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1.
Cell Rep Methods ; 3(11): 100643, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37989083

ABSTRACT

A deep understanding of immunotherapy response/resistance mechanisms and a highly reliable therapy response prediction are vital for cancer treatment. Here, we developed scCURE (single-cell RNA sequencing [scRNA-seq] data-based Changed and Unchanged cell Recognition during immunotherapy). Based on Gaussian mixture modeling, Kullback-Leibler (KL) divergence, and mutual nearest-neighbors criteria, scCURE can faithfully discriminate between cells affected or unaffected by immunotherapy intervention. By conducting scCURE analyses in melanoma and breast cancer immunotherapy scRNA-seq data, we found that the baseline profiles of specific CD8+ T and macrophage cells (identified by scCURE) can determine the way in which tumor microenvironment immune cells respond to immunotherapy, e.g., antitumor immunity activation or de-activation; therefore, these cells could be predictive factors for treatment response. In this work, we demonstrated that the immunotherapy-associated cell-cell heterogeneities revealed by scCURE can be utilized to integrate the therapy response mechanism study and prediction model construction.


Subject(s)
Breast Neoplasms , Melanoma , Humans , Female , Melanoma/therapy , Prognosis , Breast Neoplasms/therapy , Immunotherapy , Macrophages/pathology , Tumor Microenvironment/genetics
2.
Front Oncol ; 13: 1171582, 2023.
Article in English | MEDLINE | ID: mdl-37519793

ABSTRACT

Background: Most patients with high-grade serous ovarian cancer (HGSOC) experienced disease recurrence with cumulative chemoresistance, leading to treatment failure. However, few biomarkers are currently available in clinical practice that can accurately predict chemotherapy response. The tumor immune microenvironment is critical for cancer development, and its transcriptomic profile may be associated with treatment response and differential outcomes. The aim of this study was to develop a new predictive signature for chemotherapy in patients with HGSOC. Methods: Two HGSOC single-cell RNA sequencing datasets from patients receiving chemotherapy were reinvestigated. The subtypes of endoplasmic reticulum stress-related XBP1+ B cells, invasive metastasis-related ACTB+ Tregs, and proinflammatory-related macrophage subtypes with good predictive power and associated with chemotherapy response were identified. These results were verified in an independent HGSOC bulk RNA-seq dataset for chemotherapy. Further validation in clinical cohorts used quantitative real-time PCR (qRT-PCR). Results: By combining cluster-specific genes for the aforementioned cell subtypes, we constructed a chemotherapy response prediction model containing 43 signature genes that achieved an area under the receiver operator curve (AUC) of 0.97 (p = 2.1e-07) for the GSE156699 cohort (88 samples). A huge improvement was achieved compared to existing prediction models with a maximum AUC of 0.74. In addition, its predictive capability was validated in multiple independent bulk RNA-seq datasets. The qRT-PCR results demonstrate that the expression of the six genes has the highest diagnostic value, consistent with the trend observed in the analysis of public data. Conclusions: The developed chemotherapy response prediction model can be used as a valuable clinical decision tool to guide chemotherapy in HGSOC patients.

3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-329310

ABSTRACT

In this study, the mechanical properties of a self-made jet injector and a foreign product are tested from three aspects: penetration ability, injection completeness and injection dispersion. Correspondingly, three different experiments are designed and performed: dynamic pressure measurement, injection into silicon rubbers with fixed hardness yet different thickness and injection into polyacrylamide gels with fixed hardness. The results show similar mechanical properties between self-made system and the foreign system. The evaluation of the mechanical performance of jet injectors that consists of penetration ability, injection completeness and injection dispersion can describe the jet injection process effectively.


Subject(s)
Hardness , Injections, Jet , Materials Testing
4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-329290

ABSTRACT

A liquid jet injector employs compressed gas or spring to produce a high-velocity stream to deliver liquid drug into human body through skin. There are many clinical jet injection products available, none of which is domestic. A new liquid jet injector is designed based on a comprehensive analysis of the current products. The injector consists of an ejector, trigger and a re-positioning mechanism. The jets characteristics of sample injector are tested, and the results show that the maximum exit pressure is above 15 MPa, a threshold value for penetrating into the skin.


Subject(s)
Humans , Equipment Design , Injections, Intradermal , Methods , Injections, Jet , Methods
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