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Article ; Online: β2-adrenergic receptor expression in patients receiving bevacizumab therapy for metastatic melanoma.

Schuster, Cornelia / Akslen, Lars A / Straume, Oddbjørn

2023 Volume 12, Issue 17, Page(s) 17891–17900

Abstract: Background: Vascular endothelial growth factor (VEGF) was initially known as vascular permeability factor and identified as a driver of tumour angiogenesis. Recently, its role in supporting an immunosuppressive tumour microenvironment was demonstrated, ... ...

Abstract	Background: Vascular endothelial growth factor (VEGF) was initially known as vascular permeability factor and identified as a driver of tumour angiogenesis. Recently, its role in supporting an immunosuppressive tumour microenvironment was demonstrated, and anti-VEGF treatment combined with immune checkpoint blockade is currently investigated. Further, beta-adrenergic signalling as a modifier of cancer hallmarks like immune response, angiogenesis and metastasis gained increased attention during past years. Methods: Focusing on the aspect of immunosuppression in upregulated beta-adrenergic signalling, we investigated predictive markers in patients with metastatic melanoma who received bevacizumab monotherapy, a specific VEGF-A binding antibody. We explored the expression of beta-2 adrenergic receptor (β2-AR), interleukin 6-receptor (IL6-R), cyclooxygenase 2 (COX2) and VEGF-A by immunohistochemistry in melanoma to assess the correlation between these proteins in melanoma cells and response to treatment. Results: Strong β2-AR expression in metastases was associated with clinical benefit of bevacizumab. Furthermore, expression of the latter was positively linked to expression of VEGF-A and COX2. β2-AR expression in melanoma metastasis appears to distinguish a subgroup of patients that might benefit from anti-VEGF treatment. Conclusion: Our results strengthen further exploration of anti-VEGF therapy in combination with immune checkpoint blockade in clinical studies and the investigation of β2-AR as predictive marker.
MeSH term(s)	Humans ; Bevacizumab/therapeutic use ; Vascular Endothelial Growth Factor A/metabolism ; Receptors, Adrenergic, beta-2 ; Cyclooxygenase 2 ; Immune Checkpoint Inhibitors/therapeutic use ; Melanoma/pathology ; Adrenergic Agents/therapeutic use ; Tumor Microenvironment
Chemical Substances	Bevacizumab (2S9ZZM9Q9V) ; Vascular Endothelial Growth Factor A ; Receptors, Adrenergic, beta-2 ; Cyclooxygenase 2 (EC 1.14.99.1) ; Immune Checkpoint Inhibitors ; Adrenergic Agents
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6424
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The link between wound healing and escape from tumor dormancy.

Dillekås, Hanna / Straume, Oddbjørn

Surgical oncology

2018 Volume 28, Page(s) 50–56

Abstract: Tumor dormancy is considered one of the major unsolved questions in cancer biology. Understanding the mechanisms responsible for maintaining and interrupting dormancy would be a major step towards preventing overt metastatic disease. Increasing evidence ... ...

Abstract	Tumor dormancy is considered one of the major unsolved questions in cancer biology. Understanding the mechanisms responsible for maintaining and interrupting dormancy would be a major step towards preventing overt metastatic disease. Increasing evidence points to tissue trauma and subsequent wound healing as contributing events in escape from dormancy. In this review, we outline relevant aspects of the wound healing process, and relate this to mechanisms of tumor dormancy and metastatic progression. In addition to important findings in epidemiological and experimental studies, more direct evidence of such a link has recently been presented. These results can have major implications for treatment and prevention of cancer.
MeSH term(s)	Disease Progression ; Humans ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/physiopathology ; Neoplasms/physiopathology ; Tumor Microenvironment ; Wound Healing
Language	English
Publishing date	2018-11-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1107810-8
ISSN	1879-3320 ; 0960-7404
ISSN (online)	1879-3320
ISSN	0960-7404
DOI	10.1016/j.suronc.2018.11.009
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Article ; Online: Distant metastasis dynamics following subsequent surgeries after primary breast cancer removal.

Demicheli, Romano / Dillekås, Hanna / Straume, Oddbjørn / Biganzoli, Elia

Breast cancer research : BCR

2019 Volume 21, Issue 1, Page(s) 57

Abstract: Background: The aim of the research was to separate the distant metastasis (DM) enhancing effect due to breast tumour removal from that due to surgical manoeuvre by itself.: Methods: DM dynamics following surgery for ipsilateral breast tumour ... ...

