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Pancreatic Neoplasms: HELP
Articles by Tim Meyer
Based on 10 articles published since 2009
(Why 10 articles?)

Between 2009 and 2019, Tim Meyer wrote the following 10 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review Streptozocin-based chemotherapy is not history in neuroendocrine tumours. 2012

Weatherstone, Katie / Meyer, Tim. ·Department of Oncology, Royal Free Hospital, London, UK. ·Target Oncol · Pubmed #22899468.

ABSTRACT: Streptozocin (STZ)-based chemotherapy has been used for over 30 years in the treatment of neuroendocrine tumours (NET); however, there have been few randomised trials in homogeneous and well-characterised patient populations. With the recent approval of sunitinib and everolimus for pancreatic NET (PNET) and the emergence of a more stratified approach to cancer therapy, it is timely to reevaluate the role of chemotherapy. Here we review the evidence base for STZ-based chemotherapy, the toxicity associated with treatment and the role of predictive markers such as Ki67 to select patients who may benefit most from therapy. Although there are no trials comparing chemotherapy with best supportive care, there is evidence that multi-agent STZ-containing regimens are associated with improved survival compared with control therapy. Compared with other therapies, chemotherapy appears to be associated with the highest response rate, particularly in PNET and remains the first-line treatment of choice for those patients in whom response is required. This includes those who are symptomatic from tumour burden and those with locally advanced disease who may be down-staged for resection. The role of Ki67 and other predictive markers requires further assessment in prospective studies as does the relative efficacy of alternative agents such as temozolomide.

2 Review Role of everolimus in pancreatic neuroendocrine tumors. 2011

Goldstein, Robert / Meyer, Tim. ·UCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6BT, UK. ·Expert Rev Anticancer Ther · Pubmed #21932937.

ABSTRACT: Survival from pancreatic neuroendocrine tumors has not improved over the past two decades and, until recently, streptozocin was the last therapeutic agent approved for this malignancy. Everolimus blocks mTOR, which plays an integral role in cell growth, mitosis and angiogenesis. Abnormal PI3K-Akt/PKB-mTOR pathway signaling has been implicated in the pathogenesis of pancreatic neuroendocrine tumors. In a Phase III study, patients with low- and intermediate-grade advanced pancreatic neuroendocrine tumors were randomized to receive everolimus 10 mg/day or placebo. Median progression-free survival was significantly greater in patients treated with everolimus than placebo - 11 versus 4.6 months - and drug-related adverse events were consistent with the known side-effect profile of everolimus. Everolimus represents a significant treatment development for pancreatic neuroendocrine tumors.

3 Review Malignant somatostatinoma presenting with diabetic ketoacidosis and inhibitory syndrome: pathophysiologic considerations. 2010

Theodoraki, Aikaterini / Khoo, Bernard / Hamda, Arif / Grillo, Frederica / Meyer, Tim / Bouloux, Pierre-Marc Gilles. ·Department of Endocrinology, Royal Free Hampstead NHS Trust, London, United Kingdom. aikaterini.theodoraki@royalfree.nhs.uk ·Endocr Pract · Pubmed #20497932.

ABSTRACT: OBJECTIVE: To describe a patient with diabetic ketoacidosis secondary to a malignant somatostatinoma. METHODS: We present the clinical, laboratory, radiologic, and pathologic findings of a patient with diabetic ketoacidosis secondary to a malignant somatostatinoma. We also review the potential effects of somatostatin on glucose homeostasis and discuss the underlying pathophysiologic mechanisms. RESULTS: A 30-year-old woman presented with diabetic ketoacidosis and had a malignant somatostatinoma with hepatic, bone, and lymph node metastasis. She exhibited features of somatostatinoma "inhibitory syndrome" characterized by mild nonketotic hyperglycemia, hypochlorhydria, cholelithiasis, steatorrhea, anemia, and weight loss. In these tumors, the absence of ketoacidosis is thought to arise from the somatostatin-induced simultaneous suppression of the secretion of insulin and glucagon. The patient's primary tumor could not be located. CONCLUSIONS: Diabetic ketoacidosis may occur in somatostatinomas. The secretion of larger molecular weight forms of somatostatin from the tumor may contribute to the ketogenesis.

