oru.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Infection induced chronic inflammation and it's association with prostate cancer initiation and progression
Örebro universitet, Institutionen för hälsovetenskap och medicin.
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

An association between cancer development and inflammation has long been suggested. Approximately 20% of all human cancers in adults are assumed to result from chronic inflammation. The aim of this thesis was to investigate if infection-induced chronic inflammation plays a role in prostate carcinogenesis.

Our results revealed a greater infiltration of the bacterium Propionibacterium acnes in the prostate tissue obtained from men with prostate cancer compared to men without any histological evidence of the disease. These findings indicate that prostate cancer could potentially be included in the list of cancers with an infectious etiology.

Further, we investigated whether chronic inflammation has a role in disease progression. Our results demonstrated that men with lethal prostate cancer had pronounced infiltration of immune cells with suppressive function of the anti-tumor immune response compared to men with a more indolent prostate cancer.

Confirmation of our results may open up avenues for targeted prostate cancer treatment by offering men with chronic inflammation alternative therapies such as anti-inflammatory drugs. If the involvement of P. acnes in prostate cancer development is replicated in other studies, vaccination therapies may be feasible. To further individualize prostate cancer therapy, bolstering the anti-tumor immune response in order to reduce tumor progression may be determined to be advantageous for some patients.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro universitet , 2013. , s. 65
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 86
Nyckelord [en]
Prostate cancer, chronic inflammation, CD4 helper T cells, CD8 cytotoxic T cells, regulatory T cells, Propionibacterium acnes
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Medicin
Identifikatorer
URN: urn:nbn:se:oru:diva-28466ISBN: 978-91-7668-920-2 (tryckt)OAI: oai:DiVA.org:oru-28466DiVA, id: diva2:612760
Disputation
2013-05-31, Wilandersalen, Universitetssjukhuset i Örebro, Södra Grev Rosengatan 18, 703 62 Örebro, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2013-03-25 Skapad: 2013-03-25 Senast uppdaterad: 2017-10-17Bibliografiskt granskad
Delarbeten
1. Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer
Öppna denna publikation i ny flik eller fönster >>Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer
Visa övriga...
2011 (Engelska)Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, nr 10, s. 2280-2287Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. Methods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. Results: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). Conclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. Impact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease. Cancer Epidemiol Biomarkers Prev; 20(10); 2280-7. (C) 2011 AACR.

Nationell ämneskategori
Urologi och njurmedicin
Forskningsämne
Medicin
Identifikatorer
urn:nbn:se:oru:diva-30105 (URN)10.1158/1055-9965.EPI-11-0373 (DOI)000295717900034 ()
Tillgänglig från: 2013-08-02 Skapad: 2013-08-02 Senast uppdaterad: 2018-05-05Bibliografiskt granskad
2. Multilocus sequence typing and repetitive-sequence-based PCR (DiversiLab) for molecular epidemiological characterization of Propionibacterium acnes isolates of heterogeneous origin
Öppna denna publikation i ny flik eller fönster >>Multilocus sequence typing and repetitive-sequence-based PCR (DiversiLab) for molecular epidemiological characterization of Propionibacterium acnes isolates of heterogeneous origin
Visa övriga...
2012 (Engelska)Ingår i: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 18, nr 4, s. 392-399Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Propionibacterium acnes is a gram-positive bacillus predominantly found on the skin. Although it is considered an opportunistic pathogen it is also been associated with severe infections. Some specific P. acnes subtypes are hypothesized to be more prone to cause infection than others. Thus, the aim of the present study was to investigate the ability to discriminate between P. acnes isolates of a refined multilocus sequence typing (MLST) method and a genotyping method, DiversiLab, based on repetitive-sequence-PCR technology.

The MLST and DiversiLab analysis were performed on 29 P. acnes isolates of diverse origins; orthopedic implant infections, deep infections following cardiothoracic surgery, skin, and isolates from perioperative tissue samples from prostate cancer. Subtyping was based on recA, tly, and Tc12S sequences.

The MLST analysis identified 23 sequence types and displayed a superior ability to discriminate P. acnes isolates compared to DiversiLab and the subtyping. The highest discriminatory index was found when using seven genes. DiversiLab was better able to differentiate the isolates compared to the MLST clonal complexes of sequence types.

Our results suggest that DiversiLab can be useful as a rapid typing tool for initial discrimination of P. acnes isolates. When better discrimination is required, such as for investigations of the heterogeneity of P. acnes isolates and its involvement in different pathogenic processes, the present MLST protocol is valuable.