Abstract	Background: The aim of the research was to separate the distant metastasis (DM) enhancing effect due to breast tumour removal from that due to surgical manoeuvre by itself. Methods: DM dynamics following surgery for ipsilateral breast tumour recurrence (IBTR), contralateral breast cancer (CBC) and delayed reconstruction (REC), which was performed after the original breast cancer surgical removal, was analysed. A total of 338 patients with IBTR, 239 with CBC and 312 with REC were studied. Results: The DM dynamics following IBTR, CBC and REC, when assessed with time origin at their surgical treatment, is similar to the analogous pattern following primary tumour removal, with a first major peak at about 18 months and a second lower one at about 5 years from surgery. The time span between primary tumour removal and the second surgery is influential on DM risk levels for IBTR and CBC patients, not for REC patients. Conclusions: The role of breast tumour removal is different from the role of surgery by itself. Our findings suggest that the major effect of reconstructive surgery is microscopic metastasis acceleration, while breast tumour surgical removal (either primary or IBTR or CBC) involves both tumour homeostasis interruption and microscopic metastasis growth acceleration. The removal of a breast tumour would eliminate its homeostatic restrains on metastatic foci, thus allowing metastasis development, which, in turn, would be supported by the forwarding action of the mechanisms triggered by the surgical wounding.
MeSH term(s)	Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Female ; Humans ; Mastectomy/adverse effects ; Mastectomy/methods ; Middle Aged ; Neoplasm Metastasis ; Postoperative Period ; Tumor Burden ; Young Adult
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2019-05-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-019-1139-7
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Zs.A 5494: Show issues

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Article ; Online: Are 90% of deaths from cancer caused by metastases?

Dillekås, Hanna / Rogers, Michael S / Straume, Oddbjørn

Cancer medicine

2019 Volume 8, Issue 12, Page(s) 5574–5576

Abstract: Numerous publications have stated that metastases are responsible for 90% of cancer deaths, but data underlying this assertion has been lacking. Our objective was to determine what proportions of cancer deaths are caused by metastases. Population-based ... ...

Abstract	Numerous publications have stated that metastases are responsible for 90% of cancer deaths, but data underlying this assertion has been lacking. Our objective was to determine what proportions of cancer deaths are caused by metastases. Population-based data from the Cancer Registry of Norway for the years 2005-2015 was analyzed. We compared all deaths in the Norwegian population where a cancer diagnosis was registered as cause of death. Deaths caused by cancer, with and without metastases, were analyzed, by sex and tumor group. For solid tumors, 66.7% of cancer deaths were registered with metastases as a contributing cause. Proportions varied substantially between tumor groups. Our data support the idea that the majority of deaths from solid tumors are caused by metastases. Thus, a better understanding of the biology of metastases and identification of druggable targets involved in growth at the metastatic site is a promising strategy to reduce cancer mortality.
MeSH term(s)	Cause of Death ; Female ; Humans ; Male ; Neoplasm Metastasis ; Neoplasms/mortality ; Norway/epidemiology ; Registries
Language	English
Publishing date	2019-08-08
Publishing country	United States
Document type	Journal Article
ISSN	2045-7634
ISSN (online)	2045-7634
DOI	10.1002/cam4.2474
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Article ; Online: HSP27 Expression as a Novel Predictive Biomarker for Bevacizumab: is it Cost Effective?

Seo, Mikyung Kelly / Straume, Oddbjørn / Akslen, Lars A / Cairns, John

PharmacoEconomics - open

2020 Volume 4, Issue 3, Page(s) 529–539

Abstract: Background: Despite the extensive use of bevacizumab in a range of oncology indications, the US FDA revoked its approval for breast cancers, and multiple negative trials in several solid malignancies have been reported, so the need for predictive ... ...

