Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model

Bagalagel, Alaa; Diri, Reem; Noor, Ahmed K.; Almasri, Deina; Bakhsh, Hussain T.; Kutbi, Hussam Ibrahim; Al‐Gayyar, Mohammed M.H.

doi:10.7759/cureus.32519

Cited by 8 publications

(7 citation statements)

References 29 publications

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“…There are only hints obtained from a recent mouse model of NASH-associated HCC that suggest that TNF-α neutralization may prevent anti-PD-1 exacerbation of HCC, which, however, warrants further mechanistic studies [16]. Previous preclinical studies testing anti-TNF agents in xenograft HCC [124] or chemically induced HCC mouse models [125], but not in obesity-or NASH-associated HCC mouse models, demonstrated that the blockade of TNF-α signaling hampered tumor progression by diminishing the expression of proinflammatory mediators within HCC tissue and promoting apoptosis in HCC cell. In addition, the combination of anti-TNF with 5-fluorouracil (FU), a classic chemotherapeutic agent, also inhibited tumor growth and improved survival of a mouse model of xenograft HCC [44].…”

Section: Treatment Considerations For Nafld-associated Hccmentioning

confidence: 99%

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Vachliotis,

Valsamidis,

Polyzos

2023

Cancers

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Nonalcoholic fatty liver disease (NAFLD) is emerging as an important risk factor for hepatocellular carcinoma (HCC), whose prevalence is rising. Although the mechanisms of progression from NAFLD to HCC are not fully elucidated, tumor necrosis factor-α (TNF-α) and adiponectin, as well as their interplay, which seems to be antagonistic, may contribute to the pathophysiology of NAFLD-associated HCC. TNF-α initially aims to protect against hepatocarcinogenesis, but during the progression of NAFLD, TNF-α is increased, thus probably inducing hepatocarcinogenesis in the long-term, when NAFLD is not resolved. On the other hand, adiponectin, which is expected to exert anti-tumorigenic effects, is decreased during the progression of the disease, a trend that may favor hepatocarcinogenesis, but is paradoxically increased at end stage disease, i.e., cirrhosis and HCC. These observations render TNF-α and adiponectin as potentially diagnostic biomarkers and appealing therapeutic targets in the setting of NAFLD-associated HCC, possibly in combination with systematic therapy. In this regard, combination strategy, including immune checkpoint inhibitors (ICIs) with anti-TNF biologics and/or adiponectin analogs or medications that increase endogenous adiponectin, may warrant investigation against NAFLD-associated HCC. This review aims to summarize evidence on the association between TNF-α and adiponectin with NAFLD-associated HCC, based on experimental and clinical studies, and to discuss relevant potential therapeutic considerations.

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Section: Treatment Considerations For Nafld-associated Hccmentioning

confidence: 99%

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Vachliotis,

Valsamidis,

Polyzos

2023

Cancers

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“…It was also reported that, cycloastragenol suppressed the expression of SphK, MIP-1α, NF-κB, TNF-α, BAX, and cleaved caspase-3 in the UC rat model, associated with the overexpression of miR-143 and BCL2 (Bagalagel et al, 2022). Consequently, cycloastragenol could protect against UC by regulating SphK/MIP-1α/miR-143 axis, hence suppressing the inflammation and apoptosis-related signals (Bagalagel et al, 2022). miR-24 has been reported to be specifically upregulated in the colonic biopsies from patients with active UC, down-regulating the mRNA and protein expression of the tight junction-associated protein Cingulin and thus impairing the intestinal epithelial barrier formation (Soroosh et al, 2019).…”

Section: Micrornasmentioning

confidence: 86%

“…miR-141-3p is remarkably upregulated in the IECs of the mice model of UC and might affect the infiltration of inflammatory cells by targeting the chemokines CXCL9 or CXCL16 (Lee et al, 2015). It was also reported that, cycloastragenol suppressed the expression of SphK, MIP-1α, NF-κB, TNF-α, BAX, and cleaved caspase-3 in the UC rat model, associated with the overexpression of miR-143 and BCL2 (Bagalagel et al, 2022). Consequently, cycloastragenol could protect against UC by regulating SphK/MIP-1α/miR-143 axis, hence suppressing the inflammation and apoptosis-related signals (Bagalagel et al, 2022).…”

Section: Micrornasmentioning

confidence: 92%

Epigenetic regulation and therapeutic strategies in ulcerative colitis

Yan,

Gu,

Gao

et al. 2023

Front. Genet.

