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https://www.readbyqxmd.com/read/28541474/postmarketing-surveillance-study-of-erlotinib-plus-gemcitabine-for-pancreatic-cancer-in-japan-polaris-final-analysis
#1
Junji Furuse, Akihiko Gemma, Wataru Ichikawa, Takuji Okusaka, Akihiro Seki, Tadashi Ishii
Objective: Erlotinib plus gemcitabine is approved in Japan for the treatment of metastatic pancreatic cancer. The POLARIS surveillance study investigated safety (focusing on interstitial lung disease [ILD]) and efficacy of erlotinib plus gemcitabine in Japanese pancreatic cancer patients. Methods: Patients receiving erlotinib plus gemcitabine for pancreatic cancer in Japan between July 2011 and August 2012 were enrolled. ILD-like events were independently confirmed by a review committee...
May 24, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28534865/the-impact-of-smad4-loss-on-outcome-in-patients-with-advanced-pancreatic-cancer-treated-with-systemic-chemotherapy
#2
Steffen Ormanns, Michael Haas, Anna Remold, Stephan Kruger, Stefan Holdenrieder, Thomas Kirchner, Volker Heinemann, Stefan Boeck
The role of the tumor suppressor mothers against decapentaplegic homolog 4 (SMAD4) has not yet been defined in patients (pts) with advanced pancreatic cancer (aPC). This translational research study was designed to evaluate the impact of tumoral SMAD4 loss on clinicopathological parameters and outcome in PC patients receiving palliative chemotherapy. Using immunohistochemistry, we examined SMAD4 expression in tumor tissue of 143 aPC pts treated within completed prospective clinical and biomarker trials. In uni- and multivariate analyses, SMAD4 expression status was correlated to clinicopathological patient characteristics and outcome...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534079/failure-to-treat-audit-of-an-institutional-cancer-registry-database-at-a-large-comprehensive-cancer-center-reveals-factors-affecting-the-treatment-of-pancreatic-cancer
#3
Jennifer L Miller-Ocuin, Mazen S Zenati, Lee M Ocuin, Patrick R Varley, Stephanie M Novak, Sharon Winters, Amer H Zureikat, Herbert J Zeh, Melissa E Hogg
BACKGROUND: National Cancer Database analysis showed 70% of patients with stage I pancreatic adenocarcinoma (PDA) did not have surgery. We sought to analyze adherence to expected treatment (ET) by stage for PDA and identify factors that led to no treatment (NT) or unexpected treatment (UT) in a recent cohort. METHODS: Using our Institutional Cancer Registry (ICR), we identified patients with PDA from 2004 to 2013. ET was defined as surgery ± chemotherapy ± radiation for stages I and II, chemotherapy ± radiation for stage III, and chemotherapy for stage IV, while UT was defined as no surgery for stages I and II, surgery for stage III, or ± surgery ± XRT for stage IV...
May 22, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28529645/tumor-penetrating-theranostic-nanoparticles-for-enhancement-of-targeted-and-image-guided-drug-delivery-into-peritoneal-tumors-following-intraperitoneal-delivery
#4
Ning Gao, Erica N Bozeman, Weiping Qian, Liya Wang, Hongyu Chen, Malgorzata Lipowska, Charles A Staley, Y Andrew Wang, Hui Mao, Lily Yang
The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery...
2017: Theranostics
https://www.readbyqxmd.com/read/28516291/downstaging-in-stage-iv-pancreatic-cancer-a-new-population-eligible-for-surgery
#5
Isabella Frigerio, Paolo Regi, Alessandro Giardino, Filippo Scopelliti, Roberto Girelli, Claudio Bassi, Stefano Gobbo, Paolo Tinazzi Martini, Paola Capelli, Mirko D'Onofrio, Giuseppe Malleo, Laura Maggino, Elena Viviani, Giovanni Butturini
BACKGROUND: Recent papers consider surgery as an option for synchronous liver oligometastatic patients [metastatic pancreatic ductal adenocarcinoma (mPDAC)]. In this study, we present our series of resected mPDACs after neoadjuvant chemotherapy (nCT). PATIENTS AND METHODS: All patients resected after downstaging of mPDAC were included in this study. Downstaging criteria were disappearance of liver metastasis and a decrease in cancer antigen (CA) 19-9. The type and duration of nCT, last nCT surgery interval, histology, morbidity, and mortality were recorded, and overall survival (OS) and disease-free survival (DFS) were analyzed...
