Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermatofibrosarcoma protuberans (DFSPs) are an uncommon malignancy that commonly recur, but rarely metastasize. The origin of DFSPs is controversial; however, they stain with the progenitor marker CD34. DFSPs usually show increased stromal mucin, mainly hyaluronic acid (HA). HA increases cellular proliferation, delays differentiation and increases cellular motion. We evaluated the pretreatment of DFSPs with intralesional injections of hyaluronidase (HD) prior to the surgical excision. Five of nine cases of DFSPs were pretreated with HD. In HD-pretreated cases the margins for excision of the residual tumor were reduced. HD pretreatment also decreased CD34 staining and increased polarizable collagen in the residual tumor.
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PMID:Pretreatment with intralesional hyaluronidase prior to excision of dermatofibrosarcoma protuberans. 983 27

The mechanisms leading to rapid invasive growth of malignant gliomas are poorly understood. Expression of the hyaluronic acid (HA) receptor CD44 and adhesion to HA are involved in invasive properties. Our previous studies have shown that malignant glioma cells are able to adhere to extracellular HA. Here we investigated expression of the hyaluronic acid receptor CD44 protein in five human (T98G, A172, U87MG, 86HG39, 85HG66) and two rat (C6, 9L) glioma cell lines. Influence of anti-CD44 antibody and hyaluronidase-preincubation on the HA-binding was determined using HA/BSA (bovine serum albumin)-coated culture plates. While all gliomas were highly positive for CD44 with no differences in the number of positive staining cells, median fluorescence intensity decreased as follows: C6>T98G>9L>85HG66> 86HG39>A172>U87MG. Using HA/BSA coated culture plates the relative levels of specific adhesion to HA were determined as T98G>A172>9L>86HG39>U87MG> 85HG66. C6 cells failed to bind HA specifically. Incubation with anti-human-CD44 MAb significantly decreased HA-adhesion of T98G, A172, 85HG66 and U87MG human glioma cells. However the binding capacity was completely blocked only in 85HG66 cells. The three other cell lines kept a specific HA-adhesion after saturation of the receptor. Hyaluronidase pretreatment markedly enhanced HA-adhesion of C6 and 9L rat glioma cells. These results suggest that (i) HA-adhesion of malignant glioma cells is mainly, but not only, mediated by CD44, (ii) expression of CD44 does not correspond with adhesion capacity and (iii) cell-bound glycosaminoglycans may influence glioma cell adhesion to extracellular HA.
Clin Exp Metastasis 1999 Feb
PMID:CD44 expression and hyaluronic acid binding of malignant glioma cells. 1039 Jan 50

Urine cytology remains the gold standard for bladder cancer screening. It is the test against which all others are compared when evaluating potential bladder tumor markers. The answer to whether urine cytology possess the optimal combination of sensitivity and specificity to retain consideration as the best screening device depends on the goals of the clinical practice. Urine cytology has excellent specificity with few false-positive cases. Its overall sensitivity is poor, but this drawback is explained for the most part by poor criteria for identifying well-differentiated, low-grade TCC. The natural history of such lesions is the occurrence of multiple superficial recurrences in 70% to 80% of patients, with only a minority (10% to 15%) progressing to muscle invasive or metastatic disease. Because patients with low-grade TCC are at low risk for progression, they are monitored primarily for the development of a subsequent tumor. One might argue that the detection of new low-grade lesions is of secondary importance to the early detection of disease progression. The performance characteristics of urine cytology in this regard are much improved. Urine cytology often results in the identification of high-grade malignant cells even before a cystoscopically distinguishable gross lesion is present. Routinely diagnosing grade I TCC may be clinically irrelevant. Ancillary techniques to improve the sensitivity of urine cytology have been insufficiently additive to have much clinical value. Several promising bladder tumor markers have been investigated as potential screening tools and are summarized in Table 3. BTA, nuclear matrix proteins, and fibrin/fibrinogen degradation products share lower specificities than urine cytology and may have high rates of false positivity. Telomerase is highly sensitive and highly specific but is not readily available as a point-of-service test. Hyaluronidase and hyaluronic acid are promising prognostic markers, but hyaluronidase does not detect grade I TCC. Early results from studies of this marker await verification. Combining some of these new markers may optimize their performance status, allowing the advantages of one test to correct the shortcomings of another. Likewise, their combination with urine cytology may prove beneficial. Although adding urine cytology has not increased the sensitivity of some point-of-service tests, few studies have addressed the effect on specificity. Until an obvious winner is declared in the race to find a bladder tumor marker, urine cytology will remain the gold standard screening method because of its comfortable familiarity.
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PMID:Urine cytology. It is still the gold standard for screening? 1069 42

