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Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.

Summary: In this paper, an out‐of‐band suppression enhanced high‐efficiency millimeter‐wave (mm‐wave) gallium nitride (GaN) microwave monolithic integrated circuit (MMIC) filtering power amplifier (FPA) is presented. A modified elliptic response bandpass filtering (BPF) output matching network (OMN) is used to achieve low loss and high out‐of‐band rejection. The circuit of the presented BPF OMN is given and its synthesized method is introduced. The simulated S‐parameters show that the OMN has a low‐loss in‐band response and a desired out‐of‐band rejection performance with two transmission zeros (TZs). To demonstrate this idea, a two‐stage 24–28‐GHz GaN MMIC PA is designed and implemented in a 0.15‐μm GaN‐on‐SiC process, with a mask area of 2.4 × 1.0 mm2. Experimental results show that the realized MMIC PA achieves a small signal gain of 18.8 dB from 24 to 28 GHz with ±1.2‐dB gain flatness and 40‐dB rejection at 19.43 and 33.8 GHz. The saturated power‐added efficiency (PAE) is higher than 29% from 24 to 28 GHz, with a peak PAE of 36.3% at 27 GHz. The output power is within the range of 33.8 to 35.6 dBm in the operating band. For a 100‐MHz five‐carrier LTE signal, the PA can achieve ACLR better than −40 dBc over the band with digital predistortion. [ABSTRACT FROM AUTHOR]

Summary: This paper presents a broadband monolithic millimeter‐wave integrated circuit GaN power amplifier (PA) with arbitrary two‐port complex‐impedance matching method. The proposed matching topology has been applied to interstage matching network design by modifying traditional coupling matrix and synthesizing a desired network. The optimum load traction technique is introduced to provide some more suitable Zopts. After continuous‐wave test, the three‐stage MMIC PA achieves a peak PAE of 39.1% with a 34.9 dBm output power from 23 to 29.5 GHz and the measured S21 is 32.5 dB with a ±2.5 dB gain variation. When driven by a 400 MHz OFDM modulation signal with a PAPR of 8.5 dB, the measured ACPR is improved to −40.6/−40.7 dBc with DPD. In this case, the PA achieves an average PAE of 11.7% and a 26.7 dBm average output power. [ABSTRACT FROM AUTHOR]

Abstract Background Catenin is a gene family composed of three subfamilies; p120, beta and alpha. Beta and p120 are homologous subfamilies based on sequence and structural comparisons, and are members of the armadillo repeat protein superfamily. Alpha does not appear to be homologous to either beta or p120 based on the lack of sequence and structural similarity, and the alpha subfamily belongs to the vinculin superfamily. Catenins link the transmembrane protein cadherin to the cytoskeleton and thus function in cell-cell adhesion. To date, only the beta subfamily has been evolutionarily analyzed and experimentally studied for its functions in signaling pathways, development and human diseases such as cancer. We present a detailed evolutionary study of the whole catenin family to provide a better understanding of how this family has evolved in metazoans, and by extension, the evolution of cell-cell adhesion. Results All three catenin subfamilies have been detected in metazoans used in the present study by searching public databases and applying species-specific BLAST searches. Two monophyletic clades are formed between beta and p120 subfamilies using Bayesian phylogenetic inference. Phylogenetic analyses also reveal an array of duplication events throughout metazoan history. Furthermore, numerous annotation issues for the catenin family have been detected by our computational analyses. Conclusions Delta2/ARVCF catenin in the p120 subfamily, beta catenin in the beta subfamily, and alpha2 catenin in the alpha subfamily are present in all metazoans analyzed. This implies that the last common ancestor of metazoans had these three catenin subfamilies. However, not all members within each subfamily were detected in all metazoan species. Each subfamily has undergone duplications at different levels (species-specific, subphylum-specific or phylum-specific) and to different extents (in the case of the number of homologs). Extensive annotation problems have been resolved in each of the three catenin subfamilies. This resolution provides a more coherent description of catenin evolution.

Gastric cancer, one of the most common types of cancers, develops over a series of consecutive histopathological stages. As such, the analysis and research of the gastric precancerous lesions (GPLs) play an important role in preventing the occurrence of gastric cancer. Ginsenoside Rg3 (Rg3), an herbal medicine, plays an important role in the prevention and treatment of various cancers. Studies have demonstrated a correlation between glycolysis and gastric cancer progression. Herein, the aim of the present study was to clarify the potential role for glycolysis pathogenesis in Rg3-treated GPL in Atp4a−/− mice. The GPL mice model showed chronic gastritis, intestinal metaplasia, and more atypical hyperplasia in gastric mucosa. According to the results of HE and AB-PAS staining, it could be confirmed that GPL mice were obviously reversed by Rg3. Additionally, the increased protein levels of PI3K, AKT, mTOR, HIF-1α, LDHA, and HK-II, which are crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis in the model group, were downregulated by Rg3. Meanwhile, the miRNA-21 expression was decreased and upregulated by Rg3. Furthermore, the increased gene levels of Bcl-2 and caspase-3 were attenuated in Rg3-treated GPL mice. In conclusion, the findings of this study imply that abnormal glycolysis in GPL mice was relieved by Rg3 via regulation of the expressions of PI3K, AKT, mTOR, HIF-1α, LDHA, HK-II, and miRNA-21. Rg3 is an effective supplement for GPL treatment and can be harnessed to inhibit proliferation and induce apoptosis of GPL cells. [ABSTRACT FROM AUTHOR]