scholarly journals Analysis of failed therapy evaluations in radioembolization of primary and secondary liver cancers

2020 ◽  
Author(s):  
Max Masthoff ◽  
Philipp Schindler ◽  
Fabian Harders ◽  
Walter Heindel ◽  
Christian Wilms ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Tumor Burden ◽  
Meld Score ◽  
Hepatic Tumor ◽  
Careful Patient ◽  
Transarterial Radioembolization ◽  
Number Of Patients ◽  
Liver Cancers ◽  
Elevated Bilirubin ◽  
Tracer Accumulation

Abstract Purpose To analyze patients’ characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after 99mTc-labeled macroaggregated albumin (99mTc-MAA) evaluation. Methods In this retrospective single-center cohort, all patients undergoing 99mTc-MAA evaluation prior to planned TARE for primary or secondary liver cancer between 2009 and 2018 were analyzed. Patients were assigned to either “TARE” or “no TARE” group. Patients’ characteristics, arising reasons for not performing the planned TARE treatment as well as predictive factors for occurrence of these causes were analyzed. Results 436 patients [male = 248, female = 188, median age 62 (23–88) years] with 99mTc-MAA evaluation prior to planned TARE of primary or secondary liver cancer were included in this study. 148 patients (33.9%) did not receive planned TARE. Patients with a hepatic tumor burden > 50%, no liver cirrhosis, no previous therapies and a higher bilirubin were significantly more frequent in “no TARE” compared to “TARE” group. Main reasons for not performing TARE were extrahepatic tracer accumulation (n = 70, 40.5%), non-target accumulation of 99mTc-MAA (n = 27, 15.6%) or a hepatopulmonary shunt fraction of more than 20% (n = 23, 13.3%). Independent preprocedural parameters for not performing planned TARE were elevated bilirubin (p = 0.021) and creatinine (p = 0.018) and lower MELD score (p = 0.031). Conclusion A substantial number of patients are precluded from TARE following 99mTc-MAA evaluation, which is, therefore, implicitly needed to determine contraindications to TARE and should not be refrained from in pretreatment process. However, a preceding careful patient selection is needed especially in patients with high hepatic tumor burden and alteration in lab parameters.

Assessment of miR-212 and Other Biomarkers in the Diagnosis and Treatment of HBV-infection-related Liver Diseases

2019 ◽  
Vol 20 (10) ◽  
pp. 785-798 ◽  
Author(s):  
Yigan Zhang ◽  
Huaze Xi ◽  
Xin Nie ◽  
Peng Zhang ◽  
Ning Lan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Liver Diseases ◽  
Meld Score ◽  
Hbv Infection ◽  
Expression Level ◽  
Control Group

Objective: Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers. Methods: We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients’ clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction. Results: Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBVinfection liver cancer group (P<0.05). The expression of miR-212 was increased in patients’ Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein. Conclusion: There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker used for the diagnosis and assessment of patients with HBV-infection-related liver diseases.

Use of in vivo bioluminescence imaging to predict hepatic tumor burden in mice

2004 ◽  
Vol 120 (2) ◽  
pp. 249-255 ◽  
Author(s):  
Shiva Sarraf-Yazdi ◽  
Jing Mi ◽  
Mark W. Dewhirst ◽  
Bryan M. Clary
Keyword(s):  
Bioluminescence Imaging ◽  
Tumor Burden ◽  
Hepatic Tumor ◽  
In Vivo Bioluminescence Imaging

scholarly journals Liver Radioembolization: a New Chapter in Russian Oncology

2019 ◽  
Vol 29 (5) ◽  
pp. 7-12
Author(s):  
A. D. Kaprin ◽  
S. A. Ivanov ◽  
V. V. Kucherov ◽  
A. P. Petrosyan ◽  
K. V. Mayorov ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Average Energy ◽  
Hepatocellular Cancer ◽  
Beta Particle ◽  
Research Centre ◽  
Gamma Line ◽  
Average Particle ◽  
Liver Tumours ◽  
Number Of Patients ◽  
Yttrium 90

