patient-derived-heterogeneous-xenograft-model-pancreatic-cancer-using

Patient-derived Heterogeneous Xenograft Model of Pancreatic Cancer Using Zebrafish Larvae as Hosts for Comparative Drug Assessment

Patient-derived tumor xenograft (PDX) and cell-derived tumor xenograft (CDX) are important techniques for preclinical assessment, medication guidance and ...

National Human Genetic Resources Sharing Service Platform (2005DKA21300)

Fudan University Shanghai Cancer Center

Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis). How then is the repair choice made in S/G2 cells? Here we provide evidence demonstrating that APC plays a critical role in choosing the repair pathways in S/G2 cells. Our results suggest that the default for all DSBs is to recruit 53BP1 and RIF1. BRCA1 is blocked from being recruited to broken ends because its recruitment signal, K63-linked poly-ubiquitin chains on histones, is actively destroyed by the deubiquitinating enzyme USP1. We show that the removal of USP1 depends on APC and requires Chk1 activation known to be catalysed by ssDNA-RPA-ATR signalling at the ends designated for HDR, linking the status of end processing to RIF1 or BRCA1 recruitment.

The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites.

Most plant bacterial pathogens rely on type III effectors to cause diseases. Although it is well known that the plant hormone salicylic acid (SA) plays an essential role in defense, whether the master regulator of SA signaling, NPR1, is targeted by any plant pathogen effectors is unknown. SA facilitates the reduction of cytosolic NPR1 oligomers into monomers, which enter the nucleus and function as transcriptional coactivators of plant defense genes. We show that SA promotes the interaction between the Pseudomonas syringae type III effector AvrPtoB and NPR1. In the presence of SA, AvrPtoB mediates the degradation of NPR1 via the host 26S proteasome in a manner dependent on AvrPtoB's E3 ligase activity. Intriguingly, we found that NPR1 plays an important role in MAMP-triggered immunity (MTI), inducing the expression of MTI marker genes. Thus, this work uncovers a strategy in which AvrPtoB targets NPR1 and represses NPR1-dependent SA signaling, thereby subverting plant innate immunity.

A Bacterial Type III Effector Targets the Master Regulator of Salicylic Acid Signaling, NPR1, to Subvert Plant Immunity.

Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). The choice between these two pathways is largely influenced by cell cycle phases. HDR can occur only in S/G2 when sister chromatid can provide homologous templates, whereas NHEJ can take place in all phases of the cell cycle except mitosis. Central to NHEJ repair is the Ku70/80 heterodimer which forms a ring structure that binds DSB ends and serves as a platform to recruit factors involved in NHEJ. Upon completion of NHEJ repair, DNA double strand-encircling Ku dimers have to be removed. The removal depends on ubiquitylation and proteasomal degradation of Ku80 by the ubiquitin E3 ligases RNF8. Here we report that RNF8 is a substrate of APC and the latter keeps RNF8 level in check at DSBs to prevent premature turnover of Ku80.

The anaphase promoting complex promotes NHEJ repair through stabilizing Ku80 at DNA damage sites.

As a member of the p160 steroid receptor coactivator (SRC) family, nuclear receptor coactivator 2 (NCOA2) is known to play essential roles in many physiological and pathological processes, including development, endocrine regulation, and tumorigenesis. However, the biological function of NCOA2 in breast cancer is not fully understood. We found that the copy number of the  gene was frequently amplified in four breast cancers datasets, varying from 6 to 10%, and the mRNA levels of  were also upregulated in 11% of the sequenced cases/patients (TCGA provisional dataset). Next, we confirmed that  silencing significantly suppressed cell proliferation in different breast cancer cell lines, by inducing cell cycle arrest and apoptosis. Mechanistically, whole-transcriptome sequencing (RNA-Seq) analysis showed that  depletion leads to downregulation of the MAPK/ERK signaling cascade, possibly via downregulating NCOA2's downstream target RASEF. In conclusion, our results suggest NCOA2 as a potential target of therapeutics against breast cancer.

Nuclear Receptor Coactivator 2 Promotes Human Breast Cancer Cell Growth by Positively Regulating the MAPK/ERK Pathway.

Despite the successful application of laser in animal experiments and clinics, the adjustment of laser parameters during surgery is still unclear. This study aimed to investigate the effect of different 980-nm diode laser parameters in hepatectomy. This could provide a clear protocol for using 980-nm diode laser in hepatectomy.

