scholarly journals Roles of Lysyl Oxidase Family Members in the Tumor Microenvironment and Progression of Liver Cancer

2020 ◽  
Vol 21 (24) ◽  
pp. 9751
Author(s):  
Hung-Yu Lin ◽  
Chia-Jung Li ◽  
Ya-Ling Yang ◽  
Ying-Hsien Huang ◽  
Ya-Tze Hsiau ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Lysyl Oxidase ◽  
Primary Liver Cancer ◽  
Target Therapy ◽  
Family Members ◽  
Clinical Value ◽  
Ecm Remodeling ◽  
Liver Cancers ◽  
Advanced Stages

The lysyl oxidase (LOX) family members are secreted copper-dependent amine oxidases, comprised of five paralogues: LOX and LOX-like l-4 (LOXL1-4), which are characterized by catalytic activity contributing to the remodeling of the cross-linking of the structural extracellular matrix (ECM). ECM remodeling plays a key role in the angiogenesis surrounding tumors, whereby a corrupt tumor microenvironment (TME) takes shape. Primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), ranked as the seventh most common cancer globally, with limited therapeutic options for advanced stages. In recent years, a growing body of evidence has revealed the key roles of LOX family members in the pathogenesis of liver cancer and the shaping of TME, indicating their notable potential as therapeutic targets. We herein review the clinical value and novel biological roles of LOX family members in tumor progression and the TME of liver cancers. In addition, we highlight recent insights into their mechanisms and their potential involvement in the development of target therapy for liver cancer.

The role of Lysyl oxidase in tumor microenvironment of primary liver cancer

2018 ◽  
Vol 68 ◽  
pp. S675
Author(s):  
M. Lewinska ◽  
M.J. Perugorria ◽  
J. Banales ◽  
J. Andersen
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Lysyl Oxidase ◽  
Primary Liver Cancer

THU-473-Role of intracellular lysyl oxidase in progression of primary liver cancer

2019 ◽  
Vol 70 (1) ◽  
pp. e368
Author(s):  
Monika Lewinska ◽  
Deepak Kumar Bhatt ◽  
Letizia Satriano ◽  
Douglas VNP Oliveira ◽  
Friederike Mahn ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Lysyl Oxidase ◽  
Primary Liver Cancer

scholarly journals The Heterogeneity of Liver Cancer Metabolism

2021 ◽  
pp. 127-136
Author(s):  
Javier Salazar ◽  
Anne Le
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Metabolism ◽  
Primary Liver Cancer ◽  
Cancer Death ◽  
The World ◽  
Advanced Stages ◽  
New Biomarkers ◽  
Cancer Tissues

AbstractPrimary liver cancer is the fourth leading cause of cancer death around the world. Histologically, it can be divided into two major groups, hepatocellular carcinoma (75% of all liver cancer) and intrahepatic cholangiocarcinoma (15% of all liver cancer) [1, 2]. Primary liver cancer usually happens in liver disease or cirrhosis patients [1], and the risk factors for developing HCC depend on the etiology [3] and the country of provenance [1]. There is an urgent need for an accurate diagnostic test given the high proportion of false positives and false negatives for alpha-fetoprotein (AFP), a common HCC biomarker [4]. Due to often being diagnosed in advanced stages, HCCrelated deaths per year have doubled since 1999 [3]. With the use of metabolomics technologies [5], the aberrant metabolism characteristics of cancer tissues can be discovered and exploited for the new biomarkers and new therapies to treat HCC [6, 7].

scholarly journals Treatment of Combined Hepatocellular and Cholangiocarcinoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 794 ◽  
Author(s):  
Simona Leoni ◽  
Vito Sansone ◽  
Stefania De Lorenzo ◽  
Luca Ielasi ◽  
Francesco Tovoli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Unmet Needs ◽  
Primary Liver Cancer ◽  
Therapeutic Options ◽  
Neoplastic Cells ◽  
Dual Nature ◽  
Risk Of Recurrence ◽  
Combined Hepatocellular And Cholangiocarcinoma ◽  
Liver Cancers

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary liver cancer. It is constituted by neoplastic cells of both hepatocellular and cholangiocellular derivation. Different histology types of HCC-CC have been reported, hinting at heterogeneous carcinogenic pathways leading to the development of this cancer. Due to its rarity and complexity, mixed HCC-CC is a scantly investigated condition with unmet needs and unsatisfactory outcomes. Surgery remains the preferred treatment in resectable patients. The risk of recurrence, however, is high, especially in comparison with other primary liver cancers such as hepatocellular carcinoma. In unresectable or recurring patients, the therapeutic options are challenging due to the dual nature of the neoplastic cells. Consequently, the odds of survival of patients with HCC-CC remains poor. We analysed the literature systematically about the treatment of mixed HCC-CC, reviewing the main therapeutic options and their outcomes and analysing the most interesting developments in this topic with a focus on new potential therapeutic avenues.

