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Biomedical subjects

T Wu

Publications and source records attributed to T Wu.

At least 253 records · Page 14Linked to original sources
PubMed1986

Frequency and partial characterization of adenylate cyclase-stimulating activity in tumors associated with humoral hypercalcemia of malignancy.

Parathyroid hormone-like adenylate cyclase-stimulating activity (ACSA) has previously been identified in small numbers of tumors or tumor-conditioned tissue culture medium derived from patients or animals with humoral hypercalcemia of malignancy (HHM). We examined the frequency with which this ACSA occurred in a large group of tumor extracts derived from patients with HHM (n = 20), and compared this to three control groups: normocalcemia-associated tumors (n = 20), hypercalcemic control tumors (n = 7), and normal, nonmalignant tissue samples (n = 10). Eighteen of 20 HHM-associated tumor extracts displayed ACSA whereas only 4 of 37 controls contained detectable ACSA. ACSA in one tumor was partially purified, using sequential extraction steps and reverse-phase, high-performance liquid chromatography. Highly purified ACSA (4800-fold) also contained potent in vitro bone-resorbing activity. The molecular weight as assessed by gel filtration was approximately 40,000 D. These findings provide strong support for the thesis that the humoral factor which is responsible for the syndrome of HHM is a parathyroid hormone-like adenylate cyclase-stimulating protein.

Animals↗
PubMed1986

Oncogene-induced transformation of a rat embryo fibroblast cell line is enhanced by tumor promoters.

Rat embryo fibroblast cell line 6 was transfected with plasmid pT24, which contains the activated human bladder c-Ha-ras oncogene, and the cells were grown continuously in the absence or presence of the tumor promoters 12-O-tetradecanoyl phorbol-13-acetate (TPA) or teleocidin. The presence of TPA or teleocidin led to a 6- to 14-fold increase in the number of morphologically transformed foci. No transformed foci were seen when rat 6 cells were transfected with the normal c-Ha-ras oncogene in the absence or presence of TPA, or in cells simply treated with TPA or teleocidin. Enhancement of pT24-induced foci was seen even when the addition of TPA was delayed until day 16. In transfection studies with the drug resistance genes gpt and neo, TPA and teleocidin did not increase the number of Gpt+ or Neo+ colonies. When rat 6 cells were cotransfected with pT24 and neo genes and grown in the absence or presence of TPA, the presence of TPA did not increase the yield of Neo+ colonies but caused a fivefold increase in the number of Neo+ colonies that displayed a transformed morphology. Southern blot analyses of DNAs obtained from these clones indicated that TPA treatment did not influence the extent of integration of either the pT24 or neo gene. DNA samples from all of the morphologically transformed cells displayed a characteristic 2-kilobase SacI fragment homologous to pT24 DNA and expressed relatively high levels of the corresponding mRNA. Our findings indicate that in this system tumor promoters do not simply enhanced the process of DNA transfection per se. Thus, this model system may be useful for analyzing synergistic interactions between tumor promoters and activated oncogenes during multistage carcinogenesis. It may also serve as a simple screening test for detecting new tumor promoters.

Animals↗
PubMed1983

Monoclonal versus polyclonal antibody radioimmunoassay against the beta-subunit of human chorionic gonadotropin in patients with gestational trophoblastic neoplasia.

The level of human chorionic gonadotropin (hCG) in series of sera from eight patients with gestational trophoblastic neoplasia was measured by monoclonal antibody and polyclonal antibody radioimmunoassay. A comparative analysis was performed. Three commercially available monoclonal anti-beta-subunit of hCG (beta-hCG) antibodies were evaluated and the most specific and sensitive one was chosen to develop a quantitative beta-hCG radioimmunoassay. beta-hCG radioimmunoassay kits from Nuclear Medical Systems, Inc., and Clinical Assays served as polyclonal antibody assays. Results obtained with the monoclonal antibody radioimmunoassays demonstrated a high degree of correlation (r greater than 0.95, p less than 0.01) with those obtained by the polyclonal antibody techniques; however, the sera from one patient continuously demonstrated a low level of hCG in the monoclonal antibody radioimmunoassay while registering undetectable levels in the polyclonal antibody assays. Although the monoclonal antibody radioimmunoassay appears to be specific and fairly sensitive, the results indicate that, with current technology, there is no special advantage to employing this assay to measure hCG in patients with gestational trophoblastic neoplasia.

