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Data mining of microarray for differentially expressed genes in liver metastasis from gastric cancer

Ling XU MM, Feng WANG MM, Xuan-Fu XU MD, Wen-Hui MO BM, Rong WAN MD, Chuan-Yong GUO MD, Xing-Peng WANG MD,

《医学前沿(英文)》 2010年 第4卷 第2期   页码 247-253 doi: 10.1007/s11684-010-0027-4

摘要: Tumor metastasis is the leading cause of death for gastric cancer. Metastasis is the main reason for the failure of clinical treatment for gastric cancer. In order to find metastasis-related genes and abnormal signal transduction pathway of high-invasive gastric cancer, samples of gastric cancer with liver metastasis were collected for microarray detection; up-regulated or down-regulated genes in all three cases were simultaneously screened out. Subsequently, from the preliminary screened genes, molecular pathways possibly impacting liver metastasis from gastric cancer were investigated by the Gene Cluster with Literature Profiles (GenCLip) analysis software. Many biological effects including apoptosis have been validated. Functional analysis of differentially expressed genes revealed that a variety of biological pathways, such as blood circulation and gas exchange, vasodilation and vasoconstriction regulation, and immune defense, could be significantly activated. Besides, gene sequences, specific keywords or gene regulatory networks were further searched by GenCLiP. We conclude that data mining allows to quickly identify a series of special signal transduction pathways involving abnormally expressed genes.

关键词: gastric carcinoma     metastasis     signal transduction     gene chips    

Tumor growth and metastasis can be inhibited by maintaining genomic stability in cancer cells

null

《医学前沿(英文)》 2015年 第9卷 第1期   页码 57-62 doi: 10.1007/s11684-015-0389-8

摘要:

The existence of cancer stem cells, stem-like cancer cells (SLCCs), or tumor-initiating cells is considered as the cause of tumor formation and recurrence, indicating the importance of studying novel therapy that targets SLCCs. The origin of SLCCs is controversial because of two competing hypotheses: SLCCs are either transformed from tissue adult stem cells or dedifferentiated from transformed progenitor cells. Our previous research demonstrates that SLCCs are inducible by increasing genomic instability in cancer cells. In this study, to block the emergence of SLCCs, aminoethyl isothiourea (AET), a compound that clears free radicals and is used to protect patients from radioactive exposure, was used as an agent that maintains genomic stability in combination with mitomycin C (MMC), a commonly used chemotherapeutic drug that damages DNA. Using a rabbit tumor model with VX2 hepatic carcinoma, we found that MMC alone increased lung metastases and disadvantaged survival outcome, but the combination of MMC and AET reversed this effect and even prolonged overall survival. Moreover, in a VX2 xenograft model by immunocompromised mice, MMC alone enriched tumor-initiating cells, but the administration of MMC in combination with AET eliminated tumor cells effectively. Furthermore, MMC alone enhanced genomic instability, but MMC combined with AET attenuated the extent of genomic instability in primary VX2 tumor tissue. Taken together, our data suggest that the genomic protector AET can inhibit the induction of SLCCs, and this combination treatment by AET and cytotoxic agents should be considered as a promising strategy for future clinical evaluation.

关键词: rabbit VX2 liver tumor     mitomycin C     AET     stem-like cancer cells     genomic instability    

Analysis of 100 consecutive cases of resectable pancreatic neuroendocrine neoplasms: clinicopathological characteristics and long-term outcomes

null

《医学前沿(英文)》 2016年 第10卷 第4期   页码 444-450 doi: 10.1007/s11684-016-0471-x

摘要:

