Abstract 29: Addition of Galunisertib to DC101 increased angiogenesis inhibition and tumor growth control in hepatocellular carcinoma (HCC)

303 Background: Hepatocellular carcinoma (HCC) is the most common liver cancer. Radiofrequency ablation (RFA), transarterial chemoembolization (TACE) or chemotherapy (CT) can be considered at each stage of HCC. The efficacy of these DNA damage inducing treatments could be enhanced by DNA damage repair inhibition. DT01 inhibits the complete DNA double-strand break repair machinery. Here, we assess the combination of DT01 with RFA, TACE or CT in preclinical models. Methods: For association with RFA, mice bearing flank-grafted tumors were sham treated (n=18), treated by DT01 (n=22), RFA (n=21) or a combination of DT01 and RFA (n=19). Mice were either sacrificed for pathological study or followed for survival. For association with TACE, rabbits bearing VX2 hepatocellular carcinoma in liver were untreated (n=9), treated with TACE (n=13) or treated with TACE and DT01 (n=14). Tumor growth, vascularization, necrosis and metastases were assessed with ultrasound scanning, color Doppler, pathology and autopsy respectively. For association with CT, mice bearing orthotopic liver tumors were administered NaCl (n=7), CT (doxorubicin) (n=10), systemic DT01 treatment (n=7) or an association of DT01 and CT (n=10). Tumor growth and pathological studies were assessed. Results: Mice treated by RFA and DT01 have longer survival compared to RFA alone (median survival: 57 vs 40 days) with 54% of complete responses while RFA alone improved survival moderately (median survival: 40 vs 28 days for control). Rabbits treated with TACE and DT01, in comparison to CT alone, show efficient tumor growth control, an increase of tumor necrosis (61% vs 40%), a decrease of metastases (21 vs 54%) and an absence of neoangiogenesis rebound. Mice treated with CT in combination with DT01 show a significant decrease in tumor volume and tumor necrosis, compared to the mice treated with CT alone. In all models, DT01 addition to treatments did not add any toxicity. Conclusions: Our results show that the addition of DT01 to RFA, TACE or CT enhances their antitumor activities and provide an experimental basis for the use of DT01 as an adjuvant therapy at each stage of HCC treatment.

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Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth

10.1101/168823 ◽

2017 ◽

Author(s):

Sebastien Benzekry ◽

Clare Lamont ◽

Dominique Barbolosi ◽

Lynn Hlatky ◽

Philip Hahnfeldt

Keyword(s):

Tumor Growth ◽

Growth Control ◽

Proliferation Inhibition ◽

Secondary Tumor ◽

Angiogenesis Inhibition ◽

Post Surgery ◽

Distant Interactions ◽

Global Action ◽

Single Cancer ◽

Concomitant Resistance

AbstractInteractions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, p<0.05). The competition model had to be rejected while the angiogenesis inhibition and proliferation inhibition models were able to describe the data. Additional models including a theory based on distant cytotoxic log-kill effects were unable to fit the data. The proliferation inhibition model was identifiable and minimal (4 parameters), and its descriptive power was validated against the data, including consistency in predictions of single tumor growth when no secondary tumor was present. This theory may also shed new light on single cancer growth insofar as it offers a biologically translatable picture of how local and global action may combine to control local tumor growth, and in particular, the role of tumor-tumor inhibition. This model offers a depiction of concomitant resistance that provides an improved theoretical basis for tumor growth control and may also find utility in therapeutic planning to avoid post-surgery metastatic acceleration.

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Faculty Opinions recommendation of Transforming growth factor-beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.5261961.5217056 ◽

2010 ◽

Author(s):

Grace Guo ◽

Guodong Li

Keyword(s):

Hepatocellular Carcinoma ◽

Growth Factor ◽

Tumor Growth ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells ◽

Growth Factor Beta

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Faculty Opinions recommendation of MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717647954.793152961 ◽

2012 ◽

Author(s):

Grace Guo ◽

Guodong Li

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Growth ◽

Akt Pathway ◽

Tumor Growth And Metastasis ◽

Phosphoinositide 3 Kinase

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KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

