%0 Journal Article
%~ PubMed
%A Agrawal, Nishant
%A Jiao, Yuchen
%A Sausen, Mark
%A Leary, Rebecca
%A Bettegowda, Chetan
%A Roberts, Nicholas J
%A Bhan, Sheetal
%A Ho, Allen S
%A Khan, Zubair
%A Bishop, Justin
%A Westra, William H
%A Wood, Laura D
%A Hruban, Ralph H
%A Tufano, Ralph P
%A Robinson, Bruce
%A Dralle, Henning
%A Toledo, Sergio P A
%A Toledo, Rodrigo A
%A Morris, Luc G T
%A Ghossein, Ronald A
%A Fagin, James A
%A Chan, Timothy A
%A Velculescu, Victor E
%A Vogelstein, Bert
%A Kinzler, Kenneth W
%A Papadopoulos, Nickolas
%A Nelkin, Barry D
%A Ball, Douglas W
%T Exomic Sequencing of Medullary Thyroid Cancer Reveals Dominant and Mutually Exclusive Oncogenic Mutations in RET and RAS.
%B Journal of Clinical Endocrinology and Metabolism
%D 2013
%C United States
%I The Endocrine Society
%V 98
%N 2
%P E364-E369
%@ 1945-7197
%X 
%Z FOR Codes: 60407 111201


%0 Journal Article
%~ PubMed
%A Dwight, Trisha
%A Benn, Diana E
%A Clarkson, Adele
%A Vilain, Ricardo
%A Lipton, Lara
%A Robinson, Bruce G
%A Clifton-Bligh, Roderick J
%A Gill, Anthony J
%T Loss of SDHA Expression Identifies SDHA Mutations in Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumors.
%B American Journal of Surgical Pathology
%D 2013
%C United States
%I Lippincott Williams & Wilkins
%V 37
%N 2
%P 226-233
%@ 1532-0979
%X 
%Z FOR Codes: 111202


%0 Journal Article
%~ PubMed
%A Bullock, Martyn
%A Duncan, Emma L
%A O'Neill, Christine
%A Tacon, Lyndal
%A Sywak, Mark
%A Sidhu, Stan
%A Delbridge, Leigh
%A Learoyd, Diana
%A Robinson, Bruce G
%A Ludgate, Marian
%A Clifton-Bligh, Roderick J
%T Association of FOXE1 Polyalanine Repeat Region with Papillary Thyroid Cancer.
%B Journal of Clinical Endocrinology and Metabolism
%D 2012
%C United States
%I The Endocrine Society
%V 97
%N 9
%P E1814-E1819
%@ 1945-7197
%X Context:Polyalanine tract variations in transcription factors have been identified for a wide spectrum of developmental disorders. The thyroid transcription factor forkhead factor E1 (FOXE1) contains a polymorphic polyalanine tract with 12-22 alanines. Single-nucleotide polymorphisms (SNP) close to this locus are associated with papillary thyroid cancer (PTC), and a strong linkage disequilibrium block extends across this region.Objective:The objective of the study was to assess whether the FOXE1 polyalanine repeat region was associated with PTC and to assess the effect of polyalanine repeat region variants on protein expression, DNA binding, and transcriptional function on FOXE1-responsive promoters.Design:This was a case-control study.Setting:The study was conducted at a tertiary referral hospital.Patients and Methods:The FOXE1 polyalanine repeat region and tag SNP were genotyped in 70 PTC, with a replication in a further 92 PTC, and compared with genotypes in 5767 healthy controls (including 5667 samples from the Wellcome Trust Case Control Consortium). In vitro studies were performed to examine the protein expression, DNA binding, and transcriptional function for FOXE1 variants of different polyalanine tract lengths.Results:All the genotyped SNP were in tight linkage disequilibrium, including the FOXE1 polyalanine repeat region. We confirmed the strong association of rs1867277 with PTC (overall P = 1 ?? 10(-7), odds ratio 1.84, confidence interval 1.31-2.57). rs1867277 was in tight linkage disequilibrium with the FOXE1 polyalanine repeat region (r(2) = 0.95). FOXE1(16Ala) was associated with PTC with an odds ratio of 2.23 (confidence interval 1.42-3.50; P = 0.0005). Functional studies in vitro showed that FOXE1(16Ala) was transcriptionally impaired compared with FOXE1(14Ala), which was not due to differences in protein expression or DNA binding.Conclusions:We have confirmed the previous association of FOXE1 with PTC. Our data suggest that the coding polyalanine expansion in FOXE1 may be responsible for the observed association between FOXE1 and PTC.
%Z FOR Codes: 110306 60407


%0 Journal Article
%~ PubMed
%A ÿkerström, Tobias
%A Crona, Joakim
%A Delgado Verdugo, Alberto
%A Starker, Lee F
%A Cupisti, Kenko
%A Willenberg, Holger S
%A Knoefel, Wolfram T
%A Saeger, Wolfgang
%A Feller, Alfred
%A Ip, Julian
%A Soon, Patsy
%A Anlauf, Martin
%A Alesina, Pier F
%A Schmid, Kurt W
%A Decaussin, Myriam
%A Levillain, Pierre
%A Wängberg, Bo
%A Peix, Jean-Louis
%A Robinson, Bruce
%A Zedenius, Jan
%A Bäckdahl, Martin
%A Caramuta, Stefano
%A Iwen, K Alexander
%A Botling, Johan
%A Stålberg, Peter
%A Kraimps, Jean-Louis
%A Dralle, Henning
%A Hellman, Per
%A Sidhu, Stan
%A Westin, Gunnar
%A Lehnert, Hendrik
%A Walz, Martin K
%A ÿkerström, Göran
%A Carling, Tobias
%A Choi, Murim
%A Lifton, Richard P
%A Björklund, Peyman
%T Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter.
%B PLoS One
%D 2012
%C United States
%I Public Library of Science
%V 7
%N 7
%P e41926
%@ 1932-6203
%X 
%Z FOR Codes: 111203


%0 Journal Article
%~ PubMed
%A , NICE-SUGAR Study Investigators
%A Finfer, Simon
%A Liu, Bette
%A Chittock, Dean R
%A Norton, Robyn
%A Myburgh, John A
%A McArthur, Colin
%A Mitchell, Imogen
%A Foster, Denise
%A Dhingra, Vinay
%A Henderson, William R
%A Ronco, Juan J
%A Bellomo, Rinaldo
%A Cook, Deborah
%A McDonald, Ellen
%A Dodek, Peter
%A Hébert, Paul C
%A Heyland, Daren K
%A Robinson, Bruce G
%T Hypoglycemia and risk of death in critically ill patients.
%B The New England Journal of Medicine
%D 2012
%C United States
%I Massachusetts Medical Society
%V 367
%N 12
%P 1108-1118
%@ 1533-4406
%X 
%Z FOR Codes: 110306 110310


%0 Journal Article
%~ PubMed
%A Goulston, K
%A Oates, K
%A Shinfield, S
%A Robinson, B
%T Medical student education: what it costs and how it is funded.
%B Internal Medicine Journal
%D 2012
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 42
%N 10
%P 1149-1152
%@ 1445-5994
%X 
%Z FOR Codes: 1302


%0 Journal Article
%~ PubMed
%A Prichard, Ruth S
%A Lee, James C
%A Gill, Anthony J
%A Sywak, Mark S
%A Fingleton, Larry
%A Robinson, Bruce G
%A Sidhu, Stanley B
%A Delbridge, Leigh W
%T Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis.
%B Thyroid
%D 2012
%C United States
%I Mary Ann Liebert, Inc. Publishers
%V 22
%N 2
%P 205-209
%@ 1557-9077
%X BACKGROUND: Primary mucoepidermoid carcinoma (MEC) of the thyroid is a rare clinical and pathological entity that accounts for <0.5% of all thyroid malignancies. Although the histogenesis has been controversial, most investigators now favor it as arising from either metaplasia of thyroid follicular epithelium or heterologous de-differentiation from papillary thyroid carcinoma (PTC). We report three cases of thyroid MEC found in continuity with, and clearly arising from de-differentiation of, well-differentiated thyroid carcinomas (WDTCs). PATIENT FINDINGS AND SUMMARY: The cases presented here included two women (aged 22 and 52) and one man (aged 58). One of these cases arose in conjunction with PTC, one with follicular thyroid carcinoma (FTC), and one with Hurthle cell carcinoma (HCC). In all three cases, there was a gradual transition in morphology between the areas of typical WDTC and the areas showing MEC differentiation. In addition, immunohistochemistry demonstrated a gradual loss of thyroid specific markers (thyroid transcription factor-1, thyroglobulin) mirroring the change in morphology. CONCLUSION: We conclude that thyroid MEC can arise from metaplastic de-differentiation of WDTC, including FTC or HCC in addition to PTC. Currently, we recommend that after excision, each of the WDTC and MEC components of these tumors be treated with targeted adjuvant therapies, which may involve radioactive-iodine ablation, thyrotropin suppression, and external beam radiotherapy.
%Z FOR Codes: 111202


%0 Journal Article
%~ PubMed
%A Lee, James C
%A Zhao, Jing Ting
%A Clifton-Bligh, Roderick J
%A Gill, Anthony J
%A Gundara, Justin S
%A Ip, Julian
%A Sywak, Mark S
%A Delbridge, Leigh W
%A Robinson, Bruce G
%A Sidhu, Stanley B
%T Papillary Thyroid Carcinoma in Pregnancy: A Variant of the Disease?
%B Annals of Surgical Oncology
%D 2012
%C United States
%I Springer New York LLC
%V 19
%N 13
%P 4210-4216
%@ 1068-9265
%X BACKGROUND: There are conflicting reports in the literature regarding the prognostic influence of pregnancy on patients with papillary thyroid carcinoma (PTC), and there is no literature on specific microRNA (miRNA) profiles of PTC in the context of pregnancy. We aim to examine clinically if pregnancy is an adverse factor in PTC, and if pregnancy-associated PTC are biologically different from those in nonpregnant women in terms of their miRNA profiles. METHODS: Women diagnosed with PTC during or soon after pregnancy were recruited into the pregnancy group. Age-matched nonpregnant females were recruited into the nonpregnancy group. MiRNA microarray was performed on PTC tissue of pregnant patients (10), nonpregnant patients (10), and normal thyroids (5). There were 6 differentially expressed miRNAs from the microarray comparisons validated with RT-PCR. RESULTS: There were 24 patients in the clinical pregnancy group and 30 in the nonpregnancy group. Tumors from the pregnancy group were significantly larger and showed more regional lymph node metastases. The microarray data showed a total of 27 miRNAs that were potential differentiators of PTC tissue samples from pregnant and nonpregnant patients. Of the 6 selected for validation, no significant difference in expression was found. CONCLUSIONS: Our clinical data suggests that PTC during pregnancy may be more locoregionally aggressive. However, no difference in survival or recurrence is demonstrated. The miRNA profiles of the pregnancy-associated PTC have not been shown to be different to the nonpregnancy counterparts. This likely suggests that the differences seen clinically are related to patient factors rather than the disease itself.
%Z FOR Codes: 111202


%0 Journal Article
%A Pacini, Furio
%A Ito, Yasuhiro
%A Luster, Markus
%A Pitoia, Fabian
%A Robinson, Bruce
%A Wirth, Lori
%T Radioactive iodine-refractory differentiated thyroid cancer: Unmet needs and future directions
%B Expert Review of Endocrinology and Metabolism
%D 2012
%C United Kingdom
%I Expert Reviews Ltd.
%V 7
%N 5
%P 541-554
%@ 1744-6651
%X 
%Z FOR Codes: 111208


%0 Journal Article
%~ PubMed
%A Bullock, Martyn
%A O'Neill, Christine
%A Chou, Angela
%A Clarkson, Adele
%A Dodds, Tristian
%A Toon, Christopher
%A Sywak, Mark
%A Delbridge, Leigh
%A Robinson, Bruce G
%A Learoyd, Diana
%A Capper, David
%A von Deimling, Andreas
%A Clifton-Bligh, Roderick
%A Gill, Anthony
%T Utilisation of a monoclonal antibody for BRAFV600E detection in papillary thyroid carcinoma.
%B Endocrine-Related Cancer
%D 2012
%C United Kingdom
%I BioScientifica Ltd.
%V 19
%N 6
%P 779-784
%@ 1479-6821
%X 
%Z FOR Codes: 111202


%0 Journal Article
%~ PubMed
%A Wells, Samuel A
%A Robinson, Bruce G
%A Gagel, Robert F
%A Dralle, Henning
%A Fagin, James A
%A Santoro, Massimo
%A Baudin, Eric
%A Elisei, Rossella
%A Jarzab, Barbara
%A Vasselli, James R
%A Read, Jessica
%A Langmuir, Peter
%A Ryan, Anderson J
%A Schlumberger, Martin J
%T Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial.
%B Journal of Clinical Oncology
%D 2012
%C United States
%I American Society of Clinical Oncology
%V 30
%N 2
%P 134-141
%@ 1527-7755
%X PURPOSEThere is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. PATIENTS AND METHODSPatients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments.ResultsBetween December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%). CONCLUSIONVandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00322452).
%Z FOR Codes: 111204


%0 Journal Article
%~ PubMed
%A Tacon, Lyndal J
%A Prichard, Ruth S
%A Soon, Patsy S H
%A Robinson, Bruce G
%A Clifton-Bligh, Roderick J
%A Sidhu, Stan B
%T Current and emerging therapies for advanced adrenocortical carcinoma.
%B Oncologist
%D 2011
%C United States
%I AlphaMed Press, Inc.
%V 16
%N 1
%P 36-48
%@ 1549-490X
%X Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with a poor prognosis. Complete surgical resection offers the only potential for cure; however, even after apparently successful excision, local or metastatic recurrence is frequent. Treatment options for advanced ACC are severely limited. Mitotane is the only recognized adrenolytic therapy available; however, response rates are modest and unpredictable whereas systemic toxicities are significant. Reported responses to conventional cytotoxic chemotherapy have also been disappointing, and the rarity of ACC had hampered the ability to undertake randomized clinical studies until the establishment of the First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma. This yet-to-be reported study seeks to identify the most effective first- and second-line cytotoxic regimens. The past decade has also seen increasing research into the molecular pathogenesis of ACCs, with particular interest in the insulin-like growth factor signaling pathway. The widespread development of small molecule tyrosine kinase inhibitors in broader oncological practice is now allowing for the rational selection of targeted therapies to study in ACC. In this review, we discuss the currently available therapeutic options for patients with advanced ACC and detail the molecular rationale behind, and clinical evidence for, novel and emerging therapies.
%Z FOR Codes: 110306 110306


