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2.
Cancer Cell ; 41(11): 1927-1944.e9, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37738973

ABSTRACT

Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1ß-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells. This is mediated by IL-1ß secretion via ß-glucan/Dectin-1/CARD9 pathway. Analysis of human samples confirms that enriched A. sydowii is associated with immunosuppression and poor patient outcome. Our findings suggest that intratumor mycobiome, albeit at low biomass, promotes lung cancer progression and could be targeted at the strain level to improve patients with LUAD outcome.


Subject(s)
Lung Neoplasms , Mycobiome , Myeloid-Derived Suppressor Cells , Humans , Animals , Mice , Lung Neoplasms/genetics , CD8-Positive T-Lymphocytes , Lung
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-852748

ABSTRACT

Objective: To develop a bioassay method to quantify the antiplatelet aggregation bioactivity (AAB) of crude Chuanxiong Rhizoma, decotion pieces, and its Chinese patent medicine for quality assessment. Methods: Chuanxiong Rhizoma sample was extracted in water by reflux. The level of AAB in extract was quantified in vitro. The blood was taken from the heart of rabbit. The platelet aggregating in platelet-rich plasma was induced by adenosine-5'-diphosphate disodium salt. The ratio of platelet inhibition was chosen as AAB marker. Sodium ferulate was a reference. The amount of AAB in aqueous extract was quantified by the Amount reaction of parallel line analysis (2.2) method. The AAB data of herbal sample was calculated by combining the AAB of extract with its extraction rate. Moreover, AAB amounts were quantified in the eight samples including crude Chuanxiong Rhizoma, decoction pieces, and Chinese patent medicines to verify this developed method. Results: Both sodium ferulate and Chuanxiong extract showed significant AAB (P < 0.01). The reliability test for quantifying AAB in solidum ferulate and Chuanxiong Rhizoma extract was passed through, and the measured value was valid. The correlation coefficient was 0.993 4 (n = 4) between the amounts of solidum ferulate in the concentration range of 15-60 mg/mL and their ratios of platelet inhibition. The RSD for the amounts of AAB was 3.43% (n = 6) by six replicated tests with the confidence limit rate of 23.90% (n = 6). The AAB amounts were significantly different among tested samples, i.e. 3.183, 2.068, 1.957, and 1.931 U/g for four Chuanxiong Rhizoma crude samples, 1.304 and 1.021 U/g for Chuanxiong Rhizoma decotion pieces and processed slice with yellow wine, 0.506 and 0.919 U/g for Suxiao Jiuxin Pills and Lemai Granule. Conclusion: The developed method can accurately quantify the level of AAB in Chuanxiong Rhizoma crude, decoction pieces, and Chinese patent medicines, which can be used to assess the product quality of Chuanxiong Rhizoma.

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