LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway.

BACKGROUND: LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC). METHOD: qRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis. RESULTS: Arg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism. CONCLUSION: CRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.

Advances in Renal Cell Carcinoma Drug Resistance Models.

Renal cell carcinoma (RCC) is the most common form of kidney cancer. Systemic therapy is the preferred method to eliminate residual cancer cells after surgery and prolong the survival of patients with inoperable RCC. A variety of molecular targeted and immunological therapies have been developed to improve the survival rate and prognosis of RCC patients based on their chemotherapy-resistant properties. However, owing to tumor heterogeneity and drug resistance, targeted and immunological therapies lack complete and durable anti-tumor responses; therefore, understanding the mechanisms of systemic therapy resistance and improving clinical curative effects in the treatment of RCC remain challenging. In vitro models with traditional RCC cell lines or primary cell culture, as well as in vivo models with cell or patient-derived xenografts, are used to explore the drug resistance mechanisms of RCC and screen new targeted therapeutic drugs. Here, we review the established methods and applications of in vivo and in vitro RCC drug resistance models, with the aim of improving our understanding of its resistance mechanisms, increasing the efficacy of combination medications, and providing a theoretical foundation for the development and application of new drugs, drug screening, and treatment guidelines for RCC patients.

Endoplasmic reticulum stress: Multiple regulatory roles in hepatocellular carcinoma.

BACKGROUND: Endoplasmic reticulum (ER) stress is a basic cellular stress response that maintains cellular protein homeostasis under endogenous or exogenous stimuli, which depends on the stimulus, its intensity, and action time. The ER produces a corresponding cascade reaction for crosstalk of adaptive and/or pro-death regulation with other organelles. Hepatocellular carcinoma(HCC) is one of the most common malignant solid tumors with an extremely poor prognosis. Viral hepatitis infection, cirrhosis, and steatohepatitis are closely related to the occurrence and development of HCC, and ER stress has gradually been shown to be a major mechanism. Moreover, an increasing need for protein and lipid products and relative deficiencies of oxygen and nutrients for rapid proliferation and endoplasmic reticulum stress are undoubtedly involved. Therefore, to fully and comprehensively understand the regulatory role of endoplasmic reticulum stress in the occurrence and progression of HCC is of vital importance to explore its pathogenesis and develop novel anti-cancer strategies. METHODOLOGY: We searched for relevant publications in the PubMed databases using the keywords "Endoplasmic reticulum stress", "hepatocellular carcinoma" in last five years,and present an overview of the current knowledge that links ER stress and HCC, which includes carcinogenesis, progression, and anti-cancer strategies, and propose directions of future research. RESULT: ER stress were confirmed to be multiple regulators or effectors of cancer, which also be confirmed to drive tumorigenesis and progression of HCC. Targeting ER stress signaling pathway and related molecules could play a critical role for anti-HCC and has become a research hotspot for anti-cancer in recent years. CONCLUSION: ER stress are critical for the processes of the tumorigenesis and progression of tumors. For HCC, ER stress was associated with tumorigenesis, development, metastasis, angiogenesis and drug resistance, targeting ER stress has emerged as a potential anti-tumor strategy.

An essential technique for modern hepato-pancreato-biliary surgery: minimally invasive biliary reconstruction.

Introduction: Minimally invasive reconstruction of the biliary tract is complex and involves multiple steps. The procedure is challenging and has been an essential technique in modern hepato-pancreato-biliary surgery in recent years. Additionally, the quality of the reconstruction directly affects long-and short-term complications and affects the prognosis and quality of life. Various minimally invasive reconstruction methods have been developed to improve the reconstruction effect; however, the optimal method remains controversial. Areas covered: In this study, were viewed published studies of minimally invasive biliary reconstruction within the last 5 years and discussed the current status and main complications of minimally invasive biliary reconstruction. More importantly, we introduced the current reconstruction strategies and technical details of minimally invasive biliary reconstruction, which may be potentially helpful for surgeons to choose reconstruction methods and improve reconstruction quality. Expert opinion: Although several improved and modified methods for biliary reconstruction have been developed recently, no single approach is optimal or adaptable to all situations. Patient-specific selection of appropriate technical strategies according to different situations combined with sophisticated and skilled minimally invasive techniques effectively improves the quality of anastomosis and reduces complications.

Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: causes, characteristics and clinical applications.

Pancreatic cancer is one of the most malignant tumors worldwide, and pancreatic ductal adenocarcinoma is the most common type. In pancreatic cancer, glycolysis is the primary way energy is produced to maintain the proliferation, invasion, migration, and metastasis of cancer cells, even under normoxia. However, the potential molecular mechanism is still unknown. From this perspective, this review mainly aimed to summarize the current reasonable interpretation of aerobic glycolysis in pancreatic cancer and some of the newest methods for the detection and treatment of pancreatic cancer. More specifically, we reported some biochemical parameters, such as newly developed enzymes and transporters, and further explored their potential as diagnostic biomarkers and therapeutic targets.

