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Review genomic pancreatic cancer

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https://www.readbyqxmd.com/read/29051346/data-driven-prioritization-and-review-of-targets-for-molecular-based-theranostic-approaches-in-pancreatic-cancer
#1
Marjory Koller, Elmire Hartmans, Derk Jan A de Groot, Xiao Juan Zhao, Gooitzen Michell van Dam, Wouter Nagengast, Rudolf S N Fehrmann
Molecular targeted therapeutical and imaging strategies directed at aberrant signaling-pathways in pancreatic tumor cells may improve the poor outcome of pancreatic ductal adenocarcinoma (PDA). Therefore, relevant molecular targets need to be identified. Methods: We collected publicly available expression profiles of patient derived normal pancreatic tissue (n = 77) and PDA samples (n = 103). Functional Genomic mRNA (FGmRNA) profiling was applied to predict target upregulation on the protein level. We prioritized these targets based on current status of (pre)-clinical therapeutical and imaging evaluation in PDA...
October 19, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#2
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28915699/biological-effects-and-epidemiological-consequences-of-arsenic-exposure-and-reagents-that-can-ameliorate-arsenic-damage-in-vivo
#3
REVIEW
Chinthalapally V Rao, Sanya Pal, Altaf Mohammed, Mudassir Farooqui, Mark P Doescher, Adam S Asch, Hiroshi Y Yamada
Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide "hot spots" where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914620/new-developments-in-the-molecular-mechanisms-of-pancreatic-tumorigenesis
#4
Matthäus Felsenstein, Ralph H Hruban, Laura D Wood
Pancreatic cancer is an aggressive disease with a dismal prognosis in dire need of novel diagnostic and therapeutic approaches. The past decade has witnessed an explosion of data on the genetic alterations that occur in pancreatic cancer, as comprehensive next-generation sequencing analyses have been performed on samples from large cohorts of patients. These studies have defined the genomic landscape of this disease and identified novel candidates whose mutations contribute to pancreatic tumorigenesis. They have also clarified the genetic alterations that underlie multistep tumorigenesis in precursor lesions and provided insights into clonal evolution in pancreatic neoplasia...
September 13, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28869888/pancreatic-ductal-adenocarcinoma-state-of-the-art-2017-and-new-therapeutic-strategies
#5
REVIEW
Marta Chiaravalli, Michele Reni, Eileen M O'Reilly
Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an overall 5-year survival of 8% for all stages combined. The majority of patients present with stage IV disease at diagnosis and these patients have an overall 5-year survival of 3%. Currently, the standard of care for metastatic pancreas adenocarcinoma is combination cytotoxic therapy, namely FOLFIRINOX or gemcitabine plus nab-paclitaxel for good performance status patients. Given the challenges and the rising incidence of PDAC expected to become the second leading cause of cancer-related death by 2030, there is a major unmet need to develop more effective therapies...
August 23, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28858862/pancreas-cancer-precision-treatment-using-avatar-mice-from-a-bioinformatics-perspective
#6
Javier Perales-Patón, Elena Piñeiro-Yañez, Héctor Tejero, Pedro P López-Casas, Manuel Hidalgo, Gonzalo Gómez-López, Fátima Al-Shahrour
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death among solid malignancies. Unfortunately, PDAC lethality has not substantially decreased over the past 20 years. This aggressiveness is related to the genomic complexity and heterogeneity of PDAC, but also to the absence of an effective screening for the detection of early-stage tumors and a lack of efficient therapeutic options. Therefore, there is an urgent need to improve the arsenal of anti-PDAC drugs for an effective treatment of these patients...
2017: Public Health Genomics
https://www.readbyqxmd.com/read/28858227/the-role-of-palb2-in-the-dna-damage-response-and-cancer-predisposition
#7
REVIEW
Thales C Nepomuceno, Giuliana De Gregoriis, Francisco M Bastos de Oliveira, Guilherme Suarez-Kurtz, Alvaro N Monteiro, Marcelo A Carvalho
The deoxyribonucleic acid (DNA) damage response (DDR) is a major feature in the maintenance of genome integrity and in the suppression of tumorigenesis. PALB2 (Partner and Localizer of Breast Cancer 2 (BRCA2)) plays an important role in maintaining genome integrity through its role in the Fanconi anemia (FA) and homologous recombination (HR) DNA repair pathways. Since its identification as a BRCA2 interacting partner, PALB2 has emerged as a pivotal tumor suppressor protein associated to hereditary cancer susceptibility to breast and pancreatic cancers...
