Comparison of transhepatic and extrahepatic routes for EUS-guided rendezvous procedure for distal CBD obstruction.

Science.gov (United States)

Dhir, Vinay; Bhandari, Suryaprakash; Bapat, Mukta; Joshi, Nitin; Vivekanandarajah, Suhirdan; Maydeo, Amit

2013-04-01

EUS-guided rendezvous procedure (EUS-RV) can be done by the transhepatic (TH) or the extrahepatic (EH) route. There is no data on the preferred access route when both routes are available. To compare the success, complications, and duration of hospitalization for patients undergoing EUS-RV by the TH or the EH route. Patients with distal common bile duct (CBD) obstruction, who failed selective cannulation, underwent EUS-RV by the TH route through the stomach or the EH route through the duodenum. A total of 35 patients were analysed (17 TH, 18 EH). The mean procedure time was significantly longer for the TH group (34.4 vs. 25.7 min; p = 0.0004). There was no difference in the technical success (94.1 vs. 100%). However, the TH group had a higher incidence of post-procedure pain (44.1 vs. 5.5%; p = 0.017), bile leak (11.7 vs. 0; p = 0.228), and air under diaphragm (11.7 vs. 0; p = 0.228). All bile leaks were small and managed conservatively. Duration of hospitalization was significantly higher for the TH group (2.52 vs. 0.17 days; p = 0.015). EUS-RV has similar success rate by the TH or the EH route. However, the TH route has higher post-procedure pain, longer procedure time, and longer duration of hospitalization. The EH route should be preferred for EUS-RV in patients with distal CBD obstruction when both access routes are technically feasible.

Identifying indications for percutaneous (PTC) vs. endoscopic ultrasound (EUS)- guided "rendezvous" procedure in biliary obstruction and incomplete endoscopic retrograde cholangiography (ERC).

Science.gov (United States)

Albert, J G; Finkelmeier, F; Friedrich-Rust, M; Kronenberger, B; Trojan, J; Zeuzem, S; Sarrazin, C

2014-10-01

The variety of rendezvous (RV) procedures has recently been extended by EUS- and PTCD-guided procedures as a complementary means to conventional ERCP. We have identified indication criteria and the potential of biliary PTCD-guided vs. EUS-guided RV. Consecutive patients with bile duct obstruction who underwent RV were included. In all, ERCP alone was unable to achieve treatment success. Indication, technical success, and outcome in PTCD- vs. EUS-guided RV were retrospectively compared to identify criteria that indicate preference of RV technique. Site of obstruction, clinical scenario (stenosis with abscess vs. no abscess) and reason for previous failure of ERC were evaluated. In 32 patients, three different indications for RV procedures were identified: First, a one-step access to assist in failed ERCP (type 1, intra-ductal RV); second, temporary drainage for prolonged treatment of complex biliary disease (type 2, intra-ductal RV), and drainage of cholangio-abscess with re-establishing bile outflow (type 3, intra-abscess RV). Indication of PTCD- vs. EUS-guided rendezvous was competitive in type 1, but exclusive in favor of PTCD in types 2 and 3. The site of biliary obstruction indicated the anatomic location of RV procedures. This classification may help to define inclusion criteria for prospective studies on biliary RV procedures. Choice of therapeutic strategy depends on the anatomic location of the biliary obstruction and the type of the biliary lesion. PTCD-guided RV might improve outcome in cholangio-abscess. © Georg Thieme Verlag KG Stuttgart · New York.

Impact of EUS-guided FNA on management of gastric carcinoma

DEFF Research Database (Denmark)

Hassan, Hazem; Vilmann, Peter; Sharma, Vijay

2010-01-01

EUS is an integral part of the pretherapeutic evaluation program for patients with upper GI cancer.......EUS is an integral part of the pretherapeutic evaluation program for patients with upper GI cancer....

Rescue EUS-guided intrahepatic biliary drainage for malignant hilar biliary stricture after failed transpapillary re-intervention.

Science.gov (United States)

Minaga, Kosuke; Takenaka, Mamoru; Kitano, Masayuki; Chiba, Yasutaka; Imai, Hajime; Yamao, Kentaro; Kamata, Ken; Miyata, Takeshi; Omoto, Shunsuke; Sakurai, Toshiharu; Watanabe, Tomohiro; Nishida, Naoshi; Kudo, Masatoshi

2017-11-01

Treatment of unresectable malignant hilar biliary stricture (UMHBS) is challenging, especially after failure of repeated transpapillary endoscopic stenting. Endoscopic ultrasonography-guided intrahepatic biliary drainage (EUS-IBD) is a recent technique for intrahepatic biliary decompression, but indications for its use for complex hilar strictures have not been well studied. The aim of this study was to assess the feasibility and safety of EUS-IBD for UMHBS after failed transpapillary re-intervention. Retrospective analysis of all consecutive patients with UMHBS of Bismuth II grade or higher who, between December 2008 and May 2016, underwent EUS-IBD after failed repeated transpapillary interventions. The technical success, clinical success, and complication rates were evaluated. Factors associated with clinical ineffectiveness of EUS-IBD were explored. A total of 30 patients (19 women, median age 66 years [range 52-87]) underwent EUS-IBD for UMHBS during the study period. Hilar biliary stricture morphology was classified as Bismuth II, III, or IV in 5, 13, and 12 patients, respectively. The median number of preceding endoscopic interventions was 4 (range 2-14). EUS-IBD was required because the following procedures failed: duodenal scope insertion (n = 4), accessing the papilla after duodenal stent insertion (n = 5), or achieving desired intrahepatic biliary drainage (n = 21). Technical success with EUS-IBD was achieved in 29 of 30 patients (96.7%) and clinical success was attained in 22 of these 29 (75.9%). Mild peritonitis occurred in three of 30 (10%) and was managed conservatively. Stent dysfunction occurred in 23.3% (7/30). There was no procedure-related mortality. On multivariable analysis, Bismuth IV stricture predicted clinical ineffectiveness (odds ratio = 12.7, 95% CI 1.18-135.4, P = 0.035). EUS-IBD may be a feasible and effective rescue alternative with few major complications after failed transpapillary endoscopic re-intervention in patients

An international multicenter study comparing EUS-guided pancreatic duct drainage with enteroscopy-assisted endoscopic retrograde pancreatography after Whipple surgery.

Science.gov (United States)

Chen, Yen-I; Levy, Michael J; Moreels, Tom G; Hajijeva, Gulara; Will, Uwe; Artifon, Everson L; Hara, Kazuo; Kitano, Masayuki; Topazian, Mark; Abu Dayyeh, Barham; Reichel, Andreas; Vilela, Tiago; Ngamruengphong, Saowanee; Haito-Chavez, Yamile; Bukhari, Majidah; Okolo, Patrick; Kumbhari, Vivek; Ismail, Amr; Khashab, Mouen A

2017-01-01

Endoscopic management of post-Whipple pancreatic adverse events (AEs) with enteroscopy-assisted endoscopic retrograde pancreatography (e-ERP) is associated with high failure rates. EUS-guided pancreatic duct drainage (EUS-PDD) has shown promising results; however, no comparative data have been done for these 2 modalities. The goal of this study is to compare EUS-PDD with e-ERP in terms of technical success (PDD through dilation/stent), clinical success (improvement/resolution of pancreatic-type symptoms), and AE rates in patients with post-Whipple anatomy. This is an international multicenter comparative retrospective study at 7 tertiary centers (2 United States, 2 European, 2 Asian, and 1 South American). All consecutive patients who underwent EUS-PDD or e-ERP between January 2010 and August 2015 were included. In total, 66 patients (mean age, 57 years; 48% women) and 75 procedures were identified with 40 in EUS-PDD and 35 in e-ERP. Technical success was achieved in 92.5% of procedures in the EUS-PDD group compared with 20% of procedures in the e-ERP group (OR, 49.3; P procedures in the EUS-PDD group compared with 23.1% in the e-ERP group (OR, 23.3; P Procedure time and length of stay were not significantly different between the 2 groups. EUS-PDD is superior to e-ERP in post-Whipple anatomy in terms of efficacy with acceptable safety. As such, EUS-PDD should be considered as a potential first-line treatment in post-pancreaticoduodenectomy anatomy when necessary expertise is available. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Feasibility Study of EUS-NOTES as a Novel Approach for Pancreatic Cancer Staging and Therapy

DEFF Research Database (Denmark)

Săftoiu, Adrian; Bhutani, Manoop S; Vilmann, Peter

2012-01-01

-guided transgastric approach was tested for ease of access to the tail of the pancreas. Gastric wound closure was finally performed in several animals using various commercial and prototype endoscopic accessories. Results: The results showed the ability of EUS-NOTES technology to facilitate a transgastric approach...

EUS – Fine- Needle Aspiration Biopsy (FNAB in the Diagnosis of Pancreatic Adenocarcinoma: A Review

Directory of Open Access Journals (Sweden)

Kalogeraki Alexandra

2016-03-01

Full Text Available Solid masses of the pancreas represent a variety of benign and malignant neoplasms of the exocrine and endocrine tissues of the pancreas. A tissue diagnosis is often required to direct therapy in the face of uncertain diagnosis or if the patient is not a surgical candidate either due to advanced disease or comorbidities. Endoscopic ultrasound (EUS is a relatively new technology that employs endoscopy and high-frequency ultrasound (US. EUS involves imaging of the pancreatic head and the uncinate from the duodenum and imaging of the body and tail from the stomach. It has been shown to be a highly sensitive method for the detection of pancreatic masses. It is superior to extracorporeal US and computed tomographic (CT scans, especially when the pancreatic tumor is smaller than 2-3 cm. Although EUS is highly sensitive in detecting pancreatic solid masses, its ability to differentiate between inflammatory masses and malignant disease is limited. Endoscopic retrograde cholangiopancreatography (ERCP brushing, CT-guided biopsies, and transabdominal ultrasound (US have been the standard nonsurgical methods for obtaining a tissue diagnosis of pancreatic lesions, but a substantial false-negative rate has been reported. Transabdominal US-guided fine-needle aspiration biopsy (US-FNAB has been used for tissue diagnosis in patients with suspected pancreatic carcinoma. It has been shown to be highly specific, with no false-positive diagnoses. With the advent of curvilinear echoendoscopes, transgastric and transduodenal EUS-FNAB of the pancreas have become a reality EUS with FNAB has revolutionized the ability to diagnose and stage cancers of the gastrointestinal tract and assess the pancreas. Gastrointestinal cancers can be looked at with EUS and their depth of penetration into the intestinal wall can be determined. Any suspicious appearing lymph nodes can be biopsied using EUS/FNAB. The pancreas is another organ that is well visualized with EUS. Abnormalities

EUS-guided rendezvous for difficult biliary cannulation using a standardized algorithm: a multicenter prospective pilot study (with videos).

Science.gov (United States)

Iwashita, Takuji; Yasuda, Ichiro; Mukai, Tsuyoshi; Iwata, Keisuke; Ando, Nobuhiro; Doi, Shinpei; Nakashima, Masanori; Uemura, Shinya; Mabuchi, Masatoshi; Shimizu, Masahito

2016-02-01

Biliary cannulation is necessary in therapeutic ERCP for biliary disorders. EUS-guided rendezvous (EUS-RV) can salvage failed cannulation. Our aim was to determine the safety and efficacy of EUS-RV by using a standardized algorithm with regard to the endoscope position in a prospective study. EUS-RV was attempted after failed cannulation in 20 patients. In a standardized approach, extrahepatic bile duct (EHBD) cannulation was preferentially attempted from the second portion of the duodenum (D2) followed by additional approaches to the EHBD from the duodenal bulb (D1) or to the intrahepatic bile duct from the stomach, if necessary. A guidewire was placed in an antegrade fashion into the duodenum. After the guidewire was placed, the endoscope was exchanged for a duodenoscope to complete the cannulation. The bile duct was accessed from the D2 in 10 patients, but from the D1 in 5 patients and the stomach in 4 patients because of no dilation or tumor invasion at the distal EHBD. In the remaining patient, biliary puncture was not attempted due to the presence of collateral vessels. The guidewire was successfully manipulated in 80% of patients: 100% (10/10) with the D2 approach and 66.7% (6/9) with other approaches. The overall success rate was 80% (16/20). Failed EUS-RV was salvaged with a percutaneous approach in 2 patients, repeat ERCP in 1 patient, and conservative management in 1 patient. Minor adverse events occurred in 15% of patients (3/20). EUS-RV is a safe and effective salvage method. Using EUS-RV to approach the EHBD from the D2 may improve success rates. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

EUS-FNA for the Diagnosis of Retroperitoneal Primitive Neuroectodermal Tumor

Directory of Open Access Journals (Sweden)

Aijaz A. Sofi

2011-01-01

Full Text Available Primitive neuroectodermal tumor (PNET is a rare “small round blue cell tumor” that is diagnosed by open biopsy or percutaneous biopsy of the lesion under radiologic guidance. In this case report, we present a novel approach to the diagnosis of a retroperitoneal PNET by endoscopic ultrasound- (EUS- guided fine needle aspiration (FNA. A 35-year-old man presented with the history of left-sided flank pain and swelling of 3-weeks duration. Computerized tomography (CT scan of his abdomen revealed a 12.8 × 13 × 12.5 cm cystic and solid mass arising from the retroperitoneum and displacing the third and fourth portions of the duodenum. He underwent EUS which revealed a well-circumscribed heterogeneous mass abutting the inferior portion of the stomach. EUS-FNA of the mass revealed malignant cells consistent with primitive neuroectodermal tumor (PNET/Ewing's sarcoma. EUS-guided FNA is an appropriate technique for diagnosing retroperitoneal PNET/Ewing's sarcoma.

Fluid collection after partial pancreatectomy: EUS drainage and long-term follow-up.

Science.gov (United States)

Caillol, Fabrice; Godat, Sebastien; Turrini, Olivier; Zemmour, Christophe; Bories, Erwan; Pesenti, Christian; Ratone, Jean Phillippe; Ewald, Jacques; Delpero, Jean Robert; Giovannini, Marc

2018-03-29

Postoperative fluid collection due to pancreatic leak is the most frequent complication after pancreatic surgery. Endoscopic ultrasound (EUS)-guided drainage of post-pancreatic surgery fluid collection is the gold standard procedure; however, data on outcomes of this procedure are limited. The primary endpoint of our study was relapse over longterm followup, and the secondary endpoint was the efficiency and safety of EUS-guided drainage of post-pancreatic surgery fluid collection. This retrospective study was conducted at a single center from December 2008 to April 2016. Global morbidity was defined as the occurrence of an event involving additional endoscopic procedures, hospitalization, or interventional radiologic or surgical procedures. EUS-guided drainage was considered a clinical failure if surgery was required to treat a relapse after stent removal. Fortyone patients were included. The technical success rate was 100%. Drainage was considered a clinical success in 93% (39/41) of cases. Additionally, 19 (46%) complications were identified as global morbidity. The duration between surgery and EUS-guided drainage was not a significantly related factor for morbidity rate (P = 0.8); however, bleeding due to arterial injuries (splenic artery and gastroduodenal artery) from salvage drainage procedures occurred within 25 days following the initial surgery. There was no difference in survival between patients with and without complications. No relapse was reported during the followup (median: 44.75 months; range: 29.24 to 65.74 months). EUSguided drainage for post-pancreatic surgery fluid collection was efficient with no relapse during longterm followup. Morbidity rate was independent of the duration between the initial surgery and EUS-guided drainage; however, bleeding risk was likely more important in cases of early drainage.

Feasibility study of EUS-NOTES as a novel approach for peroral cholecysto-gastrostomy

DEFF Research Database (Denmark)

Saftoiu, Adrian; Vilmann, P; Bhutani, M S

2013-01-01

EUS-guided cholecysto-gastrostomy might be a useful minimally invasive procedure used for salvage drainage in advanced pancreaticobiliary cancers, but also for drainage of the gallbladder in acute cholecystitis in patients deemed unfit for laparoscopic surgery.......EUS-guided cholecysto-gastrostomy might be a useful minimally invasive procedure used for salvage drainage in advanced pancreaticobiliary cancers, but also for drainage of the gallbladder in acute cholecystitis in patients deemed unfit for laparoscopic surgery....

Fluorescence cytology with 5-aminolevulinic acid in EUS-guided FNA as a method for differentiating between malignant and benign lesions (with video).

Science.gov (United States)

Ikeura, Tsukasa; Takaoka, Makoto; Uchida, Kazushige; Shimatani, Masaaki; Miyoshi, Hideaki; Kato, Kota; Ohe, Chisato; Uemura, Yoshiko; Kaibori, Masaki; Kwon, A-Hon; Okazaki, Kazuichi

2015-01-01

EUS-guided FNA (EUS-FNA) has been increasingly performed to obtain specimens for the pathological evaluation of patients with GI and pancreaticobiliary masses as well as lymphadenopathies of unknown origin. Photodynamic diagnosis by using 5-aminolebulinic acid (ALA) has been reported to be useful for enabling the visual differentiation between malignant and normal tissue in various cancers. To evaluate the diagnostic accuracy of fluorescence cytology with ALA in EUS-FNA. A prospective study. A single center. A total of 28 consecutive patients who underwent EUS-FNA for the pathological diagnosis of a pancreaticobiliary mass lesion or intra-abdominal lymphadenopathy of unknown origin. Patients were orally administered ALA 3 to 6 hours before EUS-FNA. The sample was obtained via EUS-FNA for fluorescence cytology and conventional cytology. A single gastroenterologist performed the fluorescence cytology by using fluorescence microscopy after the procedure, independently of the conventional cytology by pathologists. The accuracy of fluorescence cytology with ALA in the differentiation between benign and malignant lesions by comparing the results of fluorescence cytology with the final diagnosis. Of the 28 patients included in the study, 22 were considered as having malignant lesions and 6 patients as having benign lesions. Fluorescence cytology could correctly discriminate between benign and malignant lesions in all patients. Therefore, both the sensitivity and specificity of fluorescence cytology were 100% in our study. Fluorescence cytology was performed by only 1 gastroenterologist with a small number of patients. Fluorescence cytology with ALA in EUS-FNA may be an effective and simple method for differentiating between benign and malignant lesions. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

EUS needle identification comparison and evaluation (NICE) study (with videos)

Science.gov (United States)

Tang, Shou-jiang; Vilmann, Andreas S.; Saftoiu, Adrian; Wang, Wanmei; Streba, Costin; Fink, Peter P.; Griswold, Michael; Wu, Ruonan; Dietrich, Christoph F.; Jenssen, Christian; Hocke, Michael; Kantowski, Marcus; Pohl, Jürgen; Fockens, Paul; Annema, Jouke T.; van der Heijden, Erik H.F.M.; Havre, Roald Flesland; Pham, Khanh Do-Cong; Kunda, Rastislav; Deprez, Pierre H.; Mariana, Jinga; Vazquez-Sequeiros, Enrique; Larghi, Alberto; Buscarini, Elisabetta; Fusaroli, Pietro; Lahav, Maor; Puri, Rajesh; Garg, Pramod Kumar; Sharma, Malay; Maluf-Filho, Fauze; Sahai, Anand; Brugge, William R.; Lee, Linda S.; Aslanian, Harry R.; Wang, Andrew Y.; Shami, Vanessa M.; Markowitz, Arnold; Siddiqui, Ali A.; Mishra, Girish; Scheiman, James M.; Isenberg, Gerard; Siddiqui, Uzma D.; Shah, Raj J.; Buxbaum, James; Watson, Rabindra R.; Willingham, Field F.; Bhutani, Manoop S.; Levy, Michael J.; Harris, Cynthia; Wallace, Michael B.; Nolsøe, Christian Pállson; Lorentzen, Torben; Bang, Niels; Sørensen, Sten Mellerup; Gilja, Odd Helge; D’Onofrio, Mirko; Piscaglia, Fabio; Gritzmann, Norbert; Radzina, Maija; Sparchez, Zeno Adrian; Sidhu, Paul S.; Freeman, Simon; McCowan, Timothy C.; de Araujo, Cyrillo Rodrigues; Patel, Akash; del Ali, Mohammad A; Campbell, Garth; Chen, Edward; Vilmann, Peter

2017-01-01

Background and Aims Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) or biopsy is widely practiced. Optimal sonographic visualization of the needle is critical for image guided interventions. There are several commercially available needles but no bench-top testing and direct comparison of these needles to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development. Methods Descriptive bench-top testing and comparison. Bench-top testing of 8 commonly used EUS-FNA needles (all of 22 gauge in size): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition, (Cook Medical); ClearView (Conmed); EZ Shot2 (Olympus); BNX (Beacon Endoscopic); and 2 new prototype needles that are coated by echogenic polymers by Medi-Globe. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in gastrointestinal ultrasound examination that is unfamiliar with EUS needle devices. Results There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, one prototype needle was rated as the best, ranking 10% to 40% higher than all other needles (p<0.01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%–75% worse, p<0.001). Conclusions All FNA needles have their inherent and different echogenicity, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity. PMID:26873530

Accuracy of EUS for estimating the depth of tumor invasion and for diagnosing lymph node metastasis and recurrence in patients with m3 and sm esophageal carcinomas

International Nuclear Information System (INIS)

Arima, Miwako; Tada, Masahiro; Tanaka, Youichi; Arima, Hideaki

2006-01-01

Esophagus-preserving therapy has been increasingly used to treat esophageal cancer invading the m 3 and sm, thereby avoiding radical surgery. However, many problems remain to be solved, including the diagnosis of lymph node metastasis and recurrence and the assessment of long-term outcomes. We studied 132 patients who had esophageal cancer with m 3 and sm invasion. Clinical course after esophagus-preserving therapy, and the accuracy and roles of endoscopic ultrasonography (EUS) for diagnosing the depth of tumor invasion, lymph node metastasis, and recurrence were assessed. EUS can be used to examine the cervical, thoracic, and abdominal regions, without being affected by heat beats. Therefore, EUS can more clearly depict lymph nodes than CT or US. The accuracy of EUS was 86.4% for estimating the depth of tumor invasion and 82% for diagnosing lymph node metastasis. All cases of nodal recurrence were diagnosed by EUS. Among patients who received chemoradiotherapy, enlarged lymph nodes often appeared around 3 years after treatment, and recurrence was diagnosed slightly later than that in patients who underwent endoscopic mucosal resection. Endoscopic ultrasound-guided fine-needle aspiration biopsy was sometimes performed to determine the treatment policy. Patients who receive chemoradiotherapy should undergo regular long-term follow-up by CT, US, and EUS. EUS is essential for the earlier detection of recurrence. (author)

Endoscopy/EUS-guided fiducial marker placement in patients with esophageal cancer: a comparative analysis of 3 types of markers.

Science.gov (United States)

Machiels, Melanie; van Hooft, Jeanin; Jin, Peng; van Berge Henegouwen, Mark I; van Laarhoven, Hanneke M; Alderliesten, Tanja; Hulshof, Maarten C

2015-10-01

Markers placed at the borders of esophageal tumors are potentially useful to facilitate radiotherapy (RT) target delineation, which offers the possibility of image-guided RT. To evaluate and compare the feasibility and technical benefit of endoscopy/EUS-guided marker placement of 3 different types of markers in patients with esophageal cancer referred for RT. Prospective, single-center, feasibility and comparative study. Tertiary-care medical center. Thirty patients with esophageal cancer who were referred for RT. Patients underwent endoscopy/EUS-guided implantation of 1 type of marker. A solid gold marker (SM) with fixed dimensions, a flexible coil-shaped gold marker (FM) with hand-cut length (2-10 mm), and a radiopaque hydrogel marker (HG) were used. Technical feasibility and adverse events were registered. CT scans and cone-beam CT scans (CBCT) acquired during RT were analyzed to determine and compare the visibility and continuous clear visibility of the implanted markers. Technical feasibility, technical benefit, and adverse events of 3 types of markers. A total of 101 markers were placed in 30 patients. Implantation was technically feasible in all patients without grade 3 to 4 adverse events. Two patients with asymptomatic mediastinitis and one with asymptomatic pneumothorax were seen. Visibility on CT scan of all 3 types of implanted markers was adequate for target delineation. Eighty percent of FMs remained continuously visible over the treatment period on CBCT, significantly better than SMs (63%) and HGs (11%) (P = .015). When we selected FMs ≥5 mm, 90.5% remained visible on CBCT between implantation and the end of RT. Single-center, nonrandomized design. Endoscopy/EUS-guided fiducial marker placement for esophageal cancer is both safe and feasible and can be used for target volume delineation purposes on CT. Our results imply a significant advantage of FMs over SMs and HGs, regarding visibility and continuous clear visibility over the treatment period

Metastatic tonsillar squamous cell carcinoma masquerading as a pancreatic cystic tumor and diagnosed by EUS-guided FNA.

Science.gov (United States)

Glass, Ryan; Andrawes, Sherif A; Hamele-Bena, Diane; Tong, Guo-Xia

2017-11-01

Metastatic carcinoma to the pancreas is uncommon and head and neck squamous carcinoma metastatic to the pancreas is extremely rare. Metastatic squamous cell carcinoma to the pancreas presents a unique diagnostic challenge: in addition to mimicking the rare primary squamous cell carcinoma of the pancreas based on cytologic, histologic, and immunohistochemical features, it may be mistaken for a cystic neoplasm of the pancreas because of its high predilection for cystic degeneration in metastatic sites. Herein, we report a case of tonsillar squamous cell carcinoma with a cystic pancreatic metastasis diagnosed by ultrasound-guided fine needle aspiration biopsy (EUS-FNA). This represents a third reported case of metastatic squamous cell carcinoma to the pancreas from the head and neck region. Metastatic squamous cell carcinoma should be considered in the differential diagnosis of EUS-FNA during evaluation of pancreatic cystic lesion. © 2017 Wiley Periodicals, Inc.

EUS Elastography: Advances in Diagnostic EUS of the Pancreas

International Nuclear Information System (INIS)

Lee, Tae Hee; Cha, Sang Woo; Cho, Young Deok

2012-01-01

Elastography is an imaging modality for the evaluation of tissue stiffness, which has been used for the analysis of superficial organs, such as those of the breast and prostate. The measurement of tissue elasticity has been reported to be useful for the diagnosis and differentiation of tumors, which are stiffer than normal tissues. Endoscopic ultrasonography elastography (EUS-EG) is a promising imaging technique with a high degree of accuracy for the differential diagnosis of solid pancreatic tumors. Recent introduction of second generation EUS-EG allows for the quantitative analysis of tissue stiffness. Here, we review our knowledge and preliminary experience with the use of EUS-elastography for the diagnosis of pancreatic disease.

Preoperative noninvasive EUS evaluation in patients with esophageal cancer considered for esophagectomy.

Science.gov (United States)

Gheorghe, Cristian; Stanescu, Codrut; Gheorghe, Liana; Bancila, Ion; Herlea, Vlad; Becheanu, Gabriel; Voinea, Daniela; Iacob, Razvan; Lupescu, Ioana; Anghel, Rodica; Croitoru, Adina; Popescu, Irinel

2006-06-01

Worldwide, esophageal cancer ranks fifth in the mortality rate regarding tumor locations. EUS is an essential tool in the evaluation of these patients allowing accurate staging and permitting stratified treatment options. AIM. We have studied prospectively the impact of EUS in the evaluation and decision for therapy of patients with esophageal cancer diagnosed in our center. From March 2001 through March 2006, 220 patients were hospitalized at the Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, with the diagnosis of esophageal cancer. Out of the 220 patients, 41 patients, with no major comorbidities contraindicating esophagectomy already having been screened by abdominal and thoracic CT to disclose distant metastases, had EUS with the definite purpose of staging esophageal carcinoma and selecting adequate therapy. Assuming that without preoperative staging by EUS, all 41 patients in the study group would have been offered surgical treatment, we evaluated the number of patients and the modality in which EUS resulted in changes to the therapeutic plan. Depth of invasion was recorded for the 41 patients as follows: T1 in 2 patients (4.9%), T2 in 6 patients (14.6%), T3 in 24 patients (58.5%), and T4 in 10 patients (22%). Regional lymph node (N) status as determined by EUS criteria was as follows: N0 in 7 patients (17%) and N1 in 34 patients (83%). Assessment of distant metastases (M) was recorded showing 4 patients with celiac axis lymph nodes metastases (M1). Preoperative EUS staging changed the decision for surgery in 18 of 41 patients (44%) (p<0.0001) and allowed primary esophagectomy in only 6 patients (15%) (p<0.0001). Compared to histopathology, the overall accuracy of EUS staging for pT1 and pT2 was 80% for staging pT3 and pT4 77% and for lymph node evaluation was approximately 75%. Esophageal EUS offers useful information to clinicians caring for patients with esophageal cancer, impacts clinical decision making, and should be used in

Safe and successful endoscopic initial treatment and long-term eradication of gastric varices by endoscopic ultrasound-guided Histoacryl (N-butyl-2-cyanoacrylate) injection

OpenAIRE

Gubler, Christoph; Bauerfeind, Peter

2014-01-01

OBJECTIVE: Optimal endoscopic treatment of gastric varices is still not standardized nowadays. Actively bleeding varices may prohibit a successful endoscopic injection therapy of Histoacryl® (N-butyl-2-cyanoacrylate). Since 2006, we have treated gastric varices by standardized endoscopic ultrasound (EUS) guided Histoacryl injection therapy without severe adverse events. MATERIAL AND METHODS: We present a large single-center cohort over 7 years with a standardized EUS-guided sclerotherapy o...

Quantitative contrast-enhanced harmonic EUS in differential diagnosis of focal pancreatic masses (with videos)

DEFF Research Database (Denmark)

Săftoiu, Adrian; Vilmann, Peter; Dietrich, Christoph F

2015-01-01

BACKGROUND: The role of EUS with contrast agents can be expanded through the use of time-intensity curve (TIC) analysis and computer-aided interpretation. OBJECTIVE: To validate the use of parameters derived from TIC analysis in an artificial neural network (ANN) classification model designed......-guided FNA (EUS-FNA), TIC analysis, and ANN processing. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive and negative predictive values (PPV, NPV) for EUS-FNA, CEH-EUS, and the ANN. RESULTS: After excluding all of the recordings that did not meet the technical and procedural criteria, 112 cases...... rise time, mean transit time, and time to peak. For the ANN, sensitivity was 94.64%, specificity 94.44%, PPV 97.24%, and NPV 89.47%. LIMITATIONS: Only PC and CP lesions were included. CONCLUSION: Parameters obtained through TIC analysis can differentiate between PC and CP cases and can be used...

Impact of antitumor therapy on nutrition

International Nuclear Information System (INIS)

Kokal, W.A.

1985-01-01

The treatment of the cancer patient by surgery, chemotherapy or radiation therapy can impose significant nutritional disabilities on the host. The nutritional disabilities seen in the tumor-bearing host from antitumor therapy are produced by factors which either limit oral intake or cause malabsorption of nutrients. The host malnutrition caused as a consequence of surgery, chemotherapy or radiation therapy assumes even more importance when one realizes that many cancer patients are already debilitated from their disease

EUS-guided drainage of pancreatic fluid collections using a novel lumen-apposing metal stent on an electrocautery-enhanced delivery system : a large retrospective study (with video)

NARCIS (Netherlands)

Rinninella, Emanuele; Kunda, Rastislav; Dollhopf, Markus; Sanchez-Yague, Andres; Will, Uwe; Tarantino, Ilaria; Gornals Soler, Joan; Ullrich, Sebastian; Meining, Alexander; Esteban, Josè Miguel; Enz, Thomas; Vanbiervliet, Geoffroy; Vleggaar, FP; Attili, Fabia; Larghi, Alberto

2015-01-01

BACKGROUND AND AIMS: A lumen-apposing, self-expanding metal stent incorporated in an electrocautery-enhanced delivery system for EUS-guided drainage of pancreatic fluid collections (PFCs) recently has become available. The aim of this study was to analyze the safety and clinical effectiveness of

Self-aggregation of magnetic semiconductor EuS nanocrystals

International Nuclear Information System (INIS)

Tanaka, Atsushi; Hasegawa, Yasuchika; Kamikubo, Hironari; Kataoka, Mikio; Kawai, Tsuyoshi

2009-01-01

Controlled formation of aggregates having organized structure of cube-shaped EuS nanocrystals is reported. The EuS aggregates in liquid media (methanol) were obtained by means of van der Waals interaction between EuS nanocrystals. The packing structure of the EuS aggregates is characterized with transmission electron microscopy (TEM) and small angle X-ray scattering measurements (SAXS). TEM image indicates the EuS nanocrystals form self-aggregated 2D orthogonal lattice structure. The diffraction peak of (111) of SAXS profile shows that the cube-shaped EuS form 3D cubic superlattice. We successfully demonstrated that the aggregates of cube-shaped EuS nanocrystals formed cubic stacking structure.

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer.

Science.gov (United States)

Telli, M L; Stover, D G; Loi, S; Aparicio, S; Carey, L A; Domchek, S M; Newman, L; Sledge, G W; Winer, E P

2018-05-07

Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of 'immune cold' TNBCs.

EUS-guided drainage of pancreatic fluid collections using a novel lumen-apposing metal stent on an electrocautery-enhanced delivery system: a large retrospective study (with video).

Science.gov (United States)

Rinninella, Emanuele; Kunda, Rastislav; Dollhopf, Markus; Sanchez-Yague, Andres; Will, Uwe; Tarantino, Ilaria; Gornals Soler, Joan; Ullrich, Sebastian; Meining, Alexander; Esteban, Josè Miguel; Enz, Thomas; Vanbiervliet, Geoffroy; Vleggaar, Frank; Attili, Fabia; Larghi, Alberto

2015-12-01

A lumen-apposing, self-expanding metal stent incorporated in an electrocautery-enhanced delivery system for EUS-guided drainage of pancreatic fluid collections (PFCs) recently has become available. The aim of this study was to analyze the safety and clinical effectiveness of this newly developed device in this clinical setting. This was a retrospective analysis of all consecutive patients with PFCs who underwent EUS-guided drainage using the study device in 13 European centers. Ninety-three patients with PFCs (80% with complex collections) underwent drainage using the study device. Penetration of the PFC was accomplished directly with the study device in 74.2% of patients, and successful stent placement was accomplished in all but 1 patient, mostly without fluoroscopic assistance. Direct endoscopic necrosectomy (DEN) was carried out in 31 of 52 cases (59.6%) of walled-off necrosis and in 2 of 4 cases (50%) of acute peripancreatic fluid collection. Complete resolution of the PFC was obtained in 86 cases (92.5%), with no recurrence during follow-up. Treatment failure occurred in 6 patients because of persistent infection requiring surgery (n = 3), perforation and massive bleeding caused by the nasocystic drainage catheter (NCDC) (n = 2), and the need for a larger opening to extract large necrotic tissue pieces (n = 1). Major adverse events occurred in 5 patients (perforation and massive bleeding caused by the NCDC in 2 patients, 1 pneumoperitoneum and 1 stent dislodgement during DEN, and 1 postdrainage infection) and were mostly not related to the drainage procedure. EUS-guided drainage with the electrocautery-enhanced delivery system is a safe, easy to perform, and a highly effective minimally invasive treatment modality for PFCs. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Endoscopic Ultrasound-Guided Biliary Drainage

International Nuclear Information System (INIS)

Artifon, Everson L.A.; Ferreira, Fla'vio C.; Sakai, Paulo

2012-01-01

To demonstrate a comprehensive review of published articles regarding endoscopic ultrasound (EUS)-guided biliary drainage. Review of studies regarding EUS-guided biliary drainage including case reports, case series and previous reviews. EUS-guided hepaticogastrostomy, coledochoduodenostomy and choledoantrostomy are advanced biliary and pancreatic endoscopy procedures, and together make up the echo-guided biliary drainage. Hepaticogastrostomy is indicated in cases of hilar obstruction, while the procedure of choice is the coledochoduodenostomy or choledochoantrostomy in distal lesions. Both procedures must be performed only after unsuccessful ERCPs. The indication of these procedures must be made under a multidisciplinary view while sharing information with the patient or legal guardian. Hepaticogastrostomy and coledochoduodenostomy or choledochoantrostomy are feasible when performed by endoscopists with expertise in biliopancreatic endoscopy. Advanced echo-endoscopy should currently be performed under a rigorous protocol in educational institutions.

Endoscopic Ultrasound-Guided Biliary Drainage

Energy Technology Data Exchange (ETDEWEB)

Artifon, Everson L.A.; Ferreira, Fla& #x27; vio C.; Sakai, Paulo [University of Saeo Paulo, Saeo Paulo (Brazil)

2012-02-15

To demonstrate a comprehensive review of published articles regarding endoscopic ultrasound (EUS)-guided biliary drainage. Review of studies regarding EUS-guided biliary drainage including case reports, case series and previous reviews. EUS-guided hepaticogastrostomy, coledochoduodenostomy and choledoantrostomy are advanced biliary and pancreatic endoscopy procedures, and together make up the echo-guided biliary drainage. Hepaticogastrostomy is indicated in cases of hilar obstruction, while the procedure of choice is the coledochoduodenostomy or choledochoantrostomy in distal lesions. Both procedures must be performed only after unsuccessful ERCPs. The indication of these procedures must be made under a multidisciplinary view while sharing information with the patient or legal guardian. Hepaticogastrostomy and coledochoduodenostomy or choledochoantrostomy are feasible when performed by endoscopists with expertise in biliopancreatic endoscopy. Advanced echo-endoscopy should currently be performed under a rigorous protocol in educational institutions.

OFFICIAL MEDICATIONS FOR ANTI-TUMOR GENE THERAPY

Directory of Open Access Journals (Sweden)

E. R. Nemtsova

2016-01-01

Full Text Available This is a review of modern literature data of official medications for anti-tumor gene therapy as well as of medications that finished clinical trials.The article discusses the concept of gene therapy, the statistical analysis results of initiated clinical trials of gene products, the most actively developing directions of anticancer gene therapy, and the characteristics of anti-tumor gene medications.Various delivery systems for gene material are being examined, including viruses that are defective in  replication (Gendicine™ and Advexin and oncolytic (tumor specific conditionally replicating viruses (Oncorine™, ONYX-015, Imlygic®.By now three preparations for intra-tumor injection have been introduced into oncology clinical practice: two of them – Gendicine™ and Oncorine™ have been registered in China, and one of them – Imlygic® has been registered in the USA. Gendicine™ and Oncorine™ are based on the wild type p53 gene and are designed for treatment of patients with head and neck malignancies. Replicating adenovirus is the delivery system in Gendicine™, whereas oncolytic adenovirus is the vector for gene material in Oncorine™. Imlygic® is based on the  recombinant replicating HSV1 virus with an introduced GM–CSF gene and is designed for treatment of  melanoma patients. These medications are well tolerated and do not cause any serious adverse events. Gendicine™ and Oncorine™ are not effective in monotherapy but demonstrate pronounced synergism with chemoand radiation therapy. Imlygic® has just started the post marketing trials.

Alleviating Pancreatic Cancer-Associated Pain Using Endoscopic Ultrasound-Guided Neurolysis

Science.gov (United States)

Takenaka, Mamoru; Kamata, Ken; Yoshikawa, Tomoe; Nakai, Atsushi; Omoto, Shunsuke; Miyata, Takeshi; Yamao, Kentaro; Imai, Hajime; Sakamoto, Hiroki; Kitano, Masayuki; Kudo, Masatoshi

2018-01-01

The most common symptom in patients with advanced pancreatic cancer is abdominal pain. This has traditionally been treated with nonsteroidal anti-inflammatory drugs and opioid analgesics. However, these treatments result in inadequate pain control or drug-related adverse effects in some patients. An alternative pain-relief modality is celiac plexus neurolysis, in which the celiac plexus is chemically ablated. This procedure was performed percutaneously or intraoperatively until 1996, when endoscopic ultrasound (EUS)-guided celiac plexus neurolysis was first described. In this transgastric anterior approach, a neurolytic agent is injected around the celiac trunk under EUS guidance. The procedure gained popularity as a minimally invasive approach and is currently widely used to treat pancreatic cancer-associated pain. We focus on two relatively new techniques of EUS-guided neurolysis: EUS-guided celiac ganglia neurolysis and EUS-guided broad plexus neurolysis, which have been developed to improve efficacy. Although the techniques are safe and effective in general, some serious adverse events including ischemic and infectious complications have been reported as the procedure has gained widespread popularity. We summarize reported clinical outcomes of EUS-guided neurolysis in pancreatic cancer (from the PubMed and Embase databases) with a goal of providing information useful in developing strategies for pancreatic cancer-associated pain alleviation. PMID:29462851

Endoscopic ultrasound-guided pancreaticobiliary intervention in patients with surgically altered anatomy and inaccessible papillae: A review of current literature

Science.gov (United States)

Martin, Aaron; Kistler, Charles Andrew; Wrobel, Piotr; Yang, Juliana F.; Siddiqui, Ali A.

