Fatty Liver Disease and Hepatocellular Carcinoma: The Pathologist’s View

Tiniakos, Dina; Maurício, João; Reeves, Helen L.

doi:10.1007/978-3-319-98788-0_4

Cited by 12 publications

(7 citation statements)

References 84 publications

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“…Numerous studies have shown that inhibiting IRE1α activity decreases tumor cell proliferation and increases chemosensitivity in various cancer types, such as breast cancer, colorectal cancer and HCC, establishing the IRE1-XBP1 signaling branch as a promising anti-cancer target (15,31,32).Moreover, increased IRE1-XBP1 activity has been attributed to different liver pathologies that precede HCC initiation. For instance, dysregulated IRE1-XBP1 signaling has been associated with human non-alcoholic steatohepatitis, one of the prime causes of HCC in Western countries (33,34). Upregulated IRE1 signaling has also been demonstrated as crucial for liver cirrhosis development (35).…”

Section: Accepted Articlementioning

confidence: 99%

“…Moreover, increased IRE1‐XBP1 activity has been attributed to different liver pathologies that precede HCC initiation. For instance, dysregulated IRE1‐XBP1 signaling has been associated with human nonalcoholic steatohepatitis, one of the prime causes of HCC in Western countries [33,34]. Upregulated IRE1 signaling has also been demonstrated as crucial for liver cirrhosis development [35].…”

Section: The Upr’s Link To Hepatocarcinogenesismentioning

confidence: 99%

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Targeting ER stress in the hepatic tumor microenvironment

Pavlović

Heindryckx

2021

The FEBS Journal

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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It currently ranks as one of the most aggressive and deadly cancers worldwide, with an increasing mortality rate and limited treatment options. An important hallmark of liver pathologies, such as liver fibrosis and HCC, is the accumulation of misfolded and unfolded proteins in the lumen of the endoplasmic reticulum (ER), which induces ER-stress and leads to the activation of the unfolded protein response (UPR). Upon accumulation of misfolded proteins, ER-stress is sensed through three transmembrane proteins, IRE1α, PERK and ATF6, which trigger the UPR to either alleviate ER-stress or induce apoptosis. Increased expression of ER-stress markers has been widely shown to correlate with fibrosis, inflammation, drug resistance and overall HCC aggressiveness, as well as poor patient prognosis. While preclinical in vivo cancer models and in vitro approaches have shown promising results by pharmacologically targeting ER-stress mediators, the major challenge of this therapeutic strategy lies in specifically and effectively targeting ER-stress in HCC. Furthermore, both ER-stress inducers and inhibitors have been shown to ameliorate HCC progression, adding to the complexity of targeting ER-stress players as an anti-cancer strategy.More studies are needed to better understand the dual role and molecular background of ERstress in HCC, as well as its therapeutic potential for patients with liver cancer.

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Section: Accepted Articlementioning

confidence: 99%

Section: The Upr’s Link To Hepatocarcinogenesismentioning

confidence: 99%

Targeting ER stress in the hepatic tumor microenvironment

Pavlović

Heindryckx

2021

The FEBS Journal

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“…The amount of fatty acid in the liver depends on the balance between the processes of delivery and removal. Fatty liver may be accompanied by hepatic inflammation to fibrosis and cirrhosis and finally leads to HCC [16][17][18]. However, with proper and timely diagnosis and with subsequent change in its management at the stage of fibrosis, this disease can be reversible [19,20].…”

Section: Introductionmentioning

confidence: 99%

Fluorescent carbon dots tailored iron oxide nano hybrid system for in vivo optical imaging of liver fibrosis

Nazeer

Saraswathy²,

Nimi

et al. 2023

Methods Appl. Fluoresc.