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Ulcerative colitis (UC) is an inflammatory bowel disease, and is characterized by the diffuse inflammation and ulceration in the colon and rectum mucosa, even extending to the caecum. Epigenetic modifications, including DNA methylations, histone modifications and non-coding RNAs, are implicated in the differentiation, maturation, and functional modulation of multiple immune and non-immune cell types, and are influenced and altered in various chronic inflammatory diseases, including UC. Here we review the relevant studies revealing the differential epigenetic features in UC, and summarize the current knowledge about the immunopathogenesis of UC through epigenetic regulation and inflammatory signaling networks, regarding DNA methylation, histone modification, miRNAs and lncRNAs. We also discuss the epigenetic-associated therapeutic strategies for the alleviation and treatment of UC, which will provide insights to intervene in the immunopathological process of UC in view of epigenetic regulation.

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“…The gene expression of Wnt, β-catenin, cadherin, SMAD4, and GAPDH mRNA levels in rat muscle lysate was performed as described previously by our group [7][8][9]. Table 1 shows the gene-specific PCR primers we used.…”

Section: Quantitative Real-time Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Antitumor Activity of Luteolin Against Ehrlich Solid Carcinoma in Rats via Blocking Wnt/β-Catenin/SMAD4 Pathway

Aljohani,

Khodier,

Al-Gayyar

2023

Cureus

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BackgroundEhrlich solid carcinoma (ESC) is characterized by rapid proliferation and a short survival time. Because Ehrlich ascites carcinoma (EAC) resembles human cancer cells, Ehrlich solid and ascetic forms are commonly used to determine the anticancer effects of various compounds. Luteolin is a flavonoid compound found in many dietary sources, including carrots, peppers, celery, olive oil, peppermint, and oregano. Luteolin has potent anti-inflammatory, antidiabetic, antitumor, and antiapoptotic activities. AimsThis study aims to investigate the antitumor activity of luteolin against ESC in rats by affecting the Wnt/βcatenin/SMAD4 pathway. MethodsWe introduced 0.15 ml of Ehrlich cells (2 × 10 6 ) ESC into the left hind thighs of rats. After eight days of inoculation, the rats orally received 25 mg/kg of luteolin daily. We stained sections of tumor tissues with Masson's trichrome. We used another part of the tumor tissue to assess gene and protein expression of Wnt, β-catenin, E-cadherin, and SMAD4. ResultsTreatment of carcinoma rats with luteolin increased the mean survival time and reduced tumor volume and weight. In addition, examination of tumor tissue stained with Masson's trichrome showed loosely to densely packed collagen fibers in between neoplastic cells and scattered papillary expansion of a loose blue band of collagen expression along the covering adipose connective tissue and extending in a fine strand in between muscle fibers, which was ameliorated by treating rats with luteolin. Finally, treating ESC in rats with luteolin overexpressed E-cadherin and downregulated Wnt, β-catenin, and SMAD4. ConclusionsWe found luteolin has antineoplastic activity against ESC by reducing tumor size and weight while improving the structure of muscle cells. It works by suppressing Wnt, β-catenin, and SMAD4, resulting in decreased tumor cell proliferation and differentiation. Additionally, luteolin overexpresses E-cadherin, leading to reduced tumor cell invasion and metastasis.

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Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model

Cited by 8 publications

References 29 publications

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Epigenetic regulation and therapeutic strategies in ulcerative colitis

Antitumor Activity of Luteolin Against Ehrlich Solid Carcinoma in Rats via Blocking Wnt/β-Catenin/SMAD4 Pathway

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