2016-01-01

The management of pancreaticobiliary disease in patients with surgically altered anatomy is a growing problem for gastroenterologists today. Over the years, endoscopic ultrasound (EUS) has emerged as an important diagnostic and therapeutic modality in the treatment of pancreaticobiliary disease. Patient anatomy has become increasingly complex due to advances in surgical resection of pancreaticobiliary disease and EUS has emerged as the therapy of choice when endoscopic retrograde cholangiopancreatography failed cannulation or when the papilla is inaccessible such as in gastric obstruction or duodenal obstruction. The current article gives a comprehensive review of the current literature for EUS-guided intervention of the pancreaticobiliary tract in patients with altered surgical anatomy. PMID:27386471

Fractionated photothermal antitumor therapy with multidye nanoparticles

Directory of Open Access Journals (Sweden)

Gutwein LG

2012-01-01

Full Text Available Luke G Gutwein1, Amit K Singh2, Megan A Hahn2, Michael C Rule3, Jacquelyn A Knapik4, Brij M Moudgil2, Scott C Brown2, Stephen R Grobmyer11Division of Surgical Oncology, Department of Surgery, College of Medicine, 2Particle Engineering Research Center, 3Cell and Tissue Analysis Core, McKnight Brain Institute, 4Department of Pathology, University of Florida, Gainesville, FL, USAPurpose: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs for fractionated photothermal antitumor therapy.Methods: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice.Results: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026 in experimental tumor-bearing mice

Endoscopic Ultrasonography-Guided Techniques for Accessing and Draining the Biliary System and the Pancreatic Duct.

Science.gov (United States)

Rimbaş, Mihai; Larghi, Alberto

2017-10-01

When endoscopic retrograde cholangiopancreatography (ERCP) fails to decompress the biliary system or the pancreatic duct, endoscopic ultrasonography (EUS)-guided biliary or pancreatic access and drainage can be used. Data show a high success rate and acceptable adverse event rate for EUS-guided biliary drainage. The outcomes of EUS-guided biliary drainage seem equivalent to percutaneous drainage and ERCP, whereas only retrospective studies are available for pancreatic duct drainage. In this article, revision of the technical and clinical status and the current evidence of interventional EUS-guided biliary and pancreatic duct access and drainage are presented. Copyright © 2017 Elsevier Inc. All rights reserved.

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results

Science.gov (United States)

Mut-Salud, Nuria; Álvarez, Pablo Juan; Garrido, Jose Manuel; Carrasco, Esther; Aránega, Antonia; Rodríguez-Serrano, Fernando

2016-01-01

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency. PMID:26682013

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results

Directory of Open Access Journals (Sweden)

Nuria Mut-Salud

2016-01-01

Full Text Available The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous or incorporated through the diet and nutritional supplements (exogenous. In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency.

Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy.

Science.gov (United States)

Li, Jian-Wei; Wu, Zhong-Ming; Magetic, Davor; Zhang, Li-Jun; Chen, Zhi-Long

2015-12-01

In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

Safe and successful endoscopic initial treatment and long-term eradication of gastric varices by endoscopic ultrasound-guided Histoacryl (N-butyl-2-cyanoacrylate) injection.

Science.gov (United States)

Gubler, Christoph; Bauerfeind, Peter

2014-09-01

Optimal endoscopic treatment of gastric varices is still not standardized nowadays. Actively bleeding varices may prohibit a successful endoscopic injection therapy of Histoacryl® (N-butyl-2-cyanoacrylate). Since 2006, we have treated gastric varices by standardized endoscopic ultrasound (EUS) guided Histoacryl injection therapy without severe adverse events. We present a large single-center cohort over 7 years with a standardized EUS-guided sclerotherapy of all patients with gastric varices. Application was controlled by fluoroscopy to immediately detect any glue embolization. Only perforating veins located within the gastric wall were treated. In the follow up, we repeated this treatment until varices were eradicated. Utmost patients (36 of 40) were treated during or within 24 h of active bleeding. About 32.5% of patients were treated while visible bleeding. Histoacryl injection was always technically successful and only two patients suffered a minor complication. Acute bleeding was stopped in all patients. About 15% (6 of 40) of patients needed an alternative rescue treatment in the longer course. Three patients got a transjugular portosystemic shunt and another three underwent an orthotopic liver transplantation. Mean long-term survival of 60 months was excellent. Active bleeding of gastric varices can be treated successfully without the necessity of gastric rinsing with EUS-guided injection of Histoacryl.

Real time elastography endoscopic ultrasound (RTE-EUS), a comprehensive review

Energy Technology Data Exchange (ETDEWEB)

Dietrich, C.F., E-mail: christoph.dietrich@ckbm.de [Med. Klinik 2, Caritas-Krankenhaus Bad Mergentheim (Germany); Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova (Romania); Klinik für Innere Medizin, Krankenhaus Märkisch Oderland (Germany); Săftoiu, A.; Jenssen, C. [Med. Klinik 2, Caritas-Krankenhaus Bad Mergentheim (Germany); Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova (Romania); Klinik für Innere Medizin, Krankenhaus Märkisch Oderland (Germany)

2014-03-15

Real-time elastography (RTE) performed during endoscopic ultrasound (EUS) is a relatively new technique which allows the evaluation of tissue stiffness, with the intent of better characterising lesions during EUS examinations. The aim of this comprehensive review was to describe the technique of RTE-EUS, as well as the clinical applications, including the study of pancreatic lesions, but also hepatobiliary, gastrointestinal (GI) tract pathology (including anal canal), lymph nodes, adrenal glands, lung and mediastinum, as well as urogenital applications. One of the advantages of the RTE-EUS technique is especially the possibility to be used in various locations accessible from the GI tract. Future developments are also briefly discussed, as elastography is a tissue characterising technique that will certainly not replace biopsy, but will rather be an adjunct during EUS examinations, due to its ease of use and low cost.

Real time elastography endoscopic ultrasound (RTE-EUS), a comprehensive review

International Nuclear Information System (INIS)

Dietrich, C.F.; Săftoiu, A.; Jenssen, C.

2014-01-01

Real-time elastography (RTE) performed during endoscopic ultrasound (EUS) is a relatively new technique which allows the evaluation of tissue stiffness, with the intent of better characterising lesions during EUS examinations. The aim of this comprehensive review was to describe the technique of RTE-EUS, as well as the clinical applications, including the study of pancreatic lesions, but also hepatobiliary, gastrointestinal (GI) tract pathology (including anal canal), lymph nodes, adrenal glands, lung and mediastinum, as well as urogenital applications. One of the advantages of the RTE-EUS technique is especially the possibility to be used in various locations accessible from the GI tract. Future developments are also briefly discussed, as elastography is a tissue characterising technique that will certainly not replace biopsy, but will rather be an adjunct during EUS examinations, due to its ease of use and low cost

Targeting Gene-Viro-Therapy with AFP driving Apoptin gene shows potent antitumor effect in hepatocarcinoma

Directory of Open Access Journals (Sweden)

Zhang Kang-Jian

2012-02-01

Full Text Available Abstract Background Gene therapy and viral therapy are used for cancer therapy for many years, but the results are less than satisfactory. Our aim was to construct a new recombinant adenovirus which is more efficient to kill hepatocarcinoma cells but more safe to normal cells. Methods By using the Cancer Targeting Gene-Viro-Therapy strategy, Apoptin, a promising cancer therapeutic gene was inserted into the double-regulated oncolytic adenovirus AD55 in which E1A gene was driven by alpha fetoprotein promoter along with a 55 kDa deletion in E1B gene to form AD55-Apoptin. The anti-tumor effects and safety were examined by western blotting, virus yield assay, real time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide assay, Hoechst33342 staining, Fluorescence-activated cell sorting, xenograft tumor model, Immunohistochemical assay, liver function analysis and Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay. Results The recombinant virus AD55-Apoptin has more significant antitumor effect for hepatocelluar carcinoma cell lines (in vitro than that of AD55 and even ONYX-015 but no or little impair on normal cell lines. Furthermore, it also shows an obvious in vivo antitumor effect on the Huh-7 liver carcinoma xenograft in nude mice with bigger beginning tumor volume till about 425 mm3 but has no any damage on the function of liver. The induction of apoptosis is involved in AD55-Apoptin induced antitumor effects. Conclusion The AD55-Apoptin can be a potential anti-hepatoma agent with remarkable antitumor efficacy as well as higher safety in cancer targeting gene-viro-therapy system.

Endoscopic Ultrasound Guided Rendezvous Drainage of Biliary Obstruction Using a New Flexible 19-Gauge Fine Needle Aspiration Needle.

Science.gov (United States)

Tang, Zhouwen; Igbinomwanhia, Efehi; Elhanafi, Sherif; Othman, Mohamed O

2016-01-01

Background and Aim. A successful endoscopic ultrasound guided rendezvous (EUS-RV) biliary drainage is dependent on accurate puncture of the bile duct and precise guide wire manipulation across the ampulla of Vater. We aim to study the feasibility of using a flexible 19-gauge fine aspiration needle in the performance of EUS-RV biliary drainage. Method. This is a retrospective case series of EUS-RV biliary drainage procedures at a single center. Patients who failed ERCP during the same session for benign or malignant biliary obstruction underwent EUS-RV using a flexible, nitinol covered, 19-gauge needle for biliary access and guide wire manipulation. Result. 24 patients underwent EUS-RV biliary drainage via extrahepatic access while 1 attempt was via intrahepatic access. The technical success rate was 80%, including 83.3% of cases via extrahepatic access. There was no significant difference in success rate of inpatient and outpatient procedures, benign or malignant indications, or type of guide wire used. Adverse events included mild pancreatitis (3 patients) and cholangitis (1 patient). Conclusion. A flexible 19-gauge needle for biliary access can be safe and effective when used to perform EUS-RV biliary drainage. Direct comparison between the nitinol needle and conventional metal needles in the performance of EUS guided biliary drainage is needed.

Selected anti-tumor vaccines merit a place in multimodal tumor therapies

Energy Technology Data Exchange (ETDEWEB)

Weiss, Eva-Maria; Wunderlich, Roland [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Ebel, Nina [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Rubner, Yvonne [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Schlücker, Eberhard [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Meyer-Pittroff, Roland [Competence Pool Weihenstephan, Technische Universität München, Freising (Germany); Ott, Oliver J.; Fietkau, Rainer; Gaipl, Udo S.; Frey, Benjamin, E-mail: benjamin.frey@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany)

2012-10-09

Multimodal approaches are nowadays successfully applied in cancer therapy. Primary locally acting therapies such as radiotherapy (RT) and surgery are combined with systemic administration of chemotherapeutics. Nevertheless, the therapy of cancer is still a big challenge in medicine. The treatments often fail to induce long-lasting anti-tumor responses. Tumor recurrences and metastases result. Immunotherapies are therefore ideal adjuncts to standard tumor therapies since they aim to activate the patient's immune system against malignant cells even outside the primary treatment areas (abscopal effects). Especially cancer vaccines may have the potential both to train the immune system against cancer cells and to generate an immunological memory, resulting in long-lasting anti-tumor effects. However, despite promising results in phase I and II studies, most of the concepts finally failed. There are some critical aspects in development and application of cancer vaccines that may decide on their efficiency. The time point and frequency of medication, usage of an adequate immune adjuvant, the vaccine's immunogenic potential, and the tumor burden of the patient are crucial. Whole tumor cell vaccines have advantages compared to peptide-based ones since a variety of tumor antigens (TAs) are present. The master requirements of cell-based, therapeutic tumor vaccines are the complete inactivation of the tumor cells and the increase of their immunogenicity. Since the latter is highly connected with the cell death modality, the inactivation procedure of the tumor cell material may significantly influence the vaccine's efficiency. We therefore also introduce high hydrostatic pressure (HHP) as an innovative inactivation technology for tumor cell-based vaccines and outline that HHP efficiently inactivates tumor cells by enhancing their immunogenicity. Finally studies are presented proving that anti-tumor immune responses can be triggered by combining RT with selected

Preparation of EuSe nanoparticles from Eu(III) complex containing selenides

International Nuclear Information System (INIS)

Adachi, Taka-aki; Tanaka, Atsushi; Hasegawa, Yasuchika; Kawai, Tsuyoshi

2008-01-01

The EuSe nanoparticles were prepared by the thermal reduction of Europium nitrate with new organic selenium compound, tetraphenylphosphonium diphenylphosphinediselenide (PPh 4 )(Se 2 P(C 6 H 5 ) 2 ), for the first time. EuSe nanoparticles were identified by the X-ray diffraction (XRD), the transmission electron microscope (TEM) and the energy dispersive X-ray spectroscopy (EDX) measurements. The average size of the EuSe nanoparticles was found to be 19 nm. The energy gap in EuSe nanoparticles of 19 nm was estimated by edge of absorption band, giving the energy gap of 1.86 eV

Diagnostic accuracy of endoscopic ultrasonography (EUS) for the preoperative locoregional staging of primary gastric cancer.

Science.gov (United States)

Mocellin, Simone; Pasquali, Sandro

2015-02-06

accuracy can be considered clinically useful to guide physicians in the locoregional staging of people with gastric cancer. However, it should be noted that between-study heterogeneity was not negligible: unfortunately, we could not identify any consistent source of the observed heterogeneity. Therefore, all accuracy measures reported in the present work and summarizing the available evidence should be interpreted cautiously. Moreover, we must emphasize that the analysis of positive and negative likelihood values revealed that EUS diagnostic performance cannot be considered optimal either for disease confirmation or for exclusion, especially for the ability of EUS to distinguish T1a (mucosal) versus T1b (submucosal) cancers and positive versus negative lymph node status. By analyzing the data from the largest series ever considered, we found that the diagnostic accuracy of EUS might be considered clinically useful to guide physicians in the locoregional staging of people with gastric carcinoma. However, the heterogeneity of the results warrants special caution, as well as further investigation for the identification of factors influencing the outcome of this diagnostic tool. Moreover, physicians should be warned that EUS performance is lower in diagnosing superficial tumors (T1a versus T1b) and lymph node status (positive versus negative). Overall, we observed large heterogeneity and its source needs to be understood before any definitive conclusion can be drawn about the use of EUS can be proposed in routine clinical settings.

Electron-spin polarization in tunnel junctions with ferromagnetic EuS barriers

International Nuclear Information System (INIS)

Hao, X.; Moodera, J.S.; Meservey, R.

1989-01-01

The authors report here spin-polarized tunneling experiments using non-ferromagnetic electrodes and ferromagnetic EuS barriers. Because of the conduction band in EuS splits into spin-up and spin-down subbands when the temperature is below 16.7 K, the Curie temperature of EuS, the tunnel barrier for electrons with different spin directions is different, therefore giving rise to tunnel current polarization. The spin-filter effect, as it may be called, was observed earlier, directly or indirectly, by several groups: Esaki et al. made a tunneling study on junctions having EuS and EuSe barriers; Thompson et al. studied Schottky barrier tunneling between In and doped EuS; Muller et al. and Kisker et al. performed electron field emission experiments on EuS-coated tungsten tips. The field emission experiments gave a maximum polarization of (89 + 7)% for the emitted electrons. Although the previous tunneling studies did not directly show electron polarization, their results were explained by the same spin- filter effect. This work uses the spin-polarized tunneling technique to show directly that tunnel current is indeed polarized and polarization can be as high as 85%

Impact of endoscopic ultrasonography (EUS) on surgical decision-making in upper gastrointestinal tract cancer

DEFF Research Database (Denmark)

Mortensen, Michael Bau; Edwin, B; Hünerbein, M

2007-01-01

BACKGROUND: Endoscopic ultrasonography (EUS) is an integrated part of the pretherapeutic evaluation program for patients with upper gastrointestinal (GI) tract cancer. Whether the clinical impact of EUS differs between surgeons from different countries is unknown. The same applies to the potential...... clinical influence of EUS misinterpretations. The aim of this study was to evaluate the interobserver agreement on predefined treatment strategies between surgeons from four different countries, with and without EUS, and to evaluate the clinical consequences of EUS misinterpretations. METHODS: One hundred...... patients with upper GI tract cancer were randomly selected from all upper GI tract cancer patients treated at Odense University Hospital between 1997 and 2000. Based on patient records and EUS database results, a case story was created with and without the EUS result for each patient. Four surgeons were...

Smart Mesoporous Nanomaterials for Antitumor Therapy

Directory of Open Access Journals (Sweden)

Marina Martínez-Carmona

2015-11-01

Full Text Available The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc. or external (temperature, light, magnetic field, etc. stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.

Multicenter randomized controlled trial comparing the performance of 22 gauge versus 25 gauge EUS-FNA needles in solid masses

DEFF Research Database (Denmark)

Vilmann, Peter; S?ftoiu, Adrian; Hollerbach, Stephan

2013-01-01

Few randomized studies have assessed the clinical performance of 25-gauge (25G) needles compared with 22-gauge (22G) needles during endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy of intra-abdominal lesions. We aimed to compare the diagnostic yield, as well as performance...

Therapeutic aspects of endoscopic ultrasound

Science.gov (United States)

Woodward, Timothy A.

1999-06-01

Endoscopic ultrasound (EUS) is a technology that had been used primarily as a passive imaging modality. Recent advances have enabled us to move beyond the use of EUS solely as a staging tool to an interventional device. Current studies suggest that interventional applications of EUS will allow for minimally invasive assessment and therapies in a cost-effective manner. Endoscopic ultrasound with fine needle aspiration (EUS-FNA) has been demonstrated to be a technically feasible, relatively safe method of obtaining cytologic specimens. The clinical utility of EUS- FNA appears to be greatest in the diagnosis and staging of pancreatic cancer and in the nodal staging of gastrointestinal and pulmonary malignancies. In addition, EUS-FNA has demonstrated utility in the sampling pleural and ascitic fluid not generally appreciated or assessable to standard interventions. Interventional applications of EUS include EUS-guided pseudocyst drainage, EUS-guided injection of botulinum toxin in the treatment of achalasia, and EUS- guided celiac plexus neurolysis in the treatment of pancreatic cancer pain. Finally, EUS-guided fine-needle installation is being evaluated, in conjunction with recent bimolecular treatment modalities, as a delivery system in the treatment of certain gastrointestinal tumors.

Value of computed tomography for evaluating the injection site in endosonography-guided celiac plexus neurolysis

International Nuclear Information System (INIS)

Sakamoto, Hiroki; Kitano, Masayuki; Nishio, Takeshi; Takeyama, Yoshifumi; Yasuda, Chikao; Kudo, Masatoshi

2006-01-01

Endosonography-guided celiac plexus neurolysis (EUS-CPN) safely and effectively relieves pain associated with intra-abdominal malignancies when the neurolytic is accurately injected. We applied contrast medium to evaluate the ethanol injection sites in patients who received EUS-CPN due to abdominal pain caused by malignancies. We injected, under the guidance of endoscopic ultrasonography (EUS), ethanol containing 10% contrast medium into the celiac plexus of patients with intra-abdominal pain due to malignancies. Immediately after the endoscopic therapy, patients underwent computed tomography (CT) to confirm the injection site. Images of distribution of injected solutions were classified into three groups. Injected solution dispersed in unilateral and bilateral anterocrural space was defined as ''unilateral injection'' or bilateral injection'', respectively. Injected solution located out of the anterocrural space was defined as ''inappropriate injection''. Pre- and postprocedure pain was assessed using a standard analog scale. Before and 2, 4, 8, 12, and 16 weeks after the procedure, pain scores were evaluated. From April 2003 to May 2005, 13 patients were enrolled in this study. Improvement of pain score in the ''bilateral injection'' and ''unilateral injection'' groups was significantly superior to the change in the ''inappropriate injection'' group. Although EUS-CPN was effective in eight of 13 patients (61.5%), additional EUS-CPN to the ''inappropriate injection group'' increased the response rate to 84.6%. Injection of ethanol to the anterocrural space by EUS-CPN produced adequate pain relief. Immediate examination by CT for confirmation of injection sites after EUS-CPN would increase the likelihood of induction of pain relief. (author)

Anti-tumor effects of Egr-IFN gamma gene therapy combined with {sup 125}I-UdR radionuclide therapy

Energy Technology Data Exchange (ETDEWEB)

Jingguo, Zhao [No.403 Hospital of PLA, Dalian (China); Yanjun, Ni; Xiangfu, Song; Yanyi, Li; Wei, Yang; Ting, Sun; Qingjie, Ma; Fengtong, Gao

2008-12-15

Objective: To explore the anti-tumor effects of Egr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNgamma mixed with liposome was injected into tumor. 48 h later, 370 kBq {sup 125}I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNgamma in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNgamma + {sup 125}I-UdR group were obviously lower than those of control group, {sup 125}I-UdR group and pcDNAEgr-1 + {sup 125}I-UdR group 6-15 d after gene-radionuclide therapy. IFNgamma protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNgamma + {sup 125}I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNgamma + {sup 125}I-UdR group was significantly higher than that in the other groups (P<0.01). Conclusions: The anti-tumor effects in vivo of pcDNAEgr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy are better than those of {sup 125}I-UdR therapy. (authors)

EUS for the staging of gastric cancer: a meta-analysis.

Science.gov (United States)

Mocellin, Simone; Marchet, Alberto; Nitti, Donato

2011-06-01

The role of EUS in the locoregional staging of gastric carcinoma is undefined. We aimed to comprehensively review and quantitatively summarize the available evidence on the staging performance of EUS. We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE databases for relevant studies published until July 2010. Formal meta-analysis of diagnostic accuracy parameters was performed by using a bivariate random-effects model. Fifty-four studies enrolling 5601 patients with gastric cancer undergoing disease staging with EUS were eligible for the meta-analysis. EUS staging accuracy across eligible studies was measured by computing overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). EUS can differentiate T1-2 from T3-4 gastric cancer with high accuracy, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.86 (95% CI, 0.81-0.90), 0.91 (95% CI, 0.89-0.93), 9.8 (95% CI, 7.5-12.8), 0.15 (95% CI, 0.11-0.21), and 65 (95% CI, 41-105), respectively. In contrast, the diagnostic performance of EUS for lymph node status is less reliable, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.69 (95% CI, 0.63-0.74), 0.84 (95% CI, 0.81-0.88), 4.4 (95% CI, 3.6-5.4), 0.37 (95% CI, 0.32-0.44), and 12 (95% CI, 9-16), respectively. Results regarding single T categories (including T1 substages) and Bayesian nomograms to calculate posttest probabilities for any target condition prevalence are also provided. Statistical heterogeneity was generally high; unfortunately, subgroup analysis did not identify a consistent source of the heterogeneity. Our results support the use of EUS for the locoregional staging of gastric cancer, which can affect the therapeutic management of these patients. However, clinicians must be aware of the performance limits of this staging tool. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Endoscopic ultrasonography-guided pancreatic duct access: techniques and literature review of pancreatography, transmural drainage and rendezvous techniques.

Science.gov (United States)

Itoi, Takao; Kasuya, Kazuhiko; Sofuni, Atsushi; Itokawa, Fumihide; Kurihara, Toshio; Yasuda, Ichiro; Nakai, Yousuke; Isayama, Hiroyuki; Moriyasu, Fuminori

2013-05-01

Endoscopic ultrasonography-guided (EUS)-guided pancreatic interventions have gained increasing attention. Here we review EUS-guided pancreatic duct (PD) access techniques and outcomes. EUS-guided PD intervention is divided into two types, antegrade and rendezvous techniques, following EUS-guided pancreatography. In the antegrade technique, pancreaticoenterostomy is carried out by stent placement between the PD and the stomach, duodenum, or jejunum. Transenteric antegrade PD stenting is conducted by stent placement, advancing anteriorly into the PD through the pancreatic tract. The rendezvous technique is carried out by using a guidewire through the papilla or anastomotic site for retrograde stent insertion. In terms of EUS-guided PD stenting, 11 case reports totaling 75 patients (35 normal anatomy, 40 altered anatomy) have been published. The technical success rate was greater than 70%. Early adverse events, including severe hematoma and severe pancreatitis,occurred in seven (63.6%) of 11 reports. Regarding the rendezvous technique, 12 case reports totaling 52 patients (22 normal anatomy, 30 altered anatomy) have been published. The technical success rate ranged from 25% to 100%. It was 48% in one report that involved more than 20 cases. Once stents were placed, all patients became free of symptoms. Early mild adverse events occurred in four (36.4%) of 11 reports. In conclusion, although it can be risky because of possible serious or even fatal adverse events, including pancreatic juice leakage, perforation and severe acute pancreatitis, EUS-PD access seems to be promising for treating symptomatic pancreatic diseases caused by PD stricture and pancreaticoenterostomy stricture. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

Endoscopic ultrasound-guided pancreatic fluid collections' transmural drainage outcomes in 100 consecutive cases of pseudocysts and walled off necrosis: a single-centre experience from the United Kingdom.

Science.gov (United States)

Shekhar, Chander; Maher, Ben; Forde, Colm; Mahon, Brinder Singh

2017-11-09

Endoscopic ultrasound-guided drainage is a minimally invasive first-line modality for the drainage of pancreatic fluid collection (PFC) resulting in a shorter hospital stay and less morbidity compared with surgical cystogastrostomy. Our aim is to evaluate potential differences in the outcomes of endoscopic ultrasound (EUS) guided transmural drainage (EUS-TD) drainage of pancreatic pseudocyst (PP) and walled-off necrosis (WON). We retrospectively reviewed 100 consecutive EUS-guided drainages of PFC utilising EUS reports; clinical notes and imaging with follow-up (FU) to 12 months. All procedures were undertaken under conscious sedation with EUS guidance alone (without fluoroscopy) and placement of plastic double pigtail stents. In these 100 sequential cases, there were 78 cases of PP and 22 cases of WON. All 22/22(100%) cases of WON had successful EUS-guided stent placement. In 2/22(9%), there was little or no clinical improvement. These two patients required further computed tomography (CT)-guided drainage and one of these patients (1/22) (4.5%) developed recurrence within 12 months FU after removal of stents. In case of PP, overall stent placement was successful in 76/78 (97%) patients, but 6/78(8%) required 2nd EUS procedure after failure to show clinical improvement; 3/78(2.5%) required further CT-guided drainage. The overall complication rate was 9%(9/100) with 4%(4/100) requiring endoscopic or CT-guided intervention with no overall 30-day mortality. This is the largest series from a single UK centre demonstrating that EUS-guided cystogastrostomy of PFC drainage using plastic double pigtail stents is sufficient in majority of cases with PFC including that of WON, with or without infection.

Endoscopic Ultrasound-Guided Fine Needle Aspiration versus Percutaneous Ultrasound-Guided Fine Needle Aspiration in Diagnosis of Focal Pancreatic Masses.

Science.gov (United States)

Okasha, Hussein Hassan; Naga, Mazen Ibrahim; Esmat, Serag; Naguib, Mohamed; Hassanein, Mohamed; Hassani, Mohamed; El-Kassas, Mohamed; Mahdy, Reem Ezzat; El-Gemeie, Emad; Farag, Ali Hassan; Foda, Ayman Mohamed

2013-10-01

Pancreatic carcinoma is one of the leading cancer morbidity and mortality world-wide. Controversy has arisen about whether the percutaneous approach with computed tomography/ultrasonography-guidance fine needle aspiration (US-FNA) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the preferred method to obtain diagnostic tissue. Our purpose of this study is to compare between the diagnostic accuracy of EUS-FNA and percutaneous US-FNA in diagnosis of pancreatic cancer. A total of 197 patients with pancreatic masses were included in the study, 125 patients underwent US-FNA (Group 1) and 72 patients underwent EUS-FNA (Group 2). EUS-FNA has nearly the same accuracy (88.9%) as US-FNA (87.2%) in diagnosis of pancreatic cancer. The sensitivity, specificity, positive predictive value and negative predictive value for EUS-FNA was 84%, 100%, 100%, 73.3% respectively. It was 85.5%, 90.4%, 94.7%, 76% respectively for US-FNA. EUS-FNA had a lower complication rate (1.38%) than US-FNA (5.6%). EUS-FNA has nearly the same accuracy as US-FNA of pancreatic masses with a lower complication rate.

The endoscopic ultrasonography-guided rendezvous technique for biliary cannulation: a technical review.

Science.gov (United States)

Isayama, Hiroyuki; Nakai, Yousuke; Kawakubo, Kazumichi; Kawakami, Hiroshi; Itoi, Takao; Yamamoto, Natsuyo; Kogure, Hirofumi; Koike, Kazuhiko

2013-04-01

Steady progress is being made in endoscopic biliary intervention, especially endoscopic ultrasonography (EUS)-guided procedures. The EUS-guided rendezvous technique (EUS-RV) is a salvage method for failed selective biliary cannulation. The overall success rate of EUS-RV in 247 cases from seven published articles was 74 % and the incidence of complications was 11 %. The main cause of failed rendezvous cannulation was difficulty passing a biliary stricture or papilla due to poor guidewire (GW) manipulation. A recent large study found a 98.3 % success rate and superiority to precutting. This report suggested using a hydrophilic guidewire. Major complications were bleeding (0.8 %), bile leakage (1.2 %), peritonitis (0.4 %), pneumoperitoneum (0.2 %), and pancreatitis (1.6 %). The approach routes for EUS-RV were transgastric, transduodenal short position, and transduodenal long position. The appropriate route for each patient should be used. GW selection for EUS-RV is critical, and a hydrophilic GW might be the most useful. The catheter can be inserted through the papilla alongside or over the wire. Alongside cannulation is convenient, but difficult. The problem with the over-the-wire technique is withdrawal of the GW in the accessory channel. EUS-RV is effective and safe, but is not established. The efficacy should be confirmed in a prospective comparative trial, and the necessary specialist equipment should be developed.

Endoscopic ultrasound-guided coil or glue injection in post-cyanoacrylate gastric variceal re-bleed.

Science.gov (United States)

Mukkada, Roy J; Antony, Rajesh; Chooracken, Mathew J; Francis, Jose V; Chettupuzha, Antony P; Mathew, Pradeep G; Augustine, Philip; Koshy, Abraham

2018-04-09

N-butyl-cyanoacrylate injection is recommended in bleeding/recently bled gastric varices. However, cyanoacrylate injection is associated with re-bleed in 25% to 50% of patients. Endoscopic ultrasound (EUS)-guided coil application is an emerging treatment modality for bleeding gastric varices. The aim of this study was to compare EUS-guided coil application combined with or without cyanoacrylate glue injection to injection alone in post-glue gastric variceal re-bleed. A retrospective analysis of a prospectively maintained database was performed. Thirty patients who re-bled after cyanoacrylate injection and who had EUS-guided coil application to gastric varices were included. The comparison was done with data of 51 patients who had only repeat cyanoacrylate injection. Both groups had a follow up for 12 months. EUS-guided coil application was done under endosonographic guidance. A single coil was placed in 7, two coils in each of 13 patients, three in 5, four in 3, five in one, and 6 coils in one patient. In addition, cyanoacrylate glue injection was given in 15 patients. Eight patients had repeat EUS-guided coil application 1 month later. Re-bleed and mortality were assessed. Coilng: Six out of 30 (20%) patients re-bled during follow up of 9 to 365 days. Three out of 30 (10%) died. One patient died 9 days after the procedure due to acute respiratory distress syndrome, one died 4 months after the procedure due to a re-bleed and one 5 months after the procedure due to spontaneous bacterial peritonitis. Glue only: 26/51 (51%) re-bled during follow up of 45 to 365 days. EUS-guided coil application resulted in significantly less re-bleed than glue-only (Kaplan-Meir survival analysis with log-rank test, z = 5.4, p guided coil application with/without cyanoacrylate injection for the obliteration of gastric varices is effective for post-cyanoacrylate gastric variceal re-bleed.

Observation of unusual critical region behavior in the magnetic susceptibility of EuSe

Science.gov (United States)

Bykovetz, N.; Klein, J.; Lin, C. L.

2018-05-01

The Europium Chalcogenides (EuCh: EuO, EuS, EuSe, and EuTe) have been regarded as model examples of simple, cubic, Heisenberg exchange coupled magnetic systems, with a ferromagnetic nearest-neighbor exchange constant J1 and an antiferromagnetic next-nearest-neighbor constant J2. Unlike the other EuCh, EuSe exhibits a range of complex magnetic behaviors, the latter being attributed to EuSe being near the point where J2=-J1, where its magnetism appears to consist of nearly de-coupled 2D ferromagnetic sheets. Analysis of precision SQUID measurements of the magnetic susceptibility χ in EuSe showed that in the region from ˜Tc to ˜2Tc, a fit of the data to the critical equation χ = χ2Tc(T/Tc-1)-γ gives γ=2.0, an exponent not predicted by any current theory. Additionally, this fit predicts that Tc should be ˜0K. We tentatively interpret this by saying that in the paramagnetic region the system "thinks" EuSe should not order above T=0. Tc=0K is predicted by the Mermin-Wagner theorem (MW) for Heisenberg-coupled 2D magnetic systems, and we can show that when J2=-J1, MW can also be applied to the J1, J2 exchange model of the EuCh to give a rigorous Tc=0 prediction. Under 10 kbar applied pressure EuSe exhibits a different γ and fitted Tc. An additional, and rather strange, critical-region effect was discovered. The EuSe sample was found to exhibit a relaxation effect in a small range of temperatures, just above and just below the actual Tc of 4.7K, with time constants of up to 5 minutes. We cannot yet fully explain this observed macroscopic effect.

Endosonography guided management of pancreatic fluid collections

DEFF Research Database (Denmark)

Vilmann, Andreas S; Menachery, John; Tang, Shou-Jiang

2015-01-01

complications of pancreatitis can include acute peri-pancreatic fluid collection, acute necrotic collection, pseudocyst formation, and walled-off necrosis. Interventional endoscopic ultrasound (EUS) has been increasing utilized in managing these local complications. After performing a PubMed search, the authors...... manually applied pre-defined inclusion criteria or a filter to identify publications relevant to EUS and pancreatic collections (PFCs). The authors then reviewed the utility, efficacy, and risks associated with using therapeutic EUS and involved EUS devices in treating PFCs. Due to the development...... to diagnose PFCs and perform image-guided interventions. After draining a PFC, the amount of tissue necrosis is the most important predictor of a successful outcome. Hence, it seems logical to classify these collections based on their percentage of necrotic component or debris present when viewed by imaging...

Regorafenib: Antitumor Activity upon Mono and Combination Therapy in Preclinical Pediatric Malignancy Models.

Science.gov (United States)

Daudigeos-Dubus, Estelle; Le Dret, Ludivine; Lanvers-Kaminsky, Claudia; Bawa, Olivia; Opolon, Paule; Vievard, Albane; Villa, Irène; Pagès, Mélanie; Bosq, Jacques; Vassal, Gilles; Zopf, Dieter; Geoerger, Birgit

2015-01-01

The multikinase inhibitor regorafenib (BAY 73-4506) exerts both anti-angiogenic and anti-tumorigenic activity in adult solid malignancies mainly advanced colorectal cancer and gastrointestinal stromal tumors. We intended to explore preclinically the potential of regorafenib against solid pediatric malignancies alone and in combination with anticancer agents to guide the pediatric development plan. In vitro effects on cell proliferation were screened against 33 solid tumor cell lines of the Innovative Therapies for Children with Cancer (ITCC) panel covering five pediatric solid malignancies. Regorafenib inhibited cell proliferation with a mean half maximal growth inhibition of 12.5 μmol/L (range 0.7 μmol/L to 28 μmol/L). In vivo, regorafenib was evaluated alone at 10 or 30 mg/kg/d or in combination with radiation, irinotecan or the mitogen-activated protein kinase kinase (MEK) inhibitor refametinib against various tumor types, including patient-derived brain tumor models with an amplified platelet-derived growth factor receptor A (PDGFRA) gene. Regorafenib alone significantly inhibited tumor growth in all xenografts derived from nervous system and connective tissue tumors. Enhanced effects were observed when regorafenib was combined with irradiation and irinotecan against PDGFRA amplified IGRG93 glioma and IGRM57 medulloblastoma respectively, resulting in 100% tumor regressions. Antitumor activity was associated with decreased tumor vascularization, inhibition of PDGFR signaling, and induction of apoptotic cell death. Our work demonstrates that regorafenib exhibits significant antitumor activity in a wide spectrum of preclinical pediatric models through inhibition of angiogenesis and induction of apoptosis. Furthermore, radio- and chemosensitizing effects were observed with DNA damaging agents in PDGFR amplified tumors.

Accuracy and Quality Assessment of EUS-FNA: A Single-Center Large Cohort of Biopsies

Directory of Open Access Journals (Sweden)

Benjamin Ephraim Bluen

2012-01-01

Full Text Available Introduction. Thorough quality control (QC study with systemic monitoring and evaluation is crucial to optimizing the effectiveness of EUS-FNA. Methods. Retrospective analysis was composed of investigating consecutive patient files that underwent EUS-FNA. QC specifically focused on diagnostic accuracy, impacts on preexisting diagnoses, and case management. Results. 268 patient files were evaluated. EUS-FNA cytology helped establish accurate diagnoses in 92.54% (248/268 of patients. Sensitivity, specificity, PPV, NPV, and accuracy were 83%, 100%, 100%, 91.6%, and 94%, respectively. The most common biopsy site was the pancreas (68%. The most accurate location for EUS-FNA was the esophagus, 13/13 (100%, followed by the pancreas (89.6%. EUS-FNA was least informative for abdominal lymph nodes (70.5%. After FNA and followup, eight false negatives for tumors were found (3%, while 7.5% of samples still lacked a definitive diagnosis. Discussion. QC suggests that the diagnostic accuracy of EUS-FNA might be improved further by (1 taking more FNA passes from suspected lesions, (2 optimizing needle selection (3 having an experienced echo-endoscopist available during the learning curve, and (4 having a cytologist present during the procedure. QC also identified remediable reporting errors. In conclusion, QC study is valuable in identifying weaknesses and thereby augmenting the effectiveness of EUS-FNA.

The Utility of Endoscopic Ultrasound Guided Fine Needle Aspiration in the Diagnosis of Infectious Diseases—Report of Three Cases

Directory of Open Access Journals (Sweden)

Mauro Ajaj Saieg

2013-01-01

Full Text Available Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA is a fast and minimally invasive methodology with a crucial impact on patients’ management. It has an important and established role in the diagnosis and staging of mediastinal and abdominal malignancies, but little is discussed in the literature on the usefulness of this technique in the diagnosis of infectious diseases. In the current report, we present three different cases where EUS was essential for reaching the diagnosis of tuberculosis and paracoccidiodomicosis in cases otherwise seen as malignant. In conclusion, EUS was successful not only in obtaining enough cells for morphological analysis, but also for the production of cell blocks and assessment of the presence of the microorganisms by special stains. EUS allied to fine needle biopsy was an important tool in determining diagnoses of enlarged lymph nodes, revealing the diagnosis of infectious diseases in cases otherwise seen as malignant. The wide use of this methodology in cases such as those reported here cannot only rule out malignancy, but also aid critically ill patients by installing early proper therapy without the need for aggressive interventions.

Therapy of Pancreatic Neuroendocrine Tumors: Fine Needle Intervention including Ethanol and Radiofrequency Ablation

Directory of Open Access Journals (Sweden)

Sundeep Lakhtakia

2017-11-01

Full Text Available Pancreatic neuroendocrine tumors (PNETs are increasingly being detected, though usually as incidental findings. Majority of the PNETs are non-functional and surgical resection is the standard of care for most of them. However, in patients with small PNETs localized within the pancreas, who are unfit or unwilling for surgery, alternate methods of treatment are needed. Direct methods of ablation of PNETs, using either ethanol injection or radiofrequency ablation (RFA, are emerging as effective methods. The limited literature available as case reports or case series on endoscopic ultrasound (EUS-guided local ablation using either ethanol or RFA has demonstrated safety and efficacy along with short- to medium-term sustained relief. Long-term benefits with these local ablative therapies are awaited. Comparative studies are needed to show which of these two competing technologies is superior. Finally, comparative trials of EUS-guided ablation with surgical resection in terms of efficacy and safety will ensure their place in the management algorithm.

Normal anatomy of the anal wall and perianal spaces: An EUS, MRI and cadaveric correlative study

International Nuclear Information System (INIS)

Chung, Soo Young; Ryu, Sie Tae; Park, Ki Soon; Lee, Yul; Bae, Sang Hoon; Kang, Heung Sik

1994-01-01

To understand the normal endosonographic anatomy of the perianal spaces, and to evaluate the diagnostic efficacy and limitation of endorectal sonography(EUS), correlative study with MRI, cadaveric sectional image and cadaveric MRI were performed. EUS images of the normal 6 perianal spaces (pelvirectal, ischiorectal, intersphincteric, subcutaneous, central, submucous space) which were bounded by internal and external anal sphincters, rectal wall and levator ani muscle were correlated with MRI in 10 normal persons, cadaveric sectional images and cadaveric MRI in 2 cadavers. Pelvirectal space located superior to levator ani muscle could be demonstrable only on anterior wall scan but could not be visualized on lateral or posterior wall scan on EUS. Five perianal spaces located inferior to levator ani muscle were well seen on anterior, lateral, and posterior wall EUS. MRI was superior to EUS in the evaluation of pelvirectal and ischiorectal spaces but equal or inferior to EUS in the evaluation of intersphincteric, subcutaneous, central and submucous spaces. EUS was valuable in the evaluation of perianal spaces inferior to levator ani muscle but was limited in the evaluation of perianal spaces superior to levator ani muscle

Regorafenib: Antitumor Activity upon Mono and Combination Therapy in Preclinical Pediatric Malignancy Models.