The incidence rate of pancreatic neuroendocrine neoplasms (pNENs) has increased rapidly in recent years. However, the clinicopathological characteristics of pNENs are poorly understood. Medical records of patients who underwent surgery and were confirmed as pNENs by pathological examination from January 2003 to February 2015 in Qilu Hospital were reviewed retrospectively. A total of 100 patients, 36 males and 64 females, were included with a mean operation age of 46.26±13.41 years. Among the 100 cases, 76 had insulinomas and 24 had non-functional pNENs. Tumor size ranged from 0.5 cm to 9 cm, and the mean size was 2.20±1.40 cm. The percentages of TNM stages I, II, III, and IV tumors were 89.0%, 8.0%, 0.0%, and 3.0%, respectively. Based on the WHO classification, pNENs were classified into three grades: G1, G2, and G3. G1, G2, and G3 tumors were confirmed in 72.9%, 23.7%, and 3.4% patients, respectively. The positive rates of CgA and Syn immunohistochemical staining were 94.5% (69/73) and 100% (74/74), respectively. Compared with insulinoma, non-functional pNENs have larger tumor sizes, more advanced TNM staging, a higher Ki-67 index, and a higher rate of liver metastasis (P<0.05). In conclusion, pNENs are heterogeneous tumors with varying clinical manifestations, diverse tumor biological characteristics, and different prognoses. Non-functional pNENs present a more aggressive behavioral model and have poorer prognosis than functional pNENs.

关键词: pancreatic neuroendocrine neoplasms     clinicopathological characteristic     Ki-67     liver metastasis     outcomes    

Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervical

null

《医学前沿(英文)》 2014年 第8卷 第1期   页码 106-112 doi: 10.1007/s11684-014-0307-5

摘要:

Cervical carcinoma is associated with high propensity for local invasion and lymph node metastasis. However, the molecular alterations that drive progression and metastasis of cervical cancer remain unclear. Cellular senescence has been proposed as the mechanism that protects an organism against cancer progression and metastasis. In addition, Twist, a basic helix-loop-helix transcription factor, has been suggested as an oncogene because it is overexpressed in many types of human cancer. This gene also exhibits a positive function in regulating invasion and metastasis. In this study, Twist was strongly and positively expressed in normal tissue, squamous cell carcinoma (SCC) IA--IIA, and SCC IIB--IIIB (4.3%, 44%, and 88.9%, respectively). The strong positive expressions of the senescence marker CBX3 were 39.1%, 32%, and 15.6%, respectively. The strong positive expressions of Twist in the SCC groups with or without lymph node metastasis were 80.8% and 50%. For CBX3, such expressions were 7.7% and 29.5%, respectively. Results also showed that the expression of Twist was inversely correlated with that of CBX3. Moreover, the knockdown of Twist with target siRNA in SiHa triggered the induction of the chromatin marker of the cellular senescence CBX3 and senescence-associated β-galactosidase activity. Our results suggested that the expression of Twist increased during the progression and metastasis of cervical cancer. Furthermore, Twist-induced senescence bypass is important in this process.

关键词: cervical cancer     senescence     Twist     CBX3     lymph node metastasis    

Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

《医学前沿(英文)》 2022年 第16卷 第6期   页码 883-895 doi: 10.1007/s11684-022-0919-0

摘要: Metastasis and drug resistance are the leading causes of poor prognosis in patients with osteosarcoma. Identifying the relevant factors that drive metastasis and drug resistance is the key to improving the therapeutic outcome of osteosarcoma. Here, we reported that autophagy was highly activated in metastatic osteosarcoma. We found increased autophagolysosomes in metastatic osteosarcoma cell lines by using electron microscopy, Western blot, and immunofluorescence experiments. We further examined the expression of the autophagy-related genes Beclin1 and LC3B in 82 patients through immunohistochemistry and found that Beclin1 and LC3B were highly related to unfavorable prognosis of osteosarcoma. Knockdown of Beclin1 and LC3B reduced invasion, metastasis, and proliferation in metastatic osteosarcoma cells. In vitro and in vivo studies also demonstrated that inhibiting by 3-MA inhibited cell growth and metastasis. Moreover, we demonstrated that autophagy-related genes were activated by SEs and that the inhibition of SEs by JQ-1 decreased the metastasis of osteosarcoma. Overall, our findings highlighted the association of autophagy with osteosarcoma progression and shed new light on autophagy-targeting therapy for osteosarcoma.

