Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bombesin (Bn) receptor subtype 3 (BRS-3) is an orphan receptor that is a predicted member of the heptahelical G-protein receptor family and so named because it shares a 50% amino acid homology with receptors for the mammalian bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide. In a recent targeted disruption study, in which BRS-3-deficient mice were generated, the mice developed obesity, diabetes, and hypertension. To date, BRS-3's natural ligand remains unknown, its pharmacology unclear, and cellular basis of action undetermined. Furthermore, there are few tissues or cell lines found that express sufficient levels of BRS-3 protein for study. To define the intracellular signaling properties of BRS-3, we examined the ability of [D-Phe6,beta-Ala11,Phe13, Nle14]Bn-(6-14), a newly discovered peptide with high affinity for BRS-3, and various Bn receptor agonists and antagonists to alter cellular function in hBRS-3-transfected BALB 3T3 cells and hBRS-3-transfected NCI-H1299 non-small cell lung cancer cells, which natively express very low levels of hBRS-3. This ligand stimulated a 4-9-fold increase in [3H]inositol phosphate formation in both cell lines under conditions where it caused no stimulation in untransfected cells and also stimulated an increase in [3H]IP1, [3H]IP2, and 3H]IP3. The elevation of [3H]IP was concentration-dependent, with an EC50 of 20-35 nM in both cell lines. [D-Phe6,beta-Ala11,Phe13,Nle14]Bn-(6-14) stimulated a 2-3-fold increase in [Ca2+]i, a 3-fold increase in tyrosine phosphorylation of p125(FAK) with an EC50 of 0.2-0.7 nM, but failed to either stimulate increases in cyclic AMP or inhibit forskolin-stimulated increases. None of nine naturally occurring Bn peptides or three synthetic Bn analogues reported to activate hBRS-3 did so with high affinity. No high affinity Bn receptor antagonists had high affinity for the hBRS-3 receptor, although two low affinity antagonists for gastrin-releasing peptide and NMB receptors, [D-Arg1,D-Trp7,9, Leu11]substance P and [D-Pro4,D-Trp7,9,10]substance P-(4-11), inhibited hBRS-3 receptor activation. The NMB receptor-specific antagonist D-Nal,Cys,Tyr,D-Trp,Lys,Val, Cys,Nal-NH2 inhibited hBRS-3 receptor activation in a competitive fashion (Ki = 0.5 microM). Stimulation of p125(FAK) tyrosine phosphorylation by hBRS-3 activation was not inhibited by the protein kinase C inhibitor, GF109203X, or thapsigargin, alone or in combination. These results show that hBRS-3 receptor activation increases phospholipase C activity, which causes generation of inositol phosphates and changes in [Ca2+]i and is also coupled to tyrosine kinase activation, but is not coupled to adenylate cyclase activation or inhibition. hBRS-3 receptor activation results in tyrosine phosphorylation of p125(FAK), and it is not dependent on activation of either limb of the phospholipase C cascade. Although the natural ligand is not a known bombesin-related peptide, the availability of [D-Phe6,beta-Ala11, Phe13,Nle14]Bn-(6-14), which functions as a high affinity agonist in conjunction with hBRS-3-transfected cell lines and the recognition of three classes of receptor antagonists including one with affinity of 0.5 microM, should provide important tools to assist in the identification of its natural ligand, the development of more potent selective receptor antagonists and agonists, and further exploration of the signaling properties of the hBRS-3 receptor.
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PMID:Ability of various bombesin receptor agonists and antagonists to alter intracellular signaling of the human orphan receptor BRS-3. 959 99

Elderly patients with lung cancer tend to have significant coexisting diseases and less aggressive treatment is often required. To investigate the clinicopathological features of non-small cell lung cancer (NSCLC) in elderly patients who were treated with radiotherapy, we reviewed the medical records at our division. Among the 189 patients 70 years or older between 1992 and 2001, 28 (14.8%) patients were treated with radiotherapy (elderly group). In the elderly group, there was a medical history of chronic obstructive pulmonary disease (COPD) (57.1%), cardiovascular disease (32.1%), diabetes mellitus (18.5%), malignant disease (18.5%), or cerebrovascular disease (10.7%). Moreover, in the elderly group, 17 (60.7%) patients had two or three coexisting diseases. There was statistical difference between the elderly group and the younger group (less than 70 years patients) with regard to COPD (p<0.001). Also there was statistical difference between the elderly group and the younger group with regard to number of coexisting diseases (p=0.002). In the elderly group, forced expiratory volume in one second (FEV1), forced expiratory volume (FVC), FEV1/FVC and diffusing capacity of the lung for carbon monoxide (DLCO) were statistically significant impaired to compare with those in the younger group (p<0.001, p=0.030, p<0.001 and p=0.024, respectively). In the elderly group, 10.7% of patients had concurrent chemoradiotherapy, however, 38.5% of patients of the younger group received concurrent chemoradiotherapy. There was a statistical difference between the two groups (p=0.026). Adequate palliative care to provide prolonged quality survival is an appropriate primary goal of therapy for lung cancer in the elderly and radiotherapy is thought be one of the less invasive treatments.
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PMID:Radiotherapy for elderly non-small cell lung cancer patients. 1237 33

