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)

To investigate the relationship between the presence of circulating tumor cells in different stages of gastrointestinal tract cancer and the subsequent relapse or distant metastasis, circulating levels of CEA mRNA was serially examined at an interval of 10.6+/-4.5 or 13.7+/-3.0 months in gastric or colorectal cancer patients, respectively. CEA mRNA was measured by means of RT-PCR amplification as an indicator for micrometastatic malignant cells. Seven of twenty-nine respectable gastric cancer patients (24.1%) [EGC: 2/9 (22.2%), AGC IIIa: 1/5 (20.0%), AGC IIIb: 4/15 (26.6%)] were positive for CEA mRNA on the initial test and 10 of 29 patients (34.4%) [EGC: 2/ 9 (22.2%), AGC IIIa: 1/5 (20.0%), AGC IIIb: 7/15 (46.7%)] were positive on a follow-up test. Only in AGC IIIb, the positive rate for CEA mRNA increased about twice and 6 of 7 positive cases (85.7%) relapsed within 2.6+/-2.4 months after the follow-up test. In colorectal cancer, 4 of 19 patients (21.1%) [B2: 1/6 (16.7%), C2: 3/13 (23.0%)] were positive on the initial test and 10 of 19 patients (52.6%) [B2: 4/6 (66.7%), C2: 6/13 (46.2%)] were positive on a follow-up test showing an increase in positive rates during a follow-up, however, no significant correlation between CEA mRNA positivity and subsequent relapse was demonstrated. These results suggest that an early tumor cell dissemination may occur in gastrointestinal tract cancer without subsequent relapse, however, the serial regular examination of CEA mRNA level may contribute to predicting a subsequent relapse in AGC IIIb in gastric cancer.
Exp Mol Med 2001 Mar 31
PMID:Detection of circulating tumor cells in patients with gastrointestinal tract cancer using RT-PCR and its clinical implications. 1132 88

Helicobacter pylori was already present in the stomach of primitive humans as they left Africa and spread through the world. Today, it still chronically infects more than 50% of the human population, causing, in some cases, severe diseases such as peptic ulcers and stomach cancer. To succeed in these long-term associations, H. pylori has developed a unique set of virulence factors, which allow survival in a unique and hostile ecological niche--the human stomach.
Nat Rev Mol Cell Biol 2001 Jun
PMID:Living dangerously: how Helicobacter pylori survives in the human stomach. 1138 69

The number of mammalian calpain protease family members has grown to 14 on last count. Overactivation of calpain 1 and calpain 2 (and their small subunit) has long been tied to acute neurological disorders (e.g. stroke and traumatic brain injury) and recently to Alzheimer's disease. Loss-of-function mutations of the calpain 3 gene have now been identified as the cause of limb-girdle muscular dystrophy 2A. Calpain 10 was recently identified as a susceptibility gene for type 2 diabetes, whereas calpain 9 appears to be a gastric cancer suppressor. This review describes our current understanding of the calpain family members and their mechanistic linkages to the aforementioned diseases as well as other emerging pathological conditions.
Trends Mol Med 2001 Aug
PMID:The calpain family and human disease. 1151 96

Inactivating mutations have been found in the cell-cell adhesion molecule E-cadherin (CDH1), which acts as a tumor suppressor gene in different kinds of cancers, e.g. primarily diffuse gastric cancer and lobular breast cancer. In this study, we screened for germline alterations in familial gastric and colon cancer cases. In total, 20 gastric and 18 colon cancer patients with both familial gastric and colon cancer were tested for germline E-cadherin alterations by using PCR/SSCP, specific restriction digestion test and sequencing. No pathogenic mutations were identified in the gastric cancer patients. In two colon cancer patients, a missense mutation in exon 12, codon 592 (Ala592Thr) was found. This alteration segregated with diffuse gastric cancer and colon cancer in one of the families. The prevalence of this alteration in the general population and colon cancer cases was almost the same. However, the fact that this alteration (Ala592Thr) segregated with colon cancer and diffuse gastric cancer in one big family, suggests that this E-cadherin missense alteration, beside predisposing to diffuse gastric cancer, also may play a role in colorectal carcinogenesis.
Int J Mol Med 2001 Oct
PMID:A germline E-cadherin mutation in a family with gastric and colon cancer. 1156 85

