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Cancer Biomarkers : Section a of... Dec 2017Prostate cancer (PCa) is the most common and the second leading cause of cancer-related death among men in America. As the molecular mechanism of PCa has not yet been...
BACKGROUND
Prostate cancer (PCa) is the most common and the second leading cause of cancer-related death among men in America. As the molecular mechanism of PCa has not yet been completely discovered, identification of hub genes and potential drug of this disease is an important area of research that could provide new insights into exploring the mechanisms underlying PCa.
OBJECTIVE
The aim of this study was to identify potential biomarkers and novel drug for prostate cancer treatment.
METHODS
The differentially expressed genes (DEGs) between prostate cancer and normal cells were screened using microarray data obtained from the Gene Expression Omnibus database. Gene ontology (GO) and pathway enrichment analyses were performed in order to investigate the functions of DEGs, and the protein-protein interaction (PPI) network of the DEGs was constructed using the Cytoscape software. DEGs were then mapped to the connectivity map database to identify molecular agents associated with the underlying mechanisms of PCa.
RESULTS
Totally, 359 genes (155 upregulated and 204 downregulated genes) were found to be differentially expressed between prostate cancer and normal cells. The GO terms significantly enriched by DEGs included cell adhesion, protein binding involved in cell-cell adhesion, response to BMP, extracellular region and extracellular region part. KEGG pathway analysis showed that the most significant pathways included cell adhesion molecules (CAMs) and TGF-beta signaling pathway. The PPI network of up-regulated DEGs and down-regulated DEGs were established, respectively. While CDH1, BMP2, NKX3-1, PPARG and PRKAR2B were identified as the hub genes in the PPI network.
CONCLUSIONS
The BMP2, PPARG and PRKAR2B genes may therefore be potential biomarkers in the treatment of PCa. Additionally, the small molecular agent phenoxybenzamine may be a potential drug for PCa.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Computational Biology; Drug Discovery; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Humans; Male; Pharmacogenomic Testing; Prostatic Neoplasms; Protein Interaction Mapping; Transcriptome
PubMed: 28800317
DOI: 10.3233/CBM-170362 -
International Journal of Clinical and... 2014To investigate methods for improving the preoperative management of patients with pheochromocytoma.
OBJECTIVE
To investigate methods for improving the preoperative management of patients with pheochromocytoma.
METHODS
We collected 155 cases diagnosed as adrenal pheochromocytoma and with hypertension. During preoperative preparation, 85 patients had antihypertensive therapy by using the selective α1-blocker doxazosin controlled-release tablets; 70 patients was controlled by using the nonselective α-blocker phenoxybenzamine; All 155 patients underwent qualitative diagnosis by determination of 24-hour urinary vanilmandelic acid (VMA) or [11C]meta-hydroxyephedrine (mHED) positron emission tomography computed tomography (PET-CT) and underwent computed tomography (CT) for tumor localization;
RESULTS
In doxazosin group, with the exception of two patients who had radical fluctuations in blood pressure during surgery, other patients showed a smooth blood pressure control during surgery. No hypertensive crisis and hypotensive shock appeared after surgery. In phenoxybenzamine group, ten patients had sharp fluctuations in blood pressure during surgery, and no hypertensive crisis and hypotensive shock appeared after surgery.
CONCLUSION
Compared with phenoxybenzamine, doxazosin has minimal adverse reactions, with high security as a preoperative preparation for adrenal pheochromocytoma, and it is easy to be taken. MHED PET-CT examination has a clear diagnostic value for patients with normal 24-hour urinary VMA.
PubMed: 25664068
DOI: No ID Found -
Chinese Medical Journal Nov 2018
Topics: Adrenal Gland Neoplasms; Catecholamines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; PAX8 Transcription Factor; Phenoxybenzamine; Pheochromocytoma
PubMed: 30381598
DOI: 10.4103/0366-6999.244126 -
Journal of Medical Case Reports Mar 2024This report presents a case of cannabinoid-induced hyperemesis syndrome causing repeated violent retching in a patient with a large (8 cm) adrenal pheochromocytoma...
