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)

Activation of tumor-reactive T lymphocytes is a promising approach for the prevention and treatment of patients with metastatic cancers. Strategies that activate CD8(+) T cells are particularly promising because of the cytotoxicity and specificity of CD8(+) T cells for tumor cells. Optimal CD8(+) T cell activity requires the co-activation of CD4(+) T cells, which are critical for immune memory and protection against latent metastatic disease. Therefore, we are developing "MHC II" vaccines that activate tumor-reactive CD4(+) T cells. MHC II vaccines are MHC class I(+) tumor cells that are transduced with costimulatory molecules and MHC II alleles syngeneic to the prospective recipient. Because the vaccine cells do not express the MHC II-associated invariant chain (Ii), we hypothesized that they will present endogenously synthesized tumor peptides that are not presented by professional Ii(+) antigen presenting cells (APC) and will therefore overcome tolerance to activate CD4(+) T cells. We now report that MHC II vaccines prepared from human MCF10 mammary carcinoma cells are more efficient than Ii(+) APC for priming and boosting Type 1 CD4(+) T cells. MHC II vaccines consistently induce greater expansion of CD4(+) T cells which secrete more IFNgamma and they activate an overlapping, but distinct repertoire of CD4(+) T cells as measured by T cell receptor Vbeta usage, compared to Ii(+) APC. Therefore, the absence of Ii facilitates a robust CD4(+) T cell response that includes the presentation of peptides that are presented by traditional APC, as well as peptides that are uniquely presented by the Ii(-) vaccine cells.
 ...
PMID:The absence of invariant chain in MHC II cancer vaccines enhances the activation of tumor-reactive type 1 CD4+ T lymphocytes. 1772 89

The introduction of organ transplantation in clinical medicine has resulted in a constantly increasing, large population of patients that are chronically on immunosuppressive medication. It is well known that skin cancer, especially SCC, in this population has higher incidence rates, behaves more aggressively and has higher rates of metastasis. OTRs who have been treated for many years with immunosuppressive medication are at the highest risk for developing malignant skin tumors. Therefore, the intensity of surveillance for cutaneous lesions is of high importance in OTRs. A full-body skin exam at least once a year and more frequently if skin cancer or precancerous cutaneous lesions develop is recommended. Clinicians should not hesitate to biopsy or to surgically excise any suspicious skin lesion. Of high importance is also the education of OTRs about their increased risk. Protection against solar and artificial UV-radiation and monthly self-examinations are good ways to prevent and to recognize any new suspicious skin lesions. Patients are advised to always wear solar UV-radiation protection (e.g., clothing, sunscreen) before going outdoors. However, investigations have revealed that solar UV-B-exposure and serum 25(OH)D levels positively correlate with decreased risk for various internal malignancies (e.g., breast, colon, prostate and ovarian cancer) and other severe diseases. As we have shown previously, renal transplant recipients are at high risk of vitamin D deficiency. A sunscreen with a sun protection factor (SPF)-8 reduces the skin's production of vitamin D by 95%. Clothing completely blocks all solar UVB-radiation and this prevents any vitamin D production. Therefore, it is important to detect and treat vitamin D deficiency in solid organ transplant recipients. Optimal management of these patients requires communication between the transplant teams and the treating dermatologist and other clinicians. For advanced or metastatic disease, collaboration between clinicians of different disciplines, including the transplant team, dermatologists and radiation oncologists is also essential. In the future, dermatology clinics that are integrated into transplant centers may make it easier to manage and to treat OTRs, may make an interdisciplinary approach more effective and may thereby improve the clinical outcome in OTRs.
 ...
PMID:Solar UV-radiation, vitamin D and skin cancer surveillance in organ transplant recipients (OTRs). 1834 58

