Treatment Of Liver Cancer Research Articles

Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer.

Liver cancer (LC) poses a significant global health challenge due to its high incidence and poor prognosis. Current systemic treatment options, such as surgery, chemotherapy, radiofrequency ablation, and immunotherapy, have shown limited effectiveness for advanced LC patients. Moreover, owing to the heterogeneous nature of LC, it is crucial to uncover more in-depth pathogenic mechanisms and develop effective treatments to address the limitations of the existing therapeutic modalities. Increasing evidence has revealed the crucial role of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in the pathogenesis of LC. The specific mechanisms driving the JAK-STAT pathway activation in LC, participate in a variety of malignant biological processes, including cell differentiation, evasion, anti-apoptosis, immune escape, and treatment resistance. Both preclinical and clinical investigations on the JAK-STAT pathway inhibitors have exhibited potential in LC treatment, thereby opening up avenues for the development of more targeted therapeutic strategies for LC. In this study, we provide an overview of the JAK-STAT pathway, delving into the composition, activation, and dynamic interplay within the pathway. Additionally, we focus on the molecular mechanisms driving the aberrant activation of the JAK-STAT pathway in LC. Furthermore, we summarize the latest advancements in targeting the JAK-STAT pathway for LC treatment. The insights presented in this review aim to underscore the necessity of research into the JAK-STAT signaling pathway as a promising avenue for LC therapy.

Abstract 3599: Recombinant chimeric antibody-based gamma-delta TCR targeting GPC3 induces potent antitumor response against hepatocellular carcinoma

Abstract Background and Significance: Hepatocellular carcinoma (HCC), a major type of primary liver cancer, is the third leading cause of cancer-related death worldwide. While Glypican-3 (GPC3) is highly upregulated in HCC, it is minimally expressed in normal tissues. The research in our laboratory has been focused on the development of GPC3 as an immunotherapeutic target for liver cancer. Despite many clinical trials, there has not been any approved therapy targeting GPC3 largely due to the combination of antigen heterogeneity, poor tumor penetration, and the inability to induce a durable, potent immune response in the tumor microenvironment (TME). Here, we made a recombinant chimeric antibody-based T cell receptors (named AbTCR) targeting GPC3 and explored its anti-tumor efficacy in xenograft mouse models. Methods: The AbTCR constructs were built by fusing an antigen recognition domain (hYP7 scFv or HN3 VH) specific for GPC3 to the gamma-delta TCR constant region along with a secondary T cell signaling activation motif. The NFAT-tdTomato reporter cell line was established and used to measure the AbTCR-triggered T cell signaling upon stimulation with tumor cells. Anti-tumor efficacy of AbTCR-T cells was determined via luciferase-based cell killing assay as well as multiple HCC xenograft mouse models. Results: The hYP7 GPC3 AbTCR-T cell not only enhances antigen-binding capacity and T cell activity, but also induces infiltration and expansion of T cells in the TME, thereby causing robust liver tumor regression in mice. Conclusion: Our data show that new hYP7-directed GPC3 AbTCR is a promising strategy for treating liver cancer. This work provides a rationale for the use of hYP7 GPC3 AbTCR in clinical studies for treating HCC and other GPC3-positive solid tumors. Citation Format: Dan Li, Tianyuzhou Liang, Zhijian Duan, Hongbing Zhang, Cheng Liu, Mitchell Ho. Recombinant chimeric antibody-based gamma-delta TCR targeting GPC3 induces potent antitumor response against hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3599.