%0 Journal Article
%~ PubMed
%A Gundara, Justin S
%A Robinson, Bruce G
%A Sidhu, Stan B
%T Evolution of the "autophagamiR"
%B Autophagy
%D 2011
%C United States
%I Landes Bioscience
%V 7
%N 12
%P 1553-1554
%@ 1554-8635
%X MicroRNAs (miRs) are increasingly important diagnostic and prognostic markers in cancer but have not been defined in medullary thyroid carcinoma (MTC). MiR microarray profiling was performed on 19 primary MTC tumors, validated with qPCR in 45 cases and correlated with clinical outcomes. MiRs-183 and 375 were overexpressed and miR-9* underexpressed in sporadic versus hereditary MTC (SMTC; HMTC). MiR-183 and 375 overexpression predicted lateral nodal metastases, residual disease, distant metastases and mortality. MiR-183 knockdown in an MTC cell line (TT cells) reduced cellular proliferation in association with elevated LC3B expression. This is suggestive of increased autophagic flux and potential cell death via autophagy induction. MiRs may subsequently be shown to serve as efficacious therapeutic strategies in MTC with a mechanism based upon autophagy.
%Z FOR Codes: 60404 110306


%0 Journal Article
%~ PubMed
%A Abraham, Deepak T
%A Low, Tsu-Hui
%A Messina, Marinella
%A Jackson, Nicole
%A Gill, Anthony
%A Chou, Angela S
%A Delbridge, Leigh
%A Learoyd, Diana
%A Robinson, Bruce G
%A Sidhu, Stan
%A Sywak, Mark
%T Medullary Thyroid Carcinoma: Long-Term Outcomes of Surgical Treatment.
%B Annals of Surgical Oncology
%D 2011
%C United States
%I Springer New York LLC
%V 18
%N 1
%P 219-225
%@ 1068-9265
%X Medullary thyroid carcinoma (MTC) accounts for 5 to 10% of all thyroid cancers but is responsible for a disproportionate number of deaths.
%Z FOR Codes: 1112


%0 Journal Article
%~ PubMed
%A Abraham, Deepack
%A Jackson, Nicole E
%A Gundara, Justin S
%A Zhao, Jingting
%A Gill, Anthony J
%A Delbridge, Leigh
%A Robinson, Bruce
%A Sidhu, Stan
%T MicroRNA profiling of sporadic and hereditary medullary thyroid cancer identifies predictors of nodal metastasis, prognosis and potential therapeutic targets.
%B Clinical Cancer Research
%D 2011
%C United States
%I American Association for Cancer Research
%V 17
%N 14
%P 4772-4781
%@ 1078-0432
%X While the molecular basis of hereditary medullary thyroid cancer (HMTC) has been well defined, little is known about the molecular pathogenesis of sporadic medullary thyroid cancer (SMTC). In addition, microRNAs (miRNAs) have been shown to be important diagnostic and prognostic markers in cancer but have not been defined in MTC. Our aim was to study the miRNA profile of MTC to identify prognostic biomarkers and potential therapeutic targets.
%Z FOR Codes: 60405


%0 Journal Article
%~ PubMed
%A Gild, Matti L
%A Bullock, Martyn
%A Robinson, Bruce G
%A Clifton-Bligh, Roderick
%T Multikinase inhibitors: a new option for the treatment of thyroid cancer.
%B Nature reviews. Endocrinology
%D 2011
%C United Kingdom
%I Nature Publishing Group
%V 7
%N 10
%P 617-24
%@ 1759-5037
%X Thyroid cancer typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation and treatment with TSH-suppressive levothyroxine. Thyroid cancers that persist or recur following these therapies have a poorer prognosis. Activation of mitogenic and angiogenic signaling pathways occurs in these cancers, and preclinical models have shown that inhibition of key kinase steps in these pathways can have antitumoral effects. Several of these kinase inhibitors have now been tested in phase II and phase III trials, with modestly encouraging results. Some promising data exist for the use of vandetanib (also known as ZD6474), motesanib, axitinib, cabozantinib (also known as XL184), sorafenib, sunitinib, pazopanib and lenvatinib (also known as E7080) in progressive thyroid cancer of medullary, papillary and follicular subtypes. These drugs are generally well-tolerated, although dose-limiting toxicities are common, and a few (probable) treatment-related deaths have been reported. Additional phase III trials will be needed to conclusively show that treatment benefit exceeds risk. Drug resistance can occur via activation of alternate mitogenic signals (pathway switching), as has been reported for the use of kinase inhibitors in other malignancies, such as melanoma. The hypothesis that combinations of kinase inhibitors targeting different pathways might produce better results is currently being tested in several clinical trials.
%Z FOR Codes: 111204


%0 Journal Article
%~ PubMed
%A Brown, Sebastian
%A O'Neill, Christine
%A Suliburk, James
%A Sidhu, Stan
%A Sywak, Mark
%A Gill, Anthony
%A Robinson, Bruce
%A Delbridge, Leigh
%T Parathyroid carcinoma: increasing incidence and changing presentation.
%B ANZ Journal of Surgery
%D 2011
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 81
%N 7-8
%P 528-532
%@ 1445-2197
%X Parathyroid carcinoma has been regarded as an exceedingly rare disease worldwide, responsible for less than 1% of cases of primary hyperparathyroidism. However, there have been anecdotal reports recently of an increasing number of patients presenting with parathyroid carcinoma. The aim of this study was to examine the changing incidence and presentation of parathyroid cancer within a single centre.
%Z FOR Codes: 111202


%0 Journal Article
%~ PubMed
%A Mevawalla, Natasha
%A McMullen, Todd
%A Sidhu, Stan
%A Sywak, Mark
%A Robinson, Bruce
%A Delbridge, Leigh
%T Presentation of Clinically Solitary Thyroid Nodules in Surgical Patients.
%B Thyroid
%D 2011
%C United States
%I Mary Ann Liebert, Inc. Publishers
%V 21
%N 1
%P 55-59
%@ 1557-9077
%X Thyroid nodules occupy a unique position in relation to clinical diagnosis since most patients with a thyroid nodule do not present with overt symptoms. There are, however, no good published data demonstrating the way in which clinically solitary thyroid nodules come to medical attention, with most of the literature being anecdotal. This study aims to evaluate the mode of presentation of solitary thyroid nodules, and to assess whether the presence of a malignancy influences that presentation.
%Z FOR Codes: 1103


%0 Journal Article
%~ PubMed
%A Gill, Anthony J
%A Pachter, Nicholas S
%A Chou, Angela
%A Young, Barbara
%A Clarkson, Adele
%A Tucker, Katherine M
%A Winship, Ingrid M
%A Earls, Peter
%A Benn, Diana E
%A Robinson, Bruce G
%A Fleming, Stewart
%A Clifton-Bligh, Roderick J
%T Renal Tumors Associated With Germline SDHB Mutation Show Distinctive Morphology.
%B The American journal of surgical pathology
%D 2011
%C United States
%I Lippincott Williams & Wilkins
%V 35
%N 10
%P 1578-85
%@ 1532-0979
%X Germline succinate dehydrogenase B (SDHB) mutation causes pheochromocytoma/paraganglioma syndrome type 4 (PGL4). PGL4 is characterized by pheochromocytoma and paraganglioma, type 2 (SDHB negative) gastrointestinal stromal tumors and renal tumors, which are usually classified as carcinoma. We report 4 kindreds with 5 PGL4-associated renal tumors. Four of the tumors occurred before the age of 30 years, 4 were in the left kidney, 3 were in female patients, and 4 demonstrated consistent but previously unrecognized morphology. The tumors were composed of cuboidal cells with bubbly eosinophilic cytoplasm and indistinct cell borders. Many of the cells displayed distinctive cytoplasmic inclusions, which were vacuolated or contained eosinophilic fluid-like material. The cells were arranged in solid nests or in tubules surrounding central spaces. The tumors were well circumscribed or lobulated and frequently showed cystic change. Benign tubules or glomeruli were often entrapped at the edges of the tumors. The fifth tumor lacked these features but displayed sarcomatoid dedifferentiation. Immunohistochemistry for SDHB was completely negative in all 4 available tumors. Death from metastatic disease occurred in the patient with dedifferentiated tumor 1 year after diagnosis, whereas the other 4 tumors were cured by local excision alone (mean follow-up, 11 y; range, 2 to 30 y). We conclude that morphology supported by negative immunohistochemistry for SDHB can be used to identify kindreds with germline SDHB mutations (PGL4 syndrome) presenting with this unique type of renal tumor. These renal tumors appear to have a good prognosis after complete excision unless there is sarcomatoid dedifferentiation.
%Z FOR Codes: 110316


%0 Journal Article
%~ PubMed
%A Gill, Anthony J
%A Pachter, Nicholas S
%A Clarkson, Adele
%A Tucker, Katherine M
%A Winship, Ingrid M
%A Benn, Diana E
%A Robinson, Bruce G
%A Clifton-Bligh, Roderick J
%T Renal tumors and hereditary pheochromocytoma-paraganglioma syndrome type 4.
%B New England Journal of Medicine
%D 2011
%C United Kingdom
%I Massachusetts Medical Society
%V 364
%N 9
%P 885-886
%@ 1533-4406
%X 
%Z FOR Codes: 110307 111209


%0 Journal Article
%~ PubMed
%A Fowler, Adam
%A Thomson, Daniel
%A Giles, Keith
%A Maleki, Sanaz
%A Mreich, Ellein
%A Wheeler, Helen
%A Leedman, Peter
%A Biggs, Michael
%A Cook, Raymond
%A Little, Nicholas
%A Robinson, Bruce
%A McDonald, Kerrie
%T miR-124a is frequently down-regulated in glioblastoma and is involved in migration and invasion.
%B European journal of cancer (Oxford, England : 1990)
%D 2011
%C United Kingdom, Belg
%I Pergamon
%V 47
%N 6
%P 953-63
%@ 1879-0852
%X Glioblastoma (GBM) represents a formidable clinical challenge for both patients and treating physicians. Due to better local treatments and prolonged patient survival, remote recurrences are increasingly observed, underpinning the importance of targeting tumour migration and attachment. Aberrant expression of microRNA (miRNA) is commonly associated with cancer and loss of miR-124a has previously been implicated to function as a tumour suppressor. The assessment of miR-124a in clinical specimens has been limited and a potential role in migration and invasion has been unexplored until now. We measured the expression levels of mature miR-124a in a retrospective series of 119 cases of histologically confirmed GBM and found its expression was markedly lower in over 80% of the GBM clinical specimens compared to normal brain tissue. The level of reduction in the clinical cohort varied significantly and patients with lower than the average miR-124a expression levels displayed shorter survival times. Endogenous miR-124a expression and the protein expression of three of its targets; IQ motif containing GTPase activating protein 1 (IQGAP1), laminin ??1 (LAMC1) and integrin ??1 (ITGB1) were significantly reciprocally associated in the majority of the clinical cases. We confirmed this association in our in vitro model. Functionally, the ectopic expression of mature miR-124a in a GBM cell line resulted in significant inhibition of migration and invasion, demonstrating a role for miR-124a in promoting tumour invasiveness. Our results suggest that miR-124a may play a role in GBM migration, and that targeted delivery of miR-124a may be a novel inhibitor of GBM invasion.
%Z FOR Codes: 111203


%0 Journal Article
%~ PubMed
%A O'Neill, Christine J
%A Bullock, Martyn
%A Chou, Angela
%A Sidhu, Stan B
%A Delbridge, Leigh W
%A Robinson, Bruce G
%A Gill, Anthony J
%A Learoyd, Diana L
%A Clifton-Bligh, Roderick
%A Sywak, Mark S
%T BRAF(V600E) mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer.
%B Surgery
%D 2010
%C United States
%I Mosby, Inc.
%V 148
%N 6
%P 1139-1146
%@ 0039-6060
%X BACKGROUND: The role of the B-isoform of the Raf kinase (BRAF) mutation BRAF(V600E) as an independent prognostic factor in papillary thyroid cancer (PTC) remains controversial. Some studies suggest that tumors containing BRAF(V600E) have decreased radioiodine avidity and present a greater risk of nodal recurrence and distant metastases. METHODS: Paraffin-embedded specimens from consecutive patients who underwent surgery for PTC before 2003 were independently reviewed by an endocrine pathologist. DNA was extracted, amplified by polymerase chain reaction, and the presence of the BRAF(V600E) mutation was determined by restriction digest. Tumor characteristics and long-term disease outcomes were analyzed according to BRAF(V600E) status. RESULTS: BRAF(V600E) was identified in 60 (59%) of 101 patients. At a median follow-up of 106 months, the overall disease-free survival was 78%. Clinically evident nodal recurrence occurred in 11% of BRAF(V600E)-positive patients, and all patients required lateral neck dissection (P = .02). In contrast, subclinical nodal recurrence occurred in 7% of BRAF(V600E)-negative patients, and all recurrences were successfully ablated with radioactive iodine. There was a trend toward poorer disease-free survival among patients with stage III/IV PTC and BRAF(V600E) mutation (P = .08). All 5 disease-related deaths occurred in patients with BRAF(V600E)-positive primary tumors (P = .06). CONCLUSION: The BRAF(V600E) mutation in PTC is associated with an increased risk of palpable nodal recurrence and the need for reoperative surgery.
%Z FOR Codes: 1103


