fibrin and Colonic-Neoplasms

Colon cancer stem cells (CSCs) have been shown to be responsible for the recurrence and metastasis of colorectal cancer (CRC). As a crucial microenvironmental factor, extracellular matrix (ECM) stiffness is known to affect the stemness of CSCs. Recently, fibrin deposition in the stroma of CRC was demonstrated to be responsible for tumor development. In this study, we used salmon fibrin gel to provide a 3D ECM for colon cancer cells and investigated its effects on cell growth as well as the underlying mechanisms. Compared with stiff 420 Pascal (Pa) and 1 050 Pa gels, 90 Pa soft fibrin gel was most efficient at isolating and enriching tumor colonies. The size and number of colony formation negatively correlated with gel stiffness. Specifically, these tumor colonies exhibited efficient tumorigenicity, upregulated stem cell markers, and had anti-chemotherapeutic properties and were thus named tumor-repopulating cells (TRCs). More importantly, the self-renewal molecule Nanog was sharply induced in 3D-cultured colon TRCs; further, Nanog siRNA significantly inhibited colony formation, suggesting the indispensable role of Nanog in TRC growth. A subsequent mechanistic study illustrated that Nanog expression could be modulated through fibrin gel stiffness-induced DAB2IP/PI3K/FOXA1 signaling in colon TRCs.

Topics: Animals; Apoptosis; Cell Proliferation; Colonic Neoplasms; Fibrin; Gels; HCT116 Cells; Hepatocyte Nuclear Factor 3-alpha; Heterografts; HT29 Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Nanog Homeobox Protein; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; ras GTPase-Activating Proteins; Salmon; Transfection

Polymyalgia rheumatica (PMR), a chronic inflammatory rheumatism, can be the expression of a paraneoplastic syndrome. The same clinical symptoms are frequently observed at the early stage of the benign and malignant forms. Here, our aim was to develop diagnostic tools to differentiate paraneoplastic PMR from essential PMR. We combined an 18FDG-PET and detection of circulating procoagulant microparticles (MPs), such as fibrin positive (FibMPs), by flow cytometry. Two patients with PMR and a similar profile were selected. In the two patients, the 18FDG-PET revealed a hypermetabolic focus. However, the concentrations of fibrin+/annexin+ microparticles detected were (10 times higher in one of the two patients, who was later found to have breast cancer. The association of 18FDG-PET and the detection of microparticle fibrin positives by flow cytometry allows separating essential PMR (hypermetabolism by 18FDG-PET, low FibMPs) from paraneoplastic PMR.

Topics: Aged; Breast Neoplasms; Cell-Derived Microparticles; Colonic Neoplasms; Female; Fibrin; Fluorodeoxyglucose F18; Humans; Middle Aged; Paraneoplastic Syndromes; Polymyalgia Rheumatica; Positron Emission Tomography Computed Tomography; Whole Body Imaging

Fibrin(ogen) mediates sustained tumor cell adhesion and survival in the pulmonary vasculature, thereby facilitating the metastatic dissemination of tumor cells. CD44 is the major functional fibrin receptor on colon carcinoma cells. Growth factors, such as platelet-derived growth factor (PDGF), induce post-translational protein modifications, which modulate ligand binding activity. In view of the roles of PDGF, fibrin(ogen) and CD44 in cancer metastasis, we aimed to delineate the effect of PDGF on CD44-fibrin recognition. By immunoprecipitating CD44 from PDGF-treated and untreated LS174T colon carcinoma cells, which express primarily CD44v, we demonstrate that PDGF enhances the adhesion of CD44v-coated beads to immobilized fibrin. Enzymatic inhibition studies coupled with flow-based adhesion assays and autoradiography reveal that PDGF augments the binding of CD44v to fibrin by significantly attenuating the extent of CD44 sulfation primarily on chondroitin and dermatan sulfate chains. Surface plasmon resonance assays confirm that PDGF enhances the affinity of CD44v-fibrin binding by markedly reducing its dissociation rate while modestly increasing the association rate. PDGF mildly reduces the affinity of CD44v-hyaluronan binding without affecting selectin-CD44v recognition. The latter is attributed to the fact that CD44v binds to selectins via sialofucosylated O-linked residues independent of heparan, dermatan and chondroitin sulfates. Interestingly, PDGF moderately reduces the sulfation of CD44s and CD44s-fibrin recognition. Collectively, these data offer a novel perspective into the mechanism by which PGDF regulates CD44-dependent binding of metastatic colon carcinoma cells to fibrin(ogen).

