| 1. |
- Luoma, M. L., et al.
(author)
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Physical performance, toxicity, and quality of life as assessed by the physician and the patient
- 2002
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In: Acta Oncol. - 0284-186X .- 1651-226X. ; 41:1, s. 44-9
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Journal article (peer-reviewed)abstract
- The aim of this study was to study the relationship between physician-assessed quality of life parameters, i.e., toxicity and physical performance, and patients' self-reports of their quality of life (QoL). QoL was assessed at baseline and before each treatment, using the EORTC QLQ-C30. The WHO performance score (PS) and toxicity were assessed in physician interviews. The correlations between the WHO PS and the QLQ-C30 functioning scale scores varied from weak to moderate, depending on the scale. Strongest associations were found in physical-, social-, and role functioning, and in the global QoL. The QLQ-C30 nausea/vomiting and diarrhea scales correlated moderately to corresponding WHO scores. A multiple linear regression analysis was used to analyze the contribution of WHO PS and toxicity variables to the global QoL. The best model explained only 16% of the variance of the global QoL score. The present findings highlight the importance of independent QoL assessments focused on those aspects of QoL not captured in clinical interviews with the physician.
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| 2. |
- Luoma, ML, et al.
(author)
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Prognostic value of quality of life scores for time to progression (TTP) and overall survival time (OS) in advanced breast cancer
- 2003
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In: European Journal of Cancer. - 1879-0852 .- 0959-8049. ; 39:10, s. 1370-1376
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Journal article (peer-reviewed)abstract
- The purpose of the study was to investigate whether baseline quality of life (QoL) and changes in QoL scores from baseline are prognostic for time to progression (TTP) and/or overall survival (OS) in patients with advanced breast cancer receiving docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Survival curves and probabilities were estimated using the Kaplan-Meier technique. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses to explore relationships between baseline QoL variables and TTP, as well as OS. In the univariate analysis, more severe pain and fatigue at baseline were predictive for a shorter OS; global QoL, physical functioning and appetite loss had a borderline significance (P=0.0130 for global QoL; P=0.0256 for physical functioning: P=0.0149 for appetite loss). World Health Organization (WHO) performance status was significantly predictive for OS. In the multivariate analysis, more severe pain at baseline was predictive for a shorter OS. In contrast, baseline QoL had no prognostic value for the duration of TTP. QoL change scores from baseline QoL predicted neither OS nor TTP. Our findings suggest that while QoL measurements are important in evaluating patients' QoL, they have no great importance in predicting primary clinical endpoints such as TTP or OS in advanced breast cancer patients. (C) 2002 Elsevier Science Ltd. All rights reserved.
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| 3. |
- Meinert, Mette, et al.
(author)
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Proteoglycans and hyaluronan in human fetal membranes
- 2001
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In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 184:4, s. 679-685
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to describe the distributions of major extracellular matrix components, such as proteoglycans, collagen acid hyaluronan, in the fetal membranes at term. STUDY DESIGN: Fetal membranes were obtained from elective cesarean deliveries at term. Guanidinium extracts were analyzed for proteoglycans with alcian blue precipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blotting and for hyaluronan with a radioimmunoassay. Collagen was measured by estimating hydroxyproline content. Tissue sections were immunostained for decorin and biglycan and stained for hyaluronan with a biotin-labeled hyaluronan-binding protein. RESULTS: The fetal membranes contained predominantly smaller proteoglycans, such as biglycan and decorin. The amnion consisted of typical fibrous connective tissue with a high concentration of collagen. The amnion was dominated by decorin located in close connection with the collagen fibrils. The chorion was composed of a fibroblastic part containing collagen and decorin and a trophoblastic part mainly containing biglycan. In addition, large amounts of hyaluronan were found, especially in the amnion and in the decidual cell layers. CONCLUSION: The distributions of proteoglycans, collagen, and hyaluronan in human fetal membranes may explain the biomechanical properties of this tissue. We suggest that changes in the relative proportions of these extracellular molecules are crucial for the proposed maturation process in the fetal membranes during the last weeks of pregnancy.
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| 4. |
- Sjostrom, J, et al.
(author)
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C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced breast cancer
- 2002
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In: European Journal of Cancer. - 1879-0852. ; 38:4, s. 535-542
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Journal article (peer-reviewed)abstract
- Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy. The predictive value of c-erbB-2 for taxane sensitivity is not yet clear. The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). A total of 283 patients with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer. Paraffin-embedded blocks of the primary tumour were available for 131 patients (46%). c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein. C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3+ scale. Staining scores 2+ or greater were considered positive, Response evaluation was performed according to World Health Organization (WHO) recommendations. Overall 54 (42%) patients had c-erbB-2-positive tumours. There was no association between treatment outcome and c-erbB-2 overexpression. The overall response rates (RR) (n = 128) among c-erbB-2 -negative and -positive patients were 35 and 44%, respectively (P=0.359). In the MF arm (n = 62), the RR was somewhat higher in the c-erbB-.2 overexpressors (33% versus 18%, P = 0. 18). In the docetaxel arm the RRs were very similar, regardless of the c-erbB-2 expression (53% versus 53%). While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer, the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial. In this study, c-erbB-2 expression could not predict response to either MF or T. Thus, tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression cannot yet be applied clinically as a predictive factor for response in advanced breast cancer.
