Small Molecule‐Induced Differentiation As a Potential Therapy for Liver Cancer

Zhang, Xu; Zhu, Xiang-Jie; Zhong, Zhi; Du, Jiang-Chuan; Fang, Guo-Xu; Cui, Xiuliang; Guan, Ling-Ting; Hu, Yanyu; Wang, Hongyang; Zhang, Pei-Lin

doi:10.1002/advs.202103619

Cited by 13 publications

(8 citation statements)

References 37 publications

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“…The poor differentiation of liver cancer refers to the high degree of malignancy. The higher the degree of malignancy, the faster the growth of liver cancer cells, and the more likely they are to have intrahepatic metastasis and distant metastasis in the early stage, which in turn leads to the poor prognosis of patients (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

Establishment and validation of a predictive model of recurrence in primary hepatocellular carcinoma after resection

Xu¹,

Han²,

Cao³

et al. 2023

J Gastrointest Oncol

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Background: In recent years, nomogram prediction models have been widely used to evaluate the prognosis of various diseases. However, studies in primary hepatocellular carcinoma (HCC) are limited. This study sought to explore the risk factors of recurrence of patients with primary HCC after surgical resection and establish a nomogram prediction model. Methods:The data of 424 patients with primary HCC who had been admitted to the Wuhan Third Hospital were retrospectively collected. The patients were followed-up for 5 years after surgery. The patients were divided into the recurrence group (n=189) and control group (n=235) according to whether the cancer recurred after surgery. The differences in the clinical characteristics between the two groups were analyzed.The risk factors of recurrence after surgical resection of primary HCC were also analyzed, and a prediction model was then established using R4.0.3 statistical software.Results: There were significant statistical differences between the two groups in terms of the tumor size, systemic immune-inflammation (SII) index, the number of lesions, tumor differentiation degree, ascites, vascular invasion, and portal vein tumor thrombus (P<0.05). The multivariate regression analysis showed that multiple foci, poorly differentiated tumors, ascites, vascular invasion, and portal vein tumor thrombus were risk factors for the recurrence of primary HCC in patients after surgical resection (P<0.05). The data set was randomly divided into a training set and verification set. The sample size of the training set was 297, and the sample size of the verification set was 127. The area under the receiver operating characteristic (ROC) curve of the training set was 0.866 [95% confidence interval (CI): 0.824-0.907], and the area under the ROC curve of the validation set was 0.812 (95% CI: 0.734-0.890). The Hosmer-Lemeshow Goodness-of-Fit Test was used to test the model with the validation set (χ 2 =11.243, P=0.188), which indicated that the model had high value in predicting the recurrence of primary HCC after surgical resection.Conclusions: This model had high value in predicting the recurrence of primary HCC in patients after surgical resection. This model could assist clinicians to assess the prognosis of patients. Intensive treatment for high-risk patients might improve the prognosis of patients.

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Section: Discussionmentioning

confidence: 99%

Establishment and validation of a predictive model of recurrence in primary hepatocellular carcinoma after resection

Xu¹,

Han²,

Cao³

et al. 2023

J Gastrointest Oncol

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“…3A). In addition, with a combination of small molecules (i.e., TGF-b inhibitor, SB431542; GSK-3b inhibitor, CHIR99021; H3K9 methyltransferase/G9a inhibitor, BIX01294; all-trans retinoic acid, ATRA), hepatoma cells can be induced to differentiate into functional hepatocytes, losing malignancy and acquiring the expression characteristics of mature hepatocytes in a mouse model, thus presenting an unexpected yet promising therapeutic strategy against this type of tumor [81] (Fig. 3A).…”

Section: In Vivo Hepatocyte Reprogramming For Clinical Therapymentioning

confidence: 99%

Hepatocyte reprogramming in liver regeneration: Biological mechanisms and applications

Jiang,

Ren,

Belmonte

et al. 2023

The FEBS Journal

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The liver is one of the few organs that retain the capability to regenerate in adult mammals. This regeneration process is mainly facilitated by the dynamic behavior of hepatocytes, which are the major functional cell type in the liver. In response to liver injury, hepatocytes undergo remarkable alterations, such as reprogramming, wherein they lose their original identity and acquire properties from other cells. This phenomenon of hepatocyte reprogramming, coupled with hepatocyte expansion, plays a central role in liver regeneration, and its underlying mechanisms are complex and multifaceted. Understanding the fate of reprogrammed hepatocytes and the mechanisms of their conversion has significant implications for the development of innovative therapeutics for liver diseases. Herein, we review the plasticity of hepatocytes in response to various forms of liver injuries, with a focus on injury‐induced hepatocyte reprogramming. We provide a comprehensive summary of current knowledge on the molecular and cellular mechanisms governing hepatocyte reprogramming, specifically in the context of liver regeneration, providing insight into potential applications of this process in the treatment of liver disorders, including chronic liver diseases and liver cancer.

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“…Chemotherapy involves the use of anticancer drugs to kill or inhibit the growth of cancer cells [13,14]. In the treatment of LC, commonly used chemotherapy drugs include sorafenib, regorafenib, and cabozantinib [15,16]. These drugs can suppress the growth of LC by inhibiting tumor angiogenesis, suppressing cell proliferation, and inducing cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer

Zeng,

Yu,

Chen

et al. 2024

World J Surg Onc

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Objective The clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE). Methods 92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments. Results the DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05). Conclusion SMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.

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Small Molecule‐Induced Differentiation As a Potential Therapy for Liver Cancer

Cited by 13 publications

References 37 publications

Establishment and validation of a predictive model of recurrence in primary hepatocellular carcinoma after resection

Establishment and validation of a predictive model of recurrence in primary hepatocellular carcinoma after resection

Hepatocyte reprogramming in liver regeneration: Biological mechanisms and applications

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer

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