Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Tight control of cellular growth is essential to ensure normal tissue patterning and prevent pathological responses. Excessive vascular smooth muscle cell (VSMC) proliferation is associated with the pathophysiology of atherosclerosis and restenosis post-angioplasty. Thus, drug targeting of pathological VSMC growth may be a suitable therapeutic intervention in vascular proliferative diseases. 2. In the present study, we investigated the mechanisms underlying VSMC growth arrest induced by the pharmacological agent PCA-4230. Addition of PCA-4230 to cultured VSMCs blocked the induction of cyclin D1 and cyclin A expression normally seen in serum-restimulated cells. Moreover, PCA-4230 inhibited cyclin-dependent kinase 2 (CDK2) activity and abrogated hyperphosphorylation of the retinoblastoma (Rb) gene product. Similarly, PCA-4230-dependent growth arrest of transformed cell lines correlated with reduced level of cyclin D1 protein and inhibition of CDK2 activity. Consistent with these findings, PCA-4230 repressed serum-inducible cyclin A promoter activity, and overexpression of either cyclin D1 or E2F1 efficiently circumvented this inhibitory effect. Importantly, adenovirus-mediated overexpression of E2F1 restored S-phase entry in PCA-4230-treated VSMCs, demonstrating that PCA-4230 represses cyclin A gene expression and VSMC growth via inhibition of the cyclin D1/E2F pathway. 3. Because of its ability to inhibit the growth of human VSMCs and transformed cell lines, future studies are warranted to assess whether PCA-4230 may be a suitable therapeutic intervention for the treatment of hyperproliferative disorders, including cardiovascular disease and cancer.
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PMID:Inhibition of the cyclin D1/E2F pathway by PCA-4230, a potent repressor of cellular proliferation. 1126 55

Dungeness crab (Cancer magister) samples were collected from various pulp mill and principal harbor sites on the West Coast of Canada. Full congener PCB analysis was performed on several composite and single hepatopancreas samples from each site, and the spatial variability of PCB patterns was explored. A recently developed direct mixing model (DMM) which relies on iteration of representative Aroclor end-members was used to make source predictions based on congener-specific PCB data from biota. Additionally, factor analysis and principal component analysis (FA/PCA) were applied to examine the intersite variability for potential PCB-source patterns. This unsupervised exploratory analysis (i.e., FA/PCA) revealed three distinct clusters of variables containing either low (di-tetra), moderate (penta-hexa), and high (hepta-nona) levels of chlorination, which were related to common Aroclor mixtures (e.g., A1242, A1248, A1254, and A1260). Overall, the PCA scores for each site qualitatively agreed with the source predictions provided by the DMM, and distinct source compositions were predicted for various sites examined.
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PMID:PCBs in dungeness crab reflect distinct source fingerprints among harbor/industrial sites in British Columbia. 1209 48

Biologically and clinically meaningful tumor classification schemes have long been sought. Some malignant epithelial neoplasms, such as those in the thyroid and endometrium, exhibit more than one pattern of differentiation, each associated with distinctive clinical features and treatments. In other tissues, all carcinomas, regardless of morphological type, are treated as though they represent a single disease. To better understand the biological and clinical features seen in the four major histological types of ovarian carcinoma (OvCa), we analyzed gene expression in 113 ovarian epithelial tumors using oligonucleotide microarrays. Global views of the variation in gene expression were obtained using PCA. These analyses show that mucinous and clear cell OvCas can be readily distinguished from serous OvCas based on their gene expression profiles, regardless of tumor stage and grade. In contrast, endometrioid adenocarcinomas show significant overlap with other histological types. Although high-stage/grade tumors are generally separable from low-stage/grade tumors, clear cell OvCa has a molecular signature that distinguishes it from other poor-prognosis OvCas. Indeed, 73 genes, expressed 2- to 29-fold higher in clear cell OvCas compared with each of the other OvCa types, were identified. Collectively, the data indicate that gene expression patterns in ovarian adenocarcinomas reflect both morphological features and biological behavior. Moreover, these studies provide a foundation for the development of new type-specific diagnostic strategies and treatments for ovarian cancer.
Cancer Res 2002 Aug 15
PMID:Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas. 1218 31