We used Bcl-2 antisense oligonucleotides (G3139) to chemosensitize human gastric cancer by downregulation of Bcl-2 expression in vivo. Oligonucleotides and cisplatin were administered systemically in a human gastric cancer SCID mouse model, and Bcl-2 expression, apoptosis, tumor size, and survival were assessed. Used alone, G3139 treatment led to downregulation of Bcl-2 and moderate tumor reduction compared to saline control. G3139 combined with cisplatin treatment markedly enhanced the antitumor effect of cisplatin (70% tumor size reduction vs. cisplatin alone), associated with increased apoptosis measured in tumor biopsy specimens. Combined treatment with G3139 and cisplatin prolonged survival of the tumor-bearing SCID mice by more than 50% without adding significant drug-related toxicity. Treatment with Bcl-2 antisense oligonucleotides is thus a promising novel approach to enhance antitumor activity of cisplatin or other drugs used in gastric cancer therapy and warrants further evaluation in clinical trials.
J Mol Med (Berl) 2001 Oct
PMID:Bcl-2 antisense oligonucleotides chemosensitize human gastric cancer in a SCID mouse xenotransplantation model. 1169 56

Large scale scanning of the human genome has become possible with the introduction of DNA microarray. The ability to survey the expression of up to 5000 to 50,000 genes in a single experiment provides significant new opportunities, as well as new challenge. It will be important to translate genomic scale information on cancer biology to functional or clinical application. This requires prioritization of hundreds of targets discovered, functional validation of these targets, as well as a thorough knowledge of the involvement of the candidate target genes in vivo in human tissue. We have developed a tissue array technology for genome scale expressional and clinical cancer research. This technology enables high-throughput molecular analysis of large number of specimens. Our tissue arrays are constructed by arranging the cylindrical biopsies of 2.0 mm diameter from 60 individual tumor tissues into a tissue array block, which is then sliced into 200 or more identical slides for probing RNA or protein targets. A single immunohistochemistry or in situ hybridization experiment provides information on all 60 specimens on the slides, while subsequent sections can be analyzed with other probes or antibodies. We produced gastric cancer tissue array slides with various kinds of subsets, including 600 subsequent cancer cases, 100 preneoplastic lesions, 60 metastatic lesions, 60 synchronous cancers, 60 metachronous cancers, 60 young age patients, and 120 familial cases. We searched the presence of Epstein-Barr virus in those cancer specimens. We also applied 10 antibodies in those samples and stratify the prognostic significance of these antibodies. Tissue array technology expand the scope of high-throughput molecular analysis of archival tissue specimens with multiple probes for specific genes or proteins for functional or clinical application.
Exp Mol Med 2001 Apr 21
PMID:[Tissue array technology for translational research. From gene discovery to application]. 1170 21

ICAT inhibits the interaction between beta-catenin and TCF transcription factors. As ICAT might be a tumor suppressor gene with the potential to negatively regulate the WNT - beta-catenin - TCF signaling pathway, ICAT related gene in the human genome draft sequence was searched for. Here, the LZIC gene, a novel gene encoding a 190-amino-acid polypeptide with leucine zipper domain and ICAT homologous domain, was cloned and characterized. Amino-acid identity between LZIC and ICAT in the ICAT homologous domain was 38%. The LZIC gene, consisting of at least 8 exons, was located in the human chromosome 1p36.32-pter region. The major 5.2-kb LZIC mRNA and minor 2.1-, 1.6-, and 1.0-kb LZIC mRNAs were expressed almost ubiquitously in normal human tissues. LZIC was expressed in all cancer cell lines examined in this study, and was significantly up-regulated in a gastric cancer cell line MKN74 and 5 cases of primary gastric cancer. As LZIC contains ICAT homologous domain, LZIC might inhibit the interaction between beta-catenin and TCF transcription factors, just like ICAT, and, up-regulation of LZIC in gastric cancer might be due to a negative feed-back mechanism to inhibit the WNT - beta-catenin - TCF signaling pathway.
Int J Mol Med 2001 Dec
PMID:Molecular cloning and characterization of LZIC, a novel gene encoding ICAT homologous protein with leucine zipper domain. 1171 74