BACKGROUND
This report presents a case of cannabinoid-induced hyperemesis syndrome causing repeated violent retching in a patient with a large (8 cm) adrenal pheochromocytoma resulting in hypertensive urgency.
CASE PRESENTATION
A 69-year-old white male patient with a previously diagnosed pheochromocytoma presented to the emergency department with nausea and vomiting and was found to have hypertensive urgency. Computed tomography scan did not show any acute abdominal pathology and history was inconsistent with a gastrointestinal etiology. Patient had a history of daily cannabinoid use for many years and repeated self-limited hyperemesis episodes, and thus a diagnosis of cannabinoid-induced hyperemesis syndrome was made. It was concluded that the likely explanation for the hypertensive urgency was from physical compression of his adrenal tumor during the episodes of retching resulting in a catecholamine surge. The patient was given antiemetics and admitted to the intensive care unit for blood pressure management. Blood pressure was initially controlled with phentolamine and a clevidipine infusion, then transitioned to oral doxazosin and phenoxybenzamine. Hyperemesis and abdominal pain resolved after 24 hours, and his blood pressure returned to baseline. The patient was discharged with the recommendation to stop all cannabis use. On follow-up, his blood pressure remained well controlled, and he subsequently underwent adrenalectomy for tumor removal.
CONCLUSION
Hyperemesis can cause hypertensive events in patients with pheochromocytoma by increasing abdominal pressure, leading to catecholamine release.
Topics: Aged; Humans; Male; Adrenal Gland Neoplasms; Cannabinoid Hyperemesis Syndrome; Cannabinoids; Catecholamines; Hypertensive Crisis; Pheochromocytoma; Vomiting
PubMed: 38500192
DOI: 10.1186/s13256-024-04497-0 -
Behavioural Brain Research Nov 2014Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior...
Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a α1/α2β-adrenergic receptor antagonist, prazosin or a non-selective β-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Antidepressive Agents; Anxiety; Disease Models, Animal; Dopamine Antagonists; Dose-Response Relationship, Drug; Haloperidol; Immobility Response, Tonic; Male; Maze Learning; Mice; Oligopeptides; Phenoxybenzamine; Prazosin; Serotonin Agents; Swimming
PubMed: 25116251
DOI: 10.1016/j.bbr.2014.08.007 -
Frontiers in Endocrinology 2023There is no consensus on whether intravenous rehydration must be added after preoperative phenoxybenzamine (PXB) administration for pheochromocytoma. The aim of this...
Abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability.
BACKGROUND
There is no consensus on whether intravenous rehydration must be added after preoperative phenoxybenzamine (PXB) administration for pheochromocytoma. The aim of this study is to investigate whether abandonment of intravenous volume expansion after PXB administration is associated with intraoperative hemodynamic instability.
METHODS
83 Patients with pheochromocytoma received surgical treatment in the Department of Urology, Handan First Hospital, between October 2014 and July 2022. All patients were subclassified into either the hemodynamic stability group (HS group) or the hemodynamic instability group (HU group) according to whether intraoperative hemodynamic instability occurred, with 51 cases in HS group and 32 cases in HU group. Differences in data between the two groups were examined, and the risk factors for intraoperative hemodynamic instability were analyzed using logistic regression.
RESULTS
The results of the analysis showed no statistically significant differences in age, sex, location of the tumor, surgical method, body mass index (BMI) ≥ 24 kg/m, blood and urine catecholamine test results, preoperative oral PXB followed by combined intravenous volume expansion, proportion of patients with hypertension or diabetes mellitus or coronary heart disease between the two groups (P>0.05). The size of the tumor in the HS group was smaller than that in the HU group (5.3 ± 1.9 cm vs 6.2 ± 2.4 cm P=0.010). Multivariate analyses demonstrated that abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability. Only the tumor size (P=0.025) was an independent risk factor for intraoperative hemodynamic instability.