%0 Journal Article
%~ PubMed
%A Hahn, Michael Anthony
%A Howell, Viive
%A Gill, Anthony
%A Clarkson, Adele
%A Weaire-Buchanan, Graham
%A Robinson, Bruce
%A Delbridge, Leigh
%A Gimm, Oliver
%A Schmitt, Wolfgang
%A Teh, Bin T
%A Marsh, Deborah
%T CDC73/HRPT2 CpG island hypermethylation and mutation of 5'-untranslated sequence are uncommon mechanisms of silencing parafibromin in parathyroid tumors.
%B Endocrine-related cancer
%D 2010
%C United Kingdom
%I Society for Endocrinology
%V 17
%N 1
%P 273-82
%@ 1479-6821
%X The tumor suppressor HRPT2/CDC73 is mutated in constitutive DNA from patients with the familial disorder hyperparathyroidism-jaw tumor syndrome and in approximately 70% of all parathyroid carcinomas. In a number of HRPT2 mutant tumors however, expression of the encoded protein parafibromin is lost in the absence of a clear second event such as HRPT2 allelic loss or the presence of a second mutation in this tumor suppressor gene. We sought to determine whether hypermethylation of a 713 bp CpG island extending 648 nucleotides upstream of the HRPT2 translational start site and 65 nucleotides into exon 1 might be a mechanism contributing to the loss of expression of parafibromin in parathyroid tumors. Furthermore, we asked whether mutations might be present in the 5''-untranslated region (5''-UTR) of HRPT2. We investigated a pool of tissue from 3 normal parathyroid glands, as well as 15 individual parathyroid tumor samples including 6 tumors with known HRPT2 mutations, for hypermethylation of the HRPT2 CpG island. Methylation was not identified in any specimens despite complete loss of parafibromin expression in two parathyroid carcinomas with a single detectable HRPT2 mutation and retention of the wild-type HRPT2 allele. Furthermore, no mutations of a likely pathogenic nature were identified in the 5''-UTR of HRPT2. These data strongly suggest that alternative mechanisms such as mutation in HRPT2 intronic regions, additional epigenetic regulation such as histone modifications, or other regulatory inactivation mechanisms such as targeting by microRNAs may play a role in the loss of parafibromin expression.
%Z FOR Codes: 1105


%0 Journal Article
%~ PubMed
%A Figtree, G A
%A Guzik, T
%A Robinson, B G
%A Channon, K M
%A Watkins, H
%T Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation.
%B International journal of cardiology
%D 2010
%C Ireland
%I Elsevier Ireland
%V 143
%N 2
%P 207-8
%@ 0167-5273
%X Estrogen receptor alpha (ERalpha) mediates beneficial actions on endothelial nitric oxide synthase (eNOS) and cholesterol metabolism. Genetic variations in the promoter of the ERalpha may therefore influence vascular function. We have identified a single nucleotide polymorphism (T>C) in the transcriptional element "ERNE" upstream of ERalpha which abolished the negative effect of this element in luciferase reporter assays and was associated with reduction in LDL cholesterol in a small association study. We have now examined for the association of this putative functional polymorphism with endothelial function. Endothelial-dependent relaxation (EDR) was measured in organ bath preparations of human saphenous vein obtained from 101 individuals (81 males and 20 females) undergoing coronary artery bypass surgery. The presence of the variant C allele was associated with enhanced EDR independently of hypercholesterolaemia, smoking and diabetes, as well as sex (ANOVA for ACh induced relaxation: p=0.033). In males, the presence of the C allele was associated with a 225% augmentation of endothelial-dependent relaxation compared to wild-type (55.5+/-10%; n=3 vs. 24.7+/-1%; n=78; p<0.001). In summary, a polymorphism in the ERalpha negative transcriptional element which results in increased transcription in vitro is associated with substantial augmentation of endothelial-dependent vasorelaxation.
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Gill, Anthony J
%A Chou, Angela
%A Vilain, Ricardo
%A Clarkson, Adele
%A Lui, Millie
%A Jin, Richard
%A Tobias, Vivienne
%A Samra, Jaswinder
%A Goldstein, David
%A Smith, Celia
%A Sioson, Loretta
%A Parker, Nicole
%A Smith, Ross C
%A Sywak, Mark
%A Sidhu, Stan B
%A Wyatt, Jenny Ma
%A Robinson, Bruce G
%A Eckstein, Robert P
%A Benn, Diana E
%A Clifton-Bligh, Roderick J
%T Immunohistochemistry for SDHB Divides Gastrointestinal Stromal Tumors (GISTs) into 2 Distinct Types.
%B American Journal of Surgical Pathology
%D 2010
%C United States
%I Lippincott Williams & Wilkins
%V 34
%N 5
%P 636-644
%@ 1532-0979
%X The Carney triad (CT) is gastrointestinal stromal tumor (GIST), paraganglioma, and pulmonary chondroma. The GISTs of CT show different clinical, molecular, and morphologic features to usual adult GISTs but are similar to the majority of pediatric GISTs. We postulated that these GISTs would show negative staining for succinate dehydrogenase B (SDHB). We performed SDHB immunohistochemistry on GISTs arising in 5 individuals with CT, 1 child, 7 individuals with GIST in young adulthood including 2 with germline KIT mutations, 3 individuals with neurofibromatosis 1, one 63-year-old female with multifocal gastric epithelioid GIST with lymph node metastases, and 104 consecutive unselected individuals with apparently sporadic GIST. The GISTs and paragangliomas arising in CT, the pediatric GIST, and the multifocal gastric GIST from the 63-year-old showed negative SDHB staining. GISTs from the 7 young adults and 3 with neurofibromatosis were SDHB positive. Of the unselected GISTs, 101 (97%) were positive. One of the negative GISTs arose in a 48-year-old female with previous recurrent multifocal gastric GISTs and the other 2 arose in females also in their 40s with gastric GISTs with epithelioid morphology. We conclude that negative staining for SDHB is characteristic of the GISTs of CT and the subgroup of pediatric GISTs which it resembles. Furthermore, when negative staining occurs in apparently sporadic GISTs in adults, the GISTs show morphologic and clinical features similar to pediatric and CT type GISTs. GISTs may therefore be divided into type 1 (SDHB positive) and type 2 (SDHB negative) subtypes.
%Z FOR Codes: 1108


%0 Journal Article
%~ PubMed
%A Gill, Anthony J
%A Benn, Diana E
%A Chou, Angela
%A Clarkson, Adele
%A Muljono, Anita
%A Meyer-Rochow, Goswin Y
%A Richardson, Anne Louise
%A Sidhu, Stan B
%A Robinson, Bruce G
%A Clifton-Bligh, Roderick J
%T Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes.
%B Human Pathology
%D 2010
%C United States
%I WB Saunders Co.
%V 41
%N 6
%P 805-814
%@ 1532-8392
%X Up to 30% of pheochromocytomas and paragangliomas are associated with germline RET, Von Hippel-Lindau (VHL), neurofibromatosis type I (NF1), and succinate dehydrogenase subunits (SDHB, SDHC, and SDHD) mutations. Genetic testing allows familial counseling and identifies subjects at high risk of malignancy (SDHB mutations) or significant multiorgan disease (RET, VHL, or NF1). However, conventional genetic testing for all loci is burdensome and costly. We performed immunohistochemistry for SDHB on 58 tumors with known SDH mutation status. We defined positive as granular cytoplasmic staining (a mitochondrial pattern), weak diffuse as a cytoplasmic blush lacking definite granularity, and negative as completely absent staining in the presence of an internal positive control. All 12 SDH mutated tumors (6 SDHB, 5 SDHD, and 1 SDHC) showed weak diffuse or negative staining. Nine of 10 tumors with known mutations of VHL, RET, or NF1 showed positive staining. One VHL associated tumor showed weak diffuse staining. Of 36 tumors without germline mutations, 34 showed positive staining. One paraganglioma with no known SDH mutation but clinical features suggesting familial disease was negative, and one showed weak diffuse staining. We also performed immunohistochemistry for SDHB on 143 consecutive unselected tumors of which 21 were weak diffuse or negative. As SDH mutations are virtually always germline, we conclude that approximately 15% of all pheochromocytomas or paragangliomas are associated with germline SDH mutation and that immunohistochemistry can be used to triage genetic testing. Completely absent staining is more commonly found with SDHB mutation, whereas weak diffuse staining often occurs with SDHD mutation.
%Z FOR Codes: 1112


%0 Journal Article
%~ PubMed
%A Abraham, Deepak
%A Delbridge, Leigh
%A Clifton-Bligh, Roderick
%A Clifton-Bligh, Phillip
%A Grodski, Simon
%A Robinson, Bruce G
%A Messina, Marinella
%A Sidhu, Stan
%T Medullary thyroid carcinoma presenting with an initial CEA elevation.
%B ANZ Journal of Surgery
%D 2010
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 80
%N 11
%P 831-833
%@ 1445-2197
%X Background:??? Carcinoembryonic antigen (CEA) is a tumour marker commonly associated with gastrointestinal malignancy. Patients presenting with an elevated CEA will therefore often undergo extensive investigations in order to elucidate an underlying gastrointestinal malignancy that may not be clinically apparent. However the GI tract is not the only source of CEA elevation. Methods:??? We present a series of patients presenting with raised CEA levels that were initially investigated for a gastrointestinal cause, but after work up were detected to have medullary thyroid cancer. Results:??? Four patients with raised CEA were evaluated for a gastrointestinal cause for the elevation. We discuss the non gastrointestinal causes for an elevated CEA. Conclusion:??? The paper highlights that in patients presenting with an elevated CEA, in whom a gastrointestinal cause has been ruled out, a tumour of neuroendocrine origin needs to be considered as a cause for the elevated CEA.
%Z FOR Codes: 110306


%0 Journal Article
%~ PubMed
%A Meyer-Rochow, Goswin Y
%A Jackson, Nicole E
%A Conaglen, John V
%A Whittle, Denis E
%A Kunnimalaiyaan, Muthusamy
%A Chen, Herbert
%A Westin, Gunnar
%A Sandgren, Johanna
%A Stalberg, Peter
%A Khanafshar, Elham
%A Shibru, Daniel
%A Duh, Quan-Yang
%A Clark, Orlo H
%A Kebebew, Electron
%A Gill, Anthony
%A Clifton-Bligh, Roderick
%A Robinson, Bruce G
%A Benn, Diana Elaine
%A Sidhu, Stan B
%T MicroRNA profiling of benign and malignant pheochromocytoma identifies novel diagnostic and therapeutic targets.
%B Endocrine-related Cancer
%D 2010
%C United Kingdom
%I Society for Endocrinology
%V 17
%N 3
%P 835-846
%@ 1479-6821
%X MicroRNAs (miRNAs) are small RNAs ( approximately 22 bp) that post-transcriptionally regulate protein expression and are found to be differentially expressed in a number of human cancers. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. We performed miRNA microarray expression profiling on a cohort of 12 benign and 12 malignant pheochromocytomas and identified a number of differentially expressed miRNAs. These results were validated in a separate cohort of ten benign and ten malignant samples using real-time quantitative RT-PCR; benign samples had a minimum follow-up of at least 2 years. It was found that IGF2 as well as its intronic miR-483-5p was over-expressed, while miR-15a and miR-16 were under-expressed in malignant tumours compared with benign tumours. These miRNAs were found to be diagnostic and prognostic markers for malignant pheochromocytoma. The functional role of miR-15a and miR-16 was investigated in vitro in the rat PC12 pheochromocytoma cell line, and these miRNAs were found to regulate cell proliferation via their effect on cyclin D1 and apoptosis. These data indicate that miRNAs play a pivotal role in the biology of malignant pheochromocytoma, and represent an important class of diagnostic and prognostic biomarkers and therapeutic targets warranting further investigation.
%Z FOR Codes: 111203


%0 Journal Article
%~ PubMed
%A Matar, Elie
%A Cook, Raymond J
%A Fowler, Adam R
%A Biggs, Michael T
%A Little, Nicholas S
%A Wheeler, Helen R
%A Robinson, Bruce G
%A McDonald, Kerrie L
%T Post-contrast enhancement as a clinical indicator of prognosis in patients with anaplastic astrocytoma.
%B Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
%D 2010
%C United Kingdom, Aust
%I Churchill Livingstone
%V 17
%N 8
%P 993-6
%@ 1532-2653
%X Diagnosis of an anaplastic astrocytoma (World Health Organization grade III) is associated with a highly variable prognosis. The identification of clinical markers that allow a more careful delineation of this prognostic spectrum is urgently needed. In this study, we analysed 48 patients with a histological diagnosis of anaplastic astrocytoma and found peritumoral post-gadolinium contrast enhancement to be a clear prognostic marker of poor prognosis. Multivariate analysis also confirmed surgery type, Karnofsky Performance Status score (<70) and increasing age as independent adverse predictors of survival. The survival differences observed in the enhancing and non-enhancing lesions in patients diagnosed with anaplastic astrocytoma supports the existence of a broad anaplastic spectrum of disease, with enhancement being a clinical marker of tumour progression along this spectrum.
%Z FOR Codes: 111208


%0 Journal Article
%~ PubMed
%A Isaacs, Joseph D
%A McMullen, Todd P W
%A Sidhu, Stan B
%A Sywak, Mark S
%A Robinson, Bruce G
%A Delbridge, Leigh W
%T Predictive value of the Delphian and level VI nodes in papillary thyroid cancer.
%B ANZ Journal of Surgery
%D 2010
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 80
%N 11
%P 834-838
%@ 1445-2197
%X Background:??? Recent published data has shown that metastatic involvement of the prelaryngeal or Delphian lymph node (DLN), the highest of the central (level VI) cervical lymph nodes, is highly predictive of advanced nodal disease in papillary thyroid cancer (PTC). The aims of this study were to determine the diagnostic accuracy of all the level VI cervical nodes in PTC and to determine which node group, if any, is the most accurate in predicting lateral node (N1b) disease. Methods:??? This was a retrospective cohort study. Data were obtained from the University of Sydney Endocrine Surgical Unit Database and through a review of the histopathology records. The study cohort was composed of 177 consecutive patients with a final diagnosis of PTC who underwent total thyroidectomy and lymph node dissection, spanning the period from May 2001 to December 2006. Results:??? Of the 177 patients with PTC, 86 had the DLN removed, 51 had a pretracheal node removed and 76 had the paratracheal group removed. DLN, paratracheal and pretracheal node disease was present in 21%, 39% and 46%, respectively. Lateral node (N1b) disease was present in 35%. Paratracheal node involvement was mildly predictive of further disease with patients 1.7 times more likely to have lateral node involvement (sensitivity???=???55%, specificity???=???68%). Pretracheal node involvement was moderately predictive of further disease with patients three times more likely to have lateral node involvement (sensitivity???=???72%, specificity???=???74%). DLN involvement was highly predictive of further node involvement with patients nine times more likely to have lateral node disease (sensitivity???=???53%, specificity???=???94%) and 40 times more likely to have any nodal disease (sensitivity???=???41%, specificity???=???100%). Conclusion:??? This is the first study to examine the diagnostic accuracy of all level VI lymph nodes in PTC. While, metastatic involvement of all central nodal groups is indicative of further disease, the DLN is the most accurate predictor.
%Z FOR Codes: 110323


