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  1. Article ; Online: Spatial determination and prognostic impact of the fibroblast transcriptome in pancreatic ductal adenocarcinoma

    Wayne Croft / Hayden Pearce / Sandra Margielewska-Davies / Lindsay Lim / Samantha M Nicol / Fouzia Zayou / Daniel Blakeway / Francesca Marcon / Sarah Powell-Brett / Brinder Mahon / Reena Merard / Jianmin Zuo / Gary Middleton / Keith Roberts / Rachel M Brown / Paul Moss

    eLife, Vol

    2023  Volume 12

    Abstract: Pancreatic ductal adenocarcinoma has a poor clinical outcome and responses to immunotherapy are suboptimal. Stromal fibroblasts are a dominant but heterogenous population within the tumor microenvironment and therapeutic targeting of stromal subsets may ... ...

    Abstract Pancreatic ductal adenocarcinoma has a poor clinical outcome and responses to immunotherapy are suboptimal. Stromal fibroblasts are a dominant but heterogenous population within the tumor microenvironment and therapeutic targeting of stromal subsets may have therapeutic utility. Here, we combine spatial transcriptomics and scRNA-Seq datasets to define the transcriptome of tumor-proximal and tumor-distal cancer-associated fibroblasts (CAFs) and link this to clinical outcome. Tumor-proximal fibroblasts comprise large populations of myofibroblasts, strongly expressed podoplanin, and were enriched for Wnt ligand signaling. In contrast, inflammatory CAFs were dominant within tumor-distal subsets and expressed complement components and the Wnt-inhibitor SFRP2. Poor clinical outcome was correlated with elevated HIF-1α and podoplanin expression whilst expression of inflammatory and complement genes was predictive of extended survival. These findings demonstrate the extreme transcriptional heterogeneity of CAFs and its determination by apposition to tumor. Selective targeting of tumor-proximal subsets, potentially combined with HIF-1α inhibition and immune stimulation, may offer a multi-modal therapeutic approach for this disease.
    Keywords pancreatic cancer ; PDAC ; cancer-associated fibroblasts ; NanoString GeoMx ; tumour microenvironment ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy

    Bathiya Ratnayake / Alina Y. Savastyuk / Manu Nayar / Colin H. Wilson / John A. Windsor / Keith Roberts / Jeremy J. French / Sanjay Pandanaboyana

    Journal of Clinical Medicine, Vol 9, Iss 2132, p

    A Comprehensive Meta-Analysis

    2020  Volume 2132

    Abstract: Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and ... ...

    Abstract Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. Methods: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. Results: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52–0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs 27% OR 0.39 (CI 0.22–0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44–0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34–0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts ( p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05–0.32), p = 0.015). Conclusion: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.
    Keywords recurrence ; neoadjuvant chemotherapy ; pancreatic ductal adenocarcinoma ; pancreatic surgery ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Cross tissue trait-pathway network reveals the importance of oxidative stress and inflammation pathways in obesity-induced diabetes in mouse.

    Shouguo Gao / Herbert Keith Roberts / Xujing Wang

    PLoS ONE, Vol 7, Iss 9, p e

    2012  Volume 44544

    Abstract: Complex disorders often involve dysfunctions in multiple tissue organs. Elucidating the communication among them is important to understanding disease pathophysiology. In this study we integrate multiple tissue gene expression and quantitative trait ... ...

    Abstract Complex disorders often involve dysfunctions in multiple tissue organs. Elucidating the communication among them is important to understanding disease pathophysiology. In this study we integrate multiple tissue gene expression and quantitative trait measurements of an obesity-induced diabetes mouse model, with databases of molecular interaction networks, to construct a cross tissue trait-pathway network. The animals belong to two strains of mice (BTBR or B6), of two obesity status (obese or lean), and at two different ages (4 weeks and 10 weeks). Only 10 week obese BTBR animals are diabetic. The expression data was first utilized to determine the state of every pathway in each tissue, which is subsequently utilized to construct a pathway co-expression network and to define trait-relevant and trait-linking pathways. Among the six tissues profiled, the adipose contains the largest number of trait-linking pathways. Among the eight traits measured, the body weight and plasma insulin level possess the most number of relevant and linking pathways. Topological analysis of the trait-pathway network revealed that the glycolysis/gluconeogenesis pathway in liver and the insulin signaling pathway in muscle are of top importance to the information flow in the network, with the highest degrees and betweenness centralities. Interestingly, pathways related to metabolism and oxidative stress actively interact with many other pathways in all animals, whereas, among the 10 week animals, the inflammation pathways were preferentially interactive in the diabetic ones only. In summary, our method offers a systems approach to delineate disease trait relevant intra- and cross tissue pathway interactions, and provides insights to the molecular basis of the obesity-induced diabetes.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Book: Fine structure of cells and tissues

    Porter, Keith R. / Bonneville, Mary A.

