Biomedical subjects

J J Yu

Publications and source records attributed to J J Yu.

At least 19 recordsLinked to original sources

PubMed2006

Reduced semen quality in chronic prostatitis patients that induce the release of apoptotic protein Omi/HtrA2 from spermatozoa.

The relationship between chronic prostatitis and fertility has been disputed for many years. Several groups have shown infection and autoimmune response against prostate antigens could have a deleterious effect on semen quality and fertility. This study was conducted to test the hypothesis that Omi/HtrA2-induced apoptosis in chronic prostatitis could be a mechanism underlying the observed clinical benefit. The Omi/HtrA2 serine protease is a nuclear-encoded mitochondrial protein, which can be released from mitochondria into the cytosol after apoptosis stimuli, inducing apoptosis in caspase-dependent and independent manners. Forty-one patients diagnosed as suffering from chronic prostatitis were included. Healthy normal individuals were included as controls. Human spermatozoa in the semen were purified by Percoll-gradient technique to separate the seminal plasma and other round cells. Measurements for sperm concentration, motility, morphology, proinflammatory cytokines, Omi/HtrA2 mRNA and protein levels in spermatozoa of chronic protatitis patients, were performed accordingly. Significantly increased levels of proinflammatory cytokines were detected in seminal plasma from these prostatitis patients. Omi/HtrA2 mRNA and protein levels were significantly higher in prostatitis men than in normal men. This study shows that chronic prostatitis patients present important alterations in their semen quality parameters, Omi/HtrA2 mRNA and protein levels of spermatozoa. We speculate that the inflammatory process involved may affect male fertility by release of proapoptotic protein Omi/HtrA2.

Adolescent↗

PubMed2004

Maternal histidinaemia: pregnancies and offspring outcomes.

Untreated pregnancies and their outcomes were studied in 10 women with histidinaemia and their 26 pregnancies. The mean maternal assigned histidine level was 727+/-186 micromol/L (range 484-1,053). Six women had classic histidinaemia (assigned level >700 micromol/L) and the remaining four had mild (atypical) histidinaemia. The pregnancies were uneventful, with only one spontaneous loss and 25 live births. Birth measurements were normal and no congenital anomalies were observed. Growth and development were normal in all offspring. IQ among the 23 offspring tested was 103+/-12 (range 79-122). Four offspring required special education for brief periods and one for several years, but this frequency, as well as that of 12% for attention deficit hyperactive disorder, was not significantly different from expected in the general population. It would appear that maternal histidinaemia, unlike maternal phenylketonuria, can be added to the list of maternal inborn errors of metabolism that are nonteratogenic.

Adolescent↗

PubMed2004

A vaccine against coccidioidomycosis is justified and attainable.

Coccidioides is a fungal pathogen of humans which can cause a life-threatening respiratory disease in immunocompetent individuals. Recurrent epidemics of coccidioidal infections in Southwestern United States has raised the specter of awareness of this soil-borne microbe, particularly among residents of Arizona and Southern California, and has galvanized research efforts to develop a human vaccine against coccidioidomycosis. In this review, we discuss the rationale for such a vaccine, examine the features of host innate and acquired immune response to Coccidioides infection, describe strategies used to identify and evaluate vaccine candidates, and provide an update on progress toward development of a vaccine against this endemic pathogen.

Animals↗

PubMed2001

An ERCC1 splicing variant involving the 5'-UTR of the mRNA may have a transcriptional modulatory function.

Human ovarian cancer cells and tissues were examined for the presence or absence of a 42-bp splicing variant of ERCC1 gene, and for a possible functional role of this 42-bp sequence. This specific sequence exists in exon I, the 5'-UTR of the gene. Loss of this 42-bp sequence was associated with increased ERCC1 mRNA expression, in an assessment of 121 ovarian cancer specimens (p2<10(-6)). In cells in tissue culture, the absence of the 42-bp segment was associated with a twofold increased ability to drive transcription in a Luciferase reporter system. Protein can be demonstrated in ovarian cancer cells based on EMSA analysis. Computer analysis shows that this 42-bp sequence contains several binding sites, including a core-binding domain for protein RFX1, transcriptional repressor. These preliminary results lay the groundwork in determination of potential roles for a negative regulatory element in NER repair pathway.

