Nanotechnology Based Approach for Hepatocellular Carcinoma Targeting

2020 ◽  
Vol 21 ◽  
Author(s):  
Abdulsalam Alhalmi ◽  
Sarwar Beg ◽  
Kanchan Kohli ◽  
Md. Waris ◽  
Tanuja Singh
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Targeting ◽  
Primary Liver Cancer ◽  
Chemotherapeutic Agents ◽  
Regulatory Requirements ◽  
Limited Success ◽  
Incidence And Mortality ◽  
High Incidence ◽  
High Site ◽  
Targeting Ability

Abstract:: Hepatocellular carcinoma (HCC) is the primary liver cancer that has shown a high incidence and mortality rate worldwide among several types of cancers. A large variety of chemotherapeutic agents employed for the treatment has a limited success rate owing to their limited site-specific drug targeting ability. Thus, there is a demand to develop novel approaches for the treatment of HCC. With advancements in nanotechnology-based drug delivery approaches, the chal-lenges of conventional chemotherapy have been continuously decreasing. Nanomedicines constituted of lipidic and poly-meric composites provide a better platform for delivering and open new pathways for HCC treatment. A score of nanocar-riers such as surface-engineered liposomes, nanoparticles, nanotubes, micelles, quantum dots, etc. has been investigated in the treatment of HCC. These nanocarriers are considered to be highly effective clinically for delivering chemotherapeutic drugs with high site-specificity ability and therapeutic efficiency. The present review highlights the current focus on the application of nanocarrier systems using various ligand-based receptor-specific targeting strategies for the treatment and management of HCC. Moreover, the article has also included information on the current clinically approved drug therapy for hepatocellular carcinoma treatment and updates of regulatory requirements for approval of such nanomedicines.

scholarly journals Molecular Bases of Drug Resistance in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1663 ◽  
Author(s):  
Jose J.G. Marin ◽  
Rocio I.R. Macias ◽  
Maria J. Monte ◽  
Marta R. Romero ◽  
Maitane Asensio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinases ◽  
Primary Liver Cancer ◽  
Chemotherapeutic Agents ◽  
Advanced Hepatocellular Carcinoma ◽  
High Refractoriness ◽  
Aggressive Tumor ◽  
Available Information ◽  
Druggable Targets ◽  
Molecular Bases

The poor outcome of patients with non-surgically removable advanced hepatocellular carcinoma (HCC), the most frequent type of primary liver cancer, is mainly due to the high refractoriness of this aggressive tumor to classical chemotherapy. Novel pharmacological approaches based on the use of inhibitors of tyrosine kinases (TKIs), mainly sorafenib and regorafenib, have provided only a modest prolongation of the overall survival in these HCC patients. The present review is an update of the available information regarding our understanding of the molecular bases of mechanisms of chemoresistance (MOC) with a significant impact on the response of HCC to existing pharmacological tools, which include classical chemotherapeutic agents, TKIs and novel immune-sensitizing strategies. Many of the more than one hundred genes involved in seven MOC have been identified as potential biomarkers to predict the failure of treatment, as well as druggable targets to develop novel strategies aimed at increasing the sensitivity of HCC to pharmacological treatments.

