Adenosine receptor 2B activity promotes autonomous growth, migration as well as vascularization of head and neck squamous cell carcinoma cells

Adenosine is a signaling molecule that exerts dual effects on tumor growth: while it inhibits immune cell function and thereby prevents surveillance by the immune system, it influences tumorigenesis directly via activation of adenosine receptors on tumor cells at the same time. However, the adenosine-mediated mechanisms affecting oncogenic processes particularly in head and neck squamous cell carcinomas (HNSCC) are not fully understood. Here, we investigated the role of adenosine receptor activity on HNSCC-derived cell lines. Targeting the adenosine receptor A2B (ADORA2B) on these cells with the inverse agonist/antagonist PSB-603 leads to inhibition of cell proliferation, transmigration as well as VEGFA secretion in vitro. At the molecular level, these effects were associated with cell cycle arrest as well as the induction of the apoptotic pathway. In addition, shRNA-mediated downmodulation of ADORA2B expression caused decreased proliferation. Moreover, in in vivo xenograft experiments, chemical and genetic abrogation of ADORA2B activity impaired tumor growth associated with decreased tumor vascularization. Together, our findings characterize ADORA2B as a crucial player in the maintenance of HNSCC and, therefore, as a potential therapeutic target for HNSCC treatment

Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

<p>Abstract</p> <p>Background</p> <p>L1 cell adhesion molecule (CD171) is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST) as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker.</p> <p>Methods</p> <p>Using a sensitive enzyme-linked immunosorbent assay (ELISA), soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data.</p> <p>Results</p> <p>Median levels of soluble L1 were significantly higher (<it>p </it>< 0.001; Mann-Whitney U test) in sera of GIST patients compared to healthy individuals. Median soluble L1 levels were particularly elevated in patients with recurrence and relapse (<it>p </it>< 0.05; Mann Whitney U test).</p> <p>Conclusion</p> <p>These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy.</p

Adenosine receptor 2B activity promotes autonomous growth, migration as well as vascularization of head and neck squamous cell carcinoma cells

Adenosine is a signaling molecule that exerts dual effects on tumor growth: while it inhibits immune cell function and thereby prevents surveillance by the immune system, it influences tumorigenesis directly via activation of adenosine receptors on tumor cells at the same time. However, the adenosine-mediated mechanisms affecting oncogenic processes particularly in head and neck squamous cell carcinomas (HNSCC) are not fully understood. Here, we investigated the role of adenosine receptor activity on HNSCC-derived cell lines. Targeting the adenosine receptor A2B (ADORA2B) on these cells with the inverse agonist/antagonist PSB-603 leads to inhibition of cell proliferation, transmigration as well as VEGFA secretion in vitro. At the molecular level, these effects were associated with cell cycle arrest as well as the induction of the apoptotic pathway. In addition, shRNA-mediated downmodulation of ADORA2B expression caused decreased proliferation. Moreover, in in vivo xenograft experiments, chemical and genetic abrogation of ADORA2B activity impaired tumor growth associated with decreased tumor vascularization. Together, our findings characterize ADORA2B as a crucial player in the maintenance of HNSCC and, therefore, as a potential therapeutic target for HNSCC treatment

Modeling Laser-Induced Incandescence of Soot: A Summary and Comparison of LII Models

Peer reviewed: YesNRC publication: Ye

Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS)

Complete macroscopic tumor resection is one of the most relevant predictors of long-term survival in pancreatic ductal adenocarcinoma. Because locally advanced pancreatic tumors can involve adjacent organs, "extended" pancreatectomy that includes the resection of additional organs may be needed to achieve this goal. Our aim was to develop a common consistent terminology to be used in centers reporting results of pancreatic resections for cancer. An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature on extended pancreatectomies and worked together to establish a consensus on the definition and the role of extended pancreatectomy in pancreatic cancer. Macroscopic (R1) and microscopic (R0) complete tumor resection can be achieved in patients with locally advanced disease by extended pancreatectomy. Operative time, blood loss, need for blood transfusions, duration of stay in the intensive care unit, and hospital morbidity, and possibly also perioperative mortality are increased with extended resections. Long-term survival is similar compared with standard resections but appears to be better compared with bypass surgery or nonsurgical palliative chemotherapy or chemoradiotherapy. It was not possible to identify any clear prognostic criteria based on the specific additional organ resected. Despite increased perioperative morbidity, extended pancreatectomy is warranted in locally advanced disease to achieve long-term survival in pancreatic ductal adenocarcinoma if macroscopic clearance can be achieved. Definitions of extended pancreatectomies for locally advanced disease (and not distant metastatic disease) are established that are crucial for comparison of results of future trials across different practices and countries, in particular for those using neoadjuvant therap

Pancreatic anastomosis after pancreatoduodenectomy: A position statement by the International Study Group of Pancreatic Surgery (ISGPS)