Long non-coding RNA CRNDE promotes malignant progression of hepatocellular carcinoma through the miR-33a-5p/CDK6 axis.

Emerging evidence has suggested that long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is upregulated in hepatocellular carcinoma (HCC) and is associated with cell invasion, migration, and growth. However, the potential modulation mechanism remains to be elucidated. MiR-33a-5p and cyclin-dependent kinase 6 (CDK6) also participate in the pathophysiology of HCC. This work aims to investigate the effect of CRNDE on HCC apoptosis, invasion, and migration and elucidate the role of miR-33a-5p and CDK6 therein. CRNDE and CDK6 were upregulated in HCC tissues and cells, while miR-33a-5p was downregulated. Inhibition of CRNDE suppressed the invasion, migration, and proliferation of HCC cells and enhanced apoptosis by modulating proteins associated with mitochondrial apoptosis (caspase 3, Bax, cytochrome-c, Bcl-2), which were the same as the function of miR-33a-5p overexpression. The dual-luciferase reporter assay demonstrated that miR-33a-5p was a target of CRNDE, and in turn, CRNDE inhibition enhanced the level of miR-33a-5p. CDK6 was also revealed as a target of miR-33a-5p, and both CRNDE inhibition and miR-33a-5p overexpression suppressed CDK6 expression and led to G0/G1 phase block in HCC cells. In vivo experiments using a mouse xenograft tumor model further verified the interaction between CRNDE and miR-33a-5p, showing that miR-33a-5p overexpression or CRNDE inhibition suppressed CDK6 expression and HCC tumorigenesis. Overall, the present work indicated that CRNDE plays an oncogenic function in HCC through regulating the miR-33a-5p/CDK6 axis, revealing a potential therapeutic target in HCC.

Achilles'heel of laparoscopic pancreatectomy: reconstruction of the remnant pancreas.

INTRODUCTION: Laparoscopic pancreatic reconstruction is a challenging procedure and is considered the Achilles' heel of laparoscopic pancreatectomy. Multiple techniques of laparoscopic pancreatic reconstruction have been reported, but the optimal technique remains unclear. AREAS COVERED: This paper provides a brief introduction to the developmental status and major related complications of laparoscopic pancreatic reconstruction. We reviewed all published literature on the technology of laparoscopic pancreatic reconstruction within the last 5 years and herein discuss the advantages and disadvantages of different reconstruction methods. We also discuss several details of different reconstruction techniques in terms of their significance to the operation and complications. EXPERT OPINION: No individual method of laparoscopic pancreatic reconstruction is considered optimal for all conditions. The reconstruction strategy should be based on the surgeon's proficiency with laparoscopic technology and the patient's individual risk factors. Personalized methods of pancreatic reconstruction may more effectively reduce morbidity and mortality.

MiR-23a-3p promoted G1/S cell cycle transition by targeting protocadherin17 in hepatocellular carcinoma.

MiR-23a-3p has been shown to promote liver cancer cell growth and metastasis and regulate that of chemosensitivity. Protocadherin17 (PCDH17) is a tumor suppressor gene and plays an essential part in cell cycle of hepatocellular carcinoma (HCC). This study aimed at evaluating the effects of miR-23a-3p and PCDH17 on HCC cell cycle and underlining the mechanism. The level of miR-23a-3p was up-regulated, while PCDH17 level was down-regulated in HCC tissues compared to adjacent tissues. For the in vitro studies, high expression of miR-23a-3p down-regulated PCDH17 level; increased cell viability; promoted G1/S cell cycle transition; up-regulated cyclin D1, cyclin E, CDK2, CDK4, p-p27, and p-RB levels; and down-regulated the expression of p27. Dual luciferase reporter assay suggested PCDH17 was a target gene of miR-23a-3p. MiR-23a-3p inhibitor and PCDH17 siRNA led to an increase in cell viability and the number of cells in the S phase and up-regulated cyclin D1 and cyclin E levels, compared with miR-23a-3p inhibitor and NC siRNA group. For the in vivo experiments, high expression of miR-23a-3p promoted tumor growth and reduced PCDH17 level in the cytoplasm. These results indicated that high expression of miR-23a-3p might promote G1/S cell cycle transition by targeting PCDH17 in HCC cells. The miR-23a-3p could be considered as a molecular target for HCC detection.

Identification of Ten Long Noncoding RNAs as Biomarkers for Hepatocellular Carcinoma

Abstract Long-chain non-encoded RNAs (lncRNAs) are important in many life activities and can participate in the occurrence of hepatocellular carcinoma (HCC). Moreover, lncRNAs can be used as basis for developing new strategies to hinder liver cancer. To investigate the utility of lncRNAs in HCC as potential biomarkers for early detection and diagnosis, we mined genomic data from the Cancer Genome Atlas (TCGA), and analyzed the gene expressions from 374 tumor patients and 50 normal patients. The abnormal expressions of 387 differentially expressed lncRNAs (DElncRNAs) were identified from a total of 3099 lncRNAs. Moreover, 18 modules were divided based on WGCNA, and 2 of the 18 modules were positively correlated with stage and grade, and negatively correlated with survival time. Finally, 10 lncRNAs were found and their main functions are the enhancement of cellular metabolic capacity and cell proliferation. These 10 lncRNAs may serve as novel prognostic markers and therapeutic targets, and may help guide subsequent studies on HCC.