Recent years have seen an increase in the number of patients with malignant tumours of the liver. In this context, new treatment methods are being actively introduced into practice, one of which is liver radioembolization utilizing microspheres embedded with yttrium-90 (90Y).Aim. To review literature data on the history of radioembolization and its application for liver tumours.Key findings. Annually, over 200 thousand patients with inoperable primary liver cancer and over 270 thousand patients with inoperable metastatic liver cancer are registered globally, for whom radioembolization is considered as the most suitable treatment method. 90Y is a pure beta emitter without its own gamma line, which is characterized by a small average particle path in the tissue of 2.5 mm (the maximum level is 11 mm), a maximum beta particle energy of 2.27 MeV (average energy of 0.937 MeV) and a half-life of 64.1 hours. Clinical research into microspheres containing 90Y has been actively conducted since 1977 all over the world. However, it was only in 2004 that the US FDA authorized the clinical use of glass microspheres containing 90Y for the treatment of hepatocellular cancer and liver colorectal cancer metastases. Until recently, radioembolization has not been applied in Russia. In 2018, the joint efforts of the A. Tsyb Medical Radiological Research Centre (MRRC) — branch of the National Medical Research Radiological Centre and BEBIG LLC resulted in the production of Russian microspheres containing yttrium-90, which were subsequently introduced into routine clinical practice. The first liver embolization in Russia using microspheres containing domestic yttrium-90 (BEBIG LLC) to a patient with hepatocellular cancer was carried out by V.V. Kucherov and A.P. Petrosyan at the A. Tsyb RMMC on April, 25 in 2019.Conclusion. The production of microspheres containing 90Y in Russia, as well as a technical improvement of the procedure, will facilitate the introduction of liver radioembolization into the routine management of patients with malignant liver tumours.

scholarly journals Tumor-Intrinsic Mechanisms Regulating Immune Exclusion in Liver Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Katherine E. Lindblad ◽  
Marina Ruiz de Galarreta ◽  
Amaia Lujambio
Keyword(s):  
Liver Cancer ◽  
Rational Design ◽  
Immune Escape ◽  
Current Knowledge ◽  
Treatment Options ◽  
Health Concern ◽  
Patient Stratification ◽  
Tumor Immune Evasion ◽  
Advanced Hcc ◽  
Liver Cancers

Representing the fourth leading cause of cancer-related mortality worldwide, liver cancers constitute a major global health concern. Hepatocellular carcinoma (HCC), the most frequent type of liver cancer, is associated with dismal survival outcomes and has traditionally had few treatment options available. In fact, up until 2017, treatment options for advanced HCC were restricted to broad acting tyrosine kinase inhibitors, including Sorafenib, which has been the standard of care for over a decade. Since 2017, a multitude of mono- and combination immunotherapies that include pembrolizumab, nivolumab, ipilumumab, atezolizumab, and bevacizumab have been FDA-approved for the treatment of advanced HCC with unprecedented response rates ranging from 20 to 30% of patients. However, this also means that ~70% of patients do not respond to this treatment and currently very little is known regarding mechanisms of action of these immunotherapies as well as predictors of response to facilitate patient stratification. With the recent success of immunotherapies in HCC, there is a pressing need to understand mechanisms of tumor immune evasion and resistance to these immunotherapies in order to identify biomarkers of resistance or response. This will enable better patient stratification as well as the rational design of combination immunotherapies to restore sensitivity in resistant patients. The aim of this review is to summarize the current knowledge to date of tumor-intrinsic mechanisms of immune escape in liver cancer, specifically in the context of HCC.

scholarly journals Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1865 ◽  
Author(s):  
Kenya Kamimura ◽  
Takeshi Yokoo ◽  
Hiroyuki Abe ◽  
Shuji Terai
Keyword(s):  
Gene Therapy ◽  
Liver Cancer ◽  
Liver Diseases ◽  
Malignant Tumors ◽  
Therapeutic Options ◽  
Endocrine Function ◽  
Current Status ◽  
Congenital Disease ◽  
Gene Therapies ◽  
Liver Cancers

