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)

Nasopharyngeal carcinoma (NPC) is a tumor derived from epithelial cells and Epstein-Barr virus infection has been reported to be a cause of this disease. Chemokine receptor CXCR4 was found to be involved in HIV infection and was highly expressed in human malignant breast tumors and the ligand for CXCR4, CXCL12 (SDF-1), exhibited high expression in organs in which breast cancer metastases are often found. The metastatic pattern of NPC is quite similar to that of malignant breast tumors. In this study, we investigated the expression of CXCR4 in nasopharyngeal carcinoma (NPC) tissues by immunohistostaining. We found different staining patterns, which included localization in the nucleus, membrane, cytoplasm or a combination of them. The staining intensity was also variable among samples. The metastatic rates in patients with high compared to low or absent expression was 38.6% versus 19.8%, respectively (P = 0.004). High expression of CXCR4 was associated with poor overall survival (OS = 67.05% versus 82.08%, P = 0.0225). These results suggest that CXCR4 may be involved in the progression of NPC and that a high level of CXCR4 expression could be used as a prognostic factor.
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PMID:Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma: pattern of expression and correlation with clinical outcome. 1597 37

The chemokine receptors CCR5 and CXCR4 serve as co-receptors for the human immunodeficiency virus 1 (HIV-1) and thus, are important cellular components during HIV-1 cell entry. In recent years, a new biological role for chemokine receptors has emerged in assisting the spread of primary tumors to distant secondary sites within the human body (metastasis). This review highlights some of the HIV-1 cell entry inhibitors (antagonists), which are currently in development and/or under evaluation in clinical trials, and discusses the therapeutic use of these new antagonists for the treatment of certain forms of metastatic cancer.
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PMID:Killing two birds with one drug: a new application for HIV-1 cell entry inhibitors in the treatment of metastatic cancer. 1615 63

Ramelton is a medication recently approved by the FDA for treatment of insomnia. Ramelton is an analogue of melatonin with a higher affinity even than that of the natural ligand. Clinically this potentially strong effect of the ligand is blunted by the fact that upon oral ingestion there is first pass metabolism of greater than 95%. This liver metabolism is mediated by the CYP1A2 enzyme. It turns out that the medication fluvoxamine approved by the FDA for the treatment of obsessive compulsive disorder is a potent inhibitor of the CYP1A2 enzyme, with the effect that co-administration of ramelton and fluvoxamine increases blood levels of ramelton by 100-200 fold. It turns out that lymphocytes bear the melatnonin receptors and stimulation of these receptors on lymphocytes cause the lymphocytes to elaborate the pro-inflammatory cytokine interleukin-2 (Il-2). Thus, here we point out that co-administration of ramelton and modest doses of fluvoxamine may be able to smoothly produce increased levels of Il-2, this may be useful in diseases and conditions such as metastatic cancer and maintenance of suppression of the HIV virus.
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PMID:Co-administration of ramelton and fluvoxamine to increase levels of interleukin-2. 1689 13

Cachexia is a common finding in various diseases such as chronic renal failure, HIV infection, malignancies, chronic obstructive pulmonary disease, congestive heart failure and rheumatoid arthritis. It is estimated that 30% of patients with malignancies will appear with cachexia, and up to 80% of patients with progressive metastatic disease will be affected. Cachexia is associated with decreased overall survival rates, and decreased beneficial effects of chemotherapy treatment. The underlying pathological processes in cachexia are not completely understood. It is believed that tumor necrosis factor alpha (TNFalpha) plays an essential rule in cachexia induction and propagation. This article reviews and discusses current anti-cachexia treatments, with special emphasis on anti-TNF-alpha treatment in malignancies and various other diseases.
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PMID:[Cachexia, malignancy and tumor necrosis factor alpha (TNF-alpha)]. 1767 50

We report a case of toxoplasmic encephalitis (TE) in a young woman without prior history of human immunodeficiency virus (HIV) infection. She was referred to our clinic with a diagnosis of multiple metastases following cerebral magnetic resonance imaging (MRI) revealing multiple ring-enhanced mass lesions. She had suffered from headaches for four weeks and there had been new onset of confusion and left hemiparesis. Soon after hospitalization, her neurological status rapidly deteriorated and she was operated for decompression. Pathology examination revealed TE and her blood samples were found to be HIV positive. We conclude that TE should be considered in the differential diagnosis of multiple lesions in sexually active individuals including cases without a prior history of HIV infection.
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PMID:HIV related toxoplasmic encephalitis mimicking multiple metastasis: case report. 1793 9

