fibrin and Colorectal-Neoplasms

At time of diagnosis, most cancer patients present with laboratory evidence of systemic coagulation activation. After treatment with curative intent, these hemostatic alterations seemingly disappear as seen in colorectal cancer with regard to prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and soluble fibrin (SF). The aim of this study was to investigate whether coagulation activation recurs with cancer recurrence and to study whether preoperative coagulation tests have any prognostic value in colorectal cancer. Plasma F1+2, TAT, and SF levels were prospectively recorded from 113 patients followed after curative resection of colorectal cancer. The patients were seen in clinic after 3, 6, 12, and 18 months, and after 2, 3, 4, and 5 years. Coagulation reactivation was observed at the time of recurrence, as demonstrated by significantly increased plasma TAT and SF, along with a non-significant increase (P = 0.09) in F1+2. Preoperative values of F1+2, TAT, and SF did not show association with prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antithrombins; Blood Coagulation; Colorectal Neoplasms; Female; Fibrin; Follow-Up Studies; Hemostasis; Humans; Male; Middle Aged; Peptide Fragments; Prognosis; Protein Precursors; Prothrombin; Recurrence; Thrombin; Time Factors

Tumor cell-induced platelet aggregation represents a critical process both for successful metastatic spread of the tumor and for the development of thrombotic complications in cancer patients. To get further insights into this process, we investigated and compared the molecular mechanisms of platelet aggregation induced by two different breast cancer cell lines (MDA-MB-231 and MCF7) and a colorectal cancer cell line (Caco-2). All the three types of cancer cells were able to induce comparable platelet aggregation, which, however, was observed exclusively in the presence of CaCl

Topics: Amino Acid Chloromethyl Ketones; Aspirin; Blood Platelets; Breast Neoplasms; Caco-2 Cells; Calcium Chloride; Colorectal Neoplasms; Female; Fibrin; Fibrinogen; Humans; Integrin alpha2; MCF-7 Cells; Platelet Activation; Platelet Aggregation; Thromboxane A2; Type C Phospholipases

Colorectal cancer (CRC) exhibited high incidence rate worldwide and the advanced CRC had a poor prognosis. Thereupon, seeking efficient treatment for CRC is critical. Apatinib is a novel vascular epithelial growth factor receptor (VEGFR) inhibitor with inspiring therapeutic effect in some malignant cancers. In our study, doxorubicin was mixed in fibrin gel and apatinib was encapsulated with self-synthesized liposome. The results showed liposomal apatinib (Lipo-Apatinib) could enhance the intracellular uptake of doxorubicin in vitro. Moreover, compared with doxorubicin loaded fibrin gel (DOX-FG) alone, the combination of DOX-FG and Lipo-Apatinib significantly improved the anti-tumor effect in mice CRC subcutaneous model and abdominal metastasis model Drug combination successfully inhibited tumor angiogenesis and tumor proliferation, and also promoted tumor apoptosis. Our data suggested that combined therapy of DOX-FG and Lipo-Apatinib would be a promising treatment approach for CRC.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Doxorubicin; Drug Combinations; Drug Liberation; Female; Fibrin; Gels; Liposomes; Mice, Inbred BALB C; Pyridines; Treatment Outcome

Topics: Aged; Biopsy; Chronic Disease; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Diagnosis, Differential; Diarrhea; Fibrin; Granulation Tissue; Humans; Hyperplasia; Inflammatory Bowel Diseases; Intestinal Mucosa; Male

Colorectal cancer is the third most often cause of morbidity and mortality due to cancer in Poland. Thromboembolic complications are common events during the course of the disease. It is well known that hemostatic proteins play an important role in cancer progression. The purpose of the study was to evaluate the in loco interactions among colorecatal cancer and coagulation factors. 21 cases of G2 colorectal adenocarcinoma obtained during surgical resection were examined. Immunohistochemical procedures according to ABC method were employed. Tissue factor (TF) and coagulation factors II, VII, X, IX were observed in cancer cells and except factors II and IX--in tumor associated macrophages. TF was also demonstrated in endothelial cells of small blood vessels. Strong expression of fibrinogen was observed among connective tissue at some distance around malignant tumor while weaker expression was found in tumor stroma. Expression of F(1+2), the by-product of thrombin generation, was revealed in cancer cells, macrophages and in the tumor stroma. The results indicate extravascular activation of blood coagulation in loco in colorectal cancer that is TF-dependent.