Background Clinically relevant postoperative pancreatic fistula (grades B and C of the ISGPS definition) remains the most troublesome complication after pancreatoduodenectomy. The approach to management of the pancreatic remnant via some form of pancreatico-enteric anastomosis determines the incidence and severity of clinically relevant postoperative pancreatic fistula. Despite numerous trials comparing diverse pancreatico-enteric anastomosis techniques and other adjunctive strategies (pancreatic duct stenting, somatostatin analogues, etc), currently, there is no clear consensus regarding the ideal method of pancreatico-enteric anastomosis. Methods An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the best contemporary literature concerning pancreatico-enteric anastomosis and worked to develop a position statement on pancreatic anastomosis after pancreatoduodenectomy. Results There is inherent risk assumed by creating a pancreatico-enteric anastomosis based on factors related to the gland (eg, parenchymal texture, disease pathology). None of the technical variations of pancreaticojejunal or pancreaticogastric anastomosis, such as duct-mucosa, invagination method, and binding technique, have been found to be consistently superior to another. Randomized trials and meta-analyses comparing pancreaticogastrostomy versus pancreaticojejunostomy yield conflicting results and are inherently prone to bias due to marked heterogeneity in the studies. The benefit of stenting the pancreatico-enteric anastomosis to decrease clinically relevant postoperative pancreatic fistula is not supported by high-level evidence. While controversial, somatostatin analogues appear to decrease perioperative complications but not mortality, although consistent data across the more than 20 studies\ua0addressing this topic are lacking. The Fistula Risk Score is useful for predicting postoperative\ua0pancreatic fistula as well as for comparing outcomes of pancreatico-enteric anastomosis across studies. Conclusion Currently, no specific technique can eliminate development of clinically relevant postoperative pancreatic fistula. While consistent practice of any standardized technique may decrease the rate of clinically relevant postoperative pancreatic fistula, experienced surgeons can have lower postoperative pancreatic fistula rates performing a variety of techniques depending on the clinical situation. There is no clear evidence on the benefit of internal or external stenting after pancreatico-enteric anastomosis. The use of somatostatin analogues may be important in decreasing morbidity after pancreatoduodenectomy, but it remains controversial. Future studies should focus on novel approaches to decrease the rate of clinically relevant postoperative pancreatic fistula with appropriate risk adjustment

Pancreatic anastomosis after pancreatoduodenectomy: A position statement by the International Study Group of Pancreatic Surgery (ISGPS)

Background Clinically relevant postoperative pancreatic fistula (grades B and C of the ISGPS definition) remains the most troublesome complication after pancreatoduodenectomy. The approach to management of the pancreatic remnant via some form of pancreatico-enteric anastomosis determines the incidence and severity of clinically relevant postoperative pancreatic fistula. Despite numerous trials comparing diverse pancreatico-enteric anastomosis techniques and other adjunctive strategies (pancreatic duct stenting, somatostatin analogues, etc), currently, there is no clear consensus regarding the ideal method of pancreatico-enteric anastomosis. Methods An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the best contemporary literature concerning pancreatico-enteric anastomosis and worked to develop a position statement on pancreatic anastomosis after pancreatoduodenectomy. Results There is inherent risk assumed by creating a pancreatico-enteric anastomosis based on factors related to the gland (eg, parenchymal texture, disease pathology). None of the technical variations of pancreaticojejunal or pancreaticogastric anastomosis, such as duct-mucosa, invagination method, and binding technique, have been found to be consistently superior to another. Randomized trials and meta-analyses comparing pancreaticogastrostomy versus pancreaticojejunostomy yield conflicting results and are inherently prone to bias due to marked heterogeneity in the studies. The benefit of stenting the pancreatico-enteric anastomosis to decrease clinically relevant postoperative pancreatic fistula is not supported by high-level evidence. While controversial, somatostatin analogues appear to decrease perioperative complications but not mortality, although consistent data across the more than 20 studies addressing this topic are lacking. The Fistula Risk Score is useful for predicting postoperative pancreatic fistula as well as for comparing outcomes of pancreatico-enteric anastomosis across studies. Conclusion Currently, no specific technique can eliminate development of clinically relevant postoperative pancreatic fistula. While consistent practice of any standardized technique may decrease the rate of clinically relevant postoperative pancreatic fistula, experienced surgeons can have lower postoperative pancreatic fistula rates performing a variety of techniques depending on the clinical situation. There is no clear evidence on the benefit of internal or external stenting after pancreatico-enteric anastomosis. The use of somatostatin analogues may be important in decreasing morbidity after pancreatoduodenectomy, but it remains controversial. Future studies should focus on novel approaches to decrease the rate of clinically relevant postoperative pancreatic fistula with appropriate risk adjustment