The role of alpha-fetoprotein in hepatocellular carcinoma drug resistance

2020 ◽  
Vol 27 ◽  
Author(s):  
Wei Li ◽  
Kun Liu ◽  
Yi Chen ◽  
Mingyue Zhu ◽  
Mengsen Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Liver Cancer ◽  
Drug Treatment ◽  
Primary Liver Cancer ◽  
Resistance Mechanisms ◽  
Alpha Fetoprotein ◽  
Major Type ◽  
High Recurrence Rate ◽  
Major Treatment

: Hepatocellular carcinoma (HCC)is a major type of primary liver cancer. It is one of the major causes of cancer-related death in the world,because of its high recurrence rate and poor prognosis. Surgical resection is currently the major treatment measure for early-and middle-stage patients. Because most patients have already missed the opportunity for surgery when the disease is confirmed, conservative chemotherapy (drug treatment)is still an important method of comprehen-sive treatment for patients with middle-and late-stage liver cancer. However, the presence of multidrugs resistance(MDR)in patients with HCC severely reduces the treatment effect and becomes an important obstacle to the success of chemothera-py. Alpha-fetoprotein (AFP)is an important biomarker for the diagnosis of HCC. The expression levels of serum AFP in many patients with HCC increase, and the persistently increased AFP level is a risk factor for HCC progression. Many stud-ies have indicated that AFP functions as an immune suppressor, and AFP can promotes malignant transformation during HCC development and might be involved in the process of MDR in patients with liver cancer. This review describes the drug resistance mechanisms during drug treatment of HCC,and reviews the relationship between the mechanism of AFP in the development and progression of HCC andHCC drug resistance

scholarly journals β-Catenin Expression and Its Association with Prognostic Factors in Hepatocellular Carcinoma: A Study on Alpha-fetoprotein, Histologic Grade, and Microvascular Invasion

2021 ◽  
Vol 9 (A) ◽  
pp. 887-893
Author(s):  
Nur Rahadiani ◽  
Ignasia Andhini Retnowulan ◽  
Marini Stephanie ◽  
Diah Rini Handjari ◽  
Ening Krisnuhoni
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Primary Liver Cancer ◽  
Microvascular Invasion ◽  
Alpha Fetoprotein ◽  
Histologic Grade ◽  
Molecular Characteristics ◽  
High Recurrence Rate ◽  
Cellular Processes ◽  
Serum Alpha Fetoprotein

Background. Hepatocellular carcinoma (HCC), the most common primary liver cancer. In addition to its high incidence, the disease burden is high due to its poor prognosis and high recurrence rate. Some of the currently known clinicopathologic prognostic factors include alpha-fetoprotein (AFP) level, histologic grade, and microvascular invasion. At the molecular level, β-catenin is one of the most common driver mutation found in HCC. The Wnt/β-catenin pathway regulates cellular processes related to initiation, growth, survival, migration, differentiation, and apoptosis. Although the underlying pathogenesis of hepatocarcinogenesis is known, clinical application warrants a greater understanding of the molecular characteristics and tumor phenotype, especially for determining the prognosis. This study aims to analyze the expression of β-catenin and its association with AFP, histologic grade, and microvascular invasion. Materials and methods. Thirty-five samples of surgically resected HCCs at Cipto Mangunkusumo National Referral Hospital were examined. Diagnoses were made based on histopathological and immunohistochemical findings followed by β-catenin staining. β-catenin expression was analyzed to determine difference between variables. Results and conclusions. Here we show that β-catenin expression is significantly associated with low serum alpha-fetoprotein and well to moderate differentiation Implications. Strong nuclear β-catenin expression implies better prognosis in HCC.

scholarly journals Profiling of tumour-associated microbiota in human hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seiga Komiyama ◽  
Takahiro Yamada ◽  
Nobuyuki Takemura ◽  
Norihiro Kokudo ◽  
Koji Hase ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Fatty Liver Disease ◽  
Primary Liver Cancer ◽  
Epithelial Barrier ◽  
Sequence Variants ◽  
Alcoholic Fatty Liver ◽  
Uncultured Bacterium ◽  
Hepatitis C Viruses ◽  
Alcoholic Fatty Liver Disease

