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pancreatic adenocarcinoma chemotherapy

Khaldoun Almhanna, Gopi K Prithviraj, Petter Veiby, Thea Kalebic
Antibody-directed cancer chemotherapy in the form of antibody-drug conjugates (ADCs) may improve the therapeutic index with the potential to enhance efficacy and decrease systemic toxicity. ADCs consist of three key components including an antibody that specifically binds to the target, a toxic agent and a linker which releases the toxic agent inside tumor cells. A novel ADC, MLN0264 (TAK-264) was recently investigated in patients with gastrointestinal (GI) malignancies. TAK-264 is an anti- guanylyl cyclase C (GCC) antibody conjugated via a protease-cleavable linker to the potent anti-microtubule agent monomethyl auristatin E (MMAE) (linker and toxin licensed from Seattle Genetics)...
October 17, 2016: Pharmacology & Therapeutics
Ryo Fujiwara, Mitsuhiro Narita, Susumu Kageyama, Akihiro Kawauchi, Takahisa Nakayama, Natsumi Nishi, Hiroyuki Sugihara, Yusaku Okada
A 67-year-old man presented at our hospital with severe edema on the left side of his neck, chest and brachial regions. He had a history of right radical nephrectomy due to renal cell carcinoma (RCC, clear cell subtype, stage II) 15 years earlier. Thereafter, metastases to the pancreatic tail and right lung, and left lung metastasis were removed at 8 years and 11 years, respectively, after the nephrectomy. Four years earlier, he had also undergone total gastrectomy for gastric carcinoma (poorly differentiated adenocarcinoma, stage IV) and subsequent maintenance chemotherapy for gastric carcinoma...
September 2016: Hinyokika Kiyo. Acta Urologica Japonica
Toru Aoyama, Masaaki Murakawa, Yosuke Atsumi, Keisuke Kazama, Manabu Shiozawa, Satoshi Kobayashi, Makoto Ueno, Manabu Morimoto, Kouta Washimi, Norio Yukawa, Yasushi Rino, Munetaka Masuda, Soichiro Morinaga
A 74-year-old man with IgG4-related cholangitis had been treated with steroids for 1 year. In the outpatient clinic, elevated levels of the tumor marker CA19-9 and serum IgG4 were observed. Abdominal enhanced CT showed a 20mm hypovascular tumor in the pancreatic head. ERCP showed narrowingof the main pancreatic duct in the pancreatic head with slight caudal dilation and stricture of the lower common bile duct. We made a diagnosis of pancreatic cancer, and the patient underwent pancreaticoduodenectomy. Pathological examination of the resected tissue revealed a well-differentiated adenocarcinoma surrounded by autoimmune pancreatitis, characteristic of lymphoplasmacytic sclerosingpancreatitis...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Yuki Homma, Goro Honda, Katsunori Sakamoto, Masanao Kurata, Masahiko Honjo, Yoshihiro Hirata, Satoshi Shinya
BACKGROUND: Although surgical resection is the only curative strategy for pancreatic cancer, the prognosis of patients with pancreatic cancer remains poor. Recently, neoadjuvant treatment has been frequently employed as a promising treatment. Here, the mid-term results of neoadjuvant chemoradiotherapy(NACRT)using S-1, which has been performed in our hospital since 2008, are reported. METHODS: Seventy-nine patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, who had been intended to undergo NACRT treatment using S-1, were enrolled...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Vanaja Konduri, Dali Li, Matthew M Halpert, Dan Liang, Zhengdong Liang, Yunyu Chen, William E Fisher, Silke Paust, Jonathan M Levitt, Qizhi Cathy Yao, William K Decker
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, exhibiting a five-year overall survival (OS) of only 7% despite aggressive standard of care. Recent advances in immunotherapy suggest potential application of immune-based treatment approaches to PDAC. To explore this concept further, we treated orthotopically established K-ras(G12D)/p53(-/-) PDAC tumors with gemcitabine and a cell-based vaccine previously shown to generate durable cell-mediated (TH1) immunity...
2016: Oncoimmunology
A Drouillard, F Puleo, J B Bachet, S Ouazzani, A Calomme, P Demetter, G Verset, J L Van Laethem, R Maréchal
BACKGROUND: There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4) as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Using immunohistochemistry (IHC) and tissue microarray (TMA), we assessed the expression patterns of DLL4, Notch1 and Notch3 in 151 patients from two independent cohorts of resected PDAC. We investigated the prognostic and the predictive significance of these proteins...
