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Alimentary Pharmacology & Therapeutics Jun 2012Vasoactive medications such as vasopressin, somatostatin and their analogues (terlipressin, vapreotide and octreotide) are commonly used for the treatment of acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vasoactive medications such as vasopressin, somatostatin and their analogues (terlipressin, vapreotide and octreotide) are commonly used for the treatment of acute variceal bleeding. However, the risks and benefits of these interventions are not well understood.
AIM
To undertake a meta-analysis of the efficacy of vasoactive medications in patients having acute variceal bleeds.
METHODS
Randomised controlled trials (RCTs) of vasopressin, somatostatin and their analogues, administered to patients with acute variceal bleeds were identified based on systematic searches of nine electronic databases and multiple sources of grey literature.
RESULTS
The search identified 3011 citations, and 30 trials with a total of 3111 patients met eligibility criteria. The use of vasoactive agents was associated with a significantly lower risk of 7-day mortality (RR 0.74; 95% CI 0.57-0.95; P = 0.02; I(2) = 0%; moderate quality of evidence), and a significant improvement in haemostasis (RR 1.21, 95% CI 1.13-1.30; P < 0.001; I(2) = 28%; very low quality of evidence), lower transfusion requirements (pooled mean difference -0.70 units of blood transfused, 95% CI -1.01 to -0.38; P < 0.001; I(2) = 82%; moderate quality of evidence), and a shorter duration of hospitalisation (pooled mean difference -0.71 days; 95% CI -1.23 to -0.19; P = 0.007; I(2) = 0%; low quality of evidence). Studies comparing different vasoactive agents did not show a difference in efficacy, although the quality of evidence was very low.
CONCLUSIONS
The use of vasoactive agents was associated with a significantly lower risk of acute all-cause mortality and transfusion requirements, and improved control of bleeding and shorter hospital stay. Studies comparing different vasoactive medications failed to demonstrate a difference in efficacy.
Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemostatics; Humans; Lypressin; Octreotide; Randomized Controlled Trials as Topic; Somatostatin; Terlipressin; Vasopressins
PubMed: 22486630
DOI: 10.1111/j.1365-2036.2012.05088.x -
Nuclear Medicine and Biology Nov 2010Radionuclide-labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. To...
BACKGROUND AND AIM
Radionuclide-labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. To those tumors without somatostatin receptor expressed, the hSSTR2 gene was transfected. Express of the hSSTR2 receptor was imaging and the radiotherapeutic effect was evaluated with (188)Re-RC-160.
METHODS
The stable hSSTR2-expressing A549 cells (pcDNA3-hSSTR2 A549) and non-somatostatin receptor expressing A549 cells (pcDNA3 A549) were selected by western blot. Later, a corresponding animal tumor model was established. Expression of the hSSTR2 reporter was imaged using (188)Re-RC-160 recognition. Tumors were evaluated for somatostatin receptor expression using immunohistochemistry. The distribution of (188)Re-RC-160 in the animal tumor model was measured and the inhibitory effects of (188)Re-RC-160 were evaluated by measurement of tumor growth and hematoxylin and eosin and TdT mediated dUTP nick end labeling (TUNEL) staining.
RESULTS
In vivo radioimaging revealed specific targeting of (188)Re-RC-160 to tumors derived from pcDNA3- hSSTR2 A549 cells, compared to those from pcDNA3 A549 cells. pcDNA3- hSSTR2 A549 tumor growth inhibition was significantly higher in the single 7.4 MBq (188)Re-RC-160 treatment group than in the 2×7.4 MBq rhenium-188, RC-160 group, control group, and pcDNA3 A549 tumors (P<.05). Furthermore, treatment fractionation group (2 × 7.4 MBq (188)Re-RC-160), induced significantly increased tumor-growth inhibition compare with single 7.4 MBq (188)Re-RC-160 treatment (P<.05).
CONCLUSION
These studies showed that (188)Re-RC-160 could be effectively used for targeting therapy the A549-derived tumors exogenously expressing hSSTR2, which will offers a potential therapeutic strategy for the treatment of somatostatin receptor-negative cancers.
Topics: Adenocarcinoma; Adenocarcinoma of Lung; Animals; Blotting, Western; Cell Line, Tumor; Cell Transformation, Neoplastic; Cloning, Molecular; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Radioisotopes; Receptors, Somatostatin; Rhenium; Somatostatin; Tomography, Emission-Computed, Single-Photon; Transfection
PubMed: 21055629
DOI: 10.1016/j.nucmedbio.2010.05.007 -
Comparative Biochemistry and... Jan 2011Somatostatin is well known as an inhibitor of growth hormone release from the anterior pituitary. Its effects are exerted via 5 subtypes of receptors, which are named...
