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ABSTRACT: Human kallikrein 2 (hK2) is a secreted, trypsin-like protease that shares 80% amino acid sequence identity with prostate-specific antigen (PSA). hK2 has been shown to be a serum marker for prostate cancer and may also play a role in cancer progression and metastasis. We have previously identified a novel complex between human kallikrein 2 (hK2) and protease inhibitor 6 (PI-6) in prostate cancer tissue. PI-6 is an intracellular serine protease inhibitor with both antitrypsin and antichymotrypsin activity. In the current study we have shown that PI-6 forms a rapid in vitro complex with hK2 but does not complex with PSA. Recombinant mammalian cells expressing both hK2 and PI-6 showed hK2-PI-6 complex in the spent media only after cell death and lysis. Similarly, LNCaP cells expressing endogenous hK2 and PI-6 showed extracellular hK2-PI-6 complex formation concurrently with cell death. Immunostaining of prostate cancer tissues with PI-6 monoclonal antibodies showed a marked preferential staining pattern in cancerous epithelial cells compared with noncancerous tissue. These results indicate that the hK2-PI-6 complex may be a naturally occurring marker of tissue damage and necrosis associated with neoplasia. Both hK2 and PI-6 were shed into the lumen of prostate cancer glands as granular material that appeared to be cellular necrotic debris. The differential staining pattern of PI6 in tissues suggests a complex regulation of PI-6 expression that may play a role in other aspects of neoplastic progression.
International Journal of Cancer 12/2001; 94(4):558-63. · 5.44 Impact Factor
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ABSTRACT: We studied the long-term effects of adenomectomy on serum levels of prostate specific antigen (PSA) in men with benign prostatic hyperplasia (BPH).
A consecutive series of 82 men undergoing adenomectomy for BPH between 1990 and 1992 was studied. PSA levels were determined before and serially after operation for as long as 5 years.
Mean PSA decreased from 4.6 ng/ml. preoperatively to 0.7 ng./ml. 6 months postoperatively. These low levels were maintained throughout the 5-year observation period. The PSA decrease correlated with grams of tissue removed (r = 0.54, p < 0.001) and averaged 0.11 ng./ml./gm. Postoperatively mean PSA velocity was 0.01 ng./ml. per year, that is essentially flat, and it was not influenced by patient age, race, type of operation, grams of tissue removed, baseline PSA, PSA density of T1a lesions (7). One to 5 years after adenomectomy 6 of the 82 men had invasive prostatic carcinoma, and PSA levels and velocities remained low.
These data support the concept of transition zone primacy in determining serum PSA. Furthermore, they suggest a possible need for a modified reference range when using PSA to screen for prostatic carcinoma in the estimated 3 million men alive in the United States who previously underwent adenomectomy for BPH.
The Journal of Urology 10/1996; 156(3):1035-9. · 3.75 Impact Factor
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ABSTRACT: Rapid detection of antibody binding to glycolipid is achieved using an enzymatically labeled probe followed by blotting substrate onto the high-performance thin-layer chromatogram.
BioTechniques 11/1990; 9(4):394, 396. · 2.67 Impact Factor
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ABSTRACT: Ascitic fluids from patients with various types of cancer were screened for the CA 19-9 and CA 125 tumor-associated antigenic activities. Two fluids exhibiting the highest activities were tested for their binding to various lectin-Sepharose columns resulting in both being bound best to wheat germ agglutinin (WGA) Sepharose. The WGA column eluate of one fluid was further chromatographed by HPLC and three peaks were obtained with approximate molecular weights of 3.65 MDa, 664 kDa and 330 kDa, of which only the largest fraction contained the CA 19-9 activity. The fluids were also fractionated on a Sephacryl S-400 column with most of the activity being present in or near the void volume. Monoclonal antibodies were used to demonstrate that the purified glycoproteins also contained the blood group A determinant, the four Lewis determinants Le(a), Le(b), Le(x) and Le(y), and the sialylated-Le(x) determinant, while other antibody analyses failed to detect other blood group and/or carbohydrate sequence determinants. Some of the blood group expressions could be separated from the CA 19-9 and CA 125 active glycoproteins by adsorption with various lectins other than the WGA.
Glycoconjugate Journal 02/1989; 6(4):511-24. · 2.12 Impact Factor
