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Article ; Online: Tumour maintenance is mediated by eNOS.

Lim, Kian-Huat / Ancrile, Brooke B / Kashatus, David F / Counter, Christopher M

2008 Volume 452, Issue 7187, Page(s) 646–649

Abstract: ... to initiate human tumour growth, only PI3K, through activation of protein kinase B (PKB; also known as AKT ...

Abstract	Tumour cells become addicted to the expression of initiating oncogenes like Ras, such that loss of oncogene expression in established tumours leads to tumour regression. HRas, NRas or KRas are mutated to remain in the active GTP-bound oncogenic state in many cancers. Although Ras activates several proteins to initiate human tumour growth, only PI3K, through activation of protein kinase B (PKB; also known as AKT), must remain activated by oncogenic Ras to maintain this growth. Here we show that blocking phosphorylation of the AKT substrate, endothelial nitric oxide synthase (eNOS or NOS3), inhibits tumour initiation and maintenance. Moreover, eNOS enhances the nitrosylation and activation of endogenous wild-type Ras proteins, which are required throughout tumorigenesis. We suggest that activation of the PI3K-AKT-eNOS-(wild-type) Ras pathway by oncogenic Ras in cancer cells is required to initiate and maintain tumour growth.
MeSH term(s)	3T3 Cells ; Animals ; Cell Line, Transformed ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Humans ; Mice ; Neoplasms/drug therapy ; Neoplasms/enzymology ; Neoplasms/pathology ; Nitric Oxide Synthase Type III/deficiency ; Nitric Oxide Synthase Type III/genetics ; Nitric Oxide Synthase Type III/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; ras Proteins/metabolism
Chemical Substances	Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2008-03-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature06778
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Zs.MO 244: Show issues

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Article: Oncogenic ras-induced expression of cytokines: a new target of anti-cancer therapeutics.

Ancrile, Brooke B / O'Hayer, Kevin M / Counter, Christopher M

Molecular interventions

2008 Volume 8, Issue 1, Page(s) 22–27

Abstract: The Ras family of small guanosine triphosphatases normally transmit signals from cell surface receptors to the interior of the cell. Stimulation of cell surface receptors leads to the activation of guanine exchange factors, which, in turn, convert Ras ... ...

Abstract	The Ras family of small guanosine triphosphatases normally transmit signals from cell surface receptors to the interior of the cell. Stimulation of cell surface receptors leads to the activation of guanine exchange factors, which, in turn, convert Ras from an inactive GDP-bound state to an active GTP-bound state. However, in one third of human cancers, RAS is mutated and remains in the constitutively active GTP-bound state. In this oncogenic state, RAS activates a constellation of signaling that is known to promote tumorigenesis. One consequence of this oncogenic RAS signal in cancer cells is the upregulation of the cytokines interleukin (IL)-6, IL-8, and chemokine growth-regulated oncogene 1 (GRO-1). We review the evidence supporting a role for these cytokines in oncogenic RAS-driven solid tumors.
MeSH term(s)	Animals ; Chemokine CXCL1/metabolism ; Cytokines/genetics ; Cytokines/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Neoplasms/drug therapy ; Neoplasms/physiopathology ; Oncogene Protein p21(ras)/genetics ; Oncogene Protein p21(ras)/metabolism ; Signal Transduction
Chemical Substances	CXCL1 protein, human ; Chemokine CXCL1 ; Cytokines ; Interleukin-6 ; Interleukin-8 ; Oncogene Protein p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2008-03-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2108819-6
ISSN	1543-2548 ; 1534-0384
ISSN (online)	1543-2548
ISSN	1534-0384
DOI	10.1124/mi.8.1.6
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Zs.A 5844: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 81: Show issues

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Article ; Online: The Safety and Efficacy of an Alcohol-Free Pancreatic Cyst Ablation Protocol.

Moyer, Matthew T / Sharzehi, Setareh / Mathew, Abraham / Levenick, John M / Headlee, Brandy D / Blandford, Jonathan T / Heisey, Heather D / Birkholz, James H / Ancrile, Brooke B / Maranki, Jennifer L / Gusani, Niraj J / McGarrity, Thomas J / Dye, Charles E

Gastroenterology

2017 Volume 153, Issue 5, Page(s) 1295–1303

Abstract: Background & aims: Endoscopic ultrasound (EUS)-guided chemoablation with ethanol lavage followed by infusion of paclitaxel is effective for the treatment of mucinous pancreatic cysts. However, complications arise in 3%-10% of patients, presumably linked ...