Abstract	Background: Despite the extensive use of bevacizumab in a range of oncology indications, the US FDA revoked its approval for breast cancers, and multiple negative trials in several solid malignancies have been reported, so the need for predictive biomarkers has increased. The development of predictive biomarkers for anti-angiogenic bevacizumab therapy has long been pursued but without success. Introduction: Heat shock protein (HSP)-27 expression has recently been identified as a predictive biomarker for bevacizumab in treating metastatic melanoma. This study aimed to evaluate the cost effectiveness of HSP27 biomarker testing before administration of bevacizumab. Methods: A partitioned survival analysis model with three mutually exclusive health states (progression-free survival, progressed disease, and death) was developed using a Norwegian health system perspective. The proportion of patients in each state was calculated using the area under the Kaplan-Meier curve for progression-free and overall survival derived from trials of bevacizumab and dacarbazine. Three strategies were compared: (1) test-treat with HSP27 biomarker and bevacizumab, (2) treat-all with dacarbazine without HSP27 testing, (3) treat-all with bevacizumab without HSP27 testing. Quality-adjusted life-years (QALYs) and costs were calculated for each strategy and discounted at 4%. A lifetime horizon was applied. Uncertainty analyses were performed. Expected value of perfect information (EVPI) was estimated to assess the potential value of further research to generate more evidence. Results: Although the test-treat strategy was cost effective compared with treat-all with dacarbazine, it was not cost effective compared with treat-all with bevacizumab without HSP27 testing. However, EVPI results showed very minimal or no value in conducting further research efforts to reduce uncertainties around current information. Conclusion: The results of this study suggested that testing for HSP27 expression before administering bevacizumab is not cost effective compared with treat-all with bevacizumab without testing. It indicates that HSP27 expression is not cost effective as a potential predictive biomarker for bevacizumab. This may not necessarily mean that HSP27 is a bad biomarker for bevacizumab, but it may mean that bevacizumab is much better than dacarbazine regardless of HSP27 expression, so patient stratification according to HSP27 status is meaningless. Or, indeed, it may imply that HSP27 is not sufficiently good at identifying the right patients for bevacizumab.
Language	English
Publishing date	2020-01-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2874287-4
ISSN	2509-4254 ; 2509-4262
ISSN (online)	2509-4254
ISSN	2509-4262
DOI	10.1007/s41669-019-00193-8
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Article ; Online: Elevated plasma interleukin 6 predicts poor response in patients treated with sunitinib for metastatic clear cell renal cell carcinoma.

Pilskog, Martin / Nilsen, Gry Hilde / Beisland, Christian / Straume, Oddbjørn

Cancer treatment and research communications

2019 Volume 19, Page(s) 100127

Abstract: Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common type among renal cell carcinomas, and anti-angiogenic treatment is currently first line therapy in metastatic ccRCC (mccRCC). Response rates and duration of response show ... ...

Abstract	Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common type among renal cell carcinomas, and anti-angiogenic treatment is currently first line therapy in metastatic ccRCC (mccRCC). Response rates and duration of response show considerable variation, and adverse events have major influence on patient's quality of life. The need for predictive biomarkers to select those patients most likely to respond to receptor tyrosine kinase inhibitors (rTKI) upfront is urgent. We investigated the predictive value of plasma interleukin-6 (pIL6), interleukin-6 receptor α (pIL6Rα) and interleukin 6 signal transducer (pIL6ST) in mccRCC patients treated with sunitinib. Material and methods: Forty-six patients with metastatic or non-resectable ccRCC treated with sunitinib were included. Full blood samples were collected at baseline before start of sunitinib and after every second cycle of treatment during the study time. pIL6, pIL6R and pIL6ST at baseline and week 12 samples were analysed by ELISA. The predictive potential of the candidate markers was assessed by correlation with response rates (RECIST). In addition, progression free survival (PFS) and overall survival (OS) were analysed. Results: Low pIL6 at baseline was significantly associated with improved response to sunitinib (Fisher's exact test, p < 0.01). Furthermore, low pIL6 at baseline was significantly associated with improved PFS (log rank, p = 0.04). In addition, patients with a decrease in concentration of pIL6R between baseline and week 12 showed significantly improved PFS (log rank, p = 0.04) and patients with high pIL6ST at baseline showed significantly improved OS (log rank, p = 0.03). Conclusion: Low pIL6 at baseline in mccRCC patients treated with sunitinib predicts improved treatment response, and might represent a candidate predictive marker.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/blood ; Carcinoma, Renal Cell/blood ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/secondary ; Cytokine Receptor gp130/blood ; Female ; Follow-Up Studies ; Humans ; Interleukin-6/blood ; Kidney Neoplasms/blood ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/pathology ; Male ; Middle Aged ; Prognosis ; Quality of Life ; Receptors, Interleukin-6/blood ; Sunitinib/therapeutic use ; Survival Rate
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor ; IL6 protein, human ; IL6R protein, human ; IL6ST protein, human ; Interleukin-6 ; Receptors, Interleukin-6 ; Cytokine Receptor gp130 (133483-10-0) ; Sunitinib (V99T50803M)
Language	English
Publishing date	2019-03-14
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2468-2942
ISSN (online)	2468-2942
DOI	10.1016/j.ctarc.2019.100127
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Article ; Online: Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years.

Haaland, Gry S / Falk, Ragnhild S / Straume, Oddbjørn / Lorens, James B

JAMA internal medicine

2018 Volume 177, Issue 12, Page(s) 1774–1780

Abstract: Importance: In cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and ... ...