Topics: Binding, Competitive; Cell Adhesion; Cell Culture Techniques; Cell Line, Tumor; Chondroitin; Colonic Neoplasms; Dermatan Sulfate; Fibrin; Fibrinogen; Flow Cytometry; HL-60 Cells; Humans; Hyaluronan Receptors; Hyaluronic Acid; Immobilized Proteins; Immunoprecipitation; Microspheres; Platelet-Derived Growth Factor; Protein Binding; Selectins; Stress, Mechanical; Sulfates

The features of radiation or chemotherapy cystitis mimicking invasive urothelial cancer are not widely known.. A search of the consultation files from our institution between January 1996 and September 2003 identified 20 patients with bladder biopsies showing cystitis mimicking invasive urothelial cancer.. The mean age at diagnosis was 69 years (range, 40-85 years); 80% were males. Complete history was not available in 1 patient. Seventeen patients had a history of pelvic irradiation (15 prostate cancer and 2 endometrial cancer). Two patients had systemic chemotherapy (1 metastatic colon cancer and 1 mixed connective tissue disease). All patients presented with hematuria. The mean time from radiation and/or chemotherapy to presentation was 27 months (range, 0-84 months). All cases showed epithelial proliferation that mimicked invasive cancer within the lamina propria, with marked proliferation seen in 45% of cases. Mild to moderate nuclear pleomorphism was seen in all cases. A characteristic feature was the presence of pseudoinvasive urothelial nests wrapping around the vessels associated with fibrin deposition. Most cases did not show any mitoses (75%). Ulceration was seen in 39% of cases. All cases showed some degree of hemorrhage, fibrin deposition and fibrin thrombi, fibrosis, and acute and chronic inflammation, with hemosiderin identified in 60% of cases. Edema and vascular congestion were common features (95% and 80%, respectively). Thickened vessels and vascular changes associated with radiation injury were identified in 75% of cases. Seventeen patients were followed for a mean of 9 months (range, 0.25-37 months), and none developed bladder cancer.. Radiation or chemotherapy cystitis can show epithelial proliferations that may be confused with invasive urothelial carcinomas. Other findings characteristic of radiation or chemotherapy cystitis, such as hemorrhage, fibrin, and vascular changes, are often seen in association with the epithelial proliferations and are helpful in distinguishing it from invasive cancer. Pathologists must be aware that these changes may be seen with a remote radiation or chemotherapy history, where this information may not be provided or known at the time of the biopsy evaluation.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Colonic Neoplasms; Cystitis; Diagnosis, Differential; Endometrial Neoplasms; Epithelium; Female; Fibrin; Follow-Up Studies; Hemorrhage; Histocytochemistry; Humans; Male; Middle Aged; Mixed Connective Tissue Disease; Prostatic Neoplasms; Radiation Injuries; Radiotherapy; Thrombosis; Time Factors; Urinary Bladder; Urinary Bladder Neoplasms

This study was undertaken to investigate the kinetics and molecular requirements of platelet binding to tumor cells in bulk suspensions subjected to a uniform linear shear field, using a human colon adenocarcinoma cell line (LS174T) as a model. The effects of shear rate (20-1000 s(-1)), shear exposure time (30-300 s), shear stress (at constant shear rate by adjusting the viscosity of the medium from 1.3-2.6 cP), cell concentration, and platelet activation on platelet-LS174T heteroaggregation were assessed. The results indicate that hydrodynamic shear-induced collisions augment platelet-LS174T binding, which is further potentiated by thrombin/GPRP-NH(2). Peak adhesion efficiency occurs at low shear and decreases with increasing shear. Intercellular contact duration is the predominant factor limiting heteroaggregation at shear rates up to 200 s(-1), whereas these interactions become shear stress-sensitive at > or = 400 s(-1). Heteroaggregation increases with platelet concentration due to an elevation of the intercellular collision frequency, whereas adhesion efficiency remains nearly constant. Moreover, hydrodynamic shear affects the receptor specificity of activation-dependent platelet binding to LS174T cells, as evidenced by the transition from a P-selectin-independent/Arg-Gly-Asp (RGD)-dependent process at 100 s(-1) to a P-selectin/alpha(IIb)beta(3)-dependent interaction at 800 s(-1). This study demonstrates that platelet activation and a fluid-mechanical environment representative of the vasculature affect platelet-tumor cell adhesive interactions pertinent to the process of blood-borne metastasis.