Abstract 7579: Dual inhibition of enhancer of zeste homolog 1 2 induces pyroptosis, modulates oncogenic signaling pathways & sensitizes hepatocellular carcinoma to valemetostat & docetaxel treatments

Abstract HCC is a global health concern, with chemotherapy resistance and patient recurrence posing significant challenges to liver cancer treatment. EZH2 is a crucial part of the polycomb repressive complex 2 (PRC2). It, along with its homolog EZH1, is a focus for cancer therapeutic targets. Dysregulation of EZH1/2 can cause cancer development due to significant changes in geneexpression. The current study aims to investigate the interaction between EZH1/2 and oncogenic signals responsible for HCC progression and pyroptosis induction. Two cell lines, HepG2 and SK-Hep1, were subjected to two FDA-approved drugs, Valemetostat (Val) and Docetaxel (Doc), to determine the impact of EZH1/2 on tumorigenicity and drug resistance. The WST-1 assay was utilized to gauge cell proliferation. The results indisputablydemonstrated a synergistic effect of the drugs after 48 h of treatment. The inhibition of viability was attributed to apoptosis induction in both tested cell lines, and the maximum effect was observed in the combined treatment as compared to either the control or each drug alone. Furthermore, our datashowed activation of caspase-3, upregulation of BAX, indicating apoptotic induction, and downregulation of Bcl-2, Bcl-XL, AKT, S6k, oncogenic β-catenin, and Stat3 protein expression levels, suggesting a modulation of oncogenic signaling pathways at the protein level. After 24 h of Val/Doc treatment, pyroptosis was observed, characterized by cell swelling and bubbles on themembrane and a significant release of lactate dehydrogenase, indicating pyroptotic cell cytotoxicity. The antitumor effects and pyroptosis were enhanced by using a dual inhibitor, UNC1999, for EZH1/2, resulting in a marked increase in the sensitivity of tested cells to the Val/Doc treatment invitro. The present study unequivocally demonstrated that dual inhibition of EZH1/2 acts as a potent sensitizer of HCC cells to Val/Doc treatment, which might be a promising therapeutic approach for inducing cellular pyroptosis in HCC cell lines. Citation Format: Asmaa Elkhder Harira, Adham Maher, Ahmed Sultan. Dual inhibition of enhancer of zeste homolog 1 2 induces pyroptosis, modulates oncogenic signaling pathways & sensitizes hepatocellular carcinoma to valemetostat & docetaxel treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7579.

Abstract 7520: NRT-YHD_001, targeting CD47 for liver cancer immunotherapy

Abstract Previously, we demonstrated that recovery of histone deacetylase 6 (HDAC6) suppressed let-7i-5p expression to de-repress the thrombospondin-1 (TSP1) expression, and thereby it occupied CD47 receptor to block CD47-SIRPα mediated anti-phagocytosis of macrophage in liver cancer. NRT-YHD_001 is a modified antisense miRNA of let-7i-5p for liver cancer treatment. In addition, N-acetylgalactosamine was attached to NRT-YHD_001 for specific delivery to the liver. In vitro phagocytosis assay showed better macrophage phagocytosis activity than non-modified antisense let-7i-5p. To investigate the in vivo efficacy of NRT-YHD_001, spontaneous (Ras-transgenic) mouse liver cancer model was used and compared with that of sorafenib treatment. This mouse liver cancer model usually develops spontaneous liver cancer mass after 15 ~ 20 weeks of birth. We confirmed that both weekly i.v. injection of 1mg/kg and biweekly i.v. injection of 2mg/kg NRT-YHD_001 showed more significant therapeutic efficacy than the sorafenib-treated group. Furthermore, xenograft assay with Hep3B human liver cancer cells in athymic-nude mouse also showed that weekly i.v. injection of 1mg/kg NRT-YHD_001 exhibited better survival and tumor growth inhibition compared to non-treated group. In mouse and cynomolgus monkey maximum tolerated dose (MTD) studies, no toxicity of NRT-YHD_001 was found at doses up to 500 mg/kg intravenously. These results showed that NRT-YHD_001 had a robust anticancer effect by converting the macrophage of “don't eat me” into “eat me signal” in the tumor microenvironment of liver cancer, thereby removing or inhibiting liver cancer cells. Keywords: let-7i-5p, macrophage, phagocytosis, liver cancer, CD47 Citation Format: Suk Woo Nam, Sangyean Kim, Minjeong Na, Eunbi Shin, Jin Woong Ha, Soyoung Jeon, Sungpil Yoon. NRT-YHD_001, targeting CD47 for liver cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7520.

