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Pancreatic Neoplasms: HELP
Articles by Yves Boucher
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, Yves Boucher wrote the following 8 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Clinical Trial A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. 2014

Hong, Theodore S / Ryan, David P / Borger, Darrell R / Blaszkowsky, Lawrence S / Yeap, Beow Y / Ancukiewicz, Marek / Deshpande, Vikram / Shinagare, Shweta / Wo, Jennifer Y / Boucher, Yves / Wadlow, Raymond C / Kwak, Eunice L / Allen, Jill N / Clark, Jeffrey W / Zhu, Andrew X / Ferrone, Cristina R / Mamon, Harvey J / Adams, Judith / Winrich, Barbara / Grillo, Tarin / Jain, Rakesh K / DeLaney, Thomas F / Fernandez-del Castillo, Carlos / Duda, Dan G. ·Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: tshong1@partners.org. · Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts. ·Int J Radiat Oncol Biol Phys · Pubmed #24867540.

ABSTRACT: PURPOSE: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS AND MATERIALS: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood. RESULTS: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05). CONCLUSIONS: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS(G12D) status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.

2 Article Use of Angiotensin System Inhibitors Is Associated with Immune Activation and Longer Survival in Nonmetastatic Pancreatic Ductal Adenocarcinoma. 2017

Liu, Hao / Naxerova, Kamila / Pinter, Matthias / Incio, Joao / Lee, Hang / Shigeta, Kohei / Ho, William W / Crain, Jonathan A / Jacobson, Alex / Michelakos, Theodoros / Dias-Santos, Daniella / Zanconato, Andrea / Hong, Theodore S / Clark, Jeffrey W / Murphy, Janet E / Ryan, David P / Deshpande, Vikram / Lillemoe, Keith D / Fernandez-Del Castillo, Carlos / Downes, Michael / Evans, Ronald M / Michaelson, James / Ferrone, Cristina R / Boucher, Yves / Jain, Rakesh K. ·Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Leder Human Biology and Translational Medicine, Biology and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts. · Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. · Laboratory for Quantitative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Gene Expression Laboratory, Salk Institute for Biological Studies in La Jolla, La Jolla, California. · Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. yves@steele.mgh.harvard.edu jain@steele.mgh.harvard.edu. ·Clin Cancer Res · Pubmed #28600474.

ABSTRACT:

3 Article Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy. 2016

Incio, Joao / Liu, Hao / Suboj, Priya / Chin, Shan M / Chen, Ivy X / Pinter, Matthias / Ng, Mei R / Nia, Hadi T / Grahovac, Jelena / Kao, Shannon / Babykutty, Suboj / Huang, Yuhui / Jung, Keehoon / Rahbari, Nuh N / Han, Xiaoxing / Chauhan, Vikash P / Martin, John D / Kahn, Julia / Huang, Peigen / Desphande, Vikram / Michaelson, James / Michelakos, Theodoros P / Ferrone, Cristina R / Soares, Raquel / Boucher, Yves / Fukumura, Dai / Jain, Rakesh K. ·Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Department of Internal Medicine, Hospital S. Joao, Porto, Portugal. I3S, Institute for Innovation and Research in Heath, Metabolism, Nutrition and Endocrinology Group, Biochemistry Department, Faculty of Medicine, Porto University, Porto, Portugal. · Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Biology and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts. · Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Department of Botany and Biotechnology, St. Xaviers College, Thumba, Trivandrum, Kerala, India. · Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Harvard School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts. · Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Department of Zoology, Mar Ivanios College, Nalanchira, Trivandrum, Kerala, India. · Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Laboratory for Quantitative Medicine, and Division of Surgical Oncology, Gillette Center for Women's Cancers, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Departments of Gastroenterology and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Departments of Gastroenterology and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · I3S, Institute for Innovation and Research in Heath, Metabolism, Nutrition and Endocrinology Group, Biochemistry Department, Faculty of Medicine, Porto University, Porto, Portugal. · Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. jain@steele.mgh.harvard.edu dai@steele.mgh.harvard.edu. ·Cancer Discov · Pubmed #27246539.

