scholarly journals Involvement of Kynurenine Pathway in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5180
Author(s):  
Shivani Krishnamurthy ◽  
David Gilot ◽  
Seong Beom Ahn ◽  
Vincent Lam ◽  
Joo-Shik Shin ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Immune Cell ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Immune Surveillance ◽  
Unmet Need ◽  
Kynurenine Pathway ◽  
Diagnostic Technology ◽  
Proliferation And Metastasis

As the second and third leading cancer-related death in men and the world, respectively, primary liver cancer remains a major concern to human health. Despite advances in diagnostic technology, patients with primary liver cancer are often diagnosed at an advanced stage. Treatment options for patients with advanced hepatocarcinoma (HCC) are limited to systemic treatment with multikinase inhibitors and immunotherapy. Furthermore, the 5-year survival rate for these late-stage HCC patients is approximately 12% worldwide. There is an unmet need to identify novel treatment options and/or sensitive blood-based biomarker(s) to detect this cancer at an early stage. Given that the liver harbours the largest proportion of immune cells in the human body, understanding the tumour–immune microenvironment has gained increasing attention as a potential target to treat cancer. The kynurenine pathway (KP) has been proposed to be one of the key mechanisms used by the tumour cells to escape immune surveillance for proliferation and metastasis. In an inflammatory environment such as cancer, the KP is elevated, suppressing local immune cell populations and enhancing tumour growth. In this review, we collectively describe the roles of the KP in cancer and provide information on the latest research into the KP in primary liver cancer.

scholarly journals The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3740
Author(s):  
Chunye Zhang ◽  
Ming Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Fatty Liver ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Underlying Mechanism ◽  
Diagnostic Methods ◽  
T Cell Therapy ◽  
Nonalcoholic Fatty Liver

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.

scholarly journals Contextual Regulation of TGF-β Signaling in Liver Cancer

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1235 ◽  
Author(s):  
Tu ◽  
Huang ◽  
Huang ◽  
Luo ◽  
Yan
Keyword(s):  
Liver Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Receptor Activation ◽  
Membrane Receptors ◽  
Cancer Cell Survival

Primary liver cancer is one of the leading causes for cancer-related death worldwide. Transforming growth factor beta (TGF-β) is a pleiotropic cytokine that signals through membrane receptors and intracellular Smad proteins, which enter the nucleus upon receptor activation and act as transcription factors. TGF-β inhibits liver tumorigenesis in the early stage by inducing cytostasis and apoptosis, but promotes malignant progression in more advanced stages by enhancing cancer cell survival, EMT, migration, invasion and finally metastasis. Understanding the molecular mechanisms underpinning the multi-faceted roles of TGF-β in liver cancer has become a persistent pursuit during the last two decades. Contextual regulation fine-tunes the robustness, duration and plasticity of TGF-β signaling, yielding versatile albeit specific responses. This involves multiple feedback and feed-forward regulatory loops and also the interplay between Smad signaling and non-Smad pathways. This review summarizes the known regulatory mechanisms of TGF-β signaling in liver cancer, and how they channel, skew and even switch the actions of TGF-β during cancer progression.

scholarly journals Clinical research of primary liver cancer mimicking liver abscess

2017 ◽  
Vol 4 (3) ◽  
pp. 1033
Author(s):  
Kong Jun ◽  
Leng Tongmin ◽  
Gong Jianping ◽  
Tang Maoming
Keyword(s):  
Liver Cancer ◽  
Liver Abscess ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Clinical Manifestations ◽  
Pyogenic Liver Abscess ◽  
Diagnosis And Treatment ◽  
Hepatic Arteriography ◽  
Laboratory Findings ◽  
Post Operation

Background: Aiming at diagnosing at an early stage, minimizing the misdiagnosis rate and improving the prognosis, the author has investigated the clinical characteristics, diagnosis and treatment of primary liver cancer mimicking liver abscess with a summary and discussion.Methods: All of the 11 cases of primary liver cancer mimicking liver abscess, diagnosed during January 2009 to December 2015, were retrospectively viewed in terms of clinical manifestations, laboratory tests, radiological feature, diagnosis and treatment. And statistic analysis was made in all aspects mentioned above with that of pyogenic liver abscess and other types of liver cancer diagnosed in the corresponding period.  Results: The clinical manifestations of the 11 cases were mostly characterized by fever, abdominal pain and weight loss. There was no significantly statistic difference between the study group and any of the three matched groups in underlying disease and lab results. All of the 11 patients were treated with enhanced antibiotics as basic therapy. Furthermore, eight cases accepted surgical operation, among them, one object underwent puncture and drainage of the liver abscess by ultrasound (PDLA) twice pre-operation, one object underwent PDLA and hepatic arteriography pre-operation and death in hospital post-operation, one object suffered myocardial infarction post-operation. In addition, three cases received conservative treatment only, in which, one object died in hospital.Conclusions: It is difficult to distinguish primary liver cancer mimicking liver abscess from pyogenic liver abscess as there are no specific clinical manifestations and laboratory findings which is prone to leading to misdiagnosis. What’s worse, the prognosis is so poor that high alert and close follow-up are required as well as early diagnosis and treatment. 