关键词: osteosarcoma     autophagy     metastasis     drug resistance     Beclin1     LC3B    

Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

null

《医学前沿(英文)》 2014年 第8卷 第1期   页码 24-32 doi: 10.1007/s11684-014-0312-8

摘要:

In this review, we summarize the novel findings from our series of studies on the leading metastasis-related gene, osteopontin (OPN). In our previous gene expression profiling study, OPN was identified as one of the leading genes associated with the metastasis of hepatocellular carcinoma (HCC). We focused on OPN to evaluate its prognostic values and important roles in HCC metastasis. A retrospective study of large cohorts of HCC patients demonstrated that plasma OPN level was one of the leading independent prognostic factors for HCC patients, even in the early stage of HCC, and could serve as a surrogate serologic biomarker for monitoring the treatment response and tumor recurrence after HCC resection. Using both in vitro and in vivoinvestigations, we found that OPN has an important role in metastasis and tumor growth of HCC and is an attractive potential therapeutic target for combating HCC metastasis. We also found that OPN+ HCC cells have much more amplifications at chromosomal regions, and promoter polymorphisms are important in the regulation of OPN expression and tumor growth and lung metastasis of HCC.

关键词: osteopontin (OPN)     hepatocellular carcinoma     metastasis     prognosis     therapeutic target     biomarker     genetic polymorphism    

Partial liver transplantation

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 1-7 doi: 10.1007/s11684-010-0105-7

摘要:

Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situto ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.

关键词: partial liver transplantation     reduced-size liver transplantation     split liver transplantation     living donor liver transplantation    

γδ T cells in liver diseases

null

《医学前沿(英文)》 2018年 第12卷 第3期   页码 262-268 doi: 10.1007/s11684-017-0584-x

摘要:

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词: γδT cells     liver infection     non-alcoholic fatty liver disease     autoimmune hepatitis     liver fibrosis and cirrhosis     liver cancer     liver regeneration    

NKT cells in liver diseases

null

《医学前沿(英文)》 2018年 第12卷 第3期   页码 249-261 doi: 10.1007/s11684-018-0622-3

摘要:

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

关键词: natural killer T cells     hepatitis B virus and hepatitis C virus infection     autoimmune liver diseases     alcoholic liver disease     nonalcoholic fatty liver disease     hepatocellular carcinoma    

Natural killer cells in liver diseases

null

《医学前沿(英文)》 2018年 第12卷 第3期   页码 269-279 doi: 10.1007/s11684-018-0621-4

摘要:

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

关键词: natural killer cell     phenotype     immune activation     immune tolerance     liver diseases    

The “Traditional Chinese medicine regulating liver regeneration” treatment plan for reducing mortalityof patients with hepatitis B-related liver failure based on real-world clinical data

Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu

《医学前沿(英文)》 2021年 第15卷 第3期   页码 495-505 doi: 10.1007/s11684-020-0790-9

摘要: On the basis of real-world clinical data, the study aimed to explore the effect and mechanisms of the treatment plan of “traditional Chinese medicine (TCM) regulating liver regeneration.” A total of 457 patients with HBV-related liver failure were retrospectively collected. The patients were divided into three groups: the modern medicine control group (MMC group), patients treated with routine medical treatment; the control group combining traditional Chinese and Western medicine (CTW), patients treated with routine medical treatment plus the common TCM formula; and the treatment group of “TCM regulating liver regeneration” (RLR), patients treated with both routine medical treatment and the special TCM formula of RLR. After 8 weeks of treatment, the mortality of patients in the RLR group (12.31%) was significantly lower than those in the MMC (50%) and CTW (29.11%) groups. Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups ( <0.05). In addition, there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group. RLR treatment can decrease jaundice, improve liver function, and significantly reduce the mortality in patients with HBV-related liver failure. The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.

关键词: hepatitis B virus-related liver failure     traditional Chinese medicine     liver regeneration     liver regeneration microenvironment     cytokines    

Assessment of liver volume variation to evaluate liver function

null

《医学前沿(英文)》 2012年 第6卷 第4期   页码 421-427 doi: 10.1007/s11684-012-0223-5

摘要:

