scholarly journals Co-Upregulation of 14-3-3ζ and P-Akt is Associated with Oncogenesis and Recurrence of Hepatocellular Carcinoma

2018 ◽  
Vol 45 (3) ◽  
pp. 1097-1107 ◽  
Author(s):  
Yufu Tang ◽  
Ruoyu Wang ◽  
Yibing Zhang ◽  
Shenhui Lin ◽  
Na Qiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hazard Analysis ◽  
Survival Rates ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Cox Proportional Hazard ◽  
Advanced Tumor ◽  
Cumulative Recurrence Rate ◽  
Combined Detection

Background/Aims: 14-3-3ζ is involved in the regulation of PI3K/Akt pathway which is closely associated with carcinogenesis. However, the clinical significance of combined detection of 14-3-3ζ and p-Akt in hepatocellular carcinoma (HCC) remains unclear. Methods: Two-hundred pairs of HCC and adjacent liver specimens were subjected to tissue microarray. The association of 14-3-3ζ and p-Akt levels with the postoperative survival and recurrence in HCC patients was analyzed with univariate and multivariate methods. Moreover, the effects of 14-3-3ζ overexpression on the growth of HCC and the expressions of p-Akt and HIF-1α were assessed in a xenograft mouse model. Results: Elevated levels of 14-3-3ζ and p-Akt were detected in HCC and a positive correlation between the levels of 14-3-3ζ and p-Akt was verified. HCC patients with satellite nodules, microvascular invasion, portal vein tumor thrombosis, poor tumor differentiation and an advanced tumor stage tended to have higher levels of 14-3-3ζ and p-Akt. In addition, the postoperative 3-, 5-, and 7-year overall survival rates in HCC patients with 14-3-3ζhigh and p-Akthigh were significantly lower compared with those with 14-3-3ζlow and p-Aktlow, and the cumulative recurrence rate in HCC patients with 14-3-3ζhigh and p-Akthigh was significantly higher than that in those with 14-3-3ζlow and p-Aktlow. The multivariate Cox proportional hazard analysis indicated that concomitant upregulation of 14-3-3ζ and p-Akt was an independent factor that predicted poor survival and high recurrence in HCC patients. Furthermore, animal experiment showed that overexpression of 14-3-3ζ accelerated the growth of HCC xenograft tumors and induced the expressions of p-Akt and HIF-1α in vivo. Conclusion: Co-upregulation of 14-3-3ζ and p-Akt predicts poor prognosis in patients with HCC, and 14-3-3ζ-induced activation of the Akt signaling pathway contributes to HCC progression.

scholarly journals Type III TGF-β Receptor Down-Regulation Promoted Tumor Progression via Complement Component C5a Induction in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1503
Author(s):  
Oscar Wai Ho Yeung ◽  
Xiang Qi ◽  
Li Pang ◽  
Hui Liu ◽  
Kevin Tak Pan Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Progression ◽  
Tumor Stage ◽  
Complement Component ◽  
Soluble Form ◽  
Advanced Tumor Stage ◽  
Down Regulation ◽  
Type Iii ◽  
Advanced Tumor ◽  
Β Receptor

Background and Aims—Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods—For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results—Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFβR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFβR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFβR3 knockout hepatocyte and HCC cells, increased complement component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion—TGFβR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting complement C5a.

scholarly journals Interleukin-19 in Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ying-Yin Chen ◽  
Chien-Feng Li ◽  
Ching-Hua Yeh ◽  
Ming-Shi Chang ◽  
Chung-Hsi Hsing
Keyword(s):  
Breast Cancer ◽  
Therapeutic Potential ◽  
Endotoxic Shock ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Duct Carcinoma ◽  
Advanced Tumor ◽  
And Migration

Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL-) 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored bothin vitroandin vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

scholarly journals Liprin-β1 is upregulated in human hepatocellular carcinoma and is associated with advanced tumor stage

2019 ◽  
Vol 71 (3) ◽  
pp. 469-474
Author(s):  
Xinying Li ◽  
Jingmei Li ◽  
Jiao Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Stage ◽  
Tumor Stage ◽  
Human Hepatocellular Carcinoma ◽  
Advanced Tumor Stage ◽  
Advanced Clinical Stage ◽  
Advanced Tumor ◽  
Elevated Expression ◽  
Clinicopathological Significance ◽  
Liver Tissues

Liprin-?1 is one of the broadly-expressed liprin family members. Dysregulation of liprin-?1 has been implicated in several types of human cancers. However, the expression of liprin-?1 and its clinicopathological significance in human hepatocellular carcinoma (HCC) remains elusive. We evaluated the protein expression of liprin-?1 in HCC and non-tumor liver tissues by immunohistochemistry, and investigated the relationship between liprin-?1 expression and the clinicopathological attributes of HCC. We found that liprin-?1 expression was significantly higher in HCC than in non-tumor liver tissues. Further analysis showed that higher levels of liprin-?1 in HCC were significantly associated with the advanced clinical stage. Interestingly, liprin-?1 was not detected in cholangiocellular carcinoma specimens. These findings suggest that an elevated expression of liprin-?1 may be involved in HCC progression, providing the rationale that upregulation of liprin-?1 may serve as a novel biomarker for human HCC.