5' Untranslated Regions↗

PubMed2001

Cloning and expression of the gene which encodes a tube precipitin antigen and wall-associated beta-glucosidase of Coccidioides immitis.

We report the structure and expression of the Coccidioides immitis BGL2 gene which encodes a previously characterized 120-kDa glycoprotein of this fungal respiratory pathogen. The glycoprotein is recognized by immunoglobulin M tube precipitin (TP) antibody present in sera of patients with coccidioidomycosis, a reaction which has been used for serodiagnosis of early coccidioidal infection. The deduced amino acid sequence of BGL2 shows 12 potential N glycosylation sites and numerous serine-threonine-rich regions which could function as sites for O glycosylation. In addition, the protein sequence includes a domain which is characteristic of family 3 glycosyl hydrolases. Earlier biochemical studies of the purified 120-kDa TP antigen revealed that it functions as a beta-glucosidase (EC 3.2.1.21). Its amino acid sequence shows high homology to several other reported fungal beta-glucosidases which are members of the family 3 glycosyl hydrolases. Results of previous studies have also suggested that the 120-kDa beta-glucosidase participates in wall modification during differentiation of the parasitic cells (spherules) of C. immitis. In this study we showed that expression of the BGL2 gene is elevated during isotropic growth of spherules and the peak of wall-associated BGL2 enzyme activity correlates with this same phase of parasitic cell differentiation. These data support our hypothesis that the 120-kDa beta-glucosidase plays a morphogenetic role in the parasitic cycle of C. immitis.

Amino Acid Sequence↗

PubMed2001

Recombinant urease and urease DNA of Coccidioides immitis elicit an immunoprotective response against coccidioidomycosis in mice.

Coccidioides immitis antigens which stimulate a T helper cell 1 (Th1) pathway of host immune response are considered to be essential components of a vaccine against coccidioidomycosis. Recombinant urease (rURE) and recombinant heat shock protein 60 (rHSP60) of C. immitis were expressed in Escherichia coli and tested as vaccine candidates in BALB/c mice. A synthetic oligodeoxynucleotide which contained unmethylated CpG dinucleotides and was previously shown to enhance a murine Th1 response was used as an immunoadjuvant. T cells isolated from the spleens and lymph nodes of the rURE- and rHSP60-immune mice showed in vitro proliferative responses to the respective recombinant protein, but only those T lymphocytes from rURE-immunized mice revealed markedly elevated levels of expression of selected Th1-type cytokine genes. BALB/c mice immunized subcutaneously with rURE and subsequently challenged by the intraperitoneal (i.p.) route with a lethal inoculum of C. immitis arthroconidia demonstrated a significant reduction in the level of C. immitis infection compared to control animals. rHSP60 was much less effective as a protective antigen. Evaluation of cytokine gene expression in lung tissue and levels of recombinant urease-specific immunoglobulins (immunoglobulin G1 [IgG1] versus IgG2a) in murine sera at 12 days after challenge provided additional evidence that immunization with rURE stimulated a Th1 response to the pathogen. Urease was further evaluated by expression of the URE gene in a mammalian plasmid vector (pSecTag2A.URE) which was used to immunize mice by the intradermal route. In this case, 82% of the vector construct-immunized animals survived more than 40 days after i.p. infection, compared to only 10% of the mice immunized with the vector alone. In addition, 87% of the pSecTag2A.URE-immunized survivors had sterile lungs and spleens. These data support the need for further evaluation of the C. immitis urease as a candidate vaccine against coccidioidomycosis.

Animals↗

PubMed2001

Effect of the proteasome inhibitor ALLnL on cisplatin sensitivity in human ovarian tumor cells.

