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)

We present a retrospective series of 16 cases of undifferentiated squamous carcinoma in cervical metastatic nodes of unknown primary. We review their clinical and radiological evaluation in search of a possible primary tumor, their response to treatment and the eventual development of a primary tumor. Furthermore, we study the presence of Epstein-Barr virus in the metastases as a predictor of their nasopharyngeal origin, in relation to the finding of primary lesions in the nasopharynx during further follow-up of the cases.
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PMID:[Neck lymph node metastases of unknown origin: nasopharyngeal origin and EBV (Epstein-Barr virus)]. 1061 98

Type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP9 are implicated in tumor invasion and metastasis. In patients with nasopharyngeal carcinoma (NPC), poor prognosis due to development of local and distant metastasis has been reported to be predicted by antibody titers against the Z protein which is an AP-1 family transcription factor encoded by the EBV BZLF1 immediate-early gene. Here we report that in patients with NPC, expression of Z in tumor cells correlates with advanced cervical lymph node metastasis which may suggest that Z affects tumor invasion and metastasis. We therefore tested if Z would induce expression of type IV collagenases. Transfection of Z expression plasmid into the C33A epithelial cell line increased expression of MMP9, but MMP2 expression was unaltered. Mutational analysis of the Z protein revealed that, in addition to all three functional domains of Z (dimerization domain, DNA binding domain, and activation domain), the carboxyl terminal 17 amino acids which stabilize the Z protein were necessary for induction of MMP9 expression. Analysis of the MMP9 promoter demonstrated that only AP-1 site close to the transcriptional start-site was essential for transactivation by Z. Previously we reported that Epstein-Barr virus latent membrane protein 1 (LMP1) stimulates MMP9 expression (Yoshizaki et al. Proc. Natl. Acad. Sci. 1998; 95: 3621-6). Thus, Z together with LMP1 may contribute to invasion and metastasis of NPC by inducing expression of MMP9.
Clin Exp Metastasis 1999 Jul
PMID:Matrix metalloproteinase 9 is induced by the Epstein-Barr virus BZLF1 transactivator. 1065 10

Squamous carcinoma is the most common malignancy of the head and neck, but it rarely occurs in the nasal vestibule. Epstein-Barr virus (EBV) has been detected in and is causally linked to various head and neck tumors, particularly nasopharyngeal carcinoma. The possible role of EBV in squamous carcinoma of the anterior nasal cavity, particularly of the nasal vestibule, has not been previously investigated. Histologic sections from 17 patients with nasal vestibular squamous carcinoma were examined. Material for EBV detection by immunohistochemistry and by in situ hybridization was available in 15 of the 17 cases. The study group consisted of eight men and nine women ranging in age from 40 to 82 years (mean age, 64 years). None of the patients was of Asian descent. The squamous carcinomas were graded as well differentiated (one case), moderately differentiated (11 cases), and poorly differentiated (five cases). Fourteen patients were smokers; the history of smoking ranged from 20 to 60 pack-years. Treatment modalities included surgical resection, radiation, chemotherapy, or a combined approach. The clinical follow-up periods ranged from 7 months to 16 years. Three patients developed metastases, one of whom died of disease after 1 year. Epstein-Barr virus was not detected in any of the 15 of 17 cases tested by either immunohistochemistry or by in situ hybridization. Squamous carcinoma of the nasal vestibule is an uncommon cancer that is not causally related to EBV.
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PMID:Epstein-Barr virus in squamous carcinoma of the anterior nasal cavity. 1068 74

We describe a 27-year-old woman with systemic chemoresistant and radioresistant metastatic disease secondary to a recurrence of human papillomavirus (HPV) 18 infected cervical adenocarcinoma of the uterine cervix who received adoptive transfer of peripheral blood T cells stimulated with HPV 18 E7-pulsed autologous dendritic cells (DC). Extensive in vitro characterization of the DC-activated T cells derived from peripheral blood mononuclear cells (PBMC) included phenotypic analysis, cytotoxicity and intracellular cytokine production. High cytotoxicity activity was observed by CD8+T cells against autologous tumor cells, but not against NK-sensitive K562 cells, autologous Con-A lymphoblasts, or autologous Epstein-Barr virus-transformed lymphoblastoid cells. Blocking studies demonstrated that lytic activity was significantly inhibited by pretreatment of tumor targets with MAb specific for HLA class I as well as that of effector cells with anti-CD8, anti-LFA-1, but not anti CD3 MAb. Two-color flow cytometric analysis of the cytotoxic T cells revealed that a significant proportion of CD8+ cells was also CD56+. These double positive CTLs were thymically derived, as shown by expression of heterodimeric CD8 molecules (alpha/beta CD8) and were endowed with high cytotoxic activity against tumor cells. Analysis of intracellular cytokine expression showed that the striking majority of E7-pulsed DC activated CD8+ T cells strongly expressed IFN-gamma, TNF-alpha and IL-2 but not IL-4. The patient received two infusions of cytotoxic tumor-specific T cells at 2 week intervals, and in vivo distribution of the T cells was followed by 111 oxine labeling and serial gamma camera imaging. Persistent accumulation of radioactivity in the lungs, which harbored extensive metastatic disease, was detected up to 120 hrs after the infusion. Taken together, these results illustrate the potential of E7-specific and tumor-specific CTL-based immunotherapy for the treatment of patients with invasive cervical cancer.
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PMID:Development, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix. 1072 12

