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

Nasopharyngeal carcinoma (NPC) is an epithelial cancer that is causally associated with Epstein-Barr virus (EBV) infection. NPC tumor biopsies are characterized histopathologically by an abundant infiltration of nonmalignant lymphocytes. We analyzed the expression of various cytokines in NPC tissues to investigate the interaction of the infiltrating lymphocytes and tumor cells. Analysis using reverse transcriptase-PCR revealed the expression of a panel of cytokines in the NPC biopsies: interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma, tumor necrosis factor-alpha, transforming growth factor-beta, and IL-1 receptor types I and II. Elevated expression of IL-1alpha and IL-1beta was observed in primary tumors and NPC metastases compared to control tissues. Interestingly, this increased expression correlated with the EBV-encoded viral IL-10 transcript. To determine which cells were responsible for producing IL-1, we determined the cellular constituents of NPC biopsies by immunoflow cytometric analysis. On the basis of data from these analyses, the three major specific cell populations, epithelial cells, CD4+ T cells, and CD8+ T cells, were selected from five NPC tumors using specific, antibody-coated paramagnetic beads. Reverse transcriptase-PCR of RNA from these fractionated cells showed that transcripts of IL-1alpha and IL-1beta were present not only in the malignant epithelial cells but also in CD4+ T cells infiltrating the tumor, a finding confirmed by immunohistochemical staining. We hypothesize that the unusual synthesis of IL-1alpha and IL-1beta by EBV-positive epithelial cells as well as by CD4+ T cells might contribute to lymphocyte infiltration and/or tumor growth during NPC development.
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PMID:Profile of cytokine expression in nasopharyngeal carcinomas: a distinct expression of interleukin 1 in tumor and CD4+ T cells. 1019 35

Nasopharyngeal carcinoma (NPC) is predominantly of the undifferentiated histological subtype. Histological differentiation is of limited prognostic significance in NPC. Recent studies have suggested that downregulation of the cadherin-catenin cell adhesion complex may play a crucial role in the initial stage of cancer invasion and metastasis and is associated with poor prognosis in human cancers. Expression of E-cadherin has not been reported previously in NPC, and its prognostic value in NPC is unknown. The purpose of this study was to examine the expression pattern of E-cadherin and its associated partner, beta-catenin, in NPC and their possible applications as prognostic markers to predict the clinical outcome of NPC. Expression of the E-cadherin and beta-catenin was examined by immunohistochemical methods in 74 cases of primary NPC and 17 of their corresponding lymph node metastases. Normal nasopharyngeal epithelium showed strong and homogeneous immunocytochemical staining of E-cadherin and beta-catenin at the cell membranes and intercellular junctions. In contrast, primary NPC showed variable and heterogeneous staining patterns of E-cadherin and beta-catenin. Loss of membranous E-cadherin expression was significantly associated with advanced stages of diseases (P<.001). Eighty percent to ninety percent of NPC in stages IV and V (Ho's staging), respectively, showed a reduced (<35%) membranous staining of E-cadherin compared with normal nasopharyngeal epithelium. Expression of beta-catenin also was downregulated in advanced NPC. Ninety percent to one hundred percent of NPC in stages IV and V (Ho's staging) expressed a reduction (<35%) of imnmunocytochemical staining of beta-catenin. The expression pattern of beta-catenin staining was strongly associated with the expression of E-cadherin (P<.001). Unlike E-cadherin, nuclear staining of beta-catenin expression was observed in some of the primary NPC and lymph node metastasis. Reduced expression of E-cadherin and beta-catenin expression was associated with a shorter survival of NPC patients (P<.001). In advanced NPC patients (stages IV and V), a significant difference in survival was observed in tumors with higher or lower levels of E-cadherin expression (P=.0224, log-rank test). These observations suggests that expression of E-cadherin and beta-catenin may have prognostic values in NPC patients.
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PMID:Downregulation and abnormal expression of E-cadherin and beta-catenin in nasopharyngeal carcinoma: close association with advanced disease stage and lymph node metastasis. 1020 69

