Changes in DNA superhelicity during DNA replication are mediated primarily by the activities of DNA helicases and topoisomerases. If these activities are defective, the progression of the replication fork can be hindered or blocked, which can lead to double-strand breaks, elevated recombination in regions of repeated DNA, and genome instability. Hereditary diseases like Werner's and Bloom's Syndromes are caused by defects in DNA helicases, and these diseases are associated with genome instability and carcinogenesis in humans. Here we report a Saccharomyces cerevisiae gene, MGS1 (Maintenance of Genome Stability 1), which encodes a protein belonging to the AAA ؉ class of ATPases, and whose central region is similar to Escherichia coli RuvB, a Holliday junction branch migration motor protein. The Mgs1 orthologues are highly conserved in prokaryotes and eukaryotes. The Mgs1 protein possesses DNA-dependent ATPase and single-strand DNA annealing activities. An mgs1 deletion mutant has an elevated rate of mitotic recombination, which causes genome instability. The mgs1 mutation is synergistic with a mutation in top3 (encoding topoisomerase III), and the double mutant exhibits severe growth defects and markedly increased genome instability. In contrast to the mgs1 mutation, a mutation in the sgs1 gene encoding a DNA helicase homologous to the Werner and Bloom helicases suppresses both the growth defect and the increased genome instability of the top3 mutant. Therefore, evolutionarily conserved Mgs1 may play a role together with RecQ family helicases and DNA topoisomerases in maintaining proper DNA topology, which is essential for genome stability.

Background/Aim: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. Patients and Methods: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. Results: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI-patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. Conclusion: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS. Lung cancer is one of the leading causes of mortality worldwide. Immune checkpoint inhibitor (ICI) monotherapy or combination chemotherapy with cytotoxic agents has been developed for patients with advanced non-small cell lung cancer (NSCLC). However, median progression-free survival (PFS) is limited (1, 2). Applying more effective sequential chemotherapy is important for the prolongation of life. Recently, salvage cytotoxic chemotherapy after ICI treatment has been reported to increase antitumor effects (3-6). Moreover, it has been suggested that the efficacy of sequential cytotoxic chemotherapy may improve both the overall response rate (ORR) and PFS, regardless of the efficacy of previous ICI treatment and programmed death-ligand 1 (PD-L1) expression (4). Some studies have reported that activation of the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) inhibitory (VEGF/VEGFR) signal is one of the ICI resistant mechanisms, and that combination therapy of a VEGF/VEGFR inhibitor with ICI had a synergistic and improved antitumor effect (7). It has also been reported that using docetaxel with ramucirumab, a VEGFR inhibitor combination therapy (DOC+RAM) for ICI-treated patients may be more effective than for patients in historical case controls (6). Therefore, we conducted a retrospective comparative study on the efficacy and toxicity of DOC+RAM therapy at our hospital.

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Recruitment of CXCR4+ cells into infarcted myocardial tissues via stimulation of the CXCR4/SDF-1 axis plays a critical role in the beneficial effects of G-CSF.

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Intra-abdominal cystic lymphangiomas are rare lesions that can be difficult to diagnose. We present a report of a patient with a giant multilocular cystic lesion in the abdomen. Ultrasonography and computed tomography scans of the abdomen revealed that the cyst had originated in the gall-bladder fossa. There was some calcification and thickening of the cyst wall. Endoscopic retrograde cholangiopancreatography demonstrated a medially deviated common bile duct, an elongated cystic duct and an inferior compressed gallbladder. There was no apparent communication between the cyst and the biliary tract; however, an abdominal angiogram revealed that the lesion was supplied by a branch of the cystic artery. Histological findings obtained intra-operatively were consistent with a cystic lymphangioma. Its characteristic histology was observed in the subserous layer of the gall-bladder. This case is a rare instance of a cystic lymphangioma originating in the gall-bladder.

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A new furopyranone, phellifuropyranone A, was isolated from fruit bodies of wild Phellinus linteus as well as phelligridin G, and their chemical structures were determined by various spectroscopic methods including measurement of NMR spectra. Phellifuropyranone A together with meshimakobnol A and meshimakobnol B showed antiproliferative activity against mouse melanoma cells and human lung cancer cells in vitro.