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  1. Article ; Online: Treatment de-intensification for low-risk biochemical recurrence after radical prostatectomy: rational or risky?

    Roberts, Matthew J / Hruby, George / Kneebone, Andrew / Martin, Jarad M / Williams, Scott G / Frydenberg, Mark / Murphy, Declan G / Namdarian, Ben / Yaxley, John W / Hofman, Michael S / Davis, Ian D / Emmett, Louise

    BJU international

    2023  Volume 132, Issue 2, Page(s) 146–148

    MeSH term(s) Male ; Humans ; Prostate ; Prostatectomy ; Risk ; Seminal Vesicles ; Neoplasm Recurrence, Local ; Prostate-Specific Antigen ; Retrospective Studies
    Chemical Substances Prostate-Specific Antigen (EC 3.4.21.77)
    Language English
    Publishing date 2023-06-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/bju.16086
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  2. Article ; Online: Blocking CHOP-dependent TXNIP shuttling to mitochondria attenuates albuminuria and mitigates kidney injury in nephrotic syndrome.

    Park, Sun-Ji / Kim, Yeawon / Li, Chuang / Suh, Junwoo / Sivapackiam, Jothilingam / Goncalves, Tassia M / Jarad, George / Zhao, Guoyan / Urano, Fumihiko / Sharma, Vijay / Chen, Ying Maggie

    Proceedings of the National Academy of Sciences of the United States of America

    2022  Volume 119, Issue 35, Page(s) e2116505119

    Abstract: Albuminuria is a hallmark of glomerular disease of various etiologies. It is not only a symptom of glomerular disease but also a cause leading to glomerulosclerosis, interstitial fibrosis, and eventually, a decline in kidney function. The molecular ... ...

    Abstract Albuminuria is a hallmark of glomerular disease of various etiologies. It is not only a symptom of glomerular disease but also a cause leading to glomerulosclerosis, interstitial fibrosis, and eventually, a decline in kidney function. The molecular mechanism underlying albuminuria-induced kidney injury remains poorly defined. In our genetic model of nephrotic syndrome (NS), we have identified CHOP (C/EBP homologous protein)-TXNIP (thioredoxin-interacting protein) as critical molecular linkers between albuminuria-induced ER dysfunction and mitochondria dyshomeostasis. TXNIP is a ubiquitously expressed redox protein that binds to and inhibits antioxidant enzyme, cytosolic thioredoxin 1 (Trx1), and mitochondrial Trx2. However, very little is known about the regulation and function of TXNIP in NS. By utilizing
    MeSH term(s) Albuminuria/complications ; Albuminuria/genetics ; Albuminuria/prevention & control ; Animals ; Apoptosis ; Carrier Proteins/metabolism ; Cell Nucleus/metabolism ; Gene Deletion ; Inflammasomes/metabolism ; Kidney/metabolism ; Kidney/pathology ; MAP Kinase Kinase Kinase 5/metabolism ; Mice ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nephrotic Syndrome/complications ; Nephrotic Syndrome/genetics ; Nephrotic Syndrome/pathology ; Nephrotic Syndrome/prevention & control ; Reactive Oxygen Species/metabolism ; Thioredoxins/metabolism ; Transcription Factor CHOP/deficiency ; Transcription Factor CHOP/genetics ; Transcription Factor CHOP/metabolism
    Chemical Substances Carrier Proteins ; Ddit3 protein, mouse ; Inflammasomes ; Mitochondrial Proteins ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, mouse ; Reactive Oxygen Species ; Txnip protein, mouse ; Transcription Factor CHOP (147336-12-7) ; Thioredoxins (52500-60-4) ; MAP Kinase Kinase Kinase 5 (EC 2.7.11.25) ; Map3k5 protein, mouse (EC 2.7.11.25)
    Language English
    Publishing date 2022-08-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2116505119
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  3. Article ; Online: Albumin contributes to kidney disease progression in Alport syndrome.

    Jarad, George / Knutsen, Russell H / Mecham, Robert P / Miner, Jeffrey H

    American journal of physiology. Renal physiology

    2016  Volume 311, Issue 1, Page(s) F120–30

    Abstract: Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky ... ...

