Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel association, Epstein-Barr virus-positive Ki-1+/CD30+ anaplastic large cell non-Hodgkin's lymphoma of B-cell phenotype in immunosuppressed renal transplant recipients is reported. Case 1 involved an aggressive clinical evolution, whereas case 2 followed a more "benign" clinical course. Both lymphomas were Epstein-Barr virus-positive as assessed by in situ hybridization, Southern blot, polymerase chain reaction, and immunohistochemical analysis. Both lymphomas contained a single clonal Epstein-Barr virus terminal-repeat fragment. In case 1, clonality was confirmed by the detection of bi-allelic immunoglobulin (Ig) heavy chain gene rearrangement. Case 2 showed germline Ig genes at presentation and oligoclonal Ig heavy chain gene rearrangements at relapse. These results are consistent with the notion that anaplastic large cell lymphoma might arise in a B cell transformed by Epstein-Barr virus at a very early stage, before Ig gene rearrangement. The latter may occur later in the course of clonal evolution, thus permitting investigators to trace intermediate and late stages within a process of multistep lymphomagenesis and/or tumor progression.
 ...
PMID:Epstein-Barr virus-associated anaplastic large cell lymphoma in renal transplant patients. 132 90

The t(14;18) chromosomal translocation that results in the juxtaposition of the bcl-2 proto-oncogene with the heavy chain JH locus is a common cytogenetic abnormality in human lymphoma. In particular, it is seen in about 85% of follicular lymphoma (FL) and up to one-third of diffuse lymphomas (DL). The chromosome 18 breakpoints have been shown to cluster into two regions. The major breakpoint region (mbr) within the 3' untranslated region of the bcl-2 proto-oncogene accounts for approximately 60% of the cases and the minor cluster region (mcr) 30 kb 3' of bcl-2 accounts for approximately 25% of the breakpoints. Because of variability in the position of the breakpoint, detection of the t(14;18) by Southern blot analysis provides an important clonal marker for the tumor. However, conventional electrophoresis (CE) fails to detect the translocation in 15% to 25% of cases. We have applied pulsed-field gel electrophoresis (PFGE) to the detection of the t(14;18) in a series of lymphoma prospectively analyzed by CE, polymerase chain reaction (PCR), and cytogenetic analysis. PFGE readily detected t(14;18) rearrangements as indicated by comigration of bands detected with probes for the mbr region (chromosome 18) and the JH locus (chromosome 14). In a series of 40 patients with FL, this method proved to be the most comprehensive for detection of the translocation compared with standard methods; in fact, in one case only PFGE was able to detect the chromosomal rearrangement. Ten percent of the FL cases were negative by all methods tested. In a separate analysis of matched tissue specimens from cases of tumor progression of FL to diffuse lymphoma, PFGE detected a common t(14;18) rearrangement confirming a clonal origin in seven of seven cases, whereas CE detected a rearrangement in only three of seven cases. Overall, PFGE was able to detect a translocation in 8 of 12 cases that were negative by CE and four of eight negative by cytogenetic analysis. In conclusion, PFGE analysis is more comprehensive than CE, PCR, and cytogenetic analysis for the detection of the t(14;18) breakpoint in tissue biopsies of malignant lymphoma.
 ...
PMID:Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis. 188 22

The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has been described for NHLs with this translocation. We examined a panel of NHLs with t(11;14) for overexpression of p53 and correlated the results with single-strand conformation polymorphism (SSCP) analysis, karyotypic features, and clinical course. NHLs with t(11;14) were identified from 30 patients. The diagnosis was MCL for 23 of 30, small lymphocytic lymphoma for 4 of 30, and diffuse large-cell lymphoma for 3 of 30 cases. The results of immunohistochemistry analysis using a monoclonal anti-p53 antibody on paraffin-embedded specimens were compared with the SSCP data, the tumor karyotypes, and clinical course of each patient. DNA sequencing of exons was performed on cases that showed conformational changes by SSCP analysis. NHLs from 5 of 23 patients with MCL were positive for p53 overexpression. Deletions of chromosome 17p were identified in 2 of 30 cases, both of which were MCLs showing p53 overexpression. Two of the five MCLs with p53 overexpression showed evidence for TP53 mutations. None of the 18 MCLs negative for p53 overexpression showed conformational changes by SSCP. For these 18 patients with MCLs that did not overexpress p53, the median survival was 63 months, compared with 12 months for the 5 patients with MCLs positive for p53 overexpression (P < .001). These results suggest that p53 overexpression in MCL with t(11;14)(q13;q32) may serve as a marker of poor prognosis.
 ...
PMID:p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32). 757 80