Abstract 362: Arsenic sulfide triggers ferroptosis in hepatocellular carcinoma cells via TRPC6/GPX4 signaling

Abstract Background: Ferroptosis is critically involved in the pathological process of various human diseases, including cancer. Due to this, ferroptosis-inducing drugs are gaining more attention for the clinical treatment of tumors. Methods: The cell counting kit-8 (CCK-8) assay was conducted to observe cell viability of hepatocellular carcinoma (HCC) cell lines. Ferroptosis was determined by levels of Fe2+, lipid reactive oxygen species (ROS), malondialdehyde (MDA) and transmission electron microscopy. Enzyme-linked immunosorbent assay (ELISA), western blot, quantitative polymerase chain reaction and immunofluorescence staining were utilized to evaluate glutathione peroxidase 4 (GPX4) and transient receptor potential channel 6 (TRPC6). Co-immunoprecipitation assay was conducted to determine the binding between GPX4 and TRPC6. Results: Arsenic sulfide initiated ferroptotic cell death in HCC cells, which was concomitant with ROS accumulation, lipid peroxidation, and GSH depletion. Arsenic sulfide -mediated cell death in HCC cells was blocked by ferroptosis inhibitors ferrostatin-1 (Fer-1), but not Z-VAD-FMK, necrosulfonamide, or chloroquine, suggesting that ferroptosis contributed to arsenic sulfide -induced cell death. Furthermore, TRPC6 expression was notably inhibited under arsenic sulfide intervention and the overexpression of TRPC6 rescued the effects of arsenic sulfide on cell viability and ferroptosis of HCC cells. Furthermore, GPX4 was identified to interact with TRPC6 through confocal microscopy images and co-immunoprecipitation assay. Conclusion: Our findings led us to conclude that arsenic sulfide could be considered as a prospective drug for liver cancer treatment. Citation Format: Shumin Lu, Yu Cai, Chuanying Zhu, Zhuowei Feng, Shuxian Chen, Siyu Chen. Arsenic sulfide triggers ferroptosis in hepatocellular carcinoma cells via TRPC6/GPX4 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 362.

Abstract 1821: Conessine inhibits cell proliferation, migration and invasion, and induces apoptosis in liver cancer cells

Abstract Cancer-related deaths from hepatocellular carcinoma (HCC) rank first worldwide. Although many attempts have been made to treat HCC, the survival rate remains unsatisfactory. Many plants from the family Apocynaceae, such as Holarrhena floribunda, contain conessine, a steroidal alkaloid. Several studies have indicated that conessine acts as an antihistamine with cancer therapy and antimicrobial resistance, but it hasn't been tested for its anti-cancer activity against liver cancer. Our study aimed to investigate the anticancer properties of conessine against liver cancer. We tested the effects of conessine on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) markers using both Huh7 and Mahlavu cells. Our experimental results indicated that conessine inhibited cell proliferation, migration, motility, and invasion in Huh7 and Mahlavu cells. Results of Western blot analysis showed that conessine induced apoptosis and EMT in liver cancer cells. Taken together, our results demonstrated that conessine exhibits anticancer activity in liver cancer through suppressing cell proliferation, migration, and invasion, and inducing apoptosis, suggesting it may have benefits for liver cancer treatment. Citation Format: Chia-Yang Li, Yu-Sheng Lin. Conessine inhibits cell proliferation, migration and invasion, and induces apoptosis in liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1821.

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors.