A new orthotopic esophageal cancer model was developed by implanting fragments of xenografts of T.T human esophageal squamous carcinoma cells into the cervical esophagus of athymic rats. The rats had symptoms analogous to the human clinical course such as respiratory distress, dysphagia, vomiting of blood, or Horner syndrome, followed by death resulting from suffocation. Microscopic metastases of lymph node were observed around the tumor in 3 of 18 rats. A new cell line (T.T-1) was established from these metastases. Flow cytometry showed that T.T-1 and T.T parental cells had nearly the same surface levels of beta1-integrin, alpha2-integrin, alpha3-integrin and E-cadherin, and no expression of CD44v3, CD44v6 and alpha5-integrin. T.T-1 cells had a higher level of CD44H, however, and a greater binding efficiency to the extracellular matrix components; laminin, type IV collagen, hyaluronic acid, and fibronectin than T.T cells. Anti-CD44H antibody significantly decreased the binding efficiency of T.T-1 cells. T.T-1 cells were also significantly more invasive than T.T cells through all the extracellular matrix components except hyaluronic acid. After orthotopic implantation histological examination showed that T.T-1 tumors invaded beyond the esophageal mucosa and tracheal muscle layer and obstructed the esophagus and trachea. No invasion was observed with T.T tumors. Rats with T.T-1 or T.T tumors survived an average of 32.0 and 50.7 days, respectively (p < 0.01). In addition T.T-1 tumors expressed higher levels of CD44H mRNA than T.T tumors. In summary, our newly developed orthotopic implantation model is a valid model of esophageal cancer because it followed the same clinical course experienced by humans. Moreover, using cells derived from this model, we were able to demonstrate that CD44H is involved in esophageal cancer cell invasion.
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PMID:A novel orthotopic implantation model of human esophageal carcinoma in nude rats: CD44H mediates cancer cell invasion in vitro and in vivo. 1130 82

The morphological features of iridociliary epithelial tumors in 100 dogs and 17 cats were reviewed. Twenty-seven cases were in either Golden Retrievers or Labrador Retrievers. Affected globes were stained for light microscopy with alcian blue, periodic acid Schiff (PAS) and hematoxylin and eosin stains. Selected tissues were examined by immunohistochemistry for vimentin, desmin, cytokeratin, S-100, neuron-specific enolase (NSE), and glial fibrillary acid protein (GFAP). The presence or absence of hyaluronic acid was recorded by staining with alcian blue before and after digestion of the tissue with hyaluronidase. Canine tumors were divided into papillary and solid tumors based on the pattern of growth. Twenty-eight of 57 papillary tumors exhibited invasive behavior including eight of the 57 which showed infiltration of the sclera. Twenty-nine of 43 solid tumors were invasive including 13 of 43 with scleral invasion. Tumors with scleral invasion were designated adenocarcinoma. Tumors of both types could be pigmented or nonpigmented and often contained smooth basement membranes reminiscent of the inner membrane of the nonpigmented ciliary body epithelial cell. All of the feline tumors were nonpigmented and 14 of 16 feline tumors were solid and two of the tumors were papillary. Eighteen of 20 canine tumors and three of four feline tumors stained positive for vimentin. Cytokeratin stain was positive only in a few of the highly aggressive tumors. The finding of pigmented epithelial cells, thick, smooth basement membrane structures, positive staining for vimentin, S-100, and NSE as well as hyaluronic acid deposition were considered to be features which define iridociliary epithelial tumors in dogs. The positive staining for vimentin and NSE are highly specific markers which help to characterize iridociliary epithelium and distinguish this tumor from metastatic epithelial tumors. The finding of solid nonpigmented tumors with small epithelial cells packeted by thin PAS-positive membranes staining positive for vimentin were considered significant features defining iridociliary epithelial tumors in cats. Follow-up information on survival and cause of death was obtained on 43 canine cases and only two feline cases. The average follow-up interval in dogs was 25 months and only two dogs died with lesions that could have been due to metastasis although neither was confirmed. We concluded that neither iridociliary adenomas nor adenocarcinomas is likely to metastasize.
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PMID:Iridociliary epithelial tumors in 100 dogs and 17 cats: a morphological study. 1139 34

