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Sökning: WFRF:(Karlsson Mats G 1960 )

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1.
  • Hellquist, H. B., et al. (författare)
  • Bcl-2 immunoreactivity in salivary gland neoplasms is unrelated to the expression of mRNA for natural killer cell stimulatory cytokines interleukin (IL)-2 and IL-12
  • 1996
  • Ingår i: Virchows Archiv. - New York, USA : Springer. - 0945-6317 .- 1432-2307. ; 429:2-3, s. 149-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. We aimed to study the mRNA expression of interleukin (IL)-2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. T IL were predominantly composed of T lymphocytes and NK cells. We found evidence for the homing of T cells, and for generation of NK cells in the vicinity of the tumours. mRNA for IL-2 and IL-12, were identified but IL-4 mRNA was not found. The cytokine profiles and the composition of TIL of the two tumour categories were indistinguishable, suggesting that these host-response variables do not explain the differences in biological behaviour of these particular tumours. The results support a shift towards Th 1 (T helper 1) cells and interferon-gamma production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases. Most infiltrating lymphocytes showed strong expression of bcl-2; an interesting observation with regard to lymphocytic apoptosis in neoplastic diseases. The immunoreactivity for the bcl-2 protein varied considerably between and within tumours, and almost all benign tumours showed strong bcl-2 positively whereas several of the malignant tumours showed weak or absent staining. The variable expression of bcl-2 protein suggests a different susceptibility of tumour cells to apoptosis. The results also indicate that bcl-2 cannot pla a major role as protective agent in the specific apoptotic pathway induced by NK cells.
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2.
  • Mattsson, Johanna Sofia Margareta, 1985-, et al. (författare)
  • Prognostic impact of COX-2 in non-small cell lung cancer : a comprehensive compartment-specific evaluation of tumor and stromal cell expression
  • 2015
  • Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 356:2, s. 837-845
  • Tidskriftsartikel (refereegranskat)abstract
    • Cyclooxygenase-2 (COX-2) is an enzyme that has been extensively investigated as a prognostic marker in cancer. In non-small cell lung cancer (NSCLC) previous results regarding the prognostic impact of COX-2 expression are inconsistent. Therefore we evaluated the association between transcript levels and overall survival in nine publicly available gene expression data sets (total n = 1337) and determined in situ compartment-specific tumor and stromal cell protein expression in two independent cohorts (n = 616). Gene expression did not show any correlation with clinical parameters or with overall survival. Protein expression in tumor and stromal cells did not correlate with any clinical parameter or with overall survival in one of the analyzed cohorts, while a significant association of high stromal expression with longer survival was observed in both univariate and multivariate analysis in the other cohort. Stromal expression of COX-2 has not been separately evaluated in NSCLC previously and may be a subject of further investigation, whereas the presented findings from this comprehensive compartment specific evaluation clearly reject the hypothesis of COX-2 tumor cell expression having a prognostic value in NSCLC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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3.
  • Dreifaldt, Mats, et al. (författare)
  • The ‘‘no-touch’’ harvesting technique for vein grafts in coronary artery bypass surgery preserves an intact vasa vasorum
  • 2011
  • Ingår i: The Internet Journal of Thoracic and Cardiovascular Surgery. - New York, USA : Elsevier. - 1524-0274 .- 0022-5223. ; 141:1, s. 145-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Our objective was to evaluate the impact of vein graft harvesting technique on structure and function of vasa vasorum.Methods: Paired segments of great saphenous veins harvested either with conventional harvesting technique or no-touch technique were obtained from 9 consecutive patients undergoing coronary artery bypass grafting. Quantitative measurements, using immunohistochemistry and morphometry, were performed. Ultrastructural analyses of vasa vasorum were performed with electron microscopy. Video footage of superficial vasa vasorum in an implanted saphenous vein graft harvested with the no-touch technique was captured during a coronary bypass operation and is presented for online viewing.Results: The total area of vasa vasorum in vein grafts harvested with the conventional technique was significantly reduced both in the media (P¼.007) and in the adventitia (P¼.014) compared with vein grafts harvested with the no-touch technique. Ultrastructural findings indicated that the no-touch technique preserved an intact vasa vasorum whereas the conventional technique did not. Video footage showed retrograde flow in the vasa vasorum in vein graft harvested with the no-touch technique.Conclusions: These findings showthat the no-touch technique for saphenous vein graft harvesting for coronary bypass grafting preserves an intact vasa vasorum. This could represent one of the mechanisms underlying the improved patency of saphenous vein grafts harvested with this technique.
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4.
  • Hadgu, Endale, et al. (författare)
  • Distribution and characteristics of androgen receptor (AR) in breast cancer among women in Addis Ababa, Ethiopia : A cross sectional study
  • 2020
  • Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Evaluation of the role of androgen receptor (AR) in the biology of breast cancer is an emerging area of research. There are compelling evidences that AR expression may be used to further refine breast cancer molecular subtyping with prognostic and therapeutic implications. Many studies indicated co-expression of AR with the hormonal receptors in breast cancer has a favorable prognosis. AR is also investigated by many researchers as a potential therapeutic target in treatment of breast cancer. Studies on the frequency and distribution of AR in breast cancer among Africans is barely available. Given the heightened interest to understand its role in breast cancer, we determined AR expression and assessed its association with clinicopathological parameters among Ethiopian women. In this study, 112 newly diagnosed patient with invasive breast cancer at Tikur Anbessa Specialized Hospital were enrolled. Immunohistochemical assessment of AR, ER, PR, Ki67 and HER2 were performed using tissue microarrays (TMA) constructed from their primary tumor block. Out of the 112 participants, 91 (81%) were positive for AR expression and the remaining 21 participants (19%) were negative for AR expression. Expression of AR in ER+, HER2+ and TNBC cases were 93%, 83% and 48% respectively. Our study reveals AR is expressed in a significant number of breast cancers patients and this may indicate that breast cancers cases in Ethiopia have favorable prognosis and could benefit from progresses in AR targeted treatments. Since AR expression has important consequences on the prognosis and treatment of breast cancer, further studies with an increased number of participants is necessary to confirm our reports.
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5.