Intrapulmonary spread of a sarcoma via lymphatics is a rare cause of death in a young adult. A 31-year old man was admitted to our hospital complaining of dyspnea and malaise of 2 months' duration. A chest radiography revealed bilateral hilar enlargement, and reticulonodular infiltrations. Thoracic CT-scans demonstrated mediastinal lymphadenopathy, thickening of interlobular septa, polygonal lines, and thickening of bronchovascular bundles. The diagnosis was made by open-lung biopsy. The patient died within 3 months after diagnosis. Pulmonary lymphangitic sarcomatosis is a rare but important manifestation of an angiosarcoma. Optimal treatment of these patients is not well defined, but a trial of chemotherapy may be warranted.
Clin Exp Metastasis 2009
PMID:Pulmonary lymphangitic sarcomatosis and a review of the literature. 1850 85

Merkel cell carcinoma is an uncommon and aggressive primary cutaneous neuroendocrine carcinoma with a high rate of recurrence and metastasis. Optimal management is controversial; consequently, it is imperative to identify the signaling pathways involved in the pathogenesis of Merkel cell carcinoma so that effective therapeutic targeting agents can be developed. We previously reported that K homology domain-containing protein overexpressed in cancer is expressed in high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. The K homology domain-containing protein overexpressed in cancer (KOC), also known as L523S and IMP-3, is an insulin-like growth factor II messenger RNA-binding protein that promotes tumor cell proliferation by enhancing insulin-like growth factor II protein expression. Expression of KOC in Merkel cell carcinoma has not been investigated. We studied 20 Merkel cell carcinomas by immunohistochemistry using a monoclonal antibody against L523S/KOC. Of 20 Merkel cell carcinomas, 18 (90%) overexpressed KOC, with 11 (55%) overexpressing KOC in greater than 90% of tumor cells, 3 (15%) overexpressing KOC in 50% to 90% of tumor cells, 3 (15%) overexpressing KOC in 10% to 50% of tumor cells, and 1 (5%) overexpressing KOC in less than 10% of tumor cells. The immunostaining intensity was variable, with moderate to strong staining in 14 cases and weak staining in the remaining 4. Extent of expression of K homology domain-containing protein overexpressed in cancer predicted metastasis (P = .04) and was weakly correlated with increased tumor size (P = .08). In conclusion, Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer with an expression pattern similar to high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. We propose K homology domain-containing protein overexpressed in cancer as a potential target molecule for the treatment of high-grade neuroendocrine carcinomas, irrespective of anatomical location, and a potential marker to predict metastatic disease.
 ...
PMID:Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas. 1883 27

Accurate staging of disease is necessary in patients with newly diagnosed esophageal cancer in order to prompt appropriate curative or palliative therapy. Computed tomography (CT) may be used to evaluate for local spread into adjacent structures (T4 disease) and to diagnose distant metastases (M1). Endoscopic ultrasonography (EUS) is the modality of choice for distinguishing T1 tumors from higher stage lesions and for detecting and sampling regional lymph nodes (N1 disease). Positron emission tomography (PET) scanning is most helpful for detecting previously occult distant metastases. Optimal staging generally requires a multimodality approach.
 ...
PMID:Staging esophageal cancer. 1885 79

Over the past decade, there have been a number of substantial changes in the treatment of invasive bladder cancer. Muscle-invasive bladder cancer is an aggressive disease that often presents at an advanced stage with or without distant metastases. The potential for cure is highest when the disease is confined to the bladder. Optimal management depends on our understanding of disease biology, refinements to our clinical staging, and improvements in the quality of treatment. This review will focus on the contemporary management of muscle-invasive urothelial carcinoma of the bladder and will discuss the role of radical cystectomy, extended lymphadenectomy, neoadjuvant/ adjuvant chemotherapy, and various forms of bladder-preservation strategies.
 ...
PMID:Contemporary management of muscle-invasive bladder cancer. 1909 77

