Reposition of the anti-inflammatory drug diacerein in an in-vivo colorectal cancer model

Abdel-Latif, Raghda T.; Wadie, Walaa; Abdel–Mottaleb, Yousra; Abdallah, Dalaal M.; El-Maraghy, Nabila N.; El‐Abhar, Hanan S.

doi:10.1016/j.jsps.2021.12.009

Cited by 7 publications

(4 citation statements)

References 126 publications

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“… 9 CCSA-2 plays an important role in evaluating the prognosis of diseases, which is a colon cancer-specific molecule. 10 In the present study, the levels of CCSA-2, PTN and SIL2 in the study group were lower than those in the control group after treatment. These data further reveal that compared with open radical surgery, laparoscopic surgery can remove tumor tissues more thoroughly, and also has a lower risk of postoperative recurrence.…”

Section: Discussioncontrasting

confidence: 49%

Effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer

Zhang

Qi²,

Li³

et al. 2023

Pak J Med Sci

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Objective: To determine the effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer. Methods: This is a clinical comparative study. Eighty elderly patients with colon cancer hospitalized in the No.2 Hospital of Baoding from May 2020 to May 2022 were randomly divided into two groups, with 40 cases in each group. Patients in the study group received laparoscopic complete mesocolic resection combined with ubenimex orally. While patients in the control group received routine open surgery. The surgical indexes, surgical complications, and the changes of immune molecules and tumor markers before and after treatment were compared between the two groups. Results: The amount of intraoperative bleeding, retention time of drainage tube and postoperative length of stay in the hospital in the study group were significantly better than those in the control group (p=0.000). The incision length of the study group was significantly shorter than that of the control group, the number of lymph nodes removed during the operation was significantly higher than that of the control group, and the incidence of surgical complications was significantly lower than that of the control group (p<0.05). After treatment, the levels of immune molecules in the study group were remarkably higher than those in the control group (p<0.05), while the levels of tumor markers were much lower than those in the latter group (p=0.000). Conclusion: Laparoscopic complete mesocolic excision combined with immunotherapy exhibits a superior therapeutic effect to traditional open surgery in elderly patients with colon cancer, and is worthy of clinical promotion. doi: https://doi.org/10.12669/pjms.39.5.7090 How to cite this: Zhang T, Lin Q, Liu Z, Yang H. Effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer. Pak J Med Sci. 2023;39(5):---------. doi: https://doi.org/10.12669/pjms.39.5.7090 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section: Discussioncontrasting

confidence: 49%

Effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer

Zhang

Qi²,

Li³

et al. 2023

Pak J Med Sci

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“…Notably, studies have implicated CBD in suppressing the NF-kB pathway, strongly indicating its anti-proliferative and anti-inflammatory activities [ 92 ]. Conversely, THC demonstrates a propensity to induce the NF-kB pathways, which in turn assumes a multifaceted role as a consequential epigenetic regulator of diverse gene expression in malignant tumors, thereby implicating its involvement in EMT [ 93 , 94 ]. Nonetheless, the mechanisms underlying the functional selectivity of NF-kB signaling in the context of CB receptors remain to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Functional Selectivity of Cannabinoid Type 1 G Protein-Coupled Receptor Agonists in Transactivating Glycosylated Receptors on Cancer Cells to Induce Epithelial–Mesenchymal Transition Metastatic Phenotype

