bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of cell‐to‐cell communication in non‐tumorigenic and malignant human prostate epithelial cells
Authors: Carruba Giuseppe , Webber Mukta M. , Quader Salmaan T.A. , Amoroso Maria , Cocciadiferro Letizia , Saladino Francesca , Trosko James E. , Castagnetta Luigi A.M. 
Published: October 2004

AbstractBACKGROUNDGap‐junction‐mediated intercellular communication (GJIC) is required for normal development and tissue homeostasis. However, the role of GJIC in human prostate carcinogenesis and progression remains ill‐defined.METHODSThe ability of hormones, anti‐hormones, and the anti‐hypertensive drug, forskolin, to restore GJIC in non‐tumorigenic (RWPE‐1 and PWR‐1E) and malignant (RWPE‐2, LNCaP, DU‐145) human prostate epithelial cell lines, was examined by Scrape‐Loading/Dye Transfer (SL/DT) and Fluorescence Recovery After Photobleaching (FRAP) methods using an Ultima laser cytometer.RESULTSResults from both assays show that PWR‐1E, RWPE‐2, LNCaP, and DU‐145 cells have weak or absent GJIC activity. However, the non‐tumorigenic RWPE‐1 cells showed restoration of some GJIC (nearly 10%) after 1 hr in the FRAP assay. Forskolin and estrone, which increase intracellular cAMP levels, induced a significant and consistent increase (2.8‐ and 4.4‐fold, respectively) in cell‐to‐cell communication only in the non‐tumorigenic RWPE‐1 cells. Furthermore, estrone induced a two‐fold increase in connexin 43 (Cx43) and a 30% decrease in Cx32 expression, while forskolin caused a 50% reduction in Cx32 with no effect on Cx43 expression in RWPE‐1 cells.CONCLUSIONSThese data suggest that agents that increase Cx43:Cx32 ratio may be used to restore GJIC in junctionally‐deficient, non‐tumorigenic immortalized cells, thus providing insights into potential mechanisms responsible for the multistep carcinogenesis in the human prostate. Prostate 50: 73–82, 2002. © 2002 Wiley‐Liss, Inc.
Androgens modulate the balance between VEGF and angiopoietin expression in prostate epithelial and smooth muscle cells
Authors: Richard Christian , Kim Gilbert , Koikawa Yasuhiro , Salm Sarah N. , Tsujimura Akira , Wilson E. Lynette , Moscatelli David 
Published: October 2004

AbstractBACKGROUNDThe vasculature of the prostate responds to androgens. Androgens most likely affect the vasculature indirectly by modulating the expression of angiogenic factors in the cells of the prostate. Most studies to date have examined the production of angiogenic factors by the prostate luminal epithelium. Here we examine the effects of androgen on production of three angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin‐1, and angiopoietin‐2, by the three major cell types in the prostate.METHODSThe ability of androgen to modulate VEGF, angiopoietin‐1, and angiopoietin‐2 production in cultured mouse prostate luminal epithelial, basal epithelial, and smooth muscle cells (SMCs) was assessed by Western blot and RT‐PCR.RESULTSThe production of VEGF was modulated by androgens in both luminal epithelial and prostate SMCs but not in basal epithelial cells. However, in prostate luminal epithelial cell cultures, VEGF was predominately secreted apically, suggesting that in vivo most of the epithelium‐derived VEGF is unavailable to the underlying blood vessels. In addition, prostate luminal epithelial cells produced angiopoietin‐2, an angiogenesis inhibitor. In contrast, prostate SMCs produced angiopoietin‐1, a positive modulator of angiogenesis. Synthesis of the angiopoietins did not respond to androgen treatment.CONCLUSIONSProstate smooth muscle may play an important role in regulating vascular responses to androgen. Prostate 50: 83–91, 2002. © 2002 Wiley‐Liss, Inc.
Down‐regulation of human X‐box binding protein 1 (hXBP‐1) expression correlates with tumor progression in human prostate cancers
Authors: Takahashi Satoru , Suzuki Shugo , Inaguma Shingo , Ikeda Yoshihisa , Cho Young‐Man , Nishiyama Naoki , Fujita Tamio , Inoue Takahiro , Hioki Takuichi , Sugimura Yoshiki , Ushijima Toshikazu , Shirai Tomoyuki 
Published: October 2004

