Aberrant β-catenin activity in hepatoid adenocarcinoma of the stomach

2020 ◽  
Vol 20 ◽  
Author(s):  
Nan Wang ◽  
Rui Kong ◽  
Wei Han ◽  
Jie Lu

Background: Hepatoid adenocarcinoma of the stomach (HAS) has been recognized as a rare primary gastric tumor characterized by hepatocellular carcinoma-like histology. HAS often causes diagnostic confusion with conventional gastric adenocarcinoma (CGA) due to the difficulty to detect hepatoid differentiation solely based on findings from hematoxylin and eosin (H&E) staining. Hence, HAS should be distinguished from solid-type CGA based on their different biological behaviors. β-catenin is highly expressed in hepatocellular carcinoma (HCC), which is involved in the maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. Methods and Results: Given the dearth of HAS cases, systematic examination of the expression of β-catenin in HAS remains under-explored. In this study, 14 cases were subjected to immunostaining with with AFP, β-catenin, glypican3, hepar-1 and CerbB-2. In parallel, the clinicopathological characteristics of these patients were collected. We detected statistically significant difference in the expression of β-catenin (P = 0.000), glypican3 (P = 0.019), and hepar-1 (P = 0.007) between HAS cancer tissues and the adjacent non-cancerous tissues. Furthermore, a significant correlation was observed between the expression of β-catenin in HAS cancer tissue and adjacent tissue (Pearson correlation coefficient: 0.686, P = 0.007). Moreover, in cancer tissues, a significant correlation was observed between the expression of β-catenin and survival time (Spearman correlationcoefficient= - 0.482, P = 0.003). However, we found the expression of β-catenin did not correlate with the degree of tumor differentiation and tumor size, age, gender, serum AFP levels, microinvasion, and metastasis (P > 0.05). Conclusion: Our findings establish β-catenin as a useful marker that can distinguish HAS from CGA and may improve the early diagnosis to guide the appropriate and timely treatment of HAS patients.

2006 ◽  
Vol 53 (1) ◽  
pp. 237-241 ◽  
Author(s):  
Hanna Czeczot ◽  
Dorota Scibior ◽  
Michał Skrzycki ◽  
Małgorzata Podsiad

We investigated glutathione level, activities of selenium independent GSH peroxidase, selenium dependent GSH peroxidase, GSH S-transferase, GSH reductase and the rate of lipid peroxidation expressed as the level of malondialdehyde in liver tissues obtained from patients diagnosed with cirrhosis or hepatocellular carcinoma. GSH level was found to be lower in malignant tissues compared to adjacent normal tissues and it was higher in cancer than in cirrhotic tissue. Non-Se-GSH-Px activity was lower in cancer tissue compared with adjacent normal liver or cirrhotic tissue, while Se-GSH-Px activity in cancer was found to be similar to its activity in cirrhotic tissue and lower compared to control tissue. An increase in GST activity was observed in cirrhotic tissue compared with cancer tissue, whereas the GST activity in cancer was lower than in adjacent normal tissue. The activity of GSH-R was similar in cirrhotic and cancer tissues, but higher in cancer tissue compared to control liver tissue. An increased level of MDA was found in cancer tissue in comparison with control tissue, besides its level was higher in cancer tissue than in cirrhotic tissue. Our results show that the antioxidant system of cirrhosis and hepatocellular carcinoma is severely impaired. This is associated with changes of glutathione level and activities of GSH-dependent enzymes in liver tissue. GSH and enzymes cooperating with it are important factors in the process of liver diseases development.


