Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosomal copy number changes were investigated in 16 prostate carcinomas, 12 prostatic intraepithelial neoplasias (PIN; 4 low-grade and 8 high-grade) adjacent to the invasive tumour areas, and 5 regional lymph node metastases. For this purpose, comparative genomic hybridization (CGH) was performed and a copy number karyotype for each histomorphological entity was created. CGH on microdissected cells from non-neoplastic glands was carried out on 3 different cases to demonstrate the reliability of the overall procedure. None of the non-neoplastic tissue samples revealed chromosome copy number changes. In PIN areas, chromosomal imbalances were detected on chromosomes 7, 8q, Xq (gains), and on 4q, 5q, 8p, 13q and 18q (losses). In the primary tumours, recurrent (at least 25% of cases) gains on chromosomes 12q and 15q, and losses on 2q, 4q, 5q, Xq, 13q and 18q became apparent. Losses on 8p and 6q as well as gains on 8q and of chromosome 7 were also detected at lower frequencies than previously reported. The pooled CGH data from the primary carcinomas revealed a novel region of chromosomal loss on 4q which is also frequently affected in other tumour entities like oesophageal adenocarcinomas and is supposed to harbour a new tumour suppressor gene. Gains on chromosome 9q and of chromosome 16 and loss on chromosome 13q were observed as common aberrations in metastases and primary tumours. These CGH results indicate an accumulation of chromosomal imbalances during the PIN-carcinoma-metastasis sequence and an early origin of tumour-specific aberrations in PIN areas.
...
PMID:Chromosomal changes during development and progression of prostate adenocarcinomas. 1116 78

For several reasons, chromosome 3p is thought to be involved in the pathogenesis of sporadic endocrine pancreatic tumours (EPTs): von Hippel-Lindau's disease (VHL gene at 3p25.5) is associated with EPTs; 3p is frequently involved in solid human tumours; and comparative genomic hybridization has identified frequent losses at 3p in EPTs. This study investigated 99 benign and malignant tumours, including 20 metastases, from 82 patients, by microsatellite loss of heterozygosity (LOH) analysis and fluorescence in situ hybridization (FISH) in order to evaluate the importance of chromosome 3p deletions in the molecular pathogenesis and biological behaviour of EPTs, to elaborate a common region of deletion, and to narrow down putative tumour suppressor gene loci. Allelic losses of 3p were found in 58/99 (58.6%) of tumours in 45/82 (54.9%) patients; analysis of seven microsatellite markers (3p26-p21) revealed a common region of LOH at 3p25.3-p23. The LOH frequency was significantly higher in malignant than in benign neoplasms (70.2% versus 28.0%; p=0.001). In addition, a strong correlation was found between the loss of alleles on chromosome 3p and clinically metastatic disease (LOH of 73.7% in metastasizing versus 41.5% in non-metastasizing tumours; p=0.008). EPTs from these patients showed a tendency towards losing large parts or the entire short arm of chromosome 3 with tumour progression. Furthermore, FISH analysis revealed complete loss of chromosome 3 in ten out of 37 EPTs (27%). These results indicate that a putative tumour suppressor gene at 3p25.3-p23 may play a role in the oncogenesis of sporadic EPTs and that losses of larger centromeric regions are associated with metastatic progression.
...
PMID:Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression. 1152 53

Maspin is an inhibitor of serine proteinases with tumour suppressor activity. Its expression appears to be reduced in advanced stages of breast cancer. A large series of archival breast tissue specimens has been examined, including normal glands (n=7), fibrocystic change (n=22), ductal carcinoma in situ (DCIS, n=12), infiltrating carcinomas (n=128) and their lymph node metastases (n=65), using a specific monoclonal antibody. Myoepithelium invariably showed strong maspin expression. In epithelial cells, the strongest expression was found in normal breast and fibrocystic change. A significant stepwise decrease in maspin expression (p<0.0001) occurred in the sequence DCIS - invasive cancer - lymph node metastasis. However, a subset of infiltrating carcinomas showed strong maspin expression, significantly associated with a lower rate of lymph node metastasis at the time of diagnosis (p<0.01). This was independent of tumour size and grade. The in vivo observations presented here are in keeping with data obtained in prior in vitro experiments. Maspin emerges as an indicator of tumour progression and metastatic potential, and might be exploited to predict breast cancer prognosis. According to in vitro data, its tumour suppressor activity is likely to involve both the modulation of cell motility/invasiveness and the inhibition of angiogenesis.
...
PMID:Decline in the expression of the serine proteinase inhibitor maspin is associated with tumour progression in ductal carcinomas of the breast. 1201 53