Directory of Open Access Journals (Sweden)

Estelle Daudigeos-Dubus

Full Text Available The multikinase inhibitor regorafenib (BAY 73-4506 exerts both anti-angiogenic and anti-tumorigenic activity in adult solid malignancies mainly advanced colorectal cancer and gastrointestinal stromal tumors. We intended to explore preclinically the potential of regorafenib against solid pediatric malignancies alone and in combination with anticancer agents to guide the pediatric development plan. In vitro effects on cell proliferation were screened against 33 solid tumor cell lines of the Innovative Therapies for Children with Cancer (ITCC panel covering five pediatric solid malignancies. Regorafenib inhibited cell proliferation with a mean half maximal growth inhibition of 12.5 μmol/L (range 0.7 μmol/L to 28 μmol/L. In vivo, regorafenib was evaluated alone at 10 or 30 mg/kg/d or in combination with radiation, irinotecan or the mitogen-activated protein kinase kinase (MEK inhibitor refametinib against various tumor types, including patient-derived brain tumor models with an amplified platelet-derived growth factor receptor A (PDGFRA gene. Regorafenib alone significantly inhibited tumor growth in all xenografts derived from nervous system and connective tissue tumors. Enhanced effects were observed when regorafenib was combined with irradiation and irinotecan against PDGFRA amplified IGRG93 glioma and IGRM57 medulloblastoma respectively, resulting in 100% tumor regressions. Antitumor activity was associated with decreased tumor vascularization, inhibition of PDGFR signaling, and induction of apoptotic cell death. Our work demonstrates that regorafenib exhibits significant antitumor activity in a wide spectrum of preclinical pediatric models through inhibition of angiogenesis and induction of apoptosis. Furthermore, radio- and chemosensitizing effects were observed with DNA damaging agents in PDGFR amplified tumors.

[Endoscopic ultrasound guided rendezvous for biliary drainage].

Science.gov (United States)

Knudsen, Marie Høxbro; Vilmann, Peter; Hassan, Hazem; Karstensen, John Gésdal

2015-04-27

Endoscopic retrograde cholangiography (ERCP) is currently standard treatment for biliary drainage. Endoscopic ultrasound guided rendezvous (EUS-RV) is a novel method to overcome an unsuccessful biliary drainage procedure. Under endoscopic ultrasound guidance a guidewire is passed via a needle from the stomach or duodenum to the common bile duct and from there on to the duodenum enabling ERCP. With a relatively high rate of success EUS-RV should be considered as an alternative to biliary drainage and surgical intervention.

Spin fluctuations in EuS

International Nuclear Information System (INIS)

Hartmann, A.

1996-02-01

Demagnetization effects break the isotropy of spin waves. During spring 1995, Peter Boeni et al. performed polarized neutron measurements on EuS using the triple axis spectrometer IN14 at the ILL in Grenoble, in order to investigate the influence of dipolar interactions on the spin waves. In the following work the analysis of the experimental data is described. (author) 25 figs., 2 tabs., 9 refs

Search for Spin Filtering By Electron Tunneling Through Ferromagnetic EuS Barriers in Pbs

Science.gov (United States)

Figielski, T.; Morawski, A.; Wosinski, T.; Wrotek, S.; Makosa, A.; Lusakowska, E.; Story, T.; Sipatov, A. Yu.; Szczerbakow, A.; Grasza, K.;

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

NARCIS (Netherlands)

Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

2010-01-01

OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

[Diagnostic utility of endoscopic ultrasonography elastography and contrast-enhanced harmonic endoscopic ultrasonography in a patient with type 2 autoimmune pancreatitis].

Science.gov (United States)

Yokode, Masataka; Shiomi, Hideyuki; Itai, Ryosuke; Mikami, Sakae; Yamashita, Yukimasa; Nakano, Ryota; Ezaki, Takeshi; Masuda, Atsuhiro; Zen, Yoh

2018-01-01

A referring hospital diagnosed a 57-year-old man with a pancreatic head mass. The initial endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) was inconclusive because of the small sample size. Endoscopic ultrasonography elastography (EUS-EG) and contrast-enhanced harmonic endoscopic ultrasonography (CE-EUS), conducted at our institute, raised the possibility of mass-forming pancreatitis or autoimmune pancreatitis (AIP). A repeat EUS-FNA revealed inflammatory changes, including a neutrophilic duct injury suggestive of type 2 AIP. The pancreatic lesion responded well to the steroid therapy. The present case suggests that EUS-EG and CE-EUS may be useful for diagnostic exclusion of pancreatic cancers, and the combined use of EUS-EG and CE-EUS, with EUS-FNA, may help characterize inflammatory pancreatic lesions.

Endoscopic Ultrasound-guided Drainage of Pancreatic Pseudocysts

DEFF Research Database (Denmark)

Ng, Pui Yung; Nytoft Rasmussen, Ditlev; Vilmann, Peter

2013-01-01

or by telephonic interview. RESULTS: A total of 61 procedures were performed. The symptoms that indicated drainage were abdominal pain (n = 43), vomiting (n = 7) and jaundice (n = 5). The procedure was technically successful in 57 of the 61 procedures (93%). The immediate complication rate was 5%. At a mean follow......-up of 45 weeks, the treatment success was 75%. The medium term complications appeared in 25% of cases, which included three cases each of stent clogging, stent migration, infection and six cases of recurrence. There was no mortality. CONCLUSION: EUS-guided drainage is an effective treatment for PPC...... with a successful outcome in most of patients. Most of the complications require minimal invasive surgical treatment or repeated EUS-guided drainage procedures....

Geometric programming facilities of EusLisp and assembly goal planner

International Nuclear Information System (INIS)

Matsui, Toshihiro; Sakane, Shigeyuki; Hirukawa, Hirohisa

1994-01-01

For robots in power plants to accomplish intelligent tasks such as maintenance, inspection, and assembly, the robots must have planning capabilities based on shape models of the environment. Such shape models are defined and manipulated by a program called a geometric modeler or a solid modeler. Although there are commercial solid modelers in the market, they are not always suitable for robotics research, since it is hard to integrate higher level planning functions which frequently access internal model representation. In order to accelerate advanced robotics research, we need a generic, extensible, efficient, and integration-oriented geometric modeler. After reviewing available modelers, we concluded that the object-oriented Lisp can be the best implementation language for solid modeling. The next section introduces the programming language, 'EusLisp', tuned for implementing a solid modeler for intelligent robot programming. The design philosophy and the structure and functions of EusLisp are stated. In the following sections, EusLisp's applications, i.e., viewpoint and light-source location planning, derivation of motion constraint, and assembly goal planning, are discussed. (J.P.N.)

Advances in the Management of Upper Gastrointestinal Subepithelial Tumor: Pathologic Diagnosis Using Endoscopy without Endoscopic Ultrasound-Guided Biopsy

Directory of Open Access Journals (Sweden)

Hang Lak Lee

2016-05-01

Full Text Available Until now, biopsy methods for subepithelial tumors (SETs have focused on endoscopic ultrasound (EUS-guided biopsy; however, these methods have several limitations. We devised a simple method for pathologic diagnosis of SETs. SETs are occasionally diagnosed during endoscopy, and lesions are generally small and asymptomatic. It can be challenging to decide on a management plan for large asymptomatic SETs. EUS imaging provides information regarding the size, layer, and echo pattern of the lesions. Patient management plans have traditionally been determined based on EUS images, whereby the endoscopist chooses to either monitor or remove the tumor. However, EUS alone cannot diagnose and evaluate upper gastrointestinal SETs with high accuracy. As sufficient tissue samples are required for the accurate diagnosis of SETs, EUS-guided biopsy techniques such as EUS fine-needle aspiration and trucut biopsy are currently used. However, these methods have a relatively low diagnostic accuracy and do not always provide information upon immunohistochemical staining. Endoscopists can easily detect a submucosal mass after creating an iatrogenic mucosal ulcer, after which tissue sampling is performed by using endoscopic biopsy. Furthermore, pathologic results can differentiate between benign and premalignant lesions. Here, we introduce a simple method for the pathologic diagnosis of SETs.

A novel lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections

DEFF Research Database (Denmark)

Walter, Daisy; Will, Uwe; Sanchez-Yague, Andres

2015-01-01

BACKGROUND AND STUDY AIMS: A novel large-diameter, lumen-apposing, self-expanding metal stent with bilateral flanges was recently developed for endoscopic ultrasound (EUS)-guided transmural drainage of symptomatic pancreatic fluid collections (PFCs). The aim of this study was to evaluate the effi......BACKGROUND AND STUDY AIMS: A novel large-diameter, lumen-apposing, self-expanding metal stent with bilateral flanges was recently developed for endoscopic ultrasound (EUS)-guided transmural drainage of symptomatic pancreatic fluid collections (PFCs). The aim of this study was to evaluate...

Determination of optimal ultrasound planes for the initialisation of image registration during endoscopic ultrasound-guided procedures.

Science.gov (United States)

Bonmati, Ester; Hu, Yipeng; Gibson, Eli; Uribarri, Laura; Keane, Geri; Gurusami, Kurinchi; Davidson, Brian; Pereira, Stephen P; Clarkson, Matthew J; Barratt, Dean C

2018-06-01

Navigation of endoscopic ultrasound (EUS)-guided procedures of the upper gastrointestinal (GI) system can be technically challenging due to the small fields-of-view of ultrasound and optical devices, as well as the anatomical variability and limited number of orienting landmarks during navigation. Co-registration of an EUS device and a pre-procedure 3D image can enhance the ability to navigate. However, the fidelity of this contextual information depends on the accuracy of registration. The purpose of this study was to develop and test the feasibility of a simulation-based planning method for pre-selecting patient-specific EUS-visible anatomical landmark locations to maximise the accuracy and robustness of a feature-based multimodality registration method. A registration approach was adopted in which landmarks are registered to anatomical structures segmented from the pre-procedure volume. The predicted target registration errors (TREs) of EUS-CT registration were estimated using simulated visible anatomical landmarks and a Monte Carlo simulation of landmark localisation error. The optimal planes were selected based on the 90th percentile of TREs, which provide a robust and more accurate EUS-CT registration initialisation. The method was evaluated by comparing the accuracy and robustness of registrations initialised using optimised planes versus non-optimised planes using manually segmented CT images and simulated ([Formula: see text]) or retrospective clinical ([Formula: see text]) EUS landmarks. The results show a lower 90th percentile TRE when registration is initialised using the optimised planes compared with a non-optimised initialisation approach (p value [Formula: see text]). The proposed simulation-based method to find optimised EUS planes and landmarks for EUS-guided procedures may have the potential to improve registration accuracy. Further work will investigate applying the technique in a clinical setting.

Endoscopic ultrasound-guided transmural drainage of postoperative pancreatic collections.

Science.gov (United States)

Tilara, Amy; Gerdes, Hans; Allen, Peter; Jarnagin, William; Kingham, Peter; Fong, Yuman; DeMatteo, Ronald; D'Angelica, Michael; Schattner, Mark

2014-01-01

Pancreatic leak is a major cause of morbidity after pancreatectomy. Traditionally, peripancreatic fluid collections have been managed by percutaneous or operative drainage. Data for endoscopic ultrasound (EUS)-guided drainage of postoperative fluid collections are limited. Here we report on the safety, efficacy, and timing of EUS-guided drainage of postoperative peripancreatic collections. This is a retrospective review of 31 patients who underwent EUS-guided drainage of fluid collections after pancreatic resection. Technical success was defined as successful transgastric deployment of at least one double pigtail plastic stent. Clinical success was defined as resolution of the fluid collection on follow-up CT scan and resolution of symptoms. Early drainage was defined as initial transmural stent placement within 30 days after surgery. Endoscopic ultrasound-guided drainage was performed effectively with a technical success rate of 100%. Clinical success was achieved in 29 of 31 patients (93%). Nineteen of the 29 patients (65%) had complete resolution of their symptoms and collection with the first endoscopic procedure. Repeat drainage procedures, including some with necrosectomy, were required in the remaining 10 patients, with eventual resolution of collection and symptoms. Two patients who did not achieve durable clinical success required percutaneous drainage by interventional radiology. Seventeen (55%) of 31 patients had successful early drainage completed within 30 days of their operation. Endoscopic ultrasound-guided drainage of fluid collections after pancreatic resection is safe and effective. Early drainage (collections was not associated with increased complications in this series. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Nonfluoroscopic endoscopic ultrasound-guided transmural drainage of pancreatic pseudocysts at atypical locations

Directory of Open Access Journals (Sweden)

Surinder Singh Rana

2016-01-01

Full Text Available Background: Pancreatic pseudocysts (PP at atypical locations are a therapeutic challenge and are usually managed surgically. Objective: We evaluated safety and efficacy of nonfluoroscopic endoscopic ultrasound (NF-EUS-guided transmural drainage in the management of PP at atypical locations. Patients and Methods: Retrospective analysis of 11 patients (all males; age range: 28-46 years with PP at atypical locations who were treated with NF-EUS-guided transmural drainage during the last 18 months was done. Results: Four patients had intra/peri-splenic, three patients had mediastinal, three patients had intrahepatic, and one patient had renal PP. Nine patients had chronic pancreatitis whereas two patients had acute pancreatitis. Alcohol was the etiology of pancreatitis in ten patients. The size of PP ranged from 4 to 10 cm. All patients had abdominal pain, and two patients had fever whereas one patient with mediastinal PP also had dysphagia. NF-EUS-guided transmural drainage could be done successfully in all patients. 7 Fr transmural stent (s was/were placed in six patients whereas single-time complete aspiration of PP was done in five patients. On endoscopic retrograde pancreatography, six patients had partial duct disruption whereas five patients had complete disruption. Bridging transpapillary stent (5 Fr was placed in all patients with partial disruption. All PP healed in 10/11 (91% patients within 2-4 weeks, and there has been no recurrence in 9 of these patients during a follow-up period of 4-18 months. One patient with splenic PP needed surgery for gastrointestinal bleed. Conclusion: PP at atypical locations can be effectively and safely treated with NF-EUS-guided transmural drainage.

Training and certification in endobronchial ultrasound-guided transbronchial needle aspiration

Science.gov (United States)

Konge, Lars; Nayahangan, Leizl Joy; Clementsen, Paul Frost

2017-01-01

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) plays a key role in the staging of lung cancer, which is crucial for allocation to surgical treatment. EBUS-TBNA is a complicated procedure and simulation-based training is helpful in the first part of the long learning curve prior to performing the procedure on actual patients. New trainees should follow a structured training programme consisting of training on simulators to proficiency as assessed with a validated test followed by supervised practice on patients. The simulation-based training is superior to the traditional apprenticeship model and is recommended in the newest guidelines. EBUS-TBNA and oesophageal ultrasound-guided fine needle aspiration (EUS-FNA or EUS-B-FNA) are complementary to each other and the combined techniques are superior to either technique alone. It is logical to learn and to perform the two techniques in combination, however, for lung cancer staging solely EBUS-TBNA simulators exist, but hopefully in the future simulation-based training in EUS will be possible. PMID:28840013

Irregular echogenic foci representing coagulation necrosis: a useful but perhaps under-recognized EUS echo feature of malignant lymph node invasion.

Science.gov (United States)

Bhutani, Manoop S; Saftoiu, Adrian; Chaya, Charles; Gupta, Parantap; Markowitz, Avi B; Willis, Maurice; Kessel, Ivan; Sharma, Gulshan; Zwischenberger, Joseph B

2009-06-01

Coagulation necrosis has been described in malignant lymph nodes. Our aim was to determine if coagulation necrosis in mediastinal lymph nodes imaged by EUS could be used as a useful echo feature for predicting malignant invasion. Patients with known or suspected lung cancer who had undergone mediastinal lymph node staging by EUS. Tertiary Care university hospital. An expert endosonographer blinded to the final diagnosis, reviewed the archived digital EUS images of lymph nodes prior to being sampled by FNA. LNs positive for malignancy by FNA were included. The benign group included lymph node images with either negative EUS-FNA or lymph nodes imaged by EUS but not subjected to EUS-FNA, with surgical correlation of their benign nature. 24 patients were included. 8 patients were found to have coagulation necrosis. 7/8 patients had positive result for malignancy by EUS-FNA. One patient determined to have coagulation necrosis had a non-malignant diagnosis indicating a false positive result. 16 patients had no coagulation necrosis. In 6 patients with no coagulation necrosis, the final diagnosis was malignant and in the remaining 10 cases, the final diagnosis was benign. For coagulation necrosis as an echo feature for malignant invasion, sensitivity was 54%, specificity was 91%, positive predictive value was 88%, negative predictive value was 63% and accuracy was 71%. Coagulation necrosis is a useful echo feature for mediastinal lymph node staging by EUS.

Electrocautery vs non-electrocautery dilation catheters in endoscopic ultrasonography-guided pancreatic fluid collection drainage

Science.gov (United States)

Kitamura, Katsuya; Yamamiya, Akira; Ishii, Yu; Nomoto, Tomohiro; Honma, Tadashi; Yoshida, Hitoshi

2016-01-01

AIM: To investigate the safety and utility of an electrocautery dilation catheter for endoscopic ultrasonography (EUS)-guided pancreatic fluid collection drainage. METHODS: A single-center, exploratory, retrospective study was conducted between August 2010 and August 2014. This study was approved by the Medical Ethics Committee of our institution. Informed, written consent was obtained from each patient prior to the procedure. The subjects included 28 consecutive patients who underwent EUS-guided transmural drainage (EUS-TD) for symptomatic pancreatic and peripancreatic fluid collections (PFCs) by fine needle aspiration using a 19-gauge needle. These patients were retrospectively divided into two groups based on the use of an electrocautery dilation catheter as a fistula dilation device; 15 patients were treated with an electrocautery dilation catheter (electrocautery group), and 13 patients were treated with a non-electrocautery dilation catheter (non-electrocautery group). We evaluated the technical and clinical successes and the adverse events associated with EUS-TD for the treatment of PFCs between the two groups. RESULTS: There were no significant differences in age, sex, type, location and diameter of PFCs between the groups. Thirteen patients (87%) in the electrocautery group and 10 patients (77%) in the non-electrocautery group presented with infected PFCs. The technical success rates of EUS-TD for the treatment of PFCs were 100% (15/15) and 100% (13/13) for the electrocautery and the non-electrocautery groups, respectively. The clinical success rates of EUS-TD for the treatment of PFCs were 67% (10/15) and 69% (9/13) for the electrocautery and the non-electrocautery groups, respectively (P = 0.794). The procedure time of EUS-TD for the treatment of PFCs in the electrocautery group was significantly shorter than that of the non-electrocautery group (mean ± SD: 30 ± 12 min vs 52 ± 20 min, P electrocautery and the non-electrocautery groups, respectively (P

The anti-tumor effect and biological activities of the extract JMM6 ...

African Journals Online (AJOL)

Juglans mandshurica Maxim is a traditional herbal medicines in China, and its anti-tumor bioactivities are of research interest. Bioassay-guided fractionation method was employed to isolate anti-tumor compounds from the stem barks of the Juglans mandshurica Maxim. The anti-tumor effect and biological activities of the ...

Induced spin-polarization of EuS at room temperature in Ni/EuS multilayers

Energy Technology Data Exchange (ETDEWEB)

Poulopoulos, P., E-mail: poulop@upatras.gr [Laboratory of High-Tech Materials, School of Engineering, University of Patras, 26504 Patras (Greece); Materials Science Department, University of Patras, 26504 Patras (Greece); Goschew, A.; Straub, A.; Fumagalli, P. [Institut für Experimentalphysik, Freie Universität Berlin, Arnimallee 14, D-14195 Berlin-Dahlem (Germany); Kapaklis, V.; Wolff, M. [Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala (Sweden); Delimitis, A. [Chemical Process and Energy Resources Institute (CPERI), Centre for Research and Technology Hellas (CERTH), 57001 Thermi, Thessaloniki (Greece); Wilhelm, F.; Rogalev, A. [European Synchrotron Radiation Facility (ESRF), B.P.220, 38043 Grenoble (France); Pappas, S. D. [Laboratory of High-Tech Materials, School of Engineering, University of Patras, 26504 Patras (Greece); Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala (Sweden)

2014-03-17

Ni/EuS multilayers with excellent multilayer sequencing are deposited via e-beam evaporation on the native oxide of Si(100) wafers at 4 × 10{sup −9} millibars. The samples have very small surface and interface roughness and show sharp interfaces. Ni layers are nanocrystalline 4–8 nm thick and EuS layers are 2–4 nm thick and are either amorphous or nanocrystalline. Unlike for Co/EuS multilayers, all Eu ions are in divalent (ferromagnetic) state. We show a direct antiferromagnetic coupling between EuS and Ni layers. At room temperature, the EuS layers are spin-polarized due to the proximity of Ni. Therefore, Ni/EuS is a candidate for room-temperature spintronics applications.

Combination Therapy with NHS-muIL12 and Avelumab (anti-PD-L1) Enhances Antitumor Efficacy in Preclinical Cancer Models.

Science.gov (United States)

Xu, Chunxiao; Zhang, Yanping; Rolfe, P Alexander; Hernández, Vivian M; Guzman, Wilson; Kradjian, Giorgio; Marelli, Bo; Qin, Guozhong; Qi, Jin; Wang, Hong; Yu, Huakui; Tighe, Robert; Lo, Kin-Ming; English, Jessie M; Radvanyi, Laszlo; Lan, Yan

2017-10-01

Purpose: To determine whether combination therapy with NHS-muIL12 and the anti-programmed death ligand 1 (PD-L1) antibody avelumab can enhance antitumor efficacy in preclinical models relative to monotherapies. Experimental Design: BALB/c mice bearing orthotopic EMT-6 mammary tumors and μMt - mice bearing subcutaneous MC38 tumors were treated with NHS-muIL12, avelumab, or combination therapy; tumor growth and survival were assessed. Tumor recurrence following remission and rechallenge was evaluated in EMT-6 tumor-bearing mice. Immune cell populations within spleen and tumors were evaluated by FACS and IHC. Immune gene expression in tumor tissue was profiled by NanoString® assay and plasma cytokine levels were determined by multiplex cytokine assay. The frequency of tumor antigen-reactive IFNγ-producing CD8 + T cells was evaluated by ELISpot assay. Results: NHS-muIL12 and avelumab combination therapy enhanced antitumor efficacy relative to either monotherapy in both tumor models. Most EMT-6 tumor-bearing mice treated with combination therapy had complete tumor regression. Combination therapy also induced the generation of tumor-specific immune memory, as demonstrated by protection against tumor rechallenge and induction of effector and memory T cells. Combination therapy enhanced cytotoxic NK and CD8 + T-cell proliferation and T-bet expression, whereas NHS-muIL12 monotherapy induced CD8 + T-cell infiltration into the tumor. Combination therapy also enhanced plasma cytokine levels and stimulated expression of a greater number of innate and adaptive immune genes compared with either monotherapy. Conclusions: These data indicate that combination therapy with NHS-muIL12 and avelumab increased antitumor efficacy in preclinical models, and suggest that combining NHS-IL12 and avelumab may be a promising approach to treating patients with solid tumors. Clin Cancer Res; 23(19); 5869-80. ©2017 AACR . ©2017 American Association for Cancer Research.

Role of endoscopic ultrasound-guided fine-needle aspiration in adrenal lesions: analysis of 32 patients

Directory of Open Access Journals (Sweden)

Rakesh K Gupta

2018-01-01

Full Text Available Objective: Endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC is a precise and safe technique that provides both radiological and pathological diagnosis with a better diagnostic yield and minimal adverse events. EUS-FNAC led to the remarkable increase in the detection rate of incidentaloma found during radiologic staging or follow-up in various malignancy or unrelated conditions. Aims: We did this preliminary study with an aim to evaluate the role of EUS-FNA in diagnosing and classifying adrenal lesions, clinical impact, and compare the outcome with the previously published literature. Materials and Methods: We included 32 consecutive cases (both retrospective and prospective of EUS-guided adrenal aspirate performed over a period of 3.3 years. The indications for the aspirate in decreasing order were metastasis (most common carcinoma gall bladder > primary adrenal mass > disseminated tuberculosis > pyrexia of unknown origin. On EUS, 28 cases revealed space occupying lesion or mass (two cases bilateral and four cases revealed diffuse enlargement (two cases bilateral with a mean size of 21 mm. Results: The cytology reports were benign adrenal aspirate (43.8%, metastatic adenocarcinoma (15.6%, histoplasmosis (9.4%, tuberculosis (9.4%, round cell tumor (6.2%, adrenocortical carcinoma (3.1%, and descriptive (3.1%. Three cases (9.4% yielded inadequate sample. The TNM staging was altered in 22.23% of the cases by result of adrenal aspirate. Conclusions: EUS-FNA of the adrenal gland is a safe, quick, and sensitive and real-time diagnostic technique, which requires an integrated approach of clinician, endoscopist, and cytopathologist for high precision in diagnosis. Although the role of EUS-FNA for right adrenal is not much described, we found adequate sample yield in all the four patients that underwent the procedure.

Comparison of diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration cytology and cell block in solid lesions

Directory of Open Access Journals (Sweden)

Avinash Bhat Balekuduru

2017-01-01

Full Text Available Background and Aim: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA is a procedure of choice for the diagnostic evaluation of submucosal and periluminal lesions. Tissue sample can be obtained by EUS-FNA cytology (FNAC or cell block (CB. The aim of the present study is to compare diagnostic yield of EUS-FNA CB and cytology in the absence of onsite pathologist following a protocol-based EUS-FNA approach in solid lesions. Patients and Methods: Participants who underwent EUS-FNA at our center for solid submucosal or periluminal lesions (pancreas, lymph node, and liver between 2014 and 2016 were included, retrospectively. The indication for the procedure along with the clinical and other investigation details and the final etiological diagnosis were recorded on uniform structured data forms. The diagnostic yield of cytology and CB were compared using McNemar's test. The P < 0.05 was considered statistically significant. Results: EUS-FNA for solid lesion was performed in 130 lesions in 101 patients during the study period. Their mean age was 52.5 ± 12 years and 42.5% were female. Pancreatic masses were the most common lesions (37.7% followed by lymph nodes (36.9%. Submucosal lesions (17.7% and liver lesions (7.7% accounted for rest of the cases. The overall diagnostic yield for EUS-FNAC (70% and CB (74.6% was not significantly different (P = 0.3 and their combined yield was 85.3%. For the 23 patients with submucosal lesion, diagnostic yield of CB (82.6% was significantly better than cytology (47.8%, P = 0.04. Conclusions: EUS-guided CB has better yield compared to cytology in gastrointestinal submucosal lesions. The combination of CB with cytology improves the overall yield of the procedure; and hence, they should be considered complimentary rather than alternatives.

Anti-tumor effects of Egr-IFN γ gene therapy combined with 125I-UdR radionuclide therapy

International Nuclear Information System (INIS)

Zhao Jingguo; Ni Yanjun; Song Xiangfu; Li Yanyi; Yang Wei; Sun Ting; Ma Qingjie; Gao Fengtong

2008-01-01

Objective: To explore the anti-tumor effects of Egr-IFNγ gene therapy combined with 125 I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNγ mixed with liposome was injected into tumor. 48 h later, 370 kBq 125 I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNγ in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNγ + 125 I-UdR group were obviously lower than those of control group, 125 I-UdR group and pcDNAEgr-1 + 125 I-UdR group 6-15 d after gene-radionuclide therapy. IFNγ protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNγ + 125 I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNγ + 125 I-UdR group was significantly higher than that in the other groups (P 125 I-UdR radionuclide therapy are better than those of 125 I-UdR therapy. (authors)

Endoscopic ultrasound-guided evaluation of the pleura and cases of pleural effusion.

Science.gov (United States)

Sharma, Malay; Rameshbabu, Chittapuram Srinivasan

2017-01-01

The most efficient and cost-effective approach for the diagnosis of pleural exudates remains uncertain and is a subject of controversy. Essential factors to be considered include the respective diagnostic yields of thoracocentesis, closed pleural biopsy, and thoracoscopy. The role of endoscopic ultrasound (EUS) of the esophagus as a modality for the evaluation of pleural exudates has not yet been evaluated. The applied anatomy of the pleura has been discussed. The techniques involved in the EUS imaging of different aspects of the pleura in normal cases and in cases with pleural effusion are elaborated. The practical application of this knowledge can be useful in EUS-guided sampling of the pleural wall, pleural nodules, and in cases of pleural effusion.

Diagnostic accuracy of transabdominal high-resolution US for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with EUS.

Science.gov (United States)

Lee, Jeong Sub; Kim, Jung Hoon; Kim, Yong Jae; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Jae Young; Han, Joon Koo

2017-07-01

To compare the diagnostic accuracy of transabdominal high-resolution ultrasound (HRUS) for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with endoscopic ultrasound (EUS) and pathology. Among 125 patients who underwent both HRUS and EUS, we included 29 pathologically proven cancers (T1 = 7, T2 = 19, T3 = 3) including 15 polypoid cancers and 50 surgically proven polyps (neoplastic = 30, non-neoplastic = 20). We reviewed formal reports and assessed the accuracy of HRUS and EUS for diagnosing cancer as well as the differential diagnosis of neoplastic polyps. Statistical analyses were performed using chi-square tests. The sensitivity, specificity, PPV, and NPV for gallbladder cancer were 82.7 %, 44.4 %, 82.7 %, and 44 % using HRUS and 86.2 %, 22.2 %, 78.1 %, and 33.3 % using EUS. HRUS and EUS correctly diagnosed the stage in 13 and 12 patients. The sensitivity, specificity, PPV, and NPV for neoplastic polyps were 80 %, 80 %, 86 %, and 73 % using HRUS and 73 %, 85 %, 88 %, and 69 % using EUS. Single polyps (8/20 vs. 21/30), larger (1.0 ± 0.28 cm vs. 1.9 ± 0.85 cm) polyps, and older age (52.5 ± 13.2 vs. 66.1 ± 10.3 years) were common in neoplastic polyps (p diagnostic accuracy for GB cancer compared with EUS. • HRUS and EUS showed similar diagnostic accuracy for differentiating neoplastic polyps. • Single, larger polyps and older age were common in neoplastic polyps. • HRUS is less invasive compared with EUS.

Endoscopic ultrasound-guided radiofrequency ablation of the pancreas

DEFF Research Database (Denmark)

Silviu, Ungureanu Bogdan; Daniel, Pirici; Claudiu, Mărgăritescu

2015-01-01

ultrasound (EUS)-guided radiofrequency ablation (RFA) probe through a 19G needle in order to achieve a desirable necrosis area in the pancreas. Radiofrequency ablation of the head of the pancreas was performed on 10 Yorkshire pigs with a weight between 25 kg and 35 kg and a length of 40-70 cm. Using an EUS...... analysis revealed increased values of amylase, alkaline phosphatase, and gamma-glutamyl transpeptidase on the 3rd day but a decrease on the 5th day. After necropsy and isolation of the pancreas, the ablated area was easily found, describing a solid necrosis. The pathological examination revealed...

Usefulness of {sup 18}F-FDG PET, combined FDG-PET/CT and EUS in diagnosing primary pancreatic carcinoma: A meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Tang Shuang [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Huang Gang, E-mail: huang2802@163.com [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Liu Jianjun [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Liu Tao [Department of Orthopedics, Soochow University, Suzhou (China); Treven, Lyndal [Faculty of Public Health, University of Sydney, Sydney (Australia); Song Saoli; Zhang Chenpeng; Pan Lingling [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Zhang Ting [Department of Anesthesiology, Renji Hospital, Shanghai (China)

2011-04-15

The aim was to evaluate the diagnostic value of {sup 18}F-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG PET), combined {sup 18}F-fluorodeoxyglucose-positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) and endoscopic ultrasonography (EUS) in diagnosing patients with pancreatic carcinoma. MEDLINE, EMBASE, Cochrane library and some other databases, from January 1966 to April 2009, were searched for initial studies. All the studies published in English or Chinese relating to the diagnostic value of {sup 18}F-FDG PET, PET/CT and EUS for patients with pancreatic cancer were collected. Methodological quality was assessed. The statistic software called 'Meta-Disc 1.4' was used for data analysis. Results: 51 studies were included in this meta-analysis. The pooled sensitivity estimate for combined PET/CT (90.1%) was significantly higher than PET (88.4%) and EUS (81.2%). The pooled specificity estimate for EUS (93.2%) was significantly higher than PET (83.1%) and PET/CT (80.1%). The pooled DOR estimate for EUS (49.774) was significantly higher than PET (32.778) and PET/CT (27.105). SROC curves for PET/CT and EUS showed a little better diagnostic accuracy than PET alone. For PET alone, when interpreted the results with knowledge of other imaging tests, its sensitivity (89.4%) and specificity (80.1%) were closer to PET/CT. For EUS, its diagnostic value decreased in differentiating pancreatic cancer for patients with chronic pancreatitis. In conclusion, PET/CT was a high sensitive and EUS was a high specific modality in diagnosing patients with pancreatic cancer. PET/CT and EUS could play different roles during different conditions in diagnosing pancreatic carcinoma.

Endoscopic ultrasound-guided fine-needle aspiration cytology in the evaluation of suspected tuberculosis in patients with isolated mediastinal lymphadenopathy

DEFF Research Database (Denmark)

Puri, R.; Vilmann, P.; Sud, R.

2010-01-01

Patients with suspected tuberculosis without pulmonary lesions and with mediastinal lymphadenopathy often pose a diagnostic challenge. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) cytology is an established modality to evaluate mediastinal and abdominal lesions. The aim...... of the present study was to evaluate the role of EUS-FNA in isolated mediastinal lymphadenopathy in patients suspected of having tuberculosis....

The cryo-thermal therapy eradicated melanoma in mice by eliciting CD4+ T-cell-mediated antitumor memory immune response.

Science.gov (United States)

He, Kun; Liu, Ping; Xu, Lisa X

2017-03-23

Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used. The cryo-thermal therapy induced regression of implanted melanoma and prolonged long-term survival while inhibiting lung metastasis. It also promoted the activation of CD4 + CD25 - conventional T cells, while reduced the percentage of CD4 + CD25 + regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the spleen, lung and blood. Furthermore, the cryo-thermal therapy enhanced the cytolytic function of CD8 + T cells and induced differentiation of CD8 + T cells into memory stem T cell (T SCM ), and differentiation of CD4 + T cells into dominant CD4-CTL, Th1 and Tfh subsets in the spleen for 90 days after the treatment. It was found that good therapeutic effect was mainly dependent on CD4 + T cells providing a durable memory antitumor immune response. At the same time, significant increase of serum IFN-γ was also observed to provide an ideal microenvironment of antitumor immunity. Further study showed that the rejection of re-challenge of B16F10 but not GL261 tumor in the treated mice in 45 or 60 days after the treatment, implied a strong systemic and melanoma-specific memory antitumor immunity induced by the treatment. Thus the cryo-thermal therapy would be considered as a new therapeutic strategy to prevent tumor recurrence and metastasis with potential clinical applications in the near future.

Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor Alpha Therapy for the Treatment of Crohn's Disease

Directory of Open Access Journals (Sweden)

Tetsuya Ishida

2014-01-01

Full Text Available We report a 45-year-old female patient who developed acute hepatic disorder during anti-tumor necrosis factor α therapy for the treatment of Crohn's disease (CD. She was diagnosed as colonic CD and placed on infliximab (IFX. She was negative for hepatitis B surface antigen at the initiation of IFX therapy, but developed acute hepatitis after the 30th administration of IFX 4 years and 1 month after the first administration. She was suspected to have had occult hepatitis B virus infection before IFX therapy, and de novo hepatitis B was considered the most likely diagnosis. Hepatitis subsided after discontinuation of anti-tumor necrosis factor α therapy and initiation of treatment with entecavir. She started to receive adalimumab to prevent relapse of CD. She has continued maintenance therapy with entecavir and adalimumab and has since been asymptomatic. As de novo hepatitis B may be fatal, virological testing for hepatitis B is essential for patients who are being considered for treatment that may weaken the immune system.

Clinical impact of endoscopic ultrasound-guided fine needle aspiration biopsy in patients with upper gastrointestinal tract malignancies. A prospective study

DEFF Research Database (Denmark)

Mortensen, M B; Pless, T; Durup, J

2001-01-01

BACKGROUND AND STUDY AIMS: Several studies have evaluated the accuracy of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) in the upper gastrointestinal tract, but so far no studies have specifically evaluated the clinical impact of EUS-FNAB in upper gastrointestinal tract......% in esophageal, gastric, and pancreatic cancer, respectively. The staging-related clinical impact was similar for all three types of cancer (11-12.5%), whereas the diagnosis-related impact was highest in pancreatic cancer patients (86%). EUS-FNAB was inadequate in 13% and gave false-negative results in 5......%. The overall sensitivity, specificity and accuracy for EUS-FNAB were 80%, 78% and 80%, respectively. No complications related to the biopsy procedure were seen. CONCLUSIONS: If EUS-FNAB was performed only in cases where a positive malignant result would change patient management, then approximately one out...

Infectious peritonitis after endoscopic ultrasound-guided biliary drainage in a patient with ascites

Directory of Open Access Journals (Sweden)

Nozomi Okuno

2018-04-01

Full Text Available Summary of Event: Bacterial, mycotic peritonitis and Candida fungemia developed in a patient with moderate ascites who had undergone endoscopic ultrasound-guided biliary drainage (EUS-BD. Antibiotics and antifungal agent were administered and ascites drainage was performed. Although the infection improved, the patient’s general condition gradually deteriorated due to aggravation of the primary cancer and he died.Teaching Point: This is the first report to describe infectious peritonitis after EUS-BD. Ascites carries the potential risk of severe complications. As such, in patients with ascites, endoscopic retrograde cholangiopancreatography (ERCP is typically preferred over EUS-BD or percutaneous drainage to prevent bile leakage. However, ERCP may not be possible in some patients with tumor invasion of the duodenum or with surgically altered anatomy. Thus, in patients with ascites who require EUS-BD, we recommend inserting the drainage tube percutaneously and draining the ascites before and after the intervention in order to prevent severe infection.

Utility and Safety of Endoscopic Ultrasound With Bronchoscope-Guided Fine-Needle Aspiration in Mediastinal Lymph Node Sampling: Systematic Review and Meta-Analysis.

Science.gov (United States)

Dhooria, Sahajal; Aggarwal, Ashutosh N; Gupta, Dheeraj; Behera, Digambar; Agarwal, Ritesh

2015-07-01

The use of endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA) has been described in the evaluation of mediastinal lymphadenopathy. Herein, we conduct a meta-analysis to estimate the overall diagnostic yield and safety of EUS-B-FNA combined with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), in the diagnosis of mediastinal lymphadenopathy. The PubMed and EmBase databases were searched for studies reporting the outcomes of EUS-B-FNA in diagnosis of mediastinal lymphadenopathy. The study quality was assessed using the QualSyst tool. The yield of EBUS-TBNA alone and the combined procedure (EBUS-TBNA and EUS-B-FNA) were analyzed by calculating the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each study, and pooling the study results using a random effects model. Heterogeneity and publication bias were assessed for individual outcomes. The additional diagnostic gain of EUS-B-FNA over EBUS-TBNA was calculated using proportion meta-analysis. Our search yielded 10 studies (1,080 subjects with mediastinal lymphadenopathy). The sensitivity of the combined procedure was significantly higher than EBUS-TBNA alone (91% vs 80%, P = .004), in staging of lung cancer (4 studies, 465 subjects). The additional diagnostic gain of EUS-B-FNA over EBUS-TBNA was 7.6% in the diagnosis of mediastinal adenopathy. No serious complication of EUS-B-FNA procedure was reported. Clinical and statistical heterogeneity was present without any evidence of publication bias. Combining EBUS-TBNA and EUS-B-FNA is an effective and safe method, superior to EBUS-TBNA alone, in the diagnosis of mediastinal lymphadenopathy. Good quality randomized controlled trials are required to confirm the results of this systematic review. Copyright © 2015 by Daedalus Enterprises.

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis

DEFF Research Database (Denmark)

Wyse, Jonathan M; Battat, Robert; Sun, Siyu

2017-01-01

OBJECTIVES: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN). METHODS: Six important clinical...

