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T M Chu

Publications and source records attributed to T M Chu.

At least 55 records · Page 3Linked to original sources
PubMed1990

Comparison of prostate acid phosphatase with acid phosphatase isoenzymes from the lung and spleen.

Acid phosphatase was purified to electrophoretic homogeneity from human normal lung and spleen and was characterized biochemically and immunologically in comparison with prostate acid phosphatase (PAP). The apparent MW of lung acid phosphatase (LAP) and spleen acid phosphatase (SAP) was 110,000 and 100,000, respectively, similar to that of PAP (100,000). All three enzymes exhibited similar electrophoretic mobility, optimal pH, substrate, and inhibitor specificity, except that PAP dephosphorylated profoundly the phosphate group from tyrosine phosphate in phosphoangiotensin (19,700 fmol/mg/min), whereas only marginal activities were detected for LAP and SAP (19 and 73 fmol/mg/min, respectively). Amino acid analysis revealed more similarity between SAP and LAP than PAP and LAP or PAP and SAP. An immunological cross-reactivity among these three acid phosphatases was detected by polyclonal and monoclonal antibodies raised against purified PAP, although unique epitopes were detected on the PAP molecule. This study provides data explaining why conventional biochemical methods are not specific for PAP measurement and why immunologic methods still detect other acid phosphatases, as observed in clinical laboratory assays. The data also suggest the possibility of using a new substrate or antibody reagent for a more specific assay for PAP.

Acid Phosphatase↗
PubMed1990

Prostate-specific antigen: questions often asked.

In conclusion, an effective new marker for prostatic tissue has been identified and is commonly known as PSA. A review of the literature indicates that although PSA is not tumor specific, its organ-site and cell-type specificity provide the basis for making PSA the marker of choice for use in patients with prostate cancer. The clinical utility of PSA includes monitoring therapeutic efficacy, screening and early diagnosis in high-risk patients, prognosis, staging, and tumor volume evaluation, prediction of disease progression, detection of recurrent disease after radical prostatectomy, and the differential diagnosis and confirmation of tissue for prostatic origin. PSA is not a "magic bullet" for patients with prostate cancer. Many questions must still be answered. For example, with an increase in sensitivity for screening of high-risk populations, how does the urologist/oncologist determine which patients with latent curable early cancer will develop into clinically significant metastasis? Is PSA a more reliable method for detection of early prostate cancer than rectal examination? What procedure should be followed for an asymptomatic patient who presents a 35 ng/ml level of PSA during a routine physical examination? Clearly, further studies are required to answer these questions as well as to assess the malignant potential of the prostatic tumor cell. For now, the combination of PSA, rectal examination, and transrectal ultrasonography guided needle biopsy would appear to be the method of choice to decrease the yearly fatalities due to cancer of the prostate.

Antigens, Neoplasm↗
PubMed1990

Prostate cancer-associated markers.

Immunodiagnosis of prostate cancer is at a more advanced stage than that of most other tumors. Two well-known markers, prostatic acid phosphatase and prostate-specific antigen, have been used in the clinical management of patients. Prostate-specific antigen is a more sensitive and reliable marker than prostatic acid phosphatase. Serum prostate-specific antigen is effective in monitoring disease status, predicting recurrence, and detecting residual disease. Prostate-specific antigen is a tool for the histological differential diagnosis of metastatic carcinomas, especially in the identification of metastatic prostate tumor cells in distant organs and in the differentiation of primary prostate carcinoma from poorly differentiated transitional cell carcinoma of the bladder. Few data on biological function are available. Prostatic acid phosphatase functions as a phosphotyrosyl-protein phosphatase and prostate-specific antigen as a protease. Physiological function in the prostate remains to be elucidated. Several of the prostate-specific and prostate-tumor-associated antigens, as well as a putative prostate tumor-specific antigen, as recognized by monoclonal antibodies are available. Clinical evaluation of these potential markers is not yet available.

Acid Phosphatase↗
PubMed1990

The in vivo distribution of murine lymphokine activated killer cells in splenectomized host.

