Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SOX proteins are a family of transcription factors with high-mobility-group DNA-binding domain (HMG box) homologous to SRY, which are implicated in embryogenesis. Xenopus Sox17 alpha, Sox17 beta, and Sox3 are reported to negatively modulate the WNT - beta-catenin - TCF signaling pathway. Here, human SOX17 gene fragments were identified in human genome draft sequences by using bioinformatics, and SOX17 cDNAs were isolated by using cDNA-PCR. Human SOX17 was found to encode a 414-amino-acid protein with a HMG box, which was homologous to SOX18 and SOX7. SOX17 gene, consisting of 2 exons, was located in human chromosome 8q12-q13 region. SOX17 mRNAs of 2.5- and 2.2-kb in size were detected in adult heart, lung, spleen, testis, ovary, placenta, fetal lung, and kidney. In normal gastrointestinal tract, SOX17 mRNA was preferentially expressed in esophagus, stomach and small intestine than in colon and rectum. SOX17 mRNA was almost undetectable in human cancer cell lines HL-60, HeLa S3, K-562, MOLT-4, Raji, SW480, A549, G-361, and also in 66 cases of human primary tumors derived from various tissues, except one case of primary cervical cancer. This is the first report on molecular cloning and characterization of human SOX17.
Int J Mol Med 2002 Feb
PMID:Molecular cloning and characterization of human SOX17. 1178 26

TA-HPV (therapeutic antigen-human papilloma virus) is a vaccine being developed by Xenova (formerly Cantab) for the potential treatment of cervical cancer. The antigen is intended to activate HPV-specific cytotoxic T-cells to attack tumor cells containing the viral antigen. Over 70% of patients with cervical cancer have tumor cells containing papillomavirus DNA [173070]. TA-HPV has reached phase IIa trials in 60 patients with high-grade anogenital intraepithelial neoplasia, including VIN3 (grade 3 vulvar intraepithelial neoplasia), to evaluate clinical efficacy [381386], [427159], [429895]. In addition, a phase II 'prime-boost' study of TA-HPV in combination with TA-CIN has been initiated at three centers across the UK [427159].
Curr Opin Mol Ther 2001 Dec
PMID:Technology evaluation: T-cell activator, Xenova. 1180 73

Recently, a procedure for detecting ROS-sensitive proteins that contain active cysteine residues was devdoped. The method is based on the fact that biotin-conjugated iodoacetamide (BIAM) and ROS competitively and selectively react with the active cysteine residues in ROS-sensitive proteins. To investigate the role of ROS in cervical cancer, BIAM labeling on cytosolic proteins in normal and cancer tissues was performed, respectively. The BIAM labeling proteins are separated by 2-dimensional electrophoresis, and then identified by MALDI-TOF mass analysis. ROS-sensitive protein is identified as creatine kinase B containing cysteine residue in active center. Activity of creatine kinase B in normal tissue is higher than that of oxidized form in cervical cancer tissues. The result suggests that ROS play an important role in metabolic regulation in cervical cancer cells. However, molecular mechanisms that ROS and creatine kinase B are integrated into a physiological signal leading to the cellular transformation remain to be elucidated.
Mol Cells 2001 Dec 31
PMID:Creatine kinase B is a target molecule of reactive oxygen species in cervical cancer. 1180 44

Human papillomaviruses (HPVs) are intimately associated with the development of cervical cancer. The virus encodes two oncoproteins, E6 and E7, that are primarily responsible for inducing malignant transformation. The last few years have seen significant progress in elucidating the mechanisms by which these two viral proteins bring about cell transformation. Both proteins interact with a large number of cellular targets, many of which are involved in regulating diverse functions such as cell cycle regulation, transcription, differentiation and apoptosis. However both E6 and E7 are normally present at low levels within the virally infected cell, and how all these interactions are achieved and regulated has, until recently, been unclear. We have found that both E6 and E7 are subject to differential phosphorylation, the net results of which regulate their abilities to interact with some of their respective target proteins. In the case of E6, phosphorylation by Protein Kinase A (PKA) negatively regulates its ability to interact with the Discs Large (Dlg) tumour suppressor. In the case of E7, phosphorylation by Casein Kinase II (CKII) significantly increases its ability to interact with the TATA Box Binding Protein (TBP). Further, CKII regulation of E7 appears to vary during the cell cycle, therefore this provides a means of specifically targeting E7 to a given substrate at a given point within the cell cycle. This differential regulation of E6 and E7 by phosphorylation thus provides specificity to a diverse set of protein-protein interactions.
Mol Cell Biochem 2001 Nov
PMID:Regulation of the human papillomavirus oncoproteins by differential phosphorylation. 1182 65

