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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood coagulation test results were collected prospectively in patients with previously untreated, advanced lung or colon cancer who entered into a clinical trial. In patients with colon cancer, reduced survival was associated (in univariate analysis) with higher values obtained at entry to the study for fibrinogen, fibrin(ogen) split products, antiplasmin, and fibrinopeptide A and accelerated euglobulin lysis times. In patients with non-small cell lung cancer, reduced survival was associated (in univariate analysis) with higher fibrinogen and fibrin(ogen) split products, platelet counts and activated partial thromboplastin times. In patients with small cell carcinoma of the lung, only higher activated partial thromboplastin times were associated (in univariate analysis) with reduced survival in patients with disseminated disease. In multivariate analysis, higher activated partial thromboplastin times were a significant independent predictor of survival for patients with non-small cell lung cancer limited to one hemithorax and with disseminated small cell carcinoma of the lung. Fibrin(ogen) split product levels were an independent predictor of survival for patients with disseminated non-small cell lung cancer as were both the fibrinogen and fibrinopeptide A levels for patients with disseminated colon cancer. These results suggest that certain tests of blood coagulation may be indicative of prognosis in lung and colon cancer. The heterogeneity of these results suggests that the mechanism(s), intensity, and pathophysiological significance of coagulation activation in cancer may differ between tumour types.
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PMID:Prognostic significance of blood coagulation tests in carcinoma of the lung and colon. 133 24

Platelet counts were evaluated in 714 patients with advanced non-small cell lung cancer (N-SCLC), small cell carcinoma of the lung (SCCL), and colon cancer entered to a clinical trial. Patients had not received prior chemotherapy. Platelet counts were not different in patients who had received radiation therapy prior to entry to the study. In comparison to the other tumor types, patients with N-SCLC demonstrated an increased prevalence of thrombocytosis (counts greater than 400,000/mm3), higher platelet counts at the time of entry to the study, higher over all mean platelet counts, relative preservation of high platelet levels during disease progression, and no relationship between platelet numbers and the amount of chemotherapy given. By contrast, platelet counts in patients with SCCL were negatively correlated with the absolute amount of cyclophosphamide and adriamycin given, and declined most dramatically with disease progression and death. Platelet numbers did not correlate with fibrinopeptide A or fibrin split product levels suggesting that disseminated intravascular coagulation or fibrinolysis may have had less influence on platelet numbers than certain other factors. By contrast, significant correlations were found for all three tumor types between platelet numbers and other indicators of bone marrow function including anemia, total leukocyte count, and absolute neutrophil count; and the fibrinogen level. Based upon these findings, we postulate that the host response to malignancy, possibly in the form of production of bone marrow-stimulating cytokines, may play a prominent role in regulation of platelet counts in these (and perhaps other) neoplasms, and that a particularly prominent and persistent degree of marrow stimulation exists in patients with N-SCLC.
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PMID:The platelet count in carcinoma of the lung and colon. 196 50

Disturbances of coagulation were measured in breast cancer, colon cancer and benign breast disease using an enzyme immunoassay against total plasma fibrinogen and fibrin degradation products (TDP). Results were compared with measurements of fibrinopeptide A (FPA) and of serum fibrinogen-related antigen (FRA). Plasma TDP before surgery was significantly higher in colon cancer than in breast cancer patients (p = 0.0009) or in benign breast disease (p = 0.0292). A post-operative rise in TDP at 4 months (colon cancer) or 9 months (breast cancer) was associated with early recurrent disease (p less than 0.0173 for colon cancer, p less than 0.1835 for breast cancer). No such association was noted with FPA or FRA measurements. TDP may prove to be of value in detecting activation of coagulation by malignant disease.
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PMID:Coagulation disturbances in cancer of the breast and colon measured with specific monoclonal antibody enzyme immunoassay for fibrin-fibrinogen degradation products. 218 96

Systemic activation of the coagulation mechanism is known to exist in patients with colon cancer. The mechanism of such activation was investigated using immunohistochemical techniques applied to fresh frozen sections of resected primary colon cancer specimens. Tumor cells stained for tissue factor, factor V, and urokinase-type plasminogen activator. Perivascular and intercellular areas stained for fibrinogen and the "a" subunit of factor XIII. Staining was minimal or absent for protein C, protein S, plasminogen activator inhibitors 1-3, factor VII, factor X, and fibrin (the antigenic site on the amino-terminal portion of B beta chain that is exposed following thrombin cleavage of fibrinopeptide B was not detected). The lack of an intact thrombin-generating pathway in situ associated with viable colon cancer cells is consistent with the findings of others that coagulation activation in colon cancer may be triggered by a soluble tumor product that exerts its effect at sites distant from the tumor. These results may explain the absence of clinical responsiveness of colon cancer to antithrombotic drug therapy and may clarify therapeutic strategies for this common tumor.
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PMID:Indirect activation of blood coagulation in colon cancer. 269 22