Somatostatin is well known as an inhibitor of growth hormone release from the anterior pituitary. Its effects are exerted via 5 subtypes of receptors, which are named SSTR1 through 5. We recently reported that intracerebroventricular (ICV) injection of somatostatin stimulates feeding behavior in chicks. However, the specific receptors which mediate this orexigenic effect have not been identified in chicks. Thus, the purpose of the present study was to identify the receptor subtypes involved in somatostatin-induced feeding using 5 somatostatin analogs. Chicks that received vapreotide and octreotide (less than 3nmol), which are agonist of SSTR2 and SSTR5, increased their food intake. Additionally, chicks ICV injected with BIM23056 or L-817,818 (SSTR3 and SSTR5 agonists, respectively) also had increased food intake. However, ICV injection of the SSTR4 agonist L-803,087 did not cause an orexigenic effect, suggesting that SSTR4 might not be important in somatostatin-induced feeding behavior. In summary, results from this study may be interpreted as SSTR2, SSTR3 and SSTR5 are related to somatostatin-associated feeding behavior in chicks.
Topics: Amides; Animals; Chickens; Eating; Feeding Behavior; Injections, Intraventricular; Naphthalenes; Octreotide; Oligopeptides; Receptors, Somatostatin; Somatostatin; Structure-Activity Relationship
PubMed: 20826222
DOI: 10.1016/j.cbpa.2010.08.027 -
Nuclear Medicine and Biology Apr 2010We investigated the anti-tumor effect induced by the combination of the radiotherapeutic agent (131)I-RC-160 and the prodrug 5-FC in human non-small cell lung cancer...
BACKGROUND AND AIM
We investigated the anti-tumor effect induced by the combination of the radiotherapeutic agent (131)I-RC-160 and the prodrug 5-FC in human non-small cell lung cancer (NSCLC) A549 cells that were co-expressing the human somatostatin receptor 2 gene (hSSTR2) and E. coli cytosine deaminase gene (CD).
METHODS
We cloned both hSSTR2 and CD into a bicistronic mammalian expression plasmid and stably transfected it into A549 cells (pCIS-A549 cells). After antibiotic selection, SSTR expression in stable clones was determined by reverse transcription and polymerase chain reaction (RT-PCR), Western blot, flow cytometry and immunofluorescence analyses. To assess the in vivo targeting efficiency of the "engineered" A549 cells, the cells were subcutaneously injected into nude mice and the biodistribution of (99m)Tc-RC-160 was assessed at different time points. The tumor inhibitory effects of (131)I-RC-160 and/or 5-FC were evaluated by measurement of tumor growth and immunohistochemical analysis.
RESULTS
Multiple analyses demonstrated the successful expression of hSSTR2 in A549 cells. In vivo radioimaging revealed specific targeting of RC-160 to the tumors derived from pCIS-A549 cells when compared to those from control A549 cells. The tumor inhibitory rate of pCIS-A549 tumors in the (131)I-RC-160 plus 5-FC-treated group was significantly higher than that in the single agent-treated group, control group and control tumors.
CONCLUSION
Co-expression of the hSSTR2 and CD genes in tumor cells can selectively sensitize these cells to the infra-additive effects of radioisotope-labeled RC-160 and 5-FC in vivo. This approach offers a potential therapeutic strategy for the treatment of lung cancer.
Topics: Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Combined Modality Therapy; Flucytosine; Humans; Iodine Radioisotopes; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Radiopharmaceuticals; Somatostatin; Treatment Outcome
PubMed: 20346871
DOI: 10.1016/j.nucmedbio.2009.11.009 -
The Cochrane Database of Systematic... Feb 2010Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce complications following pancreatic surgery, however their use is controversial.
OBJECTIVES
To determine whether prophylactic somatostatin analogues should be used routinely in pancreatic surgery.
SEARCH STRATEGY
We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 4), MEDLINE, EMBASE and Science Citation Index Expanded to November 2009.
SELECTION CRITERIA
We included randomised controlled trials comparing prophylactic somatostatin or one of its analogues versus no drug or placebo during pancreatic surgery (irrespective of language or publication status).
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and the random-effects models using Review Manager (RevMan). We calculated the risk ratio (RR), mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. When it was not possible to perform either of the above, we performed per protocol analysis.
MAIN RESULTS
We identified 17 trials (of high risk of bias) involving 2143 patients. The overall number of patients with postoperative complications was lower in the somatostatin analogue group (RR 0.71; 95% CI 0.62 to 0.82) but there was no difference in the perioperative mortality, re-operation rate or hospital stay between the groups. The incidence of pancreatic fistula was lower in the somatostatin analogue group (RR 0.64; 95% CI 0.53 to 0.78). The proportion of these fistulas that were clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was no difference between the two groups (RR 0.69; 95% CI 0.34 to 1.41). Subgroup analysis revealed a shorter hospital stay in the somatostatin analogue group than the controls for patients with malignant aetiology (MD -7.57; 95% CI -11.29 to -3.84).
