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

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

This study examined the behaviour of nine human malignant oral keratinocyte cell lines following orthotopic transplantation to the floor of the mouth of athymic mice. Tumourigenesis, local spread, and metastatic dissemination were correlated with known cellular responses to transforming growth factor-beta 1 (TGF-beta 1). Six of nine cell lines were tumourigenic; four of these cell lines showed local spread which was characterized by vascular and bone invasion. Metastatic spread was uncommon, with only 9% of animals with primary tumours developing metastases and these were almost exclusively found in the regional lymph nodes; there was one pulmonary metastasis and no liver deposits. Tumour cell behaviour did not reflect the clinical stage of the original tumours. Cell lines that were resistant to TGF-beta 1-induced growth inhibition were more likely to form primary tumours, exhibit local spread, and metastasize than cells that were growth-inhibited by the ligand. The data demonstrate that tumourigenicity and tumour behaviour in this orthotopic mouse model varied between cell lines and that the pattern of local invasion and metastasis was similar to that seen in human oral cancer. Furthermore, cell lines that were refractory to the growth inhibitory effects of TGF-beta 1 behaved more aggressively than cells that underwent ligand-induced cell-cycle arrest.
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PMID:Metastatic dissemination of human malignant oral keratinocyte cell lines following orthotopic transplantation reflects response to TGF-beta 1. 1525 95

Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in two isoforms: the constitutive COX-1 and the inducible COX-2. Hyper-expression of COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans but it appears to play a significant role as a tumour progression factor also in other forms of human cancer, including oral cancer. The aim of this study was to analyze the expression of COX-2, at the protein level, in 45 cases of oral squamous cell carcinoma. Standard immunohistochemical streptavidin-biotin peroxidase analysis was carried out with highly specific antibody against human COX-2 and cell specific markers, in 45 oral squamous cell carcinomas. Our study revealed a moderate to high COX-2 expression in 35 out of the 45 oral squamous cell carcinoma specimens (77.8%). COX-2 expression appeared particularly abundant in the superficial ulcerated layers of relatively well differentiated carcinomas. However, we were unable to assess any statistically significant association between COX-2 hyper-expression and tumor site, tumor grading, tumor size, presence of lymph node metastases, tumor stage and age at onset, respectively. Interestingly, COX-2 expression was detected not only in areas of epithelial dysplasia adjacent to the primary layers (86% of the cases) but also in normal-appearing epithelium at the boundaries of squamous cell carcinoma (77%), indicating a possible involvement in tumour progression by the apparently normal tissue surrounding the lesion. Moreover, intense COX-2 staining was observed in endothelial cells of intra-tumour vessels and extra-tumour vessels adjacent to the tumour nests, in a high proportion of cases (82%). COX-2 positivity was associated with CD34 and VEGF positivity, indicating that these vessels were probably neo-formed ones. From this study as well as from other works, it appears that indeed COX-2 is over-expressed in this important human malignancy. However, further studies are necessary to understand the exact magnitude of this over-expression and, mostly, the possible role of COX-2 in the pathogenesis and progression of oral cancer.
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PMID:Cyclooxygenase-2 expression in oral squamous cell carcinoma. 1546 61

The role of vascularity as a predictor of the likelihood of lymph node metastases in oral cancer is not clear. To that end, the vascularity and expression of vascular endothelial growth factor (VEGF) was assessed at three specific regions: the tumour (inside and around the tumour); the resection margin; and the regional lymph nodes. Formalin-fixed paraffin-embedded specimens from 26 oral cancers (11 with no involved nodes and 15 with involved nodes) were stained immunohistochemically and examined. Staining for VEFG was significantly greater in the tumour than in the other sites. No significant differences were found in the intensity of staining in the primary tumour, resection margins, or nodes between cases in which the nodes were involved and in which they were not involved. We found no correlation between vascularity and VEGF staining, suggesting that VEGF is not the primary or only stimulator of angiogenesis in oral cancer. Greater understanding of the mechanisms of metastasis will lead to new treatments. The evidence that is accumulating for oral cancer suggests that such treatments may be better targeted at preventing lymphatic spread, rather than vascular spread.
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PMID:Vascularity and expression of vascular endothelial growth factor in oral squamous cell carcinoma, resection margins, and nodal metastases. 1714 25

