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)

The development of malignancy has been associated with both the activation of oncogenes and the inactivation of tumor suppressor genes. Whereas recent data implicate tumor suppressor genes as cell-cycle check-points, the nature and timing of tumor suppressor gene inactivation during multistage carcinogenesis is still largely uncharacterized. To address this issue, we used a syngeneic mouse epidermal model system. By creating somatic-cell hybrids between nontumorigenic x benign (291 x 291.09RAT), nontumorigenic x malignant (291 x 291.05RAT and 291 x 291.03RAT), benign x malignant (291.09RAT x 291.03RAT) and malignant x malignant (291.03RAT x 291.05RAT) clones, multiple tumor suppressor activities were detected. Most importantly, we demonstrated the first example of the complete suppression of benign papillomas in vivo, thus implicating tumor suppressor gene activity loss an early event in skin carcinogenesis. In addition, the carcinoma phenotype was suppressed in vivo by nontumorigenic, benign, and heterologous malignant keratinocytes. The somatic-cell hybrids expressed the differentiation-specific keratins, K1 and K10, in response to high extracellular calcium concentrations (1.4 mM) in vitro. All of the hybrids had fewer local metastases than did the parental lines, and when tumor formation was not suppressed, the resulting tumors were highly differentiated. Polymerase chain reaction analysis of the neomycin-resistance gene at nontumorigenic injection sites indicated an absence of injected hybrids, and subsequent analyses failed to detect nontumorigenic 291 cells 1 wk after transplantation. These data demonstrate that distinct tumor suppressor gene activities are lost at discrete stages during multistage carcinogenesis and are consistent with the hypothesis that tumor suppression can occur through induction of terminal differentiation.
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PMID:Induced terminal differentiation and tumorigenic suppression in murine keratinocyte somatic-cell hybrids. 776 11

Reproducible multi-stage progression to invasive squamous carcinoma of the epidermis has been achieved in transgenic mice expressing the HPV16 early-region genes, including the E6/E7 oncogenes, under the control of the human keratin-14 promoter/enhancer. Although 100% of K14-HPV16 transgenic animals develop hyperplastic and/or dysplastic lesions in several inbred backgrounds, including C57BL/6, BALB/c, and SSIN/SENCAR, only mice backcrossed into the FVB/n background progress to malignant squamous cell carcinomas of two pathological grades, well differentiated and moderate/poorly differentiated (WDSC or MPDSC, respectively), each displaying characteristic patterns of malignant behavior. WDSCs typically arise within the epidermis of the ear and invade deeply into the underlying dermis but fail to metastasize, whereas MPDSCs develop on the chest and truncal skin and invariably metastasize to regional lymph nodes. The transition to the malignant state, in 21% of FVB/n transgenic mice, is characterized by alteration of the repertoire of keratin intermediate filament proteins expressed within neoplastic epidermis, such that WDSCs maintain expression of keratins common to terminally differentiating stratified keratinocytes (K10), whereas MPDSCs are distinguished from WDSCs by activation of embryonic and mucosal keratins (K13, K8, and K19). Precursor hyperplastic and dysplastic lesions are characterized by a progressively increased proliferative index, striking morphological alterations in keratinocyte cell-cell and cell-matrix interactions, and extensive remodeling of the underlying dermal stroma. Remarkably, this extensive stromal remodeling, which may facilitate both angiogenesis and eventual tumor cell invasion, develops early at the dysplastic stage in all animals well before malignant conversion.
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PMID:Genetic predisposition and parameters of malignant progression in K14-HPV16 transgenic mice. 895 26

Despite its relative rarity compared with the common adult cancers, scientific and clinical interest in germ cell cancer is increasing. From the point of view of epidemiology, the controversy about the relative importance of intrauterine versus postpubertal risk factors has continued. Evidence to support the importance of intrauterine factors comes from reports from Norway, Canada, and the US, confirming the Danish observation that the rising incidence of germ cell cancer is linked to a birth cohort effect; evidence in support of the importance of postpubertal risk comes from three case/control studies demonstrating increased risk linked to postpubertal exposures such as pesticides, plastics, electromagnetic radiation, trauma, and infections. There has been increasing interest in human endogenous retrovirus K10 as a possible factor explaining genetic susceptibility and providing a linkage between the two groups of risk factors. In cytogenetics, progress was reported in identifying the deletion point of the suspected tumor suppressor gene responsible for the i12p marker chromosome abnormality and development of FISH probes for diagnostic purposes. In molecular biology, the importance of DNA repair deficiency in normal germ cells as a factor in the exquisite chemosensitivity of germ cell cancer has been high-lighted by a report demonstrating a low level of the xeroderma pigmentosa group A (XPA) protein and induction of resistance in vitro by adding XPA. In the clinic, progress in positron emission tomography scanning and laparoscopic lymph node staging are leading to changes in outlook on management of stage 1 cases and patients with small residual masses postchemotherapy. Salvage chemotherapy regimens integrating dose dense and vertical dose intensification strategies reported 60% progression-free survival. New drugs such as gemcitabine demonstrated continued therapeutic potential for chemotherapy in these tumors. A report demonstrating the inadequacies of hormone replacement after bilateral orchidectomy and a report of the first child born after testis-conserving therapy highlight the need for more attention to testis conservation as a quality of life issue. With the cure rates so high, the need for central referral is once again debated both for stage 1 and metastatic disease. With new ways of defining poor risk stage 1 patients and reports on impact of experience highlighting the worse outcome of patients treated in centers treating small numbers, views on this issue remain clearcut.
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PMID:Current opinion in germ cell cancer 2000. 1084 Nov 97