%0 Journal Article
%~ PubMed
%A McDonald, Kerrie L
%A McDonnell, Julie
%A Muntoni, Alessandra
%A Henson, Jeremy D
%A Hegi, Monika E
%A von Deimling, Andreas
%A Wheeler, Helen R
%A Cook, Ray J
%A Biggs, Michael T
%A Little, Nicholas S
%A Robinson, Bruce G
%A Reddel, Roger R
%A Royds, Janice A
%T Presence of Alternative Lengthening of Telomeres Mechanism in Patients With Glioblastoma Identifies a Less Aggressive Tumor Type With Longer Survival.
%B Journal of neuropathology and experimental neurology
%D 2010
%C United States
%I Lippincott Williams & Wilkins
%V 69
%N 7
%P 729-36
%@ 0022-3069
%X Patients with glioblastoma (GBM) have variable clinical courses, but the factors that underlie this heterogeneity are not understood. To determine whether the presence of the telomerase-independent alternative lengthening of telomeres (ALTs) mechanism is a significant prognostic factor for survival, we performed a retrospective analysis of 573 GBM patients. The presence of ALT was identified in paraffin sections using a combination of immunofluorescence for promyelocytic leukemia body and telomere fluorescence in situ hybridization. Alternative lengthening of telomere was present in 15% of the GBM patients. Patients with ALT had longer survival that was independent of age, surgery, and other treatments. Mutations in isocitrate dehydrogenase (IDH1mut) 1 frequently accompanied ALT, and in the presence of both molecular events, there was significantly longer overall survival. These data suggest that most ALT+ tumors may be less aggressive proneural GBMs, and the better prognosis may relate to the set of genetic changes associated with this tumor subtype. Despite improved overall survival of patients treated with the addition of chemotherapy to radiotherapy and surgery, ALT and chemotherapy independently provided a survival advantage, but these factors were not found to be additive. These results suggest a critical need for developing new therapies to target these specific GBM subtypes.
%Z FOR Codes: 111299


%0 Journal Article
%~ PubMed
%A Meyer-Rochow, Goswin
%A Schembri, Geoff
%A Benn, Diana
%A Sywak, Mark
%A Delbridge, Leigh
%A Robinson, Bruce
%A Roach, Paul
%A Sidhu, Stan
%T The Utility of Metaiodobenzylguanidine Single Photon Emission Computed Tomography/Computed Tomography (MIBG SPECT/CT) for the Diagnosis of Pheochromocytoma.
%B Annals of Surgical Oncology
%D 2010
%C United States
%I Springer New York LLC
%V 17
%N 2
%P 392-400
%@ 1068-9265
%X The enhancement of metaiodobenzylguanidine single photon emission computed tomography (MIBG SPECT) imaging through the addition of CT images fused with SPECT data (coregistered MIBG SPECT/CT imaging) is new technology that allows direct correlation of anatomical and functional information. We hypothesized that MIBG SPECT/CT imaging would provide additional information and improve diagnostic confidence for the radiological localization of a pheochromocytoma, in particular for patients at high risk of multifocal or recurrent disease.
%Z FOR Codes: 604


%0 Journal Article
%~ PubMed
%A Robinson, Bruce G
%A Paz-Ares, Luis
%A Krebs, Annetta
%A Vasselli, James
%A Haddad, Robert
%T Vandetanib (100 Milligrams) in Patients with Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer.
%B The Journal of clinical endocrinology and metabolism
%D 2010
%C United States
%I The Endocrine Society
%V 95
%N 6
%P 2664-71
%@ 1945-7197
%X Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC.
%Z FOR Codes: 111207


%0 Journal Article
%~ PubMed
%A Howell, Viive M
%A Gill, Anthony
%A Clarkson, Adele
%A Nelson, Anne E
%A Dunne, Robert
%A Delbridge, Leigh W
%A Robinson, Bruce G
%A Teh, Bin Tean
%A Gimm, Oliver
%A Marsh, Deborah J
%T Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma.
%B The Journal of clinical endocrinology and metabolism
%D 2009
%C United States
%I The Endocrine Society
%V 94
%N 2
%P 434-41
%@ 0021-972X
%X Parafibromin, encoded by HRPT2, is the first marker with significant benefit in the diagnosis of parathyroid carcinoma. However, because parafibromin is only involved in up to 70% of parathyroid carcinomas and loss of parafibromin immunoreactivity may not be observed in all cases of HRPT2 mutation, a complementary marker is needed.
%Z FOR Codes: 111202 110306 110316


%0 Journal Article
%~ Isi
%A Neumann, H. P. H.
%A Erlic, Z.
%A Boedeker, C. C.
%A Rybicki, L. A.
%A Robledo, M.
%A Hermsen, M.
%A Schiavi, F.
%A Falcioni, M.
%A Kwok, P.
%A Bauters, C.
%A Lampe, K.
%A Fischer, M.
%A Edelman, E.
%A Benn, D. E.
%A Robinson, B. G.
%A Wiegand, S.
%A Rasp, G.
%A Stuck, B. A.
%A Hoffmann, M. M.
%A Sullivan, M.
%A Sevilla, M. A.
%A Weiss, M. M.
%A Peczkowska, M.
%A Kubaszek, A.
%A Pigny, P.
%A Ward, R. L.
%A Learoyd, D.
%A Croxson, M.
%A Zabolotny, D.
%A Yaremchuk, S.
%A Draf, W.
%A Muresan, M.
%A Lorenz, R. R.
%A Knipping, S.
%A Strohm, M.
%A Dyckhoff, G.
%A Matthias, C.
%A Reisch, N.
%A Preuss, S. F.
%A Esser, D.
%A Walter, M. A.
%A Kaftan, H.
%A Stover, T.
%A Fottner, C.
%A Gorgulla, H.
%A Malekpour, M.
%A Zarandy, M. M.
%A Schipper, J.
%A Brase, C.
%A Glien, A.
%A Kuhnemund, M.
%A Koscielny, S.
%A Schwerdtfeger, P.
%A Valimaki, M.
%A Szyfter, W.
%A Finckh, U.
%A Zerres, K.
%A Cascon, A.
%A Opocher, G.
%A Ridder, G. J.
%A Januszewicz, A.
%A Suarez, C.
%A Eng, C.
%T Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out
%B Cancer Research
%D 2009
%C United States
%I American Association for Cancer Research (A AC R)
%V 69
%N 8
%P 3650-3656
%@ 0008-5472
%X 
%Z FOR Codes: 111203


%0 Journal Article
%~ PubMed
%A Meyer-Rochow, Goswin Y
%A Smith, Janine M
%A Richardson, Anne-Louise
%A Marsh, Deborah J
%A Sidhu, Stan B
%A Robinson, Bruce G
%A Benn, Diana E
%T Denaturing High Performance Liquid Chromatography Detection of SDHB, SDHD, and VHL Germline Mutations in Pheochromocytoma.
%B Journal of Surgical Research
%D 2009
%C United Kingdom
%I Expert Reviews Ltd.
%V 157
%N 1
%P 55-62
%@ 1095-8673
%X Pheochromocytomas are neuroendocrine tumors of chromaffin cell origin which arise from the adrenal medulla and less commonly the extra-adrenal sympathetic paraganglia. Pheochromocytomas are component tumors of the familial syndromes multiple endocrine neoplasia Type 2, von Hippel Lindau disease, Neurofibromatosis Type 1, and the pheochromocytoma/paraganglioma syndromes caused by mutations in the RET, VHL, NF1, SDHB, and SDHD genes, respectively. The aim of this study was to evaluate denaturing high performance liquid chromatography (dHPLC) as a screening tool for the detection of germline mutations within VHL, SDHB, and SDHD in pheochromocytoma patients.
%Z FOR Codes: 110323 111203


%0 Journal Article
%~ PubMed
%A Elston, Marianne S
%A McDonald, Kerrie L
%A Clifton-Bligh, Roderick J
%A Robinson, Bruce G
%T Familial pituitary tumor syndromes.
%B Nature reviews. Endocrinology
%D 2009
%C United States
%I Nature Publishing Group
%V 5
%N 8
%P 453-61
%@ 1759-5037
%X The vast majority of pituitary tumors are benign and occur sporadically; however, they can still result in significant morbidity and even premature mortality through mass effects and hormone dysfunction. The etiology of sporadic tumors is still poorly understood; by contrast, advances have been made in our understanding of familial pituitary adenoma syndromes in the past decade. Currently, four genes are known to be associated with familial pituitary tumor syndromes: MEN1, CDKN1B, PRKAR1A and AIP. The first three genes are associated with a variety of extrapituitary pathologies, for example, primary hyperparathyroidism with multiple endocrine neoplasia type 1, which might aid identification of these syndromes. By contrast, AIP mutations seem to occur in the setting of isolated familial pituitary adenomas, particularly of the growth-hormone-secreting subtype. Awareness and identification of familial pituitary tumor syndromes is important because of potential associated pathologies and important implications for family members. Here, we review the current knowledge of familial pituitary tumor syndromes.
%Z FOR Codes: 110306 111203


%0 Journal Article
%~ PubMed
%A , NICE-SUGAR Study Investigators
%A Finfer, Simon
%A Chittock, Dean R
%A Su, Steve Yu-Shuo
%A Blair, Deborah
%A Foster, Denise
%A Dhingra, Vinay
%A Bellomo, Rinaldo
%A Cook, Deborah
%A Dodek, Peter
%A Henderson, William R
%A Hébert, Paul C
%A Heritier, Stephane
%A Heyland, Daren K
%A McArthur, Colin
%A McDonald, Ellen
%A Mitchell, Imogen
%A Myburgh, John A
%A Norton, Robyn
%A Potter, Julie
%A Robinson, Bruce G
%A Ronco, Juan J
%T Intensive versus conventional glucose control in critically ill patients.
%B New England Journal of Medicine
%D 2009
%C United States
%I Massachusetts Medical Society
%V 360
%N 13
%P 1283-1297
%@ 1533-4406
%X BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)
%Z FOR Codes: 110309 10402


%0 Journal Article
%~ PubMed
%A Meyer-Rochow, Goswin Y
%A McMullen, Todd P
%A Gill, Anthony J
%A Sywak, Mark S
%A Robinson, Bruce G
%T Intra-abdominal insular thyroid carcinoma metastasis.
%B Thyroid
%D 2009
%C United States
%I Mary Ann Liebert, Inc. Publishers
%V 19
%N 5
%P 527-530
%@ 1557-9077
%X BACKGROUND: In thyroid cancer, metastases to intra-abdominal solid organs are uncommon and intra-peritoneal metastases are extremely rare. Here we present the management and outcome of a young patient with a large radioiodine resistant intra-peritoneal metastasis of insular thyroid cancer. SUMMARY: A 28-year-old woman with known radioiodine resistant metastatic insular (poorly differentiated) thyroid carcinoma and multiple previous resected metastases presented with acute onset of bowel obstruction due to a large pelvic mass. The pelvic mass was resected and histologically confirmed to be an insular thyroid carcinoma metastasis. She made an uneventful recovery from her surgery and continues to have a good quality of life despite low volume metastatic disease. CONCLUSION: As this patient demonstrates, a rational but aggressive surgical approach is warranted for patients with radioiodine-resistant metastatic thyroid disease.
%Z FOR Codes: 110316 110323 110306


%0 Journal Article
%~ PubMed
%A McCormack, Ann I
%A McDonald, Kerrie L
%A Gill, Anthony J
%A Clark, Susan J
%A Burt, Morton G
%A Campbell, Kirsten A
%A Braund, Wilton J
%A Little, Nicholas S
%A Cook, Raymond J
%A Grossman, Ashley B
%A Robinson, Bruce G
%A Clifton-Bligh, Roderick J
%T Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours.
%B Clinical endocrinology
%D 2009
%C United Kingdom
%I Wiley-Blackwell Publishing Ltd.
%V 71
%N 2
%P 226-33
%@ 0300-0664
%X Recent case reports detail the successful use of temozolomide in the management of aggressive pituitary tumours. O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that counteracts the effect of temozolomide.
%Z FOR Codes: 110306 1101


%0 Journal Article
%~ PubMed
%A Soon, Patsy
%A Gill, Anthony
%A Benn, Diana
%A Clarkson, Adele
%A Robinson, Bruce
%A McDonald, Kerrie
%A Sidhu, Stan
%T Microarray gene expression and immunohistochemistry analyses of adrenocortical tumours identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas.
%B Endocrine-Related Cancer
%D 2009
%C United Kingdom
%I Society for Endocrinology
%V 16
%N 2
%P 573-583
%@ 1351-0088
%X The management of adrenocortical tumors (ACTs) is complex. The Weiss score is the present most widely used system for ACT diagnosis. An ACT is scored from 0 to 9, with a higher score correlating with increased malignancy. However, ACTs with a score of 3 can be phenotypically benign or malignant. Our objective is to use microarray profiling of a cohort of adrenocortical carcinomas (ACCs) and adrenocortical adenomas (ACAs) to identify discriminatory genes that could be used as an adjunct to the Weiss score. A cohort of Weiss score defined ACCs and ACAs were profiled using Affymetrix HGU133plus2.0 genechips. Genes with high-discriminatory power were identified by univariate and multivariate analyses and confirmed by quantitative real-time reverse transcription PCR and immunohistochemistry (IHC). The expression of IGF2, MAD2L1, and CCNB1 were significantly higher in ACCs compared with ACAs while ABLIM1, NAV3, SEPT4, and RPRM were significantly lower. Several proteins, including IGF2, MAD2L1, CCNB1, and Ki-67 had high-diagnostic accuracy in differentiating ACCs from ACAs. The best results, however, were obtained with a combination of IGF2 and Ki-67, with 96% sensitivity and 100% specificity in diagnosing ACCs. Microarray gene expression profiling accurately differentiates ACCs from ACAs. The combination of IGF2 and Ki-67 IHC is also highly accurate in distinguishing between the two groups and is particularly helpful in ACTs with Weiss score of 3.
%Z FOR Codes: 1112


