Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to investigate in vivo immunomodulatory properties of hematopoietic growth factors. The influence on the activation of cytokine synthesis and on the expression of surface antigens associated with cellular activation of G-CSF or GM-CSF was investigated in cancer patients receiving these factors. One single dose of growth factor was administered to patients with bladder cancer (G-CSF group) or small cell lung cancer (GM-CSF group) before chemotherapy. After cytoreductive chemotherapy patients received supportive therapy with G-CSF or GM-CSF. Peripheral blood mononuclear cells and plasma samples were obtained for flow cytometry, Northern blot analysis, and assessment of cytokine protein levels after single-dose as well as after continuous cytokine administration. Our results demonstrate differences in the induction of biological activities by GM-CSF and G-CSF in vivo which correlate well with in vitro findings. Among mature hematopoietic cells the effect of G-CSF is restricted to the granulocyte lineage. With GM-CSF moderate but unequivocal modulation of monocyte function was observed. On peripheral blood monocytes expression of MHC class-II molecules and CD44 was markedly stimulated. After one single dose of GM-CSF, plasma levels of sCD25 and IL-1RA were significantly induced (p < 0.0001, p = 0.032, respectively) and a trend to increased IL-8 levels was observed. The changes in plasma proteins were not correlated with shifts of mRNA expression for IL-8 and IL-1RA. T-cell activation was not observed with either cytokine. These results suggest that immunomodulatory features are differentially regulated by G-CSF and GM-CSF. The clinical relevance of a selective use of both hematopoietic growth factors in various disease settings remains to be determined.
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PMID:Regulation of immunomodulatory functions by granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in vivo. 895 41

CD44 is a ubiquitous multistructural and multifunctional cells surface adhesion molecule involved in cell-cell and cell-matrix interactions. Twenty exons are involved in the genomic organization of this molecule. The first five and the last 5 exons are constant, whereas the 10 exons located between these regions are subjected to alternative splicing, resulting in the generation of a variable region. Differential utilization of the 10 variable region exons, as well as variations in N-glycosylation, O-glycosylation, and glycosaminoglycanation (by heparan sulfate or chondroitin sulfate), generate multiple isoforms (at least 20 are known) of different molecular sizes (85-230 kDa). The smallest CD44 molecule (85-95 kDa), which lacks the entire variable region, is standard CD44 (CD44s). As it is expressed mainly on cells of lymphohematopoietic origin, CD44s is also known as hematopoietic CD44 (CD44H). CD44s is a single-chain molecule composed of a distal extracellular domain (containing, the ligand-binding sites), a membrane-proximal region, a transmembrane-spanning domain, and a cytoplasmic tail. The molecular sequence (with the exception of the membrane-proximal region) displays high interspecies homology. After immunological activation, T lymphocytes and other leukocytes transiently upregulate CD44 isoforms expressing variant exons (designated CD44v). A CD44 isform containing the last 3 exon products of the variable region (CD44V8-10, also known as epithelial CD44 or CD44E), is preferentially expressed on epithelial cells. The longest CD44 isoform expressing in tandem eight exons of the variable region (CD44V3-10) was detected in keratinocytes. Hyaluronic acid (HA), an important component of the extracellular matrix (ECM), is the principal, but by no means the only, ligand of CD44. Other CD44 ligands include the ECM components collagen, fibronectin, laminin, and chondroitin sulfate. Mucosal addressin, serglycin, osteopontin, and the class II invariant chain (Ii) are additional, ECM-unrelated, ligands of the molecule. In many, but not in all cases, CD44 does not bind HA unless it is stimulated by phorbol esters, activated by agonistic anti-CD44 antibody, or deglycosylated (e.g., by tunicamycin). CD44 is a multifunctional receptor involved in cell-cell and cell-ECM interactions, cell traffic, lymph node homing, presentation of chemokines and growth factors to traveling cells, and transmission of growth signals. CD44 also participates in the uptake and intracellular degradation of HA, as well as in transmission of signals mediating hematopoiesis and apoptosis. Many cancer cell types as well as their metastases express high levels of CD44. Whereas some tumors, such as gliomas, exclusively express standard CD44, other neoplasms, including gastrointestinal cancer, bladder cancer, uterine cervical cancer, breast cancer and non-Hodgkin's lymphomas, also express CD44 variants. Hence CD44, particularly its variants, may be used as diagnostic or prognostic markers of at least some human malignant diseases. Furthermore, it has been shown in animal models that injection of reagents interfering with CD44-ligand interaction (e.g., CD44s- or CD44v-specific antibodies) inhibit local tumor growth and metastatic spread. These findings suggest that CD44 may confer a growth advantage on some neoplastic cells and, therefore, could be used as a target for cancer therapy. It is hoped that identification of CD44 variants expressed on cancer but not on normal cells will lead to the development of anti-CD44 reagents restricted to the neoplastic growth.
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PMID:CD44: structure, function, and association with the malignant process. 911 68