The term radial segmentation (RS) is applied to a characteristic nuclear deformation observed in peripheral blood in vitro in some neoplastic and normal cells. It concerns al mononuclear cells. RS positive lymphocytes were found as CD 4 cells. Different conditions and substances, i.e. anticoagulant or cyclosporin can induce the formation of RS nuclei in vitro. Elevated ratio of RS nuclei in peripheral blood has been observed in patients with some autoimmunological diseases i.e. rheumatoid arthritis, diabetes mellitus insulin-dependent, sarcoidosis. Reduced ratio of RS nuclei was observed in neoplastic diseases. The aim of the study was to analyze the incidence of RS nuclei of lymphocytes in vitro in peripheral blood (induced by cyclosporin) in patients with non-small cell lung cancer (NSCLC). Heparinized peripheral blood was obtained from controls and patients with primary NSCLC. The blood was incubated with cyclosporin, and then lymphocytes were isolated by Lymphoprep. RS positive lymphocytes were counted in smears stained with MGG stain. In peripheral blood from healthy donors the average incidence of lymphocytes RS was 3.314% and in patients with NSCLC 4.481% respectively. The difference between controls and patients with NSCLC was not significant. No correlation was found between incidence of RS and stadium of lung cancer.
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PMID:[Radial segmentation of lymphocytes in peripheral blood of patients with non-small cell lung cancer ]. 1260 4

A 76-year-old man was admitted because of bloody sputum persisting for 3 months. Right upper lobectomy had been performed for non-small cell lung cancer (well-differentiated adenocarcinoma, pT1NOMO) 6 years prior, and the patient had uncontrolled diabetes. Chest computed tomography on admission showed a 1-cm nodule (fungus ball) in a cavitary lesion and consolidation with an air bronchogram were present in the right lung. Aspergillus flavus was detected in the patient's sputum, and laboratory tests were positive for Aspergillus antigen and antibody. Chronic necrotizing pulmonary aspergillosis (CNPA) was diagnosed in the surgically treated lung.
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PMID:[Chronic necrotizing pulmonary aspergillosis in the surgically treated lung]. 1749 19

Despite documented superiority of positron emission tomography over other investigative modalities in the preoperative staging of non-small cell lung cancer, a proportion of patients will have an inaccurate staging of their mediastinal nodes. The aim of this retrospective review is to analyse the clinicopathological factors responsible for inaccurate nodal staging by integrated PET-CT. A total of 100 consecutive patients with histologically proven non-small cell lung cancer underwent staging with PET-CT prior to lung resection. Thirty-three patients, inaccurately staged by PET-CT, were analysed. Univariate analysis identified the following as significant in causing inaccurate nodal staging: history of tuberculosis (P=0.039) and non-insulin dependant diabetes (P=0.014). In multivariate analysis, we have identified the following as independent factors in causing inaccurate staging of mediastinal lymph nodes: rheumatoid arthritis, non-insulin dependent diabetes, history of tuberculosis, presence of atypical adenomatous hyperplasia and pneumonia (P<0.05). The highest rate of inaccuracy in mediastinal nodal staging was in nodal station 4 (11%, P=0.01) followed by station 7 (10%, P=0.02) and station 9 (3.5%, P=0.01). Interpretation of PET-CT staging of the mediastinum in patients with a history of the above should be with caution, as the incidence of false upstaging and down staging in these subgroups is high. Vigilance of such factors may improve the accuracy of PET-CT in staging mediastinal lymph nodes. Histological confirmation should always be sought.
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PMID:Factors causing inaccurate staging of mediastinal nodal involvement in non-small cell lung cancer patients staged by positron emission tomography. 1766 63

Evidence is scarce about the influence of comorbidity on outcome of surgery, whereas this information is highly relevant for estimating the surgical risk of cancer patients, and for optimising pre-, peri- and postoperative care. In this paper, the prognostic role of increasing age and comorbid conditions in patients diagnosed with stage I-III colorectal, stage I-II NSCLC or stage I-III breast cancer between 1995 and 2004 in the southern part of the Netherlands is summarised. Almost all patients with stage I-III colon cancer or rectal cancer underwent surgery regardless of age or comorbidity. In contrast, the resection rate among elderly patients with stage I-II NSCLC was clearly lower than among younger patients and was significantly lower when COPD, cardiovascular diseases or diabetes were present. Among patients with stage I-III breast cancer, those aged 80 or older underwent less surgery, and the resection rate appeared to be lower when cardiovascular diseases or diabetes were present. Among patients with resected colorectal cancer, postoperative morbidity and mortality were higher among those undergoing emergency surgery, and also among those with reduced pulmonary function, cardiovascular disease or neurological comorbidity. Among those with resected NSCLC, postoperative morbidity and mortality were related to reduced pulmonary function or cardiovascular disease. Since surgery for breast cancer is low risk, elective surgery, morbidity and mortality were not higher for elderly or those with comorbidity. Among patients with colorectal or breast cancer, comorbidity in general, cardiovascular diseases, COPD, diabetes (only colon and breast cancer) and venous thromboembolism had a negative effect on overall survival, whereas the effect of comorbidity on survival of stage I-II NSCLC was less clear. Elderly and those with comorbidity (especially cardiovascular diseases and COPD) among colorectal cancer and NSCLC patients had more postoperative morbidity and mortality. Prospective randomised studies are needed for refining selection criteria for surgery in elderly cancer patients and for anticipation and prevention of complications.
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PMID:Comorbidity in older surgical cancer patients: influence on patient care and outcome. 1768 80

