bluuebunny/crossref_metadata_2025_split huggingface dataset:
Montelukast does not protect against hyperoxia‐induced inhibition of alveolarization in newborn rats
Authors: Jouvencel Philippe , Fayon Michael , Choukroun Marie‐Luce , Carles Dominique , Montaudon Danielle , Dumas Eric , Begueret Hughes , Marthan Roger 
Published: May 2003

AbstractImpaired lung development has been demonstrated in neonatal animals exposed to hyperoxia. High lung cys‐leukotriene levels may be a contributing factor towards the increase in oxygen toxicity. We investigated the effect of cysteinyl‐leukotriene inhibition using the receptor antagonist, montelukast (MK, Singulair®), on hyperoxia‐induced changes in lung parenchymal structure in neonatal rat pups. Rat pups were exposed to 21% O2 (air) or 50% O2 (moderate hyperoxia) from days 1–14 after birth, and were administered the cys‐leukotriene receptor antagonist MK (1 mg/kg/day) or normal saline from days 4–14. Somatic growth and morphometric measurements were done on day 15. There was a significant increase in bronchoalveolar lavage fluid cysteinyl‐leukotriene levels (+61.9%) when animals were exposed to hyperoxia. O2 exposure significantly decreased the specific internal surface area by 13%. There was a nonsignificant 5.8% and 19.6% increase in mean chord length and mean alveolar diameter, respectively, as well as an 8.6% decrease in lung volume to body weight ratio. Inhibition of only one arm of the arachidonic‐acid cascade by MK was not sufficient to prevent these oxygen‐induced changes. Pediatr Pulmonol. 2003; 35:446–451. © 2003 Wiley‐Liss, Inc.
Determination of maximal voluntary ventilation in children with cystic fibrosis
Authors: Stein Richard , Selvadurai Hiran , Coates Allan , Wilkes Donna L. , Schneiderman‐Walker Jane , Corey Mary 
Published: May 2003

AbstractMaximal voluntary ventilation (MVV) may be determined directly by the sprint method or calculated from pulmonary function data, using the functions MVV = forced expired volume in 1 sec (FEV1) × 35 or MVV = FEV1 × 40. The purpose of this paper was to test the validity of the equation over a wide range of lung function in children. Cystic fibrosis (CF), a chronic lung disease where children typically have a wide range of pulmonary function, was chosen as the study requirement. Spirometric data from 332 children with CF who underwent pulmonary function testing between 1987–2000 were stratified according to disease severity, and box‐plots comparing the ratio of MVV to FEV1 for each category were generated. As results indicated that the equation underestimates true MVV proportionally to the degree of airflow limitation, a new function to predict MVV for this population was derived and tested. The new equation was derived using data from patients who were tested on odd‐numbered days (group A). The validity of the new equation was then tested on the patients tested on even‐numbered days (group B). To test its validity, the results were compared to the “gold standard” sprint values using a Bland and Altman plot. MVV was expressed as a function of FEV1 and predicted FEV1: MVV = 27.7(FEV1) + 8.8(PredFEV1) (R2 = 0.98, P < 0.05). In this way, the accuracy of the new equation was confirmed. Whenever possible, we recommend MVV be determined by the sprint method in accordance with ATS guidelines. If this is not feasible, we recommend considering the new prediction equation. Pediatr Pulmonol. 2003; 35:467–471. © 2003 Wiley‐Liss, Inc.
PRAC2: A new gene expressed in human prostate and prostate cancer
Authors: Olsson Pär , Motegi Akira , Bera Tapan K. , Lee Byungkook , Pastan Ira 
Published: May 2003