ABSTRACT: SIGNIFICANCE: Considering the current obesity pandemic, unraveling the mechanisms underlying obesity-induced cancer progression is an urgent need. We found that the aggravation of desmoplasia is a key mechanism of obesity-promoted PDAC progression. Importantly, we discovered that clinically available antifibrotic/inflammatory agents can improve the treatment response of PDAC in obese hosts. Cancer Discov; 6(8); 852-69. ©2016 AACR.See related commentary by Bronte and Tortora, p. 821This article is highlighted in the In This Issue feature, p. 803.

4 Article Stromal response to Hedgehog signaling restrains pancreatic cancer progression. 2014

Lee, John J / Perera, Rushika M / Wang, Huaijun / Wu, Dai-Chen / Liu, X Shawn / Han, Shiwei / Fitamant, Julien / Jones, Phillip D / Ghanta, Krishna S / Kawano, Sally / Nagle, Julia M / Deshpande, Vikram / Boucher, Yves / Kato, Tomoyo / Chen, James K / Willmann, Jürgen K / Bardeesy, Nabeel / Beachy, Philip A. ·Institute for Stem Cell Biology and Regenerative Medicine,Division of Oncology, Department of Medicine. · Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; · Molecular Imaging Program, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305; · Institute for Stem Cell Biology and Regenerative Medicine. · Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and. · Department of Chemical and Systems Biology, and. · Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; pbeachy@stanford.edu Bardeesy.Nabeel@mgh.harvard.edu. · Institute for Stem Cell Biology and Regenerative Medicine,Department of Biochemistry,Howard Hughes Medical Institute, Stanford, CA 94305 pbeachy@stanford.edu Bardeesy.Nabeel@mgh.harvard.edu. ·Proc Natl Acad Sci U S A · Pubmed #25024225.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is the most lethal of common human malignancies, with no truly effective therapies for advanced disease. Preclinical studies have suggested a therapeutic benefit of targeting the Hedgehog (Hh) signaling pathway, which is activated throughout the course of PDA progression by expression of Hh ligands in the neoplastic epithelium and paracrine response in the stromal fibroblasts. Clinical trials to test this possibility, however, have yielded disappointing results. To further investigate the role of Hh signaling in the formation of PDA and its precursor lesion, pancreatic intraepithelial neoplasia (PanIN), we examined the effects of genetic or pharmacologic inhibition of Hh pathway activity in three distinct genetically engineered mouse models and found that Hh pathway inhibition accelerates rather than delays progression of oncogenic Kras-driven disease. Notably, pharmacologic inhibition of Hh pathway activity affected the balance between epithelial and stromal elements, suppressing stromal desmoplasia but also causing accelerated growth of the PanIN epithelium. In striking contrast, pathway activation using a small molecule agonist caused stromal hyperplasia and reduced epithelial proliferation. These results indicate that stromal response to Hh signaling is protective against PDA and that pharmacologic activation of pathway response can slow tumorigenesis. Our results provide evidence for a restraining role of stroma in PDA progression, suggesting an explanation for the failure of Hh inhibitors in clinical trials and pointing to the possibility of a novel type of therapeutic intervention.

5 Article Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. 2013

Chauhan, Vikash P / Martin, John D / Liu, Hao / Lacorre, Delphine A / Jain, Saloni R / Kozin, Sergey V / Stylianopoulos, Triantafyllos / Mousa, Ahmed S / Han, Xiaoxing / Adstamongkonkul, Pichet / Popović, Zoran / Huang, Peigen / Bawendi, Moungi G / Boucher, Yves / Jain, Rakesh K. ·1] Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA [2] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [3]. ·Nat Commun · Pubmed #24084631.

