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Find video protocols related to scientific articles indexed in Pubmed.
Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer.
Cancer Immunol. Immunother.
PUBLISHED: 02-22-2014
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Pancreatic cancer (PC) mobilizes myeloid cells from the bone marrow to the tumor where they promote tumor growth and proliferation. Cancer stem cells (CSCs) are a population of tumor cells that are responsible for tumor initiation. Aldehyde dehydrogenase-1 activity in PC identifies CSCs, and its activity has been correlated with poor overall prognosis in human PC. Myeloid cells have been shown to impact tumor stemness, but the impact of immunosuppressive tumor-infiltrating granulocytic and monocytic myeloid-derived suppressor cells (Mo-MDSC) on ALDH1(Bright) CSCs and epithelial to mesenchymal transition is not well understood. In this study, we demonstrate that Mo-MDSC (CD11b(+)/Gr1(+)/Ly6G(-)/Ly6C(hi)) significantly increase the frequency of ALDH1(Bright) CSCs in a mouse model of PC. Additionally, there was significant upregulation of genes associated with epithelial to mesenchymal transition. We also found that human PC converts CD14(+) peripheral blood monocytes into Mo-MDSC (CD14(+)/HLA-DR(low/-)) in vitro, and this transformation is dependent on the activation of the STAT3 pathway. In turn, these Mo-MDSC increase the frequency of ALDH1(Bright) CSCs and promote mesenchymal features of tumor cells. Finally, blockade of STAT3 activation reversed the increase in ALDH1(Bright) CSCs. These data suggest that the PC tumor microenvironment transforms monocytes to Mo-MDSC by STAT3 activation, and these cells increase the frequency of ALDH1(Bright) CSCs. Therefore, targeting STAT3 activation may be an effective therapeutic strategy in targeting CSCs in PC.
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A simple effective method for generation of a permanent record of the Critical View of Safety during laparoscopic cholecystectomy by intraoperative "doublet" photography.
J. Am. Coll. Surg.
PUBLISHED: 01-21-2014
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The Critical View of Safety (CVS) is an established method for identifying the cystic duct during laparoscopic cholecystectomy. Its goal is to prevent misidentification of the bile ducts and avoid biliary injury. However, a visual record of CVS is not usually made. Intraoperative photography has the potential to record CVS and increase the safety of laparoscopic cholecystectomy. The objective of this study was to develop a simple and effective technique for recording CVS during laparoscopic cholecystectomy.
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Variations in definition and method of retrieval of complications influence outcomes statistics after pancreatoduodenectomy: comparison of NSQIP with non-NSQIP methods.
J. Am. Coll. Surg.
PUBLISHED: 01-18-2014
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NSQIP and the Accordion Severity Grading System have recently been used to develop quantitative methods for measuring the burden of postoperative complications. However, other audit methods such as chart reviews and prospective institutional databases are commonly used to gather postoperative complications. The purpose of this study was to evaluate discordance between different audit methods in pancreatoduodenectomy--a common major surgical procedure. The chief aim was to determine how these different methods could affect quantitative evaluations of postoperative complications.
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Down-regulation of PLC?2-?-catenin pathway promotes activation and expansion of myeloid-derived suppressor cells in cancer.
J. Exp. Med.
PUBLISHED: 10-14-2013
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Myeloid-derived suppressor cells (MDSCs) favor tumor promotion, mainly by suppressing antitumor T cell responses in many cancers. Although the mechanism of T cell inhibition is established, the pathways leading to MDSC accumulation in bone marrow and secondary lymphoid organs of tumor-bearing hosts remain unclear. We demonstrate that down-regulation of PLC?2 signaling in MDSCs is responsible for their aberrant expansion during tumor progression. PLC?2(-/-) MDSCs show stronger immune-suppressive activity against CD8(+) T cells than WT MDSCs and potently promote tumor growth when adoptively transferred into WT mice. Mechanistically, PLC?2(-/-) MDSCs display reduced ?-catenin levels, and restoration of ?-catenin expression decreases their expansion and tumor growth. Consistent with a negative role for ?-catenin in MDSCs, its deletion in the myeloid population leads to MDSC accumulation and supports tumor progression, whereas expression of ?-catenin constitutively active reduces MDSC numbers and protects from tumor growth. Further emphasizing the clinical relevance of these findings, MDSCs isolated from pancreatic cancer patients show reduced p-PLC?2 and ?-catenin levels compared with healthy controls, similar to tumor-bearing mice. Thus, for the first time, we demonstrate that down-regulation of PLC?2-?-catenin pathway occurs in mice and humans and leads to MDSC-mediated tumor expansion, raising concerns about the efficacy of systemic ?-catenin blockade as anti-cancer therapy.