Bilateral Wilms' tumor: long-term survival and some epidemiological features.

1989 ◽  
Vol 7 (3) ◽  
pp. 310-315 ◽  
Author(s):  
M J Coppes ◽  
J de Kraker ◽  
P J van Dijken ◽  
H J Perry ◽  
J F Delemarre ◽  
...  
Keyword(s):  
Wilms Tumor ◽  
Survival Rates ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Older Children ◽  
Term Survival ◽  
Contralateral Kidney ◽  
Advanced Tumor ◽  
Bilateral Wilms Tumor

Sixty-seven children with a bilateral Wilms' tumor (BWT) who were registered to the International Society of Pediatric Oncology (SIOP) nephroblastoma trial and studies 1, 2, and 5, conducted between 1971 and 1980, were analyzed. The overall 10-year survival was 64%. While most deaths due to tumor occurred within 3 years after diagnosis of bilateral disease, five patients died after 3 years (20%), three with synchronous and two with metachronous BWT. The survival rates for the 42 children with synchronous BWT (follow-up time, 6 1/2 to 14 years) and the 25 children with metachronous BWT (follow-up time, 5 to 13 years) were 69% and 56%, respectively. Due to an improvement in the synchronous group, overall survival improved over the years: 47%, 72%, and 70%, in SIOP 1, 2, and 5, respectively. Age at diagnosis and most advanced tumor stage affected prognosis. Children presenting a tumor manifestation before the age of 2 years had better prognosis than older children. This difference is significant in synchronous BWT. Prognosis for children with local stage 1 or 2 was better than for those with local stage 3. Median age at initial presentation in BWT was lower than in unilateral nephroblastoma and lower in metachronous BWT than in synchronous BWT. Young children presenting with unilateral nephroblastoma should have a careful follow-up of the contralateral kidney for at least the next 3 1/2 years, as most contralateral tumors will develop during this period.

ΔTAp73 Upregulation Correlates With Poor Prognosis in Human Tumors: Putative In Vivo Network Involving p73 Isoforms, p53, and E2F-1

2006 ◽  
Vol 24 (5) ◽  
pp. 805-815 ◽  
Author(s):  
Gemma Domínguez ◽  
José M. García ◽  
Cristina Peña ◽  
Javier Silva ◽  
Vanesa García ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Cell Transformation ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Breast Cancer Patients ◽  
Oncogenic Ras ◽  
Advanced Tumor ◽  
Tumor Tissues ◽  
Ras Status

Purpose Although full-length TAp73 variants largely mimic p53 suppressor activities, the transactivation-deficient transcripts ΔTAp73 exert an oncogenic effect by inactivating p53 and TAp73 suppressor properties. Additionally, ΔTAp73 may cooperate with oncogenic RAS to induce cell transformation, confer drug resistance, and induce the phosphorylation of phosphorylated Rb. Here, we study the expression of TAp73 and ΔTAp73 variants and assess possible associations with E2F-1, p53 and K-ras status. We address the possible clinical relevance of alterations in these genes. Patients and Methods We determine in 113 colon and 60 breast cancer patients (a) the expression levels of TAp73, ΔTAp73 (ΔEx2p73, ΔEx2/3p73, and ΔNp73), and E2F-1 transcripts by quantitative real-time reverse transcriptase polymerase chain reaction (PCR); (b) mutations in the first exon of K-ras by PCR–single-stranded confirmational polymorphism; and (c) p53 status by immunohistochemistry. Tumor characteristics were examined in each patient. Results Both suppressor and oncogenic isoforms of TP73 were significantly coupregulated in tumor tissues. Associations were observed between (a) p53 wild type status and upregulation of some TP73 variants; (b) overexpression of E2F-1 and some TP73 forms; and (c) upregulation of ΔTAp73 variants and advanced pathologic stage, lymph node metastasis, vascular invasion, presence of polyps, and tumor localization. Conclusion Overexpression of TP73 variants in tumor tissues indicates that they may be involved in colon and breast carcinogenesis. The association between upregulation of ΔTAp73 isoforms and poor prognosis features, specifically advanced tumor stage, suggests that they may be of practical clinical prognostic value. Interestingly, the in vivo associations identified here may indicate a functional network involving p73 variants, p53, and E2F-1.

