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https://www.readbyqxmd.com/read/28819385/a-randomized-open-label-safety-and-exploratory-efficacy-study-of-kanglaite-injection-klti-plus-gemcitabine-versus-gemcitabine-in-patients-with-advanced-pancreatic-cancer
#1
Lee S Schwartzberg, Francis P Arena, Bryan J Bienvenu, Edward H Kaplan, Luis H Camacho, Luis T Campos, J Paul Waymack, Mary A Tagliaferri, Michael M Chen, Dapeng Li
Background: This study was designed to assess the safety and preliminary efficacy of KLTi plus gemcitabine in patients with locally advanced or metastatic pancreatic cancer. Methods: In a randomized, open-label study, patients with locally advanced or metastatic pancreatic cancer were randomized 2:1 to receive KLTi plus gemcitabine or gemcitabine monotherapy. Three sequential cohorts were tested at 30 g/day, 50 g/day, and 30 g/day. Gemcitabine was administered at 1000 mg/m(2) on days 1, 8 and 15 of each 28 day cycle...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28817982/current-challenges-in-optimizing-systemic-therapy-for-patients-with-pancreatic-cancer-expert-perspectives-from-the-australian-gastrointestinal-trials-group-with-invited-international-faculty
#2
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...
August 18, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28814809/non-thermal-plasma-treated-solution-demonstrates-antitumor-activity-against-pancreatic-cancer-cells-in-vitro-and-in-vivo
#3
Kim Rouven Liedtke, Sander Bekeschus, André Kaeding, Christine Hackbarth, Jens-Peter Kuehn, Claus-Dieter Heidecke, Wolfram von Bernstorff, Thomas von Woedtke, Lars Ivo Partecke
Pancreatic cancer is associated with a high mortality rate. In advanced stage, patients often experience peritoneal carcinomatosis. Using a syngeneic murine pancreatic cancer cell tumor model, the effect of non-thermal plasma (NTP) on peritoneal metastatic lesions was studied. NTP generates reactive species of several kinds which have been proven to be of relevance in cancer. In vitro, exposure to both plasma and plasma-treated solution significantly decreased cell viability and proliferation of 6606PDA cancer cells, whereas mouse fibroblasts were less affected...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808501/evolving-treatment-landscape-for-early-and-advanced-pancreatic-cancer
#4
REVIEW
Sally C Lau, Winson Y Cheung
Pancreatic ductal adenocarcinoma is an infrequent cancer with a high disease related mortality rate, even in the context of early stage disease. Until recently, the rate of death from pancreatic cancer has remained largely similar whereby gemcitabine monotherapy was the mainstay of systemic treatment for most stages of disease. With the discovery of active multi-agent chemotherapy regimens, namely FOLFIRINOX and gemcitabine plus nab-paclitaxel, the treatment landscape of pancreatic cancer is slowly evolving...
July 15, 2017: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28804517/update-on-the-role-of-nanoliposomal-irinotecan-in-the-treatment-of-metastatic-pancreatic-cancer
#5
REVIEW
Fnu Asad Ur Rahman, Saeed Ali, Muhammad Wasif Saif
Median survival for patients with metastatic pancreatic cancer (MPC) treated with combination chemotherapeutic agents such as gemcitabine-based regimens and FOLFIRINOX is currently less than 12 months. This highlights the need for more efficacious first-line, as well as second-line therapies. Nanoliposomal irinotecan, in combination with 5-fluorouracil (5-FU)/folinic acid has recently been assessed as second-line therapy after initial gemcitabine-based therapy. It is the first, second-line treatment approved by the US Food and Drug Administration to treat patients with MPC based on results of the NAnoliPOsomaL Irinotecan (NAPOLI-1) study, which showed that this regimen significantly prolonged progression-free survival (3...