4 Clinical Trial Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. 2017

Neoptolemos, John P / Palmer, Daniel H / Ghaneh, Paula / Psarelli, Eftychia E / Valle, Juan W / Halloran, Christopher M / Faluyi, Olusola / O'Reilly, Derek A / Cunningham, David / Wadsley, Jonathan / Darby, Suzanne / Meyer, Tim / Gillmore, Roopinder / Anthoney, Alan / Lind, Pehr / Glimelius, Bengt / Falk, Stephen / Izbicki, Jakob R / Middleton, Gary William / Cummins, Sebastian / Ross, Paul J / Wasan, Harpreet / McDonald, Alec / Crosby, Tom / Ma, Yuk Ting / Patel, Kinnari / Sherriff, David / Soomal, Rubin / Borg, David / Sothi, Sharmila / Hammel, Pascal / Hackert, Thilo / Jackson, Richard / Büchler, Markus W / Anonymous2721324. ·University of Liverpool, Liverpool, UK; The Royal Liverpool University Hospital, Liverpool, UK. Electronic address: j.p.neoptolemos@liverpool.ac.uk. · University of Liverpool, Liverpool, UK; The Clatterbridge Cancer Centre, Wirral, UK. · The Royal Liverpool University Hospital, Liverpool, UK. · University of Liverpool, Liverpool, UK. · University of Manchester/The Christie NHS Foundation Trust, Manchester, UK. · University of Liverpool, Liverpool, UK; The Royal Liverpool University Hospital, Liverpool, UK. · The Clatterbridge Cancer Centre, Wirral, UK. · Manchester Royal Infirmary, Manchester, UK. · Royal Marsden Hospital, London, UK. · Weston Park Hospital, Sheffield, UK. · Royal Free Hospital, London, UK. · St James's University Hospital, Leeds, UK. · Karolinska Institute, Stockholm, Sweden; Clinical Research Sörmland, Eskilstuna, Sweden. · University of Uppsala, Uppsala, Sweden. · Bristol Haematology and Oncology Centre, Bristol, UK. · University of Hamburg Medical institutions UKE, Hamburg, Germany. · Royal Surrey County Hospital, Guildford, UK. · Guy's Hospital, London, UK. · Hammersmith Hospital, London, UK. · The Beatson West of Scotland Cancer Centre, Glasgow, UK. · Velindre Hospital, Cardiff, UK. · Queen Elizabeth Hospital, Birmingham, UK. · Churchill Hospital, Oxford, UK. · Derriford Hospital, Plymouth, UK. · Ipswich Hospital, Ipswich, UK. · Skåne University Hospital, Lund, Sweden. · University Hospital Coventry, Coventry, UK. · Hôpital Beaujon, Clichy, France. · University of Heidelberg, Germany. ·Lancet · Pubmed #28129987.

ABSTRACT: BACKGROUND: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer. METHODS: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m FINDINGS: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5-31·5) compared with 25·5 months (22·7-27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68-0·98], p=0·032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group. INTERPRETATION: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma. FUNDING: Cancer Research UK.