Abstract	Importance: In cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort. Objective: To examine the association between warfarin use and cancer incidence. Design, setting, and participants: This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway. The cohort comprised all persons (N = 1 256 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups-warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup. Data were collected from January 1, 2004, to December 31, 2012. Data analysis was conducted from October 15, 2016, to January 31, 2017. Exposures: Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis. If warfarin treatment started after January 1, 2006, each person contributed person-time in the nonuser group until the warfarin user criteria were fulfilled. Main outcomes and measures: Cancer diagnosis of any type during the 7-year observation period (January 1, 2006, through December 31, 2012). Results: Of the 1 256 725 persons in the cohort, 607 350 (48.3%) were male, 649 375 (51.7%) were female, 132 687 (10.6%) had cancer, 92 942 (7.4%) were classified as warfarin users, and 1 163 783 (92.6%) were classified as nonusers. Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years, and were predominantly men (57 370 [61.7%]) as compared with nonusers, who had a mean (SD) age of 63.9 (8.6) years and were mostly women (613 803 [52.7%]). Among warfarin users and compared with nonusers, there was a significantly lower age- and sex-adjusted incidence rate ratio (IRR) in all cancer sites (IRR, 0.84; 95% CI, 0.82-0.86) and in prevalent organ-specific sites (lung, 0.80 [95% CI, 0.75-0.86]; prostate, 0.69 [95% CI, 0.65-0.72]; and breast, 0.90 [95% CI, 0.82-1.00]). There was no observed significant effect in colon cancer (IRR, 0.99; 95% CI, 0.93-1.06). In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR, 0.62; 95% CI, 0.59-0.65) and in prevalent sites (lung, 0.39 [95% CI, 0.33-0.46]; prostate, 0.60 [95% CI, 0.55-0.66]; breast, 0.72 [95% CI, 0.59-0.87]; and colon, 0.71 [95% CI, 0.63-0.81]). Conclusions and relevance: Warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. This finding could have important implications for the selection of medications for patients needing anticoagulation.
MeSH term(s)	Aged ; Anticoagulants/therapeutic use ; Atrial Fibrillation/drug therapy ; Atrial Flutter/drug therapy ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/epidemiology ; Norway/epidemiology ; Registries ; Warfarin/therapeutic use
Chemical Substances	Anticoagulants ; Warfarin (5Q7ZVV76EI)
Language	English
Publishing date	2018-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2699338-7
ISSN	2168-6114 ; 2168-6106
ISSN (online)	2168-6114
ISSN	2168-6106
DOI	10.1001/jamainternmed.2017.5512
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Article ; Online: Predictive value of angiogenic proteins in patients with metastatic melanoma treated with bevacizumab monotherapy.

Schuster, Cornelia / Akslen, Lars A / Stokowy, Tomasz / Straume, Oddbjørn

The journal of pathology. Clinical research

2018 Volume 5, Issue 1, Page(s) 53–62

Abstract: The incidence of malignant melanoma is rising worldwide and survival for metastatic disease is still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In ... ...

Abstract	The incidence of malignant melanoma is rising worldwide and survival for metastatic disease is still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In this study, we investigated the predictive value of 60 angiogenic factors in patients with metastatic melanoma treated with the anti-vascular endothelial growth factor A antibody bevacizumab. Thirty-five patients were included in a clinical phase II trial and baseline serum samples were analysed by multiplex protein array. High-serum concentration of Activin A was significantly associated with objective response (OR) to treatment (p = 0.014). Candidate proteins that indicated a borderline association with treatment response were further investigated by immunohistochemistry. Strong expression of Activin A, interleukin-1β, and urokinase-type plasminogen activator receptor in metastases was significantly associated with OR (p = 0.011, p = 0.003, and p = 0.007, respectively), as well as with markers of activated angiogenesis, such as higher number of proliferating vessels and the presence of glomeruloid microvascular proliferations. Our findings indicate that these proteins may be potential predictive markers for treatment with bevacizumab monotherapy.
MeSH term(s)	Angiogenesis Inhibitors/administration & dosage ; Angiogenesis Inhibitors/therapeutic use ; Bevacizumab/therapeutic use ; Biomarkers, Tumor/metabolism ; Colorectal Neoplasms/drug therapy ; Female ; Humans ; Male ; Melanoma/drug therapy ; Melanoma/secondary ; Neovascularization, Pathologic/drug therapy
Chemical Substances	Angiogenesis Inhibitors ; Biomarkers, Tumor ; Bevacizumab (2S9ZZM9Q9V)
Language	English
Publishing date	2018-11-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2814357-7
ISSN	2056-4538 ; 2056-4538
ISSN (online)	2056-4538
ISSN	2056-4538
DOI	10.1002/cjp2.116
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Article ; Online: Expression of Heat Shock Protein 27 in Melanoma Metastases Is Associated with Overall Response to Bevacizumab Monotherapy: Analyses of Predictive Markers in a Clinical Phase II Study.