  • Jahnson, S., et al. (författare)
  • p53 and Rb immunostaining in locally advanced bladder cancer : relation to prognostic variables and predictive value for the local response to radical radiotherapy
  • 1995
  • Ingår i: European Urology. - Basel, Switzerland : S. Karger. - 0302-2838 .- 1873-7560. ; 28:2, s. 135-142
  • Tidskriftsartikel (refereegranskat)abstract
    • The association between known prognostic variables and altered immunostaining for the nuclear proteins retinoblastoma (Rb) and p53 was studied in a homogeneous series of locally advanced bladder cancer. The predictive value of this immunostaining for the local response to intended radical radiotherapy was investigated. Among 262 patients treated with intended radical radiotherapy between 1967 and 1986, a total of 154 patients were evaluable with respect to local response to treatment. The paraffin-embedded specimen from the tumour prior to irradiation was immunostained with the monoclonal antibodies PMG3-245 for Rb and 1801 for p53 nuclear proteins after heating in a microwave oven for 40 min at 650 W. An altered expression of Rb and p53 was observed in 18 and 42% of the tumours, respectively. p53 overexpression was associated with higher tumour grade. However, the results of the p53 and Rb immunostaining procedures had no predictive value for tumor response to radiation treatment, local control or cancer-specific mortality.
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6.
  • Karlsson, Christina, et al. (författare)
  • Effects of long-term storage on the detection of proteins, DNA, and mRNA in tissue microarray slides
  • 2011
  • Ingår i: Journal of Histochemistry and Cytochemistry. - : Sage Publications. - 0022-1554 .- 1551-5044. ; 59:12, s. 1113-1121
  • Tidskriftsartikel (refereegranskat)abstract
    • Storage of tissue slides has been claimed to induce dramatically reduced antigen detection particularly for immunohistochemistry (IHC). With tissue microarrays, the necessity to serially cut blocks in order to obtain as much material as possible is obvious. The presumed adverse effect of storage might hamper such an approach. The authors designed an experimental setting consisting of four different storage conditions with storage time of tissue slides of up to 1 year. Detection of proteins, DNA, and mRNA was performed using IHC and in situ hybridization techniques. Slight but significant changes in IHC occurred over time. The most important factor is the primary antibody used: four showed no significant changes, whereas limited decreases in 8 antibodies could be detected by image analysis. Whether the antigen was nuclear or cytoplasmic/membranous did not matter. No major differences between different storage conditions could be shown, but storage at 4C was overall the best procedure. Furthermore, gene copy number aberrations, chromosomal translocations, and the presence of mRNA could be detected on slides stored up to 1 year. In conclusion, in tissues optimally formalin fixed and using modern histological techniques, only minute changes in tissue antigenicity are induced by long-term storage.
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7.
  • Karlsson, Christina, 1968-, et al. (författare)
  • Oestrogen receptor ss in NSCLC : prevalence, proliferative influence, prognostic impact and smoking
  • 2012
  • Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - Malden, USA : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 120:6, s. 451-458
  • Tidskriftsartikel (refereegranskat)abstract
    • In non-small-cell lung carcinoma (NSCLC) there are gender differences. The female gender is associated with more adenocarcinomas (ADCA), among both smokers and non-smokers compared to men. Women with NSCLC have a better prognosis compared to men, regardless of other factors. A possible role for oestrogen receptor (ER) signalling has been proposed. The role for ER beta in NSCLC is still not clear, especially concerning the impact of smoking. In a material of NSCLC (n = 262), ER beta and cyclins A1 and A2 were studied by immunohistochemistry on formalin-fixed paraffin embedded tissue. In 137 of those cases, frozen material was available, on which expression analysis of ESR2 (ER beta) and cyclin A1 were performed. Data were correlated to histology, gender, smoking habits, stage and clinical outcome. ER beta was expressed in 86% of the cases. ER beta was most frequently expressed in Stage I ADCAs, especially in male subjects. A correlation between ER beta expression and cyclins was observed in ADCA, also with a male predominance. ER beta transcripts had a positive prognostic impact in ADCA. ER beta transcripts were increased in NSCLC among smokers compared to non-smokers. In conclusion, our data support a role for ER beta in lung ADCAs, proposing a role for ER beta in lungcarcinogenesis, especially among smokers.
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9.
  • Mattsson, Johanna Sofia Margareta, 1985-, et al. (författare)
  • Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer
  • 2016
  • Ingår i: BMC Cancer. - London, United Kingdom : Springer Science and Business Media LLC. - 1471-2407. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data.Methods: ALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients.Results: ALK rearrangements were detected in 1.7% in the complete cohort and 2.0% in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.9% and 1.5% when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (>99%), while the sensitivity was between 69% (Ventana) and 62% (in house Dako protocol). Furthermore, only 67% of the ALK IHC positive cases were positive in both IHC assays. Gene expression analysis revealed that 6/194 (3%) tumors showed high ALK gene expression (≥6AU) and of them only three were positive by either FISH or IHC.Conclusion: The overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC.
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10.
  • Risberg, Björn, et al. (författare)
  • Dissociated expression of Bcl-2 and Ki-67 in endometrial lesions : diagnostic and histogenetic implications
  • 2002
  • Ingår i: International Journal of Gynecological Pathology. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0277-1691 .- 1538-7151. ; 21:2, s. 155-160
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of the present study was to analyze the expression of the proliferation marker, Ki-67, and the anti-apoptotic protein, bcl-2, in various endometrial lesions. Ki-67 and bcl-2 expressions were studied in 194 specimens of endometrial hyperplasia, polyps, carcinomas, and cyclic endometrium from a defined geographic area. Results were statistically analyzed with respect to marker expression, localization to the stromal or glandular component, and intraglandular topography. The lowest glandular Ki-67 expression was seen in secretory endometrium, in polyps, and in atypical hyperplasia. The Ki-67 score was significantly higher and less heterogeneous in endometrial carcinomas than in hyperplasia (p<0.001). Endometrial hyperplasia of all types was characterized by a markedly heterogeneous glandular expression of Ki-67. The glandular expression of bcl-2 was highest in proliferative endometrium and polyps. Bcl-2 expression was significantly lower in adenocarcinomas than in hyperplastic lesions (p=0.002). Ki-67 and bcl-2 expression showed a significant association in proliferative endometrium (p=0.003). Endometrial polyps demonstrated a unique pattern of very low expression of Ki-67 and high bcl-2 expression in both stroma and glands. Our findings indicate that an imbalance between proliferation and apoptosis may be an important factor in the development of different endometrial lesions, benign as well as malignant. The specific finding of inter- and intraglandular Ki-67 heterogeneity may be valuable as an adjunct to morphology in the differential diagnosis of endometrial hyperplasia.
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11.
