bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of epidermal growth factor on prostate cancer cell line PC3 growth and invasion
Authors: Jarrard David F. , Blitz Barry F. , Smith Robert C. , Patai Barbara L. , Rukstalis Daniel B. 
Published: February 2007

AbstractElevated levels of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF‐R) have been demonstrated in prostate cancer cell lines and clinical specimens suggesting a role for polypeptide growth factors in prostate tumor cell growth and invasion. To more clearly define the role of EGF in prostate cancer invasion, we undertook a series of studies utilizing the PC3 prostate cancer cell line, an aggressive, hormone‐independent cell line derived from a metastatic lesion. No statistical differences were noted in the growth of PC3 cells under serum‐free conditions when EGF (10−10 M‐10−8 M) or monoclonal anti‐EGF‐R antibody (10−11 M‐10−8 M) were added. Utilizing the Boyden chamber microinvasion assay, EGF supplemented cells demonstrated a statistically significant augmentation in invasion (P < 0.05) when compared to control cells at each time point in the study. With increasing length of exposure to EGF, the number of concentrations that produced significant invasion increased: day 1 (10−8 M), day 3 (10−9, 10−9 M), and day 5 (10−7, 10−8, 10−10 M). Northern blot analysis of EGF supplemented cells revealed an increase in expression of urokinase plasminogen activator (uPA) RNA, a serine protease involved in the regulation of pericellular proteolysis and membrane degradation. Protein analysis confirmed these findings. Statistically significant inhibition of invasion by anti‐uPA antibodies was demonstrated for EGF‐stimulated and PC3 control cells. Our results demonstrate that certain concentrations of EGF augment invasion in the PC3 cell line. This enhancement of invasion occurs in part by an overproduction of uPA, an extracellular protease. These findings suggest that the autocrine production of EGF may potentiate tumor cell invasion. © 1994 Wiley‐Liss, Inc.
Developmental estrogenization and prostatic neoplasia
Authors: Santti Risto , Mäkelä Sari , Pylkkänen Liisa , Newbold Retha R. , McLachlan John A. 
Published: February 2007

AbstractThe association of estrogens with benign prostatic hyperplasia and prostatic cancer has been widely studied, but no conclusive evidence exists for a role of estrogens in prostatic disease. This paper reviews the literature and describes studies which have sought to show a correlation of estrogens and alterations in the prostates of humans and experimental animal models. Using the developmentally estrogenized mouse model, we propose an alternative role for estrogens as a predisposing factor for prostatic diseases: estrogen exposure during development may initiate cellular changes in the prostate which would require estrogens and/or androgens later in life for promotion to hyperplasia or neoplasia. Thus, the critical time for estrogen action would be during the development of the prostatic tissue. We further suggest that estrogen‐sensitive cells may remain in the prostate and be more responsive to estrogens later in life or less responsive to the normal controlling mechanisms of prostatic growth. © 1994 Wiley‐Liss, Inc.
In vitro radiation sensitivity of the lncap prostatic tumor cell line
Authors: Leith John T. 
Published: February 2007

AbstractBecause there is extremely limited information on the intrinsic radiosensitivity of human prostatic cancer cells, we have investigated the in vitro radiation response of exponentially growing LNCaP cells. Due to the very poor colony‐forming potential of the LNCaP cells, radiation survival was investigated using the dose‐dependent (0‐6 Gy) changes seen after X‐irradiation in the shapes of regrowth curves. Survival was described using both the single‐hit, multitarget (SHMT) equation and the linear‐quadratic (LQ) equation. The values and 95% confidence limits of the extrapolation number (n), quasi‐threshold dose (Dq), and mean lethal dose (Do) in SHMT terminology were respectively: 0.9 (0.7‐1.0), 0.0 Gy, and 1.39 (0.11) Gy. The LQ alpha and beta parameters were respectively 6.80 (1.13) and ‐0.53 (2.89). The X‐ray dose response of the LNCaP line is, therefore, purely exponential. The mean survival at the clinically relevant dose of 2 Gy (S2) was 51.2% for the LNCaP line. Comparison of the S2 value for the LNCaP line with previous investigations with other human prostatic cancer cell lines (DU145 and PC‐3) indicates a mean S2 value of 47.6%, which suggests that human prostate cancer cells might lie toward the resistant side of the spectrum for various classes of human neoplasms. © 1994 Wiey‐Liss, Inc.
Effects of 4‐MAPC, a 5α‐reductase inhibitor, and cyproterone acetate on regrowth of the rat ventral prostate
Authors: Shao Tsang C. , Kong Ann , Cunningham Glenn R. 
Published: February 2007