Retrovirus-mediated gene transfer was employed to introduce two different cDNAs of the human tumor necrosis factor alpha gene (TNF) into colon carcinoma cell lines either sensitive (LoVo) or resistant (LS174T) to the external addition of TNF. The TNF variants differed in their 5'-sequences (HTNF: authentic TNF cDNA, SPTNF: TNF cDNA with a signal sequence of the IgG heavy chain). The integration of TNF-specific DNA into the genomic DNA, the expression of TNF-specific mRNA and the translation into TNF protein was shown by Southern-, Northern- and Western analysis with TNF-specific DNA- and RNA probes and anti-TNF-antibodies, respectively. Neomycin selected tumor cell clones expressed biologically active TNF up to 40 pg/ml. As shown in a growth assay, both variants of TNF caused an up to 80% growth inhibition in colon carcinoma cells. Furthermore, the cells constitutively producing TNF had a distinguishable morphological appearance and a reduced colony growth in soft agar compared to the parental cells. The subcutaneous injection of 1 x 10(6) TNF-expressing tumor cells into nude mice resulted in a reduced tumor progression in comparison to the controls.
 ...
PMID:Retrovirus-mediated gene transfer of tumor necrosis factor alpha into colon carcinoma cells generates a growth inhibition. 823 36

Scatter factor (SF), a secretory protein of fibroblasts, dissociates and increases the motility of epithelial cells and may be involved in cell migration processes during embryogenesis and tumor progression. Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and other cells, and is thought to play a role in liver regeneration. We have presented structural and functional evidence that human SF and human HGF are identical proteins encoded by a single gene, since (i) no differences could be found by protein sequencing, by cDNA analysis, or by immunological comparison, and (ii) SF acts as a hepatocyte growth factor--i.e., stimulates DNA synthesis of primary hepatocytes and is a morphogen of kidney epithelial cells--whereas HGF exhibits SF activity--i.e., dissociates and induces invasiveness of various epithelial cells. Furthermore, there exists only one gene for human HGF-SF which is located on chromosome 7, bands q11.2-21 (Weidner et al., Proc. Natl. Acad. Sci. USA 88, 7001-7005, 1991). HGF-SF has been found to be the ligand of the c-met receptor tyrosine kinase (Naldini et al., EMBO J. 10, 2867-2878, 1991b). We have recently used transient expression of naturally occurring and in vitro mutagenized cDNAs of HGF-SF in order to delineate the protein domains necessary for biological activity and c-met receptor activation. (i) A single-chain HGF-SF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg494 to Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A HGF-SF splice variant encoding a protein with a 5 amino acid deletion in the first kringle domain was as highly active as the wild type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N-terminus and the first two kringle domains bound the met receptor, stimulated its tyrosine phosphorylation, and induced dissociation of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N-terminal region and/or the first two kringle domains of HGF-SF is sufficient for binding to and activation of the met receptor (Hartmann et al., Proc. Natl. Acad. Sci. USA, in press).
 ...
PMID:Molecular characteristics of HGF-SF and its role in cell motility and invasion. 838 Jul 39