May 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28515255/active-systemic-treatment-of-pancreatic-cancer
#6
Margaret Tempero
By 2020, pancreatic cancer is expected to be the second most common cause of cancer-related death, exceeded only by lung cancer. During her presentation at the NCCN 22nd Annual Conference, Dr. Margaret Tempero offered an update on the current state of systemic treatment of pancreatic cancer, focusing on resectable/borderline resectable, locally advanced, and metastatic disease.
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28513912/improving-theranostics-in-pancreatic-cancer
#7
Jeremy King, Michael Bouvet, Gagandeep Singh, John Williams
BACKGROUND: Pancreatic cancer is the fourth most deadly cancer in the United States, and is expected to be the second most deadly by 2030. The major difficulty in treating pancreatic cancer is the late onset of symptoms. Generally, patients show metastatic disease by the time of diagnosis, with a survival rate of 5% beyond 5 years. In patients without metastatic disease, surgical resection increases 5 year survival rate to 25%. The remaining 75% succumb to undetected metastases. Clearly, improvements to both detection, surgical intervention, and therapeutic strategies will be needed to improve patient outcome in pancreatic cancer...
May 17, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28513565/epidermal-growth-factor-receptor-cell-proliferation-signaling-pathways
#8
REVIEW
Ping Wee, Zhixiang Wang
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation...
May 17, 2017: Cancers
https://www.readbyqxmd.com/read/28511234/indications-results-and-clinical-impact-of-endoscopic-ultrasound-eus-guided-sampling-in-gastroenterology-european-society-of-gastrointestinal-endoscopy-esge-clinical-guideline-updated-january-2017
#9
Jean-Marc Dumonceau, Pierre H Deprez, Christian Jenssen, Julio Iglesias-Garcia, Alberto Larghi, Geoffroy Vanbiervliet, Guruprasad P Aithal, Paolo G Arcidiacono, Pedro Bastos, Silvia Carrara, László Czakó, Gloria Fernández-Esparrach, Paul Fockens, Àngels Ginès, Roald F Havre, Cesare Hassan, Peter Vilmann, Jeanin E van Hooft, Marcin Polkowski
For pancreatic solid lesions, ESGE recommends performing endoscopic ultrasound (EUS)-guided sampling as first-line procedure when a pathological diagnosis is required. Alternatively, percutaneous sampling may be considered in metastatic disease.Strong recommendation, moderate quality evidence.In the case of negative or inconclusive results and a high degree of suspicion of malignant disease, ESGE suggests re-evaluating the pathology slides, repeating EUS-guided sampling, or surgery.Weak recommendation, low quality evidence...
May 16, 2017: Endoscopy
https://www.readbyqxmd.com/read/28505401/the-influence-of-a-composite-hospital-volume-on-outcomes-for-gastric-cancer-surgery-a-dutch-population-based-study
#10
Linde A D Busweiler, Johan L Dikken, Daniel Henneman, Mark I van Berge Henegouwen, Vincent K Y Ho, Rob A E M Tollenaar, Michel W J M Wouters, Johanna W van Sandick
BACKGROUND: Volume-outcome associations for complex surgical procedures have motivated centralization of care worldwide. The aim of this study was to investigate the association between overall hospital experience with complex upper gastrointestinal (GI) cancer resections and outcomes after gastric cancer surgery. METHODS: Data on all patients (n = 4837) who underwent a resection for non metastatic invasive gastric cancer between 2005 and 2014 were obtained from the Netherlands Cancer Registry (NCR)...