The in vivo distribution of intravenously injected lymphokine activated killer (LAK) cells, generated in vitro with rIL-2 from normal murine splenocytes, was studied in BALB/c mice and compared with that of normal splenocytes. Both normal splenocytes and LAK cells were labeled with 51Cr, and the results were analyzed at 6, 24, and 48 hours after injection by localization index as the parameter. After injection through tail veins of mice, LAK cells were found to migrate to the spleen, lungs, liver, lymph nodes, bones and the kidneys. The apparent increased distribution pattern of LAK cells to the lung at 6 and 24 hours after injection was not detected when normal splenocytes were injected. Since almost one third of the injected LAK cells were found to localize in the spleen, it was postulated that splenectomy would affect the in vivo organ distribution of LAK cells. Accordingly, the in vivo distribution of LAK cells in splenectomized mice was further investigated. Results indicated that splenectomy enhanced the convergence of LAK cells to the lungs, liver, lymph nodes and bones. Therefore, splenectomy may augment the therapeutic effect of the adoptive transfer of LAK cells in pulmonary, hepatic, lymph node and bony metastases.

Animals↗
PubMed1990

Indirect inhibition of generation of murine lymphokine-activated killer cell activity in splenocyte cultures by interferon-gamma.

The effect of mouse recombinant interferon-gamma (rIFN-gamma) on murine lymphokine-activated killer (LAK) cell activity was investigated using natural killer (NK)-resistant, spontaneously developed, weakly immunogenic and highly tumourigenic, syngeneic murine mammary adenocarcinoma, JC, mimicking that of human disease, as the target. Murine YAC-1 also was used as a target cell line. rIFN-gamma, when used in combination with recombinant interleukin-2 (rIL-2), was shown to exhibit a suppressed effect on LAK cell activity generated from BALB/c mouse splenocytes, compared to that with rIL-2 alone. The decrease in LAK cell activity was rIFN-gamma dose-dependent. Kinetic study revealed that this inhibitory effect was demonstrated only when rIFN-gamma was added to the medium at the early phase of rIL-2 culture. The inhibitory effect on LAK cell generation by rIFN-gamma was completely abrogated when the nylon-wool-treated non-adherent 'macrophage-free' splenocytes were incubated with rIL-2 and rIFN-gamma. These results indicated that the LAK cell activity generated from murine splenocytes cultured with rIL-2 could be depressed by rIFN-gamma, and that the macrophages may be involved as mediators.

Animals↗
PubMed1990

Prostaglandin E2-mediated suppression of murine lymphokine-activated killer cell activity generated from tumor-bearing hosts by interferon-gamma.

The effect of mouse recombinant interferon-gamma (IFN-gamma) on murine lymphokine-activated killer (LAK) cell activity was investigated using a natural killer-resistant, LAK-sensitive, spontaneously developed, weakly immunogenic, syngeneic murine mammary adenocarcinoma, a tumor model mimicking that of human disease. When all of the splenocytes prepared from tumor-bearing mice were cultured with recombinant interleukin-2 (IL-2) and IFN-gamma, LAK cell activity was suppressed in an IFN-gamma dose-dependent manner. An increase in the prostaglandin E2 (PGE2) content in the corresponding culture media was detected, as was IFN-gamma dose dependent. The suppression of generation of LAK cell activity by IFN-gamma was abrogated, accompanied by the elimination of the increase in PGE2 content, when plastic dish and nylon wool-treated nonadherent macrophage-depleted splenocytes were used. These results indicated that IL-2-induced LAK cell activity generated from the splenocytes of tumor-bearing mice was suppressed by IFN-gamma, and that PGE2 secreted from the macrophages of the splenocyte cultures served as the mediator in this IFN-gamma dose-dependent suppression of IL-2-induced LAK cell activity.

Adenocarcinoma↗
PubMed1989

Serum level of cryptic tumor antigens in breast cancer patients as determined by two monoclonal antibodies (M85/F36) and its comparison with CA 15-3.