WNT signaling pathway is implicated in carcinogenesis. Here, we cloned and characterized human WNT11, which showed three amino-acid substitutions (Ala121Thr, Gly156Arg, and Ser271Trp) compared with human WNT11 cDNA previously isolated by another group. WNT11 encoded a 354 amino-acid polypeptide with five N-glycosylation sites. Gly156 of human WNT11 was conserved in other members of the human WNT family, such as WNT2B1, WNT2B2, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT10A, and WNT14. The Ala121-Gly156-Ser271 WNT11 allele isolated in this study was also identified in human genome draft sequence AC069055. Expression profile of WNT11 was next investigated. The 4.3-kb WNT11 mRNA was expressed in fetal lung, kidney, adult heart, liver, skeletal muscle, and pancreas. WNT11 mRNA was significantly up-regulated in a gastric cancer cell line MKN45 and a cervical cancer cell line SKG-IIIa. Among various types of human primary tumors, WNT11 mRNA was up-regulated in four cases of colorectal adenocarcinoma, and a case of renal cell carcinoma. Up-regulation of WNT11 mRNA might play an important role in human carcinogenesis through activation of the WNT signaling pathway.
Int J Mol Med 2001 Dec
PMID:Molecular cloning and characterization of human WNT11. 1171 81

WNT2 is one of proto-oncogenes to activate the beta-catenin - TCF signaling pathway. WNT2B is a paralogue of WNT2, which encodes WNT2B1 and WNT2B2 isoforms due to alternative splicing using alternative promoter. Here, regulation of WNT2, WNT2B1, and WNT2B2 mRNAs in MCF-7 cells (breast cancer), NT2 cells (teratocarcinoma), and MKN45 cells (gastric cancer) were investigated. WNT2B2, but not WNT2 and WNT2B1, was expressed in MCF-7 cells. beta-estradiol (100 nM) induced a transient up-regulation of WNT2 in MCF-7 cells, and also induced down-regulation of WNT2B2. WNT2B2, but not WNT2B1, was expressed in NT2 cells, and WNT2 was slightly expressed in NT2 cells. Retinoic acid (10 microM) induced a transient up-regulation of WNT2 in NT2 cells. WNT2B2, but not WNT2 and WNT2B1, was slightly expressed MKN45 cells, and tumor necrosis factor alpha did not affect expression of WNT2, WNT2B1, and WNT2B2 mRNAs in MKN45 cells. This is the first report on differential regulation of WNT2, WNT2B1, and WNT2B2 mRNAs in human cancer cell lines. Up-regulation of WNT2 mRNA by estrogen might play a key role in some cases of human breast cancer through activation of the beta-catenin - TCF signaling pathway.
Int J Mol Med 2001 Dec
PMID:Differential regulation of WNT2 and WNT2B expression in human cancer. 1171 82

Survivin is a member of the inhibitor of apoptosis protein (IAP) family. The expression of survivin has not been reported in differentiated normal tissues, but it has been observed in many cancerous tissues. Recent studies have revealed that survivin may correlate with the chemo-radio resistance of certain malignant cells. In the present study, the correlation between the occurrence of apoptosis and the level of expression of survivin messenger RNA (mRNA) was investigated in a gastric cancer cell line (MKN-45) and in patients with advanced gastric cancer during cisplatin (CDDP) treatment. In the gastric cancer cell line, the percentage of apoptotic cells (apoptotic index: AI) did not change after 48 h incubation with low-dose CDDP (1 microg/ml), whereas the AI explosively increased between 12 and 24 h treatment with high-dose CDDP (10 microg/ml). Relative levels of expression of survivin mRNA and survivin protein increased after low- and high-dose CDDP treatment. Survivin mRNA was not detected in normal gastric mucosas. Also, in 13 patients with advanced gastric cancer who underwent CDDP-based preoperative chemotherapy, survivin mRNA was detected in only 2 cases (15.4%). Survivin mRNA was observed in the resected tumor specimens of two cases. No significant correlation between survivin mRNA expression and the occurrence of apoptosis in resected tumors or between survivin mRNA expression and patient survival was observed. These findings indicate that survivin may play an important role for the chemoresistance of this cancer cell line. However, the clinical importance of survivin expression remains unclear in patients with gastric cancer.
Int J Mol Med 2001 Dec
PMID:Changes in survivin messenger RNA level during cisplatin treatment in gastric cancer. 1171 83


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