May 15, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28500236/identification-of-the-serine-biosynthesis-pathway-as-a-critical-component-of-braf-inhibitor-resistance-of-melanoma-pancreatic-and-non-small-cell-lung-cancer-cells
#11
Kayleigh C Ross, Andrew J Andrews, Christopher D Marion, Timothy J Yen, Vikram Bhattacharjee
Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors (BRAFis). In this study, we identified serine biosynthesis as a critical mechanism of resistance. Proteomic assays revealed differential protein expression of serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi) treatment in sensitive versus acquired resistant melanoma cells. Ablation of PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting the folate cycle, directly downstream of serine synthesis, with methotrexate also displayed similar sensitization...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28499439/the-role-of-tgf-%C3%AE-and-its-crosstalk-with-rac1-rac1b-signaling-in-breast-and-pancreas-carcinoma
#12
REVIEW
Catharina Melzer, Ralf Hass, Juliane von der Ohe, Hendrik Lehnert, Hendrik Ungefroren
This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers...
May 12, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28495639/safety-and-tolerability-of-the-first-in-class-agent-cpi-613-in-combination-with-modified-folfirinox-in-patients-with-metastatic-pancreatic-cancer-a-single-centre-open-label-dose-escalation-phase-1-trial
#13
Angela Alistar, Bonny B Morris, Rodwige Desnoyer, Heidi D Klepin, Keyanoosh Hosseinzadeh, Clancy Clark, Amy Cameron, John Leyendecker, Ralph D'Agostino, Umit Topaloglu, Lakmal W Boteju, Asela R Boteju, Rob Shorr, Zuzana Zachar, Paul M Bingham, Tamjeed Ahmed, Sandrine Crane, Riddhishkumar Shah, John J Migliano, Timothy S Pardee, Lance Miller, Gregory Hawkins, Guangxu Jin, Wei Zhang, Boris Pasche
BACKGROUND: Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells...
May 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28489753/effect-of-folfirinox-as-second-line-chemotherapy-for-metastatic-pancreatic-cancer-after-gemcitabine-based-chemotherapy-failure
#14
Noritoshi Kobayashi, Takeshi Shimamura, Motohiko Tokuhisa, Ayumu Goto, Itaru Endo, Yasushi Ichikawa
BACKGROUND: This study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicity, and efficacy of second-line chemotherapy with FOLFIRINOX after gemcitabine (GEM)-based chemotherapy failure in metastatic pancreatic cancer (MPC). METHODS: We studied 18 histopathologically proven MPC patients. The schedule was 85 mg/m oxaliplatin, irinotecan, and 400 mg/m leucovorin, followed by 400 mg/m 5-fluorouracil (5-FU) as a bolus on day 1 and 2400 mg/m 5-FU as a 46-hour continuous infusion biweekly...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28489577/pancreatic-cancer-ascites-xenograft-an-expeditious-model-mirroring-advanced-therapeutic-resistant-disease
#15
Talia Golan, Chani Stossel, Michael Schvimer, Dikla Atias, Sharon Halperin, Ella Buzhor, Maria Raitses-Gurevich, Keren Cohen, Sara Pri-Chen, Julie Wilson, Robert E Denroche, Ilinca Lungu, John M S Bartlett, Faridah Mbabaali, Yosef Yarden, Nishanth Belugali Nataraj, Steven Gallinger, Raanan Berger
Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20-30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts.Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487999/chemotherapy-induced-neutropenia-as-a-prognostic-factor-in-patients-with-metastatic-pancreatic-cancer-treated-with-gemcitabine
#16
Aki Otake, Daiki Tsuji, Keisei Taku, Yohei Kawasaki, Mari Yokoi, Harumi Nakamori, Marika Osada, Megumi Matsumoto, Kazuyuki Inoue, Keita Hirai, Kunihiko Itoh
PURPOSE: Chemotherapy-induced neutropenia (CIN) is a common side effect of chemotherapy and an important dose-limiting factor. However, an association between CIN development and longer survival was recently reported in several solid cancers. In the present study, we aimed to assess whether CIN could be a prognostic factor and clarify other prognostic factors for patients with metastatic pancreatic cancer. METHODS: We retrospectively analyzed the medical records of 84 patients who received gemcitabine monotherapy as first-line chemotherapy for metastatic pancreatic cancer to assess whether CIN could be a prognostic factor...
