Effect of repeated invitations on uptake of colorectal cancer screening using faecal occult blood testing: analysis of prevalence and incidence screening

Colorectal cancer (CRC) is a major cause of worldwide morbidity and
mortality and is the second most common cause of cancer death in Europe
and the United States causing more than 56 000 deaths in the US and 16 000
in the UK each year [1-3]. In China, CRC occupies the fifth position in
the mortalities caused by cancer, and its incidence still continues to
increase [4]. Tumour invasion and metastasis is the major cause of
morbidity and mortality from colorectal cancer, while improvements in
quality of life and patient survival have been made over the past 10
years, the majority of patients with metastatic colorectal cancer will die
from their disease [5]. Currently, there are increasing evidences that the
possible role of tissue factor (TF) in CRC. A correlation between TF
expression and the histological grade of malignancy, and a correlation
between TF expression and overall survival have been validated in CRC [6].
All of this suggested that TF correlated significantly with angiogenesis.
TF is a 47 kD transmembrane glycoprotein, which is distributed along the
boundaries of organs and in the adventitia of blood vessels [7,8]. TF can
serve as a major physiologic initiator of blood coagulation, its
extracellular domain can act as receptor for coagulation factor FVII,
activation of FVIIa leads to thrombin generation, platelet activation and
fibrin formation [6,9]. The interaction between hematogenous metastasis
and tumor procoagulant activity has been recognized [10]. Considerable
experiment datas suggested that coagulation and fibrinolysis play an
important role in the invasion and metastasis of CRC [6,11].

TF plays an important role during normal haemostasis, accompanied
with that it is locally expressed and subsequently activates the
coagulation cascade [12]. In addition to that, TF also palys an key role
in a range of pathological considerations, including intrascular
coagulation in sepsis, arteriosclerosis and cancer [6,13]. It believed
that angiogenesis, a hallmarker of tumor invasion and metastasis, is also
required for growth and dissemination of malignant tumors [7,14]. Among
the known proangiogenic factors, VEGF is considered as the predominant
initiator of angiogenesis, including tumour-associated angiogenesis [15].
Overexpression of TF up-regulates the proangiogenic vascular endothelial
growth factor (VEGF) and down-regulates the antiangiogenic thrombospondin
gene, so that it will increase vascularization of tumors in vivo and
improve tumor angiogenesis, which is crucial to tumor invasion and
metastasis [7,16].
In addition, TF and VEGF are both up-regulated by hypoxia in tumors [17].
TF augument the balance that normally maintain endothelial cell quiescence
by inherent proganiogenic and antiangiogenic facors. It participates in
the regulation of important factors including VEGF and the antiangiogenic
peptide thrombospondin [18,19]. Moreover, local thrombin generation may
lead to the activation of endothelial cells, up-regulation of adhesive
molecules and loosening of cell-cell junctions, which promote tumor cells
adhension and junctions [20]. Through all of this, TF stimulated the
angiogenesis of CRC.
In a word, TF is known as a key regulator in the role of invasion and
metastasis in CRC by stimulation of angiogenesis.

Since TF plays a prominent role in the process of invasion and
metastasis in CRC by stimulation of angiogenesis, we hypothesize that a
blocking anti-TF monoclonal antibody, Fab fragments, or the others therapy
as a novel means to treat CRC and can inhibit the invation and metastasis
of CRC. Therefore, we can direct against regulation of the coagulation
competence with TF as one of the primary target. Recombinant adeno-
associated viral (rAAV) vectors are selected as anti-TF gene vector.
Recombinant adeno-associated viral vectors have gained attention as a
potentially alternative to the more commonly used retroviral vectors
because rAAV vectors are thought to be safer and more effective than other
in vivo gene delivery methods and have to date not been associated with
any malignant disease. In addition, they possess good transduction
efficiency [21]. In our opinion, the adeno-associated viral human anti-TF
gene seems to hold interesting future prospects for the treatment of CRC
and inhibit the invation and metastasis of CRC by the suitable injection
of vein.

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Yiyi Sun, Zhihe Zang, Xiaohong Xu, Zhonglin Zhang, Ling Zhong, Ming
Wu, Qing Su, Xiurong Gao, Zan Wang, Yan Zhao

From The Chengdu Medical College, Chengdu 610083, Sichuan Province,
China.

Correspondence to: Yan Zhao, yanzhao22@live.cn; Yiyi Sun,
yiyisun0363@sina.com; Tel: 86-28-68289237, Fax: 86-28- 68289242

Competing interests: None declared