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A Study of Zoledronic Acid as Neo-Adjuvant, Perioperative Therapy in Patients with Resectable Pancreatic Ductal Adenocarcinoma.
J Cancer Ther
PUBLISHED: 10-04-2013
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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by abundant granulocytic myeloid-derived suppressor cells (G-MDSC = CD45(+)/Lin(-)/CD33(+)/CD11b(+)/CD15(+)), which infiltrate tumors and suppress anti-tumor immunity. We have previously demonstrated in a murine model of PDAC that zoledronic acid (ZA) depletes G-MDSC resulting in decreased tumor growth and improved survival. We report here the results of a phase 1 clinical trial (NCT00892242) using ZA as neo-adjuvant, perioperative therapy in patients with non-metastatic, resectable pancreatic adenocarcinoma.
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Are readmission rates on a neurosurgical service indicators of quality of care?
J. Neurosurg.
PUBLISHED: 04-26-2013
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The goal of this study was to examine the reasons for early readmissions within 30 days of discharge to a major academic neurosurgical service.
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Jaundice: an important, poorly recognized risk factor for diminished survival in patients with adenocarcinoma of the head of the pancreas.
HPB (Oxford)
PUBLISHED: 01-26-2013
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OBJECTIVES: Jaundice impairs cellular immunity, an important defence against the dissemination of cancer. Jaundice is a common mode of presentation in pancreatic head adenocarcinoma. The purpose of this study was to determine whether there is an association between preoperative jaundice and survival in patients who have undergone resection of such tumours. METHODS: Thirty possible survival risk factors were evaluated in a database of over 400 resected patients. Univariate analysis was used to determine odds ratio for death. All factors for which a P-value of <0.30 was obtained were entered into a multivariate analysis using the Cox model with backward selection. RESULTS: Preoperative jaundice, age, positive node status, poor differentiation and lymphatic invasion were significant indicators of poor outcome in multivariate analysis. Absence of jaundice was a highly favourable prognostic factor. Interaction emerged between jaundice and nodal status. The benefit conferred by the absence of jaundice was restricted to patients in whom negative node status was present. Five-year overall survival in this group was 66%. Jaundiced patients who underwent preoperative stenting had a survival advantage. CONCLUSIONS: Preoperative jaundice is a negative risk factor in adenocarcinoma of the pancreas. Additional studies are required to determine the exact mechanism for this effect.
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Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses.
Cancer Res.
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Tumor-infiltrating immune cells can promote chemoresistance and metastatic spread in aggressive tumors. Consequently, the type and quality of immune responses present in the neoplastic stroma are highly predictive of patient outcome in several cancer types. In addition to host immune responses, intrinsic tumor cell activities that mimic stem cell properties have been linked to chemoresistance, metastatic dissemination, and the induction of immune suppression. Cancer stem cells are far from a static cell population; rather, their presence seems to be controlled by highly dynamic processes that are dependent on cues from the tumor stroma. However, the impact immune responses have on tumor stem cell differentiation or expansion is not well understood. In this study, we show that targeting tumor-infiltrating macrophages (TAM) and inflammatory monocytes by inhibiting either the myeloid cell receptors colony-stimulating factor-1 receptor (CSF1R) or chemokine (C-C motif) receptor 2 (CCR2) decreases the number of tumor-initiating cells (TIC) in pancreatic tumors. Targeting CCR2 or CSF1R improves chemotherapeutic efficacy, inhibits metastasis, and increases antitumor T-cell responses. Tumor-educated macrophages also directly enhanced the tumor-initiating capacity of pancreatic tumor cells by activating the transcription factor STAT3, thereby facilitating macrophage-mediated suppression of CD8(+) T lymphocytes. Together, our findings show how targeting TAMs can effectively overcome therapeutic resistance mediated by TICs.
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Presentation and management of gastrointestinal stromal tumors of the duodenum: a multi-institutional analysis.
Ann. Surg. Oncol.
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Duodenal gastrointestinal stromal tumors (GISTs) are a small subset of GISTs, and their management is poorly defined. We evaluated surgical management and outcomes of patients with duodenal GISTs treated with pancreaticoduodenectomy (PD) versus local resection (LR) and defined factors associated with prognosis.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.