bluuebunny/crossref_metadata_2025 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

BACKGROUND

Gap‐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.

METHODS

The 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.

RESULTS

Results 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.

CONCLUSIONS

These 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

BACKGROUND

The 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.

METHODS

The 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.

RESULTS

The 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.

CONCLUSIONS

Prostate 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

BACKGROUND

In 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.

METHODS

Expression 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.

RESULTS

Expression 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.

CONCLUSIONS

These 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

BACKGROUND

Neuroendocrine (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.

METHODS

Tumor‐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.

RESULTS

Proliferative 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.

CONCLUSIONS

Androgen 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

BACKGROUND

This 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.

METHODS

A 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.

RESULTS

Men 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).

CONCLUSIONS

Men 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

BACKGROUND

When 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.

METHODS

Several 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.

RESULTS

The 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.

CONCLUSIONS

With 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

BACKGROUND

The 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.

METHODS

Cell 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.

RESULTS

Cytokeratins 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.

CONCLUSIONS

This 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

BACKGROUND

High‐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.

METHODS

Twenty 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.

RESULTS

Of 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.

CONCLUSIONS

The 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

BACKGROUND

Prostatic 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.

METHODS

Cell viability was examined in LNCaP cells, an in vitro model for hormonal therapy‐resistant prostatic tumor.

RESULTS

We 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.

CONCLUSIONS

It 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

BACKGROUND

Almost 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.

METHODS

Cell 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.

RESULTS

All 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.

CONCLUSIONS

Relative 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

BACKGROUND

Androgens 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.

METHODS

We 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).

RESULTS

The 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.

CONCLUSIONS

Here, 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

BACKGROUND

Neuroendocrine (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.

METHODS

Double 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.

RESULTS

It 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.

CONCLUSIONS

This 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.
Effects of Bowman–Birk inhibitor concentrate (BBIC) in patients with benign prostatic hyperplasia*†
Authors: Malkowicz S. Bruce , McKenna W. Gillies , Vaughn David J. , Wan X. Steven , Propert Kathleen J. , Rockwell Kenneth , Marks Sheldon H.F. , Wein Alan J. , Kennedy Ann R.
Published: October 2004

BACKGROUND

The Bowman–Birk inhibitor is a soybean‐derived protease inhibitor that has anti‐inflammatory and anticarcinogenic activities.

METHODS

A Phase I trial of Bowman–Birk inhibitor concentrate (BBIC) in 19 male subjects with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) has been performed.

RESULTS

The results of the trial indicated that there was no dose‐limiting toxicity of BBIC. There was a statistically significant decrease in serum PSA levels in all BBIC‐treated patients. Some BBIC‐treated patients exhibited a relatively large reduction in serum PSA levels, ranging up to a 43% reduction. There was also a statistically significant decrease in serum triglyceride levels and a decrease in prostate volume in the treated patients. The scores recorded in response to a urinary symptom questionnaire indicated improved urinary activities in the BBIC‐treated patients; however, the control subjects exhibited similar improvements in urinary activities during the course of the trial.

CONCLUSIONS

The data obtained in this trial, particularly the data suggesting that BBIC treatment may lead to reduced serum PSA levels and reduced prostate volumes, suggest that a Phase II clinical trial of BBIC for the therapy of BPH is warranted. Prostate 48:16–28, 2001. © 2001 Wiley‐Liss, Inc.
Anti‐interleukin‐6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice
Authors: Smith Peter C. , Keller Evan T.
Published: October 2004

BACKGROUND

Despite clinical associations and in vitro data suggesting that autocrine interleukin‐6 (IL‐6) production contributes to prostate cancer progression or chemotherapy resistance, there have been no reports that explore the role of IL‐6 on prostate tumors in vivo. In the present study, we investigated the effect of IL‐6 inhibition on the growth of human prostate cancer xenografts in nude mice.

