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| 1 | 肿瘤出芽和PDC分级是错配修复缺陷的结直肠癌临床转归分期的独立预测因子显示文摘错配修复缺陷(dMMR)的结直肠癌(CRC)在临床、病理及分子特征方面与无错配修复缺陷(pMMR)的CRC存在区别,其好发于右半结肠,具有低分化、多黏液成分、大量肿瘤细胞浸润淋巴组织及克罗恩样的宿主反应等特征。已有研究显示dMMR CRC预后比pMMR CRC好。dMMR CRC很少发生淋巴结转移(LNM)及同期肝脏转移。dMMR CRC虽具有高级别肿瘤特征,却有较好的预后,对这种违背常理的情况,有学者提出传统的WHO分级可能无法明确判断其预后。 | Ryan E Khaw Y L Creavin B 黄爱清 余英豪 | 2018 | 临床与实验病理学杂志2018，34，9： | 14 |
| 2 | In vivo radiometric analysis of glucose uptake and distribution in mouse bone显示文摘Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts,particularly during periods of rapid bone growth.Despite increasing evidence linking bone cell activity to global energy homeostasis,little is known about the relative energy requirements or substrate utilization of bone cells.In these studies,we measured the uptake and distribution of glucose in the skeleton in vivo using positron-emitting^(18)F-fluorodeoxyglucose([^(18)F]-FDG) and non-invasive,high-resolution positron emission tomography/computed tomography(PET/CT) imaging and ex vivo autoradiography.Assessment of [^(18)F]-FDG uptake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog.Skeletal accumulation was greatest in young mice undergoing the rapid bone formation that characterizes early development.PET/CT imaging revealed that [^(18)F]-FDG uptake was greatest in the epiphyseal and metaphyseal regions of long bones,which accords with the increased osteoblast numbers and activity at this skeletal site.Insulin administration significantly increased skeletal accumulation of [^(18)F]-FDG,while uptake was reduced in mice lacking the insulin receptor specifically in osteoblasts or fed a high-fat diet.Our results indicated that the skeleton is a site of significant glucose uptake and that its consumption by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism. | Meredith L Zoch Diane S Abou Thomas L Clemens Daniel LJ Thorek Ryan C Riddle | 2016 | Bone Research2016，4，1： | 9 |
| 3 | 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 |
| 4 | 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 |
| 5 | 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 |
| 6 | Evidence for colorectal sarcomatoid carcinoma arising from tubulovillous adenoma显示文摘Sarcomatoid carcinomas of the colorectum are rare tu- mors that display both malignant epithelial and stromal components. Clinically, they are aggressive tumors with early metastasis. Due to their infrequent occurrence, the pathogenesis is poorly understood. We report a case of a 52-year-old woman who presented with a rectal mass and intermittent hematochezia. Superficial biopsies during colonoscopy revealed a tubulovillous adenoma with high-grade dysplasia. Endoscopic ultra- sonography confirmed an invasive nature of the mass, and deeper biopsies revealed the presence of neoplasm with mixed histological components. The surgically- excised specimen demonstrated the presence of poorly differentiated spindle cells underneath the tubulovillous adenoma and an intermediate stage of invasive adeno- carcinoma. Based on the histological appearance and immunohistochemical studies, a diagnosis of sarcoma- toid carcinoma was made. Only nine cases of sarcoma- toid carcinomas of the colorectum have been reported to date. As a result, the terminology and pathogenesis of sarcomatoid carcinoma remain speculative. To the best of our knowledge, this is the first report of co- existence of sarcomatoid carcinoma and invasive ad- enocarcinoma with tubulovillous adenoma; all stages represented within the same tumor. This observation supports the 'monoclonal theory' of pathogenesis with an adenoma-sarcoma progression with or without an intermediate stage of carcinoma. | Jeffrey K Lee Pradipta Ghosh Valerie McWhorter Misty Payne Ryan Olson Mary L Krinsky Sonia Ramamoorthy John M Carethers | 2008 | World Journal of Gastroenterology2008，14，27： | 2 |