Topics: Blood Coagulation; Blood Coagulation Factors; Carcinoma; Colorectal Neoplasms; Factor IXa; Factor VII; Factor X; Fibrin; Fibrinogen; Humans; Immunohistochemistry; Neovascularization, Pathologic; Prothrombin; Thromboplastin

Although angiogenesis is a prerequisite for the growth of most human solid tumours, alternative mechanisms of vascularisation can be adopted. We have previously described a non-angiogenic growth pattern in liver metastases of colorectal adenocarcinomas (CRC) in which tumour cells replace hepatocytes at the tumour-liver interface, preserving the liver architecture and co-opting the sinusoidal blood vessels. The aim of this study was to determine whether this replacement pattern occurs during liver metastasis of breast adenocarcinomas (BC) and whether the lack of an angiogenic switch in such metastases is due to the absence of hypoxia and subsequent vascular fibrinogen leakage. The growth pattern of 45 BC liver metastases and 28 CRC liver metastases (73 consecutive patients) was assessed on haematoxylin- and eosin-stained tissue sections. The majority of the BC liver metastases had a replacement growth pattern (96%), in contrast to only 32% of the CRC metastases (P<0.0001). The median carbonic anhydrase 9 (CA9) expression (M75 antibody), as a marker of hypoxia, (intensity x % of stained tumour cells) was 0 in the BC metastases and 53 in the CRC metastases (P<0.0001). There was CA9 expression at the tumour-liver interface in only 16% of the BC liver metastases vs 54% of the CRC metastases (P=0.002). There was fibrin (T2G1 antibody) at the tumour-liver interface in only 21% of the BC metastases vs 56% of the CRC metastases (P=0.04). The median macrophage count (Chalkley morphometry; KP-1 anti-CD68 antibody) at the interface was 4.3 and 7.5, respectively (P<0.0001). Carbonic anhydrase 9 score and macrophage count were positively correlated (r=0.42; P=0.002) in all metastases. Glandular differentiation was less in the BC liver metastases: 80% had less than 10% gland formation vs only 7% of the CRC metastases (P<0.0001). The liver is a densely vascularised organ and can host metastases that exploit this environment by replacing the hepatocytes and co-opting the vasculature. Our findings confirm that a non-angiogenic pattern of liver metastasis indeed occurs in BC, that this pattern of replacement growth is even more prevalent than in CRC, and that the process induces neither hypoxia nor vascular leakage.

Topics: Adenocarcinoma; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Breast Neoplasms; Carbonic Anhydrases; Cell Hypoxia; Colorectal Neoplasms; Fibrin; Glycoproteins; Humans; Immunohistochemistry; Liver Neoplasms; Macrophages; Neovascularization, Pathologic; Vesicular Transport Proteins

In a prospective study, coagulation test results were compared in 137 patients with colorectal cancer (CRC) and 39 subjects with benign colorectal diseases. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and soluble fibrin (SF) were measured in plasma before and after surgery. CRC patients presented with significantly higher values of F1+2 and TAT than controls. Patients with localised CRC had elevated values of F1+2 and TAT, whereas patients with advanced CRC also had elevated SF values. TAT and SF levels correlated with tumour spread, and normal values virtually excluded advanced cancer. Postoperative deep venous thrombosis (DVT) was diagnosed by phlebography in 20% of the CRC patients. Preoperative values of the markers did not predict postoperative DVT, but postoperative values did.