METHODS

To determine if autocrine IL‐6 production contributes to prostate cancer growth and chemotherapy resistance in vivo, xenografts of a human prostate cancer cell line that produces IL‐6 (PC‐3) were established in nude mice. The mice were randomly divided into four treatment groups: (1) saline (vehicle control) + murine IgG (isotype control); (2) etoposide + murine IgG; (3) saline + anti‐IL‐6 monoclonal antibody; and (4) etoposide + anti‐IL‐6 monoclonal antibody. Tumors were measured twice weekly during a 4‐week treatment period. At the conclusion of the study, all mice were sacrificed, and in addition to final volume, tumors were evaluated for the degree of apoptosis by TUNEL analysis.

RESULTS

Anti‐IL‐6 Ab (with saline or etoposide) induced tumor apoptosis and regression (∼60% compared to initial tumor size). Etoposide alone did not induce tumor regression or apoptosis in this animal model, and there was no synergy between anti‐IL‐6 Ab and etoposide.

CONCLUSIONS

These studies suggest that IL‐6 contributes to prostate cancer growth in vivo, and that targeting IL‐6 may contribute to prostate cancer therapy. Prostate 48:47–53, 2001. © 2001 Wiley‐Liss, Inc.
Computation of a penetration measure between 3D convex polyhedral objects for collision detection
Authors: Sridharan K. , Keerthi S. S.
Published: October 2004

Measures to characterize the penetration between a pair of intersecting objects are given, based on translating one object to separate from the other. Algorithms to compute a measure between convex polyhedral objects in ℜ3are presented for two different input representations. These algorithms have linear expected running time. Details of experiments in collision detection for 3D objects using the penetration measure are also presented. © 2001 John Wiley & Sons, Inc.
Vertex‐distinguishing edge colorings of random graphs
Authors: Balister P. N.
Published: October 2004

A proper edge coloring of a simple graph G is called vertex‐distinguishing if no two distinct vertices are incident to the same set of colors. We prove that the minimum number of colors required for a vertex‐distinguishing coloring of a random graph of order n is almost always equal to the maximum degree Δ(G) of the graph. © 2002 John Wiley & Sons, Inc. Random Struct. Alg., 20, 89–97, 2002
Testing the diameter of graphs
Authors: Parnas Michal , Ron Dana
Published: October 2004

We propose a general model for testing graph properties, which extends and simplifies the bounded degree model of Goldreich and Ron [Property Testing in Bounded Degree Graphs, Proc. 31st Annual ACM Symposium on the Theory of Computing, 1997, pp. 406–415.] In this model, we present a family of algorithms that test whether the diameter of a graph is bounded by a given parameterD, or is ϵ‐far from any graph with diameter at most β(D). The function β(D) ranges betweenD+4 and 4D+2, depending on the algorithm. All our algorithms run in time polynomial in 1/ϵ. © 2002 Wiley Periodicals, Inc. Random Struct. Alg. 20: 165–183, 2002
Extremal problems on set systems
Authors: Frankl Peter , Rödl Vojtěch
Published: October 2004

For a family \documentclass{article}\pagestyle{empty}\begin{document}$\boldmath{F}(k) = \{{\mathcal F}_1^{(k)}, {\mathcal F}_2^{(k)},\ldots,{\mathcal F}_t^{(k)}\}$\end{document} of k‐uniform hypergraphs let ex (n,F(k)) denote the maximum number of k‐tuples which a k‐uniform hypergraph on n vertices may have, while not containing any member of F(k). Let rk(n) denote the maximum cardinality of a set of integers Z⊂[n], where Z contains no arithmetic progression of length k. For any k≥3 we introduce families \documentclass{article}\pagestyle{empty}\begin{document}$\boldmath{F}(k) = \{{\mathcal F}_1^{(k)},{\mathcal F}_2^{(k)}\}$\end{document} and prove that
nk−2rk(n)≤ex (nk2,F(k))≤cknk−1
holds. We conjecture that ex(n,F(k))=o(nk−1) holds. If true, this would imply a celebrated result of Szemerédi stating that rk(n)=o(n). By an earlier result o Ruzsa and Szemerédi, our conjecture is known to be true for k=3. The main objective of this article is to verify the conjecture for k=4. We also consider some related problems. © 2002 Wiley Periodicals, Inc. Random Struct. Alg. 20: 131–164, 2002.
Testing properties of directed graphs: acyclicity and connectivity*
Authors: Bender Michael A. , Ron Dana
Published: October 2004

