38 research outputs found
Transplantable human prostate cancer (PC-82) in athymic nude mice : a model for the study of androgen-regulated tumor growth
This thesis describes the characterization and further application of a model system for
prostate cancer, the human prostatic adenocarcinoma PC-82 which is transplantable in
athymic nude mice.
The mortality rate of patients suffering from prostatic carcinoma is high, in spite of the
high response rates which are initially achieved with hormonal treatment ofthese patients.
Growth and function of the prostate are primarily dependent on androgenic stimuli.
Hormonal treatment of prostatic carcinoma is based upon the suppression of the testicular
production of androgens. This can be achieved directly by surgical removal of the testes or
indirectly by inhibiting the hypophyseal gonadotropin release through treatment with
estrogens or analogues of luteinizing hormone-releasing hormone (LHRH). However, in
the majority of patients relapse of the tumor occurs following a favorable response to
androgen-ablation therapy. Progression is caused mainly by a loss of androgen-sensitivity of
the tumor.
Since many investigations relevant to prostate cancer cannot be performed in patients,
there is a great need for well-characterized model systems which reflect the properties of
clinical prostate cancer. Relevant aspects of the prostate in general and of prostatic
carcinoma in particular are described in chapter 1, which also contains a summary of the
current knowledge of androgen action in the prostate and information on the available
model systems for prostatic cancer
Isolation and characterization of the immunosuppressant- and temperature-sensitive its4 mutant of fission yeast
ć棫ïŒć»ćŠïŒç„æžć€§
The human prostatic cancer cell line LNCaP and its derived sublines: An in vitro model for the study of androgen sensitivity
__Abstract_
The LNCaP-FGC (fast growing colony) cell line, a subline derived from the LNCaP cell line, shares all the main characteristics, including its androgen sensitivity, described for the parental line. A number of sublines originating from the FGC line were characterized with respect to their response to steroid-depleted medium and to the synthetic androgen R1881. The growth of FGC cells in DCC medium with 0.1 nM R1881 was stimulated 2â3-fold compared to growth in DCC medium only. FGC cells that were continuously grown in DCC medium did not die, but their growth rate was clearly slowed down, and the cells remained responsive to androgen. These cells, therefore, have the androgen-sensitive, rather than the androgen-dependent phenotype. As cells of the subline FGC-JB could not be maintained in DCC medium, these cells better represent the androgen-dependent cell type. In contrast to the FGC line, cells of the R line, grew equally well in medium with complete or DCC serum. Under none of these culture conditions, R cells could significantly be stimulated further with R1881. Further analysis of the LNCaP-FGC sublines should provide valuable information concerning the development of androgen resistance in human prostate cancer
Neuroendocrine cells in the normal, hyperplastic and neoplastic prostate
Neuroendocrine cells can be demonstrated in normal, hyperplastic and neoplastic prostatic tissues. The products secreted by these cells can be used as tissue and/or serum markers but may also have biological effects. Neuroendocrine cells in prostate cancer most probably do not contain the androgen receptor and are therefore primarily androgen independent. Some of the neuropeptides secreted by the neuroendocrine cells may act as growth factor by activation of membrane receptors in an autocrine-paracrine fashion or by ligand-independent activation of the androgen receptor in neighboring non-neuroendocrine cells. Evidence is accumulating from experiments with tumor models that neuropeptides indeed can influence the growth of prostatic tumor cells. Future research on neuroendocrine differentiation may answer some questions concerning the biological behavior of clinical prostatic tumors
Decreased levels of topoisomerase IIα human renal cell carcinoma lines resistant to etoposide
Determination of Ki-67 defined growth fraction by monoclonal antibody MIB- I in formalin-fixed, paraffin-embedded prostatic cancer tissues
The applicability of MIBâ1, a monoclonal antibody directed against the Kiâ67 antigen, was studied in the PCâ82 and LNCaP prostatic tumor models at various levels of proliferative activity. Statistically significant correlations were found in LNCaP cultures between Kiâ67 and MIBâ1 scores (r = 0.84, P < 0.001), and in PCâ82 tumors between MIBâ1 scores and paraffin tissue Kiâ67 (pKiâ67) (r = 0.90, P < 0.001), frozen tissue Kiâ67 (fKiâ67) (r = 0.86, P < 0.001), and BrdU uptake (r = 0.70, P < 0.001), respectively. pKiâ67 scores were double the fKiâ67 scores, which may be due to methodological differences. MIBâ1 scores exceeded both the fKiâ67 and pKiâ67 scores. The affinity of MIBâ1 for the antigen is much higher than the affinity of Kiâ67, which may explain the differences. MIBâ1 is a promising means of evaluating the presence of only minute amounts of the Kiâ67 antigen in paraffinâembedded human tumor material, especially in relatively slowly growing tumors
Effects of low testosterone levels and of adrenal androgens on growth of prostate tumor models in nude mice
Abstract
Two transplantable, androgen dependent prostate tumor models of human origin, PC-82 and PC-EW, were used to study the effect of low androgen levels and adrenal androgens on prostate tumor cell proliferation. Tumor load of the PC-82 and PC-EW tumors could be maintained constant when plasma testosterone levels were 0.8 and 0.9 nmol/l, respectively, corresponding with an intratissue 5α-dihydrotestosterone level of 3â4 pmol/g tissue. This critical androgen level for prostate tumor growth stimulation amounted to 2â3 times the castration level and proved to be similar for both tumor models. Relatively high levels of androstenedione resulted in physiological levels of plasma testosterone causing androgen concentrations in PC-82 tumor tissue exceeding the critical level for tumor growth. These results indicate that submaximal suppression of androgens can stop tumor growth in these prostate tumor models
MIB-1 (KI-67) proliferation index and cyclin-dependent kinase inhibitor p27(Kip1) protein expression in nephroblastoma
Kinetics of neuroendocrine differentiation in an androgen-dependent human prostate xenograft model
It was previously shown in the PC-295 xenograft that the number of
chromogranin A (CgA)-positive neuroendocrine (NE) cells increased after
androgen withdrawal. NE cells did not proliferate and differentiated from
G0-phase-arrested cells. Here we further characterized NE differentiation,
androgen receptor status, and apoptosis-associated Bcl-2 expression in the
PC-295 model after androgen withdrawal to assess the origin of NE cells.
PC-295 tumor volumes decreased by 50% in 4 days. Intraperitoneal
bromodeoxyuridine (BrdU) incorporation and MIB-1 labeling decreased to 0%,
and the apoptosis was maximal at day 4. Androgen receptor expression and
prostate-specific antigen (PSA) serum levels decreased rapidly within 2
days. The number of NE cells increased 6-fold at day 4 and 30-fold at day
7. Five and ten percent of the CgA-positive cells were BrdU positive after
continuous BrdU labeling for 2 and 4 days, respectively. However, no MIB-1
expression was observed in CgA-positive cells. NE cells expressed the
regulated secretory pathway marker secretogranin III but were negative for
androgen receptor and Bcl-2. Bcl-2 expression did increase in the non-NE
tumor cells. In conclusion, androgen withdrawal leads to a rapid PC-295
tumor regression and a proliferation-independent induction of NE
differentiation. The strictly androgen-independent NE cells that were
still present after 21 days differentiated mainly from G0-phase-arrested
cells