Many reports have shown the anticancer effects of iron deficient on cancer cells, but the effects of iron-chelators on gastric cancer have not been clearly elucidated. Recently, we reported that iron chelators induced an antiproliferative effect in human malignant lymphoma and myeloid leukemia cells. In the present study, we investigated the antitumor activity of these two iron-chelating agents, deferoxamine (DFO) and deferasirox (DFX), with gastric cancer cell lines, and their apoptosis-inducing effects as the potential mechanism. We found that iron chelators displayed significant antiproliferative activity in human gastric cancer cell lines, which may be attributed to their induction of G1 phase arrest and apoptosis. We also found that iron chelators induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in gastric cancer cells. Taken together, our data suggest that iron chelators induced apoptosis in gastric cancer, involving ROS formation ER stress and JNK activation.

BackgroundReactive oxygen species modulator-1 (Romo1) is a novel protein that has been reported to be crucial for cancer cell proliferation and invasion. However, its clinical implications in colorectal cancer patients are not well-known. For the first time, we investigated the association between Romo1 and the clinical outcomes of colorectal cancer patients.StudyWe examined Romo1 expression in resected tumor tissues immunohistochemically and assessed it with histological scores. We conducted survival analyses for patients who had curative resection (n = 190) in accordance with clinical parameters including level of Romo1 expression, and we examined the association between Romo1 expression and cell invasion using Matrigel invasion assay in colorectal cancer cells.ResultsWe observed significantly longer mean disease-free survival in the low Romo1 group compared with the high Romo1 group (161 vs 127.6 months, p = 0.035), and the median overall survival of the low Romo1 group was significantly longer than that of the high Romo1 group (196.9 vs 171.3 months, p = 0.036). Cell invasiveness decreased in the Romo1 knockdown colorectal cancer cells in contrast to the controlled cells. Romo1 overexpression in tumor tissue was associated with a high lymph node ratio between the metastatic and examined lymph nodes (p = 0.025).ConclusionsRomo1 overexpression in tumor tissue was significantly associated with survival in curatively resected colorectal cancer patients, suggesting Romo1 expression as a potential adverse prognostic marker. Increased Romo1 expression was found to be associated with high lymph node ratio. Cancer invasiveness appeared to be a key reason for the poor survival related to highly expressed Romo1.

Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres' cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.

BackgroundThis study investigated the prognostic effects of venous thromboembolism (VTE)-related factors in patients with metastatic pancreatic cancer receiving palliative chemotherapy. Predictive factors for VTE were also investigated.MethodsA total of 216 patients diagnosed with metastatic pancreatic cancer who received gemcitabine-based palliative chemotherapy at our institution were retrospectively evaluated.ResultsVTE occurred in 51 (23.6%) patients during treatment and did not affect survival. However, patients who were diagnosed with VTE at the beginning of chemotherapy showed poor prognosis compared with patients diagnosed with VTE during chemotherapy: all patients (hazard ratio [HR] 1.897, p = 0.008); patients diagnosed with VTE (HR = 3.768, p = 0.001). Low serum sodium (Na) (< 135 mmol/L) and high Khorana score (≥3) were strong predictive factors of early VTE (odds ratio [OR] 5.109; 95% confidence interval [95% CI] = 1.010–25.845; p = 0.049 for Khorana score, OR 10.304; 95% CI = 1.036–102.466; p = 0.047) for hyponatremia).ConclusionsOur study demonstrated that occurrence and detection of VTE in the early period of chemotherapy was the most significant VTE-related prognostic factor in patients with metastatic pancreatic cancer receiving chemotherapy. Prediction using the Khorana score and serum Na levels would be helpful in early diagnosis of VTE.

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