| 1. |
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| 2. |
- Cui, Baoxia, et al.
(author)
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Mutation of PIK3CA : possible risk factor for cervical carcinogenesis in older women
- 2009
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In: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 34:2, s. 409-416
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Journal article (peer-reviewed)abstract
- PIK3CA encodes the p110alpha catalytic subunit of PI 3-kinase, which regulates signaling pathways important for neoplasia, cell proliferation and apoptosis. Somatic mutations in this gene have been detected in several solid human tumors. We investigated these mutations in cervical carcinoma and its precursors, and their association with HPV infection and patient clinical data. The mutations were analyzed using post-PCR direct genomic DNA sequencing. Samples included 9 cervical cancer cell lines, 184 invasive cervical carcinomas, and 30 cervical neoplasias. Missense mutations of PIK3CA were identified in 15/184 (8.15%) invasive cervical carcinomas. One novel mutation G1638C (Q546H) was found. Three mutations were identified in the cervical cancer lines. No mutations were found in the precursors. The difference in mutation frequency between invasive and pre-invasive lesions was not significant (p=0.1372). In relation to age and HPV, the mutation rate was significantly higher in patients>or=60 years (p=0.001), while the rate of HPV infection was higher in patients
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| 3. |
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| 4. |
- Hedman, Håkan, et al.
(author)
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LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix
- 2010
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 49:6, s. 812-815
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Journal article (peer-reviewed)abstract
- BACKGROUND: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises LRIG1, 2, and 3. LRIG1 negatively regulates growth factor signaling and is a proposed tumor suppressor. In early stage uterine cervical carcinoma, expression of LRIG1 is associated with good survival. Less is known about the function and expression of LRIG2; it has not been studied in cervical carcinoma, previously. MATERIALS AND METHODS: LRIG2 expression was studied by immunohistochemistry in 129 uterine cervical squamous cell carcinomas and 36 uterine cervical adenocarcinomas. Possible associations between LRIG2 immunoreactivity and patient survival were evaluated. RESULTS: In early-stage squamous cell carcinoma (stages IB-IIB), high expression of LRIG2 was associated with poor survival (Kaplan-Meier, log-rank, p=0.02). The 10-year survival rate for patients with high expression of LRIG2 was 60%, compared to 87% in patients with low expression (odds ratio 0.22, 95% CI 0.07-0.64). In multivariate analysis including the previously studied tumor suppressor LRIG1 and clinical stage, LRIG2 emerged as an independent prognostic factor (odds ratio 0.22, 95% CI 0.09-0.50). For patients with both high expression of LRIG2 and low expression of LRIG1, the 10-year survival rate was only 26% compared to 66% for the remaining study population. There was no correlation between LRIG2 expression and prognosis in the limited adenocarcinoma series. DISCUSSION AND CONCLUSION: LRIG2 appears to be a significant predictor of poor prognosis in early-stage squamous cell carcinoma of the uterine cervix. A combination of high LRIG2 expression and low LRIG1 expression identified women with a very poor prognosis.
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| 5. |
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| 6. |
- Hellberg, Dan, et al.
(author)
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Differences in expression of tumor markers between pre- and postmenopausal women with invasive cervical cancer
- 2008
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:3B, s. 1793-1795
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Journal article (peer-reviewed)abstract
- The aim of the present study was to investigate the differences in the expression of tumor markers in squamous cell and in adenomatous carcinomas in pre- and postmenopausal women, respectively. Patients and Methods: The study population comprised 53 premenopausal and 107 postmenopausal women. Thirty-four tumors were adenomatous (n=31) or adenosquamous carcinomas (n=3), distributed between 13 premenopausal and 21 postmenopausal women. The remaining 126 squamous cell carcinomas were diagnosed in 40 pre- and 86 postmenopausal women. Expression of ten tumor markers of possible clinical importance in cervical cancer was evaluated. Results: Expression of three tumor markers, p53 (> ;0% vs. 0%), p27 (> , 20% vs. < ;20%) and cyclooxygenase-2 (COX-2) (high intensity vs. moderate/none) differed significantly between pre- compared to postmenopausal women with squamous cell (p27, 54% vs. 72%, p=0.009) or adenomatous carcinomas (p53, 8% vs. 63%, p=0.006 and COX-2, 46% vs. 20%, p=0.03). All results were adjusted for clinical cancer stage. Conclusion: The unusual age-specific incidence curve in cervical cancer has rarely been related to expression of tumor markers. Age-related differences in expression of tumor markers could reflect some age-related different biological mechanisms in cervical cancer.