2021 ◽  
Author(s):  
sanaz razmkhah

Abstract BACKGROUND: miRNAs show to play fundamental roles in diverse cellular processes and associate with a variety of cancers. DROSHA and DICER are two major enzymes in the miRNA maturation process. OBJECTIVE: Dicer and Drosha genes expression investigated Ovarian Cancer and analyzed the impact of clinicopathological characteristics on their expression. METHODS: The present study has performed on 50 cancer patients (50 tumor tissue samples and 50 marginal tissue samples) overall, 100 specimens referred to Al-Zahra Hospital's surgical department in Tabriz and Motahari Hospital Urmia for identification and treatment during 2018 and 2019. After extracting total RNA and cDNA Synthesis, using the HRM-PCR method, the rate of change in the expression of DROSHA and DICER genes assessed using the 2-ΔΔCT method. Data were analyzed using Paired t-test and Kolmogorov–Smirnov test. RESULTS: Our study showed a significant difference in the rate of expression changes in DROSHA and DICER genes in tumor tissue compared to marginal tissue. This difference was associated with an increase in DROSHA and DICER gene expression.CONCLUSIONS: Up-regulated expression of miRNAs biogenesis machinery enzymes (Dicer and Drosha) during ovarian cancer can alter the miRNA expression involved in the pathogenesis of malignancy.


2013 ◽  
Vol 60 (2) ◽  
Author(s):  
Małgorzata Borzym-Kluczyk ◽  
Iwona Radziejewska

Sialic acid and sialyl Lewisa/x are found on N- and O-glycans of many human malignant cells. Carbohydrate antigens can be used as tumor markers, and an increase of their levels in cancer cells is associated with tumor progression. The aim of this study was to assess the level of some Lewis blood group antigens on glycoproteins in tumor (cancer tissue), intermediate zone (adjacent to tumor tissue), and normal renal cortex/medulla (uninvolved by tumor). The study was performed on tissues taken from 30 patients. Relative amounts of sugar structures of proteins with molecular masses above 30 kDa were determined by ELISA-like test with biotinylated lectins: MAA (Maackia amurensis), SNA (Sambucus nigra), and monoclonal antibodies anti-sialyl Lewisa/x.∙ Higher expression of all examined structures was revealed in cancer tissues. Significant increases were observed for sialic acid linked α 2-3 in cancer tissues when compared to healthy ones and also among intermediate and healthy tissues. The sialic acid linked α 2-6 and sialyl Lewisx structures were significantly increased in cancerous cells when compared to normal and intermediate renal tissue. In case of sialyl Lewisa antigen, a significant difference was discovered between normal and intermediate tissue. Our results confirm that the examined Lewis antigens can be involved in tumor development. Their increase in cancer tissues can suggest their specific role in the process.


2021 ◽  
Author(s):  
Ying Xu ◽  
Hu Tian ◽  
Chao Guang Luan ◽  
Kai Sun ◽  
peng Jin Bao ◽  
...  

Abstract Background: Hepatocellular carcinoma(HCC) in China is considered as a familiar malignant tumor with poor prognosis, high metastasis and disease relapse. Telocytes(TCs) have been verified to participate in progresses of tumorigenesis, invasions and migrations by secreting functional proteins and transmitting cell-to-cell information. Extracellular signal-regulared protein kinase(ERK) signal pathway is a vital mechanism driving cell proliferation, metastasis and apoptosis, but whether this molecular signaling mechanism contributes to matrix metalloproteinase-9(MMP) expression of TCs remains unclear. Methods: Telocytes and MMP9 expression in the liver cancer tissues are measured by immunohistochemistry assay, Westen blot assay and RT-PCR technique, meanwhile primary telocytes from liver para-cancer tissues are cultured in vitro. To demonstrate the function of telocytes for hepatocellular carcinoma, the metastatic cancer animal model is established by three typs of liver cancer cell-lines in vivo. Results: In our study, we elucidate that TCs in the para-cancer tissue can promote the metastasis of HCC cells by MMP-9 expression, in vitro and in vivo. PDGF derived from HCC cells has a capacity to activate Ras/ERK signaling pathway of TC as a result of accelerating MMP-9 expression, but it’s no significant for proliferative potential and apoptotic rate of TCs. While tyrosine kinase inhibitors and miR-942-3p suppress MMP-9 expression to make loss functions of TCs. Various mutations of TCs are also tested and single nucleotide polymorphisms of MMP-9 may be the potentially molecular mechanism of increasing protein expression in the invasive process of HCC. Conclusion: Our results demonstrate two potential mechanisms between HCC cells and TCs, suggesting that TC is a novel marker and target on deciphering reasons of cancer metastasis.