  • Stjernström, Annika, et al. (författare)
  • Alterations of INPP4B, PIK3CA and pAkt of the PI3K pathway are associated with squamous cell carcinoma of the lung
  • 2014
  • Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 3:2, s. 337-348
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to investigate how alterations in the PI3K pathway correlate with non-small cell lung cancer subtypes squamous cell carcinoma (SSC) and adenocarcinoma (ADCA). We analyzed copy number variation and protein expression of INPP4B, protein expression of pAkt, PDPK1, and PTEN and mutational status of PIK3CA and PTEN in 180 cases. Nineteen% displayed loss of INPP4B copy, whereas 47% lacked expression, both showing correlation with SCC. Elevated pAkt expression was seen in 63% of all cases, also correlating to SCC. PDPK1 was expressed in 70%, more in male than female patients. Regarding PTEN, 50% displayed loss of expression, of which seven were identified with mutations in the phosphatase domain. We detected nine cases (5%) of PIK3CA mutations, all identified as the E545K hot spot mutation in the helical domain, all except one in SCC. When analyzing all PI3K pathway components together, we show that patients with at least one alteration in the PI3K pathway are twice as likely to have SCC, than ADCA. Interestingly, we also found a strong correlation between high pAkt expression and PTEN expression. As comparison, we also analyzed mitogen-activated protein kinase (MAPK) pathway genes, where we identified fifteen KRAS mutations (8%) and one BRAF mutation (1%), significantly associated to ADCA. No association was found to the Gly972Arg polymorphism of IRS-1, involved in activation of both PI3K and MAPK pathways. In conclusion, we show here that several components of the PI3K pathway, alone and in combination, are correlated to development of SCC of the lung.
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12.
  • Andersson, Patiyan, 1978-, et al. (författare)
  • PIK3CA, HRAS and KRAS gene mutations in human penile cancer
  • 2008
  • Ingår i: Journal of Urology. - New York, USA : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 179:5, s. 2030-2034
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways. Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors. Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma. Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.
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13.
  • Bergengren, Lovisa, 1972-, et al. (författare)
  • Effectiveness and costs of an implemented primary HPV cervical screening programme in Sweden : A population based cohort study
  • 2022
  • Ingår i: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 25
  • Tidskriftsartikel (refereegranskat)abstract
    • Swedish guidelines recommend cervical screening with primary HPV for women ≥ 30 years of age. The aim of this study was to compare an implemented HPV cervical screening programme in the Region of Örebro County from September 1, 2016, with the former cytology-based screening programme.The clinical effectiveness by means of number of high-grade squamous intraepithelial lesions (HSILs) and cervical cancer cases detected in histology within 12 months after the screening test, together with cost implications were the main outcomes. Data were retrieved from the Swedish National Cervical Screening Registry between the years 2014-2015 (cytology based screening) and 2017-2018(HPV based screening), including screening information such as invitations and cytology and histology diagnoses.The detection rate of HSIL + among women ≥ 30 years of age was 1.2 times higher with HPV screening, but data revealed an increase in direct colposcopy referral rate by 54% and a higher percentage of irrelevant findings (≤LSIL). Screening based on HPV for women ≥ 30 has increased yearly cost from 1 to 1.3 million EUR, while increasing the number of HSIL + identified. Two thirds of the total costs are from visits for screening samples in the programme.HPV screening detected more cases of HSIL + compared to cytology screening among women ≥ 30 although high colposcopy rate, high rate of clinical irrelevant findings and higher costs were shown in the HPV-based screening programme, which implies that alterations in the screening programme in the future are important to consider.
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14.
  • Bergengren, Lovisa, 1971-, et al. (författare)
  • HPV-based screening for cervical cancer among women 55-59 years of age
  • 2019
  • Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 14:6
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: Many cervical cancers occurs among women over 65 and prevalence of HPV genotypes in this age cohort is sparingly studied. One aim of this study was to study the prevalence and distribution of HPV genotypes in women 55-59 years, with normal cytology when exiting the screening program. Secondly, HPV clearance as well as the value of HPV genotyping and/or liquid based cytology as triage tests for identifying histological dysplasia among women with persistent HPV was studied.METHODS: Women that exited the screening program with normal cytology, between the years 2012-2014, in Örebro County, Sweden, were invited to this study. A total of 2946 samples were analyzed with a broad-spectrum assay to detect both hrHPV and lrHPV in order to investigate the distribution of genotypes. In the consent group, women with a positive hrHPV test were offered a follow-up test and a cone biopsy for histological confirmation, and a follow up sample 6 months post cone.RESULTS: The overall prevalence of hrHPV was 7.4% and 59% of them remained hrHPV positive in a follow-up test after 12 months. A total of 99 women had a cone biopsy done, where 19% showed histological dysplasia. HPV 53 was the most common genotype, and among women with histology confirmed LSIL or HSIL, HPV 31 was most common. A positive hrHPV result showed a PPV of 25% for LSIL+ and 12.5%for HSIL+. Using detection of HPV 16/18 genotypes as a triage test for hrHPV positive tests, indicated FNR for histological LSIL+ and HSIL+ of 94% and 87.5% respectively, whilst triage based on cervical cytology had a FNR of 69% for LSIL+ and 37.5% for HSIL+.CONCLUSION: The most common hrHPV genotypes among women 55-59 years of age were non HPV16/18 genotypes, and in this population, these genotypes represented most of the histological verified HSIL lesions. This result does not support the proposition of a HPV 16/18 triaging test after a positive hrHPV test as a marker of histological HSIL+ cervical lesions in women over 55 years of age. Similarly, cytological triage after a positive hrHPV showed no additional benefit in this population. Specific triaging tests should be validated to follow post-menopausal women with a positive hrHPV test.
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16.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate
  • 2013
  • Ingår i: BMC Cancer. - London, United Kingdom : BioMed Central (BMC). - 1471-2407. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate. Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers. Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified. Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.
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19.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer
  • 2016
  • Ingår i: Infectious Agents and Cancer. - London, United Kingdom : BioMed Central (BMC). - 1750-9378. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.
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20.