Several genetic alterations have been implicated in the development of malignant melanoma, but the expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes and their interactions in melanoma have not been completely clarified. We simultaneously examined the expression of p73, c-erbB-2, ras, p53, Mdm2, p27, DCC, hMLH-1, hMSH-2, bcl-2, Bax and NF-kappaB, by immunocytochemistry, in both primary and metastatic melanoma cell lines derived from melanoma patients. p73 was expressed in 7/8 cell lines, but stronger expressed in the metastatic cells than in the primary melanoma cells. c-erbB-2 was detected in all 8 cell lines and ras in 2/5 metastases. p53 was found in all the cell lines and Mdm2 in 1/8 of the cell lines. In the same patient, the intensity of p27 expression was decreased from the primary to the metastatic tumours. bcl-2 was expressed in all the cell lines. Bax was absent in 5/8 cell lines. In the same patient, Bax was weakly expressed in the primary tumour but lacking in the metastases. The data demonstrate that overexpression of p73, c-erbB-2, p53 and bcl-2, and loss of Mdm2 and Bax may interact and play important roles in the development and aggressiveness of human melanoma.
...
PMID:Expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes in primary and metastatic melanoma cells. 1171 83

Many oncogenes and tumour suppressor genes are connected with the steps of carcinogenesis. Fifteen patients with endometrial cancer were immunohistochemically examined for the presence of abnormal p53 protein. The immunopositivity was comparted in the cancer tissues and analyzed with the conventional clinicopathological prognostic factors as grade, stage, depth of myometrial invasion, lymph-vascular space invasion, metastases in the lymph nodes and metastases in the abdominal cavity. Abnormal expression of p53 was observed in 7 women with endometrial cancer and in 5 patients we observed moderate cytoplasmatic reaction for BCL-2. The correlation between the positive reaction reaction for p53 and BCL-2 means more aggressive tumor, respectively is a bad prognostic factor. The overexpression of p53 is a very important parameter for the progression of the endometrial cancer.
...
PMID:[Expression of p53 protein in women with endometrial cancer]. 1180 62

Prostatic adenocarcinoma (CaP) is the most common, non-cutaneous malignancy and the second-leading cause of cancer death in men. The disease has two distinct phases: the androgen-dependent phase, which can be treated effectively with androgen ablation therapies, and the androgen-independent phase, for which there is no effective life-prolonging therapy. An estimated 32,000 men will die this year from androgen-independent, metastatic CaP. Efforts to understand the metastatic progression of CaP and the emergence of androgen-independent disease have begun to illuminate the molecular events involved. Recent work suggests that CaP progression to androgen-independent, metastatic disease involves a dampened apoptotic response, a release from the cell cycle block that initially follows androgen withdrawal and a shift from dependence on paracrine-derived growth and survival factors to autonomous production of these key proteins. Functional loss of the tumour suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN) and subsequent activation of the AKT pathway, have been prominently implicated in the progression of CaP to androgen-independence. Activation of the AKT pathway can suppress the apoptotic response, undermine cell cycle control and selectively enhance the production of key growth and survival factors. Though many proteins and intracellular signalling pathways can influence these biological processes, activation of the AKT pathway may be a particularly potent signal involved in CaP progression to androgen-independence and therefore presents a series of potential targets for therapy of advanced androgen-independent CaP.
...
PMID:Emerging targets in the AKT pathway for treatment of androgen-independent prostatic adenocarcinoma. 1190 76

Deleted in malignant brain tumours 1 (DMBT1), a candidate tumour suppressor gene located on chromosome 10q25.3-q26.1, has recently been identified and found to be deleted in several different types of human tumours. In melanomas, the chromosomal region 10q22-qter is commonly affected by losses, hence we screened primary melanoma samples for losses of heterozygosity (LOH), and acquired melanocytic naevi and melanomas for transcription of DMBT1 and protein expression. Of 38 informative melanomas, 1 nodular melanoma and 2 subcutaneous metastases showed LOH of both microsatellites flanking the gene, suggesting loss of 1 DMBT1 allele. Three further melanomas showed LOH at 1 informative locus but were heterozygous for the second marker. Applying reverse-transcription polymerase chain reaction (RT-PCR), DMBT1 transcription was not found in melanomas. However, DMBT1 transcription was also absent from the majority of naevi from which melanomas frequently arise, making down-regulation of gene transcription during transformation from naevus to melanoma unlikely. Immunohistochemistry showed nerves, sweat glands and the stratum spinosum of the epidermis to be DMBT1 protein positive, whereas the naevi and melanoma cells themselves were negative. All considered, the candidate tumour suppressor gene DMBT1 does not appear to be a major inactivation target in the development of melanomas.
...
PMID:Analysis of losses of heterozygosity of the candidate tumour suppressor gene DMBT1 in melanoma resection specimens. 1223 52