An enzyme immunoassay system that measures cryptic epitopes on breast cancer mucinlike antigens (BCM-EIA) was evaluated in a double-blind manner in sera from 58 normal blood donors, 36 sex- and age-matched controls, 36 patients with benign breast diseases, and 47 patients with breast cancer. Two murine monoclonal antibodies, M85 (IgM) as the solid-phase and F36/22 (IgG3) as the probe, were used in the configuration of the assay kit. The assay additionally utilized neuraminidase to remove terminal sialic acid from carbohydrate side-chains to expose cryptic epitopes that were masked in serum specimens. BCM-EIA monoclonal assay from the normal healthy blood donors resulted in 17.34 +/- 7.04 units/ml (mean +/- 1 S.D.) with an upper normal cutoff of 31.4 units/ml. The distributions of serum BCM in the sex- and age-matched controls (17.77 +/- 11.17) and benign breast diseases (14.34 +/- 11.46) were similar to that of normal blood donors. A mean value of 66.04 units/ml and 27.74 units/ml was obtained from breast cancer patients with active disease and without evidence of disease, respectively, a level much greater than those of normals, controls, and benign breast diseases. Simultaneous analysis of CA 15-3, a putative breast tumor marker, in the normal donors and breast cancer patients revealed correlation regression of (CA 15-3) = 0.876 (BCM) + 1.972, r = 0.856; and (CA 15-3) = 0.66 (BCM) + 16.094, r = 0.730, respectively. These data showed that there is a statistically significant correlation of CA 15-3 and BCM in normal blood donors' specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1989

Effect of indomethacin on tumor-infiltrating lymphocytes of a spontaneously developed murine mammary adenocarcinoma.

The effect of indomethacin on tumor-infiltrating lymphocytes (TIL) was investigated in a spontaneously developed and weakly immunogenic murine mammary adenocarcinoma (designated JC) in syngeneic immunocompetent BALB/c mice, a tumor model mimicking human disease. Unlike other chemically and virally induced tumors, the expansion of TIL was only possible with an enriched population of lymphocytes, isolated on a discontinuous density gradient then cultured in complete medium containing recombinant human interleukin-2 (rIL-2). The freshly isolated TIL exhibited no cytotoxicity against either the natural-killer-sensitive YAC-1 or the natural-killer-resistant JC cells lines. After culture in rIL-2, the TIL of the JC tumor lysed both YAC-1 and JC. The cytotoxicity of the TIL reached a maximum between the 2nd and 3rd week of culture and decreased thereafter. Antibody- and complement-depletion tests revealed that the cells bearing asialo-GM1 antigen represented the major precursor cells of the cytotoxic TIL, which may explain its nonspecific cytotoxicity. Indomethacin was shown to accelerate the cell proliferation of the rIL-2-activated TIL, but only in the initial 2 weeks of culture and not in later culture. The addition of indomethacin to the rIL-2-containing medium at the beginning of culture resulted in a fast-acting and long-lasting enhancement in cytotoxicity. These results provided a basis for the clinical use of indomethacin, i.e. acceleration in proliferation and augmentation in cytotoxicity. However, the addition of indomethacin at the end of the fourth week after rIL-2 culturing produced neither accelerated proliferation nor augmented cytotoxicity. This study also suggested that a prolonged administration of indomethacin may not be advantageous in clinical trials, since the long-term continuous presence of indomethacin in the culture has resulted in a negative effect on the growth of TIL.

Adenocarcinoma↗
PubMed1989

Characterization of a new spontaneously developed murine mammary adenocarcinoma in syngeneic BALB/c hosts.