July 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28795609/comparison-of-treatment-patterns-and-economic-outcomes-among-metastatic-pancreatic-cancer-patients-initiated-on-nab-paclitaxel-gemcitabine-or-folfirinox
#6
Ali McBride, Machaon Bonafede, Qian Cai, Nicole Princic, Oth Tran, Corey Pelletier, Monika Parisi, Manish Patel
ABSRTACT Background: The economic burden of metastatic pancreatic cancer (mPC) is substantial while treatment options are limited. Little is known about the treatment patterns and healthcare costs among mPC patients who initiated first-line gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-P+G) and FOLFIRINOX. RESEARCH DESIGN AND METHODS: The MarketScan® claims databases were used to identify adults with ≥2 claims for pancreatic cancer, 1 claim for a secondary malignancy, completed ≥1 cycle of nab-P+G or FOLFIRINOX during 4/1/2013 and 3/31/2015, and had continuous plan enrollment for ≥6 months pre- and 3 months after the first-line treatment...
August 10, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28794500/para-aortic-lymph-node-metastases-in-pancreatic-cancer-should-not-be-considered-a-watershed-for-curative-resection
#7
Sebastian Hempel, Verena Plodeck, Franz Mierke, Marius Distler, Daniela E Aust, Hans-Detlev Saeger, Jürgen Weitz, Thilo Welsch
No international consensus regarding the resection of the para-aortic lymph node (PALN) station Ln16b1 during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) has been reached. The present retrospectively investigated 264 patients with PDAC who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005-2015. In 95 cases, the PALN were separately labelled and histopathologically analysed. Metastatic PALN (PALN+) were found in 14.7% (14/95). PALN+ stage was associated with increased regional lymph node metastasis...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790031/blimp1-induces-transient-metastatic-heterogeneity-in-pancreatic-cancer
#8
Shin-Heng Chiou, Viviana I Risca, Gordon X Wang, Dian Yang, Barbara M Grüner, Arwa S Kathiria, Rosanna K Ma, Dedeepya Vaka, Pauline Chu, Margaret Kozak, Laura Castellini, Edward E Graves, Grace E Kim, Philippe Mourrain, Albert C Koong, Amato J Giaccia, Monte M Winslow
Pancreatic ductal adenocarcinoma (PDAC) is one of the most metastatic and deadly cancers. Despite the clinical significance of metastatic spread, our understanding of molecular mechanisms that drive PDAC metastatic ability remains limited. Using a novel genetically engineered mouse model of human PDAC, we uncover a transient subpopulation of cancer cells with exceptionally high metastatic ability. Global gene expression profiling and functional analyses uncovered the transcription factor Blimp1 as a key driver of PDAC metastasis...
August 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28782557/yb-1-expression-promotes-pancreatic-cancer-metastasis-that-is-inhibited-by-microrna-216a
#9
Jingjing Lu, Xiaohong Li, Fei Wang, Yibing Guo, Yan Huang, Hui Zhu, Yao Wang, Yuhua Lu, Zhiwei Wang
Pancreatic cancer is one of the most aggressive cancers. The vast majority of patients are diagnosed with advanced, unresectable disease because of early invasive growth and metastatic spread. The aim of this study was to examine YB-1 expression in pancreatic cancer and determine its effects on cell invasion. YB-1 is overexpressed in pancreatic cancer cell lines and patient tissue samples. In patient tissues, high YB-1 levels correlated with perineural invasion. Silencing of YB-1 significantly reduced cell invasion with decreased expression of MMPs in vitro...
August 3, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28782087/germline-brca-mutations-in-asian-patients-with-pancreatic-adenocarcinoma-a-prospective-study-evaluating-risk-category-for-genetic-testing
#10
Kyoungmin Lee, Changhoon Yoo, Kyu-Pyo Kim, Kyoung-Jin Park, Heung-Moon Chang, Tae Won Kim, Jae-Lyun Lee, Woochang Lee, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Sang Hyun Shin, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Song Cheol Kim, Baek-Yeol Ryoo
Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy...
August 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28774338/-18-f-fdg-pet-ct-response-in-a-phase-1-2-trial-of-nab-paclitaxel-plus-gemcitabine-for-advanced-pancreatic-cancer
#11
Ronald L Korn, Daniel D Von Hoff, Mitesh J Borad, Markus F Renschler, Desmond McGovern, R Curtis Bay, Ramesh K Ramanathan
BACKGROUND: Positron emission tomography (PET) is poised to become a useful imaging modality in staging and evaluating therapeutic responses in patients with metastatic pancreatic cancer (mPC). This analysis from a phase 1/2 study examined the utility of early PET imaging in patients with mPC treated with nab-paclitaxel plus gemcitabine. METHODS: Tumors were measured by [(18)F]2-fluoro-2-deoxyglucose PET/computed tomography (CT) in patients who received nab-paclitaxel 100 (n = 13), 125 (n = 38), or 150 (n = 1) mg/m(2) plus gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle...
