Background. Oxaliplatin is the first‐choice chemotherapy method for patients with advanced colon cancer. However, its resistance leads to treatment failure for many patients. In our experiments, we aim to elucidate the associations among TRIM29 protein, mutant P53, and the resistance of colon cancer cells to oxaliplatin. Methods. HCT116 and HT‐29 cells were cultured and transfected with plasmids pIRES2‐ZsGreen1‐TRIM29‐flag. Western blot and real‐time qRT‐PCR were utilized to examine the protein and mRNA expressions of TRIM29 and other related markers, respectively. MTT assay was utilized to determine the cell growth rate and generate the inhibition curve. Continuous culture in low‐concentration oxaliplatin was conducted to construct oxaliplatin‐resistant cell lines. The coimmunoprecipitation method and immunofluorescence detection were used to examine the interaction between TRIM29 and mutant P53 protein in HT29 cells. Results. We successfully transfected pIRES2‐ZsGreen1‐TRIM29‐flag into HCT116 and HT29 cells, which were utilized in the whole experiments. TRIM29 significantly increased the sensitivity of P53 mutant colon cancer cell HT29 to oxaliplatin. The oxaliplatin‐resistant model of P53 mutant colon cancer cell HT29 was successfully constructed. TRIM29 physically bound with mutant P53 and retained it in the cytoplasm from the nucleus, which inhibited its transcription function of downstream genes such as MDR1. In addition, TRIM29 successfully reversed the resistance of HT29‐OX resistant cell model to oxaliplatin. Conclusion. In mutant P53 colon cancer cell HT29, TRIM29 greatly increased the sensitivity of HT29 to oxaliplatin and reverse oxaliplatin resistance. The underlying mechanism is TRIM29 may increase the sensitivity of HT29 to oxaliplatin by blocking the transcriptional function of mutant P53, which inhibits the transcription function of its downstream gene such as MDR1.

Liver cancer is the sixth most common cancer and the third leading cause of cancer‐related death globally. Despite efforts being made in last two decades in cancer diagnosis and treatment, the 5‐year survival rate of liver cancer remains extremely low. TRIM21 participates in cancer metabolism, glycolysis, immunity, chemosensitivity and metastasis by targeting various substrates for ubiquitination. TRIM21 serves as a prognosis marker for human hepatocellular carcinoma (HCC), but the mechanism by which TRIM21 regulates HCC tumorigenesis and progression remains elusive. In this study, we demonstrated that TRIM21 protein levels were elevated in human HCC. Elevated TRIM21 expression was associated with HCC progression and poor survival. Knockdown of TRIM21 in HCC cell lines significantly impaired cell growth and metastasis and enhanced sorafenib‐induced toxicity. Mechanistically, we found that knockdown of TRIM21 resulted in cytosolic translocation and inactivation of YAP. At the molecular level, we further identified that TRIM21 interacted and induced ubiquitination of MST1, which resulted in MST1 degradation and YAP activation. Knockdown of MST1 or overexpression of YAP reversed TRIM21 knockdown‐induced impairment of HCC growth and chemosensitivity. Taken together, the current study demonstrates a novel mechanism that regulates the Hippo pathway and reveals TRM21 as a critical factor that promotes growth and chemoresistance in human HCC.

Heat shock protein B8 (HSPB8) has been recently discovered to be participated in the regulation of tumor progression. However, the function of HSPB8 in intrahepatic cholangiocarcinoma (ICC) has not yet been elucidated. This study studied the function of HSPB8 in ICC progression. ICC patients (n = 150) were enrolled. The relationship between clinicopathological characteristics and HSPB8 expression was analyzed. RBE cells were transfected and treated by 3-MA. The RBE cells morphology was observed under a transmission electron microscope. Cell counting kit-8 assay, wound healing assay and Transwell experiment was conducted to detect RBE cells proliferation, migration and invasion. Quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, Western blot and immunofluorescence were used for genes detection in clinical tissues and RBE cells. HSPB8 was up-regulated in ICC tissues than that in adjacent normal tissues. High HSPB8 expression in ICC indicated poor prognosis of patients. HSPB8 expression was mainly expressed in cell cytoplasm and aberrantly increased in RBE cells (P < 0.01). HSPB8 up-regulation promoted RBE cells proliferation, migration and invasion (P < 0.05). HSPB8 down-regulation reduced RBE cells proliferation, migration and invasion (P < 0.01). HSPB8 overexpression facilitated Vimentin expression, LC3-II/LC3-I ratio and inhibited E-cadherin, p62 expression in RBE cells (P < 0.05). Treatment of 3-MA partially reversed HSPB8 promotion on RBE cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) (P < 0.05 or P < 0.01). HSPB8 promoted ICC progression by enhancing EMT and autophagy. HSPB8 might be an effective target for ICC treatment.