| 7 | Appendectomy and Clostridium difficile colitis:Relationships revealed by clinical observations and immunology显示文摘Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in the colon.These advances have been made despite long standing clinical observations that the appendectomy is a safe and effective procedure.However,more recent clinical data show that an appendectomy puts patients at increased risk for recurrent Clostridium difficile(C.difficile)-associated colitis,and probably other diseases associated with an altered microbiome.At the same time,appendectomy does not apparently put patients at risk for an initial onset of C.difficile-associated colitis.These clinical observations point toward the idea that the vermiform appendix might not effectively protect the microbiome in the face of broad spectrum antibiotics,the use of which precedes the initial onset of C.difficile-associated colitis.Further,these observations point to the idea that historically important threats to the microbiome such as infectious gastrointestinal pathogens have been supplanted by other threats,particularly the use of broad spectrum antibiotics. | Nathan L Sanders R Randal Bollinger Ryan Lee Steven Thomas William Parker | 2013 | World Journal of Gastroenterology2013，19，34： | 2 |
| 8 | Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone显示文摘The hypoxia inducible factors(Hifs) are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone(PTH). Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of b-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH. | Julie L Frey David P Stonko Marie-Claude Faugere Ryan C Riddle | 2014 | Bone Research2014，2，1： | 2 |
| 9 | Relaxin increases secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 during uterine and cervical growth and remodeling in the pig 显示文摘 | LENHART J A RYAN P L OHLETH K M | 2001 | Endocrinology2001，142，9： | 1 |
| 10 | A controlled trial of nonoxynol-9 film to reduce male-to-female transmission of sexually transmitted diseases显示文摘 | Roddy RE Zekeng L Ryan KA | 1998 | N Engl J Med1998，399，8： | 1 |
| 11 | The laser drilling of multi-layer aerospace material systems显示文摘 | A Corcoran L Sexton B Seaman P Ryan G Byrne | 2002 | Journal of Materials Processing Tech2002，，1： | 1 |
| 12 | Self-determination theory and the facilitation of intrinsic motivation, social develop- ment, and well-being 显示文摘 | Ryan R M Deci E L | 2000 | American Psychologist2000，55，1： | 1 |
| 13 | Accuracy of computer navigation for aeetabular component placement in THA显示文摘 | Ryan J A Jamali A A Bargar W L | 2010 | Clin Oahop Relat Res2010，468，1： | 1 |
| 14 | Stable isotope incorporation triples the upper mass limit for determination of elemental composition by accurate mass measurement显示文摘 | Rodgers Ryan P Blumer Erin N Hendrickson Christopher L | 2000 | Journal of the American Society for Mass Spectrometry2000，10，11： | 1 |
| 15 | A meta-analytic review of experiments examining the effects of extrinsic rewards on in- trinsic motivation 显示文摘 | Deci E L Koestner R Ryan R M | 1999 | Psychological Bulletin1999，125，6： | 1 |
| 16 | The pharmacology of impulsive behaviour in rats Ⅵ: the effects of ethanol and selective serotonergic drugs on response choice with varying delays of reinforcement显示文摘 | Evenden J L Ryan C N | 1999 | Psychopharmacology1999，146，： | 1 |
| 17 | Apolipoprotein A-I is necessary for the in vivo formation of high density lipoprotein competent for scavenger receptor BI-mediated cholesterol ester-selective uptake显示文摘 | Ryan E Temel Rosemary L Walzem Carole L | 2002 | J Biol Chem2002，277，26： | 1 |
| 18 | A redeseription of Cryptosporidium galli Pavlasek, 1999 (Apicompl- exa: Cryptosporidiidae) from birds 显示文摘 | Ryan U M Xiao L Read C | 2003 | J Parasitol2003，89，： | 1 |
| 19 | 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 |
| 20 | Adjuvant active specific immunotheropy for stage Ⅱ and Ⅲ colon cancer with an autologous tumor cell vaccine:Eastern Cooperative Oncology Group Study E5283显示文摘 | Harris JE Ryan L Hoover Hc Jr | 2000 | J Clin Oncol2000，18，： | 1 |
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