Schuster, Cornelia / Akslen, Lars A / Straume, Oddbjørn

PloS one

2016 Volume 11, Issue 5, Page(s) e0155242

Abstract: The aim of this study was to identify potential predictive biomarkers in 35 patients with metastatic melanoma treated with anti-angiogenic bevacizumab monotherapy in a clinical phase II study. The immunohistochemical expression of various angiogenic ... ...

Abstract	The aim of this study was to identify potential predictive biomarkers in 35 patients with metastatic melanoma treated with anti-angiogenic bevacizumab monotherapy in a clinical phase II study. The immunohistochemical expression of various angiogenic factors in tissues from primary melanomas and metastases as well as their concentration in blood samples were examined. Strong expression of Heat Shock Protein 27 (HSP27) in metastases correlated significantly with complete or partial response to bevacizumab (p = 0.044). Furthermore, clinical benefit, i.e., complete or partial response or stable disease for at least 6 months, was more frequent in patients with strong expression of HSP27 in primary tumors (p = 0.046). Tissue expression of vascular endothelial growth factor (VEGF-A), its splicing variant VEGF165b or basic fibroblast growth factor (bFGF) did not correlate with response, and the concentration of HSP27, VEGF-A or bFGF measured in blood samples before treatment did not show predictive value. Further, microvessel density, proliferating microvessel density and presence of glomeruloid microvascular proliferations were assessed in sections of primary tumors and metastases. Microvessel density in primary melanomas was significantly higher in patients with clinical benefit than in non-responders (p = 0.042). In conclusion, our findings suggest that strong HSP27 expression in melanoma metastases predicts response to bevacizumab treatment.
MeSH term(s)	Adult ; Angiogenesis Inhibitors/therapeutic use ; Bevacizumab/therapeutic use ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics ; Female ; Fibroblast Growth Factor 2/blood ; Fibroblast Growth Factor 2/genetics ; Gene Expression Regulation, Neoplastic ; HSP27 Heat-Shock Proteins/blood ; HSP27 Heat-Shock Proteins/genetics ; Humans ; Liver Neoplasms/blood supply ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/secondary ; Lung Neoplasms/blood supply ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Melanoma/blood supply ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/secondary ; Middle Aged ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/pathology ; Prognosis ; Signal Transduction ; Skin Neoplasms/blood supply ; Skin Neoplasms/drug therapy ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Vascular Endothelial Growth Factor A/blood ; Vascular Endothelial Growth Factor A/genetics
Chemical Substances	Angiogenesis Inhibitors ; Biomarkers, Tumor ; HSP27 Heat-Shock Proteins ; HSPB1 protein, human ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Fibroblast Growth Factor 2 (103107-01-3) ; Bevacizumab (2S9ZZM9Q9V)
Language	English
Publishing date	2016-05-11
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0155242
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Article ; Online: Expression of Heat Shock Protein 27 in Melanoma Metastases Is Associated with Overall Response to Bevacizumab Monotherapy

Cornelia Schuster / Lars A Akslen / Oddbjørn Straume

PLoS ONE, Vol 11, Iss 5, p e

Analyses of Predictive Markers in a Clinical Phase II Study.

2016 Volume 0155242

Abstract	The aim of this study was to identify potential predictive biomarkers in 35 patients with metastatic melanoma treated with anti-angiogenic bevacizumab monotherapy in a clinical phase II study. The immunohistochemical expression of various angiogenic factors in tissues from primary melanomas and metastases as well as their concentration in blood samples were examined. Strong expression of Heat Shock Protein 27 (HSP27) in metastases correlated significantly with complete or partial response to bevacizumab (p = 0.044). Furthermore, clinical benefit, i.e., complete or partial response or stable disease for at least 6 months, was more frequent in patients with strong expression of HSP27 in primary tumors (p = 0.046). Tissue expression of vascular endothelial growth factor (VEGF-A), its splicing variant VEGF165b or basic fibroblast growth factor (bFGF) did not correlate with response, and the concentration of HSP27, VEGF-A or bFGF measured in blood samples before treatment did not show predictive value. Further, microvessel density, proliferating microvessel density and presence of glomeruloid microvascular proliferations were assessed in sections of primary tumors and metastases. Microvessel density in primary melanomas was significantly higher in patients with clinical benefit than in non-responders (p = 0.042). In conclusion, our findings suggest that strong HSP27 expression in melanoma metastases predicts response to bevacizumab treatment.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 610
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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