In patients with malignant diseases, characteristic alterations in the expression of CD44 protein and their variants were found. For the present study, the serum concentrations of the standard isoform CD44 std and the two variant isoforms CD44 v5 amd CD44 v6 were measured by ELISA in patients with prostate cancer (n = 49), benign prostatic hyperplasia (n = 30), renal cell carcinoma (n = 31) and bladder cancer (n = 29). The data were compared with the results of 30 healthy men and 30 healthy women. The sCD44 v5 concentrations in patients with prostate cancer (p < 0.01), benign prostatic hyperplasia (p < 0.01) and men with renal cell cancer (p < 0.01) were significantly lower than those measured in the male control group. The sCD44 v5 concentrations observed in male patients with bladder cancer were lower than in the male control group (p < 0.05). Only in one group the concentration of sCD44 std differed significantly from the others. The sCD44 std concentration in male patients with renal cell cancer was significantly lower than in the male control group (p < 0.01). Other significant differences were not found. In contrast to results observed in other carcinomas, the determination of soluble CD44 proteins in serum cannot be recommended as a marker for urological malignancies.
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PMID:Soluble CD44 variants in the serum of patients with urological malignancies. 914 4

Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization were used to detect exon V6-containing isoforms of CD44 gene in 42 surgical bladder specimens (20 cases of bladder cancer, 10 cases of corresponding normal bladder tissue, 8 non-neoplastic bladder tissue from the benign prostatic hyperplasia, and 4 cystitis). All samples of bladder cancer tissue showed over-expression of many abnormal alternatively-spliced products containing transcripts from exon V6 of the CD44 gene except those from 22 non-neoplastic tissue. Furthermore, the band pattern permitted differentiation between the 2 cases of metastatic bladder tumors and the 18 cases of non metastatic tissue. Our results suggest that there is a remarkable relationship between the abnormal CD44 gene expression (inappropriate splicing and overexpression) and malignant phenotype and metastasis of bladder cancer. The CD44 splice variants may prove to be a more ideal tumor marker for the early diagnosis of bladder cancer and for the early detection of metastatic potential in surgical biopsy specimens, which deserves further evaluation.
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PMID:[Relationship between the abnormal expression of CD44 gene and bladder cancer]. 959 Jul 47

The expression of the standard CD44 (CD44s) and its v6 isoform (CD44v6) was analysed immunohistochemically in 173 cases of transitional cell bladder cancer. The results of immunohistochemical analyses were related to established prognostic factors and clinical follow-up data. The expression intensity of CD44s in non-basal tumour cells was significantly related to TN classification, S-phase fraction (SPF), mitotic index, grade, density of tumour infiltrating lymphocytes. The expression intensity of CD44v6 in non-basal tumour cells was inversely related to DNA ploidy, SPF, and mitotic index. The expression intensity of CD44v6 in basal tumour cells was also inversely related to T-category, grade, papillary status, DNA ploidy, SPF, and mitotic index. Strong expression of CD44s in non-basal tumour cells was related to unfavourable outcome in univariate analysis (p = 0.008), whereas the strong expression of CD44v6 in both non-basal cells (p = 0.005) and basal cells (p = 0.0008) was related to high survival probability. In multivariate survival analysis, the expression intensity of CD44v6 was independently related to favourable outcome in muscle invasive tumours, while in superficial tumours, CD44s was an independent prognostic factor. The results suggest that the expression of CD44s and CD44v6 is associated with malignant features and prognosis in bladder cancer.
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PMID:Expression of CD44 standard and variant-v6 proteins in transitional cell bladder tumours and their relation to prognosis during a long-term follow-up. 992 31