ABSTRACT: Cancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels, thus reducing vascular perfusion. Tumour interstitial matrix also contributes to solid stress, with hyaluronan implicated as the primary matrix molecule responsible for vessel compression because of its swelling behaviour. Here we show, unexpectedly, that hyaluronan compresses vessels only in collagen-rich tumours, suggesting that collagen and hyaluronan together are critical targets for decompressing tumour vessels. We demonstrate that the angiotensin inhibitor losartan reduces stromal collagen and hyaluronan production, associated with decreased expression of profibrotic signals TGF-β1, CCN2 and ET-1, downstream of angiotensin-II-receptor-1 inhibition. Consequently, losartan reduces solid stress in tumours resulting in increased vascular perfusion. Through this physical mechanism, losartan improves drug and oxygen delivery to tumours, thereby potentiating chemotherapy and reducing hypoxia in breast and pancreatic cancer models. Thus, angiotensin inhibitors -inexpensive drugs with decades of safe use - could be rapidly repurposed as cancer therapeutics.

6 Article Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. 2012

Stylianopoulos, Triantafyllos / Martin, John D / Chauhan, Vikash P / Jain, Saloni R / Diop-Frimpong, Benjamin / Bardeesy, Nabeel / Smith, Barbara L / Ferrone, Cristina R / Hornicek, Francis J / Boucher, Yves / Munn, Lance L / Jain, Rakesh K. ·Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ·Proc Natl Acad Sci U S A · Pubmed #22932871.

ABSTRACT: The presence of growth-induced solid stresses in tumors has been suspected for some time, but these stresses were largely estimated using mathematical models. Solid stresses can deform the surrounding tissues and compress intratumoral lymphatic and blood vessels. Compression of lymphatic vessels elevates interstitial fluid pressure, whereas compression of blood vessels reduces blood flow. Reduced blood flow, in turn, leads to hypoxia, which promotes tumor progression, immunosuppression, inflammation, invasion, and metastasis and lowers the efficacy of chemo-, radio-, and immunotherapies. Thus, strategies designed to alleviate solid stress have the potential to improve cancer treatment. However, a lack of methods for measuring solid stress has hindered the development of solid stress-alleviating drugs. Here, we present a simple technique to estimate the growth-induced solid stress accumulated within animal and human tumors, and we show that this stress can be reduced by depleting cancer cells, fibroblasts, collagen, and/or hyaluronan, resulting in improved tumor perfusion. Furthermore, we show that therapeutic depletion of carcinoma-associated fibroblasts with an inhibitor of the sonic hedgehog pathway reduces solid stress, decompresses blood and lymphatic vessels, and increases perfusion. In addition to providing insights into the mechanopathology of tumors, our approach can serve as a rapid screen for stress-reducing and perfusion-enhancing drugs.

7 Article Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. 2011

Diop-Frimpong, Benjamin / Chauhan, Vikash P / Krane, Stephen / Boucher, Yves / Jain, Rakesh K. ·Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ·Proc Natl Acad Sci U S A · Pubmed #21282607.

ABSTRACT: The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan--a clinically approved angiotensin II receptor antagonist with noted antifibrotic activity--can enhance the penetration and efficacy of nanomedicine. We found that losartan inhibited collagen I production by carcinoma-associated fibroblasts isolated from breast cancer biopsies. Additionally, it led to a dose-dependent reduction in stromal collagen in desmoplastic models of human breast, pancreatic, and skin tumors in mice. Furthermore, losartan improved the distribution and therapeutic efficacy of intratumorally injected oncolytic herpes simplex viruses. Finally, it also enhanced the efficacy of i.v. injected pegylated liposomal doxorubicin (Doxil). Thus, losartan has the potential to enhance the efficacy of nanotherapeutics in patients with desmoplastic tumors.

8 Minor Compression of pancreatic tumor blood vessels by hyaluronan is caused by solid stress and not interstitial fluid pressure. 2014

Chauhan, Vikash P / Boucher, Yves / Ferrone, Cristina R / Roberge, Sylvie / Martin, John D / Stylianopoulos, Triantafyllos / Bardeesy, Nabeel / DePinho, Ronald A / Padera, Timothy P / Munn, Lance L / Jain, Rakesh K. ·Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. · Department of Surgery, Pancreas and Biliary Surgery Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. · Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. · Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: jain@steele.mgh.harvard.edu. ·Cancer Cell · Pubmed #25026209.

ABSTRACT: -- No abstract --