Cases of hyperfractionated radiotherapy and adjuvant chemotherapy for nasopharyngeal cancer are reported. Seven patients received hyperfractionated radiotherapy (76.8-81.6 Gy/64-68 fractions to primary tumor) and two cycles of cisplatin (80 mg/m2 i.v. on day 1) plus 5-FU (800 mg/m2 continuous infusion on days 2-6). Mucositis was the most frequent side effect in hyperfractionated radiotherapy. Moderate leukopenia was the major side effect of adjuvant chemotherapy. With a mean follow-up time of 34 months (range 25-48 months), five of the seven patients were locoregionally controlled. Two developed distant metastases. Two patients suffered late complications (posterior nasopharyngeal wall necrosis and brain necrosis). These results suggested that our regimen was almost well tolerated and might be of use in locoregional control of nasopharyngeal cancer. However, it carries some risk of late complications and might be inadequate for preventing distant metastases. A three-dimensional conformal boost irradiation technique and adequate dose intensity chemotherapy might be encouraged.
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PMID:Hyperfractionated radiotherapy followed by adjuvant chemotherapy for nasopharyngeal cancer: report of seven cases. 1022

The current standards of treatment for nasopharyngeal cancer include 1. In early disease (stage I and stage II), radiotherapy is the treatment of choice, and the chance for cure is usually high. 2. In locally advanced disease (stage III and stage IV) combination chemotherapy and radiation therapy is indicated. Further clinical trials are warranted, which may include the newer active chemotherapeutic agents. 3. Patients with distant metastases may be treated with chemotherapy alone or other palliative measures.
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PMID:Nasopharyngeal cancer. 1049 17

A group of twenty patients with nasopharyngeal cancer treated in Lower Silesian Oncological Centre from year 1991 to 1995 have been presented. In seven of them the extent of the primary tumor was small (T1 or T2), but the rest of them (thirteen) had large extent of it (T3 or T4). In seven patients metastases to the cervical lymphonodes were not observed. The histopathology exam showed in eight cases well differentiated carcinoma, in another eight--lymphoepitelioma, in three--undifferentiated carcinoma and in one case adenocarcinoma. All of the patients were treated with radiotherapy using variable schedules of fractionaction, and three of them were given chemotherapy. Only seven (35%) are still alive without symptoms of disease. Such unsatisfactory results should be ascribed to a very high extent of illness in most patients, a result of coming to the doctor late and of big difficulties in diagnosis. Only several patients (20%) had CT of the head made before the treatment, which could be a reason for an incorrect location of the planning target volume (PTV).
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PMID:[The level of diagnosis and treatment results in nasopharyngeal cancer patients]. 1058 47

Amplification of the c-erbB-2 gene has been associated with poor prognosis in different types of cancer. However, there are no data on the c-erbB-2 expression levels in nasopharyngeal cancer. In this study, amplification of the gene has been investigated in the tumor tissue of patients with nasopharyngeal cancer by competitive polymerase chain reaction c-erbB-2 amplification was observed in 43.3% of the patients. The increase in the gene copy number correlated with the T stage. No correlation was found with lymph node involvement, histologic grade, differentiation, presence of metastases, or age and sex. We conclude that c-erbB-2 amplification may contribute to the pathogenesis of nasopharyngeal cancer. Our report is the first study investigating the expression of the c-erbB-2 gene in nasopharyngeal cancer at the DNA level.
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PMID:c-erbB-2 gene amplification in nasopharyngeal carcinoma. 1070 61

In nowadays development in radiotherapy head and neck cancers has been achieved step by step in 3 main fields: technological, radiobiological and general strategy of oncological treatment. One of the most important technical changes are: the introducing of three dimensional treatment planning (3 DCRT) system and application of new radiological imaging methods (CT, MRI) in treatment planning with a computer technology calculation of dose distribution. From the radiobiological point of view a very important fact has been to distinguishing two kinds of tissue (acute and late reacting tissue) which response depends on change in fraction dose. It has given the theoretical basis to clinical trials of new methods of fractionation (hyper-, accelerated hyperfractionation). The dynamic development of surgery and chemotherapy have established a new place for radiation therapy in the complex treatment of tumours (adjuvant, elective, concomitant treatment). It has been established that in advanced tumours, the first modality of treatment is surgery in conjunction with postoperative radiotherapy. Routine application of chemotherapy in head and neck cancer is still controversial with exception of radiochemotherapy of nasopharyngeal cancer, particularly in cases of lymph nodes metastases.
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PMID:[Possibility of the achieving of the therapeutic gain in radiotherapy of head and neck cancer]. 1096 Oct 83

