Author Interviews, Pancreatic, Stem Cells / 14.09.2015

Patricia Sancho, PhD, Lecturer Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London EC1M 6BQ MedicalResearch.com Interview with: Patricia Sancho, PhD, Lecturer Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London Medical Research: What is the background for this study? What are the main findings? Dr. Sancho: Cancer cells commonly rely on glycolysis, the type of metabolism that does not use oxygen to generate their energy however, we have now found that not all cancer cells are alike when it comes to metabolism. Pancreatic Cancer Stem cells (PancCSCs) can make use of a more efficient form of metabolism, called oxidative phosphorylation or OXPHOS, which does use oxygen. OXPHOS uses a part of the cell called mitochondria and it is this which can be targeted with anti-diabetic drug, metformin. Some PancSCs are however able to escape this treatment by being much more flexible in their metabolism, leading to a recurrence of the cancer, but we also found a way to prevent such resistance and force all Pancreatic Cancer Stem cells to keep using OXPHOS. (more…)
Author Interviews, Biomarkers, Pancreatic / 28.08.2015

Jenny Permuth Wey, PhD, MS Assistant Member Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer Cente MedicalResearch.com Interview with: Jenny Permuth Wey, PhD, MS Assistant Member Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer Center   Medical Research: What is the background for this study? What are the main findings? Dr. Wey: Pancreatic cancer is one of the deadliest cancers world-wide. It is currently the fourth leading cause of cancer-related deaths in the United States, and is predicted to become the second leading cause by 2030. Currently there are no accurate methods to diagnose pancreatic cancer early when a patient may be eligible for surgery to remove the tumor and hopefully survive longer. To beat this disease, early detection is key, and our team has dedicated efforts to studying pancreatic cancer in its ‘precancerous’ state because we and other researchers believe that the identification and treatment of precancerous pancreatic lesions offers a promising strategy to reduce the number of people losing their lives to this disease. Similar to how colon polyps can progress into colon cancer, we now know that certain types of pancreatic cystic lesions can progress into pancreatic cancer. Pancreatic cancer precursors/pre-cancers known as intraductal papillary mucinous neoplasms (IPMNs) account for nearly one-half of the estimated 150,000 asymptomatic pancreatic cysts detected as ‘incidental findings’ on computed tomography (CT) scans or magnetic resonance imaging (MRI) scans each year during the clinical work-up for an unrelated condition. Imaging alone cannot reliably distinguish between benign, pre-cancerous, and cancerous cysts, and cannot differentiate ‘low-risk’intraductal papillary mucinous neoplasms' (defined as low- or moderate-grade disease) that can be monitored from ‘high-risk’ IPMNs (defined as high-grade or invasive disease) that should be surgically removed. The decision to undergo pancreatic surgery is not trivial for the patient and medical team since pancreatic surgery can be associated with an estimated 40% chance of complications and a 4% chance of death. Noninvasive tests are needed to accurately detect precancerous lesions of the pancreas so that personalized risk assessment and care can be provided. microRNAs (miRNAs) are small molecules that act as ‘master-regulators’ of cancer-related processes in the body. One of the main purposes of our ‘proof of principle’ study was to measure miRNAs in the blood and determine whether a set of miRNAs could distinguish patients with IPMNs from healthy individuals. We then sought to determine whether a set of miRNAs could distinguish patients known to have ‘low-risk’ IPMNs from those with ‘high-risk’ IPMNs. We show that new, relatively inexpensive digital technology could reliably measure miRNAs in blood plasma (the pale yellow liquid component of blood) from individuals newly-diagnosed with pancreatic cancer precursors (IPMNs) and healthy individuals. Thirty miRNAs out of 800 tested showed higher levels in IPMN patients compared to healthy individuals, providing a preliminary ‘miRNA signature’ that may be found only in people with early pancreatic disease, suggesting it could serve as an early diagnostic tool. Furthermore, we also provide preliminary data to suggest that a 5-miRNA signature can partially distinguish high-risk IPMNs that warrant resection from low-risk IPMNs that can be watched. This is important clinically because it would be opportune to personalize care such that high-risk IPMNs that warrant resection are properly identified while individuals with low-risk IPMNs are spared the substantial risks of mortality and morbidity associated with overtreatment from unnecessary surgery. (more…)
Author Interviews, Biomarkers, Pancreatic / 17.08.2015

