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Mechanistic insights into the anticancer effect of pyridopyrimidine derivatives in Gastric Adenocarcinoma

ABSTRACT: This study presents the design, synthesis, and in vitro evaluation of novel pyridopyrimidine derivatives as potential anticancer agents against gastric cancer. Several compounds showed strong cytotoxic and selective antiproliferative effects in AGS cells. To uncover the mode of action of representative compound, label-free quantitative proteomics was performed, revealing key alterations in proteins linked to various spotted pathways as indicated in IPA analysis.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Mohamed Metwaly

PROVIDER: PXD066330 | JPOST Repository | Mon Jul 20 00:00:00 BST 2026

REPOSITORIES: jPOST

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			Action	DRS
	20250113_092126_250110_USYD_MF_CVRN%20-GroupIII.sne	Other
	250110_USYD_MF_015.wiff	Wiff
	250110_USYD_MF_015.wiff.scan	Wiff
	250110_USYD_MF_015_16.wiff	Wiff
	250110_USYD_MF_015_16.wiff.scan	Wiff

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Project description:A major impediment to the effective treatment of patients with PDAC (Pancreatic Ductal Adenocarcinoma) is the molecular heterogeneity of the disease, which is reflected in an equally diverse pattern of clinical responses to therapy. We developed an efficient strategy in which PDAC samples from 17 consecutively patients were obtained by EUS-FNA or surgery, their cells maintained as a primary culture and tumors as breathing tumors by xenografting in immunosuppressed mice. For these patients a clinical follow up was obtained. On the breathing tumors we studied the RNA expression profile by an Affymetrix approach. We observed a significant heterogeneity in their RNA expression profile, however, the transcriptome was able to discriminate patients with long- or short-time survival which correspond to moderately- or poorly-differentiated PDAC tumors respectively. Cells allowed us the possibility to analyze their relative sensitivity to several anticancer drugs in vitro by developing a chimiogram, like an antibiogram for microorganisms, with several anticancer drugs for obtaining an individual profile of drug sensitivity and as expected, the response was patient-dependent. Interestingly, using this approach, we also found that the transcriptome analysis could predict the sensitivity to some anticancer drugs of patients with a PDAC. In conclusion, using this approach, we found that the transcriptome analysis could predict the sensitivity to some anticancer drugs and the clinical outcome of patients with a PDAC. PDAC samples from 17 consecutively patients were obtained by Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) or surgery. Consents of informed patients were collected, and the ethics review board of the three centers approved the study. All samples were anonymized and obtained in accordance with institutional review boards. EUS-FNA cells were maintained as a primary culture and tumors as breathing tumors by xenografting in immunosuppressed mice. We characterized 17 PDAC-derived xenografts by duplicate. Total RNA was extracted and hybridized on Human Gene 2.0 (Genechip, Affymetrix) as described previously (Hamidi et al. JCI 122: 2092-2103, 2012).

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Mechanistic insights into the anticancer effect of pyridopyrimidine derivatives in Gastric Adenocarcinoma

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