We describe a 65-year-old woman with a large surgically unresectable and chemoresistant liver metastasis of endometrial carcinoma who was treated by infusion with peripheral blood T cells stimulated with tumor lysate-pulsed autologous dendritic cells (DC). Extensive in vitro characterization of the DC-activated T cells included phenotypic analysis, cytotoxicity, and intracellular cytokine secretion. High cytotoxicity was observed against autologous tumor cells, but not against NK-sensitive K562 cells, autologous Con-A lymphoblasts, or autologous Epstein-Barr virus-transformed lymphoblastoid cells. Blocking studies demonstrated that lytic activity was HLA class I restricted. Two-color flow cytometric analysis revealed that a significant proportion of CD8+ T cells was also CD56+, and analysis of intracellular IFN-gamma and IL-4 expression suggested a type 1 cytokine bias. The patient was treated by three infusions of tumor-specific T cells at 3- to 4-week intervals, and in vivo distribution of the T cells was followed by (111)In oxine labeling and serial gamma camera imaging. Tumor localization and accumulation of labeled lymphocytes was consistently detected at serial time points following each injection. However, deep infiltration of the large tumor mass by activated T cells was minimal, as evaluated in 3 dimensions by single photon emission computerized tomography (SPECT) imaging. Transient serum increases of the tumor marker lactate dehydrogenase (LDH), were detectable after each injection. Similar posttreatment elevations were seen for serum uric acid and potassium. Clinically, stabilization of the large liver metastasis was obtained during treatment. Collectively, these results indicate that tumor-specific CD8+ cytotoxic T-cell responses can be generated in patients with endometrial cancer, and suggest that T-cell immunotherapy may be of therapeutic value in patients harboring metastatic disease.
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PMID:Development and therapeutic effect of adoptively transferred T cells primed by tumor lysate-pulsed autologous dendritic cells in a patient with metastatic endometrial cancer. 1072 62

Laryngeal lymphoepithelioma is a rare tumor (16 cases in the literature). It is an association of undifferentiated, non-keratinizing cells and normal lymphocytes and plasma cells. The Epstein-Barr virus is rarely found. To determine the actual nature of the tumor, a complete histochemical workup and/or electron microscopy often are needed. Cervical lymph node involvement is common. We report the cases of two men. In one patient, the tumor was located in the glossoepiglottic fold and in the other it was located in the left ventricule and false vocal cord. EB virus was absent in both cases. Cervical lymph node metastases were found, but not distant metastases. One patient was treated by irradiation and the second underwent surgery (supraglottic laryngectomy and cervical dissection) and was referred to radiotherapy for further treatment.
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PMID:[Lymphoepithelial carcinoma of the larynx. Report of 2 cases]. 1098 65

The Epstein-Barr virus LMP2A protein was expressed in a human keratinocyte cell line, HaCaT, and effects on epithelial cell growth were detected in organotypic raft cultures and in vivo in nude mice. Raft cultures derived from LMP2A-expressing cells were hyperproliferative, and epithelial differentiation was inhibited. The LMP2A-expressing HaCaT cells were able to grow anchorage independently and formed colonies in soft agar. HaCaT cells expressing LMP2A were highly tumorigenic and formed aggressive tumors in nude mice. The LMP2A tumors were poorly differentiated and highly proliferative, in contrast to occasional tumors that arose from parental HaCaT cells and vector control cells, which grew slowly and remained highly differentiated. Animals injected with LMP2A-expressing cells developed frequent metastases, which predominantly involved lymphoid organs. Involucrin, a marker of epithelial differentiation, and E-cadherin, involved in the maintenance of intercellular contact, were downregulated in LMP2A tumors. Whereas activation of the mitogen-activated protein kinase pathway was not observed, phosphatidylinositol-3-kinase (PI3-kinase)-dependent activation of the serine-threonine kinase Akt was detected in LMP2A-expressing cells and LMP2A tumors. Inhibition of this pathway blocked growth in soft agar. These data indicate that LMP2A greatly affects cell growth and differentiation pathways in epithelial cells, in part through activation of the PI3-kinase-Akt pathway.
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PMID:Epstein-Barr virus LMP2A transforms epithelial cells, inhibits cell differentiation, and activates Akt. 1104 12