In order to assess the value of liver volumetry in cirrhosis and acute liver failure (ALF) patients, we explored the correlation between hepatic volume and severity of the hepatic diseases. The clinical data of 48 cirrhosis patients with 60 normal controls and 39 ALF patients were collected. Computed tomography-derived liver volume (CTLV) and body surface area (BSA) of normal controls were calculated to get a regression formula for standard liver volume (SLV) and BSA. Then CTLV and SLV of all patients were calculated and grouped by Child-Turcotte-Pugh classification for cirrhosis patients and assigned according to prognosis of ALF patients for further comparison. It turned out that the mean liver volume of the control group was 1 058±337 cm3. SLV was correlated with BSA according to the regression formula. The hepatic volume of cirrhosis patients in Child A, B level was not reduced, but in Child C level it was significantly reduced with the lowest liver volume index (CTLV/SLV). Likewise, in the death group of ALF patients, the volume index was significantly lower than that of the survival group. Based on volumetric study, we proposed an ROC (receiver operating characteristic) analysis to predict the prognosis of ALF patients that CTLV/SLV<83.9% indicates a poor prognosis. In conclusion, the CTLV/SLV ratio, which reflects liver volume variations, correlates well with the liver function and progression of cirrhosis and ALF. It is also a very useful marker for predicting the prognosis of ALF.

关键词: liver volume variation     cirrhosis     acute liver failure (ALF)    

Bone metastasis of hepatocellular carcinoma: facts and hopes from clinical and translational perspectives

《医学前沿(英文)》 2022年 第16卷 第4期   页码 551-573 doi: 10.1007/s11684-022-0928-z

摘要: Patients with hepatocellular carcinoma (HCC) and bone metastasis (BM) suffer from greatly reduced life quality and a dismal prognosis. However, BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades. To date, no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM. Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention. The risk factors, diagnosis, prognosis, and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists. We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions. We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities. Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms, as well as the development of novel effective therapies for HCC patients with BM.

关键词: HCC     bone     osteotropism     clinical     basic researches     advances    

Gut microbial balance and liver transplantation: alteration, management, and prediction

null

《医学前沿(英文)》 2018年 第12卷 第2期   页码 123-129 doi: 10.1007/s11684-017-0563-2

摘要:

Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia–reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.

关键词: gut microbial balance     liver transplantation     ischemia–reperfusion     acute rejection    

Molecular mechanisms of fatty liver in obesity

null

《医学前沿(英文)》 2015年 第9卷 第3期   页码 275-287 doi: 10.1007/s11684-015-0410-2

摘要:

Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of liver disorders ranging from simple steatosis to advanced pathologies, including nonalcoholic steatohepatitis and cirrhosis. NAFLD significantly contributes to morbidity and mortality in developed societies. Insulin resistance associated with central obesity is the major cause of hepatic steatosis, which is characterized by excessive accumulation of triglyceride-rich lipid droplets in the liver. Accumulating evidence supports that dysregulation of adipose lipolysis and liver de novo lipogenesis (DNL) plays a key role in driving hepatic steatosis. In this work, we reviewed the molecular mechanisms responsible for enhanced adipose lipolysis and increased hepatic DNL that lead to hepatic lipid accumulation in the context of obesity. Delineation of these mechanisms holds promise for developing novel avenues against NAFLD.

关键词: nonalcoholic fatty liver disease     insulin resistance     obesity    

标题 作者 时间 类型 操作

Data mining of microarray for differentially expressed genes in liver metastasis from gastric cancer

Ling XU MM, Feng WANG MM, Xuan-Fu XU MD, Wen-Hui MO BM, Rong WAN MD, Chuan-Yong GUO MD, Xing-Peng WANG MD,

期刊论文

Tumor growth and metastasis can be inhibited by maintaining genomic stability in cancer cells

null

期刊论文

Analysis of 100 consecutive cases of resectable pancreatic neuroendocrine neoplasms: clinicopathological characteristics and long-term outcomes

null

期刊论文

Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervical

null

期刊论文

Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

期刊论文

Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

null

期刊论文

Partial liver transplantation

null

期刊论文

γδ T cells in liver diseases

null

期刊论文

NKT cells in liver diseases

null

期刊论文

Natural killer cells in liver diseases

null

期刊论文

The “Traditional Chinese medicine regulating liver regeneration” treatment plan for reducing mortalityof patients with hepatitis B-related liver failure based on real-world clinical data

Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu

期刊论文

Assessment of liver volume variation to evaluate liver function

null

期刊论文

Bone metastasis of hepatocellular carcinoma: facts and hopes from clinical and translational perspectives

期刊论文

Gut microbial balance and liver transplantation: alteration, management, and prediction

null

期刊论文

Molecular mechanisms of fatty liver in obesity

null

期刊论文