Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

Korean Cancer Patients' Awareness of Clinical Trials, Perceptions on the Benefit and Willingness to Participate / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients. MATERIALS AND METHODS: From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea. RESULTS: A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026). CONCLUSION: The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.

Implantation Metastasis of Lung Cancer to Chest Wall after Percutaneous Fine-Needle Aspiration Biopsy / 결핵

The implatnation of malignant cells along the needle tract is an extremely rare complication after a percutaneous fine-needle aspiration biopsy(FNAB). However, it is very serious and may result in a change in the prognosis of lung cancer, especially in the curable early stage(T1-2,N0,M0). Recently, we experienced two cases of such complications. A 43 years old female underwent a fine needle aspiration biopsy and a right middle lobectomy with adjuvant chemotherapy due to an adenocarcinoma(T2N0M0). Two years later, a new tumor developed at the site of the needle aspiration biopsy. It had the same pathological findings as the previous lung cancer. Therefore, it was concluded to be an implantation metastasis, and she was treated successfully by a right pneumonectomy and a resection of the chest wall mall with adjuvant radiotherapy. In another case, a 62 years old man was diagnosed with squamous cell lung cancer by a fine needle aspiration biopsy and underwent a right upper lobectomy(T2N0M0) with adjuvant chemotherapy. eight months later, a protruding chest wall mass developed at the aspiration site. It showed the same pathological findings as the previous lung cancer. Consequently, a total excision of the mass with adjuvant radiotherapy was done. Two years after the second operation, although the right lung was intace a metachronous squamous cell lung cancer was found at the left lower lobe. The two patients were still alive 15 and 37 months after thenresection of the chest wall mass, respectively.