Treatment of patients with unresectable recurrent oral cancer is quite difficult. In particular,there is no scientific evidence to select anti-cancer drugs for patients who were given previous radiation therapy. To select optional chemotherapy regimens, we have employed a new chemosensitivity testing method, a collagen gel droplet embedded culture sensitivity test (CD-DST) for patients with unresectable oral cancer. Six oral cancer patients with recurrence and/or metastatic disease were treated with the optional chemotherapy based on the results of CD-DST. No result was obtained due to a problem of poor growth of tumor cells in one case. In another case, we could not find a sensitive anti-cancer drug among the agents we examined. These 2 patients were treated with selected palliative pain control therapy. Optional chemotherapy based on the results of CD-DST was given to 4 patients showing sensitivity to the anti-cancer drugs examined. Tumor recession or tumor dormancy was observed clinically during a definite period. Toxicity was mild and the median survival was 10.9 months. We therefore conclude that the examination with CD-DST may provide important scientific evidence to determine a suitable chemotherapy for patients with advanced oral cancer.
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PMID:[Clinical trial of chemotherapy identified according to chemosensitivity assay for oral cancer patients with unresectable recurrent lesions]. 1653 18

The presence of lymph node metastasis is the most important prognostic factor in oral cancer. The purpose of this study was to find useful markers for predicting occult cervical lymph node metastasis in patients with stage I or II squamous cell carcinoma of the oral cavity. We investigated 6 clinicopathologic factors and 2 genetic markers to predict late or occult cervical metastasis in 33 patients with stage I and II oral squamous cell carcinoma who underwent partial glossectomy through the mouth without elective neck dissection. In this study, we performed fluorescence in situ hybridization (FISH) with specimens obtained by fine-needle aspiration biopsies (FNA biopsies) of primary oral cancer material, to investigate numerical aberration of the gene. Late cervical lymph node metastasis occurred in 16 of the 33 patients (48.5%) during follow-up after treatment of the primary tumor. Factors significantly associated with the development of cervical metastasis were the mode of invasion (p = 0.009), cyclin D1 (p = 0.003) and EGFR numerical aberration (p = 0.024). The rate of disease-free survival from metastatic disease was significantly lower in patients with mode of invasion 4 C-4 D than in those with 1-3, and was significantly lower in patients with cyclin D 1 or EGFR gene numerical aberrations than in those without such aberrations (log rank test, p = 0.0064, p = 0.0016 or p = 0.0150). Our results indicate that patients with stage I - II squamous cell carcinoma of the oral cavity with the mode of invasion 4 C or 4 D, cyclin D 1 and EGFR gene numerical aberration should be considered a high-risk group for late cervical lymph node metastasis.
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PMID:[Prediction of occult cervical lymph node metastasis in patients with stage I -II squamous cell carcinoma of the oral cavity]. 1662 76

Oral squamous cell carcinoma is a disfiguring, highly invasive and metastatic cancer. Despite advances in detection and therapy, many patients will continue to face a poor prognosis. It is well established that the predominate factor determining overall survival in patients with oral squamous cell carcinoma is lymph node involvement. Tumor growth and progression to invasive cancer requires tumor cell interactions with the extracellular matrix. An understanding of how the extracellular matrix influences tumor development and invasion is fundamental in the development of new prognostic indicators and treatment strategies for oral squamous cell carcinoma. In this review, we summarize how changes in the extracellular matrix contribute to oral cancer development.
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PMID:The extracellular matrix in oral squamous cell carcinoma: friend or foe? 1664 14