scholarly journals Non-Coding RNA-Based Biosensors for Early Detection of Liver Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 964
Author(s):  
Sedigheh Falahi ◽  
Hossain-Ali Rafiee-Pour ◽  
Mashaalah Zarejousheghani ◽  
Parvaneh Rahimi ◽  
Yvonne Joseph
Keyword(s):  
Survival Rate ◽  
Liver Cancer ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Detection Methods ◽  
Comprehensive Overview ◽  
Non Coding Rna ◽  
Recent Developments ◽  
Non Coding Rnas ◽  
Potential Biomarkers

Primary liver cancer is an aggressive, lethal malignancy that ranks as the fourth leading cause of cancer-related death worldwide. Its 5-year mortality rate is estimated to be more than 95%. This significant low survival rate is due to poor diagnosis, which can be referred to as the lack of sufficient and early-stage detection methods. Many liver cancer-associated non-coding RNAs (ncRNAs) have been extensively examined to serve as promising biomarkers for precise diagnostics, prognostics, and the evaluation of the therapeutic progress. For the simple, rapid, and selective ncRNA detection, various nanomaterial-enhanced biosensors have been developed based on electrochemical, optical, and electromechanical detection methods. This review presents ncRNAs as the potential biomarkers for the early-stage diagnosis of liver cancer. Moreover, a comprehensive overview of recent developments in nanobiosensors for liver cancer-related ncRNA detection is provided.

scholarly journals DIAGNOSTIC AND THERAPEUTIC PROBLEMS OF EARLY STAGE OF PRIMARY LIVER CANCER

1985 ◽  
Vol 18 (4) ◽  
pp. 773-778 ◽  
Author(s):  
Hidekazu SANO ◽  
Yoshimi NAKANISHI ◽  
Shuichi WATANABE ◽  
Isao SAIKI ◽  
Tetsuro KONNO ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Early Stage ◽  
Primary Liver Cancer

Liver cancer

2019 ◽  
Vol 13 (7) ◽  
pp. 322-328
Author(s):  
Ian Peate
Keyword(s):  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Signs And Symptoms ◽  
Normal Structure ◽  
Multiple Choice Questions ◽  
Anatomy And Physiology ◽  
Reflective Questions ◽  
And Function ◽  
Healthcare Assistant

To understand liver cancer and to provide care that is patient-centred, safe and effective, the healthcare assistant and the assistant practitioner (HCA and AP) need to know about the normal structure and function of the liver. This article provides an overview and insight regarding primary liver cancer. A brief overview of the anatomy and physiology of the liver is provided, along with a discussion of liver cancer. The signs and symptoms of the condition are described and treatment options discussed. The HCA and AP have a role to play as members of the multidisciplinary team who offer care to those people with liver cancer and their families. A glossary of terms is provided, as well as multiple-choice questions to aid retention and recall, and 3 CPD reflective questions.

scholarly journals Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1053 ◽  
Author(s):  
Carolin Czauderna ◽  
Darko Castven ◽  
Friederike L. Mahn ◽  
Jens U. Marquardt
Keyword(s):  
Liver Cancer ◽  
Malignant Transformation ◽  
Immune Cell ◽  
Primary Liver Cancer ◽  
Dominant Role ◽  
Therapeutic Interventions ◽  
Chronic Inflammatory Cell ◽  
Therapeutic Implications ◽  
Pathway Activation