    Abstract Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb(-/-)) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb(+/-) mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3(-/-)) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3(-/-);Alb(-/-) mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3(-/-);Alb(+/+) and Col4a3(-/-);Alb(+/-) mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy.
    MeSH term(s) Albumins/deficiency ; Albumins/genetics ; Albumins/metabolism ; Animals ; Autoantigens/genetics ; Autoantigens/metabolism ; Blood Pressure ; Collagen Type IV/biosynthesis ; Collagen Type IV/genetics ; Collagen Type IV/metabolism ; Disease Progression ; Kidney/pathology ; Kidney Diseases/etiology ; Kidney Diseases/metabolism ; Kidney Diseases/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nephritis, Hereditary/complications ; Nephritis, Hereditary/metabolism ; Nephritis, Hereditary/pathology ; Survival Analysis ; Transforming Growth Factor beta1/biosynthesis ; Triglycerides/blood
    Chemical Substances Albumins ; Autoantigens ; Collagen Type IV ; Transforming Growth Factor beta1 ; Triglycerides ; type IV collagen alpha3 chain
    Language English
    Publishing date 2016-07-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00456.2015
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  4. Article ; Online: Albuminuria, wherefore art thou?

    Jarad, George / Miner, Jeffrey H

    Journal of the American Society of Nephrology : JASN

    2009  Volume 20, Issue 3, Page(s) 455–457

    MeSH term(s) Albuminuria/etiology ; Albuminuria/physiopathology ; Animals ; Capillaries/physiopathology ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/physiopathology ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/physiopathology ; Fluorescent Dyes ; Humans ; Kidney Glomerulus/blood supply ; Kidney Glomerulus/physiopathology ; Kidney Tubules/physiopathology ; Models, Biological ; Rats
    Chemical Substances Fluorescent Dyes
    Language English
    Publishing date 2009-02-25
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2009010075
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    Zs.A 3344: Show issues Location:
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  5. Article ; Online: Update on the glomerular filtration barrier.

    Jarad, George / Miner, Jeffrey H

    Current opinion in nephrology and hypertension

    2009  Volume 18, Issue 3, Page(s) 226–232

    Abstract: Purpose of review: The nephrology community lacks a unified view of protein sieving through the glomerular capillary wall. The glomerular capillary wall consists of three distinct but closely interacting layers: the fenestrated endothelium, with its ... ...

    Abstract Purpose of review: The nephrology community lacks a unified view of protein sieving through the glomerular capillary wall. The glomerular capillary wall consists of three distinct but closely interacting layers: the fenestrated endothelium, with its glycocalyx; the podocytes, with their interdigitated foot processes and slit diaphragms; and the intervening glomerular basement membrane. Proteinuria is associated with abnormalities in any one layer, suggesting that each contributes to the glomerular filtration barrier (GFB). Proteinuria can also be induced in the context of a normal glomerular capillary wall. Here, we review some classic studies as well as some newer concepts and present competing hypotheses about the GFB.
    Recent findings: Two almost forgotten concepts have recently emerged. One group has challenged the exquisite selectivity of the GFB to albumin and suggested that proteinuria is the result of abnormal tubular uptake. There has also been a reemphasis on diffusion through the glomerular basement membrane as the driving force behind macromolecular filtration. New evidence suggests that the endothelial glycocalyx is an important charge-selective barrier.
    Summary: We suggest viewing the GFB as a dynamic rather than as a rigid barrier, requiring three healthy layers and a hemodynamic steady state. Multiple challenges to studying the endothelium, the tubular handling of albumin, and the role of hemodynamic forces will require new tools, new hypotheses, and open minds.
    MeSH term(s) Animals ; Endothelium/physiology ; Filtration ; Glomerular Basement Membrane/metabolism ; Humans ; Kidney Glomerulus/physiology ; Kidney Tubules/metabolism ; Podocytes/metabolism ; Proteins/metabolism
    Chemical Substances Proteins
    Language English
    Publishing date 2009-04-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1151092-4
    ISSN 1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
    ISSN (online) 1473-6543 ; 1535-3842
    ISSN 1062-4813 ; 1062-4821
    DOI 10.1097/mnh.0b013e3283296044
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    Zs.A 3686: Show issues Location:
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  6. Article ; Online: The Pax3-Cre transgene exhibits a rostrocaudal gradient of expression in the skeletal muscle lineage.

    Jarad, George / Miner, Jeffrey H

    Genesis (New York, N.Y. : 2000)

    2009  Volume 47, Issue 1, Page(s) 1–6

    Abstract: Pax3-Cre (P3Pro-Cre) transgenic mice have been used for conditional gene deletion and/or lineage tracing in derivatives of neural crest, neural tube, metanephric mesenchyme, and ureteric mesenchyme. However, the extent of its expression in skeletal ... ...

