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.

Complications of thermal ablation of hepatic tumors: Comparison of radiofrequency and microwave techniques.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15040-e15040 ◽  
Author(s):  
Xiang Jing ◽  
Jianmin Ding ◽  
Jibin Liu ◽  
Yandong Wang ◽  
Fengmei Wang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Thermal Ablation ◽  
Liver Tumors ◽  
Major Complication ◽  
Mortality Rates ◽  
Complication Rates ◽  
Hepatic Tumors ◽  
Ablation Therapy ◽  
Liver Cancers ◽  
Significant Difference

e15040 Background: The efficacy and safety of radiofrequency ablation (RFA) have been reported in the literatures, which are considered as frontline choice for treatment of liver cancer. Recently, microwave ablation (MWA) has emerged and gained great attention over RFA. However, in comparison to RFA, the safety of MWA for treatment of liver cancer has not been fully reported in the literatures. Studies with large clinical data sets are still needed to understand the technique and avoid the complications. The objective of this study was to retrospectively investigate the common complications of thermal ablations of liver tumors using both RFA and MWA techniques, and compare the safety between these two procedures. Methods: This retrospective study protocol was approved by our institutional ethics committee to allow investigators to review the existing patient’s medical records. A total of 879 patients with hepatic tumors underwent thermal ablation. There were 323 cases having the RFA procedures and 556 cases having MWA procedures. The complications of thermal ablations of liver tumors were compared using both RFA and MWA techniques. Results: A total of 1,030 thermal ablation sessions was performed in 879 patients with a total of 1,652 tumors. There were 323 patients with 562 tumors received a total of 376 RFA with averaged 1.16±0.48 sessions per patient. The other 556 patients with 1,090 tumors received a total of 654 MWA with averaged1.18±0.51 sessions per patient. The mortality rates were 0.31% (1/323) and 0.36% (2/556) in RFA and MWA group. In RFA and MWA group, the major complication rates were 3.5% (13/376) and 3.1% (20/654) (Table 1), meanwhile the minor complication rates were 5.9% (22/376) and 5.7% (37/654). There was no statistical significant difference for the mortality rates, the major complications, the minor complications between the RFA and MWA groups (P>0.05). Conclusions: Thermal ablation therapy in the treatment of liver cancers is relatively safe with low mortality and low incidence of serious complications. The types and incidences of complications caused by RFA and MWA are similar and comparable for safety consideration in clinical settings.

scholarly journals The mutational features of aristolochic acid-induced mouse and human liver cancers

2018 ◽  
Author(s):  
Zhao-Ning Lu ◽  
Qing Luo ◽  
Li-Nan Zhao ◽  
Yi Shi ◽  
Xian-Bin Su ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Human Liver ◽  
Aristolochic Acid ◽  
Human Cancer ◽  
Herbal Remedies ◽  
Dependent Manner ◽  
Genetic Event ◽  
Recurrent Mutations ◽  
Liver Cancers ◽  
Human Liver Cancer

AbstractAristolochic acid (AA) derived from traditional Chinese herbal remedies has recently been statistically associated with human liver cancer; however, the causal relationships between AA and liver cancer and the underlying evolutionary process of AA-mediated mutagenesis during tumorigenesis are obscure. Here, we subjected mice, including Pten-deficient ones, to aristolochic acid I (AAI) alone or a combination of AAI and carbon tetrachloride (CCl4), which may induce liver injury. Significantly, AAI promoted the development of liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, in a dose-dependent manner, and it increased the incidence of liver cancer, together with CCl4 or Pten deficiency. AAI could lead to DNA damage and AAI-DNA adducts that initiate liver cancer via characteristic A>T transversions, as indicated by the comprehensive genomic analysis, which revealed recurrent mutations in Hras and some genes encoding components of the Ras/Raf, PI3K, Notch, Hippo, Wnt, DNA polymerase family and the SWI/SNF complex, some of which are also often found in human liver cancer. Mutational signature analysis across human cancer types revealed that the AA-related dominant signature was especially implicated in liver cancer in China, based on very stringent criteria derived from the animal cancer form, in which mutations of TP53 and JAK1 are prone to be significantly enriched. Interestingly, AAI-mediated characteristic A>T mutations were the earliest genetic event driving malignant subclonal evolution in mouse and human liver cancer. In general, this study provides documented evidence for AA-induced liver cancer with featured mutational processes during malignant clonal evolution, laying a solid foundation for the prevention and diagnosis of AA-associated human cancers, especially liver cancer.

