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)

Effective targeting of vectors to tumor cells that have metastasized to multiple different tissue sites remains a major challenge for gene therapy. Tumor-specific cytotoxic T lymphocytes (CTLs) have been shown in animal models and in humans to be able to cross tissue barriers and traffic to tumor cells. However, their capacity to eliminate malignancy has been limited by tumor immune evasion strategies. We now use a model of Epstein-Barr virus-mediated malignancy to show that human CTLs themselves may be modified to release therapeutic vectors following engagement of their antigen-specific receptors and that these vectors will effectively transduce and destroy tumor targets. We generated EBV-specific CTLs that were transgenic for the adenoviral E1 gene under the control of the cell activation-dependent CD40 ligand (CD40L) promoter. Following transduction with E1-deficient adenoviral vectors, these CTLs produced infectious virus when exposed to HLA-matched EBV-expressing targets, but not on exposure to major histocompatibility complex (MHC)-mismatched or otherwise irrelevant cells. This approach provides a means of delivering oncolytic/therapeutic vectors not only to locally accessible macroscopic tumors as is presently the case, but also to disseminated metastatic disease, while avoiding the risks associated with systemic administration of large doses of adenoviral vectors.
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PMID:Targeted delivery of adenoviral vectors by cytotoxic T cells. 1516 64

Immune responses to three Epstein-Barr virus (EBV) lytic proteins, DNase, thymidine kinase (TK), and BMRF-1 gene products (50/52 kDa diffused early antigen, EA-D complex) were determined in EBV-infected control individuals and patients with nasopharyngeal carcinoma (NPC). Immunofluorescence assays (IFA) were used to detect their humoral immune responses using recombinant EBV lytic proteins expressed in a baculovirus system as antigens. Cell proliferation assays were performed to evaluate their cellular immune responses by monitoring 3H-thymidine incorporation. Seventy patients with NPC and 32 non-cancer controls were analyzed. The results of IFA showed antibody titers to all three EBV lytic proteins to be higher in the patients with NPC especially for the IgA class. Positivity rates of the three IgA antibodies also were higher in the patients with NPC population. Furthermore, the profiles of the IgA antibodies correlated with those to total early antigens (EA) expressed in the early phase and viral capsid antigen (VCA) expressed in the late phase, of EBV replication. The most interesting finding was that antibody titers to the three EBV lytic proteins were associated significantly with metastases of cervical lymph nodes in patients with NPC. As for cellular immunity to the EA-D complex and DNase, weak responses were observed in the cell proliferation assays. Peripheral blood cells from most individuals could not be stimulated to proliferate, except for a few patients with NPC whose antibody titers against the EA-D complex and DNase also were very high.
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PMID:Immune responses to Epstein-Barr virus lytic proteins in patients with nasopharyngeal carcinoma. 1522 2

Nasopharyngeal carcinoma is intimately associated with the Epstein-Barr virus (EBV), which we have exploited therapeutically by constructing an EBV-specific synthetic enhancer sequence, within an adenoviral vector, denoted as adv.oriP. The achievement of tumor targeting provides therapeutic potential when delivered systemically, which could impact on distant metastases. We demonstrate here the feasibility and potential utility of combined, minimally invasive in vivo bioluminescence and fluorescence imaging to monitor adenoviral infection of subcutaneous C666-1 nasopharyngeal xenograft tumors stably expressing the DsRed2 gene. Fluorescence imaging was used to monitor the location and size of the C6661.DsRed2 tumors, whereas bioluminescence imaging demonstrated the distribution and specificity of a transcriptionally targeted adenoviral vector, adv.oriP.fluc, expressing the firefly luciferase gene. Fluorescence, bioluminescence, and photographic images were aligned using grids to examine colocalization of adenovirus and tumors. Bioluminescence and fluorescence co-localized in 92% (11/12) of tumors at 24 hr and 100% (12/12) at 96 hr after adv.oriP.fluc (10(9) ifu) was administered intravenously. Nonspecific luciferase signal was detected in the liver area. The combined imaging was therefore successful in monitoring the uptake of systemically administered adenovirus in implanted tumors. This may ultimately lead to an effective noninvasive method to monitor the response of metastases to adenoviral gene therapy.
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PMID:Combined in vivo bioluminescence and fluorescence imaging for cancer gene therapy. 1580 52

Recently, we showed that Epstein-Barr virus (EBV)-positive gastric carcinoma (GC) forms a distinct clinicopathologic entity with a better prognosis due to lower incidence of lymph node metastases (LN+). Here we investigated whether in EBV-positive GC more pronounced activation of cellular immune responses is associated with absence of (micro)metastases. Twenty EBV-positive primary tumors (PT) (9 LN+) were matched with 28 EBV-negative GC (11 LN+) for T- and N-stage, gender, and age. The PT (n = 28) and its LNs were analyzed by EBER RNA in situ hybridization and by immunohistochemistry for MHC class I and II expression, for CD3, CD8, CD4, CD20, CD56, CD83, and Granzyme B (GzB) expression. In LN metastases of EBV-positive GC, the EBV genome is maintained, excluding tumor escape by virus deletion. All GC express MHC class I independently of EBV status. In comparison with EBV-negative GC, EBV-positive GC have higher expression of MHC class II on the tumor cells (P = 0.029) and a more extensive infiltrate (P < 0.0001) of activated GzB+ CD8+ T cells (P = 0.028), which is most abundant in those EBV-positive tumors that do not metastasize (P < 0.0001). In addition, in EBV-positive GC without metastases, the infiltrate contains higher numbers of mature dendritic cells (DC) (P = 0.018). At present, the antigenic target has to be determined. These data support the notion that local triggering of cellular immune responses in EBV-positive GC prevents lymph node metastasis formation.
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PMID:Morphological evidence of an activated cytotoxic T-cell infiltrate in EBV-positive gastric carcinoma preventing lymph node metastases. 1633 Sep 43