AbstractLiver cancer is the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) is a primary liver cancer that results from chronic hepatitis caused by multiple predisposing factors such as viral infection, alcohol consumption, and non-alcoholic fatty liver disease. Accumulating studies have indicated that dysfunction of the gut epithelial barrier and hepatic translocation of gut microbes may be implicated in the pathogenesis of HCC. However, the translocated bacteria in HCC patients remains unclear. Here, we characterised tumour-associated microbiota in patients with liver cancer and focused on HCC. We observed that the number of amplicon sequence variants in tumour-associated microbiota was significantly higher compared with that in non-tumour regions of the liver. The tumour-associated microbiota consisted of Bacteroidetes, Firmicutes, and Proteobacteria as the dominant phyla. We identified an unclassified genus that belonged to the Bacteroides, Romboutsia, uncultured bacterium of Lachnospiraceae as a signature taxon for primary liver cancer. Additionally, we identified Ruminococcus gnavus as a signature taxon for HCC patients infected with hepatitis B and/or hepatitis C viruses. This study suggests that tumour microbiota may contribute to the pathology of HCC.

scholarly journals Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1715
Author(s):  
Macus Hao-Ran Bao ◽  
Carmen Chak-Lui Wong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Liver Cancer ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Metabolic Reprogramming ◽  
Combination Therapies ◽  
Low Oxygen ◽  
Treatment Regimens

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

scholarly journals The Association between Diet and Hepatocellular Carcinoma: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 172
Author(s):  
Elena S. George ◽  
Surbhi Sood ◽  
Anna Broughton ◽  
Georgia Cogan ◽  
Megan Hickey ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Liver Cancer ◽  
Dietary Pattern ◽  
Quantitative Research ◽  
Primary Liver Cancer ◽  
Healthy Eating Index ◽  
Vitamin B9 ◽  
Related Risk ◽  
Monounsaturated Fats

Globally, liver cancer is the sixth most common cause of cancer mortality, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. Emerging evidence states that diet is recognised as a potential lifestyle-related risk factor for the development of HCC. The aim of this systematic review is to determine whether there is an association between diet and the development of HCC. Using the PRISMA guidelines, three databases (MEDLINE Complete, CINAHL and Embase) were systematically searched, and studies published until July 2020 were included. Thirty observational studies were selected. The protocol was registered with PROSPERO (CRD42019135240). Higher adherence to the Mediterranean dietary pattern, Alternative Healthy Eating Index-2010, the Urban Prudent Dietary Pattern, the Traditional Cantonese Dietary Pattern, intake of vegetables, wholegrains, fish, poultry, coffee, macronutrients such as monounsaturated fats and micronutrients such as vitamin E, vitamin B9, β-carotene, manganese and potassium were associated with a reduced risk of HCC. The results suggest a potential role of diet in the development of HCC. Further quantitative research needs to be undertaken within a range of populations to investigate diet and the relationship with HCC risk.

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 452 Preliminary analysis of a real-world study (RWS) of camrelizumab treatment in primary liver cancer (PLC)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A479-A480
Author(s):  
Zhendong Chen ◽  
Nianfei Wang ◽  
Dayong Luo ◽  
Bo Jiang ◽  
Mu Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Group Performance ◽  
Primary Liver Cancer ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Open Label ◽  
Patient Disposition ◽  
Ecog Ps