AbstractBACKGROUNDThe database of human Expressed Sequence Tags was previously used to identify PRAC (Prostate 47:125–131, 2001), a novel gene specifically expressed in human prostate, prostate cancer, rectum, and distal colon. In this report, we have identified PRAC2, another gene with a similar expression pattern that is located adjacent to the original PRAC gene on chromosome 17q21.3.METHODSUsing a computer‐based analysis, a cluster of sequence homologous ESTs was identified that is mainly derived from human prostate cDNA libraries. The tissue specificity was examined by multiple tissue RNA dot blots and RT‐PCR. The PRAC2 transcript and protein were identified using Northern blot analysis, RACE‐PCR, primer extension, and Western blots.RESULTSPRAC2 encodes a 564 nucleotide RNA found in prostate, rectum, distal colon, and testis. Weak expression was also found in placenta, peripheral blood leukocytes, skin, and in two prostate cancer cell lines: LNCaP and PC‐3. The transcript seems to encode a 10.5‐kDa nuclear protein. The PRAC2 gene is located on chromosome 17 at position 17q21, between the Hoxb‐13 gene and the recently discovered PRAC gene.CONCLUSIONSBecause of the higher expression of PRAC2 in prostate and its proximity to Hoxb‐13, PRAC2 may have a function in prostate growth and development. Prostate 56: 123–130, 2003. © 2003 Wiley‐Liss, Inc.
Anti‐proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: Implication of epidermal growth factor receptor down‐regulation and ceramide production
Authors: Mimeault Murielle , Pommery Nicole , Wattez Nicole , Bailly Christian , Hénichart Jean‐Pierre 
Published: May 2003

AbstractBACKGROUNDAnandamide (ANA) is an endogenous lipid which acts as a cannabinoid receptor ligand and with potent anticarcinogenic activity in several cancer cell types.METHODSThe inhibitory effect of ANA on the epidermal growth factor receptor (EGFR) levels expressed on the EGF‐stimulated prostatic cancer cells LNCaP, DU145, and PC3 was estimated by ELISA tests. The anti‐proliferative and cytotoxic effects of ANA were also evaluated on these human prostatic cancer cell lines by growth tests, flow cytometric analyses, trypan blue dye exclusion assays combined with the Papanicolaou cytological staining method.RESULTSANA induced a decrease of EGFR levels on LNCaP, DU145, and PC3 prostatic cancer cells by acting through cannabinoid CB1 receptor subtype and this leaded to an inhibition of the EGF‐stimulated growth of these cells. Moreover, the G1 arrest of metastatic DU145 and PC3 growth was accompanied by a massive cell death by apoptosis and/or necrosis while LNCaP cells were less sensitive to cytotoxic effects of ANA. The apoptotic/necrotic responses induced by ANA on these prostatic cancer cells were also potentiated by the acidic ceramidase inhibitor, N‐oleoylethanolamine and partially inhibited by the specific ceramide synthetase inhibitor, fumonisin B1 indicating that these cytotoxic actions of ANA might be induced via the cellular ceramide production.CONCLUSIONSThe potent anti‐proliferative and cytotoxic effects of ANA on metastatic prostatic cancer cells might provide basis for the design of new therapeutic agents for effective treatment of recurrent and invasive prostatic cancers. Prostate 56: 1–12, 2003. © 2003 Wiley‐Liss, Inc.
Disabled infectious single cycle herpes simplex virus (DISC‐HSV) is a candidate vector system for gene delivery/expression of GM‐CSF in human prostate cancer therapy
Authors: Parkinson Richard J. , Mian Shahid , Bishop Michael C. , Gray Trevor , Li Geng , McArdle Stephanie E.B. , Ali Selman , Rees Robert C. 
Published: May 2003

AbstractBACKGROUNDDISC‐HSV is a replication incompetent herpes simplex virus that is a highly efficient vector for the transduction of genes in vivo and in vitro. We examine the ability of DISC‐HSV to infect human prostate cancer cell‐lines and xenograft tumor models, and induce expression of reporter and therapeutic cytokine genes.METHODSInfection was confirmed by cellular staining for the beta‐galactosidase reporter gene product, and by EM. Human GM‐CSF production following DISC‐hGMCSF infection was measured using ELISA. The metabolic activity of infected cells was determined by NADP/NADPH assay. Cell death was estimated by cell‐cycle analysis using flow cytometry with propidium iodide staining.RESULTSInfection of DU145, PC3 and LNCaP cells with DISC‐HSV was dose dependent. Cells infected with DISC‐hGM‐CSF released significant levels of hGM‐CSF for 3 days. NADP/NADPH assay suggested that infected cells continued to be metabolically active for 3 days post‐infection, which was consistent with flow cytometry findings that cell death did not occur within 7 days of infection. Tumor xenografts injected with DISC‐HSV expressed beta‐galactosidase, and intracellular viral particles were demonstrated using EM.CONCLUSIONSWe have previously reported the rejection of established tumors following intra‐tumoral injection of DISC‐GMCSF. This study demonstrates the ability of DISC‐HSV to infect prostate cancer and express GMCSF at significant levels. We suggest that prostate cancer is a potential target for therapy using DISC‐HSV containing GM‐CSF. Prostate 56: 65–73, 2003. © 2003 Wiley‐Liss, Inc.
Prostate‐specific antigen (PSA) protein does not affect growth of prostate cancer cells in vitro or prostate cancer xenografts in vivo
Authors: Denmeade Samuel R. , Litvinov Ivan , Sokoll Lori J. , Lilja Hans , Isaacs John T. 
Published: May 2003