The pathologic approach to metastases of unknown primary cancer (UPC) is stepwise and uses the clinical context, morphology, and, where necessary, immunohistochemistry (IHC). This review covers the initial approach to a UPC biopsy; the diagnosis of malignancy and broad tumor typing into carcinoma, melanoma, lymphoma, or sarcoma; and further subtyping of carcinoma into germ cell (broadly included), squamous, neuroendocrine, and solid organ including liver and renal, and adenocarcinomas. Finally, for adenocarcinoma, the prediction of primary tumor site, including lung, pancreas, stomach, colon, ovary, prostate, and breast, is discussed. For each tumor type, the morphologic features are presented alongside established useful IHC markers, with a description of their staining patterns and common diagnostic dilemmas. Optimal tissue handling and IHC interpretation, quality assurance, and limitations also are discussed. The target readership is oncologists, but other clinicians and trainee pathologists also may find the content of use.
 ...
PMID:Pathologic evaluation of unknown primary cancer. 1917 85

The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with metastatic progression. Nk4 (also known as Interleukin (IL)32b) is a competitive antagonist of the HGF c-Met system and inhibits c-Met signalling and tumour metastasis. Nk4 has an additional anti-angiogenic activity independent of its HGF-antagonist function. Angiogenesis-inhibitory as well as cancer-specific apoptosis inducing effects make the Nk4 sequence an attractive candidate for gene therapy of cancer. This study investigates the inhibition of tumour metastasis by gene therapy mediated production of Nk4 by the primary tumour. Optimal delivery of anti-cancer genes is vital in order to achieve the highest therapeutic responses. Non-viral plasmid delivery methods have the advantage of safety and ease of production, providing immediate transgene expression, albeit short-lived in most tumours. Sustained presence of anti-angiogenic molecules is preferable with anti-angiogenic therapies, and the long-term expression mediated by Adeno-associated Virus (AAV) might represent a more appropriate delivery in this respect. However, the incubation time required by AAV vectors to reach appropriate gene expression levels hampers efficacy in many fast-growing murine tumour models. Here, we describe murine trials assessing the effects of Nk4 on the spontaneously metastatic Lewis Lung Carcinoma (LLC) model when delivered to primary tumour via plasmid lipofection or AAV2 vector. Intratumoural AAV-Nk4 administration produced the highest therapeutic response with significant reduction in both primary tumour growth and incidence of lung metastases. Plasmid-mediated therapy also significantly reduced metastatic growth, but with moderate reduction in primary subcutaneous tumour growth. Overall, this study demonstrates the potential for Nk4 gene therapy of metastatic tumours, when delivered by AAV or non-viral methods.
 ...
PMID:Anti-metastatic effects of viral and non-viral mediated Nk4 delivery to tumours. 1927 40

Primary spindle cell sarcoma of the left atrium is a rare tumour. Optimal treatment is to obtain complete surgical clearance of the tumour. The anatomic location of the tumour, infiltration into vital structures and difficult access provides a surgical challenge for resection of the lesion and reconstruction of the defect. The prognosis of patients with a primary cardiac sarcoma is very poor because of their resistance to treatment with chemotherapy and radiotherapy. Metastases and local recurrences are common despite optimal multimodality treatment. This report describes a 48-year-old gentleman who underwent multiple surgeries to achieve an 11-year survival since the diagnosis. The operative techniques have been described.
 ...
PMID:Prolonged survival with left atrial spindle cell sarcoma. 1930 72

Magnetic resonance imaging (MRI) is a valuable tool in the assessment of the full spectrum of pancreatic disease. A standard MR protocol including noncontrast T1-weighted fat-suppressed and dynamic gadolinium-enhanced gradient-echo imagings is sensitive for the evaluation of pancreatic cancer. Optimal use of MRI in the investigation of pancreatic cancer occurs in the following circumstances: (1) detection of small non-contour-deforming tumors, (2) evaluation of local extension and vascular encasement, (3) determination of the presence of lymph node and peritoneal metastases, and (4) determination and characterization of associated liver lesions and liver metastases. The objective of this study was to describe the attribute of MRI for evaluating pancreatic cancer.
 ...
PMID:Magnetic resonance imaging of adenocarcinoma of the pancreas. 1968 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>