scholarly journals The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro

2021 ◽  
Vol 22 (19) ◽  
pp. 10731
Author(s):  
Yu Jin Kim ◽  
Nayeong Yuk ◽  
Hee Jeong Shin ◽  
Hye Jin Jung
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Potential ◽  
Apoptotic Cell ◽  
Primary Liver Cancer ◽  
Therapeutic Effects ◽  
Bacterial Strains ◽  
Nuclear Condensation ◽  
Incidence And Mortality ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is a malignant type of primary liver cancer with high incidence and mortality, worldwide. A major challenge in the treatment of HCC is chemotherapeutic resistance. It is therefore necessary to develop novel anticancer drugs for suppressing the growth of HCC cells and overcoming drug resistance for improving the treatment of HCC. Violacein is a deep violet-colored indole derivative that is produced by several bacterial strains, including Chromobacterium violaceum, and it possesses numerous pharmacological properties, including antitumor activity. However, the therapeutic effects of violacein and the mechanism underlying its antitumor effect against HCC remain to be elucidated. This study is the first to demonstrate that violacein inhibits the proliferation and stemness of Huh7 and Hep3B HCC cells. The antiproliferative effect of violacein was attributed to cell cycle arrest at the sub-G1 phase and the induction of apoptotic cell death. Violacein induced nuclear condensation, dissipated mitochondrial membrane potential (MMP), increased generation of reactive oxygen species (ROS), activated the caspase cascade, and upregulated p53 and p21. The anticancer effect of violacein on HCC cells was also associated with the downregulation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2 signaling. Violacein not only suppressed the proliferation and formation of tumorspheres of Huh7 and Hep3B cancer stem-like cells but also reduced the expression of key markers of cancer stemness, including CD133, Sox2, Oct4, and Nanog, by inhibiting the signal transducer and activator of transcription 3 (STAT3)/AKT/ERK pathways. These results suggest the therapeutic potential of violacein in effectively suppressing HCC by targeting the proliferation and stemness of HCC cells.

Advancement in Nanotheranostics for Effective Skin Cancer Therapy: State of the Art

2020 ◽  
Vol 10 (2) ◽  
pp. 90-104 ◽  
Author(s):  
Md. Habban Akhter ◽  
Mohamed Jawed Ahsan ◽  
Mahfoozur Rahman ◽  
Siraj Anwar ◽  
Md. Rizwanullah
Keyword(s):  
Skin Cancer ◽  
Mortality Rate ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Carcinoma Cells ◽  
Passive Targeting ◽  
Polymeric Nanoparticle ◽  
Enhanced Permeability And Retention ◽  
Incidence And Mortality ◽  
High Incidence

: The skin cancer has become a leading concern worldwide as a result of high mortality rate. The treatment modality involves radiation therapy, chemotherapy or surgery. More often combination therapy of chemotherapeutic agents gives better solution over single chemotherapeutic agent. The Globocon report suggested that high incidence and mortality rate in skin cancer is growing day-to-day. This type of cancer is more prevalent in that area where a person is highly exposed to sunlight. The nanotechnology-based therapy is nowadays drawing attention and becoming a more important issue to be discussed. The nanotherapy of skin cancer is dealt with various approaches and strategies. The strategic based approaches imply nanoparticles targeting carcinoma cells, functionalized nanoparticles for specific targeting to cancer cells, receptor-mediated active targeting as nanoshells, nanostrutured lipid carriers, liposome, ethosome, bilosome, polymeric nanoparticle, nanosphere, dendrimers, carbon nanotubes, quantum dots, solid lipid nanoparticles and fullerenes which are highly efficient in specific killing of cancer cells. The passive targeting of chemotherapeutic agents is also helpful in dealing with carcinoma due to enhanced permeability and retention effect (EPR). : The article outlines nano-based therapy currently focused globally, and the outcomes of the therapy as well.

scholarly journals Role of LncRNAs in the Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyong Ge ◽  
Yuan Yao ◽  
Jing Li ◽  
Zhaonan Li ◽  
Xinwei Han
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Epigenetic Modification ◽  
Primary Liver Cancer ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Incidence And Mortality ◽  
Complex Procedure ◽  
Advanced Stages

Hepatocellular carcinoma (HCC) is a type of primary liver cancer with a high incidence and mortality rate. HCC develops insidiously, and most newly diagnosed cases are in the middle and advanced stages. The epithelial-mesenchymal transition (EMT) is a vital mechanism underlying metastasis in patients with advanced HCC. EMT is a multistep and complex procedure. The promotion and inhibition of EMT directly affect the migration and invasion of HCC. LncRNAs are involved in the epigenetic modification of genes, regulation of gene transcription, and posttranslational modification of proteins. LncRNAs also play important roles in regulating EMT progression in HCC and are promising biomarkers and therapeutic targets. This review focused on summarizing the mechanism by which lncRNAs regulate EMT in HCC. In particular, lncRNAs were reported to primarily act as RNA sponges, and the regulation of EMT involves major signaling pathways. Finally, we reviewed the mechanisms by which lncRNAs are involved in drug resistance and discussed the clinical prospects and potential challenges of utilizing lncRNAs to treat HCC.