    Abstract Pax3-Cre (P3Pro-Cre) transgenic mice have been used for conditional gene deletion and/or lineage tracing in derivatives of neural crest, neural tube, metanephric mesenchyme, and ureteric mesenchyme. However, the extent of its expression in skeletal muscle has not been reported. We investigated the expression of P3Pro-Cre in the skeletal muscle lineage using the R26R reporter and found an unexpected rostrocaudal gradient of expression. By X-gal staining, head, neck, forelimb, diaphragm, and most of the chest wall muscles did not show evidence of Cre expression, whereas all muscle groups posterior of the diaphragm stained blue. Intercostal muscles exhibited a rostrocaudal gradient of staining. The consistency of this expression pattern was demonstrated by using P3Pro-Cre to mutate a conditional dystroglycan allele. The result was loss of dystroglycan from caudal muscles, which exhibited the histological signs of muscle fiber injury and regeneration characteristic of muscular dystrophy. The lack of dystroglycan in regenerating myofibers suggests that the P3Pro-Cre transgene is active in satellite cells and/or in their precursors. In contrast, rostral muscles, including feeding and breathing muscles, maintained dystroglycan expression and were spared from disease. Accordingly, the mutants were viable for over a year. Its unique gradient of activity makes the P3Pro-Cre transgene a previously unappreciated yet powerful tool for manipulating gene expression in skeletal muscle and its precursors.
    MeSH term(s) Animals ; Cell Lineage ; Gene Expression Regulation, Developmental ; Integrases/genetics ; Integrases/metabolism ; Mice ; Mice, Transgenic ; Muscle, Skeletal/cytology ; Muscle, Skeletal/growth & development ; Muscle, Skeletal/metabolism ; PAX3 Transcription Factor ; Paired Box Transcription Factors/genetics ; Paired Box Transcription Factors/metabolism ; Transgenes/genetics
    Chemical Substances PAX3 Transcription Factor ; Paired Box Transcription Factors ; Pax3 protein, mouse (138016-91-8) ; Cre recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-)
    Language English
    Publishing date 2009-01
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2004544-X
    ISSN 1526-968X ; 1526-954X
    ISSN (online) 1526-968X
    ISSN 1526-954X
    DOI 10.1002/dvg.20447
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  7. Article ; Online: The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) trial protocol: a multicentre, randomised trial of salvage radiotherapy versus surveillance for low-risk biochemical recurrence after radical prostatectomy.

    Roberts, Matthew J / Conduit, Ciara / Davis, Ian D / Effeney, Rachel M / Williams, Scott / Martin, Jarad M / Hofman, Michael S / Hruby, George / Eapen, Renu / Gianacas, Chris / Papa, Nathan / Lourenço, Richard De Abreu / Dhillon, Haryana M / Allen, Ray / Fontela, Antoinette / Kaur, Baldeep / Emmett, Louise

    BJU international

    2023  Volume 133 Suppl 3, Page(s) 39–47

    Abstract: Background: Salvage radiation therapy (SRT) and surveillance for low-risk prostate-specific antigen (PSA) recurrence have competing risks and benefits. The efficacy of early SRT to the prostate bed with or without pelvic lymph nodes compared to ... ...

    Abstract Background: Salvage radiation therapy (SRT) and surveillance for low-risk prostate-specific antigen (PSA) recurrence have competing risks and benefits. The efficacy of early SRT to the prostate bed with or without pelvic lymph nodes compared to surveillance in patients with PSA recurrence after radical prostatectomy and no identifiable recurrent disease evident on prostate specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) is unknown.
    Study design: The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) is an open-label, multicentre, randomised Phase II trial.
    Endpoints: The primary endpoint is 3-year event-free survival, with events comprising one of PSA recurrence (PSA ≥0.2 ng/mL higher than baseline), radiological evidence of metastatic disease, or initiation of systemic or other salvage treatments. Secondary endpoints include patient-reported outcomes, treatment patterns, participant perceptions, and cost-effectiveness.
    Eligibility criteria: Eligible participants have PSA recurrence of prostate cancer after radical prostatectomy, defined by serum PSA level of 0.2-0.5 ng/mL, deemed low risk according to modified European Association of Urology biochemical recurrence risk criteria (International Society for Urological Pathology Grade Group ≤2, PSA doubling time >12 months), with no definite/probable recurrent prostate cancer on PSMA-PET/CT.
    Patients and methods: A total of 100 participants will be recruited from five Australian centres and randomised 1:1 to SRT or surveillance. Participants will undergo 6-monthly clinical evaluation for up to 36 months. Androgen-deprivation therapy is not permissible. Enrolment commenced May 2023.
    Trial registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622001478707).
    MeSH term(s) Male ; Humans ; Prostate-Specific Antigen ; Prostatic Neoplasms/diagnostic imaging ; Prostatic Neoplasms/radiotherapy ; Prostatic Neoplasms/surgery ; Prostate/pathology ; Positron Emission Tomography Computed Tomography/methods ; Androgen Antagonists/therapeutic use ; Neoplasm Recurrence, Local/pathology ; Australia/epidemiology ; Prostatectomy/methods ; Salvage Therapy/methods ; Gallium Radioisotopes/therapeutic use ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic
    Chemical Substances Prostate-Specific Antigen (EC 3.4.21.77) ; Androgen Antagonists ; Gallium Radioisotopes
    Language English
    Publishing date 2023-09-14
    Publishing country England
    Document type Clinical Trial Protocol ; Journal Article
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/bju.16158
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    Zs.MO 13: Show issues