The differential diagnosis between Helicobacter pylori (H pylori-associated chronic gastritis and low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) and the assessment of endoscopic biopsy specimens after treatment of lymphoma can be problematic. Although immunocytochemistry can be used to identify clonal B-cell populations, which are characteristic of MALT lymphoma, its application to small biopsy specimens and the subsequent interpretation can be difficult. The polymerase chain reaction (PCR) can detect clonal B-cell populations by analysis of the Ig heavy chain gene in routinely fixed paraffin-embedded material and might provide a useful tool in the assessment of these specimens. We have investigated the value of histology and PCR in the diagnosis of lymphoma and its followup in formalin-fixed paraffin-embedded gastric endoscopy biopsy specimens from 69 sequential patients selected on the basis of a dense mucosal lymphoid infiltrate associated with H pylori infection. Histologic evidence of MALT lymphoma was identified in 13 cases, 9 of which showed PCR-detected monoclonality. In 12 of 13 cases, H pylori was eradicated, and in 11 of 12 cases, histologic regression of the lymphoma followed. PCR evidence of monoclonality disappeared in 6 of 9 originally monoclonal cases. This was synchronous with histologic remission in 1 case, but lagged in the remaining 5 cases by up to 28 months. Two of the 3 of the 9 cases originally monoclonal by PCR that have not shown molecular regression have monoclonal-amplified products 17 and 24 months after negative histology. In 3 cases, the histology of the biopsies was considered indeterminate or discordant. In 1 of these cases, the histologic features were obscured by crush artefact. In a second case, there was molecular evidence of monoclonality in the absence of histologic features suggestive of lymphoma; this persisted after H pylori eradication. An additional single case originally diagnosed as reactive developed a PCR detectable clonal population 29 months after original evaluation in the absence of histologic features of lymphoma but in the presence of persistent H pylori infection. These findings suggest that the histologic assessment of gastric biopsies remains the method of choice for the diagnosis of lymphoma in gastric endoscopic biopsies with a dense mucosal lymphoid infiltrate. PCR provides a useful technique to support the diagnosis if clonal amplification products are found. The significance of PCR detected clonality in the absence of histologic evidence of lymphoma in uncertain but may represent a stage of tumor progression/regression when the clonal population is insufficient to be detected by conventional histology. This is supported by the evidence that PCR-detectable monoclonality can persist after treatment and the disappearance of histologically detectable lymphoma.
 ...
PMID:Diagnosis and posttreatment follow-up of Helicobacter pylori-positive gastric lymphoma of mucosa-associated lymphoid tissue: histology, polymerase chain reaction, or both? 860 13

Western blots, enzyme assays, protein glycosylation studies, and immunohistochemical staining were used to characterize cathepsin B expression at successive stages of colorectal tumor progression. In normal colon mucosa and premalignant adenomas, cathepsin B expression was predominantly due to mature two-chain protein detected on Western blots as the nonglycosylated 27-kDa form, with overexpression of this protein occurring in only 4 of 18 adenomas. Overexpression increased significantly in Dukes A and B carcinomas (26 of 37 cases), with cathepsin B protein generally detectable in carcinomas as a combination of both 27-kDa nonglycosylated and 28-kDa glycosylated mature two-chain forms. Glycosylated cathepsin B protein in carcinoma extracts was sensitive to PNGase F but resistant to Endo H, indicating a pattern consistent with complex rather than high mannose type glycosylation. When sorted by advancing tumor stage, peak expression of cathepsin B protein occurred in carcinomas involved in local invasion compared with adenomas or metastatic cancers. At all stages, cathepsin B activity correlated significantly with the levels of heavy chain mature cathepsin B protein (r = 0.6682, p < 0.0001) irrespective of glycosylation. Immunohistochemical staining of cathepsin B protein revealed fine diffuse cytoplasmic staining in both adenomas and carcinomas compared with coarse granular cytoplasmic staining (typical of lysosomes) seen in matched normal mucosa. Our results demonstrate several sequential, apparently independent changes in cathepsin B expression during colorectal tumor progression including early changes in subcellular localization, up-regulation of cathepsin B protein and activity in invasive cancers, and altered protein glycosylation detected in malignant tumors at all stages.
 ...
PMID:Elevations in cathepsin B protein content and enzyme activity occur independently of glycosylation during colorectal tumor progression. 936 Sep 97

