bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer
Authors: Ghosh Arundhati , Heston Warren D.W. 
Published: January 2004

AbstractProstate specific membrane antigen (PSMA), is a unique membrane bound glycoprotein, which is overexpressed manifold on prostate cancer as well as neovasculature of most of the solid tumors, but not in the vasculature of the normal tissues. This unique expression of PSMA makes it an important marker as well as a large extracellular target of imaging agents. PSMA can serve as target for delivery of therapeutic agents such as cytotoxins or radionuclides. PSMA has two unique enzymatic functions, folate hydrolase and NAALADase and found to be recycled like other membrane bound receptors through clathrin coated pits. The internalization property of PSMA leads one to consider the potential existence of a natural ligand for PSMA. In this review we have discussed the regulation of PSMA expression within the cells, and significance of its expression in prostate cancer and metastasis. © 2003 Wiley‐Liss, Inc.
Prostate carcinoma: Opportunities for translational research
Authors: FitzGerald T.J. , Simon Edmund , Meyer Joshua 
Published: January 2004

AbstractAdenocarcinoma of the prostate continues to be a major health concern. Although modern screening techniques have increased the number of men presenting with early stage disease, a significant population of men will present with intermediate or advanced pathological risk factors for recurrence. There are defined limitations in outcome with traditional therapies including surgery, radiation therapy, and hormone manipulation. Patients with intermediate and high‐risk factors for treatment failure are candidates for protocols using translational research strategies incorporated into studies currently in development. These strategies may be able to selectively treat expression products of tumor and thus be more selective in the target for treatment. Carefully designed studies using these translational strategies have great potential in improving clinical outcome, tumor kill, and normal tissue tolerance in the care of these patients. © 2003 Wiley‐Liss, Inc.
Prostate cancer association studies: Pitfalls and solutions to cancer misclassification in the PSA era
Authors: Platz Elizabeth A. , De Marzo Angelo M. , Giovannucci Edward 
Published: January 2004

AbstractWidespread screening of American men for elevated PSA has changed the characteristics of prostate cancer cases in the U.S. The influence of the changed nature of prostate cancer cases in the PSA era and the need for careful consideration of who is a “case” and who is a “control” on the ability to detect associations of risk factors with prostate cancer in etiologic epidemiologic studies merits discussion. Issue 1: prostate cancer cases diagnosed in the PSA era are enriched with a pool of early lesions, which may differ in etiology, and are deficient in advanced lesions, which are the most likely to be the product of promotion and progression events. By admixing the two types of cases (i.e., imperfect specificity), the associations previously detected using epidemiologic designs when the majority of cases were clinically detected may no longer be apparent in the PSA era when the majority of cases are now detected in the pre‐clinical phase. Researchers must now tailor hypotheses such that they are testable using early stage cases or specifically augment the number of advanced cases when testing hypotheses related to extraprostatic growth and progression. Issue 2: even when controls are screened for elevated PSA to rule out the presence of prostate cancer, some proportion of those controls currently will have one or more foci of prostate cancer. The imperfect sensitivity of the PSA test coupled with diagnostic work‐up may in part result from (a) lack of PSA elevation in some men with prostate cancer or (b) failure of biopsy to sample the tumor focus in men with elevated PSA. Misclassification of men with undetected prostate cancer as controls usually produces a bias that tends to deflate associations. Given this type of disease misclassification, whether an association still can be statistically detected depends on the extent of misclassification, the magnitude of the true association, the prevalence of the exposure in the true controls, and the sample size, although in general moderate nondifferential misclassification does not lead to profound attenuation. However, under the same scenario attenuation does not occur in cohort or case‐cohort studies in which the rate or risk ratio (RR) is calculated. That prostate cancer cases diagnosed in the PSA era are enriched with early stage, minimally invasive disease in our opinion is likely to pose a far more serious obstacle to epidemiologic research on the etiology of clinically important prostate cancer than the issue of inclusion as controls some men who have undiagnosed prostate cancer because of imperfect sensitivity of PSA screening and biopsy sampling error. © 2003 Wiley‐Liss, Inc.
Angiopoietin 1, PDGF‐B, and TGF‐β gene regulation in endothelial cell and smooth muscle cell interaction
Authors: Nishishita Toshishita , Lin Pengnian Charles 
Published: January 2004