To study the early and non-invasive diagnostic value of CD44 splice variants in urine exfoliated cells of bladder cancer. We used reverse transcriptionpolymerase chain resection (RT-PCR) and southern blot hybridization to detect CD44 splice variants in exfoliated cells in 40 urine samples (20 bladder cancers, 20 non-neoplastic controls), and compared with the results of urine cytology on the same set of samples. 90% (18/20) of the urine samples of bladder cancer showed overexpression of CD44 splice variants while none of the 20 controls did so. This method not only has a sensitivity of 90% (18/20) which was much higher than that of 65% (13/20) by using urine cytology, but also is non-invasive and comfortable. The results suggest that CD44 splice variants in exfoliated cells in urine samples are a new tumor marker for early and non-invasive diagnosis of bladder cancer.
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PMID:[Diagnostic value of CD44 splice variants in urine exfoliated cells of bladder cancer]. 1067 25

The purpose of this study was to assess the prognostic effect of the expression of E-cadherin, beta-catenin and CD44 adhesion molecules in bladder carcinoma. 22 superficial and 18 invasive bladder tumour samples were studied by immunohistochemistry. The median follow-up was 24 months (range: 1-50 months). Loss of E-cadherin and beta-catenin immunoreactivity was found in 14 (35%) and 17 (43%) tumours, respectively, and was significantly associated with invasiveness, high grade and p53 overexpression. There was no correlation between CD44 variant expression and clinicopathological findings. Loss of E-cadherin expression was an independent predictor of poor survival in a multivariate analysis, when assessed with age, grade, stage and p53 status (hazards ratio adjusted (HRa)=4.45 [95% confidence interval (CI), 1.06-18.63]). This effect was particularly augmented in patients with invasive bladder cancer. When expression of E-cadherin and beta-catenin were evaluated simultaneously, loss of immunoreactivity of both proteins was a strong predictor of poor survival (HRa=13.06 [95% CI, 0.95-178.55]). The same pattern was found when progression-free survival in relation to these variables was assessed. In conclusion, assessment of E-cadherin and beta-catenin immunoreactivity may be a useful prognostic marker in bladder cancer complementary to established prognostic factors.
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PMID:Prognostic value of the expression of E-cadherin and beta-catenin in bladder cancer. 1070 37

Recently, we developed a novel molecular approach, CD44 v8-10/CD44 v10 competitive reverse transcription-polymerase chain reaction (CC-RT-PCR), to detect a sparse population of cancer cells overexpressing CD44v8-10 among a much larger population of nonneoplastic cells in body fluids by the measurement of the transcriptional level of CD44v8-10 relative to that of CD44v10. We have shown the utility of CC-RT-PCR in diagnosing disease using urine samples from patients with bladder cancer. In this study, we initially examined the expression of CD44 splice variants in human upper urinary tract transitional-cell carcinomas (UUT-TCCs) and their adjacent normal urinary tissues by RT-PCR. Any CD44 variant isoforms were barely detectable in normal urinary tissues, whereas CD44v8-10 was predominantly expressed in 21 of the 25 UUT-TCC specimens (84%). We then applied CC-RT-PCR to spontaneously voided urine samples from 40 patients with UUT-TCC and 40 patients with benign urologic diseases. The CC-RT-PCR analysis revealed that all of the samples from patients with benign diseases presented a predominant expression of the CD44v10 transcript, whereas 26 of the 40 samples from patients with UUT-TCC dominantly expressed the CD44v8-10 transcript. In addition, the positive rate obtained by the CC-RT-PCR analysis was significantly higher than that obtained by cytologic examination, especially in patients with low-grade UUT-TCC. These findings strongly suggest that CC-RT-PCR is a useful noninvasive tool for the diagnosis of UUT-TCC.
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PMID:Utility of Competitive Reverse Transcription-Polymerase Chain Reaction Analysis of Specific CD44 Variant RNA for Detecting Upper Urinary Tract Transitional-Cell Carcinoma. 1085 Dec 97

