Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induced hypertension chemotherapy (IHC) using angiotensin II was applied for patients with lung cancer who had not been treated previously, and the results compared with those of preceding conventional chemotherapy as a sequential control. Twenty-nine patients with non-small cell lung cancer (non-SCLC) were treated with MTX and MMC. Response rate among evaluable cases was 23.1% (3/13) for conventional chemotherapy and 18.2% (2/11) for IHC. Twenty-eight patients with small cell lung cancer (SCLC) were treated with VCR, CPA and ACNU. Among evaluable cases, both chemotherapy groups with and without IHC showed the same response rate, 66.7% (8/12). With respect to response rate, there were no differences between conventional chemotherapy and IHC for non-SCLC or SCLC.
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PMID:[Experience with induced hypertension chemotherapy for lung cancer]. 298 59

Forty-one patients with advanced non-small cell lung cancer (NSCLC) were entered into a phase II study of high dose recombinant interferon (rIFN)-beta. Patients received intravenous (i.v.) rIFN-beta on a Monday, Wednesday, Friday schedule with a weekly dose escalation until > or = grade 3 toxicity or 720 x 10(6) IU/dose was achieved. Thirty-eight patients were eligible. Seventeen patients received the highest planned dose of rIFN-beta and 11 experienced dose-limiting toxicity at lower doses. Ten patients developed progressive disease before grade 3 toxicity was reached. There were no objective responses observed. Significant and dose-limiting toxicities included nausea and vomiting, fever, rigors, severe dyspnea, hypotension, and hypertension. IFN-beta has no measurable antitumor activity against NSCLC even at maximum tolerated doses (MTDs).
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PMID:A phase II study of recombinant beta-interferon at maximum tolerated dose in patients with advanced non-small cell lung cancer: a cancer and leukemia group B study. 803 44

Non-small cell lung cancer is the most frequently encountered malignant neoplasm. Brain metastases occur in about 30% of patients with NSCLC The recent data from Poland indicate that there were about 6000 patients with NSCLC and brain metastasis in the year 1993. The first symptoms in those patients are usually of neurological nature, because brain metastases have high dynamics of growth and accompanying brain oedema accelerates increase of intracranial hypertension. Although the surgical treatment of NSCLC with brain metastases has been known for 50 years there is still controversy over indications for such treatment and possibility of improvement in results by combining surgery with other methods of treatment. There is good evidence in literature on the surgical treatment of lung cancer and synchronous brain metastasis. In some papers the results of treatment of many hundreds of patients are presented. They show, that thoracic and neurological surgery operations coordinated in time provide a chance to extend the survival time of the majority of patients, and enable even 5-year survival in up to 20% of patients. Polish experience on this subject resulted in only a few publications. Majority of those papers come from neurosurgical centres related to the results of treatment of brain metastases. Patients with single brain metastasis and a resectable primary lung tumour have the best prognosis for radical treatment. Presented study suggests that it is still worth undertaking the combined neurosurgical and thoraco-surgical treatment in patients with NSCLC and brain metastasis.
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PMID:[Current views on surgical treatment of non-small cell lung neoplasms with metastasis to the central nervous system]. 950 88

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

Vinorelbin is an important tumouricidal substance. The (cardio-)vascular side effects are not well known. We report on four patients in highly palliative situations who were treated with vinorelbine for non-small cell lung cancer. Case one presented with myocardial infarction eleven days after onset of therapy. The second and third cases had to be admitted immediately after the beginning of vinorelbine treatment because of hypertension and angina pectoris. The fourth case suffered from angina abdominalis. A critical review of the literature showed 17 cardiac ischaemias with seven myocardial infarctions, three of them with lethal outcome.
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PMID:[Adverse (cardio-)vascular effects of vinorelbine in non-small-cell bronchial carcinoma]. 1073 57

Percutaneous stenting of the pulmonary arteries (PAs) represents a potential option in cases of PA compression due to a variety of conditions. We present the first reported case of successful bilateral percutaneous stenting of the PAs in a patient with non-small cell lung cancer and severe right ventricular hypertension due to mediastinal lymphadenopathy compressing both PAs. Although the natural course of the disease was not altered, the patient had significant symptomatic relief without adverse effects. Additionally, there was objective evidence of improvement. This case suggests that endovascular stenting is a feasible palliative management option in patients with right ventricular failure due to malignant extrinsic compression of the PAs.
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PMID:Percutaneous stenting of bilateral pulmonary artery stenosis caused by malignant extrinsic compression. 1237 83

