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981.
Kishore Guda Martina L. Veigl Vinay Varadan Arman Nosrati Lakshmeswari Ravi James Lutterbaugh Lydia Beard James K. V. Willson W. David Sedwick Zhenghe John Wang Neil Molyneaux Alexander Miron Mark D. Adams Robert C. Elston Sanford D. Markowitz Joseph E. Willis 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(4):1149-1154
We used whole-exome and targeted sequencing to characterize somatic mutations in 103 colorectal cancers (CRC) from African Americans, identifying 20 new genes as significantly mutated in CRC. Resequencing 129 Caucasian derived CRCs confirmed a 15-gene set as a preferential target for mutations in African American CRCs. Two predominant genes, ephrin type A receptor 6 (EPHA6) and folliculin (FLCN), with mutations exclusive to African American CRCs, are by genetic and biological criteria highly likely African American CRC driver genes. These previously unsuspected differences in the mutational landscapes of CRCs arising among individuals of different ethnicities have potential to impact on broader disparities in cancer behaviors.Colorectal cancer (CRC) is a leading cause of cancer mortality world-wide. CRC incidence and mortality rates are both increased in African Americans (AA) compared with Caucasians Americans (1–3). Although several factors likely play a role, the contribution of potential differences in tumor genetics to this disparity have yet to be fully explored (1, 3). In particular, AA CRCs were notably underrepresented in the four major published CRC sequencing studies (4–7), accounting for only two annotated AA cases of the 333 total CRCs studied (4–7). Accordingly, we initiated this study to compare the mutational landscapes of CRCs from AA individuals versus Caucasians. 相似文献
982.
Patrick Celis Nicolas Ferry Marit Hystad Martina Schü?ler-Lenz Pieter A. Doevendans Egbert Flory Claire Beuneu Ilona Reischl Paula Salmikangas 《Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie》2015,42(3):194-199
On September 11, 2014, a workshop entitled ‘Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Product Successfully to the Market’ was held at the 47th annual meeting of the German Society for Transfusion Medicine and Immunohematology (DGTI), co-organised by the European Medicines Agency (EMA) and the DGTI in collaboration with the German Stem Cell Network (GSCN). The workshop brought together over 160 participants from academia, hospitals, small- or medium-sized enterprise developers and regulators. At the workshop, speakers from EMA, the Committee for Advanced Therapies (CAT), industry and academia addressed the regulatory aspects of development and authorisation of advanced therapy medicinal products (ATMPs), classification of ATMPs and considerations on cell-based therapies for cardiac repair. The open forum discussion session allowed for a direct interaction between ATMP developers and the speakers from EMA and CAT.Key Words: Advanced therapy medicinal products, ATMP, Committee for Advanced Therapies, CAT 相似文献
983.
Bonelli L Aste H Bovo P Cavallini G Felder M Gusmaroli R Morandini E Ravelli P Briglia R Lombardo L De Micheli A Pugliese V 《Pancreas》2003,27(2):143-149
The role of cigarette smoking and diabetes mellitus as risk factors for exocrine pancreatic cancer (PC) was investigated in a hospital based case-control study. Current smokers were at increased risk for PC (OR = 2.36, 95% CI 1.53-3.63): the magnitude of the risk was related to the lifetime amount of smoking (chi2(trend) = 17.00; P < 0.0001). Among former smokers, after 15 years from ceasing smoking, the risk for PC dropped to the level of a lifetime non-smoker, whichever the lifetime smoking amount. Diabetes was associated with a 2.89-fold increased risk for PC (95% CI 1.71-4.86): the risk was 4.76 (95% CI 1.99-11.53) for diabetes diagnosed up to 2 years before the diagnosis of PC and dropped to 2.07 (95% CI 1.02-4.20) for diabetes diagnosed more than 5 years before PC. The risk for PC was estimated according to the treatment used to control diabetes: it was 6.49 (95% CI 2.28-18.48) for insulin treated diabetes and 2.12 (95% CI 1.16-3.87) for diabetes treated with oral hypoglycemic drugs. The risk of PC for diabetes treated for more than 5 years before the diagnosis of PC was 6.21 (95% CI 1.61-23.96) for patients treated with insulin and 1.21 (95% CI 0.50-2.92) for those treated with oral hypoglycemic drugs: the type of treatment needed to control the disease may discriminate between the diabetes that represents a consequence of cancer from the diabetes that could represent an etiological co-factor. More studies are needed to clarify whether long-lasting insulin-treated diabetes is an etiological co-factor in PC. 相似文献
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Clinical perspectives: Practical insights from clinical experience with cabazitaxel in Australia 下载免费PDF全文
Phillip Parente Howard Gurney Siobhan Ng Martina Bahre 《Asia-Pacific Journal of Clinical Oncology》2015,11(3):199-207
Prostate cancer, and in particular the management options for patients with metastatic castration‐resistant prostate cancer (mCRPC), remains an important health issue. The approval of cabazitaxel provides a new treatment option for patients who have progressed despite docetaxel therapy. Clinical use of cabazitaxel in mCRPC is based on the results of the TROPIC study, which demonstrated an approximately 30% reduction in the risk of death compared with mitoxantrone. In this paper, we draw on accumulating clinical experience with cabazitaxel in Australia to discuss important questions such as how to select the right patient for treatment and how to proactively prevent and manage toxicities associated with this therapy. Recognizing the need for a multidisciplinary approach to patient care, opinion and insight has been sought from medical oncologists, nurses and pharmacists. While lack of trial data means that a number of questions remain unanswered, local clinical experience has helped to guide treatment decisions and refine management protocols. Appropriate patient selection, careful ongoing monitoring and proactive management of adverse events will ensure optimal treatment of patients. Nurses in particular play an important role in educating patients and identifying patients at increased risk of developing adverse events with cabazitaxel. The oncology team must work together to educate patients; taking a proactive approach to issues such as adverse events will help maximize the clinical outcome of cabazitaxel treatment and impact positively on the patient's quality of life. 相似文献
989.
Rachel Isaksson Vogel Kathleen Coughlin Alessandra Scotti Yoshie Iizuka Ravi Anchoori Richard B. S. Roden Mauro Marastoni Martina Bazzaro 《Oncotarget》2015,6(6):4159-4170
Breast cancer is one of the leading causes of cancer death among women in the United States. Patients expressing the estrogen and progesterone receptor (ER and PR) and human epidermal growth factor 2 (HER-2) tumor markers have favorable prognosis and efficacious therapeutic options. In contrast, tumors that are negative for these markers (triple-negative) have a disproportionate share of morbidity and mortality due to lack of a validated molecular target.Deubiquitinating enzymes (DUBs) are a critical component of ubiquitin-proteasome-system degradation and have been shown to be differentially expressed and activated in a number of cancers, including breast, with their aberrant activity linked to cancer prognosis and clinical outcome. We evaluated the effect of the DUB inhibitors b-AP15 and RA-9 alone and in combination with early- and late-stage lysosomal inhibitors on cell viability in a panel of triple negative breast cancer (TNBC) cell lines.Our results indicate small-molecule DUB inhibitors have a profound effect on TNBC viability and lead to activation of autophagy as a cellular mechanism to compensate for ubiquitin-proteasome-system stress. Treatment with sub-optimal doses of DUB and lysosome inhibitors synergistically kills TNBC cells. This supports the evaluation of DUB inhibition, in combination with lysosomal inhibition, as a therapeutic approach for the treatment of TNBC. 相似文献
990.
Martina D'Aronzo Manlio Vinciguerra Tommaso Mazza Concetta Panebianco Chiara Saracino Stephen P. Pereira Paolo Graziano Valerio Pazienza 《Oncotarget》2015,6(21):18545-18557