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51.
Patrick Demkowicz BS Renelle Pointdujour-Lim MD Sofia Miguez BA Yesung Lee BS Bailey S. C. L. Jones BS Christopher A. Barker MD Marcus Bosenberg MD PhD David H. Abramson MD Alexander N. Shoushtari MD Harriet Kluger MD Jasmine H. Francis MD Mario Sznol MD Mathieu F. Bakhoum MD PhD 《Cancer》2023,129(20):3275-3286
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Michala G. Rolver Lya K. K. Holland Muthulakshmi Ponniah Nanditha S. Prasad Jiayi Yao Julie Schnipper Signe Kramer Line Elingaard-Larsen Elena Pedraz-Cuesta Bin Liu Luis A. Pardo Kenji Maeda Albin Sandelin Stine Falsig Pedersen 《International journal of cancer. Journal international du cancer》2023,152(8):1668-1684
The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pHe) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pHe, but not at acidic pHe. Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulated, at least in part by increased fatty acid uptake. PPARα upregulates genes driving increased mitochondrial and peroxisomal mass and β-oxidation capacity, including mitochondrial lipid import proteins CPT1A, CPT2 and SLC25A20, electron transport chain components, peroxisomal proteins PEX11A and ACOX1, and thioredoxin-interacting protein (TXNIP), a negative regulator of glycolysis. This endows acid-adapted cancer cells with increased capacity for utilizing fatty acids for metabolic needs, while limiting glycolysis. As a consequence, the acid-adapted cells exhibit increased sensitivity to PPARα inhibition. We conclude that PPARα is a key upstream regulator of metabolic changes favoring cancer cell survival in acidic tumor niches. 相似文献
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Lauren E. Barber Kimberly A. Bertrand Shanshan Sheehy Laura F. White Hemant K. Roy Lynn Rosenberg Julie R. Palmer Jessica L. Petrick 《International journal of cancer. Journal international du cancer》2023,153(12):1978-1987
Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women. 相似文献
54.
Eileen M. Dryden PhD Meaghan A. Kennedy MD MPH Jennifer Conti MPH Jacqueline H. Boudreau MPH Chitra P. Anwar MA Kathryn Nearing PhD MA Camilla B. Pimentel PhD MPH William W. Hung MD MPH Lauren R. Moo MD 《Health services research》2023,58(Z1):26-35
Objective
Explore the perceived benefits of a Veterans Health Administration (VHA) geriatric specialty telemedicine service (GRECC Connect) among rural, older patients and caregivers to contribute to an assessment of its quality and value.Data Sources
In Spring 2021, we interviewed a geographically diverse sample of rural, older patients and their caregivers who participated in GRECC Connect telemedicine visits.Study Design
A cross-sectional qualitative study focused on patient and caregiver experiences with telemedicine, including perceived benefits and challenges.Data Collection
We conducted 30 semi-structured qualitative interviews with rural, older (≥65) patients enrolled in the VHA and their caregivers via videoconference or phone. Interviews were recorded, transcribed, and analyzed using a rapid qualitative analysis approach.Principal Findings
Participants described geriatric specialty telemedicine visits focused on cognitive assessments, tailored physical therapy, medication management, education on disease progression, support for managing multiple comorbidities, and suggestions to improve physical functioning. Participants reported that, in addition to prescribing medications and ordering tests, clinicians expedited referrals, coordinated care, and listened to and validated both patient and caregiver concerns. Perceived benefits included improved patient health; increased patient and caregiver understanding and confidence around symptom management; and greater feelings of empowerment, hopefulness, and support. Challenges included difficulty accessing some recommended programs and services, uncertainty related to instructions or follow-up, and not receiving as much information or treatment as desired. The content of visits was well aligned with the domains of the Age-Friendly Health Systems and Geriatric 5Ms frameworks (Medication, Mentation, Mobility, what Matters most, and Multi-complexity).Conclusions
Alignment of patient and caregiver experiences with widely-used models of comprehensive geriatric care indicates that high-quality geriatric care can be provided through virtual modalities. Additional work is needed to develop strategies to address challenges and optimize and expand access to geriatric specialty telemedicine. 相似文献55.
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Two-year results after combined phacoemulsification and iris-fixated phakic intraocular lens removal
Gaurisankar Zoraida Solaiga van Rijn Gwyneth A. Cheng Yanny Y. Y. Luyten Gregorius P. M. Beenakker Jan-Willem M. 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2022,260(4):1367-1375
Graefe's Archive for Clinical and Experimental Ophthalmology - To describe and present results after a technique for cataract surgery combined with explantation of an iris-fixated phakic... 相似文献
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