The liver is a key organ for metabolism, protein synthesis, detoxification, and endocrine function, and among liver diseases, including hepatitis, cirrhosis, malignant tumors, and congenital disease, liver cancer is one of the leading causes of cancer-related deaths worldwide. Conventional therapeutic options such as embolization and chemotherapy are not effective against advanced-stage liver cancer; therefore, continuous efforts focus on the development of novel therapeutic options, including molecular targeted agents and gene therapy. In this review, we will summarize the progress toward the development of gene therapies for liver cancer, with an emphasis on recent clinical trials and preclinical studies.

scholarly journals Roles of Lysyl Oxidase Family Members in the Tumor Microenvironment and Progression of Liver Cancer

2020 ◽  
Vol 21 (24) ◽  
pp. 9751
Author(s):  
Hung-Yu Lin ◽  
Chia-Jung Li ◽  
Ya-Ling Yang ◽  
Ying-Hsien Huang ◽  
Ya-Tze Hsiau ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Lysyl Oxidase ◽  
Primary Liver Cancer ◽  
Target Therapy ◽  
Family Members ◽  
Clinical Value ◽  
Ecm Remodeling ◽  
Liver Cancers ◽  
Advanced Stages

The lysyl oxidase (LOX) family members are secreted copper-dependent amine oxidases, comprised of five paralogues: LOX and LOX-like l-4 (LOXL1-4), which are characterized by catalytic activity contributing to the remodeling of the cross-linking of the structural extracellular matrix (ECM). ECM remodeling plays a key role in the angiogenesis surrounding tumors, whereby a corrupt tumor microenvironment (TME) takes shape. Primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), ranked as the seventh most common cancer globally, with limited therapeutic options for advanced stages. In recent years, a growing body of evidence has revealed the key roles of LOX family members in the pathogenesis of liver cancer and the shaping of TME, indicating their notable potential as therapeutic targets. We herein review the clinical value and novel biological roles of LOX family members in tumor progression and the TME of liver cancers. In addition, we highlight recent insights into their mechanisms and their potential involvement in the development of target therapy for liver cancer.

scholarly journals Diclofenac Potentiates Sorafenib-Based Treatments of Hepatocellular Carcinoma by Enhancing Oxidative Stress

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1453 ◽  
Author(s):  
Duval ◽  
Troquier ◽  
de Souza Silva ◽  
Demartines ◽  
Dormond
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Hepatocellular Cancer ◽  
Tumor Burden ◽  
Anticancer Efficacy ◽  
Cancer Cell Death ◽  
Liver Cancers ◽  
Valuable Treatment ◽  
Anti Oxidant

Sorafenib is the first developed systemic treatment for advanced forms of hepatocellular carcinoma, which constitutes the most frequent form of primary liver cancers and is a major global health burden. Although statistically significant, the positive effect of sorafenib on median survival remains modest, highlighting the need to develop novel therapeutic approaches. In this report, we introduce diclofenac, a nonsteroidal anti-inflammatory drug, as a potent catalyzer of sorafenib anticancer efficacy. Treatment of three different hepatocellular cancer cells (Huh-7, HepG2, and PLC-PRF-5) with sorafenib (5 µM, 24 h) and diclofenac (100 µM, 24 h) significantly increased cancer cell death compared to sorafenib or diclofenac alone. Anti-oxidant compounds, including N-acetyl-cysteine and ascorbic acid, reversed the deleterious effects of diclofenac/sorafenib co-therapy, suggesting that the generation of toxic levels of oxidative stress was responsible for cell death. Accordingly, whereas diclofenac increased production of mitochondrial oxygen reactive species, sorafenib decreased concentrations of glutathione. We further show that tumor burden was significantly diminished in mice bearing tumor xenografts following sorafenib/diclofenac co-therapy when compared to sorafenib or diclofenac alone. Taken together, these results highlight the anticancer benefits of sorafenib/diclofenac co-therapy in hepatocellular carcinoma. They further indicate that combining sorafenib with compounds that increase oxidative stress represents a valuable treatment strategy in hepatocellular carcinoma.