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  8. Article ; Online: Klotho regulation by albuminuria is dependent on ATF3 and endoplasmic reticulum stress.

    Delitsikou, Vasiliki / Jarad, George / Rajaram, Renuga Devi / Ino, Frédérique / Rutkowski, Joseph M / Chen, Ci-Di / Santos, Celio X C / Scherer, Philipp E / Abraham, Carmela R / Shah, Ajay M / Feraille, Eric / Miner, Jeffrey H / de Seigneux, Sophie

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2019  Volume 34, Issue 2, Page(s) 2087–2104

    Abstract: Proteinuria is associated with renal function decline and cardiovascular mortality. This association may be attributed in part to alterations of Klotho expression induced by albuminuria, yet the underlying mechanisms are unclear. The presence of albumin ... ...

    Abstract Proteinuria is associated with renal function decline and cardiovascular mortality. This association may be attributed in part to alterations of Klotho expression induced by albuminuria, yet the underlying mechanisms are unclear. The presence of albumin decreased Klotho expression in the POD-ATTAC mouse model of proteinuric kidney disease as well as in kidney epithelial cell lines. This downregulation was related to both decreased Klotho transcription and diminished protein half-life, whereas cleavage by ADAM proteases was not modified. The regulation was albumin specific since it was neither observed in the analbuminemic Col4α3
    MeSH term(s) Activating Transcription Factor 3/genetics ; Activating Transcription Factor 3/metabolism ; Albuminuria/genetics ; Albuminuria/metabolism ; Albuminuria/pathology ; Animals ; Autoantigens/genetics ; Autoantigens/metabolism ; Collagen Type IV/genetics ; Collagen Type IV/metabolism ; Down-Regulation ; Endoplasmic Reticulum Stress ; Glucuronidase/biosynthesis ; Glucuronidase/genetics ; Humans ; Kidney Tubules/metabolism ; Kidney Tubules/pathology ; Klotho Proteins ; Mice ; Mice, Knockout ; Transcription, Genetic
    Chemical Substances Activating Transcription Factor 3 ; Atf3 protein, mouse ; Autoantigens ; Collagen Type IV ; type IV collagen alpha3 chain ; Glucuronidase (EC 3.2.1.31) ; Klotho Proteins (EC 3.2.1.31)
    Language English
    Publishing date 2019-12-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.201900893R
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  9. Article ; Online: The Role of FDG-PET in the Initial Staging and Response Assessment of Anal Cancer: A Systematic Review and Meta-analysis.

    Jones, Michael / Hruby, George / Solomon, Michael / Rutherford, Natalie / Martin, Jarad

    Annals of surgical oncology

    2015  Volume 22, Issue 11, Page(s) 3574–3581

    Abstract: Purpose: The aim of this systematic review and meta-analysis was to compare the role of FDG-positron emission tomography (PET) or PET/computed tomography (CT) with conventional imaging in the detection of primary and nodal disease in anal cancer, and to ...