A mouse mammary tumor cell line, designated JC, has been established from a spontaneously developed primary adenocarcinoma of an aged virgin female BALB/c mouse. Isoenzyme analyses including glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and peptidase proved that this cell line is of murine origin and devoid of contamination from other species. Karyotyping revealed that the number of chromosome ranged from 26 to 100, with a modal number of 40. Electron microscopic examination detected the presence of tonofilament and desmosomes confirming its epithelial nature. In addition, no type B or C virus particle was detected, although intracysternal A particle was observed occasionally. Tumorigenicity in immunocompetent syngeneic hosts was easily established by s.c., i.p., and i.v. injection of viable JC tumor cells. A very weak immunogenicity of the JC tumor was demonstrated through its immunization-challenging on syngeneic immunocompetent hosts. Although no rejection of JC tumor was noted, a significant prolongation for the incubation period before an obvious and palpable tumor growth was detected between the experimental and the control animals. Development of a concomitant immunity was also detected. The JC tumor represents a valuable murine mammary tumor model which is different from other available models because of its unique origin, absence of virus particles, very weak immunogenicity, and high tumorigenicity in syngeneic hosts. The cell line has been maintained for more than 5 yr and has been used for experimental immunotherapy in our laboratory.

Adenocarcinoma↗
PubMed1989

Prostate-specific antigenic domain of human prostate specific antigen identified with monoclonal antibodies.

With the use of five murine monoclonal antibodies (1A5, 2A4, 3F1, F5 and 3A12) and an antigen-affinity purified goat polyclonal IgG antibody, the presence of a prostate-specific antigenic domain in human prostate-specific antigen molecule was identified. The results were based upon a series of quantitative competitive inhibition assays of each 125I-labeled monoclonal antibody and polyclonal antibody binding to prostate-specific antigen by unlabeled monoclonal antibodies as inhibitors, and immunohistochemical examination of an extensive panel of human tissue specimens. A cluster of two epitopes that are spatially related or in close topographical proximity and represent a prostate-specific antigenic domain are defined by the monoclonal antibodies 1A5, 2A4, 3F1, and F5, 3A12, respectively.

Animals↗
PubMed1989

Role of the kidney in metabolic change of interleukin-2.

The metabolic change of human recombinant interleukin-2 (IL-2) was investigated by the use of 125I-labeled IL-2 (125I-IL-2). After intravenous injection into mice, the distribution of 125I-IL-2 in various organs revealed that the major portion of injected 125I-IL-2 was rapidly accumulated in the kidney. Simultaneous injection of an excess amount of cold IL-2 greatly reduced the distribution of 125I-IL-2 to the kidney, suggesting that the accumulation of 125I-IL-2 by the kidney was a specific reactivity between 125I-IL-2 and the kidney. The gel filtration profile of 125I-IL-2 in the serum specimens remained the same as that of the originally injected sample, and differed completely from that in the urine specimens, suggesting that 125I-IL-2 was metabolized in the kidney. To confirm this notion, 125I-IL-2 was incubated in vitro with kidney homogenate, which degraded 125I-IL-2 in acidic pH. After subcellular fractionation, the cytosol fraction of the kidney was shown to hydrolyze 125I-IL-2 with an optimal pH of 4. The reactivity of the kidney cytosol fraction with 125I-IL-2 was inhibitable by pepstatin, an acid protease inhibitor, but not by TLCK or TPCK. Additional experiments using a heat-treated kidney cytosol fraction plus cathepsin D, and pepstatin inhibition on the degradation of 125I-IL-2 by cathepsin D, a major acid protease in the kidney, resulted in the identification of this enzyme to be responsible for the degradation of 125I-IL-2. Overall, these results demonstrated that the kidney is the organ to metabolize IL-2 and that cathepsin D, a renal acid protease, is involved in the degradation of IL-2.

Animals↗
PubMed1989

Augmentation of murine lymphokine (rIL-2)-activated killer cell activity by indomethacin.

The effect of indomethacin on murine lymphokine-activated killer (LAK) cell activity was investigated using a natural killer-resistant, spontaneously developed, weakly immunogenic, and highly tumorigenic syngeneic murine mammary adenocarcinoma, mimicking that of human disease, as the target. When used in combination with human recombinant interleukin-2 (rIL-2), indomethacin was found to augment LAK cell activity, which was generated from culture of the normal mouse splenocytes with rIL-2, as compared to that with rIL-2 alone. This increase in LAK cell activity was shown to be indomethacin dose-dependent, and was demonstrated only when indomethacin was added to the rIL-2-containing medium at the beginning of culture. The enhancement of LAK cell activity by indomethacin was abrogated when the nylon-wool nonadherent "macrophage-poor" splenocytes were incubated with rIL-2 plus indomethacin. These results indicated that the rIL-2-induced LAK cell activity generated from murine splenocytes could be augmented by indomethacin, and the macrophages may be involved as the mediator.

