Invasion and Metastasis as a Central Hallmark of Breast Cancer.

Hanahan and Weinberg introduced the "hallmarks of cancer" and typified essential biological abilities acquired by human cancer. Since then, a growing understanding of hallmark principles associated with breast cancer has assisted knowledge-based therapeutics development; however, despite the rapidly increasing number of targeted therapeutics, enduring disease-free responses for most forms of breast cancer is rare. Invasion and metastasis are the most defining feature of breast cancer malignancy and the leading cause of patient mortality.

Are We Ready for Migrastatics?

Metastasis accounts for the highest mortality rates in solid tumor cancer patients. However, research and development have neglected this most lethal characteristic and, instead, have concentrated on the hallmarks of cancer that make tumor cells highly proliferative and distinctive from nonmalignant cells. The concentration on invasion and metastasis can be one of the most meaningful advancements in cancer investigation.

Pyk2 regulates cell-edge protrusion dynamics by interacting with Crk.

Focal adhesion kinase (FAK) is well established as a regulator of cell migration, but whether and how the closely related proline-rich tyrosine kinase 2 (Pyk2) regulates fibroblast motility is still under debate. Using mouse embryonic fibroblasts (MEFs) from Pyk2 mice, we show here, for the first time, that lack of Pyk2 significantly impairs both random and directed fibroblast motility. Pyk2 MEFs show reduced cell-edge protrusion dynamics, which is dependent on both the kinase and protein-protein binding activities of Pyk2.

Author Correction: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex.

The anticancer agent indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. To delineate the precise mechanism by which indisulam mediates the DCAF15-RBM39 interaction, we solved the DCAF15-DDB1-DDA1-indisulam-RBM39(RRM2) complex structure to a resolution of 2.

Safety and efficacy of amniotic cytokine extract in the treatment of dry eye disease.

Evaluate the safety and efficacy of cryopreserved amniotic cytokine extract (ACE) in the treatment of subjects with dry eye disease (DED). This was a retrospective, multicenter, chart review of adult patients with DED that instilled cryopreserved ACE drops twice-daily for 4 or 12 weeks. Patients had corneal fluorescein staining (0-20 range) and/or a lissamine green conjunctival staining score (0-18 range) of ≥3 and ≤9 in at least 1 eye and a score ≥40 (0-100 range) of eye dryness/irritation on a visual analog scale (VAS).

Toric outcomes: Computer-assisted registration versus intraoperative aberrometry.

Purpose: To compare refractive outcomes of intraoperative computer-assisted registration and intraoperative aberrometry for the reduction of cylinder during toric intraocular lens (IOL) placement.

Setting: Bowie Vision Institute, Bowie, Maryland, USA.

Design: Prospective randomized case series.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013).

Chemical ordering in substituted fluorite oxides: a computational investigation of HoZrO and REThO (RE=Ho, Y, Gd, Nd, La).

Fluorite-structured oxides find widespread use for applications spanning nuclear energy and waste containment, energy conversion, and sensing. In such applications the host tetravalent cation is often partially substituted by trivalent cations, with an associated formation of charge-compensating oxygen vacancies. The stability and properties of such materials are known to be influenced strongly by chemical ordering of the cations and vacancies, and the nature of such ordering and associated energetics are thus of considerable interest.

Continuous Curvilinear Capsulorhexis Performed With the VERUS Ophthalmic Caliper.

Purpose: To compare size, circularity, and centration outcomes of continuous curvilinear capsulorhexis (CCC) performed with or without assistance from the VERUS ophthalmic caliper (Mile High Ophthalmics, Denver, CO).

Methods: This was a multicenter retrospective consecutive case controlled series review.

Results: Data from 40 consecutive cases using the VERUS device for CCC were compared to 40 consecutive cases with standard manual CCC.

U(v) in metal uranates: a combined experimental and theoretical study of MgUO4, CrUO4, and FeUO4.

Although pentavalent uranium can exist in aqueous solution, its presence in the solid state is uncommon. Metal monouranates, MgUO4, CrUO4 and FeUO4 were synthesized for detailed structural and energetic investigations. Structural characteristics of these uranates used powder X-ray diffraction, synchrotron X-ray absorption spectroscopy, X-ray photoelectron spectroscopy, and (57)Fe-Mössbauer spectroscopy.

Englerin A Agonizes the TRPC4/C5 Cation Channels to Inhibit Tumor Cell Line Proliferation.

Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A.

Integrated compound profiling screens identify the mitochondrial electron transport chain as the molecular target of the natural products manassantin, sesquicillin, and arctigenin.

Phenotypic compound screens can be used to identify novel targets in signaling pathways and disease processes, but the usefulness of these screens depends on the ability to quickly determine the target and mechanism of action of the molecules identified as hits. One fast route to discovering the mechanism of action of a compound is to profile its properties and to match this profile with those of compounds of known mechanism of action. In this work, the Novartis collection of over 12,000 pure natural products was screened for effects on early zebrafish development.

Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi.

Ivermectin (IVM) is a broad-spectrum anthelmintic used in filariasis control programs. By binding to nematode glutamate-gated chloride channels (GluCls), IVM disrupts neurotransmission processes regulated by GluCl activity. IVM treatment of filarial infections is characterized by an initial dramatic drop in the levels of circulating microfilariae, followed by long-term suppression of their production, but the drug has little direct effect on microfilariae in culture at pharmacologically relevant concentrations.

Wear behavior and in vitro cytotoxicity of wear debris generated from hydroxyapatite-carbon nanotube composite coating.

This work evaluates the effect of carbon nanotube (CNT) addition to plasma-sprayed hydroxyapatite (HA) coating on its tribological behavior, biocompatibility of the coating, and cytotoxicity of CNT-containing wear debris. Biological response of the CNT-containing wear debris is critical for osteoblasts, the bone-forming cells, and macrophages, the cells that clear up wear debris from blood stream. The addition of 4 wt % CNTs to HA coating reduces the volume of wear debris generation by 80% because of the improved elastic modulus and fracture toughness.

Posterior capsule opacity as initial manifestation of metastatic cutaneous melanoma.

Background: Cutaneous metastatic melanoma usually is locoregional, and represents less than 5% of malignancies known to metastasize to the eye and orbit. When there is intraocular involvement, it most commonly occurs in the choroid, vitreous, and retina.

Methods: We report a case of a 71-year-old woman with metastatic melanoma presenting as a pigmented posterior capsular opacity in a pseudophakic eye 14 months after excisional biopsy of an ulcerative cutaneous melanoma of the upper arm.

Outcomes of corneal spherical aberration-guided cataract surgery measured by the OPD-scan.

Purpose: To determine based on preoperative corneal spherical aberration, the practicality of targeting zero total ocular postoperative spherical aberration when selecting an aspheric intraocular lens (IOL).

Methods: Consecutive cataract patients were selected to receive an aspheric IOL based on corneal spherical aberration. A target of zero postoperative total spherical aberration Z(4,0) was calculated.

A signal from inside the peroxisome initiates its division by promoting the remodeling of the peroxisomal membrane.

We define the dynamics of spatial and temporal reorganization of the team of proteins and lipids serving peroxisome division. The peroxisome becomes competent for division only after it acquires the complete set of matrix proteins involved in lipid metabolism. Overloading the peroxisome with matrix proteins promotes the relocation of acyl-CoA oxidase (Aox), an enzyme of fatty acid beta-oxidation, from the matrix to the membrane.