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| 5. |
- Sjostrom, J, et al.
(author)
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The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer
- 2002
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In: Clinical Cancer Research. - 1078-0432. ; 8:3, s. 811-816
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Journal article (peer-reviewed)abstract
- Purpose: The purpose was to evaluate the utility of some bcl-2 family proteins fas and fasL as predictive indicators for chemotherapy response in advanced breast cancer. Experimental Design: Between October 1994 and October 1997, 283 patients with advanced breast cancer were included in a multicenter randomized study comparing docetaxel (D) to sequential methotrexate and 5-fluorouracil (MF) after anthracycline failure. The response rates (complete response + partial response) were 42 and 21% in the D and MF arms, respectively (P < 0.001). In 126 patients, histological blocks of primary tumors were available for inummohistochemical analysis of bax, bcl-2, bcl-xL, bag-1, fas and fasL. Results: Of the investigated factors, bag-1 correlated positively with bax, bcl-2, and fasL, and fasL correlated positively with fas and bax. None of these apoptosis-related factors was associated with a response to chemotherapy either in the whole patient population or in the D or MF arms. Interestingly, low bcl-2 expression was associated with shorter time to progression (P = 0.02) and shorter overall survival (OS; P = 0.001). High fasL expression showed a trend toward shorter OS. In multivariate backwards stepwise Cox analysis, in which histological grade and estrogen receptor status (ER) were also included, bcl-2 (P = 0.01) and fasL (P = 0.005) remained highly significantly associated with OS, whereas histological grade and ER lost their significance. Conclusions: None of the investigated apoptosis-related factors of primary tumor could predict the later response to either D or MF treatment. However, fasL and bcl-2 were strong prognostic factors. Patients who had tumors with high fasL and low bcl-2 expression had the shortest OS.
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| 6. |
- Tynninen, O, et al.
(author)
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Tumour microvessel density as predictor of chemotherapy response in breast cancer patients
- 2002
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 86:12, s. 1905-1908
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate the predictive value of intratumoural microvessel density in breast cancer. We studied immunohistochemically primary tumours of 104 patients with metastasised breast cancer who took part in a randomised multicentre trial comparing docetaxel to sequential methotrexate and 5-fluorouracil. Vessels were highlighted with factor VIII staining and counted microscopically. Microvessel density was compared with clinical response to chemotherapy and patient survival. The microvessel density of the primary tumour was not significantly associated with patient's response to chemotherapy, time to progression or overall survival in the whole patient population or in the docetaxel or methotrexate and 5-fluorouracil groups. However, disease-free survival was longer in patients with low microvessel density (P=0.01). These findings suggest that microvessel density of the primary tumour cannot be used as a predictive marker for chemotherapy response in advanced breast cancer.
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| 7. |
- Xia, Guoqing, et al.
(author)
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Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus, type 1
- 2002
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In: Journal of Biological Chemistry. - 1083-351X. ; 277:40, s. 37912-37919
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Journal article (peer-reviewed)abstract
- Heparan sulfate 3-O-sulfotransferase transfers sulfate to the 3-OH position of a glucosamine residue of heparan sulfate (HS) to form 3-O-sulfated HS. The 3-O-sulfated glucosamine residue contributes to two important biological functions of HS: binding to antithrombin and thereby carrying anticoagulant activity, and binding to herpes simplex viral envelope glycoprotein D to serve as an entry receptor for herpes simplex virus 1. A total of five HS 3-O-sulfotransferase isoforms were reported previously. Here we report the isolation and characterization of a novel HS 3-O-sulfotransferase isoform, designated as HS 3-O-sulfotransferase isoform 5 (3-OST-5). 3-OST-5 cDNA was isolated from a human placenta cDNA library and expressed in COS-7 cells. The disaccharide analysis of 3-OST-5-modified HS revealed that 3-OST-5 generated at least three 3-O-sulfated disaccharides as follows: IdoUA2S-AnMan3S, GlcUA-AnMan3S6S, and IdoUA2S-AnMan3S6S. Transfection of the plasmid expressing 3-OST-5 rendered wild type Chinese hamster ovary cells susceptible to the infection by herpes simplex virus 1, suggesting that 3-OST-5-modified HS serves as an entry receptor for herpes simplex virus 1. In addition, 3-OST-5-modified HS bound to herpes simplex viral envelope protein glycoprotein D. Furthermore, we found that 3-OST-5-modified HS also bound to antithrombin, suggesting that 3-OST-5 also produces anticoagulant HS. In summary, our results indicate that a new member of 3-OST family generates both anticoagulant HS and an entry receptor for herpes simplex virus 1. These results provide a new insight regarding the mechanism for the biosynthesis of biologically active HS.
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