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis

NARCIS (Netherlands)

Wyse, J.M. (Jonathan M.); Battat, R. (Robert); Sun, S. (Siyu); A. Saftoiu (Adrian); Siddiqui, A.A. (Ali A.); Leong, A.T. (Ang Tiing); Arias, B.L.A. (Brenda Lucia Arturo); Fabbri, C. (Carlo); Adler, D.G. (Douglas G.); Santo, E. (Erwin); Kalaitzakis, E. (Evangelos); Artifon, E. (Everson); Mishra, G. (Girish); Okasha, H.H. (Hussein Hassan); J.-W. Poley (Jan-Werner); Guo, J. (Jintao); Vila, J.J. (Juan J.); Lee, L.S. (Linda S.); Sharma, M. (Malay); Bhutani, M.S. (Manoop S.); M. Giovannini (Marcello); Kitano, M. (Masayuki); Eloubeidi, M.A. (Mohamad Ali); Khashab, M.A. (Mouen A.); Nguyen, N.Q. (Nam Q.); Saxena, P. (Payal); Vilmann, P. (Peter); Fusaroli, P. (Pietro); Garg, P.K. (Pramod Kumar); Ho, S. (Sammy); Mukai, S. (Shuntaro); Carrara, S. (Silvia); Sridhar, S. (Subbaramiah); S. Lakhtakia (S.); Rana, S.S. (Surinder S.); Dhir, V. (Vinay); Sahai, A.V. (Anand V.)

2017-01-01

textabstractObjectives: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN). Methods: Six important

Endoscopic Ultrasound-Guided Biliary Drainage Using Self-Expandable Metal Stent for Malignant Biliary Obstruction

Directory of Open Access Journals (Sweden)

Lei Lu

2017-01-01

Full Text Available Purpose. Endoscopic ultrasound-guided biliary drainage (EUS-BD has been increasingly reported worldwide. However, studies concerning EUS-BD from Mainland China are sporadic. This study aims to investigate the feasibility, efficacy, and safety of EUS-BD using SEMS in a single center from Mainland China. Methods. Between November 2011 and August 2015, 24 patients underwent EUS-BD using a standardized algorithm. Results. Three patients underwent rendezvous technique (RV, 4 underwent hepaticogastrostomy (HGS, and 17 underwent choledochoduodenostomy (CDS. The technical and clinical success rates were 95.8% (23/24 and 100% (23/23, respectively. Mean procedure time for the CDS group (35.9 ± 5.0 min or HGS group (39.3 ± 5.0 min was significantly shorter than that for the RV group (64.7 ± 9.1 min (P<0.05. Complications (13% included (1 cholangitis and (2 postprocedure hemorrhage. During the follow-up periods (mean 6.4 months, 22 (91.7% patients died of tumor progression with mean stent patency of 5.8 ± 2.2 months. Stent occlusion occurred in 2 (8.7% patients. Conclusion. EUS-BD using SEMS is a feasible, effective, and safe alternative for biliary decompression after failed ERCP. EUS-RV may not be the first-line choice for EUS-BD in a medium volume center. Further evaluation and experience of this method are needed.

A novel "hitch-and-ride" deep biliary cannulation method during rendezvous endoscopic ultrasound-guided ERCP technique.

Science.gov (United States)

Nakai, Yousuke; Isayama, Hiroyuki; Matsubara, Saburo; Kogure, Hirofumi; Mizuno, Suguru; Hamada, Tsuyoshi; Takahara, Naminatsu; Nakamura, Tomoka; Sato, Tatsuya; Takeda, Tsuyoshi; Hakuta, Ryunosuke; Ishigaki, Kazunaga; Saito, Kei; Tada, Minoru; Koike, Kazuhiko

2017-10-01

Background and study aim Endoscopic ultrasound-guided rendezvous (EUS-RV) is increasingly reported as a treatment option after failed endoscopic retrograde cholangiopancreatography. We developed a novel "hitch-and-ride" catheter for biliary cannulation to reduce the risk of guidewire loss during EUS-RV. Patients and methods We retrospectively evaluated safety and technical success of EUS-RV between June 2011 and May 2016. Biliary cannulation during EUS-RV using three methods - over-the-wire, along-the-wire, and hitch-and-ride - were compared. Results A total of 30 EUS-RVs were attempted and the technical success rate was 93.3 %, with two failures (one bile duct puncture and one guidewire insertion). After 28 cases of successful guidewire passage, cannulation was attempted by the over-the-wire (n = 13), along-the-wire (n = 4) or hitch-and-ride (n = 11) method. Only the hitch-and-ride method achieved biliary cannulation without guidewire loss or conversion to the other methods. Time to cannulation was shorter with the hitch-and-ride method (4 minutes) than with over-the-wire and along-the-wire methods (9 and 13 minutes, respectively). The adverse event rate of EUS-RV was 23.3 %. Conclusion A novel hitch-and-ride catheter was feasible for biliary cannulation after EUS-RV. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical utility of an endoscopic ultrasound-guided rendezvous technique via various approach routes.

Science.gov (United States)

Kawakubo, Kazumichi; Isayama, Hiroyuki; Sasahira, Naoki; Nakai, Yousuke; Kogure, Hirofumi; Hamada, Tsuyoshi; Miyabayashi, Koji; Mizuno, Suguru; Sasaki, Takashi; Ito, Yukiko; Yamamoto, Natsuyo; Hirano, Kenji; Tada, Minoru; Koike, Kazuhiko

2013-09-01

The endoscopic ultrasound-guided rendezvous techniques (EUS-rendezvous) provide reliable biliary access after failed endoscopic retrograde cholangiopancreatography (ERCP) cannulation. We evaluated the clinical utility of an EUS-rendezvous technique using various approach routes. Patients undergoing EUS-rendezvous for biliary access after failed bile duct cannulation in ERCP were included. EUS-rendezvous was performed via three approach routes depending on the patient's condition: transgastric, transduodenal in a short endoscopic position, or transduodenal in a long endoscopic position. The main outcomes were the technical success rates. Secondary outcomes were procedure time and complications. Fourteen patients (median age, 77 years) underwent EUS-rendezvous for biliary access resulting from failed biliary cannulation. The reasons for biliary drainage were malignant biliary obstruction in five patients and choledocholithiasis in nine. Transgastric, transduodenal in a short position, and transduodenal in a long position EUS-rendezvous was performed in five, five, and four patients, respectively. Bile duct puncture occurred in the left intrahepatic duct in four patients, right hepatic duct in one, middle common bile duct in four, and lower common bile duct in five. The technical success rate was 100 %. In four patients, the approach route was modified from transduodenal in a short position to transduodenal in a long position or transgastric route. The median procedure time was 81 min. One case each of biliary peritonitis and pancreatitis occurred and were managed conservatively. EUS-rendezvous provided safe and reliable transpapillary bile duct access after failed ERCP cannulation. The selection of the appropriate approach routes, depending on patient condition, is critical.

Diagnostic performance of EUS in predicting advanced cancer among patients with Barrett's esophagus and high-grade dysplasia/early adenocarcinoma: systematic review and meta-analysis.

Science.gov (United States)

Qumseya, Bashar J; Brown, Jessica; Abraham, Merna; White, Donna; Wolfsen, Herbert; Gupta, Neil; Vennalaganti, Prashanth; Sharma, Prateek; Wallace, Michael B

2015-04-01

The role of EUS among patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD) or suspected mucosal carcinoma is controversial. To define the role of EUS in detecting advanced disease among patients with BE. Systematic review and meta-analysis. MEDLINE, Embase, Web of Science, and Cochrane Central databases. Patients with BE and HGD or esophageal adenocarcinoma (EAC) who were referred for endoscopic evaluation and underwent EUS. EUS. Pooled proportion of patients with advanced EAC identified by EUS among patients with BE who are referred for HGD or EAC (with or without visible lesions). Forest plots were used to contrast effect sizes in each of the studies and random effect models when tests of heterogeneity were significant (I(2) > 50% or P statistic). Of 1278 articles, 47 were reviewed in full text, and 11 articles met the inclusion criteria, including a total of 656 patients. Based on a random-effects model, the proportion of patients with advanced disease detected on EUS was 14% (95% confidence interval, 8%-22%; P advanced disease on EUS in the absence of nodules was 4% (95% confidence interval, 2%-6%, P < .0001). Significant heterogeneity among studies. EUS will result in a change in the therapeutic approach among in a significant minority of patients with BE who are referred for HGD or EAC. Copyright © 2015. Published by Elsevier Inc.

Neutron Scattering from Heisenberg Ferromagnets EuO and EuS

DEFF Research Database (Denmark)

Als-Nielsen, Jens Aage; Dietrich, O. W.; Passell, L.

1976-01-01

Neutron scattering has been used to study the magnetic ordering process in the isotropic exchange coupled ferromagnets EuO and EuS. Quantities investigated include the critical coefficients B and F+ and the critical exponents β, ν, and γ describing respectively the temperature dependence...

Endoscopic Ultrasound-guided Rendezvous Technique after Failed Endoscopic Retrograde Cholangiopancreatography: Which Approach Route Is the Best?

Science.gov (United States)

Okuno, Nozomi; Hara, Kazuo; Mizuno, Nobumasa; Hijioka, Susumu; Tajika, Masahiro; Tanaka, Tsutomu; Ishihara, Makoto; Hirayama, Yutaka; Onishi, Sachiyo; Niwa, Yasumasa; Yamao, Kenji

2017-12-01

Objective The endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a salvage method for failed selective biliary cannulation. Three puncture routes have been reported, with many comparisons between the intra-hepatic and extra-hepatic biliary ducts. We used the trans-esophagus (TE) and trans-jejunum (TJ) routes. In the present study, the utility of EUS-RV for biliary access was evaluated, focusing on the approach routes. Methods and Patients In 39 patients, 42 puncture routes were evaluated in detail. EUS-RV was performed between January 2010 and December 2014. The patients were prospectively enrolled, and their clinical data were retrospectively collected. Results The patients' median age was 71 (range 29-84) years. The indications for endoscopic retrograde cholangiopancreatography (ERCP) were malignant biliary obstruction in 24 patients and benign biliary disease in 15. The technical success rate was 78.6% (33/42) and was similar among approach routes (p=0.377). The overall complication rate was 16.7% (7/42) and was similar among approach routes (p=0.489). However, mediastinal emphysema occurred in 2 TE route EUS-RV patients. No EUS-RV-related deaths occurred. Conclusion EUS-RV proved reliable after failed ERCP. The selection of the appropriate route based on the patient's condition is crucial.

The role of routine preoperative EUS when performed after contrast enhanced CT in the diagnostic work-up in patients suspected of pancreatic or periampullary cancer.

Science.gov (United States)

Cieslak, Kasia P; van Santvoort, Hjalmar C; Vleggaar, Frank P; van Leeuwen, Maarten S; ten Kate, Fibo J; Besselink, Marc G; Molenaar, I Quintus

2014-01-01

In patients suspected of pancreatic or periampullary cancer, abdominal contrast-enhanced computed tomography (CT) is the standard diagnostic modality. A supplementary endoscopic ultrasonography (EUS) is often performed, although there is only limited evidence of its additional diagnostic value. The aim of the study is to evaluate the additional diagnostic value of EUS over CT in deciding on exploratory laparotomy in patients suspected of pancreatic or periampullary cancer. We retrospectively analyzed 86 consecutive patients who routinely underwent CT and EUS before exploratory laparotomy with or without pancreatoduodenectomy for suspected pancreatic or periampullary carcinoma between 2007 and 2010. Primary outcomes were visibility of a mass, resectability on CT/EUS and resection with curative intent. A mass was visible on CT in 72/86 (84%) patients. In these 72 patients, EUS demonstrated a mass in 64/72 (89%) patients. Resectability was accurately predicted by CT in 65/72 (90%) and by EUS in 58/72 (81%) patients. In 14/86 (16%) patients no mass was seen on CT. EUS showed a mass in 12/14 (86%) of these patients. A malignant lesion was histological proven in 11/12 (92%) of these patients. Overall, resectability was accurately predicted by CT and EUS in 90% (77/86) and 84% (72/86), respectively. In patients with a visible mass on CT, suspected for pancreatic or periampullary cancer, EUS has no additional diagnostic value, does not influence the decision to perform laparotomy and should therefore not be performed routinely. In patients without a visible mass on CT, EUS is useful to confirm the presence of a tumor. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Eosinophilic esophageal myositis diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report.

Science.gov (United States)

Igarashi, Ryo; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Sato, Ai; Maki, Takumi; Arakawa, Noriyuki; Yoshida, Yoshitsugu; Yamamoto, Shogo; Ikeda, Tsunehiko

2016-10-01

Eosinophilic esophagitis (EoE) is diagnosed by microscopic findings of eosinophilic infiltration into the squamous epithelium. In contrast, another disease concept termed "eosinophilic esophageal myositis (EoEM)" has been proposed, whereby there is eosinophilic infiltration into the muscularis propria instead. A 60-year-old man was referred to our hospital for chest pain, dysphagia, and several episodes of esophageal food impaction. Although EoE was suspected based on clinical features, biopsy specimens showed no mucosal eosinophilic infiltration. Endoscopic ultrasound (EUS) showed thickening of the muscularis propria layer and subsequent EUS-guided fine-needle aspiration biopsy (EUS-FNA) revealed eosinophilic infiltration into the muscularis propria. Although the patient's symptoms gradually improved after steroid administration, complete remission was not achieved after 1 year of treatment. This case may reflect a disorder distinct from typical EoE based on eosinophilic infiltration of the muscularis propria but not the squamous epithelium, and we, therefore, diagnosed it as EoEM using the EUS-FNA findings as reference.

A review of electroporation-based antitumor skin therapies and investigation of betulinic acid-loaded ointment.

Science.gov (United States)

Bakonyi, Monika; Berko, Szilvia; Eros, Gabor; Varju, Gabor; Dehelean, Cristina; Szucs, Maria Budai; Csanyi, Erzsebet

2017-11-13

Electrochemotherapy is a novel treatment for cutaneous and subcutaneous tumors utilizing the combination of electroporation and chemotherapeutic agents. Since tumors have an increasing incidence nowadays as a result of environmental and genetic factors, electrochemotherapy could be a promising treatment for cancer patients. The aim of this article is to summarize the novel knowledge about the use of electroporation for antitumor treatments and to present a new application of electrochemotherapy with a well-known plant derived antitumor drug betulinic acid. For the review we have searched the databases of scientific and medical research to collect the available publications about the use of electrochemotherapy in the treatment of various types of cancer. By the utilization of the available knowledge, we investigated the effect of electroporation on the penetration of a topically applied betulinic acid formulation into the skin by ex vivo Raman spectroscopy on hairless mouse skin Results: Raman measurements have demonstrated that the penetration depth of betulinic acid can be remarkably ameliorated by the use of electroporation, so this protocol can be a possibility for the treatment of deeper localized cancer nodules. Furthermore, it proved the influence of various treatment times, since they caused different spatial distributions of the drug in the skin. The review demonstrates that electrochemotherapy is a promising tool to treat different kinds of tumors with high efficiency and with only a few moderate adverse effects. Moreover, it presents a non-invasive method to enhance the penetration of antitumor agents, which can offer novel prospects for antitumor therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optical third harmonic generation in the magnetic semiconductor EuSe

Science.gov (United States)

Lafrentz, M.; Brunne, D.; Kaminski, B.; Pavlov, V. V.; Pisarev, R. V.; Henriques, A. B.; Yakovlev, D. R.; Springholz, G.; Bauer, G.; Bayer, M.

2012-01-01

Third harmonic generation (THG) has been studied in europium selenide EuSe in the vicinity of the band gap at 2.1-2.6 eV and at higher energies up to 3.7 eV. EuSe is a magnetic semiconductor crystalizing in centrosymmetric structure of rock-salt type with the point group m3m. For this symmetry the crystallographic and magnetic-field-induced THG nonlinearities are allowed in the electric-dipole approximation. Using temperature, magnetic field, and rotational anisotropy measurements, the crystallographic and magnetic-field-induced contributions to THG were unambiguously separated. Strong resonant magnetic-field-induced THG signals were measured at energies in the range of 2.1-2.6 eV and 3.1-3.6 eV for which we assign to transitions from 4f7 to 4f65d1 bands, namely involving 5d(t2g) and 5d(eg) states.

Balanced Propofol Sedation in Patients Undergoing EUS-FNA: A Pilot Study to Assess Feasibility and Safety

Directory of Open Access Journals (Sweden)

N. Pagano

2011-01-01

Full Text Available Introduction and aims. Balanced propofol sedation (BPS administered by gastroenterologists has gained popularity in endoscopic procedures. Few studies exist about the safety of this approach during endosonography with fine needle aspiration (EUS-FNA. We assessed the safety of BPS in EUS-FNA. Materials and methods. 112 consecutive patients, referred to our unit to perform EUS-FNA, from February 2008 to December 2009, were sedated with BPS. A second gastroenterologist administered the drugs and monitorized the patient. Results. All the 112 patients (62 males, mean age 58.35 completed the examination. The mean dose of midazolam and propofol was, respectively, of 2.1 mg (range 1–4 mg and 350 mg (range 180–400. All patients received oxygen with a mean flux of 4 liter/minute (range 2–6 liters/minute. The mean recovery time after procedure was 25 minutes (range 18–45 minutes. No major complications related to sedation were registered during all procedures. The oxygen saturation of all patients never reduced to less than 85%. Blood systolic pressure during and after the procedure never reduced to less than 100 mmHg. Conclusions. In our experience BPS administered by non-anaesthesiologists provided safe and successful sedation in patients undergoing EUS-FNA.

Endoscopic ultrasound guided biopsy performed routinely in lung cancer staging spares futile thoracotomies

DEFF Research Database (Denmark)

Larsen, Soeren S; Vilmann, Peter; Krasnik, Mark

2005-01-01

BACKGROUND: Up to 45% of operations with curative intent for non-small-cell lung cancer (NSCLC) can be regarded as futile, apparently because the stage of the disease is more advanced than expected preoperatively. During the past decade several studies have evaluated the usefulness of endoscopic...... ultrasound guided fine needle aspiration biopsy (EUS-FNA) in lung cancer staging with promising results. However, no randomised trials have been performed, in which a staging strategy with EUS-FNA performed in all patients is compared with a conventional workup. METHODS: Before surgery (i.e. mediastinoscopy...

Spatially modulated magnetic structure of EuS due to the tetragonal domain structure of SrTiO3 APS

CERN Document Server

Rosenberg, Aaron J.; Kirtley, John R.; Gedik, Nuh; Moodera, Jagadeesh S.; Moler, Kathryn A.

2017-12-15

The combination of ferromagnets with topological superconductors or insulators allows for new phases of matter that support excitations such as chiral edge modes and Majorana fermions. EuS, a wide-bandgap ferromagnetic insulator with a Curie temperature around 16 K, and SrTiO3 (STO), an important substrate for engineering heterostructures, may support these phases. We present scanning superconducting quantum interference device measurements of EuS grown epitaxially on STO that reveal micron-scale variations in ferromagnetism and paramagnetism. These variations are oriented along the STO crystal axes and only change their configuration upon thermal cycling above the STO cubic-to-tetragonal structural transition temperature at 105 K, indicating that the observed magnetic features are due to coupling between EuS and the STO tetragonal structure. We speculate that the STO tetragonal distortions may strain the EuS, altering the magnetic anisotropy on a micron scale. This result demonstrates that local variation in...

Hypoxia-targeting antitumor prodrugs and photosensitizers

International Nuclear Information System (INIS)

Zhang Zhouen; Nishimoto, S.I.

2006-01-01

Tumor hypoxia has been identified as a key subject for tumor therapy, since hypoxic tumor cells show resistance to treatment of tumor tissues by radiotherapy, chemotherapy and phototherapy. For improvement of tumor radiotherapy, we have proposed a series of radiation-activated prodrugs that could selectively release antitumor agent 5-fluorouracil or 5-fluorodeoxyuridine under hypoxic conditions. Recently, we attempted to develop two families of novel hypoxia-targeting antitumor agents, considering that tumor-hypoxic environment is favorable to biological and photochemical reductions. The first family of prodrugs was derived from camptothecin as a potent topoisomerase I inhibitor and several bioreductive motifs. These prodrugs could be activated by NADPH-cytochrome P450 reductase or DT-diaphorase to release free camptothecin, and thereby showed hypoxia-selective cytotoxictiy towards tumor cells. These prodrugs were also applicable to the real-time monitoring of activation and antitumor effect by fluorometry. Furthermore, the camptothecin-bioreductive motif conjugates was confirmed to show an oxygen-independent DAN photocleaving activity, which could overcome a drawback of back electron transfer occurring in the photosensitized one-electron oxidation of DNA. Thus, these camptothecin derivatives could be useful to both chemotherapy and phototherapy for hypoxic tumor cells. The second family of prodrugs harnessed UV light for cancer therapy, incorporating the antitumor agent 5-fluorourcil and the photolabile 2-nitrobenzyl chromophores. The attachment of a tumor-homing cyclic peptide CNGRC was also employed to construct the prototype of tumor-targeting photoactiaved antitumor prodrug. These novel prodrugs released high yield of 5-fluorourcil upon UV irradiation at λ ex =365 nm, while being quite stable in the dark. The photoactivation mechanism was also clarified by means of nanosecond laser flash photolysis. (authors)

Granulomatous salmonella osteomyelitis associated with anti-tumor necrosis factor therapy in a non-sickle cell patient: a case report

Energy Technology Data Exchange (ETDEWEB)

Gould, Elaine S.; Gilet, Anthony G. [State University of New York at Stony Brook, Department of Radiology, Stony Brook, NY (United States); Vigorita, Vincent J. [SUNY Health Sciences Center Brooklyn, Department of Pathology and Orthopedics, Brooklyn, NY (United States)

2010-08-15

Salmonella osteomyelitis is seen most commonly in patients with sickle cell disease and in those with compromised immune systems. We report on the clinical, histological and imaging findings of salmonella osteomyelitis with intraosseous abscess formation occurring in a non-sickle cell patient receiving anti-tumor necrosis factor (TNF) alpha therapy. (orig.)

Granulomatous salmonella osteomyelitis associated with anti-tumor necrosis factor therapy in a non-sickle cell patient: a case report

International Nuclear Information System (INIS)

Gould, Elaine S.; Gilet, Anthony G.; Vigorita, Vincent J.

2010-01-01

Salmonella osteomyelitis is seen most commonly in patients with sickle cell disease and in those with compromised immune systems. We report on the clinical, histological and imaging findings of salmonella osteomyelitis with intraosseous abscess formation occurring in a non-sickle cell patient receiving anti-tumor necrosis factor (TNF) alpha therapy. (orig.)

Fluoroscopy-assisted vs fluoroless endoscopic ultrasound-guided transmural drainage of pancreatic fluid collections: A comparative study.

Science.gov (United States)

Consiglieri, Claudia F; Gornals, Joan B; Busquets, Juli; Peláez, Nuria; Secanella, Lluis; De-La-Hera, Meritxell; Sanzol, Resurrección; Fabregat, Joan; Castellote, José

2018-01-01

The need for fluoroscopy guidance in patients undergoing endoscopic ultrasound-guided transmural drainage (EUS-TMD) of peripancreatic fluid collections (PFCs) remains unclear. The aim of this study was to compare general outcomes of EUS-TMD of PFCs under fluoroscopy (F) vs fluoroless (FL). This is a comparative study with a retrospective analysis of a prospective and consecutive inclusion database at a tertiary centre, from 2009 to 2015. All patients were symptomatic pseudocyst (PSC) and walled-off pancreatic necrosis (WON). Two groups were assigned depending on availability of fluoroscopy. The groups were heterogeneous in terms of their demographic characteristics, PFCs and procedure. The main outcome measures included technical and clinical success, incidences, adverse events (AEs), and follow-up. Fifty EUS-TMD of PFCs from 86 EUS-guided drainages were included during the study period. Group F included 26 procedures, PSC 69.2%, WON 30.8%, metal stents 61.5% (46.1% lumen-apposing stent) and plastic stents 38.5%. Group FL included 24 procedures, PSC 37.5%, WON 62.5%, and metal stents 95.8% (lumen-apposing stents). Technical success was 100% in both groups, and clinical success was similar (F 88.5%, FL 87.5%). Technical incidences and intra-procedure AEs were only described in group F (7.6% and 11.5%, respectively) and none in group FL. Procedure time was less in group FL (8min, p=0.0341). Fluoroless in the EUS-TMD of PFCs does not involve more technical incidences or intra-procedure AEs. Technical and clinical success was similar in the two groups. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

EUS-guided biliary drainage by using a standardized approach for malignant biliary obstruction: rendezvous versus direct transluminal techniques (with videos).

Science.gov (United States)

Khashab, Mouen A; Valeshabad, Ali Kord; Modayil, Rani; Widmer, Jessica; Saxena, Payal; Idrees, Mehak; Iqbal, Shahzad; Kalloo, Anthony N; Stavropoulos, Stavros N

2013-11-01

EUS-guided biliary drainage (EGBD) can be performed via direct transluminal or rendezvous techniques. It is unknown how both techniques compare in terms of efficacy and adverse events. To describe outcomes of EGBD performed by using a standardized approach and compare outcomes of rendezvous and transluminal techniques. Retrospective analysis of prospectively collected data. Two tertiary-care centers. Consecutive jaundiced patients with distal malignant biliary obstruction who underwent EGBD after failed ERCP between July 2006 and December 2012 were included. EGBD by using a standardized algorithm. Technical success, clinical success, and adverse events. During the study period, 35 patients underwent EGBD (rendezvous n = 13, transluminal n = 20). Technical success was achieved in 33 patients (94%), and clinical success was attained in 32 of 33 patients (97.0%). The mean postprocedure bilirubin level was 1.38 mg/dL in the rendezvous group and 1.33 mg/dL in the transluminal group (P = .88). Similarly, length of hospital stay was not different between groups (P = .23). There was no significant difference in adverse event rate between rendezvous and transluminal groups (15.4% vs 10%; P = .64). Long-term outcomes were comparable between groups, with 1 stent migration in the rendezvous group at 62 days and 1 stent occlusion in the transluminal group at 42 days after EGBD. Retrospective analysis, small number of patients, and selection bias. EGBD is safe and effective when the described standardized approach is used. Stent occlusion is not common during long-term follow-up. Both rendezvous and direct transluminal techniques seem to be equally effective and safe. The latter approach is a reasonable alternative to rendezvous EGBD. Copyright © 2013. Published by Mosby, Inc.

Endoscopic ultrasonography-guided rendezvous technique.

Science.gov (United States)

Tsuchiya, Takayoshi; Itoi, Takao; Sofuni, Atsushi; Tonozuka, Ryosuke; Mukai, Shuntaro

2016-04-01

Endoscopic retrograde cholangiopancreatography (ERCP) requires deep biliary cannulation. When deep biliary cannulation is failed, the endoscopic ultrasonography rendezvous technique (EUS-RV) is a useful salvage method. From the previous 15 articles that included 382 EUS-RV cases, the overall success rate of EUS-RV is 81 % with a complication rate of 10 %. In EUS-RV, the bile duct is punctured under EUS guidance and a guidewire is advanced into the duodenum via the papilla. The EUS scope is then switched to a duodenoscope and inserted into the bile duct over the guidewire exiting the papilla, or the guidewire is grasped with forceps and passed through the working channel; the catheter can then be inserted through the papilla over the wire. There are three puncture routes for EUS-RV: transgastric puncture of the intrahepatic bile duct (IHBD), transduodenal puncture of the extrahepatic bile duct (EHBD) via the proximal duodenum (D1), and transduodenal puncture of the EHBD via the second portion of the duodenum (D2). The puncture route for each patient should be selected based on the patient condition. GW selection for EUS-RV is critical, a hydrophilic GW is useful for this procedure. Although EUS-RV is now performed relatively routinely in a few high-volume centers, procedure standardization and the development of exclusive devices for EUS-RV are still underway. The development of exclusive devices for EUS-RV and prospective comparative studies with other salvage methods are needed to truly evaluate the procedure's usefulness and safety.

Endoscopic ultrasound in the evaluation of chronic upper abdominal pain of unknown etiology: a retrospective chart review examining the efficacy of EUS in determining a new diagnosis.

Science.gov (United States)

Thompson, Michelle B; Ramirez, Jonathan C; De La Rosa, Lisa M; Wood, Adam S; Desai, Shiv; Arjunan, Ananth; Song, Juhee; Erickson, Richard A

2015-02-01

To explore the utility of endoscopic ultrasound (EUS) in the evaluation of chronic upper abdominal pain (UAP) of undetermined etiology. Chronic UAP is a common problem with a challenging diagnosis and management. The role of EUS in the diagnosis of UAP may minimize additional testing; however, few studies describe the percentage of new diagnoses yielded in these patients. We conducted a retrospective analysis by reviewing electronic medical records at Scott and White Memorial Hospital, Texas A&M Health Sciences Center for patients with abdominal pain for ≥ 12 months not explained by previous workup referred for EUS for chronic UAP from January 1, 1998 through October 1, 2007. Patients with previous EUS in past 12 months were excluded from the study. Patient demographic data and imaging performed 6 months before and 24 months after EUS were reviewed and results documented. EUS was successful at diagnosing a new clinical etiology of chronic UAP in 33 patients (8.89%) with previous workup that was unrevealing for a definitive diagnosis. The most frequent diagnoses included pancreaticobiliary tree abnormalities, chronic pancreatitis, and fatty liver disease. Our results support the fact that the majority of patients UAP with prior imaging will have no identifiable organic etiology found on EUS to explain their pain; however, we suggest that EUS be considered in patients with suspected pancreatic or biliary pathology.

Biomarker Guided Therapy in Chronic Heart Failure

Science.gov (United States)

Bektas, Sema

2015-01-01

This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

Directory of Open Access Journals (Sweden)

Way-Seah Lee

2017-10-01

Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

Comparison of 22G reverse-beveled versus standard needle for endoscopic ultrasound-guided sampling of solid pancreatic lesions

Science.gov (United States)

Alatawi, Abdullah; Beuvon, Frédéric; Grabar, Sophie; Leblanc, Sarah; Chaussade, Stanislas; Terris, Benoit; Barret, Maximilien

2015-01-01

Objectives Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using standard needles has a high diagnostic value in the evaluation of solid pancreatic masses. Fenestrated needles have been developed to improve the quality of EUS-guided tissue sampling by providing core biopsies (FNB). Methods Patients with solid pancreatic masses of >2 cm were prospectively included in our study and randomized to receive EUS sampling, using either a standard 22G FNA or a 22G Procore® FNB needle. The main study endpoint was the number of needle passes required to obtain a diagnosis in more than 90% of cases. Results We included 100 patients (male = 63, female = 37; mean age = 68.4 years) in our study. We found that 88% of the lesions were malignant, with a mean size of 32 mm. A sample adequate for diagnosis was obtained in more than 90% of cases after the second needle pass in the FNB group, versus the third needle pass in the FNA group. Slide cellularity and presence of tissue microfragments were significantly higher in the FNB group. Sensitivity for the diagnosis of malignancy was 88.4% versus 97.8% for the EUS-FNA and EUS-FNB group, respectively, while specificity for both techniques was 100%. No complications were recorded. Conclusions Although the accuracy of both needle types for proving malignancy was similar, a lower number of passes was required with the FNB needles to achieve the same contributive sample rate as with the FNA needles. FNB also improved the histopathological quality of specimens, suggesting an overall superiority of FNB sampling. PMID:26279842

Failed common bile duct cannulation during pregnancy: Rescue with endoscopic ultrasound guided rendezvous procedure.

Science.gov (United States)

Singla, Vikas; Arora, Anil; Tyagi, Pankaj; Sharma, Praveen; Bansal, Naresh; Kumar, Ashish

2016-01-01

Common bile duct (CBD) stones can lead to serious complications and require intervention with either endoscopic retrograde cholangiopancreatography (ERCP) or laparoscopic techniques for urgent relief. On an average 10%-20% of the patients with gall bladder stones can have associated CBD stones. CBD stones during pregnancy can be associated with hazardous complications for both the mother and the fetus. Failed cannulation while performing ERCP during pregnancy is a technically demanding situation, which requires immediate rescue with special techniques. Conventional rescue techniques may not be feasible and can be associated with hazardous consequences. Endoscopic ultrasound (EUS) guided rendezvous technique has now emerged as a safe alternative, and in one of our patients, this technique was successfully attempted. To the best of our knowledge, this is the first case report in the literature on EUS-guided rendezvous procedure during pregnancy.

Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.

Directory of Open Access Journals (Sweden)

Shujing Shi

Full Text Available INTRODUCTION: Cytokine-induced killer cells (CIK cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. METHODS: We combined recombinant human endostatin (rh-endostatin and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. RESULTS: Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. CONCLUSIONS: Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells

Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

Science.gov (United States)

Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

2015-07-01

The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Endoscopic ultrasound-guided radiofrequency ablation for management of benign solid pancreatic tumors.

Science.gov (United States)

Choi, Jun-Ho; Seo, Dong-Wan; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

2018-05-04

 Radiofrequency ablation (RFA) has been increasingly employed in experimental and clinical settings for the management of pancreatic lesions. This study aimed to assess the safety and efficacy of endoscopic ultrasound (EUS)-guided RFA for benign solid pancreatic tumors.  In a single-center, prospective study, 10 patients with benign solid pancreatic tumors underwent EUS-RFA. After the RFA electrode had been inserted into the pancreatic mass, the radiofrequency generator was activated to deliver 50 W of ablation power.  Among the 10 patients, 16 sessions of EUS-RFA were successfully performed. Diagnoses included nonfunctioning neuroendocrine tumor (n = 7), solid pseudopapillary neoplasm (n = 2), and insulinoma (n = 1); the median largest diameter of the tumors was 20 mm (range 8 - 28 mm). During follow-up (median 13 months), radiologic complete response was achieved in seven patients. Two adverse events (12.4 %; 1 moderate and 1 mild) occurred.  EUS-RFA may be a safe and potentially effective treatment option in selected patients with benign solid pancreatic tumors. Multiple sessions may be required if there is a remnant tumor, and adverse events must be carefully monitored. © Georg Thieme Verlag KG Stuttgart · New York.

Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

Science.gov (United States)

Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

2015-04-01

Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Studies on anti-tumor effect of electromagnetic waves

International Nuclear Information System (INIS)

Kadota, Ikuhito; Wakabayashi, Toshio; Ogoshi, Kyoji; Kamijo, Akemi

1995-01-01

Hyperthermia have treated cancer with thermal effect of electromagnetic waves for biological systems, but the expected effect is not shown. Also non-thermal effect of electromagnetic waves is out of consideration. If irradiation conditions of electromagnetic waves with non-thermal anti-tumor effect are obtained, we can expect newly spread in cancer therapy. We had in vivo experiments that electromagnetic waves were irradiated to mice. In some irradiation conditions, the non-thermal anti-tumor effect of electromagnetic waves showed. In order to specify the irradiation conditions, we had in vitro experiments. We found that activity ratio of tumor cells which was measured by MTT method depended on irradiation time and power of electromagnetic waves. These results are useful for the cancer therapy. (author)

Targeting PEPT1: a novel strategy to improve the antitumor efficacy of doxorubicin in human hepatocellular carcinoma therapy.

Science.gov (United States)

Gong, Yanxia; Wu, Xiang; Wang, Tao; Zhao, Jia; Liu, Xi; Yao, Zhi; Zhang, Qingyu; Jian, Xu

2017-06-20

Proton coupled oligopeptide transporter 1 (PEPT1) is a member of the peptide transporter superfamily and plays important role in the absorption of oligopeptide and peptidomimetic drugs. Our previous research verified that PEPT1 expressed specifically in human Hepatocellular carcinoma (HCC) tissue and cell lines and showed potential transport activity to be a new candidate of the tumor therapeutic target. In this study, we aim to explore the feasibility of a novel tumor target therapeutic strategy: Targeting PEPT1 to improve the antitumor efficacy of Doxorubicin in human HCC therapy. First, Doxorubicin was conjugated with Glycylglycylglycine (Gly-Gly-Gly) - a tripeptide which was known as the substrate of PEPT1 and characterized by HPLC and MS successfully. Doxorubicin-tripeptide conjugate was then observed to clarify the target delivery by PEPT1 and the antitumor effect on human hepatocarcinoma in vivo and in vitro. Furthermore, the improvement of the toxic and side effect of Doxorubicin after conjugation was also evaluated by some biochemical tests. Our results reveal that targeting PEPT1 may contribute to the efficient delivery of Doxorubicin to hepatocarcinoma cells and the reduction of drug toxicity. PEPT1 has the prospect to be a novel target of HCC therapy.

Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

Science.gov (United States)

Felker, G Michael; Ahmad, Tariq; Anstrom, Kevin J; Adams, Kirkwood F; Cooper, Lawton S; Ezekowitz, Justin A; Fiuzat, Mona; Houston-Miller, Nancy; Januzzi, James L; Leifer, Eric S; Mark, Daniel B; Desvigne-Nickens, Patrice; Paynter, Gayle; Piña, Ileana L; Whellan, David J; O'Connor, Christopher M

2014-10-01

The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of study are followed up at regular intervals and after treatment adjustments for a minimum of 12 months. The primary endpoint of the study is time to cardiovascular death or first hospitalization for HF. Secondary endpoints include time to cardiovascular death and all-cause mortality, cumulative mortality, health-related quality of life, resource use, cost-effectiveness, and safety. The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840). Copyright © 2014 American College of Cardiology Foundation

E1B-attenuated onco lytic adenovirus enhances antitumor effect of radionuclide therapy by P53-independent way: cellular basic for radionuclide-viral therapy

Energy Technology Data Exchange (ETDEWEB)

Zhenwei, Zhang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Hua, Wu; Xuemei, Zhang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xinyuan, Liu [Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)

2004-07-01

Purpose: Chemotherapy or external radiation therapy can potentiate the therapeutic effect of E1 B-attenuated oncolytic adenovirus. In this study, the antitumor efficacy of oncolytic adenovirus combined with internal radionuclide therapy was evaluated. Methods: Firstly, viral replication was examined by plaque assay and Southern blotting, after oncolytic adenovirus, ZD55, was exposed to iodine-131. Cell viability was evaluated qualitatively by crystal violet staining and quantitatively by MTT assay. FACS analysis was performed to determine the synergic proapoptotic effect of iodine-131 combined with ZD55. Results: Irradiation of iodine-131 does not influence ZD55 viral DNA replication. In combination with ZD55, iodine-131 can efficiently kill tumor cells in a p53-independent model. ZD55 augments the proapoptotic effect of iodine-131. Conclusion: Radionuclide-viral therapy might be a novel tool for treatment of hepatocarcinoma. (authors)

The anti-tumor effect of ACNU and x-irradiation on mouse glioma

International Nuclear Information System (INIS)

Nakagawa, Hidemitsu; Hori, Masaharu; Hasegawa, Hiroshi; Mogami, Heitaro; Hayakawa, Toru.

1979-01-01

Anti-tumor activities of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and x-irradiation on methylcholanthrene induced glioma in C 57 BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and x-irradiation in M phase. As to the combined therapy of ACNU and x-irradiation, the anti-tumor effect was most remarkable when the cells were treated by x-irradiation in the G 2 , M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and x-irradiation on the cells in G 1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and x-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local x-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or x-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of x-ray was remarkably effective. Evidence obtained indicated that the combination therapy of ACNU and x-irradiation have synergistic anti-tumor effect on experimental mouse glioma. (author)

Endoscopic Ultrasound-Guided Rendezvous Technique for Failed Biliary Cannulation in Benign and Resectable Malignant Biliary Disorders.

Science.gov (United States)

Shiomi, Hideyuki; Yamao, Kentaro; Hoki, Noriyuki; Hisa, Takeshi; Ogura, Takeshi; Minaga, Kosuke; Masuda, Atsuhiro; Matsumoto, Kazuya; Kato, Hironari; Kamada, Hideki; Goto, Daisuke; Imai, Hajime; Takenaka, Mamoru; Noguchi, Chishio; Nishikiori, Hidefumi; Chiba, Yasutaka; Kutsumi, Hiromu; Kitano, Masayuki

2018-03-01

Endoscopic ultrasound-guided rendezvous technique (EUS-RV) has emerged as an effective salvage method for unsuccessful biliary cannulation. However, its application for benign and resectable malignant biliary disorders has not been fully evaluated. To assess the efficacy and safety of EUS-RV for benign and resectable malignant biliary disorders. This was a multicenter prospective study from 12 Japanese referral centers. Patients who underwent EUS-RV after failed biliary cannulation for biliary disorder were candidates for this study. Inclusion criteria were unsuccessful biliary cannulation for therapeutic endoscopic retrograde cholangiopancreatography with benign and potentially resectable malignant biliary obstruction. Exclusion criteria included unresectable malignant biliary obstruction, inaccessible papillae due to surgically altered upper gastrointestinal anatomy or duodenal stricture, and previous sphincterotomy and/or biliary stent placement. The primary outcome was the technical success rate of biliary cannulation; procedure time, adverse events, and clinical outcomes were secondary outcomes. Twenty patients were prospectively enrolled. The overall technical success rate and median procedure time were 85% and 33 min, respectively. Guidewire manipulation using a 4-Fr tapered tip catheter contributed to the success in advancing the guidewire into the duodenum. Adverse events were identified in 15% patients, including 2 with biliary peritonitis and 1 mild pancreatitis. EUS-RV did not affect surgical maneuvers or complications associated with surgery, or postoperative course. EUS-RV may be a safe and feasible salvage method for unsuccessful biliary cannulation for benign or resectable malignant biliary disorders. Use of a 4-Fr tapered tip catheter may improve the overall EUS-RV success rate.

