Somatic mutations in FAT cadherin family members constitute an underrecognized subtype of colorectal adenocarcinoma with unique clinicopathologic features

BACKGROUND: The FAT cadherin family members (FAT1, FAT2, FAT3 and FAT4) are conserved tumor suppressors that are recurrently mutated in several types of human cancers, including colorectal carcinoma (CRC). AIM: To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members. METHODS: We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset. CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in RESULTS: This CRC study cohort had frequent mutations in the CONCLUSION

Ghost on the Shell: An Expressive Representation of General 3D Shapes

The creation of photorealistic virtual worlds requires the accurate modeling of 3D surface geometry for a wide range of objects. For this, meshes are appealing since they 1) enable fast physics-based rendering with realistic material and lighting, 2) support physical simulation, and 3) are memory-efficient for modern graphics pipelines. Recent work on reconstructing and statistically modeling 3D shape, however, has critiqued meshes as being topologically inflexible. To capture a wide range of object shapes, any 3D representation must be able to model solid, watertight, shapes as well as thin, open, surfaces. Recent work has focused on the former, and methods for reconstructing open surfaces do not support fast reconstruction with material and lighting or unconditional generative modelling. Inspired by the observation that open surfaces can be seen as islands floating on watertight surfaces, we parameterize open surfaces by defining a manifold signed distance field on watertight templates. With this parameterization, we further develop a grid-based and differentiable representation that parameterizes both watertight and non-watertight meshes of arbitrary topology. Our new representation, called Ghost-on-the-Shell (G-Shell), enables two important applications: differentiable rasterization-based reconstruction from multiview images and generative modelling of non-watertight meshes. We empirically demonstrate that G-Shell achieves state-of-the-art performance on non-watertight mesh reconstruction and generation tasks, while also performing effectively for watertight meshes.Comment: Technical Report (26 pages, 16 figures, Project Page: https://gshell3d.github.io/

Recombinant immunotoxin anti-c-Met/PE38KDEL inhibits proliferation and promotes apoptosis of gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Our study aims to evaluate the anti-growth effects of recombinant immunotoxin (IT) anti-c-Met/PE38KDEL on gastric cancer cells, and its mechnisms.</p> <p>Methods</p> <p>Gastric cancer cells were treated with increasing doses of IT and c-Met protein was quantified by Western blotting. Cell proliferation was determined by Cell Counting Kit-8 assay (CCK). [³H]-leucine incorporation assay was used to evaluate IT inhibition of protein synthesis. Cell apoptosis was quantified by flow cytometry. Caspase activities were measured using colorimetric protease assays.</p> <p>Results</p> <p>Cell growth and protein synthesis of the gastric cancer cell lines were suppressed by IT in a dose- and time-dependent manner. IT also induced apoptosis in a dose-dependent manner. The apoptosis rates of gastric cancer cell lines MKN-45 and SGC7901 were 19.19% and 27.37%, respectively when treated with 50 ng/ml of IT. There were significant increase ofcaspase-3 activity at 24 hr of IT treatment (100 ng/ml) (P < 0.01) in these gastric cancer cell lines.</p> <p>Conclusions</p> <p>IT anti-c-Met/PE38KDEL has anti-growth effects on the gastric cancer cell lines <it>in vitro</it>, and it provides an experimental basis for c-Met-targeted therapy towards <it>in vivo </it>testing.</p

PACAP neuropeptide promotes Hepatocellular Protection via CREB-KLF4 dependent autophagy in mouse liver Ischemia Reperfusion Injury.

Organ ischemia reperfusion injury (IRI), associated with acute hepatocyte death, remains an unresolved problem in clinical orthotopic liver transplantation (OLT). Autophagy, an intracellular self-digesting progress, is responsible for cell reprograming required to regain post-stress homeostasis. Methods: Here, we analyzed the cytoprotective mechanism of pituitary adenylate cyclase-activating polypeptide (PACAP)-promoted hepatocellular autophagy in a clinically relevant mouse model of extended hepatic cold storage (4 °C UW solution for 20 h) followed by syngeneic OLT. Results: In contrast to 41.7% of liver graft failure by day 7 post-transplant in control group, PACAP treatment significantly improved graft survival (91.7% by day 14), and promoted autophagy-associated regeneration programs in OLT. In parallel in vitro studies, PACAP-enhanced autophagy ameliorated cellular damage (LDH/ALT levels), and diminished necrosis in H2O2-stressed primary hepatocytes. Interestingly, PACAP not only induced nuclear cAMP response element-binding protein (CREB), but also triggered reprogramming factor Kruppel-like factor 4 (KLF4) expression in IR-stressed OLT. Indeed, CREB inhibition attenuated hepatic autophagy and recreated hepatocellular injury in otherwise PACAP-protected livers. Furthermore, CREB inhibition suppressed PACAP-induced KLF4 expression, whereas KLF4 blockade abolished PACAP-promoted autophagy and neutralized PACAP-mediated hepatoprotection both in vivo and in vitro. Conclusion: Current study documents the essential neural regulation of PACAP-promoted autophagy in hepatocellular homeostasis in OLT, which provides the emerging therapeutic principle to combat hepatic IRI in OLT

