Cancer has become one of the leading causes of death, with approximately ten million people worldwide dying from cancer each year. In most cases, cancer spreads to remote organs and develops a resistance to therapy. To reduce the deadly impact of cancer, novel targets for markers for early detection are necessary. Given the notable influence of rapid chemical turnover on isotope effects, the heightened turnover rate of cholesterol in cancer offers a promising way for investigation. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) offers a valuable tool of tracking cholesterol dynamics. Consequently, we employed ToF-SIMS to assess cholesterol alterations, aiming to uncover potential diagnostic vulnerabilities stemming from heightened cholesterol synthesis. Our study explored the chemical profile of cholesterol influenced by cancer cell metabolism using mammary glands from mice, both with and without cancer. Results revealed a significant increase in the fractional abundance of fragment cholesterol peaks (C₂₇H₄₅⁺) in cancerous tissues, indicating dysregulated cholesterol metabolism within cancer cells. This suggests potential structural weaknesses or incomplete synthesis. Further investigation into carbon isotope incorporation suggests that the isotopic patterns might be due to the integration of heavier carbon isotopes, although these patterns could be affected by other isotopic influences. Nevertheless, understanding isotope effect of cholesterol profiles have the potential to advance our understanding of cancer biology and improve diagnostic approaches.

中文翻译：

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用 ToF-SIMS 追踪的癌组织中胆固醇化学特征的改变


癌症已成为主要死亡原因之一，全球每年约有 1000 万人死于癌症。在大多数情况下，癌症会扩散到远处器官并产生对治疗的耐药性。为了减少癌症的致命影响，需要用于早期检测的标志物的新靶点。鉴于快速化学周转对同位素效应的显着影响，癌症中胆固醇周转率的增加提供了一种有前途的研究方法。飞行时间二次离子质谱法 （ToF-SIMS） 是追踪胆固醇动力学的宝贵工具。因此，我们采用 ToF-SIMS 来评估胆固醇改变，旨在发现由胆固醇合成增加引起的潜在诊断漏洞。我们的研究使用小鼠的乳腺探索了受癌细胞代谢影响的胆固醇的化学特征，包括患有癌症和不患有癌症的小鼠。结果显示癌组织中片段胆固醇峰 （C₂₇H₄₅⁺） 的分数丰度显着增加，表明癌细胞内的胆固醇代谢失调。这表明潜在的结构弱点或不完全综合。对碳同位素掺入的进一步研究表明，同位素模式可能是由于较重的碳同位素的整合，尽管这些模式可能受到其他同位素影响的影响。然而，了解胆固醇谱的同位素效应有可能促进我们对癌症生物学的理解并改进诊断方法。