AbstractThe vascular wall is mainly composed of endothelial cells (ECs) and smooth muscle cells (SMCs). The crosstalking between these two cell types is critical in the vascular maturation process. Genetic studies suggest that the Tie2/angiopoietin 1 (Ang1) pathway regulates vascular remodeling. However, the molecular mechanism is unclear. PDGF is a potent chemoattractant for SMCs, and TGF‐β regulates SMC differentiation. Here, we examined gene regulation. PDGF‐B stimulation upregulated Ang1 expression in SMCs through the PI3K and PKC pathways. PDGF‐B stimulation also produced an acute induction of TGF‐β expression in SMCs through the MAPK/ERK pathway. Interestingly, TGF‐β negatively regulated Ang1 expression induced by the PDGF‐B stimulation in SMCs. Reciprocally, we observed that stimulation of ECs with either Ang1 or TGF‐β slightly downregulated PDGF expression. A combination of both TGF‐β with Ang1 produced much stronger downregulation of PDGF. Our data showed complex gene regulations that include both positive and negative regulations between ECs and SMCs to maintain vascular homeostasis. © 2003 Wiley‐Liss, Inc.
Chemoprevention of prostate cancer with selenium: An update on current clinical trials and preclinical findings
Authors: Meuillet Emmanuelle , Stratton Suzanne , Prasad Cherukuri Durga , Goulet Anne‐Christine , Kagey Jacob , Porterfield Bruce , Nelson Mark A. 
Published: January 2004

AbstractProstate cancer is the most common cancer diagnosed and the second leading cause of cancer‐related deaths in men in the United States. The etiological factors that give rise to prostate cancer are not known. Therefore, it is not possible to develop primary intervention strategies to remove the causative agents from the environment. However, secondary intervention strategies with selenium (Se) compounds and other agents represent a viable option to reduce the morbidity and mortality of prostate cancer. In this review, we discuss ongoing clinical trials. In addition, we discuss preclinical mechanistic studies that provide insights into the biochemical and molecular basis for the anti‐carcinogenic activity of both inorganic and organic forms of Se. © 2003 Wiley‐Liss, Inc.
GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancer
Authors: Nakayama Masashi , Gonzalgo Mark L. , Yegnasubramanian Srinivasan , Lin Xiaohui , De Marzo Angelo M. , Nelson William G. 
Published: January 2004

AbstractSomatic hypermethylation of CpG island sequences at GSTP1, the gene encoding the π‐class glutathione S‐transferase, appears to be characteristic of human prostatic carcinogenesis. To consider the potential utility of this epigenetic alteration as a biomarker for prostate cancer, we present here a comprehensive review of the literature describing somatic GSTP1 changes in DNA from prostate cells and tissues. GSTP1 CpG island hypermethylation has been detected in prostate cancer DNA using a variety of assay techniques, including (i) Southern blot analysis (SB), after treatment with 5‐mC‐sensitive restriction endonucleases, (ii) the polymerase chain reaction, following treatment with 5‐mC‐sensitive restriction endonucleases (RE‐PCR), (iii) bisulfite genomic sequencing (BGS), and (iv) bisulfite modification followed by the polymerase chain reaction, using primers selective for target sequences containing 5‐mC (MSP). In the majority of the case series so far reported, GSTP1 CpG island hypermethylation was present in DNA from at least 90% of prostate cancer cases. When analyses have been carefully conducted, GSTP1 CpG island hypermethylation has not been found in DNA from normal prostate tissues, or from benign prostatic hyperplasia (BPH) tissues, though GSTP1 CpG island hypermethylation changes have been detected in DNA from candidate prostate cancer precursor lesions proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN). Using PCR methods, GSTP1 CpG island hypermethylation has also been detected in urine, ejaculate, and plasma from men with prostate cancer. GSTP1 CpG island hypermethylation, a somatic epigenetic alteration, appears poised to serve as a molecular biomarker useful for prostate cancer screening, detection, and diagnosis. © 2003 Wiley‐Liss, Inc.
Pathological and molecular mechanisms of prostate carcinogenesis: Implications for diagnosis, detection, prevention, and treatment
Authors: De Marzo Angelo M. , DeWeese Theodore L. , Platz Elizabeth A. , Meeker Alan K. , Nakayama Masashi , Epstein Jonathan I. , Isaacs William B. , Nelson William G. 
Published: January 2004

