| 11. |
- Jögi, Annika, et al.
(författare)
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Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype.
- 2002
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 99:10, s. 7021-7026
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Tidskriftsartikel (refereegranskat)abstract
- Insufficient oxygen and nutrient supply often restrain solid tumor growth, and the hypoxia-inducible factors (HIF) 1 alpha and HIF-2 alpha are key transcription regulators of phenotypic adaptation to low oxygen levels. Moreover, mouse gene disruption studies have implicated HIF-2 alpha in embryonic regulation of tyrosine hydroxylase, a hallmark gene of the sympathetic nervous system. Neuroblastoma tumors originate from immature sympathetic cells, and therefore we investigated the effect of hypoxia on the differentiation status of human neuroblastoma cells. Hypoxia stabilized HIF-1 alpha and HIF-2 alpha proteins and activated the expression of known hypoxia-induced genes, such as vascular endothelial growth factor and tyrosine hydroxylase. These changes in gene expression also occurred in hypoxic regions of experimental neuroblastoma xenografts grown in mice. In contrast, hypoxia decreased the expression of several neuronal/neuroendocrine marker genes but induced genes expressed in neural crest sympathetic progenitors, for instance c-kit and Notch-1. Thus, hypoxia apparently causes dedifferentiation both in vitro and in vivo. These findings suggest a novel mechanism for selection of highly malignant tumor cells with stem-cell characteristics.
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| 12. |
- Naumburg, Estelle, et al.
(författare)
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Perinatal exposure to infection and risk of childhood leukemia
- 2002
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Ingår i: Medical and Pediatric Oncology. - : Wiley. - 0098-1532 .- 1096-911X. ; 38, s. 391-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A population-based case-control study was conducted to investigate the association between childhood leukemia and infectious exposures during pregnancy and early neonatal period.PROCEDURE: Children born and diagnosed with leukemia between 1973 and 1989 in Sweden (578 lymphatic, 74 myeloid) were selected as cases. One control was randomly selected for each case and individually matched by sex, month, and year of birth. Children with Down's syndrome were excluded. Exposure data were blindly abstracted from antenatal, obstetric, and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression.RESULTS: A history of maternal infection was not significantly associated with childhood leukemia, OR = 1.25 (95% CI 0.95-1.65). Maternal lower genital tract infection significantly increased the risk of childhood leukemia, OR = 1.78 (95% CI 1.17-2.72), and especially for children over 4 years of age at diagnosis, OR = 2.01 (95% CI 1.12-3.80). Neonatal infection was not associated with the risk of leukemia. The results remained unaltered after adjustment for potential confounders, and separate analyses for myeloid and lymphoid leukemia.CONCLUSIONS: We could document an association between exposure to maternal lower genital tract infection in utero, and a subsequent risk for childhood leukemia, which indicate the importance of an early exposure.
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| 13. |
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| 14. |
- Graflund, Marianne, et al.
(författare)
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Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma : Correlation with clinical outcome
- 2002
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Ingår i: International Journal of Gynecological Cancer. - Malden, USA : BMJ. - 1048-891X .- 1525-1438. ; 12:3, s. 290-298
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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.
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| 15. |
- Graflund, Marianne, et al.
(författare)
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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
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Ingår i: International Journal of Oncology. - Athens, Greece : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 20:5, s. 1041-1047
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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.
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| 16. |
- Graflund, Marianne, et al.
(författare)
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The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas
- 2002
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Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:2, s. 149-157
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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.
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| 17. |
- Graflund, Marianne, et al.
(författare)
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The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix
- 2002
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Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:1, s. 32-41
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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.
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| 18. |
- Suo, Zhenhe, et al.
(författare)
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The expression of EGFR family ligands in breast carcinomas
- 2002
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Ingår i: International Journal of Surgical Pathology. - Thousand Oaks, USA : Sage Publications. - 1066-8969 .- 1940-2465. ; 10:2, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- Expression of EGF, HB-EGF, TGF-alpha, HRG-alpha, HRG-beta1, and HRG-beta3 in 100 frozen breast carcinoma materials was immunohistochemically studied. Among these tumors, 67% were positive for EGF, 53% for HB-EGF, 57% for TGF-alpha, 60% for HRG-alpha, 53% for HRG-beta1, and 63% for HRG-beta3 in the neoplastic epithelial cells. No significant associations between expression of the growth factors and clinicopathological features like tumor size, histologic grade, node status, ploidy, ER status, and c-erbB-4 expression were observed, with the exceptions that significant relations were present between EGF expression and tumor size (p = 0.01) and between HRG-beta3 expression and node status (p = 0.02). The expressions of these growth factors showed no association with cancer-specific survival by the Kaplan Meier analysis.
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| 19. |
- Villman, Kenneth, et al.
(författare)
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Topoisomerase II-α expression in different cell cycle phases in fresh human breast carcinomas
- 2002
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Ingår i: Modern Pathology. - Baltimore : Lippincott Williams & Wilkins. - 0893-3952 .- 1530-0285. ; 15:5, s. 486-491
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Tidskriftsartikel (refereegranskat)abstract
- Topoisomerase II-alfa (topo IIalfa) is the key target enzyme for the topoisomerase inhibitor class of anti-cancer drugs. In normal cells, topo IIalfa is expressed predominantly in the S/G2/M phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo IIalfa is both higher and less dependent on proliferation state in the cell. We studied fresh specimens from 50 cases of primary breast cancer. The expression of topo IIalfa in different cell cycle phases was analyzed with two-parameter flow cytometry using the monoclonal antibody SWT3D1 and propidium iodide staining. The expression of topo IIalfa was significantly higher in the S/G2/M phase of the cell cycle than in the G0/G1 phase in both DNA diploid and DNA nondiploid tumors. In 18 of 21 diploid tumors, and in 25 of 29 nondiploid tumors, >50% of the topo IIalfa–positive cells were in the G0/G1 phase. This significant expression of topo IIalfa in the G0/G1 phase of the cell cycle may have clinically important implications for treatment efficacy of topoisomerase II inhibitors.
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| 20. |
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