    Abstract Purpose: The aim of this systematic review and meta-analysis was to compare the role of FDG-positron emission tomography (PET) or PET/computed tomography (CT) with conventional imaging in the detection of primary and nodal disease in anal cancer, and to assess the impact of PET or PET/CT on the management of anal cancer.
    Methods: A systematic review of the literature was performed. Eligible studies included those comparing PET or PET/CT with conventional imaging in the staging of histologically confirmed anal squamous cell carcinoma (SCC), or studies that performed PET or PET/CT imaging to assess response following treatment.
    Results: Twelve studies met the inclusion criteria. For the detection of primary disease, CT and PET had a sensitivity of 60 % (95 % confidence interval [CI] 45.5-75.2) and 99 % (95 % CI 96-100), respectively. Compared with conventional imaging, PET upstaged 15 % (95 % CI 10-21) and downstaged 15 % (95 % CI 10-20) of nodal disease. This led to a change in nodal staging in 28 % of patients (95 % CI 18-38). When only studies performing contemporary PET/CT were considered, the rate of nodal upstaging was 21 % (95 % CI 13-30) and the TNM stage was altered in 41 % of patients. Following chemoradiotherapy, 78 % (95 % CI 65-88) of patients had a complete response on PET.
    Conclusion: Compared with conventional imaging, PET or PET/CT alters the nodal status in a sufficient number of cases to justify its routine use in the staging of patients with anal SCC.
    MeSH term(s) Anus Neoplasms/diagnostic imaging ; Anus Neoplasms/pathology ; Anus Neoplasms/therapy ; Carcinoma, Squamous Cell/diagnostic imaging ; Carcinoma, Squamous Cell/secondary ; Carcinoma, Squamous Cell/therapy ; Chemoradiotherapy ; Fluorodeoxyglucose F18 ; Humans ; Lymphatic Metastasis ; Multimodal Imaging ; Neoplasm Staging ; Positron-Emission Tomography ; Radiopharmaceuticals ; Tomography, X-Ray Computed ; Treatment Outcome
    Chemical Substances Radiopharmaceuticals ; Fluorodeoxyglucose F18 (0Z5B2CJX4D)
    Language English
    Publishing date 2015-10
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Meta-Analysis ; Review
    ZDB-ID 1200469-8
    ISSN 1534-4681 ; 1068-9265
    ISSN (online) 1534-4681
    ISSN 1068-9265
    DOI 10.1245/s10434-015-4391-9
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  10. Article ; Online: FDG-PET parameters predict for recurrence in anal cancer – results from a prospective, multicentre clinical trial

    Michael Peter Jones / George Hruby / Ur Metser / Swetha Sridharan / Anne Capp / Mahesh Kumar / Sarah Gallagher / Natalie Rutherford / Carl Holder / Christopher Oldmeadow / Jarad Martin

    Radiation Oncology, Vol 14, Iss 1, Pp 1-

    2019  Volume 6

    Abstract: Abstract Background To investigate the prognostic significance of positron emission tomography (PET) parameters from F-18 fluorodeoxyglucose (FDG) PET scans performed pre- and post- chemo-radiotherapy (CRT) for squamous cell carcinoma of the anal canal ( ... ...

    Abstract Abstract Background To investigate the prognostic significance of positron emission tomography (PET) parameters from F-18 fluorodeoxyglucose (FDG) PET scans performed pre- and post- chemo-radiotherapy (CRT) for squamous cell carcinoma of the anal canal (AC). Methods From January 2013 to January 2017, 19 patients with non-metastatic AC enrolled on a prospective trial underwent FDG-PET/CT imaging before and 12 weeks following CRT. A computer-generated volume of interest (VOI) was snapped around the primary tumour using six different standard uptake value (SUV) thresholds and the following parameters were extracted: SUV max, mean, median, standard deviation and peak as well as metabolic tumour volume (MTV) and total lesion glycolysis. Exact logistic regression and ROC AUC analyses were performed for each metric at each timepoint. Results With a median follow up of 15.8 months, 3/19 patients had a local recurrence and 5/19 had any recurrence. On post-CRT PET, the median SUV within a VOI bounded by an SUV of 3 correlated with local recurrence (p < 0.01) and demonstrated excellent discrimination (ROC AUC 1.00, perfect separation was achieved at a median SUV of 3.38). The mean SUV at this threshold did not quite reach significance for prediction of local recurrence (p = 0.06) but demonstrated excellent discrimination (ROC AUC 0.91). The MTV bounded by a threshold of 41% SUVmax on the pre-CRT PET predicted for any recurrence (p = 0.03) and showed excellent discrimination (ROC AUC 0.89). Conclusions FDG-PET parameters are predictive of recurrence in AC. FDG-PET may represent a valuable tool for prognostication and response assessment in AC. Trial registration ANZCTR, ACTRN12614001219673. Registered 19 November 2014 - Retrospectively registered.
    Keywords Anal cancer ; Positron emission tomography ; Chemo-radiotherapy ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 610
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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