Effects of Different 980-nm Diode Laser Parameters in Hepatectomy.

The interaction of environmental factors and genetic factors may contribute to the risk of type 2 diabetes (T2D). We aimed to investigate whether age, gender, body mass index (BMI) and lifestyle factors have an effect on the association between the CDKAL1 polymorphisms and T2D.

A Novel Polymorphism (rs35612982) in CDKAL1 Is a Risk Factor of Type 2 Diabetes: A Case-Control Study.

X-ray cholangiography is of great value in the imaging of biliary tract diseases; however, occupational radiation exposure is unavoidable. Moreover, clinicians must manually inject the contrast dye, which may result in a relatively high incidence of adverse reactions due to unstable injection pressure. Thus, there is a need to develop a novel remote-controlled cholangiography injection device.

Remote-controlled cholangiography injection device: first clinical study in China.

Although marginal donor livers expand the donor pool, an ideal method for quantitatively evaluating the quality of donor livers has not been developed. This study aimed to explore the feasibility of indocyanine green (ICG) fluorescence imaging for estimating liver function in an ischemia-reperfusion model.

Near-infrared fluorescence imaging with indocyanine green for assessment of donor livers in a rat model of ischemia-reperfusion.

Liver cancer is characterized by hypervascularization. Anti-angiogenic agents may normalize the tumor vasculature and improve the efficacy of other treatments. The present study aims to investigate the anti-angiogenic effect of  infection in a mouse model of implanted liver cancer cells. HepG2 cells were injected into the left liver lobe of nude mice as a model of  hepatic tumorigenesis.  parasitized erythrocytes were administered in the animal model of liver cancer to introduce  infection. The tumor growth and microvascular density were determined in the presence or absence of  infection. The expression levels of hypoxia-inducible factor 1α (HIF-1α) and angiogenesis-related factors were evaluated using western blotting and reverse transcription-quantitative PCR analysis. The results demonstrated that  infection suppressed tumor growth and vascularization in the mouse model of implanted HepG2 cells.  parasites reduced the expression of pro-angiogenic factors (vascular endothelial growth factor A and angiopoietin 2), matrix metalloproteinases [(MMP)2 and MMP9] and inflammatory cytokines [tumor necrosis factor α, interleukin 6 (IL)-6) and IL-1β] in both hepatic and tumor tissues. HIF-1α was downregulated in both hepatic and tumor tissues upon  infection, and HIF-1α overexpression rescued angiogenesis and tumor growth under the condition of  infection. In conclusion, the results of the present study demonstrated the anti-angiogenic and anti-tumorigenic effects of  infection on liver cancer through downregulating HIF-1α expression, indicating that  parasites could be developed as an intervention strategy to restrain neo-angiogenesis in liver cancer.

Article	Year
The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites. Nature communications\| PubMed ID: 28604711	2017
A Bacterial Type III Effector Targets the Master Regulator of Salicylic Acid Signaling, NPR1, to Subvert Plant Immunity. Cell host & microbe\| PubMed ID: 29174403	2017
The anaphase promoting complex promotes NHEJ repair through stabilizing Ku80 at DNA damage sites. Cell cycle (Georgetown, Tex.)\| PubMed ID: 29895199	2018
Nuclear Receptor Coactivator 2 Promotes Human Breast Cancer Cell Growth by Positively Regulating the MAPK/ERK Pathway. Frontiers in oncology\| PubMed ID: 30941313	2019
Effects of Different 980-nm Diode Laser Parameters in Hepatectomy. Lasers in surgery and medicine\| PubMed ID: 31090100	2019
A Novel Polymorphism (rs35612982) in CDKAL1 Is a Risk Factor of Type 2 Diabetes: A Case-Control Study. Kidney & blood pressure research\| PubMed ID: 31639799	2019
Remote-controlled cholangiography injection device: first clinical study in China. BMC gastroenterology\| PubMed ID: 34996384	2022
Near-infrared fluorescence imaging with indocyanine green for assessment of donor livers in a rat model of ischemia-reperfusion. BMC gastroenterology\| PubMed ID: 35057742	2022
infection downregulates hypoxia‑inducible factor 1α expression to suppress the vascularization and tumorigenesis of liver cancer. Oncology letters\| PubMed ID: 39483968	2024

Huan Chen

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