  • Davidsson, Åke, 1956-, et al. (författare)
  • Allergen-induced changes of B-cell phenotypes in patients with allergic rhinitis
  • 1994
  • Ingår i: Rhinology. - Amsterdam, Netherlands : International Rhinologic Society. - 0300-0729 .- 1996-8604. ; 32:4, s. 184-190
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated sub-populations of B-lymphocytes in nasal mucosa and peripheral blood of 17 patients with seasonal allergic rhinitis (birch pollen) and 10 controls. The study included provocation with allergen during the non-pollen season, during which no participant used medication. Samples were also taken during the pollen season. Subsets of B-cells as expressed by different CD antigens were investigated by immunohistochemistry on frozen sections and by flow cytometry of peripheral blood. Nasal CD23+ B-cells decreased in allergic patients during provocation, indicating that mature virgin CD23+ B-cells switch into a memory B-cell phenotype with loss of CD23 expression. This indicates differentiation towards cells that can represent a local source for IgE synthesis. No decrease was observed during the pollen season when the patients used medication. Serum IgE was significantly higher in allergic patients on all occasions. The observed up-regulation of CD40 expression on peripheral blood B-cells in allergic patients during the pollen season clearly indicate B-cell activation. Furthermore, a relative increase of CD19+ B-cells was observed in peripheral blood during provocation. Upregulation (by IL-4) of CD40 on B-cells which then may be stimulated by gp39 (CD40 ligand) can constitute an early and important event in the IgE-mediated allergic reaction.
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21.
  • Davidsson, Åke, 1956-, et al. (författare)
  • Positive identification in situ of mRNA expression of IL-6, and IL-12, and the chemotactic cytokine RANTES in patients with chronic sinusitis and polypoid disease. Clinical relevance and relation to allergy
  • 1996
  • Ingår i: Acta Oto-Laryngologica. - Oxfordshire, United Kingdom : Taylor & Francis. - 0001-6489 .- 1651-2251. ; 116:4, s. 604-610
  • Tidskriftsartikel (refereegranskat)abstract
    • Interleukins 6 (IL-6) and 12 (IL-12), and the chemoattractant chemokine RANTES were studied in ethmoidal mucosa, using reverse transcriptase polymerase chain reaction. The 49 patients had chronic sinusitis or nasal/paranasal polyposis, and some also allergy. To the best of our knowledge, this is the first study that demonstrates RANTES and IL-12 on mRNA level in human sinonasal mucosa in situ. mRNA for IL-6, IL-12 and RANTES were detected in 2, 8 and 6 patients with chronic sinusitis, respectively, and in mucosa from patients with polyposis a positive expression was observed in 4, 14 and 10 cases. There were no statistically significant differences. Analysing the entire group of 49 patients, disregarding type of mucosal disease, the number of patients with positive RANTES was significantly higher than that for IL-6. Similarly, IL-12 positivity was more frequently expressed than IL-6. mRNA for IL-6 was expressed in only 2 of the allergic patients. The cytokine production studied thus seems to be unrelated to the clinically defined entities. There is thus a local production in human diseased sinonasal mucosa of RANTES, as well as of IL-6 and IL-12. The local production of RANTES is an important prerequisite for recruitment and migration of inflammatory cells into the tissue. IL-12 is a co-stimulator of antigen-specific responses of established T helper 1 (Th1) clones, and regulates the responsiveness of the clones to a number of T cell growth factors. The study supports a shift towards Th1 cells in these disease entities.
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22.
  • Dorofte, Luiza, 1982-, et al. (författare)
  • Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care
  • 2022
  • Ingår i: Virchows Archiv. - : Springer. - 0945-6317 .- 1432-2307. ; 480:4, s. 879-886
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02-0.48) and 0.23 (range: 0.07-0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02-0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen's kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors. 
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23.
  • Fergedal, May, et al. (författare)
  • Differences in CD14 and alpha-naphthyl acetate esterase positivity and relation to prognosis in AML
  • 1998
  • Ingår i: Leukemia Research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 22:1, s. 25-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Alpha-naphthyl acetate esterase (ANAE) and CD14 expression, used for determination of monocytic cells, were compared and related to prognosis in 65 AML patients. Bone marrow aspiration material from AML patients has been used for the cytochemistry as well as flow cytometry. All non-erythroid cells have been included in the evaluation in both methods. 17/65 cases showed at least 15% difference between the proportion CD14 and ANAE positive cells. Cases with 20% or more CD14 positivity had poorer prognosis. For FAB classes M0-M3, presence of 10% or more CD14 was negative for overall survival (P = 0.01). ANAE did not show significant prognostic influence.
  •  
24.
  • Fernandes, Oswaldo J. C. B., et al. (författare)
  • Prognostic factors for the survival of surgically treated patients for non-small cell lung cancer
  • 2003
  • Ingår i: Acta Oncologica. - Oslo, Norway : Taylor & Francis. - 0284-186X .- 1651-226X. ; 42:4, s. 338-341
  • Tidskriftsartikel (refereegranskat)abstract
    • The survival and outcome rates of 284 patients who underwent surgical treatment for non-small cell lung cancer were assessed retrospectively. Resectability rate was 94.1%, hospital mortality 3.9% (n = 11) and the mortality rates in patients who underwent pneumonectomy or lobectomy were 8.9% and 0.6%, respectively. The overall 5-year survival was 43.6%. Female gender, earlier stages of disease and a complete resection were strongly predictive for a long-term survival. Women in stage IA disease had a 5-year survival rate of 92.7%. The 5-year survival rate for patients in stages IIIA and N2 disease who underwent a complete resection was 21.9%, and 9% for those who did not undergo a complete resection. It is concluded that the best surgical results were observed in women who were operated on at an early stage of disease. A complete resection also contributed to a better outcome, even for patients in stage IIIA and N2 disease.
  •  
25.
  • Graflund, M., et al. (författare)
  • HPV-DNA, vascular space invasion, and their impact on the clinical outcome in early-stage cervical carcinomas
  • 2014
  • Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 14:5, s. 896-902
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study was designed to analyze the relationship of human papillomavirus (HPV)-DNA, microvessel density, and their impact on clinical outcome in early cervical carcinoma. HPV-DNA was evaluated in 171 cases of cervical carcinoma treated from 1965 to 1990. In 110 cases, the analyses could be performed. A polymerase chain reaction technique was used on paraffin-embedded specimens obtained before the start of therapy. HPV-DNA of any type was detected in 78% (86/110) of all evaluable tumors. HPV16 was the predominant type and was detected in 56% (62/110), HPV18 in 8% (9/110), and HPV35 in 21% (23/110). Patients with tumors containing HPV16 or HPV18 were significantly (P = 0.011) younger than patients with tumors not containing either of these two subtypes. Vascular space invasion and lymph node metastases were observed more frequently in tumors expressing HPV16 and HPV18 (P = 0.002, P = 0.047) than in tumors negative for these HPV strains. Tumors containing HPV16 and HPV18 were significantly (P = 0.012) larger and more frequently (P = 0.005) associated with higher FIGO stages. The cancer-specific survival rate was lower for patients with HPV16- and HPV18-positive tumors, but the difference was not statistically significant. The microvessel density was a non-significant prognostic factor. The overall 5-year survival rate of the complete series was 91%. It was concluded that HPV-DNA was a prognostic factor in early-stage cervical cancer and was associated with the age of the patient, vascular space invasion, lymph node metastases, tumor size, and FIGO stage.
