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J C Romijn

Publications and source records attributed to J C Romijn.

At least 91 records · Page 5Linked to original sources
PubMed1986

Arrest of the proliferation of renal and prostate carcinomas of human origin by inhibition of mitochondrial protein synthesis.

The results described in this paper demonstrate that proliferation arrest by low concentrations of tetracyclines, which has previously been shown in experiments with animal tumor systems, can also be achieved in tumor systems of human origin. Tetracyclines specifically inhibit mitochondrial protein synthesis. Prolonged and continuous impairment of protein synthesis inside the mitochondria leads to reduction of the cellular concentration of the polypeptide products which are coded and synthesized within mitochondria. These products are part of the oxidative phosphorylative system of the cell. Long-term tetracycline treatment leads to a decrease of oxidative ATP-generating capacity as monitored by cytochrome c oxidase activity. This may cause severe energetic or metabolic disturbances which explain the proliferation arrest observed. Proliferation arrest, provided that mitochondrial protein synthesis is blocked effectively, is found in vitro as well as in vivo. It is shown that the effect of doxycycline is not limited to cytostasis; prolonged doxycycline treatment is clearly cytotoxic for the tumor cells.

Animals↗
PubMed1986

Enhanced success rate of transplantation with human tumors in cyclophosphamide-treated nude mice.

Immunosuppression was investigated to enhance the take rate of various human tumor types in nude BALB/c or B10.LP/Cpb mice. Cyclophosphamide (CY), known as an immunosuppressive agent, was injected ip at a dose of 100 mg/kg 24 hours prior to subcutaneous implantation of tumor fragments obtained from established xenograft lines or from patients. In 3 out of 8 ovarian adenocarcinoma tumor lines, with a take of 50% or less in untreated control animals, tumor take was significantly increased by CY treatment to values between 75 and 100%. No effect of CY treatment on tumor take was seen with squamous cell carcinomas of the head and neck region and with lung and prostatic carcinomas. The growth rate of these xenografts was not affected by CY pretreatment. These results indicate that immunologic mechanisms indeed can play a role in the inhibition of tumor growth in nude mice. CY pretreatment may enhance the success rate of transplantation, but this effect appears to be limited to certain tumors.

Adenocarcinoma↗
PubMed1985

Expression of cellular oncogenes in human prostatic carcinoma cell lines.

Prostatic cancer is one of the most frequent forms of malignancy in Western countries. Initially, growth of the majority of prostate tumors can be manipulated by endocrine therapy. However, ultimately androgen independent tumors continue to grow. We studied the expression of oncogenes in four different human prostatic carcinoma cell lines: PC 3, PC 133, PC 135, which are androgen independent, and the hormone dependent PC 82 cell line. Large amounts of Ha-ras and myc mRNA were present in all cell lines. Transcripts of fes, int-1 and abl were never detected. In some of the cell lines the presence of N-ras, Ki-ras, myb, fos, fms and sis mRNA was observed. The PC 82 cell line showed, in addition to myc and Ha-ras high levels of fos expression. Inhibition of tumor cell proliferation by withdrawal of androgen was accompanied by a tenfold reduction of the fos mRNA level and a twofold reduction of Ha-ras transcripts. In contrast, the expression of myc was not changed.

Animals↗
PubMed1985

Growth of tumor cells with different sensitivities for murine natural killer cells in young and adult athymic nude mice.

Of four tumor cell lines, the murine YAC lymphoma, the human K562 lymphoma, and the human prostatic carcinomas PC3 and PC93, the susceptibility to murine natural killer (NK) cells as well as the tumorigenicity in young (3.5-4 weeks old) and in adult (8-10 weeks old) nude mice were studied. In young nude mice, which exhibited a lower level of NK cell activity than adult nude mice, the formation of solid tumors after inoculation of tumor cell suspensions occurred more frequently and with a shorter time lag than in adult animals. These effects were observed not only with the NK-sensitive YAC cells, but also with the relatively NK-insensitive PC3 and PC93 cells, indicating that also factors other than NK cell susceptibility may influence the growth of tumor cells in nude mice. Therefore, the use of young nude mice may enhance the rate of success of heterotransplantation of human tumors, regardless of the NK cell susceptibility of the tumor cells.

Age Factors↗
PubMed1985

[Androgen receptor and 5 alpha-reductase activity in the epithelium and the stroma of human benign prostatic hyperplasia].

An average of 20 X 10(6) nucleated cells were obtained from 1 g tissue of human benign prostatic hyperplasia by mechanical separation technique. Of these cells, 96.2% showed acid phosphatase activity and this was 10 times higher than the remaining stromal fraction on a protein base. The total activity of 5 alpha-reductase was 81 times higher in stroma than epithelium and the total activity of 3(beta)-oxidoreductase was 29 times higher in stroma. Androgen receptor amount measured in total tissue, epithelium and stroma were 100, 29 and 62 fmol R1881/mg DNA, respectively. These results suggest that androgen metabolism takes place mainly in the stroma of human BPH tissue, and that BPH is probably the disease of prostatic stroma.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

Unresponsiveness of the reproductive organs of the male mouse to treatment with a potent luteinizing hormone-releasing hormone agonist (ICI-118,630).

