Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy

Although important strides have been made in targeted therapy for certain leukemias and subtypes of breast cancer, the standard of care for most carcinomas still involves chemotherapy, radiotherapy, surgery, or a combination of these. Two processes serve as obstacles to the successful treatment of carcinomas. First, a majority of deaths from these types of cancers occurs as a result of distant metastases and not the primary tumors themselves. Second, subsets of cells that are able to survive conventional therapy drive the aggressive relapse of the tumors, often in forms that are resistant to treatment. A frequently observed feature of malignant carcinomas is the loss of epithelial traits and the gain of certain mesenchymal ones that are programmed by the cell-biological program termed the epithelial-to-mesenchymal transition (EMT). The EMT program can confer (i) an ability to disseminate, (ii) an ability to become stem-like tumor-initiating cells, (iii) an ability to found new tumor colonies at distant anatomical sites, and (iv) an elevated resistance to therapy. These multiple powers of the EMT program explain why it has become an attractive target for therapeutic intervention. Recent work has revealed the variable nature of the EMT, with multiple versions of the program being observed depending on the tissue context and the stage of tumor progression. In this review, we attempt to crystallize emerging concepts in the research on EMTand stemness and discuss the benefits of using a differentiation-based therapeutic strategy for the eradication of stem-like populations that have adopted various versions of the EMT program.National Institutes of Health (U.S.) (grant R01 CA078461)National Institutes of Health (U.S.) (grant (P01 CA080111)Samuel Waxman Cancer Research FoundationMassachusetts Institute of Technology. Ludwig Center for Cancer Researc

Carbon materials as electrocatalysts for oxygen reduction in phosphoric acid medium

The behaviour of acstylene black (Indian grade) as catalyst support material is reported. The acetylene black is heat treated (activated) at variour temperatures in nitrogen atmosphere. The surface area of the various heat treated samples is obtained. Platinum is deporited into the carbon bye reported technique. The of platinum agglomeration on the carbon in identified through scanning electron microscope. The above catalyst is applied to glassy carbon disc. The electrochemical surface area of the catalyst ie determined by the hydrogen absorption and oxidation in alkaline medium. Similar electrodes (disc, dia 6 mm) are used in H3PO4 medium. Cyclic vottammograms are obtained in the oxygen evolution region and oxygen reduction region. The exchange current density of the catalyst for oxygen evolution and reduction ir reported for different catalyst loadings

Synthesis and characterization of LaCo03 based cathode and its chemical compatibility with Ce02 based electrolytes for intermediate temperature solid oxide fuel cell (ITSOFC)

The use of alternate cathode materials with improved performance and without any chemical reaction with adjoining electrolyte is required for a reduction in operating temperature of SOFC from 1273 K to about 1073 K (lTSOFC). Cobalt containing perovskite oxides such as LaCoOJ tend to exhibit a higher ionic conductivity due to a greater concentration of oxygen vacancies than other perovskite oxides. The mixed ionic and electronic conducting cathode of the Lal_xSr,CoOJ_o systems has shown the lowest cathodic overpotential for an SOFC air electrode. In this research work, fine powders of Lau.70SrO.JOCoOJ_o (LSC) cathode and Ceo.90Gdo.1002_o (GOC) and Ce080SmO.2002-5 (SOC) are synthesized by glycine nitrate combustion synthesis and systematically characterized by XRO and panicle characteristics. The electrical properties or LSC cathode and GOC and SOC electrolytes are also studied. I3ut, the crucial requirement for applicability of LSC cathode is its chemical compatibility in conjunction with the alternate solid electrolytes, GOC and SOC without any phase formation. The XRO studies showed no reaction products when the LaO.70SrO.JOCoOJ_o cathode is mixed and calcined with GOC and SOC electrolyte at 1573 K. Hence, the LSC cathode may be combined with Ce02 based electrolytes in ITSOFC application

Tackling the cancer stem cells — what challenges do they pose?

