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| 2. |
- Aaron, F. D., et al.
(författare)
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Combined measurement and QCD analysis of the inclusive e(+/-)p scattering cross sections at HERA
- 2010
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q(2), and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.
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| 3. |
- Aaron, F. D., et al.
(författare)
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Events with an isolated lepton and missing transverse momentum and measurement of W production at HERA
- 2010
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2010:3, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- A search for events containing an isolated electron or muon and missing trans verse momentum produced in e(+/-)p collisions is performed with the H1 and ZEUS detectors at HERA. The data were taken in the period 1994-2007 and correspond to an integrated luminosity of 0.98 fb(-1). The observed event yields are in good overall agreement with the Standard Model prediction, which is dominated by single W production. In the e(+)p data, at large hadronic transverse momentum P-T(X) > 25GeV, a total of 23 events are observed compared to a prediction of 14.0 +/- 1.9. The total single W boson production cross section is measured as 1.06 +/- 0.16 (stat.) +/- 0.07 (sys.) pb, in agreement with an Standard Model (SM) expectation of 1.26 +/- 0.19 pb.
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| 4. |
- Aaron, F. D., et al.
(författare)
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Multi-leptons with high transverse momentum at HERA
- 2009
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Ingår i: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
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Tidskriftsartikel (refereegranskat)abstract
- Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb(-1). The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e(+)p collision data with a scalar sum of the lepton transverse momenta above 100 GeV while 1.94 +/- 0.17 events are expected. Such events are not observed in e(-)p collisions for which 1.19 +/- 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions.
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| 5. |
- Aljabery, Firas, et al.
(författare)
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M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer
- 2018
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 36:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTumor-associated macrophages (TAMs) constitute a subset of nonneoplastic cells in tumor stroma and influence cancer progression in solid tumors. The clinical significance of TAMs in urinary bladder cancer(UBC) is controversial.MethodsWe prospectively studied 103 patients with stage pT1–T4 UBC treated with cystectomy and pelvic lymph node dissection. Tumor sections were immunostained with M2-specific macrophage marker CD163 and proliferation marker Ki-67. The expression of these markers in cancer cells as well as macrophage infiltration (MI) in tumor stroma was analyzed in relation to clinical data and outcome.ResultsThe mean rate of CD163 and Ki-67 expressed by cancer cells were 35% and 78%, respectively. With borderline significance, MI was associated with lower rate of lymph node metastasis (P = 0.06). CD163 expression in cancer cells was proportional to MI (P<0.014). Patients with CD163-positive tumors and strong MI had significantly longer cancer-specific survival (CSS) (76 months), compared to patient with CD163-positive tumors and weak MI (28 months) (P = 0.02).ConclusionsM2-specific MI tends to be inversely correlated with LN metastasis and improved CSS in UBC. MI might have protective impact in CD163-positive tumors. Expression of CD163 in cancer cells is significantly correlated with MI and might have a tumor promoting impact.
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| 6. |
- Aljabery, Firas, et al.
(författare)
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Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer : a prospective clinical study.
- 2017
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Ingår i: BJU International. - : Wiley-Blackwell Publishing Inc.. - 1464-4096 .- 1464-410X. ; 120:3, s. 329-336
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.
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| 7. |
- Aljabery, Firas
(författare)
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Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.
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| 8. |
- Aljabery, Firas, et al.