scholarly journals Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 78 ◽  
Author(s):  
Yewei Liu ◽  
Shuncong Wang ◽  
Xiaohui Zhao ◽  
Yuanbo Feng ◽  
Guy Bormans ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Liver Cancer ◽  
Human Liver ◽  
Cellular Differentiation ◽  
Liver Tumors ◽  
Pancreatic Tumors ◽  
Imaging Biomarkers ◽  
Vascular Disrupting Agents ◽  
Liver Cancers ◽  
Vascular Disrupting

Vascular disrupting agents (VDAs) have entered clinical trials for over 15 years. As the leading VDA, combretastatin A4 phosphate (CA4P) has been evaluated in combination with chemotherapy and molecular targeting agents among patients with ovarian cancer, lung cancer and thyroid cancer, but still remains rarely explored in human liver cancers. To overcome tumor residues and regrowth after CA4P monotherapy, a novel dual targeting pan-anticancer theragnostic strategy, i.e., OncoCiDia, has been developed and shown promise previously in secondary liver tumor models. Animal model of primary liver cancer is time consuming to induce, but of value for more closely mimicking human liver cancers in terms of tumor angiogenesis, histopathological heterogeneity, cellular differentiation, tumor components, cancer progression and therapeutic response. Being increasingly adopted in VDA researches, multiparametric magnetic resonance imaging (MRI) provides imaging biomarkers to reflect in vivo tumor responses to drugs. In this article as a chapter of a doctoral thesis, we overview the construction and clinical relevance of primary and secondary liver cancer models in rodents. Target selection for CA4P therapy assisted by enhanced MRI using hepatobiliary contrast agents (CAs), and therapeutic efficacy evaluated by using MRI with a non-specific contrast agent, dynamic contrast enhanced (DCE) imaging, diffusion weighted imaging (DWI) are also described. We then summarize diverse responses among primary hepatocellular carcinomas (HCCs), secondary liver and pancreatic tumors to CA4P, which appeared to be related to tumor size, vascularity, and cellular differentiation. In general, imaging-histopathology correlation studies allow to conclude that CA4P tends to be more effective in secondary liver tumors and in more differentiated HCCs, but less effective in less differentiated HCCs and implanted pancreatic tumor. Notably, cirrhotic liver may be responsive to CA4P as well. All these could be instructive for future clinical trials of VDAs.

scholarly journals Dietary Agents and Phytochemicals in the Prevention and Treatment of Hepatocellular Carcinoma: Review Article

Med Phoenix ◽  
2017 ◽  
Vol 2 (1) ◽  
pp. 52-62
Author(s):  
Mohammad Ahmad ◽  
Anuradha Mishra ◽  
Afreen Usmani ◽  
Md. Parwez Ahmad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Epigallocatechin Gallate ◽  
Cancer Chemoprevention ◽  
Scientific Data ◽  
Anticancer Properties ◽  
Treatment And Prevention ◽  
Liver Cancers ◽  
Prevention And Treatment ◽  
Dietary Agents

Amongst all types of primary liver cancers, hepatocellular carcinoma (HCC) is the commonest form of liver cancer in the world. Cancer chemoprevention using dietary supplements and phytochemicals has attracted increasing attention in recent years. Numerous study reports suggest the role of phytochemicals and dietary compounds in the prevention and treatment of liver cancer. Certain dietary agents and related phytochemicals present in grapes, pomegranate, vegetables, beans, turmeric, soy, rice bran, and fish oils are reported to have chemopreventive potentials against hepatocellular carcinoma. Phytochemicals such as Carotenoids, Epigallocatechin gallate (EGCG), Curcumin, Resveratrol, Rutoside, Quercetin, Chrysin and Silibinin have possible therapeutic importance in tumor suppression during the initial phases of carcinogenesis. Many phytochemicals which are still under investigation lack the scientific data in support of anticancer properties of these compounds rather than anti-oxidant mechanism. So, emphasis should be given on the investigation of plausible molecular mechanism behind anticancer activity. This review summarizes the use of these dietary agents and phytochemicals in the treatment and prevention of HCC and also highlights the mechanisms responsible for their effects.Med Phoenix Vol.2(1) July 2017, 52-62

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