Cloning, expression, crystallization and preliminary X-ray crystallographic analysis of a human condensin SMC2 hinge domain with short coiled coils

Kawahara, K., Nakamura, S., Katsu, Y., Motooka, D., Hosokawa, Y., Kojima, Y., Matsukawa, K., Takinowaki, H., Uchiyama, S., Kobayashi, Y., Fukui, K. & Ohkubo, T. (2010). Acta Cryst. F66, 1067-1070

Metastatic Pulmonary Adenocarcinoma 13 Years After Curative Resection for Pancreatic Cancer: Report of a Case and Review of Japanese Literature

Context For the majority of patients, ductal adenocarcinoma of the pancreas remains a lethal disease. Currently, surgical extirpation for localized disease offers the only chance for long-term survival. Case report We report a patient who underwent successful resection of isolated lung metastasis occurring 13 years after pancreatic cancer resection. A 59-year-old woman underwent distal pancreatectomy for pancreatic cancer 13 years previously, followed by adjuvant chemotherapy, and was followed-up at the outpatient clinic of a local hospital. From around June 2010, she noticed bloody sputum, so she visited a local hospital. Since her chest X-ray and CT revealed a 1.5 cm mass shadow in the segment 10 of her right lung and she was referred to the Respiratory Disease Center of our hospital. As a result of through examinations, she was strongly suspected of having lung metastasis of pancreatic cancer, and underwent partial pneumonectomy. Postoperative histopathological examination of the resected specimen was consistent with lung metastasis of pancreatic cancer. She is still alive and currently receives third line of chemotherapy. Conclusion Patients who have achieved long-term survival after pancreatic cancer resection and can tolerate surgery may benefit from resection of a lung metastasis of pancreatic cancer in terms of survival, if it controls the metastasis

Unique thermal behavior of acrylic PSAs bearing long alkyl side groups and crosslinked by aluminum chelate

An acrylic pressure-sensitive adhesive (PSA), bearing octadecyl acrylate, methyl acrylate and acrylic acid groups, and crosslinked by aluminum acetylacetonate (AlACA), displayed behavior unique among acrylic PSAs in that its adhesion, which decreases with an increase in temperature, began to increase again from around 150 °C. In order to understand this behavior, the structure and thermal properties of the PSA were investigated in detail, along with another PSA crosslinked by a covalent crosslinking agent (Az). From thermal mechanical analysis, the PSA with ionic crosslinks (AlACA) showed three softening points at 20, 60, and 160 °C. In comparison, the PSA covalently crosslinked by Az only exhibited two softening points (at 20 and 60 °C). The softening point at 160 °C is clearly related to ionic chelate crosslinking. DSC measurements indicated that the softening point at 20 °C resulted from melting of the ordered octadecyl group, and the softening point at 60 °C was due to an increase in the mobility of the main chain. The temperature dependence of viscoelastic measurements revealed that the viscosity of the PSA crosslinked by AlACA increased at around 160 °C. From these results, we considered that the distinctive adhesion of the PSA crosslinked by AlACA could be due to ligand exchange at the aluminum crosslinking points, which are chelated by carboxy groups built in the main chain

N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition.

Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1) than their parental low metastatic counterpart (HSC-58). The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54) from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition

Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through M2-type macrophages.

Tumors formed by a highly metastatic human lung cancer cell line are characterized by activated signaling via vascular endothelial growth factor (VEGF)-C through its receptor (VEGFR-3) and aggressive lymph node metastasis. In this study, we examined how these highly metastatic cancers acquired aggressive lymph node metastasis. Compared with their lower metastatic counterparts, the highly metastatic tumors formed by this cell line expressed higher amounts of interleukin (IL)-1α, with similarly augmented expression of IL-1α and IL-1β by tumor stromal cells and of VEGF-A and VEGF-C by tumor-associated macrophages. These tumor-associated macrophages were mainly of the M2 type. Administration of a macrophage-targeting drug suppressed the production of these potent angiogenic and lymphangiogenic factors, resulting in decreased tumor growth, angiogenesis, lymphangiogenesis, and lymph node metastasis. In Matrigel plug assays, the highly metastatic cells formed tumors that were extensively infiltrated by M2-type macrophages and exhibited enhanced angiogenesis and lymphangiogenesis. All of these responses were suppressed by the IL-1 receptor (IL-1R) antagonist anakinra. Thus, the IL-1α-driven inflammatory activation of angiogenesis and lymphangiogenesis seems to provide a highly metastatic tumor microenvironment favorable for lymph node metastasis through cross-talk with macrophages. Accordingly, the IL-1R/M2-type macrophage axis may be a good therapeutic target for patients with this form of lung cancer

Comparison of protein and mRNA expression levels of various factors between low and highly metastatic gastric cancer cell lines.

<p>(A) Western blot analysis of total cell lysates shows protein expression levels of NDRG1, growth factor receptor, EMT-related proteins, Wnt/β-catenin-related proteins, and other factors in HSC-58, 58As1 and 58As9 cells. (B) Comparison of mRNA expression levels of NDRG1, E-cadherin, vimentin, Snail, MMP-1 and β-catenin in HSC-58, 58As1 and 58As9 cells by qRT-PCR analysis. (C) Immunocytochemical analysis of E-cadherin and β-catenin in HSC-58 and 58As9, using specific antibodies against E-cadherin, β-catenin and DAP1. Magnification×200. (D) Western blot analysis shows expression of β-catenin and Snail in nucleus and cytosol fraction. CREB, a nuclear marker, and α-tubulin, a cytosol marker. (E,F) Comparison of luciferase activity driven by E-cadhrin promoter and β-catenin (TopFlash) driven promoter between HSC-58 and its highly metastatic cell lines. The relative promoter activity is presented when normalized by the activity in HSC-58. *p<0.01.</p