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Sökning: WFRF:(Fjällskog Marie Louise)

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  • Föregående 123[4]567...8Nästa
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31.
  • Deb, Siddhartha, et al. (författare)
  • Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer.
  • 2014
  • Ingår i: Modern Pathology. - Nature Publishing Group. - 1530-0285. ; 27:9, s. 1223-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1α (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.Modern Pathology advance online publication, 24 January 2014; doi:10.1038/modpathol.2013.231.
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32.
  • Fjällskog, Marie-Louise (författare)
  • Current Medical Treatment of Endocrine Pancreatic Tumors and Future Aspects
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>We treated 16 patients with somatostatin analogs combined with α-interferon and achieved a biochemical and/or radiological response in 56% (median duration 22 months). We consider this treatment a good alternative for patients who fail during chemotherapy or who do not want to/cannot receive cytotoxic drugs.</p><p>Thirty-six patients with neuroendocrine tumors were treated with cisplatin combined with etoposide. Of 14 patients with evaluable EPTs, 50% responded radiologically and/or biochemically (median duration 9 months). We consider this treatment useful as first-line medical treatment in aggressive EPTs or in patients failing prior chemotherapy.</p><p>Twenty-eight tumor tissues from EPTs were examined with immunohistochemistry regarding expression of somatostatin receptors (ssts) 1 to 5 on tumor cells and in intratumoral vessels. We found that sst<sub>2</sub> and sst<sub>4</sub> were highly expressed on tumor cells and in vessels. However, sst<sub>3</sub> and sst<sub>5</sub> were lacking in half of the tumor tissues and in most of the vessels. Because of the variability in sst expression, we recommend analysis of each individual’s receptor expression before starting treatment.</p><p>Endocrine pancreatic tumors (EPTs) are rare with an incidence of 4 per million inhabitants. In the majority of cases they grow slowly, but there are exceptions with very rapidly progressing malignant carcinomas. First-line medical treatment is streptozotocin combined with 5-fluorouracil.</p><p>We examined 38 tumor samples regarding expression of tyrosine kinase receptors platelet-derived growth factor receptors (PDGFRs), c-kit and epidermal growth factor receptor (EGFR). We found that the receptors were expressed in more than half of the tumor tissues. Further studies will reveal if tyrosin kinase antagonists can be part of the future treatment arsenal.</p>
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33.
  • Fjällskog, Marie-Louise, et al. (författare)
  • Expression of molecular targets for tyrosine kinase antagonists in malignant endocrine pancreatic tumors
  • 2003
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 9:4, s. 1469-1473
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>PURPOSE:</strong></p> <p>Molecular targeting with monoclonal antibodies and tyrosine kinase inhibitors is a novel approach to cancer treatment. We have examined the expression of molecular targets in patients with malignant endocrine pancreatic tumors, which is necessary to justify additional studies investigating the potential benefit from such treatment.</p> <p><strong>EXPERIMENTAL DESIGN:</strong></p> <p>Thirty-eight tumor tissues from malignant endocrine pancreatic tumors were examined with immunohistochemistry using specific polyclonal antibodies with regard to the expression pattern of platelet-derived growth factor receptors (PDGFRs) alpha and beta, c-kit, and epidermal growth factor receptor (EGFR).</p> <p><strong>RESULTS:</strong></p> <p>All 38 tissue specimens expressed PDGFRalpha on tumor cells, and 21 of 37 specimens (57%) expressed PDGFRalpha in tumor stroma (1 specimen was nonevaluable). Twenty-eight samples (74%) stained positive for PDGFRbeta on tumor cells, and 36 of 37 samples (97%) stained positive for PDGFRbeta in the stroma (1 specimen was nonevaluable). Thirty-five tumor tissues (92%) stained positive for c-kit, and 21 (55%) stained positive for EGFR on tumor cells. No differences were seen between syndromes or between poorly differentiated or well-differentiated tumors. Previous treatment did not influence expression pattern. Receptor expression pattern varied considerably between individuals.</p> <p><strong>CONCLUSIONS:</strong></p> <p>We have found that tyrosine kinase receptors PDGFRs alpha and beta, EGFR, and c-kit are expressed in more than half of the patients with endocrine pancreatic tumors. Because these receptors represent molecular targets for STI571 and ZD1839 (tyrosine kinase inhibitors) and IMC-C225 (a monoclonal antibody), we propose that patients suffering from EPTs might benefit from this new treatment strategy. However, because of great variability in receptor expression pattern, all patients' individual receptor expression should be examined.</p>
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34.