5 Article The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner. 2018

Agerbæk, Mette Ø / Bang-Christensen, Sara R / Yang, Ming-Hsin / Clausen, Thomas M / Pereira, Marina A / Sharma, Shreya / Ditlev, Sisse B / Nielsen, Morten A / Choudhary, Swati / Gustavsson, Tobias / Sorensen, Poul H / Meyer, Tim / Propper, David / Shamash, Jonathan / Theander, Thor G / Aicher, Alexandra / Daugaard, Mads / Heeschen, Christopher / Salanti, Ali. ·Centre for Medical Parasitology at Department of Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, 2200, Copenhagen, Denmark. · Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada. · Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada. · Stem Cells in Cancer & Ageing, Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, United Kingdom. · Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, 11490, Taipei, Taiwan. · Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada. · UCL Cancer Institute, University College London, London, WC1E 6BT, United Kingdom. · Department of Medical Oncology, Barts Health NHS, London, EC1A 7BE, United Kingdom. · Stem Cells in Cancer & Ageing, Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, United Kingdom. c.heeschen@unsw.edu.au. · School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia. c.heeschen@unsw.edu.au. · Centre for Medical Parasitology at Department of Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, 2200, Copenhagen, Denmark. salanti@sund.ku.dk. ·Nat Commun · Pubmed #30115931.

ABSTRACT: Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial-mesenchymal transition of cancer cells. In 25 stage I-IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies.

6 Article Capecitabine and streptozocin ± cisplatin in advanced gastroenteropancreatic neuroendocrine tumours. 2014

Meyer, Tim / Qian, Wendi / Caplin, Martyn E / Armstrong, Graham / Lao-Sirieix, Si-Houy / Hardy, Richard / Valle, Juan W / Talbot, Denis C / Cunningham, David / Reed, Nick / Shaw, Ashley / Navalkissoor, Shaunak / Luong, Tu-Vinh / Corrie, Pippa G. ·Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK; UCL Cancer Institute, London, UK. · Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK; Medical Research Council Biostatistics Unit Hub for Trials Methodology, Cambridge, UK. · Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK. · Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK. · Department of Medical Oncology, The Christie, Manchester, UK. · Oxford Neuroendocrine Tumour Centre, Churchill Hospital, Oxford, UK. · Gastrointestinal Unit, The Royal Marsden, London, UK. · Beatson Oncology Centre, Glasgow, UK. · Oncology Centre, Addenbrooke's Hospital, Cambridge, UK. · Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK; Oncology Centre, Addenbrooke's Hospital, Cambridge, UK. Electronic address: pippa.corrie@addenbrookes.nhs.uk. ·Eur J Cancer · Pubmed #24445147.

ABSTRACT: BACKGROUND: Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin. METHODS: Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.0 g/m(2) intravenously on day 1, with or without cisplatin (Cis) 70 mg/m(2) intravenously on day 1. The primary outcome measure was objective response. Secondary outcome measures included progression-free and overall survival, quality of life, toxicity and biochemical response. RESULTS: 86 (44 CapStrep, 42 CapStrepCis) patients were randomised. Best objective response rate was 12% (95% confidence interval (CI)=2-22%) with CapStrep and 16% (95% CI=4-27.4%) with CapStrepCis. Disease-control rate was 80% with CapStrep and 74% with CapStrepCis. The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis. 44% of CapStrep and 68% of CapStrepCis patients experienced grade ≥3 adverse events. INTERPRETATION: The efficacies of the novel CapStrep±Cis regimens were very similar. CapStrep was better tolerated than CapStrepCis. The trial was registered as EudraCT: 2004-005202-71 and ISRCTN: 35124268.

7 Article CCK-2/gastrin receptor signaling pathway is significant for gemcitabine-induced gene expression of VEGF in pancreatic carcinoma cells. 2011

Kato, Hiroki / Seto, Koichi / Kobayashi, Nobuyoshi / Yoshinaga, Koji / Meyer, Tim / Takei, Mineo. ·Department of Clinical Research, Zeria Pharmaceutical Co., Ltd., Tokyo, Japan. ·Life Sci · Pubmed #21839751.