Small molecules suppressing proteasome function inhibit the post-translational ubiquitination of selected proteins. Ubiquitin H2A is an example of an abundant chromatin-associated protein that is known to be ubiquitinated, which is important for several proteins involved in the repair of DNA damage. We therefore studied the effect of the proteasome inhibitor, N-acetyl leucyl-leucyl norlucinal (ALLnL), on cisplatin sensitivity in three human ovarian tumor cell lines. The proteasome inhibitor ALLnL was administered for 4 h before cells were subsequently exposed to cisplatin for 1 h. Our results showed that ALLnL, at its respective IC20 concentration, increased cellular sensitivity to cisplatin in an additive manner in human ovarian cancer A2780, A2780/CP70, and OVCAR3 cells. We also demonstrated that ALLnL caused a 50% increase in total cellular accumulation of cisplatin, and reduced the rate of cisplatin efflux by about 50%. In addition, DNA damage levels were increased after ALLnL treatment. By contrast, DNA repair was inhibited 2 to 3-fold in ALLnL-pretreated cells, as compared to the controls. Furthermore, our study showed that ALLnL deubiquitinated nucleosomal histone H2A in these cells in a concentration-dependent fashion, as assessed by Western blot analysis. These data suggest that sublethal levels of exposure to agents that inhibit proteasome function may alter the subcellular pharmacology of platinum in human ovarian carcinoma cells.

Antineoplastic Agents↗

PubMed2001

Lactacystin enhances cisplatin sensitivity in resistant human ovarian cancer cell lines via inhibition of DNA repair and ERCC-1 expression.

Cisplatin is among the most effective chemotherapeutic agents in the treatment of human ovarian cancer. The cytotoxicity of cisplatin results primarily from its ability to bind covalently to DNA and prevent DNA replication and transcription. The ubiquitin-proteasome pathway plays important roles in a broad array of basic cellular processes. Lactacystin is a selective inhibitor of the proteasome that can inhibit the ubiquitin pathway. However, the effect of lactacystin on DNA repair and the antitumor activity of cisplatin in ovarian cancer have not been evaluated. We report in this work that lactacystin, at concentrations that do not appear harmful, increased cisplatin toxicity in three resistant human ovarian carcinoma cell lines. In addition, lactacystin significantly enhanced DNA platination and decreased DNA repair of cisplatin-DNA adducts in these cell lines, as measured by atomic absorption spectrometry. Furthermore, Northem blot analysis and in vitro nuclear transcript elongation assay demonstrated that lactacystin dramatically reduced the steady-state mRNA expression and the rate of transcription of the DNA repair gene ERCC-1 in these cells. These observations indicate that proteasome inhibition has impact on nucleotide excision repair in several ways: i/ the normal ERCC-1 message upregulation is suppressed; ii/ cisplatin-DNA adduct repair is inhibited, and iii/ DNA platination, as well as cisplatin cytotoxicity, is enhanced.

Acetylcysteine↗

PubMed2000

Increased mRNA levels of xeroderma pigmentosum complementation group B (XPB) and Cockayne's syndrome complementation group B (CSB) without increased mRNA levels of multidrug-resistance gene (MDR1) or metallothionein-II (MT-II) in platinum-resistant human ovarian cancer tissues.

Tumor tissue specimens from human ovarian cancer patients were assessed for relative mRNA abundance levels of several genes thought to be involved in the development of in vitro drug resistance in this disease. Higher mRNA levels of Xeroderma pigmentosum group B (XPB), which links DNA repair with DNA transcription, and of Cockayne's syndrome group B (CSB), which is essential for gene-specific repair, were observed in tumor tissues that were clinically resistant to platinum-based chemotherapy, as compared with tissues from patients responding to therapy. In a cohort of 27 patients, mRNA levels of XPB averaged 5-fold higher in platinum-resistant tumors (P = 0.001); and for CSB, mRNA levels averaged 6-fold higher but with greater variability (P = 0.033). Concurrently, these platinum-resistant tumor tissues did not exhibit significantly higher mRNA levels for the MDR1 (multidrug-resistance) gene (P = 0.134) or of the metallothionein-II (MT-II) gene (P = 0.598). Since these platinum-resistant tumors also show higher mRNA levels of ERCC1 and XPA, platinum resistance appears to be associated with concurrent up-regulation of four genes (XPA, ERCC1, XPB, and CSB). These four genes participate in DNA damage excision activity, gene-specific repair, and linkage of DNA repair with DNA transcription. These data suggest that concurrent up-regulation of genes involved in nucleotide excision repair may be important in clinical resistance to platinum-based chemotherapy in this disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Linear and nonlinear pathways of spectral information transmission in the cochlear nucleus.