Cellular sites of coagulation activation within complex, intact tissues have been studied by immunohistochemical techniques. Hirudin, a specific and high affinity inhibitor of the active site of thrombin, together with antibody to hirudin were applied to sections of AMeX-fixed specimens of normal lung, kidney, placenta, freshly incised skin and unperturbed skin obtained at fresh autopsy; to rheumatoid synovial tissue; and to malignant tissue from a variety of tumor types. Staining for thrombin was observed selectively on pulmonary alveolar, rheumatoid synovial, and placental macrophages that express an intact extrinsic coagulation pathway. Staining was also observed restricted to the endothelium of capillaries in freshly incised skin but not in either unperturbed skin or in aged incisions. Staining of tumor cell bodies was observed in small cell carcinoma of the lung, renal cell carcinoma, and malignant melanoma tissues that we found previously to show tumor cell-associated procoagulant activity. This staining occurred commonly on cells within the tumor mass that were distant from stromal fibrinogen/fibrin. By contrast, tumor-associated macrophage but not tumor cell staining was seen in adenocarcinoma and squamous cell carcinoma of the lung, and little or no staining was seen colon cancer tissue. Negative controls in which either the hirudin probe or its antibody were omitted failed to show staining. These results are in accord with previous findings and suggest that such techniques may be useful for studying the cellular sites of thrombin generation in intact tissues. We postulate that administration of potent and specific thrombin antagonists, such as hirudin, to patients with relevant tumor types might be followed by homing of hirudin to tumor cells in vivo so that effects of local thrombin generation on malignant progression can be determined.
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PMID:Cellular localization of enzymatically active thrombin in intact human tissues by hirudin binding. 748 5

An analogue of 1,25-dihydroxyvitamin D3, 22(S)-24-homo-26,26,26,27,27,27-hexafluoro-1 alpha,22,25-trihydroxyvitamin D3 (DD-003), showed 10-fold greater inhibiting effect than 1,25-dihydroxyvitamin D3 on the growth of HT-29 human colonic adenocarcinoma cells in culture. To examine the anticancer activity of DD-003 in vivo, a fibrin clot of HT-29 cells was prepared with fibrinogen and thrombin and implanted under the renal capsule of the severe combined immunodeficient mouse. Starting 7 days after implantation of HT-29 tumor, mice were given 3 micrograms/kg body weight of DD-003 or the vehicle i.p. every other day for 5 times. The HT-29 tumor grew rapidly in control mice; malignant growth was clearly observed with mitosis, massive tumor angiogenesis, and invasion into normal kidney tissue. Tumors in DD-003 treated mice were smaller with less invasion compared to the control. Administration of DD-003 inhibited growth of HT-29 tumor by 63%. Serum calcium concentrations and body weights of the treated mice were similar to those of the control. DD-003 inhibited growth of HT-29 tumor in a dose-dependent manner over the range of 0.1-10 micrograms/kg body weight, with no increase of serum calcium concentration observed at any dose level. When DD-003 was withdrawn after 2 weeks of treatment, tumor growth resumed. Since chemosensitivity tested by the subrenal capsule assay correlates well with clinical response, DD-003 may be clinically applicable in procedures such as postsurgical chemotherapy of colon cancer.
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PMID:Inhibition of HT-29 human colon cancer growth under the renal capsule of severe combined immunodeficient mice by an analogue of 1,25-dihydroxyvitamin D3, DD-003. 792 32

In a retrospective study of 79 consecutive patients, we evaluated characteristics of polymyositis (PM) and dermatomyositis (DM) and compared clinical presentation, biochemical findings, histologic changes, evolution, complications, and mortality rate of elderly patients (aged > or = 65 yr) and younger patients (aged < or = 64 yr) at the onset of PM/DM. We found a high prevalence of PM/DM in elderly patients: 23 patients (29%) were aged 65 years or over. We also found that esophageal involvement (34.8% versus 16.1%, respectively) and bacterial pneumonia related to both ventilatory insufficiency and esophageal impairment (21.7% versus 5.4%, respectively) were more common in elderly patients compared with younger patients, resulting in increased morbidity and mortality rates. Moreover, malignancy frequency was higher in elderly patients compared with younger patients (47.8% versus 9.1%, respectively, p = 0.0001), particularly patients with DM (10/11). Fifty percent of malignancies were colon malignancies in elderly patients. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and ferritin levels were also higher in the elderly patient group compared with the younger group, and the presence of serum hypoprotidemia, hypoalbuminemia, and anemia was more frequent. Finally, PM/DM complete remission was less frequent (13.6% versus 41.1%) and the mortality rate (47.8% versus 7.3%) was higher in elderly patients than in younger patients. The main causes of death in elderly patients were bacterial pneumonia, due to ventilatory insufficiency and esophageal impairment, and malignancies. Our findings therefore indicate that PM/DM-related esophageal and lung involvement should be systematically searched for in elderly patients. Esophageal manometry and pulmonary function tests should become an integral part of initial evaluation in elderly patients for early detection of impairment. Moreover, as we observed a marked overrepresentation of colon cancer in elderly patients with DM, we suggest that the search for malignancies in elderly patients with DM should include lower gastrointestinal tract investigations.
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PMID:Influence of age on characteristics of polymyositis and dermatomyositis in adults. 1035 46