PTEN/MMAC1, a tumour suppressor gene located on chromosome 10q23.3, has been found to be deleted in several types of human malignancies. As the chromosomal region 10q22-qter commonly is affected by losses in melanomas, we addressed this gene as tumour suppressor candidate in melanomas. Investigating PTEN/MMAC1 expression at mRNA level by semi-quantitative reverse transcription-polymerase chain reaction, we did not find a statistically significant down-regulation in melanoma resection specimens in comparison to acquired melanocytic nevi from which melanomas quite often are known to arise. Upon immunohistochemistry, PTEN/MMAC1 protein expression in melanomas was not lost. Sequencing the PTEN/MMAC1 cDNAs in 26 melanoma resection specimens (21 primary melanomas, five metastases), we detected three point mutations and two nucleotide deletions which did not represent genetic polymorphisms. With respect to the predicted protein sequences, all three point mutations were silent whereas the two frame shifts at the extreme C-terminus resulted in a loss of the putative PDZ-targeting consensus sequence. As loss of this motif possibly impairs localization and function of PTEN/MMAC1 in the two corresponding primary tumours, alterations of this tumour suppressor protein may participate in some melanomas.
...
PMID:PTEN/MMAC1 expression in melanoma resection specimens. 1245 73

Deletions in 1p36 in malignant melanoma have been found in high percentages in nodular melanomas and melanoma metastases. Despite many efforts, no candidate tumour suppressor gene associated with malignant melanoma has so far been found in this region. To further determine a possible tumour suppressor gene locus, we carried out a deletion mapping of chromosome 1p36 at nine microsatellite loci in 74 malignant melanomas. Loss of heterozygosity (LOH) in this region was found in 77% of nodular melanomas (NMs), 86% of metastatic melanomas, but only 20% of superficial spreading melanomas (SSMs). Regarding the allelic losses, the nodular and metastatic melanoma samples could be divided into three groups: one showing LOH at the more telomeric loci D1S243 and D1S468 (1p36.33), one displaying allelic loss at the more centromeric loci D1S214 and D1S253 (1p36.32-31) and one with LOH over all informative loci between D1S243 and D1S160. We did not find any significant correlation between a deletion in any of the investigated loci and the survival data of the patients. However, our results confine the deleted region in malignant melanoma to a very small area around 1p36.32, thus facilitating the search for the tumour suppressor gene with importance in malignant melanoma.
...
PMID:Microsatellite analysis at 1p36.3 in malignant melanoma of the skin: fine mapping in search of a possible tumour suppressor gene region. 1256 82

Gastric cancer, like all cancers, is considered to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumour suppressor loss. More recently, the role of epigenetic change as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes has emerged in many cancer types. The study of DNA methylation changes in gastric cancer has now provided additional clues into the pathogenesis of the disease. E-cadherin as a metastases suppressor is mutationally inactivated in both familial and sporadic forms of gastric cancers. Evidence now suggests that the transcriptional silencing of E-cadherin gene by promotor methylation plays a crucial role in the development and progression of gastric malignancies. In order to further analyze the role of E-cadherin gene promotor methylation in gastric carcinogenesis and progression, we performed the studies of promoter methylation status and protein expression of E-cadherin gene in associated progression stages of gastric cancer. DNA were extracted from the paraffin embedded gastric specimens of dysplasia(23 cases), early cancer (20 cases) and advanced cancer (20 cases). Methylation specific PCR and immunohistochemistry were used to analyze the promoter methylation status and the protein expression level of E-cadherin gene. Our results showed that E-cadherin promoter methylation occurred in all stages of gastric precancerous lesion and carcinogenesis, which suggests E-cadherin promotor methylation is an important event during gastric carcinogenesis and progression. The positive rate of E-cadherin promotor methylation in dysplasia, early gastric cancer and advanced gastric cancer was 78.3%, 80% and 90% respectively. There were significant differences between experimental groups and control group(30%), P < 0.05, but no significant differences among experimental groups, P > 0.05. All of advanced gastric cancer examined were completely E-cadherin protein-negative by immunohistochemistry. Fourteen of 20 early gastric cancer were E-cadherin-negative. And 23 dysplasia were all E-cadherin-positive. Thirty-one of 34(91%) of the E-cadherin-negative tumours had promotor methylation. This result indicated the downregulation expression of E-cadherin was associated with promotor methylation in early and advanced gastric cancer (P < 0.01).
...
PMID:[Studies of promoter methylation status and protein expression of E-cadherin gene in associated progression stages of gastric cancer]. 1277 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---