Regression of gastric malt-lymphoma under specific therapy may be predict by endoscopic ultrasound.

Science.gov (United States)

Gheorghe, Cristian; Băncilă, Ion; Stoia, Răzvan; Gheorghe, Liana; Becheanu, Gabriel; Dobre, Camelia; Brescan, Raluca

2004-06-01

Mucosa-associated lymphoid tissue (MALT) lymphomas represent a relatively new described class of rare lymphomas, characterized by an indolent course and favourable outcome with specific therapy. Gastric MALT lymphomas are associated with chronic Helicobacter pylori (HP) infection. We report the case of a 67 year old man admitted for an 8-month history of epigastric pain, anorexia and progressive weight loss. He was diagnosed with low-grade primary gastric MALT lymphoma by endoscopy, histopathological examination of gastric mucosa (light microscopy and immunohistochemistry) and endoscopic ultrasonography (EUS). The patient received a 2-week course of anti-HP therapy and chemotherapy with Chlorambucil 0.1 mg/kg/day was started. During the follow-up, continuous improvement of clinical status, endoscopic and EUS appearance was noted. We conclude that, facing the trend toward nonsurgical treatment modalities for primary gastric lymphoma, EUS appears an important tool for staging the disease and defining cases suitable for anti-HP, radio- and chemotherapy, as well as for the detection of local recurrence.

Visualization of liposomes by magnetic resonance imaging: an opportunity to improve antitumoral liposome therapies

International Nuclear Information System (INIS)

Martinez Bedoya, Darel

2012-01-01

Controlled release of drugs at the tumor site and the development of non-invasive monitoring techniques are two of the main challenges currently facing antitumoral therapies. The paper analyzes some of the potential uses of liposomes as vehicles for the transport of drugs to the tumors, particularly directionalized variants to tumor antigens through antibody coupling (immunoliposomes). These vesicles may also be used in combination with magnetic resonance, one of the most widely used imaging techniques, and one exhibiting great visualization potential at molecular level. Joint use of these two techniques makes it possible to control the amount of drug administered, as well as predict the efficacy of the treatment and monitor its progress

Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy

International Nuclear Information System (INIS)

Liu Junye; Guo Yao; Guo Guozhen

2006-01-01

Objective: To explore the effects of hypoxia-targeted suicidal gene therapy system combined with radiotherapy on pancreatic cancer. Methods: The recombinant adenovirus Ad-5HRE/hCMVmp-BCD was constructed by DNA recombinant technique. Western blot was used to detect hypoxia-induced expression of bacterial cytosine deaminase (BCD). Cell growth inhibition assay was used to determine the sensitivity of human pancreatic cancer cells MIA-PACA2 to 5-fluorocytosine (5-FC). Tumor xenograft growth delay assays was used to evaluate the effects of Ad-5HRE/hCMVmp-BCD/5-FC combined with radiotherapy on pancreatic cancer. Results: Western blot analysis demonstrated that hypoxia-induced BCD protein expression was achieved in MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD. With hypoxia treatment, the sensitivity of MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD to 5-FC significantly increased. Administration of either Ad-5HRE/hCMVmp-BCD/5-FC or radiotherapy could inhibit the growth of MIA-PACA2 xenografts in nude mice. Moreover, combination of Ad-5HRE/hCMVmp-BCD/5-FC could significantly enhance suppressing effects of radiotherapy on MIA-PACA2 xenografts. Conclusion: Hypoxia-targeted suicidal gene therapy system Ad-5HRE/hCMVmp-BCD/5-FC could enhance antitumor effects of radiotherapy on pancreatic cancer and can be used as a powerful adjunct to conventional radiotherapy. (authors)

The role of radiotherapy for the induction of antitumor immune responses

International Nuclear Information System (INIS)

Multhoff, G.; Helmholtz-Zentrum Muenchen; Gaipl, U.S.; Niedermann, G.

2012-01-01

Effective radiotherapy is aimed to control the growth of the primary carcinoma and to induce a long-term specific antitumor immune response against the primary tumor, recurrence and metastases. The contribution covers the following issues: T cells and tumor specific immune responses, dendritic cells (DCs) start adaptive immune responses, NK (natural killer) cells for HLA independent tumor control, abscopal effects of radiotherapy, combination of radiotherapy and immune therapy, radiotherapy contribution to the induction of immunogenic cell death, combinability of radiotherapy and DC activation, combinability of radiotherapy and NK cell therapy. It turns out that the combination of radio-chemotherapy and immune therapy can change the microenvironment initiating antitumor immune reactions that inhibit the recurrence risk and the development of metastases.

A Comparison of Endoscopic Ultrasound Guided Biopsy and Positron Emission Tomography with Integrated Computed Tomography in Lung Cancer Staging

DEFF Research Database (Denmark)

Larsen, Stine Schmidt; Vilmann, P; Krasnik, K

2009-01-01

BACKGROUND AND STUDY AIMS: Exact staging of patients with non-small-cell lung cancer (NSCLC) is important to improve selection of resectable and curable patients for surgery. Positron emission tomography with integrated computed tomography (PET/CT) and endoscopic ultrasound guided fine needle...... aspiration biopsy (EUS-FNA) are new and promising methods, but indications in lung cancer staging are controversial. Only few studies have compared the 2 methods. The aim of this study was to assess and compare the diagnostic values of PET/CT and EUS-FNA for diagnosing advanced lung cancer in patients, who...... had both procedures performed. PATIENTS AND METHODS: 27 patients considered to be potential candidates for resection of NSCLC underwent PET/CT and EUS-FNA. Diagnoses were confirmed either by open thoracotomy, mediastinoscopy or clinical follow-up. Advanced lung cancer was defined as tumour...

Developing Federated Services within Seismology: IRIS' involvement in the CoopEUS Project

Science.gov (United States)

Ahern, T. K.; Trabant, C. M.; Stults, M.

2014-12-01

As a founding member of the CoopEUS initiative, IRIS Data Services has partnered with five data centers in Europe and the UC Berkeley (NCEDC) in the US to implement internationally standardized web services to access seismological data using identical methodologies. The International Federation of Digital Seismograph Networks (FDSN) holds commission status within IASPEI/IUGG and as such is the international body that governs data exchange formats and access protocols within seismology. The CoopEUS project involves IRIS and UNAVCO as part of the EarthScope project and the European collaborators are all members of the European Plate Observing System (EPOS). CoopEUS includes one work package that attempts to coordinate data access between EarthScope and EPOS facilities. IRIS has worked with its partners in the FDSN to develop and adopt three key international service standards within seismology. These include 1) fdsn-dataselect, a service that returns time series data in a variety of standard formats, 2) fdsn-station, a service that returns related metadata about a seismic station in stationXML format, and 3) fdsn-event, a service that returns information about earthquakes and other seismic events in QuakeML format. Currently the 5 European data centers supporting these services include the ORFEUS Data Centre in the Netherlands, the GFZ German Research Centre for Geosciences in Potsdam, Germany, ETH Zurich in Switzerland, INGV in Rome, Italy, and the RESIF Data Centre in Grenoble France. Presently these seven centres can all be accessed using standardized web services with identical service calls and returns results in standardized ways. IRIS is developing an IRIS federator that will allow a client to seamlessly access information across the federated centers. Details and current status of the IRIS Federator will be presented.

Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models.

Science.gov (United States)

Koonce, Nathan A; Quick, Charles M; Hardee, Matthew E; Jamshidi-Parsian, Azemat; Dent, Judith A; Paciotti, Giulio F; Nedosekin, Dmitry; Dings, Ruud P M; Griffin, Robert J

2015-11-01

Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials. The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. In the 4T1 murine breast tumor model, we observed a significant reduction in the tumor interstitial fluid pressure (IFP) 24 hours after CYT-6091 alone and combined with a radiation dose of 12 Gy (P.05 vs control) despite extensive vascular damage observed. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared with all other groups (P<.05). Finally, we observed a more than twofold delay in tumor growth when CYT-6091 was combined with a single 20-Gy radiation dose-notably, irrespective of the treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied with CYT-6091 treatment, a more than five-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. Our results have demonstrated that TNF-labeled gold nanoparticles combined with single or fractionated high-dose radiation therapy is effective in reducing IFP and tumor growth and shows promise for clinical translation. Copyright © 2015 Elsevier Inc. All rights reserved.

SQUID magnetometry and magneto-optics of epitaxial EuS

International Nuclear Information System (INIS)

Rumpf, K.; Granitzer, P.; Krenn, H.; Kellner, W.; Pascher, H.; Kirchschlager, R.; Janecek, S.

2004-01-01

The complicated (H,T)-magnetic phase diagram of EuS is caused by the critical balance between nearest and next nearest neighbour exchange interaction (J NN = 0.119 K and J NNN =-0.1209 K) and leads to various spin arrangements NNSS..., NSN..., NNS, NNN... [NS denotes opposite ferromagnetic order in adjacent (111) planes]. Beside the subtle local exchange of 5d-t 2g electrons and localized holes with neighbouring Eu-4f spins, obviously also the strain status influences the occurrence of these different phases. We investigate the magnetic ordering phenomenon in a strained 2.5 μm EuS film on BaF 2 substrate by SQUID magnetometry and magneto-optics like spectral Faraday- and Kerr-effect measurements for temperatures from 2 K up to 200 K and for magnetic field up to 5 T. The magneto-optical probe monitors the local environment of the photoexcited electron-hole pair, called magnetic exciton, located within a ferromagnetic surrounding (photoinduced magnetic polaron), whereas the integral magnetization measured by SQUID is most sensitive to long-range magnetic ordering. In spite of the dissimilarity of measurement techniques we find an influence of the long-range magnetic order (e.g. of the NNS- or NNN-matrix) on the non-resonant Kerr reflection. The complementarity of SQUID and magneto-optical methods is stringent only in the (resonant) spectral range, where magnetic polarons are formed. (author)

Endoscopic ultrasound-guided fine-needle aspiration cytology in the evaluation of suspected tuberculosis in patients with isolated mediastinal lymphadenopathy

DEFF Research Database (Denmark)

Puri, R.; Vilmann, P.; Sud, R.

2010-01-01

Patients with suspected tuberculosis without pulmonary lesions and with mediastinal lymphadenopathy often pose a diagnostic challenge. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) cytology is an established modality to evaluate mediastinal and abdominal lesions. The aim...

Anti-tumor activities of a novel chlorin derivative for photodynamic therapy in vitro and in vivo

Directory of Open Access Journals (Sweden)

Li-Jun Zhang

2015-01-01

Full Text Available In this study, a novel photosensitizer meso-tetra (3-pyrrolidinomethyl-4-methoxyphenyl chlorin (TPMC was reported. It displays a characteristic long wavelength absorption peak at 656 nm and it shows a singlet oxygen quantum yield of 0.48. After light irradiation with 650 nm laser, it can kill Eca-109 and SMMC-7721 cells in vitro (25 mW/cm2, 1.2 to 3.6 J/cm2 and destroy Eca-109 tumor in nude mice (50 mW/cm2, 90 J/cm2. It has the perspective to be developed as a new anti-tumor drug in photodynamic therapy (PDT photodiagnosis, and deserves further investigation.

The role of contrast-enhanced endoscopic ultrasound in pancreatic adenocarcinoma

DEFF Research Database (Denmark)

Saftoiu, Adrian; Vilmann, Peter; Bhutani, Manoop S

2016-01-01

contrast agents for early detection, tridimensional and fusion techniques for enhanced staging and resectability assessment but also novel applications of perfusion imaging for monitoring ablative therapy, improved local detection through EUS-guided sampling of portal vein flow or enhanced drug delivery......Contrast-enhanced endoscopic ultrasound (CE-EUS) allows characterization, differentiation, and staging of focal pancreatic masses. The method has a high sensitivity and specificity for the diagnosis of pancreatic adenocarcinoma which is visualized as hypo-enhanced as compared to the rest...... of the parenchyma while chronic pancreatitis and neuroendocrine tumors are generally either iso-enhanced or hyper-enhanced. The development of contrast-enhanced low mechanical index harmonic imaging techniques used in real time during endoscopic ultrasound (EUS) allowed perfusion imaging and the quantification...

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided interventions

DEFF Research Database (Denmark)

Jenssen, C; Hocke, M; Fusaroli, P

2016-01-01

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-gu...

Issues in image-guided therapy.

OpenAIRE

Haigron , Pascal; Luo , Limin ,; Coatrieux , Jean-Louis

2009-01-01

International audience; Medical robotics, computer- assisted surgery (CAS), image-guided therapy (IGT), and the like emerged more than 20 years ago, and many advances have been made since. Conferences and workshops have been organized; scientific contributions, position papers, and patents have been published; new academic societies have been launched; and companies were created all over the world to propose methods, devices, and systems in the area. Researchers in robotics, computer vision a...

EGFR-targeted delivery of DOX-loaded Fe3O4@polydopamine multifunctional nanocomposites for MRI and antitumor chemo-photothermal therapy

Directory of Open Access Journals (Sweden)

Mu X

2017-04-01

Full Text Available Xupeng Mu,1 Fuqiang Zhang,1 Chenfei Kong,1 Hongmei Zhang,1 Wenjing Zhang,1 Rui Ge,2 Yi Liu,2 Jinlan Jiang1 1Department of Central Laboratory, China-Japan Union Hospital, 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, China Abstract: Multifunctional nanocomposites that have multiple therapeutic functions together with real-time imaging capabilities have attracted intensive concerns in the diagnosis and treatment of cancer. This study developed epidermal growth factor receptor (EGFR antibody-directed polydopamine-coated Fe3O4 nanoparticles (Fe3O4@PDA NPs for magnetic resonance imaging and antitumor chemo-photothermal therapy. The synthesized Fe3O4@PDA-PEG-EGFR-DOX NPs revealed high storage capacity for doxorubicin (DOX and high photothermal conversion efficiency. The cell viability assay of Fe3O4@PDA-PEG-EGFR NPs indicated that Fe3O4@PDA-PEG-EGFR NPs had no cell cytotoxicity. However, Fe3O4@PDA-PEG-EGFR-DOX NPs could significantly decrease cell viability (~5% of remaining cell viability because of both photothermal ablation and near-infrared light-triggered DOX release. Meanwhile, the EGFR-targeted Fe3O4@PDA-PEG-EGFR-DOX NPs significantly inhibited the growth of tumors, showing a prominent in vivo synergistic antitumor effect. This study demonstrated the potential of using Fe3O4@PDA NPs for combined cancer chemo-photothermal therapy with increased efficacy. Keywords: Fe3O4 nanoparticles, polydopamine, chemo-photothermal therapy, multifunctional nanocomposites, DOX

Drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection.

Science.gov (United States)

Xu, Chuan; Huang, Xin-En; Wang, Shu-Xiang; Lv, Peng-Hua; Sun, Ling; Wang, Fu-An; Wang, Li-Fu

2014-01-01

To compare drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection. We collect 42 patients with obstructive jaundice caused by recurrence and metastasis after tumor resection from January 2008 - August 2012, for which percutaneous transhepatic catheter drainage (pTCD)/ percutaneous transhepatic biliary stenting (pTBS) were performed. In 25 patients drainage was combined with anti-tumor treatment, antineoplastic therapy including intra/postprodure local treatment and postoperative systemic chemotherapy, the other 17 undergoing drainage only. We assessed the two kinds of treatment with regard to patient prognosis. Both treatments demonstrated good effects in reducing bilirubin levels in the short term and promoting liver function. The time to reobstruction was 125 days in the combined group and 89 days in the drainage only group; the mean survival times were 185 and 128 days, the differences being significant. Interventional drainage in the treatment of the obstructive jaundice caused by recurrence and metastasis after tumor resection can decrease bilirubin level quickly in a short term and promote the liver function recovery. Combined treatment prolongs the survival time and period before reobstruction as compared to drainage only.

Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models

Energy Technology Data Exchange (ETDEWEB)

Koonce, Nathan A. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Quick, Charles M. [Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hardee, Matthew E.; Jamshidi-Parsian, Azemat; Dent, Judith A. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Paciotti, Giulio F. [CytImmune Sciences, Rockville, Maryland (United States); Nedosekin, Dmitry [Department of Otolaryngology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Dings, Ruud P.M. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Griffin, Robert J., E-mail: RJGriffin@uams.edu [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States)

2015-11-01

Purpose: Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials. Methods and Materials: The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. Results: In the 4T1 murine breast tumor model, we observed a significant reduction in the tumor interstitial fluid pressure (IFP) 24 hours after CYT-6091 alone and combined with a radiation dose of 12 Gy (P<.05 vs control). In contrast, radiation alone (12 Gy) had a negligible effect on the IFP. In the SCCVII head and neck tumor model, the baseline IFP was not markedly elevated, and little additional change occurred in the IFP after single-dose radiation or combined therapy (P>.05 vs control) despite extensive vascular damage observed. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared with all other groups (P<.05). Finally, we observed a more than twofold delay in tumor growth when CYT-6091 was combined with a single 20-Gy radiation dose—notably, irrespective of the treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied with CYT-6091 treatment, a more than five-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. Conclusions: Our results have demonstrated that TNF-labeled gold

[Drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter pylori infection: a network Meta-analysis].

Science.gov (United States)

Gou, Q Y; Yu, R B; Shi, R H

2017-05-10

Objective: To compare the efficacy and the risk of adverse effect of drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter ( H .) pylori infection. Methods: Literature retrieval was conducted by using major databases. Related papers published up to June 2015 were considered eligible if they were randomized control trials comparing different pharmacological formulations for H. pylori infection and used in a network Meta-analysis and a single rate Meta-analysis to evaluate the relative and absolute rates of H. pylori eradication and the risk of adverse effect. The Jadad score was used to evaluate the methodological quality. Funnel plot was constructed to evaluate the risk of publication bias. Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot. Results: Twenty randomized control trials for the treatment of 6 753 initial treated patients with H. pylori infection were included. Drug susceptibility test guided therapy was significantly superior to concomitant therapy, hybrid therapy, sequential therapy and bismuth quadruple therapy. The culture-based therapy had the highest likelihood of improving clinical efficacy, with lowest risk of adverse effect. Concomitant therapy had the highest probability of causing adverse effect despite its effectiveness. Hybrid therapy and bismuth quadruple therapy were associated with lower risk of adverse effect and higher effectiveness. Conclusion: Drug susceptibility test guided therapy showed superiority to other 4 interventions for H. pylori eradication mentioned above. Hybrid therapy and bismuth quadruple therapy might be applied in the settings where the culture-based strategy is not available.

Multiple Diagnostic Imaging of a Patient with Solid Pseudopapillary Tumour of the Pancreas: EUS, CT and FDG PET/CT

International Nuclear Information System (INIS)

Chong, Ari; Ha, Jungmin; Kwon, Seong Young

2014-01-01

Solid pseudopapillary neoplam of the pancreas (SPNP) is a rare tumour, making up approximately 1 % to 3 % of pancreatic tumours. About 90 % of SPNPs occur in young women (mean age 35 years). SPNP rarely causes symptoms and is usually detected incidentally. Differentiating SPNP from other pancreatic tumours is very important, because surgical resection may provide favourable outcomes. Metastases or invasion to other organs has been reported in 15% to 20% of patients with SPNP. Histologically, the uniform, bland-appearing, epithelial cells of SPNP are similar to the cells making up other pancreatic endocrine neoplasms. However, SPNP cannot be regarded as a pure pancreatic endocrine neoplasm because of the absence of chromogranin A expression and low expression of other endocrine markers. SPNP has not been associated with specific serum tumour markers. CT and MRI are used for the diagnosis and staging of SPNP. On contrast-enhanced CT, SPNP shows isoattenuation on precontrast CT, weak enhancement during the arterial phase and gradually increased enhancement during the portal venous phase. SPNP can appear as an encapsulated lesion with cystic degeneration, necrosis, haemorrhage or calcification. MRI can characterise internal signal intensities, including a blood component, which is helpful in making a differential diagnosis. Dong et al. analysed CT and MRI findings from eight patients with SPNP and reported that four lesions showed mixed solid and cystic components, and the others appeared almost completely solid. Stoita et al. reported that EUS-guided fine-needle aspiration was a minimally invasive, safe and reliable diagnostic method for SPNP. They reported that all seven lesions examined were hypoechoic, heterogeneous and well circumscribed. Their findings are very similar to the findings in our patient. In addition, it is clear from the EUS images of our patient that EUS provides better images for evaluating SPNP lesions than US of the pancreas (Figs. 1e and f and 2

CT-guided intratumoral gene therapy in non-small-cell lung cancer

International Nuclear Information System (INIS)

Kauczor, H.U.; Heussel, C.P.; Thelen, M.; Schuler, M.; Huber, C.; Weymarn, A. von; Bongartz, G.; Rochlitz, C.

1999-01-01

The objective of this study was to prove the principle of CT-guided gene therapy by intratumoral injection of a tumor suppressor gene as an alternative treatment approach of incurable non-small-cell lung cancer. In a prospective clinical phase I trial six patients with non-small-cell lung cancer and a mutation of the tumor suppressor gene p53 were treated by CT-guided intratumoral gene therapy. Ten milliliters of a vector solution (replication-defective adenovirus with complete wild-type p53 cDNA) were injected under CT guidance. In four cases the vector solution was completely applied to the tumor center, whereas in two cases 2 ml aliquots were injected into different tumor areas. For the procedure the scan room had been approved as a biosafety cabinet. Gene transfer was assessed by reverse transcription and polymerase chain reaction in biopsy specimens obtained under CT guidance 24-48 h after therapy. Potential therapeutic efficacy was evaluated on day 28 after treatment using spiral CT. The CT-guided gene therapy was easily performed in all six patients without intervention-related complications. Besides flu-like symptoms, no significant adverse effects of gene therapy were noted. Three of the four patients with central injection exhibited gene transfer in the posttreatment biopsy. Gene transfer could not be proven in the two patients with multiple 2 ml injections. After 28 days, four of the six patients showed stable disease at the treated tumor site, whereas other tumor manifestations progressed. Computed tomography-guided injections are an adequate and easy-to-perform procedure for intratumoral gene therapy. (orig.)

Relationship of pancreatic mass size and diagnostic yield of endoscopic ultrasound-guided fine needle aspiration.

Science.gov (United States)

Siddiqui, Ali A; Brown, Lauren J; Hong, Shih-Kuang S; Draganova-Tacheva, Rossitza A; Korenblit, Jason; Loren, David E; Kowalski, Thomas E; Solomides, Charalambos

2011-11-01

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is central to discerning the diagnosis of solid pancreatic tumors through tissue acquisition. Test performance is affected by a number of factors including location of mass within the pancreas, presence of onsite cytology technologist, and number of passes with the needle. The influence of tumor size has not been well studied. The objective of the current study was to determine whether the size of mass affects the diagnostic accuracy for solid pancreatic lesions aspirated under EUS guidance. Data were collected retrospectively on all patients with solid pancreatic masses undergoing EUS-FNA from June 2003 to August 2010. The cytology samples were reported as positive, suspicious for malignancy, atypical, negative, or nondiagnostic. The gold standard for a cytological diagnosis was histological confirmation or clinical follow-up of more than 6 months with repeat imaging. Patients were divided into five groups based upon lesion size as follows: (a) less than 1 cm, (b) 1-2 cm, (c) 2-3 cm, (d) 3-4 cm, and (e) greater than 4 cm. Performance characteristics of EUS-FNA including sensitivity, specificity, and accuracy were compared for each group. Accuracy was defined as the ratio of the sum of true-positive and true-negative values divided by the number of lesions. We identified 583 patients with solid pancreatic lesions in which EUS-FNA was performed and adequate cellularity was obtained (47% men, mean age 65 ± 1.4 (SE) years). Overall, 486 (83%) of lesions were pancreatic adenocarcinoma, 18 (3%) were neuroendocrine tumors, 12 (2%) were lymphomas, and 67 (12%) were benign lesions. The median size of the mass was 3 cm (range, 0.5-7 cm). A mean of 4.9 passes (range, 1-9 passes) was needed to obtain adequate samples from lesions. The overall yield of obtaining adequate samples for diagnosis was 85%. When stratified by size, the EUS-FNA sensitivity for lesions with size 4 cm was 40, 75.9, 86.9, 93

A guided interview process to improve student pharmacists' identification of drug therapy problems.

Science.gov (United States)

Rovers, John; Miller, Michael J; Koenigsfeld, Carrie; Haack, Sally; Hegge, Karly; McCleeary, Erin

2011-02-10

To measure agreement between advanced pharmacy practice experience students using a guided interview process and experienced clinical pharmacists using standard practices to identify drug therapy problems. Student pharmacists enrolled in an advanced pharmacy practice experience (APPE) and clinical pharmacists conducted medication therapy management interviews to identify drug therapy problems in elderly patients recruited from the community. Student pharmacists used a guided interview tool, while clinical pharmacists' interviews were conducted using their usual and customary practices. Student pharmacists also were surveyed to determine their perceptions of the interview tool. Fair to moderate agreement was observed on student and clinical pharmacists' identification of 4 of 7 drug therapy problems. Of those, agreement was significantly higher than chance for 3 drug therapy problems (adverse drug reaction, dosage too high, and needs additional drug therapy) and not significant for 1 (unnecessary drug therapy). Students strongly agreed that the interview tool was useful but agreed less strongly on recommending its use in practice. The guided interview process served as a useful teaching aid to assist student pharmacists to identify drug therapy problems.

Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

Directory of Open Access Journals (Sweden)

Mavroudi M

2014-01-01

Full Text Available Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The grim statistics speak for themselves with reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem guided gene therapy. Stem cells have the unique potential for self-renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for therapeutic use of stem cells is their cancerous transformation. Therefore, we

Image-guided radiation therapy: physician's perspectives

International Nuclear Information System (INIS)

Gupta, T.; Anand Narayan, C.

2012-01-01

The evolution of radiotherapy has been ontogenetically linked to medical imaging. Over the years, major technological innovations have resulted in substantial improvements in radiotherapy planning, delivery, and verification. The increasing use of computed tomography imaging for target volume delineation coupled with availability of computer-controlled treatment planning and delivery systems have progressively led to conformation of radiation dose to the target tissues while sparing surrounding normal tissues. Recent advances in imaging technology coupled with improved treatment delivery allow near-simultaneous soft-tissue localization of tumor and repositioning of patient. The integration of various imaging modalities within the treatment room for guiding radiation delivery has vastly improved the management of geometric uncertainties in contemporary radiotherapy practice ushering in the paradigm of image-guided radiation therapy (IGRT). Image-guidance should be considered a necessary and natural corollary to high-precision radiotherapy that was long overdue. Image-guided radiation therapy not only provides accurate information on patient and tumor position on a quantitative scale, it also gives an opportunity to verify consistency of planned and actual treatment geometry including adaptation to daily variations resulting in improved dose delivery. The two main concerns with IGRT are resource-intensive nature of delivery and increasing dose from additional imaging. However, increasing the precision and accuracy of radiation delivery through IGRT is likely to reduce toxicity with potential for dose escalation and improved tumor control resulting in favourable therapeutic index. The radiation oncology community needs to leverage this technology to generate high-quality evidence to support widespread adoption of IGRT in contemporary radiotherapy practice. (author)

Usefulness of combined percutaneous-endoscopic rendezvous techniques after failed therapeutic endoscopic retrograde cholangiography in the era of endoscopic ultrasound guided rendezvous.

Science.gov (United States)

Yang, Min Jae; Kim, Jin Hong; Hwang, Jae Chul; Yoo, Byung Moo; Kim, Soon Sun; Lim, Sun Gyo; Won, Je Hwan

2017-12-01

The rendezvous approach is a salvage technique after failure of endoscopic retrograde cholangiography (ERC). In certain circumstances, percutaneous-endoscopic rendezvous (PE-RV) is preferred, and endoscopic ultrasound-guided rendezvous (EUS-RV) is difficult to perform. We aimed to evaluate PE-RV outcomes, describe the PE-RV techniques, and identify potential indications for PE-RV over EUS-RV.Retrospective analysis was conducted of a prospectively designed ERC database between January 2005 and December 2016 at a tertiary referral center including cases where PE-RV was used as a salvage procedure after ERC failure.During the study period, PE-RV was performed in 42 cases after failed therapeutic ERC; 15 had a surgically altered enteric anatomy. The technical success rate of PE-RV was 92.9% (39/42), with a therapeutic success rate of 88.1% (37/42). Potential indications for PE-RV over EUS-RV were identified in 23 cases, and either PE-RV or EUS-RV could have effectively been used in 19 cases. Endoscopic bile duct access was successfully achieved with PE-RV in 39 cases with accessible biliary orifice using one of PE-RV cannulation techniques (classic, n = 11; parallel, n = 19; and adjunctive maneuvers, n = 9).PE-RV uses a unique technology and has clinical indications that distinguish it from EUS-RV. Therefore, PE-RV can still be considered a useful salvage technique for the treatment of biliary obstruction after ERC failure.

Rhenium–platinum antitumor systems

Directory of Open Access Journals (Sweden)

A. V. Shtemenko

2017-04-01

Full Text Available This review provides an overlook of design (in short, antitumor and other biological activity of quadruple-bonded cluster dirhenium(III compounds and their synergism with cisplatin. In particular, we describe the work of the rhenium-platinum antitumor system (introduction of rhenium and platinum compounds. Among known metal-based anticancer drugs and drug candidates dirhenium(III compounds differ profoundly due to their strong antiradical and antioxidant properties determined by quadruple bond unsaturation. Such advantages of metal complexes as more expressed redox chemical propertie should be exploited for creating more efficient anticancer drugs. Combination of drugs leads to synergistic effects and/or to lowe­ring toxicity of platinides and is very promising in cancer chemotherapy. The review covers the follo­wing items: design of quadruple bonded dirhenium(III clusters, their spectral and antiradical properties (in short; interaction of the dirhenium(III compounds with lipids and formation of liposomes; interaction of the dirhenium(III compounds with erythrocytes and their antihemolytic activity in the models of hemolytic anemia; anticancer activity of dirhenium clusters and work of the rhenium-platinum antitumor system; antianemic and antioxidant properties of the dirhenium(III compounds in the model of tumor growth; interaction of the dirhenium(III compounds with nucleobases and DNA. Some modern trends in the field of bioinorganic and medicinal chemi­stry are also considered regarding their connection to the rhenium-platinum system efficiency: use of combinational therapy and nanomaterials; involvement of some biologically active ligands and redox-activation strategy, etc.

Antitumor bystander effect induced by radiation-inducible target gene therapy combined with α particle irradiation

International Nuclear Information System (INIS)

Liu Hui; Jin Chufeng; Wu Yican; Ge Shenfang; Wu Lijun; FDS Team

2012-01-01

In this work, we investigated the bystander effect of the tumor and normal cells surrounding the target region caused by radiation-inducible target gene therapy combined with α-particle irradiation. The receptor tumor cell A549 and normal cell MRC-5 were co-cultured with the donor cells irradiated to 0.5 Gy or the non-irradiated donor cells, and their survival and apoptosis fractions were evaluated. The results showed that the combined treatment of Ad-ET and particle irradiation could induce synergistic antitumor effect on A549 tumor cell, and the survival fraction of receptor cells co-cultured with the irradiated cells decreased by 6%, compared with receptor cells co-cultured with non-irradiated cells, and the apoptosis fraction increased in the same circumstance, but no difference was observed with the normal cells. This study demonstrates that Ad-ET combined with α-particle irradiation can significantly cause the bystander effect on neighboring tumor cells by inhibiting cell growth and inducing apoptosis, without obvious toxicity to normal cells. This suggests that combining radiation-inducible TRAIL gene therapy and irradiation may improve tumor treatment efficacy by specifically targeting tumor cells and even involving the neighboring tumor cells. (authors)

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice

Directory of Open Access Journals (Sweden)

Miller Joseph D

2008-05-01

Full Text Available Abstract Background Interleukin-12 (IL-12 is a cytokine well known for its role in immunity. A lesser known function of IL-12 is its role in hematopoiesis. The promising data obtained in the preclinical models of antitumor immunotherapy raised hope that IL-12 could be a powerful therapeutic agent against cancer. However, excessive clinical toxicity, largely due to repeat dose regimens, and modest clinical response observed in the clinical trials have pointed to the necessity to design protocols that minimize toxicity without affecting the anti-tumor effect of IL-12. We have focused on the lesser known role of IL-12 in hematopoiesis and hypothesized that an important clinical role for IL-12 in cancer may be as an adjuvant hematological cancer therapy. In this putative clinical function, IL-12 is utilized for the prevention of cancer therapy-related cytopenias, while providing concomitant anti-tumor responses over and above responses observed with the primary therapy alone. This putative clinical function of IL-12 focuses on the dual role of IL-12 in hematopoiesis and immunity. Methods We assessed the ability of IL-12 to facilitate hematopoietic recovery from radiation (625 rad and chemotherapy (cyclophosphamide in two tumor-bearing murine models, namely the EL4 lymphoma and the Lewis lung cancer models. Antitumor effects and changes in bone marrow cellularity were also assessed. Results We show herein that carefully designed protocols, in mice, utilizing IL-12 as an adjuvant to radiation or chemotherapy yield facile and consistent, multilineage hematopoietic recovery from cancer therapy-induced cytopenias, as compared to vehicle and the clinically-utilized cytokine granulocyte colony-stimulating factor (G-CSF (positive control, while still providing concomitant antitumor responses over and above the effects of the primary therapy alone. Moreover, our protocol design utilizes single, low doses of IL-12 that did not yield any apparent toxicity

Relaxation Therapy with Guided Imagery for Postoperative Pain Management: An Integrative Review.

Science.gov (United States)

Felix, Márcia Marques Dos Santos; Ferreira, Maria Beatriz Guimarães; da Cruz, Luciana Falcão; Barbosa, Maria Helena

2017-12-14

To identify the evidence in the literature about relaxation therapy with guided imagery for postoperative pain management. Integrative review. PubMed, Lilacs, Cochrane, Embase, Web of Science, Scopus and Cinahl, between August 2006 and December 2016. Descriptors: Postoperative Pain, Imagery (Psychotherapy) and Guided Imagery. original studies published in English, Spanish and Portuguese. 291 studies were identified and eight were selected. Descriptive data analysis, presented in detail, with a summary of the knowledge produced in each study. In the primary studies included, the use of guided imagery associated with other complementary therapies was highlighted: hand and foot "M" technique, education on postoperative pain management with analgesic drugs, relaxation exercises, respiration exercises, meditation, soothing biorhythmic music combined with positive and encouraging assertions and music with nature sounds. The knowledge synthesis resulting from this study indicates that evidence could be identified on the use of guided imagery associated with relaxation therapy as a complementary approach to drug analgesia in postoperative pain control strengthens its indication for nursing practice. This evidence, however, demonstrates that the quality of the use of this therapy is limited, and it is necessary to carry out new randomized clinical studies to fill the existing gaps in this topic. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Just-in-time tomography (JiTT): a new concept for image-guided radiation therapy

International Nuclear Information System (INIS)

Pang, G; Rowlands, J A

2005-01-01

Soft-tissue target motion is one of the main concerns in high-precision radiation therapy. Cone beam computed tomography (CBCT) has been developed recently to image soft-tissue targets in the treatment room and guide the radiation therapy treatment. However, due to its relatively long image acquisition time the CBCT approach cannot provide images of the target at the instant of the treatment and thus it is not adequate for imaging targets with intrafraction motion. In this note, a new approach for image-guided radiation therapy-just-in-time tomography (JiTT)-is proposed. Differing from CBCT, JiTT takes much less time to generate the needed tomographical, beam's-eye-view images of the treatment target at the right moment to guide the radiation therapy treatment. (note)

GE11 Peptide as an Active Targeting Agent in Antitumor Therapy: A Minireview

Directory of Open Access Journals (Sweden)

Ida Genta

2017-12-01

Full Text Available A lot of solid tumors are characterized by uncontrolled signal transduction triggered by receptors related to cellular growth. The targeting of these cell receptors with antitumor drugs is essential to improve chemotherapy efficacy. This can be achieved by conjugation of an active targeting agent to the polymer portion of a colloidal drug delivery system loaded with an antitumor drug. The goal of this minireview is to report and discuss some recent results in epidermal growth factor receptor targeting by the GE11 peptide combined with colloidal drug delivery systems as smart carriers for antitumor drugs. The minireview chapters will focus on explaining and discussing: (i Epidermal growth factor receptor (EGFR structures and functions; (ii GE11 structure and biologic activity; (iii examples of GE11 conjugation and GE11-conjugated drug delivery systems. The rationale is to contribute in gathering information on the topic of active targeting to tumors. A case study is introduced, involving research on tumor cell targeting by the GE11 peptide combined with polymer nanoparticles.

CT guided percutaneous renal cysts puncture with ethanol therapy

International Nuclear Information System (INIS)

Zhang Xuezhe; Lu Yan; Wang Wu; Huang Zhengguo; Ren An

2002-01-01

Objective: To analyse our clinical experience with CT guided percutaneous renal cysts puncture and ethanol therapy. Methods: Five hundred and ten renal cysts in 445 patients were undergone CT guided percutaneous renal cysts puncture and ethanol therapy. Among the 445 cases, 385 cases had solitary renal cyst, 53 multiple renal cysts, and 7 polycystic kidneys. The renal cysts varied in size from 1.9 to 13.5 cm in diameter. The amount of aspirated fluid varied from 3 to 780 ml. A 18-21 gauge aspiration needles were used for all patients. A 25.0% cyst volume replacement with 99.7% ethanol was approved to be appropriate. Results: 427 renal cysts in 396 patients were followed up by computed tomographic (CT) or ultrasound for less than 3 months to more than one year duration. The curative effective rate and disappearance rate of the renal cystic cavity in solitary renal cysts were 97% and 82%, respectively. In multiple renal cysts, the corresponding values were 95% and 79%. In polycystic kidneys, the curative rate was 67%. The complications such as local abdominal pain (28 cases) and hematuria (four cases) were observed in this series. There were no fatal complications. Conclusions: CT guided percutaneous renal cyst puncture and ethanol therapy is an useful procedure for the treatment of solitary renal cysts and multiple renal cysts

USES 2.0, The Uniform System for the Evaluation of Substances, version 2.0 ; supplement to EUSES

NARCIS (Netherlands)

Linders JBHJ; Jager DT (eds.); CSR; ECO

1997-01-01

Dit interimrapport beschrijft het risicobeoordelingssysteem voor landbouw- en niet-landbouwbestrijdingsmiddelen. Het zal worden geintegreerd met het European Union System for the Evaluation of Substances, EUSES 1.0, tot USES 2.0, de tweede versie van het Uniforme Beoordelingssysteem voor

Multifunctional reduction-responsive SPIO and DOX-loaded PEGylated polymeric lipid vesicles for magnetic resonance imaging-guided drug delivery

International Nuclear Information System (INIS)

Wang, Sheng; Yang, Weitao; Wang, Hanjie; Chang, Jin; Gong, Xiaoqun; Du, Hongli; Guo, Fangfang; Zhang, Bingbo

2016-01-01

Multifunctional superparamagnetic iron-oxide (SPIO)-based nanoparticles have been emerging as candidate nanosystems for cancer diagnosis and therapy. Here, we report the use of reduction- responsive SPIO/doxorubicin (DOX)-loaded poly(ethylene glycol) monomethyl ether (PEG)ylated polymeric lipid vesicles (SPIO and DOX-PPLVs) as a novel theranostic system for tumor magnetic resonance imaging (MRI) diagnosis and controlled drug delivery. These SPIO and DOX-PPLVs are composed of SPIOs that function as MR contrast agents for tumor enhancement and PPLVs as polymer matrices for encapsulating SPIO and antitumor drugs. The in vitro characterizations show that the SPIO and DOX-PPLVs have nanosized structures (∼80 nm), excellent colloidal stability,  good biocompatibility, as well as T _2-weighted MRI capability with a relatively high T _2 relaxivity (r _2 = 213.82 mM"−"1 s"−"1). In vitro drug release studies reveal that the release rate of DOX from the SPIO and DOX-PPLVs is accelerated in the reduction environment. An in vitro cellular uptake study and an antitumor study show that the SPIO and DOX-PPLVs have magnetic targeting properties and effective antitumor activity. In vivo studies show the SPIO and DOX-PPLVs have excellent T _2-weighted tumor targeted MRI capability, image-guided drug delivery capability, and high antitumor effects. These results suggest that the SPIO and DOX-PPLVs are promising nanocarriers for MRI diagnosis and cancer therapy applications. (paper)

Transcutaneous carbon dioxide enhances the antitumor effect of radiotherapy on oral squamous cell carcinoma.

