients' survival, suggesting that they may be potential markers for the prognosis of patients with EC.