  •  
26.
  • Graflund, Marianne, et al. (författare)
  • Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma : Correlation with clinical outcome
  • 2002
  • Ingår i: International Journal of Gynecological Cancer. - Malden, USA : BMJ. - 1048-891X .- 1525-1438. ; 12:3, s. 290-298
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.
  •  
27.
  • Graflund, Marianne, et al. (författare)
  • MIB-1, p53, bcl-2, and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas : correlation with clinical outcome
  • 2002
  • Ingår i: International Journal of Oncology. - Athens, Greece : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 20:5, s. 1041-1047
  • Tidskriftsartikel (refereegranskat)abstract
    • A complete series of 40 cervical carcinomas with pelvic lymph node metastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamous carcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 tumors (30%) were moderately differentiated, and 27 tumors (67.5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymph node metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and multivariate proportional hazard Cox analyses.
  •  
28.
  • Graflund, M., et al. (författare)
  • Relation between HPV-DNA and expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA ploidy in early cervical carcinoma : correlation with clinical outcome
  • 2004
  • Ingår i: Oncology Reports. - Athens, Greece : Spandidos Publications. - 1021-335X .- 1791-2431. ; 12:1, s. 169-176
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.
  •  
29.
  • Graflund, Marianne, et al. (författare)
  • The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas
  • 2002
  • Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:2, s. 149-157
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim-Meigs) for FIGO stage I-II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables-pattern of invasion and host response-were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients.
  •  
30.
  • Graflund, Marianne, et al. (författare)
  • The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix
  • 2002
  • Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:1, s. 32-41
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to investigate the prognostic importance of clinical and histopathologic factors, including malignancy grading systems (MGS), partial index (PI), invasive front grading (IFG), and microvessel density. A complete geographic series of 172 early stage (FIGO I-II) cervical carcinomas treated by Wertheim-Meigs surgery during the period 1965-1990 was studied. The patients were followed up for at least 10 years. Significant prognostic factors for disease-free survival were lymph node status (P < 0.0000001), radical surgical margins (P = 0.00003), and tumor size (P = 0.008). In a multivariate Cox analysis it was shown that lymph node status was the single most important prognostic factor with regard to disease-free survival. The total MGS and the PI scores were highly significantly (P = 0.0001) associated with pelvic lymph node metastases and disease-free survival rate in squamous cell carcinomas. The MGS and the PI systems were superior to the IFG system in predicting lymph node metastases. The total IFG score was also a statistically highly significant (P = 0.003) prognostic factor with regard to disease-free survival in both univariate and multivariate analyses. Microvessel density was a nonsignificant prognostic factor. There was a highly significant (P = 0.002) association between vascular space invasion of tumor cells and the presence of lymph node metastases. In conclusion, histopathologic malignancy grading systems provide valuable prognostic information in patients with early stage squamous cell carcinomas of the uterine cervix.
  •  
31.
  • Hellman, Urban, 1966-, et al. (författare)
  • Presence of hyaluronan in lung alveoli in severe Covid-19 : an opening for new treatment options?
  • 2020
  • Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 295:45, s. 15418-15422
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe corona virus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined.The aim of the study was to demonstrate if the lungs of fatal Covid-19 contain hyaluronan as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly.Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue.Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up for new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.
  •  
32.
  • Hellquist, H. B., et al. (författare)
  • Activated T cells in the nasal mucosa of patients with grass-pollen allergy. A pilot study
  • 1992
  • Ingår i: Rhinology. - Amsterdam, Netherlands : International Rhinologic Society. - 0300-0729 .- 1996-8604. ; 30:1, s. 57-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Six patients with grass-pollen allergy were provoked with water-soluble grass pollen until a pronounced allergic reaction occurred. This was performed outside the grass-pollen season, and the allergen was administered on the edge of the inferior turbinate. Biopsies were taken both before provocation and during the reaction, 15-30 minutes after provocation. The nasal population of immunohistochemically positive cells for HLA-DR, CD1, interleukin-2-receptor, IgE, CD4 and CD8 were studied. There was a marked increase of IL2-R-positive cells (activated T lymphocytes) in the nasal mucosa after provocation, whilst the other cell populations approximately remained unchanged (apart from a certain increase of IgE). The increase of activated T lymphocytes may imply that certain subsets of T cells play a role in the allergic response, and that the role of helper T cells very likely is much more complex than the regulation of mast cells and eosinophils. The concomitant presence of Langerhans' cells (CD1-positive) and activated T lymphocytes may indicate a possible association on site between an antigen-presenting cell and both effector as well as memory cells in allergic reactions.
  •  
33.
  • Hellquist, H. B., et al. (författare)
  • Basaloid squamous cell carcinoma of the palate
  • 1994
  • Ingår i: Histopathology. - Oxon, United Kingdom : Blackwell Publishing. - 0309-0167 .- 1365-2559. ; 25:2, s. 178-180
  • Tidskriftsartikel (refereegranskat)
  •  
34.
  • Hellquist, H. B., et al. (författare)
  • Nasal memory T lymphocytes capable of producing IL-4 in the allergic reaction
  • 1992
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - West Sussex, United Kingdom : Wiley-Blackwell. - 0105-4538 .- 1398-9995. ; 47:4 Pt 1, s. 334-336
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper reports the presence of memory T cells in the nasal mucosa of allergic patients. The demonstration of CD4+/CD29+ (CD4+/CD45RO+) T lymphocytes, which are capable of interleukin-4 production, can indicate a complementary cell-mediated regulatory mechanism for mast cell proliferation and IgE synthesis in human nasal allergy. No substantial IgE production can be obtained in the absence of IL-4. Therefore, the existence of IL-4 producing cells on site in the nasal mucosa of allergic subjects probably implies a complementary interaction between cytokines and different immunocompetent nasal cells in the regulation of B cells and IgE synthesis.
  •  
35.