Bunsick,

Matsukubo,

Aldbai

et al. 2024

Cells

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Understanding the role of biased G protein-coupled receptor (GPCR) agonism in receptor signaling may provide novel insights into the opposing effects mediated by cannabinoids, particularly in cancer and cancer metastasis. GPCRs can have more than one active state, a phenomenon called either ‘biased agonism’, ‘functional selectivity’, or ‘ligand-directed signaling’. However, there are increasing arrays of cannabinoid allosteric ligands with different degrees of modulation, called ‘biased modulation’, that can vary dramatically in a probe- and pathway-specific manner, not from simple differences in orthosteric ligand efficacy or stimulus-response coupling. Here, emerging evidence proposes the involvement of CB1 GPCRs in a novel biased GPCR signaling paradigm involving the crosstalk between neuraminidase-1 (Neu-1) and matrix metalloproteinase-9 (MMP-9) in the activation of glycosylated receptors through the modification of the receptor glycosylation state. The study findings highlighted the role of CB1 agonists AM-404, Aravnil, and Olvanil in significantly inducing Neu-1 sialidase activity in a dose-dependent fashion in RAW-Blue, PANC-1, and SW-620 cells. This approach was further substantiated by findings that the neuromedin B receptor inhibitor, BIM-23127, MMP-9 inhibitor, MMP9i, and Neu-1 inhibitor, oseltamivir phosphate, could specifically block CB1 agonist-induced Neu-1 sialidase activity. Additionally, we found that CB1 receptors exist in a multimeric receptor complex with Neu-1 in naïve, unstimulated RAW-Blue, PANC-1, and SW-620 cells. This complex implies a molecular link that regulates the interaction and signaling mechanism among these molecules present on the cell surface. Moreover, the study results demonstrate that CB1 agonists induce NFκB-dependent secretory alkaline phosphatase (SEAP) activity in influencing the expression of epithelial–mesenchymal markers, E-cadherin, and vimentin in SW-620 cells, albeit the impact on E-cadherin expression is less pronounced compared to vimentin. In essence, this innovative research begins to elucidate an entirely new molecular mechanism involving a GPCR signaling paradigm in which cannabinoids, as epigenetic stimuli, may traverse to influence gene expression and contribute to cancer and cancer metastasis.

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“…MDA‐MB‐231 and BT549 cells transfected with and without MTDH (1.0 × 10 6 in 0.15 mL) were injected subcutaneously into 4‐week‐old female nude mice. Treatment was initiated when the tumors reached a mean volume of approximately 50 mm 3 (Abdel‐Latif et al., 2022). Nude mice bearing xenograft tumors were randomly assigned to four treatment groups, with three mice in each group: (1) MK‐2206 only (100 mg/kg/2 days, oral gavage, 11 times) (Wang et al., 2015), (2) PTX only (10 mg/kg, once a week by four intraperitoneal injections) (Wu et al., 2019), (3) MK2206 (100 mg/kg) and PTX (10 mg/kg), and (4) PBS only (control).…”

Section: Methodsmentioning

confidence: 99%

Metadherin inhibits chemosensitivity of triple‐negative breast cancer to paclitaxel via activation of AKT/GSK‐3β signaling pathway

Chang,

Jia,

et al. 2023

Chem Biol Drug Des

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Triple‐negative breast cancer (TNBC) has an aggressive clinical course, and paclitaxel (PTX)‐based chemotherapy remains the main therapeutic drug. Metadherin (MTDH) acts as an oncogene that regulates proliferation, invasion, metastasis, and chemoresistance. This study aimed to investigate whether TNBC chemosensitivity to PTX was related to the MTDH/AKT/glycogen synthase kinase‐3beta (GSK‐3β) pathway. Clinical baseline characteristics and immunohistochemistry (IHC) were used to evaluate the expression and prognosis of MTDH and AKT (protein kinase B, PKB) in TNBC patient samples. MTDH shRNA, MTDH overexpression vector, MK‐2206, and PTX intervention were used in cell models and mouse tumor‐bearing models. Afterwards, mRNA and protein levels were assessed using quantitative real‐time polymerase chain reaction and Western blot. Evaluate the level of tumor cell apoptosis and cell cycle using flow cytometry. Cell viability was detected using Cell Count Kit 8. The in vivo imaging system is used to analyze the growth of tumors. We found that higher expression of MTDH or AKT resulted in poorer disease‐free survival and a lower Miller–Payne grade. MTDH promotes cell proliferation and increases p‐AKT and p‐GSK‐3β expression in TNBC cells. Notably, suppression of AKT terminated MTDH overexpression‐induced cell proliferation and apoptosis. MTDH knockdown or the AKT inhibitor MK2206 reduced the p‐AKT and p‐GSK‐3β ratio, reduced cell viability and proliferation, increased cell apoptosis, and increased chemosensitivity to PTX. In vivo, xenograft tumors of an MTDH knockdown+MK2206 group treated with PTX were the smallest compared to other groups. In short, MTDH inhibits TNBC chemosensitivity to PTX by activating the AKT/GSK‐3β signaling pathway.

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Reposition of the anti-inflammatory drug diacerein in an in-vivo colorectal cancer model

Cited by 7 publications

References 126 publications

Effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer

Effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer

Functional Selectivity of Cannabinoid Type 1 G Protein-Coupled Receptor Agonists in Transactivating Glycosylated Receptors on Cancer Cells to Induce Epithelial–Mesenchymal Transition Metastatic Phenotype

Metadherin inhibits chemosensitivity of triple‐negative breast cancer to paclitaxel via activation of AKT/GSK‐3β signaling pathway

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