Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines: less involvement of metallothionein

BACKGROUND: Heptaplatin is a new platinum derivative with anticancer activity against various cancer cell lines, including cisplatin-resistant cancer cell lines (Cancer Chemother Pharmacol 1995; 35: 441). METHODS: Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines has been investigated in connection with metallothionein (MT). Cytotoxicity was determined by an MTT assay. MT mRNA, was determined by RT-PCR assay. Transfection study was carried out to examine the function of MT. RESULTS: Of various gastric cancer cell lines, SNU-638 and SNU-601 showed the highest and lowest levels of MT mRNA, respectively, showing 80-fold difference. The IC(50 )values of SNU-638 to cisplatin, carboplatin and heptaplatin were 11.2-fold, 5.1-fold and 2.0-fold greater than those of SNU-601, respectively. Heptaplatin was more effective against cisplatin-resistant and MT-transfected gastric cancer sublines than cisplatin or carboplatin was. In addition, heptaplatin attenuated cadmium, but not zinc, induction of MT. CONCLUSION: These results indicate that molecular mechanisms of heptaplatin effective against cisplatin-resistant gastric cancer sublines is at least in part due to the less involvement of MT in heptaplatin resistance as well as its attenuation of MT induction

Clinical Application of 7.0 T Magnetic Resonance Images in Gamma Knife Radiosurgery for a Patient with Brain Metastases

In the study we assessed the distortion of 7.0 T magnetic resonance (MR) images in reference to 1.5 T MR images in the radiosurgery of metastatic brain tumors. Radiosurgery with Gamma Knife Perfexion® was performed for the treatment of a 54-yr-old female patient with multiple brain metastases by the co-registered images of the 7.0 T and 1.5 T magnetic resonance images (MRI). There was no significant discrepancy in the positions of anterior and posterior commissures as well as the locations of four metastatic brain tumors in the co-registered images between 7.0 T and 1.5 T MRI with better visualization of the anatomical details in 7.0 T MR images. This study demonstrates for the first time that 7.0 T MR images can be safely utilized in Perfexion® Gamma Knife radiosurgery for the treatment of metastatic brain tumors. Furthermore 7.0 T MR images provide better visualization of brain tumors without image distortion in comparison to 1.5 T MR images

Harvey: A Greybox Fuzzer for Smart Contracts

We present Harvey, an industrial greybox fuzzer for smart contracts, which are programs managing accounts on a blockchain. Greybox fuzzing is a lightweight test-generation approach that effectively detects bugs and security vulnerabilities. However, greybox fuzzers randomly mutate program inputs to exercise new paths; this makes it challenging to cover code that is guarded by narrow checks, which are satisfied by no more than a few input values. Moreover, most real-world smart contracts transition through many different states during their lifetime, e.g., for every bid in an auction. To explore these states and thereby detect deep vulnerabilities, a greybox fuzzer would need to generate sequences of contract transactions, e.g., by creating bids from multiple users, while at the same time keeping the search space and test suite tractable. In this experience paper, we explain how Harvey alleviates both challenges with two key fuzzing techniques and distill the main lessons learned. First, Harvey extends standard greybox fuzzing with a method for predicting new inputs that are more likely to cover new paths or reveal vulnerabilities in smart contracts. Second, it fuzzes transaction sequences in a targeted and demand-driven way. We have evaluated our approach on 27 real-world contracts. Our experiments show that the underlying techniques significantly increase Harvey's effectiveness in achieving high coverage and detecting vulnerabilities, in most cases orders-of-magnitude faster; they also reveal new insights about contract code.Comment: arXiv admin note: substantial text overlap with arXiv:1807.0787

Incidence and Seroprevalence of Hepatitis A Virus Infections among Young Korean Soldiers

This study was performed to determine the incidence and seroprevalence of hepatitis A virus (HAV) infections in young soldiers in the Republic of Korea Army. From January 2000 through December 2004, a total of 147 hepatitis A cases were reported to the Armed Forces Medical Command. The annual incidence rates were 7.4 per 100,000 persons in 2000, 1.6 in 2001, 4.4 in 2002, 9.8 in 2003, and 6.2 in 2004, based on the reported cases among approximately 500,000 soldiers. All patients were males with a median age of 21 yr (range, 19-27). The most common symptom was nausea (86.5%), and all patients had recovered without complications. In addition, in order to evaluate the seroprevalence of HAV infection in young adults, serum samples were obtained from randomly selected young subjects among those who had been admitted to the Armed Forces Capital Hospital from September 2005 to February 2006. A total of 200 subjects were enrolled in the study to analyze the anti-HAV immune status. The overall anti-HAV IgG seropositive rate was 2% (4/200, 95% CI, 0.60-5.21%). Given the changing epidemiology of the disease and the associated increase in morbidity, it was suggested that the routine HAV vaccination for Korean military personnel might be necessary

Lactic Acidosis Triggers Starvation Response with Paradoxical Induction of TXNIP through MondoA

Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenvironmental stresses: lactic acidosis, glucose deprivation, and hypoxia. We found that lactic acidosis and glucose deprivation trigger highly similar transcriptional responses, each inducing features of starvation response. In contrast to their comparable effects on gene expression, lactic acidosis and glucose deprivation have opposing effects on glucose uptake. This divergence of metabolic responses in the context of highly similar transcriptional responses allows the identification of a small subset of genes that are regulated in opposite directions by these two conditions. Among these selected genes, TXNIP and its paralogue ARRDC4 are both induced under lactic acidosis and repressed with glucose deprivation. This induction of TXNIP under lactic acidosis is caused by the activation of the glucose-sensing helix-loop-helix transcriptional complex MondoA:Mlx, which is usually triggered upon glucose exposure. Therefore, the upregulation of TXNIP significantly contributes to inhibition of tumor glycolytic phenotypes under lactic acidosis. Expression levels of TXNIP and ARRDC4 in human cancers are also highly correlated with predicted lactic acidosis pathway activities and associated with favorable clinical outcomes. Lactic acidosis triggers features of starvation response while activating the glucose-sensing MondoA-TXNIP pathways and contributing to the “anti-Warburg” metabolic effects and anti-tumor properties of cancer cells. These results stem from integrative analysis of transcriptome and metabolic response data under various tumor microenvironmental stresses and open new paths to explore how these stresses influence phenotypic and metabolic adaptations in human cancers

Interferometric tomography: Reconstruction algorithm, experiment, and comparison with a numerical study.

Interferometric tomography: Reconstruction algorithm, experiment, and comparison with a numerical study