    1973  

    Language English
    Size VII, 204 S. : Ill.
    Edition 4.ed.
    Publisher Lea & Febiger
    Publishing place Philadelphia
    Publishing country United States
    Document type Book
    Old title Früher u.d.T. An introduction to the fine structure of cells and tissues
    HBZ-ID HT005175125
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    1975 A 2086 order for loan Magazin

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  5. Book: Einführung in die Feinstruktur von Zellen und Geweben

    Porter, Keith R. / Bonneville, Mary Agnes

    1965  

    Title translation An introduction to the fine structure of cells and tissues
    Author's details von Keith R. Porter und Mary A. Bonneville. [Dt. Übers. der 2. Aufl. von H. F. Kern]
    Keywords Gewebe ; Ultrastruktur ; Zelle ; Struktur
    Language German
    Size [66] Bl. : zahlr. Ill.
    Publisher Springer
    Publishing place Berlin u.a.
    Publishing country Germany
    Document type Book
    HBZ-ID HT002636908
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    1965 A 831 order for loan Magazin
    1965 A 831a order for loan Magazin

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  6. Article ; Online: Increased hepcidin expression in colorectal carcinogenesis

    Douglas G Ward, Keith Roberts, Matthew J Brookes, Howard Joy, Ashley Martin, Tariq Ismail, Robert Spychal, Tariq Iqbal, Chris Tselepis

    World Journal of Gastroenterology, Vol 14, Iss 9, Pp 1339-

    2008  Volume 1345

    Abstract: AIM: To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anaemia and whether it might have a role in colorectal carcinogenesis.METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to ... ...

    Abstract AIM: To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anaemia and whether it might have a role in colorectal carcinogenesis.METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilized to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localization was determined using immunohistochemistry.RESULTS: We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was positively associated with increasing T-stage of colorectal cancer (P < 0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repression. This was supported by hepcidin immunoreactivity in colorectal cancer tissue.CONCLUSION: We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.
    Keywords Iron ; Hepcidin ; Colon ; Cancer ; Anaemia ; Mass spectrometry ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 616 ; 610
    Language English
    Publishing date 2008-03-01T00:00:00Z
    Publisher Baishideng Publishing Group Co. Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Use of Stable Calcium Isotopes (42Ca & 44Ca) in Evaluation of Calcium Absorption in Beijing Adolescents with Low Vitamin D Status

    Lee, Warren Tak Keung / David Charles Keith Roberts / Jack Chun Yiu Cheng / Ji Jiang / Pei Hu / Xiaopeng Hu

    Food and nutrition bulletin. , v. 23, no. 3_suppl1

    2002  

    Abstract: Female adolescent populations with low calcium intakes and sub-optimal vitamin D status are found in northern China. Whether these individuals are able to adapt by enhancing calcium absorption and reducing calcium excretion for maximizing calcium ... ...

    Abstract Female adolescent populations with low calcium intakes and sub-optimal vitamin D status are found in northern China. Whether these individuals are able to adapt by enhancing calcium absorption and reducing calcium excretion for maximizing calcium retention is unknown. This study examined the association between true-fractional-calcium-absorption (TFCA), plasma 25-hydroxyvitamin-D, and urinary calcium excretion among adolescents in Northern China. Twelve healthy girls 9 to 17 years old were recruited from Beijing during a winter. Calcium intake, anthropometry, pubertal status, plasma 25-hydroxyvitamin-Ds (25-OHD), serum calcium, and urinary calcium were determined. TFCA was evaluated by dual stable calcium isotopes. The mean ± SD calcium intake, 24-hour urinary calcium excretion, plasma 25-OHD and TFCA were 591 ± 164 mg/day, 79.9 ± 49.6 mg/day, 30.5 ± 9.8 nmol/L, and 60.4 ± 14.4%, respectively. TFCA was inversely correlated with 25-OHD (r = −0.73, p = .008). Urinary calcium was correlated with the onset of menarche (r = 0.63, p = .027). Post-menarcheal girls had a higher urinary calcium output than premenarcheal girls (p = .03). Adolescents from north China with sub-optimal vitamin-D status are able to adapt by enhancing TFCA and reducing urinary calcium excretion to retain calcium for bone development. TFCA was inversely correlated with plasma 25-OHD. Whether a higher efficiency of calcium absorption is sustainable if the shortfall of vitamin D persisting remains to be studied.
    Keywords adolescents ; anthropometric measurements ; blood serum ; calcium ; excretion ; females ; girls ; intestinal absorption ; isotopes ; menarche ; skeletal development ; vitamin D ; vitamin status ; winter ; China
    Language English
    Size p. 42-47.
    Publishing place SAGE Publications
    Document type Article
    ZDB-ID 449173-7
    ISSN 0379-5721
    ISSN 0379-5721
    DOI 10.1177/15648265020233S108
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 4308: Show issues

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  8. Book: Introduction to the fine structure of plant cells

    Ledbetter, Myron C / Porter, Keith Roberts

    1970  

    Author's details Myron C. Ledbetter; Keith R. Porter
    Language English
    Size IX, 188 S, Ill
    Publisher Springer
    Publishing place Berlin u.a.
    Document type Book
    Note Literaturangaben
    ISBN 0387051953 ; 3540051953 ; 9780387051956 ; 9783540051954
    Database Former special subject collection: coastal and deep sea fishing

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  9. Book: Introduction to the fine structure of plant cells

    Ledbetter, Myron C / Porter, Keith Roberts

    1970  

    Language English
    Size IX, 188 S., with 51 plates and 8 text figures
    Publisher Springer
    Publishing place Berlin ;Heidelberg ;New York
    Document type Book
    Database Johann Heinrich von Thünen-Institut, Federal Research Institute for Rural Areas, Forestry and Fisheries

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  10. Book: Introduction to the fine structure of plant cells

    Ledbetter, Myron C / Porter, Keith Roberts

    1970  

    Author's details Myron C. Ledbetter; Keith R. Porter
    Language English
    Size IX, 188 S, Ill
    Document type Book
    Note Literaturangaben
    ISBN 0387051953 ; 3540051953 ; 9780387051956 ; 9783540051954
    Database Leibniz Institute of Plant Genetics and Crop Plant Research

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