Abstract	Background & aims: Endoscopic ultrasound (EUS)-guided chemoablation with ethanol lavage followed by infusion of paclitaxel is effective for the treatment of mucinous pancreatic cysts. However, complications arise in 3%-10% of patients, presumably linked to the inflammatory effects of ethanol. We aimed to determine whether alcohol is required for effective pancreatic cyst ablation, if removing alcohol from the ablation process would improve complication rates, and whether a multi-agent chemotherapeutic cocktail could increase the rate of complete cyst resolution compared with findings reported from previous trials using alcohol followed by paclitaxel alone. Methods: Between November 2011 and December 2016, we conducted a single-center, prospective, double-blind trial of 39 patients with mucinous-type pancreatic cysts. Patients were randomly assigned to 1 of 2 groups that underwent EUS-guided pancreatic cyst lavage with either 80% ethanol (control) or normal saline (alcohol-free group). Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation 12 months after the procedure, and rates of serious and minor adverse events within 30 days of the procedure. Results: At 12 months, 67% of patients who underwent alcohol-free EUS-guided cyst chemoablation had complete ablation of cysts compared with 61% of patients in the control group. Serious adverse events occurred in 6% of patients in the control group vs none of the patients in the alcohol-free group. Minor adverse events occurred in 22% of patients in the control group and none of the patients in the alcohol-free group. The overall rate of complete ablation was 64%. Conclusions: In this prospective, randomized, controlled trial, we found that alcohol is not required for effective EUS-guided pancreatic cyst ablation, and when alcohol is removed from the ablation process, there is a significant reduction in associated adverse events. A multi-agent chemotherapeutic ablation admixture did not appear to significantly improve rates of complete ablation compared with the current standard of alcohol lavage followed by paclitaxel alone. ClinicalTrials.gov ID: NCT01475331.
Language	English
Publishing date	2017-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2017.08.009
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Zs.MO 572: Show issues

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Article: Cholecalciferol (vitamin D3) and the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) are synergistic for chemoprevention of prostate cancer.

Tokar, Erik J / Ancrile, Brooke B / Ablin, Richard J / Webber, Mukta M

Journal of experimental therapeutics & oncology

2006 Volume 5, Issue 4, Page(s) 323–333

Abstract: Prostate cancer, the most commonly diagnosed cancer among American men, develops slowly over many years. The long latent period of 20 to 30 years, involved in the multistep process of carcinogenesis, provides an important opportunity to block or reverse ... ...

Abstract	Prostate cancer, the most commonly diagnosed cancer among American men, develops slowly over many years. The long latent period of 20 to 30 years, involved in the multistep process of carcinogenesis, provides an important opportunity to block or reverse progression to a malignant state. Vitamin A (retinoids) and vitamin D not only have the ability to block steps in the process of carcinogenesis but they can also modulate or reverse some malignant characteristics of cancer cells. However, at high levels, vitamins A and D have undesirable side effects, thus, limiting effective dose levels and efficacy. Therefore, combination treatment at low doses, to increase efficacy and avoid toxicity, is of special interest. This study examines the effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in combination with cholecalciferol (vitamin D3) on growth, and on the expression of vimentin, matrix metalloproteinase-2 (MMP-2), and retinoid and vitamin D receptor expression, using the non-tumorigenic, human prostate epithelial cell line RWPE-1. Treatment with 4-HPR and cholecalciferol resulted in synergistic growth inhibition when compared to that caused by each agent alone. A decrease in vimentin expression and MMP-2 activity, and up-regulation of vitamin D receptor (VDR) and some of the retinoid-X (RXRs) and retinoic acid receptor (RARs) subtypes, was observed. These results suggest that combined treatment with 4-HPR and cholecalciferol, at doses lower than what might be effective with single agents, increases their efficacy and suggest that this may serve as an effective strategy for chemoprevention and treatment of prostate cancer.
MeSH term(s)	Anticarcinogenic Agents/pharmacology ; Cholecalciferol/pharmacology ; Drug Synergism ; Fenretinide/pharmacology ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Matrix Metalloproteinase 2/metabolism ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/therapy ; Retinoids/metabolism ; Up-Regulation ; Vimentin/metabolism ; Vitamins/metabolism
Chemical Substances	Anticarcinogenic Agents ; Retinoids ; Vimentin ; Vitamins ; Fenretinide (187EJ7QEXL) ; Cholecalciferol (1C6V77QF41) ; Matrix Metalloproteinase 2 (EC 3.4.24.24)
Language	English
Publishing date	2006
Publishing country	United States
Document type	Journal Article
ZDB-ID	1329377-1
ISSN	1359-4117
ISSN	1359-4117
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Zs.A 4562: Show issues

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Article: Stem/progenitor and intermediate cell types and the origin of human prostate cancer.