There is an urgent need for new therapies to treat non-small cell lung cancer (NSCLC), as progress with current chemotherapy regimens has been limited. The roles of vascular endothelial growth factor (VEGF) in promoting tumor angiogenesis, maintaining existing vasculature, and contributing to resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin; Genentech Inc., South San Francisco, CA), a monoclonal antibody directed against VEGF, has shown promise in treating a number of different cancers. In a recent phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy produced a significantly longer time to progression (32.1 versus 18.4 weeks) and greater response rate (31% versus 19% [not significant]) than chemotherapy alone. In the subset of patients with nonsquamous histologies, response rates and survival were further enhanced, with a mean survival time of 17.9 months versus 12.3 months with chemotherapy alone. Bevacizumab was generally well tolerated and did not appear to increase the incidences or severities of the nausea/vomiting, neuropathy, and renal toxicity that are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) appear to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor. Further work is needed to identify the best way to use bevacizumab in NSCLC, including use in combination with other biologic agents and in the adjuvant setting.
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PMID:Non-small cell lung cancer and antiangiogenic therapy: what can be expected of bevacizumab? 1517 12

There is an urgent need for new therapies to treat non-small cell lung cancer (NSCLC) because current chemotherapy regimens are of limited effectiveness. The role of vascular endothelial growth factor in promoting tumor angiogenesis, in maintaining existing vasculature, and in resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin), a monoclonal antibody directed against vascular endothelial growth factor, has shown promise in treating a number of different cancers. In a recent Phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy significantly increased the time to progression and increased the response rate when compared with chemotherapy alone. This was particularly impressive in the subset of patients with non-squamous histology. Bevacizumab is generally well tolerated and did not appear to increase the incidence or severity of nausea/vomiting, neuropathy and renal toxicity, which are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in Phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) seem to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor. Present ongoing studies are under way in NSCLC including (a) a Phase II neo-adjuvant study in combination with paclitaxel and carboplatin in patients with stage IB-IIA NSCLC; (b) a Phase I/II study of bevacizumab in combination with the epidermal growth factor receptor tyrosine kinase inhibitor agent, Tarceva, in patients with previously treated NSCLC; and (c) an Eastern Cooperative Group randomized Phase III study of paclitaxel and carboplatin with/without bevacizumab in patients with previously untreated IIIB (malignant pleural effusion) or metastatic NSCLC. These studies will help to establish the role of bevacizumab in NSCLC.
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PMID:Anti-vascular endothelial growth factor monoclonals in non-small cell lung cancer. 1521 70

Non-small cell lung cancer with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is rare. A case of squamous bronchogenic carcinoma with SIADH is reported. A 64-year-old man was admitted with 2 cm nodule of the left lung on chest radiography. Transbronchial lung biopsy revealed the squamous cell carcinoma. His past history included hypertension and hemiparesis due to brain infarction. Serum sodium level was low (122 mEq/l) and serum osmolarity was low (271 mOsm/kgH2O). However, urine sodium level was high (82 mEg/l) and urine osmolarity was high (461 mOsm/kgH2O). Renal and adrenal function was normal. He was diagnosed with cT1N0M0 squamous bronchogenic carcinoma accompanied by SIADH. He underwent left upper lobectomy with lymph node dissection. Five months after the operation, serum sodium level returned to normal. He remains well 20 months after the operation.
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PMID:[Squamous cell bronchogenic carcinoma with syndrome of inappropriate secretion of antidiuretic hormone]. 1536 68

Antiangiogenic therapy has emerged as an important concept in the treatment of solid tumors, including non-small cell lung cancer (NSCLC). Vascular endothelial growth factor (VEGF) represents an important therapeutic target, as it is the primary mediator of angiogenesis and is induced by multiple tumor-relevant stimuli. The anti-VEGF monoclonal antibody bevacizumab has demonstrated a significant clinical benefit in patients with non-squamous cell NSCLC in a randomized phase III trial. The addition of bevacizumab to chemotherapy with paclitaxel plus carboplatin provided a significant survival benefit over chemotherapy alone. Bevacizumab is associated with an increased risk of severe bleeding; thus, patients should be carefully selected for bevacizumab treatment. Hypertension is also seen with bevacizumab but can be managed with antihypertensive agents. Ongoing studies are evaluating bevacizumab in other NSCLC settings and are attempting to identify predictive factors for responses to bevacizumab. Antiangiogenic approaches other than bevacizumab are also being investigated, including several small-molecule tyrosine kinase inhibitors that have demonstrated activity in small studies. In some cases, combination therapy with different targeted agents may provide the most comprehensive treatment approach. In a randomized phase II study, bevacizumab in combination with the epidermal growth factor receptor inhibitor erlotinib demonstrated efficacy similar to chemotherapy plus bevacizumab. Ongoing studies are continuing to investigate new agents and identify the patients most likely to benefit from antiangiogenic therapy.
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PMID:Angiogenesis inhibition in the treatment of lung cancer. 1714 57


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