Pain is one of the most important considerations in the care of thoracic surgical patients. Failure in pain management is associated with increased mortality and morbidity. Acute pain management aspires to stop the painful stimuli before it is transferred to the CNS. The authors recommend (1) a thorough explanation of the operation and the expected outcome to the patient, (2) preoperative pulmonary rehabilitation for those with marginal lung function, (3) choosing the least painful surgical approach with acceptable exposure, (4) minimizing tissue trauma during surgery, (5) preemptive analgesia, and (6) early ambulation as prophylactic measures that should be employed during hospitalization. Good acute pain control should reduce the incidence of chronic pain. Mediansternotomy and VATS seem to be less acutely painful approaches than thoracotomy for most thoracic surgery. One should rule out recurrent malignancy as the etiology for chronic or recurrent pain. Opioids and NSAIDs are sufficient to produce optimal pain control in patients who undergo VATS and sternotomv. TEA is typically reserved for patients who have a thoracotomy. Opioid PCA can be used instead of-or after the discontinuation of-the epidural catheter. Chronic pain can be treated in many ways, and input from a pain clinic might be beneficial. The single best approach to chronic pain is to prevent it. This can be achieved by selecting the right incisional approach, instituting early physical therapy, and achieving optimal postoperative pain control.
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PMID:Acute and chronic pain syndromes after thoracic surgery. 1247 33

The clinical management of pancreatic disease is often hampered by a lack of tissue diagnosis. Endoscopic pancreatography offers the opportunity to investigate exfoliated cells. However, the significance of mere cytological investigation is compromised by an insufficient sensitivity. The evaluation of the molecular background of carcinogenesis hopefully is capable of providing more sensitive diagnostic markers. The p16INK4a-/retinoblastoma tumour-suppressive pathway has been shown to be involved in the development of near to all pancreatic neoplasms. p14ARF is another tumour suppressor located in the immediate neighbourhood of p16INK4a. Promoter methylation has been demonstrated to be a major inactivating mechanism of both genes. We sought to further evaluate the role of the gene locus INK4a methylation status in the endoscopic differentiation of chronic inflammatory and neoplastic pancreatic disease. Pancreatic fluid specimens of 61 patients with either pancreatic carcinoma (PCA: 39), chronic pancreatitis (CP: 16) or a normal pancreatogram (NAD: 6) were retrieved. In order to detect methylation of either the p14ARF or the p16INK4a promoter a methylation-specific PCR protocol was applied. While 19 out of 39 patients with PCA showed p16 promoter methylation (49%), none of the 16 patients with CP revealed p16 promoter methylation. p14ARF methylation was found in a lower percentage of PCA specimens and in none of the samples of patients with CP. These results suggest a specific significance of INK4a for the development of malignant pancreatic disease. Our data further indicate a potential role for INK4a methylation as a diagnostic marker in the endoscopic differentiation of benign and malignant pancreatic disease.
Br J Cancer 2003 Jan 27
PMID:Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions. 1261 May 6

A multivariate analysis of the National Cancer Institute gene expression database is reported here. The soft independent modelling of a class analogy approach achieved cell line classification according to histological origin. With the PCA method, based on the expression of 9605 genes and ESTs, classification of colon, leukaemia, renal, melanoma and CNS cells could be performed, but not of lung, breast and ovarian cells. Another multivariate procedure, called partial least squares discriminant analysis (PLS-DA), provides bioinformatic clues for the selection of a limited number of gene transcripts most effective in discriminating different tumoral histotypes. Among them it is possible to identify candidates in the development of new diagnostic tests for cancer detection and unknown genes deserving high priority in further studies. In particular, melan-A, acid phosphatase 5, dopachrome tautomerase, S100-beta and acid ceramidase were found to be among the most important genes for melanoma. The potential of the present bioinformatic approach is exemplified by its ability to identify differentiation and diagnostic markers already in use in clinical settings, such as protein S-100, a prognostic parameter in patients with metastatic melanoma and a screening marker for melanoma metastasis.
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PMID:A bioinformatic approach to the identification of candidate genes for the development of new cancer diagnostics. 1267 27

Ketoprofen is a NSAIDs of the 2-aryl propionic acid class commonly used in the treatment of inflammatory rheumatic disease, acute pain and fever. Clinically, ketoprofen seems to reduce morphine requirements by 33 to 40% with ketoprofen's supposed central mechanism of analgesia. We evaluated the efficacy and safety of intravenous (IV) ketoprofen as an adjuvant to IV PCA (patient controlled analgesia) with tramadol after major gynecological cancer surgery for postoperative analgesia. Fifty patients were enrolled in this double-blinded, randomized, placebo-controlled study. Patients were allocated randomly to two groups: group I (25 patients) served as a control group, with patients receiving saline; group II (25 patients) received ketoprofen. Patients received an intravenous bolus of saline or 100 mg ketoprofen at the end of surgery. Then, PCA was given as a 20 mg tramadol bolus and 10 min lockout time. Pain relief was regularly assessed using a visual analog scale. Tramadol consumption, side-effects, and patient satisfaction were noted during the 24 hours after the surgery. No significant difference was observed in pain score, side-effects and patient satisfaction between the groups (p > 0.05). The cumulative PCA-tramadol consumption was lower in the ketoprofen-treated patients than placebo-treated patients (p < 0.05). Our results demonstrate that a single dose of 100 mg ketoprofen reduced tramadol consumption for treatment of postoperative pain after major gynecological cancer surgery.
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PMID:Adding ketoprofen to intravenous patient-controlled analgesia with tramadol after major gynecological cancer surgery: a double-blinded, randomized, placebo-controlled clinical trial. 1270 75