AbstractBACKGROUNDIn our previous study, the gene encoding the human X‐box binding protein 1 (hXBP‐1) was isolated as a down‐regulated gene in advanced prostate cancers using cDNA‐representational difference analysis (RDA). In the present investigation, we characterized alterations of hXBP‐1 in prostate cancer specimens.METHODSExpression patterns of hXBP‐1 in a series of human prostate cancers were examined by Northern blotting, mRNA in situ hybridization or immunohistochemistry. Loss of heteozygosity (LOH) analysis using microsatellite markers and gene mutation analysis in the hXBP‐1 region were also performed.RESULTSExpression of hXBP‐1 was localized in epithelial and adenocarcinoma cells of the prostate. An inverse correlation between hXBP‐1 expression and histological differentiation was found in a series of prostate cancers without hormonal therapy. Majority of refractory cancer cases exhibited weak hXBP‐1 expression. No allelic loss or gene mutations were found in the hXBP‐1 region and its open reading frame, respectively, in the prostate cancer examined.CONCLUSIONSThese results suggest that reduction of hXBP‐1 expression may be a useful marker for prostate adenocarcinoma differentiation and progression. Prostate 50: 154–161, 2002. © 2002 Wiley‐Liss, Inc.
Different profiles of neuroendocrine cell differentiation evolve in the PC‐310 human prostate cancer model during long‐term androgen deprivation
Authors: Jongsma Johan , Oomen Monique H. , Noordzij Marinus A. , Van Weerden Wytske M. , Martens Gerard J. M. , van der Kwast Theodorus H. , Schröder Fritz H. , van Steenbrugge Gert J. 
Published: October 2004

AbstractBACKGROUNDNeuroendocrine (NE) cells are androgen‐independent cells and secrete growth‐modulating peptide hormones via a regulated secretory pathway (RSP). We studied NE differentiation after long‐term androgen withdrawal in the androgen‐dependent human prostate cancer xenograft PC‐310.METHODSTumor‐bearing nude mice were killed at 0, 2, 5, 7, 14, 21, 47, 84, and 154 days after castration. The half‐life of the PC‐310 tumor was 10 days, with a stable residual tumor volume of 30–40% after 21 days and longer periods of androgen deprivation.RESULTSProliferative activity and prostate‐specific antigen serum levels decreased to zero after castration, whereas cell‐cycle arrest was manifested by increased p27kip1 expression. A temporary downregulation of androgen receptor (AR) expression was noted after androgen deprivation. The expression of chromogranin A, secretogranin III, and secretogranin V (7B2) increased 5 days after castration and later. Subsequently, pro‐hormone convertase 1 and peptidyl α–amidating monooxygenase as well as vascular endothelial growth factor were expressed from 7 days after castration on. Finally, such growth factors as gastrin‐releasing peptide and serotonin were expressed in a small part of the NE cells 21 days after castration, but strong expression was induced late during androgen deprivation, that is, 84 and 154 days after castration, respectively.CONCLUSIONSAndrogen deprivation of the NE‐differentiated PC‐310 model induced the formation of NE‐differentiated AR− and non‐NE AR+ tumor residues. The NE‐differentiated cells actively produced growth factors via an RSP that may lead to hormone‐refractory disease. The dormant non‐NE AR+ tumor cells were shown to remain androgen sensitive even after long‐term androgen deprivation. In the PC‐310 xenograft, time‐dependent NE differentiation and subsequent maturation were induced after androgen depletion. The androgen‐dependent PC‐310 xenograft model constitutes an excellent model for studying the role of NE cells in the progression of clinical prostate cancer. Prostate 50: 203–215, 2002. © 2002 Wiley‐Liss, Inc.
Role of family history and ethnicity on the mode and age of prostate cancer presentation*
Authors: Cotter Michael P. , Gern Robert W. , Ho Gloria Y. F. , Chang Richard Y. , Burk Robert D. 
Published: October 2004

AbstractBACKGROUNDThis study was conducted to investigate the role of family history of prostate cancer and ethnic variation on age at diagnosis and the mode of prostate cancer presentation among a multiracial cohort of men in the Bronx and on Long Island.METHODSA retrospective hospital‐based study of 953 men (62% white, 24% African‐American, 9% Hispanic, and 5% other ethnicities) with biopsy‐confirmed prostate cancer diagnosed between 1991 and 1996. Data were collected between 1996 and 1998 using self‐administered questionnaires that assessed age at diagnosis, ethnicity, family history of prostate cancer, and first indication of potential prostate cancer.RESULTSMen with a family history of prostate cancer were diagnosed at an earlier mean age than those who lacked a family history (P < 0.001). Prostate cancer patients with an affected father had a significantly lower mean age at diagnosis than those patients who indicated that at least one brother (but not their father) was affected (P < 0.001). African‐Americans reported a family history of prostate cancer more often than whites (P < 0.01) and were younger at diagnosis (P < 0.0001). Hispanic patients were less likely to be identified by screening and more likely to present with symptoms compared with whites (P < 0.0001) and African‐Americans (P < 0.001).CONCLUSIONSMen with an affected father were more likely to have disease diagnosed at an early age. The lower rates of presentation by prostate cancer screening of Hispanic men with prostate cancer suggests that increased surveillance may be warranted in this population. Prostate 50: 216–221, 2002. © 2002 Wiley‐Liss, Inc.
Application of tissue‐marking ink to prostate biopsy specimens*
Authors: Terris Martha K. , McNeal John E. 
Published: October 2004

AbstractBACKGROUNDWhen sextant prostate biopsy specimens are performed, noting the location from which cancer‐containing cores were taken aids in treatment planning. However, many institutions include several cores in a single container, to cut costs. We have tried several methods of ink application and combining ink‐labeled biopsy specimens into fewer containers with the goal of maintaining information regarding location while minimizing the expense.METHODSSeveral approaches to the application of tissue‐marking ink to biopsy cores, core‐preparation methods, color combinations, and numbers of cores in each container were assessed.RESULTSThe ink adheres well to dry cores, but these cores often exhibit dehydration artifact. Placing the cores on a wet sponge avoids dehydration but causes ink spread. Excessive ink application occurs with eyedroppers and syringes but is avoided by touching each core with an ink‐moistened cotton swab. Application of 1% acetic acid to the inked core promotes congealing of the ink onto the tissue. Yellow, orange, and red ink are more difficult to distinguish than blue, black, or green. Deciphering distinct cores when three or more cores are combined is difficult, especially if cores are fragmented.CONCLUSIONSWith our current protocol, all biopsy specimens are placed on separate moistened gauze sponges. Specimens from the right side of the prostate are marked by green ink, and those from the left side are marked by black ink with a cotton swab. After applying 1% acetic acid to each core, the left and right cores from each location are placed in a single container. This method curbs pathology expenses and maintains tumor location information. Prostate 50: 247–251, 2002. © Wiley‐Liss, Inc.
Human cell lines as an in vitro/in vivo model for prostate carcinogenesis and progression
Authors: Webber Mukta M. , Quader Salmaan T.A. , Kleinman Hynda K. , Bello‐DeOcampo Diana , Storto Patrick D. , Bice Gillian , DeMendonca‐Calaca Wanderley , Williams Daniel E. 
Published: October 2004

AbstractBACKGROUNDThe study of prostate carcinogenesis and tumor progression is made difficult by the lack of appropriate in vitro and in vivo models. High prevalence of prostatic intra‐epithelial neoplasia and latent prostatic carcinoma, representing multiple steps in carcinogenesis to invasive carcinoma, are relevant targets for cancer prevention. From the RWPE‐1, immortalized, non‐tumorigenic, human prostate epithelial cell line, we have derived four tumorigenic cell lines with progressive malignant characteristics.METHODSCell lines were derived by exposure of RWPE‐1 to N‐methyl‐N‐nitrosourea (MNU), selected and cloned in vivo and in vitro, and characterized by prostatic epithelial and differentiation markers, karyotype analysis, anchorage‐independent growth, invasiveness, tumorigenicity, and pathology of the derived tumors.RESULTSCytokeratins 8 and 18, androgen receptor, and prostate‐specific antigen expression in response to androgen, confirm prostatic epithelial origin. RWPE‐1 cells do not grow in agar and are not tumorigenic in mice, but the growth, tumorigenicity, and tumor pathology of the MNU cell lines correlate with their invasive ability. The WPE1‐NA22 (least malignant) form small, well‐differentiated, and WPE1‐NB26 cells (most malignant) form large, poorly differentiated, invasive tumors. Overall, loss of heterozygosity for chromosomes 7q, 13q, 18q, and 22, and gain of 5, 9q, 11q, and 20, was observed. The MNU cell lines, in order of increasing malignancy are; WPE1‐NA22, WPE1‐NB14, WPE1‐NB11, and WPE1‐NB26.CONCLUSIONSThis family of cell lines with a common lineage represents a unique and relevant model which mimics stages in prostatic intra‐epithelial neoplasia (PIN) and progression to invasive cancer, and can be used to study carcinogenesis, progression, intervention, and chemoprevention. Prostate 47:1–13, 2001. © 2001 Wiley‐Liss, Inc.
High‐grade prostate intraepithelial neoplasia shares cytogenetic alterations with invasive prostate cancer
Authors: Alcaraz Antonio , Barranco Miguel A. , Corral Juan M. , Ribal Maria J. , Carrió Ana , Mallofré Carme , Llopis Juan , Cetina Alfredo , Alvarez‐Vijande Ricardo 
Published: October 2004

AbstractBACKGROUNDHigh‐grade prostate intraepithelial neoplasia (PIN) is the most likely precursor of prostate adenocarcinoma. However, the relationship between this lesion and prostate cancer has not yet been established. The detection of cytogenetic changes in the lesions prior to prostate adenocarcinoma would be useful in demonstrating such a pathogenic relationship.METHODSTwenty eight high‐grade PIN cases were found among 57 specimens of radical prostatectomy performed for clinically localized prostate cancer. Fluorescence in situ hybridization (FISH) analysis using centromeric probes to enumerate chromosomes 7, 8, 10, and 12 was performed to study the numerical chromosome alterations. FISH analysis was carried out over isolated nuclei obtained from high‐grade PIN areas and prostate cancer foci in the same prostatectomy specimen.RESULTSOf the 28 suitable cases it was possible to complete the study in 26 tumor and 20 PIN areas. The remaining cases were excluded because of insufficient tissue or poor preservation. Cytogenetic alterations (aneuploidy) were found in 16 of the 26 (62%) tumors studied. The most frequent chromosome alteration was trisomy 7, detected in 12 (75%) aneuploid tumors, followed by monosomy 8 present in 5 (31%) aneuploid tumors. Trisomy 7 was also the most frequent isolated chromosome alteration since it was detected in 7 (44%) tumors. Thirteen of 20 (65%) PIN cases were aneuploid when studied by FISH. Trisomy 7, trisomy 8, and monosomy 8 were the most common cytogenetic alterations in the 20 PIN areas studied, being observed in nine (45%), six (30%), and four (20%) cases, respectively. FISH analysis showed a high correlation (75% cases) in ploidy and pattern of cytogenetic alterations between high‐grade PIN areas and the paired prostate cancer focus in the same specimen.CONCLUSIONSThe above results show a cytogenetic link between high‐grade PIN and prostate cancer, suggesting that the former could be an early form of prostate cancer. Prostate 47:29–35, 2001. © 2001 Wiley‐Liss, Inc.
Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells
Authors: Iguchi Kazuhiro , Okumura Naoya , Usui Shigeyuki , Sajiki Hironao , Hirota Kosaku , Hirano Kazuyuki 
Published: October 2004

AbstractBACKGROUNDProstatic tumors are well known to progress to hormonal therapy‐resistant terminal states. At this stage, there are no chemotherapeutic agents to affect clinical outcome. An effective cell death inducer for these prostate cells may be a candidate as an attractive antitumor agent. The extracts from S. repens have been used to improve the state of prostatic diseases and we have attempted to identify the effective component from the extract.METHODSCell viability was examined in LNCaP cells, an in vitro model for hormonal therapy‐resistant prostatic tumor.RESULTSWe found that exposure of the extract from S. repens resulted in cell death of LNCaP cells. We also identified myristoleic acid as one of the cytotoxic components in the extract. The cell death exhibited both apoptotic and necrotic nuclear morphology as determined by Hoechst 33342 staining. Cell death was also partially associated with caspase activation.CONCLUSIONSIt was demonstrated that the extract from S. repens and myristoleic acid induces mixed cell death of apoptosis and necrosis in LNCaP cells. These results suggest that the extract and myristoleic acid may develop attractive new tools for the treatment of prostate cancer. Prostate 47:59–65, 2001. © 2001 Wiley‐Liss, Inc.
Androgen receptor expression in androgen‐independent prostate cancer cell lines
Authors: Chlenski Alexandre , Nakashiro Koh‐ichi , Ketels Kathleen V. , Korovaitseva Galina I. , Oyasu Ryoichi 
Published: October 2004

AbstractBACKGROUNDAlmost all attempts at establishing prostate carcinoma cell lines have resulted in generation of cells that are androgen‐independent, including commonly used LNCaP which expresses androgen receptor (AR) and AR‐negative Du145 and PC‐3. We attempted to clarify the mechanism(s) responsible for the failure to respond to androgen.METHODSCell lines LNCaP, CWR22R, PC‐3, Du145, and CA7T2CL were used to examine the AR promoter function with a reporter gene assay and its methylation status by Southern blot, PCR of bisulfite‐converted DNA, and 5‐aza‐2′‐deoxycytidine treatment. Structural abnormalities of the AR were identified by sequencing of reverse‐transcribed mRNA.RESULTSAll tested AR‐positive prostate carcinoma cells were capable of AR transcription at a significantly higher level than PC‐3 and Du145, thus suggesting relative deficiency of the transcription factors in the AR‐negative cells, further associated with methylation. Examination of CWR22R cells, which express the AR but are androgen‐independent, identified an in‐frame duplication of exon 3, which resulted in insertion of 39 amino acids in the DNA‐binding domain.CONCLUSIONSRelative deficiency of transcription factors associated with methylation is responsible for the lack of AR promoter function in most of AR‐negative cell lines. Mutations in the AR gene are present in the cells that express the AR but are androgen‐independent. Prostate 47:66–75, 2001. © 2001 Wiley‐Liss, Inc.
Vasoactive intestinal peptide (VIP) stimulates rat prostatic epithelial cell proliferation
Authors: Juarranz Maria G. , Bodega Guillermo , Prieto Juan C. , Guijarro Luis G. 
Published: October 2004

AbstractBACKGROUNDAndrogens play a major role in supporting normal growth and functional maintenance in the prostate. However, this gland contains an array of neuroendocrine peptides that can play a regulatory role in its physiopathology. Among these peptides, one of the best studied is vasoactive intestinal peptide (VIP), which is abundant in autonomic nerves surrounding both human and rat prostatic acini. This neuropeptide may act through interaction with two types of high‐affinity receptors, named VPAC1 and VPAC2 receptors. Another regulatory peptide, the pituitary adenylate cyclase‐activating peptide (PACAP), interacts with these receptors with the same affinity as VIP, but binds with higher affinity to PAC1 receptors. Human prostate tumors and rat prostate show a major presence of VPAC1 receptors, whereas various findings suggest a role for VIP in prostatic development. Here we studied the effects of VIP on the proliferation of rat prostatic epithelial cells in culture.METHODSWe studied the [3H]‐thymidine uptake by rat prostatic epithelial cells in culture, characterized previously by using biomarkers such as cytokeratin and vimentin. In these cells we tested the effect of VIP and PACAP‐27 on two different signaling pathways, the cyclic AMP (cAMP) and the inositol phosphate (IPs).RESULTSThe rat prostatic cells in culture were cytokeratin (5,6,8) and vimentin positive, indicating that the culture was predominantly epithelial. The proliferation curves showed that the cells followed different states of growth: a quiescent, an exponential proliferative, and a steady state. Cyclic AMP production, but not inositol phosphate production, was increased in the presence of VIP and PACAP‐27, which suggests the expression of VPAC1 and/or VPAC2 receptors primarily. VIP significantly increased prostatic cell proliferation in a bimodal manner, as shown for dibutyryl cyclic AMP (dbcAMP), which suggests that the effect of VIP upon prostatic proliferation is cAMP‐dependent.CONCLUSIONSHere, we demonstrate that VIP increased [3H]thymidine uptake by rat prostatic epithelial cells in culture, conceivably by the activation of the adenylate cyclase. Prostate 47:285–292, 2001. © 2001 Wiley‐Liss, Inc.
Neuroendocrine cells in human prostate over‐express the anti‐apoptosis protein survivin
Authors: Xing Nianzeng , Qian Junqi , Bostwick David , Bergstralh Erik , Young Charles Y.F. 
Published: October 2004

AbstractBACKGROUNDNeuroendocrine (NE) differentiation may be related to the growth and progression of prostate cancer, especially androgen‐insensitive tumors. Recently the over‐expression of a new anti‐apoptosis protein, survivin, has attracted attention for its potential implication in many human cancers. The fact that NE cells in prostate are bcl‐2 negative prompted us to investigate if the prostatic NE cells over‐express survivin.METHODSDouble immunohistochemical staining and immunofluorescence of chromogranin A (CgA) and survivin were performed in 57 patients with localized prostate cancer who underwent radical prostatectomy. The terminal deoxynucleotidyl transferase (TDT)‐mediated dUTP‐digoxigenin nick end‐labeling (TUNEL) method was used for apoptosis detection in three prostate cancer specimens with NE differentiation. The relationship between NE differentiation and clinicopathological characteristics, disease progression as well as patient survival, were analyzed retrospectively.RESULTSIt was found that NE cells in both benign and malignant prostate tissues over‐expressed the anti‐apoptosis protein survivin. While apoptosis was detected in non‐NE epithelial cells, all NE cells were negative for apoptosis detection. During the period of follow‐up, 17 (63%) of 27 patients with NE differentiation had prostate cancer progression, while 12 (40%) of 30 patients without NE differentiation had systemic prostate cancer progression. 10 (37%) of 27 patients with NE differentiation died from prostate cancer during the period of follow up, while 6 (20%) of 30 patients without NE differentiation died from prostate cancer. However, none of these characteristics reached statistical significance, probably because of the small number of cases enrolled.CONCLUSIONSThis study discovers that all the prostatic NE cells express the new anti‐apoptosis protein survivin. This provides a strong molecular basis for the hypothesis that NE cells may endure stressful conditions and escape from apoptosis. While our results suggest a trend of NE differentiation with poorer prognosis, the prognosis implication cannot be concluded due to our small sample size. Prostate 48:7–15, 2001. © 2001 Wiley‐Liss, Inc.