Prognostic Significance of Cytokeratin 19 and Squamous Cell Cancer Antigen in Histologically Negative Sentinel Lymph Nodes of Cervical Squamous Cell Carcinoma.

OBJECTIVE: The aim of the study was to evaluate the prognostic value of positive cytokeratin 19 (CK19) and squamous cell cancer antigen (SCCAg) expression in histologically negative sentinel lymph nodes after surgery for cervical squamous cell carcinoma. METHODS: Immunohistochemistry was performed to detect the expression of CK19 and SCCAg using polyclonal antibody on 149 pair of formalin-fixed, paraffin-embedded cervical squamous cell carcinoma and histologically negative sentinel lymph node tissue samples, and results were compared with data from the prospectively registry of cervical squamous cell carcinoma by univariate and multivariate logistic regression model focusing specifically on recurrence. The survival was assessed by the Kaplan-Meier method and proportional hazards model. RESULTS: Cytokeratin 19 and SCCAg expression in histologically negative sentinel lymph nodes were documented in 15.4% (n = 23) and 20.8% (n = 31) patients and were associated with a higher incidence of tumor progression and poorer disease-free survival (DFS, P < 0.05). Multivariate logistic regression analysis demonstrated that CK19 (P = 0.001) and SCCAg (P = 0.001) expression in histologically negative sentinel lymph nodes, International Federation of Gynecology and Obstetrics staging (P = 0.000), and cervical stroma infiltration depth (P = 0.005) were independent predictive factors for recurrence. The proportional hazards model identified CK19 (P = 0.001) and SCCAg (P = 0.005) expression in histologically negative sentinel lymph nodes, International Federation of Gynecology and Obstetrics staging (P = 0.003), and cervical stroma infiltration depth (P = 0.005), as independently related to DFS. Using subgroup analysis, we found that the CK19+/SCCAg + subgroup has the poorest prognosis, whereas the CK19-/SCCAg - subgroup has the best prognosis (P = 0.000). CONCLUSIONS: Immunohistochemical assessment of both CK19 and SCCAg status in histologically negative sentinel lymph nodes may be a valuable approach for predicting recurrence and survival after curative surgery for cervical squamous cell carcinoma.

Danusertib Induces Apoptosis, Cell Cycle Arrest, and Autophagy but Inhibits Epithelial to Mesenchymal Transition Involving PI3K/Akt/mTOR Signaling Pathway in Human Ovarian Cancer Cells.

Ovarian carcinoma (OC) is one of the most common gynecological malignancies, with a poor prognosis for patients at advanced stage. Danusertib (Danu) is a pan-inhibitor of the Aurora kinases with unclear anticancer effect and underlying mechanisms in OC treatment. This study aimed to examine the cancer cell killing effect and explore the possible mechanisms with a focus on proliferation, cell cycle progression, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT) in human OC cell lines C13 and A2780cp. The results showed that Danu remarkably inhibited cell proliferation, induced apoptosis and autophagy, and suppressed EMT in both cell lines. Danu arrested cells in G2/M phase and led to an accumulation of polyploidy through the regulation of the expression key cell cycle modulators. Danu induced mitochondria-dependent apoptosis and autophagy in dose and time-dependent manners. Danu suppressed PI3K/Akt/mTOR signaling pathway, evident from the marked reduction in the phosphorylation of PI3K/Akt/mTOR, contributing to the autophagy inducing effect of Danu in both cell lines. In addition, Danu inhibited EMT. In aggregate, Danu exerts potent inducing effect on cell cycle arrest, apoptosis, and autophagy, but exhibits a marked inhibitory effect on EMT. PI3K/Akt/mTOR signaling pathway contributes, partially, to the cancer cell killing effect of Danu in C13 and A2780cp cells.

Eukaryotic initiation factor 3, subunit C silencing inhibits cell proliferation and promotes apoptosis in human ovarian cancer cells.

Ovarian cancer remains the leading cause of death among all gynaecological cancers, illustrating the urgent need to understand the molecular mechanisms involved in this disease. Eukaryotic initiation factor 3c (EIF3c) plays an important role in protein translation and cancer cell growth and proliferation, but its role in human ovarian cancer is unclear. Our results showed that EIF3c silencing significantly up-regulated 217 and down-regulated 340 genes. Ingenuity Pathway Analysis (IPA) indicated that the top differentially expressed genes are involved in 'Classical Pathways', 'Diseases and Functions' and 'Networks', especially those involved in signalling and cellular growth and proliferation. In addition, eIF3c silencing inhibited cellular proliferation, enhanced apoptosis and regulated the expression of apoptosis-associated proteins. In conclusion, these results indicate that by dysregulating translational initiation, eIF3c plays an important role in the proliferation and survival of human ovarian cancer cells. These results should provide experimental directions for further in-depth studies on important human ovarian cancer cell pathways.