The association between cervical cancer and human papillomavirus (HPV) is well known, but its association with human immunodeficiency virus (HIV) is controversial. Coinfection with HPV and HIV is to be expected and recent epidemiological data from Africa show that cervical cancer is the most common AIDS defining neoplasm in women. Unlike other AIDS defining neoplasms, the occurrence of cervical cancer is not dependent on immune compromise. HIV alters the natural history of HPV infection, with decreased regression rates and more rapid progression to high grade and invasive lesions, which are refractory to treatment, requiring more stringent intervention and monitoring. The more aggressive behaviour is mirrored by a different molecular pathway. HIV associated cervical cancers are thought to progress through the microsatellite instability pathway, whereas HIV negative ones progress through loss of heterozygosity. Interaction is probably via viral proteins, with HIV proteins enhancing effectiveness of HPV proteins, and perhaps contributing to cell cycle disruption. Dysregulation of the cellular and humoral arms of the local and systemic immune systems may ensure disease progression. Furthermore, HPV infection may predispose to HIV infection and facilitate its progression.
Mol Pathol 2002 Feb
PMID:Postmodern cancer: the role of human immunodeficiency virus in uterine cervical cancer. 1183 42

Specific assays capable of distinguishing normal and atypical cervical changes from pre-cancerous lesions are direly needed to improve screening for cervical cancer. Specific genes transcripts that are up-regulated in dysplastic and cancer cells can be exploited as new markers for cervical cancer screening provided that they can be detected in heterogeneous populations such as those collected for Papanicolaou tests. We hypothesized that expression of the HPV early region gene E7 might distinguish between normal samples (absent expression) and high-grade lesions (detectable E7 expression). Our goal was to detect and measure gene expression in cells scraped from the cervix using real time quantitative reverse transcription-polymerase chain reaction (TaqMan). We have optimized collection and extraction procedures to provide suitable RNA for TaqMan analysis in clinical samples collected for cervical cancer screening and have demonstrated efficient measurements of housekeeping genes in these samples. HPV 16 or 18 early gene E7 transcripts were detected in 47% of samples with a clinical diagnosis of high-grade SIL and in 0% of cytologically normal samples (P = 0.006). Our study demonstrates that the TaqMan assay can be reliably applied to samples collected for cervical cancer screening, and that presence of detectable HPV E7 transcripts can distinguish between normal and abnormal samples.
J Mol Diagn 2002 May
PMID:Measurements of human papillomavirus transcripts by real time quantitative reverse transcription-polymerase chain reaction in samples collected for cervical cancer screening. 1198

Effectiveness of radiotherapy is influenced by several genetic properties of the targeted cells. The aim of this study was the identification of prognostic indicators of tumor response to radiation in cervical and endometrial cancer. Using microsatellite DNA analysis, we investigated 31 markers, located on 1p, 2p, 2q, 3p, 9p, 9q, 13q, 17p and 17q for genomic alterations in 37 cervical and 21 endometrial cancer cases, with complete follow-up data. Genetic alterations of the initial tumor genotypes were observed after radiation in 86.5% of cervical and 81.0% of endometrial cases. Reversions to the original normal genotype were observed in 40.5 and 28.6% respectively, predominantly in cured patients rather than in recurred cases. Survival curves by the Kaplan-Meier method showed a worse prognosis for cervical cancer patients whose tumors harbor allelic imbalance (AI) on 3p or 13q, and for endometrial cancer patients whose tumors harbor AI on 13q. Our data suggest a possible association of the hMLH1 or BRCA2 genes, implicated in distinct DNA repair pathways and located on 3p and 13q respectively, with response of cervical and endometrial cancer to radiotherapy. Moreover, microsatellite DNA analysis before and after radiation treatment could be used as a marker of the clinical outcome of patients.
Int J Mol Med 2002 Jul
PMID:Allelic imbalance in hMLH1 or BRCA2 loci associated with response of cervical and endometrial cancer to radiotherapy. 1206 Aug 51