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| 7. |
- Hellberg, Dan, et al.
(author)
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Pitfalls in immunohistochemical validation of tumor marker expression : exemplified in invasive cancer of the uterine cervix
- 2009
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 112:1, s. 235-240
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To study if immunohistochemical expression of tumor markers as prognostic predictors is influenced by clinical stage, adjustments for expression of other tumor markers and histological type in cervical cancer. METHODS: The study included 129 women with squamous cell cancer and 29 women with adenocarcinomas. Expression of 9 tumor markers relevant for cervical cancer and selected to represent different mechanisms in carcinogenesis was analysed. These were Ki-67, c-myc, LRIG1, p-53, p-27, CD44, VEGF, Cox-2 and CD4+. RESULTS: In late-stage cancer a higher number of tumor-infiltrating CD4 positive cells were associated with a favourable prognosis while a higher Ki-67 index with a poor prognosis. In early-stage cancer a high LRIG1 expression was associated with a favourable prognosis. Significantly different expressions were found at early-stage versus at late-stage squamous cell cancer for VEGF, p27 and LRIG1 which were all more strongly expressed in early stages. Adjustments for all selected tumor markers and clinical stage converted VEGF and LRIG1 expression from non-significant to significant prognostic predictors while the association between p53 expression and good prognosis was strengthened. Adjustments for Cox-2 and c-myc had the strongest impact on VEGF as a prognosis predictor and LRIG1 was most influenced by adjustment for p53. All correlations became non-significant when women with adenocarcinoma and other invasive tumor types were included. CONCLUSIONS: Failure to analyse clinical stages separately, failure to adjust for expression of relevant concurrent tumor markers and inclusion of different histological subtypes into the same study group may lead to false conclusions regarding the significance of prognostic tumor markers.
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| 8. |
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| 9. |
- Lindström, Annika, 1953-, et al.
(author)
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Correlations between serum progesterone and smoking, and the growth fraction of cervical squamous cell carcinoma
- 2000
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 20, s. 1-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Possible correlations between growth fraction of squamous cervical carcinomas and serum progesterone (se-P) concentrations, smoking habits and DNA ploidy were studied. MATERIALS AND METHODS: The DNA S-phase fraction (SPF), measured by flow cytometry was used as a marker of tumour growth in 103 cases of squamous cervical cancer stage IB-IV. DNA-ploidy (peridiploidy vs. aneuploidy), Se-P, se-Estradiol, smoking habits, parity, menopausal status, clinical stage and histopathological grading were compared to SPF < 14% vs. SPF > or = 14%. RESULTS: Aneuploidy, (odds ratio (OR) 10.0), se-P > or = 2.6 nmol/l (OR 7.5) and smoking (OR 3.0) were significantly associated with SPF > or = 14%, after adjustments for all factors included in the study. The association with se-P and smoking was attributed to an increased risk for the premenopausal women in the study. DISCUSSION: In this study an increased tumour growth was associated with increased leves of se-P, smoking and aneuploidy in women with invasive squamous cervical carcinoma. This study seems to experimentally confirm epidemiological studies, where smoking and long-term use of oral contraceptives have been linked to cervical neoplasms.
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| 10. |
- Lindström, Annika K., et al.
(author)
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Associations between ten biological tumor markers in squamous cell cervical cancer and serum estradiol, serum progesterone and smoking
- 2007
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:3B, s. 1401-1406
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Journal article (peer-reviewed)abstract
- Background and Aim: To study possible associations between selected tumor markers and co-factors in squamous cell cervical cancer. Materials and Methods: Ten biological tumor markers representing different functions in carcinogenesis were diagnosed in 128 cases of squamous cell cervical cancer. These were p53, c-myc, EGFR, COX-2, CD4+, VEGF, E-cadherin, CD44, Ki-67 (MIB-1), and p27. Smoking habits and previous oral contraceptive use were registered. Serum estradiol and progesterone levels were evaluated in 80 women. Each marker was compared to these four variables. Results: Highly significant associaions were found between strong c-myc staining (≥50%) and increased serum progesterone (p=0.01), a low EGFR staining (<20%) and high serum estradiol (p=0.0007), and an absence of p53 staining and smoking (p=0.008). There was a association between the absence of p53 and high serum progesterone (p=0.046). Conclusion: The study supports a role of progesterone as a promoter of cervical cancer and indicates that smoking is associated with tumor development.
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| 11. |
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| 12. |
- Lindström, Annika K, et al.