AUTHORS' CONCLUSIONS
Somatostatin analogues reduce perioperative complications but do not reduce perioperative mortality. In those undergoing pancreatic surgery for malignancy, they shorten hospital stay. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in patients undergoing pancreatic resection for malignancy. There is currently no evidence to support their routine use in pancreatic surgeries performed for other indications.
Topics: Humans; Octreotide; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Postoperative Complications; Somatostatin
PubMed: 20166101
DOI: 10.1002/14651858.CD008370 -
Proceedings of the National Academy of... Sep 2009Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant...
Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone overproduction. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4-71 and LHRH antagonist Cetrorelix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors.
Topics: 2-Hydroxyphenethylamine; Adrenal Gland Neoplasms; Adrenal Glands; Aniline Compounds; Animals; Cell Line, Tumor; Cell Proliferation; Cytostatic Agents; Doxorubicin; Gene Expression; Humans; Neuropeptides; Oligonucleotide Array Sequence Analysis; PC12 Cells; Pyrroles; RNA, Messenger; Rats; Receptors, LHRH; Receptors, Neuropeptide; Receptors, Somatostatin; Somatostatin
PubMed: 19717419
DOI: 10.1073/pnas.0907843106 -
Expert Opinion on Pharmacotherapy Oct 2009Portal hypertension is a clinically important consequence of cirrhosis that can lead to morbidities such as variceal bleeding, hepatic encephalopathy and ascites. All of... (Review)
Review
BACKGROUND
Portal hypertension is a clinically important consequence of cirrhosis that can lead to morbidities such as variceal bleeding, hepatic encephalopathy and ascites. All of these outcomes carry high mortality rates. There have been several drugs created to assist with endoscopic therapy for the treatment of acute variceal bleeding. Recently, vapreotide has been studied in patients to evaluate its efficacy as treatment for acute variceal hemorrhage. Although no comparisons have been made between vapreotide and other somatostatin analogues, this drug has been shown to have efficacy in the control of acute variceal bleeding as well as reducing the risk of recurrent bleeding and death, especially when started prior to endoscopy.
OBJECTIVE
This paper reviews the literature regarding the basic science and clinical efficacy of vapreotide in acute variceal bleeding.
METHODS
We used a PubMed/Medline search in order to review the literature regarding the drug, vapreotide.
RESULTS/CONCLUSIONS
Vapreotide appears to have benefit in the control of acute variceal bleeding. It is easy to administer and has few side effects, which are minor. These findings endorse the need for future trials to evaluate vapreotide and its use in acute variceal hemorrhage, a morbidity among patients with cirrhosis.
Topics: Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Somatostatin; Treatment Outcome; Vasoconstrictor Agents
PubMed: 19708854
DOI: 10.1517/14656560903207019 -
Expert Opinion on Investigational Drugs Sep 2009Somatostatin agonists (SM-As) are capable of achieving durable symptomatic relief and significant clinical responses in certain tumours. Herein, we review the diverse... (Review)
Review
Somatostatin agonists (SM-As) are capable of achieving durable symptomatic relief and significant clinical responses in certain tumours. Herein, we review the diverse direct and indirect mechanisms of antineoplastic activity elicited by SM-As as well as the hurdles that complicate their use as monotherapies in a broader range of malignancies. Emphasis is placed on recent clinical attempts to neutralise the IGF-mediated survival factor effects in the bone metastasis microenvironment in advanced prostate cancer. The first clinical trials of this 'anti-survival factor manipulation' strategy utilised the ability of SM-As to suppress the growth hormone-dependent liver-derived IGF-I bioavailability in combination with other drugs, such as dexamethasone, zolendronate and oestrogens, acting systemically and at the bone metastasis microenvironment. These regimens restored androgen ablation responsiveness in stage D3 prostate cancer patients and successfully produced objective clinical responses while only mild toxicities were observed. Furthermore, we focus on the preclinical experimental data of a targeted SM-A coupled to the super-potent doxorubicin derivative AN-201. The resulting conjugate (AN-238) has shown increased antitumour potency with a favourable toxicity profile. The potential use of novel SM-As as anticancer drugs is discussed in relation to data suggesting other direct and indirect treatment approaches pertaining to the somatostatin system.
Topics: Animals; Antineoplastic Agents; Humans; Neoplasm Metastasis; Neoplasms; Octreotide; Peptides, Cyclic; Receptors, Somatostatin; Somatostatin; Tachyphylaxis
PubMed: 19678799
DOI: 10.1517/13543780903176399