4 results on '"Kay, Kristen E"'
Search Results
2. Use of amniotic membrane in hard-to-heal wounds: a multicentre retrospective study.
- Author
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Ditmars, Frederick S, Kay, Kristen E, Broderick, T Christopher, and Fagg, W Samuel
- Subjects
TREATMENT of diabetic foot ,WOUND healing ,MEDICAL quality control ,LEG ulcers ,T-test (Statistics) ,RESEARCH funding ,RETROSPECTIVE studies ,DESCRIPTIVE statistics ,FINANCIAL stress ,AMNION ,RESEARCH ,QUALITY of life ,ONE-way analysis of variance ,COMPARATIVE studies ,WOUND care ,DATA analysis software ,CONFIDENCE intervals ,CHRONIC wounds & injuries - Abstract
Objective: Hard-to-heal (chronic) wounds negatively impact patients and are a source of significant strain on the healthcare system and economy. These wounds are often resistant to standard of care (SoC) wound healing approaches due to a diversity of underlying pathologies. Cellular, acellular, and matrix-like products, such as amniotic membranes (AM), are a potential solution to these challenges. A growing body of evidence suggests that AM may be useful for treatment-resistant wounds; however, limited information is available regarding the efficacy of dehydrated amniotic membrane (DHAM) on multi-aetiology, hard-to-heal wounds. Therefore, we analysed the efficacy of DHAM treatment in reducing the size of hard-to-heal diabetic and venous leg ulcers (VLUs) that had failed to improve after SoC-based treatments. Method: In this multicentre retrospective study, we analysed wound size during clinic visits for patients being treated for either diabetic or VLUs. During each visit, the treatment consisted of debridement followed by application of DHAM. Each wound was measured after debridement and prior to DHAM application, and wound volumes over time or number of DHAM applications were compared. Results: A total of 18 wounds in 11 patients were analysed as part of this study. Wounds showed a significant reduction in volume after a single DHAM application, and a 50% reduction in wound size was observed after approximately two DHAM applications. These findings are consistent with reports investigating DHAM treatment of diabetic ulcers that were not necessarily resistant to treatment. Conclusion: To our knowledge, this study is the first to directly compare the efficacy of standalone DHAM application to hard-to-heal diabetic and venous leg ulcers, and our findings indicate that DHAM is an effective intervention for resolving these types of wounds. This suggests that implementing this approach could lead to fewer clinic visits, cost savings and improved patient quality of life. Declaration of interest: This research was supported in part by Merakris Therapeutics, US, and facilitated access to deidentified patient datasets, which may represent a perceived conflict of interest; however, the primary data analysis was performed by FSB who is unaffiliated with Merakris Therapeutics. TCB is a founder, employee of and shareholder in Merakris Therapeutics; WSF is a co-founder of, consultant for, and shareholder in Merakris Therapeutics, and was also supported by the National Institutes of Health National Center for Advancing Translational Sciences Clinical and Translational Science Awards Grant KL2 Scholars Program (KL2TR001441). The research was also supported through endowments to WSF from the University of Texas Medical Branch Mimmie and Hallie Smith Endowed Chair of Transplant Research and the John L Hern University Chair in Transplant Surgery. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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3. Androgen loss weakens anti-tumor immunity and accelerates brain tumor growth.
- Author
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Lee J, Chung YM, Curtin L, Silver DJ, Hao Y, Li C, Volovetz J, Hong ES, Jarmula J, Wang SZ, Kay KE, Berens M, Nicosia M, Swanson KR, Sharifi N, and Lathia JD
- Abstract
Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this sex bias are unclear but likely involve differences in tumor cell state and immune response. This effect is further amplified by sex hormones, including androgens, which have been shown to inhibit anti-tumor T cell immunity. Here, we show that androgens drive anti-tumor immunity in brain tumors, in contrast to its effect in other tumor types. Upon castration, tumor growth was accelerated with attenuated T cell function in GBM and brain tumor models, but the opposite was observed when tumors were located outside the brain. Activity of the hypothalamus-pituitary-adrenal gland (HPA) axis was increased in castrated mice, particularly in those with brain tumors. Blockade of glucocorticoid receptors reversed the accelerated tumor growth in castrated mice, indicating that the effect of castration was mediated by elevated glucocorticoid signaling. Furthermore, this mechanism was not GBM specific, but brain specific, as hyperactivation of the HPA axis was observed with intracranial implantation of non-GBM tumors in the brain. Together, our findings establish that brain tumors drive distinct endocrine-mediated mechanisms in the androgen-deprived setting and highlight the importance of organ-specific effects on anti-tumor immunity., Competing Interests: Competing interests N.S. is a co-inventor on a Cleveland Clinic patent on HSD3B1. The other authors declare no competing interest.
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- 2024
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4. miR-644a is a tumor cell-intrinsic mediator of sex bias in glioblastoma.
- Author
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Hong ES, Wang SZ, Ponti AK, Hajdari N, Lee J, Mulkearns-Hubert EE, Volovetz J, Kay KE, Lathia JD, and Dhawan A
- Abstract
Background: Biological sex is an important risk factor for glioblastoma (GBM), with males having a higher incidence and poorer prognosis. The mechanisms for this sex bias are thought to be both tumor intrinsic and tumor extrinsic. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have been previously linked to sex differences in various cell types and diseases, but their role in the sex bias of GBM remains unknown., Methods: We leveraged previously published paired miRNA and mRNA sequencing of 39 GBM patients (22 male, 17 female) to identify sex-biased miRNAs. We further interrogated a separate single-cell RNA sequencing dataset of 110 GBM patients to examine whether differences in miRNA target gene expression were tumor cell intrinsic or tumor cell extrinsic. Results were validated in a panel of patient-derived cell models., Results: We identified 10 sex-biased miRNAs ( a
djusted < 0.1), of which 3 were more highly expressed in males and 7 more highly expressed in females. Of these, miR-644a was higher in females, and increased expression of miR-644a target genes was significantly associated with decreased overall survival (HR 1.3, p = 0.02). Furthermore, analysis of an independent single-cell RNA sequencing dataset confirmed sex-specific expression of miR-644a target genes in tumor cells ( p < 10-15 ). Among patient derived models, miR-644a was expressed a median of 4.8-fold higher in females compared to males., Conclusions: Our findings implicate miR-644a as a candidate tumor cell-intrinsic regulator of sex-biased gene expression in GBM., Competing Interests: Conflict of Interest: All authors declare no conflicts of interest.- Published
- 2024
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