Animals↗
PubMed1988

Serum alpha 1-acid glycoprotein in epithelial ovarian cancer.

Fifty-six patients with ovarian adenocarcinoma receiving chemotherapy were monitored with serum alpha 1-acid glycoprotein (AGP) levels. The mean and standard deviation of serum AGP levels for 63 healthy controls were 0.88 +/- 0.469 mg/ml. A serum level above 1.80 mg/ml was considered as above normal level. Five patients had evidence of persistent ovarian carcinoma and had elevated AGP levels. Sixteen patients had normal serum AGP levels and had no evidence of persistent ovarian cancer at second-look laparotomy. However, 35 patients had false-negative AGP levels at the time they had persistent tumor. Although the specificity of the AGP level was 100%, the sensitivity was only 12.5% and the overall accuracy 37%. Therefore, it would appear that serum AGP levels are not of value in monitoring patients with ovarian adenocarcinoma.

Adenocarcinoma↗
PubMed1988

Antitumor activity of doxorubicin-monoclonal antibody conjugate on human bladder cancer.

Doxorubicin (adriamycin) was conjugated via the dextran bridge method to a murine IgG3 monoclonal antibody, 1G3.10, directed against human bladder cancer. The drug-antibody conjugate, prepared from using 25% oxidized dextran as the linker, retained essentially the original immunological activity of the antibody using ELISA as tested against an antigen-positive target cell line (TSGH-8301), which has been shown to express an antigen recognized by the monoclonal antibody 1G3.10. Antitumor effect of the conjugate in vitro was evaluated by its inhibition on 3H-uridine incorporation into the established human bladder cancer cells. The conjugate exhibited a significantly higher cytotoxicity on target TSGH-8301 cells than that by a control antibody-doxorubicin conjugate prepared identically from an irrelevant mouse IgG3 monoclonal antibody. No apparently different cytotoxicity was detected on control antigen-negative bladder tumor cells of J82 between these two drug-antibody conjugates. Verapamil, a calcium channel blocker, enhanced the in vitro cytotoxicity of doxorubicin-1G3.10 monoclonal antibody conjugate. Results obtained from in vivo evaluation using xenografted target TSGH-8301 bladder tumor indicated that the 1G3.10 monoclonal antibody conjugate containing doxorubicin injected 4X, i.p., significantly inhibited TSGH-8301 bladder tumor growth in nude mice, whereas free monoclonal antibody, free drug and the mixture of both showed only moderate inhibition of tumor growth as compared to the untreated control. Verapamil also enhanced in vivo antitumor activity of the conjugate. There was no side effect (weight loss) detected on the conjugate-treated mice. Results obtained from in vivo evaluation using xenografted control J82 bladder tumor showed no specific antitumor activity as exhibited by doxorubicin-1G3.10 monoclonal antibody conjugate in comparison with free drug, mixture of drug and antibody without conjugation, or doxorubicin conjugated to the irrelevant antibody. These results suggested that doxorubicin conjugated with bladder tumor associated monoclonal antibody could be useful as a potentially cytotoxic agent in immunochemotherapy of human bladder cancer.

Animals↗
PubMed1987

Immunotherapy in a spontaneously developed murine mammary carcinoma with syngeneic monoclonal antibody.