%0 Journal Article
%~ PubMed
%A Elston, Marianne S
%A Gill, Anthony J
%A Conaglen, John V
%A Clarkson, Adele
%A Cook, Raymond J
%A Little, Nicholas S
%A Robinson, Bruce G
%A Clifton-Bligh, Roderick J
%A McDonald, Kerrie L
%T Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas.
%B Journal of Clinical Endocrinology and Metabolism
%D 2009
%C United States
%I The Endocrine Society
%V 94
%N 4
%P 1436-1442
%@ 0021-972X
%X CONTEXT: Loss of the cell adhesion protein E-cadherin is associated with invasion and metastasis in a number of malignancies. Recent studies have highlighted that loss of E-cadherin cell membrane expression may be accompanied by its detection in the nucleus, suggesting cellular redistribution during neoplasia. Pituitary tumors, although typically benign, may be locally invasive, and loss of membranous E-cadherin has been reported as a marker of invasion in prolactinomas. OBJECTIVE: Our objective was to study E-cadherin expression in pituitary adenomas, specifically whether nuclear redistribution occurs in this setting. METHODS: Immunohistochemistry, RT-PCR, and direct sequencing were performed. RESULTS: Strong cytoplasmic membrane staining was present in all eight normal samples but completely absent in 21 of 44 adenomas (48%) with weak staining in an additional 11 adenomas using an antibody against the extracellular domain of E-cadherin. To identify nuclear translocation of the protein, immunohistochemistry was performed using an antibody against the cytoplasmic domain. Nuclear staining was present in 38 of 44 adenomas (86%) and absent in normal tissue. Nuclear E-cadherin inversely correlated with loss of E-cadherin cytoplasmic membrane staining and was associated with tumor invasion (P = 0.009). To investigate the mechanism of nuclear redistribution of E-cadherin, we performed RT-PCR of mRNA and sequenced tumor DNA. E-cadherin mRNA expression was reduced in only one of 30 samples (3%). No mutations were detected. CONCLUSIONS: E-cadherin was frequently lost at the cytoplasmic membrane but detected in the nucleus, suggesting that cleavage of the extracellular domain and nuclear translocation of E-cadherin is a common event that may determine local invasion in pituitary adenomas.
%Z FOR Codes: 110306


%0 Journal Article
%~ PubMed
%A Meyer-Rochow, Goswin Y
%A Soon, Patsy S H
%A Delbridge, Leigh W
%A Sywak, Mark S
%A Bambach, Chris P
%A Clifton-Bligh, Roderick J
%A Robinson, Bruce G
%A Sidhu, Stan B
%T Outcomes of minimally invasive surgery for phaeochromocytoma.
%B ANZ Journal of Surgery
%D 2009
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 79
%N 5
%P 367-370
%@ 1445-1433
%X Laparoscopic adrenalectomy is now accepted as the procedure of choice for the resection of benign adrenocortical tumours, but few studies have assessed whether the outcomes of laparoscopic adrenalectomy for adrenal phaeochromocytoma are similar to that of other adrenal tumour types. This is a retrospective cohort study. Clinical and operative data were obtained from an adrenal tumour database and hospital records. A total of 191 patients had laparoscopic adrenalectomy, of which 36 were for phaeochromocytoma, over a 12-year period. Length of hospital stay (4.8 vs 3.6 days, P= 0.03) and total operating times (183 vs 157 min, P= 0.01) were greater in the laparoscopic phaeochromocytoma resection group. Despite the greater size of the phaeochromocytomas compared to the remaining adrenal tumour types (44 mm vs 30 mm, P < 0.01), however, rate of conversion and morbidity were no different. Laparoscopic adrenalectomy for phaeochromocytoma is a safe procedure with similar outcomes to laparoscopic adrenalectomy for other adrenal tumour types.
%Z FOR Codes: 110323


%0 Journal Article
%~ PubMed
%A Figtree, G A
%A Robinson, B G
%A Channon, K M
%A Watkins, H
%T Polymorphism upstream of estrogen receptor alpha reverses negative regulation of transcription.
%B International journal of cardiology
%D 2009
%C Ireland
%I Elsevier Ireland
%V 144
%N 1
%P 86-8
%@ 0167-5273
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Warusavitarne, Janindra
%A McDougall, Fiona
%A de Silva, Keshani
%A Barnetson, Rebecca
%A Messina, Marinella
%A Robinson, Bruce
%A Schnitzler, Margaret
%T Restoring TGFbeta function in microsatellite unstable (MSI-H) colorectal cancer reduces tumourigenicity but increases metastasis formation.
%B International journal of colorectal disease
%D 2009
%C Germany
%I Springer
%V 24
%N 0
%P 139-44
%@ 0179-1958
%X TGFbeta is an important cell growth regulator which may have a role in metastasis formation. Microsatellite unstable (MSI-H) colon cancer serves as a unique model to demonstrate this as most MSI-H colon cancers have a mutation in the transforming growth factor beta receptor II (TGFbetaRII) gene and a low metastatic rate.
%Z FOR Codes: 110323


%0 Journal Article
%~ PubMed
%A Tacon, Lyndal J
%A Soon, Patsy S
%A Gill, Anthony J
%A Chou, Angela S
%A Clarkson, Adele
%A Botling, Johan
%A Stalberg, Peter L H
%A Skogseid, Britt M
%A Robinson, Bruce G
%A Sidhu, Stanley B
%A Clifton-Bligh, Roderick J
%T The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors.
%B Journal of Clinical Endocrinology and Metabolism
%D 2009
%C United States
%I The Endocrine Society
%V 94
%N 11
%P 4591-4599
%@ 1945-7197
%X CONTEXT: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. The Weiss score is the most widely accepted method for distinguishing an ACC from an adrenocortical adenoma (ACA); however, in borderline cases, accurate diagnosis remains problematic. We recently discovered that the glucocorticoid receptor (GR) gene NR3C1 is significantly up-regulated in ACCs compared with ACAs in global gene expression studies. OBJECTIVE: Our objective was to study GR expression in adrenocortical tumors (ACTs) and to assess its utility as an adjunct to the Weiss score. DESIGN: Microarray analysis, real-time quantitative RT-PCR (qPCR), immunohistochemistry, Western blot, and direct sequencing were performed. RESULTS: Analysis of 28 ACTs by microarray and 49 ACTs by qPCR found NR3C1 expression to be up-regulated in ACCs compared with ACAs (P < 0.001). Western blotting and RT-PCR confirmed the presence of the GRalpha isoform in ACCs, and no mutations were detected on direct sequencing. Immunohistochemistry for GR in an overlapping cohort of ACTs demonstrated strongly positive nuclear staining in 31 of 33 ACCs (94%), with negative staining in 40 of 41 ACAs (98%) (P < 0.001). This finding was validated in an external cohort of ACTs, such that 14 of 18 ACCs (78%) demonstrated positive nuclear staining whereas 32 of 33 ACAs (94%) were negative (P < 0.001). CONCLUSIONS: The immunohistochemical finding of nuclear GR staining identified ACCs with high diagnostic accuracy. We propose that GR immunohistochemistry may complement the Weiss score in the diagnosis of ACC in cases that display borderline histology. The possibility that GR is transcriptionally active in these tumors, and may therefore be a therapeutic target, requires further study.
%Z FOR Codes: 1101


%0 Journal Article
%~ PubMed
%A Soon, Patsy Siok Hwa
%A Tacon, Lyndal J
%A Gill, Anthony J
%A Bambach, Christopher P
%A Sywak, Mark S
%A Campbell, Peter R
%A Yeh, Michael W
%A Wong, Steven G
%A Clifton-Bligh, Roderick J
%A Robinson, Bruce G
%A Sidhu, Stan B
%T miR-195 and miR-483-5p Identified as Predictors of Poor Prognosis in Adrenocortical Cancer.
%B Clinical Cancer Research
%D 2009
%C United States
%I American Association for Cancer Research
%V 15
%N 24
%P 7684-7692
%@ 1078-0432
%X PURPOSE: Adrenocortical adenomas are common, whereas adrenocortical carcinomas are rare. Discriminating between benign and malignant adrenocortical tumors using conventional histology can be difficult. In addition, adrenocortical carcinomas generally have poor prognosis and limited treatment options. MicroRNAs are short noncoding RNAs that are involved in regulation of gene transcription. EXPERIMENTAL DESIGN: To identify microRNAs involved in the pathogenesis of adrenocortical tumors, expression profiling of microRNAs was done on a cohort of 22 adrenocortical carcinomas, 27 adrenocortical adenomas, and 6 normal adrenal cortices. RESULTS: Twenty-three microRNAs were found to be significantly differentially expressed between adrenocortical carcinomas and adrenocortical adenomas. miR-335 and miR-195 were significantly downregulated in adrenocortical carcinomas compared with adrenocortical adenomas. This result was further validated in an external cohort of six adrenocortical carcinomas and four adrenocortical adenomas. Using Kaplan-Meier analysis, downregulation of miR-195 and upregulation of miR-483-5p in adrenocortical carcinomas were significantly associated with poorer disease-specific survival. CONCLUSIONS: These findings indicate that deregulation of microRNAs is a recurring event in human adrenocortical carcinomas and that aberrant expression of miR-195 and miR-483-5p identifies a subset of poorer prognosis adrenocortical carcinomas. (Clin Cancer Res 2009;15(24):7684-92).
%Z FOR Codes: 111201


%0 Journal Article
%~ PubMed
%A Figtree, Gemma A
%A Grieve, Stuart M
%A Speller, Bridget
%A Geiger, Mary-Jane
%A Robinson, Bruce G
%A Channon, Keith M
%A Ragoussis, Jiannis
%A Collins, Peter
%A Watkins, Hugh
%T A commonly occurring polymorphism upstream of the estrogen receptor alpha alters transcription and is associated with increased HDL.
%B Atherosclerosis
%D 2008
%C Ireland
%I Elsevier Ireland Ltd
%V 199
%N 2
%P 354-61
%@ 0021-9150
%X Given the role of estrogen in the regulation of lipid metabolism, we screened for functional polymorphisms in the estrogen receptor alpha (ER*), and examined for their influence on serum cholesterol.
%Z FOR Codes: 110399 110299


%0 Journal Article
%~ PubMed
%A Lee, Jia-Jing
%A Au, Amy Y M
%A Foukakis, Theodoros
%A Barbaro, Michela
%A Kiss, Nimrod
%A Clifton-Bligh, Roderick
%A Staaf, Johan
%A Borg, Ake
%A Delbridge, Leigh
%A Robinson, Bruce G
%A Wallin, Göran
%A Höög, Anders
%A Larsson, Catharina
%T Array-CGH identifies cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinoma.
%B Endocrine-Related Cancer
%D 2008
%C United Kingdom
%I Society for Endocrinology
%V 15
%N 3
%P 801-815
%@ 1351-0088
%X Anaplastic thyroid cancer (ATC) is a rare but highly aggressive disease with largely unexplained etiology and molecular pathogenesis. In this study, we analyzed genome-wide copy number changes, BRAF (V-raf sarcoma viral oncogene homolog B1) mutations, and p16 and cyclin D1 expressions in a panel of ATC primary tumors. Three ATCs harbored the common BRAF mutation V600E. Using array-comparative genomic hybridisation (array-CGH), several distinct recurrent copy number alterations were revealed including gains in 16p11.2, 20q11.2, and 20q13.12. Subsequent fluorescence in situ hybridization revealed recurrent locus gain of UBCH10 in 20q13.12 and Cyclin D1 (CCND1) in 11q13. The detection of a homozygous loss encompassing the CDKN2A locus in 9p21.3 motivated the examination of p16 protein expression, which was undetectable in 24/27 ATCs (89%). Based on the frequent gain in 11q13 (41%; n=11), the role of CCND1 was further investigated. Expression of cyclin D1 protein was observed at varying levels in 18/27 ATCs (67%). The effect of CCND1 on thyroid cell proliferation was assessed in vitro in ATC cells by means of siRNA and in thyroid cells after CCND1 transfection. In summary, the recurrent chromosomal copy number changes and molecular alterations identified in this study may provide an insight into the pathogenesis and development of ATC.
%Z FOR Codes: 1112


%0 Journal Article
%~ PubMed
%A Grodski, Simon
%A Brown, Tani
%A Sidhu, Stan
%A Gill, Anthony
%A Robinson, Bruce
%A Learoyd, Diana
%A Sywak, Mark
%A Reeve, Tom
%A Delbridge, Leigh
%T Increasing incidence of thyroid cancer is due to increased pathologic detection.
%B Surgery
%D 2008
%C United States
%I Mosby
%V 144
%N 6
%P 1038-1043
%@ 0039-6060
%X BACKGROUND: There has been a marked increase in the incidence of thyroid cancer worldwide over recent decades. Patients with retrosternal goiter (RSG) are not picked up generally by common surveillance techniques such as ultrasound. The aim of this project was to study the incidence of thyroid cancer in patients with RSG. METHODS: This is a retrospective cohort study. Documented were patient demographics as well as the size, type, and numbers of thyroid cancers. The number of routine histologic blocks examined for multinodular goiter in the different time periods was also examined. RESULTS: Within a cohort of 13,793 thyroidectomies performed over 40 years, there were 2,260 patients (14%) who underwent surgery for RSG. The percentage of patients with RSG containing thyroid cancer increased from 3.6 to 7.5% (P < .05); however, once papillary microcarcinomas (PMC) (</=10 mm) were excluded there was no increase in cancer incidence (3.4-3.5%, P = .9). The increase in the number of PMC''s diagnosed is associated with the increase in the routine number of blocks sampled over the 40-year time period (P < .01). CONCLUSION: This study has confirmed an increase in the incidence of thyroid cancer over 4 decades. However, that increase appears to be due to an increase in the diagnosis of PMC associated with increased sampling of resected specimens by pathologists, raising the possibility that the current epidemic of thyroid cancer may be largely manmade.
%Z FOR Codes: 110306


%0 Journal Article
%~ PubMed
%A Soon, P S H
%A Yeh, M W
%A Delbridge, L W
%A Bambach, C P
%A Sywak, M S
%A Robinson, B G
%A Sidhu, S B
%T Laparoscopic surgery is safe for large adrenal lesions.
%B European Journal of Surgical Oncology
%D 2008
%C UK
%I WB Saunders Co. Ltd
%V 34
%N 1
%P 67-70
%@ 0748-7983
%X Laparoscopic adrenalectomy has surpassed open adrenalectomy as the gold standard for excision of benign adrenal lesions. The size threshold for offering laparoscopic adrenalectomy is controversial as the prevalence of adrenocortical carcinoma increases with increasing tumour size. The aim of this paper was to assess the safety of laparoscopic adrenalectomy for large adrenal tumours (tumours > or = 60 mm).
%Z FOR Codes: 111204