2020 ◽  
Author(s):  
Sinuo Zhu ◽  
Yunping Zhao ◽  
Yanan Bao ◽  
Yue Cui ◽  
Xingming Zhu ◽  
...  

Abstract Background:Increasing evidences have unveiled the connection between microbiome and lung cancer. This study aims to identify the characteristics of microbial communities in the lung cancer tissues from patients in southwestern China, and to compare the distinct microbial genes at different clinical stages of lung cancer for uncovering potential immunotherapy targets.Methods:Forty samples of primary lung adenocarcinoma tissue were performed by 16S rRNA gene sequencing. The subjects were grouped according to TNM stages (T and N group), clinical stage and smoke status. To identify the taxa composition of each sample, Operational Taxonomic Units (OTUs) were classified on the Effective Tags with 97% identity. The linear discriminant analysis effect size (LEfSe) method was utilized to compare relative abundances of all bacterial taxa between non-metastasis group and metastasis group. The Shannon index of the 97% identity OTUs was calculated to evaluate alpha diversity. Beta diversity measurement was calculated using Principal Co-ordinates Analysis (PCoA).Results:A total of 951 OTUs were identified in the cancer tissues, including 224 overlapping genera. No significant difference has been found in the alpha diversity within all the groups. Beta diversity was significantly different in N group, T group and clinical stage group. By LEfSe analysis, nine differential species were identified in the N group, of which the relative abundance of genus Bifidobacterium was 10.78%±11.59% in the N0 group and 20.15%±13.44% in the N+ group (p<0.05). In the T1 and T2 group, the LEfSe result identified 4 phylum and 10 genera. The differential genera were Moraxella, Dolosigranulum, Corynebacteriaceae and Citrobacter in the T2 group and Bifidobacterium, Alistipes, Akkermansia, Blautia, Lactobacillus as well as Facelibacterium in the T1 group. Differential bacterial composition and abundance were also observed in the clinical stage group.Conclusions:In conclusion, by 16S RNA sequencing, we identified dominant species of lung cancer tissue in different groups of AD patients. Bifidobacterium plays important role both in lymph node metastasis and tumor progression, which could provide specific immunotherapy strategy for lung cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yakun Wang ◽  
Lei Yang ◽  
Xichen Dong ◽  
Xin Yang ◽  
Xinxue Zhang ◽  
...  

Nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) is a long noncoding RNA (lncRNA) that has been shown to be overexpressed in hepatocellular carcinoma (HCC). However, the molecular mechanism involving NNT-AS1 in HCC remains to be extensively investigated. The activation of TGF-β signaling inhibits tumor-infiltrating lymphocytes (TILs) and results in tumor immune evasion. We thus planned to explore the mechanism by which NNT-AS1 activates the TGF-β signaling pathway and inhibits TILs in HCC. High levels of NNT-AS1 were detected in HCC tissues by both RNAscope and real-time quantitative PCR (RT-qPCR) assays. The levels of proteins involved in TGF-β signaling and those of CD4 T lymphocytes were quantified by immunohistochemistry (IHC). HCC cell lines (HepG2 and Huh7) were used to explore the effects of NNT-AS1 on TGF-β signaling activation. In these analyses, RNAscope detection demonstrated that NNT-AS1 levels were significantly increased in HCC cancer tissues ( P = 0.0001 ). In addition, the elevated NNT-AS1 levels in cancer tissue were further confirmed by RT-qPCR analysis of HCC cancer tissues ( n = 64 ) and normal tissues ( n = 26 ) ( P = 0.0003 ). Importantly, the overall survival time of HCC patients who exhibited higher levels of NNT-AS1 expression was significantly shorter than that of HCC patients who had lower levels of NNT-AS1 expression ( P = 0.0402 ). Further mechanistic investigation indicated that NNT-AS1 inhibition significantly decreased the levels of TGF-β, TGFBR1, and SMAD5 in HCC cells. In HCC tissues, IHC detection showed that relatively high NNT-AS1 levels were associated with a reduction in infiltrated CD4 lymphocyte numbers. In conclusion, this research identifies a novel mechanism by which NNT-AS1 impairs CD4 T cell infiltration via activation of the TGF-β signaling pathway in HCC.