AbstractInhibitors of 5α‐reductase activity cause less involution of the rat ventral prostate (VP) than does castration. Studies were conducted in adult Sprague Dawley rats to evaluate the effects of a potent 5α‐reductase inhibitor, 4‐MAPC, and the antiandrogen, cyproterone acetate (CA), on DNA synthesis and apoptosis. In experiment 1, VP weight fell 33%, 53%, and 83%, and DNA per ventral prostate was reduced 24%, 46%, and 71%, by 4‐MAPC, CA, and castration, respectively. In experiment 2, adult rats were castrated, and the VP involuted for 7 days prior to 3 daily injections of testosterone propionate (TP; 1 mg/kg/d) ± 10 mg/kg/d of 4‐MAPC or CA. 3H‐thymidine incorporation into VP DNA was increased in castrated animals treated with TP, and 4‐MAPC and CA reduced uptake. In experiment 3, animals were treated for 14 days with the same protocol as that used in experiment 2. VP weight was increased in all animals treated with TP when compared with castration, and was reduced by both 4‐MAPC and CA. DNA in rats treated with TP was similar to that in intact animals. DNA was not reduced by 4‐MAPC, but was reduced by CA. The mRNA for TRPM‐2, a marker of apoptosis, was increased only in untreated castrated rats. It appears that CA has a greater inhibitory effect than 4‐MAPC on DNA synthesis. A major reason why castration reduces DNA more than either 4‐MAPC or CA is that neither of these agents was able to increase programmed cell death to the degree seen with castration. © 1994 Wiley‐Liss, Inc.
Interleukin‐2 transfected prostate cancer cells generate a local antitumor effect in vivo
Authors: Moody D. Branch , Robinson John C. , Ewing Charles M. , Lazenby Audrey J. , Isaacs William B. 
Published: February 2007

AbstractIn an effort to stimulate host‐mediated antitumor response against prostate cancer in an animal model, highly malignant Dunning MAT‐LyLu rat prostate carcinoma cells were transfected with the interleukin‐2 (IL‐2) cDNA, resulting in their ability to secrete large amounts of biologically active IL‐2. Although parental cells form lethal tumors when injected subcutaneously into syngeneic hosts at doses of ≥5,000, injections of IL‐2 secreting cells initially formed tumors and regressed completely in each of over 200 animals at all doses tested (104‐8 × 107 cells). Mixtures of parental and IL‐2 transfected cells were similarly rejected, demonstrating the non‐cell autonomous nature of the response. Histological analysis of regressing tumors revealed a vigorous, predominantly lymphocytic and macrophage infiltrate at day 2 and marked tumor necrosis by day 6. Immunohistochemical staining of infiltrating lymphocytes at this latter time point demonstrated numerous T cells bearing either CD4 or CD8 surface markers, suggesting these cells as possibly mediating the tumor rejection. The ability of athymic mice to reject the IL‐2 secreting tumor cells, however, suggests a non‐T‐cell‐mediated mechanism. Although splenic natural killer (NK) activity is increased following injection of IL2 secreting tumor cells, this activity appears to be unnecessary for tumor elimination since syngeneic animals injected with asialo‐GM1 antiserum to decrease NK activity also rejected IL‐2 transfected cells, albeit slightly less effectively than untreated animals. Immunization of animals with subcutaneous injections of IL‐2 transfected cells protected animals against a subsequent challenge of 104 wild‐type cells 1 to 2 weeks later in 19 of 51 cases; however, immunization did not confer protection against larger doses of parental tumor. These studies indicate that high local concentrations of IL‐2 stimulate the elimination of large local burdens of prostate cancer in this model system, and this elimination results in a weak, but detectable systemic immune response against wild‐type prostate cancer cells. © 1994 Wiley‐Liss, Inc.
Metastatic prostate cancer pulmonary nodules: Beneficial effects of combination therapy and subsequent withdrawal of flutamide
Authors: Cusan Leonello , Gomez José‐Luis , Dupont Andé , Diamond Pierre , Lemay Martin , Labrie Fernand , Moore Sean 
Published: February 2007

