Data_Sheet_1_Pre-clinical Models for Malignant Mesothelioma Research: From Chemical-Induced to Patient-Derived Cancer Xenografts.XLSX

<p>Malignant mesothelioma (MM) is a rare disease often associated with environmental exposure to asbestos and other erionite fibers. MM has a long latency period prior to manifestation and a poor prognosis. The survival post-diagnosis is often less than a year. Although use of asbestos has been banned in the United States and many European countries, asbestos is still being used and extracted in many developing countries. Occupational exposure to asbestos, mining, and migration are reasons that we expect to continue to see growing incidence of mesothelioma in the coming decades. Despite improvements in survival achieved with multimodal therapies and cytoreductive surgeries, less morbid, more effective interventions are needed. Thus, identifying prognostic and predictive biomarkers for MM, and developing novel agents for targeted therapy, are key unmet needs in mesothelioma research and treatment. In this review, we discuss the evolution of pre-clinical model systems developed to study MM and emphasize the remarkable capability of patient-derived xenograft (PDX) MM models in expediting the pre-clinical development of novel therapeutic approaches. PDX disease model systems retain major characteristics of original malignancies with high fidelity, including molecular, histopathological and functional heterogeneities, and as such play major roles in translational research, drug development, and precision medicine.</p

Network analyses for CACNA1G (A), CANA1H (B) and CACNA1I (C).

<p>Red color is more intense when associated with higher percentage of up-regulation in cancer samples. Blue lines mean: “controls the state change of”; green lines mean: “controls the expression of”; brown lines mean: “in complex with”.</p

Association of TTCC gene signature with outcome in gastric cancer.

<p>Association of TTCC gene signature with outcome in gastric cancer.</p

Interaction of TMCC1 with ribosomal proteins.

<p>(A) HEK293T cells were transfected with FLAG-tagged TMCC1 plasmid or the vector; 24 h post-transfection, cell lysates were prepared for anti-FLAG immunoprecipitation. Immunoprecipitated proteins were visualized on the protein gel by staining with Coomassie Brilliant Blue R-250. The protein bands marked in the figure were identified by mass spectrometry. Vector, pFLAG-CMV2 vector. (B) HeLa cell lysates were collected for TMCC1 immunoprecipitation, and samples were immunoblotted for TMCC1 and the ribosomal protein RPS6. (C) HEK293T cells were transfected with plasmids encoding FLAG-tagged TMCC1 full-length protein or fragments; 24 h post-transfection, cell lysates were collected for anti-FLAG immunoprecipitation. Ribosomal and FLAG-tagged proteins were analyzed by western blotting. Vector, pFLAG-CMV2 vector. FL, full-length TMCC1. (D) Ribosomes prepared from HeLa cells were incubated with purified GST or GST-TMCC1(101–350) protein and then pulled down using GSH-beads; ribosomal and GST-tagged proteins were analyzed by western blotting.</p

Association of the TTCC gene signature with outcome in gastric cancer: Subgroup analyses for first progression (Fig 1A) and overall survival (Fig 1B).

<p><b>Abbreviations:</b> HR (95%CI), hazard ratio (95% confidence interval); p, p-value; 5-FU, 5-fluorouracil; CT, chemotherapy.</p

Mass Selective Ion Transfer and Accumulation in Ion Trap Arrays

The concept and method for mass selective ion transfer and accumulation within quadrupole ion trap arrays have been demonstrated. Proof-of-concept experiments have been performed on two sets of ion trap arrays: (1) a linear ion trap with axial ion ejection plus a linear ion trap with radial ion ejection; (2) a linear ion trap with axial ion ejection plus a linear ion trap with axial ion ejection. In both sets of ion trap arrays, ions trapped in the first ion trap could be mass selectively transferred and accumulated into the second ion trap, while keeping other ions reserved in the first ion trap. Different operating modes have been implemented and tested, including transferring all ions, ions within a selected mass range, ions with a mass-to-charge ratio of 1, and randomly selected ions. Unit mass resolution for ion transfer and ∼90% ion transfer efficiency has been achieved. A new tandem mass spectrometry scheme for analyzing multiple precursor ions in a single sample injection has been demonstrated, which would improve instrument duty cycle and sample utilization rate (especially for very limited samples), potentially facilitate applications like single cell analyses, and improve electron transfer dissociation efficiency

Association of CACNA-1G, CACNA-1H and CACNA-1I with outcome in gastric cancer.

<p>Association of CACNA-1G, CACNA-1H and CACNA-1I with outcome in gastric cancer.</p

Thermo-mechanical fatigue crack growth in a nickel-based powder metallurgy superalloy

Fatigue crack growth is studied in a nickel-based powder metallurgy (PM) superalloy (FGH4099) subjected to in-phase (IP) and out-of-phase (OP) thermo-mechanical fatigue (TMF), as well as isothermal fatigue (IF) at peak temperature. The crack growth rate and path are evaluated for both coarse grain (CG) and fine grain (FG) FGH4099, especially the effects of phase angle and polycrystalline microstructure. The results show that the TMF crack propagation is mainly transgranular in OP condition; while in IP condition, fatigue crack propagates intergranularly at low ΔK and transforms to transgranular after passing the transition region. The crack propagation resistance for FG microstructure is lower than that for CG microstructure at elevated temperature, as a result of secondary cracks and grain boundary weakening effect. Crystallographic slip controls the crack propagation process, while the twin boundaries (TB) and special grain boundaries also exert a significant influence on crack deflection. The formation of secondary cracks is closely related to local misorientation and crystallographic deformation during TMF crack propagation. The crack deflection in a single grain reveals a competition mechanism between crystallographic slip and grain boundary effect, which explains the lower crack growth rate for OP when compared to IP or IF.</p

Homo- or hetero-dimerization or oligomerization of TMCC proteins.

<p>(A) HEK293T cells were co-transfected with plasmids encoding GFP-TMCC1 and FLAG-tagged TMCC1 fragments; 24 h post-transfection, cell lysates were collected for anti-FLAG immunoprecipitation to test for interactions between FLAG- and GFP-tagged proteins by performing western blotting. A schematic representation of the TMCC1 constructs is presented alongside the blots. Vector, pFLAG-CMV2 vector. FL, full-length TMCC1. (B) HEK293T cells were transfected with GFP-tagged TMCC1(571–653), TMCC2, or TMCC3 plasmids; 24 h post-transfection, cell lysates were prepared for TMCC1 immunoprecipitation to test for interaction between TMCC1 and exogenous proteins. TMCC1 and GFP-tagged proteins were analyzed by western blotting.</p

Sequence alignment of TMCC proteins.

<p>(A) Human TMCC family members. (B) Domain structures of human TMCC proteins. (C) TMCC1 in various organisms. Hs, <i>Homo sapiens</i>; Mm, <i>Mus musculus</i>; Gg, <i>Gallus gallus</i>; Xl, <i>Xenopus laevis</i>; Dr, <i>Danio rerio</i>; Dm, <i>Drosophila melanogaster</i>; Ce, <i>Caenorhabditis elegans</i>.</p