Chronic inflammatory cell death is a major risk factor for the development of diverse cancers including liver cancer. Herein, disruption of the hepatic microenvironment as well as the immune cell composition are major determinants of malignant transformation and progression in hepatocellular carcinomas (HCC). Considerable research efforts have focused on the identification of predisposing factors that promote induction of an oncogenic field effect within the inflammatory liver microenvironment. Among the most prominent factors involved in this so-called inflammation-fibrosis-cancer axis is the NF-κB pathway. The dominant role of this pathway for malignant transformation and progression in HCC is well documented. Pathway activation is significantly linked to poor prognostic traits as well as stemness characteristics, which places modulation of NF-κB signaling in the focus of therapeutic interventions. However, it is well recognized that the mechanistic importance of the pathway for HCC is highly context and cell type dependent. While constitutive pathway activation in an inflammatory etiological background can significantly promote HCC development and progression, absence of NF-κB signaling in differentiated liver cells also significantly enhances liver cancer development. Thus, therapeutic targeting of NF-κB as well as associated family members may not only exert beneficial effects but also negatively impact viability of healthy hepatocytes and/or cholangiocytes, respectively. The review presented here aims to decipher the complexity and paradoxical functions of NF-κB signaling in primary liver and non-parenchymal cells, as well as the induced molecular alterations that drive HCC development and progression with a particular focus on (immune-) therapeutic interventions.

scholarly journals Development of Alpha-emitting radioembolization for Hepatocellular Carcinoma: Longitudinal Monitoring of Actinium-225’s Daughters Through SPECT Imaging

2020 ◽  
Author(s):  
Yong Du ◽  
Angel Cortez ◽  
Mohammadreza Zarisfi ◽  
Anders Josefsson ◽  
Rebecca Krimins ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Mouse Model ◽  
Normal Tissue ◽  
Liver Tumors ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Spect Imaging ◽  
Hepatic Tumors

Abstract Hepatocellular carcinoma is the most common primary liver cancer and the fifth most frequently diagnosed cancer worldwide. Most patients with advanced disease are offered non-surgical palliative treatment options. This work explores the first α-emitting radioembolization for the treatment and monitoring of hepatic tumors. Furthermore, this works demonstrates the first in vivo simultaneous multiple-radionuclide SPECT images of the complex decay chain of an [225Ac]Ac-labeled agent using a clinical SPECT system to monitor the temporal distribution. Methods: A DOTA chelator was modified with a lipophilic moiety and radiolabeled with Actinium-225. The resulting agent, [225Ac]Ac-DOTA-TDA, was emulsified in Lipiodol® and evaluated in vivo in mouse model and the VX2 rabbit technical model of liver cancer. SPECT imaging was performed to monitor distribution of the TAT agent and the free daughters.Results: [225Ac]Ac-DOTA-TDA was shown to retain within the HEP2G tumors and VX2 tumor, with minimal uptake within normal tissue. In the mouse model, significant improvements in overall survival were observed. SPECT imaging was able to distinguish between the Actinium-225 agent (Francium-221) and the loss of the longer lived daughter, Bismuth-213. Conclusion: A TAT agent emulsified in Lipiodol® is capable of targeting liver tumors with minimal accumulation in normal tissue, providing a potential therapeutic agent for the treatment of HCC as well as a variety of hepatic tumors. In addition, SPECT imaging presented here provides a foundation for imaging methodology and protocols that can be rapidly translated into the clinic to monitor Actinium-225-labeled agents.

scholarly journals A Novel Orthotopic Liver Cancer Model for Creating a Human-like Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3997
Author(s):  
Rong Qiu ◽  
Soichiro Murata ◽  
Chao Cheng ◽  
Akihiro Mori ◽  
Yunzhong Nie ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Tumor Growth ◽  
Early Stage ◽  
Treatment Options ◽  
Human Tumor ◽  
Alcoholic Fatty Liver ◽  
Huh7 Cells ◽  
Human Ipsc

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. This study aims to develop a new method to generate an HCC mouse model with a human tumor, and imitates the tumor microenvironment (TME) of clinical patients. Here, we have generated functional, three-dimensional sheet-like human HCC organoids in vitro, using luciferase-expressing Huh7 cells, human iPSC-derived endothelial cells (iPSC-EC), and human iPSC-derived mesenchymal cells (iPSC-MC). The HCC organoid, capped by ultra-purified alginate gel, was implanted into the disrupted liver using an ultrasonic homogenizer in the immune-deficient mouse, which improved the survival and engraftment rate. We successfully introduced different types of controllable TME into the model and studied the roles of TME in HCC tumor growth. The results showed the role of the iPSC-EC and iPSC-MC combination, especially the iPSC-MC, in promoting HCC growth. We also demonstrated that liver fibrosis could promote HCC tumor growth. However, it is not affected by non-alcoholic fatty liver disease. Furthermore, the implantation of HCC organoids to humanized mice demonstrated that the immune response is important in slowing down tumor growth at an early stage. In conclusion, we have created an HCC model that is useful for studying HCC development and developing new treatment options in the future.

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