Since their identification in 1994, cancer stem cells (CSCs) have been objects of intensive study. Their properties and mechanisms of formation have become a major focus of current cancer research, in part because of their enhanced ability to initiate and drive tumour growth and their intrinsic resistance to conventional therapeutics. The discovery that activation of the epithelial-to-mesenchymal transition (EMT) programme in carcinoma cells can give rise to cells with stem-like properties has provided one possible mechanism explaining how CSCs arise and presents a possible avenue for their therapeutic manipulation. Here we address recent developments in CSC research, focusing on carcinomas that are able to undergo EMT. We discuss the signalling pathways that create these cells, cell-intrinsic mechanisms that could be exploited for selective elimination or induction of their differentiation, and the role of the tumour microenvironment in sustaining them. Finally, we propose ways to use our current knowledge of the complex biology of CSCs to design novel therapies to eliminate them.National Institutes of Health (U.S.) (Grant U54-CA163109)United States. Army Research Office (Grant 1210095

Emerging Biological Principles of Metastasis

Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge

A Composite Chiral Pair of Rotational Bands in the odd-A Nucleus 135Nd

High-spin states in 135Nd were populated with the 110Pd(30Si,5n)135Nd reaction at a 30Si bombarding energy of 133 MeV. Two Delta(I)=1 bands with close excitation energies and the same parity were observed. These bands are directly linked by Delta(I)=1 and Delta(I)=2 transitions. The chiral nature of these two bands is confirmed by comparison with three-dimensional tilted axis cranking calculations. This is the first observation of a three-quasiparticle chiral structure and established the primarily geometric nature of this phenomenon.Comment: 10 pages, 5 figures (1 in color), 1 table, submitted to Physics Review Letters, written in REVTEX4 forma

High-spin structure and Band Termination in 103^{103}Cd

Excited states of the neutron deficient $^{103}$Cd nucleus have been investigated via the $^{72}$Ge($^{35}$Cl, p3n) reaction at beam energy of 135 MeV by use of in-beam spectroscopic methods. Gamma rays depopulating the excited states were detected using the Gammasphere spectrometer with high-fold $\gamma$-ray coincidences. A quadrupole $\gamma$-ray coincidence analysis ($\gamma^{4}$) has been used to extend the known level scheme. The positive parity levels have been established up to $J = 35/2\hbar$ and $E_{x} = 7.071$ MeV. In addition to the observation of highly-fragmented level scheme belonging to the positive-parity sequences at E$_{x}\sim$ 5 MeV, the termination of a negative-parity sequence connected by $E2$ transitions has been established at $J = 47/2 \hbar$ and $E_{x} = 11.877$ MeV. The experimental results corresponding to both the positive- and negative-parity sequences have been theoretically interpreted in the framework of the core particle coupling model. Evidence is presented for a shape change from collective prolate to non-collective oblate above the $J^{\pi} = 39/2^{-}$ (8011 keV) level and for a smooth termination of the negative-parity band.Comment: 19 pages, 8 figures. Submitted to Phys. Rev.

Ontology Based Disease Information System

AbstractHuman body systems are interconnected and dependent and they can’t function separately. Diseases which affect any of these systems will affect other systems as well. In existing disease diagnosis systems, diseases were classified based on different dimensions such as cause, treatment, types of diseases, etc. On the other hand the existing disease information systems are for pest control management and they cannot be extended to human diseases. In existing systems traditional database approach was used. A database provides queried information and the retrieval method is not efficient in the case of biomedical systems. The proposed system will classify the diseases into the ‘system-wise diseases’ instead of many dimensions. The system needs careful handling of disease information. A disease information system would be appreciable instead of databases since the information systems may provide more precise and descriptive information. Therefore it is required to develop a disease information system by providing more relevant information as per the user query. The ontology based disease information system is being build and semantic based rules are designed to respond to the corresponding user query. The proposed information system is mainly focusing on improving the query results and also supports ease of use to the user

Lifetime measurements of Triaxial Strongly Deformed bands in 163^{163}Tm

With the Doppler Shift Attenuation Method, quadrupole transition moments, $Q_t$, were determined for the two recently proposed Triaxial Strongly Deformed (TSD) bands in $^{163}$Tm. The measured $Q_t$ moments indicate that the deformation of these bands is larger than that of the yrast, signature partners. However, the measured values are smaller than those predicted by theory. This observation appears to be valid for TSD bands in several nuclei of the regionComment: 8 pages, 5 figures. Submitted to Physical Review