Multidrug resistance (MDR) lines from a murine T-cell lymphoid leukemia were selected in increasing vincristine (VCR) or doxorubicin (DOX) concentrations. Surface markers were determined by flow cytometry in both resistant (LBR-V 160 and LBR-D 160) and sensitive (LBR-) cell lines. Results obtained revealed similar expression of CD25, CD24, CD8, CD4, C18 and CD44, while differences in binding to hyaluronic acid (HA) were found. LBR- and LBR-D 160 bound to HA only after phorbol ester (PMA) activation, while LBR-V160 failed to bind HA even after PMA treatment. Histopathological analysis disclosed that LBR-V160 was less invasive than LBR- and LBR-D160 cell lines. In vitro growth of cell lines analyzed by sulforhodamine-B uptake showed that doubling time for the three lines was 10.24 h (LBR-), 16.75 h (LBR-V160) and 16.29 h (LBR-D160). Mortality rate was determined after i.p. injection of 10(4) cells. Mice inoculated with LBR- died at 23 2.11) days, while those inoculated with LBR-V160 or LBR-D160 died at 41 (+/- 9.53) or 41 (+/- 4.96) days, respectively. Our results demonstrated that leukemic murine T cells cultured in the long-term presence of VCR or DOX not only presented changes in the resistance phenotype but also variations in their growth and metastatic pattern.
Clin Exp Metastasis 2002
PMID:Dissimilar invasive and metastatic behavior of vincristine and doxorubicin-resistant cell lines derived from a murine T cell lymphoid leukemia. 1209 Apr 68

The mechanisms underlying the inflammatory and metastatic processes share a number of similar pathways, such as those involving adhesion, migration and extravasation. In this article, the effects of pro-inflammatory cytokines on metastatic-related activities of colon cancer cells were tested. The expression and biological activity of the proteoglycan CD44 in low (LS174T) and high metastatic (HM7) cell lines following exposure to TNFalpha and IL-8 were assessed. Treated cells expressed more CD44 splice variants (CD44v), while CD44 standard protein (CD44s) expression remained unchanged. Treatment with TNFalpha induced IL-8 secretion and IL-8 gene transcription in a time-dependent manner. Both cytokines enhanced the ability of the cells to adhere to the CD44-specific ligand hyaluronic acid, an effect that was specifically blocked by an anti-IL-8 antibody. These results suggest that the effect of TNFalpha on IL-8 is responsible for the regulation of the expression of CD44 isoforms. Additional experiments showed that neither of the cytokines tested regulate the expression of CD44 gene regulation via activation of a well-characterized specific 22-bp epidermal growth factor regulatory element present in the CD44 promoter sequence, suggesting that this is not the mechanism of activation. We conclude that immuno-modulatory mediators can modify the expression of cell-to-cell or cell-to-matrix adhesion proteins, implicated in the determination of phenotypes associated with aggressiveness and metastasis of colon cancer cells.
Clin Exp Metastasis 2002
PMID:TNFalpha and IL-8 regulate the expression and function of CD44 variant proteins in human colon carcinoma cells. 1209 Apr 73

Hyaluronate and hyaluronate synthase expression were examined in primary tumours and if present in metastatic deposits of human breast, colon, ovarian and small-cell lung cancer cell lines transplanted into scid mice using biotinylated hyaluronectin and immunohistochemical staining of hyaluronate synthase. Very intensive hyaluronate and hyaluronate synthase expression could be observed in peripheral areas of tumours derived from highly metastatic cell lines (HT29, MCF-7). Even smaller lung metastases of up to 15 cells showed typically a focal binding of hyaluronectin predominantly at the host-tumour interface of the metastases, indicating that increased expression is closely correlated with the degree of invasiveness and metastatic potential of malignant tumours.
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PMID:Expression of hyaluronate and hyaluronate synthase in human primary tumours and their metastases in scid mice. 1240 63

In this review we focus on a promising novel histone deacetylase (HDAC) inhibitor (HA-But) obtained by the esterification of butyric acid (BA), the smallest HDAC inhibitor, with hyaluronic acid (HA), the main constituent of the extracellular matrix which selectively recognizes a transmembrane receptor (CD44) overexpressed in most primary cancers and associated with tumor progression. In vitro, HA-But has proved to be 10-fold more effective than BA in inhibiting the proliferation of a panel of human cancer cell lines, representative of the most common human cancers, and, similar to BA, to regulate the expression of some cell cycle-related proteins, to induce growth arrest in the G1/G0 phase of the cell cycle and to increase histone acetylation. In vivo, HA-But treatment has demonstrated a marked potency in inhibiting primary tumor growth and lung metastases formation from murine Lewis lung carcinoma (LL3) as well as liver metastases formation from intrasplenic implantation of LL3 or B16-F10 murine melanoma cells. In particular, the effect of s.c. and i.p. treatment with HA-But on liver metastases resulted, respectively, in 87 and 100% metastases-free animals, and in a significant prolongation of the survival time compared to the control groups. The results suggest that the presence of the HA backbone does not interfere with the biological activity of butyric residues and that HA-But could represent a promising cell-targetable antineoplastic agent for the treatment of primary and metastatic tumors.
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PMID:Hyaluronic acid butyric esters in cancer therapy. 1574 73

Chronic inflammation is implicated in the pathophysiology of ovarian cancer. Tumor necrosis factor-alpha (TNF-alpha), a major inflammatory cytokine, is abundant in the ovarian cancer microenvironment. TNF-alpha modulates the expression of CD44 in normal T lymphocytes and CD44 is implicated in ovarian carcinogenesis and metastases. However, little is known about the role of TNF-alpha in CD44 expression of cancer cells. Recent clinical work using TNF-alpha inhibitors for the treatment of ovarian cancer makes the study of TNF-alpha interactions with CD44 crucial to determining treatment a success or a failure. We studied the effect of TNF-alpha on ovarian cancer cells viability, CD44 expression, and in vitro migration/invasion. Our results revealed that TNF-alpha differentially modulates the expression of CD44 in TNF-alpha-resistant ovarian cancer cells, affecting their in vitro migration, invasion, and binding to hyaluronic acid. TNF-alpha up-regulation of CD44 expression was dependent on the activation of c-Jun NH(2)-terminal kinase (JNK) and this activation was accompanied by an increase in their invasive phenotype. On the contrary, if TNF-alpha failed to induce JNK phosphorylation, the end result was down-regulation of both CD44 expression and the invasive phenotype. These results were confirmed by the use of JNK inhibitors and a TNF receptor competitive inhibitor.
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PMID:Tumor necrosis factor-alpha differentially modulates CD44 expression in ovarian cancer cells. 1690 92


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