Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C1 esterase inhibitor deficiency is an unusual cause of acute upper airway angioedema. This case of angioedema is secondary to acquired C1 esterase inhibitor deficiency associated with neoplastic disease and triggered by the use of angiotensin converting enzyme inhibitors. It was sufficiently severe to require emergency airway management. A guide to the evaluation and management of angioedema is presented.
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PMID:Acute upper airway obstruction from acquired angioedema. 1730 64

The aim of this study was to investigate whether depletion of CD4(+)CD25(+) regulatory T cells (Treg) from melanoma patients affects immune responses against tumors. By application of recombinant IL-2-diphteria toxin fusion protein, also known as ONTAK, we were able to significantly reduce the frequency of Treg in peripheral blood, whereas other cell populations remained unaffected. The reduction of Treg started immediately after the first bolus of ONTAK with a dose of 5 microg ONTAK per kg bodyweight and lasted for 13 days with subsequent recovery thereafter. Successive ONTAK treatments further reduced the number of circulating Treg. Using the contact sensitizer DCP we show that all patients developed vast eczema after Treg depletion, whereas no or only mild eczematous reactions were detectable before ONTAK treatment. Corresponding induction of DCP-specific CD4(+) and CD8(+) T cells were detectable. Moreover, after immunization of ONTAK treated patients with tumor antigen peptides, MelanA/MART-1 and gp100, significant induction of peptide specific CD8(+) T cells could be observed in 90% of the patients treated. These cells displayed effector functions, as they were able to lyse peptide-pulsed target cells and secreted IFNgamma upon restimulation. In aggregate, our data indicate that ONTAK depletes Treg in vivo significantly, resulting in enhanced immune functions and substantial development of antigen-specific CD8(+) T cells in vaccinated individuals.
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PMID:Depletion of CD4+CD25+ human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro. 1731 89

Replication-competent retrovirus (RCR) vectors are intrinsically incapable of infecting quiescent cells and have been shown to achieve highly efficient and tumor-restricted replicative spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. However, i.v. delivery of RCR vectors expressing therapeutic genes has never previously been tested, particularly in an immunocompetent tumor model. Therefore, in the present study, we sought to test the therapeutic effect of an RCR vector (ACE-CD) carrying the yeast cytosine deaminase (CD) gene, which converts the nontoxic prodrug 5-fluorocytosine (5FC) into the chemotoxin 5-fluorouracil, after delivery by infusion into the locoregional circulation in a multifocal hepatic metastasis model of colon cancer. After confirmation of suicide gene cytotoxicity in vitro, multifocal hepatic tumors were established in syngeneic mice with murine CT26 colorectal cancer cells expressing firefly luciferase (CT26-Luc), and the ACE-CD vector was infused via intrasplenic injection into the portal circulation. Fourteen days after locoregional infusion, systemic administration of 5FC resulted in significant inhibition of bioluminescent signals in mice whose tumors had been infected with RCR but not in control mice. Notably, there was no detectable RCR vector spread to normal liver or bone marrow by quantitative PCR analysis. Our results thus show that locoregional delivery of a suicide gene by RCR vectors infused into the portal circulation results in progressive transduction of multiple tumor foci in the liver, without evidence of spread to adjacent normal parenchyma or extrahepatic tissues, and can achieve significant tumor growth inhibition.
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PMID:Therapeutic efficacy of replication-competent retrovirus vector-mediated suicide gene therapy in a multifocal colorectal cancer metastasis model. 1754 15

Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodule in the liver detected by enhanced computed tomography along with elevation of the tumor markers, namely, alpha-fetoprotein (AFP) and lectin-reactive demarcation (AFP-L3), suggesting the presence of latent HCC. After oral administration of VK and ACE-I, the serum levels of both AFP and AFP-L3 gradually decreased without any marked alteration of the serum aminotransferase activity. After one-year treatment, not only the serum levels of AFP and AFP-L3 returned to the normal ranges, but also the dysplastic nodule disappeared. Since both VK and ACE-I are widely used without serious side effects, this combined regimen may become a new strategy for chemoprevention against HCC.
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PMID:Combined treatment of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis. 1758 9

Desmopressin is a synthetic analogue of the hypothalamic peptide vasopressin and binds to specific pituitary vasopressin (V3) receptors. The V3-receptor is overexpressed in pituitary corticotrope tumors and the injection of desmopressin induces a marked ACTH and cortisol release in human patients with pituitary- (PDH), but not adrenal tumor (AT) dependent hyperadrenocorticism. In this prospective study, we investigated the effects of desmopressin on serum cortisol levels in 80 dogs suspected of Cushing's syndrome. The aim was to find a sensitive and specific test to exclude AT. According to standard tests the dogs were divided into 3 groups (group 1=other disease, n=27; group 2=PDH, n=46; group 3=AT, n=7). Desmopressin was injected as an i.v. bolus of 4microg and serial blood samples were collected before and after 30, 60 and 90min. Desmopressin significantly stimulated cortisol release in dogs with PDH (median 51%, range -24 to 563%; p<0.0001), whereas no increase was seen in dogs with AT (median -12%, range -44 to 5%; p=0.063) and in controls (median +7%, range -36 to 196%; p=0.131). Using a cut off value of 10% increase over baseline, it was possible to exclude AT in 75% of patients. The results of this study suggest that the desmopressin test could be a useful tool in differentiating pituitary from adrenal dependent Cushing's syndromes. Additional dogs with adrenocortical tumor must be tested in order to recommend its use in clinical practice.
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PMID:The desmopressin stimulation test in dogs with Cushing's syndrome. 1785 Oct 17