A 56-year-old woman was transferred from an outside hospital owing to concern about pancreatic duct (PD) obstruction and a pancreatic head mass. The patient had been admitted 1 week prior to the transfer with abdominal pain radiating to the waist and back, accompanied by nausea and vomiting. Her symptoms had since resolved with supportive measures, including anti-inflammatories and analgesics. Physical examination on admission did not reveal a jaundiced complexion and her abdomen was soft without tenderness. Outpatient laboratory results demonstrated a mildly elevated cancer antigen 199 (CA199) at 41.02 U/mL, but liver function panel, and serum and urinary amylase were within the normal ranges. Abdominal computed tomography (CT) at the previous hospital had shown PD dilatation and pancreatic head enlargement ([Fig. 1]). After admission, the patient underwent endoscopic ultrasonography (EUS). EUS from the stomach showed the PD dilatation in the body and tail of the pancreas ([Fig. 2 a]). The scan of the neck of the pancreas revealed a solid round hyperechoic lesion without acoustic shadowing in the PD ([Fig. 2 b]), so PD stones were ruled out. A linear hyperechoic area was seen in the PD within the pancreatic head during scanning from the duodenal bulb, but there was no central hypoechoic rim (“innertube” sign) ([Fig. 2 c]). Side-viewing endoscopy showed the shape and size of the duodenal papilla were normal and no worms were noticed within the intestines. EUS from ampulla demonstrated the PD and bile duct openings were normal. A repeat pancreatic head scan from the descending duodenum was performed, and a solid round hyperechoic area without acoustic shadowing was again seen in the PD ([Fig. 2 d]). A diagnosis of an Ascaris in the PD was considered. Accordingly, an endoscopic retrograde cholangiopancreatography (ERCP) was performed. After successful intubation, pancreatography showed that the PD was dilated. A stripe-like filling defect was seen in the PD ([Fig. 3]). An endoscopic sphincterotomy was then performed and the papillary sphincter was dilated to 4 mm with balloon dilation catheters. Another stone extraction balloon was used for foreign body removal. A moving, white round worm was discharged from the papilla in a folded shape ([Fig. 4]; [Video 1]). The Ascaris was extracted with foreign body forceps and taken out from the mouth ([Fig. 5]). Subsequently, a PD stent was placed to complete the procedure. The patient recovered well and was treated with anthelminthic agents. Video 1 Endoscopic ultrasonography showed the linear hyperecho in pancreatic duct (PD), pancreatography showed PD dilation and a stripe-like filling defect in PD. An endoscopic sphincterotomy was then performed. A moving white round worm was discharged from the papilla by a stone extraction balloon after papillary sphincter dilated to 4 mm and successfully extracted by foreign body forceps. Unlike in the more common cases of pancreatic ascariasis that are associated with either a large worm burden in the duodenum, part of the worm being visible through the duodenal papilla [1], or accompanying biliary ascariasis [2], which is easy to diagnose, in this case there was only a single worm that had completely entered the PD, meaning it could be easily misdiagnosed as pancreatic head cancer. The risk of misdiagnosis is due to the following aspects: (i) an Ascaris has no characteristic manifestation on CT or magnetic resonance imaging, but appears as a long curved and transparent shadow, meaning intraductal ascariasis could be easily mistaken for a dilated PD; (ii) pancreatitis caused by Ascaris is commonly mild [3] and the clinical symptoms could completely disappear before the patient sees a doctor, meaning the subsequent pancreatic head enlargement caused by pancreatitis could be easily misdiagnosed as a pancreatic head mass; (iii) the level of cancer antigens, such as CA199, frequently increase in cases of pancreatic ascariasis; however, such increases are mild and reversible. It is therefore important to keep PD ascariasis in the differential diagnosis when one encounters an unexplained pancreatic head mass and PD dilatation, especially in patients with upper abdominal pain at the time of onset. EUS and ERCP are effective methods for the diagnosis and management of this condition. Endoscopy_UCTN_Code_TTT_1AR_2AH Article published online: 25 May 2022 © 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany