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PURPOSE:We aimed to evaluate the imaging features of computed tomography (CT) and angiography and the efficacy of transcatheter arterial embolization (TAE) in patients with hemobilia of different iatrogenic causes.METHODS:Thirty patients with hemobilia were divided into two groups according to their iatrogenic causes, i.e., group 1, 11 patients (36.7%) with transhepatic intervention and group 2, 19 patients (63.3%) with surgical procedures in the hilar area. Seventeen patients (56.7%) underwent abdominal contrast-enhanced CT before selective angiography. Polyvinyl alcohol particles, gelatin sponges, and coils were used for TAE. Data from the two groups were compared using Fisher’s exact test and the Mann-Whitney U test.RESULTS:Contrast-enhanced CT showed a hematoma, extravasation of contrast material, and pseudoaneurysm. The bleeding source was determined by angiographic features in all patients, which were not significantly different between the two groups (P = 0.127), and pseudoaneurysm was the most common. The embolic material and number of coils used for TAE were significantly different between the two groups (P < 0.001), but the embolization was technically successful in all patients. The clinical success rate of the first embolization was 100% in group 1 vs. 84.2% in group 2. The overall clinical success rate of TAE was 100% in all patients. The complication rate was 63.6% in group 1 vs. 68.4% in group 2 (P = 1.000).CONCLUSION:CT was useful in diagnosing hemobilia, and angiograms enabled determination of the bleeding source. Pseudoaneurysm was one of the most common angiographic features. TAE was successfully performed with different embolic materials on the basis of the iatrogenic cause and bleeding location.

Hepatocellular carcinoma (HCC) is insidious and prone to metastasis and recurrence. Currently, no effective treatment is available for HCC. Furthermore, HCC does not respond to various radio- and chemotherapies, and the molecular mechanism of treatment resistance is unclear. Here, we found that p53 n6-methyladenosine (m6A) played a decisive role in regulating HCC sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. Our results reveal that p53 activation plays a crucial role in chemotherapy-induced apoptosis and reducing cell viability. Moreover, decreasing m6A methyltransferase (e.g., methyltransferase-like 3, METTL3) expression through chemotherapeutic drug combinations reduced p53 mRNA m6A modification. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy. Importantly, we observed that downregulation of METTL3 and upregulation of p53 expression by oral administration of chemotherapy drugs triggered apoptosis and xenograft tumor growth inhibition in nude mice. Based on these findings, we hypothesize that a METTL3–m6A–p53 axis could be a potential target in HCC therapy. [ABSTRACT FROM AUTHOR]

N6-methyladenosine [m(6)A/m6A] methylation is one of the most common RNA modifications in eukaryotic cell mRNA and plays an important regulatory role in mRNA metabolism, splicing, translocation, stability, and translation. Previous studies have demonstrated that the m6A modification is highly associated with tumor cell proliferation, migration, and invasion. In the present study, five m6A regulatory factors have been revealed, namely heterogeneous nuclear ribonucleoprotein A2/B1(HNRNPA2B1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), Vir like m6A methyltransferase associated protein (KIAA1429/VIRMA), RNA binding motif protein 15 (RBM15) and methyltransferase like 3 (METTL3), which are closely related to the overall survival (OS) of patients with lung adenocarcinoma (LUAD). These five m6A regulatory factors exhibited potential prognostic value for the 1, 3, and 5-years survival outcomes of LUAD patients. Our findings revealed that several signaling pathways, such as cell cycle, DNA replication, RNA degradation, RNA polymerase, nucleotide excision repair and basal transcription factors, are activated in the high-risk group of LUAD patients. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a highly aggressive and chemoresistant liver malignancy. Thus, identification of strategies to overcome insensitivity to apoptosis and growth inhibition is a growing focus of research in this malignancy. This study evaluated the potential anti-cancer effects of an ethanol extract from the Actinidia arguta (Hardy Kiwi) root (RAE) on CCA. Our data demonstrated that RAE decreased cell viability and induced apoptosis by activation of Caspase 3, Caspase 8, and Poly (ADP-ribose) polymerase (PARP) in two CCA cell lines. RAE induced a decrease in Mcl-1 in cultured CCA cells and in xenograft CCA tumors. Administration of RAE every other day led to significant growth inhibition in tumor burden xenograft CCA mice. Western blotting analysis of paired human CCA and normal adjacent tissues from the same patient revealed that CCA tissues exhibited significantly higher Mcl-1 expression than normal tissues. Taken together, our findings demonstrated the anti-cancer effects of RAE on CCA both in vitro and in vivo. These data suggest that RAE may be a promising anti-CCA agent and could be beneficial in the treatment of CCA through the targeting of Mcl-1. [ABSTRACT FROM AUTHOR]

Interventional therapy has become the first choice of non - surgical treatment for hepatocellular carcinoma (HCC) due to its advantages such as little trauma and marked local effect. However, the clinical efficiency is less than expected. One of the possibilities is the resistance of cancer cells to anti - cancer drugs. Increasing attention has been paid to the combination of traditional Chinese medicine (TCM) and interventional therapy in HCC treatment. This paper reviews the progress in TCM combined with interventional therapy for HCC at animal experiment and clinical study levels in recent ten years. It is pointed out that the combination therapy with TCM and intervention for HCC has a unique advantage. [ABSTRACT FROM AUTHOR]

N 6 -methyladenosine [m(6)A/m 6 A] methylation is one of the most common RNA modifications in eukaryotic cell mRNA and plays an important regulatory role in mRNA metabolism, splicing, translocation, stability, and translation. Previous studies have demonstrated that the m 6 A modification is highly associated with tumor cell proliferation, migration, and invasion. In the present study, five m 6 A regulatory factors have been revealed, namely heterogeneous nuclear ribonucleoprotein A2/B1(HNRNPA2B1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), Vir like m 6 A methyltransferase associated protein (KIAA1429/VIRMA), RNA binding motif protein 15 (RBM15) and methyltransferase like 3 (METTL3), which are closely related to the overall survival (OS) of patients with lung adenocarcinoma (LUAD). These five m 6 A regulatory factors exhibited potential prognostic value for the 1, 3, and 5-years survival outcomes of LUAD patients. Our findings revealed that several signaling pathways, such as cell cycle, DNA replication, RNA degradation, RNA polymerase, nucleotide excision repair and basal transcription factors, are activated in the high-risk group of LUAD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Zhao and Lu.)

Pancreatic cancer has one of the lowest survival rates of all cancers. The mechanism underlying chemo-resistance of pancreatic cancer is not well understood. Our previous article reported that small molecule YM155 induced apoptosis in pancreatic cancer cells via activation of death receptor 5. In this study, we aim to continuously address death receptor 5-mediated apoptosis in chemo-resistant pancreatic carcinoma. We found that in comparison to paired pancreatic cancer tissues and adjacent normal tissues, five of the six cancer tissues had downregulated death receptor 5 and upregulated Bcl-xL. Mono treatment with lexatumumab was not sufficient to induce apoptosis in pancreatic cancer cells, whereas focal adhesion kinase inhibitor PF573228 significantly sensitized lexatumumab-induced apoptosis. Western blotting analysis revealed that lexatumumab and PF573228 combination treatment increased death receptor 5 but decreased Bcl-xL expression. Interestingly, pre-treatment with Bcl-xL inhibitor ABT263 reversed the insensitivity of panc-1 cells to lexatumumab or PF573228-induced apoptosis. Specific small interfering RNA-mediated gene silencing of Bcl-xL effectively sensitized pancreatic cancer cells to lexatumumab or PF573228-induced apoptosis. Furthermore, lexatumumab and PF573228 combination was shown to exhibit significant xenograft pancreatic tumor growth inhibition in SCID mice. Our data provide fundamental evidence to support the notion that lexatumumab and PF573228 co-treatment could be a potentially effective regime for patients with pancreatic cancer.

Objective: To explore the relationship of Ghrelin gene polymorphism with the occurrence of human anorectal malformations (ARMs) and Hirschsprung disease(HSCR)., Methods: PCR and DNA sequencing were used to detect the single nucleotide polymorphism (SNPs) of 3 loci (rs139684563, rs149447194, rs186599567) genotype of Ghrelin gene in 100 children with ARMs, 100 children with HSCR, and 100 healthy children (normal group). Genovariation and gene mutation were analyzed with case-control method., Results: Three loci SNPs were in accordance with Hardy-Weinberg genetic equilibrium. No significant differences were found in rs139684563 allele and genotype frequencies between the cases and the normal groups (P>0.05). The allele and genotype frequencies of rs149447194 and rs186599567 were significantly different between cases and normal group (P<0.05). DNA sequencing results showed that wild-type homozygous deletion (176th and 191th base A deletion, respectively) were found in rs149447194 and rs186599567of ARMs and HSCR children, and single base substitution was detected in rs149447194 of ARMs children (194th codon nucleotide CCT to CTC)., Conclusions: The rs149447194 and the rs186599567 polymorphism changes may be associated with the pathogenesis of ARMs and HSCR.