الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 70 |  |  |
| | | from | 70 | | |
Abstract
Lung cancer is a common cause of mortality all over the world. Lung cancer is classified according to histological type into two groups; Non-small-cell lung carcinoma and small-cell lung carcinoma. There are three main subtypes of NSCLC which are adenocarcinoma, squamous-cell carcinoma and large-cell carcinoma.
The emergence of the lung cancer epidemic in the 20th century has no doubt been attributed to cigarette smoking. Lung cancer will remain among the top killers for decades due to cigarette smoking.
Metastasis and thromboembolic complications are serious complications of lung cancer.
The main role of the tissue factor pathway is to generate a ”thrombin burst”, a process by which thrombin, the most important constituent of the coagulation cascade in terms of its feedback activation roles, is released very rapidly. Following damage to the blood vessel, tissue factor (TF) is expressed on tissue-factor-bearing cells (stromal fibroblasts and leukocytes), forming an activated complex (TF-FVIIa).
TFPI is synthesized primarily by the vascular endothelium under normal physiologic conditions. In immunohistochemical analysis of normal human tissues, TFPI was present primarily in the microvascular endothelial surface and megakaryocytes.
TFPI binds to factor Xa and, in this combination, binds to and inhibits tissue factor/factor VIIa complex and activated FX (FXa) and thus TFPI is currently being included as a natural coagulation inhibitor.
Heparan sulphate is considered one of matrix proteins which are collagen, laminin, fibronectin and heparan sulphate.
Heparanase cleaves heparan sulfate (HS) and hence participates in degradation and remodeling of the extracellular matrix (ECM).
Heparanase is preferentially expressed in human tumors. The enzyme also releases angiogenic factors from the ECM and thereby induces an angiogenic response in vivo. Heparanase upregulation correlates with increased tumor vascularity and poor postoperative survival of cancer patients so heparanase is implicated in angiogenesis and tumor progression.
Heparanase was discovered to affect hemostatic system by a non- enzymatic manner by up-regulating the expression of the blood coagulation initiator - tissue factor (TF) and interact with tissue factor pathway inhibitor (TFPI) on cell surface, leading to dissociation of TFPI from cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity.
The current study was carried out on 30 patients with non small cell lung cancer and 10 controls of matching age and sex.
They were classified into three groups:
group I): SCC group included 6 females and 17 males.
group II): Adenocarcinoma group included 5 females and 2 males.
group III): Control group included 3 females and 7 males.
The following battery of investigations was carried on all subjects and it included; CBC including platelet count, PT, TF level, Heparanase level and histopathological examination.
Our results in this study revealed that:
1. Both heparanase level and TF level are increased.
2. There was a positive correlation between heparanse level and thromboembolic complications.
3. There was a positive correlation between heparanse level and distant metastasis.
4. There was a positive correlation between TF level and thromboembolic complications.
5. There was a positive correlation between TF level and distant metastasis.
6. There was a positive correlation between platelet count and thromboembolic complications.
Over expression of TF in tumor cells, the cysteine protease procoagulant that activates factor X, and acquired activated protein C resistance, are thought to be the main factors for coagulopathy in malignant disorders. In the present study the activation of the coagulation system was demonstrated.
Elevated heparanase level and its procoagulant activity in plasma, demonstrated in patients with NSCLC could contribute to activation of coagulation system and progression of metastasis.