As part of our screening program for cancer inhibitory agents effective specifically in the promotion stage of cancer development, we have evaluated the possible inhibitory effects of 36 non-steroidal anti-inflammatory drugs (NSAIDs) on the Epstein-Barr virus early antigen (EBV-EA) activation which was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. All the drugs were observed to inhibit the EBV-EA activation at low doses with low toxicity. The two most active anti-tumor promoting agents were the arylacetic acid derivatives, etodolac and sulindac. We also report for the first time the activities of 14 new NSAIDs belonging to different classes as potential cancer chemopreventive agents. A structure-activity relationship study showed that among the salicylic acid derivative tested, the oxidation of the thiol group to dithiol derivatives results in the reduction of the activity. Introduction of amino group on the salicylic acid molecules also results in the reduction of activity in the EBV-EA assay. The results are of great interest in the development of NSAIDs as cancer chemopreventive agents, which halt cancer progression in multistage carcinogenesis, where successive activities are required to evolve into fully-fledged and metastatic cancer.
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PMID:Inhibition of epstein-barr virus early antigen activation promoted by 12-O-tetradecanoylphorbol-13-acetate by the non-steroidal anti-inflammatory drugs. 1109 Sep 73

For poorly differentiated rhinopharyngeal carcinomas, the clinical presentation (association with the Epstein-Barr virus, paraneoplastic syndromes, onset of lymphoma) and the histopathological features can be polymorphous and they can confound or delay diagnosis and preparation of an adequate treatment plan (radio-chemotherapy). Often these neoplasms arise as clinically primitive laterocervical metastases, masked by clinical findings and a history that can lead to the mistaken diagnosis of systemic lymphoproliferative processes such as Hodgkin's disease. Here an observation of this type is presented in a young patient (19 years old) who came under observation for a laterocervical tumefaction recurrent from a previous exeresis performed at another hospital and symptoms of serotine febricula, dysphagia and serology positive for the Epstein-Barr virus (EBV). The patient underwent surgery and then radiotherapy and has been under close post-operative follow-up for two years. To date the patient's condition--both local and general--is good. The particular histology of the neoformation lies in the abundant infiltration of plasma cell and lymphocyte eosinophils, at times in blastic form. Moreover, elements with a large clear nucleus and evident nucleolus (Hodgkin-like) and scattered multinucleate Langhans-type giant cells can be seen. Immunohistologically the tumor cells markedly express for cytokeratin and the latent membrane protein (LMP1) of the Epstein-Barr virus (EBV) and show a high growth fraction. Under the electron microscope, the plurinucleate giant cells present large nuclei with morphology similar to that of tumor cells. The clear cytokeratin-positivity of the tumor elements and the histological and ultrastructural features mentioned led to the diagnosis of a massive metastasis from lymphoepithelial carcinoma, the Schmincke variant, plus EBV infection of the neoplastic cells. The authors conclude assuming that the particular granulomatous reaction is due to the host's reaction to the tumor cells, but also to the reaction to the viral antigens. In the former case we find an attempt to limit the carcinomatous process; in the latter it is a response caused by the EBV and is not, apparently, aimed at protecting against the neoplasm rather it facilitates the neoplastic process.
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PMID:[Description of a particular case of the so-called Schmincke lymphoepithelioma and study of the correlation with Epstein-Barr virus]. 1128 63

A 59-year-old man was admitted presenting systemic rash and muscle weakness. He was diagnosed to have dermatomyositis and a check was made for internal malignancy. Gastrointestinal endoscopy revealed a Borrmann type II tumor on the middle body of the stomach. Biopsy specimens showed a well differentiated adenocarcinoma, and total gastrectomy was performed. The final diagnosis was moderately differentiated adenocarcinoma invading into the proper muscular layer, with metastases to regional lymph nodes. Most of the neoplastic cells were shown to be positive for Epstein-Barr virus by means of EBV-encoded RNA in situ hybridization. The symptoms of dermatomyositis disappeared completely after surgery.
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PMID:Epstein-Barr virus-associated gastric cancer in a patient with dermatomyositis. 1130 Jan 69


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