Patients with liver cancer complicated by portal hypertension present complex challenges in treatment. To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition. Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group (n = 50) and a control group (n = 50) according to the treatment regimen. The research group received radiofrequency ablation (RFA) in combination with sorafenib, and the control group only received RFA. The short-term efficacy of both the research and control groups was observed. Liver function and portal hypertension were compared before and after treatment. Alpha-fetoprotein (AFP), glypican-3 (GPC-3), and AFP-L3 levels were compared between the two groups prior to and after treatment. The occurrence of adverse reactions in both groups was observed. The 3-year survival rate was compared between the two groups. Basic data were compared between the survival and non-surviving groups. To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension, multivariate logistic regression analysis was employed. When comparing the two groups, the research group's total effective rate (82.00%) was significantly greater than that of the control group (56.00%; P < 0.05). Following treatment, alanine aminotransferase and aspartate aminotransferase levels increased, and portal vein pressure decreased in both groups. The degree of improvement for every index was substantially greater in the research group than in the control group (P < 0.05). Following treatment, the AFP, GPC-3, and AFP-L3 levels in both groups decreased, with the research group having significantly lower levels than the control group (P < 0.05). The incidence of diarrhea, rash, nausea and vomiting, and fatigue in the research group was significantly greater than that in the control group (P < 0.05). The 1-, 2-, and 3-year survival rates of the research group (94.00%, 84.00%, and 72.00%, respectively) were significantly greater than those of the control group (80.00%, 64.00%, and 40.00%, respectively; P < 0.05). Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade, history of hepatitis, number of tumors, tumor size, use of sorafenib, stage of liver cancer, histological differentiation, history of splenectomy and other basic data (P < 0.05). Logistic regression analysis demonstrated that high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, no use of sorafenib, liver cancer stage IIIC, and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension (P < 0.05). Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates. The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, lack of sorafenib use, liver cancer at stage IIIC, and prior splenectomy.

Liver cancer treatment with mitochondrial homeostasis

Systemic treatment, including molecular targeted therapy, immunotherapy, and chemotherapy, is an important means of achieving long-term survival in patients with intermediate-and advanced-stage liver cancer. However, some patients are insensitive to treatment and even develop drug resistance. Mitochondria are the center of cellular energy metabolism and, at the same time, are the priority targets for systemic therapy. Mitochondrial homeostasis plays an important role in the treatment of liver cancer. The relationship between the two advances is elucidated so as to provide better ideas for the clinical treatment of liver cancer.

Investigation of apoptotic effects of Cucurbitacin D, I, and E mediated by Bax/Bcl-xL, caspase-3/9, and oxidative stress modulators in HepG2 cell line.

Cucurbitacins, natural compounds highly abundant in the Cucurbitaceae plant family, are characterized by their anticancer, anti-inflammatory, and hepatoprotective properties. These compounds have potential as therapeutic agents in the treatment of liver cancer. This study investigated the association of cucurbitacin D, I, and E (CuD, CuI, and CuE) with the caspase cascade, Bcl-2 family, and oxidative stress modulators in the HepG2 cell line. We evaluated the antiproliferative effects of CuD, CuI, and CuE using the MTT assay. We analyzed Annexin V/PI double staining, cell cycle, mitochondrial membrane potential, and wound healing assays at different doses of the three compounds. To examine the modulation of the caspase cascade, we determined the protein and gene expression levels of Bax, Bcl-xL, caspase-3, and caspase-9. We evaluated the total antioxidant status (TAS), total oxidant status(TOS), superoxide dismutase (SOD), glutathione (GSH), Total, and Native Thiol levels to measure cellular redox status. CuD, CuI, and CuE suppressed the proliferation of HepG2 cells in a dose-dependent manner. The cucurbitacins induced apoptosis by increasing caspase-3, caspase-9, and Bax activity, inhibiting Bcl-xL activation, causing loss of ΔΨm, and suppressing cell migration. Furthermore, cucurbitacins modulated oxidative stress by increasing TOS levels and decreasing SOD, GSH, TAS, and total and native Thiol levels. Our findings suggest that CuD, CuI, and CuE exert apoptotic effects on the hepatocellular carcinoma cell line by regulating Bax/Bcl-xL, caspase-3/9 signaling, and causing intracellular ROS increase in HepG2 cells.

Development of pH-Responsive, Thermosensitive, Antibacterial, and Anticancer CS/PVA/Graphene Blended Hydrogels for Controlled Drug Delivery.

Drug delivery techniques based on polymers have been investigated for their potential to improve drug solubility, reduce systemic side effects, and controlled and targeted administration at infection site. In this study, we developed a co-polymeric hydrogel composed of graphene sheets (GNS), polyvinyl alcohol (PVA), and chitosan (CS) that is loaded with methotrexate (MTX) for in vitro liver cancer treatment. Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM) was employed to check the structural properties and surface morphology. Moreover, tests were conducted on the cytotoxicity, hemolytic activity, release kinetics, swelling behaviour and degradation of hydrogels. A controlled release of drug from hydrogel in PBS at pH 7.4 was examined using release kinetics. Maximal drug release in six hours was 97.34%. The prepared hydrogels did not encourage the HepG2 growth and were non-hemolytic. The current study highlights the potential of GNS-based hydrogel loaded with MTX as an encouraging therapy for hepatocellular carcinoma. HepG2 cell viability of MTX-loaded CS-PVA-GNS hydrogel was (IC50 5.87 µg/200 mL) in comparison to free MTX (IC50 5.03 µg/200 mL). These outcomes recommend that hydrogels with GNS ensure improved drug delivery in cancer microenvironment while lessening adverse consequences on healthy cells.

Lianhua Qingwen exerts anti-liver cancer effects and synergistic efficacy with sorafenib through PI3K/AKT pathway: Integrating network pharmacology, molecular docking, and experimental validation

Liver cancer is one of the most lethal malignancies and sorafenib resistance is the main treatment obstacle for patients with advanced liver cancer. Developing drugs that sensitize liver cancer patients to sorafenib is of great importance. Lianhua Qingwen (LHQW), a sort of Traditional Chinese Medicine (TCM) approved by the Chinese Food and Drug Administration (CFDA), is reported to exert synergistic effects with oseltamivir against Influenza virus. However, whether LHQW could exhibit anti-liver cancer effects and enhance the efficacy of sorafenib against liver cancer have not been reported. In the present study, the potential anti-liver cancer effects of LHQW and its synergistic effects with sorafenib were investigated via applying network pharmacology, molecular docking, and in vitro experiments. An “ingredient-compound- target-liver cancer” network was constructed which included 12 ingredients, 164 compounds, and 402 targets. AKT1 was identified as the most hub gene and the PI3K/AKT pathway was revealed as the most enriched pathway. Subsequently, the molecular docking results showed that kaempferol, luteolin, and quercetin were screened as the top 3 compounds which showed the tightest binding to AKT1. Further, the in vitro experiments verified that LHQW significantly inhibited liver cancer cell proliferation and induced apoptosis. Western blot assays confirmed that LHQW could attenuate the PI3K/AKT pathway. Interestingly, LHQW showed a synergistic effect with sorafenib against liver cancer via reducing cell viability, inducing apoptosis, and down- regulating PI3K/AKT pathway. This study broadens the potential application of LHQW and provides insights for liver cancer treatment.

High-resolution extracellular pH imaging of liver cancer with multiparametric MR using Deep Image Prior.

Noninvasive extracellular pH (pHe) mapping with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) using MR spectroscopic imaging (MRSI) has been demonstrated on 3T clinical MR scanners at 8 mm3 spatial resolution and applied to study various liver cancer treatments. Although pHe imaging at higher resolution can be achieved by extending the acquisition time, a postprocessing method to increase the resolution is preferable, to minimize the duration spent by the subject in the MR scanner. In this work, we propose to improve the spatial resolution of pHe mapping with BIRDS by incorporating anatomical information in the form of multiparametric MRI and using an unsupervised deep-learning technique, Deep Image Prior (DIP). Specifically, we used high-resolution , , and diffusion-weighted imaging (DWI) MR images of rabbits with VX2 liver tumors as inputs to a U-Net architecture to provide anatomical information. U-Net parameters were optimized to minimize the difference between the output super-resolution image and the experimentally acquired low-resolution pHe image using the mean-absolute error. In this way, the super-resolution pHe image would be consistent with both anatomical MR images and the low-resolution pHe measurement from the scanner. The method was developed based on data from 49 rabbits implanted with VX2 liver tumors. For evaluation, we also acquired high-resolution pHe images from two rabbits, which were used as ground truth. The results indicate a good match between the spatial characteristics of the super-resolution images and the high-resolution ground truth, supported by the low pixelwise absolute error.

Tumor Microenvironment Activatable Nanoprodrug System for In Situ Fluorescence Imaging and Therapy of Liver Cancer.

The development of new imaging and treatment nanoprodrug systems is highly demanded for diagnosis and therapy of liver cancer, a severe disease characterized by a high recurrence rate. Currently, available small molecule drugs are not possible for cancer diagnosis because of the fast diffusion of imaging agents and low efficacy in treatment due to poor water solubility and significant toxic side effects. In this study, we report the development of a tumor microenvironment activatable nanoprodrug system for the diagnosis and treatment of liver cancer. This nanoprodrug system can accumulate in the tumor site and be selectively activated by an excess of hydrogen peroxide (H2O2) in the tumor microenvironment, releasing near-infrared solid-state organic fluorescent probe (HPQCY-1) and phenylboronic acid-modified camptothecin (CPT) prodrug. Both HPQCY-1 and CPT prodrugs can be further activated in tumor sites for achieving more precise in situ near-infrared (NIR) fluorescence imaging and treatment while reducing the toxic effects of drugs on normal tissues. Additionally, the incorporation of hydrophilic multivalent chitosan as a carrier effectively improved the water solubility of the system. This research thus provides a practical new approach for the diagnosis and treatment of liver cancer.

Chinese expert consensus on composite ablation system for the treatment of primary liver cancer (2023 edition)

Chinese expert consensus on composite ablation system for the treatment of primary liver cancer (2023 edition)

Short-term efficacy of oxaliplatin as interventional therapy for liver cancer, and its effect on serum CD163 and AFU

Purpose: To investigate the short-term effectiveness of oxaliplatin in the interventional treatment of liver cancer, and its effect on serum CD163 and α-L-glucosidase (AFU). &#x0D; Methods: Eighty liver carcinoma patients treated in The Affiliated Hospital of Shaoxing University, Shaoxing, China from January 2022 to January 2023 were allotted to 2 cohorts (each with 40 patients). Subjects in control group were treated with hepatic Transarterial Chemoembolization (TACE), while study group was treated with combination of hepatic TACE and oxaliplatin. Efficacy, serological indicators, health status and cancer-related fatigue were determined and compared between both cohorts. &#x0D; Results: DCR was significantly higher in study group than in the control. There were significantly reduced post-treatment amounts of CYFRA21-1, CA125 and VGEF in the study cohort, relative to pre-treatment and control levels (p &lt; 0.05). Post-treatment values of CD4+/CD8+ and CD4+ were significantly low, relative to levels before treatment, while CD8+ in both groups were significantly increased after treatment (p &lt; 0.05). However, post-treatment T lymphocyte level was comparable in both groups. There was significantly higher post-treatment KPS score in study cohort than pre-treatment and control scores, but RPFS score was significantly reduced, relative to the corresponding pre-treatment and control scores. Post-treatment serum amounts of CD163 and AFU were significantly down-regulated in both cohorts, with lower levels in the study cohort. &#x0D; Conclusion: The combined use of liver TACE and oxaliplatin produces good clinical outcome in the treatment of liver cancer. It is beneficial in reducing serum levels of CD163 and AFU, inhibits proliferation of tumor cells, reduces tumor volume, and improves cancer prognosis in patients.

SPARC Stabilizes ApoE to Induce Cholesterol-Dependent Invasion and Sorafenib Resistance in Hepatocellular Carcinoma.

Intracellular SPARC boosts cholesterol availability to fuel invasion and drug resistance in hepatocellular carcinoma, providing a rational approach to improve the treatment of advanced liver cancer.

HBV DNA polymerase upregulates the transcription of PD-L1 and suppresses T cell activity in hepatocellular carcinoma

BackgroundIn HBV-associated HCC, T cells often exhibit a state of functional exhaustion, which prevents the immune response from rejecting the tumor and allows HCC to progress. Moreover, polymerase-specific T cells exhibit more severe T-cell exhaustion compared to core-specific T cells. However, whether HBV DNA polymerase drives HBV-specific CD8+ T cell exhaustion in HBV-related HCC remains unclear.MethodsWe constructed a Huh7 cell line stably expressing HA-HBV-DNA-Pol and applied co-culture systems to clarify its effect on immune cell function. We also examined how HBV-DNA-Pol modulated PD-L1 expression in HCC cells. In addition, HBV-DNA-Pol transgenic mice were used to elucidate the underlying mechanism of HBV-DNA-Pol/PD-L1 axis-induced T cell exhaustion.ResultsBiochemical analysis showed that Huh7 cells overexpressing HBV-DNA-Pol inhibited the proliferation, activation, and cytokine secretion of Jurkat cells and that this effect was dependent on their direct contact. A similar inhibitory effect was observed in an HCC mouse model. PD-L1 was brought to our attention during screening. Our results showed that the overexpression of HBV-DNA-Pol upregulated PD-L1 mRNA and protein expression. PD-L1 antibody blockade reversed the inhibitory effect of Huh7 cells overexpressing HBV-DNA-Pol on Jurkat cells. Mechanistically, HBV-DNA-Pol interacts with PARP1, thereby inhibiting the nuclear translocation of PARP1 and further upregulating PD-L1 expression.ConclusionsOur findings suggest that HBV-DNA-Pol can act as a regulator of PD-L1 in HCC, thereby directing anti-cancer immune evasion, which further provides a new idea for the clinical treatment of liver cancer.

Research Progress of Interferon in the Treatment of Liver Cancer

Research Progress of Interferon in the Treatment of Liver Cancer

Dual drug-loaded cubosome nanoparticles for hepatocellular carcinoma: a design of experiment approach for optimization and in vitro evaluation

BackgroundLiver cancer, a formidable and complex disease, poses a significant global health threat, stemming from various causes, including chronic infections like hepatitis B and C, cirrhosis, and lifestyle factors. In liver cancer treatment, targeted delivery revolutionizes precision therapy, minimizing side effects by directing drugs specifically to cancer cells. This study aims to develop and statistically optimize cubosomal formulations containing piperine and quercetin with the goal of augmenting their activity against hepatocellular carcinoma.ResultsEmploying a central-composite design, we utilized Design-Expert® software to guide the experiment. The key formulation variables were the concentration of glyceryl monooleate (GMO) and Poloxamer-407, while the dependent responses were particle size (PS) and entrapment efficiency (EE%). The optimized cubosomal formulation was validated through the utilization of high-resolution transmission electron microscopy (HR-TEM), in vitro release studies, and an in vitro cell proliferation assay conducted on the HepG2 cell line. High-performance liquid chromatography was employed for the determination of piperine and quercetin in the optimized cubosomal nanoparticle. The optimized formulation had a composition of 2.5 (w/w%) GMO and 0.5 (w/w%) Poloxamer 407. The predicted values for PS and EE% were 102.34 and 75.11%, respectively. The cytotoxicity of the optimized cubosomal formulation exhibited enhanced efficacy on the HepG2 cancer cell line, even at lower concentrations, when compared to the standard. Notably, it demonstrated a superior cytotoxic effect on the liver cancer cell line.ConclusionThe findings of the study indicated that cubosomes exhibit promise as an effective carrier for delivering piperine and quercetin, addressing hepatocellular carcinoma effectively.Graphical abstract

Reactive oxygen species mediated apoptosis induction in human liver cancer cells by Emblica officinalis (Amla): a new trend in liver cancer treatment

Reactive oxygen species mediated apoptosis induction in human liver cancer cells by Emblica officinalis (Amla): a new trend in liver cancer treatment