Science.gov (United States)

Iwata, Eiji; Hasegawa, Takumi; Ueha, Takeshi; Takeda, Daisuke; Saito, Izumi; Kawamoto, Teruya; Akisue, Toshihiro; Sakai, Yoshitada; Sasaki, Ryohei; Kuroda, Ryosuke; Komori, Takahide

2018-05-16

Radiotherapy (RT) is one of the main treatment modalities for oral squamous cell carcinoma (OSCC), however, radioresistance is a major impediment to its clinical success and poses as a concern that needs to be addressed. Tumor hypoxia is known to be significantly associated with radioresistance in various malignancies, hence, resolving the hypoxic state of a tumor may improve the antitumor effect of RT on OSCC. We have previously revealed that transcutaneous CO2 induced mitochondrial apoptosis and suppressed tumor growth in OSCC by resolving hypoxia. Considering the previous study, we hypothesized that transcutaneous CO2 may enhance the antitumor effect of RT on OSCC by improving intratumoral hypoxia, thereby overcoming radioresistance. In the present study, the combination of transcutaneous CO2 and RT significantly inhibited tumor growth compared with other treatments. This combination therapy also led to decreased expression of HIF-1α in parallel with increased expression of the cleaved forms of caspase-3-8-9 and PARP, which play essential roles in mitochondrial apoptosis. Additionally, the combination therapy increased the expression of ROS modulator 1 and subsequent mitochondrial ROS production, compared to RT alone. These results indicated that transcutaneous CO2 could potentially improve the antitumor effect of RT by decreasing the intratumoral hypoxia and increasing the mitochondrial apoptosis. Our findings indicated that CO2 therapy may be a novel adjuvant therapy in combination with RT for OSCC.

Image-guided interventions and computer-integrated therapy: Quo vadis?

Science.gov (United States)

Peters, Terry M; Linte, Cristian A

2016-10-01

Significant efforts have been dedicated to minimizing invasiveness associated with surgical interventions, most of which have been possible thanks to the developments in medical imaging, surgical navigation, visualization and display technologies. Image-guided interventions have promised to dramatically change the way therapies are delivered to many organs. However, in spite of the development of many sophisticated technologies over the past two decades, other than some isolated examples of successful implementations, minimally invasive therapy is far from enjoying the wide acceptance once envisioned. This paper provides a large-scale overview of the state-of-the-art developments, identifies several barriers thought to have hampered the wider adoption of image-guided navigation, and suggests areas of research that may potentially advance the field. Copyright © 2016. Published by Elsevier B.V.

Just-in-time tomography (JiTT): a new concept for image-guided radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Pang, G; Rowlands, J A [Toronto-Sunnybrook Regional Cancer Centre, 2075 Bayview Avenue, Toronto M4N 3M5 (Canada); Imaging Research, Sunnybrook and Women' s College Health Sciences Centre, Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto (Canada)

2005-11-07

Soft-tissue target motion is one of the main concerns in high-precision radiation therapy. Cone beam computed tomography (CBCT) has been developed recently to image soft-tissue targets in the treatment room and guide the radiation therapy treatment. However, due to its relatively long image acquisition time the CBCT approach cannot provide images of the target at the instant of the treatment and thus it is not adequate for imaging targets with intrafraction motion. In this note, a new approach for image-guided radiation therapy-just-in-time tomography (JiTT)-is proposed. Differing from CBCT, JiTT takes much less time to generate the needed tomographical, beam's-eye-view images of the treatment target at the right moment to guide the radiation therapy treatment. (note)

MRI-guided biopsies and minimally invasive therapy for prostate cancer

Directory of Open Access Journals (Sweden)

Sangeet Ghai

2015-01-01

Full Text Available Recent advances in multiparametric magnetic resonance imaging (mp-MRI have led to a paradigm shift in the diagnosis and management of prostate cancer (PCa. Its sensitivity in detecting clinically significant cancer and the ability to localize the tumor within the prostate gland has opened up discussion on targeted diagnosis and therapy in PCa. Use of mp-MRI in conjunction with prostate-specific antigen followed by targeted biopsy allows for a better diagnostic pathway than transrectal ultrasound (TRUS biopsy and improves the diagnosis of PCa. Improved detection of PCa by mp-MRI has also opened up opportunities for focal therapy within the organ while reducing the incidence of side-effects associated with the radical treatment methods for PCa. This review discusses the evidence and techniques for in-bore MRI-guided prostate biopsy and provides an update on the status of MRI-guided targeted focal therapy in PCa.

Behandling af insulinom med alkoholsklerosering

DEFF Research Database (Denmark)

Schnack, Christina; Christensen, Carina Ørts; Beck-Nielsen, Henning

2012-01-01

The efficacy and safety of endoscopic ultrasound (EUS)-guided alcohol ablation of an insulinoma in a patient not candidate for surgery is being evaluated. A 89 year-old male patient with insulinoma and serious cardiac disease was treated with EUS-guided alcohol ablation. The only complication...... was a slight degree of pancreatitis. Two months after the ablation values of plasma glucose and serum pro-insulin were normalized. EUS-guided alcohol ablation is a safe and efficient alternative to surgical resection of insulinomas in poor surgical candidates....

Experimental study on anti-tumor effect of pcEgr-IFNγ gene-radiotherapy

International Nuclear Information System (INIS)

Wu Congmei; Li Xiuyi; Liu Shuzheng

2001-01-01

Objective: To study the anti-tumor effect of IFN γ gene-radiotherapy to murine melanoma and its immunologic mechanism. Methods: pcEgr-IFNγ plasmids were injected locally into tumor, and 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different time, IFN γ expression 3 days later and immunologic indexes 15 days later were detected. Results: At 3-15 days after pcEgr-IFNγ gene-radiotherapy, the tumor growth rate was lower than that of irradiation alone group. It was also lower than that of gene therapy alone group and control plasmid combined with X-ray irradiation group significantly. Day 3 tumor IFN γ expression was higher than that of plasmid treatment alone group. NK activity, IL-2 and IFN γ secretion activities were higher than those of gene therapy alone and irradiation alone groups significantly. Conclusion: The antitumor effect of IFN γ gene-radiotherapy is better than that of either of them applied solely. Its mechanism might be concerned with the higher expression of IFN γ induced by irradiation in tumors and activation of anti-tumor immunologic functions

Effective photodynamic therapy in drug-resistant prostate cancer cells utilizing a non-viral antitumor vector (a secondary publication).

Science.gov (United States)

Yamauchi, Masaya; Honda, Norihiro; Hazama, Hisanao; Tachikawa, Shoji; Nakamura, Hiroyuki; Kaneda, Yasufumi; Awazu, Kunio

2016-03-31

There is an urgent need to develop an efficient strategy for the treatment of drug-resistant prostate cancer. Photodynamic therapy (PDT), in which low incident levels of laser energy are used to activate a photosensitizer taken up by tumor cells, is expected as a novel therapy for the treatment of prostate cancer because of the minimal invasive nature of PDT. The present study was designed to assess the efficacy of a novel vector approach combined with a conventional porphyrin-based photosensitizer. Our group focused on a non-viral vector (hemagglutinating virus of Japan envelope; HVJ-E) combined with protoporphyrin IX (PpIX) lipid, termed the porphyrus envelope (PE). It has been previously confirmed that HVJ-E has drug-delivering properties and can induce cancer-specific cell death. The PE (HVJ-E contained in PpIX lipid) was developed as a novel photosensitizer. In this study, the antitumor and PDT efficacy of the PE against hormone-antagonistic human prostate cancer cells (PC-3) were evaluated. Our results demonstrated that, under specific circumstances, PDT using the PE was very effective against PC-3 cells. A novel therapy for drug-resistant prostate cancer based on this vector approach is eagerly anticipated.

Synthesis of sulfadimethoxine based surfactants and their evaluation as antitumor agents

Directory of Open Access Journals (Sweden)

Manal Mohmed Khowdiary

2016-01-01

Summary: The main goal of cancer therapy is to attain the maximum therapeutic damage of tumor cells in combination with a minimum concentration of the drug. This can be achieved in principle via selective antitumor preparations, the cytostatic effects of which would be restricted within tumor tissue. While 100% selectivity may be impractical, the achievement of reasonably high selectivity seems to be a feasible aim. Platinum and cobalt complex surfactants in our research affect tumor tissue at a very low concentration at values lower than their CMC values; this indicate that the sulfadimethoxine complexes merit further investigation as potential antitumor drugs.

A Comprehensive Guide to Music Therapy

DEFF Research Database (Denmark)

Wigram, Anthony Lewis; Pedersen, Inge Nygaard; Bonde, Lars Ole

A detailed guide to music therapy from an international perspective, covering theory, practice, assessment, research and training. 2nd Edition of the first Danish Handbook in music theory, clinical practice, research and training. The Danish version "Musikterapi: Når ord ikke slår til......" was published in 2001 by KLIM, Aarhus DK. The English Edition has a more international orientation and a broader view on research and extended bibliography. The book includes a music CD and a CD rom....

Sentinel lymph node imaging guided IMRT for prostate cancer: Individualized pelvic radiation therapy versus RTOG guidelines

Directory of Open Access Journals (Sweden)

Chien P. Chen, MD, PhD

2016-01-01

Conclusions: SLN-guided pelvic radiation therapy can be used to either treat the most critical nodes only or as an addition to RTOG guided pelvic radiation therapy to ensure that the most important nodes are included.

Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System.

Science.gov (United States)

Duan, Haifeng

2018-05-22

The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. © 2018 The Author(s). Published by S. Karger AG, Basel.

Functional image guided radiation therapy planning in volumetric modulated arc therapy for patients with malignant pleural mesothelioma

Directory of Open Access Journals (Sweden)

Yoshiko Doi, MD

2017-04-01

Conclusions: Significant reductions in fV5, fV10, fMLD, V5, and MLD were achieved with the functional image guided VMAT plan without negative effects on other factors. LAA-based functional image guided radiation therapy planning in VMAT is a feasible method to spare the functional lung in patients with MPM.

Can Independent Judges Recognize Different Psychotherapies? An Experience with Manual-Guided Therapies.

Science.gov (United States)

Luborsky, Lester; And Others

1982-01-01

Tested whether independent judges could recognize three different manual-guided psychotherapies, drug counseling, supportive-expressive psychotherapy, and cognitive-behavioral using a special rating form containing scales for the characteristic aspects of each type. Results indicated that manual-guided therapies can be reliably recognized.…

USES 2.0, The Uniform System for the Evaluation of Substances, version 2.0 ; supplement to EUSES

NARCIS (Netherlands)

Linders JBHJ; Jager DT; CSR; ECO

1997-01-01

This interim report describes the updated risk assessment system for agricultural and non-agricultural pesticides. It will be integrated with the European Union System for the Evaluation of Substances, EUSES 1.0, into USES 2.0, the second version of the Uniform System for the Evaluation of

Intravenous Fluid Therapy Course for the Licensed Practical Nurse. Instructor Guide.

Science.gov (United States)

Missouri Univ., Columbia. Instructional Materials Lab.

This curriculum guide provides materials for a 10-unit intravenous (IV) therapy course for licensed practical nurses. Units contain from one to nine lessons. The first unit provides an introduction and orientation to the course. Subsequent units concern documentation, anatomy and physiology as applied to IV therapy, fundamental aspects of fluid…

A novel, polymer-coated oncolytic measles virus overcomes immune suppression and induces robust antitumor activity

Directory of Open Access Journals (Sweden)

Kaname Nosaki

2016-01-01

Full Text Available Although various therapies are available to treat cancers, including surgery, chemotherapy, and radiotherapy, cancer has been the leading cause of death in Japan for the last 30 years, and new therapeutic modalities are urgently needed. As a new modality, there has recently been great interest in oncolytic virotherapy, with measles virus being a candidate virus expected to show strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the host immune response in previous clinical trials. To enhance and prolong the antitumor activity of virotherapy, we combined the use of two newly developed tools: the genetically engineered measles virus (MV-NPL and the multilayer virus-coating method of layer-by-layer deposition of ionic polymers. We compared the oncolytic effects of this polymer-coated MV-NPL with the naked MV-NPL, both in vitro and in vivo. In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than did the naked MV-NPL in vitro. We also examined antitumor activities in virus-treated mice. Complement-dependent cytotoxicity and antitumor activities were higher in mice treated with polymer-coated MV-NPL than in mice treated with the naked virus. This novel, polymer-coated MV-NPL is promising for clinical cancer therapy in the future.

Anti-tumor therapy with macroencapsulated endostatin producer cells

Directory of Open Access Journals (Sweden)

Balduino Keli N

2010-03-01

Full Text Available Abstract Background Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Results Mice were inoculated subcutaneously with melanoma (B16F10 cells or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. Conclusions This study indicates that

Anti-tumor therapy with macroencapsulated endostatin producer cells.

Science.gov (United States)

Rodrigues, Danielle B; Chammas, Roger; Malavasi, Natália V; da Costa, Patrícia L N; Chura-Chambi, Rosa M; Balduino, Keli N; Morganti, Ligia

2010-03-02

Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. This study indicates that immunoisolation devices containing endostatin

Image-guided surgery and therapy: current status and future directions

Science.gov (United States)

Peters, Terence M.

2001-05-01

Image-guided surgery and therapy is assuming an increasingly important role, particularly considering the current emphasis on minimally-invasive surgical procedures. Volumetric CT and MR images have been used now for some time in conjunction with stereotactic frames, to guide many neurosurgical procedures. With the development of systems that permit surgical instruments to be tracked in space, image-guided surgery now includes the use of frame-less procedures, and the application of the technology has spread beyond neurosurgery to include orthopedic applications and therapy of various soft-tissue organs such as the breast, prostate and heart. Since tracking systems allow image- guided surgery to be undertaken without frames, a great deal of effort has been spent on image-to-image and image-to- patient registration techniques, and upon the means of combining real-time intra-operative images with images acquired pre-operatively. As image-guided surgery systems have become increasingly sophisticated, the greatest challenges to their successful adoption in the operating room of the future relate to the interface between the user and the system. To date, little effort has been expended to ensure that the human factors issues relating to the use of such equipment in the operating room have been adequately addressed. Such systems will only be employed routinely in the OR when they are designed to be intuitive, unobtrusive, and provide simple access to the source of the images.

Treating anxiety and depression in young adults: A randomised controlled trial comparing clinician-guided versus self-guided Internet-delivered cognitive behavioural therapy.

Science.gov (United States)

Dear, Blake F; Fogliati, Vincent J; Fogliati, Rhiannon; Johnson, Bareena; Boyle, Olivia; Karin, Eyal; Gandy, Milena; Kayrouz, Rony; Staples, Lauren G; Titov, Nickolai

2017-10-01

Internet-delivered cognitive behaviour therapy may increase access by young adults to evidence-based treatments for anxiety and depression. The aim of this study was to compare the efficacy of an Internet-delivered cognitive behaviour therapy intervention designed for adults aged 18-24 years, when delivered in clinician-guided versus self-guided formats. The intervention, the Mood Mechanic Course, is a transdiagnostic treatment that simultaneously targets symptoms of anxiety and depression using cognitive and behavioural skills. The brief intervention comprised four lessons, delivered over 5 weeks. Following a brief telephone interview, young adults ( n = 191) with symptoms of anxiety and depression were randomly allocated to either (1) clinician-guided treatment ( n = 96) or (2) self-guided treatment ( n = 95). At post treatment, large reductions (average improvement; clinician guided vs self-guided) were observed in symptoms of anxiety (44% vs 35%) and depression (40% vs 31%) in both groups. Significant improvements were also observed in general psychological distress (33% vs 29%), satisfaction with life (18% vs 15%) and disability (36% vs 29%). No marked or consistent differences in clinical outcomes emerged between conditions at post-treatment, at 3-month or 12-month follow-up. Satisfaction was high with both treatment formats, but slightly higher for clinician-guided treatment. These results indicate the potential of carefully developed Internet-delivered cognitive behaviour therapy interventions for young adults with anxiety and depression provided in either self or therapist-guided format. Further large-scale research is required to determine the short- and long-term advantages and disadvantages of different models of support.

Studies on Preparation of Photosensitizer Loaded Magnetic Silica Nanoparticles and Their Anti-Tumor Effects for Targeting Photodynamic Therapy

Directory of Open Access Journals (Sweden)

Chen Zhi-Long

2009-01-01

Full Text Available Abstract As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl-13,17-bis-(3-hydroxypropyl porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe3O4 and PHPP were incorporated into silica nanoparticles by microemulsion and sol–gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20–30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.

The counsellor's guide to parks inner child therapy The counsellor's guide to parks inner child therapy Parks P Souvenir 266pp £10.66 0-258-63172-1.

Science.gov (United States)

1994-07-13

The Counsellor's Guide to Parks Inner Child Therapy is the second book by Penny Parks about working with survivors of childhood abuse, the first being Rescuing the Inner Child, published in 1990, which introduced Parks Inner Child Therapy (PICT) as a specifically structured approach to inner child work.

Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis

Directory of Open Access Journals (Sweden)

Lindhofer Horst

2009-02-01

Full Text Available Abstract Peritoneal carcinomatosis (PC from epithelial tumors is a fatal diagnosis without efficient treatment. Trifunctional antibodies (trAb are novel therapeutic approaches leading to a concerted anti-tumor activity resulting in tumor cell destruction. In addition, preclinical data in mouse tumor models demonstrated the induction of long lasting tumor immunity after treatment with trAb. We describe the induction of anti-tumor specific T-lymphocytes after intraperitoneal administration of trAb in patients with PC. 9 patients with progressive PC from gastric (n = 6 and ovarian cancer (n = 2, and cancer of unknown primary (n = 1 received 3 escalating doses of trAb after surgery and/or ineffective chemotherapy. The trAb EpCAM × CD3 (10, 20, 40 μg or HER2/neu × CD3 (10, 40, 80 μg were applicated by intraperitoneal infusion. Four weeks after the last trAb application, all patients were restimulated by subdermal injection of trAb + autologous PBMC + irradiated autologous tumor cells. Immunological reactivity was tested by analyzing PBMC for specific tumor reactive CD4+/CD8+ T lymphocytes using an IFN-γ secretion assay. In 5 of 9 patients, tumor reactive CD4+/CD8+ T-lymphocytes increased significantly, indicating specific anti-tumor immunity. A clinical response (stable disease, partial regression has been observed in 5 of 9 patients, with a mean time to progression of 3.6 months. Follow-up showed a mean survival of 11.8 months (median 8.0 months after trAb therapy. TrAb are able to induce anti-tumor immunity after intraperitoneal application and restimulation. The induction of long-lasting anti-tumor immunity may provide an additional benefit of the intraperitoneal therapy with trAb and should be further elevated in larger clinical trials.

Endoscopic ultrasound rendezvous for bile duct access using a transduodenal approach: cumulative experience at a single center. A case series.

Science.gov (United States)

Kim, Y S; Gupta, K; Mallery, S; Li, R; Kinney, T; Freeman, M L

2010-06-01

Endoscopic ultrasound (EUS)-assisted biliary access is utilized when conventional endoscopic retrograde cholangiopancreatography (ERCP) fails. We report a 10-year experience utilizing a transduodenal EUS rendezvous via a transpapillary route without dilation of the transduodenal tract, followed by immediate ERCP access. Patients included all EUS-guided rendezvous procedures for biliary access that were performed following ERCP failure. EUS-assisted bile duct puncture was performed via a transduodenal approach and a guide wire was advanced through the papilla without any dilation or bougienage of the tract; ERCP was performed immediately afterwards. EUS-assisted biliary rendezvous was attempted in 15 patients (mean age 66 +/- 18.2 years; malignant = 10, benign = 5). Mean diameter of measured bile ducts was 14.3 +/- 5.17 mm (range 4-23 mm). The reasons for initial ERCP failure were tumor infiltration or edema (n = 9), intradiverticular papilla (n = 2), pre-existing duodenal stent (n = 1), and anatomic anomalies (n = 3). Successful EUS-guided bile duct puncture and wire passage were achieved in all 15 patients (100 %), with drainage being successful in 12 / 15 (80 %). Failures occurred in three patients due to inability to traverse the biliary stricture (n = 2) or dissection of a choledochocele with the guide wire (n = 1); all were subsequently drained via percutaneous methods. Stents placed were metallic in eight patients and plastic in four. Complications consisted of moderate pancreatitis after a difficult ERCP attempt in one patient, and bacteremia after percutaneous biliary drainage in another. There were no instances of perforation, extraluminal air or fluid collections. EUS-assisted biliary drainage utilizing a transduodenal rendezvous approach demonstated a high success rate without any complications directly attributable to the EUS access. Advantages over percutaneous biliary and other methods of EUS biliary access include performance under the same

Anti-tumor Activity of Toll-Like Receptor 7 Agonists

Directory of Open Access Journals (Sweden)

Huju Chi

2017-05-01

Full Text Available Toll-like receptors (TLRs are a class of pattern recognition receptors that play a bridging role in innate immunity and adaptive immunity. The activated TLRs not only induce inflammatory responses, but also elicit the development of antigen specific immunity. TLR7, a member of TLR family, is an intracellular receptor expressed on the membrane of endosomes. TLR7 can be triggered not only by ssRNA during viral infections, but also by immune modifiers that share a similar structure to nucleosides. Its powerful immune stimulatory action can be potentially used in the anti-tumor therapy. This article reviewed the anti-tumor activity and mechanism of TLR7 agonists that are frequently applied in preclinical and clinical investigations, and mainly focused on small synthetic molecules, including imiquimod, resiquimod, gardiquimod, and 852A, etc.

Nanovectorized radiotherapy, a new strategy to induce anti-tumor immunity

Directory of Open Access Journals (Sweden)

Claire eVanpouille-Box

2012-10-01

Full Text Available Recent experimental findings show that activation of the host immune system is required for the success of chemo- and radio-therapy. However, clinically-apparent tumors have already developed multiple mechanisms to escape anti-tumor immunity. The fact that tumors are able to induce a state of tolerance and immunosuppression is a major obstacle in immunotherapy. Hence, there is an overwhelming need to develop new strategies that overcome this state of immune tolerance and induce an anti-tumor immune response both at primary and metastatic sites. Nanovectorized radiotherapy that combines ionizing radiation and nano-devices, is one strategy that could boost the quality and magnitude of an immune response in a predictable and designable fashion. The potential benefits of this emerging treatment may be based on the unique combination of immuno-stimulatory properties of nanoparticles with the ability of ionizing radiation to induce immunogenic tumor cell death. In this review, we will discuss available data and propose that the nanovectorized radiotherapy could be a powerful new strategy to induce anti-tumor immunity required for positive patient outcome.

Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy

DEFF Research Database (Denmark)

Stenvang, Jan; Kümler, Iben; Nygård, Sune Boris

2013-01-01

-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I (Top1...

Cisplatin carbonato complexes. Implications for uptake, antitumor properties, and toxicity.

Science.gov (United States)

Centerwall, Corey R; Goodisman, Jerry; Kerwood, Deborah J; Dabrowiak, James C

2005-09-21

The reaction of aquated cisplatin with carbonate which is present in culture media and blood is described. The first formed complex is a monochloro monocarbonato species, which upon continued exposure to carbonate slowly forms a biscarbonato complex. The formation of carbonato species under conditions that simulate therapy may have important implications for uptake, antitumor properties, and toxicity of cisplatin.

Anti-tumoral effect of recombinant vaccinia virus through US guided injection in a rabbit model of hepatic VX2 carcinoma

Energy Technology Data Exchange (ETDEWEB)

Oh, Jong Young; Park, Byeong Ho; Kang, Myong Jin; Cho, Jin Han; Choi, Jong Cheol; Choi, Sun Seob; Nam, Kyung Jin; Hwang, Tae Ho; Jeong, Jin Sook [College of Medicine, Dong-A University, Busan (Korea, Republic of)

2006-02-15

The purpose of this study was to evaluate the anti-tumoral effect of recombinant vaccinia virus (rVV) (Thymidine kinase (-)/GM-CSF (+)) that was administered as a US guided intratumoral injection in a rabbit model of hepatic VX2 carcinoma. VX2 carcinoma was implanted in the livers of 12 rabbits. US was performed at every week interval to detect hepatic mass after the implantation of VX2 carcinoma. The accurate tumor size and volume was evaluated with CT when the tumor was detected on US. US guided injection of rVV (10{sup 9} pfu/ml) was preformed in three rabbits, intravenous injection of the same dose of rVV was done in two rabbits and another seven rabbits that were without any treatment were selected as a control group. We evaluated the change of the hepatic tumor size and extrahepatic metastasis on serial CT. Tumor specimens were harvested from rabbits that were killed at 8 weeks after VX2 implantation. These tissues were histoimmuopathologically compared to each other (the virus injection group and the control group). The differences between these groups were statistically assessed with student t-tests. Tumor growth was significantly suppressed in the US guided injection group compared with the intravenous injection group or the control group ({rho} < 0.01). The intravenous injection group showed statistically significant tumor suppression compared to the control group ({rho} < 0.01) until 2 weeks after virus injection. Quantification of the pulmonary metastatic nodules was performed in view of both the number and volume. The average number or volume of the pulmonary metastatic nodules in the US injection group was much smaller than these in the control group. Histopathologically, the tumors of the US guided injection group showed less extensive necrosis than those of the control group. Immunohistochemically, the tumor of the US guided injection group showed more prominent infiltration of CD4 (+) and CD8 (+) lymphocytes than did the tumors of the other group

Pretherapeutic evaluation of patients with upper gastrointestinal tract cancer using endoscopic and laparoscopic ultrasonography.

Science.gov (United States)

Mortensen, Michael Bau

2012-12-01

A detailed and correct pretherapeutic evaluation of stage and resectability is mandatory for an optimal treatment strategy and results in patients with cancer of the esophagus, stomach or pancreas (UGIC). Curative surgery should only be attempted in patients with limited extent of their disease, patients with locally advanced disease should be allocated for neo-adjuvant therapy, while the remaining patients should be referred for palliative measures following a quick, lenient and correct pretherapeutic evaluation. This thorough evaluation and subsequent treatment assignment is also valuable in the identification of uniform patient cohorts for new treatment protocols as well as for the continuing comparison of research data. But despite the importance of accurate pretherapeutic assessment being repeatedly emphasized insufficient staging has been - and is still accepted as - leading to high rates of explorative surgery as well as heterogeneous selection of patients for new treatment trials. Based on the results from the authors PhD thesis he concluded that endoscopic ultrasonography (EUS) as a single imaging modality provided detailed information that hitherto had been inaccessible. EUS was considered a significant progress regarding the loco-regional assessment of stage and resectability, but it was also evident that EUS alone was incapable of providing all the necessary information. In addition, there were no evidence regarding the EUS safety profile, patient tolerance of the procedure and no data on the clinical impact of both EUS and EUS guided fine-needle aspiration biopsy (EUS-FNA) in UGIC patients. Therefore, the author chose to conduct additional EUS trials and to test the use of EUS-FNA, laparoscopy (LAP), laparoscopic ultrasonography (LUS) and LUS guided biopsy in order to improve the overall pretherapeutic evaluation and thus the patient selection. The aim of this thesis was to describe the sequential development, testing and clinical results of a new

Effect of immunomodifier on radiation-induced antitumor immunity following local irradiation to tumor, 2

International Nuclear Information System (INIS)

Mukae, Shiro; Norimura, Toshiyuki; Tsuchiya, Takehiko

1988-01-01

This study was carried out to clarify whether or not the antitumor cell-mediated immunity of host is more effectively induced by the combined use of mouse interferon-α/β (MuIFN-α/β) with local irradiation than by simple local irradiation to tumor. C3H/He female mice, MM46 tumor cells and mouse interferon-α/β (MuIFN-α/β) were used in the experiment. Antitumor activity in mice was evaluated by the inhibition of tumor growth and mean survival days after treatment. Spleen cell killing activity to MM46 tumor cells was measured to evaluate the antitumor activity in vitro. In the case of single use of MuIFN-α/β, tumor growth was more rapid than in the non-treated group (control) in vivo. The mean survival days were also reduced. There was no siginificant difference in tumor growth inhibition between combined therapy using X-irradiation and MuIFN-α/β, and single therapy by local irradiation. However, in the case of administration of MuIFN-α/β after irradiation, the mean survival days was significantly increased compared with the group receiving X-ray irradiation only. (author)

Taming the Wildness of "Trojan-Horse" Peptides by Charge-Guided Masking and Protease-Triggered Demasking for the Controlled Delivery of Antitumor Agents.

Science.gov (United States)

Shi, Nian-Qiu; Qi, Xian-Rong

2017-03-29

Cell-penetrating peptide (CPP), also called "Trojan Horse" peptide, has become a successful approach to deliver various payloads into cells for achieving the intracellular access. However, the "Trojan Horse" peptide is too wild, not just to "Troy", but rather widely distributed in the body. Thus, there is an urgent need to tame the wildness of "Trojan Horse" peptide for targeted delivery of antineoplastic agents to the tumor site. To achieve this goal, we exploit a masked CPP-doxorubicin conjugate platform for targeted delivery of chemotherapeutic drugs using charge-guided masking and protease-triggered demasking strategies. In this platform, the cell-penetrating function of the positively CPP (d-form nonaarginine) is abrogated by a negatively shielding peptide (masked CPP), and between them is a cleavable substrate peptide by the protease (MMP-2/9). Protease-triggered demasking would occur when the masked CPP reached the MMP-2/9-riched tumor. The CPP-doxorubicin conjugate (CPP-Dox) and the masked CPP-Dox conjugate (mCPP-Dox) were used as models for the evaluation of masking and demasking processes. It was found that exogenous MMP-2/9 could effectively trigger the reversion of CPP-cargo in this conjugate, and this trigger adhered to the Michaelis-Menten kinetics profile. This conjugate was sensitive to the trigger of endogenous MMP-2/9 and could induce enhanced cytotoxicity toward MMP-2/9-rich tumor cells. In vivo antitumor efficacy revealed that this masked conjugate had considerable antitumor activity and could inhibit the tumor growth at a higher level relative to CPP-cargo. Low toxicity in vivo showed the noticeably decreased wildness of this conjugate toward normal tissues and more controllable entry of antitumor agents into "Troy". On the basis of analyses in vitro and in vivo, this mCPP-cargo conjugate delivery system held an improved selectivity toward MMP-2/9-rich tumors and would be a promising strategy for tumor-targeted treatment.

II Brazilian consensus statement on endoscopic ultrasonography.

Science.gov (United States)

Maluf-Filho, Fauze; de Oliveira, Joel Fernandez; Mendonça, Ernesto Quaresma; Carbonari, Augusto; Maciente, Bruno Antônio; Salomão, Bruno Chaves; Medrado, Bruno Frederico; Dotti, Carlos Marcelo; Lopes, César Vivian; Braga, Cláudia Utsch; M Dutra, Daniel Alencar; Retes, Felipe; Nakao, Frank; de Sousa, Giovana Biasia; de Paulo, Gustavo Andrade; Ardengh, Jose Celso; Dos Santos, Juliana Bonfim; Sampaio, Luciana Moura; Okawa, Luciano; Rossini, Lucio; de Brito Cardoso, Manoel Carlos; Ribeiro Camunha, Marco Antonio; Clarêncio, Marcos; Lera Dos Santos, Marcos Eduardo; Franco, Matheus; Schneider, Nutianne Camargo; Mascarenhas, Ramiro; Roda, Rodrigo; Matuguma, Sérgio; Guaraldi, Simone; Figueiredo, Viviane

2017-01-01

At the time of its introduction in the early 80s, endoscopic ultrasonography (EUS) was indicated for diagnostic purposes. Recently, EUS has been employed to assist or to be the main platform of complex therapeutic interventions. From a series of relevant new topics in the literature and based on the need to complement the I Brazilian consensus on EUS, twenty experienced endosonographers identified and reviewed the pertinent literature in databases. The quality of evidence, strength of recommendations, and level of consensus were graded and voted on. Consensus was reached for eight relevant topics: treatment of gastric varices, staging of nonsmall cell lung cancer, biliary drainage, tissue sampling of subepithelial lesions (SELs), treatment of pancreatic fluid collections, tissue sampling of pancreatic solid lesions, celiac neurolysis, and evaluation of the incidental pancreatic cysts. There is a high level of evidence for staging of nonsmall cell lung cancer; biopsy of SELs as the safest method; unilateral and bilateral injection techniques are equivalent for EUS-guided celiac neurolysis, and in patients with visible ganglia, celiac ganglia neurolysis appears to lead to better results. There is a moderate level of evidence for: yield of tissue sampling of pancreatic solid lesions is not influenced by the needle shape, gauge, or employed aspiration technique; EUS-guided and percutaneous biliary drainage present similar clinical success and adverse event rates; plastic and metallic stents are equivalent in the EUS-guided treatment of pancreatic pseudocyst. There is a low level of evidence in the routine use of EUS-guided treatment of gastric varices.

Medicinal Plants and Other Living Organisms with Antitumor Potential against Lung Cancer

Directory of Open Access Journals (Sweden)

Luara de Sousa Monteiro

2014-01-01

Full Text Available Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer.

Antitumor effects of traditional Chinese medicine targeting the cellular apoptotic pathway

Directory of Open Access Journals (Sweden)

Xu HL

2015-05-01

Full Text Available Huanli Xu,1 Xin Zhao,2 Xiaohui Liu,1 Pingxiang Xu,1 Keming Zhang,2 Xiukun Lin11Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, 2Department of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation Army, Beijing, People’s Republic of ChinaAbstract: Defects in apoptosis are common phenomena in many types of cancer and are also a critical step in tumorigenesis. Targeting the apoptotic pathway has been considered an intriguing strategy for cancer therapy. Traditional Chinese medicine (TCM has been used in the People’s Republic of China for thousands of years, and many of the medicines have been confirmed to be effective in the treatment of a number of tumors. With increasing cancer rates worldwide, the antitumor effects of TCMs have attracted more and more attention globally. Many of the TCMs have been shown to have antitumor activity through multiple targets, and apoptosis pathway-related targets have been extensively studied and defined to be promising. This review focuses on several antitumor TCMs, especially those with clinical efficacy, based on their effects on the apoptotic signaling pathway. The problems with and prospects of development of TCMs as anticancer agents are also presented.Keywords: traditional Chinese medicine, antitumor effects, apoptotic pathway

The study of combination therapy for arterial infusion chemotherapy and radiation therapy in unresectable gallbladder cancer

International Nuclear Information System (INIS)

Goto, Takuma; Saito, Hiroya; Yanagawa, Nobuyuki; Fujinaga, Akihiro; Saito, Yoshinori

2013-01-01

In this study, we investigated an effective strategy of treatment for unresectable gallbladder cancer (GBC) by the retrospective analysis of prognostic factors and anti-tumor therapies, especially combination therapy of arterial infusion chemotherapy and radiation therapy (AI+PT). Forty-three patients with unresectable GBC were enrolled, and prognostic factors were investigated by multivariate analysis using a proportional hazard model. In addition, we examined the indication and after-therapy by analyzing the each factor cumulative survival rates and anti-tumor effect about the AI + RT group (n=24). AI + RT and the responders to the first-line therapy were significant prognostic factors. In AI + RT group, median survival time, progression-free survival and the 1-year survival rate, the response and disease control rates was 15.5 months, 7.1 months, 62.5%. 54.2% and 95.8%, respectively; which suggested prolonged survival and high anti-tumor effect. Cumulative survival rate was significantly shorter in cases with distant metastasis except liver metastases, and has been tendency to extend in the group who underwent systemic chemotherapy as after-therapy. The treatment strategy, using the Al + RT as first-line with the systemic chemotherapy as after-therapy, suggested contribute to the prolonged survival in locally advanced and liver metastases cases of GBC. (author)

Image-Based Monitoring of Magnetic Resonance-Guided Thermoablative Therapies for Liver Tumors

Energy Technology Data Exchange (ETDEWEB)

Rempp, Hansjoerg, E-mail: hansjoerg.rempp@med.uni-tuebingen.de; Clasen, Stephan [Eberhard Karls University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Pereira, Philippe L. [SLK-Kliniken, Clinic for Radiology, Nuclear Medicine, and Minimal Invasive Therapies (Germany)

2012-12-15

Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.

Image-Based Monitoring of Magnetic Resonance-Guided Thermoablative Therapies for Liver Tumors

International Nuclear Information System (INIS)

Rempp, Hansjörg; Clasen, Stephan; Pereira, Philippe L.

2012-01-01

Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.

Short-term outcome of fluoroscopic-guided steroid injection therapy of lumber facet cyst-induced radicular pain

Energy Technology Data Exchange (ETDEWEB)

Kwon, Mi Ri; Kwon, Jong Won; Lee, Jong Seo; Kim, Eu Sang [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2015-04-15

To determine the short-term effect of fluoroscopic-guided steroid injection therapy of lumbar facet cyst-induced radicular pain. Seventeen patients with radiculopathy due to lumbar synovial cysts, who were treated with fluoroscopically guided injection, were retrospectively evaluated. All plain radiographic images and MR images before the therapy were reviewed. Five patients underwent only the facet joint injection, whereas twelve patients underwent the facet joint injection with perineural injection therapy. The clinical course of pain was evaluated on the first follow-up after therapy. Effective pain relief was achieved in 11 (64.7%) of the 17 patients. Among 12 patients who underwent facet joint injection with perineural injection, 9 patients (75%) had an effective pain relief. Of 5 patients, 2 (40%) patients only took the facet joint injection and had an effective pain relief. Fluoroscopic-guided steroid injection therapy shows a good short-term effect in patients with symptomatic lumbar facet joint synovial cysts.

Autologous US-guided PRP injection versus US-guided focal extracorporeal shock wave therapy for chronic lateral epicondylitis: A minimum of 2-year follow-up retrospective comparative study.

Science.gov (United States)

Alessio-Mazzola, Mattia; Repetto, Ilaria; Biti, Besmir; Trentini, Roberto; Formica, Matteo; Felli, Lamberto

2018-01-01

To compare the efficacy of two independent groups of patients treated with ultrasound (US)-guided extracorporeal shock wave (ESW) therapy and with US-guided injection of platelet-rich plasma (PRP) for chronic lateral epicondylitis (LE) with a minimum of 2-year follow-up. We retrospectively evaluated 63 patients treated for chronic LE (31 patients with autologous US-guided PRP injection and 32 patients with US-guided focal ESW therapy) from 2009 to 2014. All the patients were evaluated by means of Roles-Maudsley (RM) score, quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, visual analogic scale (VAS) and patient-rated tennis elbow evaluation (PRTEE) to retrospectively assess the pain relief, level of activity, the self-reported function and subjective satisfaction at minimum of 2-year follow-up. Both US-guided autologous PRP injection and US-guided focal ESW administration proved effective in chronic LE with significant improvement in the QuickDASH, VAS, RM and PRTEE scores ( p 0.05). The mean time between treatment and symptom resolution was significantly shorter for the PRP treatment ( p = 0.0212); furthermore, the mean time to return to the normal activities was quicker for PRP group ( p = 0.0119). Both PRP injection and ESW therapy are feasible and safe options for the treatment of chronic LE with low risk of complications and with good long-term follow-up results. US-guided PRP injection has quick efficacy when compared with US-guided focal ESW therapy.

Future of medical physics: Real-time MRI-guided proton therapy.

Science.gov (United States)

Oborn, Bradley M; Dowdell, Stephen; Metcalfe, Peter E; Crozier, Stuart; Mohan, Radhe; Keall, Paul J

2017-08-01

With the recent clinical implementation of real-time MRI-guided x-ray beam therapy (MRXT), attention is turning to the concept of combining real-time MRI guidance with proton beam therapy; MRI-guided proton beam therapy (MRPT). MRI guidance for proton beam therapy is expected to offer a compelling improvement to the current treatment workflow which is warranted arguably more than for x-ray beam therapy. This argument is born out of the fact that proton therapy toxicity outcomes are similar to that of the most advanced IMRT treatments, despite being a fundamentally superior particle for cancer treatment. In this Future of Medical Physics article, we describe the various software and hardware aspects of potential MRPT systems and the corresponding treatment workflow. Significant software developments, particularly focused around adaptive MRI-based planning will be required. The magnetic interaction between the MRI and the proton beamline components will be a key area of focus. For example, the modeling and potential redesign of a magnetically compatible gantry to allow for beam delivery from multiple angles towards a patient located within the bore of an MRI scanner. Further to this, the accuracy of pencil beam scanning and beam monitoring in the presence of an MRI fringe field will require modeling, testing, and potential further development to ensure that the highly targeted radiotherapy is maintained. Looking forward we envisage a clear and accelerated path for hardware development, leveraging from lessons learnt from MRXT development. Within few years, simple prototype systems will likely exist, and in a decade, we could envisage coupled systems with integrated gantries. Such milestones will be key in the development of a more efficient, more accurate, and more successful form of proton beam therapy for many common cancer sites. © 2017 American Association of Physicists in Medicine.

Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials.

Directory of Open Access Journals (Sweden)

Gianluigi Savarese

Full Text Available BACKGROUND: The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF. METHODOLOGY/PRINCIPAL FINDINGS: MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005 and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000, but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077. When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007 and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003, but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438, whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371, HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142 or all-cause hospitalization (OR:0.726; CI:0.509 to 1.035; p = 0.077. [corrected]. CONCLUSIONS/SIGNIFICANCE: Use of cardiac peptides to guide

Biomarkers in T cell therapy clinical trials

Directory of Open Access Journals (Sweden)

Kalos Michael

2011-08-01

Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

Ultrasound-guided interventional therapy for recurrent ovarian chocolate cysts.

Science.gov (United States)

Wang, Lu-Lu; Dong, Xiao-Qiu; Shao, Xiao-Hui; Wang, Si-Ming

2011-10-01

The aim of this study was to determine the effectiveness of ultrasound-guided interventional therapy in the treatment of postoperative recurrent chocolate cysts. The 198 patients enrolled in this study were divided into three groups. In group 1, the saline washing group, the cavity of the cyst was washed thoroughly with warm saline. In group 2, the ethanol short-time retention group, after washing with saline, the cyst was injected with 95% ethanol with a volume of half of the fluid aspirated from the cyst. Ten minutes later, the rest of the ethanol was aspirated. In group 3, the ethanol retention group, the procedures were the same as with the ethanol short-time retention group, except that 95% of the ethanol was retained in the cyst. An ultrasound examination was performed in the third, sixth and 12th months after therapy. The chocolate cyst cure rate was significantly higher in the ethanol retention group (96%, 66/69) than in the ethanol short-time retention group (82%, 56/68) and no case was cured in the first group (saline washing). We conclude that ultrasound-guided injection and 95% ethanol retention are an effective therapy for the treatment of postoperative recurrent chocolate cysts. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity.

Science.gov (United States)

Ma, Xingzhe; Bi, Enguang; Huang, Chunjian; Lu, Yong; Xue, Gang; Guo, Xing; Wang, Aibo; Yang, Maojie; Qian, Jianfei; Dong, Chen; Yi, Qing

2018-05-09

CD8 + T cells can be polarized into IL-9-secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. © 2018 Ma et al.

Biosignal-guided personalized therapy

Directory of Open Access Journals (Sweden)

von Stülpnagel Lukas

2017-09-01

Full Text Available Sudden cardiac death (SCD is the leading single cause of death in the industrialized world. Current guidelines recommend a prophylactic implantation of an implantable cardioverter-defibrillator (ICD in patients with reduced left-ventricular ejection fraction (LVEF ≤ 35%. However, most deaths after myocardial infarction (MI occur in patients with normal or moderately reduced LVEF (>35%. There is a large body of evidence that cardiac autonomic dysfunction after MI is linked to increased susceptibility to malignant arrhythmias. Deceleration capacity of heart rate (DC and periodic repolarization dynamics (PRD are novel ECG-based risk markers, which capture different facets of cardiac autonomic dysfunction. Both parameters are strong and independent predictors of mortality and SCD after MI. Previous studies indicated that combined assessment of DC and PRD allows identification of a new high-risk group among post-infarction patients that is not addressed by current guidelines, thus opening new perspectives for biosignal-guided personalized therapies.

Antioxidants Impair Anti-Tumoral Effects of Vorinostat, but Not Anti-Neoplastic Effects of Vorinostat and Caspase-8 Downregulation

OpenAIRE

Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

2014-01-01

We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat...

Comparison of Histologic Core Portions Acquired from a Core Biopsy Needle and a Conventional Needle in Solid Mass Lesions: A Prospective Randomized Trial.

Science.gov (United States)

Lee, Ban Seok; Cho, Chang-Min; Jung, Min Kyu; Jang, Jung Sik; Bae, Han Ik

2017-07-15

The superiority of endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) over EUS-guided fine needle aspiration (EUS-FNA) remains controversial. Given the lack of studies analyzing histologic specimens acquired from EUS-FNB or EUS-FNA, we compared the proportion of the histologic core obtained from both techniques. A total of 58 consecutive patients with solid mass lesions were enrolled and randomly assigned to the EUS-FNA or EUS-FNB groups. The opposite needle was used after the failure of core tissue acquisition using the initial needle with up to three passes. Using computerized analyses of the scanned histologic slide, the overall area and the area of the histologic core portion in specimens obtained by the two techniques were compared. No significant differences were identified between the two groups with respect to demographic and clinical characteristics. Fewer needle passes were required to obtain core specimens in the FNB group (pcore (11.8%±19.5% vs 8.0%±11.1%, p=0.376) or in the diagnostic accuracy (80.6% vs 81.5%, p=0.935) between two groups. The proportion of histologic core and the diagnostic accuracy were comparable between the FNB and FNA groups. However, fewer needle passes were required to establish an accurate diagnosis in EUS-FNB.

Pretreatment Dysphagia in Esophageal Cancer Patients May Eliminate the Need for Staging by Endoscopic Ultrasonography.

Science.gov (United States)

Ripley, R Taylor; Sarkaria, Inderpal S; Grosser, Rachel; Sima, Camelia S; Bains, Manjit S; Jones, David R; Adusumilli, Prasad S; Huang, James; Finley, David J; Rusch, Valerie W; Rizk, Nabil P

2016-01-01

Neoadjuvant therapy is commonly administered to patients with localized disease who have T3-4 esophageal disease as staged by endoscopic ultrasound (EUS). Previously, we noted that patients who present with dysphagia have a higher EUS T stage. We hypothesized that the presence of dysphagia is predictive of EUS T3-4 disease and that staging EUS could be forgone for esophageal cancer patients with dysphagia. We performed a prospective, intent-to-treat, single-cohort study in which patients with potentially resectable esophageal cancer completed a standardized four-tier dysphagia score survey. EUS was performed as part of our standard evaluation. To determine whether the presence of dysphagia predicted EUS T3-4 disease, the dysphagia score was compared with EUS T stage. The study enrolled 114 consecutive patients between August 2012 and February 2014: 77% (88 of 114) received neoadjuvant therapy, 18% (20 of 114) did not, and 5% (6 of 114) pursued treatment elsewhere. In total, 70% (80 of 114) underwent esophagectomy; of these, 54% (61 of 114) had dysphagia and 46% (53 of 114) did not. Dysphagia scores were 66% (40 of 61) grade 1, 25% (15 of 61) grade 2, and 10% (6 of 61) grade 3 to 4. Among patients with dysphagia, 89% (54 of 61) had T3-4 disease by EUS; among those without dysphagia, only 53% (28 of 53) had T3-4 disease by EUS (p < 0.001). The presence of dysphagia in patients with esophageal cancer was highly predictive of T3-4 disease by EUS. On the basis of this finding, approximately 50% of patients currently undergoing staging EUS at our institution could potentially forgo EUS before neoadjuvant therapy. Patients without dysphagia, however, should still undergo EUS. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Image-guided conformation arc therapy for prostate cancer: Early side effects

International Nuclear Information System (INIS)

Soete, Guy; Verellen, Dirk; Michielsen, Dirk; Rappe, Bernard; Keuppen, Frans; Storme, Guy

2006-01-01

Purpose: To evaluate early side effects in prostate cancer patients treated with image-guided conformation arc therapy (IGCAT) using a minimultileaf collimator and daily X-ray-assisted patient positioning. Methods and Materials: Between May 2000 and November 2004, 238 cT1-T3N0M0 tumors were treated with doses of 70 or 78 Gy. Seventy patients also received neoadjuvant or concurrent hormonal treatment. Median follow-up is 18 months (range, 4-55 months). Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity scoring system was used to evaluate early side effects. Results: Grade 1, 2, and >2 acute side effects occurred in 19, 6, and 0% (gastrointestinal) and 37, 16, and 0% (genitourinary) of the patients. No relation between radiation dose and early side effects was observed. Conclusion: Patients treated with image-guided conformation arc therapy experience a low rate of Grade 2 (i.e., requiring medication) early side effects. The definitive evaluation of late side effects and biochemical control requires further follow-up

Molecular image guided radiation therapy-MIGRT in radiobioluminescence and nanoradioguidance

International Nuclear Information System (INIS)

Rao, V.L. Papineni

2014-01-01

Accurate dose delivery to malignant tissue in radiotherapy is essential for enhancing the treatment efficacy while minimizing morbidity of surrounding normal tissues. Advances in therapeutic strategies and diagnosis technologies along with our understanding of the biology of tumor response to radiation therapy have paved way to allow nearly 60% of current cancer patients to be treated with Radiation Therapy. The confluence of molecular imaging and nanotechnology fields are bridging physics and medicine and are quickly making strides in opening new avenues and therapeutic strategies that complement radiation therapy - with a distinct footprint in immunotherapy, adoptive cell therapy, and targeted chemotherapy. Incorporating optical imaging in radiation therapy in my laboratory, endogenous bioluminescence resulting from whole body irradiation in different organs, and in different animals, which is distinct from the Cherenkov radiation. The endogenous bioluminescence in response to irradiation is coined recently as radiobioluminescence. Thus with the necessity, the design, construction, and validation of Molecular Image Guided Radiation Therapy (MIGRT) instrumentation for preclinical theragnostics is carried out

Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model.

Science.gov (United States)

Wang, Meng; Yan, Shi-Ju; Zhang, Hong-Tao; Li, Nan; Liu, Tao; Zhang, Ying-Long; Li, Xiao-Xiang; Ma, Qiong; Qiu, Xiu-Chun; Fan, Qing-Yu; Ma, Bao-An

2017-02-01

The treatment of malignant tumors following surgery is important in preventing relapse. Among all the post-surgery treatments, immunomodulators have demonstrated satisfactory effects on preventing recurrence according to recent studies. Ginsenoside is a compound isolated from panax ginseng, which is a famous traditional Chinese medicine. Ginsenoside aids in killing tumor cells through numerous processes, including the antitumor processes of ginsenoside Rh2 and Rg1, and also affects the inflammatory processes of the immune system. However, the role that ginsenoside serves in antitumor immunological activity remains to be elucidated. Therefore, the present study aimed to analyze the effect of ginsenoside Rh2 on the antitumor immunological response. With a melanoma mice model, ginsenoside Rh2 was demonstrated to inhibit tumor growth and improved the survival time of the mice. Ginsenoside Rh2 enhanced T-lymphocyte infiltration in the tumor and triggered cytotoxicity in spleen lymphocytes. In addition, the immunological response triggered by ginsenoside Rh2 could be transferred to other mice. In conclusion, the present study provides evidence that ginsenoside Rh2 treatment enhanced the antitumor immunological response, which may be a potential therapy for melanoma.

NMR guided focused ultrasound for myoma therapy - results from the first radiology-gynecology expert meeting

International Nuclear Information System (INIS)

Beck, A.; Charite Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin; David, M.; Kroencke, T.; Charite Universitaetsmedizin Berlin, Campus Charite Mitte, Berlin

2013-01-01

The contribution on the results from the first radiology-gynecology expert meeting concerning NMR guided focused ultrasound (MRgFUS) for myoma therapy covers the following topics: structural prerequisites for MRgFUS therapy; required examinations before MRgFUS therapy; indication for MRgFUS therapy; success criteria for the MRgFUS therapy; contraindications; MRgFUS therapy for patients that want to have children; side effects and complications of MRgFUS therapy; post-examination after MRgFUS therapy.

Endoscopic ultrasound-guided biliary drainage using a newly designed metal stent with a thin delivery system: a preclinical study in phantom and porcine models.

Science.gov (United States)

Minaga, Kosuke; Kitano, Masayuki; Itonaga, Masahiro; Imai, Hajime; Miyata, Takeshi; Yamao, Kentaro; Tamura, Takashi; Nuta, Junya; Warigaya, Kenji; Kudo, Masatoshi

2017-12-08

This study was designed to evaluate the feasibility and safety of a newly designed self-expandable metal stent for endoscopic ultrasound-guided biliary drainage (EUS-BD) when it was delivered via three different stent delivery systems: a 7.5Fr delivery catheter with a bullet-shaped tip (7.5Fr-bullet), a 7Fr catheter with a bullet-shaped tip (7Fr-bullet), or a 7Fr catheter with a tee-shaped tip (7Fr-tee). This experimental study utilized a porcine model of biliary dilatation involving ten pigs. In the animal study, technical feasibility and clinical outcomes of the stent when placed with each of the delivery systems were examined. In addition, a phantom model was used to measure the resistance of these delivery systems to advancement. Phantom experiments showed that, compared with 7Fr-bullet, 7Fr-tee had less resistance force to the advancement of the stent delivery system. EUS-BD was technically successful in all ten pigs. Fistulous tract dilation was necessary in 100% (2/2), 75% (3/4), and 0% (0/4) of the pigs that underwent EUS-BD using 7.5Fr-bullet, 7Fr-bullet, and 7Fr-tee, respectively. There were no procedure-related complications. Our newly designed metal stent may be feasible and safe for EUS-BD, particularly when delivered by 7Fr-tee, because it eliminates the need for fistulous tract dilation.

RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer.

Science.gov (United States)

Vishnu, Prakash; Colon-Otero, Gerardo; Kennedy, Gregory T; Marlow, Laura A; Kennedy, William P; Wu, Kevin J; Santoso, Joseph T; Copland, John A

2012-03-01

The aim was to evaluate antitumor activity of the combination of ixabepilone and sunitinib in pre-clinical models of chemotherapy naïve and refractory epithelial ovarian tumors, and to investigate the mechanism of synergy of such drug combination. HOVTAX2 cell line was derived from a metastatic serous papillary epithelial ovarian tumor (EOC) and a paclitaxel-resistant derivative was established. Dose response curves for ixabepilone and sunitinib were generated and synergy was determined using combination indexes. The molecular mechanism of antitumor synergy was examined using shRNA silencing. The combination of ixabepilone and sunitinib demonstrated robust antitumor synergy in naïve and paclitaxel-resistant HOVTAX2 cell lines due to increased apoptosis. The GTPase, RhoB, was synergistically upregulated in cells treated with ixabepilone and sunitinib. Using shRNA, RhoB was demonstrated to mediate antitumor synergy. These results were validated in two other EOC cell lines. Ixabepilone plus sunitinib demonstrated antitumor synergy via RhoB in naïve and paclitaxel-resistant cells resulting in apoptosis. This study demonstrates a novel mechanism of action leading to antitumor synergy and provides 'proof-of-principle' for combining molecular targeted agents with cytotoxic chemotherapy to improve antitumor efficacy. RhoB could be envisioned as an early biomarker of response to therapy in a planned Phase II clinical trial to assess the efficacy of ixabepilone combined with a receptor tyrosine kinase inhibitor such as sunitinib. To the best of our knowledge, this is the first demonstration of antitumor synergy between these two classes of drugs in EOC and the pivotal role of RhoB in this synergy. Copyright © 2011 Elsevier Inc. All rights reserved.

Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo.

Science.gov (United States)

Inami, Koichi; Abe, Masaaki; Takeda, Kazuyoshi; Hagiwara, Yoshiaki; Maeda, Masahiro; Segawa, Tatsuya; Suyama, Masafumi; Watanabe, Sumio; Hino, Okio

2010-04-01

Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C-ERC/mesothelin and N-ERC/mesothelin. In this study, we investigated the antitumor activity of C-ERC/mesothelin-specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC-MESO-4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC-MESO-4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab')(2) fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody-dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell-mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C-ERC/mesothelin-expressing cancers including mesothelioma.

Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy.

Science.gov (United States)

Tsai, Y-S; Shiau, A-L; Chen, Y-F; Tsai, H-T; Tzai, T-S; Wu, C-L

2010-01-01

The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope-modified ones had extended viral tropism to human HER2-expressing bladder cancer cell lines, induced apoptosis, and affected cell cycle progression despite lower viral titers. Moreover, animal studies showed that envelope-modified gammaretroviruses carrying IL-12 gene exerted higher antitumor activity in terms of retarding tumor growth and prolonging the survival of tumor-bearing mice than unmodified ones, which were associated with enhanced tumor cell apoptosis as well as increased intratumoral levels of IL-12, interferon-gamma, IL-1beta, and tumor necrosis factor-alpha proteins. Therefore, the antitumor activity of gammaretroviruses carrying the IL-12 gene was enhanced through genetic modification of the envelope targeting HER2 receptor, which may be a promising strategy for bladder cancer therapy.

NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide)-Guided Therapy in Acute Decompensated Heart Failure: PRIMA II Randomized Controlled Trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?).

Science.gov (United States)

Stienen, Susan; Salah, Khibar; Moons, Arno H; Bakx, Adrianus L; van Pol, Petra; Kortz, R A Mikael; Ferreira, João Pedro; Marques, Irene; Schroeder-Tanka, Jutta M; Keijer, Jan T; Bayés-Genis, Antoni; Tijssen, Jan G P; Pinto, Yigal M; Kok, Wouter E

2018-04-17

The concept of natriuretic peptide guidance has been extensively studied in patients with chronic heart failure (HF), with only limited success. The effect of NT-proBNP (N-terminal probrain natriuretic peptide)-guided therapy in patients with acute decompensated HF using a relative NT-proBNP target has not been investigated. This study aimed to assess whether NT-proBNP-guided therapy of patients with acute decompensated HF using a relative NT-proBNP target would lead to improved outcomes compared with conventional therapy. We conducted a prospective randomized controlled trial to study the impact of in-hospital guidance for acute decompensated HF treatment by a predefined NT-proBNP target (>30% reduction from admission to discharge) versus conventional treatment. Patients with acute decompensated HF with NT-proBNP levels >1700 ng/L were eligible. After achieving clinical stability, 405 patients were randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point was dual: a composite of all-cause mortality and HF readmissions in 180 days and the number of days alive out of the hospital in 180 days. Secondary end points were all-cause mortality within 180 days, HF readmissions within 180 days, and a composite of all-cause mortality and HF readmissions within 90 days. Significantly more patients in the NT-proBNP-guided therapy group were discharged with an NT-proBNP reduction of >30% (80% versus 64%, P =0.001). Nonetheless, NT-proBNP-guided therapy did not significantly improve the combined event rate for all-cause mortality and HF readmissions (hazard ratio, 0.96; 95% confidence interval, 0.72-1.37; P =0.99) or the median number of days alive outside of the hospital (178 versus 179 days for NT-proBNP versus conventional patients, P =0.39). Guided therapy also did not significantly improve any of the secondary end points. The PRIMA II trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure

MRI-guided prostate focal laser ablation therapy using a mechatronic needle guidance system

Science.gov (United States)

Cepek, Jeremy; Lindner, Uri; Ghai, Sangeet; Davidson, Sean R. H.; Trachtenberg, John; Fenster, Aaron

2014-03-01

Focal therapy of localized prostate cancer is receiving increased attention due to its potential for providing effective cancer control in select patients with minimal treatment-related side effects. Magnetic resonance imaging (MRI)-guided focal laser ablation (FLA) therapy is an attractive modality for such an approach. In FLA therapy, accurate placement of laser fibers is critical to ensuring that the full target volume is ablated. In practice, error in needle placement is invariably present due to pre- to intra-procedure image registration error, needle deflection, prostate motion, and variability in interventionalist skill. In addition, some of these sources of error are difficult to control, since the available workspace and patient positions are restricted within a clinical MRI bore. In an attempt to take full advantage of the utility of intraprocedure MRI, while minimizing error in needle placement, we developed an MRI-compatible mechatronic system for guiding needles to the prostate for FLA therapy. The system has been used to place interstitial catheters for MRI-guided FLA therapy in eight subjects in an ongoing Phase I/II clinical trial. Data from these cases has provided quantification of the level of uncertainty in needle placement error. To relate needle placement error to clinical outcome, we developed a model for predicting the probability of achieving complete focal target ablation for a family of parameterized treatment plans. Results from this work have enabled the specification of evidence-based selection criteria for the maximum target size that can be confidently ablated using this technique, and quantify the benefit that may be gained with improvements in needle placement accuracy.

Experimental study of anti-tumor activity of direct current

International Nuclear Information System (INIS)

Ito, Hisao; Hashimoto, Shozo

1989-01-01

The anti-tumor activity of direct current combined with radiation was studied. The experiments were performed with fibrosarcomas (FSA, NFSA) syngenetic to C3H mice. Direct current (0.6mA, 120min) alone was effective to reduce the tumor sizes, but could not cure the tumors. When the direct current therapy (DC therapy) was combined with radiation the DC therapy following radiation was more effective than that before radiation. Using TCD 50 assay, the DC therapy enhanced the effect of a single dose of radiation with the dose-modifying factor of 1.2. However, tumor control rates by the combination therapy were more improved at the smaller doses of radiation than at the larger ones. When the single DC therapy (0.6mA, 120min) was applied immediately after the first radiation of fractionated one the combination therapy still showed the enhanced effect. However, both DC therapy and the radiation therapy were divided in three fractions, and the DC therapy (0.6mA, 40min) was applied after each radiation. Tumor growth retardation by the combination therapy was no different from that by radiation alone. This result suggests that there might be a minimum required dose of coulombs to show the effect of the combination therapy. (author)

Utility of core biopsy with concurrent ROSE FNA in the diagnosis of pancreatic tumor-does the biopsy add any diagnostic benefit?

Science.gov (United States)

Yan, Lei; Ikemura, Kenji; Park, Ji-Weon

2018-02-01

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided core-needle biopsy (EUS-CNB) are widely used for diagnosis of pancreatic tumors. The aim of our study was to compare the diagnostic performance of ROSE EUS-FNA and EUS-CNB for diagnosis of pancreatic malignancy during the same EUS. Patients who underwent both FNA and CNB during the same EUS for pancreatic solid lesion were reviewed retrospectively. Sample adequacy, diagnostic yield (defined as percentage of definitive diagnosis), sensitivity and specificity for malignancy were compared between FNA and CNB. A total of 48 patients with solid pancreatic lesions were evaluated. The proportions of adequate samples were 48/48 (100%) for FNA and 45/48 (93.7%) for core biopsy (P = .24). The diagnostic yield was 42/48 (87.5%) and 33/48 (68.7%) for FNA and CNB respectively (P = .046). The incremental increase in diagnostic yield by combining both methods was 2/48 (4%). The diagnostic yield for malignancy was 30/32 (93.7%) for FNA and 23/32 (71.8%) for CNB (P = .043). The sensitivity for the diagnosis of malignancy for FNA and CNB were 90.6% and 69%, respectively (P = .045). The specificity was 100% for both methods. The sensitivity for diagnosing malignancy increased to 93.8% when the two methods were combined. The difference in diagnostic yield was not associated with lesion size or location. EUS-guided FNA is a superior method of assessing solid pancreatic lesion and pancreatic malignancy with better diagnostic yield and higher sensitivity than EUS-CNB. © 2017 Wiley Periodicals, Inc.

USES 2.0, The Uniform System for the Evaluation of Substances, version 2.0 ; supplement to EUSES

OpenAIRE

Linders JBHJ; Jager DT (eds.); CSR; ECO

1997-01-01

This interim report describes the updated risk assessment system for agricultural and non-agricultural pesticides. It will be integrated with the European Union System for the Evaluation of Substances, EUSES 1.0, into USES 2.0, the second version of the Uniform System for the Evaluation of Substances. The report is primarily made as preparation to the programming and testing of USES 2.0.

Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

Directory of Open Access Journals (Sweden)

Xi Lin

2017-11-01

Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

Science.gov (United States)

Georgianos, Panagiotis I; Champidou, Eleni; Liakopoulos, Vassilios; Balaskas, Elias V; Zebekakis, Pantelis E

2018-04-01

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

The role of surveillance cultures in guiding ventilator-associated pneumonia therapy.

Science.gov (United States)

Luna, Carlos M; Bledel, Ignacio; Raimondi, Alejandro

2014-04-01

Ventilator-associated pneumonia (VAP) is the most frequent cause of death among the nosocomial infections acquired in the ICU. Routine surveillance endotracheal aspirate (ETA) cultures in patients on mechanical ventilation have been proposed to predict the cause of VAP. Our aim is to review the available experience regarding the role of surveillance ETA cultures in guiding VAP antimicrobial therapy. Microorganisms arrive in the lower respiratory tract by aspiration from the oropharynx or gastric reflux, extension from a contiguous infection, air contamination or by hematogenous seeding. Bacterial colonization of the airway leads to the development of VAP and may result from the aspiration of oropharyngeal or gastric secretions. Recent studies have suggested that surveillance cultures could provide a rationale for prescribing appropriate antibiotics, while waiting for culture results, in up to 95% of patients in whom VAP is ultimately diagnosed by bronchoalveolar lavage fluid culture. However, some authors observed that guiding therapy with those routine surveillance cultures leads to unacceptably low coverage of the pathogens producing VAP. This article describes the evidence supporting the use of routine ETA cultures to prescribe appropriate initial empirical therapy compared with the current practice dictated by guidelines.

The cost of molecular-guided therapy in oncology: a prospective cost study alongside the MOSCATO trial.

Science.gov (United States)

Pagès, Arnaud; Foulon, Stéphanie; Zou, Zhaomin; Lacroix, Ludovic; Lemare, François; de Baère, Thierry; Massard, Christophe; Soria, Jean-Charles; Bonastre, Julia

2017-06-01

There is increasing use of molecular technologies to guide cancer treatments, but few cost data are available. Our objective was to assess the costs of molecular-guided therapy for patients with advanced solid tumors alongside the Molecular Screening for Cancer Treatment and Optimization (MOSCATO) trial. The study population consisted of 529 patients. The molecular diagnosis included seven steps from tumor biopsy to the multidisciplinary molecular tumor board. The cost of a complete molecular diagnosis was assessed by micro-costing. Direct costs incurred from enrollment until progression were assessed from the French National Health Insurance perspective. The patients' mean age was 54 years (range: 3-82) and the mean follow-up period was 145 days (range: 1-707 days). A complete molecular diagnosis cost [euro ]2,396. There were 220 patients with an actionable target (42%), among whom 105 (20%) actually received a targeted therapy. The cost of molecular-guided therapy per patient was [euro ]31,269. The main cost drivers were anticancer drugs (54%) and hospitalizations (35%). This prospective cost analysis showed that molecular diagnosis accounts for only 6% of the cost of molecular-guided therapy per patient. The costs of drugs and hospitalizations are the main cost drivers.Genet Med advance online publication 01 December 2016.

Diagnostic Yield and Safety of Endoscopic Ultrasound Guided Fine Needle Aspiration of Central Mediastinal Lung Masses

Directory of Open Access Journals (Sweden)

Enrique Vazquez-Sequeiros

2013-01-01

Full Text Available Background and Aims. EUS-FNA is an accurate and safe technique to biopsy mediastinal lymph nodes. However, there are few data pertaining to the role of EUS-FNA to biopsy central lung masses. The aim of the study was to assess the diagnostic yield and safety of EUS-FNA of indeterminate central mediastinal lung masses. Methods. Design: Retrospective review of a prospectively maintained database; noncomparative. Setting: Tertiary referral center. From 10/2004 to 12/2010, all patients with a lung mass located within proximity to the esophagus were referred for EUS-FNA. Main Outcome Measurement: EUS-FNA diagnostic accuracy and safety. Results. 73 consecutive patients were included. EUS allowed detection in 62 (85% patients with lack of visualization prohibiting FNA in 11 patients. Among sampled lesions, one patient (1/62 = 1.6% had a benign lung mass (hamartoma, while the remaining 61 patients (61/62 = 98.4% had a malignant mass (primary lung cancer: 55/61 = 90%; lung metastasis: 6/61 = 10%. The sensitivity, specificity, and accuracy of EUS-FNA were 96.7%, 100%, and 96.7%, respectively. The sensitivity was 80.8% when considering nonvisualized masses. One patient developed a pneumothorax (1/62 = 1.6%. Conclusions. EUS-FNA appears to be an accurate and safe technique for tissue diagnosis of central mediastinal lung masses.

A qualitative examination of psychology graduate students' experiences with guided Internet-delivered cognitive behaviour therapy

Directory of Open Access Journals (Sweden)

Lindsay N. Friesen

2014-04-01

Full Text Available Guided Internet-delivered cognitive behaviour therapy (ICBT is efficacious for the treatment of a variety of clinical disorders (Spek et al., 2007, yet minimal research has investigated training students in guided ICBT. To contribute to the training literature, through qualitative interviews, this study explored how ICBT was perceived by student therapists (n = 12 trained in guided ICBT. Additionally, facilitators and challenges encountered by students learning guided ICBT were examined. Qualitative analysis revealed that students perceived training to enhance their professional skills in guided ICBT such as how to gain informed consent, address emergencies, and facilitate communication over the Internet. Students described guided ICBT as beneficial for novice therapists learning cognitive behavior therapy as asynchronous communication allowed them to reflect on their clinical emails and seek supervision. Further, students perceived guided ICBT as an important skill for future practice and an avenue to improve patient access to mental health care. Specific facilitators of learning guided ICBT included having access to formal and peer supervision as well as technical assistance, ICBT modules, a functional web application, and detailed policies and procedures for the practice of guided ICBT. Challenges in delivering guided ICBT were also identified by participants such as finding time to learn the approach given other academic commitments, working with non-responsive clients, addressing multiple complex topics over email, and communicating through asynchronous emails. Based on the feedback collected from participants, recommendations for training in guided ICBT are offered along with future research directions.

Image-guided macular laser therapy: design considerations and progress toward implementation

Science.gov (United States)

Berger, Jeffrey W.; Shin, David S.

1999-06-01

Laser therapy is currently the only treatment of proven benefit for exudative age related macular degeneration and diabetic retinopathy. To guide treatment for macular diseases, investigations were initiated to permit overlay of previously-stored angiographic images and image sequences superimposed onto the real-time biomicroscopic fundus image. Prior to treatment, a set of partially overlapping fundus images is acquired and montaged in order to provide a map for subsequent tracking operations. A binocular slit-lamp biomicroscope interfaced to a CCD camera, framegrabber board, and PC permits acquisition and rendering of retinal images. Computer-vision algorithms facilitate robust tracking, registration, and near-video-rate image overlay of previously-stored retinal photographic and angiographic images onto the real-time fundus image. Laser treatment is guided in this augmented reality environment where the borders of the treatment target--for example, the boundaries of a choroidal neovascularization complex--are easily identified through overlay of angiographic information superimposed on, and registered with, the real-time fundus image. During periods of misregistration as judged by the amplitude of the tracking similarity metric, laser function is disabled, affording additional safety. Image-guided macular laser therapy should facilitate accurate targeting of treatable lesions and less unintentional retinal injury when compared with standard techniques.

Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies.

Science.gov (United States)

Monjazeb, Arta M; Kent, Michael S; Grossenbacher, Steven K; Mall, Christine; Zamora, Anthony E; Mirsoian, Annie; Chen, Mingyi; Kol, Amir; Shiao, Stephen L; Reddy, Abhinav; Perks, Julian R; T N Culp, William; Sparger, Ellen E; Canter, Robert J; Sckisel, Gail D; Murphy, William J

2016-09-01

Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects. These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR. ©2016 American Association for Cancer Research.

Anti-tumor effect of a recombinant plasmid expressing human interleukin-12: an initial research

International Nuclear Information System (INIS)

Zheng Chuansheng; Xia Xiangwen; Feng Gansheng; Li Xin; Liang Huimin; Liang Bin

2010-01-01

Objective: To study the anti-tumor effect of a recombinant plasmid expressing human interleukin-12 (pEGFP-CI I L- 12) in vivo and in vitro. Methods: We transduct the recombinant gene (pEGFP-CI I L-12) to liver cancer cell HepG 2 in vitro, and detect reproductive activity of the cell using MTT and the activity of expressing vascular endothelial growth factor(VEGF) using semiquantitative PCR. And then, we deliver the gene to rabbit liver tumor tissue intraarterial and combine with chemoembolization to observe the anti- tumor effect to VX 2 tumor in vivo. Results: There are no statistical difference compared With control group in activity of reproductive and expressing VEGF in vitro. In vivo, tumor growth rate significantly reduce in gene therapy combined with chemoembolization group. Conclusion: Recombinant gene (pEGFP-Cl I L-12) exhibit significant anti-tumor effect in vivo but not in vitro, perhaps the anti-tumor effect is associated with an indirect pathway instead of a direct pathway. (authors)

How does ionizing irradiation contribute to the induction of anti-tumor immunity?

Directory of Open Access Journals (Sweden)

Yvonne eRubner

2012-07-01

Full Text Available Radiotherapy (RT with ionizing irradiation is commonly used to locally attack tumors. It induces a stop of cancer cell proliferation and finally leads to tumor cell death. During the last years it has become more and more evident that besides a timely and locally restricted radiation-induced immune suppression, a specific immune activation against the tumor and its metastases is achievable by rendering the tumor cells visible for immune attack. The immune system is involved in tumor control and we here outline how RT induces anti-inflammation when applied in low doses and contributes in higher doses to the induction of anti-tumor immunity. We especially focus on how local irradiation induces abscopal effects. The latter are partly mediated by a systemic activation of the immune system against the individual tumor cells. Dendritic cells are the key players in the initiation and regulation of adaptive anti-tumor immune responses. They have to take up tumor antigens and consecutively present tumor peptides in the presence of appropriate co-stimulation. We review how combinations of RT with further immune stimulators such as AnnexinA5 and hyperthermia foster the dendritic cell-mediated induction of anti-tumor immune responses and present reasonable combination schemes of standard tumor therapies with immune therapies. It can be concluded that RT leads to targeted killing of the tumor cells and additionally induces non-targeted systemic immune effects. Multimodal tumor treatments should therefore tend to induce immunogenic tumor cell death forms within a tumor microenvironment that stimulates immune cells.

How Does Ionizing Irradiation Contribute to the Induction of Anti-Tumor Immunity?

International Nuclear Information System (INIS)

Rubner, Yvonne; Wunderlich, Roland; Rühle, Paul-Friedrich; Kulzer, Lorenz; Werthmöller, Nina; Frey, Benjamin; Weiss, Eva-Maria; Keilholz, Ludwig; Fietkau, Rainer; Gaipl, Udo S.

2012-01-01

Radiotherapy (RT) with ionizing irradiation is commonly used to locally attack tumors. It induces a stop of cancer cell proliferation and finally leads to tumor cell death. During the last years it has become more and more evident that besides a timely and locally restricted radiation-induced immune suppression, a specific immune activation against the tumor and its metastases is achievable by rendering the tumor cells visible for immune attack. The immune system is involved in tumor control and we here outline how RT induces anti-inflammation when applied in low doses and contributes in higher doses to the induction of anti-tumor immunity. We especially focus on how local irradiation induces abscopal effects. The latter are partly mediated by a systemic activation of the immune system against the individual tumor cells. Dendritic cells are the key players in the initiation and regulation of adaptive anti-tumor immune responses. They have to take up tumor antigens and consecutively present tumor peptides in the presence of appropriate co-stimulation. We review how combinations of RT with further immune stimulators such as AnnexinA5 and hyperthermia foster the dendritic cell-mediated induction of anti-tumor immune responses and present reasonable combination schemes of standard tumor therapies with immune therapies. It can be concluded that RT leads to targeted killing of the tumor cells and additionally induces non-targeted systemic immune effects. Multimodal tumor treatments should therefore tend to induce immunogenic tumor cell death forms within a tumor microenvironment that stimulates immune cells.

How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

Science.gov (United States)

Ward, Mark G; Irving, Peter M; Sparrow, Miles P

2015-10-28

In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.

Harmonic Contrast-Enhanced Endoscopic Ultrasonography for the Guidance of Fine-Needle Aspiration in Solid Pancreatic Masses

DEFF Research Database (Denmark)

Seicean, A; Badea, R; Moldovan-Pop, A

2015-01-01

Purpose: The global accuracy of fine-needle aspiration guided by endoscopic ultrasound (EUS-FNA) for pancreatic adenocarcinoma is about 85 %. The use of contrast agents during EUS to highlight vessels and the necrotic parts of pancreatic masses may improve biopsy guidance. Our aim was to assess...... whether the guidance of FNA by harmonic contrast-enhanced endoscopic ultrasound (CH-EUS) would increase diagnostic accuracy relative to conventional EUS-FNA in the same pancreatic masses. Patients and Methods: In a prospective study, EUS-FNA was performed in patients with pancreatic masses on CT scan......, followed by harmonic CH-EUS using SonoVue. A second cluster of CH-EUS-FNA was performed on contrast-enhanced images. The final diagnosis was based on the results of EUS-FNA and surgery, or the findings after 12 months' follow-up. Results: The final diagnosis was adenocarcinoma (n = 35), chronic...

Benzimidazole as Novel Therapy for Hormone-Refractory Metastatic Prostate Cancer

Science.gov (United States)

2011-05-01

8 4 INTRODUCTION The focus of this project is to evaluate the anti-tumor effects of benzimidazoles as a...potential anti-metastatic prostate cancer therapy. We identified benzimidazoles , a class of anti-parasitic drug, in a drug screening process for...preferential anti-tumor activity on metastatic prostate cancer cells. We have data indicate that benzimidazoles have potent anti-tumor activities

Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

Science.gov (United States)

Yang, Chen; Huang, Junlin; Huang, Xiaowen; Huang, Shaozhuo; Cheng, Jiaxin; Liao, Weixin; Chen, Xuewen; Wang, Xueyi; Dai, Shixue

2018-05-12

The association between anti-tumor necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumor necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. MEDLINE, EMBASE and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumor necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. Twelve studies comprising 285811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumor necrosis factor alpha agents exposed and anti-tumor necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR], 1.43 95%CI, 0.91-2.25, p= 0.116; random effects: risk ratio [RR], 0.83 95%CI, 0.47-1.48, p=0.534). However, monotherapy of anti-tumor necrosis factor alpha agents (random effects: IRR=1.65, 95%CI, 1.16-2.35; p=0.006; random effects: RR=1.00, 95%CI, 0.39-2.59; p=0.996) or combination therapy (random effects: IRR=3.36, 95%CI, 2.23-5.05; ptumor necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumor necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters

NARCIS (Netherlands)

Martinez, Esteban; Visnegarwala, Fehmida; Grund, Birgit; Thomas, Avis; Gibert, Cynthia; Shlay, Judith; Drummond, Fraser; Pearce, Daniel; Edwards, Simon; Reiss, Peter; El-Sadr, Wafaa; Carr, Andrew

2010-01-01

Objective: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or

Endoscopic Ultrasound-Guided Perirectal Abscess Drainage without Drainage Catheter: A Case Series

Directory of Open Access Journals (Sweden)

Eun Kwang Choi

2017-05-01

Full Text Available A perirectal abscess is a relatively common disease entity that occurs as a postsurgical complication or as a result of various medical conditions. Endoscopic ultrasound (EUS-guided drainage was recently described as a promising alternative treatment. Previous reports have recommended placement of a drainage catheter through the anus for irrigation, which is inconvenient to the patient and carries a risk of accidental dislodgement. We report four cases of perirectal abscess that were successfully treated with only one or two 7 F double pigtail plastic stent placements and without a drainage catheter for irrigation.

