News Article | December 5, 2016
SAN ANTONIO -- The American Association for Cancer Research (AACR) will honor two renowned researchers for their work in breast cancer at the 2016 San Antonio Breast Cancer Symposium, held Dec. 6-10. Fergus J. Couch, PhD, of the Mayo Clinic in Rochester, Minnesota, will receive the ninth annual AACR Outstanding Investigator Award for Breast Cancer Research, funded by Susan G. Komen, and Max S. Wicha, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor, will receive the ninth annual AACR Distinguished Lectureship in Breast Cancer Research. The AACR Outstanding Investigator Award for Breast Cancer Research recognizes an investigator of no more than 50 years of age whose novel and significant work has had or may have a far-reaching impact on the etiology, detection, diagnosis, treatment, or prevention of breast cancer. Such work may involve any discipline across the continuum of biomedical research, including basic, translational, clinical, and epidemiological studies. Couch, who is the Zbigniew and Anna M. Scheller professor of medical research, and chair of the Division of Experimental Pathology and Laboratory Medicine in the Department of Laboratory Medicine and Pathology at the Mayo Clinic, is being honored for his seminal work in identifying the inherited genes and mutations that predispose to breast cancer. Much of his research has focused on determining the clinical relevance of inherited variants of uncertain significance (VUS) in breast cancer predisposition genes using genetic epidemiology and molecular biology approaches. Couch will present his Outstanding Investigator Award for Breast Cancer Research lecture, "Decoding Breast Cancer Predisposition Genes," Friday, Dec. 9, at 11:30 a.m. CT, in Hall 3 of the Henry B. Gonzalez Convention Center. A distinguished national leader in cancer genetics, Couch is a founder and member of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, and a leader in the BRCA Challenge and the Prospective Registry of Multiplex Testing (PROMPT) initiatives aimed at understanding alterations in cancer predisposition genes. He is also a co-founder of the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a Triple Negative Breast Cancer Consortium (TNBCC), and is a long-term member of the Breast Cancer Association Consortium. Working with members of these consortia, Couch has led genome-wide association studies to identify common genetic variants that influence risk of estrogen receptor (ER) negative and triple negative breast cancer and modify risks of breast cancer among carriers of germline BRCA1 and BRCA2 mutations. In more recent research, Couch has been working to estimate risks of breast cancer associated with pathogenic variants identified by clinical genetic testing using multigene panels, and is leading an effort to identify genetic factors that account for the missing heritability of breast cancer. The AACR Distinguished Lectureship in Breast Cancer Research was established to recognize outstanding science that has inspired or has the potential to inspire new perspectives on the etiology, diagnosis, treatment, or prevention of breast cancer. Wicha, director emeritus of the University of Michigan Comprehensive Cancer Center, is being recognized for his leadership in breast cancer research and as a pioneer in the field of cancer stem cells (CSCs). Wicha is among the most highly cited investigators in the field. His group was part of the team that first identified CSCs in human breast cancers, the first in any solid tumor. His laboratory has developed many of the techniques and assays used to study these cells and to elucidate the pathways which regulate their behavior. These pathways have provided targets for the development of drugs aimed at targeting CSCs. He will present his Distinguished Lectureship in Breast Cancer Research award lecture, "Targeting Breast Cancer Stem Cells: Challenges and Opportunities," Thursday, Dec. 8, at 11:30 a.m. CT, in Hall 3 of the Henry B. Gonzalez Convention Center. Wicha is co-founder of OncoMed Pharmaceuticals, a company focused on developing CSC therapeutics, which has produced five agents currently in clinical testing. After training at the National Cancer Institute in clinical oncology and cancer biology, Wicha joined the faculty of the University of Michigan in 1980, where he served as chief in the Division of Hematology/Oncology in the Department of Internal Medicine. He served as director of the University of Michigan Comprehensive Cancer Center since its inception in 1986 until 2015, when he became director emeritus. He remains an active clinician, specializing in the treatment of patients with breast cancer. The mission of the 2016 San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR), and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR's scientific prestige in basic, translational, and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit http://www. .
