application-robot-assisted-pancreaticobiliary-junction-resection

Application of Robot-assisted Pancreaticobiliary Junction Resection in Benign Duodenal Tumors

Robot-assisted pancreaticobiliary junction resection is a surgical technique employed to treat benign duodenal tumors. The procedure involves several key ...

Sun Yat-sen University

Stress-Inducible Protein-1 (STIP1) is a co-chaperone that associates directly with heat shock proteins, and regulates motility of various types of cancer. In the present study, we investigated the role of STIP1 on metastasis of gastric cancer (GC).

Stress-inducible Protein-1 promotes metastasis of gastric cancer via Wnt/β-catenin signaling pathway.

SSR subunit γ (SSR3), an SSR family member, is heavily involved in cell growth and differentiation and closely associated with many tumor types. However, the role of this protein in HCC remains unknown. In this study, we used data from public databases to analyze SSR3 expression in HCC. We subjected 20 pairs of fresh-frozen tissues to quantitative real-time polymerase chain reaction to investigate SSR3 expression. We also subjected 95 formalin-fixed, paraffin-embedded HCC tissues to immunohistochemistry to detect SSR3 expression and determine the clinical significance of SSR3 expression in HCC. Bioinformatics analysis and quantitative real-time polymerase chain reaction results showed that compared with that in adjacent normal liver tissues, SSR3 was highly expressed in HCC tissues. High SSR3 expression was positively correlated with tumor size (P < .01), cancer embolus (P = .01), TNM stages (P = .02), and differentiation grades (P < .01). Kaplan-Meier and Cox proportional hazards analyses indicated that high SSR3 expression was significantly associated with poor survival in HCC patients and that SSR3 was an independent prognostic factor for overall survival in HCC patients. In conclusion, SSR3 acts as an oncogene in HCC and can therefore serve as a biomarker for the prognoses of HCC patients.

Overexpression of signal sequence receptor γ predicts poor survival in patients with hepatocellular carcinoma.

The role of transarterial chemoembolization (TACE) as the standard treatment for intermediate-stage hepatocellular carcinoma (HCC) is being challenged by increasing studies supporting liver resection (LR); but evidence of survival benefits of LR is lacking. We aimed to compare the overall survival (OS) of LR with that of TACE for the treatment of intermediate-stage HCC in cirrhotic patients.

Liver resection versus transarterial chemoembolization for the treatment of intermediate-stage hepatocellular carcinoma.

Tissue factor (TF) is a transmembrane glycoprotein to initiate blood coagulation and frequently overexpressed in a variety of tumors. Our previous study has showed that the expression of TF is upregulated and correlated with prognosis in hepatocellular carcinoma (HCC). However, the role and molecular mechanism of TF in the growth of HCC are still unclear.  and  functional experiments were performed to determine the effect of TF on the growth of HCC cells. A panel of biochemical assays was used to elucidate the underlying mechanisms. TF could promote the growth of HCC  and  by activating both ERK and AKT signaling pathways. TF induced EGFR upregualtion, and inhibition of EGFR suppressed TF-mediated HCC growth. In addition, TF protein expression was correlated with EGFR in HCC tissues. TF promotes HCC growth by upregulation of EGFR, and TF as well as EGFR may be potential therapeutic targets of HCC.

Targeting TF-AKT/ERK-EGFR Pathway Suppresses the Growth of Hepatocellular Carcinoma.

Recurrent hepatocellular carcinoma (rHCC) patients with microvascular invasive (MVI) positive at first resection usually had poorly differentiated tumors and worse survivals. The optimal treatment for this population remains to be elucidated.

Treatment selection of recurrent hepatocellular carcinoma with microvascular invasion at the initial hepatectomy.

Incomplete radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) could initiate malignant transition. Patient-derived xenograft (PDX) mice model was established to investigate the effect of VEGF pathway in incomplete RFA of HCC with high fidelity. Cancer stem cell markers and metastatic markers were increased after incomplete RFA, with increased VEGFR1 and decreased VEGFR2 expression. In vitro experiments revealed sublethal heat treatment promoted migration ability of HepG2, HCCLM3, and SMMC7721 cells, which coincided with enhanced ability of sphere formation and up-regulation of VEGFR1, CD133, CD44, and EpCAM. Moreover, HCC cells secreted more VEGF after heat-treatment. VEGF promoted migration and enhanced stemness of HCC cells, which could not be suppressed by VEGFR2 inhibitor. PIGF, the ligand of VEGFR1, significantly increased migration and stemness of HCC cells. Blocking VEGFR1 reduced heat-induced enhancement of migration and stemness, whereas inhibition of VEGFR2 could not. In conclusion, VEGFR1 plays a critical role in sublethal heat treatment-induced enhancement of migration and stemness in HCC, suggesting that VEGFR1 may serve as a potential and promising therapeutic target for preventing recurrence after RFA.