scholarly journals YAP and TAZ Heterogeneity in Primary Liver Cancer: An Analysis of Its Prognostic and Diagnostic Role

2019 ◽  
Vol 20 (3) ◽  
pp. 638 ◽  
Author(s):  
Matthias Van Haele ◽  
Iván Moya ◽  
Ruçhan Karaman ◽  
Guy Rens ◽  
Janne Snoeck ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Liver Tumors ◽  
Primary Liver Cancer ◽  
Hippo Pathway ◽  
Disease Free Survival ◽  
Decisive Role ◽  
Binding Motif ◽  
Keratin 19 ◽  
Liver Cancers

Primary liver cancer comprises a diverse group of liver tumors. The heterogeneity of these tumors is seen as one of the obstacles to finding an effective therapy. The Hippo pathway, with its downstream transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), has a decisive role in the carcinogenesis of primary liver cancer. Therefore, we examined the expression pattern of YAP and TAZ in 141 patients with hepatocellular carcinoma keratin 19 positive (HCC K19+), hepatocellular carcinoma keratin 19 negative (HCC K19−), combined hepatocellular–cholangiocarcinoma carcinoma (cHCC-CCA), or cholangiocarcinoma (CCA). All cHCC-CCA and CCA patients showed high expression levels for YAP and TAZ, while only some patients of the HCC group were positive. Notably, we found that a histoscore of both markers is useful in the challenging diagnosis of cHCC-CCA. In addition, positivity for YAP and TAZ was observed in the hepatocellular and cholangiocellular components of cHCC-CCA, which suggests a single cell origin in cHCC-CCA. Within the K19− HCC group, our results demonstrate that the expression of YAP is a statistically significant predictor of poor prognosis when observed in the cytoplasm. Nuclear expression of TAZ is an even more specific and independent predictor of poor disease-free survival and overall survival of K19− HCC patients. Our results thus identify different levels of YAP/TAZ expression in various liver cancers that can be used for diagnostics.

scholarly journals Mitochondrial Dynamics and Liver Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2571
Author(s):  
María Isabel Hernández-Alvarez ◽  
Antonio Zorzano
Keyword(s):  
Liver Cancer ◽  
Liver Tumors ◽  
Mitochondrial Dynamics ◽  
Primary Liver Cancer ◽  
Mitochondrial Morphology ◽  
Mitochondrial Dynamic ◽  
Mitochondrial Homeostasis ◽  
Liver Cancers ◽  
Rising Incidence ◽  
Novel Therapeutic Strategies

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Due to its rising incidence and limited therapeutic options, HCC has become a leading cause of cancer-related death worldwide, accounting for 85% of all deaths due to primary liver cancers. Standard therapy for advanced-stage HCC is based on anti-angiogenic drugs such as sorafenib and, more recently, lenvatinib and regorafenib as a second line of treatment. The identification of novel therapeutic strategies is urgently required. Mitochondrial dynamics describes a group of processes that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial morphology and distribution, and connectivity mediated by tethering and fusion/fission events. In recent years, mitochondrial dynamic processes have emerged as key processes in the maintenance of liver mitochondrial homeostasis. In addition, some data are accumulating on the role played by mitochondrial dynamics during cancer development, and specifically on how such dynamics act directly on tumor cells or indirectly on cells responsible for tumor aggression and defense. Here, we review the data that suggest mitochondrial dynamics to be involved in the development of liver tumors.

scholarly journals Somatic mutation landscape reveals differential variability of cell-of-origin for primary liver cancer

2019 ◽  
Author(s):  
Kyungsik Ha ◽  
Masashi Fujita ◽  
Rosa Karlić ◽  
Sungmin Yang ◽  
Yujin Hoshida ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Progenitor Cells ◽  
Genome Sequencing ◽  
Primary Liver Cancer ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Cell Of Origin ◽  
Sequencing Data ◽  
Liver Cancers ◽  
Cancer Types

AbstractBackgroundPrimary liver tissue cancers display consistent increase in global disease burden and mortality. Identification of cell-of-origins for primary liver cancers would be a necessity to expand options for designing relevant therapeutics and preventive medicine for these cancer types. Previous reports on cell-of-origin for primary liver cancers was mainly from animal studies, and integrative research utilizing human specimen data was poorly established.MethodsWe analyzed a whole-genome sequencing data set for a total of 363 tumor and progenitor tissues along with 423 normal tissue epigenomic marks to predict the cell-of-origin for primary liver cancer subtypes.ResultsDespite the mixed histological features, the predicted cell-of-origin for mixed hepatocellular carcinoma / intrahepatic cholangiocarcinoma were uniformly predicted as a hepatocytic origin. Individual sample-level prediction revealed differential level of cell-of-origin heterogeneity depending on the primary liver cancer types, with more heterogeneity observed in intrahepatic cholangiocarcinomas. Additional analyses on the whole genome sequencing data of hepatic progenitor cells suggest these progenitor cells might not a direct cell-of-origin for liver cancers.ConclusionsThese results provide novel insights on the heterogeneous nature and potential contributors of cell-of-origin predictions for primary liver cancers.