scholarly journals Hsa_circ_0062682 Promotes Serine Metabolism and Tumor Growth in Colorectal Cancer by Regulating the miR-940/PHGDH Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Shengbai Sun ◽  
Chaoqun Li ◽  
Kaisa Cui ◽  
Bingxin Liu ◽  
Mingyue Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Stage ◽  
Inhibitory Effect ◽  
Circular Rnas ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Serine Metabolism

Colorectal cancer (CRC) is one of the most common malignancies globally. Increasing evidence indicates that circular RNAs (circRNAs) play a pivotal role in various cancers. The present study focused on exploring the role of a functionally unknown circRNA, hsa_circ_0062682 (circ_0062682), in CRC. By online analyses and experimental validations, we showed that circ_0062682 expression was aberrantly increased in CRC tissues compared with paired normal tissues. Increased expression of circ_0062682 in CRC notably correlated with a poor prognosis and advanced tumor stage. Functional experiments showed that circ_0062682 knockdown reduced CRC growth both in vitro and in vivo. Mechanistically, we revealed that circ_0062682 could sponge miR-940 and identified D-3-phosphoglycerate dehydrogenase (PHGDH), a key oxidoreductase involved in serine biosynthesis, as a novel target of miR-940. Silencing miR-940 expression could mimic the inhibitory effect of circ_0062682 knockdown on CRC proliferation. The expression of PHGDH was downregulated in circ_0062682-depleted or miR-940 overexpressing CRC cells at both the mRNA and protein levels. Circ_0062682 knockdown suppressed CRC growth by decreasing PHGDH expression and serine production via miR-940. Taken together, these data demonstrate, for the first time, that circ_0062682 promotes serine metabolism and tumor growth in CRC by regulating the miR-940/PHGDH axis, suggesting circ_0062682 as a potential novel therapeutic target for CRC.

Decreased expression of p27 protein is associated with advanced tumor stage in hepatocellular carcinoma

2000 ◽  
Vol 89 (4) ◽  
pp. 350-355 ◽  
Author(s):  
Andrea Tannapfel ◽  
Dorothee Grund ◽  
Alexander Katalinic ◽  
Dirk Uhlmann ◽  
Ferdinand K�ckerling ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Advanced Tumor

scholarly journals The interplay of UBE2T and Mule in regulating Wnt/β-catenin activation to promote hepatocellular carcinoma progression

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Nicole Pui Yu Ho ◽  
Carmen Oi Ning Leung ◽  
Tin Lok Wong ◽  
Eunice Yuen Ting Lau ◽  
Martina Mang Leng Lei ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Stage ◽  
Attractive Potential ◽  
Advanced Tumor Stage ◽  
E3 Ligases ◽  
Related Data ◽  
Protein Levels ◽  
Advanced Tumor ◽  
Ubiquitin Conjugating Enzyme

AbstractEmerging evidence indicates the role of cancer stem cells (CSCs) in tumor relapse and therapeutic resistance in patients with hepatocellular carcinoma (HCC). To identify novel targets against liver CSCs, an integrative analysis of publicly available datasets involving HCC clinical and stemness-related data was employed to select genes that play crucial roles in HCC via regulation of liver CSCs. We revealed an enrichment of an interstrand cross-link repair pathway, in which ubiquitin-conjugating enzyme E2 T (UBE2T) was the most significantly upregulated. Consistently, our data showed that UBE2T was upregulated in enriched liver CSC populations. Clinically, UBE2T overexpression in HCC was further confirmed at mRNA and protein levels and was correlated with advanced tumor stage and poor patient survival. UBE2T was found to be critically involved in the regulation of liver CSCs, as evidenced by increases in self-renewal, drug resistance, tumorigenicity, and metastasis abilities. Mule, an E3 ubiquitin ligase, was identified to be the direct protein binding partner of UBE2T. Rather than the canonical role of acting as a mediator to transfer ubiquitin to E3 ligases, UBE2T is surprisingly able to physically bind and regulate the protein expression of Mule via ubiquitination. Mule was found to directly degrade β-catenin protein, and UBE2T was found to mediate liver CSC functions through direct regulation of Mule-mediated β-catenin degradation; this effect was abolished when the E2 activity of UBE2T was impaired. In conclusion, we revealed a novel UBE2T/Mule/β-catenin signaling cascade that is involved in the regulation of liver CSCs, which provides an attractive potential therapeutic target for HCC.

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