CONCLUSION
The purpose of general preoperative intravenous fluid expansion is to prevent hypotension after the tumor has been resected. In the current study, we indicated that preoperative management of pheochromocytomas using the α-blocker PXB in combination with intravenous volume expansion does not further reduce the risk of intraoperative hemodynamic instability or postoperative complications compared with oral PXB alone. Therefore, our study supports preoperative management of pheochromocytoma with a single α-blocker, PXB, as sufficient.
Topics: Humans; Adrenergic alpha-Antagonists; Pheochromocytoma; Phenoxybenzamine; Risk Factors; Hemodynamics; Adrenal Gland Neoplasms
PubMed: 37152944
DOI: 10.3389/fendo.2023.1131564 -
Bioorganic & Medicinal Chemistry Letters Jul 2019Histone deacetylase (HDAC) inhibitors as an important epigenetic therapeutic strategy affect signaling networks and act synergistically with kinase inhibitors for the...
Histone deacetylase (HDAC) inhibitors as an important epigenetic therapeutic strategy affect signaling networks and act synergistically with kinase inhibitors for the treatment of cancer. Herein we presented a series of novel phenoxybenzamide analogues with inhibition of Raf and HDAC. Among them, compound 10e showed potent antiproliferative activities against Hepg2 and MDA-MB-468 in cellular assays. This work may lay the foundation for developing novel dual Raf/HDAC inhibitors as potential anticancer therapeutics.
Topics: Histone Deacetylase Inhibitors; Humans; Phenoxybenzamine; Structure-Activity Relationship
PubMed: 31053508
DOI: 10.1016/j.bmcl.2019.04.047 -
Medicine Aug 2021Bladder paraganglioma is characterized by headache, palpitations, hypertension, blurred vision, or sweating during voiding. Transurethral holmium laser resection is a...
RATIONALE
Bladder paraganglioma is characterized by headache, palpitations, hypertension, blurred vision, or sweating during voiding. Transurethral holmium laser resection is a safe and efficacious alternative method for the resection of bladder neoplasms.
PATIENT CONCERNS
A 24-year-old female had a 2-year history of intermittent headaches, palpitation, and sweating during micturition.
DIAGNOSIS
Physical examination revealed a rise in the patient's blood pressure to 180/90 mmHg after micturition. Laboratory examination found that the blood catecholamine metabolites were significantly increased. Abdominal ultrasound and computed tomography (CT) scan indicated a 37 mm × 31 mm paraganglioma situated at the right anterolateral wall of the bladder. A diagnosis of bladder paraganglioma was considered based on a comprehensive evaluation of the physical examination, laboratory examination, ultrasound and computerized tomography scan.
INTERVENTIONS
Preoperative oral administration of a nonselective α-adrenergic receptor antagonist (phenoxybenzamine, 10 mg three times a day,) accompanied by a high-sodium diet and generous fluid intake, was initiated 2 weeks before the surgery to stabilize intraoperative hemodynamics. As the patient was newly married and nulligravid, management with transurethral resection was considered superior to open or partial cystectomy and was selected as the treatment method.
OUTCOMES
Transurethral holmium resection of the bladder paraganglioma was successfully performed with blood loss less than 20 ml and well-controlled intraoperative blood pressure. The 1-year follow-up results demonstrated well-controlled symptoms. Cystoscopy and evaluation of blood catecholamine metabolites revealed no disease recurrence.
LESSONS
Transurethral holmium laser resection is a good alternative approach for the resection of bladder paraganglioma, given its advantages of safety and efficacy.
Topics: Female; Humans; Lasers, Solid-State; Paraganglioma; Urinary Bladder Neoplasms; Urologic Surgical Procedures; Young Adult
PubMed: 34449457
DOI: 10.1097/MD.0000000000026909 -
Journal of Animal Science Sep 2022Vasoconstriction is a known effect associated with ergot alkaloid consumption. The vascular contractile responses are often sustained for an extended period after...