PED (phosphoprotein enriched in diabetes) is a death-effector domain (DED) family member with a broad anti-apoptotic action. PED inhibits the assembly of the death-inducing signalling complex (DISC) of death receptors following stimulation. Recently, we reported that the expression of PED is increased in breast cancer cells and determines the refractoriness of these cells to anticancer therapy. In the present study, we focused on the role of PED in non-small cell lung cancer (NSCLC), a tumour frequently characterized by evasion of apoptosis and drug resistance. Immunohistochemical analysis of a tissue microarray, containing 160 lung cancer samples, indicated that PED was strongly expressed in different lung tumour types. Western blotting performed with specimens from NSCLC-affected patients showed that PED was strongly up-regulated (>6 fold) in the areas of tumour compared to adjacent normal tissue. Furthermore, PED expression levels in NSCLC cell lines correlated with their resistance to tumour necrosis factor related apoptosis-inducing ligand (TRAIL)-induced cell death. The involvement of PED in the refractoriness to TRAIL-induced cell death was investigated by silencing PED expression in TRAIL-resistant NSCLC cells with small interfering (si) RNAs: transfection with PED siRNA, but not with cFLIP siRNA, sensitized cells to TRAIL-induced cell death. In conclusion, PED is specifically overexpressed in lung tumour tissue and contributes to TRAIL resistance.
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PMID:PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer. 1828 7

Dysregulated expression of microRNAs (miRNAs) in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.
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PMID:Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. 1883 86

There is little information on chemotherapy-induced peripheral neuropathy (PN) for community-dwelling patients with cancer. We studied 65,316 patients with breast cancer, 9242 with ovarian cancer, and 86,278 with non-small cell lung cancer from 1991 through 2002 identified from the 16 areas of Surveillance, Epidemiology and End Results. The incidence density of PN was 15.3, 21.5, and 18.3 per 1000 person-years for patients with breast, ovarian, and lung cancer who received platinum-taxane combination chemotherapy, respectively. Patients with breast, ovarian, and lung cancer receiving taxanes were more than twice as likely to develop PN compared with those not receiving chemotherapy (adjusted hazard ratio = 2.22, 95% confidence interval = 1.85-2.66 in patients with breast cancer), whereas patients who received platinum-taxane combination chemotherapy were more than 3 times as likely to develop PN compared with women who did not receive chemotherapy (adjusted hazard ratio = 3.33, 95% confidence interval = 2.05-5.05). In patients with ovarian or lung cancer receiving taxanes or platinum-taxane combination therapy, the risk of PN was increased with increasing number of chemotherapy cycles. These findings remained similar after adjusting for the history of preexisting PN or diabetes. Close monitoring for PN in patients receiving taxanes alone or in combination with platinum compounds may be warranted.
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PMID:Risk of chemotherapy-induced peripheral neuropathy in large population-based cohorts of elderly patients with breast, ovarian, and lung cancer. 1941 86

PED (phosphoprotein enriched in diabetes) is a 15 kDa protein involved in many cellular pathways and human diseases including type II diabetes and cancer. We recently reported that PED is overexpressed in human cancers and mediates resistance to induced apoptosis. To better understand its role in cancer, we investigated on PED interactome in non-small cell lung cancer (NSCLC). By the Tandem Affinity Purification (TAP), we identified and characterized among others, Rac1, a member of mammalian Rho GTPase protein family, as PED-interacting protein. In this study we show that PED coadiuvates Rac1 activation by regulating AKT mediated Rac1-Ser(71) phosphorylation. Furthermore, we show that the expression of a constitutively active Rac, affected PED-Ser(104) phosphorylation, which is important for PED-regulated ERK 1/2 nuclear localization. Through specific Rac1-siRNA or its pharmacological inhibition, we demonstrate that PED augments migration and invasion in a Rac1-dependent manner in NSCLC. In conclusion, we show for the first time that PED and Rac1 interact and that this interaction modulates cell migration/invasion processes in cancer cells through ERK1/2 pathway.
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PMID:PED interacts with Rac1 and regulates cell migration/invasion processes in human non-small cell lung cancer cells. 2064 24


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