Background/aim: Inhibition of cyclooxygenase-2 has been proposed to be a potential mechanism for the chemoprevention of gastrointestinal tumors by nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer cell lines and its downstream signaling pathway.
Methods: Two gastric cancer cell lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and apoptosis. The involvement of mitogen-activated protein kinase and Akt kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were studied in the AGS cell line.
Results: SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor SB203580 and the dominant-negative stress-activated protein kinase/jun kinase both failed, while the constitutively active form of Akt/PKB was able to block SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of cytochrome c and activation of caspases.
Conclusion: One of the pathways involved in SC-236-induced apoptosis in gastric cancer cells is through downregulation of Akt and then release of cytochrome c.
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http://dx.doi.org/10.1159/000092747 | DOI Listing |
J Transl Med
January 2025
Scientia Clinical Research and Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia.
Background: A novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial.
Methods: In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks.
BMC Cancer
January 2025
Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
BMC Gastroenterol
January 2025
Department of General Surgery (Gastrointestinal Surgery, Unit 1), The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, China.
Purpose: The survival benefits of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) patients are inconsistent. This study aims to investigate how different tumor regression grades (TRG) influence the survival gains associated with NAC treatment.
Methods: This study compared the treatment outcomes of patients who underwent CSC (neoadjuvant chemotherapy - surgery - adjuvant chemotherapy) with those receiving traditional SC (surgery - adjuvant chemotherapy) treatment.
Invest New Drugs
January 2025
Department of Pharmacy, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-Ku, Nagoya, Aichi, 464-8681, Japan.
Anamorelin, a highly selective ghrelin receptor agonist, enhances appetite and increases lean body mass in patients with cancer cachexia. However, the predictors of its therapeutic effectiveness are uncertain. This study aimed to investigate the association between the Glasgow prognostic score (GPS), used for classifying the severity of cancer cachexia, the therapeutic effectiveness of anamorelin, and the feasibility of early treatment based on cancer types.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Due to considerable tumour heterogeneity, stomach adenocarcinoma (STAD) has a poor prognosis and varies in response to treatment, making it one of the main causes of cancer-related mortality globally. Recent data point to a significant role for metabolic reprogramming, namely dysregulated lactic acid metabolism, in the evolution of STAD and treatment resistance. This study used a series of artificial intelligence-related approaches to identify IGFBP7, a Schlafen family member, as a critical factor in determining the response to immunotherapy and lactic acid metabolism in STAD patients.
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