Cervical cancer is known to be highly associated with viral oncogene E6 and E7 of human papilloma virus. Down-regulation of oncogene expression by antisense-based gene therapy has been extensively studied. To investigate the effect of HPV 16 E6 antisense nucleic acid (AS) on cervical cancer cells, human cervical cancer cell lines, CaSki and SiHa cells harboring HPV 16 genome were transfected with plasmid containing E6(AS). The decreased viability and the apoptotic morphology were observed in E6(AS)-transfected cervical cancer cell lines. By 6 h after transfection, inhibition of E6 splicing, rapid upregulations of p53 and a p53-responsive protein, GADD45, were displayed in E6(AS)-transfected CaSki cells. Furthermore, E6(AS) induced loss of mitochondrial transmembrane potential, release of mitochondrial cytochrome c into the cytoplasm, and subsequent activation of caspase-9 and caspase-3. These results indicate that HPV 16 E6(AS) induces apoptosis in CaSki cells via upregulation of p53 and release of cytochrome c into cytoplasm, consequently activating procaspase-9 and procaspase-3.
Exp Mol Med 2002 May 31
PMID:HPV E6 antisense induces apoptosis in CaSki cells via suppression of E6 splicing. 1208 99

Arsenic trioxide (As(2)O(3)) has been found to induce apoptosis in leukemia cell lines and clinical remissions in patients with acute promyelocytic leukemia. In this study, we investigated the cytotoxic effect and mechanisms of action of As(2)O(3) in human tumor cell lines. As(2)O(3) caused inhibition of cell growth (IC(50) range, 3-14 microM) in a variety of human solid tumor cell lines, including four human non-small-cell lung cancer cell lines (H460, H322, H520, H661), two ovarian cancer cell lines (SK-OV-03, A2780), cervical cancer HeLa, and breast carcinoma MCF-7, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry analysis showed that As(2)O(3) treatment resulted in a time-dependent accumulation of cells in the G(2)/M phase. We observed, using Wright-Giemsa and 4',6-diamidine-2-phenylindole-dihydrochloride staining, that As(2)O(3) blocked the cell cycle in mitosis. In vitro examination revealed that As(2)O(3) markedly promoted tubulin polymerization without affecting GTP binding to beta-tubulin. Immunocytochemical and EM studies of treated MCF-7 cells showed that As(2)O(3) treatment caused changes in the cellular microtubule network and formation of polymerized microtubules. Similar to most anti-tubulin agents, As(2)O(3) treatment induced up-regulation of the cyclin B1 levels and activation of p34(cdc2)/cyclinB1 kinase, as well as Bcl-2 phosphorylation. Furthermore, activation of caspase-3 and -7 and cleavage of poly(ADP-ribose) polymerase and beta-catenin occurred only in As(2)O(3)-induced mitotic cells, not in interphase cells, suggesting that As(2)O(3)-induced mitotic arrest may be a requirement for the activation of apoptotic pathways. In addition, As(2)O(3) exhibited similar inhibitory effects against parental MCF-7, P-glycoprotein-overexpressing MCF-7/doxorubicin cells, and multidrug resistance protein (MRP)-expressing MCF-7/etoposide cells (resistance indices, 2.3 and 1.9, respectively). Similarly, As(2)O(3) had similar inhibitory effect against parental ovarian carcinoma A2780 cells and tubulin mutation paclitaxel-resistant cell lines PTx10 and PTx22 (resistance indices, 0.86 and 0.93, respectively), suggesting that its effect on tubulin polymerization and G(2)/M phase arrest is distinct from that of paclitaxel. Taken together, our data demonstrate that As(2)O(3) has a paclitaxel-like effect, markedly promotes tubulin polymerization, arrests cell cycle at mitosis, and induces apoptosis. In addition, As(2)O(3) is a poor substrate for transport by P-glycoprotein and MRP, and non-cross-resistant with paclitaxel resistant cell lines due to tubulin mutation, suggesting that As(2)O(3) may be useful for treatment of human solid tumors, particularly in patients with paclitaxel resistance.
Mol Pharmacol 2002 Sep
PMID:Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apoptosis in human tumor cell lines. 1218 29

The present study examined the relationship between lipid peroxidation and antioxidant status in plasma, erythrocyte and erythrocyte membrane of cervical cancer patients and an equal number of age and sex matched normal subjects as well as patients with cervicitis. Lipid peroxidation was significantly increased with concomitant decrease in antioxidant levels in cervical cancer patients as compared to normal subjects and patients with cervicitis. The elevated lipid peroxidation and disturbed antioxidant status was also noticed in cervicitis patients as compared to normal subjects. This increase in lipid peroxidation can be attributed to possible breakdown of antioxidant mechanisms in cervicitis and cervical cancer patients.
J Biochem Mol Biol Biophys 2002 Jun
PMID:Lipid peroxidation and antioxidant status in cervical cancer patients. 1218 59


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