Sublethal heat treatment of hepatocellular carcinoma promotes intrahepatic metastasis and stemness in a VEGFR1-dependent manner.

Emerging evidence has revealed that lncRNA small nucleolar RNA host gene 3 (SNHG3) is involved in cell proliferation, migration, and invasion in various tumors. However, the underlying molecular mechanism of SNHG3 in hepatocellular carcinoma (HCC) is still not fully explored.

LncSNHG3/miR-139-5p/BMI1 axis regulates proliferation, migration, and invasion in hepatocellular carcinoma.

Limited effective intervention for advanced hepatocellular carcinoma (HCC) is available. This study aimed to investigate the potential clinical utility of apatinib, a highly selective inhibitor of the vascular endothelial growth factor receptor-2 (VEGFR2) tyrosine kinase, as a radiosensitizer in the treatment of HCC.

Apatinib potentiates irradiation effect via suppressing PI3K/AKT signaling pathway in hepatocellular carcinoma.

Altered expression of Urea Cycle (UC) enzymes occurs in many tumors, resulting a metabolic hallmark termed as UC dysregulation. Polyamines are synthesized from ornithine, and polyamine synthetic genes are elevated in various tumors. However, the underlying deregulations of UC/ polyamine synthesis in cancer remain elusive. Here, we characterized a hypoxia-induced lncRNA LVBU (lncRNA regulation via BCL6/urea cycle) that is highly expressed in colorectal cancer (CRC) and correlates with poor cancer prognosis. Increased LVBU expression promoted CRC cells proliferation, foci formation and tumorigenesis. Further, LVBU regulates urea cycle and polyamine synthesis through BCL6, a negative regulator of p53. Mechanistically, overexpression of LVBU competitively bound miR-10a/miR-34c to protect BCL6 from miR-10a/34c-mediated degradation, which in turn allows BCL6 to block p53-mediated suppression of genes (arginase1 ARG1, ornithine transcarbamylase OTC, ornithine decarboxylase 1 ODC1) involved in UC/polyamine synthesis. Significantly, ODC1 inhibitor attenuated the growth of patient derived xenografts (PDX) that sustain high LVBU levels. Taken together, elevated LVBU can regulate BCL6-p53 signaling axis for systemic UC/polyamine synthesis reprogramming and confers a predilection toward CRC development. Our data demonstrates that further drug development and clinical evaluation of inhibiting UC/polyamine synthesis are warranted for CRC patients with high expression of LVBU.

Roles of lncRNA LVBU in regulating urea cycle/polyamine synthesis axis to promote colorectal carcinoma progression.

Chromodomain helicase DNA binding protein (CHD) family plays critical roles in regulating gene transcription. The family is linked to cancer disease, but the family member's role in tumorigenesis remains largely unknown. Here, we report that CHD6 is highly expressed in colorectal cancer (CRC). CHD6 knockdown inhibited cancer cell proliferation, migration, invasion, and tumorigenesis. Consistently, Villin-specific Chd6 knockout in mice attenuates cancer formation in AOM/DSS model. We found that aberrant EGF signals promoted the stability of CHD6 by diminishing ubiquitin-mediated degradation. EGF signal inhibits GSK3β activity, which in turn prevents phosphodegron formation of CHD6, thereby hindering E3 ligase FBXW7-mediated CHD6 ubiquitination and degradation. CHD6's chromatin remodeler activity engages in binding Wnt signaling transcription factor TCF4 to facilitate the transcriptional expression of TMEM65, a mitochondrial inner membrane protein involved in ATP production and mitochondrial dynamics. In addition, Wnt signaling is also an upstream regulator of CHD6. CHD6 promoter contains TCF4 and β-catenin binding site, and CHD6 can be transcriptionally activated by Wnt ligand to facilitate TMEM65 transcription. Thus CHD6-TMEM65 axis can be regulated by both EGF and Wnt signaling pathways through two different mechanisms. We further illustrate that CHD6-TMEM65 axis is deregulated in cancer and that co-administration of Wnt inhibitor LGK974 and the anti-EGFR monoclonal antibody cetuximab largely restricted the growth of patient-derived xenografts of CRC. Targeting CHD6-TMEM65 axis may be effective for cancer intervention.

The chromatin remodeler CHD6 promotes colorectal cancer development by regulating TMEM65-mediated mitochondrial dynamics via EGF and Wnt signaling.