(author)
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Discrepancies in expression and prognostic value of tumor markers in adenocarcinoma and squamous cell carcinoma in cervical cancer
- 2009
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:7, s. 2577-2578
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Journal article (peer-reviewed)abstract
- The expression of 11 tumor markers in 129 women with squamous cell compared to 31 women with adenomatous cervical cancer was investigated to detect differences in expression. There was a significantly higher expression of p53, CD4, epidermal growth factor receptor (EGFR), CD44 and stratifin in squamous cell, compared to adenocarcinoma, while there was a higher expression of c-myc in adenocarcinoma. P-53, cyclooxygenase-2 (Cox-2) and c-myc significantly correlated to prognosis in squamous cell carcinoma, but none of the 11 investigated tumor markers had any prognostic value in adenocarcinomas. The prognostic value of individual tumor markers differs with the histological subtype in cervical cancer.
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| 13. |
- Lindström, Annika K., et al.
(author)
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Predicting the outcome of squamous cell carcinoma of the uterine cervix using combinations of individual tumor marker expressions
- 2007
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:3B, s. 1609-1615
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Journal article (peer-reviewed)abstract
- Aim: To evaluate if combining the individual expression patterns of biomarkers targeting different molecular alterations in tumor development will improve prognosis prediction in invasive squamous cell carcinoma of the uterine cervix. Patients and Methods: Ten-year follow-up results in 128 women with cervical cancer were compared to the expression of 10 relevant tumor markers, assessed with immunohistochemistry. The markers were selected to represent cell proliferation, tumor suppression, cell-cell adhesion, angiogenesis, apoptosis, inflammation and immune response. All analyses were adjusted for stage. Results: p53 expression, and low expression of c-myc and COX-2 correlated significantly with survival. In addition CD4+ expression was included in the analyses of combinations. When these four tumor markers were combined, two-by-two, ten combinations correlated significantly with 10-year survival. The overall 10-year survival rate with a low COX-2 and a high CD4+ expression was 76% versus 53% in the remaining women (odds ratio 3.73, 95% CI 1.42-11.0). The survival rate with absent p53 and high COX-2 expression in the tumors was 42% versus 71% (odds ratio 0.25, 95% CI 0.10-0.37), while the corresponding figures for the combination of high COX-2 intensity and expression of c-myc were 27% versus 62% (odds ratio 0.13, 95% CI 0.02-0.52). None of the single markers correlated significantly with outcome in the final Cox regression analyses, while five combinations did. Conclusion: Combinations of selected, biologically plausible tumor markers might be more useful for predicting the outcome than using single markers.
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| 14. |
- Lindström, Annika, 1953-, et al.
(author)
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LRIG1 and squamous epithelial uterine cervical cancer : correlation to prognosis, other tumor markers, sex steroid hormones, and smoking
- 2008
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In: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 18:2, s. 312-317
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Journal article (peer-reviewed)abstract
- The aim is to evaluate LRIG1 as a prognosis predictor and correlations to cofactors in squamous cell cervical cancer. LRIG1 expression was studied in 128 cervical carcinomas and was compared with expression of nine other tumor markers. Smoking history was registered and pretreatment serum estradiol and progesterone levels were evaluated in 79 women. At clinical stage IB, 58% of the tumors showed LRIG1 expression, but there was a decline by increasing stage (33% in stage IV). Ninety percent of women with stage IB cancer and LRIG1 positivity survived, as compared to 64% without expression (P = 0.02). LRIG1 expression did not predict prognosis in advanced stages, but in stage IIA there was a marked relative difference, with 75% survival in tumors expressing LRIG1, as compared to 43% in those without. No correlation was found between LRIG1 and the other nine tumor markers studied. A high serum progesterone and smoking correlated to absent LRIG1 expression. We conclude that LRIG1 appears to be a significant prognosis predictor in early-stage cervical cancer, independent of the other tumor markers that were studied. Diminished expression in advanced stages and the inverse correlation to serum progesterone and smoking indicates that LRIG1 is a tumor suppressor in cervix.