scholarly journals Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets

2021 ◽  
Vol 12 ◽  
Author(s):  
Haijun Wang ◽  
Jie Yang ◽  
Ke Zhang ◽  
Jia Liu ◽  
Yushan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Signaling Pathway ◽  
Biological Activities ◽  
Primary Liver Cancer ◽  
Genetic Alterations ◽  
Research Progress ◽  
Fibroblast Growth ◽  
Incidence And Mortality

Hepatocellular carcinoma (HCC) is a type of primary liver cancer with poor prognosis, and its incidence and mortality rate are increasing worldwide. It is refractory to conventional chemotherapy and radiotherapy owing to its high tumor heterogeneity. Accumulated genetic alterations and aberrant cell signaling pathway have been characterized in HCC. The fibroblast growth factor (FGF) family and their receptors (FGFRs) are involved in diverse biological activities, including embryonic development, proliferation, differentiation, survival, angiogenesis, and migration, etc. Data mining results of The Cancer Genome Atlas demonstrate high levels of FGF and/or FGFR expression in HCC tumors compared with normal tissues. Moreover, substantial evidence indicates that the FGF/FGFR signaling axis plays an important role in various mechanisms that contribute to HCC development. At present, several inhibitors targeting FGF/FGFR, such as multikinase inhibitors, specific FGFR4 inhibitors, and FGF ligand traps, exhibit antitumor activity in preclinical or early development phases in HCC. In this review, we summarize the research progress regarding the molecular implications of FGF/FGFR-mediated signaling and the development of FGFR-targeted therapeutics in hepatocarcinogenesis.

Biomarker Identification for Liver Hepatocellular Carcinoma and Cholangiocarcinoma Based on Gene Regulatory Network Analysis

2020 ◽  
Vol 15 ◽  
Author(s):  
Qiuyan Huo ◽  
Yuying Ma ◽  
Yu Yin ◽  
Guimin Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regulatory Networks ◽  
Primary Liver Cancer ◽  
Endocrine Resistance ◽  
Molecular Characteristics ◽  
Network Clustering ◽  
Resistance Pathway ◽  
Gene Regulatory ◽  
Tf Gene ◽  
Liver Hepatocellular Carcinoma

Aims: We aimed to find common and distinct molecular characteristics between LIHC and CHOL based on miRNA-TF-gene FFL. Background: Liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL) are two main histological subtypes of primary liver cancer with a unified molecular landscape, and feed-forward loops (FFLs) have been shown to be relevant in these complex diseases. Objective: To date, there has been no comparative analysis of the pathogenesis of LIHC and CHOL based on regulatory relationships. Therefore, we investigated the common and distinct regulatory properties of LIHC and CHOL in terms of gene regulatory networks. Method: Based on identified FFLs and an analysis of pathway enrichment, we constructed pathway-specific co-expression networks and further predicted biomarkers for these cancers by network clustering. Resul: We identified 20 and 36 candidate genes for LIHC and CHOL, respectively. The literature from PubMed supports the reliability of our results. Conclusion: Our results indicated that the hsa01522-Endocrine resistance pathway was associated with both LIHC and CHOL. Additionally, six genes (SPARC, CTHRC1, COL4A1, EDIL3, LAMA4 and OLFML2B) were predicted to be highly associated with both cancers, of which SPARC was significantly highly ranked. Other: In addition, we inferred that the Collagen gene family, which appeared more frequently in our overall prediction results, might be closely related to cancer development.