In head and neck squamous cell carcinomas (HNSCC), metastasis to cervical lymph nodes is a major determinant of patient outcome. To detect metastases, we used the MET oncogene as marker, which encodes the receptor for hepatocyte growth factor/scatter factor, mediating epithelial cell motility and invasiveness. The MET gene is expressed in epithelia and over-expressed in carcinomas of specific histotypes, but not in lymphatic tissue. A total of 151 lymph nodes from 20 squamous cell carcinomas were studied with both in-depth histology and end-point and real-time quantitative RT-PCR. MET-encoded sequences were found in 61 of 151 nodes (40%), of which 24 (16%) were found metastatic by in-depth histopathology. Parallel routine histopathologic analysis of 654 lymph nodes from the same cases identified 36 metastases (5%). Real-time quantitative RT-PCR was used to measure MET gene-specific mRNA in normal tissues, primary tumors and lymphatic metastases and showed a 2-8-fold increased expression in tumor cells which metastasize. RT-PCR for 3 cytokeratins expressed in HNSCC (K4, K10 and K13) proved to be less sensitive in detecting occult lymphatic metastases. Western blot analysis demonstrated the presence of the full-size MET receptor in primary tumors and lymph node metastases; immunohistochemistry showed receptor localization in tumor cells. Altogether, these data demonstrate that the MET gene product is a valuable marker with which to detect occult tumor cells in lymph nodes, thanks to its high expression in metastatic cells. After RT-PCR analysis we were able to attribute a more advanced stage to 10 out of 20 HNSCC cases, including 5 cases classified as tumor-free after routine histopathology.
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PMID:Staging of head and neck squamous cell carcinoma using the MET oncogene product as marker of tumor cells in lymph node metastases. 1086 6

In surgically resected specimens of squamous cell carcinoma (SCC) of the lung from 45 patients, we immunohistochemically examined the expression of 13 subtypes of cytokeratin (CK), the intermediate filament in cytoplasm of epithelial cells. To investigate heterogeneity of CK, its expression was compared among tumor cell nests with or without keratinization and stratification. Furthermore, the relationship between CK expression and Ki-67 labeling index or p53 expression was investigated. The tumor cell nests with keratinization showed the expression of CK1 and CK10 as a central pattern and the expression of CK14 as a peripheral pattern. The nests with stratification showed CK14 expression as a peripheral pattern, whereas those without stratification showed the expression as a diffuse pattern. The tumor cell nests showing stromal invasion with fibrosis in the marginal zone were diffusely positive for CK14. Ki-67 antigen labeling index was significantly higher in the nests where CK14 expression was diffuse or peripheral than in the nests where the expression was focal or negative. In lymph node metastases, the tumor cells often showed CK14 expression, like trabecular nests in the primary carcinoma. These results suggest that CK14 is a parameter of proliferative activity and metastatic potential of SCC of the lung.
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PMID:Heterogeneity of expression of cytokeratin subtypes in squamous cell carcinoma of the lung: with special reference to CK14 overexpression in cancer of high-proliferative and lymphogenous metastatic potential. 1203 Oct 84

Adenosquamous carcinomas of the small intestine are extremely rare, with only three documented jejunal and three ileal cases being reported in the English-language medical literature. Presented herein is a case of primary jejunal adenosquamous carcinoma in an 80-year-old woman. The jejunal carcinoma consisted predominantly of a squamous component throughout the tumor but peritoneal nodules carrying metastases from the adenocarcinoma element were noted, making it the first case of jejunal adenosquamous carcinoma with metastases from the adenocarcinoma component. The finding that metastases could arise from the minor component of a jejunal adenosquamous carcinoma indicates that an accurate diagnosis must be based upon thorough examination of both the primary and the metastases, not just mesenteric nodule biopsy alone. Histological foci of closely intermingled squamous and glandular components with apparent morphological transition were noted, indicating the pathogenetic possibility that the squamous component might arise by transformation from the glandular element. The squamous component was strongly positive with immunostaining for p63 (nuclear staining) and for cytokeratin 10/13 (cytoplasmic staining), while the adenocarcinoma element was negative. The immunohistochemical results suggest that p63 and cytokeratin 10/13 might be useful in identifying squamous differentiation in jejunal carcinoma.
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PMID:Primary adenosquamous carcinoma of the jejunum. 1614 36