%0 Journal Article
%~ PubMed
%A Soon, Patsy S H
%A Libe, Rossella
%A Benn, Diana E
%A Gill, Anthony
%A Shaw, Janet
%A Sywak, Mark S
%A Groussin, Lionel
%A Bertagna, Xavier
%A Gicquel, Christine
%A Bertherat, Jerome
%A McDonald, Kerrie L
%A Sidhu, Stan B
%A Robinson, Bruce G
%T Loss of heterozygosity of 17p13, with possible involvement of ACADVL and ALOX15B, in the pathogenesis of adrenocortical tumors.
%B Annals of Surgery
%D 2008
%C United States
%I Lippincott Williams and Wilkins
%V 247
%N 1
%P 157-164
%@ 0003-4932
%X OBJECTIVE: To determine the minimal common region of loss on 17p13 in a cohort of adrenocortical carcinomas (ACCs) (defined by a Weiss score > or =3) and adrenocortical adenomas (ACAs) (defined by a Weiss score <3) and subsequently to assess 3 genes in this region that could be involved in adrenocortical tumorigenesis. SUMMARY BACKGROUND DATA: Loss of heterozygosity (LOH) of 17p13 has been demonstrated to occur more frequently in ACCs compared with ACAs. METHODS: Using 12 microsatellite markers across 17p13, LOH analysis was performed on 37 paired blood and adrenocortical tumor samples (23 ACC and 14 ACA samples) to determine the minimal common region of loss for ACCs and ACAs. From this minimal region of loss, 3 genes were selected for quantitative real time reverse transcription polymerase chain reaction analysis on 20 ACCs and 30 ACAs. RESULTS: LOH at 17p13 was found in 74% of ACCs compared with 14% of ACAs. There was a 10.4-Mb common minimal region of loss in ACCs whereas no minimal region of loss in ACAs could be demonstrated. Expression of Acyl coenzyme-A dehydrogenase very long chain (ACADVL) and Arachidonate 15-lipoxygenase second type (ALOX15B) was significantly down-regulated in ACCs compared with ACAs whereas there was no difference in expression of Potassium channel tetramerization domain containing 11 (KCTD11) in ACCs and ACAs. CONCLUSIONS: We demonstrated a minimal common region of loss of 10.4-Mb on 17p13 in ACCs and within this region, we found that ACADVL and ALOX15B expression are good discriminators between ACCs and ACAs.
%Z FOR Codes: 111201


%0 Journal Article
%~ PubMed
%A Payne, Cathy A
%A Maleki, Sanaz
%A Messina, Marinella
%A O'Sullivan, Maree G
%A Stone, Glenn
%A Hall, Nathan R
%A Parkinson, Jonathon F
%A Wheeler, Helen R
%A Cook, Raymond J
%A Biggs, Michael T
%A Little, Nicholas S
%A Teo, Charles
%A Robinson, Bruce G
%A McDonald, Kerrie L
%T Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma.
%B Molecular Cancer Therapeutics
%D 2008
%C United States
%I American Association for Cancer Research
%V 7
%N 10
%P 3420-3428
%@ 1535-7163
%X Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D(2) (PGD(2)) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system, is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival. In vitro, the addition of the main PGDS metabolite, PGD(2), to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD(2) substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early interventional efforts for the grade 2 and 3 astrocytomas. [Mol Cancer Ther 2008;7(10):3420-8].
%Z FOR Codes: 110399 1101


%0 Journal Article
%~ PubMed
%A Low, Tsu-Hui
%A Delbridge, Leigh
%A Sidhu, Stan
%A Learoyd, Dianna
%A Robinson, Bruce
%A Roach, Paul
%A Sywak, Mark
%T Lymph Node Status Influences Follow-Up Thyroglobulin Levels in Papillary Thyroid Cancer.
%B Annals of Surgical Oncology
%D 2008
%C United States
%I Springer New York LLC
%V 15
%N 10
%P 2827-2832
%@ 1534-4681
%X Elevated thyroglobulin (Tg) levels post surgery are associated with disease recurrence in papillary thyroid carcinoma (PTC). The aim of this study is to determine which clinicopathological factors influence Tg elevation following surgery and radio-iodine ablation (RAI) for PTC.
%Z FOR Codes: 110323


%0 Journal Article
%~ PubMed
%A Soon, Patsy S H
%A McDonald, Kerrie L
%A Robinson, Bruce G
%A Sidhu, Stan B
%T Molecular markers and the pathogenesis of adrenocortical cancer.
%B The Oncologist
%D 2008
%C United States
%I AlphaMed Press
%V 13
%N 5
%P 548-561
%@ 1083-7159
%X Adrenal tumors are common, with an estimated incidence of 7.3% in autopsy cases, while adrenocortical carcinomas (ACCs) are rare, with an estimated prevalence of 4-12 per million population. Because the prognoses for adrenocortical adenomas (ACAs) and ACCs are vastly different, it is important to be able to accurately differentiate the two tumor types. Advancement in the understanding of the pathophysiology of ACCs is essential for the development of more sensitive means of diagnosis and treatment, resulting in better clinical outcome. Adrenocortical tumors (ACTs) occur as a component of several hereditary tumor syndromes, which include the Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia 1, Carney complex, and congenital adrenal hyperplasia. The genes involved in these syndromes have also been shown to play a role in the pathogenesis of sporadic ACTs. The adrenocorticotropic hormone-cAMP-protein kinase A and Wnt pathways are also implicated in adrenocortical tumorigenesis. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in adrenocortical tumorigenesis, including results of comparative genomic hybridization, loss of heterozygosity, and microarray gene-expression profiling studies.
%Z FOR Codes: 111201


%0 Journal Article
%~ PubMed
%A Grodski, Simon
%A Gill, Anthony
%A Robinson, Bruce G
%A Sidhu, Stan
%T Nonfunctioning parathyroid cancer presenting as a cervical mass.
%B Thyroid
%D 2008
%C United States
%I Mary Ann Liebert, Inc. Publishers
%V 18
%N 4
%P 473-474
%@ 1050-7256
%X 
%Z FOR Codes: 111202


%0 Journal Article
%~ PubMed
%A Kim, Leo
%A Holland, Andrew J A
%A Srinivasan, Shubha
%A Cowell, Chris T
%A Benn, Dindy E
%A Robinson, Bruce G
%T Paediatric bilateral adrenal phaeochromocytomas in association with a novel mutation in the von Hippel Lindau gene.
%B Journal of paediatrics and child health
%D 2008
%C United Kingdom
%I Wiley-Blackwell Publishing Ltd.
%V 44
%N 9
%P 514-516
%@ 1440-1754
%X Functional phaeochromocytoma and paraganglioma are rare in children and adolescents. We report a 12-year-old male with bilateral phaeochromocytoma in whom germ line testing identified a novel mutation in the von Hippel Lindau gene. Early age of onset, bilateral phaeochromocytoma and other clinical features should prompt germ line DNA testing for mutations in genes associated with familial phaeochromocytoma and paraganglioma syndromes.
%Z FOR Codes: 111403 110311


%0 Journal Article
%~ PubMed
%A Adler, Joel T
%A Meyer-Rochow, Goswin Y
%A Chen, Herbert
%A Benn, Diana E
%A Robinson, Bruce G
%A Sippel, Rebecca S
%A Sidhu, Stan B
%T Pheochromocytoma: current approaches and future directions.
%B The Oncologist
%D 2008
%C United States
%I AlphaMed Press, Inc
%V 13
%N 7
%P 779-793
%@ 1083-7159
%X Pheochromocytomas are rare catecholamine-secreting tumors that arise from chromaffin tissue within the adrenal medulla and extra-adrenal sites. Because of the excess secretion of hormones, these tumors often cause debilitating symptoms and a poor quality of life. While medical management plays a significant role in the treatment of pheochromocytoma patients, surgical excision remains the only cure. Improved medical management and surgical techniques and an increased understanding of hereditary disease have improved the outcome of pheochromocytoma patients with benign disease; however, the outcome of patients with malignant disease remains poor. In this review, we discuss the presentation, diagnosis, management, and future directions in the management of this disease.
%Z FOR Codes: 111299


%0 Journal Article
%~ PubMed
%A Learoyd, Diana L
%A Robinson, Bruce G
%T Routine screening for germline RET mutations is recommended for all patients with medullary thyroid cancer.
%B Nature clinical practice. Endocrinology & metabolism
%D 2008
%C United Kingdom
%I Nature Publishing Group
%V 5
%N 1
%P 6-7
%@ 1745-8374
%X 
%Z FOR Codes: 111299 110306


%0 Journal Article
%~ PubMed
%A Learoyd, Diana L
%A Robinson, Bruce G
%T Does genetic screening increase detection of familial medullary thyroid cancer in apparently sporadic cases?
%B Nature clinical practice. Endocrinology & metabolism
%D 2007
%C United Kingdom
%I Nature Publishing Group
%V 4
%N 0
%P 132-3
%@ 1745-8374
%X 
%Z FOR Codes: 111204


%0 Journal Article
%~ PubMed
%A McDonald, Kerrie L
%A O'Sullivan, Maree G
%A Parkinson, Jonathon F
%A Shaw, Janet M
%A Payne, Cathy A
%A Brewer, Janice M
%A Young, Lawrence
%A Reader, Dianne J
%A Wheeler, Helen T
%A Cook, Raymond J
%A Biggs, Michael T
%A Little, Nicholas S
%A Teo, Charlie
%A Stone, Glenn
%A Robinson, Bruce G
%T IQGAP1 and IGFBP2: valuable biomarkers for determining prognosis in glioma patients.
%B Journal of Neuropathology and Experimental Neurology
%D 2007
%C United States.
%I Lippincott Williams & Wilkins, Inc.
%V 66
%N 5
%P 405-417
%@ 0022-3069
%X Clinical treatment decisions and the survival outcomes of patients with gliomas are directly impacted by accurate tumor classification. New and more reliable prognostic markers are needed to better identify the variable duration of survival among histologically defined glioma grades. Microarray expression analysis and immunohistochemistry were used to identify biomarkers associated with gliomas with more aggressive biologic behaviors. The protein expression of IQGAP1 and IGFBP2, when used in conjunction with the World Health Organization grading system, readily identified and defined a subgroup of patients with grade III gliomas whose prognosis was poor. In addition, in patients with glioblastoma multiforme, in whom IQGAP1 and IGFBP2 were absent, long-term survival of more than 3 years was observed. The use of these markers confirmed a nonuniform distribution of survival in those with World Health Organization grade III and IV tumors. Thus, IQGAP1 and IGFBP2 immunostaining supplements current histologic grading by offering additional prognostic and predictive information.
%Z FOR Codes: 111299


%0 Journal Article
%~ Isi
%A Benn, DE
%A Robinson, BG
%T Pheochromocytoma - quo vadis?
%B Nature Clinical Practice Endocrinology & Metabolism
%D 2007
%C United Kingdom
%I Nature Publishing Group
%V 3
%N 5
%P 377-377
%@ 1745-8366
%X 
%Z FOR Codes: 110306


%0 Journal Article
%~ PubMed
%A Grodski, Simon
%A Stalberg, Peter
%A Robinson, Bruce G
%A Delbridge, Leigh W
%T Surgery versus Radioiodine Therapy as Definitive Management for Graves' Disease: The Role of Patient Preference.
%B Thyroid
%D 2007
%C United States
%I Mary Ann Liebert, Inc. Publishers
%V 17
%N 2
%P 157-160
%@ 1050-7256
%X Background: Thyroidectomy is an option for the definitive management of Graves'' disease. The aim of this study was to examine the role of patient preference for selecting surgery as definitive treatment. Patients and Methods: This is a retrospective cohort study comprising all patients (n = 63) presenting to a single surgeon for surgical management of Graves'' disease over 3 years. Documented reasons for surgery were compared with accepted indications, as well as patients'' perceptions as assessed by questionnaire. Results: The most frequent absolute indication was the presence of a large goiter (n = 8; 13%) or associated thyroid nodule (n = 6; 10%). Ophthalmopathy, a relative indication, comprised the largest single group overall (n = 18; 29%); however, a significant number of patients (n = 17; 27%) elected surgery in the absence of a recognized indication. There was strong concordance (73%) between the recorded indication and the patients'' survey response. Overall, there was a high level of satisfaction with surgery with 88% of respondents giving a satisfaction score of 7 or greater on a visual analog scale (VAS) (0-10). Conclusions: One-third of all patients electing surgery as definitive management do so in the absence of a specific indication. Overall, there is a high level of satisfaction with the decision for surgery as definitive management of Graves'' disease.
%Z FOR Codes: 111208


%0 Journal Article
%~ PubMed
%A Lundgren, Catharina Ihre
%A Delbridg, Leigh
%A Learoyd, Diana
%A Robinson, Bruce
%T Surgical approach to medullary thyroid cancer.
%B Arquivos Brasileiros de Endocrinologia e Metabologia
%D 2007
%C Brazil
%I Universidade de Sao Paulo
%V 51
%N 5
%P 818-824
%@ 0004-2730
%X Medullary thyroid cancer (MTC) compromises 3-5% of all thyroid cancers and arises from parafollicular or calcitonin-producing C cells. It may be sporadic (75% of cases), or may occur as a manifestation of either the hereditary syndrome Multiple Endocrine Neoplasia type 2 (MEN 2A or MEN 2B) (25% of cases), or rarely as an isolated familial syndrome (FMTC). Complete surgical resection comprising in most cases total thyroidectomy with central lymph node dissection at an early stage of the disease is the only potential cure for MTC. The familial form of the disease, MEN-2A occupies a unique place in surgical history, having been the first disease where surgical removal of an affected organ was undertaken before the development of malignancy, solely on the basis of genetic testing. Total thyroidectomy prior to the development of invasive cancer completely avoids an otherwise lethal malignancy. Timing of prophylactic surgery is based on models that utilise genotype-phenotype correlations, which have now been stratified into three risk groups based on the specific codon involved. MTC should be followed with postoperative serial serum calcitonin levels to survey for persistent or recurrent disease as indicated by detectable levels. The challenge however, if calcitonin levels are increased, is to find the source of its production. The first localisation technique recommended would be ultrasound of the neck, since there is a high frequency of local recurrence and cervical node metastasis, followed by a total body CT scan and bone scintigraphy.
%Z FOR Codes: 111204


