Characterizing Novel Kras/p53 Derived NSCLC Cell Lines

https://openworks.mdanderson.org/sumexp22/1026/thumbnail.jp

Rotating Black Holes in Higher Dimensions with a Cosmological Constant

We present the metric for a rotating black hole with a cosmological constant and with arbitrary angular momenta in all higher dimensions. The metric is given in both Kerr-Schild and Boyer-Lindquist form. In the Euclidean-signature case, we also obtain smooth compact Einstein spaces on associated S^{D-2} bundles over S^2, infinitely many for each odd D\ge 5. Applications to string theory and M-theory are indicated.Comment: 8 pages, Latex. Short version, with more compact notation, of hep-th/0404008. To appear in Phys. Rev. Let

K811 acetylation regulates ZEB1 dimerization, protein stability, and NuRD complex interactions to promote lung adenocarcinoma progression and metastasis

View full abstracthttps://openworks.mdanderson.org/leading-edge/1010/thumbnail.jp

Pan-urologic cancer genomic subtypes that transcend tissue of origin

AbstractUrologic cancers include cancers of the bladder, kidney, prostate, and testes, with common molecular features spanning different types. Here, we show that 1954 urologic cancers can be classified into nine major genomic subtypes, on the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy number, and RNA and protein expression). Tissue dominant effects are first removed computationally in order to define these subtypes, which reveal common processes—reflecting in part tumor microenvironmental influences—driving cellular behavior across tumor lineages. Six of the subtypes feature a mixture of represented cancer types as defined by tissue or cell of origin. Differences in patient survival and in the manifestation of specific pathways—including hypoxia, metabolism, NRF2-ARE, Hippo, and immune checkpoint—can further distinguish the subtypes. Immune checkpoint markers and molecular signatures of macrophages and T cell infiltrates are relatively high within distinct subsets of each cancer type studied. The pan-urologic cancer genomic subtypes would facilitate information sharing involving therapeutic implications between tissue-oriented domains.</jats:p

Lysosomal transmembrane protein TMEM106B alters TFEB signaling and the tumor immune microenvironment

View full abstracthttps://openworks.mdanderson.org/leading-edge/1001/thumbnail.jp

Priorities in policy and management when existing biodiversity stressors interact with climate-change

There are three key drivers of the biodiversity crisis: (1) the well known existing threats to biodiversity such as habitat loss, invasive pest species and resource exploitation; (2) direct effects of climate-change, such as on coastal and high elevatio

Exploring anti-PD-1 resistance mechanisms for therapeutic targeting in NSCLC

View full abstracthttps://openworks.mdanderson.org/leading-edge/1035/thumbnail.jp

Ultrahigh-throughput generation and characterization of cellular aggregates in laser-ablated microwells of poly(dimethylsiloxane)

Aggregates of cells, also known as multicellular aggregates (MCAs), have been used as microscale tissues in the fields of cancer biology, regenerative medicine, and developmental biology for many decades. However, small MCAs (fewer than 100 cells per aggregate) have remained challenging to manufacture in large quantities at high uniformity. Forced aggregation into microwells offers a promising solution for forming consistent aggregates, but commercial sources of microwells are expensive, complicated to manufacture, or lack the surface packing densities that would significantly improve MCA production. To address these concerns, we custom-modified a commercial laser cutter to provide complete control over laser ablation and directly generate microwells in a poly(dimethylsiloxane) (PDMS) substrate. We achieved ultra rapid microwell production speeds (>50000 microwells per h) at high areal packing densities (1800 microwells per cm2) and over large surface areas for cell culture (60 cm2). Variation of the PDMS substrate distance from the laser focal plane during ablation allowed for the generation of microwells with a variety of sizes, contours, and aspect ratios. Casting of high-fidelity microneedle masters in polyurethane allowed for non-ablative microwell reproduction through replica molding. MCAs of human bone marrow derived mesenchymal stem cells (hMSCs), murine 344SQ metastatic adenocarcinoma cells, and human C4-2 prostate cancer cells were generated in our system with high uniformity within 24 hours, and computer vision software aided in the ultra-high-throughput analysis of harvested aggregates. Moreover, MCAs maintained invasive capabilities in 3D migration assays. In particular, 344SQ MCAs demonstrated epithelial lumen formation on Matrigel, and underwent EMT and invasion in the presence of TGF-β. We expect this technique to find broad utility in the generation and cultivation of cancer cell aggregates, primary cell aggregates, and embryoid bodies