October 18, 2016: British Journal of Cancer
Min Yuen Teo, Eileen M O'Reilly
Pancreatic cancer is a highly lethal malignancy which tends to present with late stage disease. To date, identification of oncogenic drivers and aberrations has not led to effective targeted therapy. Approximately 5-15% of pancreatic cancer has an inheritable component. In fact, pancreatic adenocarcinoma is now recognized as a BRCA1/2-related cancer. Germline BRCA1/2 mutations can be found in up to 3.6-7% of unselected pancreatic cancer patients although the rates are significantly higher amongst patients with Ashkenazi Jewish ancestry...
October 2016: Journal of Gastrointestinal Oncology
Namrata Vijayvergia, Steven J Cohen
Pancreatic adenocarcinoma is the fourth leading cause of cancer related death in the United States. Most patients are diagnosed at a late stage and despite recent advances in chemotherapeutic approaches, outcomes are poor. With the introduction of combination chemotherapy, novel biomarkers are clearly needed to identify subsets of patients likely to benefit from these therapies. Advances in our understanding of the molecular drivers of pancreatic cancer offer the hope of personalized therapy that may benefit our patients...
October 2016: Journal of Gastrointestinal Oncology
Naru Kondo, Yoshiaki Murakami, Kenichiro Uemura, Naoya Nakagawa, Shinya Takahashi, Hiroki Ohge, Taijiro Sueda
BACKGROUND: Although serum carbohydrate antigen 19-9 (CA19-9), s-pancreas antigen-1 (SPan-1), and duke pancreatic monoclonal antigen type 2 (DUPAN-II) are commonly utilized tumor markers in pancreatic ductal adenocarcinoma (PDAC), it is still unclear which is the most useful for predicting prognosis after surgical resection. Here, we aimed to compare the prognostic impact of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC. METHODS: Pre-operative CA19-9, SPan-1, and DUPAN-II levels were analyzed to compare their prognostic values for resectable PDAC in 198 patients whose pre-operative tumor markers were available...
October 11, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Georg Dimcevski, Spiros Kotopoulis, Tormod Bjånes, Dag Hoem, Jan Schjøt, Bjørn Tore Gjertsen, Martin Biermann, Anders Molven, Halfdan Sorbye, Emmet McCormack, Michiel Postema, Odd Helge Gilja
BACKGROUND: The primary aim of our study was to evaluate the safety and potential toxicity of gemcitabine combined with microbubbles under sonication in inoperable pancreatic cancer patients. The secondary aim was to evaluate a novel image-guided microbubble-based therapy, based on commercially available technology, towards improving chemotherapeutic efficacy, preserving patient performance status, and prolonging survival. METHODS: Ten patients were enrolled and treated in this Phase I clinical trial...
October 12, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Lucy Ireland, Almudena Santos, Muhammad S Ahmed, Carolyn Rainer, Sebastian R Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D Engle, Pedro Perez-Mancera, Sarah E Coupland, Azzam F Taktak, Thomas Bogenrieder, David A Tuveson, Fiona Campbell, Michael C Schmid, Ainhoa Mielgo
Tumor associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors 1 and 2 (IGF), which activate Insulin/IGF receptors on pancreatic cancer cells...
October 14, 2016: Cancer Research
Florence K Keane, Jennifer Y Wo, Cristina R Ferrone, Jeffrey W Clark, Lawrence S Blaszkowsky, Jill N Allen, Eunice L Kwak, David P Ryan, Keith D Lillemoe, Carlos Fernandez-Del Castillo, Theodore S Hong
OBJECTIVES: Improved outcomes with FOLFIRINOX or gemcitabine with nab-paclitaxel in the treatment of metastatic pancreatic adenocarcinoma (PDAC) have prompted incorporation of these regimens into neoadjuvant treatment of locally advanced unresectable PDAC. Whereas some patients remain unresectable on surgical exploration, others are able to undergo resection after intensive neoadjuvant treatment. We evaluated outcomes and toxicity associated with use of intensive neoadjuvant treatment followed by intraoperative radiotherapy (IORT) in combination with resection or exploratory laparotomy...
October 12, 2016: American Journal of Clinical Oncology
P Karásek, M Hermanová
BACKGROUND: Pancreatic ductal adenocarcinoma is a highly aggressive disease with 5-year overall survival not exceeding 5%. In the Czech Republic, the incidence of this tumor has been increasing; according to recent statistics, the Czech Republic is already number one worldwide in the occurrence of this malignancy. Delayed diagnosis due to asymptomatic course of the disease in the early stages is characteristic for this disease. AIM: The objective of this article is to give an overview of the most important factors, which according to current knowledge of pancreatic adenocarcinoma have a prognostic and predictive potential...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Jason W Denbo, Morgan L Bruno, Jordan M Cloyd, Laura Prakash, Jeffrey E Lee, Michael Kim, Christopher H Crane, Eugene J Koay, Sunil Krishnan, Prajnan Das, Bruce D Minsky, Gauri Varadhachary, Rachna Shroff, Robert Wolff, Milind Javle, Michael J Overman, David Fogelman, Thomas A Aloia, Jean-Nicolas Vauthey, Jason B Fleming, Matthew H G Katz
BACKGROUND: The impact of preoperative chemoradiation on postoperative morbidity and mortality of patients with pancreatic adenocarcinoma remains controversial. METHODS: Consecutive pancreatectomies for adenocarcinoma performed between 2011 and 2015 were prospectively monitored for 90 days by using a previously reported surveillance system to determine the association between preoperative chemoradiation and adverse events, pancreatic fistulae, readmissions, and mortality...