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| 15. |
- Lindström, Annika, 1953-
(author)
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Prognostic factors for squamous cell cervical cancer : tumor markers, hormones, smoking, and S-phase fraction
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Cervical cancer is the second most common malignancy in women worldwide and one of the leading causes of cancer mortality globally. In patients with invasive cervical cancer prognostic factors are of value for the choice of treatment, monitoring of treatment and follow-up. The most important clinical prognostic factors are stage, tumor volume, parametrial infiltration, vascular invasion, lymph node metastases, and distant metastases. An improved estimation of the prognosis of cervical cancer is desirable, especially in early cancer stages.The aim of this research was to study possible associations between tumor markers, female sex steroids, smoking, S-phase fraction (SPF), and prognosis in invasive squamous cell cervical cancer (SCC). The study comprised 190 patients with SCC, stages IB-IV, admitted to the Department of Gynecologic Oncology at Norrland University Hospital in Umeå between September 1984 and October1990. Ten year mortality was estimated.In study I, of a total of 103 patients, it was found that increased tumor growth, measured by the DNA SPF, was associated with elevated serum progesterone and smoking in the premenopasual patients and with aneuploidy in the whole group.In study II, comprising 128 patients, survival length related to hormone levels and SPF was evaluated in women who died of cervical cancer. In both pre- and postmenopausal women, who died of cervical cancer, SPF at or above 12% was correlated with reduced survival. There was significant positive correlation between a low serum estradiol/progesterone ratio and short survival in those premenopausal women who died of cancer (p=0.02).In study III, ten-year follow-up results in 128 women were compared with the expression of ten relevant tumor markers, assessed by immunohistochemistry. The overall ten-year survival rate in patients with low COX-2 and high CD4+ expression was 76%, versus 53% in the remaining women. The survival rate with absent p53 and high COX-2 expression in the tumors was 42%, versus 71%, while the corresponding figure for the combination of high COX-2 intensity and expression of c-myc was 27%, versus 62%. None of the single markers correlated significantly with outcome in the final Cox regression analyses, while five combinations did.Study IV addressed possible associations between selected tumor markers and cofactors in SCC. Ten tumor markers were examined in 128 patients. Smoking habits and previous oral contraceptive use were recorded. Serum estradiol and progesterone levels were evaluated in 80 women. Highly significant associations were found between strong c-myc staining and increased progesterone, low EGFR staining and high serum estradiol, and absence of p53 staining and smoking. There was an association between absence of p53 and high serum progesterone.In study V, LRIG1 expression was studied in 128 patients and was compared with expression of nine other tumor markers, smoking history, hormone levels, and prognosis. LRIG1 appears to be a significant prognostic predictor in early stage SCC, independent of the other tumor markers that were studied. Diminished expression in advanced cancer stages and the inverse correlation to serum progesterone and smoking indicate that LRIG1 is a tumor suppressor in squamous cell cervical cancer.Conclusion: The results of these studies support a role of progesterone as a promoter of cervical cancer and indicate that smoking is associated with tumor progression. A combination of tumor markers might be of help in prognostic prediction. LRIG1 acts as a tumor suppressor. These findings might contribute towards greater understanding of prognostic prediction of squamous cell cervical cancer.
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| 16. |
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| 17. |
- Riklund, Katrine, et al.
(author)
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Radioimmunodetection of ovarian cancer.
- 1993
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 32:7-8, s. 729-734
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Journal article (peer-reviewed)abstract
- Radioimmunoscintigraphy (RIS) is a potentially valuable method for the detection of primary, secondary and recurrent malignant tumours. Antigens that have been used for monitoring as well as for RIS of ovarian carcinomas include CA 125, PLAP, HMFG, and CA 19-9. Between 70 and 100% of the tumours have been detected at RIS when these antigens have been used. Conventional methods, e.g., computerized tomography (CT) and ultrasonography (US), demonstrate similar or lower detection rate than RIS for tumour diagnosis. RIS gives additional information to conventional radiological methods (CT and US) for the detection of occult ovarian carcinomas. A review of earlier investigations is given and our own recent results using PLAP as a target antigen are presented. The future potential of the technology is discussed.
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| 18. |
- Riklund, Katrine, et al.
(author)
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Radioimmunoscintigraphy of gynecologic tumors with 131I-labeled anti-PLAP monoclonal antibodies.
- 1991
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In: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 32:5, s. 375-380
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Journal article (peer-reviewed)abstract
- Radioimmunoscintigraphy (RIS) was performed in 20 patients with gynecologic tumors, 14 ovarian, 5 cervical, and one endometrial carcinoma. One murine monoclonal antibody (mab) against placental alkaline phosphatase (H7) was used after radiolabeling with 131I. The labeling procedure yielded antibodies with specific activity varying between 60 and 73 MBq/mg mab. Each patient received 57 to 100 MBq of the preparation. RIS was performed 7 to 35 days later. Patients with ovarian adenocarcinoma had an accumulation of activity on RIS at tumor sites (79%, 11/14) verified by ultrasonography, CT, and clinical examination. A low or absent accumulation of activity was seen in patients with cervical tumors. The patient with an endometrial adenocarcinoma was seen to have an activity accumulation at RIS corresponding to tumor sites determined by ultrasound and/or CT. It is concluded that RIS using monoclonal antibodies against placental alkaline phosphatase can provide information which will supplement that gained from other investigations of patients with ovarian adenocarcinomas.