2018 ◽  
Vol 7 (4) ◽  
pp. 42-49 ◽  
Author(s):  
Korkmaz YİĞİTER ◽  
Hakan TOSUN

The aim of this study is to investigate the effects of participation in a 1-week summer camp on thehopelessness and self-esteem of the university students attending Sport Sciences Faculty. Participants were 36university students assigned to experiment group using a random procedure. Coopersmith Self-esteem and Beck Hopelessness Scales were completed at the beginning and end of the summer camp by designed the university. The obtained data were analysed in the SPSS 18.0 program and the significance level was taken as 0.05. The descriptive statistics, independent simple t test, paired simple t test and Pearson correlation were used for analyse the data in the study. According to the results of the research, no significant difference was observed in the comparison of the hopelessness and self-esteem levels between pre and post-test. In addition, there was a significant difference in the hopelessness level of male and female students but any significant difference was not observed in terms of self-esteem. There was a significant relationship between hopelessness and self-esteem pre and post-test. These result shows that a 1-week summer camp cannot change the hopelessness or self-esteem level. However, as the self-esteem rises, the rate of despair decreases whereas as the despair rises, the selfesteem decreases.


2019 ◽  
Author(s):  
Chem Int

Coriander (Coriandrum sativum L.) is one of the herbs which is used for medicinal and food purposes. In the present study the levels of selected metals in coriander leaves were determined in the samples collected from four different farmlands (Sebeta, Mekanisa, Holeta and Gefersa) in Ethiopia where its cultivation is common. The levels of metals were determined after digestion of samples with the mixture of 4 mL of HNO3 and 4 mL of HClO4 at 300 oC for 3:00 hours by flame atomic absorption spectrometry. The optimized wet digestion method for coriander leaves analysis was validated through the recovery experiment and a good percentage recovery was obtained (93.2-101%). The levels of metals were found in the range Ca, 2319–3503 mg/kg; Zn, 33.4–54.8 mg/kg and Cr, 5.55-9.86 mg/kg while the trace metals Cu, Ni, Cd and Pb were too low to be detected. The results indicated that Ethiopian coriander is a good source of essential metals and free from the toxic metals Pb and Cd. A statistical analysis of variance (ANOVA) at 95% confidence level indicated that there is significant difference (p &lt; 0.05) in the levels of all detected metals between the four sample means. The Pearson correlation was used to predict the dependence of metal levels on one another. The levels of the metals determined in this study compared well with those reported for coriander leaves from some other parts of the world.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.


2021 ◽  
Vol 28 ◽  
pp. 107327482098682
Author(s):  
Min Shi ◽  
Biao Zhou

Background: The incidence of pancreatic neuroendocrine tumors (PNETs) has increased significantly. The purpose of this study was to analyze the clinical characteristics and prognosis of patients under 50 years old. Methods: Patients with PNETs recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 were analyzed. The clinical characteristics were analyzed by Chi-square test. The Kaplan-Meier method was used to estimate overall survival (OS). Multivariate Cox proportional risk regression analysis was used to determine independent prognostic factors. Results: 2,303 patients included, of which 547 (23.8%) patients were younger than 50 years old. The number of younger patients has increased steadily, while the proportion in total PNETs decreased recently. Compared with older group, the proportion of the Black, grade I/II, and surgery were higher in early-onset PNETs. Liver was the most frequent metastatic site. There was no significant difference in the incidence of different metastatic sites between younger and older PNETs patients, while younger patients had better OS (P < 0.05). Grade, N stage, M stage, and surgery were independent prognostic factors for OS in early-onset PNETs. Conclusions: Younger patients have unique clinicopathological characteristics compared with older patients in PNETs. Better OS was observed in younger patients which might due to the higher proportion of well-differentiated tumor and surgery than older patients.


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