Biomedical subjects

C Iacobuzio-Donahue

Publications and source records attributed to C Iacobuzio-Donahue.

5 recordsLinked to original sources

PubMed2001

Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE).

PURPOSE: Effective new markers of pancreatic carcinoma are urgently needed. In a previous analysis of gene expression in pancreatic adenocarcinoma using serial analysis of gene expression (SAGE), we found that the tag for the mesothelin mRNA transcript was present in seven of eight SAGE libraries derived from pancreatic carcinomas but not in the two SAGE libraries derived from normal pancreatic duct epithelial cells. In this study, we evaluate the potential utility of mesothelin as a tumor marker for pancreatic adenocarcinoma. EXPERIMENTAL DESIGN: Mesothelin mRNA expression was evaluated in pancreatic adenocarcinomas using reverse-transcription PCR (RT-PCR) and in situ hybridization, whereas mesothelin protein expression was evaluated by immunohistochemistry. RESULTS: Using an online SAGE database (http://www.ncbi.nlm.gov/SAGE), we found the tag for mesothelin to be consistently present in the mesothelioma, ovarian cancer, and pancreatic cancer libraries but not in normal pancreas libraries. Mesothelin mRNA expression was confirmed by in situ hybridization in 4 of 4 resected primary pancreatic adenocarcinomas and by RT-PCR in 18 of 20 pancreatic cancer cell lines, whereas mesothelin protein expression was confirmed by immunohistochemistry in all 60 resected primary pancreatic adenocarcinomas studied. The adjacent normal pancreas in these 60 cases did not label, or at most only rare benign pancreatic ducts showed weak labeling for mesothelin. CONCLUSIONS: Mesothelin is a new marker for pancreatic adenocarcinoma identified by gene expression analysis. Mesothelin overexpression in pancreatic adenocarcinoma has potential diagnostic, imaging, and therapeutic implications.

Adenocarcinoma↗

PubMed1999

Cytomegaloviral enterocolitis: clinical associations and outcome.

PURPOSE: Cytomegaloviral enterocolitis is an uncommon disorder that can complicate inflammatory bowel disease. It is more common in patients with acquired immunodeficiency syndrome and can occur in patients on immunosuppressive therapy for autoimmune or inflammatory diseases and in allograft recipients. Mortality rates of up to 71 percent have been reported for cytomegaloviral enterocolitis. The aims of this study were 1) to identify the presentation, underlying medical conditions, treatment, and outcome of patients with cytomegaloviral enterocolitis and 2) to determine the prevalence of this infection in patients undergoing intestinal resection for inflammatory bowel disease. METHODS: A retrospective chart review of patients with pathologic evidence of cytomegaloviral enterocolitis from 1985 through 1996 was performed. To determine the prevalence of this condition, the hospital discharge database was searched for the diagnoses of ulcerative colitis and Crohn's disease in patients who underwent bowel resection. RESULTS: 93 patients (mean age, 44 years; 66 percent males) had cytomegaloviral infection in the small intestine (n = 6), large intestine (n = 86), or appendix (n = 1). Patients with acquired immunodeficiency syndrome (n = 42), with ulcerative colitis (n = 11), with Crohn's disease (n = 11), receiving organ transplant (n = 12), receiving bone marrow transplant (n = 8), and in other immunosuppressed states (n = 11) comprised this study. Seventeen patients (18 percent) underwent intestinal resection, and the remaining 76 patients were treated medically. Abdominal pain (77 vs. 37 percent; P < 0.01) and gastrointestinal bleeding (65 vs. 34 percent; P < 0.05) were more common presenting symptoms in patients who required resection than patients in the medically managed group. Mortality was 17.6 percent in the surgically managed group and 14.5 percent in the patients who were managed medically. The median duration of ulcerative colitis in patients with coexisting cytomegaloviral infection was 12 months. The prevalence of cytomegaloviral enterocolitis was 4.6 percent in patients with ulcerative colitis and 0.8 percent in patients with Crohn's disease. CONCLUSIONS: These data suggest that cytomegaloviral infection more frequently complicates ulcerative colitis than Crohn's disease. Furthermore, a short and fulminant course of ulcerative colitis may indicate coexisting cytomegaloviral infection. The overall low mortality in this retrospective study suggests that aggressive medical and surgical treatment improves survival in patients with cytomegaloviral enterocolitis.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Cathepsin B activity and protein levels in thyroid carcinoma, Graves' disease, and multinodular goiters.

Cathepsin B (CB) is involved in the hydrolysis of thyroglobulin (Tg) and thought to be regulated by thyroid stimulating hormone (TSH) in the normal thyroid. Our analyses of 91 thyroid tissues from 71 patients with Graves' disease (GD), multinodular goiter (MNG), papillary carcinoma (PC), or follicular carcinoma (FC), demonstrated a 2-fold increase in expression of CB in GD and an average increase of 1.5-fold in MNG (varying from 10-fold below normal to 6-fold above normal in MNG nodules), as might be predicted by the altered functional status of thyroid follicular cells in those diseases. However, CB activity was not downregulated in conjunction with the known "blocking effect" of malignancy on many thyroid functions, but rather increased on average 9-fold in papillary carcinomas (n = 33), and also showed a marked increase in 2 follicular carcinomas. Activity measurements were confirmed by CB protein detection on Western blot with moderately increased CB protein levels demonstrated in GD, variable expression in nodules of MNG, and markedly increased protein expression in carcinomas. In all diseased states, increased protein was detected primarily as overexpression of the 27 kd heavy chain of 2-chain mature CB and less frequently as overexpression of 31 kd single-chain mature CB. However, an additional 35 kd protein form was noted in 3 of 9 PCs, 1 of 2 FCs, and 1 of 4 GD cases but in none of 10 MNG cases. In conjunction with elevated CB activity plus additional protein bands on Western blots, altered patterns of CB immunohistochemical staining were observed, irrespective of the type of thyroid disease, suggesting certain common changes in CB expression, posttranslational processing, and vesicular trafficking. In summary, GD and MNG thyroid tissues demonstrated altered CB expression in keeping with predicted functional changes in thyroid follicular cells, while increased CB expression in carcinomas indicated a more pathological role for CB in thyroid cancers, possibly related to the processes of invasion or metastasis.

Blotting, Western↗

PubMedDate not supplied

Molecular pathology of pancreatic cancer.

Until recently, pancreatic cancer was a poorly understood disease. Research in the past decade has shown conclusively, however, that pancreatic cancer is primarily genetic in nature. Inactivation with a variety of tumor-suppressor genes such as p16, DPC4, and p53, coupled with activation of oncogenes such as K-ras, are a few of the mutations that trigger the growth of cancerous cells. Understanding these mutations is critical to a better understanding of familial pancreatic cancer and to the development of gene-based screening tests and therapies. In this article, we review the genetic alterations identified in pancreatic cancer and provide examples of how this information can be applied to patient care.

DNA, Mitochondrial↗

PubMedDate not supplied

Characterizing human colorectal carcinomas by proteolytic profile.

Clinicopathologic staging of colorectal cancers cannot always predict aggressiveness of prognosis for a particular patient. We have used activity assays for cysteine proteinases, cathepsins B, L and H (CB, CL and CH) and matrix metalloproteinases, MMP-2 and MMP-9, to identify several distinctive, reproducible proteolytic profiles in a large set of colorectal carcinomas. We observed that individual proteinases demonstrated specific and distinct levels of activity at different cancer stages, possible reflecting non-random steps in a proteolytic cascade related to tumor development. We also observed that individual colon cancers fell into relatively few categories when characterized for the combined expression of three proteinases: CB, CL and MMP-9. Four proteolytic profiles, designated "Early", "Middle", "Late", and "High", could be used to define almost 80% of the colorectal carcinomas analyzed. Such profiles, based on the expression of several proteinases in a given tumor, provided information independent of clinical stage and may identify crucial variations in tumor behavior.

Biomarkers, Tumor↗