May 9, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28484197/autopsy-of-invasive-ductal-pancreatic-carcinoma-that-transformed-into-a-tumor-producing-granulocyte-colony-stimulating-factor
#17
Hirohito Naruse, Norihiko Shimoyama, Taiki Kudo, Yoshiya Yamamoto, Kazuteru Hatanaka, Masayoshi Ohno, Kazuharu Suzuki, Hajime Hirata, Marina Suzuki
A 64-year-old woman was diagnosed with unresectable pancreatic cancer and underwent chemotherapy. However, the number of leukocytes significantly increased as the disease progressed. Serum G-CSF values also increased, and she eventually died on day 511 after diagnosis. Immediately after autopsy, immunohistochemical staining with an anti-G-CSF monoclonal antibody was positive in the poorly differentiated adenocarcinoma area of the primary pancreatic cancer and liver metastatic foci, but negative in the well-differentiated tubular adenocarcinoma part of the primary pancreatic cancer...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/28481424/evaluating-hepatocellular-carcinoma-cell-lines-for-tumor-samples-using-within-sample-relative-expression-orderings-of-genes
#18
Lu Ao, You Guo, Xuekun Song, Qingzhou Guan, Weicheng Zheng, Jiahui Zhang, Haiyan Huang, Yi Zou, Zheng Guo, Xianlong Wang
BACKGROUND & AIMS: Concerns are raised about the representativeness of cell lines for tumors due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma (HCC) cell lines. Therefore, it is of crucial importance to understand how well they can represent HCC. METHODS: The HCC-specific gene pairs with highly stable relative expression orderings (REOs) in more than 99% of HCC but with reversed REOs in at least 99% of one of the six types of cancer, colorectal carcinoma (CRC), breast carcinoma (BRC), non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified...
May 8, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28476943/patterns-of-chemotherapy-use-in-a-u-s-based-cohort-of-patients-with-metastatic-pancreatic-cancer
#19
Thomas A Abrams, Gary Meyer, Jeffrey A Meyerhardt, Brian M Wolpin, Deborah Schrag, Charles S Fuchs
PURPOSE: Few population studies have examined patterns of systemic therapy administration in metastatic pancreatic cancer (MPC) or the predictors associated with specific treatment choices. PATIENTS AND METHODS: We assessed 4,011 consecutive MPC patients who received chemotherapy between January 2005 and December 2015 at academic, private, and community-based oncology practices subscribing to a U.S.-wide chemotherapy order entry system capturing disease, patient, provider, and treatment data...
May 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28475592/lsl-krasg12d-lsl-trp53r172h-ink4flox-ptf1-p48-cre-mice-are-an-applicable-model-for-locally-invasive-and-metastatic-pancreatic-cancer
#20
Lixiang Ma, Hexige Saiyin
Pancreatic cancer (PC) accumulates multiple genetic mutations, including activating KRAS mutations and inactivating TP53, SMAD4 and CDKN2A mutations, during progression. The combination of mutant KRAS with a single inactivating TP53, SMAD4 or CDKN2A mutation in genetically engineered mouse models (GEMMs) showed that these mutations exert different synergistic effects in PC. However, the effect of the combination of TP53, CDKN2A and KRAS mutations on the trajectory of PC progression is unknown. Here, we report a GEMM that harbors KRAS (KrasG12D), TP53 (Trp53R172H/+), CDKN2A (Ink4flox/+) and Ptf1/p48-Cre (KPIC) mutations...
2017: PloS One
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