scholarly journals Effects Which M6A RNA Methylation Regulation Exerts on the Prognosis of Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Baoxue Jia ◽  
Xiaojian Pei ◽  
Yue Sun ◽  
Yaming Xing ◽  
Jinna Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Human Cancer ◽  
Primary Liver Cancer ◽  
Lasso Regression ◽  
Rna Methylation ◽  
Normal Tissues ◽  
Liver Cancers ◽  
M6a Rna Methylation ◽  
The Relationship

Abstract Background: Hepatocellular carcinoma (HCC) ,which has been known as the most common subtype in the range of primary liver cancer . Besides, it hails as one of China ’s common cancers , giving rise to the major cancer death cause in men. N6 methyladenosine (m6A) RNA methylation is under the regulation of m6A RNA methylation regulators in dynamic way (the proteins of "writer" "eraser"; "reader"). More and more evidences show that the m6A modification level is connected with self-renewal of tumor stem cells, the growth, proliferation, anti chemotherapy and radiosensitivity of tumor cells. The relationship between m6A RNA and human cancer types has been confirmed in a variety of cancers. This research aims to investigate the relationship betwixt m6A RNA methylation regulators and liver cancer. Methods: firstly, the comparison of the expression levels harbored by 13 major m6A RNA methylation regulators in liver cancer with normal tissues was conducted by means of the data of TCGA database. Secondly, we cluster the presentation data of m6A RNA methylated regulator uniformly and dissect HCC tissue into two subgroups (group 1 and 2) by comparing these subgroups according to the overall survival rate (OS), WHO phase and pathological level . Thirdly, based on the combination of least absolute contraction with selection operator (lasso) regression, the risk characteristics of m6A RNA methylation regulators was constructed , which affected OS in TCGA analysis. Results: there were significant differences in the presentation degrades held by 12 major m6A RNA methylation regulators in liver cancers and normal tissues. The primary liver cancer was divided into 1 and 2 groups. It was found that the OS of 1 subgroup was poor, the WHO stage was high and the pathological grade was high. In TCGA analysis, five m6A methylation regulators (YTHDF1, ZC3H13, YTHDF2, METTL3 and KIAA1429) were selected to affect OS, and a risk marker significantly related to who staging was constructed, which was also an independent prognostic marker of OS. Conclusion: m6A RNA methylation regulator is a key player in the progression of HCC and has potential value in the prediction and treatment of HCC.

Comparative the clinical value of contrast-enhanced ultrasonography, enhancement CT and MRI for diagnosing of liver lesions

2021 ◽  
pp. 1-11
Author(s):  
Gang Zhang ◽  
Dandan Liu
Keyword(s):  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Pathological Examination ◽  
Liver Lesions ◽  
Clinical Value ◽  
Contrast Enhanced ◽  
Enhanced Ct ◽  
Significant Difference ◽  
Contrast Enhanced Ultrasonography ◽  
Ct And Mri

BACKGROUND: To investigate the accuracy of contrast-enhanced ultrasonography, CT-enhancement and MRI in the diagnosis of liver-occupying lesions. METHODS: 176 patients with suspected liver lesions in our hospital were retrospectively studied from July 2014 to July 2016. All of the 176 patients were diagnosed by contrast-enhanced ultrasonography, enhanced CT and MRI, and the pathological examination was performed. The results of pathological examination were regarded as the results of the diagnosis. The diagnostic accuracywas then compared among contrast-enhanced ultrasound, enhanced CT and MRI of these patients. RESULTS: The results of contrast-enhanced ultrasonography showed that 164 of the 176 patients had liver-occupying lesions, and the accuracy of the diagnosis was 95.35%, which was significantly higher than that of CT enhancement and MRI (80.23% 84.30%). The accuracy of contrast-enhanced ultrasonography, in the diagnosis of primary liver cancer was significantly higher than that of CT enhancement and MRI (P <  0.05), and the difference was significant difference (P <  0.05). CONCLUSIONS: The examination of contrast-enhanced ultrasonography is relatively simple, and the patients can get duplicateexamination, so we should choose the contrast-enhanced ultrasonography as the preferred method of diagnosis in liver mass, especially primary liver cancer.

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