  • Hellquist, Henrik B., et al. (författare)
  • Salivary duct carcinoma : a highly aggressive salivary gland tumour with overexpression of c-erbB-2
  • 1994
  • Ingår i: Journal of Pathology. - West Sussex, United Kingdom : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 172:1, s. 35-44
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinicopathological and immunocytochemical features of nine cases of salivary duct carcinoma are described. This relatively rare tumour, which only recently has been widely recognized as a separate entity, is highly malignant and caused the death in eight of the patients. The tumour cells are arranged in cribriform and solid growth patterns, where the solid tumour nests frequently have comedo necrosis, and a fibrous, often sclerotic, stroma is present. The infiltrating desmoplasmic component and the diffuse invasive growth into adjacent adipose parotid tissue have similarities to ductal breast carcinoma. Immunocytochemical investigation of salivary duct carcinoma showed constant overexpression of c-erbB-2 as detected by membrane accentuation, and high proliferative activity as detected by nuclear positivity for MIB 1 (Ki-67). Changes in the expression of p53 and retinoblastoma gene product do not constitute a constant event in salivary duct carcinoma. A few of the tumours showed scattered cells with distinct nuclear positivity for both progesterone and oestrogen receptors. We emphasize that this highly malignant salivary gland tumour has a characteristic morphology, may not be as rare as previously considered, and that prompt and aggressive therapy is needed.
  •  
36.
  • Jahnson, Staffan, et al. (författare)
  • Predictive value of p53 and pRb immunostaining in locally advanced bladder cancer treated with cystectomy
  • 1998
  • Ingår i: Journal of Urology. - Philadelphia, USA : Elsevier. - 0022-5347 .- 1527-3792. ; 160:4, s. 1291-1296
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We elucidate the association between altered immunostaining for retinoblastoma gene protein (pRb) and p53 nuclear proteins, and cancer specific death in patients treated with cystectomy for locally advanced bladder cancer.Materials and Methods: The hospital records of 173 patients treated with cystectomy for advanced urothelial bladder cancer between 1967 and 1992 were retrospectively reviewed. Representative biopsies obtained before treatment were sectioned and stained using the standard immunohistochemical technique with antibody DO-7 (p53) and antibody PMG3-245 (pRb). A tumor was considered to have an altered p53 expression if 20% or more of tumor cells exhibited nuclear staining. Similarly, if no tumor cell had nuclear immunostaining the tumor was considered to have an altered pRb expression.Results: An altered expression was observed for p53 in 98 tumors (57%) and for pRb in 60 (35%). In a proportional hazards analysis no association was found between an altered expression of pRb or p53 and cancer specific death. This finding was also true in another analysis when the results of immunostaining for pRb and p53 were combined.Conclusions: An altered expression for pRb and/or p53 was not correlated to cancer specific death. Thus, these parameters could not be used as predictors of treatment outcome after cystectomy for locally advanced bladder cancer.
  •  
37.
  • Jahnson, Staffan, et al. (författare)
  • Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally advanced bladder carcinoma
  • 2000
  • Ingår i: Cancer. - New York, USA : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 89:3, s. 619-629
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma.Methods: The hospital records from all 173 patients treated with cystectomy for locally advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively reviewed. Three consecutive sections from biopsies taken before any treatment were stained using the standard immunohistochemical technique for p53, p21, and mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression and 10% or more for positive p21 and mdm2 expression.Results: Positive immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors (51%), and for mdm2 in only 16 tumors (9%). The only association found between immunostaining for the three antibodies was that most mdm2-positive tumors had positive p21 expression. Tumor mapping of regional immunostaining showed no association between immunostaining for p53 and p21. In a proportional hazards analysis, no association was found between the results of immunostaining for the three antibodies and treatment outcome.Conclusions: Positive or negative expression of p53, p21, or mdm2, or combinations of these, was not associated with cancer specific mortality after cystectomy for bladder carcinoma. There was no association between immunostaining for p21 and p53, whereas positive immunostaining for mdm2 was observed in a minority of the tumors. These results indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins and tumor suppressor proteins along the p53 pathway that are involved in tumor development and progression.
  •  
38.
  •  
39.
  • Kaliff, Malin, 1985-, et al. (författare)
  • Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy
  • 2018
  • Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 9:27, s. 18786-18796
  • Tidskriftsartikel (refereegranskat)abstract
    • Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression. Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing. Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.
  •  
40.
  •  
41.
  • Kaliff, Malin, 1985- (författare)
  • Human papillomavirus and cellular biomarkers in cervical cancer
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cervical cancer (CC) is caused by a persistent infection of certain types of the human papillomavirus (HPV). Even though great progress has been made in strategies for prevention, and treatment of CC, there is still a need for improved methods in screening and management of women diagnosed with CC. The aim of this thesis was to gain further knowledge of CC by studying HPV-related or cellular biomarkers in precursors and established cancer.Mostly molecular methods were used for analysis of both tumour and screening samples. Among the studied biomarkers were HPV genotype, HPV multiplicity, viral load and methylation.Initially, HPV was detected in only 86% of the tumours; after careful reinvestigation of the negative samples, the final prevalence was 93%. The results show that analysis of long-term archived samples may require thorough and repeated analysis to obtain accurate results. In the HPV-positive tumour samples, 13% tested positive for multiple genotypes. This finding was associated with poor prognosis for the woman and could be a useful biomarker for prognostic assessment in CC. Viral load was analysed as a potential contributing factor for prognosis differences, however, no such association was detected.In the screening cohort, 40% of women with high-grade abnormalities were positive for HPV16 and 18, genotypes included in the vaccine used since 2012 in Sweden, while 88% were positive for the genotypes in the updated vaccine used since 2019. This indicates a large future reduction of high-grade abnormalities in the vaccinated cohorts, and baseline data like these are valuable for surveillance of genotype distribution in the coming decades. A methylation test targeting two human genes, proposed for use in screening, was tested on the screening samples. We detected no association between hypermethylation and HPV, but it was associated with increasing age, something that needs to be considered if using this method in screening.
  •  
42.
  • Karlsson, Mats G., 1960-, et al. (författare)
  • Endothelial adhesion molecules for nasal-homing T cells in allergy
  • 1996
  • Ingår i: Virchows Archiv. - Heidelberg, Germany : Springer. - 0945-6317 .- 1432-2307. ; 429:1, s. 49-54
  • Tidskriftsartikel (refereegranskat)abstract
    • During the allergic reaction mucosal T cells are activated and a local increase in numbers occurs. In peripheral blood, a concomitant T cell activation and switch towards memory phenotype appears. E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were studied in nasal mucosal biopsies taken during a time-course provocation study, including patients with seasonal allergic rhinitis and healthy controls. Allergic patients were also studied during the natural pollen season with particular attention to the influence of local corticosteroid treatment. Before provocation allergic patients and controls did not differ concerning the expression of endothelial adhesion molecules. However, the epithelial ICAM-1 expression was increased among allergics (P < 0.05). Repetitive allergen provocation induces an increased endothelial expression of VCAM-1 in allergic patients (P < 0.01). Similarly, VCAM-1 expression was increased during the natural pollen season (P < 0.05). Interestingly, the increased VCAM-1 expression was inhibited by the use of local corticosteroids. The present data demonstrate a putative integrin-VCAM-1 mechanism for selective homing of T memory cells to the allergic nasal mucosa and new in vivo effects of local corticosteroid treatment are demonstrated.