This article initiates the study of testing properties of directed graphs. In particular, the article considers the most basic property of directed graphs—acyclicity. Because the choice of representation affects the choice of algorithm, the two main representations of graphs are studied. For the adjacency‐matrix representation, most appropriate for dense graphs, a testing algorithm is developed that requires query and time complexity of\documentclass{article}\pagestyle{empty}\begin{document}$\widetilde{O}(1/\epsilon^2)$\end{document}, where ϵ is a distance parameterindependentof the size of the graph. The algorithm, which can probe the adjacency matrix of the graph, accepts every graph that is acyclic, and rejects, with probability at least 2/3, every graph whose adjacency matrix should be modified in at least ϵ fraction of its entries so that it becomes acyclic. For the incidence list representation, most appropriate for sparse graphs, an Ω(|V|1/3) lower bound is proved on the number of queries and the time required for testing, whereVis the set of vertices in the graph. Along with acyclicity, this article considers the property ofstrong connectivity. Contrasting upper and lower bounds are proved for the incidence list representation. In particular, if the testing algorithm can query on both incoming and outgoing edges at each vertex, then it is possible to test strong connectivity in\documentclass{article}\pagestyle{empty}\begin{document}$\widetilde{O}(1/\epsilon)$\end{document}time and query complexity. On the other hand, if the testing algorithm only has access to outgoing edges, then\documentclass{article}\pagestyle{empty}\begin{document}$\Omega(\sqrt{N})$\end{document}queries are required to test for strong connectivity. © 2002 Wiley Periodicals, Inc. Random Struct. Alg. 20: 184–205, 2002
Inexpensived‐dimensional matchings
Authors: Huang Bae‐Shi , Perković Ljubomir , Schmutz Eric
Published: October 2004

Suppose that independentU(0, 1) weights are assigned to the\documentclass{article}\pagestyle{empty}\begin{document}${d\choose 2}n^{2}$\end{document}edges of the completed‐partite graph withnvertices in each of thedmaximal independent sets. Then the expected weight of the minimum‐weight perfectd‐dimensional matching is at least\documentclass{article}\pagestyle{empty}\begin{document}$\frac{3}{16}n^{1-(2/d)}$\end{document}. We describe a randomized algorithm that finds a perfectd‐dimensional matching whose expected weight is at most 5d3n1−(2/d)+d15for alld≥3 andn≥1. © 2002 John Wiley & Sons, Inc. Random Struct. Alg., 20, 50–58, 2002
Facial caricature drawing based on subjective impressions
Authors: Iwashita Shino , Onisawa Takehisa
Published: October 2004

In conventional studies of facial caricature drawing, image processing of a face picture is performed, and feature points are extracted. A caricature is drawn based on these points. On the other hand, there have been few studies of facial caricature drawing based on impressions, which are subjective and dependent on the person who views the face. The purpose of this paper is to draw a facial caricature using linguistic expressions in order to reflect personal impressions of a face. Cheerfulness, gentleness, and so on are considered as impressions of a face. The drawn facial caricature can be modified by the use of linguistic terms. The concept of exaggeration, which is important for emphasis of personality in a caricature drawing, is also introduced by considering the line thickness and the exaggeration rate. Facial caricatures are evaluated by subjects who themselves draw them by the presented method, and also by other subjects, and the validity of the process is discussed.© 2001 Scripta Technica, Syst Comp Jpn, 32(10): 1–12, 2001
On the computational capability of recurrent higher‐order neural networks
Authors: Tanaka Ken , Hasegawa Daigo
Published: October 2004