Low dose rate brachytherapy is well established treatment modality of oral cancer. Data about high dose rate brachytherapy (HDR BT) are still scarce with heterogenous results. The aim of our study was to evaluate preliminary results in a small group of oral cancer patients treated by HDR BT. Seventeen applications were performed on 16 patients in years 2001-2004, in 15 cases for new tumor (mobile tongue 10x, floor of mouth 2x, lip 3x) and in 2 cases for local recurrence after radiotherapy. Ten treatments (for T1-2N0 tumors and recurrences) were performed with brachytherapy alone (18 x 3 Gy twice daily), seven patients (T2-3 N0-2 tumors) were treated with a combination of external beam radiotherapy (40-68 Gy) and brachytherapy (2-6 x 3 Gy twice daily). The plastic tubes technique was used for brachytherapy. Follow-up periods were between 8-46 months (median 17). Fifteen patients were disease free during follow-up period. One patient (brachytherapy alone for T2N0M0 mobile tongue cancer) died immediately after neck dissection for the neck recurrence due to the heart failure. The other one died due to distant metastases but without local recurrence. Acute complications were mucositis gr. II at maximum, late complications were ulcer of soft tissues in 3 and superficial bone necrosis in 2 cases. The evaluation of the brachytherapy implants was done according ICRU 58 recommendations. Hyperfractionated high dose rate brachytherapy alone or as a boost to external beam radiotherapy is feasible with promising local control. Carefull planning of the implant and mandibular shielding are necessary to avoid complications.
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PMID:High dose rate brachytherapy in the treatment of oral cancer--the preliminary one institution experience. 1665 93

Oral cavity squamous cell carcinoma (OSCC) is one of the leading causes of cancer deaths worldwide and most of these deaths result from local-regional recurrence and metastases. Evasion of apoptosis is an important hallmark of cancer development and progression, and previous studies have shown that evasion of anoikis, or detachment-induced apoptosis, correlates with a more aggressive phenotype of carcinoma cells in OSCC. To elucidate the cytogenetic and molecular characteristics of anoikis resistance, we generated several cell lines and clones that displayed this cellular phenotype. To test the hypothesis that chromosomal alterations may underlie this phenotypic transformation, we used karyotype analysis to observe changes in the chromosomal structure of anoikis-sensitive and anoikis-resistant cell lines. We further hypothesized that a unique pattern of gene expression was induced by cell-detachment of anoikis-resistant cell lines, and cDNA microarray analysis was performed using a panel of anoikis-resistant oral cancer cell lines grown under attached and detached growth conditions. We identified S100P, KLK6 and CTNNAL1 as genes whose expression levels were differentially regulated in the anoikis-resistant cell lines compared to the anoikis-sensitive cells under detached conditions. These results were verified using real-time RT-PCR. The anoikis-resistant phenotype of squamous cell carcinoma has a distinct genetic expression pattern that is marked by chromosomal alterations that may contribute to differential expression of genes involved in diverse cellular functions. Therapies targeting these potential mediators of anoikis resistance may prove to be beneficial in the treatment of metastatic squamous cell carcinoma.
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PMID:Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma. 1697 12

Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p > 0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy.
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PMID:High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy. 1718 60

Disturbances in expression of apoptosis-associated proteins take part in the development and progression of many human malignancies. The aim of this study was the assessment of correlations among proteins involved in apoptosis-Bcl-xL, Bax, and p53-as well as relationships of these proteins with selected clinicopathological features in oral squamous cell carcinoma. Consequently, we examined by immunohistochemistry, using the avidin-biotin-peroxidase method, Bcl-xL, Bax, and p53 expression in 56 samples of primary oral squamous cell carcinoma and in 22 matched pairs of primary and metastatic tumors. The evaluation of immunostaining of Bcl-xL, Bax, and p53 was analyzed in 10 different tumor fields, and the mean percentage of tumor cells with positive staining was evaluated. The significance of the associations was determined using Spearman correlation analysis and the chi-square test. We found positive Bcl-xL, Bax, and p53 immunostaining in 44.6%, 28.6%, and 58.9% of the studied primary tumors and in 63.6%, 45.5%, and 72.7% of lymph node metastases, respectively. Analysis of associations among studied proteins revealed positive correlation between Bcl-xL and Bax in primary tumors (P<0.03, r=0.307). Statistically significant relationship between p53 expression in primary oral cancers and its expression in lymph node metastases (P<0.02) as well as increased expression of Bcl-xL, Bax, and p53 in metastatic sites compared with primary tumors could indicate an association of these proteins with oral cancer progression and development of metastases. Moreover, we suppose that knowledge about heterogeneity between primary and metastatic tumor might help to understand mechanisms of oral cancer progression.
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PMID:Expression of Bcl-xL, Bax, and p53 in primary tumors and lymph node metastases in oral squamous cell carcinoma. 1738 43


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