Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phosphatidylinositol 3' kinase (PI3'K) pathway, which regulates cell survival, is antagonized by the PTEN tumor suppressor. The regulation of PTEN is unclear. A genetic screen of Drosophila gain-of-function mutants identified DJ-1 as a suppressor of PTEN function. In mammalian cells, DJ-1 underexpression results in decreased phosphorylation of PKB/Akt, while DJ-1 overexpression leads to hyperphosphorylation of PKB/Akt and increased cell survival. In primary breast cancer samples, DJ-1 expression correlates negatively with PTEN immunoreactivity and positively with PKB/Akt hyperphosphorylation. In 19/23 primary non-small cell lung carcinoma samples, DJ-1 expression was increased compared to paired nonneoplastic lung tissue, and correlated positively with relapse incidence. DJ-1 is thus a key negative regulator of PTEN that may be a useful prognostic marker for cancer.
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PMID:DJ-1, a novel regulator of the tumor suppressor PTEN. 1576 64

Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.
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PMID:Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models. 1658 92

Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). It binds to the ATP-binding site of the target kinase and prevents the transfer of phosphate from ATP to the tyrosine residues of various substrates. At oral doses of 200-600 mg, the majority of patients with chronic myeloid leukaemia, Philadelphia chromosome-positive acute lymphoblastic leukemia expressing the BCR-ABL fusion protein and gastrointestinal stromal tumours (GIST) achieve a bio-molecular and clinical response, frequently complete, associated with limited toxicity. Several other human cancers, as small-cell lung carcinoma, melanoma, seminoma, some sarcomas, and adenoid cystic carcinomas may over-express KIT or PDGF-R, and clinical trials to evaluate the role of IM in the treatment of such cancers are currently ongoing. We determined c-KIT with Dako CD 117 antibody in 5 cases of advanced ocular melanoma (OM) and we found positive immuno-reactivity for CD 117 in three patients. We treated all patients with palliative-use IM at the oral dose of 400 mgr daily. We obtained in expressing positive immuno-reactivity for CD 117 patients: a reduction of malignant ascites in one, a partial remission in the neck nodes in another, and progression of liver metastases in the third. Evidences of progression has been reported in the other two patients expressing negative immuno-reactivity for CD 117. We conclude that the effect of IM should be assessed only in OM with positive immuno-histochemical c-kit (CD 117) expression. IM might be a potential therapeutic strategy for these patients.
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PMID:Tyrosine kinase inhibitor imatinib mesylate as anticancer agent for advanced ocular melanoma expressing immunoistochemical C-KIT (CD 117): preliminary results of a compassionate use clinical trial. 1676

Halothane is a volatile anaesthetic, which is known to induce alterations in cellular plasma membranes, modulating the physical state of the membrane lipids and/or interacting directly with membrane-bound proteins, such as integrin receptors. Integrin-mediated cell adhesion is a general property of eukaryotic cells, which is closely related to cell viability. Our previous investigations showed that halothane is toxic for A 549 lung carcinoma cells when applied at physiologically relevant concentrations and causes inhibition of adhesion to collagen IV. The present study is focused on the mechanisms underlying halothane toxicity. Our results imply that physiologically relevant concentrations of halothane disrupt focal adhesion contacts in A 549 cells, which is accompanied with suppression of focal adhesion kinase activity and paxillin phosphorylation, and not with proteolytic changes or inhibition of vinculin and paxillin expression.We suggest that at least one of the toxic effects of halothane is due to a decreased phosphorylation of the focal contact proteins.
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PMID:Halothane affects focal adhesion proteins in the A 549 cells. 1685 89

Herein, we report that marine-derived sulfated polysaccharide (MSP), a new kind of polysaccharide extracted from brown alga, exhibits the anti-migration effect in vitro and potently suppress metastasis of Lewis lung carcinoma in vivo. Adhesion assays demonstrated that MSP inhibits the heterogenous adhesion on fibronectin. Further studies revealed that MSP decreased FN-induced MDA-MB-435 migration, accompanied by its potent regulatory effect on actin filament reassembling. In addition, MSP significantly inactivated the phosphorylation of FAK and subsequent ERK1/2 in MDA-MB-435 cells. All these actions may be the results of MSP binding to FN, promising the therapeutic potential of MSP in tumor metastasis.
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PMID:A new marine-derived sulfated polysaccharide from brown alga suppresses tumor metastasis both in vitro and in vivo. 1701 53

We present our experience with skeletal involvement of Pneumocystis jiroveci (ex P. carinii) infection in an HIV-seropositive patient. The objective of this study was to alert clinicians to the possibility that extrapulmonary P. jiroveci could affect the skeletal system in HIV-infected patients with extremely rapid progression. P. jiroveci infection of skeletal system has been rarely described elsewhere. A 51-year-old man complained of fever for six weeks, cough, anorexia, fatigue, and chest pain. He was found to be HIV seropositive. Repetitive (six samples) sputum and bronchoalveolar lavage fluid microbiologic tests were negative. High-resolution chest computed tomography (CT) scan revealed a small pulmonary mass. Abdominal CT scan revealed lesions in liver, spleen, kidneys, adrenal glands, lumbar vertebrae, and sacrum. Brain and skull CT scan was normal. A fine-needle biopsy of the lung mass was unrevealing. Cytological examination of sputum specimens showed findings consistent with non-small-cell lung carcinoma. Nineteen weeks post-presentation, the patient reported low-back pain. Within 24 hours after the onset of low-back pain, he developed focal neurological deficits, and a magnetic resonance imaging (MRI) of the skull and spine showed osteolytic lesions of the temporal bones bilaterally, multiple vertebral lesions, and lesions of sacrum and iliac bones. Radiotherapy of the lumbar spine and pelvis was given. Sternal aspiration was performed. Cytological examination revealed P. jiroveci. In conclusion, we describe a rare case of disseminated P. jiroveci infection in an HIV-seropositive patient, with multiple skeletal lesions, especially in the skull and in vertebrae region, and concomitant non-small-cell lung cancer, with a very poor prognosis.
Int J STD AIDS 2007 Feb
PMID:Multi-skeletal Pneumocystis jiroveci (carinii) in an HIV-seropositive patient. 1733 Dec 92

