DIAGNOSTIC AND THERAPEUTIC PROBLEMS OF EARLY STAGE OF PRIMARY LIVER CANCER

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.

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Contextual Regulation of TGF-β Signaling in Liver Cancer

Cells ◽

10.3390/cells8101235 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1235 ◽

Cited By ~ 4

Author(s):

Tu ◽

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.

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Involvement of Kynurenine Pathway in Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13205180 ◽

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.

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Clinical research of primary liver cancer mimicking liver abscess

International Surgery Journal ◽

10.18203/2349-2902.isj20170857 ◽

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.

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

Biomedicines ◽

10.3390/biomedicines9080964 ◽

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.

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Exploring molecular basis of therapy response in patient derived primary liver cancer cell lines

10.1055/s-0038-1677199 ◽

2019 ◽

Author(s):

D Castven ◽

D Becker ◽

C Czauderna ◽

D Wilhelm ◽

JB Andersen ◽

...

Keyword(s):

Liver Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Molecular Basis ◽

Primary Liver Cancer ◽

Therapy Response ◽

Cancer Cell Lines ◽

Liver Cancer Cell

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Dual role of Transforming Growth Factor Beta1&2 during Tumor Promotion and Metastasis in Primary Liver Cancer

10.1055/s-0039-3402231 ◽

2020 ◽

Author(s):

S Pereira ◽

L Rodrigues ◽

D Castven ◽

FL Mahn ◽

S Dooley ◽

...

Keyword(s):

Growth Factor ◽

Liver Cancer ◽

Transforming Growth Factor ◽

Primary Liver Cancer ◽

Tumor Promotion ◽

Dual Role ◽

Transforming Growth Factor Beta1

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Biological and Phytochemical Screening of Fumaria indica extract on Chemically Induced Hepatocellular Carcinoma with Reference to Biochemical Parameters

International Journal of Pharmaceutical Quality Assurance ◽

10.25258/ijpqa.10.2.1 ◽

2019 ◽

Vol 10 (02) ◽

Author(s):

Irfan Aziz ◽

Birendra Shrivastava ◽

Chandana Venkateswara Rao2 ◽

Sadath Ali

Keyword(s):

Free Radicals ◽

Liver Disease ◽

Liver Cancer ◽

Early Stage ◽

Food Additives ◽

Ethanolic Extract ◽

Hepatoprotective Activity ◽

Control Group ◽

Industrial Chemicals ◽

Toxic Industrial Chemicals

Liver disease or liver cancer is the sixth most common cancer and the third leading cause of cancer mortality in the world. Hepatitis viral infection, food additives, alcohol, fungal toxins (aflatoxins), toxic industrial chemicals, air and water pollutants are the major risk factors of liver cancer. Moreover, due to high tolerance of liver, HCC is seldom detected at an early stage and once detected treatment faces a poor prognosis in most cases.Fumaria indica possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Fumaria indica would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Fumaria indicais very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of a Fumaria indicaof 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt. Fumaria indica extract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Fumaria indicaextract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats. In addition to this, studies on molecular aspect of hepatoprotective therapy will give mechanistic information in hepatoprotective therapy and also critical balance should be there between the animal model and clinical research. The hepatoprotective properties of Fumaria indicashould provide useful information in the possible application in hepatic liver disease.

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