AbstractBackgroundProstate‐specific antigen (PSA) is produced in high amounts by normal and malignant prostate cancer cells. PSA is a serine protease with substrates that include semenogelin I and II, insulin‐like growth factor binding protein 3, fibronectin, and laminin. PSA, via its enzymatic activity, may play a role in growth, invasion, and metastasis of prostate cancer cells. Recent data also suggest that the PSA protein itself, independent of enzymatic activity, may also function as an endothelial cell‐specific inhibitor of angiogenesis.MethodsHuman (PC3, DU145) and rat (AT2, AT6) prostate cancer cell lines were transfected with the full PSA gene encoding preproPSA protein. PSA‐producing clones of each cell line were selected and the amount of enzymatically active PSA produced by each cell line determined using a PSA‐specific fluorescent peptide substrate. In vitro and in vivo growth characteristics of PSA‐producing transfectants were compared to neomycin controls and wild type cells.ResultsAll selected clones produced and secreted PSA (5–120 ng/ml/105 cells). None of the PSA‐transfected cell lines produced detectable amounts of enzymatically active PSA. Production of enzymatically inactive PSA by prostate cancer cell lines did not alter growth kinetics in vitro. PSA‐producing xenograft doubling times in vivo were similar to neomycin controls and wild type.ConclusionAlthough recent reports suggest the PSA protein itself may be antiangiogenic, our results demonstrate that production of PSA protein by prostate cancer cells does not significantly alter growth in vitro or in vivo. Prostate 56: 45–53, 2003. © 2003 Wiley‐Liss, Inc.
Luteinizing hormone β polymorphism and risk of familial and sporadic prostate cancer
Authors: Elkins David A. , Yokomizo Akira , Thibodeau Stephen N. , J. Schaid Daniel , Cunningham Julie M. , Marks Angela , Christensen Eric , McDonnell Shannon K. , Slager Susan , J. Peterson Brett , J. Jacobsen Steven , R. Cerhan James , L. Blute Michael , J. Tindall Donald , Liu Wanguo 
Published: May 2003

AbstractBackgroundCirculating testosterone plays an important role in maintenance and growth of prostate cells. Luteinizing hormone (LH), secreted from the anterior pituitary, signals testicular Leydig cells to secrete testosterone. A genetic variant of the LH‐β protein, LH‐βV, exists in up to 40% of Caucasians and is more bioactive than the wild‐type protein. We hypothesized that genetically determined variation in LH function might affect susceptibility to prostate cancer via altered testosterone secretion.MethodsWe determined the frequency of the LH‐βV polymorphism (two linked polymorphisms: Trp8 → Arg and Ile15 → Thr) in familial prostate cancer patients (n = 446), in sporadic prostate cancer patients (n = 388), and in population‐based controls without prostate cancer (n = 510) to assess the role of this polymorphism in susceptibility to prostate cancer.ResultsA higher frequency of this variant genotype (LH‐βV: Arg8/Thr15) was observed in familial prostate cancer patients (18.6%) than in controls (13.7%), and after taking into account the correlation of the familial cases and adjusting for age and body mass index (BMI), there was a weak positive association between the variant LH‐β genotype, and risk of familial prostate cancer (OR = 1.29; 95% CI 0.96–1.75). The sporadic case group was also slightly more likely to have a variant genotype (15.2%) compared to the controls (13.7%), and after adjustment for age and BMI, a similar association with this variant was found (OR = 1.33; 95% CI 0.86–02.07). Surgical cases showed a slightly stronger association for the variant LH‐β genotype compared to non‐surgical cases, but among the surgical cases there was little variability in risk across nodal status, stage, and tumor grade.ConclusionsThese data are consistent with the hypothesis that the LH‐β variant is a weak risk factor for prostate cancer. Prostate 56: 30–36, 2003. © 2003 Wiley‐Liss, Inc.
Development of a quantitative RT‐PCR method to study 5α‐reductase mRNA isozymes in rat prostate in different androgen status
Authors: Torres Jesus M. , Ruiz Estrella , Ortega Esperanza 
Published: May 2003

