Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of pertussis toxin on somatostatin-induced K+ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K+ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma 1, 0/10 in adenoma 2). Spontaneous action potentials, K+, Na+, and Ca2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [32P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.
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PMID:Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells. 244 Mar 14

ADP-ribosylation is a posttranslational modification of proteins that has been related to many cellular events, such as DNA replication and repair, cell proliferation and differentiation. The present studies were performed in order to explore the possible relationship between nuclear protein ADP-ribosylation and RNA transcription in the thyroid gland. Inhibition of RNA transcription by alpha-amanitin and actinomycin D caused a decrease in ADP-ribosylation of 27 and 17%, respectively. Nicotinamide caused a dose-related inhibition of ADP-ribosylation, which was highest at 2 mM (around 90%). At this dose nicotinamide inhibited total RNA transcription by 46%, while the activity due to RNA polymerase II decreased by 50% and that related to RNA polymerases I+III dropped by 24%. These results suggest that inhibition of total nuclear protein ADP-ribosylation is accompanied by a parallel decrease in RNA transcription. Since our previous work has shown that TSH stimulates both nuclear ADP-ribosylation and RNA transcription it may be concluded that these activities follow parallel changes within the thyroid. When the same activities were assayed in normal human and in glands bearing follicular adenoma, RNA polymerase II was increased 4 fold in the latter group, without change in nuclear ADP-ribosylation. These results would suggest that a mechanism, distinct from ADP-ribosylation, may also be involved in the regulation of RNA transcription. This latter might be altered under this pathologic condition.
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PMID:Relationship between nuclear ADP-ribosylation and RNA transcription in calf and human thyroid. 244 64

We have studied the effects of plasma and of cumene hydroperoxide (CUM) on adenosine diphosphate ribosyl transferase (ADPRT) from mononuclear leukocytes (HML) of patients with colonic adenomatous polyps (n = 22), with colonic hyperplastic polyps (n = 5) and with neither type of polyp (controls) (n = 6). ADPRT was measured after incubation of HML with plasma alone (termed the plasma value), and with plasma plus CUM (50 microM) (the activated value); the difference elicited by CUM was termed the induced value. There was no significant difference in values between the control and hyperplastic polyp groups: these were combined for further analysis. The plasma (P = 0.038), activated (P = 0.009) and induced (P = 0.0024) values of the combined group all differed significantly from those of the adenoma group. At low exposures, CUM stimulated both ADPRT and unscheduled DNA synthesis and, at higher exposures, inactivated both. Pretreatment of HML with vitamin E protected against these effects of CUM, while pretreatment with diamide (which depletes GSH) accentuated the effects. This study demonstrates a differential reaction of ADPRT in patients harboring colonic adenomas and suggests that the origin of this difference may lie in cellular responses to oxidative stress.
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PMID:Effects of cumene hydroperoxide on adenosine diphosphate ribosyl transferase in mononuclear leukocytes of patients with adenomatous polyps in the colon. 312 91

It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has its own action in the regulation of adenylate cyclase. A human non-functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 43 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADP-ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP-ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness.
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PMID:Cholera toxin can ADP-ribosylate Gs as well as Gi in ACTH-unresponsive human adrenocortical cancer. 788 22

Mitochondrial membrane permeabilization (MMP) is a rate-limiting step of apoptosis, including in anticancer chemotherapy. Adenine nucleotide translocase (ANT) mediates the exchange of ADP and ATP on the inner mitochondrial membrane in healthy cells. In addition, ANT can cooperate with Bax to form a lethal pore during apoptosis. Humans possess four distinct ANT isoforms, encoded by four genes, whose transcription depends on the cell type, developmental stage, cell proliferation, and hormone status. Here, we show that the ANT2 gene is up-regulated in several hormone-dependent cancers. Knockdown of ANT2 by RNA interference induced no major changes in the aspect of the mitochondrial network or cell cycle but provoked minor increase in mitochondrial transmembrane potential and reactive oxygen species level and reduced intracellular ATP concentration without affecting glycolysis. At expression and functional levels, ANT2 depletion was not compensated by other ANT isoforms. Most importantly, ANT2, but not ANT1, silencing facilitated MMP induction by lonidamine, a mitochondrion-targeted antitumor compound already used in clinical studies for breast, ovarian, glioma, and lung cancer as well as prostate adenoma. The combination of ANT2 knockdown with lonidamine induced apoptosis irrespective of the Bcl-2 status. These data identify ANT2 as an endogenous inhibitor of MMP and suggest that its selective inhibition could constitute a promising strategy of chemosensitization.
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PMID:Chemosensitization by knockdown of adenine nucleotide translocase-2. 1698 57

In previous studies, we reported that indole-3-carbinol (I3C) and myo-inositol (MI) inhibit lung adenoma induced by tobacco smoke carcinogens in A/J mice. In this paper, we extended our work and examined the effects of I3C (70 or 30 micromol/g diet) and MI (56 micromol/g diet) against vinyl carbamate (VC)-induced lung adenocarcinoma by administering the agents from 1 week after the second of two injections of VC until termination of the study at week 18. The higher dose of I3C decreased multiplicities of tumors on the surface of the lung (26%, P = 0.0005), carcinoma incidence (38%), multiplicity (67%, P < 0.0001) and size (complete abolition of carcinoma with an area of >1.0 cm(2)) as well as adenoma with cellular pleomorphism (46%, P < 0.0001). The lower dose of I3C was less effective. MI decreased multiplicities of pulmonary surface tumors (20%, P = 0.0005), adenoma with cellular pleomorphism (40%, P < 0.0001) and lung adenoma (52%, P < 0.0001) and the proportion of the biggest carcinoma (carcinoma with an area of >1.0 cm(2), P < 0.05). Immunoblot analyses of lung tissues for potential target identification showed that I3C (70 micromol/g diet) inhibits IkappaBalpha degradation, nuclear factor-kappaB activation, expression of cyclooxygenase-2, phospho-Akt and fatty acid synthase (FAS) and activates caspase-3 and poly ADP ribose polymerase cleavage. The effect of MI was limited to inhibition of phospho-Akt and FAS expression. Our data show that I3C and MI inhibit lung carcinoma and provide a basis for future evaluation of these compounds in clinical trials as chemopreventive agents for current and former smokers.
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PMID:Inhibition of vinyl carbamate-induced pulmonary adenocarcinoma by indole-3-carbinol and myo-inositol in A/J mice. 1962 46

Adenomatous ductal proliferation/hyperplasia (ADP/H) of the salivary gland, a rare asymptomatic nonneoplastic lesion that histopathologically resembles basal cell adenoma, is typically incidentally identified in resected specimens of other salivary diseases such as tumors and chronic sialadenitis. A 70-year-old male was referred to our hospital with a 9-month history of continuous swelling in the left parotid region. A physical examination revealed a soft mass in the left parotid gland, which was identified as a cystic mass by computed tomography. A parotid tumor with cystic components was suspected, and partial parotidectomy was performed under general anesthesia. The histopathological findings were consistent with the diagnosis of ADP/H of the salivary gland. This case report emphasizes the necessity for a proper diagnosis of ADP/H of the salivary gland. Further large case series are required for a modification of the definition of ADP/H for its correct diagnosis.
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PMID:A Symptomatic Case of Adenomatous Ductal Proliferation/Hyperplasia with a Large Cystic Lesion. 2887 49