AbstractProstate cancer is an increasing threat throughout the world. As a result of a demographic shift in population, the number of men at risk for developing prostate cancer is growing rapidly. For 2002, an estimated 189,000 prostate cancer cases were diagnosed in the U.S., accompanied by an estimated 30,200 prostate cancer deaths [Jemal et al., 2002]. Most prostate cancer is now diagnosed in men who were biopsied as a result of an elevated serum PSA (>4 ng/ml) level detected following routine screening. Autopsy studies [Breslow et al., 1977; Yatani et al., 1982; Sakr et al., 1993], and the recent results of the Prostate Cancer Prevention Trial (PCPT) [Thompson et al., 2003], a large scale clinical trial where all men entered the trial without an elevated PSA (<3 ng/ml) were subsequently biopsied, indicate the prevalence of histologic prostate cancer is much higher than anticipated by PSA screening. Environmental factors, such as diet and lifestyle, have long been recognized contributors to the development of prostate cancer. Recent studies of the molecular alterations in prostate cancer cells have begun to provide clues as to how prostate cancer may arise and progress. For example, while inflammation in the prostate has been suggested previously as a contributor to prostate cancer development [Gardner and Bennett, 1992; Platz, 1998; De Marzo et al., 1999; Nelson et al., 2003], research regarding the genetic and pathological aspects of prostate inflammation has only recently begun to receive attention. Here, we review the subject of inflammation and prostate cancer as part of a “chronic epithelial injury” hypothesis of prostate carcinogenesis, and the somatic genome and phenotypic changes characteristic of prostate cancer cells. We also present the implications of these changes for prostate cancer diagnosis, detection, prevention, and treatment. © 2003 Wiley‐Liss, Inc.
Distinctive regulation and function of PI 3K/Akt and MAPKs in doxorubicin‐induced apoptosis of human lung adenocarcinoma cells
Authors: Zhao Yanqiu , You Han , Yang Yu , Wei Lin , Zhang Xin , Yao Libo , Fan Daiming , Yu Qiang 
Published: January 2004

AbstractRegulation and function of PI 3K/Akt and mitogen‐activated protein kinases (MAPKs) in doxorubicin‐induced cell death were investigated in human lung adenocarcinoma cells. Doxorubicin induced dose‐dependent apoptosis of human lung adenocarcinoma NCI‐H522 cells. Prior to cell death, both Akt and the MAPK family members (MAPKs: ERK1/2, JNK, and p38) were activated in response to the drug treatment. The kinetics of the inductions for Akt and MAPKs are, however, distinct. The activation of Akt was rapid and transient, activated within 30 min of drug addition, then declined after 3 h, whereas the activations of three MAPKs occurred later, 4 h after addition of the drug and sustained until cell death occurred. Inhibition of PI 3K/Akt activation had no effect on MAPKs' activation, suggesting that the two pathways are independently activated in response to the drug treatment. Inhibition of PI 3K/Akt and p38 accelerated and enhanced doxorubicin‐induced cell death. On the contrary, inhibition of ERK1/2 or JNK had no apparent effect on the cell death. Taken together, these results suggest that PI 3K/Akt and MAPKs signaling pathways are all activated, but with distinct mechanisms, in response to doxorubicin treatment. Activation of PI 3K/Akt and p38 modulates apoptotic signal pathways and inhibits doxorubicin‐induced cell death. These responses of tumor cells to cancer drug treatment may contribute to their drug resistance. Understanding of the mechanism and function of the responses will be beneficial for the development of novel therapeutic approaches for improvement of drug efficacy and circumvention of drug resistance. © 2003 Wiley‐Liss, Inc.
A LIM protein, Hic‐5, functions as a potential coactivator for Sp1
Authors: Shibanuma Motoko , Kim‐Kaneyama Joo‐ri , Sato Shotaro , Nose Kiyoshi 
Published: January 2004