Patients with malignant mesothelioma (MM), an aggressive cancer associated with asbestos exposure, usually present clinically with advanced disease and this greatly reduces the likelihood of curative treatment. MM is difficult to diagnose without invasive techniques; the development of non-invasively detectable molecular markers would therefore be highly beneficial. DNA methylation changes in cancer cells provide powerful markers that are potentially detectable non-invasively in DNA shed into bodily fluids. Here we examined the methylation status of 28 loci in 52 MM tumors to investigate their potential as molecular markers for MM. To exclude candidate MM markers that might be positive in biopsies/pleural fluid due to contaminating surrounding non-tumor lung tissue/DNA, we also examined the methylation of these markers in lung samples (age- or environmentally induced hypermethylation is frequently observed in non-cancerous lung). Statistically significantly increased methylation in MM versus non-tumor lung samples was found for estrogen receptor 1 (ESR1; p = 0.0002), solute carrier family 6 member 20 (SLC6A20; p = 0.0022) and spleen tyrosine kinase (SYK; p=0.0003). Examination of associations between methylation levels of the 28 loci and clinical parameters suggest associations of the methylation status of metallothionein genes with gender, histology, asbestos exposure, and lymph node involvement, and the methylation status of leucine zipper tumor suppressor 1 (LZTS1) and SLC6A20 with survival.
Lung Cancer 2007 Nov
PMID:DNA methylation profile of 28 potential marker loci in malignant mesothelioma. 1765 10

This review is focused on "new drugs" that might be developed for thyroid cancer treatment. Thyroid cancer is frequently associated to the activation of specific protein (RET, BRAF) and lipid [PI(3)K] kinases. There is good evidence that these genetic lesions are causative events in thyroid cancer initiation or progression. Therefore, novel compounds able to target these kinases might be useful for thyroid cancer treatment. The power of this approach is witnessed by the examples of BCR-ABL, c-KIT and EGFR inhibitors in the treatment of chronic myelogenous leukemia (CML), gastro-intestinal stromal tumors (GIST) and non-small cell lung carcinoma (NSCLC).
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PMID:New drugs in thyroid cancer. 1789 Dec 51

Using the structured group methods (nominal and focus group) and the theory in instrument development, the quality of life instrument for lung cancer (QLICP-LU) with Chinese cultural background was developed, and evaluated based on the data from a sample of 85 in-patients of lung cancer. Statistical methods used were correlation analysis, factor analysis and paired t-test, etc. The results showed that test-retest reliability of the overall scale was 0.78, and test-retest reliability and internal consistency alpha for most domains were higher than 0.70; correlation and factor analysis demonstrated good construct validity; criterion-related validity were confirmed given FACT-L and QLQ-LC43 (QLQ-C30 plus QLQ-LC13) as the criterions; statistically significant changes were found for each domain and the overall scale with standardized response mean SRM being greater than 0.80 except for the social function domain. We conclude that the QLICP-LU can be used to measure QOL for patients with lung cancer with better validity, reliability and responsiveness in China.
Lung Cancer 2008 Apr
PMID:Development and validation of the system of quality of life instruments for cancer patients: lung cancer (QLICP-LU). 1796 86

Tumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Osteopontin (OPN), which is abundantly expressed in bone matrix, is involved in cell adhesion, migration, invasion and cell proliferation via interaction with its receptor, alphavbeta3 integrin. However, the effect of OPN on migration activity in human lung cancer cells is mostly unknown. Here we found that OPN increased the migration via activation of alphavbeta3 integrin in human lung cancer cells (A549 cells). Phosphatidylinositol 3-kinase inhibitor (PI3K; Ly294002), Akt inhibitor or ERK inhibitor (PD98059) inhibited the OPN-induced increase in the migration of lung cancer cells. OPN stimulation increased the phosphorylation of focal adhesion kinase (FAK), p85 subunit of PI3K, serine 473 of Akt and ERK. In addition, treatment of A549 cells with NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) inhibited OPN-induced migration of lung cancer cells. Stimulation of A549 cells with OPN also induced IkappaB kinase alpha/beta (IKK alpha/beta) phosphorylation, IkappaBalpha phosphorylation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity. The OPN-mediated increases in IKK alpha/beta, IkappaBalpha and p65 Ser(536) phosphorylation were inhibited by Ly294002, Akt inhibitor and PD98059. Co-transfection with FAK, p85, Akt and ERK mutants also reduced the OPN-induced kappaB-luciferase activity. Taken together, these results suggest that OPN acts through alphavbeta3 integrin, which in turn activates the FAK, PI3K, Akt, ERK and NF-kappaB pathways, contributing to the migration of lung cancer cells.
Lung Cancer 2009 Jun
PMID:Osteopontin increases lung cancer cells migration via activation of the alphavbeta3 integrin/FAK/Akt and NF-kappaB-dependent pathway. 1899 13


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