A neural network composed of a finite number of continuous value output neurons is known to be able to simulate any deterministic Turing machine. Several simulation models have been proposed, but there remains the problem that a massive number of neurons is needed to simulate the tape part in real time. In this paper the authors demonstrate that a recurrent higher‐order neural network can simulate any Turing machine, then specify the lower limit for the number of neurons required and the time needed for the simulation. First, the authors show that a recurrent higher‐order neural network consisting of a limited number of neurons using a threshold input/output function and a linear input/output function can simulate any deterministic Turing machine in real time, and that the number of neurons required to simulate the tape can be reduced to six. Then the authors show that if a saw‐type function is used, the number of neurons required for the simulation can be reduced to four. A simplified simulation model is then offered as a viable framework for learning formal language using a neural network. © 2001 Scripta Technica, Syst Comp Jpn, 32(10): 42–50, 2001
Self windowing for high‐speed vision
Authors: Ishii Idaku , Ishikawa Masatoshi
Published: October 2004

With high‐speed vision systems such as vision chips that support frame rates much higher than video signal (NTSC 30 Hz), image variation is small from frame to frame. Using this feature of high‐speed vision, various image processing algorithms can be simplified. In particular, this paper proposes the Self Windowing algorithm for image segmentation and matching. Operability of the proposed algorithm was validated experimentally on S3PE vision chip architecture. © 2001 Scripta Technica, Syst Comp Jpn, 32(10): 51–58, 2001
Structure estimation of an articulated object by motion image analysis based on factorization method
Authors: Nagasaki Takeshi , Kawashima Toshio , Aoki Yoshinao
Published: October 2004

A method for obtaining the structure of a target object from a motion image sequence observed from the motions of an articulated object or a multiple number of objects is proposed. By this technique, the motion and structure of each rigid body part are estimated and the restricting relationships between rigid bodies are estimated in two stages when estimating the structure of an object with a large number of degrees of freedom such as an articulated object. In the first stage, the structure and motion of each rigid body are estimated based on observed information obtained by grouping observed feature points for each rigid body, by using a factorization method having robustness against observation noise. In the second stage, the restricting relationships between rigid bodies are estimated by using the motion parameters of each rigid body. In this paper, the presence and absence of joints and the order numbers of the restricting relationships between rigid bodies are classified in terms of the ranks of the coefficient matrices by considering rotating joints and expressing the restricting relationships as linear simultaneous equations. The proposed method is applied to simulations and observations of the motions of the hand and the back of the hand and its effectiveness is verified. © 2001 Scripta Technica, Syst Comp Jpn, 32(10): 69–79, 2001
Embryolethal and teratogenic effects of carbendazim in rats
Authors: Sitarek Krystyna
Published: October 2004

This study was performed to evaluate the effects of prenatal development of rats. Females were exposed to carbendazim by gavage every day on days 6–15 of gestation at doses 8, 35, 160 mg/kg b.w. Carbendazim administered at doses of 35 and 160 mg/kg was associated with significant maternal toxicity, embryonal lethality, congenital defects, and retarded fetal development. It produced encephalocele, umbilical hernia, missing or shorter tail, and internal malformations of brain, kidneys, and skeletal malformations of ribs, arch, and vertebrae. NOEL for the dam and fetus in our study was 8 mg/kg/day. Teratogenesis Carcinog. Mutagen. 21:335–340, 2001. © 2001 Wiley‐Liss, Inc.
Modeling layered distributed communication systems
Authors: Herzberg D. , Broy M.
Published: October 2004

Today, component-based software and system development has gained considerable attention and is wide-spread. Components and/or modules manifest the well-proven engineering principle of divide and conquer. Formal approaches have helped to provide a theoretical foundation to component-orientation. There is a broad range of system architectures in practice today in terms of layered distributed open systems (as for example known in telecommunications). However, the mathematical formalisms developed so far are rarely applied to these practical architectures. In fact, the notion of distribution and stacked communication layers is hardly understood precisely and not supported by architecture description languages. This article addresses this gap. The formal conditions of distribution and layering are investigated and a mathematical model for layered distributed systems is presented. Communication refinement and so-called complex connectors turn out to be vital concepts which are not addressed in today’s modeling languages. In addition to that, two important design approaches are derived for the architectural design of complex communication systems: A node-centric and a network-centric design approach. Both can significantly improve the design process.
Influence of age on natriuretic peptides in patients with chronic heart failure: a comparison between ANP/NT‐ANP and BNP/NT‐proBNP
Authors: Hogenhuis Jochem , Voors Adriaan A. , Jaarsma Tiny , Hillege Hans L. , Boomsma Frans , van Veldhuisen Dirk J.
Published: October 2004

Background:

Natriuretic peptides are currently used in the diagnosis and follow‐up of patients with Chronic Heart Failure (CHF). However, it is unknown whether there are different influences of age on atrial natriuretic peptide (ANP)/N‐terminal‐ANP (NT‐ANP) or B‐type natriuretic peptide (BNP)/N‐terminal‐proBNP (NT‐proBNP).