AbstractA case is presented of a middle‐aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed. © 1994 Wiley‐Liss, Inc.
Nuclear shape and prognosis following orchiectomy in stage D2 prostate cancer
Authors: Miller John , Horsfall David J. , Marshall Villis R. , Skinner John M. , Rao Dora M. , Leong Anthony S. Y. 
Published: February 2007

AbstractIn this study, we have examined whether tumor grade and morphometric nuclear features can predict the outcome of treatment by orchiectomy in patients with stage D2 prostate cancer. Two outcome groups based on duration of survival postorchiectomy were examined, a bad outcome group of 63 patients who died from prostate cancer within 12 months and a good outcome group of 34 patients who survived beyond 5 years. Tumors were histologically classified as well (17%), moderate (17%), or poorly differentiated (66%). Tumor grade and patient outcome were significantly associated (Mann‐Whitney test; P < 0.005), with 76% of poorly differentiated tumors in the bad outcome group, and 65% of well‐differentiated tumors in the good outcome group. Using discriminant function analysis, tumor grade correctly predicted outcome in 70% of cases.A statistically significant difference was also detected in nuclear shape values between the two outcome groups (P < 0.05) and histological grades (P < 0.05). Using discriminant function analysis, 51% of cases were correctly classified into outcome groups using nuclear shape factors, a figure which rose to 65% when all nuclear morphometric features were used. This demonstrates that nuclear morphometric features are of no clinical value in predicting the outcome of treatment in stage D2 disease. Furthermore, these evaluations cannot select patients who might be spared orchiectomy on the basis of a predicted poor response.However, nuclear shape and variance measurements of benign glandular epithelial cells within cancerous prostates were significantly different from those of malignant cells (P < 0.005). We conclude that, while video image analysis of prostatic nuclear shape can reliably discriminate between benign and malignant cells, nuclear morphometric features are of minimal prognostic value in men with stage D2 prostate cancer treated by androgen ablation. © 1994 Wiley‐Liss, Inc.
Cathepsin D cytosolic assay and immunohistochemical quantification in human prostate tumors
Authors: Chambon M. , Rochefort H. , Brouillet J. P. , Baldet P. , Maudelonde T. , Rebillard X. , Guiter J. 
Published: February 2007

AbstractWe quantified cathepsin D by immunoradiometric assay (IRMA) and quantitative immunohistochemistry in fifteen human prostate cancers, seventeen BPH, and nine normal prostates. The cytosolic cathepsin D concentration was higher in prostatic carcinoma (mean: 31.5 pmol/mg cytosol proteins; range: 10.2‐66.2) than in normal prostate (16.0 pmol/mg cytosol proteins; 7.2‐25.5; P = 0.01). Prostatic hyperplasia showed intermediate values (20.2 pmol/mg cytosol proteins; 7.6‐33.9). Immunostaining of cathepsin D and prostatic acid phosphatase on serial frozen sections of prostate tissues was only observed in glandular epithelial cells. Immunostaining was quantified by computer‐assisted image analysis as an quantitative immuno‐cytochemical score (QIC score) expressed in arbitrary units (A.U.). QIC scores for cathepsin D were dispersed and had a tendency to be higher in benign prostatic hyperplasia (mean: 178.3 A.U.; range: 95‐297) compared to normal prostate (85.2 A.U.; 2‐173 P < 0.01) and prostatic carcinoma (90.0 A.U.; 21‐179 P = 0.0002). Prostatic cathepsin D levels in cytosols or immunostaining sections were independent of other clinicobiological parameters. © 1994 Wiley‐Liss, Inc.
Estrogen treatment postpones the castration‐induced dedifferentiation of dunning R3327‐PAP prostatic adenocarcinoma
Authors: Landström M. , Damber J.‐E. , Bergh A. 
Published: February 2007

AbstractMale Copenhagen × Fisher F1 rats, transplanted with the androgen‐sensitive Dunning R3327 PAP rat prostatic adenocarcinoma, were castrated when tumor volumes were approximally 1300 mm3. The rats were thereafter followed with measurements of tumor volume. Castration stopped tumor growth, but some of the tumors started to regrow after 7‐36 weeks. These tumors relapsing from castration treatment were now considered to be androgen‐insensitive. In this study, we defined relapse as the time when the tumor volume had increased to 200% of the volume at the time for castration. At this time, the rats were treated either with estradiol‐17β (E2, 50 μg s.c. daily) or vehicle for 8 weeks. After this period, tumor morphology was examined.The tumors in the vehicle‐treated group were heterogeneous, and both highly and more dedifferentiated parts were present. The tumor growth rate was correlated to the epithelial cell nuclear size and its variance, and to the mitotic index. In the E2‐treated group, tumor growth rate was retarded throughout the treatment period, and dedifferentiated tumor areas were rare. Estrogen treatment resulted in a reduction of nuclear area and mitotic index, a changed nuclear shape, and an increased apoptotic index compared to that in vehicle‐treated tumors.By castration, it is possible to induce an alteration of the androgen‐sensitive Dunning R3327 PAP tumor phenotype to an androgen‐insensitive tumor with an altered morphology. Estradiol‐17β apparently inhibits not only the growth, but also postpones the castration‐induced dedifferentiation of the tumor. © 1994 Wiley‐Liss, Inc.
Magnetic resonance spectroscopy detects metabolic differences between seven dunning rat prostate tumor sublines with different biological behavior
Authors: Cornel E. B. , Heerschap A. , Smits G. A. H. J. , Oosterhof G. O. N. , Debruyne F. M. J. , Schalken J. A. 
Published: February 2007

AbstractIn this study, it was investigated whether prostate tumor biological parameters correlate with metabolic profiles. 1H and 31P magnetic resonance spectra were acquired from perchloric acid extracts of seven Dunning R‐3327 prostate tumor sublines. Several metabolic ratios, for example, phosphocholine/total phosphate, choline/total creatine, and inositol/total creatine, did not correlate specifically with one biological characteristic but, based on each of these ratios, the well‐differentiated, nonmetastatic, and hormone‐dependent sublines could be discriminated from the poorly differentiated or anaplastic, metastatic, and hormone‐independent sublines. The glycerophosphoethanolamine/total phosphate, glycerophosphocholine/total phosphate, and phosphocreatine/total phosphate ratios correlated with differentiation grade, and the differences in glycerophosphorylglycerol/total phosphate ratio between metastatic and nonmetastatic sublines was highly significant. No correlation for hormonal sensitivity with any of the metabolites measured could be found, neither by 31P nor by 1H MRS. © 1994 Wiley‐Liss, Inc.
Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia
Authors: Hasui Yoshihiro , Marutsuka Kousuke , Asada Yujiro , Ide Hisamitsu , Nishi Shohei , Osada Yukio 
Published: February 2007

AbstractThe relationship between the serum values of prostate specific antigen (PSA) and the extent of histological prostatitis was investigated in 42 patients undergoing transurethral resection of the prostate for benign hyperplasia (BPH) without clinical evidence of prostatitis. Histological prostatitis was divided into three groups: acute, chronic‐active, and chronic‐inactive inflammation. The extent of histological prostatitis was expressed as the number of prostatic acinar and ductal glands with inflammatory infiltrate per total number of glands (%). The serum PSA values significantly correlated with the extent of acute and chronic‐active prostatitis (correlation coefficient r = 0.765 and 0.656, P < 0.01). A relationship between PSA values and the extent of chronic‐inactive prostatitis was not found. In the immunohistochemical study, prostatic epithelial cells with acute and chronic‐active inflammation showed negative staining for PSA antigen. These results indicate that histological acute and chronic‐active prostatitis is considered an important factor for inducing the high increase in serum PSA values via the leak phenomenon. © 1994 Wiley‐Liss, Inc.
Bioenergetic theory of prostate malignancy
Authors: Costello L. C. , Franklin R. B. 
Published: February 2007