scholarly journals YAP and TAZ Heterogeneity in Primary Liver Cancer: An Analysis of Its Prognostic and Diagnostic Role

2019 ◽  
Vol 20 (3) ◽  
pp. 638 ◽  
Author(s):  
Matthias Van Haele ◽  
Iván Moya ◽  
Ruçhan Karaman ◽  
Guy Rens ◽  
Janne Snoeck ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Liver Tumors ◽  
Primary Liver Cancer ◽  
Hippo Pathway ◽  
Disease Free Survival ◽  
Decisive Role ◽  
Binding Motif ◽  
Keratin 19 ◽  
Liver Cancers

Primary liver cancer comprises a diverse group of liver tumors. The heterogeneity of these tumors is seen as one of the obstacles to finding an effective therapy. The Hippo pathway, with its downstream transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), has a decisive role in the carcinogenesis of primary liver cancer. Therefore, we examined the expression pattern of YAP and TAZ in 141 patients with hepatocellular carcinoma keratin 19 positive (HCC K19+), hepatocellular carcinoma keratin 19 negative (HCC K19−), combined hepatocellular–cholangiocarcinoma carcinoma (cHCC-CCA), or cholangiocarcinoma (CCA). All cHCC-CCA and CCA patients showed high expression levels for YAP and TAZ, while only some patients of the HCC group were positive. Notably, we found that a histoscore of both markers is useful in the challenging diagnosis of cHCC-CCA. In addition, positivity for YAP and TAZ was observed in the hepatocellular and cholangiocellular components of cHCC-CCA, which suggests a single cell origin in cHCC-CCA. Within the K19− HCC group, our results demonstrate that the expression of YAP is a statistically significant predictor of poor prognosis when observed in the cytoplasm. Nuclear expression of TAZ is an even more specific and independent predictor of poor disease-free survival and overall survival of K19− HCC patients. Our results thus identify different levels of YAP/TAZ expression in various liver cancers that can be used for diagnostics.

scholarly journals Mitochondrial Dynamics and Liver Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2571
Author(s):  
María Isabel Hernández-Alvarez ◽  
Antonio Zorzano
Keyword(s):  
Liver Cancer ◽  
Liver Tumors ◽  
Mitochondrial Dynamics ◽  
Primary Liver Cancer ◽  
Mitochondrial Morphology ◽  
Mitochondrial Dynamic ◽  
Mitochondrial Homeostasis ◽  
Liver Cancers ◽  
Rising Incidence ◽  
Novel Therapeutic Strategies

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Due to its rising incidence and limited therapeutic options, HCC has become a leading cause of cancer-related death worldwide, accounting for 85% of all deaths due to primary liver cancers. Standard therapy for advanced-stage HCC is based on anti-angiogenic drugs such as sorafenib and, more recently, lenvatinib and regorafenib as a second line of treatment. The identification of novel therapeutic strategies is urgently required. Mitochondrial dynamics describes a group of processes that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial morphology and distribution, and connectivity mediated by tethering and fusion/fission events. In recent years, mitochondrial dynamic processes have emerged as key processes in the maintenance of liver mitochondrial homeostasis. In addition, some data are accumulating on the role played by mitochondrial dynamics during cancer development, and specifically on how such dynamics act directly on tumor cells or indirectly on cells responsible for tumor aggression and defense. Here, we review the data that suggest mitochondrial dynamics to be involved in the development of liver tumors.