Tumor associated gene-1/L amino acid transporter-1 (TA1/LAT-1) was recently identified as a light chain of the CD98 amino acid transporter and cellular activation marker. Our previous studies with primary rat hepatocyte cultures demonstrated that TA1 RNA levels were responsive to media amino acid concentrations, suggesting adaptive regulation. High level TA1 expression associated with transformed cells also suggested a role in tumor progression. The present study examined the relationship of TA1/CD98 expression, adaptive response, and associated amino acid transport to neoplastic transformation using a panel of well characterized rat hepatic cell lines. We found 1) increased expression of TA1 in response to amino acid depletion, specific for arginine but not glutamine; 2) loss of TA1 response to arginine in gamma-glutamyl transpeptidase-positive transformed and tumorigenic cells; 3) no appreciable response of 4F2/CD98 heavy chain to arginine levels; and 4) correlation of system L amino acid transport activity in response to arginine with changes in TA1/LAT-1 mRNA but not total immunoreacting protein. Our results suggest this CD98 light chain may act as an environmental sensor, responding to amino acid availability and that its regulation is complex. We hypothesize that altered TA1 expression is an early event in hepatocarcinogenesis giving neoplastic cells a growth or survival advantage, particularly under conditions of limited amino acid availability.
 ...
PMID:TA1/LAT-1/CD98 light chain and system L activity, but not 4F2/CD98 heavy chain, respond to arginine availability in rat hepatic cells. Loss Of response in tumor cells. 1068 8

Chromosomal translocations involving Ig heavy chain switch regions and an oncogene, like Myc, represent early initiating events in the development of many B cell malignancies. These translocations are widely believed to result from aberrant class switch recombination (CSR). Recent reports have produced conflicting models for the role of activation-induced cytidine deaminase (AID) in this process. Here, we discuss possible roles of AID, CSR, and somatic hypermutation in generating chromosomal translocations and in tumor progression.
 ...
PMID:AID and Igh switch region-Myc chromosomal translocations. 1678 1

Changes in the human leukocyte antigen (HLA) class I expression and cytokine and chemokine production both by cancer cells and by normal surrounding tissue are believed to be responsible for immune escape and tumor progression. In this study, we compared the tumor expression levels of HLA heavy chain (HLAhc), beta-2-microglobulin (beta2m), chemokines (Interferon-gamma-inducible Protein-10 (IP-10), Interferon-inducible T-cell Alpha-Chemoattractant (I-TAC), Stromal cell-Derived Factor-1 (SDF-1), Macrophage Inflammatory Protein-1-alpha (MIP-1-alpha) and Regulated upon Activation, Normally T-Expressed, and presumably Secreted (RANTES)) and cytokines (Vascular Endothelial Growth Factor (VEGF), Interferon-gamma (IFN-gamma), Interleukin-10 (IL-10), Tumor Growth Factor-beta (TGB-beta)) in primary tumors and adjacent normal tissues from patients with localized and metastatic renal cell carcinoma (RCC) using a quantitative real-time polymerase chain reaction technique. We report that the expression of HLAhc, beta2m and the studied cytokines and chemokines (except for SDF-1) was significantly higher in the tumor (29 samples) than in the normal tissue (14 samples). When we compared the tumor expression levels between patients with localized RCC and patients with advanced metastatic stage, we found that the messenger RNA expression levels of HLAhc and beta2m were much lower in patients with metastatic RCC (6 cases) than in patients with localized cancer (23 cases), with levels similar to those in normal tissue. This was also confirmed on a protein level by immunohistological labeling of tumor tissues. Thirty-nine percent of the analyzed RCC tumors showed partial loss of HLA class I molecules, while 6% of the tumors showed HLA class I total loss. The expression of IP-10, SDF-1 and VEGF-c was also significantly lower in patients with advanced tumor, while the IFN-gamma expression in metastatic RCC was not detectable. Our findings show that primary RCC tumors are characterized by a high expression of HLAhc and a presence of proinflammatory mediators and chemokines. We also observed that disease progression and development of metastasis in RCC are associated with decreased expression of HLAhc, beta2m, IP-10, SDF-1 and IFN-gamma. This microenvironment may suppress the cytotoxic response, creating conditions that favor tumor escape and cancer progression.
 ...
PMID:Analysis of the expression of HLA class I, proinflammatory cytokines and chemokines in primary tumors from patients with localized and metastatic renal cell carcinoma. 1702 65


1 2 3 4 Next >>