Antibodies↗
PubMed1983

Cytotoxic activity of 5'-deoxy-5-fluorouridine in cultured human tumors.

The cytotoxic activity of 5'-deoxy-5-fluorouridine (5'-ddFUrd) was established in six cultured human tumor lines: 47-DN and MCF-7 breast carcinomas, MG-63 osteosarcoma, HCT-8 colon carcinoma, Colo-357 pancreatic carcinoma, and HL-60 promyelocytic leukemia. Cells were exposed to a wide range of 5'-dFUrd concentrations (from 0.1 microM to 1.0 mM) for 3, 6, or 24 hrs, and then cloned using standard in vitro clonogenic assays. 5'-dFUrd exhibited its best activity in the 47-DN and MCF-7 breast cell lines and in the MG-63 osteosarcoma line (3-hr LD50 values of 32, 34, and 38 microM, respectively). Less activity was observed in the HCT-8 colon (LD50 = 195 microM) and Colo-357 pancreatic (LD50 = 155 microM) tumor lines, and ver poor activity was noted in the HL-60 leukemia cell line (LD50 = 465 microM). The metabolism of 5'-dFUrd to 5-FU (FUra) and FUra-nucleotides was determined and found to directly correlate with the potency of 5'-FUrd in these cell lines. These results suggest that: (a) there is a marked variation in sensitivity of human cancer cells of different tissue origin to 5'-dFUrd, (b) there is a direct relationship between the sensitivity of human cells to 5'-dFUrd and the ability of the cell to metabolize 5'-dFUrd to FUra, and (c) increasing exposure period of cells to 5'-dFUrd did not markedly alter 5'-dFUrd potency in all human cancer cells examined, with the exception of the 47-DN breast cancer cells.

Breast Neoplasms↗
PubMed1983

Tamoxifen and 5-fluorouracil in breast cancer: cytotoxic synergism in vitro.

The cytokinetic and cytotoxic interactions involved in combining tamoxifen, methotrexate, and 5-fluorouracil were studied in two hormone-dependent human breast cancer cell lines, 47-DN and MCF-7. These cells had measurable cytosol and nuclear estrogen receptor and cytosol progesterone receptor. Growth of the MCF-7 cells in medium containing gelding serum was stimulated maximally by addition of 10 pM estradiol. Both MCF-7 and 47-DN cells showed dose-dependent in vitro growth inhibition on exposure to tamoxifen, and toxicity from tamoxifen at concentrations up to 10 microM could be prevented by 1 nM estradiol. After exposure of 47-DN cells to 10 microM tamoxifen, cytosol progesterone and nuclear estrogen receptor levels were still detectable at 30 and 60% of control values. With this same concentration of tamoxifen, 47-DN cells in S phase declined 50% in association with a buildup of G0-1 cells. By clonogenic assay, tamoxifen enhanced 47-DN and MCF-7 cytotoxicity to 5-fluorouracil and 5-fluorouridine, but not to methotrexate alone. When given either concurrently or using a pretreatment-synchronizing schedule, tamoxifen enhanced markedly the growth inhibition of sequentially combined methotrexate and 5-fluorouracil. Isobologram analysis was used to prove that the cytotoxic interaction between tamoxifen and 5-fluorouracil was synergistic.

Breast Neoplasms↗
PubMed1981

[Prostaglandin and luteinized unruptured follicles: the follicles of gilts treated with the inhibitors of prostaglandin production (author's transl)].

