Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GH-secreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amounts of activity were also found in two other tumors (carcinoid and small cell carcinoma of lung) unassociated with GH hypersecretion. Each of the tumors contained somatostatin-like immunoreactivity but the levels did not correlate with the net biologic expression of the tumor. Sephadex G-75 gel filtration indicated the GH-releasing activity to have an apparent molecular size of slightly greater than 6,000 daltons. The GH-releasing activity was adsorbed onto DEAE-cellulose at neutral pH and low ionic strength, from which it could be eluted by increasing ionic strength. The GH-releasing activity was further purified by high pressure liquid chromatography using an acetonitrile gradient on a cyanopropyl column to yield a preparation that was active at 40 ng protein/ml. Partially purified GH-releasing activity, from which most of the bioactive somatostatin had been removed, increased GH release by pituitary monolayer cultures to five times base line. Enzymatic hydrolysis studies revealed that the GH-releasing activity was resistant to carboxypeptidase, leucine-aminopeptidase, and pyroglutamate-amino-peptidase but was destroyed by trypsin and chymotrypsin, indicating that internal lysine and/or arginine and aromatic amino acid residues are required for biologic activity and that the NH2-terminus and CO9H-terminus are either blocked or not essential. The results provide an explanation for the presence of GH-secreting tumors in some patients with the multiple endocrine neoplasia syndrome, type I, and warrant the addition of GH-releasing activity to the growing list of hormones secreted by tumors of amine precursor uptake and decarboxylation cell types.
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PMID:Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly. 624 40

We report 4 cases of acinar cell carcinoma of the pancreas, 3 presenting as metastases in the ovary, the first report of this circumstance, which may pose a broad differential diagnosis and caused significant diagnostic difficulty in all the cases. The average patient age was 57 (range: 28 to 81) years. In 3 cases, the ovarian tumors were detected before the pancreatic tumor; in 1 case, a large abdominal mass and ovarian tumors were discovered synchronously. The ovarian tumors were large, solid, white-tan on gross examination, and bilateral in 3 cases; the single case involving only 1 ovary had 2 discrete masses of tumor. Microscopic examination showed highly cellular neoplasms with a small amount of fibrous stroma. Two cases had a predominant acinar growth pattern of cells with brightly eosinophilic, granular cytoplasm. In 2 cases, the pattern was predominantly solid-cribriform with areas of comedolike necrosis, and the cells had pale eosinophilic, finely granular cytoplasm. Nuclei in all cases were uniform with prominent nucleoli. The main differential diagnostic consideration was well-differentiated neuroendocrine neoplasm (carcinoid tumor); positive immunostaining with antibodies against chymotrypsin and trypsin and negative immunostaining with antibodies against synaptophysin and chromogranin helped exclude this diagnosis. We observed focal alpha-inhibin immunostaining in 2 cases, which may represent a potential diagnostic pitfall, as a Sertoli cell tumor or unusual granulosa cell tumor may also enter the differential diagnosis. Inclusion of antibodies against the pancreatic enzymes chymotrypsin and trypsin in the immunohistochemical panel is critical in establishing the correct diagnosis and should be considered when evaluating ovarian tumors with architectural (mainly acinar) and cytologic (granular eosinophilic cytoplasm) characteristics that should bring a metastatic acinar cell carcinoma into consideration.
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PMID:Acinar cell carcinoma of the pancreas metastatic to the ovary: a report of 4 cases. 1872 47