scholarly journals Presentation, Management, and Outcomes across the Rural-Urban Continuum for Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Kali Zhou ◽  
Trevor A Pickering ◽  
Christina S Gainey ◽  
Myles Cockburn ◽  
Mariana C Stern ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rural Communities ◽  
Urban Areas ◽  
Tumor Stage ◽  
The United States ◽  
Population Based ◽  
Urban Residents ◽  
Place Of Residence ◽  
Incidence And Mortality ◽  
Receive Treatment

Abstract Background Hepatocellular carcinoma is one of few cancers with rising incidence and mortality in the United States. Little is known about disease presentation and outcomes across the rural-urban continuum. Methods Using the population-based SEER registry, we identified adults with incident hepatocellular carcinoma between 2000–2016. Urban, suburban and rural residence at time of cancer diagnosis were categorized by the Census Bureau’s percent of the population living in non-urban areas. We examined association between place of residence and overall survival. Secondary outcomes were late tumor stage and receipt of therapy. Results Of 83,368 cases, 75.8%, 20.4%, and 3.8% lived in urban, suburban, and rural communities, respectively. Median survival was 7 months (IQR 2–24). All stage and stage-specific survival differed by place of residence, except for distant stage. In adjusted models, rural and suburban residents had a respective 1.09-fold (95% CI = 1.04–1.14, p < .001) and 1.08-fold (95% CI = 1.05–1.10, p < .001) increased hazard of overall mortality as compared to urban residents. Furthermore, rural and suburban residents had 18% (OR = 1.18, 95% CI 1.10–1.27, p < .001) and 5% (OR = 1.05, 95% CI = 1.02–1.09, p = .003) higher odds of diagnosis at late stage and were 12% (OR = 0.88, 95% CI = 0.80–0.94, p < .001) and 8% (OR = 0.92, 95% CI = 0.88–0.95, p < .001) less likely to receive treatment, respectively, compared to urban residents. Conclusions Residence in a suburban and rural community at time of diagnosis was independently associated with worse indicators across the cancer continuum for liver cancer. Further research is needed to elucidate the primary drivers of these rural-urban disparities.

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 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 Regulation of TREM1-Mediated Inflammation in Hepatocellular Carcinoma Cells

Reports ◽  
2021 ◽  
Vol 4 (2) ◽  
pp. 17
Author(s):  
Vikrant Rai ◽  
Devendra K. Agrawal
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vitamin D ◽  
Chronic Inflammation ◽  
Therapeutic Target ◽  
Primary Liver Cancer ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Mediators Of Inflammation ◽  
Tnf Α ◽  
Hcc Cells

Hepatocellular carcinoma (HCC), accounting for more than 90% of cases of primary liver cancer, is the third most common cause of cancer-related death worldwide. Chronic inflammation precedes the development of cirrhosis and HCC. TREM (triggering receptor expressed on myeloid cell)-1 is an inflammatory marker and amplifier of inflammation that signals through PI3K and ERK1/2 to activate transcription factors, resulting in increased secretion of pro-inflammatory cytokines, causing chronic inflammation and predisposing the liver to carcinogenesis. Thus, targeting TREM-1 in HCC might be a potential therapeutic target. A low level of vitamin D has been associated with chronic inflammation and poor prognosis in HCC. Thus, we evaluated the effect of vitamin D on TREM-1 expression in the HCC cell line. Additionally, the effects of high mobility group box-1, lipopolysaccharide, and transcription factor PU.1 on the expression of TREM-1 in normal liver cells and HCC cells have been investigated in the presence and absence of vitamin D. The results showed increased expression of TREM-1 in HCC cells and with IL-6, TNF-α, LPS, and rHMGB-1 and decreased expression with calcitriol. Calcitriol also attenuated the effect of IL-6, TNF-α, LPS, and rHMGB-1 on TREM-1. Calcitriol treatment attenuated the proliferation, migration, and invasion of HCC cells. These results (in vitro) provide molecular and biochemical evidence that calcitriol significantly attenuates the expression of mediators of inflammation, and thus might be used therapeutically together with conventional treatment to delay the progression of HCC. Additionally, the negative regulation of TREM-1 by PU.1 suggests PU.1 as a potential therapeutic target.

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