umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Wang, Wanzhong
Publications (10 of 12) Show all publications
Franklin, O., Billing, O., Öhlund, D., Berglund, A., Herdenberg, C., Wang, W., . . . Sund, M. (2019). Novel prognostic markers within the CD44-stromal ligand network in pancreatic cancer. Journal of Pathology, 5(2), 130-141
Open this publication in new window or tab >>Novel prognostic markers within the CD44-stromal ligand network in pancreatic cancer
Show others...
2019 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 5, no 2, p. 130-141Article in journal (Refereed) Published
Abstract [en]

The dense stroma in pancreatic cancer tumours is rich in secreted extracellular matrix proteins and proteoglycans. Secreted hyaluronan, osteopontin and type IV collagen sustain oncogenic signalling by interactions with CD44s and its variant isoform CD44v6 on cancer cell membranes. Although well established in animal and in vitro models, this oncogenic CD44-stromal ligand network is less explored in human cancer. Here, we use a pancreatic cancer tissue microarray from 69 primary tumours and 37 metastatic lymph nodes and demonstrate that high tumour cell expression of CD44s and, surprisingly, low stromal deposition of osteopontin correlate with poor survival independent of established prognostic factors for pancreatic cancer. High stromal expression of hyaluronan was a universal trait of both primary tumours and metastatic lymph nodes. However, hyaluronan species of different molecular mass are known to function differently in pancreatic cancer biology and immunohistochemistry cannot distinguish between them. Using gas-phase electrophoretic molecular mobility analysis, we uncover a shift towards high molecular mass hyaluronan in pancreatic cancer tissue compared to normal pancreas and at a transcriptional level, we find that hyaluronan synthesising HAS2 correlates positively with CD44. The resulting prediction that high molecular mass hyaluronan would then correlate with poor survival in pancreatic cancer was confirmed in serum samples, where we demonstrate that hyaluronan >27 kDa measured before surgery is an independent predictor of postoperative survival. Our findings confirm the prognostic value of CD44 tissue expression and highlight osteopontin tissue expression and serum high molecular mass hyaluronan as novel prognostic markers in pancreatic cancer.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
CD44, biomarkers, hyaluronan, osteopontin, pancreatic cancer, type IV collagen
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-154564 (URN)10.1002/cjp2.122 (DOI)000465218700006 ()30456933 (PubMedID)2-s2.0-85064472279 (Scopus ID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-05-20Bibliographically approved
Winsö, O., Kral, J., Wang, W., Kralova, I., Abrahamsson, P., Johansson, G. & Blind, P.-J. (2018). Thoracic epidural anaesthesia reduces insulin resistance and inflammatory response in experimental acute pancreatitis. Upsala Journal of Medical Sciences, 123(4), 207-215
Open this publication in new window or tab >>Thoracic epidural anaesthesia reduces insulin resistance and inflammatory response in experimental acute pancreatitis
Show others...
2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 207-215Article in journal (Refereed) Published
Abstract [en]

AIMS: The activity of the sympathetic nervous system (SNS) is crucial at an early stage in the development of an inflammatory reaction. A study of metabolic events globally and locally in the early phase of acute pancreatitis (AP), implying hampered SNS activity, is lacking. We hypothesized that thoracic epidural anaesthesia (TEA) modulates the inflammatory response and alleviates the severity of AP in pigs.

MATERIAL AND METHODS: The taurocholate (TC) group (n = 8) had only TC AP. The TC + TEA group (n = 8) had AP and TEA. A control group (n = 8) underwent all the preparations, without having AP or TEA. Metabolic changes in the pancreas were evaluated by microdialysis and by histopathological examination.

RESULTS: The relative increase in serum lipase concentrations was more pronounced in the TC group than in TC + TEA and control groups. A decrease in relative tissue oxygen tension (PtiO2) levels occurred one hour later in the TC + TEA group than in the TC group. The maintenance of normoglycaemia in the TC group required a higher glucose infusion rate than in the TC + TEA group. The relative decrease in serum insulin concentrations was most pronounced in the TC + TEA group.

CONCLUSION: TEA attenuates the development of AP, as indicated by changes observed in haemodynamic parameters and by the easier maintenance of glucose homeostasis. Further, TEA was associated with attenuated insulin resistance and fewer local pathophysiological events.