%0 Journal Article
%~ PubMed
%A Messina, Marinella
%A Robinson, Bruce G
%T Technology insight: gene therapy and its potential role in the treatment of medullary thyroid carcinoma.
%B Nature Clinical Practice Endocrinology & Metabolism
%D 2007
%C United Kingdom
%I Nature Publishing Group
%V 3
%N 3
%P 290-301
%@ 1745-8366
%X Metastatic medullary thyroid cancer (MTC) responds poorly to conventional treatments with chemotherapy and radiotherapy. Gene therapy--the transfer of genetic material for therapeutic purposes--might have therapeutic potential for patients with progressive metastatic MTC that is incurable by conventional treatments. To date, a number of gene-therapy strategies have been explored, primarily those that use replication-deficient adenovirus vectors to transfer therapeutic genes to tumor cells. Tissue-specific expression of the promoter for calcitonin and calcitonin-related polypeptide alpha has allowed therapeutic genes to be specifically expressed in calcitonin-secreting cells and in the MTC tumors derived from them; such tissue-specific expression contributes to improved safety of gene therapies and has the potential to increase their therapeutic index. In addition, the identification of an MTC-specific peptide ligand raises the possibility of developing an MTC-selective vector. In this article, we have described the exciting area of gene therapy in the management of MTC with a focus on preclinical in vitro and in vivo MTC models.
%Z FOR Codes: 100401


%0 Journal Article
%~ PubMed
%A Yan, Warren
%A Roach, Paul J
%A Bautovich, George J
%A Learoyd, Diana L
%A Robinson, Bruce G
%T Timing of iodine-123 scintigraphy following use of recombinant human thyrotropin in differentiated thyroid carcinoma.
%B Clinical Nuclear Medicine
%D 2007
%C US
%I Lippincott Williams & Wilkins
%V 32
%N 5
%P 375-377
%@ 0363-9762
%X 
%Z FOR Codes: 111204


%0 Journal Article
%~ PubMed
%A Parkinson, Jonathon
%A Wheeler, Helen
%A Clarkson, Adele
%A McKenzie, Catriona
%A Biggs, Michael
%A Little, Nicholas
%A Cook, Raymond
%A Messina, Marinella
%A Robinson, Bruce
%A McDonald, Kerrie
%T Variation of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in serial samples in glioblastoma.
%B Journal of neuro-oncology
%D 2007
%C United States
%I Springer New York LLC
%V 87
%N 0
%P 71-8
%@ 0167-594X
%X Methylation of the promoter region of the O ( 6 ) -methylguanine-DNA methyltransferase (MGMT) gene is known to be predictive of response to temozolomide treatment in patients with glioblastoma. Contrastingly, little is known about variation in the methylation status of the MGMT promoter after treatment or across different regions of the same tumor. About 22 samples from 10 patients who had undergone multiple resections of a glioblastoma were examined with promoter sequencing. Of these, 20 were also analyzed using Methylation Specific PCR (MSP). The methylation status of the MGMT promoter was altered in the specimens obtained pre and post treatment in 2 of 9 samples as assessed by MSP and 7 out of 10 patients as assessed by promoter sequencing. In four patients, the MGMT promoter was unmethylated at primary surgery, but displayed some methylation (32, 44, 12, and 4%) on post-treatment sampling. Alteration in MSP status from unmethylated to methylated was also observed in 2 of these 4 patients. In another patient, methylation increased from 40% on initial sampling to 68% on the second sample. The remaining two patients initially demonstrated some degree of methylation (72% and 12%); subsequent sampling showed no methylation of the MGMT promoter. To ensure variable methylation status was not due to intra-tumoral variability, three to four specimens were sampled from different regions of large glioblastomas (n = 7). Promoter sequencing revealed minimal variation in methylation in all but two sites examined. Immunohistochemistry also demonstrated minimal change in MGMT expression across the tumors. This suggests that variation in MGMT promoter methylation can occur within the same tumor after treatment, necessitating caution in clinical decision-making based on this analysis.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Elston, Marianne S
%A Gill, Anthony J
%A Conaglen, John V
%A Clarkson, Adele
%A Shaw, Janet M
%A Law, Andrew Jj
%A Cook, Raymond J
%A Little, Nicholas S
%A Clifton-Bligh, Roderick J
%A Robinson, Bruce G
%A McDonald, Kerrie L
%T Wnt pathway inhibitors are strongly down-regulated in pituitary tumors.
%B Endocrinology
%D 2007
%C United States
%I Endocrine Soc
%V 149
%N 3
%P 1235-42
%@ 0013-7227
%X The etiology of sporadic pituitary tumors is currently unknown. The Wnt pathways have been implicated in the pathogenesis of a variety of human tumors, but the role of these pathways in pituitary tumors is unclear. Microarray analysis using the Affymetrix HG U133 plus 2.0 GeneChips identified four secreted frizzled-related protein (sFRP) family members of Wnt pathway inhibitors that were differentially expressed in both nonfunctioning and clinically functioning pituitary tumors (n = 20) compared with normal pituitary controls (n = 3). Reduced tumor expression of Wnt inhibitory factor-1 (WIF1), sFRP2, and sFRP4 mRNA was confirmed by real-time quantitative RT-PCR (P <0.001 and P = 0.002 and 0.013, respectively) in all pituitary subtypes. Hypermethylation of the WIF1 promoter was present in 88% of the pituitary tumors (n = 41). Seventy-six percent of pituitary tumors demonstrated absent or weak cytoplasmic WIF1 staining by immunohistochemistry (n = 41), although preserved staining was seen in some functioning tumors, with strong staining in 92% of normal pituitary controls (n = 13). The Wnt pathway target gene cyclin D1 was found to be up-regulated specifically in the nonfunctioning pituitary tumors compared with controls at both mRNA and protein level, supportive of activation of the Wnt-beta-catenin pathway. Nuclear accumulation of beta-catenin, however, was not observed in any pituitary tumors (n = 70). By transfecting GH3 cells with WIF1, decreased cell proliferation and colony formation was observed compared with empty vector controls. In conclusion, our data suggest that WIF1 may be a tumor suppressor, specifically in nonfunctioning pituitary tumors, and that the Wnt pathways are important in pituitary tumorigenesis.
%Z FOR Codes: 110306


%0 Journal Article
%~ PubMed
%A Warusavitarne, Janindra
%A Ramanathan, Palaniappan
%A Kaufman, Anthony
%A Robinson, Bruce
%A Schnitzler, Margaret
%T 5-Fluorouracil (5FU) treatment does not influence invasion and metastasis in microsatellite unstable (MSI-H) colorectal cancer.
%B International journal of colorectal disease
%D 2006
%C Germany
%I Springer-Verlag
%V 21
%N 7
%P 625-31
%@ 0179-1958
%X Microsatellite instability is a recognised pathway of colorectal carcinogenesis responsible for about 15% of all sporadic colorectal cancers. Recent evidence has suggested that these tumours may not have the same response as microsatellite stable colon cancers to 5-fluorouracil (5FU)-based chemotherapy. The response to 5FU in four microsatellite unstable (MSI-H) cell lines was examined by cell viability assays and invasion assays. Flow cytometry was used to assess the effect of 5FU on MSI-H cell lines. In vivo response to 5FU was assessed by intraperitoneal injection of 5FU or control to 80 nude mice that had received intrasplenic injections of an MSI-H cell line KM12C prior to commencing treatment. There was inhibition of cell growth in MSI-H cell lines when treated with 5FU. There was no difference in invasiveness in the MSI-H cell lines when treated with 5FU. Primary tumours formed in 27 of the untreated and 25 of the 5FU treated mice (p=NS). There was a 36% reduction in splenic weight in those mice treated with 5FU (p<0.03). Metastases formed in 5 of the untreated and 9 of the treated mice (p=0.12). 5FU treatment of MSI-H tumours results in a reduction in growth but does not result in a reduction in invasion or metastasis.
%Z FOR Codes: 111204


%0 Journal Article
%~ Isi
%A Taylor, J. C.
%A Gough, S. C.
%A Hunt, P. J.
%A Brix, T. H.
%A Chatterjee, K.
%A Connell, J. M.
%A Franklyn, J. A.
%A Hegedus, L.
%A Robinson, B. G.
%A Wiersinga, W. M.
%A Wass, J. A. H.
%A Zabaneh, D.
%A Mackay, I.
%A Weetman, A. P.
%T A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease.
%B Journal of Clinical Endocrinology and Metabolism
%D 2006
%C United States
%I The endocrine society
%V 91
%N 2
%P 646-653
%@ 0021-972X
%X 
%Z FOR Codes:


%0 Journal Article
%~ Isi
%A Elston, M. S.
%A Benn, D.
%A Robinson, B. G.
%A Conaglen, J. V.
%T An apparently sporadic paraganglioma with an SDHB gene germline mutation presenting at age 68 years.
%B Internal Medicine Journal
%D 2006
%C Australia
%I Blackwell Publishing Asia
%V 36
%N 2
%P 129-131
%@ 1444-0903
%X 
%Z FOR Codes:


%0 Journal Article
%~ Isi
%A Giordano, T. J.
%A Au, A. Y. M.
%A Kuick, R.
%A Thomas, D. G.
%A Rhodes, D. R.
%A Wilhelm, K. G.
%A Vinco, M.
%A Misek, D. E.
%A Sanders, D.
%A Zhu, Z. W.
%A Ciampi, R.
%A Hanash, S.
%A Chinnaiyan, A.
%A Clifton-Bligh, R. J.
%A Robinson, B. G.
%A Nikiforov, Y. E.
%A Koenig, R. J.
%T Delineation, functional validation, and bioinformatic evaluation of gene expression in thyroid follicular carcinomas with the PAX8-PPARG translocation.
%B Clinical Cancer Research
%D 2006
%C United States
%I American Association for Cancer Research
%V 12
%N 7
%P 1983-1993
%@ 1078-0432
%X 
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Stewart, Inge
%A Roddie, Claire
%A Gill, Anthony
%A Clarkson, Adele
%A Mirams, Michiko
%A Coyle, Luke
%A Ward, Christopher
%A Clifton-Bligh, Philip
%A Robinson, Bruce G
%A Mason, Rebecca S
%A Clifton-Bligh, Roderick J
%T Elevated serum FGF23 concentrations in plasma cell dyscrasias.
%B Bone
%D 2006
%C United States
%I Elsevier Science
%V 39
%N 2
%P 369-376
%@ 8756-3282
%X Fibroblast growth factor 23 (FGF23) is now recognized as a key regulator of phosphate metabolism. Numerous reports have found elevated serum FGF23 concentrations in oncogenic osteomalacia associated with mesenchymal tumors. Hypophosphatemic osteomalacia more rarely occurs in non-mesenchymal tumors. We identified elevated serum FGF23 levels in one patient with chronic lymphatic leukemia (CLL) and hypophosphatemia, prompting us to examine FGF23 concentrations in other patients with B-cell neoplasms. FGF23 levels were elevated in several patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS), and were significantly associated with serum paraprotein and beta-2 microglobulin concentrations in these patients. Hypophosphatemia was not observed even in those patients with elevated FGF23, and a weak positive correlation was noted between serum FGF23 and phosphate concentrations. Malignant plasma cells in bone marrow trephines from patients with myeloma showed cytoplasmic expression of FGF23, similar to the cytoplasmic localization of FGF23 already described in mesenchymal tumors associated with oncogenic osteomalacia. Our findings contribute to an expanding literature regarding abnormal FGF/FGF receptor-signaling in myeloma. The absence of hypophosphatemia in these cases suggests either that FGF23 produced by clonal B-cells lacks systemic bioactivity or that other factors contribute to maintain serum phosphate. We suggest that the relationship between FGF23 and skeletal disease associated with plasma cell dyscrasias deserves further study.
%Z FOR Codes: 110306 111699


%0 Journal Article
%~ Isi
%A Warner, J.
%A Nyholt, D. R.
%A Busfield, F.
%A Epstein, M.
%A Burgess, J.
%A Stranks, S.
%A Hill, P.
%A Perry-Keene, D.
%A Learoyd, D.
%A Robinson, B.
%A Teh, B. T.
%A Prins, J. B.
%A Cardinal, J. W.
%T Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3-14.
%B Journal of Medical Genetics
%D 2006
%C British Med Assoc Ho
%I British Med Journal Publ Group
%V 43
%N 3
%P e12
%@ 0022-2593
%X 
%Z FOR Codes: 604


%0 Journal Article
%~ Isi
%A Bolland, M. J.
%A Benn, D. E.
%A Croxson, M. S.
%A McCall, J.
%A Shaw, J. H. F.
%A Baillie, T.
%A Robinson, B. G.
%T Gastrointestinal stromal tumour in succinate dehydrogenase subunit B mutation-associated familial phaeochromocytoma/paraganglioma.
%B Anz Journal of Surgery
%D 2006
%C United Kingdom
%I Blackwell Publishing Ltd
%V 76
%N 8
%P 763-764
%@ 1445-1433
%X 
%Z FOR Codes: 1112


%0 Journal Article
%~ PubMed
%A Benn, Diana E
%A Robinson, Bruce G
%T Genetic basis of phaeochromocytoma and paraganglioma.
%B Best Practice & Research. Clinical Endocrinology and Metabolism
%D 2006
%C United Kingdom
%I Bailliere Tindall
%V 20
%N 3
%P 435-450
%@ 1521-690X
%X Advances in the knowledge of the genetics of phaeochromocytoma have broadened our understanding about the mechanisms of tumorigenesis. Formerly it was believed that 10% of phaeochromocytomas were associated with familial cancer syndromes, but it is now recognised that up to 30% of these tumours may be familial. In particular, attention has been focused on those patients with apparently sporadic presentations where 12-24% of patients have been shown to carry germline mutations indicating hereditary disease. Consideration of genetic testing is now recommended for all apparently sporadic cases and, following the identification of a mutation-positive carrier, the offering of genetic testing to first degree relatives. There is a need for lifelong follow up of affected individuals and asymptomatic mutation-positive carriers, but validation of screening protocols has yet to be determined.
%Z FOR Codes: 60499


%0 Journal Article
%~ PubMed
%A Benn, Diana E
%A Richardson, Anne Louise
%A Marsh, Deborah J
%A Robinson, Bruce G
%T Genetic testing in pheochromocytoma- and paraganglioma-associated syndromes.
%B Annals of the New York Academy of Sciences
%D 2006
%C United States
%I Blackwell Publishing, Inc.
%V 1073
%N 
%P 104-111
%@ 0077-8923
%X Genetic understanding of pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes has recently expanded with the identification of the involvement of the mitochondrial complex II peptides, namely the succinate dehydrogenase subunit B (SDHB), subunit C (SDHC), and subunit D (SDHD). In patients with PHEO and/or PGL genetic testing for germline mutations in SDHD and SDHB has been recommended, in addition to the PHEO susceptibility genes VHL and RET. After careful clinical assessment of the patient, suspected familial disease may direct the clinician to the appropriate gene for testing. In the absence of obvious features of familial disease, the decision regarding the appropriate gene for testing is more difficult. Such testing can be costly and time consuming, but a rational prioritization of gene testing can streamline the process. Therefore in order to achieve this for apparently sporadic cases we propose a decision matrix based on site of tumor, functionality, and age at presentation.
%Z FOR Codes: 60499