scholarly journals Ultrasound ablation for metastatic liver cancer and unresectable pancreatic tumors

2018 ◽  
Vol 23 (2) ◽  
pp. 50-58 ◽  
Author(s):  
O. E. Karpov ◽  
P. S. Vetshev ◽  
S. V. Bruslik ◽  
T. I. Sviridova ◽  
A. L. Levchuk ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Pancreatic Tumor ◽  
De Novo ◽  
Liver Tumors ◽  
Combined Treatment ◽  
Pain Syndrome ◽  
Pancreatic Tumors ◽  
Metastatic Liver Cancer ◽  
Ultrasound Ablation ◽  
Metastatic Liver

Material and methods. Ultrasound ablation has been performed in 165 patients with metastatic liver cancer (metastases of colorectal cancer as a rule) and in 17 patients with unresectable pancreatic neoplasms for the period from April 2009 to December 2017. All patients with metastatic liver cancer underwent previous surgery for primary tumor. In 53% of cases unresectable pancreatic tumor was complicated by mechanical jaundice that required biliary drainage and stenting before ablation. Ultrasound and contrast-enhanced CT were applied to assess changes of tumor dimensions, its structure compared with initial data, vascularization grade, continued growth or de novo metastases with positive changes within destruction area. Percutaneous biopsy of liver and pancreatic tumors was carried out in 136 patients (75%) to assess morphological changes of tumor in pre- and postoperative period. Results. There were no intra – and postoperative complications. Three types of changes occurring within destruction area were revealed. Positive changes including changes of tumor structure, reduced dimensions and volume were observed in 76 (46%) patients. 38 (23%) patients had either augmentation of dimensions and volume of destruction area or appearance of additional tumor tissue on the periphery of metastasis. De novo liver metastases or other distant ones occurred in 51 (31%) patients with positive changes in destruction area. Oncologists of our center evaluated immediate and long-term outcomes of combined treatment. Reduced tumor dimension on the background of mild or absent pain syndrome were confirmed in 12 (72%) patients after ablation of pancreatic tumor. In 8 out of 12 patients weight gain and absent pain syndrome were observed within 48 months. Conclusion. Ultrasound ablation is effective and safe for local destruction of secondary liver tumors and unresectable pancreatic tumors. This approach is indicated for inoperable cases and as a stage of combined treatment.

scholarly journals Irreversible Electroporation in Liver Cancers and Whole Organ Engineering

2018 ◽  
Vol 8 (1) ◽  
pp. 22 ◽  
Author(s):  
Aman Saini ◽  
Ilana Breen ◽  
Sadeer Alzubaidi ◽  
Yash Pershad ◽  
Rahul Sheth ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Liver Tumors ◽  
Early Stage ◽  
Irreversible Electroporation ◽  
Local Treatment ◽  
Liver Transplants ◽  
Organ Engineering ◽  
Bridge To Transplant ◽  
Liver Cancers ◽  
Whole Organ Engineering

Liver cancers contribute significantly to cancer-related mortality worldwide and liver transplants remain the cornerstone of curative treatment for select, early-stage patients. Unfortunately, because of a mismatch between demand and supply of donor organs, liver cancer patients must often wait extended periods of time prior to transplant. A variety of local therapies including surgical resection, transarterial chemoembolization, and thermal ablative methods exist in order to bridge to transplant. In recent years, a number of studies have examined the role of irreversible electroporation (IRE) as a non-thermal local ablative method for liver tumors, particularly for those adjacent to critical structures such as the vasculature, gall bladder, or bile duct. In addition to proving its utility as a local treatment modality, IRE has also demonstrated promise as a technique for donor organ decellularization in the context of whole-organ engineering. Through complete non-thermal removal of living cells, IRE allows for the creation of an acellular extra cellular matrix (ECM) scaffold that could theoretically be recellularized and implanted into a living host. Here, we comprehensively review studies investigating IRE, its role in liver cancer treatment, and its utility in whole organ engineering.

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