Place, publisher, year, edition, pages
Abingdon: Taylor & Francis, 2018
Keywords
Acute pancreatitis, epidural anaesthesia, insulin, microdialysis, sodium-taurocholic acid, sympathetic nervous system
National Category
Anesthesiology and Intensive Care Surgery
Identifiers
urn:nbn:se:umu:diva-153672 (URN)10.1080/03009734.2018.1539054 (DOI)000455702800003 ()30468105 (PubMedID)
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2019-02-25Bibliographically approved
Na, M., Wang, W., Fei, Y., Josefsson, E., Ali, A. & Jin, T. (2017). Both anti-TNF and CTLA4 Ig treatments attenuate the disease severity of staphylococcal dermatitis in mice. PLoS ONE, 12(3), Article ID e0173492.
Open this publication in new window or tab >>Both anti-TNF and CTLA4 Ig treatments attenuate the disease severity of staphylococcal dermatitis in mice
Show others...
2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0173492Article in journal (Refereed) Published
Abstract [en]

Background RA patients being treated with biologics are known to have an increased risk of infections. We recently demonstrated that both CTLA4 Ig and anti-TNF treatment aggravate systemic Staphylococcus aureus (S. aureus) infection in mice, but with distinct clinical manifestations. However, the effects of CTLA4 Ig and anti-TNF treatments on a local S. aureus infection (e.g., skin infection) might differ from their effects on a systemic infection. Aims The aim of this study was to examine the differential effects of anti-TNF versus CTLA4 Ig treatment on S. aureus skin infections in mice. Method Abatacept (CTLA4 Ig), etanercept (anti-TNF treatment) or PBS was given to NMRI mice subcutaneously inoculated with S. aureus strain SH1000. The clinical signs of dermatitis, along with histopathological changes due to skin infection, were compared between the groups. Results Both CTLA4 Ig and anti-TNF treatment resulted in less severe skin infections and smaller post-infectious hyperpigmentation compared with controls. Consistent with the clinical signs of dermatitis, smaller lesion size, more epithelial hyperplasia and more granulation were found in skin biopsies from mice receiving anti-TNF compared with PBS controls. However, both CTLA4 Ig and anti-TNF therapy tended to prolong the healing time, although this finding was not statistically significant. Serum MCP-1 levels were elevated in the anti-TNF group relative to the CTLA4 Ig and PBS groups, whereas IL-6 levels were higher in PBS controls than in the other two groups. Both anti-TNF and CTLA4 Ig treatments tended to down-regulate the necrosis/apoptosis ratio in the locally infected skin tissue. Importantly, no tangible difference was found in the bacterial burden among groups. Conclusion Both CTLA4 Ig and anti-TNF therapies attenuate disease severity but may prolong the healing time required for S. aureus skin infections. Neither treatment has an impact on bacterial clearance in skin tissues.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2017
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-132789 (URN)10.1371/journal.pone.0173492 (DOI)000396054300066 ()
Available from: 2017-05-12 Created: 2017-05-12 Last updated: 2019-05-10Bibliographically approved
Elmwall, J., Kwiecinski, J., Na, M., Ali, A. A., Osla, V., Shaw, L. N., . . . Karlsson, A. (2017). Galectin-3 Is a Target for Proteases Involved in the Virulence of Staphylococcus aureus. Infection and Immunity, 85(7), Article ID e00177-17.
Open this publication in new window or tab >>Galectin-3 Is a Target for Proteases Involved in the Virulence of Staphylococcus aureus
Show others...
2017 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 85, no 7, article id e00177-17Article in journal (Refereed) Published
Abstract [en]

Staphylococcus aureus is a major cause of skin and soft tissue infection. The bacterium expresses four major proteases that are emerging as virulence factors: aureolysin (Aur), V8 protease (SspA), staphopain A (ScpA), and staphopain B (SspB). We hypothesized that human galectin-3, a beta-galactoside-binding lectin involved in immune regulation and antimicrobial defense, is a target for these proteases and that proteolysis of galectin-3 is a novel immune evasion mechanism. Indeed, supernatants from laboratory strains and clinical isolates of S. aureus caused galectin-3 degradation. Similar proteolytic capacities were found in Staphylococcus epidermidis isolates but not in Staphylococcus saprophyticus. Galectin-3-induced activation of the neutrophil NADPH oxidase was abrogated by bacterium-derived proteolysis of galectin-3, and SspB was identified as the major protease responsible. The impact of galectin-3 and protease expression on S. aureus virulence was studied in a murine skin infection model. In galectin-3 (+)/(+) mice, SspB-expressing S. aureus caused larger lesions and resulted in higher bacterial loads than protease-lacking bacteria. No such difference in bacterial load or lesion size was detected in galectin-3 (+)/(+) mice, which overall showed smaller lesion sizes than the galectin-3 (+)/(+) animals. In conclusion, the staphylococcal protease SspB inactivates galectin-3, abrogating its stimulation of oxygen radical production in human neutrophils and increasing tissue damage during skin infection.