A novel cell line, SACHI, was established from a pericardial effusion developed during the course of primary plasma cell leukemia (PCL). The cell line SACHI cells were the same as the infiltrating plasma cells with regard to surface markers (CD38(+)CD19(-)PCA-1(+)VLA-5(-)CD56(-)TdT(+)) and immunoglobulin gene rearrangements. Analysis of SACHI cells showed a complex hypertriploid (karyotype mode 70-73) including 7p32, 14q32, and Xq24 structural abnormalities, which were found also in the original leukemia cells. Dual-color fluorescence in situ hybridization revealed that the c-MYC gene was juxtaposed with a constant region of IgG (Cgamma) on 14q32. The split Cgamma locus was fused near the MAFB gene on chromosome 20. The SACHI cells had increased amounts of c-MYC and MAFB transcripts. Injection of SACHI cells into NOD/SCID mice generated leukemic plasmacytosis with invasion to liver, spleen, and bone marrow. This cell line may be useful for therapeutic testing as well as analyzing the molecular pathogenesis of PCL.
Cancer Genet Cytogenet 2003 Jul 01
PMID:A xeno-transplantable plasma cell leukemia line with a split translocation of the IgH gene. 1281 Feb 53

Reactive free radicals and reactive oxygen species (ROS) induced by ultraviolet irradiation in human skin are strongly involved in the occurrence of skin damages like aging and cancer. In the present work an ex vivo method for the detection of free radicals/ROS in human skin biopsies during UV irradiation is presented. This method is based on the Electron Spin Resonance (ESR) spectroscopy and imaging and uses the radical trapping properties of nitroxides. The nitroxides 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO), 3-Carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCM), and 3-Carboxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCA), were investigated for their applicability of trapping reactive free radicals and reactive oxygen species in skin during UV irradiation. As a result of the trapping process the nitroxides were reduced to the EPR silent hydroxylamins. The reduction rate of TEMPO was due to both the UV radiation and the enzymatic activity of the skin. The nitroxides PCM and PCA are sufficiently stable in the skin and are solely reduced by UV-generated free radicals/ROS. The nitroxide PCA was used for imaging the spatial distribution of UV-generated free radicals/ROS. As a result of the homogeneous distribution of PCA in the skin, it was possible to estimate the penetration of UVA and UVB irradiation: The UV irradiation decreased the PCA intensity corresponding to its irradiance and penetration into the skin. This reduction was shown to be caused mainly by UVA radiation (320-400 nm).
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PMID:UV-induced free radicals in the skin detected by ESR spectroscopy and imaging using nitroxides. 1282 56

In this study, we measured the antiallergic activities of ginsenosides isolated from the root of Panax ginseng ( Araliaceae), and of their metabolites, as produced by human intestinal bacteria. Compound K, which was identified as a main metabolite, had the most potent inhibitory activity on beta-hexosaminidase release from RBL-2H3 cells and on the PCA reaction. The inhibitory activity of compound K was more potent than that of disodium cromoglycate, one of the commercial anti-allergic drugs. This compound demonstrated a membrane stabilizing action on differential scanning calorimetry. However, compound K did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that the antiallergic action of compound K originates from its cell membrane stabilizing activity and that the ginsenosides of ginseng are prodrugs with extensive antiallergic properties. Abbreviations. compound K:20- O-beta- D-glucopyranosyl-20( S)-protopanaxadiol DNP:dinitrophenol DSCG:disodium cromoglycate DPPC:dipalmitoylphosphatidylcholine DPPH:1,1-diphenyl-2-picrylhydrazyl HSA:human serum albumin IC 50 :50% inhibitory concentration EC 50 :50% effective concentration XOD:xanthine oxidase ICR:Institute of Cancer Research PBS:phosphate buffered saline PCA:passive cutaneous anaphylaxis RAW264.7:mouse monocyte leukemiaRBL-2H3: rat basophil leukemia SD:Sprague-Dawley
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PMID:Antiallergic activity of ginseng and its ginsenosides. 1286 69


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