At the level of the cochlear nucleus (CN), the auditory pathway divides into several parallel circuits, each of which provides a different representation of the acoustic signal. Here, the representation of the power spectrum of an acoustic signal is analyzed for two CN principal cells-chopper neurons of the ventral CN and type IV neurons of the dorsal CN. The analysis is based on a weighting function model that relates the discharge rate of a neuron to first- and second-order transformations of the power spectrum. In chopper neurons, the transformation of spectral level into rate is a linear (i.e., first-order) or nearly linear function. This transformation is a predominantly excitatory process involving multiple frequency components, centered in a narrow frequency range about best frequency, that usually are processed independently of each other. In contrast, type IV neurons encode spectral information linearly only near threshold. At higher stimulus levels, these neurons are strongly inhibited by spectral notches, a behavior that cannot be explained by level transformations of first- or second-order. Type IV weighting functions reveal complex excitatory and inhibitory interactions that involve frequency components spanning a wider range than that seen in choppers. These findings suggest that chopper and type IV neurons form parallel pathways of spectral information transmission that are governed by two different mechanisms. Although choppers use a predominantly linear mechanism to transmit tonotopic representations of spectra, type IV neurons use highly nonlinear processes to signal the presence of wide-band spectral features.

Acoustic Stimulation↗

PubMed2000

Absence of evidence for allelic loss or allelic gain for ERCC1 or for XPD in human ovarian cancer cells and tissues.

We have previously reported on mRNA expression of ERCC1, XPA and XPD in human ovarian cancer cells and tissues. Several factors can influence mRNA expression for any given gene. Alterations in gene copy number for ERCC1 and/or XPD have been reported to occur in malignant glioma specimens. Human ovarian cancer cell lines and tissues were therefore examined for evidence of altered gene copy number in selected genes within the nucleotide excision repair (NER) pathway. Six ovarian cancer cell lines were studied: A2780, A2780/CP70, SKOV3, MCAS, QvCar3 and Caov4. Cellular sensitivity to cisplatin varies by more than 1 log between some of these cells. In each of these cell lines, the genes examined included ERCC1, XPA, XPB, XPD, XPG, CSB and p53. Genomic DNA was also extracted from ovarian cancer specimens taken from 22 patients and assessed for evidence of allelic loss and/or allelic gain for ERCC1 and XPD. Twelve of the clinical specimens were from patients with platinum-sensitive tumors and ten were from patients with platinum-resistant tumors. In no case could we demonstrate a reproducible variation in gene copy number in any cell line. Among the human tissues studied, there was one case of allelic gain out of 22 specimens. We therefore conclude that alterations in gene copy number is not a common event in human ovarian cancer. Other mechanisms must be invoked to explain differences in mRNA expression for these genes.

Blotting, Southern↗

PubMed2000

Sequence, expression and functional analysis of the Coccidioides immitis ODC (ornithine decarboxylase) gene.

The ornithine decarboxylase (ODC) gene of the human respiratory fungal pathogen, Coccidioides immitis (Ci) was cloned, sequenced, chromosome-mapped, and expressed in Escherichia coli (Ec). The genomic, cDNA and translated sequences are presented. Transformation of an ODC null mutant strain of Ec (EWH 319) with the Ci ODC gene was conducted to confirm function of the protein encoded by the fungal gene. Activity of the enzyme by the bacterial transformant was inhibited by 1, 4-diamino-2-butanone (DAB), a known inhibitor of eukaryotic ODC. Temporal expression of the Ci ODC gene during the parasitic cell cycle is constitutive, based on results of RT PCR. However, results of enzyme activity assays of cell homogenates obtained at different stages of parasitic cell development in vitro showed that the functional protein is present only during periods of isotropic growth and segmentation, and these morphogenetic events can be arrested by the addition of DAB. The observed absence of a difference in steady-state mRNA transcript amounts, and the developmentally correlated variation in levels of enzyme activity, suggest a translational or post-translational mechanism of ODC regulation. Since no PEST sequence was detected in the Ci ODC, enzyme regulation by programmed protein degradation as reported for many other eukaryotic ODCs may not occur in this case. ODC activity appears to play a key role in the morphogenesis of Ci, and the enzyme could be a rational target for therapy of disseminated coccidioidomycosis.

Amino Acid Sequence↗

PubMed2000

Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.