ABSTRACT: AIMS: As activation and overexpression of the cholecystokinin-2 (CCK-2)/gastrin receptor can lead to carcinogenesis, it has been explored as a therapeutic target in pancreatic cancer. We demonstrated that Z-360, a CCK-2/gastrin receptor antagonist, combined with gemcitabine prolonged survival and reduced gemcitabine-induced vascular endothelial growth factor (VEGF) expression in a pancreatic carcinoma orthotopic xenograft mouse. In this study, we investigated the role of the CCK-2/gastrin signaling pathway on gemcitabine-induced VEGF expression in PANC-1 human pancreatic carcinoma cells. MAIN METHODS: In PANC-1 cells treated with Z-360, anti-gastrin IgG or kinase inhibitors, the gene expression levels were analyzed by quantitative real-time RT-PCR, and the protein levels of Akt and phosphorylated Akt (p-Akt) in cellular extracts were measured by ELISA. KEY FINDINGS: Gemcitabine-induced expression of VEGF and hypoxia-inducible factor-1 alpha (HIF-1 alpha) were suppressed by the treatment with an anti-gastrin antibody. In addition, VEGF and HIF-1 alpha gene expression was inhibited by treatment with an inhibitor of phosphatidylinositol 3-kinase (PI3K), which is involved in the downstream signaling pathway of the CCK-2/gastrin receptor, and was also suppressed by treatment with Z-360. Moreover, although Akt phosphorylation was increased by treatment with gemcitabine, this elevation was partially, but significantly, inhibited by an exposure of Z-360. SIGNIFICANCE: Gemcitabine might induce gene expression of VEGF via the PI3K/Akt signaling pathway in the downstream of the CCK-2/gastrin receptor. The suppression of the CCK-2/gastrin signaling pathway by treatment with Z-360 could be a useful approach for potentiating prolonged survival of pancreatic cancer patients receiving gemcitabine therapy.

8 Article Z-360, a novel therapeutic agent for pancreatic cancer, prevents up-regulation of ephrin B1 gene expression and phosphorylation of NR2B via suppression of interleukin-1 β production in a cancer-induced pain model in mice. 2010

Orikawa, Yuki / Kato, Hiroki / Seto, Koichi / Kobayashi, Nobuyoshi / Yoshinaga, Koji / Hamano, Hiroki / Hori, Yuko / Meyer, Tim / Takei, Mineo. ·Central Research Laboratories, Zeria Pharmaceutical Co,, Ltd,, 2512-1 Numagami, Oshikiri, Kumagaya-shi, Saitama, Japan. yuki-orikawa@zeria.co.jp ·Mol Pain · Pubmed #20979661.

ABSTRACT: BACKGROUND: Z-360 is an orally active cholecystokinin-2 (CCK2)/gastrin receptor antagonist currently under development as a therapeutic drug for pancreatic cancer. It was previously reported that Z-360 treatment in combination with gemcitabine prolonged the survival period in a lethal pancreatic cancer xenograft model in mice. In a phase Ib/IIa clinical study, Z-360 treatment displayed a trend of reduced pain in patients with advanced pancreatic cancer in combination with gemcitabine including analgesics such as opioids. Here, we investigated the mechanism of analgesic action of Z-360 in a severe cancer-induced pain model in mice, which is considered to be opioid-resistant, by examining ephrin B1 gene expression, N-methyl-D-aspartate receptor NR2B subunit phosphorylation, and interleukin-1β (IL-1β) production. RESULTS: In a mouse model of cancer-induced pain, ephrin B1 gene expression in dorsal root ganglia (DRGs) and the phosphorylation of NR2B in the spinal cord were induced. Z-360 treatment inhibited both ephrin B1 gene expression and the phosphorylation of NR2B. In addition, IL-1β production increased in the cancer-inoculated hind paw of mice, but could be suppressed by treatment with Z-360. Moreover, we observed that the CCK1 receptor antagonist devazepide similarly suppressed up-regulation of ephrin B1 gene expression and IL-1β production, and that the intraperitoneal injection of sulfated CCK-8 induced the production of IL-1β in the cancer-inoculated region. CONCLUSIONS: We have identified a novel pain cascade, in which IL-1β production in cancer-inoculated regions induces ephrin B1 gene expression in DRGs and then ephrin B1 enhances the tyrosine phosphorylation of NR2B via Eph B receptor in the spinal cord. Notably, Z-360 relieves cancer-induced pain by preventing this pain cascade through the suppression of IL-1β production, likely via the blockade of CCK1 receptor. The pre-clinical results presented here support the analgesic action of Z-360 in pancreatic cancer patients with severe, opioid-resistant pain. Pre-clinical and clinical results have demonstrated that Z-360 combined with gemcitabine represents a promising pancreatic cancer therapy approach with characteristic analgesic effects in addition to the prolongation of survival.

9 Article Identification of Mac-2-binding protein as a putative marker of neuroendocrine tumors from the analysis of cell line secretomes. 2010

Srirajaskanthan, Rajaventhan / Caplin, Martyn E / Waugh, Mark G / Watkins, Jennifer / Meyer, Tim / Hsuan, J Justin / Beaumont, Nicholas J. ·Centre of Gastroenterology, Royal Free Hospital, London, United Kingdom. rs3856@doctors.org.uk ·Mol Cell Proteomics · Pubmed #20019050.

ABSTRACT: Neuroendocrine tumors (NETs) can arise from a variety of organs. They can vary widely in clinical behavior; consequently, optimizing their treatment plan can be problematic. NETs display diverse tumor biology; however, most secrete peptides such as chromogranin A into the circulation, consistent with their neuroendocrine origin. In this study, we sought to identify other potential markers for NETs by analyzing the secreted proteomes of three neuroendocrine cell lines. BON-1, NCI-H727, and SHP-77 cells were grown in serum-free media, and the secreted proteins were separated by SDS-PAGE and identified by LC-MS/MS. We identified 205 proteins of which 61 were secreted by two or more of the cell lines and 19 were secreted by all three lines. Mac-2-binding protein (Mac-2BP) was found to be secreted by all three cell lines, and this was confirmed by Western blotting. Immunohistochemical analysis found 29 of 33 NET cases from different primary sites to be positive for Mac-2BP. Serum Mac-2BP was significantly elevated in NET patients compared with healthy controls (p < 0.001). This study demonstrated that analysis of the secreted proteomes of neuroendocrine cell lines can identify potential biomarkers for NET. Initial assessment showed that serum Mac-2BP is significantly elevated in patients with NET and is expressed by the majority of NET tissues.

10 Minor Epigenetic dysregulation and poorer prognosis in DAXX-deficient pancreatic neuroendocrine tumours. 2015

Pipinikas, Christodoulos P / Dibra, Harpreet / Karpathakis, Anna / Feber, Andrew / Novelli, Marco / Oukrif, Dahmane / Fusai, Guiseppe / Valente, Roberto / Caplin, Martyn / Meyer, Tim / Teschendorff, Andrew / Bell, Christopher / Morris, Tiffany J / Salomoni, Paolo / Luong, Tu-Vinh / Davidson, Brian / Beck, Stephan / Thirlwell, Christina. ·Medical Genomics Laboratory, University College London Cancer Institute, University College London72 Huntley Street, London, WC1E 6BT, UK. · Medical Genomics Laboratory, University College London Cancer Institute, University College London72 Huntley Street, London, WC1E 6BT, UK Medical Genomics Laboratory, University College London Cancer Institute, University College London72 Huntley Street, London, WC1E 6BT, UK. · Medical Genomics Laboratory, University College London Cancer Institute, University College London72 Huntley Street, London, WC1E 6BT, UK Medical Genomics Laboratory, University College London Cancer Institute, University College London72 Huntley Street, London, WC1E 6BT, UK christina.thirlwell@ucl.ac.uk. ·Endocr Relat Cancer · Pubmed #25900181.

ABSTRACT: -- No abstract --