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| 1 | Hematopoietic stem cell-derived adipocytes and fibroblasts in the tumor microenvironment显示文摘The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancerassociated adipocyte(CAA) and the cancer-associated fibroblast(CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumorpromoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and thetemporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics. | Ying Xiong Lindsay T Mc Donald Dayvia L Russell Ryan R Kelly Katie R Wilson Meenal Mehrotra Adam C Soloff Amanda C LaRue | 2015 | World Journal of Stem Cells2015，7，2： | 6 |
| 2 | The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia显示文摘Tumor-induced osteomalacia(TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23(FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1α(HIF-1α) in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-1α mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-1α and FGF23 were co-localized in spindleshaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-1α protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-1α expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-1α inhibitors decreased HIF-1α and FGF23 protein accumulation and inhibited HIF-1α-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-1α consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-1α inhibitor. These results show for the first time that HIF-1α is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-1α activity in TIO contributes to the aberrant FGF23 production in these patients. | Qian Zhang Michele Doucet Ryan E Tomlinson Xiaobin Han L Darryl Quarles Michael T Collins Thomas L Clemens | 2016 | Bone Research2016，4，2： | 6 |
| 3 | Clinical classification of symptomatic heterotopic pancreas of the stomach and duodenum:A case series and systematic literature review显示文摘BACKGROUND Heterotopic pancreas(HP)is an aberrant anatomic malformation that occurs most commonly in the upper gastrointestinal tract.While the majority of heterotopic pancreatic lesions are asymptomatic,many manifest severe clinical symptoms which require surgical or endoscopic intervention.Understanding of the clinical manifestations and symptoms of HP is limited due to the lack of large volume studies in the literature.The purpose of this study is to review symptomatic cases at a single center and compare these to a systematic review of the literature in order to characterize common clinical manifestations and treatment of this disease.AIM To classify the common clinical manifestations of heterotopic pancreas.METHODS A retrospective review was conducted of pathologic samples containing heterotopic pancreas from 2000-2018.Review was limited to HP of the upper gastrointestinal tract due to the frequency of presentation in this location.Symptomatic patients were identified from review of the medical records and clinical symptoms were tabulated.These were compared to a systematic review of the literature utilizing Pub Med and Embase searches for papers pertaining to heterotopic pancreas.Publications describing symptomatic presentation of HP were selected for review.Information including demographics,symptoms,presentation and treatment were compiled and analyzed.RESULTS Twenty-nine patient were identified with HP at a single center,with six of these identified has having clinical symptoms.Clinical manifestations included,gastrointestinal bleeding,gastric ulceration with/without perforation,pancreatitis,and gastric outlet obstruction.Systemic review of the literature yielded 232 publications detailing symptomatic cases with only 20 studies describing ten or more patients.Single and multi-patient studies were combined to form a cohort of 934 symptomatic patients.The majority of patients presented with abdominal pain(67%)combined with one of the following clinical categories:(1)Dyspepsia,(n=445,48%);(2)Pancreatitis(n=260,28%);(3)Gastrointestinal bleeding(n=80,9%);and(4)Gastric outlet obstruction(n=80,9%).The majority of cases(n=832,90%)underwent surgical or endoscopic resection with 85%reporting resolution or improvement in their symptoms.CONCLUSION Heterotopic pancreas can cause significant clinical symptoms in the upper gastrointestinal tract.Better understanding and classification of this disease may result in more accurate identification and treatment of this malformation. | Michael T Le Compte Brandon Mason Keenan J Robbins Motoyo Yano Deyali Chatterjee Ryan C Fields Steven M Strasberg William G Hawkins | 2022 | World Journal of Gastroenterology2022，28，14： | 3 |
| 4 | Identification of stable normalization genes for quantitative real-time PCR in porcine articular cartilage显示文摘Background: Expression levels for genes of interest must be normalized with an appropriate reference, or housekeeping gene, to make accurate comparisons of quantitative real-time PCR results. The purpose of this study was to identify the most stable housekeeping genes in porcine articular cartilage subjected to a mechanical injury from a panel of 10 candidate genes. Results: Ten candidate housekeeping genes were evaluated in three different treatment groups of mechanically impacted porcine articular cartilage. The genes evaluated were: beta actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hydroxymethylbilane synthase, hypoxanthine phosphoribosyl transferase, peptidylprolyl isomerase A (cyclophilin A), ribosomal protein L4, succinate dehydrogenase flavoprotein subunit A, TATA box binding protein, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein-zeta polypeptide. The stability of the genes was measured using geNorm, BestKeeper, and NormFinder software. The four most stable genes measured via geNorm were (most to least stable) succinate dehydrogenase flavoprotein, subunit