Tokar, Erik J / Ancrile, Brooke B / Cunha, Gerald R / Webber, Mukta M

Differentiation; research in biological diversity

2005 Volume 73, Issue 9-10, Page(s) 463–473

Abstract: Theories of cell lineage in human prostatic epithelium, based on protein expression, propose that basal and luminal cells: 1) are either independently capable of self-renewal or 2) arise from stem cells expressing a full spectrum of proteins (p63, ... ...

Abstract	Theories of cell lineage in human prostatic epithelium, based on protein expression, propose that basal and luminal cells: 1) are either independently capable of self-renewal or 2) arise from stem cells expressing a full spectrum of proteins (p63, cytokeratins CK5/14, CK8/18, and glutathione-S-transferase-pi [GST-pi]) similar to cells of the embryonic urogenital sinus (UGS). Such embryonic-like stem cells are thought to give rise to mature basal cells and secretory luminal cells. By single cell cloning of an immortalized, normal human prostate-derived, non-tumorigenic RWPE-1 cell line, we isolated and characterized two epithelial cell types, WPE-stem and WPE-int. WPE-stem cells show: i) strong, sixfold greater nuclear expression of p63; ii) nearly twofold greater expression of CK14; iii) threefold less CK18, and iv) low androgen receptor (AR) expression as compared with WPE-int cells. WPE-stem cells are androgen-independent for growth and survival. WPE-int cells express very low p63 and CK5/14, and high CK18. WPE-int cells are androgen-independent for growth and survival but are highly responsive as shown by androgen induction of AR and prostate specific antigen (PSA). Compared with WPE-int cells, WPE-stem cells are smaller and show more rapid growth. WPE-stem cells can grow in an anchorage-independent manner in agar with 4.5-fold greater cloning efficiency and as free floating "prostaspheres" in liquid medium; and express over 40-fold higher matrix metalloproteinase-2 activity. These results indicate that WPE-stem cells express several features characteristic of stem/progenitor cells present in the UGS and in adult prostatic epithelium. In contrast, WPE-int cells have an intermediate, committed phenotype on the pathway to luminal cell differentiation. We propose that in normal prostatic epithelium, cells exist at many stages in a continuum of differentiation progressing from stem cells to definitive basal and luminal cells. Establishment and characterization of clones of human prostatic epithelial cells provide novel models for determining cell lineages, the origin of prostate cancer, and for developing new strategies for tumor prevention and treatment.
MeSH term(s)	Antigens, Differentiation/biosynthesis ; Cell Differentiation/drug effects ; Cell Line ; Clone Cells ; Epithelial Cells/cytology ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Humans ; Male ; Nandrolone/analogs & derivatives ; Nandrolone/pharmacology ; Prostate-Specific Antigen/biosynthesis ; Prostatic Neoplasms/etiology ; Receptors, Androgen/metabolism ; Stem Cells/cytology ; Stem Cells/drug effects ; Stem Cells/metabolism
Chemical Substances	Antigens, Differentiation ; Receptors, Androgen ; Nandrolone (6PG9VR430D) ; mibolerone (9OGY4BOR8D) ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2005-12
Publishing country	England
Document type	Journal Article
ZDB-ID	184540-8
ISSN	1432-0436 ; 0301-4681
ISSN (online)	1432-0436
ISSN	0301-4681
DOI	10.1111/j.1432-0436.2005.00047.x
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Zs.A 1170: Show issues

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Article ; Online: Reliability of gastric access closure with the self-approximating transluminal access technique (STAT) for NOTES.

Mathew, Abraham / Tomasko, Jonathan M / Pauli, Eric M / Moyer, Matthew T / Gopal, Jegan / Ancrile, Brooke B / Rogers, Ann M / Haluck, Randy S

Surgical endoscopy

2011 Volume 25, Issue 8, Page(s) 2718–2724

Abstract: Background: STAT, or the self-approximating transluminal access technique, has been previously described and involves the dissection of a submucosal tunnel for peritoneal or mediastinal access from the esophagus and stomach. The objective of this study ... ...