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Hybridnanoparticles are innovative invention of last decade designed to overcome limitationsof single-component nanoparticles by introducing multiple functionalities throughcombining two or more different nanoparticles. In this study, we are reporting developmentof magneto-fluorescent hybrid nanoparticles by combining iron oxide and carbonnanoparticles to enable in vivo fluorescenceimaging which also has all the required characteristic properties to use as MagneticResonance Imaging (MRI) contrast agent. In order to achieve dual-functionalimaging, alginate and pullulan coated super paramagnetic iron oxidenanoparticles (ASPION and PSPION) and Carbon dots (Cdts) were synthesisedseparately. ASPIONs and PSPIONs were further chemically conjugated with Cdtsand developed dual-functional nanohybrid particles ASPION-Cdts and PSPION-Cdts.Subsequently, evaluation of the materials for its size, functionalisationefficiency, fluorescence and magnetic properties, biocompatibility and cellularuptake efficiency has been carried out. Fluorescence imaging of liver fibrosiswas performed in vivo in rodent model of liver fibrosis using the twonanohybrids, which is further confirmed by high fluorescence signalfrom the harvested liver.

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“…Moreover, other factors such as chronic alcohol consumption [7,8,9,10] increase the risk of contracting HCC by 1.5-3.6 times [11], while smokers are 2.6 times more likely to develop HCC than non-smokers. Hepatitis B infection [11,8,9,10], nonalcoholic fatty liver disease [12,11,13], and cirrhosis [11,8], as well as exposure to nitrosamines [11], aflatoxin [11,14,15], vinyl chloride monomers [11,16], among other carcinogens [8], increase the risk of contracting HCC. However, early diagnosis and prognosis of HCC with effective and potentially curative treatment for starting cancer treatment as soon as possible can increase the patient's survival rate [17,18].…”

Section: Introductionmentioning

confidence: 99%

Prediction of Survival and Analysis of prognostic factors for Hepatocellular Carcinoma: A 20-year of Imaging Diagnosis in Upper Northern Thailand

Nakharutai

Chitapanarux

Traisathit

et al. 2023

Preprint

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Background: To evaluate survival rates of hepatocellular carcinoma (HCC), the Chiang Mai Cancer Registry provided characteristics data of 6276 HCC patients diagnosed between 1998-2020 based on evolution of imaging diagnosis. Evolution can be separated into four cohorts, namely, cohort 1 (1990-2005) when we had ultrasound (US) and single-phase computed tomography (CT), cohort 2 (2006-2009) when one multi-phase CT and one magnetic resonance imaging (MRI) were added, cohort 3 (2010-2015) when MRI with LI-RADS was added, and finally, cohort 4 (2016-2020) when two upgraded MRIs with LI-RADS were added. Methods: Cox proportional hazard models were used to determine the relation between death and risk factors including methods of imagining diagnosis, gender, age of diagnosis, tumor stages, history of smoking and alcohol-use, while Kaplan–Meier curves were used to calculate survival rates. Results: The median age of diagnosis was 57.0 years (IQR: 50.0-65.0) and the median survival time was 5.8 months (IQR: 1.9–26.8) during the follow-up period. In the univariable analysis, all factors were all associated with a higher risk of death in HCC patients except age of diagnosis. In a multivariable analysis, elderly age at diagnosis, regional and metastatic stages and advanced methods of imagining diagnosis during cohorts 2 and 3 were independently associated with the risk of death in HCC patients. The survival rate of patients diagnosed during cohort 4 was significantly higher than the other cohorts. Conclusion: As a significantly increasing survival rate of HCC patients, advanced methods of imagining diagnosis in cohort 4 can be recommended as a guideline of imaging diagnosis.

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Fatty Liver Disease and Hepatocellular Carcinoma: The Pathologist’s View

Cited by 12 publications

References 84 publications

Targeting ER stress in the hepatic tumor microenvironment

Targeting ER stress in the hepatic tumor microenvironment

Fluorescent carbon dots tailored iron oxide nano hybrid system for in vivo optical imaging of liver fibrosis

Prediction of Survival and Analysis of prognostic factors for Hepatocellular Carcinoma: A 20-year of Imaging Diagnosis in Upper Northern Thailand

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