ABSTRACT
BACKGROUND: The aim of this pilot retrospective study was to investigate the immunohistochemical expression of Cathepsin S (CatS) in three cohorts of colorectal cancer (CRC) patients (n=560). METHODS: Prevalence and association with histopathological variables were assessed across all cohorts. Association with clinical outcomes was investigated in the Northern Ireland Adjuvant Chemotherapy Trial cohort (n=211), where stage II/III CRC patients were randomised between surgery-alone or surgery with adjuvant fluorouracil/folinic acid (FU/FA) treatment. RESULTS: Greater than 95% of tumours had detectable CatS expression with significantly increased staining in tumours compared with matched normal colon (P>0.001). Increasing CatS was associated with reduced recurrence-free survival (RFS; P=0.03) among patients treated with surgery alone. Adjuvant FU/FA significantly improved RFS (hazard ratio (HR), 0.33; 95% CI, 0.12-0.89) and overall survival (OS; HR, 0.25; 95% CI, 0.08-0.81) among 36 patients with high CatS. Treatment did not benefit the 66 patients with low CatS, with a RFS HR of 1.34 (95% CI, 0.60-3.19) and OS HR of 1.33 (95% CI, 0.56-3.15). Interaction between CatS and treatment status was significant for RFS (P=0.02) and OS (P=0.04) in a multivariate model adjusted for known prognostic markers. CONCLUSION: These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Cathepsins/metabolism , Chemotherapy, Adjuvant , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Cohort Studies , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/surgery , Female , Fluorouracil/administration & dosage , Humans , Immunohistochemistry , Leucovorin/administration & dosage , Male , Middle Aged , Pilot Projects , PrognosisABSTRACT
A previous investigation identified three types of cuspal movement that occur as a result of polymerization shrinkage when extracted molar teeth are filled with a microfine or hybrid composite used in conjunction with a dentine adhesive. That investigation was extended further by dye penetration and SEM studies of the margin, involving assessment of the degree of dye penetration and marginal integrity around the restoration. These studies indicate that there may be a failure of the adhesive bond between tooth and composite/adhesive complex which correlates with little or no cuspal movement. Failure within the tooth structure itself was also observed in a number of cases.
Subject(s)
Adhesives , Composite Resins , Dental Bonding , Dentin , Resin Cements , Acrylic Resins , Chemical Phenomena , Chemistry, Physical , Coloring Agents , Dental Cements , Dental Enamel/ultrastructure , Dental Leakage/diagnosis , Dental Restoration, Permanent , Dentin/ultrastructure , Humans , Microscopy, Electron, Scanning , Polymers , Polyurethanes , Surface PropertiesABSTRACT
One hundred and twenty caries-free molar teeth were stored in saline. Three types of cavities were prepared in these teeth: conventional MOD, parallel-sided MOD with no buccal or lingual extensions, and a slit cavity. Cavity dimensions were recorded. Each group of teeth were restored with either a microfine or conventional composite, used in conjunction with a dentine adhesive. Cusp movement was recorded via two linear variable displacement transducers attached to the cusps. Using dye penetration studies, the marginal adaptation of the material to the teeth was assessed. In a small number of cases, the amount and type of cuspal movement and the degree of dye penetration was variable, depending on cavity design and the composite used, but generally cusp movement was unaffected by variation in cavity outline.
Subject(s)
Composite Resins , Dental Cavity Preparation/methods , Dental Restoration, Permanent , Molar/physiology , Resin Cements , Acrylic Resins , Bisphenol A-Glycidyl Methacrylate , Coloring Agents , Dental Bonding , Dental Cements , Dental Leakage/diagnosis , Humans , Methacrylates , Polyurethanes , Stress, Mechanical , Surface Properties , TransducersABSTRACT
Forty extracted molar teeth were stored in saline. After MOD cavities were prepared and the dimensions of each cavity recorded, the teeth were restored with either a microfine or hybrid composite in conjunction with a dentine adhesive. Cusp movements were recorded from two linear variable displacement transducers attached to the cusps. Three types of movement were identified, one in which the opposing cusps moved towards one another, the second where no movement occurred at all, and the third where both cusps moved in the same direction. The degree of movement observed with the microfine material was nearly double that recorded with the hybrid. The movement appeared to relate to the polymerization shrinkage values of the materials and to the failure of the adhesive bond between the tooth and the composite-adhesive complex.