Abstract	Background: STAT, or the self-approximating transluminal access technique, has been previously described and involves the dissection of a submucosal tunnel for peritoneal or mediastinal access from the esophagus and stomach. The objective of this study was to assess the safety and reliability of gastric access and closure in a porcine experience using STAT for natural orifice transluminal endoscopic surgery (NOTES). Methods: A review of the experience using STAT access tunnels for intraperitoneal access was performed in 39 female pigs at a university animal lab. All animals underwent a predetermined NOTES surgical procedure using a STAT transgastric access tunnel based on a specific protocol. Details of the procedure, complications, and clinical course were documented. Necropsy was performed at 2 weeks. The main outcome measurements were clinical or necropsy evidence of gastrostomy site leak or inadequate access site closure. Results: STAT was successful in providing safe peritoneal access in all animals. The width of the tunnel ranged from 1.5 to 5.5 cm and the length was up to 27 cm. There was no evidence of gastrostomy site leak in any animals. One animal required a single laparoscopic suture to help with tunnel closure. Conclusion: STAT provides safe transgastric access and allows secure closure of the gastrotomy site.
MeSH term(s)	Animals ; Natural Orifice Endoscopic Surgery/methods ; Swine
Language	English
Publishing date	2011-04-13
Publishing country	Germany
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639039-0
ISSN	1432-2218 ; 0930-2794
ISSN (online)	1432-2218
ISSN	0930-2794
DOI	10.1007/s00464-011-1659-4
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Zs.A 2214: Show issues

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Article: Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis.

Ancrile, Brooke / Lim, Kian-Huat / Counter, Christopher M

Genes & development

2007 Volume 21, Issue 14, Page(s) 1714–1719

Abstract: Ras is mutated to remain in the active oncogenic state in many cancers. As Ras has proven difficult to target therapeutically, we searched for secreted, druggable proteins induced by Ras that are required for tumorigenesis. We found that Ras induces the ... ...

Abstract	Ras is mutated to remain in the active oncogenic state in many cancers. As Ras has proven difficult to target therapeutically, we searched for secreted, druggable proteins induced by Ras that are required for tumorigenesis. We found that Ras induces the secretion of cytokine IL6 in different cell types, and that knockdown of IL6, genetic ablation of the IL6 gene, or treatment with a neutralizing IL6 antibody retard Ras-driven tumorigenesis. IL6 appears to act in a paracrine fashion to promote angiogenesis and tumor growth. Inhibiting IL6 may therefore have therapeutic utility for treatment of cancers characterized by oncogenic Ras mutations.
MeSH term(s)	Animals ; Base Sequence ; Cell Line ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Genes, ras ; Humans ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/biosynthesis ; Interleukin-6/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, SCID ; Neoplasms, Experimental/etiology ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/pathology ; RNA/genetics
Chemical Substances	Interleukin-6 ; RNA (63231-63-0)
Language	English
Publishing date	2007-07-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.1549407
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Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 54: Show issues

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Article ; Online: Aurora-A phosphorylates, activates, and relocalizes the small GTPase RalA.

Lim, Kian-Huat / Brady, Donita C / Kashatus, David F / Ancrile, Brooke B / Der, Channing J / Cox, Adrienne D / Counter, Christopher M

Molecular and cellular biology

2009 Volume 30, Issue 2, Page(s) 508–523

Abstract: The small GTPase Ras, which transmits extracellular signals to the cell, and the kinase Aurora-A, which promotes proper mitosis, can both be inappropriately activated in human tumors. Here, we show that Aurora-A in conjunction with oncogenic Ras enhances ...

Abstract	The small GTPase Ras, which transmits extracellular signals to the cell, and the kinase Aurora-A, which promotes proper mitosis, can both be inappropriately activated in human tumors. Here, we show that Aurora-A in conjunction with oncogenic Ras enhances transformed cell growth. Furthermore, such transformation and in some cases also tumorigenesis depend upon S194 of RalA, a known Aurora-A phosphorylation site. Aurora-A promotes not only RalA activation but also translocation from the plasma membrane and activation of the effector protein RalBP1. Taken together, these data suggest that Aurora-A may converge upon oncogenic Ras signaling through RalA.
MeSH term(s)	ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Animals ; Aurora Kinase A ; Aurora Kinases ; Cell Line, Tumor ; GTPase-Activating Proteins/genetics ; GTPase-Activating Proteins/metabolism ; Humans ; Mice ; Mice, SCID ; Mutation ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Xenograft Model Antitumor Assays ; ral GTP-Binding Proteins/genetics ; ral GTP-Binding Proteins/metabolism ; ras Proteins/metabolism
Chemical Substances	ATP-Binding Cassette Transporters ; GTPase-Activating Proteins ; RALBP1 protein, human ; Aurka protein, mouse (EC 2.7.11.1) ; Aurora Kinase A (EC 2.7.11.1) ; Aurora Kinases (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; RALA protein, human (EC 3.6.1.-) ; ral GTP-Binding Proteins (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2009-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00916-08
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Zs.A 1666: Show issues

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Article ; Online: Targeting eNOS in pancreatic cancer.