Numerous studies have demonstrated that individual proteins can moonlight. Eukaryotic Initiation translation factor 3, f subunit (eIF3f) is involved in critical biological functions; however, its role independent of protein translation in regulating colorectal cancer (CRC) is not characterized. Here, it is demonstrated that eIF3f is upregulated in CRC tumor tissues and that both Wnt and EGF signaling pathways are participating in eIF3f's oncogenic impact on targeting phosphoglycerate dehydrogenase (PHGDH) during CRC development. Mechanistically, EGF blocks FBXW7β-mediated PHGDH ubiquitination through GSK3β deactivation, and eIF3f antagonizes FBXW7β-mediated PHGDH ubiquitination through its deubiquitinating activity. Additionally, Wnt signals transcriptionally activate the expression of eIF3f, which also exerts its deubiquitinating activity toward MYC, thereby increasing MYC-mediated PHGDH transcription. Thereby, both impacts allow eIF3f to elevate the expression of PHGDH, enhancing Serine-Glycine-One-Carbon (SGOC) signaling pathway to facilitate CRC development. In summary, the study uncovers the intrinsic role and underlying molecular mechanism of eIF3f in SGOC signaling, providing novel insight into the strategies to target eIF3f-PHGDH axis in CRC.

eIF3f Mediates SGOC Pathway Reprogramming by Enhancing Deubiquitinating Activity in Colorectal Cancer.

Eukaryotic initiation translation factor 3 subunit h (EIF3H) plays critical roles in regulating translational initiation and predicts poor cancer prognosis, but the mechanism underlying EIF3H tumorigenesis remains to be further elucidated. Here, we report that EIF3H is overexpressed in colorectal cancer (CRC) and correlates with poor prognosis. Conditional Eif3h deletion suppresses colorectal tumorigenesis in AOM/DSS model. Mechanistically, EIF3H functions as a deubiquitinase for HAX1 and stabilizes HAX1 via antagonizing βTrCP-mediated ubiquitination, which enhances the interaction between RAF1, MEK1 and ERK1, thereby potentiating phosphorylation of ERK1/2. In addition, activation of Wnt/β-catenin signaling induces EIF3H expression. EIF3H/HAX1 axis promotes CRC tumorigenesis and metastasis in mouse orthotopic cancer model. Significantly, combined targeting Wnt and RAF1-ERK1/2 signaling synergistically inhibits tumor growth in EIF3H-high patient-derived xenografts. These results uncover the important roles of EIF3H in mediating CRC progression through regulating HAX1 and RAF1-ERK1/2 signaling. EIF3H represents a promising therapeutic target and prognostic marker in CRC.

The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression.

Non-hypervascular hypointense nodules (NHHNs) can transform into hypervascular hepatocellular carcinoma (HCC) during the long-term follow-up. However, the risk factors for NHHN hypervascular transformation in chronic hepatitis B virus (HBV)-infected populations are unknown. This study assessed the predictive value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for HCC development in patients with chronic HBV infection.

Prediction of the early hepatocellular carcinoma development in patients with chronic hepatitis B virus infection using gadoxetic acid-enhanced magnetic resonance imaging.

Article	Year
Stress-inducible Protein-1 promotes metastasis of gastric cancer via Wnt/β-catenin signaling pathway. Journal of experimental & clinical cancer research : CR\| PubMed ID: 29335007	2018
Overexpression of signal sequence receptor γ predicts poor survival in patients with hepatocellular carcinoma. Human pathology\| PubMed ID: 29940286	2018
Liver resection versus transarterial chemoembolization for the treatment of intermediate-stage hepatocellular carcinoma. Cancer medicine\| PubMed ID: 30864247	2019
Targeting TF-AKT/ERK-EGFR Pathway Suppresses the Growth of Hepatocellular Carcinoma. Frontiers in oncology\| PubMed ID: 30931258	2019
Treatment selection of recurrent hepatocellular carcinoma with microvascular invasion at the initial hepatectomy. American journal of translational research\| PubMed ID: 30972210
Sublethal heat treatment of hepatocellular carcinoma promotes intrahepatic metastasis and stemness in a VEGFR1-dependent manner. Cancer letters\| PubMed ID: 31173855	2019
LncSNHG3/miR-139-5p/BMI1 axis regulates proliferation, migration, and invasion in hepatocellular carcinoma. OncoTargets and therapy\| PubMed ID: 31692508	2019
Apatinib potentiates irradiation effect via suppressing PI3K/AKT signaling pathway in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR\| PubMed ID: 31694662	2019
Roles of lncRNA LVBU in regulating urea cycle/polyamine synthesis axis to promote colorectal carcinoma progression. Oncogene\| PubMed ID: 35906392	2022
The chromatin remodeler CHD6 promotes colorectal cancer development by regulating TMEM65-mediated mitochondrial dynamics via EGF and Wnt signaling. Cell discovery\| PubMed ID: 36473865	2022
eIF3f Mediates SGOC Pathway Reprogramming by Enhancing Deubiquitinating Activity in Colorectal Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 37544925	2023
The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression. Nature communications\| PubMed ID: 38514606	2024
Prediction of the early hepatocellular carcinoma development in patients with chronic hepatitis B virus infection using gadoxetic acid-enhanced magnetic resonance imaging. BMC cancer\| PubMed ID: 39563280	2024

Huilin Jin

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