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Carlos Fernandez-del Castillo

Bio: Carlos Fernandez-del Castillo is an academic researcher from Harvard University. The author has contributed to research in topics: Pancreatic cancer & Medicine. The author has an hindex of 89, co-authored 443 publications receiving 35827 citations. Previous affiliations of Carlos Fernandez-del Castillo include Brigham and Women's Hospital & Millennium Pharmaceuticals.


Papers
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Journal ArticleDOI
01 Mar 2017-Surgery
TL;DR: This new definition and grading system of postoperative pancreatic Fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula.

2,313 citations

Journal ArticleDOI
TL;DR: This statement proposes a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy, and advocates the use of strict criteria for accepting newly proposed entities or sites as components of the IgG 4- related disease spectrum.

2,041 citations

Journal ArticleDOI
TL;DR: Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN, and some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases.

1,912 citations

Journal ArticleDOI
23 Oct 2003-Nature
TL;DR: It is reported that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN), and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis.
Abstract: Hedgehog signalling--an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer--may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis.

1,520 citations


Cited by
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Journal ArticleDOI
07 Feb 2020-Science
TL;DR: The intrinsic properties of exosomes in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases, including neurodegenerative conditions and cancer.
Abstract: The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.

3,715 citations

Journal ArticleDOI
01 Jul 2005-Surgery
TL;DR: In this article, an international panel of pancreatic surgeons, working in well-known, high-volume centers, reviewed the literature on the topic and worked together to develop a simple, objective, reliable, and easy-to-apply definition of postoperative pancreatic fistula, graded primarily on clinical impact.

3,622 citations

01 Jan 2005
TL;DR: The present definition and clinical grading of POPF should allow realistic comparisons of surgical experiences in the future when new techniques, new operations, or new pharmacologic agents that may impact surgical treatment of pancreatic disorders are addressed.
Abstract: Background. Postoperative pancreatic fistula (POPF) is still regarded as a major complication. The incidence of POPF varies greatly in different reports, depending on the definition applied at each surgical center. Our aim was to agree upon an objective and internationally accepted definition to allow comparison of different surgical experiences. Methods. An international panel of pancreatic surgeons, working in well-known, high-volume centers, reviewed the literature on the topic and worked together to develop a simple, objective, reliable, and easyto-apply definition of POPF, graded primarily on clinical impact. Results. A POPF represents a failure of healing/sealing of a pancreatic-enteric anastomosis or a parenchymal leak not directly related to an anastomosis. An all-inclusive definition is a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content greater than 3 times the serum amylase activity. Three different grades of POPF (grades A, B, C) are defined according to the clinical impact on the patient’s hospital course. Conclusions. The present definition and clinical grading of POPF should allow realistic comparisons of surgical experiences in the future when new techniques, new operations, or new pharmacologic agents that may impact surgical treatment of pancreatic disorders are addressed. (Surgery 2005;138:8-13.)

3,617 citations

Journal ArticleDOI
TL;DR: Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might lead to new therapeutic targets and better anticancer strategies.
Abstract: The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies.

3,480 citations