A, peptidylprolyl isomerase A, glyceraldehyde-3-phosphate dehydrogenase, beta actin; the four most stable genes measured via BestKeeper were glyceraldehyde-3-phosphate dehydrogenase, peptidylprolyl isomerase A, beta actin, succinate dehydrogenase flavoprotein, subunit A; and the four most stable genes measured via NormFinder were peptidylprolyl isomerase A, succinate dehydrogenase flavoprotein, subunit A, glyceraldehyde-3-phosphate dehydrogenase, beta actin. Conclusions: BestKeeper, geNorm, and NormFinder all generated similar results for the most stable genes in porcine articular cartilage. The use of these appropriate reference genes will facilitate accurate gene expression studies of porcine articular cartilage and suggest appropriate housekeeping genes for articular cartilage studies in other species. | Ryan S McCulloch Melissa S Ashwell Audrey T O'Nan Peter L Mente | 2012 | Journal of Animal Science and Biotechnology2012，3，4： | 2 |
| 5 | CD133 expression is not restricted to stem cells, and both CD133^sup +^ and CD133^sup -^ metastatic colon cancer cells initiate tumors显示文摘 | Shmelkov Sergey V Butler Jason M Hooper Andrea T Hormigo Adilia Kushner Jared Milde Till Clair Ryan St Baljevic Muhamed White Ian Jin David K Chadburn Amy Murphy Andrew J Valenzuela David M Gale Nicholas W Thurston Gavin Yancopoulos George | 2008 | Journal of Clinical Investigation2008，，： | 2 |
| 6 | Percutaneous transluminal angioplasty balloons for endoscopic ultrasound-guided pancreatic duct interventions显示文摘BACKGROUND Endoscopic ultrasound(EUS)-guided main pancreatic duct(PD)access may be used when conventional endoscopic retrograde cholangiopancreatography(ERCP)techniques fail.The use of a percutaneous transluminal angioplasty balloon(PTAB),originally developed for vascular interventions,can be used to facilitate transmural(e.g.,transgastric)PD access and to dilate high-grade pancreatic strictures.AIM To describe the technique,efficacy,and safety of PTABs for EUS-guided PD interventions.METHODS Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database.PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire.The primary outcome was technical success.Secondary outcomes included incidence of adverse events(AEs)and need for early reintervention.RESULTS A total of 23 patients were identified(48%female,mean age 55.8 years).Chronic pancreatitis was the underlying etiology in 13(56.5%)patients,surgically altered anatomy(SAA)with stricture in 7(30.4%),and SAA with post-operative leak in 3(13.0%).Technical success was achieved in 20(87%)cases.Overall AE rate was 26%(n=6).All AEs were mild and included 1 pancreatic duct leak,2 cases of post-procedure pancreatitis,and 3 admissions for post-procedural pain.No patients required early re-intervention.CONCLUSION EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails. | Jad P AbiMansour Barham K Abu Dayyeh Michael J Levy Andrew C Storm John A Martin Bret T Petersen Ryan J Law Mark D Topazian Vinay Chandrasekhara | 2022 | World Journal of Gastrointestinal Endoscopy2022，14，8： | 2 |
| 7 | The epoxyeicosatrienoic acid-stimulated phosphorylation of EGF-R involves the activation of metalloproteinases and the release of HB-EGF in cancer cells显示文摘 | Li-ming CHENG Jian-gang JIANG Zi-yong SUN Chen CHEN Ryan T DACKOR Darryl C ZELDIN Dao-wen WANG | 2010 | Acta Pharmacologica Sinica2010，31，2： | 2 |
| 8 | A MyD88-dependent IFNyR-CCR2 signaling circuit is required for mobilization of monocytes and host defense against systemic bacterial challenge显示文摘 | Eric M Pietras Lloyd S Miller Carl T Johnson Ryan M O'Connell Paul W Dempsey Genhong Cheng | 2011 | Cell Research2011，21，7： | 2 |
| 9 | Low-gain integral control of continuous-time linear systems subject to input and output nonlinearities显示文摘 | FLIEGNER T LOGEMANN H RYAN E P | 2003 | Automatica2003，39，： | 1 |
| 10 | Further examining the American dream:Differential correlates of intrinsic and extrinsic goals显示文摘 | KASSER T RYAN R M | 1996 | Personality and Social Psychology Bulletin1996，22，： | 1 |
| 11 | Wound-induced proteinase inhibitor in plant leaves:a possible defense mechanism against insects显示文摘 | GREEN T R RYAN C A | 1972 | Science1972，175，： | 1 |
| 12 | A Dark Side of the American Dream:Correlates of Financial Success as a Central Life Aspiration显示文摘 | KASSER T RYAN R M | 1993 | Journal of Personality and Social Psy- chology1993，65，： | 1 |
| 13 | Stress and neurodevelopmental processes in the emergence of psychosis显示文摘 | Holtzman C W Trotman H D Ryan A T | 2013 | Neuroscience2013，249，26： | 1 |
| 14 | Dynamics of a cantilever beam attached to a moving base显示文摘 | Kane T R Ryan R R Banerjee A K | 1987 | Journal of Guidance Control and Dynamics1987，10，2： | 1 |
| 15 | Ventriculostomy simulation using patient-specific ventricular anatomy, 3D printing, and hydrogel casting 显示文摘 | Ryan JR Chen T Nakaji P | 2015 | World Neurosurg2015，，： | 1 |
| 16 | Dynamic three - dimensional echocardiographic reconstruction of congenital cardiac septation defects显示文摘 | Tantengco MV Bates JR Ryan T | 1997 | Pediatr Cardiol1997，38，3： | 1 |
| 17 | Unmanned aerial vehicle (UAV) route selection using reactive tabu search显示文摘 | Ryan J L T G Bailey J T Moore W B Carlton | 1999 | Military Operations Research1999，4，3： | 1 |
| 18 | PAST: Paleontological Statistics Software Package for Education and Data Analysis显示文摘 | ф Hammer D A T Harper P D Ryan | 2001 | Palaeontologia Electronica2001，4，1： | 1 |
| 19 | Involvement of toll-like receptor(TLR)2 and TLR4 in cell activation by mannuronic acid polymers 显示文摘 | Flo T H Ryan L Latz E | 2002 | J Biol Chem2002，277，35： | 1 |
| 20 | Woody tissue main- tenance respiration of four conifers in contrasting climates 显示文摘 | Ryan M G Gower S T Hubbard R M | 1995 | Oecologia1995，101，2： | 1 |
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