Topics: Antibodies, Monoclonal; Biophysical Phenomena; Biophysics; Blood Platelets; Cell Adhesion; Cells, Cultured; Colonic Neoplasms; Fibrin; Flow Cytometry; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Humans; Kinetics; Microscopy, Electron; Models, Theoretical; P-Selectin; Stress, Mechanical; Tumor Cells, Cultured

This study employs fluorescent inhibitor molecules to detect both cell surface proteases and their receptor sites on colonic carcinoma cells. Present studies are concerned with the interactions of the tumour associated proteases, guanidinobenzoatase (GB) and plasminogen activators (PAs) with PAs inhibitor type 1 (PAI-1). The active enzymes on the cell surfaces in frozen sections of human colonic carcinoma tissue were located by staining with two active site directed fluorescent inhibitors, 9-aminoacridine (9-AA) and Rhodamine labelled PAI-1 (Rh-PAI-1), followed by fluorescence microscopy. Fibrin treated sections, which now lack GB but have receptor proteins for GB, fail to bind 9-AA and Rh-PAI-1. When these fibrin-treated sections were incubated with purified colonic carcinoma GB and u-PA, both enzymes were bound to the tumour cells in these sections and subsequent challenging with fluorescent probes for GB resulted in bright fluorescence under appropriate microscopic conditions. On the other hand when fibrin treated sections were incubated with t-PA, followed by challenging with Rh-PAI-1, no red fluorescence was observed. It is suggested that the GB and u-PA have similar specific binding sites which can recognise and bind to the receptors on tumour cells in fibrin-treated sections, but t-PA has no such binding site and fails to recognise the cell surface receptors for GB. These GB-receptors may have a possible role in the regulation of GB and u-PA activity during tumour cell invasion and metastasis.

Topics: Aminacrine; Carboxylic Ester Hydrolases; Colonic Neoplasms; Endopeptidases; Fibrin; Microscopy, Fluorescence; Plasminogen Activator Inhibitor 1; Receptors, Cell Surface; Rhodamines; Staining and Labeling; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

The three-dimensional growth of cultured tumor cell lines (HT29, a colon adenocarcinoma cell line; M21, a melanoma cell line; KB, a nasopharyngeal carcinoma cell line) has been investigated in an agar culture system with a fibrin matrix in vitro. The tumor cells developed to tumors 3 x 3 mm in diameter after 10 days in culture in vitro. This size was large enough to allow histologic examination. The tumor cells located in the surface area of the three-dimensional tumor seemed to grow well. However, the tumor cells in the center degenerated or did not proliferate, indicating a lack of nutrition and/or anoxia in the center. The histologic comparison between the xenografted tumors on nude mice and the three-dimensional tumors in vitro suggests that the structures of the three-dimensional tumors were comparable, especially in the surface area, to the xenografted tumors. Furthermore, the antitumor effect of mitomycin C on the three-dimensional tumors was found to be dose-dependent.

Topics: Adenocarcinoma; Agar; Animals; Cell Division; Cell Hypoxia; Colonic Neoplasms; Culture Techniques; Extracellular Matrix; Fibrin; Humans; KB Cells; Melanoma; Mice; Mice, Nude; Mitomycin; Transplantation, Heterologous; Tumor Cells, Cultured

Topics: Animals; Colonic Neoplasms; Delayed-Action Preparations; Drug Carriers; Fibrin; Gels; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Tumor Necrosis Factor-alpha

Our experience with the subcutaneous absorbable bridge for constructing a temporary loop ileostomy and loop colostomy is described. The use of this subcutaneous absorbable bridge in 15 patients - 6 with loop ileostomy and 9 with loop colostomy - was almost without complications. The absorbable bridge is a progress for maturation of the stoma and for immediate postoperative as prospective fitting of a watertight appliance. The actual trend substituting the temporary loop colostomy by the loop ileostomy may be advanced by the unlimited use of the subcutaneous absorbable bridge for constructing a temporary loop ileostomy.