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| 19. |
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| 20. |
- Stendahl, Emma, 1985-
(author)
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Headquarters' Involvement in Managing Subsidiaries
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Within contemporary research on the multinational corporation (MNC), the topic of headquarters' involvement has grown considerably in importance. As the central organisational unit in the MNC, headquarters has the potential to add value to the firm by performing an administrative and entrepreneurial role. While the administrative role concerns synergetic coordination and control activities, the entrepreneurial role pertains to developing and implementing new innovations such as management innovations at the corporate-wide level. Existing literature has generated valuable insights into headquarters' administrative and entrepreneurial role and the potential to create value for the MNC. However, more research is needed on how headquarters can advantageously involve itself and integrate subsidiaries to ensure that their activities are aligned with the MNC strategy without impinging upon subsidiaries' autonomy and without incurring their resistance to headquarters' coordination, control, and innovation activities. This thesis aims to advance our knowledge on headquarters' involvement in managing its subsidiaries. Within the administrative role, I examine coordination and control activities, and within the entrepreneurial role, I examine the process of developing and implementing management innovations and facilitating factors. The thesis draws on a single longitudinal case study of the development and implementation of a new performance management practice by a European MNC within the construction industry. During the fieldwork, I gathered empirical material from observations and interviews as well as secondary data. While this thesis has been carried out as a single case study, the outcome of the thesis is presented in four separate papers, exploring headquarters' involvement in coordination, control and innovation activities. This thesis contributes to the literature on headquarters' involvement in managing subsidiaries by suggesting a collaborative approach to subsidiary engagement and participation that addresses 1) the issue of subsidiary demotivation by feeling degraded to an implementer, 2) the suitability issue by reducing the risk of mismatch between new headquarters integration and innovation activities and subsidiary contexts. Combining headquarters' and subsidiaries' stocks of perspectives and knowledge helps transcend the spatial, cultural, institutional and political boundaries between headquarters and subsidiaries.
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| 21. |
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| 22. |
- Stigbrand, Torgny, et al.
(author)
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Alternative technologies to generate monoclonal antibodies.
- 1993
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 32:7-8, s. 841-844
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Journal article (peer-reviewed)abstract
- Several new technologies to generate and modify established hybridomas that produce monoclonal antibodies have recently been presented and further development should make them more suitable for diagnostic and therapeutic techniques. Different proteolytic procedures have been used for the fragmentation of intact antibodies to Fab2' and Fab fragments and recombinant DNA techniques have made it possible to obtain chimeric, humanized, Fv fragments and single-chain Fvs. A review of the new approaches is presented and the future implications are discussed.
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| 23. |
- Stigbrand, Torgny, et al.
(author)
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Placental alkaline phosphatase (PLAP)/PLAP-like alkaline phosphatase as tumour marker in relation to CA 125 and TPA for ovarian epithelial tumours.
- 1990
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In: European journal of gynaecological oncology. - 0392-2936. ; 11:5, s. 351-360
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Journal article (peer-reviewed)abstract
- The significance of the PLAP (Placental alkaline phosphatase)/PLAP-like isozyme as tumour marker in relation to CA 125 and TPA for the monitoring of patients with malignant ovarian epithelial tumours was evaluated. Of all patients (n = 85), 40% had all three markers elevated. CA 125 being the most sensitive (60%), and the PLAP/PLAP-like isozyme and TPA both 40%. A tendency to certain tumour marker patterns of these three antigens in serum can be seen with regard to histopathology. Serous and anaplastic adenocarcinomas usually have all three markers moderately elevated, mucinous and mesonephric adenocarcinomas both have low incidences and low average levels of all three markers. Endometrioid and non-mucinous adenocarcinomas are often associated with high levels of the PLAP/PLAP-like isozyme and CA 125, while TPA shows moderate elevation. The PLAP/PLAP-like isozyme is positively correlated to tumour burden and the outcome of the disease. It may provide additional information on CA 125 in the monitoring of patients with ovarian cancer.
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| 24. |
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