A new spontaneously arisen murine breast tumor, designated JC, has been established in immunocompetent BALB/c mice. Upon reestablishment of tumor in vitro and in vivo, the epithelial murine tumor cells retained their original papillary adenocarcinoma morphology. Various immunotherapy protocols have been performed in previously implanted and progressively growing JC tumor in syngeneic hosts with a murine monoclonal antibody (McAb), F36/22 (IgG3). Affinity of McAb binding to JC tumor cells was determined to be 6.1 x 10(7) L/M. Quantitatively 1.2 x 10(5) molecules of McAb bound to a JC tumor cell. Immunotherapeutic effectiveness in vivo on a tumor mass after its establishment is a major feature of this experimental tumor model. When four sequential administration of McAb, i.p., at a dose of 400 micrograms 4 days apart were used, McAb-treated animals showed statistically significant tumor regression and longer survival than those of control animals treated with an irrelevant McAb of the same isotype. Two temporal phases of tumoricidal activity were observed as measured by tumor volume reduction. The first phase of tumoricidal response (tumor regression) was detected within days upon the first administration of McAb. A distinct second phase followed within 3-5 weeks after the last McAb administration, which resulted in tumor necrosis even in large tumors. Histological examinations revealed heavy infiltration of inflammatory cells at the beginning of the second phase. Similar tumor regression was also obtained from animals treated with a single dose (400 micrograms) of McAb followed by injections of McAb with complete and incomplete adjuvant, respectively. These results demonstrate that this syngeneic murine mammary tumor can serve as a potential preclinical model for investigation of parameters and mechanisms associated with McAb immunotherapy.

Adenocarcinoma, Papillary↗
PubMed1987

Potential therapeutic effect of adriamycin-monoclonal anti-prostatic acid phosphatase antibody conjugate on human prostate tumor.

Adriamycin was conjugated to an IgG1 monoclonal antibody specific for human prostatic acid phosphatase via a dextran bridge. The adriamycin-monoclonal antibody conjugate retained substantially the original immunological activity of the antibody. Antitumor effect of the conjugate in vitro was studied by its inhibition on RNA synthesis in human prostate tumor cells (LNCaP), which exhibited a higher inhibition than that by an identically prepared adriamycin-normal mouse IgG conjugate but was less than that by free adriamycin. The loss in pharmacological activity of the conjugate in vitro was proportional to the extent of dextran oxidation. Antitumor effect in vivo demonstrated that adriamycin-monoclonal antibody conjugate greatly inhibited the growth of xenografted prostate tumor, as compared with control groups, only in the early phase of experiment. These results suggested that although adriamycin conjugated to monoclonal anti-PAP antibody via a dextran bridge may be a potential reagent for experimental immunochemotherapy of prostate tumor, caution must be exercised at this stage of development.

Acid Phosphatase↗
PubMed1986

Human monoclonal antibody recognizing liver-type aldolase B.

A human hybridoma clone (4E3) has been established by fusing lymphocytes from a lymph node taken from a breast cancer patient and human lymphoblastoid cells, LICR-LON-HMy2, by the poly(ethylene glycol) method. 4E3 has been stabilized and continued to secrete IgMk antibody into culture medium (greater than 10 micrograms/ml) for over 1 year. The following characteristics of the antigen strongly suggested that 4E3 recognizes liver-type aldolase B (EC 4.1.2.13): the Mr of the native molecule is 160,000 and that of the subunit is 40,000, and thus it has a tetrameric structure of identical subunits; the antigen is abundant in the liver and kidney of human, mouse and rabbit, and is localized by immunohistochemical methods in the cytoplasm of hepatocytes and in the proximal tubules of the kidney; the antigen is precipitable by 50-80% saturation with (NH4)2SO4; the antigen shows charge-dependent heterogeneity on DEAE-cellulose chromatography. To confirm this notion, aldolase B was purified to homogeneity from the liver of human, mouse and rabbit by phosphocellulose chromatography. During the chromatographic purification, the antigen activity as assayed by enzyme-linked immunosorbent assay (e.l.i.s.a.) was superimposed on the enzymic activity of aldolase. Furthermore, monoclonal antibody 4E3 strongly reacted with purified aldolase B in SDS/polyacrylamide-gel electrophoresis followed by Western blotting and also in e.l.i.s.a. using microplates coated with purified enzyme. The reaction between aldolase B and 4E3 activated the human complement system as assessed by the attachment of C3 to the immune complex of aldolase B and 4E3.

Animals↗