Lampson, Benjamin L / Kendall, S Disean / Ancrile, Brooke B / Morrison, Meghan M / Shealy, Michael J / Barrientos, Katharine S / Crowe, Matthew S / Kashatus, David F / White, Rebekah R / Gurley, Susan B / Cardona, Diana M / Counter, Christopher M

Cancer research

2012 Volume 72, Issue 17, Page(s) 4472–4482

Abstract: Mortality from pancreatic ductal adenocarcinoma cancer (PDAC) is among the highest of any cancer and frontline therapy has changed little in years. Activation of endothelial nitric oxide synthase (eNOS, NOS3, or NOS III) has been implicated recently in ... ...

Abstract	Mortality from pancreatic ductal adenocarcinoma cancer (PDAC) is among the highest of any cancer and frontline therapy has changed little in years. Activation of endothelial nitric oxide synthase (eNOS, NOS3, or NOS III) has been implicated recently in the pathogenesis of PDACs. In this study, we used genetically engineered mouse and human xenograft models to evaluate the consequences of targeting eNOS in PDACs. Genetic deficiency in eNOS limited the development of preinvasive pancreatic lesions and trended toward an extended lifespan in mice with advanced pancreatic cancer. These effects were also observed upon oral administration of the clinically evaluated NOS small molecule inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME). Similarly, other transgenic models of oncogenic KRas-driven tumors responded to l-NAME treatment. Finally, these results were recapitulated in xenograft models of human pancreatic cancer, in which l-NAME was found to broadly inhibit tumorigenic growth. Taken together, our findings offer preclinical proof-of-principle to repurpose l-NAME for clinical investigations in treatment of PDACs and possibly other KRas-driven human cancers.
MeSH term(s)	Animals ; Antihypertensive Agents/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/enzymology ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/mortality ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Mice, Transgenic ; NG-Nitroarginine Methyl Ester/administration & dosage ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide Synthase Type III/antagonists & inhibitors ; Nitric Oxide Synthase Type III/genetics ; Nitric Oxide Synthase Type III/metabolism ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/enzymology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/mortality ; Stromal Cells/metabolism ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays ; ras Proteins/genetics ; ras Proteins/metabolism
Chemical Substances	Antihypertensive Agents ; Antineoplastic Agents ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; ras Proteins (EC 3.6.5.2) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X)
Language	English
Publishing date	2012-06-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-12-0057
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Article: Is alcohol required for effective pancreatic cyst ablation? The prospective randomized CHARM trial pilot study.

Moyer, Matthew T / Dye, Charles E / Sharzehi, Setareh / Ancrile, Brooke / Mathew, Abraham / McGarrity, Thomas J / Gusani, Niraj / Yee, Nelson / Wong, Joyce / Levenick, John / Dougherty-Hamod, Brandy / Mathers, Bradley

Endoscopy international open

2016 Volume 4, Issue 5, Page(s) E603–7

Abstract: Background and study aims: In this study, we aim to determine the safety and feasibility of an alcohol-free approach to pancreatic cyst ablation using a chemotherapeutic ablation cocktail.: Patients and methods: In this prospective, randomized, ... ...

Abstract	Background and study aims: In this study, we aim to determine the safety and feasibility of an alcohol-free approach to pancreatic cyst ablation using a chemotherapeutic ablation cocktail. Patients and methods: In this prospective, randomized, double-blinded pilot study, 10 patients with known mucinous type pancreatic cysts underwent endoscopic ultrasound (EUS)-guided fine needle aspiration and then lavage with either 80 % ethanol or normal saline. Both groups were then treated with a cocktail of paclitaxel and gemcitabine. Primary outcomes were reduction in cyst volume and rates of complications. Results: At 6 months, patients randomized to the alcohol arm had an 89 % average volume reduction, with a 91 % reduction noted in the alcohol-free arm. Complete ablation was achieved in 67 % of patients in the alcohol-free arm at both 6 and 12 months, whereas the alcohol group recorded complete ablation rates of 50 % and 75 % at 6 and 12 months, respectively. One patient in the alcohol arm developed acute pancreatitis (20 %) with no adverse events in the alcohol-free arm. Conclusions: This study revealed similar ablation rates between the alcohol ablation group and the alcohol-free arm and demonstrates the safety and feasibility of an alcohol-free ablation protocol. This pilot study suggests that alcohol may not be required for effective cyst ablation.
Language	English
Publishing date	2016-05-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2761052-4
ISSN	2196-9736 ; 2364-3722
ISSN (online)	2196-9736
ISSN	2364-3722
DOI	10.1055/s-0042-105431
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