Tatjana Crnogorac-Jurcevic MD PhD Reader Centre for Molecular Oncology Barts Cancer Institute, Queen Mary, University of London London UK MedicalResearch.com Interview with: Tatjana Crnogorac-Jurcevic MD PhD Reader Centre for Molecular Oncology Barts Cancer Institute, Queen Mary University of London London UK Medical Research: What is the background for this study? What are the main findings? Dr. Crnogorac-Jurcevic: Pancreatic adenocarcinoma (PDAC) is one of the most difficult cancers to detect. More than 80% of patients usually present at a late stage, with either locally advanced or with already metastatic disease. This is one of the major reasons for a bleak prognosis of this malignancy, which is typically 3-6 months and with <5% five-year survival. However, if patients are diagnosed with stage II disease, the survival rate is 20%, and at stage I, in patients with very small tumours, the five-year survival can increase up to 60%. In order to find biomarkers for early detection of this disease, we have performed in depth GeLC/MS/MS (SDS-PAGE-liquid chromatography-tandem mass spectrometry) analysis of 18 proteomes of urine samples collected from healthy controls, chronic pancreatitis, and patients with Pancreatic adenocarcinoma and obtained around 1500 non-redundant proteins. From these, three proteins, LYVE-1, REG1A, and TFF1, were selected for further analysis based on their known biological functions and statistical difference in comparisons of the experimental groups. These biomarkers were subsequently validated using ELISA assays in a multicenter cohort of urine samples: 87 from healthy people, 92 from patients with chronic pancreatitis, and 192 from PDAC patients. Multiple logistic regression was then applied: when comparing Pancreatic adenocarcinoma with healthy urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the three biomarkers combined into a panel were 0.89 (95% confidence interval: 0.84–0.94) in the training dataset (70% of the data) and 0.92 (95% confidence interval: 0.86–0.98) in the validation dataset (30% of the data). When the results from the analysis of PDAC stage I–II (n=71) urine samples were compared with the healthy urine specimens, the panel achieved AUCs of 0.90 (95% confidence interval: 0.84–0.96) and 0.93 (95% confidence interval: 0.84–1.00) in the training and validation datasets, respectively. In comparison to matching plasma CA19.9 values, the only Pancreatic adenocarcinoma biomarker in widespread clinical use (albeit mostly for monitoring of the disease), the panel achieved a higher AUC of 0.97 (95% confidence interval: 0.94–0.99) than CA19.9 (AUC 1/4 0.88; 95% confidence interval: 0.81–0.95, P=0.005). When combined with CA19.9, increased AUC of 0.99 (95% confidence interval: 0.97–1.00, P=0.04) was achieved, but this was not seen in a panel combined with plasma CA19.9 in stage I–IIA PDAC (n =17) vs. healthy sample comparison. (more…)
Author Interviews, Biomarkers, Chemotherapy, Nature, Pancreatic / 01.07.2015

Dr. Janaiah Kota Assistant Professor, Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis, IN, MedicalResearch.com Interview with: Dr. Janaiah Kota Assistant Professor, Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis, IN, Medical Research: What is the background for this study? Dr. Kota: Pancreatic cancer tumors are surrounded by a thick fibrotic shell known as “stroma” which protects the cancer cells from anticancer drugs such as chemotherapy. However, complete depletion of tumor stroma leads to more aggressive disease and decreases survival. The stromal abundance needs to be appropriately moderated (i.e. not too much nor too little) in pancreatic tumors. None of the current anti-stromal therapies have been effective enough to resolve this problem. Unless we understand the molecular signatures associated with tumor stroma, it will be challenging to develop an effective therapeutic strategy. There is a desperate need to develop new therapies for pancreatic cancer as only 7 percent of people with the disease survive more than 5 years after diagnosis. According to the National Cancer Institute, there will be an estimated 48,960 new cases of pancreatic cancer and 40,560 deaths from the disease in 2015. Medical Research: What are the main findings? Dr. Kota: We found that the loss of microRNA-29 (miR-29) is a common phenomenon of pancreatic cancer stromal cells, and that by restoring it, the viability and growth of the cancerous cells and stromal accumulation was reduced. The use of miR-29 as a therapeutic agent may be more effective in targeting reactive stroma, as a single miRNA regulates the expression of several genes associated with disease mechanisms. We expect that this novel approach has the potential to overcome the problems associated with current anti-stromal drugs and could lead to improved therapeutic strategies, enhanced drug delivery to the tumor bed, and, in the future, improved patient survival. (more…)
Author Interviews, Genetic Research, Nature, Pancreatic, UT Southwestern / 10.04.2015