BACKGROUND: A number of recent studies have identified interleukin (IL)-6 as an important regulator of prostate cancer growth. Here, we investigate the potential interaction of IL-6 with phosphatidylinositol (PI)-3 kinase, a key growth regulatory enzyme, in prostate cancer cell lines. METHODS: Tyrosine phosphorylation of p85, the regulatory subunit of PI-3 kinase, in the human prostate cancer cell lines LNCaP and PC-3 was assessed by sequential immunoprecipitation with anti-p85 antibody and immunoblotting with anti-phosphotyrosine. The effects of wortmannin, an inhibitor of PI-3 kinase, and/or IL-6 on cell growth were assessed by MTT assays. DNA laddering experiments were performed to assay for programmed cell death. RESULTS: Tyrosine phosphorylation of p85 is upregulated by IL-6 in both LNCaP and PC-3. IL-6 promotes coprecipitation of p85 with gp130, the signal-transducing component of the IL-6 receptor. Inhibition of PI-3 kinase with wortmannin induces programmed cell death in PC-3 cells. In contrast, wortmannin has no effect on LNCaP growth when used alone; however, combined with IL-6, wortmannin promotes apoptosis in these cells. CONCLUSIONS: PI-3 kinase is involved in IL-6 signal transduction and delivers an antiapoptotic signal in human prostate cancer cell lines.

Androstadienes↗

PubMed2000

Contaminated site remedial investigation and feasibility removal of chlorinated volatile organic compounds from groundwater by activated carbon fiber adsorption.

Groundwater contaminated by dense, non-aqueous phase liquids (DNAPLs) such as chlorinated solvents has become a serious problem in some regions of Taiwan. The sources of these contaminants are due to industrial discharges. These chlorinated volatile organic compounds (VOCs) have been proven to be carcinogenic to humans. The groundwater is used for domestic drinking water supply in some cities of Taiwan and the severely contaminated groundwater has to be treated in order to meet the requirement of drinking water standards. This study covers two areas of work. In the first part, polluted groundwater samples were collected from the contaminated site and analytical results indicated measurable concentrations of 12 representative chlorinated VOCs in water samples. The primary VOCs detected included trichloroethene (TCE), tetrachloroethene (PCE), 1,1,2-trichloroethane (1,1,2-TCA), and 1,1-dichloroethene (1,1-DCE). Second, to remove VOCs groundwater was treated using adsorption on activated carbon fiber (ACF). This involved pumping groundwater through vessels containing ACF. Most VOCs, including TCE, PCE, 1,1,2-TCA, and DCE, were readily adsorbed onto ACF and are removed from the water stream. Our study showed that the technology was able to significantly reduce chlorinated VOCs concentrations in groundwater.

Adsorption↗

PubMed2000

Human microphthalmia associated with mutations in the retinal homeobox gene CHX10.

Isolated human microphthalmia/anophthalmia, a cause of congenital blindness, is a clinically and genetically heterogeneous developmental disorder characterized by a small eye and other ocular abnormalities. Three microphthalmia/anophthalmia loci have been identified, and two others have been inferred by the co-segregation of translocations with the phenotype. We previously found that mice with ocular retardation (the or-J allele), a microphthalmia phenotype, have a null mutation in the retinal homeobox gene Chx10 (refs 7,8). We report here the mapping of a human microphthalmia locus on chromosome 14q24.3, the cloning of CHX10 at this locus and the identification of recessive CHX10 mutations in two families with non-syndromic microphthalmia (MIM 251600), cataracts and severe abnormalities of the iris. In affected individuals, a highly conserved arginine residue in the DNA-recognition helix of the homeodomain is replaced by glutamine or proline (R200Q and R200P, respectively). Identification of the CHX10 consensus DNA-binding sequence (TAATTAGC) allowed us to demonstrate that both mutations severely disrupt CHX10 function. Human CHX10 is expressed in progenitor cells of the developing neuroretina and in the inner nuclear layer of the mature retina. The strong conservation in vertebrates of the CHX10 sequence, pattern of expression and loss-of-function phenotypes demonstrates the evolutionary importance of the genetic network through which this gene regulates eye development.

Adult↗

PubMed2000

Comparison of two human ovarian carcinoma cell lines (A2780/CP70 and MCAS) that are equally resistant to platinum, but differ at codon 118 of the ERCC1 gene.