Place, publisher, year, edition, pages
American Society for Microbiology, 2017
Keywords
galectin-3, Staphylococcus aureus, neutrophils, protease, staphopain, skin infection, virulence, virulence regulation, virulence factors
National Category
Immunology in the medical area Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-139157 (URN)10.1128/IAI.00177-17 (DOI)000408249700007 ()
Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2019-05-10Bibliographically approved
Braadland, P. R., Grytli, H. H., Ramberg, H., Katz, B., Kellman, R., Gauthier-Landry, L., . . . Tasken, K. A. (2016). Low beta(2)-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism. OncoTarget, 7(2), 1878-1894
Open this publication in new window or tab >>Low beta(2)-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism
Show others...
2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 2, p. 1878-1894Article in journal (Refereed) Published
Abstract [en]

The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy are not fully understood. This is the first study to address whether beta(2)-adrenergic receptor (ADRB2)- mediated signaling may affect CRPC progression in vivo. By immunohistochemical analyses, we observed that low levels of ADRB2 is associated with a more rapid development of CRPC in a Norwegian patient cohort. To elucidate mechanisms by which ADRB2 may affect CRPC development, we stably transfected LNCaP cells with shRNAs to mimic low and high expression of ADRB2. Two UDP-glucuronosyltransferases, UGT2B15 and UGT2B17, involved in phase II metabolism of androgens, were strongly downregulated in two LNCaP shADRB2 cell lines. The low-ADRB2 LNCaP cell lines displayed lowered glucuronidation activities towards androgens than high-ADRB2 cells. Furthermore, increased levels of testosterone and enhanced androgen responsiveness were observed in LNCaP cells expressing low level of ADRB2. Interestingly, these cells grew faster than high-ADRB2 LNCaP cells, and sustained their low glucuronidation activity in castrated NOD/SCID mice. ADRB2 immunohistochemical staining intensity correlated with UGT2B15 staining intensity in independent TMA studies and with UGT2B17 in one TMA study. Similar to ADRB2, we show that low levels of UGT2B15 are associated with a more rapid CRPC progression. We propose a novel mechanism by which ADRB2 may affect the development of CRPC through downregulation of UGT2B15 and UGT2B17.

Keywords
beta 2-adrenergic receptor, ADRB2, CRPC, UGT2B15, UGT2B17
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-117840 (URN)10.18632/oncotarget.6479 (DOI)000369951100061 ()
Available from: 2016-03-30 Created: 2016-03-04 Last updated: 2018-06-07Bibliographically approved
Ramberg, H., Grytli, H. H., Nygard, S., Wang, W., Ogren, O., Zhao, S., . . . Tasken, K. A. (2016). PBX3 is a putative biomarker of aggressive prostate cancer. International Journal of Cancer, 139(8), 1810-1820
Open this publication in new window or tab >>PBX3 is a putative biomarker of aggressive prostate cancer
Show others...
2016 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 139, no 8, p. 1810-1820Article in journal (Refereed) Published
Abstract [en]

There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies (R), and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081-0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46-0.93, p values < 0.001, and AUC=0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-126485 (URN)10.1002/ijc.30220 (DOI)000383284500015 ()27273830 (PubMedID)
Available from: 2016-10-27 Created: 2016-10-10 Last updated: 2019-05-10Bibliographically approved
Franklin, O., Öhlund, D., Lundin, C., Öman, M., Naredi, P., Wang, W. & Sund, M. (2015). Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma. Cancer Biomarkers, 15(1), 1-10
Open this publication in new window or tab >>Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma
Show others...
2015 (English)In: Cancer Biomarkers, ISSN 1574-0153, Vol. 15, no 1, p. 1-10Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A lack of disease-specific symptoms and good tumour markers makes early detection and diagnosis of pancreatic ductal adenocarcinoma (PDAC) challenging. OBJECTIVE: To analyse the tissue expression and circulating levels of four stroma-derived substances (type IV collagen, endostatin/type XVIII collagen, osteopontin and tenascin C) and four conventional tumour markers (CA 19-9, TPS, CEA and Ca 125) in a PDAC cohort.

METHODS: Tissue expression of markers in normal pancreas and PDAC tissue was analysed with immunofluorescence. Plasma concentrations of markers were measured before and after surgery. Patients with non-malignant disorders served as controls.

RESULTS: The conventional and stromal substances were expressed in the cancer cell compartment and the stroma, respectively. Although most patients had increased levels of many markers before surgery, 2/12 (17%) of patients had normal levels of Ca 19-9 at this stage. High preoperative endostatin/type XVIII collagen, and postoperative type IV collagen was associated with short survival. Neither the pre-nor postoperative levels of TPS, Ca 125 or CA 19-9 were associated to survival.

CONCLUSIONS: PDAC is characterized by an abundant stroma. These initial observations indicate that the stroma can be a source of PDAC tumour markers that are found in different compartments of the cancer, thus reflecting different aspects of tumour biology.