October 11, 2016: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
A Hann, W Bohle, J Egger, W G Zoller
Background: New chemotherapeutic strategies for locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) have been shown to improve survival in randomized clinical trials. Little is known about the use of such chemotherapies and their benefit in community-based hospitals. This retrospective study analyzes the overall survival of these patients under "real life conditions" before and after the introduction of FOLFIRINOX in 2011. Methods: We retrospectively identified consecutive patients with PDAC who were treated at our hospital from 2011 to June 2014 (2011+ cohort) and 2004 to 2010 (historical cohort)...
October 2016: Zeitschrift Für Gastroenterologie
Octavio Caba, Antonio Irigoyen, Cristina Jimenez-Luna, Manuel Benavides, Francisco M Ortuño, Javier Gallego, Ignacio Rojas, Carmen Guillen-Ponce, Carolina Torres, Enrique Aranda, Jose Prados
Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients...
October 6, 2016: Toxicology and Applied Pharmacology
Shutaro Hori, Kazuaki Shimada, Yoshinori Ino, Seiji Oguro, Minoru Esaki, Satoshi Nara, Yoji Kishi, Tomoo Kosuge, Yukinori Hattori, Aoi Sukeda, Yuko Kitagawa, Yae Kanai, Nobuyoshi Hiraoka
As macroscopic appearance represents tumor microenvironment, it may also reflect the biological and clinicopathological characteristics of a cancer. The aim of the study was to evaluate the clinicopathological significance of the gross appearance of pancreatic ductal adenocarcinoma (PDA). We investigated fresh macroscopic features in 352 cases of PDA and their clinicopathological significance. Three unique gross features were found: a honeycomb-like appearance (diffusely distributed microcysts and interstitial fibrotic thickening), macroscopic necrosis, and a tube/branching structure (apparent small cylindrical or linear structure)...
October 5, 2016: Virchows Archiv: An International Journal of Pathology
Yang Liu, Fan Li, Feng Gao, Lingxi Xing, Peng Qin, Xingxin Liang, Jiajie Zhang, Xiaohui Qiao, Lizhou Lin, Qian Zhao, Lianfang Du
Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths. The nucleoside analog gemcitabine has been the cornerstone of adjuvant chemotherapy in PDAC for decades. However, gemcitabine resistance develops within weeks of chemotherapy initiation, which might be intrinsic to cancer cells and influenced by tumor microenvironment. Recently, pancreatic stellate cells (PSCs) have greatly increased our attention on tumor microenvironment-mediated drug resistance. Periostin is exclusively overexpressed in PSCs and the stroma of PDAC creating a tumor-supportive microenvironment in the pancreas...
September 30, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Gaoyong Liao, Bing Gao, Yingnv Gao, Xuegan Yang, Xiaodong Cheng, Yu Ou
Pancreatic adenocarcinoma (PDA) is one of the most lethal human malignancies, and unresponsive to current chemotherapies. Here we investigate the therapeutic potential of phycocyanin as an anti-PDA agent in vivo and in vitro. Phycocyanin, a natural product purified from Spirulina, effectively inhibits the pancreatic cancer cell proliferation in vitro and xenograft tumor growth in vivo. Phycocyanin induces G2/M cell cycle arrest, apoptotic and autophagic cell death in PANC-1 cells. Inhibition of autophagy by targeting Beclin 1 using siRNA significantly suppresses cell growth inhibition and death induced by phycocyanin, whereas inhibition of both autophagy and apoptosis rescues phycocyanin-mediated cell death...
October 3, 2016: Scientific Reports
C Cassinotto, A Sa-Cunha, H Trillaud
Neoadjuvant chemotherapy has become common practice in the management of patients with non-metastatic pancreatic adenocarcinoma. This strategy helps better select patients who would benefit from surgical resection and also increase the number of patients amenable to surgical resection whose tumor seemed too locally advanced on initial imaging. However, several studies have shown that the radiological evaluation of the response after neoadjuvant therapy is difficult for pancreatic carcinoma. This article reviews the scientific basis of neoadjuvant therapy for non-metastatic pancreatic cancer and provides an update on tumor response evaluation with imaging after neoadjuvant treatment...
September 27, 2016: Diagnostic and Interventional Imaging
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