Undifferentiated carcinoma is the most frequent nasopharyngeal cancer; it has a typical pathognomonic histological pattern, a close relationship to Epstein-Barr virus (EBV), a peculiar natural history and a good prognosis. It has an early tendency to locally spread to the parapharyngeal space. Nodal involvement is highly frequent (70-90%) and bulky regardless of the size of the primary. Literature reports up to 11% distant metastases at presentation and up to 87% at autoptic studies. Pretreatment work-up should include: personal history, clinical and fiberscopic examination, magnetic resonance imaging (MRI) or computed tomography (CT) scan of the base of the skull and neck, histology of the primary and cytology of neck lumps, bone marrow aspiration and biopsy, and EBV serological profile. Clinical and pathological factors predicting possible distant spread are primary tumor and node extension, and treatment failure. Up to now no reliable predictive biological markers have been identified. After treatment, distant metastases are found in about 30% of patients within 5 years and generally have a bad prognosis. Metastatic nodes above the clavicle, in absence of locoregional failure, aggressively treated with chemoradiotherapy, have a disease-free survival longer than 5 years. The following is the suggested posttreatment work-up for early diagnosis of these salvageable patients: clinical and fiberscopic evaluation every 3 months for 2 years and later on every 6 months; skull base and neck MRI or CT scan, and chest CT scan at 6, 12, 18, 24, 36, 48 and 60 months; EBV serological evaluation.
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PMID:Distant metastases from nasopharyngeal cancer. 1140 15

At the present time the occurrence of distant metastases in patients with head and neck squamous cell carcinoma means that lifespan is measured in months. In most instances treatment is purely palliative. Isolated lung metastasis can be successfully removed with long-term disease control in selected patients. Radiotherapy can be useful for palliation of bone metastases and occasionally lung or brain metastases. Chemotherapy does not have a major impact at the present time except for the treatment of metastases from nasopharyngeal cancer. Palliative symptomatic care, along with appropriate pain control, is essential since pain management is very important in these patients. A significant change in the survival of patients with head and neck cancer is only likely to occur by the development of new approaches to treatment. Blocking tumor angiogenesis and treatment based on genetic abnormalities or cell surface receptors offer the two strategies that are most likely to be successful.
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PMID:The treatment of distant metastases in head and neck cancer--present and future. 1140 25

To investigate the feasibility and efficacy of dose escalation using three-dimensional (3-D) conformal boost technique, 21 patients with stage III or IV nasopharyngeal cancer were enrolled in a prospective protocol. All patients with node metastases initially received external radiotherapy by conventional technique up to 70.2 Gy, followed by 3-D conformal radiotherapy (3-D CRT) to the boost part up to 79.2 Gy with 9 Gy increments (daily fraction of 1.8 Gy for 5 days). A modified technique with the same dose escalation of 9 Gy using 3-D CRT was applied to 7 patients without node metastases, who were treated by conventional technique up to 54 Gy, followed by 3-D CRT to boost up to a basic dose of 70.2 Gy, and then finally with dose escalation of 9 Gy. The protocol was relatively well tolerated by the majority of patients. Acute complications during the dose escalation schedule was low, with rare occurrences of grade 3 or 4 toxicity. Although late radiation-induced complications also appeared limited, 1 patient developed a temporal lobe necrosis and 2 patients suffered from sensory-neural hearing loss. There were no radiation-induced fatal complications. At a median follow-up of 48 months, only 3 patients experienced local failure and 2 patients developed distant metastases. The 5-year overall actuarial survival rate and recurrence-free survival rate for all patients were 68% and 85%, respectively. On the basis of acceptable morbidity and encouraging treatment results, we conclude that the dose escalation in 9 Gy increments using a 3-D conformal boost technique is relatively safe and efficacious, enough to be used routinely for locally advanced nasopharyngeal cancers.
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PMID:A feasibility study using three-dimensional conformal boost technique in locally advanced carcinoma of the nasopharynx. 1166 29


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