The expression of variant isoforms of the adhesion molecule CD44 is correlated with the onset of neoplasia in many carcinomas. We have previously shown that noninvasive detection of bladder carcinoma is possible by analysis of anomalous CD44 expression in exfoliated urothelia. Although the sensitivity and specificity values obtained for the detection of bladder tumors using RT-PCR and Western blotting methods were superior to those obtained using urine cytology, the application of such techniques is inconvenient for routine diagnostic use. We now report the design and development of a sandwich-ELISA system for the reliable detection of CD44 protein extracted from sedimented urothelial cells in voided urine. Naturally micturated urine samples were obtained from 53 patients with newly diagnosed bladder cancer and from 65 subjects with no evidence of disease; patients with gross hematuria were excluded because of interference with the assay. To demonstrate the diagnostic potential of the system, a "gate" was imposed at N (max), i.e., the highest absorbance value obtained from a sample known to be tumor free. All values above this value were assumed to be indicative of the presence of a tumor. Using this parameter, 42 of 53 (81.1%) patients with histologically confirmed bladder tumors were correctly diagnosed. Correspondingly, under these conditions, the assay is 100% specific for tumor detection, with a sensitivity of 81.1%, which equates to a positive predictive value of 100% and a negative predictive value of 81.1%. A further 54 patients who had previously received treatment for bladder cancer but were currently clinically disease-free were also investigated. Of these, 47 of 54 (87%) were correctly diagnosed to be tumor-free, which in this group equates to a positive predictive value of 87% and a negative predictive value of 100%. The data presented demonstrate that the rapid and accurate detection of elevated levels of CD44 protein isoforms in exfoliated urothelial cells is applicable to the identification and monitoring of primary and recurrent bladder cancer.
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PMID:Noninvasive diagnosis of bladder carcinoma by enzyme-linked immunosorbent assay detection of CD44 isoforms in exfoliated urothelia. 1087 90

Distinction of urothelial carcinoma in situ (CIS) from reactive atypia on the basis of morphology alone may be difficult in some cases. Because this distinction is therapeutically and prognostically critical, we attempted to determine if an immunohistochemical panel would help in this differential diagnosis. The immunoprofile of 21 cases of CIS and 25 non-neoplastic urothelia (15 urothelial biopsies with reactive atypia from patients without a history of bladder cancer and 10 normal ureter sections from nephrectomies performed for renal cell carcinoma) was determined using antibodies against cytokeratin 20 (CK20), p53, and CD44 (standard isoform). In the normal urothelium CK20 showed patchy cytoplasmic immunoreactivity in only the superficial umbrella cell layer and CD44 stained only the basal cells. Nuclear immunoreactivity to p53 varied from negative to weak and patchy. Reactive urothelium also showed CK20 immunoreactivity in only the umbrella cell layer in all 15 cases, and p53 nuclear staining was predominantly negative with occasional weak positivity in the basal and parabasal intermediate cells. CD44 was overexpressed in the entire reactive urothelium in 9 cases (60%) or focally positive in intermediate cells in 6 cases (40%). In contrast, CIS showed intense CK20 and p53 positivity (81% and 57%, respectively) in the majority (>50%) of malignant cells. CD44 staining revealed residual basal cells with membranous reactivity in 44% of the cases of CIS; however, the neoplastic cells were immunonegative in all cases. At least one positive immunomarker (CK20 or p53) was abnormally expressed in all cases of CIS. Abnormal expression of CK20 (increased), p53 (increased), and CD44 (decreased) in urothelial CIS, and increased expression of CD44 in reactive atypia allows more confident distinction of urothelial CIS from non-neoplastic urothelial atypias. From a differential diagnosis perspective, use of a panel of all three antibodies with morphologic correlation would be essential.
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PMID:Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens. 1147 93


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