Microarrays have been used to identify genes involved in cancer progression. We have now developed an algorithm that identifies dysregulated pathways from multiple expression array data sets without a priori definition of gene expression thresholds. Integrative microarray analysis of pathways (IMAP) was done using existing expression array data from localized and metastatic prostate cancer. Comparison of metastatic cancer and localized disease in multiple expression array profiling studies using the IMAP approach yielded a list of about 100 pathways that were significantly dysregulated (P < 0.05) in prostate cancer metastasis. The pathway that showed the most significant dysregulation, HIV-I NEF, was validated at both the transcript level and the protein level by quantitative PCR and immunohistochemical analysis, respectively. Validation by unsupervised analysis on an independent data set using the gene expression signature from the HIV-I NEF pathway verified the accuracy of our method. Our results indicate that this pathway is especially dysregulated in hormone-refractory prostate cancer.
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PMID:Integrative microarray analysis of pathways dysregulated in metastatic prostate cancer. 1797 71

A 52-year-old patient presented himself with weight loss and night sweats. Laboratory analyses revealed a high sedimentation rate, elevated immunoglobulines and anaemia with sludge phenomenon. Differential diagnoses included Multiple Myeloma and Lymphoma. Having a risk constellation for HIV infection and just having recovered from oral thrush also made this diagnosis possible. Urinary analysis and chest x-ray were normal; however, CT-scan detected renal cell cancer with pulmonary metastases. Renal cell cancer is heterogeneous in presentation, symptoms are unspecific, therefore they are often discovered late when they have already metastasized. Paraneoplastic syndromes, e.g. hypercalcaemia or hypertension are not infrequent in renal cell cancer.
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PMID:[Weight loss and night sweats with unexpected tumor localization]. 1807 82

HIV cellular entry is a multistep process that requires the interaction of a viral envelope glycoprotein (gp120) and a host receptor (CD4) followed by binding to a co-receptor. The CC-chemokine receptor 5 (CCR5) and CXC-chemokine receptor 4 (CXCR4) have been identified as the major HIV co-receptors and therefore are promising targets for the development of new anti-HIV drugs. CXCR4 is also involved in several diseases such as angiogenesis, metabolic and neurological disorders, rheumatoid arthritis and in different forms of metastatic cancer. Herein, we present a review focusing on small molecule CXCR4 antagonists. These compounds are divided into 11 classes that include cyclic penta- and tetrapeptides, diketopiperazine mimetics, bicyclams, non-bicyclams, tetrahydroquinolines, thiazolylisothiourea derivatives, benzodiazepines, alkyl amine analogs and non-peptides derivatives, dipicolylamine-zinc(II) complexes, ampelopsin and distamycin analogs. The most advanced CXCR4 antagonists documented are bicyclam derivatives, which are specific CXCR4 antagonists and exhibit potency in the nanomolar range. Further development of selective CXCR4 antagonists continues to be crucial for the design of second generation of anti-HIV drugs. We aim to provide a comprehensive summary of diverse structural templates that could be useful for optimization and discovery of novel CXCR4 antagonists.
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PMID:Small molecules anti-HIV therapeutics targeting CXCR4. 1828 65

We present a case of an HIV-1 infected patient with history of chronic hepatitis B and chronic alcohol use without cirrhosis, who presented with aggressive hepatocellular carcinoma with multiple metastases. Systemic chemotherapy combined with use of bevacizumab (anti-vascular endothelium growth factor monoclonal antibody) was without effect and the patient succumbed to his disease within few weeks. To our knowledge, this is the first report in the English literature of bevacizumab use for metastatic hepatocellular carcinoma in HIV-infected patients.
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PMID:First-time use of bevacizumab for aggressive, metastatic hepatocellular carcinoma in an HIV/hepatitis B virus coinfected patient: a case report. 1840 51

We determined the HIV-1 RNA and Gag p24 protein expression in gastrointestinal tract-associated lymphoid tissue (GALT), deep lymph nodes (LNs), and inflammatory lesions, acquired during surgery on HIV-infected patients. Surgically excised gastrointestinal tract specimens, LNs, and cervices removed from HIV-1-infected patients for various clinical conditions were studied by immunohistochemistry (IHC) for Gag p24 HIV protein and in situ hybridization (ISH) for HIV-specific RNA. Fragments of some specimens were also submitted in glutaraldehyde for TEM analysis. Germinal centers (GC) in the GALT had at least as much HIV RNA and p24 protein deposited on their follicular dendritic cell (FDC) networks as did GC in LNs draining or associated with areas of inflammation or ulceration. The level of viral expression in the deep LNs, e.g., mesenteric and retroperitoneal, was at least equivalent to that seen in superficial LNs, i.e., inguinal, axillary, and cervical, and tonsils and adenoids. HIV expressing T and B lymphocytes and macrophages were seen in GALT and LNs. Virus-expressing mononuclear cells (MNC) were also seen in inflammatory lesions such as gastrointestinal ulcers and acute appendicitis. Abundant virus was seen in the cervix of patients with and without cancer and in LNs of patients with metastatic cancer. Individual and clusters of mature HIV particles were identified by TEM in LN GC and in GALT. Gastrointestinal tract lymphoid tissue, inflammatory lesions, and deep LNs showed levels of HIV RNA and Gag p24 protein expression in the range seen in superficial LNs.
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PMID:HIV expression in surgical specimens. 1867 77


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