Topics: Adult; Aged; Aged, 80 and over; Antithrombin III; Biomarkers; Biomarkers, Tumor; Blood Coagulation Tests; Case-Control Studies; Colorectal Neoplasms; Female; Fibrin; Humans; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Prothrombin; Severity of Illness Index; Venous Thrombosis

We determined sensitive markers of coagulation and fibrinolysis in plasma of 20 patients with malignant colorectal disease as compared to 17 patients with benign colorectal disease. Thrombin/antithrombin III complex (TAT), soluble fibrin (SF), total fibrinogen and fibrin degradation products (TDP), plasminogen activator inhibitor type-1 (PAI-1), urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) were measured preoperatively, starting anesthesia, during surgery and postoperatively. The purpose was to verify the supposed hypercoagulable state of cancer patients. In addition, we investigated whether the hemostatic alterations induced by general anesthesia and major abdominal surgery differed between the two groups. Patients with colorectal cancer showed initially an altered balance of hemostasis with a preponderance of procoagulant activity and fibrinolytic inhibition, as noted by marginally elevated TAT and PAI-1 plasma levels. The stimulus of anesthesia induction alone was sufficient to trigger not only activation of coagulation in these patients but also further activation of fibrinolysis and increased fibrinolytic inhibition. The marked activation of coagulation and fibrinolysis and enhanced fibrinolytic inhibition during surgery was more pronounced in patients with malignancy as compared to the control group. Postoperatively, a shift of the normal balance of hemostasis with a slight preponderance of fibrinolytic inhibition was observed, as evidenced by a marginally elevated PAI-1 plasma levels. The results of this study strengthen the hypothesis of a hypercoagulable state in patients with colorectal malignancy that may favor the development of thrombosis in this patient group.

Topics: Adult; Aged; Aged, 80 and over; Antithrombin III; Biomarkers; Colorectal Neoplasms; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Hemostasis, Surgical; Humans; Male; Middle Aged; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Urokinase-Type Plasminogen Activator

The aim of the present study was to study whether patients developing anastomotic leakage after colorectal resections for colorectal cancer have laboratory signs of an altered hemostatic balance in the systemic circulation, preoperatively and postoperatively, causing an impaired healing process.. Patients operated on for colorectal cancer were studied. Seventeen consecutive patients with anastomotic leakage and 17 patients without anastomotic leakage were matched according to age, gender, tumor stage, and localization of tumor. Hemostatic balance was estimated preoperatively and at one, two, and seven days and at three months after surgery by plasma levels of sensitive markers of coagulation activation and fibrinolysis, i.e., prothrombin fragment 1 + 2, thrombin-antithrombin complexes, soluble fibrin, tissue-type plasminogen activator activity, and plasminogen activator inhibitor Type 1.. Preoperatively, the hemostatic balance was comparable in patients with and without anastomotic leakage. In the early postoperative period, patients developing anastomotic leakage exhibited signs of systemic coagulation activation, i.e., elevated plasma levels of prothrombin fragment 1 + 2, thrombin-antithrombin complexes, soluble fibrin, and plasminogen activator inhibitor Type 1. The observed coagulation activation appeared before the anastomotic leakage became clinically evident. More patients with anastomotic leakage received perioperative blood transfusions than patients without leakage, despite the fact that duration of surgery and intraoperative blood loss were comparable in the two groups.. Enhanced coagulation activity was observed postoperatively in patients developing anastomotic leakage after colorectal resections for colorectal cancer. Such a hypercoagulable state may contribute to the development of anastomotic leakage by facilitating formation of microthromboses in the perianastomotic area.

Topics: Age Factors; Anastomosis, Surgical; Blood Coagulation; Colorectal Neoplasms; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Neoplasm Staging; Plasminogen Activator Inhibitor 1; Postoperative Complications; Prothrombin; Sex Factors; Surgical Wound Dehiscence; Thrombin

