A gene encoding a protein related to the serpin family of protease inhibitors was identified as a candidate tumor suppressor gene that may play a role in human breast cancer. The gene product, called maspin, is expressed in normal mammary epithelial cells but not in most mammary carcinoma cell lines. Transfection of MDA-MB-435 mammary carcinoma cells with the maspin gene did not alter the cells' growth properties in vitro, but reduced the cells' ability to induce tumors and metastasize in nude mice and to invade through a basement membrane matrix in vitro. Analysis of human breast cancer specimens revealed that loss of maspin expression occurred most frequently in advanced cancers. These results support the hypothesis that maspin functions as a tumor suppressor.

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Bulk polymers are generally regarded as thermal insulators, and typically have thermal conductivities on the order of 0.1 W m(-1) K(-1). However, recent work suggests that individual chains of polyethylene--the simplest and most widely used polymer--can have extremely high thermal conductivity. Practical applications of these polymers may also require that the individual chains form fibres or films. Here, we report the fabrication of high-quality ultra-drawn polyethylene nanofibres with diameters of 50-500 nm and lengths up to tens of millimetres. The thermal conductivity of the nanofibres was found to be as high as approximately 104 W m(-1) K(-1), which is larger than the conductivities of about half of the pure metals. The high thermal conductivity is attributed to the restructuring of the polymer chains by stretching, which improves the fibre quality toward an 'ideal' single crystalline fibre. Such thermally conductive polymers are potentially useful as heat spreaders and could supplement conventional metallic heat-transfer materials, which are used in applications such as solar hot-water collectors, heat exchangers and electronic packaging.

Surface phonon polaritons are electromagnetic waves that propagate along the interfaces of polar dielectrics and exhibit a large local-field enhancement near the interfaces at infrared frequencies. Theoretical calculations show that such surface waves can lead to breakdown of the Planck's blackbody radiation law in the near field. Here, we experimentally demonstrate that surface phonon polaritons dramatically enhance energy transfer between two surfaces at small gaps by measuring radiation heat transfer between a microsphere and a flat surface down to 30 nm separation. The corresponding heat transfer coefficients at nanoscale gaps are 3 orders of magnitude larger than that of the blackbody radiation limit. The high energy flux can be exploited to develop new radiative cooling and thermophotovoltaic technologies.

Maspin, a novel serine protease inhibitor (serpin), inhibits tumor invasion and metastasis of mammary carcinoma. We show here that recombinant maspin protein blocks the motility of these carcinoma cells in culture over 12 h, as demonstrated by time-lapse video microscopy. Lamellopodia are withdrawn but ruffling continues. Both exogenous recombinant maspin and maspin expressed by tumor transfectants exhibit inhibitory effects on cell motility and cell invasion as shown in modified Boyden chamber assays. In addition, three prostatic cancer cell lines treated with recombinant maspin exhibited similar inhibition of both invasion and motility, suggesting a similar mode of maspin action in these two glandular epithelial cancers. When mammary carcinoma cells were treated with recombinant maspin, the protein was shown by immunostaining to bind specifically to the cell surface, suggesting that maspin activity is membrane associated. When pretreated with antimaspin antibody, maspin loses its inhibitory effects on both invasion and motility. However, when maspin is added to these cells preceding antibody treatment, the activity of maspin is no longer inhibited by subsequent addition of the antibody. It is concluded therefore that the inhibition of invasion and motility by maspin is initially localized to the cell surface.Candidate tumor suppressor genes can be identified by absence of their mRNA in tumor cells compared with normal cells (1). One such gene, maspin (mammary serine protease inhibitor), was identified by subtractive hybridization (2) and was shown to have tumor suppressive activity by a number of criteria (3, 4): (i) maspin mRNA and protein are produced in normal mammary epithelial cells, partially down-regulated in primary tumor cell lines and lost in mammary carcinoma cell lines; (ii) maspin transfectants injected into nude mice are inhibited in tumor growth and metastasis; (iii) loss of maspin expression correlates with increasing malignancy in breast cancer; (iv) maspin shows sequence homology with other inhibitory serpins ranging from 30% to 40% at the protein level; (v) both recombinant maspin proteins and endogenously expressed maspin in transfectants inhibit tumor invasion across reconstituted basement membrane (Matrigel) in culture; and (vi) the reactive center of maspin is crucial for this biological activity which is lost following proteolytic cleavage (3, 5).Two serpins related to maspin, plasminogen-activator inhibitors 1 and 2 (PAI-1 and PAI-2), have been proposed to inhibit tumor invasion and metastasis (6)(7)(8). This proposal is based, first, on the in vitro biochemical evidence that both PAI-1 and PAI-2 can block the conversion of plasminogen to plasmin by inhibiting plasminogen activator (9). Plasmin in turn is considered to be a major protease involved in the destruction of the basal lamina, permitting tumor cells to enter the stroma and subsequently blood vessels. How effective either inhibitor may be in blocking the invasion process in vivo is not known.On the clinical side, PAI-1...

One of the principal biochemical characteristics of malignant cells compared to normal cells is a metabolic switch from oxidative phosphorylation to increased glycolysis, even under hypoxic conditions, and is termed the Warburg effect. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. It is elevated in many types of cancers and has been linked to tumor growth, maintenance, and invasion; therefore, its inhibition may restrict the energy supply in tumors and thereby reduce the metastatic and invasive potential of cancer cells. This enzyme is receiving a great deal of attention as a potential diagnostic marker or a predictive biomarker for many types of cancer and as a therapeutic target for new anticancer treatments. In this review, we summarize the role of LDHA in cancer, discuss its potential significance in clinical diagnosis and prognosis of cancer, and propose LDHA as a novel target for the inhibition of tumor growth and invasiveness. V C 2013 IUBMB Life, 65(11): [904][905][906][907][908][909][910] 2013

Near-field force and energy exchange between two objects due to quantum electrodynamic fluctuations give rise to interesting phenomena such as Casimir and van der Waals forces, and thermal radiative transfer exceeding Planck's theory of blackbody radiation. Although significant progress has been made in the past on the precise measurement of Casimir force related to zero-point energy, experimental demonstration of near-field enhancement of radiative heat transfer is difficult. In this work, we present a sensitive technique of measuring near-field radiative transfer between a microsphere and a substrate using a bi-material atomic force microscope (AFM) cantilever, resulting in "heat transfer-distance" curves. Measurements of radiative transfer between a sphere and a flat substrate show the presence of strong near-field effects resulting in enhancement of heat transfer over the predictions of the Planck blackbody radiation theory.Comment: 12 pages, 2 figure

Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of SARS-CoV-2 replication. Internalized 25HC accumulates in the late endosomes and potentially restricts SARS-CoV-2 spike protein catalyzed membrane fusion via blockade of cholesterol export. Our results highlight one of the possible antiviral mechanisms of 25HC and provide the molecular basis for its therapeutic development.