  • Fjällskog, Marie-Louise, et al. (författare)
  • Expression of somatostatin receptor subtypes 1 to 5 in tumor tissue and intratumoral vessels in malignant endocrine pancreatic tumors
  • 2003
  • Ingår i: Medical Oncology. - 1357-0560 .- 1559-131X. ; 20:1, s. 59-67
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Somatostatin analogs are well established in the treatment of malignant endocrine pancreatic tumors (EPTs). Our goal is to individualize their treatment using receptor-subtype-specific analogs and, therefore, exploring the receptor expression is highly important. We have examined the expression of somatostatin receptor (sst) subtypes 1–5 on tumor cells and in intratumoral vessels in 28 tumor tissues from malignant EPTs with immunohistochemistry using sst-subtype-specific polyclonal antibodies. We found that sst<sub>2</sub> and sst<sub>4</sub> stained positive in 90% and sst<sub>1</sub> in 70% of the tumor tissues, whereas sst<sub>3</sub> and sst<sub>5</sub> stained positive in only 50% of the tumor tissues. Sst expression in intratumoral vessels was high for sst<sub>2</sub> and sst<sub>4</sub> (80%), moderate for sst<sub>1</sub> (40%), and low for sst<sub>3</sub> and sst<sub>5</sub> (10%). The ssts were evenly distributed among the different tumor subtypes. However, tumors belonging to the same subgroup of EPTs showed a variable expression of receptor subtypes. No differences in receptor-subtype expression could be seen between poorly and well-differentiated tumors, nor between primary tumors and metastases. Prior medical treatment did not influence sst expression pattern. In conclusion, sst<sub>2</sub> and sst<sub>4</sub> were expressed in most tumor tissues and intratumoral vessels from EPTs. However, sst<sub>3</sub> and sst<sub>5</sub> were lacking in half of the tumor tissues and in most of the intratumoral vessels. These differences indicate the importance of determining each tumor’s subset of receptors before treatment with receptor-subtype-specific analogs is initiated. The importance of sst expression in intratumoral vessels is not yet known.</p>
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35.
  • Fjällskog, Marie-Louise H, et al. (författare)
  • Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumors
  • 2003
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 9:4, s. 1469-1473
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>PURPOSE:</strong></p> <p>Molecular targeting with monoclonal antibodies and tyrosine kinase inhibitors is a novel approach to cancer treatment. We have examined the expression of molecular targets in patients with malignant endocrine pancreatic tumors, which is necessary to justify additional studies investigating the potential benefit from such treatment.</p> <p><strong>EXPERIMENTAL DESIGN:</strong></p> <p>Thirty-eight tumor tissues from malignant endocrine pancreatic tumors were examined with immunohistochemistry using specific polyclonal antibodies with regard to the expression pattern of platelet-derived growth factor receptors (PDGFRs) alpha and beta, c-kit, and epidermal growth factor receptor (EGFR).</p> <p><strong>RESULTS:</strong></p> <p>All 38 tissue specimens expressed PDGFRalpha on tumor cells, and 21 of 37 specimens (57%) expressed PDGFRalpha in tumor stroma (1 specimen was nonevaluable). Twenty-eight samples (74%) stained positive for PDGFRbeta on tumor cells, and 36 of 37 samples (97%) stained positive for PDGFRbeta in the stroma (1 specimen was nonevaluable). Thirty-five tumor tissues (92%) stained positive for c-kit, and 21 (55%) stained positive for EGFR on tumor cells. No differences were seen between syndromes or between poorly differentiated or well-differentiated tumors. Previous treatment did not influence expression pattern. Receptor expression pattern varied considerably between individuals.</p> <p><strong>CONCLUSIONS:</strong></p> <p>We have found that tyrosine kinase receptors PDGFRs alpha and beta, EGFR, and c-kit are expressed in more than half of the patients with endocrine pancreatic tumors. Because these receptors represent molecular targets for STI571 and ZD1839 (tyrosine kinase inhibitors) and IMC-C225 (a monoclonal antibody), we propose that patients suffering from EPTs might benefit from this new treatment strategy. However, because of great variability in receptor expression pattern, all patients' individual receptor expression should be examined.</p>
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36.