Aims:

To compare the influence of age and gender on plasma levels of ANP/NT‐ANP and BNP/NT‐proBNP in CHF patients.

Methods and results:

Natriuretic peptides were measured in 311 CHF patients (68±8 years, 76% males, left ventricular ejection fraction (LVEF) 0.23±0.08). All natriuretic peptides were significantly related to age (p<0.05) on multivariate regression analysis, with partial correlation coefficients of 0.18, 0.29, 0.28 and 0.25 for ANP, NT‐ANP, BNP and NT‐proBNP, respectively. The relative increase of both BNP/NT‐proBNP were more pronounced than of ANP/NT‐ANP (p<0.01). Furthermore, the relative increase of BNP with age was markedly larger than of NT‐proBNP (p<0.01). Levels of all natriuretic peptides were also significantly related to cardiothoracic ratio, renal function and LVEF.

Conclusion:

In patients with CHF, BNP/NT‐proBNP were more related to age than ANP/NT‐ANP, and BNP was more related to age than NT‐proBNP. However, in these CHF patients the influence of age on the levels of all natriuretic peptides was modest, and comparable to several other factors.
Soluble TNF‐α and interleukin‐6 receptors in the urine of heart failure patients. Their clinical value and relationship with plasma levels
Authors: Rivera Miguel , Taléns‐Visconti Raquel , Sirera Rafael , Bertomeu Vicente , Salvador Antonio , Cortés Raquel , de Burgos Fernando García , Climent Vicente , Payá Rafael , Martinez‐Dolz Luis , Sancho‐Tello Maria Jose , González‐Molina Andrés
Published: October 2004

Background:

Proinflammatory cytokines are important mediators in heart failure (HF). Recently, urinary levels of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) have been determined.

Aims:

The purpose of this study was to measure the urinary levels of TNF‐α and IL‐6 receptors, sTNF‐RI, sTNF‐RII, sIL‐6R, and the relationship with plasma levels and NYHA classes in HF.

Methods:

Plasma and urine were collected from 114 HF patients and sTNF‐RI, sTNF‐RII and sIL‐6R (ng/ml) were analyzed.

Results:

For the whole population, plasma levels of sTNF‐RI were 2.1±0.1, of sTNF‐RII were 5.0±0.3 and of sIL‐6R were 49.8±2.5. Urinary levels were: sTNF‐RI, 2.8±0.5, r=0.5, p<0.001; sTNF‐RII, 12.6±2.1, r=0.4, p<0.001; and sIL‐6R, 4.2±0.4, NS. In NYHA III subjects, we found sTNF‐RI, r=0.6, p<0.01, sTNF‐RII, r=0.5, p<0.05, and sILR‐6, r=0.5, p<0.05. Both plasma TNF receptors and urinary levels of sTNF‐RII were higher in patients in a more severe NYHA class (p<0.05).

Conclusions:

Urine is a good environment to study sTNF‐RI and sTNF‐RII, and this fact has diagnostic and prognostic implications. Plasma and urinary levels of TNF receptors showed a fair correlation, which was increased in higher NYHA classes. Plasma and urinary levels of sIL6R showed a good correlation in NYHA III. The TNF receptor levels in urine increased in patients with more severe HF.
Relation between free triiodothyronine/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy
Authors: Kozdag Guliz , Ural Dilek , Vural Ahmet , Agacdiken Aysen , Kahraman Goksel , Sahin Tayfun , Ural Ertan , Komsuoglu Baki
Published: October 2004

Background:

Abnormalities in thyroid function are frequent in patients with heart failure and are associated with increased mortality. However, the relation between thyroid hormone levels and echocardiographic parameters has not been investigated sufficiently.