Place, publisher, year, edition, pages
IOS Press, 2015
Keywords
Pancreatic ductal adenocarcinoma (PDAC), tumour markers, stroma, type IV collagen, type XVIII llagen, endostatin, osteopontin, tenascin C, TPS, Ca 125, Ca 19-9, CEA
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-97877 (URN)10.3233/CBM-140430 (DOI)000346079800001 ()
Available from: 2015-01-16 Created: 2015-01-08 Last updated: 2018-06-07Bibliographically approved
Wang, W., Gao, L. & Wang, E. (2014). Integrin beta6: A potential marker for the early malignant transformation in prostate cancer. Virchows Archiv, 465 1, S176-S176
Open this publication in new window or tab >>Integrin beta6: A potential marker for the early malignant transformation in prostate cancer
2014 (English)In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 465 1, p. S176-S176Article in journal, Meeting abstract (Other academic) Published
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:umu:diva-98912 (URN)000344386801208 ()
Available from: 2015-01-28 Created: 2015-01-28 Last updated: 2018-06-07Bibliographically approved
Kwiecinski, J., Jacobsson, G., Karlsson, M., Zhu, X., Wang, W., Bremell, T., . . . Jin, T. (2013). Staphylokinase Promotes the Establishment of Staphylococcus aureus Skin Infections While Decreasing Disease Severity. Journal of Infectious Diseases, 208(6), 990-999
Open this publication in new window or tab >>Staphylokinase Promotes the Establishment of Staphylococcus aureus Skin Infections While Decreasing Disease Severity
Show others...
2013 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 208, no 6, p. 990-999Article in journal (Refereed) Published
Abstract [en]

Skin infections are frequently caused by Staphylococcus aureus and can lead to a fatal sepsis. The microbial mechanisms controlling the initiation and progression from mild skin infection to a severe disseminated infection remain poorly understood. Using a combination of clinical data and in vitro and ex vivo assays, we show that staphylokinase, secreted by S. aureus, promoted the establishment of skin infections in humans and increased bacterial penetration through skin barriers by activating plasminogen. However, when infection was established, the interaction between staphylokinase and plasminogen did not promote systemic dissemination but induced the opening and draining of abscesses and decreased disease severity in neutropenic mice. Also, increased staphylokinase production was associated with noninvasive S. aureus infections in patients. Our results point out the dual roles of staphylokinase in S. aureus skin infections as promoting the establishment of infections while decreasing disease severity.

Place, publisher, year, edition, pages
Oxford University Press, 2013
Keywords
staphylococcus, staphylokinase, plasminogen, skin infection, mouse model, pathogen-host relation
National Category
Immunology in the medical area Microbiology in the medical area Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-81832 (URN)10.1093/infdis/jit288 (DOI)000324510200015 ()
Available from: 2013-10-24 Created: 2013-10-22 Last updated: 2018-06-08Bibliographically approved
Blind, P.-J. -., Kral, J., Wang, W., Kralova, I., Abrahamsson, P., Johansson, G. & Winsö, O. (2012). Microdialysis in early detection of temporary pancreatic ischemia in a porcine model. European Surgical Research, 49(3-4), 113-120
Open this publication in new window or tab >>Microdialysis in early detection of temporary pancreatic ischemia in a porcine model
Show others...
2012 (English)In: European Surgical Research, ISSN 0014-312X, E-ISSN 1421-9921, Vol. 49, no 3-4, p. 113-120Article in journal (Refereed) Published
Abstract [en]

Background: Ischemic injury to the pancreas occurs in various clinical conditions. A method for online monitoring of pathophysiological events in pancreatic parenchyma is missing. Aims: To assess the timing of microdialysis (MD) technique response on temporary changes in pancreatic perfusion, and to evaluate the relationship between MD data and systemic markers of anaerobic metabolism and inflammation. Methods: In anaesthetized normoventilated pigs, MD probes were placed in right (control) and left (ischemic) pancreatic lobes, respectively. Following the clamping of the vessels, ischemia was verified by tissue oxygen tension (PtiO2) measurements. Results: PtiO2 decreased within 20 min after the clamping of the vessels, already returning to baseline levels at the first sampling point after the removal of the clamp. MD lactate levels increased, whereas pyruvate and glucose levels decreased at 20 min after the induction of ischemia. These trends continued until the end of ischemia and returned to baseline following reperfusion. Serum lactate, amylase and tumor necrosis factor-alpha levels decreased throughout the protocol time. Conclusion: MD data were in concordance with changes in PtiO2, which is indicative of local anaerobic metabolism. MD allowed the detection of pathophysiological processes within the ischemic pancreas at a stage when no elevations of systemic markers of ischemia or inflammation were observed.

Keywords
Experimental model, Ischemia, Microdialysis, Pancreas, Pig
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-63611 (URN)10.1159/000343806 (DOI)
Available from: 2013-01-08 Created: 2013-01-03 Last updated: 2018-06-08Bibliographically approved
Organisations

Search in DiVA

Show all publications