Immunohistochemical evaluation of lung carcinomas for key enzymes involved in cellular metabolism (lactate dehydrogenase LDH 1 and 5, pyruvate dehydrogenase PDH, pyruvate dehydrogenase kinase PDHK-1, monocarboxylate transporters MCT 1, 2 and 4, glucose transporter GLUT1, hypoxia inducible factors HIF1alpha and 2alpha) show a complementary metabolic profile between cancer cells and tumor-associated stroma. Cancer cells share enzyme/transporter activities suggestive of an anaerobic metabolism with high affinity for glucose absorption, anaerobic glycolysis and lactate extrusion. On the other hand, the tumour-associated fibroblasts express patterns involved in aerobic pathways and lactate oxidation. These findings bring forward the hypothesis that tumor associated stroma is an accomplice in tumor growth and survival sustaining an independent cellular and metabolic tumor domain. The development of agents exploiting such cancer specific metabolic pathways may prove of importance in the treatment of lung cancer.
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PMID:Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma. 1788 95

We studied the putative significance of angiotensin I-converting enzyme (ACE) in colorectal cancer (CRC) biology. Local expression of ACE was investigated by quantitative reverse transcription-polymerase chain reaction and by immunohistochemistry in CRCs and adenomas. ACE insertion (I)/deletion (D) polymorphism was studied in 141 CRC patients and 189 controls. ACE mRNA was upregulated in CRCs compared to corresponding nonlesional tissues (2.5-fold; P = .009). ACE protein was more commonly expressed in adenomas [17 (81%)] and cancer epithelial cells [22 (100%)] than in corresponding non-neoplastic crypt and surface epithelium [2 (10%) and 2 (9%), respectively]. Thirty-seven CRC patients (26%) carried II genotype, 69 (49%) carried ID genotype, and 35 (25%) carried DD genotype. The distribution of the genotypes did not differ from that of controls. Female CRC patients more commonly carried the ID genotype and less frequently the II and DD genotypes compared with male patients (P = .033). Men heterozygous or homozygous for the D-allele had larger tumors compared to carriers of the II genotype (P < .01). Women homozygous for the D-allele lived longer than carriers of the ID and II genotypes. Our study shows that ACE is differentially expressed in CRCs and that gene polymorphism is associated with gender-specific differences in primary tumor size and patient survival.
Neoplasia 2007 Sep
PMID:The gene polymorphism of the angiotensin I-converting enzyme correlates with tumor size and patient survival in colorectal cancer patients. 1789 67

Reninoma is a tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia via hypersecretion of renin. We describe a case of reninoma and provide a review of the literature, with a discussion emphasizing the diagnostic evaluation for such patients. The subject had persistent elevation of both plasma renin activity (PRA) and aldosterone. Imaging studies revealed the presence of a lesion in the renal cortex, which was further identified as a renin-producing lesion via selective venous catheterization following administration of an angiotensin-converting enzyme inhibitor (ACE-I). Following partial nephrectomy, the PRA and plasma aldosterone levels declined rapidly and the blood pressure and potassium supplementation requirements normalized. This case demonstrates the utility of both appropriate imaging studies and selective venous catheterization following provocative administration of an ACE-I for diagnosis.
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PMID:Reninoma: case report and literature review. 1819 52

We report three cases of metastatic renal cell carcinoma (RCC) in which combination treatment of cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin system inhibitor (angiotensin converting enzyme inhibitor or angiotensin II type 1 receptor antagonist) (CCA therapy) was effective. Case 1: A 47-year-old man who had a 12-cm right renal tumor with multiple pulmonary and hepatic metastases refused cytokine therapy for economic reasons and received CCA therapy. All of the metastases showed partial remission, which continued for 12 months. Case 2: A 62-year-old man with multiple pulmonary and mediastinal lymph node metastases from clear cell RCC refractory to interferon-alpha and interleukin-2 started CCA therapy. Partial remission has been maintained for 16 months. Case 3: A 64-year-old man with pulmonary metastases from clear cell RCC discontinued interferon-alpha treatment due to its side effects after six months and received CCA therapy. Pulmonary metastases showed partial remission for 31 months. The CCA therapy could be an alternative treatment for metastatic RCC patients unfit for cytokine therapy.
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PMID:Favorable response to combination treatment of cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin system inhibitor in metastatic renal cell carcinoma: Report of three cases. 1878 6

Paraneoplastic glomerulopathies are rare manifestations of neoplastic disease to be distinguished from iatrogenic renal damage. Solid tumors are preferentially associated with membranous nephropathy, whereas Hodgkin's lymphomas are associated with minimal change disease. The most common neoplasia associated with paraneoplastic glomerular disease are carcinomas of the lung and of the gastrointestinal tract. Nephrotic syndrome is the most frequent presentation of paraneoplastic glomerulopathy and the most critical glomerular disease regarding prognosis and patient care. Renal biopsy is recommended in patients with glomerular proteinuria or nephrotic syndrome and cancer, depending on life expectancy and therapeutic options. The primary treatment must be directed at the cancer in all cases. Symptomatic treatment of the nephrotic syndrome with diuretics and ACE inhibitors is justified. Prevention of nephrotic syndrome complications, i.e. thromboses and infections, should also be addressed and systematic regular renal follow-up is warranted. All treatments should be regularly reviewed to avoid toxicity, associated renal function loss or low albumin levels for patients receiving albumin-binding drugs. Epidemiologic studies have low evidence-based value. There is no widely accepted experimental model of the association of glomerulopathy and cancer. Thus, epidemiologic and mechanistic studies are needed to determine the true prevalence of paraneoplastic glomerulopathies and investigate new pathophysiologic approaches.
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PMID:Paraneoplastic glomerular diseases and malignancies. 1879 Jun 51


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