Aim:

The aims of this study were to investigate the correlations of thyroid hormone levels with echocardiographic parameters and to evaluate their associations with subsequent mortality in a group of patients with dilated cardiomyopathy (DCMP).

Methods:

Serum levels of thyroid hormones were measured in 111 consecutive patients with DCMP (35 female, 76 male, mean age: 62±12 years). All patients underwent echocardiographic examination and were followed‐up for a period of 12±8 months.

Results:

Twenty‐three patients (21%) had abnormalities in thyroid function tests. Free triiodothyronine (fT3)/free thyroxine (fT4) ratio was significantly correlated with most of echocardiographic parameters, such as chamber diameters and ejection fraction. Sixteen patients (14%) died during the follow‐up period; their fT3/fT4 ratio was significantly lower than the patients who survived (1.31±0.37 vs. 2.01±0.72, p<0.001). A fT3/fT4 ratio of ≤1.7 was associated with an increased risk of mortality (p<0.001), independent of other prognostic markers. Sensitivity, specificity, positive and negative predictivity of fT3/fT4 ratio ≤1.7 for cardiac mortality were 100%, 71%, 36% and 100%, respectively.

Conclusion:

Determination of FT3/FT4 ratio may be a valuable and simple predictor for identification of patients with DCMP who are at high risk of subsequent mortality.
Plasma NT‐proBNP is a potential marker of disease severity and correlates with symptoms in patients with chronic rheumatic valve disease
Authors: Davutoglu Vedat , Celik Ahmet , Aksoy Mehmet , Sezen Yusuf , Soydinc Serdar , Gunay Nurullah
Published: October 2004

Background

A noninvasive marker of disease severity and presence of symptoms is required in patients with chronic rheumatic valve disease (RVD).

Aims

We sought to test the utility of measuring of N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) in chronic phase RVD. We also evaluated whether echocardiographic measures are interrelated with NT‐proBNP levels.

Methods

The study comprised 92 patients with RVD (mean age of 40–14 years) and 50 age/gender‐matched control subjects. Functional status was assessed. Detailed echocardiographic examination was performed and mitral valve score was estimated. Venous blood samples were taken for measuring the level of NT‐proBNP.

Results

The plasma levels of NT‐proBNP rose with increasing severity of mitral valve stenosis (p<0.001), increasing severity of mitral valve score (p<0.001), increasing severity of clinical symptom (p<0.001), increasing severity of mitral regurgitation (p<0.013), presence of mitral valve calcification (p<0.001), presence of tricuspid valve stenosis (p<0.001), increasing severity of tricuspid regurgitation (p<0.011), presence of aortic stenosis (p=0.043), decreasing left ventricular ejection fraction (p<0.001), presence of left atrial thrombus (p=0.0019), and with increasing left atrium dimensions (p=0.002).

Conclusion

NT‐proBNP levels in patients with chronic RVD are a potential marker of disease severity and correlates with symptoms.
Conservation of genetic variation in harvested salmon populations
Authors: Hindar Kjetil , Tufto Jarle , Sættem Leif Magnus , Balstad Torveig
Published: October 2004

Management of a group of Atlantic salmon (Salmo salar) populations that are harvested together in the ocean, but separately in freshwater, is looked at from a genetic perspective. A model that estimates total effective population size from local effective population sizes and migration patterns is applied to a system of ten salmon populations in the Sognefjorden district, western Norway. This population system is dominated numerically by the River Lærdalselva population, which may act as a source of migrants into nine smaller populations in a “source–sink” metapopulation. The total effective population size of this system is to a large extent dependent on the effective population size of the Lærdalselva population, but the contribution per spawner to the total effective population size is greater for a fish from the smaller populations than for a fish from Lærdalselva. The results are discussed in light of conservation genetic theory, and empirical results on the fitness consequences of loss of genetic variation in salmonids. The genetic consequences of harvesting need to be assessed both at the levels of local populations and the metapopulation.