AbstractBACKGROUNDThe incidence of prostate cancer (PCa) and benign prostatic hypertrophy (BPH) continues to rise in the Western world. The development and growth of the prostate gland depends on androgen stimulation. Dihydrotestosterone (DHT) is the primary androgen responsible for prostate development and also for the pathogenesis of benign prostatic hyperplasia (BPH). DHT is synthesized in prostate from circulating testosterone (T) through the action of 5α‐Reductase (5α‐R) (EC 1.3.99.5), which occurs as two isozymes, type‐1 and type‐2. Both types are expressed in the prostate: type‐2 isozyme is predominantly expressed in prostate and is implicated in BPH and PCa; type‐1 isozyme is also increased in some prostatic adenocarcinomas. In recent years, various inhibitors of type‐2 isozyme or of both type‐1 and type‐2 isozyme have been used in prostatic diseases.METHODSWe present the first published measurements of mRNA levels of steroid 5α‐R isozymes in the ventral prostate of rats of different androgen status. We used a novel method that combines the high specificity of competitive PCR with the sensitivity of laser‐induced capillary electrophoresis (LIF‐CE).RESULTSWe demonstrated that T and DHT androgens control the expression of both 5α‐R isozymes in rat prostrate.CONCLUSIONSThis approach could be of great value for the study of prostate diseases in humans and would allow study at the transcriptional level of the effects of drugs that inhibit either or both of these isozymes. Prostate 56: 74–79, 2003. © 2003 Wiley‐Liss, Inc.
Insulin‐like growth factor binding protein‐related protein 1 (IGFBP‐rP1/mac 25) is reduced in human prostate cancer and is inversely related to tumor volume and proliferation index in Lucap 23.12 xenografts
Authors: Tennant Marie K. , Vessella Robert L. , Sprenger Cynthia C. , Sikes Robert A. , Hwa Vivian , Baker Laura D. , Plymate Stephen R. 
Published: May 2003

AbstractBACKGROUNDIn the prostate, insulin‐like growth factor binding protein‐related protein‐1 (IGFBP‐rP1/mac 25) appears to be decreased in cancer. Likewise, mice injected with prostate cells over‐expressing IGFBP‐rP1/mac 25 showed decreased tumor formation and tumor volume.METHODSImmunohistochemistry was used to determine the presence of IGFBP‐rP1/mac 25 in human prostate tissue and in LuCaP 23.12 prostate cancer xenografts.RESULTSImmunoreactivity for IGFBP‐rP1/mac 25 was detected in the cytoplasm and nuclei of benign prostate epithelium. Cancer cells also stained but the level of intensity was less than that observed in benign epithelium (P < 0.05). Within the stroma, peripheral nerves, and endothelial vessels reacted with IGFBP‐rP1/mac 25 antibodies. IGFBP‐rP1/mac 25 was also observed in the nuclei of LuCaP 23.12 cells. LuCaP xenografts with smaller tumor volumes demonstrated more staining, and larger tumor volumes had less staining (P = 0.0033, R = 0.610). There was also a significant inverse correlation between IGFBP‐rP1/mac 25 levels in LuCaP 23.12 cells and the proliferative index, measured by percent of cells staining for 5‐bromo‐2′‐deoxyuridine (Br‐dU) (P = 0.0045, R = 0.594).CONCLUSIONSIGFBP‐rP1/mac 25 is present in normal prostate epithelium and is decreased in human prostate malignancy and higher IGFBP‐rP1/mac 25 levels are associated with reduced tumor growth. Prostate 56: 115–122, 2003. © 2003 Wiley‐Liss, Inc.
Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer
Authors: Chang Bao‐li , Zheng S. Lilly , Isaacs Sarah D. , Turner Aubrey R. , Bleecker Eugene R. , Walsh Patrick C. , Meyers Deborah A. , Isaacs William B. , Xu Jianfeng 
Published: May 2003

AbstractBackgroundThe 5 alpha‐reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case–control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date.MethodsThree SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer.ResultsWeak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the “T” allele. Similarly, family‐based association tests failed to observe significant over‐transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls.ConclusionsPolymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations. Prostate 56: 37–44, 2003. © 2003 Wiley‐Liss, Inc.
Anti‐androgenic action by red clover‐derived dietary isoflavones reduces non‐malignant prostate enlargement in aromatase knockout (arko) mice
Authors: Jarred Renea A. , McPherson Stephen J. , Jones Margaret E.E. , Simpson Evan R. , Risbridger Gail P. 
Published: May 2003

