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Biomedical subjects

Paul Crotty

Publications and source records attributed to Paul Crotty.

6 recordsLinked to original sources

COX-2 overexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy.

PURPOSE: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). METHODS AND MATERIALS: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. RESULTS: Good response (TRG 1+2), moderate response (TRG 3), and poor response (TRG 4+5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3+4) to treatment than were those with normal COX-2 expression (p=0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p=0.0007, chi-square test). CONCLUSIONS: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.

Apoptosis↗

Gastric mucosal mast cells are increased in Helicobacter pylori-negative functional dyspepsia.

BACKGROUND & AIMS: Mast cells might be involved in pathogenesis of functional dyspepsia because they can release a wide range of potent mediators, capable of altering gastric nerve and muscle function. This study aimed to determine whether mast cell numbers were increased in the gastric mucosa of patients with functional dyspepsia compared to control subjects. METHODS: Biopsy samples were taken from the antrum and corpus of 111 patients: 20 asymptomatic control subjects, 62 patients with Rome criteria functional dyspepsia (33 Helicobacter pylori positive, 29 H. pylori negative), and 29 inflammatory control subjects (H. pylori positive). Mast cells were detected immunohistochemically by using a mouse monoclonal antibody specific for tryptase. Quantification was performed with light microscopy, and results were expressed as mast cells/mm(2) +/- standard error of mean. RESULTS: Mast cells were significantly increased in H. pylori negative functional dyspepsia samples compared to normal control samples in the antrum (230.1 +/- 11.3 vs. 94.8 +/- 8.4, P < 0.001) and corpus (264.1 +/- 27.1 vs. 123.9 +/- 11.5, P = 0.001). Mast cells were also significantly increased in the antrum of patients with H. pylori positive functional dyspepsia compared to asymptomatic control subjects (166.5 +/- 17.0 vs. 94.8 +/- 8.4, P < 0.03). However, there was no significant difference between mast cell numbers in patients with H. pylori positive functional dyspepsia compared to inflammatory control subjects. CONCLUSIONS: Mast cells are increased in functional dyspepsia, independently of inflammation. This might contribute to the pathogenesis of functional dyspepsia by altering signaling in the brain-gut axis.

Adolescent↗

Semireannealing, single-stranded conformational polymorphism: a novel and effective tool for the diagnosis of T-cell clonality.

Single-stranded conformational polymorphism (SSCP) is often used for the diagnosis of T-cell clonality in lymphoproliferative disorders. We introduce a semireannealing SSCP (SR-SSCP) protocol that is rapid, reproducible, and effective. By denaturing and reannealing the polymerase chain reaction (PCR) product before high-resolution polyacrylamide gel electrophoresis, it is possible to generate a diagnostic fingerprint for each case with clonal T-cell receptor-gamma (TCR-gamma) gene rearrangement detected after PCR with TCR-gamma specific consensus primers. Discrete and distinct denatured single-stranded DNA band profiles characterize the rearranged TCR-gamma clones. In the same gel, the clone size may be estimated in the reannealed double-stranded PCR DNA and can be assessed down to the 2% clonal T-cell population level. Eighty-four cases, including 37 T-cell neoplasms, 29 B-cell neoplasms, and 18 reactive lymph node samples were analyzed by SR-SSCP. Clonal TCR-gamma rearrangement was diagnosed in 32 out of 37 T-cell neoplasms but in none of the B-cell tumors or reactive lymph node samples corresponding to sensitivity and specificity of 86.5% and 100%, respectively. We compare the results of SR-SSCP to those obtained by capillary electrophoresis and direct sequence analysis with 100% correlation. This novel method is applicable to any system for identification and quantitation of microheterogeneity in PCR products.

Base Sequence↗