Expressions and clinic significance of miRNA-143, miRNA- 34A, miRNA-944, miRNA-101 and miRNA-218 in cervical cancer tissues

Purpose: To search for novel biomarkers for early diagnosis of cervical cancer, as well as novel therapeutic target for cervical cancer.Methods: A total of 96 cervical tissue specimens were collected from patients in the Second Affiliated Hospital of Zhengzhou University, out of which 10 were normal control. The remaining specimens (86) were cervical cancer specimens and were divided into 4 groups (A - D) based on tumor-biomarker levels of CA125 and SCC. Quantitative real-time polymerase chain reaction technology (qRT-PCR) was used to detect the expressions of miRNA-143, miRNA-34A, miRNA-944, miRNA-101 and miRNA-218 in the cervical cancer tissues.Results: The levels of CA125 (U/mL) and SCC (ug/L) expressed in normal control group and groups A - D were 11.75 and 0.73 (n = 10), 382 and 2.72 (n = 25), 912.9 and 3.93 (n = 21), 1675 and 5.87 (n = 29), and 2120 and 6.66 (n = 11), respectively. Furthermore, qRT-PCR results showed that the expressions of miRNA-944 and miRNA-218 in cervical cancer tissues were markedly up-regulated compared to normal control tissues (p &lt; 0.01). In contrast, the expression level of miRNA-143, miRNA-34A, and miRNA-101 were significantly decreased (p &lt; 0.01).Conclusion: The biomarkers, miRNA-143, miRNA-34A, miRNA-944, miRNA-101 and miRNA-218, can be considered novel for early diagnosis of cervical cancer.Keywords: Cervical cancer, Biomarkers, miRNA-143, miRNA-34A, miRNA-944, miRNA-101, miRNA- 21

Sesquiterpenes from the marine red alga Laurencia composita.

Four new chamigrane derivatives, laurecomin A (1). laurecomin B (2), laurecomin C (3), and laurecomin D (4), one new naturally occurring sesquiterpene, 2,10-dibromo-3-chloro-7-chamigren-9-ol acetate (5), and three known halogenated structures, deoxyprepacifenol (6), 1-bromoselin-4(14),11-diene (7), and 9-bromoselin-4(14).11-diene (8), were isolated from the marine red alga Laurencia cornposita collected from Pingtan Island, China. The structures of these compounds were unambiguously established by 1D, 2D NMR and mass spectroscopic techniques. The bioassay results showed that 2 was active against both brine shrimp and fungus Colletotrichum lagenarium. (C) 2012 Elsevier B.V. All rights reserved.Four new chamigrane derivatives, laurecomin A (1). laurecomin B (2), laurecomin C (3), and laurecomin D (4), one new naturally occurring sesquiterpene, 2,10-dibromo-3-chloro-7-chamigren-9-ol acetate (5), and three known halogenated structures, deoxyprepacifenol (6), 1-bromoselin-4(14),11-diene (7), and 9-bromoselin-4(14).11-diene (8), were isolated from the marine red alga Laurencia cornposita collected from Pingtan Island, China. The structures of these compounds were unambiguously established by 1D, 2D NMR and mass spectroscopic techniques. The bioassay results showed that 2 was active against both brine shrimp and fungus Colletotrichum lagenarium. (C) 2012 Elsevier B.V. All rights reserved

{μ-trans-N,N′-Bis[(diphenyl­phosphan­yl)meth­yl]benzene-1,4-diamine-κ2 P:P′}bis­{(acetonitrile-κN)[dipyrido[3,2-a:2′,3′-c]phenazine-κ2 N 4,N 5]copper(I)} bis­(tetra­fluoridoborate)

In the centrosymmetric dinuclear title compound, [Cu2(C2H3N)2(C18H10N4)2(C32H30N2P2)](BF4)2, the CuI centre is coordinated by two N atoms from a dipyridophenazine ligand, one P atom from an N,N′-bis­[(diphenyl­phosphan­yl)meth­yl]benzene-1,4-diamine (bpbda) ligand, and one N atom from an acetonitrile mol­ecule in a distorted tetra­hedral geometry. The bpbda ligand, lying on an inversion center, bridges two CuI centres into a Z-shaped complex. Intra­molecular π–π inter­actions between the dipyridophenazine ligand and the benzene ring of the bpbda ligand are observed [centroid–centroid distance = 3.459 (3) Å]. The crystal structure also involves inter­molecular π–π inter­actions between the dipyridophenazine ligands [centroid–centroid distance = 3.506 (3) Å], which lead to a one-dimensional supra­molecular structure