The effects of administration of a luteinizing hormone-releasing hormone (LHRH) analogue (ICI-118,630) on plasma concentrations of hormones and weights of reproductive organs were studied in male mice. A single injection of the analogue (54 micrograms/kg body weight) caused a transient elevation of the concentration of LH in the plasma, up to 7 times the level in control mice. Daily administration of the analogue for a period of 3 weeks caused a small but significant decrease of the weight of the ventral prostate. The weight of the seminal vesicles in mice treated with the analogue, however, did not differ from that in control animals. The concentration of testosterone and LH in the plasma of these mice was not significantly different from those in control mice. It is demonstrated that the LHRH-analogue has no "castration-like" effect on the accessory sex organs of the male mouse, which is therefore not a suitable model in the study of these compounds.

Animals↗
PubMed1984

Determination of the growth rate of human prostatic cells in primary culture by a morphometric technique.

A morphometric technique, based on the measurement of the area of individual cell colonies and of its increase in time, was applied to study the rate of proliferation of human prostatic cells in vitro. The reliability of the method was checked by determination of the growth rate of cultures of the continuous cell line PC93 by the morphometrical technique as well as by counting of the cell number. No significant difference was found in the population doubling times measured by either of these methods. It was therefore concluded that the morphometrical technique could be applied also to study the growth rate of primary cultures of prostatic epithelial cells, in which counting of the cell number is generally impossible. The results showed that, with primary cultures derived from hyperplastic prostates and prostatic carcinomas as well as from the prostatic tumor line PC82, rapid growth occurred during the first two or three days of culture; measurements performed at a later time appeared to be less reliable. It was demonstrated by the effect of serum deprivation on the growth of PC82 cells that the technique described here is, in principle, suitable to monitor the effect of various agents on the growth of cells in primary culture. The method is non-destructive and requires minimal amounts of tissue; it may be applied especially to cultures that cannot be dispersed easily into single cell suspensions.

Adenocarcinoma↗
PubMed1984

Biological effects of hormonal treatment regimens on a transplantable human prostatic tumor line (PC-82).

The effects of hormonal manipulation on the growth of a transplantable human prostatic carcinoma line (PC-82) were studied. The histological pattern of the PC-82 tumor, which still closely resembles the original tumor material, and the tumor growth rate did not change during the subsequent mouse passages. Growth of PC-82 tumor tissue on female and castrated male mice did not occur. Castration of tumor-bearing mice resulted in a cessation of tumor growth, after which the tumor volume decreased 50 +/- 27 per cent within 6 weeks after castration. Hormone-independent regrowth of the tumor tissue was not observed after long-term withdrawal of androgens. After a period of 10 weeks following tumor growth arrest, administration of testosterone almost directly resulted in regrowth of the tumor. Hormones, testosterone and estradiol, were administered by silastic implants. Intact male nude mice were shown to have highly fluctuating levels of testosterone. Implantation with testosterone resulted in constant levels of circulating testosterone, which could be maintained for at least 10 weeks, while the mean concentration of plasma testosterone was not different from that in control male mice. The doubling time of tumors grown on testosterone-substituted intact female and intact and castrated male mice was significantly shorter than that of tumors grown on intact male mice. Histologically the tumors grown on androgen-substituted mice were similar to those grown on untreated mice; the mitotic index, however, was much higher in the testosterone treated animals. Implantation of intact male mice with estradiol suppressed plasma testosterone to a mean level of 1 ng. per ml. and prevented the growth of PC-82 tumor tissue almost completely. Treatment of tumor-bearing mice with an estradiol implant following androgen withdrawal did not result in a further decrease of the tumor volume compared to the mice without additional estradiol implantation.

Adenocarcinoma↗
PubMed1983

Effect of hormone treatment on prostatic acid phosphatase in a serially transplantable human prostatic adenocarcinoma (PC-82).

The influence of endocrine manipulation on the tissue concentration of prostatic acid phosphatase (PAP) was studied in the hormone dependent transplantable human prostatic tumor line PC-82. Tumor bearing nude mice were left intact, castrated or treated for a 5-day period with a subcutaneous implant containing testosterone or estradiol. The concentration of PAP in castrated mice was not different from that in the controls. The DNA content of PC-82 tumor tissue obtained from 5-day castrated animals was significantly lower than that of tissue from intact animals. Therefore the concentration of PAP in tissue from castrated mice was significantly elevated when expressed per mg. of DNA (p less than 0.05). Treatment of the mice with testosterone or estradiol did not affect the PAP concentration in the tumor tissue. A significant correlation was observed between the concentration of PAP in the serum and the tumor burden of the mice. Long-term withdrawal of androgens resulted in a decrease of the concentration of PAP in the serum, as well as in a decrease of the tumor burden. The concentration of PAP in the tumor tissue remaining after castration of these animals was not significantly different from that in controls. The present data from the tumor line PC-82 do not support the hypothesis that the concentration of PAP in prostatic tumor tissue is controlled by androgens, but are in agreement with the concept that the level of PAP in plasma is related to the tumor mass.