AbstractHic‐5 is a LIM protein with striking similarity to paxillin, and shuttles between focal adhesions and the nucleus. Our previous study suggested that Hic‐5 participates in the transcriptional control of several genes such as the c‐fos and p21 genes. In the present study, we examined the function of Hic‐5 in the nucleus using the transcriptional promoter region of the p21 gene. When localized to the nucleus, Hic‐5 was found to transactivate the p21 promoter through two of five Sp1 sites in the region proximal to the TATA box. The Hic‐5 effect was mediated by a transactivation domain of Sp1 and functional interaction with p300 through the LIM4 domain. Hic‐5 was also shown to interact functionally and physically with Smad3 through the LIM domains and to potentiate p21 promoter activity together with Smad3 and Sp1. These properties were confirmed in an artificial system using GAL4‐fusion protein. Thus, Hic‐5 was suggested to have a potential function as a cofactor in the transcriptional complex that contains Sp1, playing a role in gene transcription in the nucleus as well as in integrin signaling at focal adhesion sites. © 2004 Wiley‐Liss, Inc.
Hydrocortisone increases the rate of differentiation of cultured human osteoblasts
Authors: Ireland Deborah C. , Bord Sharyn , Beavan Siân R. , Compston Juliet E. 
Published: January 2004

AbstractReduced bone formation is the main finding in glucocorticoid‐induced osteoporosis. The aim of this study was to determine whether differentiation of cultured human osteoblasts is inhibited by high concentrations of hydrocortisone. We measured the levels of mRNAs for three markers of cellular differentiation, type 1 collagen (COL1), alkaline phosphatase (ALP), and osteocalcin (OC), in four lines of human osteoblasts from female donors cultured with doses of hydrocortisone from 0 μM to 4 μM. The change in ALP/COL1 mRNA ratio over a given time was used to determine the average rate of differentiation of the cells in a culture. Although basal expression profiles and their changes with time were different for the different cell lines, all cell lines showed a dose‐dependent rise in the rate of increase of ALP mRNA relative to COL1 mRNA. However, increase in OC mRNA with time, seen here only in young donor hOBs, was significantly inhibited by 4 μM hydrocortisone, indicating that hydrocortisone can inhibit OC expression while promoting cellular differentiation. The data suggest that increasing concentrations of glucocorticoid, including concentrations similar to plasma levels in patients receiving oral glucocorticoid therapy, increase the rate of cellular differentiation. © 2003 Wiley‐Liss, Inc.
Estrogens and anti‐estrogens: Key mediators of prostate carcinogenesis and new therapeutic candidates
Authors: Ho Shuk‐Mei 
Published: January 2004

AbstractDespite the historical use of estrogens in the treatment of prostate cancer (PCa) little is known about their direct biological effects on the prostate, their role in carcinogenesis, and what mechanisms mediate their therapeutic effects on PCa. It is now known that estrogens alone, or in synergism with an androgen, are potent inducers of aberrant growth and neoplastic transformation in the prostate. The mechanisms of estrogen carcinogenicity could be mediated via induction of unscheduled cell proliferation or through metabolic activation of estrogens to genotoxic metabolites. Age‐related changes and race‐/ethnic‐based differences in circulating or locally formed estrogens may explain differential PCa risk among different populations. Loss of expression of estrogen receptor (ER)‐β expression during prostate carcinogenesis and prevention of estrogen‐mediated oxidative damage could be exploited in future PCa prevention strategies. Re‐expression of ER‐β in metastatic PCa cells raises the possibility of using ER‐β‐specific ligands in triggering cell death in these malignant cells. A variety of new estrogenic/anti‐estrogenic/selective estrogen receptor modulator (SERM)‐like compounds, including 2‐methoxyestradiol, genistein, resveratrol, licochalcone, Raloxifene, ICI 182,780, and estramustine are being evaluated for their potential in the next generation of PCa therapies. Increasing numbers of patients self‐medicate with herbal formulations such as PC‐SPES. Some of these compounds are selective ER‐β ligands, while most of them have minimal interaction with ER‐α. Although many may inhibit testosterone production by blockade of the hypothalamal–pituitary–testis axis, the most effective agents also exhibit direct cytostatic, cytotoxic, or apoptotic action on PCa cells. Some of them are potent in interfering with tubulin polymerization, blocking angiogenesis and cell motility, suppressing DNA synthesis, and inhibiting specific kinase activities. Further discovery of other compounds with potent apoptotic activities but minimal estrogen action should promote development of a new generation of effective PCa preventive or treatment regimens with few or no side‐effects due to estrogenicity. Further advancement of our knowledge of the role of estrogens in prostate carcinogenesis through metabolic activation of estrogens and/or ER‐mediated pathways will certainly result in better preventive or therapeutic modalities for PCa. © 2003 Wiley‐Liss, Inc.
Approaches to understanding the importance and clinical implications of peroxisome proliferator‐activated receptor gamma (PPARγ) signaling in prostate cancer
Authors: Jiang Ming , Shappell Scott B. , Hayward Simon W. 
Published: January 2004