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the landscape of PLC management at all evolutionary stages.1 As an anti-programmed cell death-1 (PD-1) antibody, camrelizumab monotherapy and in combination with apatinib, an anti-angiogenetic tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-2, chemotherapy or locoregional therapy, have demonstrated their efficacy in advanced hepatocellular carcinoma (HCC).2 3 4 5MethodsThis prospective, open-label, multi-center, observational RWS was conducted to evaluate efficacy and safety of camrelizumab in treatment of PLC in clinical practice. Eligible patients were histopathologically or cytologically identified HCC or intrahepatic cholangiocarcinoma, who were going to receive camrelizumab treatment, with age ≥18 ages, Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0–2 and Child-Pugh score ≤ 9. Patients were treated at clinician discretion. Three hundred patients were planned to enroll, including advanced or peri-operative PLC. The primary endpoint was progress-free survival for advanced PLC, whose efficacy was available to analysis. Efficacy was assessed per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom March 29, 2020 to June 10, 2021,a total of 147 eligible patients of advanced PLC were enrolled and included in this interim analysis, with 128 (87.1%) men, 130 (94.9%) ECOG PS of 0–1, 139 (94.6%) HCC, 74 (50.4%) Barcelona Clinic Liver Cancer stage C, 98 (66.7%) Child-Pugh B, and 72 (49.0%) with extrahepatic metastases, shown in table 1. Of the 147 patients, 45 (30.1%) patients were treated with camrelizumab monotherapy, 79 (53.8%) patients with combination with angiogenesis inhibitors, of which 55 (37.4%) in combination with apatinib, 21 (14.3%) patients with camrelizumab and chemotherapy. Patients, who had at least one efficacy assessment, were included in the efficacy analyses. Up to July 19, 2021, with a median follow time of 6.2 months, 132 patients were available for efficacy analyses. Patient disposition was shown in figure 1. Objective response rate (ORR) and disease control rate (DCR) were 10%/30.8%/35.3% and 75.0%/86.5%/70.6% in camrelizumab monotherapy/combined with apatinib/combined with chemotherapy, respectively. (table 2) The most common camrelizumab-treatment related adverse events (AEs) included reactive cutaneous capillary endothelial proliferation (RCCEP) (12, 8.2%), ICI-induced pneumonia (2, 1.4%), enterocolitis (2, 1.4%), and nephritis (1, 0.7%), of which all these AEs recovered. Other AEs included increase of transaminase (5, 3.4%) and hypertension (4, 2.7%). All AEs were 1–2 grade and no treatment-related death occurred.Abstract 452 Table 1Baseline characteristicsAbstract 452 Figure 1Patient dispositionAbstract 452 Table 2Confirmed tumor response assessed by investigators per RECIST v1.1ConclusionsCamrelizumab, combined with anti-angiogenetic agents or chemotherapy, or monotherapy, demonstrated good efficacy and safety in treatment of PLC.Trial RegistrationChiCTR2000034264ReferencesLlovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7(1):6–28.Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol 2020;21(4):571–580.Xu J, Shen J, Gu S, et al. Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Clin Cancer Res 2021;27(4):1003–1011.Mei K, Qin S, Chen Z, et al. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial. J Immunother Cancer 2021;9(3).Qin S, Bai Y, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol 2013;31(28):3501–3508.Ethics ApprovalThis study was approved by China registered clinical trial ethics review committee with No.ChiECRCT20200042.

Management of hepatocellular carcinoma

2021 ◽  
Vol 4 (1) ◽  
pp. 19-25
Author(s):  
Salem Youssef Mohamed
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Cancer ◽  
Early Diagnosis ◽  
Primary Liver Cancer ◽  
Screening Programs ◽  
Diagnosis And Management

Hepatocellular carcinoma (HCC) is a heterogeneous disease that develops most of the time on diseases liver. Early diagnosis and management are the best options for the patients, so screening programs are mandatory for those who are at risk of the development of HCC. Despite the challenge of management of HCC, there is hopeful management for HCC as the field of primary liver cancer has moved quickly

scholarly journals Treatment of Advanced Hepatocellular Carcinoma with Somatostatin Analogues: A Review of the Literature

2019 ◽  
Vol 20 (19) ◽  
pp. 4811
Author(s):  
Hendrik Reynaert ◽  
Isabelle Colle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Current Knowledge ◽  
Primary Liver Cancer ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Receptor Expression ◽  
Surrounding Tissue ◽  
Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma, one of the most dreaded complications of cirrhosis, is a frequent cancer with high mortality. Early primary liver cancer can be treated by surgery or ablation techniques, but advanced hepatocellular carcinoma remains a challenge for clinicians. Most of these patients have underlying cirrhosis, which complicates or even precludes treatment. Therefore, efficacious treatments without major side effects are welcomed. Initial results of treatment of advanced hepatocellular carcinoma with somatostatin analogues were promising, but subsequent trials have resulted in conflicting outcomes. This might be explained by different patient populations, differences in dosage and type of treatment and differences in somatostatin receptor expression in the tumor or surrounding tissue. It has been shown that the expression of somatostatin receptors in the tumor might be of importance to select patients who could benefit from treatment with somatostatin analogues. Moreover, somatostatin receptor expression in hepatocellular carcinoma has been shown to correlate with recurrence, prognosis, and survival. In this review, we will summarize the available data on treatment of primary liver cancer with somatostatin analogues and analyze the current knowledge of somatostatin receptor expression in hepatocellular carcinoma and its possible clinical impact.

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