Acid Phosphatase↗
PubMed1983

Transplantation of human pituitary adenomas into nude mice.

In vitro studies with human pituitary adenomas are limited by the small amount of tissue obtained, which may be contaminated by the surrounding normal pituitary tissue. In this study we investigated if the passage of adenoma tissue via thymusless nude mice could solve some of these problems. The secretory capacity of the transplanted human pituitary adenomas was demonstrated by the presence of hGH and/or hPRL in the plasma of the host mouse, while other human pituitary hormones (TSH, LH and FSH) were undetectable. The transplants, however, decreased in size with time although histologically viable adenoma tissue was recovered that resembled the original tumor. Upon trypsinization of the small tissue fragments no viable adenoma cells could be obtained. In contrast, an experimental malignant rat pituitary tumor grew steadily with time, resulting in high levels of rPRL in the nude mice recipients. Large numbers of viable tumor cells were recovered from these tumors. Thus, human pituitary adenomas transplanted in nude mice continue to release hormone(s), but the transplants decrease in size and cannot be used to isolate dispersed tumor cells for in vitro studies.

Adenoma↗
PubMed1982

Testosterone metabolism of fibroblasts grown from prostatic carcinoma, benign prostatic hyperplasia and skin fibroblasts.

The metabolism of [1,2,6,7-3H]testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC.

Androstanes↗
PubMed1981

The surface character of separated prostatic cells and cultured fibroblasts of prostatic tissue as determined by concanavalin-A hemadsorption.

Con-A-coated human type O red blood cells (indicator RBC) were used for ConA reactivity assay of separated epithelial cells and cultured fibroblasts of human prostatic tissue. The epithelial cells of carcinoma showed higher reactivity than those of normal tissue or hyperplastic tissue. Although both cultured fibroblasts of PC and BPH are considered to be non-malignant, it is clearly demonstrated that the PC fibroblasts have a malignant surface character in terms of ConA reactivity, whereas the BPH fibroblasts have a quite low ConA reactivity. ConA-mediated HAD appeared to be a useful tool to distinguish malignant epithelial cells of human prostate from non-malignant ones. It still remains unknown whether the alteration of PC fibroblasts is the cause or the result of carcinogenic transformation of prostatic tissue.

Cell Line↗
PubMed1981

Cell separation and characterization of epithelial cells from human benign prostatic hyperplasia.

Epithelial cells were isolated from human prostatic hyperplasia (BPH) after mechanical disruption of the tissue. The tissue was cut into small pieces, then mechanical pressure was applied. Stroma and epithelium were separated by a sequence of sedimentation steps. The recovery rate of epithelial cells was around 20 million cells per gram of tissue and more than 95% of the cells did exclude trypan blue. Epithelial cells can be identified by phase contrast microscopy and by the acid phosphatase content of the cells. In more than 95% of the cells the presence of acid phosphatase could be shown cytochemically with phosphorylcholine as a substrate. This finding indicates that the contamination with other cell types is very small. Histological study of the remaining stroma indicates that most of the epithelial cells are removed. Also, the acid phosphatase content of this fraction was found to be very low. The problem of obtaining large quantities of stromal cells in suspension has not yet been resolved. However, the technique described may be more suitable than others for the separate study of stroma and epithelium from BPH.

Acid Phosphatase↗
PubMed1978

The mechanism of reduction of the ubiquinone pool in photosynthetic bacteria at different redox potentials.

(1) A flash number dependency of flash-induced absorbance changes was observed with whole cells of Rhodospirillum rubrum and chromatophores of R. rubrum and Rhodopseudomonas sphaeroides wild type and the G1C mutant. The oscillatory behavior was dependent on the redox potential; it was observed under oxidizing conditions only. Absorbance difference spectra measured after each flash in the 275--500 nm wavelength region showed that a molecule of ubiquinone, R, is reduced to the semiquinone (R-) after odd-numbered flashes and reoxidized after even-numbered flashes. The amount of R reduced was approximately one molecule per reaction center. (2) The flash number dependency of the electrochromic shift of the carotenoid spectrum was studied with chromatophores of Rps. sphaeroides wild type and the G1C mutant. At higher values of the ambient redox potential a relatively slow phase with a rise time of 30 ms was observed after even-numbered flashes, in addition to the fast phase (completed within 0.2 ms) occurring after each flash. Evidence was obtained that the slow phase represents the formation of an additional membrane potential during a dark reaction that occurs after flashes with an even number. This reaction is inhibited by antimycin A, whereas the oscillations of the R/R- absorbance changes remain unaffected. At low potentials (E = 100 mV) no oscillations of the carotenoid shift were observed: a fast phase was followed by a slow phase (antimycin-sensitive) with a half-time of 3 ms after each flash. (3) The results are discussed in terms of a model for the cyclic electron flow as described by Prince and Dutton (Prince, R.C. and Dutton, P.L. (1976) Bacterial Photosynthesis Conference, Brussels, Belgium, September 6--9, Abstr. TB4) employing the so-called Q-cycle.

Bacterial Chromatophores↗