The aim of the present study was to correlate the preoperative plasma levels of TDP in patients with colorectal cancer to tumor stage, metastasis, and postoperative thromboembolic complications.. Ninety-one patients with colorectal cancer, 20 patients with colorectal adenoma, and 71 patients without neoplastic lesions in the colon or rectum were included in this prospective study. Before surgery, total fibrin and fibrinogen degradation products (TDP) were measured in plasma of all patients with a specific enzyme-linked immunosorbent assay test. Phlebography was performed postoperatively in 82 of 91 patients with colorectal cancer.. Median TDP in plasma of patients with colorectal cancer (805 (range, 339-5,024) ng fibrinogen equivalents (ngFE)) was significantly higher than TDP in patients with colorectal adenoma (591 (range, 417-1386) ngFE/ml) and TDP in patients without neoplastic lesions in the colon (632.8 (range, 180-2622) ngFE/ml; P < or = 0.003). In patients with colorectal cancer and liver metastasis, TDP in plasma (1085.5 (range, 468-5024) ngFE/ml) was significantly higher than in patients with localized tumor growth (753 (range, (339-2,780) ngFE/ml; P < or = 0.02). Twenty of 82 patients (24 percent) with cancer developed thromboembolic complications. TDP was preoperatively significantly higher in this group of patients (1,101 (range, 468-2,167) ngFE/ml) compared with patients without thromboembolic complications (753 (range, 339-5024) ngFE/ml; P < or = 0.04).. Preoperative plasma levels of TDP were elevated in patients with colorectal cancer, especially in patients with liver metastasis and in patients developing postoperative deep venous thrombosis.

Topics: Adenocarcinoma; Adult; Aged; Case-Control Studies; Colorectal Neoplasms; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Postoperative Complications; Prospective Studies; Thromboembolism

In a prospective study, plasma levels of soluble fibrin (SF) were assessed in 97 patients with colorectal cancer immediately before and 1, 2, 7, and 90 days after surgery, 18 patients undergoing surgery for benign colorectal disease serving as controls. Age distribution, routine blood analysis, duration of surgery, perioperative blood loss and anaesthesia was similar in the two groups. SF was quantitated using a commercial enzyme-linked immunosorbent assay. The preoperative plasma level of SF was normal in cancer patients as a whole. However, patients with disseminated colorectal cancer had higher levels of SF preoperatively compared to patients with localized colorectal cancer (p < 0.01) and controls (p < 0.005). On days 1, 2, and 7 days postoperatively, a rather pronounced increase in plasma SF was observed in cancer patients as well as in the controls. Three months after surgery, plasma SF had normalized in controls and in patients undergoing curative cancer treatment. Postoperative deep venous thrombosis (DVT) was detected in 23% of the cancer patients by means of phlebography. The preoperative values of SF in these patients were higher compared to patients not developing DVT (p < 0.05). Patients with colon cancer displayed higher SF in plasma than patients with rectal cancer (p < 0.05).

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Case-Control Studies; Colonic Diseases; Colorectal Neoplasms; Female; Fibrin; Humans; Male; Middle Aged; Postoperative Complications; Preoperative Care; Prospective Studies; Rectal Diseases; Solubility; Thrombophlebitis

The infiltration of macrophages both within and at the margin of malignant neoplasms can be extensive, but their functions are not well defined. Definitions of the antigenic phenotype defined by various monoclonal antibodies may allow insight into macrophage function. Single and double immunoenzymatic labelling techniques were used to characterize sub-populations of macrophages both within and at the margin of breast carcinoma and colorectal carcinoma using a panel of antibodies. Factor XIII, previously identified in macrophage cytoplasm, was localized at the same sites. Two major groups of tumour-associated macrophages were identified; class II MHC+, CD11c+ macrophages predominated within the neoplasm, whereas CD14+ macrophages were the major population at the invasive margin. Factor XIII+ macrophages were also seen predominantly at the invasive margin. Phenotypic variation between macrophage sub-populations may reflect functional variation such that macrophages may be beneficial or detrimental for neoplastic growth. Factor XIII derived from macrophages may be important in stabilization of fibrin deposits associated with the neoplasm.

Topics: Antibodies, Monoclonal; Antigens, Differentiation; Breast Neoplasms; CD11 Antigens; Colorectal Neoplasms; Factor XIII; Female; Fibrin; Histocompatibility Antigens Class II; Humans; Immunohistochemistry; Macrophages; Phenotype