Topics: Adult; Aged; Colonic Diseases; Colonic Neoplasms; Colostomy; Female; Fibrin; Glycerol; Humans; Ileostomy; Intestinal Obstruction; Male; Middle Aged; Ovarian Neoplasms; Prostheses and Implants; Sutures

Rapid in vivo growth of cultured human cancer or leukemia cells was achieved by implantation into the subrenal capsule of mice. A solid structure, necessary for accurate implantation and measurement of tumor growth in this model, was provided by stepwise addition of fibrinogen and thrombin to the tumor cells, leading to rapid enzymatic formation of a solid tumor-fibrin matrix. Human leukemia and epithelial cancers increased in volume between 6- and 40-fold when measured 6-10 days after implantation into normal or immunosuppressed mice. Immunosuppression of host CD-1 mice was achieved by cyclosporine given daily after tumor implantation, cyclophosphamide given preimplantation combined with cyclosporine, or whole-body irradiation given preimplantation. Confirming the validity of tumor measurements, tumor histology in the immunosuppressed mice revealed cell proliferation, invasion, and neovascularization. Similarly, no artifactual measurement of tumor growth was observed by nonviable cancer cells, implanted after in vitro exposure to a known cytotoxic concentration of thiotepa. This model provides an economical, short-term technique for the in vivo study of human tumor growth, for the evaluation of new cancer therapies, and for in vitro - in vivo drug activity correlations in specific types of human cancer or leukemia cell lines.

Topics: Animals; Colonic Neoplasms; Female; Fibrin; Humans; Immunosuppression Therapy; Karyotyping; Kidney; Leukemia, Myeloid, Acute; Melanoma; Methods; Mice; Mice, Nude; Neoplasm Transplantation; Transplantation, Heterologous; Urinary Bladder Neoplasms; Vulvar Neoplasms

The early demonstration of immunologic specificity of antibodies and the discovery of tumor antigenic specificity are reviewed in the light of experimental and clinical attempts to use such reagents in the management of cancer. Recent results in regard to tumor antigens and radiolabeled antibody preparations are shown to be practical for experimental diagnosis and therapy and potentially for similar clinical purposes.

Topics: alpha-Fetoproteins; Animals; Antibodies, Neoplasm; Antigens, Neoplasm; Carcinoembryonic Antigen; Colonic Neoplasms; Europe; Female; Fibrin; Hodgkin Disease; Humans; Immunization, Passive; Immunoglobulin G; Immunotherapy; Iodine Radioisotopes; Isotope Labeling; Male; Mice; Neoplasm Transplantation; Neoplasms; Ovarian Neoplasms; Rabbits; Radionuclide Imaging; Rats; Transplantation, Heterologous; United States

Topics: Adolescent; Adult; Aged; Amino Acids; Amino Acids, Essential; Colonic Neoplasms; Evaluation Studies as Topic; Female; Fibrin; Gastrointestinal Diseases; Humans; Hydrolysis; Male; Middle Aged; Nitrogen; Nutritional Requirements; Parenteral Nutrition; Peptide Fragments

Topics: Breast Neoplasms; Colonic Neoplasms; Esophageal Neoplasms; Fibrin; Fibrinogen; Fibrinolysis; Gallbladder Neoplasms; Humans; Lymphatic Metastasis; Neoplasms; Pancreatic Neoplasms; Rectal Neoplasms; Stomach Neoplasms

Topics: Aminocaproates; Blood Coagulation; Breast Neoplasms; Colonic Neoplasms; Female; Fibrin; Fibrinogen; Fibrinolysis; Gastrointestinal Neoplasms; Humans; Immunoelectrophoresis; Intestinal Neoplasms; Kidney Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Prostatic Neoplasms; Rectal Neoplasms; Thrombin; Urinary Bladder Neoplasms; Urogenital Neoplasms

Topics: Adenocarcinoma; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Blood Protein Disorders; Carcinoma; Colonic Neoplasms; Fibrin; Hemostatics; Humans; Immunoelectrophoresis; Kidney Neoplasms; Male; Middle Aged; Multiple Myeloma; Papain; Plasmapheresis

Topics: Aorta; Arteriosclerosis; Blood Coagulation Tests; Colonic Neoplasms; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hypertension; Hypertension, Renal; Immunoassay; Kidney; Obesity; Pyelonephritis; Renal Veins; Staphylococcus