August 3, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
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
#12
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/28768698/the-future-advances-in-therapeutic-approach-and-management-strategies-for-men1
#13
Rachel S van Leeuwaarde, Joanne M de Laat, Carolina R C Pieterman, Koen M A Dreijerink, Menno Vriens, Gerlof D Valk
Multiple endocrine neoplasia type 1 is a rare autosomal inherited disorder associated with a high risk for patients to simultaneously develop tumours of the parathyroid glands, duodeno-pancreatic neuroendocrine tumors and tumors of the anterior pituitary gland. Early identification of MEN1 in patients enables presymptomatic screening of manifestations which makes timely interventions possible with the intention to prevent morbidity and mortality. Causes of death nowadays have shifted towards local or metastatic progression of malignant neuro endocrine tumors...
August 2, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28765154/gemcitabine-induced-timp1-attenuates-therapy-response-and-promotes-tumor-growth-and-liver-metastasis-in-pancreatic-cancer
#14
Zenobia D'Costa, Keaton Jones, Abul Azad, Ruud van Stiphout, Su Y Lim, Ana L Gomes, Paul Kinchesh, Sean C Smart, W Gillies McKenna, Francesca M Buffa, Owen J Sansom, Ruth J Muschel, Eric O'Neill, Emmanouil Fokas
Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in pre-clinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28761758/the-european-society-for-medical-oncology-magnitude-of-clinical-benefit-scale-field-tested-in-infrequent-tumour-entities-an-extended-analysis-of-its-feasibility-at-the-medical-university-of-vienna
#15
Barbara Kiesewetter, Markus Raderer, Gerald W Prager, Thorsten Fuereder, Christine Marosi, Matthias Preusser, Michael Krainer, Gottfried J Locker, Thomas Brodowicz, Christoph C Zielinski
BACKGROUND: The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a new tool to quantify the clinical benefit that may be anticipated from a novel anticancer treatment. We present here an analysis on the feasibility of the ESMO-MCBS in less frequent tumour entities. METHODS: This study evaluates the practicability of the ESMO-MCBS for metastatic neuroendocrine tumours (NETs), soft tissue sarcomas, glioblastoma, thyroid cancer, pancreatic cancer, head/neck cancer, urothelial cancer and ovarian cancer at the Medical University Vienna...
2017: ESMO Open
https://www.readbyqxmd.com/read/28761731/health-related-quality-of-life-in-a-randomised-phase-iii-study-of-gemcitabine-plus-s-1-s-1-alone-and-gemcitabine-alone-for-locally-advanced-or-metastatic-pancreatic-cancer-gest-study
#16
Yasuhiro Hagiwara, Yasuo Ohashi, Takuji Okusaka, Hideki Ueno, Tatsuya Ioka, Narikazu Boku, Shinichi Egawa, Takashi Hatori, Junji Furuse, Kazuhiro Mizumoto, Shinichi Ohkawa, Taketo Yamaguchi, Kenji Yamao, Akihiro Funakoshi, Ann-Lii Cheng, Kiyohiro Kihara, Atsushi Sato, Masao Tanaka
OBJECTIVE: This study was performed to compare health-related quality of life (HRQOL) of gemcitabine plus S-1 (GS), S-1 alone and gemcitabine alone as first-line chemotherapy for locally advanced or metastatic pancreatic cancer in the GEST (Gemcitabine and TS-1 Trial) study and to assess the impacts of adverse events and tumour response on HRQOL. METHODS: Patients were randomly assigned to receive gemcitabine alone (1000 mg/m(2) weekly for 3 of 4 weeks), S-1 alone (80, 100 or 120 mg/day twice daily for 4 of 6 weeks) or GS (gemcitabine at 1000 mg/m(2) weekly plus S-1 at 60, 80 or 100 mg/day twice daily for 2 of 3 weeks)...