Vasoconstriction is a known effect associated with ergot alkaloid consumption. The vascular contractile responses are often sustained for an extended period after exposure. Ergot alkaloids exist in two molecular configurations, the C-8-(R)-isomer (R-epimer) and the C-8-(S)-isomer (S-epimer). The sustained vascular contractile response to the R-epimers has been studied previously, unlike the S-epimers which are thought to be biologically inactive. Additionally, antagonists have been utilized to attenuate the vascular contraction associated with the R-epimers of ergot alkaloids utilizing ex vivo techniques. This study utilized an arterial tissue bath to examine and compare the sustained vascular contractile response attributed to ergocristine (R) and ergocristinine (S) using dissected bovine metatarsal arteries. The contractile blocking effect of a noncompetitive alpha-adrenergic antagonist, phenoxybenzamine (POB), was also investigated in precontracted arteries. Arteries (n = 6/epimer) were exposed to a single dose of ergocristine or ergocristinine (1 × 10-6 M in buffer). Each of the epimer doses was followed by a POB (1 × 10-3 M) or methanol (control) treatment at 90 min and the response was observed for another 90 min. Both epimers produced a sustained contractile response over the 180-min incubation period in the control groups. The R-epimer caused a greater sustained contractile response from 60 to 180 min post epimer exposure, compared to the S-epimer (P < 0.05, generalized estimating equations, independent t-test). Phenoxybenzamine caused a decrease in the contractile response induced by ergocristine and ergocristinine from 105 to 180 min, compared to the control (P < 0.05, generalized estimating equations, paired t-test). Overall, these results demonstrate the presence of a sustained vascular contractile response attributed to the R- and S-epimer of an ergot alkaloid with differences in contractile response between the epimers, suggesting differences in receptor binding mechanisms. Furthermore, this study demonstrated that a noncompetitive antagonist could attenuate the sustained arterial contractile effects of both ergot configurations ex vivo. Additional investigation into S-epimers of ergot alkaloids is needed. This research contributes to the understanding of the ergot epimer-vascular receptor binding mechanisms, which may support the investigation of different approaches of minimizing ergot toxicity in livestock.
Topics: Animals; Cattle; Ergolines; Ergot Alkaloids; Methanol; Phenoxybenzamine
PubMed: 35775420
DOI: 10.1093/jas/skac235 -
Frontiers in Veterinary Science 2022Perioperative management of cases undergoing phaeochromocytoma removal should aim at normalising blood pressure and heart rate, restoring volume depletion, and...
Perioperative management of cases undergoing phaeochromocytoma removal should aim at normalising blood pressure and heart rate, restoring volume depletion, and preventing catecholamine release induced by surgical manipulation. In this case report, a novel pharmacological approach in a dog undergoing surgical tumour excision is described. A 7-year-old 25-kg spayed female Labrador Retriever presented for repeated episodes of generalised weakness, pale mucous membranes, tachycardia, tremor, panting, vomiting, and hypertension over the last month was referred for surgical treatment of a left-sided adrenal tumour with invasion of the caudal vena cava. Severe hypertensive episodes occurred repeatedly, starting early during the anaesthetic period, while clipping and cleaning the abdominal area, and continued intraoperatively when the tumour was handled. Moderate hypotension occurred once the tumour was isolated and worsened during temporary caudal vena cava flow interruption and cavotomy. The patient was treated preoperatively with phenoxybenzamine to prevent hypertensive crises. Intraoperatively, magnesium sulphate and urapidil were used to control blood pressure. This treatment was effective in reducing the magnitude of blood pressure spikes but not sufficient to prevent hypertensive peaks, especially during tumour manipulation. Hypotension was treated with synthetic colloid and crystalloid boli, and noradrenaline continuous infusion. Blood transfusion was performed in response to acute bleeding during cavotomy. The dog recovered successfully from anaesthesia and its quality of life was deemed excellent by the owner at the last follow up, 22 months after surgery. The histopathology confirmed the diagnosis of phaeochromocytoma with an invasion of the phrenicoabdominal vein. In the present case, we obtained a successful outcome but failed to provide haemodynamic stability throughout the procedure.
PubMed: 35372541
DOI: 10.3389/fvets.2022.789101