  •  
43.
  • Karlsson, Mats G., 1960-, et al. (författare)
  • Increase in CD4+ and CD45RO+ memory T cells in the nasal mucosa of allergic patients
  • 1994
  • Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - Hoboken, USA : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 102:10, s. 753-758
  • Tidskriftsartikel (refereegranskat)abstract
    • By means of immunocytochemistry we have investigated subsets of T lymphocytes in frozen sections of nasal mucosa from patients with seasonal allergic rhinitis and healthy control persons. All participants were subjected to time-course provocation during the non-pollen season, and samples were taken during provocation as well as during the natural pollen season. Computerized image analysis was applied for evaluation of the immunostained lymphocytes. CD45RO+ memory T cells outnumbered the remaining leukocyte populations in the mucosa of both allergic patients and controls on all occasions. During the repeat provocation there was no difference in numerical values, with respect to any of the five leukocyte subpopulations studied (CD4, CD8, CD25, CD45RA and CD45RO), between patients and controls. However, during continuous exposure in the pollen season a significant increase in CD4+ cells was observed in allergic patients compared to before provocation (p < 0.05). No changes were observed with respect to CD8+ and CD25+ cells. Similarly, an increase in CD45RO+ memory was found in allergic patients during the pollen season compared to the non-pollen season (p < 0.02). This latter finding was, however, only evident in the patients who did not use nasal corticosteroids. Hence the present investigation has demonstrated an allergen-induced increase in CD4+ and CD45RO+ memory T cells in the mucosa of allergic patients during the pollen season. These events may constitute a cellular basis for local continuous production of certain cytokines, particularly interleukin-4, which is essential for IgE synthesis.
  •  
44.
  • Karlsson, Mats G., 1960-, et al. (författare)
  • Nasal messenger RNA expression of interleukins 2, 4, and 5 in patients with allergic rhinitis
  • 1995
  • Ingår i: Diagnostic molecular pathology (Print). - Philadelphia, USA : Lippincott Williams & Wilkins. - 1052-9551 .- 1533-4066. ; 4:2, s. 85-92
  • Tidskriftsartikel (refereegranskat)abstract
    • In nasal biopsies from 17 adult patients with seasonal allergic rhinitis and from 10 healthy controls, cytokines were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR). The time-course study during winter included repeated local allergen provocation with subsequent nasal biopsies as well as biopsies taken during pollen season. The RT-PCR for CD44 yielded positive bands in 65 of 71 cases, in which cases mRNA for interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5) were thus investigated by means of seminested PCR. IL-4 mRNA was found almost exclusively in the allergic patients. During provocation a significant increase in IL-4 was noticed compared with controls (p = 0.043). Equally, during the natural pollen season, IL-4 mRNA expression was significantly higher in patients not using nasal corticosteroids compared with those who did (p = 0.011). No differences in IL-2 or IL-5 were observed between the groups. These findings also indicate, together with earlier observations of T-cell activation, a phenotype switch toward T-helper 2 (Th2) cells, and the accumulation (homing) of these T cells in the nasal mucosa, that T cells constitute the main source for IL-4 in the nasal mucosa. Therefore, allergic patients have an increased synthesis of IL-4 when provoked with the allergen, and during natural pollen season this synthesis can be downregulated by corticosteroids. Furthermore, this study exemplifies the versatility of molecular biology in surgical pathology and that even low-copy-number cytokine mRNA can be examined in routinely snap-frozen surgical specimens.
  •  
45.
  • Karlsson, Mats G., 1960-, et al. (författare)
  • No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation
  • 1997
  • Ingår i: Cancer Letters. - Clare, Ireland : Elsevier. - 0304-3835 .- 1872-7980. ; 120:2, s. 173-177
  • Tidskriftsartikel (refereegranskat)abstract
    • An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.
  •  
46.
  • Karlsson, Mats G., 1960-, et al. (författare)
  • Phenotype switch and activation of T lymphocytes in patients with allergic rhinitis
  • 1994
  • Ingår i: Journal for Oto-Rhino-Laryngology. - Basel, Switzerland : S. Karger. - 0301-1569 .- 1423-0275. ; 56:3, s. 166-172
  • Tidskriftsartikel (refereegranskat)abstract
    • The peripheral blood of 17 patients with seasonal allergic rhinitis (birch pollen) and of 10 healthy subjects were analysed before and during a provocation study in the non-pollen season as well as during the pollen season. Analytical flow cytometry comprised a panel of monoclonal antibodies investigating helper/suppressor T cells, activated T cells, and naive/memory T helper cells. Allergic patients showed no increase in the amount of T lymphocytes but an increased proportion of CD4+ helper T cells early during pronounced exposure (provocation) but not during natural antigen exposure (pollen season). Allergic patients showed a significant increase in activated T cells during the non-pollen season compared with healthy subjects, and furthermore, the nasal allergen provocation induced an additional increase in activated T cells among allergics. The T cell activation mainly affected helper T cells (85%) rather than suppressor T cells. Furthermore, allergic patients showed a significant increase in naive T helper cells during the pollen season. The presence of a double-positive subpopulation indicates an activated T helper subpopulation that switches its phenotype from naive (CD45RA) to memory (CD29). The results indicate at least two important differences between patients with allergic rhinitis and healthy controls. In allergic patients T helper cells become activated upon allergen exposure, and circulate in the blood and switch their phenotype. These T cells have a potential homing tendency to the nasal mucosa. These two events do not occur in non-allergic individuals and may thus constitute new insights into the basic mechanisms of allergic rhinitis.
  •  
47.
