Increased Glucose Availability Sensitizes Pancreatic Cancer to Chemotherapy

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies the suppressive effect of forced hyperglycemia in mouse models of PDAC, while rescuing this pathway mitigates anti-tumor effects observed with chemotherapy and high glucose

Data on molecular dockings of multi-epitope vaccines with human TLR 1, 2, 4, and 6.

Data on molecular dockings of multi-epitope vaccines with human TLR 1, 2, 4, and 6.</p

Schematic representation of the selection and validation of novel putative immunogenic targets against <i>P</i>. <i>gingivalis</i> using a reverse vaccinology approach.

All criteria and thresholds are shown in the flowchart. MEVs: Multi-epitope vaccines.</p

Fig 2 -

A) Demonstration of the core-pan plot between 17 P. gingivalis strains with a cut-off > 0.5. The pan and core-proteome consist of 1985 and 1418 proteins, respectively. The X-axis of this figure shows the number of strains, and the Y-axis of Fig 2A shows the percentage of core- and pan- genes among strains. Blue triangles: number of total gene families. Pink triangles: number of core gene families. B) The distribution of the core, accessory and unique proteins among metabolic pathways was compared using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The X-axis shows different categories of proteins, and the Y-axis shows the percentage (proportion) of proteins in each category. The majority of core proteins were involved in metabolism, followed by genetic information processing, and environmental information processing.</p

Ramachandran plots and ProSA-web analysis of three multi-epitope constructs.

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Physiochemical properties of 12 putative immunogenic proteins of <i>P</i>. <i>gingivalis</i>.

Physiochemical properties of 12 putative immunogenic proteins of P. gingivalis.</p

The comparative analysis of putative immunogenic targets against <i>P</i>. <i>gingivalis</i> based on quartile scoring method.

Twelve proteins with a score ≥ 20 were selected: WP_005874477.1 (26), WP_004583657.1 (25), WP_021664214.1 (25), WP_099840460.1 (25), WP_004585254.1 (23), WP_012457596.1 (23), WP_099779133.1 (23), WP_099780539.1 (23), WP_004583425.1 (21), WP_097626800.1 (21), WP_211599956.1 (21), and WP_004584259.1 (20).</p