The inhibitors of prostaglandin (PG) production (indomethacin, etc.) block ovulation. But little is known about how the inhibition of PG production effects cell function in the follicle. This study was done to clarify the morphological changes and steroidogenesis in the follicles treated with the inhibitor. Fifteen gilts treated with PMS and hCG were administered with indomethacin of 7.6 mg/kg (enough for a complete block) 24 hrs. after hCG. The morphological study of the follicles was done by serial section. The levels of estradiol-17 beta, testosterone, 17 alpha OH progesterone and progesterone were estimated by RIA in the follicular fluid, ovarian vein and peripheral blood. A histologic section of the treated follicles revealed the presence of entrapped oocytes surrounded by heavily luteinized granulosa-theca cells. No morphological changes were found in the luteal cells at any stage of the luteal phase except for retention of fluid in the central cavity of the corpus luteum. The life span of the corpus luteum (18 days) was not affected by indomethacin. No differences in steroid levels were detected in the peripheral and ovarian vein blood or in the follicular fluid at any time compared with the control. Inhibition of PG production results in the luteinized unruptured follicle without interference with steroidogenesis.

Animals↗
PubMed1981

Inhibition of superovulation in immature female rats by the antiserum to cyclooxygenase.

In order to investigate involvement of prostaglandins (PGs) in ovulation, we examined whether the antiserum to cyclooxygenase was able to inhibit superovulation in immature female rats as indomethacin did. The antiserum to cyclooxygenase was raised in rabbits using as antigen the solubilized cyclooxygenase extracted and purified from bovine seminal vesicles. The in vivo administration of the antiserum inhibited superovulation in female rats dose-dependently at doses of 0.1, 0.2 and 0.4 ml but did not affect production of progesterone. Inhibition of cyclooxygenase in the follicular cells due to the antiserum causing no effect on steroidogenesis was observed in organ cultures of the follicles excised from rats primed with PMS-hCG and the antiserum. In contrast to this, no inhibition of cyclooxygenase was detected upon adding the antiserum to the culture medium. The present study showed PG is as indispensable a factor in ovulation as are the steroids.

Animals↗
PubMed1981

In vitro production of prostaglandins E, F, and 6-keto prostaglandin F1 alpha by human pregnant uterus, decidua and amnion.

The production of prostaglandins (PGs) E and F and 6-keto PGF1 alpha was investigated by using human decidua, amnion, and pregnant myometrium obtained before and after onset of labor, and human nonpregnant myometrium collected during luteal phase. PGs produced were measured by radioimmunoassay developed in our laboratory. The radioimmunoassay for 6-keto PGF1 alpha is specific and accurate. PGE was formed at an almost constant rate regardless of the condition under which the three tissues tested were obtained, with the amnion showing the highest activity compared with decidua and myometrium. PGF production increased remarkably during labor in the myometrium and decidua but not in the amnion. In the myometrium during labor, PGF levels were three times higher than before labor. The pregnant myometrium produced more PGs than the nonpregnant myometrium. The production of 6-keto PGI1 alpha, a stable, non-enzymatically formed derivative of PGI2, was observed to be much higher in the pregnant myometrium than in decidua, amnion, or nonpregnant myometrium. Contrary to the pattern of PGF production, 6-keto PGF1 alpha was lower during labor. The physiological significance of PG production by decidua, amnion, and myometrium in relation to parturition is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

[Significance of prostaglandins (PGs) in ovulation (author's transl)].

In order to investigate involvement of prostaglandins (PGs) in ovulation, it was examined whether inhibitors of cyclooxygenase, such as indomethacin and mefenamic acid, and the antiserum to cyclooxygenase were able to inhibit superovulation in immature female rats and gilts. Indomethacin and mefenamic acid were dose-dependently effective in inhibition of superovulation in the two animals. The antiserum to cyclooxygenase was raised in rabbits using the solubilized cyclooxygenase extracted and purified from bovine seminal vesicle as antigen. The in vivo administration of the antiserum inhibited superovulation in female rats dose-dependently at the doses of 0.1, 0.2 and 0.4 ml but did not influence production of progesterone. Inhibition of cyclooxygenase in the follicular cells by the antiserum with no effect on steroidogenesis was observed in organ culture of the follicles excised from the rats primed with PMS and the antiserum. On the contrary, no inhibition of cyclooxygenase was detected in case of the addition of the antiserum to the culture medium. The present study showed PG is one of the indispensable factors in ovulation as steroids are.

Animals↗