Kagedal K.,Prince of Wales Medical Research Institute |
Kim W.S.,Prince of Wales Medical Research Institute |
Kim W.S.,University of New South Wales |
Appelqvist H.,Experimental Pathology |
And 9 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2010
The Niemann-Pick type C1 (NPC1) protein mediates the trafficking of cholesterol from lysosomes to other organelles. Mutations in the NPC1 gene lead to the retention of cholesterol and other lipids in the lysosomal compartment, and such defects are the basis of NPC disease. Several parallels exist between NPC disease and Alzheimer's disease (AD), including altered cholesterol homeostasis, changes in the lysosomal system, neurofibrillary tangles, and increased amyloid-beta generation. How the expression of NPC1 in the human brain is affected in AD has not been investigated so far. In the present study, we measured NPC1 mRNA and protein expression in three distinct regions of the human brain, and we revealed that NPC1 expression is upregulated at both mRNA and protein levels in the hippocampus and frontal cortex of AD patients compared to control individuals. In the cerebellum, a brain region that is relatively spared in AD, no difference in NPC1 expression was detected. Similarly, murine NPC1 mRNA levels were increased in the hippocampus of 12-month-old transgenic mice expressing a familial AD form of human amyloid-beta precursor protein (APP) and presenilin-1 (APP/PS1tg) compared to 12-month-old wild type mice, whereas no change in NPC1 was detected in mouse cerebellum. Immunohistochemical analysis of human hippocampus indicated that NPC1 expression was strongest in neurons. However, in vitro studies revealed that NPC1 expression was not induced by transfecting SK-N-SH neurons with human APP or by treating them with oligomeric amyloid-beta peptide. Total cholesterol levels were reduced in hippocampus from AD patients compared to control individuals, and it is therefore possible that the increased expression of NPC1 is linked to perturbed cholesterol homeostasis in AD. © 2010 Elsevier B.V. All rights reserved.
Nubile M.,University of Chieti Pescara |
Curcio C.,University of Chieti Pescara |
Lanzini M.,University of Chieti Pescara |
Calienno R.,University of Chieti Pescara |
And 4 more authors.
Ophthalmic Research | Year: 2013
Aim: Ultraviolet (UV) B irradiation induces gene expression that leads to skin cancer. Among the transcription factors induced by UVB radiation exposure, the cyclic AMP response element-binding protein (CREB) is significant. Since several factors downstream of CREB signaling are known to be involved in pterygium pathogenesis, we investigated CREB expression in pterygial and human conjunctival tissues to evaluate if a similar expression pattern is present. Moreover, we analyzed the correlation with CREB expression and other known pterygium markers. Methods: Primary pterygium samples and normal bulbar conjunctivas surgically removed were analyzed. Formalin-fixed, paraffin-embedded tissues were stained by immunohistochemistry with anti-CREB, anti-vimentin, anti-ki-67, anti-survivin, anti-MMP7, anti-p63, anti-cyclin D1, or anti-p53 antibodies. Results: 94.4% of pterygium samples were positive for CREB with a significant difference compared to the control group (p = 0.002). The staining was localized in the epithelium and absent in the stroma. An increased expression was found for cyclin D1 (p = 0.019), ki-67 (p = 0.005), vimentin (p = 0.003), survivin (p < 0.001), p63 (p = 0.003), and MMP7 (p = 0.002). CREB expression showed a significant correlation with cyclin D1 (ρ = 0.49; p = 0.035), ki-67 (ρ = 0.61; p = 0.007), and p53 (ρ = 0.57; p = 0.013) in pterygium. Conclusions: These results permit to hypothesize that CREB is involved in pterygium pathogenesis. Since various molecules have been discovered to inhibit CREB, these data could be of interest for pterygium treatment. Copyright © 2013 S. Karger AG, Basel.
News Article | December 15, 2016
The same signal that drives aggressive growth in a deadly cancer cell type also triggers coping mechanisms that make it "notoriously" hard to kill, according to a study published online December 15 in Cell. When stressed, this cell type - far more than most cancer cells - encases its genetic messages in protein globs called "stress granules" that lessen the effect of chemotherapies. Led by two researchers from NYU Langone Medical Center and Thomas Jefferson University, the study revolves around the gene KRAS, which when changed, or mutated, drives abnormal growth in 90 percent of pancreatic cancers, as well as in many lung and colorectal tumors. As a second consequence of overactive KRAS, say the study authors, cells harboring this mutation form many more stress-coping granules. "Our results explain why KRAS mutant cells are so good at resisting treatments, and suggest a way to make them many times more vulnerable to existing chemotherapies," says senior study author Dafna Bar-Sagi, PhD, Vice Dean for Science and Chief Scientific Officer at NYU Langone. "Given the lack of good treatments for these patients, the ability to interfere with this coping mechanism would be revolutionary," says Bar-Sagi, also a professor in the Department of Biochemistry and Molecular Pharmacology at NYU Langone, and associated with its Perlmutter Cancer Center. All cells are continually exposed to stresses and rely on stress-coping mechanisms to survive. A growing body of evidence suggests that such resilience is especially vital for cancer cells, with the most resistant soon coming to dominate a growing tumor. In a long-recognized stress response, cells halt the reading of DNA instructions in the middle - at the point when genetic messages are surrounded by proteins - to form protective granules. While the role of such granules in normal cellular life is established, their contribution to the stubborn survival of KRAS mutant cancer cells had not been clear. In experiments, the research team showed that cells with KRAS mutations made six times more stress granules than cells without the mutations when exposed to either radiation or oxaliplatin, a chemotherapy that damages cancer cell DNA. Researchers were also able to capture and count the first images of stress granules in cancer cells resected from human pancreatic tumors, finding a marked increase. The study found further that stressed cancer cells with KRAS mutations increase granule formation by making more of a hormone-like molecule called 15-deoxy-delta 12,14 prostaglandin J2 (15-d-PGJ2). Importantly, increases in levels of 15-d-PGJ2 triggered more stress granule formation, not only in mutated cells, but also in nearby cells without KRAS mutations (a 13-fold increase), which then became more resistant to oxaliplatin. This is because 15-d-PGJ2 is a signaling molecule secreted by cells. "Mounting evidence suggests that the cancer cells making up even a single tumor are genetically diverse, so no treatment targeting just one genetic difference can kill them all," says study author Elda Grabocka, PhD, assistant professor of Cancer Biology at Sidney Kimmel Cancer Center at Jefferson. Grabocka designed the study while a post-doctoral scholar in Bar-Sagi's lab at NYU Langone. "If we could block the action of 15-d-PGJ2, we might make many more cancer cells in a tumor sensitive to a single therapy by removing a shared coping mechanism." Moving forward, the authors plan to study whether, as hinted in past studies, adding a cyclooxygenase 2 (COX 2) inhibitor - a popular type of anti-inflammatory painkiller - to chemotherapy can improve outcomes in patients with mutant KRAS cancers. Mutant KRAS cells are known to make extra COX 2, which increases 15-d-PGJ2 levels. At the same time, the researchers will seek to identify compounds that can directly counter 15-d-PGJ2 buildup, perhaps by using HPGD, an enzyme discovered in the current study to lower levels of 15-d-PGJ2. The study was supported by National Institutes of Health grants R01CA055360 and 1F32CA13922. The study authors took advantage of the Division of Advanced Research Technologies' Cytometry and Cell Sorting Laboratory and the Experimental Pathology Shared Resource Laboratory at NYU School of Medicine, which are supported by Perlmutter Cancer Center support grant P30CA016087.
Bergfors E.,Research and Development Unit in Local Health Care |
Lundmark K.,Experimental Pathology |
Kronander U.N.,Linköping University
BMJ Case Reports | Year: 2013
A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.
PubMed | Aix - Marseille University, Experimental Pathology, University of Pennsylvania and University of Liège
Type: Journal Article | Journal: ERJ open research | Year: 2016
With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve second-line therapy of SCLC. The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development). We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models. Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies.
Baroud M.,Experimental Pathology |
Araj G.F.,American University of Beirut |
Matar G.M.,Experimental Pathology |
Matar G.M.,American University of Beirut
International Arabic Journal of Antimicrobial Agents | Year: 2011
The CTX-M type enzymes have become the most prevalent extended spectrum β-lactamases (ESBLs) worldwide. Among the CTX-M type enzymes, CTX-M-15 is the most widespread and has been reported from all continents. It has been recovered from diferent Enterobacteriaceae and has been isolated from both community and hospital acquired infections. This review primarily highlights the prevalence of CTX-M-15 in addition to other ESBLs in the Middle East. Detection of any type of ESBL is of importance in therapeutic treatment.© Under License of Creative Commons Attribution 3.0 License.