(författare)
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The expression profile of p14, p53 and p21 in tumour cells is associated with disease-specific survival and the outcome of postoperative chemotherapy treatment in muscle-invasive bladder cancer
- 2018
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 36:12, s. 530.e7-530.e18
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We investigated the effects of alterations in the biological markers p14, p53, p21, and p16 in relation to tumour cell proliferation, T-category, N- category, lymphovascular invasion, and the ability to predict prognosis in patients with muscle-invasive bladder cancer (MIBC) treated with cystectomy and, if applicable, chemotherapy.Materials and methods: We prospectively studied patients with urinary bladder cancer pathological stage pT1 to pT4 treated with cystectomy, pelvic lymph node dissection and postoperative chemotherapy. Tissue microarrays from paraffin-embedded cystectomy tumour samples were examined for expression of immunostaining of p14, p53, p21, p16 and Ki-67 in relation to other clinical and pathological factors as well as cancer-specific survival.Results: The median age of the 110 patients was 70 years (range 51-87 years), and 85 (77%) were male. Pathological staging was pT1 to pT2 (organ-confined) in 28 (25%) patients and pT3 to pT4 (non-organ-confined) in 82 (75%) patients. Lymph node metastases were found in 47 patients (43%). P14 expression was more common in tumours with higher T-stages (P = 0.05). The expression of p14 in p53 negative tumours was associated with a significantly shorter survival time (P=0.003). Independently of p53 expression, p14 expression was associated with an impaired response to chemotherapy (P=0.001). The expression of p21 in p53 negative tumours was associated with significantly decrease levels of tumour cell proliferation detected as Ki-67 expression (P=0.03).Conclusions: The simultaneous expression of the senescence markers involved in the p53-pathway shows a more relevant correlation to the pathological outcome of MIBC than each protein separately. P14 expression in tumours with non-altered (p53-) tumours is associated with poor prognosis. P14 expression is associated with impaired response to chemotherapy. P21 expression is related to decreased tumour cell proliferation.
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| 9. |
- Anasontzis, George E, 1980, et al.
(författare)
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Effects of temperature and glycerol and methanol-feeding profiles on the production of recombinant galactose oxidase in Pichia pastoris
- 2014
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Ingår i: Biotechnology Progress. - : Wiley. - 1520-6033 .- 8756-7938. ; 30:3, s. 728-735
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Tidskriftsartikel (refereegranskat)abstract
- Optimization of protein production from methanol-induced Pichia pastoris cultures is necessary to ensure high productivity rates and high yields of recombinant proteins. We investigated the effects of temperature and different linear or exponential methanol-feeding rates on the production of recombinant Fusarium graminearum galactose oxidase (EC 1.1.3.9) in a P. pastoris Mut+ strain, under regulation of the AOX1 promoter. We found that low exponential methanol feeding led to 1.5-fold higher volumetric productivity compared to high exponential feeding rates. The duration of glycerol feeding did not affect the subsequent product yield, but longer glycerol feeding led to higher initial biomass concentration, which would reduce the oxygen demand and generate less heat during induction. A linear and a low exponential feeding profile led to productivities in the same range, but the latter was characterized by intense fluctuations in the titers of galactose oxidase and total protein. An exponential feeding profile that has been adapted to the apparent biomass concentration results in more stable cultures, but the concentration of recombinant protein is in the same range as when constant methanol feeding is employed. (c) 2014 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 30:728-735, 2014
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| 10. |
- Augsten, Martin, et al.
(författare)
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Cancer-Associated Fibroblasts Expressing CXCL14 Rely upon NOS1-Derived Nitric Oxide Signaling for Their Tumor-Supporting Properties
- 2014
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Ingår i: Cancer Research. - 1538-7445. ; 74:11, s. 2999-3010
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Tidskriftsartikel (refereegranskat)abstract
- Cancer-associated fibroblasts (CAF) stimulate tumor growth and metastasis. Signals supporting CAF function are thus emerging as candidate therapeutic targets in the tumor microenvironment. The chemokine CXCL14 is a potent inducer of CAF protumorigenic functions. This study is aimed at learning how the protumoral functions of CXCL14-expressing CAF are maintained. We found that the nitric oxide synthase NOS1 is upregulated in CXCL14-expressing CAF and in fibroblasts stimulated with CXCL14. Induction of Nos1 was associated with oxidative stress and occurred together with activation of NRF2 and HIF1 alpha signaling in CXCL14-expressing CAF. Genetic or pharmacologic inhibition of NOS1 reduced the growth of CXCL14-expressing fibroblasts along with their ability to promote tumor formation following coinjection with prostate or breast cancer cells. Tumor analysis revealed reduced macrophage infiltration, with NOS1 downregulation in CXCL14-expressing CAF and lymphangiogenesis as a novel component of CXCL14-promoted tumor growth. Collectively, our findings defined key components of a signaling network that maintains the protumoral functions of CXCL14-stimulated CAF, and they identified NOS1 as intervention target for CAF-directed cancer therapy. (C) 2014 AACR.
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