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 microM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 +/- 3.9% in HNE1-LMP1 cells vs 37.89 +/- 4.9% in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 +/- 3.5 vs 65.87 +/- 5.9%), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 +/- 3.7 and 27.91 +/- 2.1%), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 +/- 3.9 vs 29.19 +/- 6.27%) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.
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PMID:Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro. 1664 6

We report a case of a primary lymphoepithelioma-like carcinoma (LELC) of the skin. The patient was a 73-year-old man with a lump on his back for 18 months. A biopsy and subsequent excision was performed. He also had axillary node clearance for metastatic disease. The tumor was composed of islands of pleomorphic cells with a lymphocytic infiltrate. Differential diagnoses included squamous cell carcinoma, adnexal carcinoma, Merkel cell tumors, lymphoepithelial lesions, lymphomas, and skin metastases. The histopathologic and immunohistochemical features were those of a LELC of the skin. It was negative for Epstein-Barr virus. Just over 30 cases of primary LELCs arising in the skin have been reported with only 1 documented fatality. We report a case with extensive vascular involvement and bilateral lymph node metastases.
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PMID:Lymphoepithelioma-like carcinoma of the skin: a case with lymph node metastases at presentation. 1677 88

Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. The annual incidence of NPC in the UK is 0.3 per million at age 0-14 years, and 1 to 2 per million at age 15-19 years. Incidence is higher in the Chinese and Tunisian populations. Although rare, NPC accounts for about one third of childhood nasopharyngeal neoplasms. Three subtypes of NPC are recognized in the World Health Organization (WHO) classification: 1) squamous cell carcinoma, typically found in the older adult population; 2) non-keratinizing carcinoma; 3) undifferentiated carcinoma. The tumor can extend within or out of the nasopharynx to the other lateral wall and/or posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx. It then typically metastases to cervical lymph nodes. Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Etiological factors include Epstein-Barr virus (EBV), genetic susceptibility and consumption of food with possible carcinogens--volatile nitrosamines. The recommended treatment schedule consists of three courses of neoadjuvant chemotherapy, irradiation, and adjuvant interferon (IFN)-beta therapy.
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PMID:Nasopharyngeal carcinoma. 1680 Aug 83

The development of new and more effective immunosuppressive agents has provided long-term survival for transplant recipients, thereby increasing the risk of de novo malignancy in chronic immunocompromised hosts. While de novo post-transplant lymphoproliferative diseases and skin cancer has been shown to have an increased incidence in long-term surviving solid organ transplant recipients, the association with gastrointestinal (GI) cancer is controversial. Over 12 yr, 20 patients (5%) out of 395 renal transplant recipients developed 23 de novo tumours; 11 skin cancer and 12 non-skin cancer. Four patients (1%) developed de novo tumours of the GI tract (three colon, and one gastric cancer). Immediately after tumour's diagnosis, immunosuppressive therapy was reduced; all patients were shifted from cyclosporine to Rapamicine within 30 d. The tumour was surgically resected with curative intent in three cases, while one patient had only palliative surgery because of metastatic disease. The post-operative courses was uneventful. All patients maintained normal graft function. However, three out of four patients (75%) died of progression of the neoplasm, within a median time from the diagnosis of 12 months. Further, we investigated a possible correlations between de novo GI cancer and HCV, HBV status, infections, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation, episodes of rejection, and blood transfusions. All cases with GI de novo cancers reported in this paper developed CMV and EBV reactivation within three months after transplantation. Thereafter we suggest a closer follow-up for de novo GI cancer in renal transplants with early CMV and EBV reactivation in order to avoid delayed diagnosis.
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PMID:De novo gastrointestinal tumours after renal transplantation: role of CMV and EBV viruses. 1684 21

Undifferentiated carcinoma of salivary glands is too poorly differentiated to be classified as any of the specific group of carcinomas. This is a rare disease, the incidence of which is rather low-to-very low in the Indian subcontinent. The tumor can assume an aggressive clinical behavior characterized by disseminated metastases. The prognosis is rated as dismal; as evidenced by this clinical report of a tumor in the submandibular salivary gland with synchronous metastases to the skull bones and in to the intracranial fossa. The putative relationship of the tumor to Epstein-Barr virus (EBV) infection is discussed.
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PMID:Undifferentiated carcinoma of the submandibular salivary gland with fulminant clinical course: a case report. 1693 43

Basaloid squamous carcinoma is a rare variant of squamous cell carcinoma. It is frequently diagnosed at an advanced stage with metastases. Histologically, it is identical to basaloid carcinoma at other anatomical sites. Some authors suggest that it may be associated with second primary tumors. Others implicate the Epstein-Barr and human papilloma viruses. All reports but one warn of its aggressive biological behavior. Our case concerns a 52-year-old man who had a small lesion in his right cord. Biopsy of the lesion was performed twice, and conventional squamous cell carcinoma was diagnosed; the patient returned 2 months later with progressed metastatic disease. The patient underwent a laryngectomy and a complete clinical and immunohistochemical investigation. Basaloid squamous carcinoma is a totipotential neoplasm with a grave prognosis. It can be misdiagnosed; therefore, the authors would like to emphasize the significance of this condition in comparison to conventional squamous cell carcinoma, and we provide a review of the relevant recent literature.
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PMID:Basaloid squamous carcinoma of the larynx. A potential diagnostic pitfall. 1697 24


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