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Southwestern MedicalResearch.com Interview with: Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Southwestern MedicalResearch: What is the background for this study? Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts. MedicalResearch: What are the main findings? Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease. Specifically, many cases harbored deregulation in pathways that are the target for drug development. For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib. Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors. Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention. (more…)
Author Interviews, Mayo Clinic, Nature, Pancreatic / 24.02.2015

Peter Storz, Ph.D. Associate Professor & Consultant Department of Cancer Biology Mayo Clinic Jacksonville, FL 32224 MedicalResearch.com Interview with: Peter Storz, Ph.D. Associate Professor & Consultant Department of Cancer Biology Mayo Clinic Jacksonville, FL 32224   Medical Research: What is the background for this study? What are the main findings? Dr. Storz: Our study focuses on cellular signaling mechanisms that lead to the initiation of pancreatic cancer. After acquisition of an oncogenic mutation of Kras, pancreatic acinar cells can undergo a transdifferentiation process to a phenotype that gives rise to pancreatic intraepithelial lesions (PanINs). These lesions then can further progress to pancreatic cancer. (more…)
Author Interviews, Cancer, Pancreatic / 24.10.2014

MedicalResearch.com Interview with: Jeremy L. Humphris MBBS The Kinghorn Cancer Center, Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia and Andrew V. Biankin Regius Professor of Surgery Director, Wolfson Wohl Cancer Research Centre, University of Glasgow Garscube Estate, Switchback Road, Bearsden, Glasgow Scotland United Kingdom Medical Research: What are the main findings of the study? Response: Familial pancreatic cancer (FPC) is a family with at least 2 first degree (parent-child or siblings) with pancreatic cancer. We found these patients represent nearly 9% of our cohort. In addition we found those with familial pancreatic cancer were more likely to have other first degree relatives with a history of extra-pancreatic cancer, in particular melanoma and endometrial cancer. Patients with familial pancreatic cancer had more high grade precursor lesions in the pancreas adjacent to the tumour but the outcome was similar. Smoking was more prevalent in sporadic pancreatic cancer and active smoking was associated with significantly younger age at diagnosis in both groups. Long-standing diabetes mellitus (> 2 years duration) was associated with poorer survival in both groups. (more…)
Author Interviews, Pancreatic / 19.09.2014

MedicalResearch.com: Interview Bashir A. Lwaleed PhD, FRCPath, CBiol FSB, FIBMS Senior Lecturer Faculty of Health Sciences University of Southampton Southampton General Hospital Southampton United Kingdom Medical Research: What are the main findings of the study? Dr. Lwaleed: That constituent(s) of Chokeberries has a supra-additive cytotoxic effect in combination with the drug gemcitabine, which is used clinically for this condition, when applied to a pancreatic carcinoma cell line in vitro. (more…)
Pancreatic / 10.07.2014

Andrea Wang-GillamMD, PhD Assistant Professor, Department of Medicine Oncology Division, Medical Oncology Section Washington University School of Medicine in St. Louis MedicalResearch.com Interview with: Andrea Wang-GillamMD, PhD Assistant Professor, Department of Medicine Oncology Division, Medical Oncology Section Washington University School of Medicine in St. Louis Medical Research: What are the main findings of the study? Dr. Wang-Gillam: This is a global randomized phase III trial of MM398 plus 5FU/LV vs. MM398 vs. 5FU/LV in patients with metastatic pancreatic cancer who had received prior gemcitabine-based therapy. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), response rate (RR), biochemical response and safety. The trial achieved its primary endpoint. The median overall survival was statistically longer with the combination of MM398 plus 5FU/LV compared with 5FU/LV alone (6.1 months vs 4.2 months; HR of 0.67; p=0.0122). A superior progression-free survival was also seen in the MM398 plus 5FU/LV group compared with the 5FU/LV alone group (3.1 months vs 1.5 months; HR of 0.56; p=0.0001). A higher response rate was observed in the combination regimen compared with the 5FU/LV group (16% vs 1%). There were no differences in overall survival or PFS between the MM 398 monotherapy and 5FU/LV groups. (more…)
Author Interviews, Johns Hopkins, Pancreatic / 21.06.2014

Lei Zheng, M.D., Ph.D. Assistant Professor of Oncology and Surgery Gastrointestinal Cancer Program Division of Immunology The Sidney Kimmel Comprehensive Cancer Center and Department of Oncology Johns Hopkins University School of Medicine The Bunting-Blaustein Cancer Research Building (CRB1) Baltimore, MD 21231 MedicalResearch.com Interview with: Lei Zheng, M.D., Ph.D. Assistant Professor of Oncology and Surgery Gastrointestinal Cancer Program Division of Immunology The Sidney Kimmel Comprehensive Cancer Center and Department of Oncology Johns Hopkins University School of Medicine The Bunting-Blaustein Cancer Research Building (CRB1) Baltimore, MD 21231 MedicalResearch: What are the main findings of the study? Dr. Zheng: This study shows for the first time that treatment with a vaccine-based immunotherapy directly re-programs the pancreatic cancer microenvironment, allowing the formation of lymphoid aggregates, which are organized, lymph node-like, functional immune structures and which convert an immunologically quiescent tumor into an immunologically active tumor. (more…)
Author Interviews, Nutrition, Pancreatic / 05.06.2014

Wai-Nang Paul Lee, M.D. Division Chief, Division of Pediatric Endocrinology and Metabolism Professor of Pediatrics Director of Biomedical Mass Spectrometry Laboratory MedicalResearch.com Interview with: Wai-Nang Paul Lee, M.D. Division Chief, Division of Pediatric Endocrinology and Metabolism Professor of Pediatrics Director of Biomedical Mass Spectrometry Laboratory Harbor-UCLA MedicalResearch: What are the main findings of the study? Dr. Wai-Nang Lee: The study reports that EGCG, the active biologic constituent in green tea, changed the metabolism of pancreatic cancer cells by suppressing the expression of an enzyme associated with cancer, LDHA. The researchers also compared the effects of EGCG with those of an enzyme inhibitor, oxamate, which is known to reduce LDHA activity, and found that they both operated in a similar manner by disrupting the pancreatic cancer cells metabolic system. Scientists had believed they needed a molecular mechanism to treat cancer, but this study shows that they can change the metabolic system and have an impact on cancer. (more…)
Author Interviews, Mayo Clinic, Pancreatic / 27.05.2014

Dr. Derek Radisky PhD Associate Professor and Consultant Mayo Clinic Cancer Center MedicalResearch.com Interview with Dr. Derek Radisky PhD Associate Professor and Consultant Mayo Clinic Cancer Center MedicalResearch: What are the main findings of the study? Dr. Radisky: The study used human tissue biopsies to find that production of matrix metalloproteinse-3 (MMP3) in pancreatic cancer biopsies was associated with poorer patient prognosis, and showed through transgenic animal and cell culture experiments that this was due to activation of the oncogenic protein Rac1b. The study thus identifies an MMP3-Rac1b signaling axis that drives pancreatic cancer progression. (more…)
Author Interviews, Cancer Research, JNCI, Pancreatic / 25.03.2014

Dr. Karolina Sjöberg Jabbar, MD, Medicine Policlinic II, Bla Straket 5, Sahlgrenska University Hospital Gothenburg, Sweden MedicalResearch.com Interview with Dr. Karolina Sjöberg Jabbar, MD, Medicine Policlinic II, Bla Straket 5, Sahlgrenska University Hospital Gothenburg, Sweden   MedicalResearch.com: What are the main findings of the study? Answer: The main finding of this study is that the presence of mucin proteins in pancreatic cyst fluid, as evaluated by mass spectrometry, can predict with high accuracy (97%) which pancreatic cysts contain premalignant and malignant tumours. This is important, given that pancreatic cystic lesions are an increasingly common incidental finding on imaging. While most of them pose no threat to the patient, a minor proportion has malignant potential, and may be considered precursors to pancreatic cancer. (more…)
Antioxidants, Author Interviews, Brigham & Women's - Harvard, Medical Research Centers, Nature, Nutrition, Pancreatic / 23.11.2013

MedicalResearch.com Interview with: dr_ying_bao Ying Bao, MD, ScD Department of Medicine, Brigham and Women's Hospital and Harvard Medical School Boston, MA. MedicalResearch.com: What are the main findings of the study? Dr. Bao: Frequent nut consumption is inversely associated with risk of pancreatic cancer in women, independent of other potential risk factors for pancreatic cancer. (more…)
Author Interviews, Pancreatic, Radiation Therapy / 26.09.2013

MedicalResearch.com Interview with: Dr. Raphael Yechieli Department of Radiation Oncology at Henry Ford Hospital in Detroit: MedicalResearch.com: What are the main findings of the study? Dr. Yechieli: The main findings of the study are that elderly patients with pancreatic cancer who also have significant co-morbidities can still be safely and effectively treated with a short course of radiation treatment. Furthermore, the local control and survival data from our study are similar to previously published data, where patients were treated with more intense and longer courses of treatment. (more…)