Bioinformatic Analysis of Circular RNA-Associated ceRNA Network Associated with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910-miR-1261-UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.

Pancreatic reconstruction techniques after pancreaticoduodenectomy: a review of the literature.

Introduction: Postoperative pancreatic fistula is the most troublesome complication after pancreaticoduodenectomy, and is an on-going area of concern for pancreatic surgeons. The specific pancreatic reconstruction technique is an important factor influencing the development of postoperative pancreatic fistula after pancreaticoduodenectomy. Areas covered: In this paper, we briefly introduced the definition and relevant influencing factors of postoperative pancreatic fistula. We performed a search of all meta-analyses published in the last 5 years and all published randomized controlled trials comparing different pancreatic anastomotic techniques, and we evaluated the advantages and disadvantages of different techniques. Expert opinion: No individual anastomotic method can completely avoid postoperative pancreatic fistula. Selecting specific techniques tailored to the patient's situation intraoperatively may be key to reducing the incidence of postoperative pancreatic fistula.

Recent Advances in Herbal Medicines for Digestive System Malignancies.

Herbal medicines, as an important part of traditional Chinese medicine (TCM), have been used to treat digestive system malignancies (DSM) for many years, and have gradually gained recognition worldwide. The role of herbal medicines in the comprehensive treatment of DSM is being improved from adjuvant treatment of the autologous immune function in cancer patients, to the treatment of both the symptoms and disease, direct inhibition of tumor cell growth and proliferation, and induction of tumor cell autophagy and apoptosis. Their specific mechanisms in these treatments are also being explored. The paper reviews the current anti-tumor mechanisms of TCM, including single herbal medicines, Chinese herbal formulations, Chinese medicine preparations and TCM extract, and their application in the comprehensive treatment of digestive system tumors, providing a reference for clinical application of TCM.

Sarcomatoid carcinoma of the pancreas: A case report and review of the literature.

Sarcomatoid carcinoma (SC) is an extremely rare and complicated malignant neoplasm that consists of both malignant epithelial components and atypical spindle cells that express an epithelial phenotype. The presents study reported a case of SC of the pancreas (SCP), along with a brief review of the literature. A 63­year­old man was admitted to The Second Hospital of Jilin University hospital with complaints of epigastralgia and jaundice of one month in duration. Based on preoperative laboratory blood tests and radiography, a mass at the distal common bile duct was suspected. Intraoperative examination discovered a 2.5x2x1.8­cm mass in the pancreatic head, with invasion of the distal bile duct. Pancreaticoduodectomy was performed. Histopathology and immunohistochemistry of the specimen confirmed the diagnosis of SCP. The patient succumbed 18 months after surgery due to multiple hepatic metastases.

Neural Mechanisms With Respect to Different Paradigms and Relevant Regulatory Factors in Empathy for Pain.

Empathy for pain is thought to activate the affective-motivational components of the pain matrix, which includes the anterior insula and middle and anterior cingulate cortices, as indicated by functional magnetic resonance imaging and other methodologies. Activity in this core neural network reflects the affective experience that activates our responses to pain and lays the neural foundation for our understanding of our own emotions and those of others. Furthermore, although picture-based paradigms can activate somatosensory components of directly experienced pain, cue-based paradigms cannot. In addition to this difference, the two paradigms evoke other distinct neuronal responses. Although the automatic "perception-action" model has long been the dominant theory for pain empathy, a "bottom-up, top-down" mechanism seems to be more comprehensive and persuasive. Indeed, a variety of factors can regulate the intensity of empathy for pain through "top-down" processes. In this paper, we integrate and generalize knowledge regarding pain empathy and introduce the findings from recent studies. We also present ideas for future research into the neural mechanisms underlying pain empathy.

Immunotherapy for Hepatocellular Carcinoma: Current Advances and Future Expectations.

Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis. Immune tolerance and suppression in tumor microenvironments are the theoretical basis of immunotherapy. Adoptive cell therapy functions by stimulating and cultivating autologous lymphocytes ex vivo and then reinfusing them into the patient to kill cancer cells. Cancer vaccination is performed using antigenic substances to activate tumor-specific immune responses. Immune checkpoint inhibitors can reactivate tumor-specific T cells and develop an antitumor effect by suppressing checkpoint-mediated signaling. Oncolytic viruses may selectively replicate in tumor cells and cause lysis without harming normal tissues. Here, we briefly introduce the mechanism of immunosuppression in hepatocellular carcinoma and summarize the rationale of the four major immunotherapeutic approaches with their current advances.