ERCC1 is an essential gene within the nucleotide excision repair process. We studied two human ovarian carcinoma cell lines for cisplatin resistance, which differed with respect to ERCC1. The A2780/CP70 cell line has been extensively studied previously, and has the wild-type ERCC1 sequence. The MCAS cell line has a recently described ERCC1 polymorphism at codon 118, which is associated with an approximate 50% reduction in codon usage. These cells did not differ with respect to p53 sequence nor p53 mRNA induction following cisplatin exposure. The induction of ERCC1 mRNA was markedly reduced in MCAS cells as compared to A2780/CP70 cells. At the IC50 cisplatin dose for each cell line, MCAS cells were less proficient at cisplatin-DNA adduct repair than A2780/CP70 cells. In absolute terms, A2780/CP70 cells repaired 3-fold as much adduct (2.7 pg/microgram DNA over 6 h vs 0.86 pg/microgram DNA); and when expressed in terms of the maximal DNA adduct load, A2780/CP70 cells repaired 50% more adduct than MCAS cells. MCAS cells had increased cytosolic inactivation of drug at the IC50 dose level, which has been previously suggested to be a compensatory cellular response for reduced DNA repair capacity. These data suggest the possibility that this specific ERCC1 polymorphism, may be associated with reduced DNA repair capacity in human ovarian cancer cells. This association may be effected through a reduction in peak production of ERCC1 mRNA, and a consequent reduction in the translation of ERCC1 mRNA into protein.

Antineoplastic Agents↗

PubMed2000

Excluding polio in areas of inadequate surveillance in the final stages of eradication in China.

In 1996, China adopted a virological classification of acute flaccid paralysis (AFP) cases for its surveillance system. Only AFP cases with wild poliovirus in stool specimens are confirmed as polio. Cases with adequate stool specimens that are negative for wild poliovirus are not counted. This paper describes a methodology to rule out poliomyelitis in AFP cases with inadequate stool specimens. National surveillance data were analysed using dot maps to detect clusters of AFP cases with high-risk factors for poliomyelitis. The surveillance system and vaccine coverage were assessed during field investigations. Four clusters of AFP cases were identified, but no poliomyelitis cases. Programmatic failures in the identified high-risk areas included low vaccination rates, poor stool specimen collection and inadequate AFP surveillance. Programme strategies were implemented to correct the identified failures. Use of this methodology provides strong evidence consistent with the absence of wild poliovirus in China.

Adolescent↗

PubMed1999

Characterization of the role of IL-6 in the progression of prostate cancer.

BACKGROUND: We recently identified IL-6, a pleiotropic cytokine implicated in the neoplastic process of a variety of neoplasms, as a mediator of prostate cancer morbidity. In the present study, we investigated the expression of members of the IL-6 supergene family and related cytokines and the potential role of IL-6 in prostate cancer growth regulation. METHODS: Five established human prostate cancer cell lines were screened by ELISA for production of granulocyte colony-stimulating factor (G-CSF), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), tumor necrosis factor (TNF), interleukin-1 (IL-1), and granulocyte macrophage colony-stimulating factor (GM-CSF). Expression of the ligand-binding component of the IL-6 receptor, IL-6Rp80, was evaluated by ELISA and RT-PCR. Sequential immunoprecipitation and immunoblotting were performed to assay for expression of the signal-transducing component of the IL-6 receptor, gp130. The effects of IL-6 on cell growth were assessed by MTT assays. RESULTS: The three hormone-refractory cell lines, DU-145, TSU, and PC-3, secreted distinct combinations of cytokines (DU-145: IL-6, GM-CSF; TSU: IL-6, LIF; PC-3: IL-6, G-CSF, LIF, IL-1, GM-CSF), each uniformly expressing IL-6. In contrast, neither of the two hormone-dependent cell lines, LNCaP-ATCC and LNCaP-GW, secreted significant quantities of any of the cytokines analyzed. None of the cell lines secreted detectable quantities of OSM, CNTF, or TNF. All cell lines, irrespective of hormone status, expressed both Il-6Rp80 and gp130. Addition of IL-6 in vitro inhibited growth of hormone-dependent cells, but had no effect on hormone-refractory lines. Anti-IL-6 neutralizing antibody inhibited growth of hormone-refractory cells. CONCLUSIONS: IL-6 appears to undergo a functional transition from paracrine growth inhibitor to autocrine growth stimulator during progression of prostate cancer to the hormone-refractory phenotype.

Cell Division↗