AbstractNormal and benign prostate hyperplasia (BPH) prostate is characterized by the presence of extraordinarily high levels of citrate. Presumably, this results from the inability of the prostate epithelial cells to oxidize citrate due to a limiting mitochondrial (m‐) aconitase. In contrast, prostate carcinoma (CA) is not characterized by high citrate levels. Malignant prostate epithelial cells apparently undergo a metabolic transformation from citrate‐producing to citrate‐oxidizing cells. A consequence of citrate production in normal and BPH cells is an inefficient and low level of ATP production. It is proposed that the process of malignancy necessitates an energy production that cannot be provided by citrate‐producing cells. Consequently, the transformation of prostate epithelial cells to citrate‐oxidizing cells which increases the energy production capability is essential to the process of malignancy and metastasis. The metabolic transformation likely occurs as a premalignant or early malignant stage. This bioenergetic theory of prostate malignancy, if correct, will provide new approaches to the diagnosis and treatment of CA. © 1994 Wiley‐Liss, Inc.
DNA ploidy measurements in prostate cancer: Differences between image analysis and flow cytometry and clinical implications
Authors: Pindur A. , Chakraborty S. , Welch D. G. , Wheeler T. M. 
Published: February 2007

AbstractThe relationship between DNA ploidy and prognostic parameters has been established in prostate cancer. However, comparison of various techniques used for DNA ploidy analysis has not been sufficiently addressed in prostate carcinoma. In the present study, grossly identified discrete carcinoma foci from 48 consecutive radical prostatectomy specimens were analyzed by flow cytometry and image analysis using both imprints and tissue sections. Correlations with other prognostically important pathological findings such as grade, size, extracapsular extension, positive surgical margin, and seminal vesicle and lymph node involvement were done. Image analysis detected 26 (54.2%) nondiploid tumors compared to 15 (31.3%) nondiploid tumors by flow cytometry. No significant differences were demonstrated between imprints and tissue sections. DNA ploidy status showed a good correlation with most other pathological findings listed above. In conclusion, DNA ploidy status determination gives clinically useful information which correlates well with the other useful pathological parameters of prognostic importance. Image analysis may be more sensitive than flow cytometry in detecting nondiploid populations. Tissue sections appear to be as reliable as imprints when properly controlled. © 1994 Wiley‐Liss, Inc.
Two‐phase short‐term culture method for cytogenetic investigations from human prostate carcinoma
Authors: Szücs Sandor , Zitzelsberger Horst , Breul Jürgen , Bauchinger Manfred , Höfler Heinz 
Published: February 2007

AbstractAn improved technique for primary short‐term culture of prostate carcinoma cells in two phases, with and without serum, for subsequent cytogenetic analysis is reported and compared with four other methods. After mechanical disaggregation and a brief collagenase treatment of tumor specimens, cell clusters were seeded in RPMI 1640 and 15% fetal calf serum (FCS) without any other supplement in the first phase. The culture medium was changed to a serum‐free medium supplemented with bovine pituitiary extract (BPE) and epidermal growth factor (EGF) when the first outgrowth became apparent. During this second phase, fibroblast growth could be virtually abolished within 48 hr. The epithelial and prostatic origin of the cultured cells was confirmed by immunocytochemical methods in each culture. Metaphase analysis revealed chromosome aberrations in over 80% of cases (both clonal and nonclonal alterations) indicating the presence of neoplastic cells. Clonal numerical chromosome aberrations, found by conventional cytogenetic analysis, were used to provide the reliability of the culture system in interphase nuclei of corresponding uncultured tumor tissue by fluorescence in situ hybridization (FISH). The main points of the described method are: 1) combined mechanical/enzymatic disaggregation, 2) seeding of the disaggregated cell clumps rather than of single cells, 3) initialization of the cultures in RPMI 1640 medium with 18% FCS without any other supplements, and (4) stimulating of selective epithelial proliferation by changing the culture conditions through serum‐free medium. © 1994 Wiley‐Liss, Inc.
Fresh tissue harvest for research from prostatectomy specimens
Authors: Wheeler Thomas M. , Lebovitz Russell M. 
Published: February 2007

AbstractAs a consequence of molecular biological and genetic techniques, the demand for fresh tissue for basic research has increased dramatically at academic medical centers. Because of the extreme lability of many biological macromolecules, tissue must be harvested with the least possible delay from the time of removal. This necessity for quick action, frequently under less than optimal circumstances, along with the obvious loss of tissue available for diagnostic purposes, presents a daunting challenge to the pathologist responsible for accurate grading and staging of the cancer. A novel approach is described for the procurement of fresh and freshly frozen prostatic tissue with acceptable limitations on subsequent morphological analysis. © 1994 Wiley‐Liss, Inc.