August 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28817982/current-challenges-in-optimizing-systemic-therapy-for-patients-with-pancreatic-cancer-expert-perspectives-from-the-australasian-gastrointestinal-trials-group-agitg-with-invited-international-faculty
#8
REVIEW
Eva Segelov, Florian Lordick, David Goldstein, Lorraine A Chantrill, Daniel Croagh, Ben Lawrence, Dirk Arnold, Ian Chau, Radka Obermannova, Timothy Jay Price
Despite recent progress, the outlook for most patients with pancreatic cancer remains poor. There is variation in how patients are managed globally due to differing interpretations of the evidence, partly because studies in this disease are challenging to undertake. This article collates the evidence upon which current best practice is based and offers an expert opinion from an international faculty on how latest developments should influence current treatment paradigms. Areas covered: Optimal chemotherapy for first and subsequent lines of therapy; optimal management of locally advanced, non-metastatic cancer including the role of neoadjuvant chemo(radio)therapy, current evidence for adjuvant chemotherapy, major advances in pancreatic cancer genomics and challenges in supportive care particularly relevant to patients with pancreatic cancer...
October 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#9
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28736626/molecular-landscape-and-sub-classification-of-gastrointestinal-cancers-a-review-of-literature
#10
REVIEW
Bita Fakhri, Kian-Huat Lim
The historical approach of diagnosing cancer types based entirely on anatomic origin and histologic features, and the "one-size-fit-all" therapeutic approach, are inadequate in modern cancer treatment. From decades of research we now know that cancer is a highly heterogeneous disease driven by complex genetic or epigenetic alterations. The advent of various high throughput molecular tools has now enabled us to view and sub-classify each cancer type based on their distinct molecular features, in addition to histologic classification, with the promise of individualized treatment strategies tailored towards each specific subtype to improve patient outcomes...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28689205/genomics-in-primary-and-secondary-prevention-of-pancreatic-cancer
#11
Núria Malats, Esther Molina-Montes, Carlo La Vecchia
BACKGROUND: Pancreatic cancer (PC) is one of the deadliest cancers worldwide for which little clinical progress has been made in the last decades. Furthermore, increased trends of PC mortality rates have been reported in Westernised countries. PC is usually diagnosed in advanced stages, precluding patients of an effective treatment. Identifying high-risk populations and early detection markers is the first and crucial step to impact on these figures and change the PC horizon. AIMS/OBJECTIVES: To discuss the published body of evidence on host and tumor genomics promising markers for primary and/or secondary personalised PC prevention, as well as the future perspectives in the field...
2017: Public Health Genomics
https://www.readbyqxmd.com/read/28682795/genetics-of-pancreatic-cyst-cancer-progression-standing-on-the-shoulders-of-giants
#12
Bhuwan Giri, Vrishketan Sethi, Vikas Dudeja, Sulagna Banerjee, Alan Livingstone, Ashok Saluja
PURPOSE OF REVIEW: Pancreatic cancer, despite years of study and some progress, presents with a grim prognosis in almost all cases. In the current review, we have discussed recent studies that have attempted to decipher the genetic makeup of pancreatic ductal adenocarcinoma and preneoplastic pancreatic cystic neoplasms. RECENT FINDINGS: With the advent of high throughput sequencing, the genetic code of pancreatic cancer is beginning to unravel and this new-found information heralds an era of precision cancer care where treatment will be guided by the genetic code of the neoplasm...
September 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28638788/histone-deacetylases-microrna-and-leptin-crosstalk-in-pancreatic-cancer
#13
REVIEW
Cynthia I Tchio Mantho, Adriana Harbuzariu, Ruben R Gonzalez-Perez
Because pancreatic cancer (PC) historically has had poor prognosis and five year survival rates, it has been intensely investigated. Analysis of PC incidence and biology has shown a link between different risk factors such as smoking, alcoholism, and obesity and disease progression. Important factors affecting PC include the epigenomic changes driven by DNA methylation and histone acetylation, and actions of microRNA inducing oncogenic or tumor suppressor effects. Studies have identified markers whose dysregulation seem to play important roles in PC progression...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28594388/gene-therapy-for-pancreatic-cancer-specificity-issues-and-hopes
#14
REVIEW
Marie Rouanet, Marine Lebrin, Fabian Gross, Barbara Bournet, Pierre Cordelier, Louis Buscail
A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes)...