%0 Journal Article
%~ PubMed
%A Stalberg, Peter
%A Sidhu, Stan
%A Sywak, Mark
%A Robinson, Bruce
%A Wilkinson, Margaret
%A Delbridge, Leigh
%T Intraoperative parathyroid hormone measurement during minimally invasive parathyroidectomy: does it "value-add" to decision-making?
%B Journal of the American College of Surgeons
%D 2006
%C United States
%I Elsevier Inc.
%V 203
%N 1
%P 1-6
%@ 1072-7515
%X BACKGROUND: Routine use of intraoperative parathyroid hormone levels (IOPTH) during minimally invasive parathyroidectomy (MIP) has been challenged simply because the test works best when needed least, ie, once a solitary adenoma has been resected, and is less accurate with multiple gland disease. It has also been shown not to be cost-effective. The aim of this study was to determine if IOPTH "value-added" to decision-making during MIP. STUDY DESIGN: The study group comprised 100 consecutive patients with sporadic hyperparathyroidism and an unequivocally positive sestamibi scan who were undergoing MIP in our unit from June 2004 until October 2005, from whom blood was collected for parathyroid hormone measurement preoperatively, preexcision, and at 10 and 30 minutes postremoval. No action was taken on the results of the test. RESULTS: Ninety-eight patients were cured by MIP alone. Two patients had persistent hyperparathyroidism, one of whom was cured with subsequent open reexploration and removal of a second adenoma, and the other remains hypercalcemic despite additional open neck exploration. IOPTH in both patients failed to fall in retrospect, only the first would have been cured by conversion at the time of operation. The value-added accuracy of IOPTH was really only 1%. In an additional nine patients, IOPTH at 10 minutes had failed to fall by > 50% from the highest level, those patients (9%) would have been subjected to an unnecessary conversion on the basis of a false-negative result. CONCLUSIONS: IOPTH does not substantially value-add to decision-making during MIP. Most patients will be cured with appropriate selection for MIP based on preoperative localization studies.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Palazzo, F F
%A Gosnell, J
%A Savio, R
%A Reeve, T S
%A Sidhu, S B
%A Sywak, M S
%A Robinson, B
%A Delbridge, L W
%T Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades.
%B European journal of Surgical Oncology
%D 2006
%C United Kingdom
%I WB Saunders Co. Ltd.
%V 32
%N 3
%P 340-344
%@ 0748-7983
%X AIMS: Lymphadenectomy in the management of papillary thyroid cancer (PTC) has evolved. The aim of this study was to examine the changing role of neck dissection as reflected in the practice of a large thyroid unit over four decades. METHODS: A retrospective cohort study of patients that underwent primary thyroid surgery for papillary cancer in a single unit in the period 1958-2002. Nine 5-year periods were considered and the data relevant to the treatment of the regional lymph nodes reviewed. RESULTS: Nine hundred patients with PTC underwent surgery between 1958 and 2002 of whom 32.7% underwent lymph node dissection (LND). The use of lymphadenectomy increased from 21.4% in 1958-1962 to 48.1% in 1998-2002 of which 84% underwent a selective lymph node dissection (SLND)-a dissection where the LND is determined by the extent of the disease encountered. The mean number of nodes removed during SLND was 12.6 (range 1-56) of which a mean of 3.1 (24.8%) (0-19) were involved by the disease. Cervical levels 6 and level 4 were those most frequently dissected. There was no statistically significant difference in the complication rates in patients undergoing neck dissection and those not. CONCLUSION: The four decade experience reflects a move away from modified radical neck dissection and cherry picking towards SLND. Growing evidence suggests that lymphadenopathy in adult PTC is an adverse prognostic factor. SLND, a lymphadenectomy tailored to the extent of the disease process, is the coherent treatment for PTC since it serves the dual purpose of staging as well as control of local disease. This can be achieved with little morbidity when performed in a specialist centre.
%Z FOR Codes: 1112


%0 Journal Article
%~ PubMed
%A Gosnell, Jessica E
%A Sywak, Mark S
%A Sidhu, Stan B
%A Gough, Ian R
%A Learoyd, Diana L
%A Robinson, Bruce G
%A Delbridge, Leigh W
%T New era: prophylactic surgery for patients with multiple endocrine neoplasia-2a.
%B ANZ Journal of Surgery
%D 2006
%C 54 University St,P O
%I Blackwell Publishing Asia
%V 76
%N 7
%P 586-590
%@ 1445-1433
%X BACKGROUND: The surgical management of patients with multiple endocrine neoplasia-2A (MEN-2A) continues to evolve with specific genotype-phenotype correlations allowing for a more tailored approach. In this study, we report the surgical management of one of the largest MEN-2A families with a rearranged during transfection (RET) codon 804 mutation. METHOD: This is a cohort study comprising all at-risk kindred within a single known MEN-2A family. Prophylactic total thyroidectomy with lymph node dissection was recommended to all mutation carriers aged 5 years and older. RESULTS: There were a total of 48 at-risk individuals in the MEN-2A kindred, with 22 patients undergoing thyroidectomy after appropriate preoperative evaluation. A total of 9 patients had medullary thyroid cancer including 5 with a normal preoperative calcitonin level. A total of 11 patients had C-cell hyperplasia and 7 showed histological evidence of parathyroid disease. Only the index case had a phaeochromocytoma. CONCLUSIONS: Genetic testing for germline mutations in the RET proto-oncogene has allowed precise identification of affected RET carriers and provided the opportunity for prophylactic or ''preclinical'' surgery to treat and in fact to prevent medullary thyroid cancer. This concept of prophylactic surgery based on a genetic test is likely to be applied more widely as the tools of molecular biology advance.
%Z FOR Codes: 110323


%0 Journal Article
%~ PubMed
%A Figtree, G A
%A Kindmark, A
%A Lind, L
%A Grundberg, E
%A Speller, B
%A Robinson, B G
%A Channon, K M
%A Watkins, H
%T Novel estrogen receptor alpha promoter polymorphism increases ventricular hypertrophic response to hypertension.
%B The Journal of steroid biochemistry and molecular biology
%D 2006
%C UK
%I Pergamon
%V 103
%N 2
%P 110-8
%@ 0960-0760
%X Given the strong genetic contribution to blood pressure and left ventricular hypertrophy (LVH), and the influence of estrogen on these parameters, we hypothesized that polymorphisms in the estrogen receptor alpha (ERalpha) promoter may influence LVH. Three novel polymorphisms were identified upstream of the ERalpha alternatively spliced exon 1E, within sequence which demonstrated significant promoter activity in vitro. Demonstration of ERalpha E isoform expression in human ventricle by RT-PCR supported a possible functional role for the 1E novel polymorphisms in estrogen signaling in the heart. Indeed, G>A (-721 E) was significantly associated with LVH after controlling for systolic blood pressure and sex in a healthy population (n=74), contributing to 23% of interventricular septum (IVS) width variance (p<0.001) and 9.4% of left ventricular mass index (LVMI) variance (p=0.035). In a separate hypertensive cohort, male carriers of the A allele (n=8) had a 17% increase in IVS (95% CI: 6-28%) and a 19% increase in LVMI (3-34%) compared to GG homozygotes (n=84). We conclude that a novel polymorphism in the promoter of a cardiac mRNA splice isoform of ERalpha is associated with LVH.
%Z FOR Codes: 60110


%0 Journal Article
%~ PubMed
%A Au, Amy Y M
%A McBride, Claire
%A Wilhelm, Kenneth G
%A Koenig, Ronald J
%A Speller, Bridget
%A Cheung, Linda
%A Messina, Marinella
%A Wentworth, John
%A Tasevski, Vitomir
%A Learoyd, Diana
%A Robinson, Bruce G
%A Clifton-Bligh, Roderick J
%T PAX8-peroxisome proliferator-activated receptor gamma (PPARgamma) disrupts normal PAX8 or PPARgamma transcriptional function and stimulates follicular thyroid cell growth.
%B Endocrinology
%D 2006
%C United States
%I The Endocrine Society
%V 147
%N 1
%P 367-376
%@ 0013-7227
%X Follicular thyroid carcinomas are associated with a chromosomal translocation that fuses the thyroid-specific transcription factor paired box gene 8 (PAX8) with the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). This study investigated the transcriptional mechanisms by which PAX8-PPARgamma regulates follicular thyroid cells. In HeLa cells, rat follicular thyroid (FRTL-5) cells, or immortalized human thyroid cells, PAX8-PPARgamma stimulated transcription from PAX8-responsive thyroperoxidase and sodium-iodide symporter promoters in a manner at least comparable with wild-type PAX8. In contrast, PAX8-PPARgamma failed to stimulate transcription from the thyroglobulin promoter and blocked the synergistic stimulation of this promoter by wild-type PAX8 and thyroid transcription factor-1. Unexpectedly, PAX8-PPARgamma transcriptional function on a PPARgamma-responsive promoter was cell-type dependent; in HeLa cells, PAX8-PPARgamma dominantly inhibited expression of the PPARgamma-responsive promoter, whereas in FRTL-5 and immortalized human thyroid cells PAX8-PPARgamma stimulated this promoter. In gel shift analyses, PAX8-PPARgamma bound a PPARgamma-response element suggesting that its transcriptional function is mediated via direct DNA contact. A biological model of PAX8-PPARgamma function in follicular thyroid cells was generated via constitutive expression of the fusion protein in FRTL-5 cells. In this model, PAX8-PPARgamma expression was associated with enhanced growth as assessed by soft agar assays and thymidine uptake. Therefore, PAX8-PPARgamma disrupts normal transcriptional regulation by stimulating some genes and inhibiting others, the net effect of which may mediate follicular thyroid cell growth and loss of differentiation that ultimately leads to carcinogenesis.
%Z FOR Codes: 111601


%0 Journal Article
%~ PubMed
%A Howell, Viive M
%A Cardinal, John W
%A Richardson, Anne-Louise
%A Gimm, Oliver
%A Robinson, Bruce G
%A Marsh, Deborah J
%T Rapid Mutation Screening for HRPT2 and MEN1 Mutations Associated with Familial and Sporadic Primary Hyperparathyroidism.
%B Journal of Molecular Diagnostics
%D 2006
%C USA
%I American Society for Investigative Pathology
%V 8
%N 5
%P 559-566
%@ 1525-1578
%X Familial hyperparathyroidism, a disease of the parathyroid glands, may occur in conjunction with pituitary and pancreatic tumors (multiple endocrine neoplasia type I), kidney and bone tumors (hyperparathyroidism jaw tumor syndrome), or alone (familial isolated hyperparathyroidism). This study describes the development and validation of rapid scanning for mutations in two tumor suppressor genes linked to familial hyperparathyroidism-MEN1 and HRPT2. Denaturing high-performance liquid chromatography mutation scanning for MEN1 was performed using a set of 10 amplicons covering the nine coding exons and flanking intronic regions and for HRPT2 using a set of three amplicons for exons 1, 2, and 7 and flanking intronic regions, in which 80% of the mutations identified to date are located. All 52 MEN1 mutations or polymorphisms, 46 known and six unknown, were successfully detected. Mutation detection in exon 9 was not confounded by the presence of the common polymorphism D418D. In addition, all 10 HRPT2 mutations were successfully detected, and a two-step approach was able to distinguish IVS2 common polymorphisms from exon 2 mutations. The development of rapid denaturing high performance liquid chromatography mutation scanning of MEN1 and HRPT2 facilitates a molecular diagnosis of the associated familial syndromes for both clinically affected and at-risk family members.
%Z FOR Codes: 60499


%0 Journal Article
%~ PubMed
%A Clarke, Jason C
%A Patel, Sanjeevkumar R
%A Raymond, Richard M
%A Andrew, Scott
%A Robinson, Bruce G
%A Dressler, Gregory R
%A Brophy, Patrick D
%T Regulation of c-Ret in the developing kidney is responsive to Pax2 gene dosage.
%B Human Molecular Genetics
%D 2006
%C United Kingdom
%I Oxford University Press
%V 15
%N 23
%P 3420-3428
%@ 0964-6906
%X During kidney development, Pax2 and Pax8 are expressed very early in the mammalian nephric duct and both precede the expression of receptor tyrosine kinase, c-Ret. However, in Pax2-/- mutant mice, expression of c-Ret is lost after embryonic day 10.5. As the Ret/Gdnf pathway is necessary for renal development and there is a temporal and spatial relationship of Pax2 and c-Ret expression in the developing genito-urinary system, we postulate that Pax2 is necessary for c-Ret expression in the developing kidney. In vitro, Pax2 protein is capable of physically interacting with a c-RET promoter, and both Pax2 and Pax8 can activate the expression of a reporter gene driven by the c-RET promoter. Compound heterozygous null mice (Pax2+/-: Ret+/-) display an increased incidence of unilateral and bilateral renal agenesis, and smaller kidneys with fewer nephrons. Furthermore, the expression of Gdnf is reduced 2-3-fold, whereas c-Ret expression is reduced 9-47-fold in Pax2 heterozygous embryonic kidneys as detected by real-time quantitative RT (QRT)-PCR. The data demonstrate that Pax2 plays an integral role in the initiation and maintenance of the Ret/Gdnf pathway by not only activating the ligand of the pathway, but by also enhancing the expression of the pathway receptor Ret. The effects of reduced Pax2 gene dosage are thus amplified resulting in a haploinsufficient phenotype.
%Z FOR Codes: 100401


%0 Journal Article
%~ Isi
%A Sundram, F.
%A Robinson, B. G.
%A Kung, A.
%A Lim-Abrahan, M. A.
%A Bay, N. Q.
%A Chuan, L. K.
%A Chung, J. H.
%A Huang, S. M.
%A Hsu, L. C.
%A Kamaruddin, N.
%A Cheah, W. K.
%A Kim, W. B.
%A Koong, S. S.
%A Da Lin, H.
%A Mangklabruks, A.
%A Paz-Pacheco, E.
%A Rauff, A.
%A Ladenson, P. W.
%T Well-differentiated epithelial thyroid cancer management in the Asia Pacific region: A report and clinical practice guideline.
%B Thyroid
%D 2006
%C USA
%I Mary Ann Liebert, Inc. Publishers
%V 16
%N 5
%P 461-469
%@ 1050-7256
%X 
%Z FOR Codes: