Cancer acid phosphatase activity

Of 13 patients with clinical extension of the cancer beyond the prostatic capsule, seven who were receiving antiandrogens and had undergone bilateral orchiectomy showed normal bone marrow and serum acid phosphatase activities. Of the remaining six patients, one had slightly elevated bone marrow acid phosphatase activity and a normal serum acid phosphatase activity. In the other five patients, both the marrow and the serum acid phosphatase values were elevated, but the former were higher. Of 13 patients who had osteoblastic changes in the skeletal system, increased acid phosphatase values were obtained in both bone marrow and serum in 10 cases, but the values in the bone marrow... 

As was previously noted (Section 6.2), the total and prostatic serum acid phosphatase levels were determined by the method of Fishman and Lerner (FI) in a series of 365 males attending a cancer-prevention clinic (D6). The values for the total acid phosphatase activities in the 315 patients of this group who had no prostatic enlargement have already been described (Table 6). In groups of the size under consideration, values within 2.5 standard deviations of the mean can be considered as normal ... 

In 1956, Fishman et al. (F2) summed up their experience with a series of 91 cases of proven cancer of the prostate and a total of 1198 patients with other diseases. Of these 91 cases, 32, or 35%, had elevated total serum acid phosphatase activities. This incidence was much lower than that, 85%, reported by Sullivan et al. (S30) in 1942 or the value of 89% reported by Herbert (H5) in 1946 for patients with carcinoma of the prostate and skeletal metastases. These investigators had used the method of Gutman and Gutman (GIO, G14), which was essentially the same method as that employed by Fishman and Lerner (FI) and gave the same ranges of normal values (Table 6). The possibility existed that treated cases had normal total serum phosphatase activities and thus weighted the overall incidence toward a low value. However, the data of Fishman et al. (F2) show that the incidence of total serum acid phosphatase activities in treated cases was 20/52, or 38%, even higher than the incidence 12/39, or 31%, in the untreated cases. 

Table 10 shows the distribution of serum acid phosphatase activities in neoplastic disease other than prostatic cancer. The incidences of elevations were 19% in patients with skeletal metastases 2% in pa-... 

Using the Bodansky (B18, 52) procedure with 8-glycerophosphate as substrate, Woodard (W8) was unable to obtain such elevations. She determined the serum acid phosphatase activities in 83 females and 342 males, or a total of 425 patients with miscellaneous diseases. Of these, 61 had various types of infectious or metabolic disorders, including 11 cases of inflammatory disease of bone and 12 cases of hepatic cirrhosis. The remainder had some type of neoplastic disease and about one-third had metastases to bone from cancer of various primary sites. There were 15 cases of osteogenic sarcoma and 32 cases of osteitis deformans. All these cases, whether their serum alkaline phosphatase activities were elevated or not, had serum acid phosphatase values that were essentially within the normal range, 0.06-0.89 Bodansky unit for females and 0.11-0.88 unit for males. In contrast to the Gutman method (GIO, G14), there-... 

G12. Gutman, A. B., Gutman, E. B., and Robinson, J. N., Determination of serum acid phosphatase activity in differentiating skeletal metastases secondary to prostatic carcinoma from Paget s disease of bone. Amer. J. Cancer 38, 103-108 (1940). 

Lin ME, DaVolio J, Garcia-Arenas R (1992) Expression of human prostatic acid phosphatase activity and the growth of prostate carcinoma cells. Cancer Res 52 4600-4607... 

Sobin LH, Hjermstad BM, Sesterhenn lA, Helwig EB. Prostatic acid phosphatase activity in carcinoid tumors. Cancer. 1986 58 136. 

Red blood cells also contain sufficient acid phenylphospha-tase for mild hemolysis to cause false elevations. Therefore, inhibitors such as ethanol, formaldehyde, copper sulfate> and 1-tartrate have been used to inhibit selectively the enzyme of one or more tissues and enhance the specificity of the test (101). Ethanol is unsuitable because it inhibits the enzyme from erythrocytes and prostate simultaneously, and because it yields serum activities which correlate poorly with prostatic disease. Formaldehyde inhibits the erythrocytic enzyme and has been said to yield clinically satisfactory results. The copoper resistant acid phosphatase of serum is elevated by metastatic carcinoma of the breast, as well as by other metastatic cancers, and is also elevated by a wide variety of non-cancerous diseases. 

Babson proposed a-naphthyl phosphate as an essentially specific substrate for the activity of prostatic acid phosphatase in serum (104). However Marshall, Price, and Amador found that this substrate is not specific for the prostatic enzyme because urine of human females contain 50 times more acid a-naphthyl phosphatase than male serum and 50% as much activity as male urine. Platelets have significant activity and the serum activity can increase to abnormal values following clotting. These workers also observed elevated activities in females with skeletal metastases of the breast. In 50 hospitalized male patients who had no evidence of prostatic cancer and 25 hospitalized female patients, the incidence of false positive results was 12%, a magnitude sufficient to preclude meaningful clinical interpretation (105). 

Provenge is a cancer vaccine using cell therapy technique. Dendritic cells are removed from patients. These cells are treated with the prostate-specific antigen prostatic acid phosphatase (PAP), which is present in 95% of prostate cancer cases. The activated dendritic cells are returned to the patients and they stimulate the T cells to destroy cancer cells expressing the PAP, thus treating the tumor. 

Acid phosphatase retains its activity for a long period and hence is useful in forensic science to detect semen but has now been superseded by DNA fingerprinting. The activity in blood was used in the diagnosis of prostatic cancer but was superseded by PSA (prostate specific antigen). 

Acid phosphatases are produced by erythrocytes, the liver, kidney, spleen, and prostate gland. The enzyme of the prostate gland is clinically important, because its increased activity in the blood can be an indication of prostate cancer. The phosphatase from the prostate gland is strongly inhibited by tartrate ion, but acid phosphatases from other tissues are not. How can this information be used to develop a specific procedure for measuring the activity of the acid phosphatase of the prostate gland in human blood serum ... 

Fig. 12.4 HT-29 colon cancer cells response to BA, AN-7, and AN-9. Amperometiic response curves for monitoring of alkaline phosphatase activity using the electrochemical array chip. The HT-29 colon cancer cells were exposed to the differentiation agents Butyric acid (2.5 mM), AN-7 and AN-9 (50 pM). The HT-29 cells with the substrate PAPP were placed into the 100 nL volume electrochemical chambers on the chip. Current was measured using the amperometric technique at 220 mV...

A transient, moderate, and reversible rise in leukocyte alkaline phosphatase, lactate dehydrogenase (LDH) and serum uric acid concentrations is usually observed in cancer patients receiving supportive treatment with GM-CSF or G-CSF. Serum LDH increased from 37 to 85% and there was a linear relation between increased leukocyte production and the rise in serum LDH (32). Increases in serum LDH activity should therefore not be interpreted as indicative of disease progression, unless LDH activity remains high after growth factor withdrawal. 

Microcystins have caused the poisoning of wild and domestic animals worldwide, and in 1996, they caused the death of 76 people in Caruaru, Brazil, which was attributed to the use of microcystin-contaminated hemodialysis water. Microcystins, like the well-documented tumor promoter, okadaic acid, strongly and specifically inhibit the protein phosphatases 1 and 2A and have a tumor-promoting activity in the rat liver. In addition to acute hepatotoxicity, microcystins pose problems to human health—which could result from low-level, chronic exposure to microcystins in drinking water, as suggested by the high incidence of primary liver cancer in the... 

There has long been the belief that DES may have a direct local action on the prostatic cancer, and it has been claimed [40] that orchidectomy and DES was clinically more effective than either form of therapy alone. The rationale behind the use of fosfestrol (DES 4,4 -diphosphoric acid ester, Honvan, (2)) in large doses (200 mg daily) is that the free and locally active form of the drug DES would be released within the tissue by the high concentrations of phosphatases present in prostatic cells. There is little evidence that fosfestrol accumulates in the prostate or that DES is released in reasonable concentrations [41]. Such evidence, however, still does not preclude the possibility that DES has a cytotoxic action in the prostatic cell and studies continue to attempt to identify this effect. 

Microcystins are also potent tumor promoters that are mediated through the inhibition of the protein phosphatase type 1 and 2A activities. Their mode of action appears to be different from that of other protein phosphatase inhibitors, such as okadaic acid for, example [93], and their effects are organ specific [70,94,95], The incidence of primary liver cancer in China, where people drink pond and ditch water, is about eight times higher than in populations that drink well water [25], and MCs were found in areas were cancer incidence was high [26],... 

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