June 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28587243/genomic-variations-in-pancreatic-cancer-and-potential-opportunities-for-development-of-new-approaches-for-diagnosis-and-treatment
#15
REVIEW
Shuangshuang Lu, Tasqeen Ahmed, Pan Du, Yaohe Wang
Human pancreatic cancer has a very poor prognosis with an overall five-year survival rate of less than 5% and an average median survival time of six months. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Although our understanding of the molecular events underlying multi-step carcinogenesis in pancreatic cancer has steadily increased, translation into more effective therapeutic approaches has been inefficient in recent decades. Therefore, it is imperative that novel and targeted approaches are designed to facilitate the early detection and treatment of pancreatic cancer...
June 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28537880/biological-effects-and-epidemiological-consequences-of-arsenic-exposure-and-reagents-that-can-ameliorate-arsenic-damage-in-vivo
#16
REVIEW
Chinthalapally V Rao, Sanya Pal, Altaf Mohammed, Mudassir Farooqui, Mark P Doescher, Adam S Asch, Hiroshi Y Yamada
Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide "hot spots" where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536860/line-1-methylation-level-and-prognosis-in-pancreas-cancer-pyrosequencing-technology-and-literature-review
#17
Kensuke Yamamura, Keisuke Kosumi, Yoshifumi Baba, Kazuto Harada, Feng Gao, Xiaobo Zhang, Lei Zhou, Yuki Kitano, Kota Arima, Takayoshi Kaida, Hideaki Takeyama, Takaaki Higashi, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Xiaodong Tan, Hideo Baba
PURPOSE: Global DNA hypomethylation plays an important role in genomic instability and carcinogenesis. The long interspersed nucleotide element-1 (LINE-1) methylation level is a good surrogate marker of the global DNA methylation level. Previously, we demonstrated a strong relationship between LINE-1 hypomethylation and poor prognosis in certain cancers. However, the relationship between the LINE-1 methylation level and the clinical outcome of pancreatic cancer (PC) remains unclear. METHODS: We used a pyrosequencing assay to measure LINE-1 methylation levels in 126 samples of resected PC and evaluated the prognostic value of the LINE-1 methylation level...
May 23, 2017: Surgery Today
https://www.readbyqxmd.com/read/28504904/application-of-panel-based-tests-for-inherited-risk-of-cancer
#18
REVIEW
Payal D Shah, Katherine L Nathanson
Next-generation or massively parallel sequencing has transformed the landscape of genetic testing for cancer susceptibility. Panel-based genetic tests evaluate multiple genes simultaneously and rapidly. Because these tests are frequently offered in clinical settings, understanding their clinical validity and utility is critical. When evaluating the inherited risk of breast and ovarian cancers, panel-based tests provide incremental benefit compared with BRCA1/2 genetic testing. For inherited risk of other cancers, such as colon cancer and pheochromocytoma-paraganglioma, the clinical utility and yield of panel-based testing are higher; in fact, simultaneous evaluation of multiple genes has been the historical standard for these diseases...
August 31, 2017: Annual Review of Genomics and Human Genetics
https://www.readbyqxmd.com/read/28460572/next-generation-sequencing-of-pancreatic-ductal-adenocarcinoma-right-or-wrong
#19
Ashton A Connor, Steven Gallinger
Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all epithelial malignancies and a paradoxically rising incidence rate. Clinical translation of next generation sequencing (NGS) of tumour and germline samples may ameliorate outcomes by identifying prognostic and predictive genomic and transcriptomic features in appreciable fractions of patients, facilitating enrolment in biomarker-matched trials. Areas covered: The literature on precision oncology is reviewed. It is found that outcomes may be improved across various malignancies, and it is suggested that current issues of adequate tissue acquisition, turnaround times, analytic expertise and clinical trial accessibility may lessen as experience accrues...
May 10, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28452926/kras-tp53-cdkn2a-smad4-brca1-and-brca2-mutations-in-pancreatic-cancer
#20
REVIEW
Jonas Cicenas, Kotryna Kvederaviciute, Ingrida Meskinyte, Edita Meskinyte-Kausiliene, Aiste Skeberdyte, Jonas Cicenas
Pancreatic cancer is a disease that has a very high fatality rate and one of the highest mortality ratios among all major cancers, remaining the fourth leading cause of cancer-related deaths in developed countries. The major treatment of pancreatic cancer is surgery; however, only 15-20% of patients are candidates for it at the diagnosis of disease. On the other hand, survival in patients, who undergo surgery, is less than 30%. In most cancers, genome stability is disturbed and pancreatic cancer is not the exception...
April 28, 2017: Cancers
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