Explore the vast range of titles available.

Although clinical and radiological examinations can be used to diagnose oral cancer, and surgical pathology remains the gold standard, these conventional methods have limitations. We evaluated the feasibility of longitudinal next-generation sequencing-based liquid biopsy for oral squamous cell carcinoma surveillance. Eleven patients were enrolled, and plasma and saliva were collected before, and 1, 3, and 6 months after surgery. Tumor-specific mutations were selected using paired, whole-exome analyses of tumor tissues and whole blood. Genes frequently mutated in head and neck cancer were identified using the Cancer Genome Atlas (TCGA) and Catalogue of Somatic Mutations in Cancer (COSMIC) databases to design targeted deep sequencing panels. In five of the six patients with recurrent cancer, circulating tumor DNA (ctDNA) was detected earlier with liquid biopsy than with conventional monitoring techniques. Moreover, patients without recurrence exhibited decreased ctDNA allele frequency post-treatment. Longitudinal liquid biopsy of plasma and saliva may be feasible for detecting somatic mutations associated with oral squamous cell carcinomas. It might be attributable to determine early tumor recurrence through genetic analysis of ctDNA.

Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial–mesenchymal transition (EMT) is not well-understood. Here we show that Snail ( SNAI 1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo . Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP. Cancer cell survival under metabolic stress is a critical step for metastasis. Here, the authors show that under glucose deprivation, Snail, a key regulator of the metastatic process, promotes survival by diverting glucose to the pentose phosphate pathway through repression of phosphofructokinase PFKP.

Phosphorylation-dependent YAP translocation is a well-known intracellular mechanism of the Hippo pathway; however, the molecular effectors governing YAP cytoplasmic translocation remains undefined. Recent findings indicate that oncogenic YAP paradoxically suppresses Wnt activity. Here, we show that Wnt scaffolding protein Dishevelled (DVL) is responsible for cytosolic translocation of phosphorylated YAP. Mutational inactivation of the nuclear export signal embedded in DVL leads to nuclear YAP retention, with an increase in TEAD transcriptional activity. DVL is also required for YAP subcellular localization induced by E-cadherin, α-catenin, or AMPK activation. Importantly, the nuclear-cytoplasmic trafficking is dependent on the p53-Lats2 or LKB1-AMPK tumor suppressor axes, which determine YAP phosphorylation status. In vivo and clinical data support that the loss of p53 or LKB1 relieves DVL-linked reciprocal inhibition between the Wnt and nuclear YAP activity. Our observations provide mechanistic insights into controlled proliferation coupled with epithelial polarity during development and human cancer. Hippo and Wnt pathways are important for cancer development, and they can cross talk; however, the mechanisms behind this connection are unknown. Here the authors show that DVL (a scaffold protein in the Wnt pathway) regulates the shuttling of YAP (a key component of the Hippo pathway) between cytoplasm and nucleus in specific tumor suppressor contexts.

Cytotoxin-associated gene A (CagA) is an oncoprotein and a major virulence factor of H. pylori . CagA is delivered into gastric epithelial cells via a type IV secretion system and causes cellular transformation. The loss of epithelial adhesion that accompanies the epithelial–mesenchymal transition (EMT) is a hallmark of gastric cancer. Although CagA is a causal factor in gastric cancer, the link between CagA and the associated EMT has not been elucidated. Here, we show that CagA induces the EMT by stabilizing Snail, a transcriptional repressor of E-cadherin expression. Mechanistically we show that CagA binds GSK-3 in a manner similar to Axin and causes it to shift to an insoluble fraction, resulting in reduced GSK-3 activity. We also find that the level of Snail protein is increased in H. pylori infected epithelium in clinical samples. These results suggest that H. pylori CagA acts as a pathogenic scaffold protein that induces a Snail-mediated EMT via the depletion of GSK-3. Gastric cancer is associated with H. pylori infection and these tumours frequently show features of epithelial–mesenchymal transition (EMT). Here, the authors show that the H. pylori virulence protein, CagA, reduces the activity of GSK3b, which leads to the stabilization of Snail, a protein that induces EMT.

Background: Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. Methods: In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated in vitro and in vivo approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer. Results: The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer. Conclusions: The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.

Injury to the external branch of the superior laryngeal nerve (eSLN) can cause a hoarse or weak voice with dysergia of the cricothyroid. The present study provided the topographic information of the eSLN in the Asian and verified anatomical validity of the landmarks previously recruited to localize the eSLN. Thirty specimens were dissected from 16 human embalmed cadavers (12 men and four women; mean age: 80.5 years). The vertical distance between the eSLN and the apical pole of the thyroid gland (AP) was 8.2 ± 4.2 mm. It descended over the AP with <1 cm distance in 51.7%, >1 cm distance in 27.6% and under the AP in 20.7%. The piercing point (PP) of the eSLN to the muscles located 26.0 ± 5.5 mm posterior and 14.7 ± 5.0 mm inferior to the laryngeal prominence. Generally, the PP located superoposterior to the midpoint of the joint between the joint of inferior constrictor and cricothyroid (ICJ). The distance between the PP and the midpoint was 8.7 ± 5.1 mm. We found that 1) the Asian had the eSLN located over the AP with <1 cm distance about half cases, 2) the PP can be a consistent reference for the eSLN identification, 3) the ICJ can be a useful landmark to preserve the eSLN at the PP.

It is well known in the fracture mechanics community that the performance of brittle materials, such as different types of ceramics which have low fracture toughness, improves significantly when fibers are added into the material. This is because the presence of fibers deters the crack propagation. Fibers bridge the gap between two adjacent surfaces of the crack and reduce the crack tip opening displacement, thus make it harder to propagate. Several investigators have experimentally studied how the length, diameter and volume fraction of fibers affect the fracture toughness of fiber reinforced brittle matrix composite materials. However, to this date not much work has been done to develope a micro-mechanics based simplified mathematical model of fiber reinforced composites that can quantitatively explain the increase of the fracture toughness and strength of a composite with volume fraction, length and diameter of fibers, used for strengthening the composite, this is what is attempted in this paper.

Despite the importance of mitochondrial fatty acid oxidation (FAO) in cancer metabolism, the biological mechanisms responsible for the FAO in cancer and therapeutic intervention based on catabolic metabolism are not well defined. In this study, we observe that Snail (SNAI1), a key transcriptional repressor of epithelial–mesenchymal transition, enhances catabolic FAO, allowing pro-survival of breast cancer cells in a starved environment. Mechanistically, Snail suppresses mitochondrial ACC2 (ACACB) by binding to a series of E-boxes located in its proximal promoter, resulting in decreased malonyl-CoA level. Malonyl-CoA being a well-known endogenous inhibitor of fatty acid transporter carnitine palmitoyltransferase 1 (CPT1), the suppression of ACC2 by Snail activates CPT1-dependent FAO, generating ATP and decreasing NADPH consumption. Importantly, combinatorial pharmacologic inhibition of pentose phosphate pathway and FAO with clinically available drugs efficiently reverts Snail-mediated metabolic reprogramming and suppresses in vivo metastatic progression of breast cancer cells. Our observations provide not only a mechanistic link between epithelial–mesenchymal transition and catabolic rewiring but also a novel catabolism-based therapeutic approach for inhibition of cancer progression.

In the world, there are several types of vibration, and these vibrations especially affect the mechanical industry. In this paper, experimental analysis of vibration modes of plates is discussed. Electronic speckle pattern interferometry (ESPI) is one of the optical nondestructive testing techniques. By using the ESPI, vibration modes of plates with various excitation points, ratio of longitudinal and lateral length, and materials are measured and qualitatively compared with the results of theoretical analysis proposed by Warburton. Finally, these vibration modes are quantitatively compared with the result of FEM analysis. The results of this study are as follows: (1) By comparing the theoretical and experimental frequencies, we confirmed qualitatively that deviations of frequencies are within 10% in accuracy. (2) By comparing the experimental vibration mode shapes with the numerical ones of the FEM analysis, we can conclude quantitatively that measuring vibration modes by using the ESPI has high accuracy.[PUBLICATION ABSTRACT]

Background The impact of human activities on the environmental resistome has been documented in many studies, but there remains the controversial question of whether the increased antibiotic resistance observed in anthropogenically impacted environments is just a result of contamination by resistant fecal microbes or is mediated by indigenous environmental organisms. Here, to determine exactly how anthropogenic influences shape the environmental resistome, we resolved the microbiome, resistome, and mobilome of the planktonic microbial communities along a single river, the Han, which spans a gradient of human activities. Results The bloom of antibiotic resistance genes (ARGs) was evident in the downstream regions and distinct successional dynamics of the river resistome occurred across the spatial continuum. We identified a number of widespread ARG sequences shared between the river, human gut, and pathogenic bacteria. These human-related ARGs were largely associated with mobile genetic elements rather than particular gut taxa and mainly responsible for anthropogenically driven bloom of the downstream river resistome. Furthermore, both sequence- and phenotype-based analyses revealed environmental relatives of clinically important proteobacteria as major carriers of these ARGs. Conclusions Our results demonstrate a more nuanced view of the impact of anthropogenic activities on the river resistome: fecal contamination is present and allows the transmission of ARGs to the environmental resistome, but these mobile genes rather than resistant fecal bacteria proliferate in environmental relatives of their original hosts. -EAr6o8ZqqRG-rMJXcUMDB Video abstract.