Transforming Growth Factor-beta1 (TGF -beta1) is a multifunctional cytokine that regulates a number of cellular processes such as cell growth, differentiation, plasticity, cell motility, adhesiveness, embryogenesis, development and apoptosis through binding to TGF-beta receptors. We have previously demonstrated that K-ras-transformed rat thyroid cells, K10, are resistant to the growth inhibitory action of TGF-beta1, because they show a decreased expression of type II receptor (TbetaRII). Clones obtained transfecting TbetaRII, partially revert their malignant phenotype, showing a reduction in the anchorage-dependent and -independent cell growth and a statistically significant decrease in tumourigenicity with respect to the highly malignant parental cells, both in spontaneous and artificial metastases, when transplanted in athymic nude mice. The purpose of the present work is to elucidate the molecular events involved in the modulation of the tumourigenic potential of K-ras-transformed rat thyroid cells overexpressing TbetaRII. Our data demonstrate that the TbetaRII overexpressed in K-ras-transformed thyroid cell clones is a functional receptor and is essential to restore in these cells behaviour similar to that of control cells. The TbetaRII overexpression is responsible for a strong reduction of adhesive and migratory behaviour of highly malignant K-ras-transformed thyroid cells. These results suggest that the restore of a functional TGF-beta receptor in these cells may be useful for the limitation of tumour spread and dissemination.
Clin Exp Metastasis 2006
PMID:Reduction of invasive potential in K-ras-transformed thyroid cells by restoring of TGF-beta pathway. 1708 61

Lymph node micrometastases in patients with squamous cell carcinoma of the larynx found node-negative by conventional histology may be discovered by immunohistochemistry, particularly by using mono- and policlonal antibodies which are reactive with epithelial cells. Then tumors classified as pN0 by routine methods may be reclassified more correctly as pN1. Authors investigated the incidence of micrometastases in the neck dissection specimens originally staged as pN0 from 22 patients with laryngeal cancer treated surgically at ENT Department Medical University of Lodz between 1998-1999 according to: the survival, using immunostaining with panel of mono- and policlonal antibodies to cytokeratins CK1, CK4, CK5, CK6, CK8, CK10, CK13 and CK18. The relationship between micro-metastases and clinical features of primary tumor and lymph nodes has been discussed.
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PMID:[Cytokeratin antigen expression in lymph nodes--prognostic significance of clinical features of the primary tumor and lymph nodes in the presence of micrometastases in laryngeal carcinoma]. 1747 62

A variety of techniques have been employed for the detection of tumor cells in the lymph nodes of patients with oral squamous cell carcinoma (OSCC). Molecular analysis has been applied to detect metastases and several reports have presented examinations of tumor markers, but no target gene that is completely reliable as a molecular biological tumor marker has been found. This study investigated whether a marker exists that is effective to detect OSCC. A total of 134 samples (biopsy and surgical specimens) from 102 OSCC patients were analyzed. Expression patterns of Cytokeratin (CK) 10, 17, 19 and SCCA mRNA in the normal oral mucosa and OSCC samples were examined using RT-PCR. Statistical analyses showed that significant differences existed in expressions of CK 10, 17, 19 and SCCA between OSCC and the normal mucosa (p<0.05). No correlation was observed between the degrees of histological differentiation of the tumor and CK 17 expression. The CK 17 expression also showed no significant differences depending on sites of primary tumors. Among the CK 10, 17, 19 and SCCA investigated, only CK 17 showed high sensitivity and negative predictive value (NPV). CK 17 might be a good biomarker because of the performance of RT-PCR in detecting mRNA of CK 17 with such high sensitivity and NPV. Further studies using a larger number of OSCC patients and other CKs should be undertaken to establish CK 17 as a useful biomarker.
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PMID:[An effective biological marker to detect oral squamous cancer cells--expression patterns of CK 10, 17, 19 and SCCA mRNA--]. 1772 67

The aim of the present study was to clinically, morphologically, and immunohistochemically correlate the expression of cytokeratins (CKs) 7, 10, 13, 14, 16, and 19 in 30 cases of tongue squamous cell carcinoma (SCC) with disease outcome, metastases, clinical stage (tumor, node, metastasis [TNM]), and histological grade of malignancy proposed by Bryne. Statistical analysis (chi2 test) showed that only histological grading was not significantly correlated with the clinical variables. CK expression varied in the samples analyzed. CK 10 expression was significantly correlated with the presence of metastases, and the expression of CK 16 was related to disease outcome and also to TNM stages III and IV. These results indicate that metastases and TNM are effective prognostic indicators. The histological grading proposed by Bryne did not reflect the biological behavior of the tongue SCC cases studied. Analysis of some intermediate CK filaments can reflect the biological behavior and aggressiveness of some tongue SCCs.
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PMID:Correlation of clinical, histological, and cytokeratin profiles of squamous cell carcinoma of the oral tongue with prognosis. 1791 44


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