Hyaluromycin, a Novel Hyaluronidase Inhibitor, Attenuates Pancreatic Cancer Cell Migration and Proliferation

Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated production and degradation of hyaluronan (HA), a major component of extracellular matrix involved in the malignant phenotype of cancer. In particular, increased hyaluronidase (HYAL) activity plays a critical role in cancer progression, at least in part, by producing low-molecular-weight- (LMW-) HA or small fragments of HA, suggesting HYAL as a target for cancer treatment. Hyaluromycin, a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces hyaluromycini as a HYAL inhibitor. We investigated the antitumor effects of hyaluromycin in PDAC cells. We examined the effects of hyaluromycin on the proliferation and migration of PDAC cells. To elucidate the mechanisms underlying the effect of hyaluromycin on PDAC cells, we examined the concentration of LMW-HA in the conditioned media after treating PDAC cells with hyaluromycin. We demonstrate that hyaluromycin inhibits proliferation and migration of PDAC cells. We also found that these antitumor effects of hyaluromycin were associated with a decreased concentration of LMW-HA and a decreased phosphorylation of ribosomal protein S6. Our results suggest that hyaluromycin is a promising new drug against this highly aggressive neoplasm

9-Hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells

AbstractThere is increasing interest in identifying potent inhibitors of telomerase because the enzyme plays a crucial role in the development of cellular immortality and carcinogenesis. We hypothesized that 9-hydroxyellipticine (9-HE), an antitumor alkaloid, would inhibit telomerase activity because the drug has a unique mechanism of inhibiting phosphorylation of mutant p53 protein via inhibition of protein kinases, thereby restoring wild-type p53 function. This study was conducted to examine the effect of 9-HE on telomerase activity in human pancreatic cancer cells with differing p53 gene status. 9-HE treatment at relatively high concentrations resulted in rapid, complete inhibition of telomerase activity, irrespective of the p53 status. We conclude that 9-HE may exert a strong inhibitory effect on telomerase activity possibly through inhibition of protein kinases rather than through restoration of functional wild-type p53

MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation

<p>Abstract</p> <p>Background</p> <p>Recently, the microRNA-200 family was reported to affect cancer biology by regulating epithelial to mesenchymal transition (EMT). Especially, the expression of <it>miR-200c </it>has been shown to be associated with upregulating the expression of <it>E-cadherin</it>, a gene known to be involved in pancreatic cancer behavior. However, the significance of <it>miR-200c </it>in pancreatic cancer is unknown.</p> <p>Methods</p> <p>In the present study, we investigated the relationship between <it>E-cadherin </it>and <it>miR-200c </it>expression in a panel of 14 pancreatic cancer cell lines and in macro-dissected formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from 99 patients who underwent pancreatectomy for pancreatic cancer. We also investigated the effects of <it>miR-200c </it>on the proliferation and invasion of pancreatic cancer cells.</p> <p>Results</p> <p>We found that patients with high levels of <it>miR-200c </it>expression had significantly better survival rates than those with low levels of <it>miR-200c </it>expression. We also found a remarkably strong correlation between the levels of <it>miR-200c </it>and <it>E-cadherin </it>expression.</p> <p>Conclusions</p> <p>These data indicate that <it>miR-200c </it>may play a role in the pancreatic cancer biology and may be a novel marker for the prognosis of pancreatic cancer.</p

Repeated Pancreatectomy for Recurrent Pancreatic Carcinoma after Pylorus-Preserving Pancreatoduodenectomy: Report of Two Patients

Repeated pancreatectomy for pancreatic carcinoma is extremely rare. We report two such patients who underwent pancreatectomy for carcinoma developing in the pancreatic remnant after pylorus-preserving pancreatoduodenectomy (PpPD) for invasive pancreatic ductal carcinoma. One patient underwent PpPD for invasive pancreatic ductal carcinoma and received adjuvant chemotherapy. Follow-up computed tomography (CT) demonstrated a low-density mass in the remnant pancreas, which was diagnosed as a carcinoma by endoscopic ultrasound-guided fine-needle aspiration cytology 5 years 10 months after PpPD. She underwent curative resection of the remnant pancreas and is alive and well 13 months after the second operation. The other patient underwent PpPD for invasive pancreatic ductal carcinoma. Follow-up CT showed a low-density mass in the remnant pancreas after 2 years 11 months. He received systemic chemotherapy with S-1 for 3 months. The tumor shrank, and the patient underwent curative resection of the remnant pancreas 3 years 1 month after the initial operation. Repeated pancreatectomy may provide a chance of long survival for patients with carcinoma developing in the remnant pancreas after pancreatectomy if the recurrence occurring at long term is limited to the remnant pancreas