2017: ESMO Open
https://www.readbyqxmd.com/read/28757253/enhancer-reprogramming-promotes-pancreatic-cancer-metastasis
#17
Jae-Seok Roe, Chang-Il Hwang, Tim D D Somerville, Joseph P Milazzo, Eun Jung Lee, Brandon Da Silva, Laura Maiorino, Hervé Tiriac, C Megan Young, Koji Miyabayashi, Dea Filippini, Brianna Creighton, Richard A Burkhart, Jonathan M Buscaglia, Edward J Kim, Jean L Grem, Audrey J Lazenby, James A Grunkemeyer, Michael A Hollingsworth, Paul M Grandgenett, Mikala Egeblad, Youngkyu Park, David A Tuveson, Christopher R Vakoc
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies, owing in part to its propensity for metastasis. Here, we used an organoid culture system to investigate how transcription and the enhancer landscape become altered during discrete stages of disease progression in a PDA mouse model. This approach revealed that the metastatic transition is accompanied by massive and recurrent alterations in enhancer activity. We implicate the pioneer factor FOXA1 as a driver of enhancer activation in this system, a mechanism that renders PDA cells more invasive and less anchorage-dependent for growth in vitro, as well as more metastatic in vivo...
July 25, 2017: Cell
https://www.readbyqxmd.com/read/28753564/exportin-1-xpo1-inhibition-leads-to-restoration-of-tumor-suppressor-mir-145-and-consequent-suppression-of-pancreatic-cancer-cell-proliferation-and-migration
#18
Asfar S Azmi, Yiwei Li, Irfana Muqbil, Amro Aboukameel, William Senapedis, Erkan Baloglu, Yosef Landesman, Sharon Shacham, Michael G Kauffman, Philip A Philip, Ramzi M Mohammad
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer related deaths in the United States with a majority of these patients dying from aggressively invasive and metastatic disease. There is growing evidence that suggests an important role for microRNAs (miRNAs) in the pathobiology of aggressive PDAC. In this study, we found that the expression of miR-145 was significantly lower in PDAC cells when compared to normal pancreatic duct epithelial cells. Here we show that inhibition of the nuclear exporter protein exportin 1 (XPO1; also known as chromosome maintenance region 1 [CRM1]) by siRNA knockdown or by the Selective Inhibitor of Nuclear Export (SINE) compound (KPT-330; selinexor) increases miR-145 expression in PDAC cells resulting in the decreased cell proliferation and migration capacities...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28739291/pancreatic-cancer-screening-still-a-delusion
#19
REVIEW
Pedro Moutinho-Ribeiro, Rosa Coelho, Marc Giovannini, Guilherme Macedo
Pancreatic adenocarcinoma represents the fourth most common cause of cancer mortality and death due to pancreatic cancer (PC) have increased since 2003. Its incidence has also raised about 30% in the past decade and it is expected to become the second cause of cancer mortality by 2020 in the USA. Most PC present with metastatic disease and improvements in treatment outcomes for this group have been disappointing. These observations support the idea that screening to identify patients at an earlier stage might be an important strategy in improving overall PC outcomes...
July 13, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28736643/comparison-of-efficacy-and-toxicity-of-folfirinox-and-gemcitabine-with-nab-paclitaxel-in-unresectable-pancreatic-cancer
#20
Tetsuhito Muranaka, Masaki Kuwatani, Yoshito Komatsu, Kentaro Sawada, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Satoshi Yuki, Yoshimasa Kubota, Kimitoshi Kubo, Shuhei Kawahata, Kazumichi Kawakubo, Hiroshi Kawakami, Naoya Sakamoto
BACKGROUND: Irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) and the combination regimen of gemcitabine and nanoparticle albumin-bound paclitaxel (GnP) (nab-PTX) improve the prognosis of patients with metastatic pancreatic cancer. However, no study has compared the efficacy of the two regimens. We compared retrospectively the efficacy and safety of the two regimens in patients with unresectable pancreatic cancer. METHODS: Thirty-eight patients with unresectable locally advanced or metastatic pancreatic cancer received FOLFIRINOX or GnP as first-line chemotherapy between December 2013 and September 2015...
June 2017: Journal of Gastrointestinal Oncology
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