AbstractThe development and maintenance of the prostate are dependent upon a complex series of interactions occurring between the epithelial and stromal tissues (Hayward and Cunha [2000]: Radiol. Clin. N. Am. 38:1–14). During the process of prostatic carcinogenesis, there are progressive changes in the interactions of the nascent tumor with its surrounding stroma and extracellular matrix. These include the development of a reactive stromal phenotype and the possible promotion, by stromal cells, of epithelial proliferation and loss of differentiated function (Hayward et al. [1996]: Ann. N. Y. Acad. Sci. 784:50–62; Grossfeld et al. [1998]: Endocr. Related Cancer 5:253–270; Rowley [1998]: Cancer Metastasis Rev. 17:411–419; Tuxhorn et al. [2002]: Clin. Cancer Res. 8:2912–2923). Many molecules play an as yet poorly defined role in establishing and maintaining a growth quiescent glandular structure in the adult. Peroxisome proliferator‐activated receptor gamma (PPARγ) is a candidate regulator of prostatic epithelial differentiation and may play a role in restricting epithelial proliferation. PPARγ agonists are relatively non‐toxic and have been used with limited success to treat some prostate cancer patients. We would propose that a more complete understanding of PPARγ biology, particularly in the context of appropriate stromal–epithelial and host–tumor interactions would allow for the selection of patients most likely to benefit from this line of therapy. In particular, it seems reasonable to suggest that the patients most likely to benefit may be those with relatively indolent low stage disease for whom this line of therapy could be a useful additive to watchful waiting. © 2003 Wiley‐Liss, Inc.
Par‐4 inducible apoptosis in prostate cancer cells
Authors: Gurumurthy Sushma , Rangnekar Vivek M. 
Published: January 2004

AbstractProstate cancer is associated with the inability of prostatic epithelial cells to undergo apoptosis rather than with increased cell proliferation. Prostate apoptosis response‐4 (Par‐4) is a unique pro‐apoptotic molecule that is capable of selectively inducing apoptosis in cancer cells when over‐expressed, sensitizing the cells to diverse apoptotic stimuli and causing regression of tumors in animal models. This review discusses the salient functions of Par‐4 that can be harnessed to prostate cancer therapy. © 2004 Wiley‐Liss, Inc.
Characterization of Gicerin/MUC18/CD146 in the rat nervous system
Authors: Taira Eiichi , Kohama Keiko , Tsukamoto Yasuhiro , Okumura Shigeki , Miki Naomasa 
Published: January 2004

AbstractGicerin is a cell adhesion molecule of an immunoglobulin (Ig) superfamily isolated from a chicken. It shows homophilic and heterophilic binding activities and has two isoforms. s‐Gicerin which has small cytoplasmic domain and the same extracellular domain as l‐gicerin shows stronger cell adhesion activity. In the chick nervous system, gicerin expression is only observed in the developmental stage when neurons extend neurites and migrate. In other tissues, gicerin participates in the tissue regeneration or oncogenesis. In this report, we identified two isoforms of rat gicerin corresponding to chicken and we concluded that gicerin is a homologue of human CD146/MUC18/MCAM. Next we generated antibody to characterize a rat gicerin in the nervous system. Gicerin is expressed in the hippocampal cells, Purkinje cells, and sensory neurons of a spinal chord of an adult rat, while expressed most abundantly in the lung. In addition to this, its expression in the hippocampus was increased by electroconvulsive shock, suggesting some role in the mature nervous system. And we also showed neurite promotion activity of gicerin from hippocampal neurons. J. Cell. Physiol. 198: 377–387, 2004© 2003 Wiley‐Liss, Inc.