Fibrinogen is a major plasma protein (350 kDa) that induces proliferative signals by serving as a scaffold to support the binding of growth factors and to promote the cellular responses of adhesion, proliferation, and migration during wound healing, angiogenesis, and tumor growth. Fibrin(ogen) degradation products generated during fibrinolysis are implicated in tissue injury. The fibrinogen gamma chain has a COOH-terminal globular domain (gamma C, residues 151-411 of the gamma chain, 30 kDa) to which several integrin cell adhesion receptors (e.g., platelet alpha(IIb)beta(3), endothelial alpha(v)beta(3), and leukocyte alpha(M)beta(2)) bind. Integrins play a critical role in signal transduction from fibrin(ogen). We found that gamma C and its truncation mutant (designated gamma C399tr), with a deletion of the COOH-terminal 12 residues, induced apoptosis of endothelial cells and blocked tube formation of endothelial cells. DLD-1 human colon cancer cells that secrete gamma C or gamma C399tr grew at similar levels in vitro but grew much slower in vivo than mock-transfected cells. The recombinant purified gamma C399tr fragment markedly suppressed tumor growth, development of intratumoral vasculature, and tumor metastasis in vivo in the highly metastatic Met-1 breast cancer model. The determinant responsible for binding to endothelial cells is cryptic in native fibrinogen but is exposed in gamma C and gamma C399tr. These results suggest that fibrinogen has a novel cryptic determinant, which can exert apoptosis-inducing activity on endothelial cells when exposed, and polypeptides containing this determinant have therapeutic potential.
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PMID:The COOH-terminal globular domain of fibrinogen gamma chain suppresses angiogenesis and tumor growth. 1701 27

Matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are involved in colon cancer progression and metastasis due to their ability to degrade extracellular matrix (ECM) components. In previous studies we described the MMP-9 hemopexin like domain (MMP-9-PEX) as an MMP-9 antagonist. In the present study it was examined whether recombinant MMP-9-PEX has an inhibitory effect on migration and adhesion of colorectal carcinoma cells. Furthermore, we searched for MMP-9 substrate binding sites within the MMP-9-PEX by surface plasmon resonance. Migration of SW620 and LS174 cells was investigated in a modified Boyden chamber assay. In the presence of 0.2 microg/ml MMP-9-PEX migration of SW620 was decreased by 34%, while addition of 0.4 microg/ml diminished migration by 56%. Migration of LS174 cells was not affected by MMP-9-PEX. Adhesion studies were performed on 96-well plates coated with gelatin, collagen type I, and laminin, respectively. In the presence of MMP-9-PEX, adhesion of SW620 cells to these coating substrates was significantly inhibited. Surface plasmon resonance studies revealed binding of collagen type I and IV, elastin, and fibrinogen to proMMP-9 as well as to MMP-9-PEX. However, equilibrium constants (Kd) indicated a higher affinity of proMMP-9 to the matrix proteins. This could indicate that there is more than one binding site for matrix components within the entire proMMP-9 molecule. Since migration and adhesion of metastatic colorectal carcinoma cells were reduced by MMP-9-PEX, this recombinant MMP-9 antagonist might be of therapeutical interest.
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PMID:MMP-9-hemopexin domain hampers adhesion and migration of colorectal cancer cells. 1733 39

Clinical trials have shown life-prolonging effects of antithrombotics in cancer patients, but the molecular mechanisms remain unknown due to the multitude of their effects. We investigated in a mouse model whether one of the targets of antithrombotic therapy, fibrin deposition, stimulates tumour development. Fibrin may provide either protection of cancer cells in the circulation against mechanical stress and the immune system, or form a matrix for tumours and/or angiogenesis in tumours to develop. Mice homozygous for Factor V Leiden (FVL), a mutation in one of the coagulation factors that facilitates fibrin formation, were used to investigate whether hypercoagulability affects tumour development in an experimental metastasis model. Liver metastases of colon cancer were induced in mice with the FVL mutation and wild-type littermates. At day 21, number and size of tumours at the liver surface, fibrin/fibrinogen distribution, vessel density and the presence of newly formed vessels in tumours were analysed. Number and size of tumours did not differ between mice with and without the FVL mutation. Fibrin/fibrinogen was found in the cytoplasm of hepatocytes and cancer cells, in blood vessels in liver and tumour tissue and diffusely distributed outside vessels in tumours, indicating leaky vessels. Vessel density and angiogenesis varied widely between tumours, but a pre-dominance for vessel-rich or vessel-poor tumours or vessel formation could not be found in either genotype. In conclusion, the FVL mutation has no effect on the development of secondary tumours of colon cancer in livers of mice. Fibrin deposition and thus inhibition of fibrin formation by anticoagulants do not seem to affect tumour development in this model.
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PMID:Colon cancer metastasis in mouse liver is not affected by hypercoagulability due to Factor V Leiden mutation. 1763 46


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