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PC Cells (pc + cell)

Distribution by Scientific Domains

Medical Sciences	71%

Selected Abstracts

Diverse roles of 2-arachidonoylglycerol in invasion of prostate carcinoma cells: Location, hydrolysis and 12-lipoxygenase metabolism

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2007
Michael P. Endsley
Abstract Endogenous 2-arachidonoylglycerol (2-AG) is antiinvasive in androgen-independent prostate carcinoma (PC-3) cells. Invasion of PC-3 cells is also inhibited by exogenously added noladin ether, a non-hydrolyzable analog of 2-AG. In contrast, exogenous 2-AG has the opposite effect. Cell invasion significantly increased with high concentrations of exogenous 2-AG. In PC-3 cells, arachidonic acid (AA) and 12-hydroxyeicosatetraenoic acid (12-HETE) concentrations increased along with exogenously added 2-AG, and 12-HETE concentrations increased with exogenously added AA. Invasion of PC-3 cells also increased with exogenously added AA and 12(S)-HETE but not 12(R)-HETE. The exogenous 2-AG-induced invasion of PC-3 cells was inhibited by 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP, an inhibitor of 2-AG hydrolysis) and baicalein (a 12-LO inhibitor). Western blot and RT-PCR analyses indicated expression of 12-HETE producing lipoxygenases (LOs), platelet-type 12-LO (P-12-LO) and leukocyte-type 12-LO (L-12-LO), in PC-3 cells. These results suggest that exogenous 2-AG induced, rather inhibited, cell invasion because of its rapid hydrolysis to free AA, and further metabolism by 12-LO of AA to 12(S)-HETE, a promoter of PC cell invasion. The results also suggest that PC-3 cells and human prostate stromal (WPMY-1) cells released free AA, 2-AG, and 12-HETE. In the microenvironment of the PC cells, this may contribute to the cell invasion. The 2-AG hydrolysis and concentration of 2-AG in microenvironment are critical for PC cell's fate. Therefore, inhibitors of 2-AG hydrolysis could potentially serve as therapeutic agents for the treatment of prostate cancer. © 2007 Wiley-Liss, Inc. [source]

Chromatic and spatial properties of parvocellular cells in the lateral geniculate nucleus of the marmoset (Callithrix jacchus)

THE JOURNAL OF PHYSIOLOGY, Issue 1 2004
Esther M. Blessing
The parvocellular (PC) division of the afferent visual pathway is considered to carry neuronal signals which underlie the red,green dimension of colour vision as well as high-resolution spatial vision. In order to understand the origin of these signals, and the way in which they are combined, the responses of PC cells in dichromatic (,red,green colour-blind') and trichromatic marmosets were compared. Visual stimuli included coloured and achromatic gratings, and spatially uniform red and green lights presented at varying temporal phases and frequencies. The sensitivity of PC cells to red,green chromatic modulation was found to depend primarily on the spectral separation between the medium- and long-wavelength-sensitive cone pigments (20 or 7 nm) in the two trichromatic marmoset phenotypes studied. The temporal frequency dependence of chromatic sensitivity was consistent with centre,surround interactions. Some evidence for chromatic selectivity was seen in peripheral PC cells. The receptive field dimensions of parvocellular cells were similar in dichromatic and trichromatic animals, but the achromatic contrast sensitivity of cells was slightly higher (by about 30%) in dichromats than in trichromats. These data support the hypothesis that the primary role of the PC is to transmit high-acuity spatial signals, with red,green opponent signals appearing as an additional response dimension in trichromatic animals. [source]

Saporin toxin-conjugated monoclonal antibody targeting prostate-specific membrane antigen has potent anticancer activity

THE PROSTATE, Issue 12 2010
Kenji Kuroda
Abstract BACKGROUND Prostate-specific membrane antigen (PSMA) provides an attractive target for monoclonal antibody targeted therapies in the treatment of prostate cancer (PC). In this study, we generated an immunotoxin by linking a humanized anti-PSMA monoclonal antibody (hJ591) to the ribosome-inactivating protein toxin saporin. The hJ591,saporin immunoconjugate was evaluated for antitumor activity against PC cells. METHODS PSMA-positive cell lines, LNCaP and CWR22Rv1 and a PSMA-negative cell line, PC-3, were used in these experiments. The hJ591 was biotinylated and mixed with streptavidin,saporin (SAZAP). The binding ability of hJ591,SAZAP and the extent of internalization into the cells were tested. The viability of cells treated with hJ591,SAZAP was also examined and the apoptotic cells were measured. Lastly, the anticancer effect of hJ591,SAZAP was investigated in vivo. RESULTS The binding ability of hJ591,SAZAP to PSMA was equivalent to that of unconjugated J591. Internalization of hJ591,SAZAP was clearly detected in PSMA-positive, but not in PSMA-negative cell lines. IC50 of hJ591,SAZAP was 0.14,nM, 1.99,nM, and more than 100,nM in LNCaP, CWR22Rv1, and PC-3 cells, respectively. After 72,hr of hJ591,SAZAP treatment, the percentage of apoptotic cells was 60.29% and 40.73% in LNCaP and CWR22Rv1 cells, respectively, compared to 4.70% in PC-3 cells. The hJ591,SAZAP also had anticancer activity in a LNCaP xenograft model. CONCLUSIONS Our findings show that hJ591,SAZAP conjugate has potent and selective antitumor effects on PSMA-positive PC cells in vitro and in vivo. This study supports development of PSMA antibody,toxin conjugates for therapy of PC. Prostate 70:1286,1294, 2010. © 2010 Wiley-Liss, Inc. [source]

Thapsigargin resistance in human prostate cancer cells

CANCER, Issue 3 2006
John P. O'Neill BS
Abstract BACKGROUND. Thapsigargin (TG) is a potent inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+ ATPases (SERCAs). TG-based prodrugs are being developed for the treatment of prostate cancer (PC). To develop optimal TG-based therapeutics it is important to understand the mechanisms of resistance to TG that may potentially occur in cancer cells. METHODS. DU145/TG and PC3/TG cells were derived from human PC DU145 and PC3 cells, respectively, by incremental exposure to TG. Growth assays, Western blot analyses, cDNA microarrays, semiquantitative and real-time polymerase chain reaction (PCR), Northern blot analyses, and immunohistochemistry were used to study these cells. RESULTS. DU145/TG cells are 1100-fold and PC3/TG cells are 1350-fold resistant to TG. Although expression of both SERCA and p-glycoprotein can mediate TG resistance in hamster cells, neither is modulated in DU145/TG cells. In contrast, in PC3/TG cells, SERCA, and not p-glycoprotein, is significantly overexpressed but cannot by itself account for the 1350-fold resistance to TG in these cells. Several genes not previously identified to be altered by TG selection are modulated in DU145/TG and PC3/TG cells. Furthermore, the spectrum of genes modulated in DU145/TG cells are distinct from that in PC3/TG cells, even though both cells are of prostate origin and share the same TG-resistant phenotype. CONCLUSIONS. PC cells can adapt to SERCA inhibition by TG. However, they demonstrate cell type-specific plasticity with respect to gene expression upon TG selection. Further, previously not described mechanisms of resistance appear to be recruited in the TG-resistant PC cells, which provide a novel model to study mechanisms of resistance and adaptation in PC on TG-mediated dysregulation of Ca2+ homeostasis. Cancer 2006. © 2006 American Cancer Society. [source]