Pancreatic cancer environment: from patient-derived models to single-cell omics

Gu, Ao; Li, Jiatong; Qiu, Shimei; Hao, Shenglin; Yue, Zhu-Ying; Zhai, Shuyang; Li, Meng-Yao; Liu, Yingbin

doi:10.1039/d3mo00250k

Mol. Omics

2024

DOI: 10.1039/d3mo00250k

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Pancreatic cancer environment: from patient-derived models to single-cell omics

Ao Gu,

Jiatong Li,

Shimei Qiu

et al.

Abstract: Pancreatic cancer (PC) is a highly malignant cancer characterized by poor prognosis, high heterogeneity, and intricate heterocellular system. Selecting an appropriate experimental model for studying its progression and treatment is...

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2024

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Cited by 12 publications

References 69 publications

(96 reference statements)

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Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti‐Tumor Activity

Li,

Gu,

2024

Chemistry & Biodiversity

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Pancreatobililary cancers are fatal solid tumors that pose a significant threat to human life. It is imperative to investigate novel small molecule active compounds for controlling these cancers. Heterocyclic compounds (e.g. gemcitabine) and multi‐substituted alkenes (e.g. resveratrol) are commonly applied in tumor treatment. Researchers have proposed that the synthesis of new trisubstituted alkenes containing heteroaromatic rings by combining these two scaffolds may be a fresh strategy to develop new active molecules. In this study, we utilized alkenyl bromide and heteroaryl boronic acid as substrates, employing Suzuki coupling to generate a series of triarylethylenes featuring nitrogen, oxygen, and sulfur atoms. Through in vitro experiments, the results indicated that some compounds exhibited remarkable anti‐tumor efficacy (e.g. IC50[3be, GBC‐SD] = 0.13 µM and IC50[3be, PANC‐1] = 0.27 µM). The results further demonstrated that the antitumor efficacy of these compounds was dependent on the heteroatom, π‐system, skeleton‐bonding site, and substituent type.

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Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti‐Tumor Activity

Li,

Gu,

2024

Chemistry & Biodiversity

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Exploration of Dan-Shen-Yin against pancreatic cancer based on network pharmacology combined with molecular docking and experimental validation

Gu,

Li,

et al. 2024

Current Research in Biotechnology

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Smad4 Heterozygous Knockout Effect on Pancreatic and Body Weight in F1 Population Using Collaborative Cross Lines

Zohud,

Lone,

Midlej

et al. 2024

Biology

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Smad4, a critical tumor suppressor gene, plays a significant role in pancreatic biology and tumorigenesis. Genetic background and sex are known to influence phenotypic outcomes, but their impact on pancreatic weight in Smad4-deficient mice remains unclear. This study investigates the impact of Smad4 deficiency on pancreatic weight in first-generation (F1) mice from diverse collaborative cross (CC) lines, focusing on the influence of genetic background and sex. F1 mice were generated by crossbreeding female CC mice with C57BL/6J-Smad4tm1Mak males. Genotyping confirmed the presence of Smad4 knockout alleles. Mice were housed under standard conditions, euthanized at 80 weeks, and their pancreatic weights were measured, adjusted for body weight, and analyzed for effects of Smad4 deficiency, sex, and genetic background. The overall population of F1 mice showed a slight but non-significant increase in adjusted pancreatic weights in heterozygous knockout mice compared to wild-type mice. Sex-specific analysis revealed no significant difference in males but a significant increase in adjusted pancreatic weights in heterozygous knockout females. Genetic background analysis showed that lines CC018 and CC025 substantially increased adjusted pancreatic weights in heterozygous knockout mice. In contrast, other lines showed no significant difference or varied non-significant changes. The interplay between genetic background and sex further influenced these outcomes. Smad4 deficiency affects pancreatic weight in a manner significantly modulated by genetic background and sex. This study highlights the necessity of considering these factors in genetic research and therapeutic development, demonstrating the value of the collaborative cross mouse population in dissecting complex genetic interactions.

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Pancreatic cancer environment: from patient-derived models to single-cell omics

Abstract: Pancreatic cancer (PC) is a highly malignant cancer characterized by poor prognosis, high heterogeneity, and intricate heterocellular system. Selecting an appropriate experimental model for studying its progression and treatment is...

Cited by 12 publications

References 69 publications

Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti‐Tumor Activity

Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti‐Tumor Activity

Exploration of Dan-Shen-Yin against pancreatic cancer based on network pharmacology combined with molecular docking and experimental validation

Smad4 Heterozygous Knockout Effect on Pancreatic and Body Weight in F1 Population Using Collaborative Cross Lines

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