Tumor-dependent secretion of close homolog of L1 results in elevation of its circulating level in mouse model for human lung tumor

Close homolog of L1 (CHL1) and its truncated form mainly play crucial roles in mouse brain development and neural functions. Herein, we newly identified that truncated form of CHL1 is produced and released from lung tumor tissue in a mouse model expressing human EML4-ALK fusion gene. Both western blot and direct ELISA analysis revealed that mouse CHL1 level in serum (including serum extracellular vesicles) was significantly elevated in EML4-ALK transgenic mice. The correlation between the tumor size and the amount of CHL1 secretion could be examined in this study, and showed a significant positive correlation in a tumor size-dependent manner. Considering these results, the measurement of circulating CHL1 level may contribute to assess a tumor progression in human lung tumor patients

Craniofacial sensations induced by transient changes of barometric pressure in healthy subjects – A crossover pilot study

Background: Changes in atmospheric pressure are suggested to trigger headaches. This pilot study was made to determine craniofacial sensations accompanying short phases of changing barometric pressure. Methods: In a crossover design, 15 adult healthy subjects were exposed in a climate chamber to 8 min phases of barometric pressure lowering by 0, 20 and 40 hPa. The subjects rated their sensations of ear pressure, head compression and the occurrence of headache every minute on a visual analogue scale (VAS, range 0–10). Pulse rate was recorded as a parameter for autonomic functions. Results: Nearly all subjects experienced ear pressure and half of them compression of their head at variable degrees. These sensations started in most subjects during the phase of lowering barometric pressure and increased to an average rating of about 3 VAS when returning to ambient atmospheric pressure. Heart rate slightly decreased during this phase. Three subjects reported mild to moderate headache for various durations within these phases. Conclusions: Changes in barometric pressure can be associated with sensations of ear pressure and head compression and may trigger headaches. The generation of these sensations is discussed with regard to convergent trigeminal innervation of the ear, the paranasal sinuses and the cranial meninges

The Global academic research organization network: Data sharing to cure diseases and enable learning health systems.

Introduction:Global data sharing is essential. This is the premise of the Academic Research Organization (ARO) Council, which was initiated in Japan in 2013 and has since been expanding throughout Asia and into Europe and the United States. The volume of data is growing exponentially, providing not only challenges but also the clear opportunity to understand and treat diseases in ways not previously considered. Harnessing the knowledge within the data in a successful way can provide researchers and clinicians with new ideas for therapies while avoiding repeats of failed experiments. This knowledge transfer from research into clinical care is at the heart of a learning health system. Methods:The ARO Council wishes to form a worldwide complementary system for the benefit of all patients and investigators, catalyzing more efficient and innovative medical research processes. Thus, they have organized Global ARO Network Workshops to bring interested parties together, focusing on the aspects necessary to make such a global effort successful. One such workshop was held in Austin, Texas, in November 2017. Representatives from Japan, Taiwan, Singapore, Europe, and the United States reported on their efforts to encourage data sharing and to use research to inform care through learning health systems. Results:This experience report summarizes presentations and discussions at the Global ARO Network Workshop held in November 2017 in Austin, TX, with representatives from Japan, Korea, Singapore, Taiwan, Europe, and the United States. Themes and recommendations to progress their efforts are explored. Standardization and harmonization are at the heart of these discussions to enable data sharing. In addition, the transformation of clinical research processes through disruptive innovation, while ensuring integrity and ethics, will be key to achieving the ARO Council goal to overcome diseases such that people not only live longer but also are healthier and happier as they age. Conclusions:The achievement of global learning health systems will require further exploration, consensus-building, funding aligned with incentives for data sharing, standardization, harmonization, and actions that support global interests for the benefit of patients

A Novel Extraction Method of Fetal Electrocardiogram From the Composite Abdominal Signal

科研費報告書収録論文(課題番号:18390306/研究代表者:木村芳孝/多電極母体腹壁誘導胎児心電図による全週数型胎児心筋虚血モニタリングの基礎研究