  • Karlsson, Mats G., 1960-, et al. (författare)
  • Quantitative computerized image analysis of immunostained lymphocytes : A methodological approach
  • 1994
  • Ingår i: Pathology, Research and Practice. - München, Germany : Elsevier. - 0344-0338 .- 1618-0631. ; 190:8, s. 799-807
  • Tidskriftsartikel (refereegranskat)abstract
    • A methodological approach by computerized image analysis to quantify immunostained objects in histological sections is described. We have investigated antibodies against CD4, CD8, CD20, CD23 and CD25 in frozen sections of human nasal mucosa; however, the methodology of standardization is of general validity. The study was designed particularly to investigate the following points: 1) light intensity, 2) the grey level for counter staining intensity, 3) the grey level threshold value for positive objects, 4) the minimal acceptable size of a positive object, 5) the influence of the brightness of the light on both the number and the area of objects. Furthermore, random sampling and determination of 6) the area per section, and 7) the number of histological sections to be measured per biopsy. Finally, a study of reproducibility of immunostaining intensity was performed. The influence of the different parameters mentioned above was studied and the values (eg. threshold value) for our particular setting of microscope, image analysis equipment, computer software etc, were defined. The method was then tested for intra- and interindividual variation which was found to be less than 5%. Correlation analysis of the reproducibility gave coefficients of correlation of 0.99, both concerning number of immunopositive objects and immunopositive area. We emphasize the importance of a highly standardized methodology if the numeric data obtained from computer assisted image analysis are to be more accurate than semiquantitative assessments by experienced observers. With a thorough standardization as described in this method it is possible to obtain numeric values, and data with low deviations, which are two obvious and important advantages.
  •  
48.
  • Larsson, Gabriella Lillsunde, 1971-, et al. (författare)
  • HPV testing of biobanked liquid-based cytology : a validation study
  • 2016
  • Ingår i: International Journal of Biological Markers. - Milan, Italy : Wichtig Publishing. - 0393-6155 .- 1724-6008. ; 31:2, s. E218-E223
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The aim of the study was to investigate whether biobanked liquid-based cytology (LBC) vaginal samples could be reanalyzed for the biomarkers HPV DNA and mRNA without loss of sensitivity.Methods: One hundred LBC samples with ASCUS or CIN1 were tested for HPV DNA and mRNA before and after biobanking. DNA analysis targeted the viral genes E6 and E7, 12 high-risk and 2 low-risk HPV types together with the human control gene HBB, using real-time PCR. The Aptima HPV assay was used for mRNA analysis of 14 high-risk HPV types.Results: With Aptima there was 84% agreement between results before and after biobanking. The sensitivity and specificity were 0.79 (95% CI, 0.68-0.88) and 0.94 (95% CI, 0.80-0.99), respectively. With the DNA-based method, the agreement between results was 87%, the sensitivity 0.85 (95% CI, 0.75-0.92) and the specificity 0.95 (95% CI, 0.77-1.00). Both methods presented a significant difference between positive results before and after biobanking; McNemar test: p = 0.004, p = 0.003, Cohen's kappa: 0.67 (95% CI, 0.53-0.81), 0.68 (95% CI, 0.52-0.84). Cycle threshold values for the DNA method were higher for all genotypes after biobanking, except for HPV-59. Some loss of sensitivity was seen after biobanking but the concordance between HPV detection before and after biobanking was good for both evaluated methods.Conclusions: Biobanking of LBC vaginal samples offers a good platform for HPV testing and could be extended to further molecular analyses. However, in order to ensure a valid test result a larger portion needs to be analyzed from the biobanked sample.
  •  
49.
  • Li, Hui-xiang, et al. (författare)
  • [Expressions of thymidine phosphorylase, thymidylate synthase and dihydropyrimidine dehydrogenase in breast cancer and their correlations with prognosis]
  • 2004
  • Ingår i: Zhonghua zhong liu za zhi [Chinese journal of oncology]. - Beijing, China : Zhongguo Yixue Kexueyuan / Cancer Hospital, Chinese Academy of Medical Sciences. - 0253-3766. ; 26:11, s. 669-672
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To study the expression of thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) mRNA in breast cancer and its correlation with prognosis.Methods: Expression levels of TP, TS and DPD mRNA in 86 micro-selected breast cancer tissues and 9 normal breast tissues were detected by real-time quantitative PCR.Results: The median expression levels of TP, TS and DPD mRNA in tumor tissue and in normal tissues were 16.54, 0.38, 2.47 and 11.75, 0.25, 8.33, respectively, there were no significant differences (P >0.05). The expression levels of TP, TS and DPD mRNA showed no association with tumor size, lymph node metastasis, pathological grade and clinical stage, except that of DPD showed a negative association with patients' ages. There was no significant difference in disease-free survival or overall survival between the patients with high and low TP or DPD mRNA levels. Disease-free survival tends to be better in the patients with low TS mRNA level than those with high TS mRNA, but the difference was not significant (P=0.069), while the overall survival showed a statistically difference (59.00 month and 70.30 month) (P=0.0496).Conclusion: The expression level of TS mRNA may serve as a prognostic marker for breast cancer patients.
  •  
50.
  • Lillsunde-Larsson, Gabriella, 1971-, et al. (författare)
  • Evaluation of HPV Genotyping Assays for Archival Clinical Samples
  • 2015
  • Ingår i: Journal of Molecular Diagnostics. - New York, USA : Elsevier. - 1525-1578 .- 1943-7811. ; 17:3, s. 293-301
  • Tidskriftsartikel (refereegranskat)abstract
    • Human papillomavirus (HPV) testing and genotyping of FFPE tissue samples is important in epidemiological investigations. Here, we compare four different HPV genotyping methods for use in FFPE clinical samples. Comparative testing was performed on 99 samples with a clinical suspicion of HPV. Specimens were analyzed with Anyplex II HPV28 detecting 28 genotypes using real-time PCR and melting curve analysis, CLART HPV2 detecting 35 genotypes using PCR and microarray detection, and MGP5+/6+ consensus primer system together with pyrosequencing. Results were compared to a real-time PCR reference protocol detecting 14 genotypes. In total, 68% of the samples were positive for an HPV genotype using the reference protocol and MGP5+/6+ primer system. Anyplex II HPV28 analysis and CLART HPV2 had 82% and 72% positive samples, respectively. All four methods showed good agreement when comparing the 14 genotypes included in the reference protocol. When evaluating all genotypes, the Anyplex II HPV28 assay and the CLART assay changed the status of the sample (individually or together) from negative with respect to the reference protocol to positive for either a Group 1 (n = 4) or Group 2 (n = 6) genotype. We conclude from this study that for an extended genotyping approach with a high sensitivity for FFPE specimens, both the Anyplex II HPV28 and CLART HPV2 assays are suitable alternatives despite minor intra-assay differences.
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