AbstractBackgroundRed clover (RC)‐derived dietary isoflavones have been implicated as potential preventative agents for the development and prevalence of non‐malignant prostate diseases. This study investigated whether dietary isoflavones inhibit prostate growth in vivo in the aromatase knock‐out (ArKO) mouse that exhibits lifelong elevation of androgens leading to prostate enlargement.MethodsAdult (11‐week‐old) wild‐type (WT) and ArKO mice were fed on protein matched isoflavones free (IF) and RC (isoflavone rich) diets for 28 days. Individual prostate lobes and testes were weighed and collected for histological analysis and serum androgens were measured. Responses were compared to castration and estrogen administration to ArKO mice to determine the mechanism of action.ResultsArKO mice fed on IF diet exhibited enlarged prostate lobes and elevated serum androgens compared to WT mice. Following 28 days of RC diet, ArKO VP, AP, and SV weights were reduced to WT weights, although testis and body weights remained unaltered. Stereological analysis of VPs revealed a reduction in all components of the tissue, particularly the lumen. The RC diet reduced ArKO serum testosterone and dihydrotestosterone to WT levels. In comparison to castration and estrogen administration, the dietary isoflavones were shown to be anti‐androgenic rather than weakly estrogenic, mimicking responses observed in the castrated ArKO, rather than estrogen treated ArKOs.ConclusionsThis study demonstrates that RC‐derived isoflavones have a significant effect on prostatic growth, and are capable of reducing the enlarged non‐malignant prostate phenotype of the adult ArKO mouse, by acting as anti‐androgenic agents rather than weak estrogenic substances. Prostate 56: 54–64, 2003. © 2003 Wiley‐Liss, Inc.
Possible mechanism of dexamethasone therapy for prostate cancer: Suppression of circulating level of interleukin‐6
Authors: Akakura Koichiro , Suzuki Hiroyoshi , Ueda Takeshi , Komiya Akira , Ichikawa Tomohiko , Igarashi Tatsuo , Ito Haruo 
Published: May 2003

AbstractBACKGROUNDGlucocorticoids may have favorable effects on prostate cancer patients showing clinical and/or biochemical failure after androgen ablation. The efficacy and mechanisms of dexamethasone therapy as possible alternative endocrine therapy were investigated.METHODSTwenty five patients with prostate cancer treated by androgen ablation and showing a steady increase in serum prostate specific antigen (PSA) were treated with low‐dose dexamethasone.RESULTSOf 25 patients, 11 demonstrated 50% or more decline of serum PSA and 9 showed improvement of pain on dexamethasone therapy. Of 8 patients who responded to dexamethasone thearpy, 5 had 80% or more decrease in serum interleukin‐6 (IL‐6). In contrast, none of 8 non‐responders showed remarkable IL‐6 suppression. Response of PSA was not correlated to the changes in serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, or androstendione.CONCLUSIONSSignificant suppression of serum IL‐6, probably through inhibition of androgen‐independent activation of androgen receptor, may be one of the mechanisms for the effect of dexamethasone therapy in prostate cancer patients with progressive disease. Prostate 56: 106–109, 2003. © 2003 Wiley‐Liss, Inc.
A novel method of generating prostate cancer metastases from orthotopic implants
Authors: Corey Eva , Quinn Janna E. , Vessella Robert L. 
Published: May 2003

AbstractBACKGROUNDSpontaneous metastasis following implantation at the orthotopic site is a highly desired feature in prostate cancer (CaP) models, since it would enable studies of mechanisms associated with tumor cell dissemination.METHODSLuCaP 23.8 and LuCaP 35, hormone‐sensitive CaP xenografts that express PSA and the wild‐type androgen receptor, were grown orthotopically in SCID mice. When tumor volumes reached ∼250–500 mg, primary tumors were removed to allow micrometastases to grow.RESULTSUsing this procedure we generated macroscopic metastases (>20 mg) in 71% (LuCaP 23.8) and 100% (LuCaP 35) of animals, respectively.CONCLUSIONSThese models may be used to evaluate new treatment modalities and study mechanisms associated with development of metastases. Prostate 56: 110–114, 2003. © 2003 Wiley‐Liss, Inc.