  • Fjällskog, Marie-Louise H., et al. (författare)
  • Treatment with Combined Streptozotocin and Liposomal Doxorubicin in Metastatic Endocrine Pancreatic Tumors
  • 2008
  • Ingår i: Neuroendocrinology. - 0028-3835 .- 1423-0194. ; 88:1, s. 53-8
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Treatment with combined streptozotocin and liposomal doxorubicin is safe and efficient in patients with endocrine pancreatic tumors (EPTs). No cardiac toxicity was reported. BACKGROUND: The combination of streptozotocin and doxorubicin has been shown to be superior to streptozotocin and fluorouracil in the treatment of metastatic EPTs. However, the risk of cardiac toxicity from anthracyclins hampers the usefulness of the drug combination. Liposomal doxorubicin has a lower frequency of cardiac adverse events compared to doxorubicin. We wanted to assess the efficacy and safety of combined streptozotocin and liposomal doxorubicin in patients with metastatic EPTs. METHODS: Thirty patients with metastatic EPTs were recruited from three medical centers in Norway and Sweden during a time period of 3 years. All patients had histopathologically confirmed diagnoses and bidimensionally measurable lesions. 30 mg/m(2) of liposomal doxorubicin was administered on day 1 of each cycle. During the first course, 1 g of streptozotocin was given on 5 consecutive days. Thereafter, 2 g of streptozotocin was given on day 1 only. Treatment was repeated every 3 weeks. RESULTS: Twelve of 30 patients (40%) achieved an objective radiological response with a median duration of 9 months. Stabilization of disease was achieved in 17 of 30 patients (57%) for a median duration of 11 months. Only one patient had progressive disease as best response. The 2-year progression-free survival was 18% and the 2-year overall survival was 72%. The treatment was well tolerated. None of the patients experienced cardiac toxicity. CONCLUSION: We conclude that combined streptozotocin and liposomal doxorubicin is a safe and efficient treatment for EPTs. The efficacy seems to be comparable to that of combined streptozotocin and doxorubicin, whereas the cardiac toxicity clearly favors using the liposomal drug combination. 2008 S. Karger AG, Basel.</p>
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37.
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38.
  • Fjällskog, Marie-Louise, et al. (författare)
  • Treatment of endocrine pancreatic tumors
  • 2005
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 44:4, s. 329-338
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Endocrine pancreatic tumors are rare with an incidence of 4 per million inhabitants. Most tumors are malignant except for insulinomas that usually are benign. They are slowly growing in the majority of cases but there are exceptions with rapidly progressing malignant carcinomas. Because of the rarity of these tumors large randomized trials are difficult to accomplish. However, most physicians treating these patients agree that surgery should be considered in all cases and that medical treatment with chemotherapy and biotherapy is well established for this group of patients.</p>
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39.
  • Fjällskog, Marie-Louise, et al. (författare)
  • Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs
  • 2002
  • Ingår i: Medical Oncology. - 1357-0560 .- 1559-131X. ; 19:1, s. 35-42
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Somatostatin analogs and alpha-interferon induce good responses as single drugs in the treatment of endocrine pancreatic tumors. We examined the efficacy and tolerability of the combination of alpha-interferon and somatostatin analogs in 16 patients with metastatic endocrine pancreatic tumors. All patients except one had received prior treatment and were in a progressive state. Doses of alpha-interferon and somatostatin analogs were individually titrated. The alpha-interferon doses varied between 9 and 25 million units per week and were combined with 100-1500 microg of octreotide or 6000 microg of lanreotide daily. Radiological response was seen in 3 of 16 (19%) patients (median duration 23 mo). Biochemical response was seen in 10 of 16 (62.5%) patients (median duration 22 mo). All three patients previously progressing on both alpha-interferon and somatostatin analog as single drugs achieved a stabilization of the disease when treated with the combination (median duration 10 mo). Seven of eight (88%) patients previously progressing on alpha-interferon treatment benefited from the combination with biochemical partial response or stabilization. All six patients previously progressing during somatostatin analog treatment achieved biochemical partial response or stabilization. More than 80% of patients who progressed during previous treatment with either drug benefited from the combined treatment, which also was well tolerated. Thus, a combination of alpha-interferon and somatostatin analogs may be considered for patients previously progressing on treatment with alpha-interferon or somatostatin analogs. However, in this study, the value of sequential treatment has not been evaluated.</p>
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40.
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