NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer. Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary.
Arsenic compounds, which are well-documented human carcinogens, are now used in cancer therapy. Knowledge of the mechanism by which arsenic exerts its toxicity may help in designing a more effective regimen for therapy. In this study, we showed that arsenite could induce prominent mitotic arrest in CGL-2 cells and demonstrated the presence of damaged DNA in arsenite-arrested mitotic cells. We then explored why these cells with arsenite-induced DNA damage were arrested at mitosis instead of G2 stage. When synchronized CGL-2 cells were treated with arsenite at stage G1, S or G2, all progressed into, and arrested at, the mitotic stage and contained damaged DNA, as demonstrated by the appearance of the DNA double-strand break marker, phosphorylated histone H2A.X (gamma-H2AX). Since X-irradiation induced G2 arrest in CGL-2 cells, these cells clearly have a functional G2 DNA damage checkpoint. However, treatment of X-irradiated CGL-2 cells with arsenite resulted in a decrease in G2 cells and an increase in mitotic cells, suggesting that arsenite may inhibit activation of the G2 DNA damage checkpoint and thus allow cells with damaged DNA to proceed from G2 into mitosis. Immunoblot analysis confirmed that arsenite treatment reduced the X-irradiation-induced phosphorylation of both ataxia-telangiectasia, mutated at serine 1981 and Cdc25C at serine 216, events which are crucial for G2 checkpoint activation and G2 arrest. Moreover, a higher frequency of apoptotic cells is observed in mitotic CGL-2 cells arrested by arsenite than those arrested by nocodazole or taxol. Our results show that the combined effects of arsenite in inducing DNA damages, inhibiting the activation of G2 checkpoint, and arresting cells with damaged DNA in the mitotic stage may subsequently enhance the induction of apoptosis in arsenite-arrested mitotic CGL-2 cells.
The aim of this study was to evaluate the prevalence, the clinicopathological variables associated with probability of lung metastases, and the impact of lung metastases on survival outcome in patients with stage IV pancreatic cancer (PC) treated with palliative chemotherapy. A total of 654 patients with stage IV PC who underwent palliative chemotherapy from 2010–2016 were retrospectively enrolled in this study. Possible clinical variables associated with lung metastases and survival outcome were examined by univariate and multivariate analysis. Lung metastases were detected in 15.0% (3.4% with isolated lung metastases and 11.6% with synchronic metastases to lung and other organs). Female gender, poorly differentiated tumor grade, and large primary tumor size were independent risk factor in multivariate analysis. The median overall survival (OS) time was 6.5 months in the entire cohort, while the median OS was 11.8, 6.9, 7.7, 10.1, and 5.0 months for patients with isolated lung, isolated liver, isolated peritoneum, isolated distant lymph nodes, and multiple sites metastases, respectively. Isolated lung metastases were a better prognosticator for OS in univariate and multivariate analysis. This study utilized real-world clinical practice data to assess the prevalence, risk factors, and survival impact of lung metastases in patients with stage IV pancreatic cancer.
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