Ort, förlag, år, upplaga, sidor
Elsevier, 2012
Nyckelord
Propionibacterium acnes; Multilocus sequence typing (MLST); DiversiLab; Discrimination index; Molecular epidemiology
Nationell ämneskategori
Mikrobiologi inom det medicinska området
Forskningsämne
Mikrobiologi
Identifikatorer
urn:nbn:se:oru:diva-25346 (URN)10.1016/j.anaerobe.2012.04.015 (DOI)000307688500003 ()22609518 (PubMedID)2-s2.0-84864371234 (Scopus ID)
Anmärkning

Funding Agencies:

Örebro County Council Research Committee

Foundation for Medical Research at Orebro University Hospital, Sweden 

Tillgänglig från: 2012-08-27 Skapad: 2012-08-27 Senast uppdaterad: 2018-04-16Bibliografiskt granskad
3. Prevalence and typing of Propionibacterium acnes in prostate tissue obtained from men with prostate cancer and from health controls
Öppna denna publikation i ny flik eller fönster >>Prevalence and typing of Propionibacterium acnes in prostate tissue obtained from men with prostate cancer and from health controls
Visa övriga...
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Urologi och njurmedicin
Forskningsämne
Medicin
Identifikatorer
urn:nbn:se:oru:diva-30106 (URN)
Tillgänglig från: 2013-08-02 Skapad: 2013-08-02 Senast uppdaterad: 2017-10-17Bibliografiskt granskad
4. CD4 helper T cells, CD8 cytotoxic T cells, and FOXP3(+) regulatory T cells with respect to lethal prostate cancer
Öppna denna publikation i ny flik eller fönster >>CD4 helper T cells, CD8 cytotoxic T cells, and FOXP3(+) regulatory T cells with respect to lethal prostate cancer
Visa övriga...
2013 (Engelska)Ingår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 26, nr 3, s. 448-455Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Prostate cancer represents a major contributor to cancer mortality, but the majority of men with prostate cancer will die of other causes. Thus, a challenge is identifying potentially lethal disease at diagnosis. Conflicting results have been reported when investigating the relationship between infiltration of lymphocytes and survival in prostate cancer. One of the mechanisms suggested is the recruitment of regulatory T cells (T(regs)), a subpopulation of T cells that have a role in promoting tumor growth. T(regs) counteract tumor rejection through suppressive functions on the anti-immune response but their prognostic significance is still unknown. We report here the results of a conducted case-control study nested in a cohort of men treated with transurethral resection of the prostate and diagnosed incidentally with prostate cancer. Cases are men who died of prostate cancer (n=261) and controls are men who survived >10 years after their diagnosis (n=474). Infiltration of both T(helper) and T(cytotoxic) cells was frequently observed and the majority of the T(regs) were CD4(+). T(helper) or T(cytotoxic) cells were not associated with lethal prostate cancer. However, we found a nearly twofold increased risk of lethal prostate cancer when comparing the highest with the lowest quartile of CD4(+) T(reg) cells (95% confidence interval: 1.3-2.9). Our conclusion is that men with greater numbers of CD4(+) T(regs) in their prostate tumor environment have an increased risk of dying of prostate cancer. Identification of CD4(+) T(regs) in tumor tissue may predict clinically relevant disease at time of diagnosis independently of other clinical factors.Modern Pathology advance online publication, 5 October 2012; doi:10.1038/modpathol.2012.164.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2013
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Medicin
Identifikatorer
urn:nbn:se:oru:diva-27801 (URN)10.1038/modpathol.2012.164 (DOI)000315664100015 ()23041830 (PubMedID)2-s2.0-84875209263 (Scopus ID)
Tillgänglig från: 2013-03-01 Skapad: 2013-03-01 Senast uppdaterad: 2018-08-27Bibliografiskt granskad

Open Access i DiVA

sammanfattning(13011 kB)387 nedladdningar
Filinformation
Filnamn SUMMARY01.pdfFilstorlek 13011 kBChecksumma SHA-512
f187e0b0a5bf5a81a865cf0d06b41326948dabc1196a4c44ce40cd3e472196146b0ea56f744df6f24d78eb14e727ba8753653dc4eca28abb3e29110d0af6b276
Typ summaryMimetyp application/pdf
omslag(1599 kB)84 nedladdningar
Filinformation
Filnamn COVER01.pdfFilstorlek 1599 kBChecksumma SHA-512
d7cdcea842624388118efe0ed7d8bc58987943330ff7d6283adb7f965603626c48fde367221b0d552a5d54f55493c026dc4c67084f99737ac47cd5a5dcbdf6b5
Typ coverMimetyp application/pdf
spikblad(42 kB)39 nedladdningar
Filinformation
Filnamn SPIKBLAD01.pdfFilstorlek 42 kBChecksumma SHA-512
36525253e21ebc0b6fc59dddf923e3e59c2a31112371573520bac186751600ab8d7bb022cd76ac3fa391343622fc0a3dc6641ddaa1bf15e6a8c2f7d1f9dd3905
Typ spikbladMimetyp application/pdf

Personposter BETA

Davidsson, Sabina

Sök vidare i DiVA

Av författaren/redaktören
Davidsson, Sabina
Av organisationen
Institutionen för hälsovetenskap och medicin
Medicin och hälsovetenskap

Sök vidare utanför DiVA

GoogleGoogle Scholar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

isbn
urn-nbn

Altmetricpoäng

isbn
urn-nbn
Totalt: 772 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf