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Article: Tumour vascularization: sprouting angiogenesis and beyond.

Hillen, Femke / Griffioen, Arjan W

2007 Volume 26, Issue 3-4, Page(s) 489–502

Abstract: Tumour angiogenesis is a fast growing domain in tumour biology. Many growth factors and mechanisms have been unravelled. For almost 30 years, the sprouting of new vessels out of existing ones was considered as an exclusive way of tumour vascularisation. ... ...

Abstract	Tumour angiogenesis is a fast growing domain in tumour biology. Many growth factors and mechanisms have been unravelled. For almost 30 years, the sprouting of new vessels out of existing ones was considered as an exclusive way of tumour vascularisation. However, over the last years several additional mechanisms have been identified. With the discovery of the contribution of intussusceptive angiogenesis, recruitment of endothelial progenitor cells, vessel co-option, vasculogenic mimicry and lymphangiogenesis to tumour growth, anti-tumour targeting strategies will be more complex than initially thought. This review highlights these processes and intervention as a potential application in cancer therapy. It is concluded that future anti-vascular therapies might be most beneficial when based on multimodal anti-angiogenic, anti-vasculogenic mimicry and anti-lymphangiogenic strategies.
MeSH term(s)	Animals ; Endothelial Cells/cytology ; Humans ; Lymphangiectasis ; Neoplasms/blood supply ; Neovascularization, Pathologic/etiology ; Stem Cells/physiology ; Vascular Endothelial Growth Factor A/physiology
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2007-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-007-9094-7
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Article ; Online: Validation and Application of a Custom-Designed Targeted Next-Generation Sequencing Panel for the Diagnostic Mutational Profiling of Solid Tumors.

Froyen, Guy / Broekmans, An / Hillen, Femke / Pat, Karin / Achten, Ruth / Mebis, Jeroen / Rummens, Jean-Luc / Willemse, Johan / Maes, Brigitte

PloS one

2016 Volume 11, Issue 4, Page(s) e0154038

Abstract: The inevitable switch from standard molecular methods to next-generation sequencing for the molecular profiling of tumors is challenging for most diagnostic laboratories. However, fixed validation criteria for diagnostic accreditation are not in place ... ...

Abstract	The inevitable switch from standard molecular methods to next-generation sequencing for the molecular profiling of tumors is challenging for most diagnostic laboratories. However, fixed validation criteria for diagnostic accreditation are not in place because of the great variability in methods and aims. Here, we describe the validation of a custom panel of hotspots in 24 genes for the detection of somatic mutations in non-small cell lung carcinoma, colorectal carcinoma and malignant melanoma starting from FFPE sections, using 14, 36 and 5 cases, respectively. The targeted hotspots were selected for their present or future clinical relevance in solid tumor types. The target regions were enriched with the TruSeq approach starting from limited amounts of DNA. Cost effective sequencing of 12 pooled libraries was done using a micro flow cell on the MiSeq and subsequent data analysis with MiSeqReporter and VariantStudio. The entire workflow was diagnostically validated showing a robust performance with maximal sensitivity and specificity using as thresholds a variant allele frequency >5% and a minimal amplicon coverage of 300. We implemented this method through the analysis of 150 routine diagnostic samples and identified clinically relevant mutations in 16 genes including KRAS (32%), TP53 (32%), BRAF (12%), APC (11%), EGFR (8%) and NRAS (5%). Importantly, the highest success rate was obtained when using also the low quality DNA samples. In conclusion, we provide a workflow for the validation of targeted NGS by a custom-designed pan-solid tumor panel in a molecular diagnostic lab and demonstrate its robustness in a clinical setting.
MeSH term(s)	High-Throughput Nucleotide Sequencing ; Humans ; Limit of Detection ; Mutation ; Neoplasms/diagnosis ; Neoplasms/genetics ; Reproducibility of Results ; Sensitivity and Specificity
Language	English
Publishing date	2016-04-21
Publishing country	United States
Document type	Journal Article ; Validation Studies
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0154038
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Article ; Online: Communicating uncertainties when disclosing diagnostic test results for (Alzheimer's) dementia in the memory clinic: The ABIDE project.

Visser, Leonie N C / Pelt, Sophie A R / Kunneman, Marleen / Bouwman, Femke H / Claus, Jules J / Kalisvaart, Kees J / Hempenius, Liesbeth / de Beer, Marlijn H / Roks, Gerwin / Boelaarts, Leo / Kleijer, Mariska / van der Flier, Wiesje M / Smets, Ellen M A / Hillen, Marij A

Health expectations : an international journal of public participation in health care and health policy

2019 Volume 23, Issue 1, Page(s) 52–62

Abstract: Background: The development of novel diagnostics enables increasingly earlier diagnosis of Alzheimer's disease (AD). Timely diagnosis may benefit patients by reducing their uncertainty regarding the cause of symptoms, yet does not always provide ... ...

Abstract	Background: The development of novel diagnostics enables increasingly earlier diagnosis of Alzheimer's disease (AD). Timely diagnosis may benefit patients by reducing their uncertainty regarding the cause of symptoms, yet does not always provide patients with the desired certainty. Objective: To examine, using both quantitative and qualitative methods, uncertainty communicated by memory clinic clinicians in post-diagnostic testing consultations with patients and their caregivers. Methods: First, we identified all uncertainty expressions of 22 clinicians in audiotaped post-diagnostic testing consultations with 78 patients. Second, we statistically explored relationships between patient/clinician characteristics and uncertainty expressions. Third, the transcribed uncertainty expressions were qualitatively analysed, determining the topic to which they pertained, their source and initiator/elicitor (clinicians/patients/caregivers). Results: Within 57/78 (73%) consultations, clinicians expressed in total 115 uncertainties, of which 37% elicited by the patient or caregiver. No apparent relationships were found between patient/clinician characteristics and whether or not, and how often clinicians expressed uncertainty. Uncertainty expressions pertained to ten different topics, most frequently patient's diagnosis and symptom progression. Expressed uncertainty was mostly related to the unpredictability of the future and limits to available knowledge. Discussion and conclusions: The majority of clinicians openly discussed the limits of scientific knowledge and diagnostic testing with patients and caregivers in the dementia context. Noticeably, clinicians did not discuss uncertainty in about one quarter of consultations. More evidence is needed on the beneficial and/or harmful effects on patients of discussing uncertainty with them. This knowledge can be used to support clinicians to optimally convey uncertainty and facilitate patients' uncertainty management.
MeSH term(s)	Aged ; Alzheimer Disease/diagnosis ; Ambulatory Care Facilities ; Caregivers/psychology ; Communication ; Diagnostic Tests, Routine ; Disclosure ; Female ; Health Personnel/statistics & numerical data ; Humans ; Male ; Middle Aged ; Netherlands ; Patients/psychology ; Patients/statistics & numerical data ; Qualitative Research ; Uncertainty
Language	English
Publishing date	2019-10-22
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2119434-8
ISSN	1369-7625 ; 1369-6513
ISSN (online)	1369-7625
ISSN	1369-6513
DOI	10.1111/hex.12964
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Article ; Online: Validation and Application of a Custom-Designed Targeted Next-Generation Sequencing Panel for the Diagnostic Mutational Profiling of Solid Tumors.

Guy Froyen / An Broekmans / Femke Hillen / Karin Pat / Ruth Achten / Jeroen Mebis / Jean-Luc Rummens / Johan Willemse / Brigitte Maes

PLoS ONE, Vol 11, Iss 4, p e

2016 Volume 0154038

Abstract	The inevitable switch from standard molecular methods to next-generation sequencing for the molecular profiling of tumors is challenging for most diagnostic laboratories. However, fixed validation criteria for diagnostic accreditation are not in place because of the great variability in methods and aims. Here, we describe the validation of a custom panel of hotspots in 24 genes for the detection of somatic mutations in non-small cell lung carcinoma, colorectal carcinoma and malignant melanoma starting from FFPE sections, using 14, 36 and 5 cases, respectively. The targeted hotspots were selected for their present or future clinical relevance in solid tumor types. The target regions were enriched with the TruSeq approach starting from limited amounts of DNA. Cost effective sequencing of 12 pooled libraries was done using a micro flow cell on the MiSeq and subsequent data analysis with MiSeqReporter and VariantStudio. The entire workflow was diagnostically validated showing a robust performance with maximal sensitivity and specificity using as thresholds a variant allele frequency >5% and a minimal amplicon coverage of 300. We implemented this method through the analysis of 150 routine diagnostic samples and identified clinically relevant mutations in 16 genes including KRAS (32%), TP53 (32%), BRAF (12%), APC (11%), EGFR (8%) and NRAS (5%). Importantly, the highest success rate was obtained when using also the low quality DNA samples. In conclusion, we provide a workflow for the validation of targeted NGS by a custom-designed pan-solid tumor panel in a molecular diagnostic lab and demonstrate its robustness in a clinical setting.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Communicating uncertainties when disclosing diagnostic test results for (Alzheimer's) dementia in the memory clinic

Leonie N. C. Visser / Sophie A. R. Pelt / Marleen Kunneman / Femke H. Bouwman / Jules J. Claus / Kees J. Kalisvaart / Liesbeth Hempenius / Marlijn H. deBeer / Gerwin Roks / Leo Boelaarts / Mariska Kleijer / Wiesje M. van derFlier / Ellen M. A. Smets / Marij A. Hillen

Health Expectations, Vol 23, Iss 1, Pp 52-

The ABIDE project

2020 Volume 62

Abstract: Abstract Background The development of novel diagnostics enables increasingly earlier diagnosis of Alzheimer's disease (AD). Timely diagnosis may benefit patients by reducing their uncertainty regarding the cause of symptoms, yet does not always provide ... ...

Abstract	Abstract Background The development of novel diagnostics enables increasingly earlier diagnosis of Alzheimer's disease (AD). Timely diagnosis may benefit patients by reducing their uncertainty regarding the cause of symptoms, yet does not always provide patients with the desired certainty. Objective To examine, using both quantitative and qualitative methods, uncertainty communicated by memory clinic clinicians in post‐diagnostic testing consultations with patients and their caregivers. Methods First, we identified all uncertainty expressions of 22 clinicians in audiotaped post‐diagnostic testing consultations with 78 patients. Second, we statistically explored relationships between patient/clinician characteristics and uncertainty expressions. Third, the transcribed uncertainty expressions were qualitatively analysed, determining the topic to which they pertained, their source and initiator/elicitor (clinicians/patients/caregivers). Results Within 57/78 (73%) consultations, clinicians expressed in total 115 uncertainties, of which 37% elicited by the patient or caregiver. No apparent relationships were found between patient/clinician characteristics and whether or not, and how often clinicians expressed uncertainty. Uncertainty expressions pertained to ten different topics, most frequently patient's diagnosis and symptom progression. Expressed uncertainty was mostly related to the unpredictability of the future and limits to available knowledge. Discussion and conclusions The majority of clinicians openly discussed the limits of scientific knowledge and diagnostic testing with patients and caregivers in the dementia context. Noticeably, clinicians did not discuss uncertainty in about one quarter of consultations. More evidence is needed on the beneficial and/or harmful effects on patients of discussing uncertainty with them. This knowledge can be used to support clinicians to optimally convey uncertainty and facilitate patients' uncertainty management.
Keywords	Alzheimer's disease ; dementia ; diagnostic work‐up ; memory clinic ; physician‐patient communication ; uncertainty ; Medicine (General) ; R5-920 ; Public aspects of medicine ; RA1-1270
Subject code	170
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
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Article ; Online: Prognostic role of vasculogenic mimicry in colorectal cancer.

Baeten, Coen I M / Hillen, Femke / Pauwels, Patrick / de Bruine, Adriaan P / Baeten, Cor G M I

Diseases of the colon and rectum

2009 Volume 52, Issue 12, Page(s) 2028–2035

Abstract: Purpose: Angiogenesis, as measured by degree of microvessel density, has been associated with tumor progression in many tumor types but does not always correlate with clinical outcome. In 1999, aggressive tumor cells were shown to form blood-conducting ... ...

Abstract	Purpose: Angiogenesis, as measured by degree of microvessel density, has been associated with tumor progression in many tumor types but does not always correlate with clinical outcome. In 1999, aggressive tumor cells were shown to form blood-conducting tubes not lined by endothelial cells, and this phenomenon was termed vasculogenic mimicry. We investigated angiogenesis and the presence of vasculogenic mimicry in colorectal carcinoma in relation to tumor stage, patient survival, and genetic indicators of tumor cell plasticity. Methods: Paraffin-embedded tissue samples were examined from a study of 117 patients with colorectal carcinoma with a 12-year follow-up. Immunohistochemical analysis was used to measure microvessel density and proliferating endothelial cells and to detect vasculogenic mimicry (scored by 3 independent observers). Cell cultures from 7 colon cell lines, real-time polymerase chain reaction (PCR) on cell lines, frozen tissue material from 4 colorectal cancer patients with and 4 without vasculogenic mimicry, and fresh colorectal cancer tissue from 2 patients were used to investigate the relationship between vasculogenic mimicry and tumor cell plasticity. Results: Microvessel density was not a prognostic marker in our patients. We found vasculogenic mimicry in 23 (19.7%) of 117 colorectal tumor samples. Cell culture experiments and real-time PCR on human colorectal carcinoma material showed evidence for vasculogenic mimicry with overexpression of EPHA2 and LAMC2, known to be important for the tube-forming capacity of melanoma tumor cells. The presence of vasculogenic mimicry was associated with significantly shortened survival, both overall (P < 0.0001) and within intermediate cancer stages (Dukes B, P = 0.0277; Dukes C, P < 0.0001). Conclusions: Vasculogenic mimicry can occur in colorectal carcinoma and appears to be comparable to vasculogenic mimicry described in other tumors. Moreover, vasculogenic mimicry in colorectal carcinoma may be a strong independent prognostic marker for survival.
MeSH term(s)	Adenocarcinoma/blood supply ; Adenocarcinoma/pathology ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms/blood supply ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Female ; Gene Expression ; Humans ; Laminin/genetics ; Male ; Microvessels/pathology ; Middle Aged ; Neovascularization, Pathologic/diagnosis ; Neovascularization, Pathologic/pathology ; Prognosis ; Receptor, EphA2/genetics ; Tumor Cells, Cultured
Chemical Substances	LAMC2 protein, human ; Laminin ; Receptor, EphA2 (EC 2.7.10.1)
Language	English
Publishing date	2009-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	212581-x
ISSN	1530-0358 ; 0012-3706
ISSN (online)	1530-0358
ISSN	0012-3706
DOI	10.1007/DCR.0b013e3181beb4ff
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Article ; Online: Cytometry by time of flight identifies distinct signatures in patients with systemic sclerosis, systemic lupus erythematosus and Sjögrens syndrome.

van der Kroef, Maarten / van den Hoogen, Lucas L / Mertens, Jorre S / Blokland, Sofie L M / Haskett, Scott / Devaprasad, Abhinandan / Carvalheiro, Tiago / Chouri, Eleni / Vazirpanah, Nadia / Cossu, Marta / Wichers, Catherina G K / Silva-Cardoso, Sandra C / Affandi, Alsya J / Bekker, Cornelis P J / Lopes, Ana P / Hillen, Maarten R / Bonte-Mineur, Femke / Kok, Marc R / Beretta, Lorenzo /

Rossato, Marzia / Mingueneau, Michaël / van Roon, Joel A G / Radstake, Timothy R D J

European journal of immunology

2019 Volume 50, Issue 1, Page(s) 119–129

Abstract: Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct systemic autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune-cells in 169 ... ...

Abstract	Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct systemic autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune-cells in 169 patients with these SADs and 44 healty controls (HC) using mass-cytometry and assessed the diagnostic value of these results. Alterations in the frequency of immune-cell subsets were present in all SADs compared to HC. Most alterations, including a decrease of CD56
MeSH term(s)	Adult ; Aged ; Female ; Flow Cytometry/methods ; Humans ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/immunology ; Male ; Middle Aged ; Phenotype ; Scleroderma, Systemic/diagnosis ; Scleroderma, Systemic/immunology ; Sjogren's Syndrome/diagnosis ; Sjogren's Syndrome/immunology
Language	English
Publishing date	2019-09-11
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.201948129
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Article: Proliferating endothelial cells, but not microvessel density, are a prognostic parameter in human cutaneous melanoma.

Hillen, Femke / van de Winkel, Anouk / Creytens, David / Vermeulen, Anton H M / Griffioen, Arjan W

Melanoma research

2006 Volume 16, Issue 5, Page(s) 453–457

Abstract: The induction of angiogenesis is crucial in the development of most human tumors. Angiogenesis is routinely assessed by the density of tumor microvessels. This technique reveals controversial results on the clinical and prognostic value of angiogenesis ... ...

Abstract	The induction of angiogenesis is crucial in the development of most human tumors. Angiogenesis is routinely assessed by the density of tumor microvessels. This technique reveals controversial results on the clinical and prognostic value of angiogenesis in melanoma. We investigated angiogenesis in tumor tissues of 58 cutaneous melanoma patients, of which a clinical follow-up of over 10 years was available, through assessment of microvessel density and by enumeration of the number of proliferating endothelial cells. To that end, vessels were immunohistochemically detected by CD31/CD34 staining, and proliferating endothelial cells were enumerated in a double staining with the proliferation marker Ki67. We found that microvessel density did not correlate with tumor stage or survival, neither in intratumoral nor in peritumoral areas. In contrast, proliferating endothelial cells were only observed in intratumoral areas and were correlated positively with tumor stage and the presence of distant metastases. In addition, a strong positive correlation was found with the number of proliferating tumor cells. Finally, high numbers of growing endothelial cells predicted short survival. Our results show that angiogenesis could best be measured by enumeration of proliferating endothelial cells and that this parameter has prognostic value in patients with cutaneous melanoma.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antigens, CD34/biosynthesis ; Cell Proliferation ; Cells, Cultured ; Endothelium, Vascular/cytology ; Female ; Humans ; Ki-67 Antigen/biosynthesis ; Male ; Melanoma/diagnosis ; Melanoma/metabolism ; Melanoma/pathology ; Microcirculation/metabolism ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis ; Skin Neoplasms/diagnosis ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology
Chemical Substances	Antigens, CD34 ; Ki-67 Antigen ; Platelet Endothelial Cell Adhesion Molecule-1
Language	English
Publishing date	2006-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1095779-0
ISSN	1473-5636 ; 0960-8931
ISSN (online)	1473-5636
ISSN	0960-8931
DOI	10.1097/01.cmr.0000232291.68666.4c
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Article ; Online: A transgenic Tie2-GFP athymic mouse model; a tool for vascular biology in xenograft tumors.

Hillen, Femke / Kaijzel, Eric L / Castermans, Karolien / oude Egbrink, Mirjam G A / Löwik, Clemens W G M / Griffioen, Arjan W

Biochemical and biophysical research communications

2008 Volume 368, Issue 2, Page(s) 364–367

Abstract: We report the generation of a transgenic Tie2-GFP athymic nude mouse, carrying green fluorescent blood vessels throughout the body. This transgenic mouse is a tool for studies in vascular biology, and is especially of interest for imaging of tumor ... ...

Abstract	We report the generation of a transgenic Tie2-GFP athymic nude mouse, carrying green fluorescent blood vessels throughout the body. This transgenic mouse is a tool for studies in vascular biology, and is especially of interest for imaging of tumor angiogenesis and the study of anti-angiogenesis strategies in (human) xenografts. Intravital microscopy identified the presence of blood conducting structures that are not lined by endothelial cells. Dedifferentiation of aggressive tumor cells can lead to acquisition of endothelial characteristics. This process of tumor cell plasticity, also referred to as vasculogenic mimicry, has been suggested to contribute to the circulatory system in a tumor. In plastic EW7 Ewing sarcoma tumors in these Tie2-GFP mice, we observed blood flow in both regular blood vessels and non-fluorescent tumor cell-lined channels, visualizing in vivo hemodynamics in vasculogenic channels. These results demonstrate that the transgenic Tie2-GFP athymic mouse model is a valuable tool for vascular biology research.
MeSH term(s)	Animals ; Disease Models, Animal ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, Transgenic ; Microscopy, Fluorescence/methods ; Molecular Probe Techniques ; Neoplasms/blood supply ; Neoplasms/metabolism ; Neoplasms/pathology ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/pathology ; Receptor, TIE-2/genetics ; Receptor, TIE-2/metabolism
Chemical Substances	Receptor, TIE-2 (EC 2.7.10.1)
Language	English
Publishing date	2008-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2008.01.080
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Article ; Online: Effects of radiotherapy and chemotherapy on angiogenesis and leukocyte infiltration in rectal cancer.

Baeten, Coen I M / Castermans, Karolien / Lammering, Guido / Hillen, Femke / Wouters, Bradly G / Hillen, Harry F P / Griffioen, Arjan W / Baeten, Cornelius G M I

International journal of radiation oncology, biology, physics

2006 Volume 66, Issue 4, Page(s) 1219–1227

Abstract: Background: We and others have shown that angiogenesis and leukocyte infiltration are important prognostic factors in rectal cancer. However, little is known about its possible changes in response to radiotherapy (RTX), which is frequently given to ... ...

Abstract	Background: We and others have shown that angiogenesis and leukocyte infiltration are important prognostic factors in rectal cancer. However, little is known about its possible changes in response to radiotherapy (RTX), which is frequently given to rectal tumors as a neoadjuvant treatment to improve the prognosis. We therefore investigated the biologic effects of RTX on these parameters using fresh-frozen biopsy samples of tumor and normal mucosa tissue before and after RTX. Methods: Biopsy samples were taken from a total of 34 patients before and after either a short course or long course of RTX combined with chemotherapy. The following parameters were analyzed by immunohistochemistry, flow cytometry, or quantitative real-time polymerase chain reaction: Microvessel density, leukocyte infiltration, proliferating epithelial and tumor cells, proliferating endothelial cells, adhesion molecule expression on endothelial cells, and the angiogenic mRNA profile. Results: The tumor biopsy samples taken after RTX treatment demonstrated a significant decrease in microvessel density and the number of proliferating tumor cells and proliferating endothelial cells (p < 0.001). In contrast, the leukocyte infiltration, the levels of basic fibroblast growth factor in carcinoma tissue, and the adhesion molecule expression on endothelial cells in normal as well as carcinoma tissue increased significantly (p < 0.05). Conclusion: Our data show that together with an overall decrease in tumor cell and endothelial cell proliferation, RTX results in an increase in the expression of adhesion molecules that stimulate leukocyte infiltration. This suggests the possibility that, in addition to its direct cytotoxic effect, radiation may also stimulate an immunologic tumor response that could contribute to the documented improvement in local tumor control and distal failure rate of rectal cancers.
MeSH term(s)	Aged ; Drug Therapy ; Female ; Humans ; Leukocytes/pathology ; Male ; Neovascularization, Pathologic/pathology ; Neovascularization, Pathologic/prevention & control ; Radiotherapy ; Rectal Neoplasms/blood supply ; Rectal Neoplasms/pathology ; Rectal Neoplasms/therapy
Language	English
Publishing date	2006-11-15
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2006.07.1362
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