Cell & Bioscience ◽

10.1186/s13578-021-00585-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yarong Guo ◽

Bao Chai ◽

Junmei Jia ◽

Mudan Yang ◽

Yanjun Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Tumor Growth ◽

Luciferase Reporter ◽

Aberrant Expression ◽

Proliferation And Invasion ◽

Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

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LncRNA-SNHG6 promotes the progression of hepatocellular carcinoma by targeting miR-6509-5p and HIF1A

Cancer Cell International ◽

10.1186/s12935-021-01835-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaoxi Fan ◽

Zhongwei Zhao ◽

Jingjing Song ◽

Dengke Zhang ◽

Fazong Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Growth ◽

Bioinformatics Analysis ◽

Carcinoma Cell ◽

Noncoding Rnas ◽

Migration And Invasion ◽

Carcinoma Cell Lines ◽

Huh7 Cells ◽

Hepatocellular Carcinoma Cell

Abstract Background Accumulating evidences have been reported that long noncoding RNAs play crucial roles in the progression of hepatocellular carcinoma (HCC). SnoRNA host gene 6 (SNHG6) is believed to be involved in several human cancers, but the specific molecular mechanism of SNHG6 in HCC is not well studied. Methods In this study, we experimentally down-regulated the SNHG6 in two hepatocellular carcinoma cell lines in vitro, and then measured the proliferation, migration and invasion abilities and the apoptotic levels. Also, we performed the xenograft assay to investigate the function of SNHG6 during the tumor growth in vivo. Results We found SNHG6 was highly expressed in HCC tissues. Next, using Hep3B and Huh7 cells, we confirmed knockdown of SNHG6 reduced the proliferation, migration and invasion abilities in vitro. Also, by bioinformatics analysis, further molecular and cellular experiments, we found miR-6509-5p bound to SNHG6 directly, and the expression level of HIF1A was regulated through SNHG6/miR-6509-5p axis. Finally, we found that down-regulation of SNHG6 dramatically reduced the tumor growth ability of Huh7 cells in vivo. Conclusions We concluded that SNHG6/miR-6509-5p/HIF1A axis functioned in the progression of hepatocellular carcinoma, and could be the promising therapeutic targets during the development of hepatocellular carcinoma drugs.

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Isomalto oligosaccharide sulfate inhibits tumor growth and metastasis of hepatocellular carcinoma in nude mice

BMC Cancer ◽

10.1186/1471-2407-11-150 ◽

2011 ◽

Vol 11 (1) ◽

Cited By ~ 11

Author(s):

Chun-Li Xiao ◽

Zhong-Hua Tao ◽

Lin Guo ◽

Wei-Wei Li ◽

Jin-Liang Wan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Growth ◽

Nude Mice ◽

Tumor Growth And Metastasis

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Long-Term Survival of a Patient with Hepatocellular Carcinoma under Treatment with Viscum album – Case Report

Research Journal of Science and Technology ◽

10.52711/2349-2988.2021.00037 ◽

2021 ◽

pp. 237-243

Author(s):

Ana Catarina Viana Valle ◽

Aloísio Cunha de Carvalho

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Growth ◽

Liver Neoplasm ◽

Viscum Album ◽

Health Condition ◽

Continuous Treatment ◽

Term Survival ◽

History Of ◽

Application Frequency

Hepatocellular carcinoma (HCC) is the most common liver neoplasm in dogs and can be treated by the Viscum album therapy in a curative or palliative way. The objective is to report a hepatocellular carcinoma case in a dog treated by homeopathic therapy, extending to Palliative Care, with a 24-month survival. A 12-year-old Schnauzer male with a history of a liver nodule was treated by intravenous and subcutaneous applications of V. album in different dynamization and combinations, chromotherapy, and oral homeopathic medicines. The tumor growth was controlled, and the health condition of the patient was stable while the medication was given as prescribed. However, as application frequency was reduced, tumor growth increased, and health deterioration was verified. Nevertheless and contrary to expectations, the patient had a 24-month survival. Therefore, these findings point to the potential of V. album on enhancing the quality of life, controlling tumor growth, and prolonging survival on patients with HCC. Patients under continuous treatment would benefit better of these properties.

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