WE-FG-BRA-07: Theranostic Nanoparticles Improve Clinical MR-Guided Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Detappe, A [Dana-Farber Cancer Institute, Boston, MA (United States); Institut Lumiere-Matiere, Lyon, FR (France); Kunjachan, S; Berbeco, R [Dana-Farber Cancer Institute, Boston, MA (United States); Sancey, L; Motto-Ros, V; Tillement, O [Institut Lumiere-Matiere, Lyon, FR (France)

2016-06-15

Purpose: MR-guided radiation therapy is a current and emerging clinical reality. We have designed and tested a silica-based gadolinium chelates nanoparticle (AGuIX) for integration with MR-guided radiation therapy. The AGuIX nanoparticles used in this study are a dual-modality probe with radiosensitization properties and better MRI contrast than current FDA-approved gadolinium chelates. In advance of an approved Phase I clinical trial, we report on the efficacy and safety in multiple animal models and clinically relevant radiation conditions. By modeling our study on current clinic workflows, we show compatibility with modern patient care, thus heightening the translational significance of this research. Methods: The dual imaging and therapy functionality of AGuIX was investigated in mice with clinical radiation beams while safety was evaluated in mice, and nonhuman primates after systemic injection of 0.25 mg/g of nanoparticles. MRI/ICP-MS were used to measure tumor uptake and biodistribution. Due to their small size (2–3 nm), AGuIX have good renal clearance (t1/2=19min). We performed in vitro cell uptake quantification and radiosensitization studies (clonogenic assays and DNA damage quantification). In vivo radiation therapy studies were performed with both 6MV and 6MV-FFF clinical radiation beams. Histology was performed to measure the increase in DNA damage in the tumor and to evaluate the toxicity in healthy tissues. Results: In vitro and in vivo results demonstrate statistically significant increase (P < 0.01) in DNA damage, tumor growth supression and survival (+100 days) compared to radiation alone. Negligible toxicity was observed in all of the animal models. The combination of 6MV-FFF/AGuIX demonstrated a substantial dose enhancement compared to 6MV/AGuIX (DEF = 1.36 vs. 1.22) due to the higher proportion of low energy photons. Conclusion: With demonstrated efficacy and negligible toxicity in mice and non-human primates, AGuIX is a biocompatible

WE-FG-BRA-07: Theranostic Nanoparticles Improve Clinical MR-Guided Radiation Therapy

International Nuclear Information System (INIS)

Detappe, A; Kunjachan, S; Berbeco, R; Sancey, L; Motto-Ros, V; Tillement, O

2016-01-01

Purpose: MR-guided radiation therapy is a current and emerging clinical reality. We have designed and tested a silica-based gadolinium chelates nanoparticle (AGuIX) for integration with MR-guided radiation therapy. The AGuIX nanoparticles used in this study are a dual-modality probe with radiosensitization properties and better MRI contrast than current FDA-approved gadolinium chelates. In advance of an approved Phase I clinical trial, we report on the efficacy and safety in multiple animal models and clinically relevant radiation conditions. By modeling our study on current clinic workflows, we show compatibility with modern patient care, thus heightening the translational significance of this research. Methods: The dual imaging and therapy functionality of AGuIX was investigated in mice with clinical radiation beams while safety was evaluated in mice, and nonhuman primates after systemic injection of 0.25 mg/g of nanoparticles. MRI/ICP-MS were used to measure tumor uptake and biodistribution. Due to their small size (2–3 nm), AGuIX have good renal clearance (t1/2=19min). We performed in vitro cell uptake quantification and radiosensitization studies (clonogenic assays and DNA damage quantification). In vivo radiation therapy studies were performed with both 6MV and 6MV-FFF clinical radiation beams. Histology was performed to measure the increase in DNA damage in the tumor and to evaluate the toxicity in healthy tissues. Results: In vitro and in vivo results demonstrate statistically significant increase (P < 0.01) in DNA damage, tumor growth supression and survival (+100 days) compared to radiation alone. Negligible toxicity was observed in all of the animal models. The combination of 6MV-FFF/AGuIX demonstrated a substantial dose enhancement compared to 6MV/AGuIX (DEF = 1.36 vs. 1.22) due to the higher proportion of low energy photons. Conclusion: With demonstrated efficacy and negligible toxicity in mice and non-human primates, AGuIX is a biocompatible

Solid Pseudopapillary Neoplasm of the Pancreas in Young Male Patients: Three Case Reports

Directory of Open Access Journals (Sweden)

Akira Aso

2017-01-01

Full Text Available A preoperative diagnosis of solid pseudopapillary neoplasms (SPNs in young male patients is difficult to achieve using radiological images. We herein present three cases of young male patients with relatively small SPNs. Endoscopic ultrasound (EUS showed well-encapsulated, smooth-surfaced, heterogeneous solid lesions in all patients, and all preoperative diagnoses were achieved by EUS-guided fine needle aspiration (EUS-FNA. The final pathological diagnosis after surgery was an SPN with a Ki-67 labeling index of <2%. SPNs should be considered even in young male patients. EUS with EUS-FNA could be a useful diagnostic modality for SPNs even in young male patients.

CT guided interventional therapy for hypertensive cerebral hemorrhage

International Nuclear Information System (INIS)

Lin Bo; Duan Bing

2009-01-01

Objective: To discuss the curative effect of CT-guided puncture and drainage in treating hypertensive cerebral hemorrhage. Methods: Adjusting the suitable point and direction of puncture according to the form and size of the haematoma and patient's status, the haematoma was eliminated by minimally invasive puncture and drainage guided under CT layer image in 40 cases of hypertensive cerebral hemorrhage. Results: Modality rate of treatment group was 12.5% (5/40), and is much lower than control group, which was 45% (13/30) (P<0.01). When asscess the Activities of Daily Living (ADL) after 6 months follow-up, the ADL1-ADL3 scale in treatment group was 27 cases (70%), and was much higher than that in control group, which was 29.4% (5/17), (P < 0.05). Conclusion: Minimal invasive therapy of cerebral hemorrhage has great superiority in elimination most part of the hematoma such as simple, accurate location, low cost, safe and effective, and is worthy of recommendation clinically. (authors)

Improvement of Antitumor Therapies Based on Vaccines and Immune-Checkpoint Inhibitors by Counteracting Tumor-Immunostimulation

Directory of Open Access Journals (Sweden)

Paula Chiarella

2018-01-01

Full Text Available Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors, counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth.

Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: a multicenter study

DEFF Research Database (Denmark)

Giovannini, Marc; Thomas, Botelberge; Erwan, Bories

2009-01-01

AIM: To evaluate the ability of endoscopic ultrasound (EUS) elastography to distinguish benign from malignant pancreatic masses and lymph nodes. METHODS: A multicenter study was conducted and included 222 patients who underwent EUS examination with assessment of a pancreatic mass (n = 121) or lymph...... node (n = 101). The classification as benign or malignant, based on the real time elastography pattern, was compared with the classification based on the B-mode EUS images and with the final diagnosis obtained by EUS-guided fine needle aspiration (EUS-FNA) and/or by surgical pathology. An interobserver...... study was performed. RESULTS: The sensitivity and specificity of EUS elastography to differentiate benign from malignant pancreatic lesions are 92.3% and 80.0%, respectively, compared to 92.3% and 68.9%, respectively, for the conventional B-mode images. The sensitivity and specificity of EUS...

Fluorescence and Magnetic Resonance Dual-Modality Imaging-Guided Photothermal and Photodynamic Dual-Therapy with Magnetic Porphyrin-Metal Organic Framework Nanocomposites

Science.gov (United States)

Zhang, Hui; Li, Yu-Hao; Chen, Yang; Wang, Man-Man; Wang, Xue-Sheng; Yin, Xue-Bo

2017-03-01

Phototherapy shows some unique advantages in clinical application, such as remote controllability, improved selectivity, and low bio-toxicity, than chemotherapy. In order to improve the safety and therapeutic efficacy, imaging-guided therapy seems particularly important because it integrates visible information to speculate the distribution and metabolism of the probe. Here we prepare biocompatible core-shell nanocomposites for dual-modality imaging-guided photothermal and photodynamic dual-therapy by the in situ growth of porphyrin-metal organic framework (PMOF) on Fe3O4@C core. Fe3O4@C core was used as T2-weighted magnetic resonance (MR) imaging and photothermal therapy (PTT) agent. The optical properties of porphyrin were well remained in PMOF, and PMOF was therefore selected for photodynamic therapy (PDT) and fluorescence imaging. Fluorescence and MR dual-modality imaging-guided PTT and PDT dual-therapy was confirmed with tumour-bearing mice as model. The high tumour accumulation of Fe3O4@C@PMOF and controllable light excitation at the tumour site achieved efficient cancer therapy, but low toxicity was observed to the normal tissues. The results demonstrated that Fe3O4@C@PMOF was a promising dual-imaging guided PTT and PDT dual-therapy platform for tumour diagnosis and treatment with low cytotoxicity and negligible in vivo toxicity.

Magnetic resonance guided focalized ultrasound thermo-ablation: A promising oncologic local therapy

International Nuclear Information System (INIS)

Iannessi, A.; Doyen, J.; Leysalle, A.; Thyss, A.

2014-01-01

Pain management of bone metastases is usually made using systemic and local therapy. Even though radiations are nowadays the gold standard for painful metastases, innovations regarding minimally invasive treatment approaches have been developed because of the existing non-responder patients [1]. Indeed, cementoplasty and thermo-ablations like radiofrequency or cryotherapy have shown to be efficient on pain [2-4]. Among thermo-therapy, magnetic resonance guided focalized ultrasound is now a new non-invasive weapon for bone pain palliation. (authors)

CT-guided periradicular therapy in cervical and lumbar radicular syndromes

International Nuclear Information System (INIS)

Nian Dingfang; Zhou Jun; Li Wenhua; Cao Qingxuan; Xia Baosu; Apitzsch, D.E.

2007-01-01

Objective: To evaluate the effectiveness of CT-guided periradicular therapy (PRT) in cervical and lumber radicular syndromes. Methods: Seventy two cases of cervical and lumbar radicular syndromes were treated by CT-guided PRT. During PRT, 10-20 mg of Triamhexal and 3-4 ml of Carbostesin 0.25%(Bupivacainhydrochlorid) were injected into the space around the corresponding spinal root, once a week, all together six times as a course. Results: Four hundreds and forty six PRT procedures were carried out in 72 patients having a successful puncture and a satisfying spread of Triamhexal and Carbostesin around the spinal nerve root space for every time. After 6 to 24 months follow up, 62 patients showed a significant pain reduction or complete disappearance. Moderate improvement was not noted in 6 and no improvement in 4. The effective rate was 94.4% without any correlative complication. Conclusions: CT-guided PRT is an effective, easy and safe procedure to treat patients with refractory cervical or lumbar radicular pain syndromes. (authors)

Bioluminescence Tomography–Guided Radiation Therapy for Preclinical Research

Energy Technology Data Exchange (ETDEWEB)

Zhang, Bin [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Wang, Ken Kang-Hsin, E-mail: kwang27@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Yu, Jingjing [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); School of Physics and Information Technology, Shaanxi Normal University, Shaanxi (China); Eslami, Sohrab; Iordachita, Iulian [Laboratory for Computational Sensing and Robotics, Johns Hopkins University, Baltimore, Maryland (United States); Reyes, Juvenal; Malek, Reem [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Department of Oncology and Urology, Brady Urological Institute, Johns Hopkins University, Baltimore, Maryland (United States); Patterson, Michael S. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario (Canada); Wong, John W. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland (United States)

2016-04-01

Purpose: In preclinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT) guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for small-animal radiation research platform (SARRP). We demonstrated BLT-guided radiation therapy and validated targeting accuracy based on a newly developed reconstruction algorithm. Methods and Materials: The BLT system was designed to dock with the SARRP for image acquisition and to be detached before radiation delivery. A 3-mirror system was devised to reflect the bioluminescence emitted from the subject to a stationary charge-coupled device (CCD) camera. Multispectral BLT and the incomplete variables truncated conjugate gradient method with a permissible region shrinking strategy were used as the optimization scheme to reconstruct bioluminescent source distributions. To validate BLT targeting accuracy, a small cylindrical light source with high CBCT contrast was placed in a phantom and also in the abdomen of a mouse carcass. The center of mass (CoM) of the source was recovered from BLT and used to guide radiation delivery. The accuracy of the BLT-guided targeting was validated with films and compared with the CBCT-guided delivery. In vivo experiments were conducted to demonstrate BLT localization capability for various source geometries. Results: Online BLT was able to recover the CoM of the embedded light source with an average accuracy of 1 mm compared to that with CBCT localization. Differences between BLT- and CBCT-guided irradiation shown on the films were consistent with the source localization revealed in the BLT and CBCT images. In vivo results demonstrated that our BLT system could potentially be applied for multiple targets and tumors. Conclusions: The online BLT/CBCT/SARRP system provides an effective solution for soft tissue targeting, particularly for small, nonpalpable, or

Bioluminescence Tomography–Guided Radiation Therapy for Preclinical Research

International Nuclear Information System (INIS)

Zhang, Bin; Wang, Ken Kang-Hsin; Yu, Jingjing; Eslami, Sohrab; Iordachita, Iulian; Reyes, Juvenal; Malek, Reem; Tran, Phuoc T.; Patterson, Michael S.; Wong, John W.

2016-01-01

Purpose: In preclinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT) guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for small-animal radiation research platform (SARRP). We demonstrated BLT-guided radiation therapy and validated targeting accuracy based on a newly developed reconstruction algorithm. Methods and Materials: The BLT system was designed to dock with the SARRP for image acquisition and to be detached before radiation delivery. A 3-mirror system was devised to reflect the bioluminescence emitted from the subject to a stationary charge-coupled device (CCD) camera. Multispectral BLT and the incomplete variables truncated conjugate gradient method with a permissible region shrinking strategy were used as the optimization scheme to reconstruct bioluminescent source distributions. To validate BLT targeting accuracy, a small cylindrical light source with high CBCT contrast was placed in a phantom and also in the abdomen of a mouse carcass. The center of mass (CoM) of the source was recovered from BLT and used to guide radiation delivery. The accuracy of the BLT-guided targeting was validated with films and compared with the CBCT-guided delivery. In vivo experiments were conducted to demonstrate BLT localization capability for various source geometries. Results: Online BLT was able to recover the CoM of the embedded light source with an average accuracy of 1 mm compared to that with CBCT localization. Differences between BLT- and CBCT-guided irradiation shown on the films were consistent with the source localization revealed in the BLT and CBCT images. In vivo results demonstrated that our BLT system could potentially be applied for multiple targets and tumors. Conclusions: The online BLT/CBCT/SARRP system provides an effective solution for soft tissue targeting, particularly for small, nonpalpable, or

Dosimetric Comparison of Real-Time MRI-Guided Tri-Cobalt-60 Versus Linear Accelerator-Based Stereotactic Body Radiation Therapy Lung Cancer Plans.

Science.gov (United States)

Wojcieszynski, Andrzej P; Hill, Patrick M; Rosenberg, Stephen A; Hullett, Craig R; Labby, Zacariah E; Paliwal, Bhudatt; Geurts, Mark W; Bayliss, R Adam; Bayouth, John E; Harari, Paul M; Bassetti, Michael F; Baschnagel, Andrew M

2017-06-01

Magnetic resonance imaging-guided radiation therapy has entered clinical practice at several major treatment centers. Treatment of early-stage non-small cell lung cancer with stereotactic body radiation therapy is one potential application of this modality, as some form of respiratory motion management is important to address. We hypothesize that magnetic resonance imaging-guided tri-cobalt-60 radiation therapy can be used to generate clinically acceptable stereotactic body radiation therapy treatment plans. Here, we report on a dosimetric comparison between magnetic resonance imaging-guided radiation therapy plans and internal target volume-based plans utilizing volumetric-modulated arc therapy. Ten patients with early-stage non-small cell lung cancer who underwent radiation therapy planning and treatment were studied. Following 4-dimensional computed tomography, patient images were used to generate clinically deliverable plans. For volumetric-modulated arc therapy plans, the planning tumor volume was defined as an internal target volume + 0.5 cm. For magnetic resonance imaging-guided plans, a single mid-inspiratory cycle was used to define a gross tumor volume, then expanded 0.3 cm to the planning tumor volume. Treatment plan parameters were compared. Planning tumor volumes trended larger for volumetric-modulated arc therapy-based plans, with a mean planning tumor volume of 47.4 mL versus 24.8 mL for magnetic resonance imaging-guided plans ( P = .08). Clinically acceptable plans were achievable via both methods, with bilateral lung V20, 3.9% versus 4.8% ( P = .62). The volume of chest wall receiving greater than 30 Gy was also similar, 22.1 versus 19.8 mL ( P = .78), as were all other parameters commonly used for lung stereotactic body radiation therapy. The ratio of the 50% isodose volume to planning tumor volume was lower in volumetric-modulated arc therapy plans, 4.19 versus 10.0 ( P guided tri-cobalt-60 radiation therapy is capable of delivering lung high

Biofeedback-guided pelvic floor exercise therapy for obstructive defecation: An effective alternative

Science.gov (United States)

ba-bai-ke-re, Ma-Mu-Ti-Jiang A; Wen, Ni-Re; Hu, Yun-Long; Zhao, Liang; Tuxun, Tuerhongjiang; Husaiyin, Aierhati; Sailai, Yalikun; Abulimiti, Alimujiang; Wang, Yun-Hai; Yang, Peng

2014-01-01

AIM: To compare biofeedback-guided pelvic floor exercise therapy (BFT) with the use of oral polyethylene glycol (PEG) for the treatment of obstructive defecation. METHODS: A total of 88 subjects were assigned to treatment with either BFT (n = 44) or oral PEG (n = 44). Constipation symptoms (including difficult evacuation, hard stool, digitation necessity, incomplete emptying sensation, laxative dependence, perianal pain at defecation, and constipation satisfaction), Wexner Scores, and quality of life scores were assessed after 1, 3, and 6 mo. RESULTS: At the 6 mo follow-up, the symptoms of the BFT group patients showed significantly greater improvements compared with the PEG group regarding difficult evacuation, hard stools, digitation necessity, laxative dependence, perianal pain at defecation, constipation satisfaction, Wexner Constipation Score, and quality of life score (P biofeedback-guided pelvic floor exercise training is superior to oral polyethylene glycol therapy for obstructive defecation. PMID:25083090

Paclitaxel-loaded KMnF3 nanoparticles for cancer imaging and therapy in vivo

Science.gov (United States)

Song, Xiao-xia; Wan, Hong-ping; Zhang, Jin-sheng; Tang, Qun

2014-11-01

Biocompatible nanoparticles (NPs) responding to the light, thermal, or magnetic excitation are attracting more attention for diagnosis and therapy of cancer. Design of an effective multifunctional complex based on those NPs is a key issue to be addressed, for example, integration of anti-tumor agents with nanoprobes has been considered as one of the successful strategies for combined cancer diagnosis and therapy. In this paper, we develop paclitaxel (PTX)-loaded PEGylation KMnF3 NP, with the size ranged from 18 to 23 nm, as MRI contrast agents for cancer imaging and drug delivery for chemotherapy. Preliminary cell tests demonstrated that PTX@PEG-KMnF3 NP is highly biocompatible. The NP has high loading capacity of PTX (0.7 mg PTX/mg Mn ions), enhanced solubility of PTX (0.16 mg PTX/ml vs 0.02 mg PTX/ml), and high releasing ratio (90 %) in the weak acid solution. As it was applied for in vivo imaging and therapy, the NP enhanced contrast of tumor's MR images and PTX's anti-tumor effect profoundly. The signal noise ratio of the cancer image increased 170 % as comparison to pre-injection with the injection dose of 1.15 mg Mn/kg. The drug delivery's efficacy was also substantially improved, as the tumor growth inhibition effects reached 50 %, meanwhile only 30 % for pristine PTX. Our studies suggest that PTX-loaded KMnF3 NP might be useful as MR image-guided drug delivery for tumor treatment.

Transesophageal Ultrasonography for Lung Cancer Staging

DEFF Research Database (Denmark)

Konge, Lars; Annema, Jouke; Vilmann, Peter

2013-01-01

Accurate mediastinal nodal staging is essential for patients with resectable non-small-cell lung cancer and is achieved by combined endobronchial ultrasound and transesophageal endoscopic ultrasound (EUS). Training requirements for EUS-guided fine-needle aspiration (FNA) for lung cancer staging...

A dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy.

Science.gov (United States)

Wang, Xu; Yang, Cheng-Xiong; Chen, Jia-Tong; Yan, Xiu-Ping

2014-04-01

The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from 3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of (1)O2 due to multiplexed Förster resonance energy transfer between APBA-UCNPs (donor) and HAC60 (acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.

New endoscopic ultrasonography techniques for pancreticobiliary diseases

Energy Technology Data Exchange (ETDEWEB)

Kamata, Ken; Kitano, Masayuki; Omoto, Shunsuke; Kadosaka, Kumpei; Miyata, Takeshi; Minaga, Kosuke; Yamao, Kentaro; Imai, Hajime; Kudo, Masatoshii [Dept. of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osaka (Japan)

2016-07-15

Endoscopic ultrasonography (EUS) is widely used to evaluate pancreaticobiliary diseases, especially pancreatic masses. EUS has a good ability to detect pancreatic masses, but it is not sufficient for the differential diagnosis of various types of lesions. In order to address the limitations of EUS, new techniques have been developed to improve the characterization of the lesions detected by EUS. EUS-guided fine needle aspiration (EUS-FNA) has been used for diagnosing pancreatic tumors. In order to improve the histological diagnostic yield, a EUS-FNA needle with a core trap has recently been developed. Contrast-enhanced harmonic EUS is a new imaging modality that uses an ultrasonographic contrast agent to visualize blood flow in fine vessels. This technique is useful in the diagnosis of pancreatic solid lesions and in confirming the presence of vascularity in mural nodules for cystic lesions. EUS elastography analyzes several different variables to measure tissue elasticity, color patterns, and strain ratio, using analytical techniques such as hue-histogram analysis, and artificial neural networks, which are useful for the diagnosis of chronic pancreatitis and pancreatic cancer.

In vivo 808 nm image-guided photodynamic therapy based on an upconversion theranostic nanoplatform

Science.gov (United States)

Liu, Xiaomin; Que, Ivo; Kong, Xianggui; Zhang, Youlin; Tu, Langping; Chang, Yulei; Wang, Tong Tong; Chan, Alan; Löwik, Clemens W. G. M.; Zhang, Hong

2015-09-01

A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the 1O2 production, resulting in the improvement of the therapeutic effect; (ii) realizing in vivo NIR 808 nm image-guided PDT with both excitation (980 nm) and emission (808 nm) light falling in the biological window of tissues, which minimized auto-fluorescence, reduced light scatting and improved the imaging contrast and depth, and thus guaranteed noninvasive diagnostic accuracy. In vivo and ex vivo tests demonstrated its favorable bio-distribution, tumor-selectivity and high therapeutic efficacy. Owing to the effective ligand exchange strategy and the excellent intrinsic photophysical properties of C60, 1O2 production yield was improved, suggesting that a low 980 nm irradiation dosage (351 J cm-2) and a short treatment time (15 min) were sufficient to perform NIR (980 nm) to NIR (808 nm) image-guided PDT. Our work enriches the understanding of UCNP-based PDT nanophotosensitizers and highlights their potential use in future NIR image-guided noninvasive deep cancer therapy.A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the 1O2 production, resulting in the improvement of the therapeutic effect; (ii

Comparing Treatment Outcome of Guided Imagery and Music and Psychodynamic Imaginative Trauma Therapy for Women with Complex PTSD

DEFF Research Database (Denmark)

Maack, Carola

2013-01-01

To investigate whether the use of recorded music enhances therapy outcome in psychodynamic trauma therapy for women with Complex PTSD, outcome measures of three groups of patients were compared. One group received 50 hours of outpatient trauma therapy with the Bonny Method of Guided Imagery and M....... Participants treated with GIM showed significantly better outcome in all measurements than participants treated with PITT. This indicates that the use of music is beneficial for women with Complex PTSD treated with psychodynamic trauma therapy.......To investigate whether the use of recorded music enhances therapy outcome in psychodynamic trauma therapy for women with Complex PTSD, outcome measures of three groups of patients were compared. One group received 50 hours of outpatient trauma therapy with the Bonny Method of Guided Imagery...... and Music (GIM), another group received 50 hours of outpatient trauma therapy with Psychodynamic Imaginative Trauma Therapy (PITT). The third group was a waiting-list control group of women who had to wait at least nine months for therapy. The participants filled out questionnaires measuring symptoms...

Rational design of a comprehensive cancer therapy platform using temperature-sensitive polymer grafted hollow gold nanospheres: simultaneous chemo/photothermal/photodynamic therapy triggered by a 650 nm laser with enhanced anti-tumor efficacy

Science.gov (United States)

Deng, Xiaoran; Chen, Yinyin; Cheng, Ziyong; Deng, Kerong; Ma, Ping'an; Hou, Zhiyao; Liu, Bei; Huang, Shanshan; Jin, Dayong; Lin, Jun

2016-03-01

Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of ``killing three birds with one stone'', that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus.Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation

Implementation of Remote 3-Dimensional Image Guided Radiation Therapy Quality Assurance for Radiation Therapy Oncology Group Clinical Trials

Energy Technology Data Exchange (ETDEWEB)

Cui Yunfeng [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Galvin, James M. [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania (United States); Parker, William [Department of Medical Physics, McGill University Health Center, Montreal, QC (Canada); Breen, Stephen [Department of Radiation Physics, Princess Margaret Hospital, Toronto, ON (Canada); Yin Fangfang; Cai Jing [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Papiez, Lech S. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Bednarz, Greg [Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Chen Wenzhou [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Xiao Ying, E-mail: ying.xiao@jefferson.edu [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania (United States)

2013-01-01

Purpose: To report the process and initial experience of remote credentialing of three-dimensional (3D) image guided radiation therapy (IGRT) as part of the quality assurance (QA) of submitted data for Radiation Therapy Oncology Group (RTOG) clinical trials; and to identify major issues resulting from this process and analyze the review results on patient positioning shifts. Methods and Materials: Image guided radiation therapy datasets including in-room positioning CT scans and daily shifts applied were submitted through the Image Guided Therapy QA Center from institutions for the IGRT credentialing process, as required by various RTOG trials. A centralized virtual environment is established at the RTOG Core Laboratory, containing analysis tools and database infrastructure for remote review by the Physics Principal Investigators of each protocol. The appropriateness of IGRT technique and volumetric image registration accuracy were evaluated. Registration accuracy was verified by repeat registration with a third-party registration software system. With the accumulated review results, registration differences between those obtained by the Physics Principal Investigators and from the institutions were analyzed for different imaging sites, shift directions, and imaging modalities. Results: The remote review process was successfully carried out for 87 3D cases (out of 137 total cases, including 2-dimensional and 3D) during 2010. Frequent errors in submitted IGRT data and challenges in the review of image registration for some special cases were identified. Workarounds for these issues were developed. The average differences of registration results between reviewers and institutions ranged between 2 mm and 3 mm. Large discrepancies in the superior-inferior direction were found for megavoltage CT cases, owing to low spatial resolution in this direction for most megavoltage CT cases. Conclusion: This first experience indicated that remote review for 3D IGRT as part of QA

Use of biomarkers to guide outpatient therapy of heart failure.

Science.gov (United States)

DeBeradinis, Benedetta; Januzzi, James L

2012-11-01

Among patients with heart failure, concentrations of natriuretic peptides are strongly linked to the presence and severity of structural heart disease and are strongly prognostic in this setting. Additionally, favorable reduction in the concentration of either B-type natriuretic peptide (BNP) or B-type natriuretic peptide and its amino-terminal cleavage fragment (NT-proBNP) may be seen during treatment of heart failure, with parallel improvement in prognosis. This has led to the hypothesis that intensified treatment directed at reducing natriuretic peptide concentrations may improve outcomes in heart failure. In chronic heart failure, studies suggest that a strategy of standard-of-care management together with a goal to suppress BNP or NT-proBNP concentrations leads to greater application of guideline-derived medical therapy and is well tolerated. In certain studies of this BNP or NT-proBNP 'guided' approach, patients treated with biomarker-guided care had superior outcomes when compared with standard heart failure management alone, particularly in younger study populations, in patients with left ventricular systolic dysfunction, and particularly when substantial reductions in natriuretic peptides were achieved in association with biomarker-guided care. Natriuretic peptide 'guided' management appears promising in patients suffering from chronic heart failure. Large-scale pivotal trials to confirm the approach are planned.

Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients.

Science.gov (United States)

Lew, Daniel; Yoon, Soon Man; Yan, Xiaofei; Robbins, Lori; Haritunians, Talin; Liu, Zhenqiu; Li, Dalin; McGovern, Dermot Pb

2017-10-28

To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations. This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure. Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients (21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the anti-TNF agent. In total: n = 66 (5%) infusion reactions; n = 49 (4%) allergic/serum sickness reactions; n = 19 (1.5%) lupus-like reactions, n = 52 (4%) rash, n = 18 (1.4%) infections. In Crohn's disease, IgA ASCA ( P = 0.04) and IgG-ASCA ( P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions ( P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT (Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. Our study shows 1 in 5 IBD patients experience an adverse

Role of endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

DEFF Research Database (Denmark)

Saftoiu, Adrian; Vilmann, Peter

2009-01-01

. The introduction of EUS-guided fine needle aspiration allows a preoperative diagnosis in patients with resectable cancer, as well as a confirmation of diagnosis before chemoradiotherapy for those that are not. This comprehensive review highlighted the diagnostic capabilities of EUS including the newest refinements...

Nursing care for patients with local recurrent rectal cancer after CT-guided 125I seed implantation therapy

International Nuclear Information System (INIS)

Yuan Li; Wei Fan; Ren Caifeng; Tu Mingmei; Qian Guixiang

2010-01-01

Objective: To discuss the nursing care strategy for patients with local recurrent rectal cancer who has been treated with CT-guided 125 I seed implantation therapy. Methods: Twenty patients with local recurrent rectal cancer received a series of nursing interventions, including comfort care and pain care. The clinical results were observed and analyzed. Results: The therapy was smoothly accomplished in all patients. The pain was remarkably relived and the anxiety was alleviated. No displacement of implanted 125 I seed occurred. Conclusion: For patients with local recurrent rectal cancer occurred after CT-guided 125 I seed implantation therapy, careful nursing can effectively relieve the pain and anxiety feeling,and the living quality can also be markedly improved. (authors)

TU-B-210-00: MR-Guided Focused Ultrasound Therapy in Oncology

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-06-15

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advanced techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.

Piezoelectrically Actuated Robotic System for MRI-Guided Prostate Percutaneous Therapy

OpenAIRE

Su, Hao; Shang, Weijian; Cole, Gregory; Li, Gang; Harrington, Kevin; Camilo, Alexander; Tokuda, Junichi; Tempany, Clare M.; Hata, Nobuhiko; Fischer, Gregory S.

2014-01-01

This paper presents a fully-actuated robotic system for percutaneous prostate therapy under continuously acquired live magnetic resonance imaging (MRI) guidance. The system is composed of modular hardware and software to support the surgical workflow of intra-operative MRI-guided surgical procedures. We present the development of a 6-degree-of-freedom (DOF) needle placement robot for transperineal prostate interventions. The robot consists of a 3-DOF needle driver module and a 3-DOF Cartesian...

Noninvasive MR-Guided HIFU Therapy of TSC-Associated Renal Angiomyolipomas

Science.gov (United States)

2014-09-01

sufficient for this application because coil array configuration is limited by small mouse anatomy. In our third year’s effort, the research plan was...therapy and a new Ingenia 1.5 Tesla MRI scanner from Philips HealthCare. Using the new instrumentation, we established a large animal MR-guided HIFU...anatomy limitation in mice MRI coil development, mouse cancer model was not used eventually. In the third year, we developed a large animal MR

Combination therapy of murine tumors with a degraded D-manno-D-glucan (DMG) from Microellobosporia grisea, and cyclophosphamide.

Science.gov (United States)

Nakajima, H; Hashimoto, S; Kita, Y; Takashi, T; Tsukada, W; Kohno, M; Ogawa, H; Abe, S; Mizuno, D

1983-12-01

DMG, a degraded D-manno-D-glucan with a host-mediated antitumor activity did not significantly enhance nor inhibit the development of suppressor cells for either the antibody-forming response or the delayed hypersensitivity reaction to sheep red blood cells. Cyclophosphamide (CY), which inhibited the generation of suppressor cells, was combined with DMG in treatment of murine syngeneic tumors to obtain a higher antitumor activity. The antitumor activity of the combination against MH134 hepatoma was synergistically higher than that of either component alone. A marked antitumor effect of the combination treatment against MM46 mammary carcinoma was also shown. High levels of antitumor delayed hypersensitivity reactions were observed with this combination therapy. The possible roles of DMG and CY in this combination therapy are discussed.

[Overal cognitive assessment in Basque-speaking people with advanced dementia. Validation to the Basque language of the Severe Mini-Mental State Examination SMMSE (SMMSE-eus)].

Science.gov (United States)

Buiza, Cristina; Yanguas, Javier; Zulaica, Amaia; Antón, Iván; Arriola, Enrique; García, Alvaro

2018-04-13

Adaptation and validation to the Basque language of tests to assess advanced cognitive impairment is a not covered need for Basque-speaking people. The present work shows the validation of the Basque version of the Severe Mini Mental State Examination (SMMSE). A total of 109 people with advanced dementia (MECinternal consistency (alpha=0.92), a good test-retest reliability (r=0.88; Pinternal consistency and inter-rater reliability, and to a lesser extent, test-retest reliability, made the SMMSE-eus a valid test for the brief assessment of cognitive status in people with advanced dementia in Basque-speaking people. For this reason, the SMMSE-eus is a usable and reliable alternative for assessing Basque-speaking people in their mother-tongue, or preferred language. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity.

Science.gov (United States)

Wang, Dongrui; Aguilar, Brenda; Starr, Renate; Alizadeh, Darya; Brito, Alfonso; Sarkissian, Aniee; Ostberg, Julie R; Forman, Stephen J; Brown, Christine E

2018-05-17

Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy.

Development of CAR T cells designed to improve antitumor efficacy and safety

OpenAIRE

Jaspers, Janneke E.; Brentjens, Renier J.

2017-01-01

Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how ...

Endosonography-related mortality and morbidity for pulmonary indications: a nationwide survey in the Netherlands.

Science.gov (United States)

von Bartheld, Martin B; Annema, Jouke T

2015-12-01

Endosonography is being implemented rapidly in pulmonary medicine for the diagnosis and staging of lung cancer, the assessment of sarcoidosis, and the assessment of mediastinal lesions. Although serious adverse events (SAEs) have been described, safety data outside cohort studies are scarce. To assess the SAE and mortality rate of EUS-guided FNA (EUS-FNA) and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal and/or hilar analysis. Nationwide, retrospective survey by using questionnaires. All hospitals in the Netherlands. All patients undergoing EUS-FNA and EBUS-TBNA for intrathoracic analysis in the period 1999 to 2011. EUS-FNA and EBUS-TBNA. Occurrence of fatal outcomes and SAEs. Detailed information was obtained for each reported case, and all cases were reviewed independently by 2 investigators, including identification of risk factors. All 89 hospitals (100%) responded. An estimated 14,075 EUS-FNA and 2675 EBUS procedures were performed. Seven patients died after endosonography (5 EUS-FNA, 2 EBUS [mortality rate 0.04%]). All fatalities occurred in patients of poor performance status (American Society of Anesthesiologists Physical Status Classification System score of III/IV). Twenty-five SAEs were reported (22 EUS-FNA, 3 EBUS [SAE rate of 0.15%; EUS-FNA 0.16%, EBUS 0.11%]). SAEs were mostly (64%) of infectious origin. No specific risk factors for infectious adverse events could be identified. Retrospective study, possible recall bias, overrepresentation of EUS-FNA cases. Endosonography appears to be a safe technique for the analysis of mediastinal and/or hilar lesions. Poor performance status is a risk factor for fatal outcomes. Mediastinitis and/or mediastinal abscess formation is rare but is a potential and dangerous adverse event of endosonography. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

In vitro and in vivo antitumor effects of 50 to 100-KDa components from B16 melanoma culture supernatant.

Science.gov (United States)

Qin, Ying-Song; Zhang, X U; Zhang, Xiang-Yu

2015-07-01

The development of immunological therapies for melanoma has been of considerable concern in recent years. Whole tumor cell lysates have been used to develop antitumor vaccines, but the effective components of the lysates have not been identified. In the present study, protein elements were purified from the B16 supernatant to analyze the in vitro chemotaxis towards mouse spleen lymphocytes using a Boyden chamber. Prior to establishing a B16 melanoma model, C57BL/6 mice were vaccinated with these proteins, and melanoma growth, tumor appearance time and behavioral changes were observed. Next, the cytotoxicity and subsets of the tumor infiltrating lymphocytes, and the histological characteristics of the melanoma were analyzed. The isolated purified fragments of B16 melanoma culture supernatant had strong antitumor effects. The possible antitumor mechanism was delineated, and was identified to possibly be through the activation of cluster of differentiation 8-positive T cells and the promotion of B16 cell differentiation. These methods will provide a novel insight into understanding antitumor immunological mechanisms and provide a potential avenue for immunotherapy.

Efficacy of self-guided internet based cognitive behavioral therapy in the treatment of depressive symptoms : A meta analysis of individual participant data

NARCIS (Netherlands)

Karyotaki, E.; Riper, Heleen; Twisk, Jos W. R.; Hoogendoorn, A.W.; Kleiboer, M.A.; Mira, Adriana; Mackinnon, A.; Meyer, B.; Botella, C.; Littlewood, Elizabeth; Andersson, G.; Christensen, H.; Klein, J.; Schröder, Johanna; Breton-Lopez, Juana; Scheider, Justin; Griffiths, J.; Farrer, L.; Huibers, M. J. H.; Phillips, Rachel; Gilbody, S.; Moritz, S.; Berger, T.; Pop, V.J.M.; Spek, V.R.M.; Cuijpers, P.

2017-01-01

Importance: Self-guided internet-based cognitive behavioral therapy (iCBT) has the potential to increase access and availability of evidence-based therapy and reduce the cost of depression treatment. Objectives: To estimate the effect of self-guided iCBT in treating adults with depressive symptoms

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.

Science.gov (United States)

Pu, Wei-Ling; Sun, Li-Kang; Gao, Xiu-Mei; Rüegg, Curzio; Cuendet, Muriel; Hottiger, Micheal O; Zhou, Kun; Miao, Lin; Zhang, Yun-Sha; Gebauer, Margaret

2017-10-01

Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

NARCIS (Netherlands)

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; van der Heide, Uulke A.; van Herk, Marcel; Heemsbergen, Wilma D.

2015-01-01

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions

Can the Growth/Differentiation Factor-15 Be a Surrogate Target in Chronic Heart Failure Biomarker-Guided Therapy?

Directory of Open Access Journals (Sweden)

Alexander E. Berezin

2017-03-01

Full Text Available Heart failure (HF biomarker-guided therapy is a promising method, which directs to the improvement of clinical status, attenuation of admission/readmission to the hospital and reduction in mortality rate. Many biological markers, like inflammatory cytokines, are under consideration as a surrogate target for HF treatment, while there are known biomarkers with established predictive value, such as natriuretic peptides. However, discovery of new biomarkers reflecting various underlying mechanisms of HF and appearing to be surrogate targets for biomarker-guided therapy is fairly promising. Nowadays, growth/differentiation factor 15 (GDF-15 is suggested a target biomarker for HF treatment. Although elevated level of GDF-15 is associated with HF development, progression, and prognosis, there is no represented evidence regarding the direct comparison of this biomarker with other clinical risk predictors and biomarkers. Moreover, GDF-15 might serve as a contributor to endothelial progenitor cells (EPC dysfunction by inducing EPC death/autophagy and limiting their response to angiopoetic and reparative effects. The short communication was discussed whether GDF-15 is good molecular target for HF biomarker-guided therapy.

Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

Directory of Open Access Journals (Sweden)

J. Iglesias García

Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

Directory of Open Access Journals (Sweden)

J. Iglesias García

2009-09-01

Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

INNOLAB- image guided surgery and therapy lab

Directory of Open Access Journals (Sweden)

Fritzsche Holger

2017-09-01

Full Text Available Incremental innovation, something better or cheaper or more effective, is the standard innovation process for medical product development. Disruptive innovation is often not recognized as disruptive, because it very often starts as a simple and easy alternative to existing products with much reduced features and bad performance. Innovation is the invention multiplied with a commercial use, or in other words something that eventually provides a value to a clinical user or patient. To create such innovation not a technology push (technology delivered from a technical need perspective but rather a pull (by learning and working with the clinical users is required. Medical technology students need to understand that only through proper observation, procedure know-how and subsequent analysis and evaluation, clinically relevant and affordable innovation can be generated and possibly subsequently used for entrepreneurial ventures. The dedicated laboratory for innovation, research and entrepreneurship- INNOLAB ego.-INKUBATOR IGT (Image Guided Therapies is financed by the state of Sachsen-Anhalt as part of the European ego.-INKUBATOR program with (EFRE funds at the university clinic operated by the technical chair for catheter technologies and image guided surgeries. It forms a network node between medicine, research and economics. It teaches students to lead innovation processes, technology transfer to the user and is designed to stimulate the start-up intentions.

Les "Questions et réponses sur les évangiles" d'Eusèbe de Césarée: étude et édition du résumé grec

OpenAIRE

Zamagni, Claudio; Junod, Eric; Le Boulluec, Alain

2005-01-01

Cette thèse propose la première édition critique de l’une des traditions les plus importantes des Questions et réponses sur les évangiles d’Eusèbe de Césarée, dont l’original est perdu. Il s’agit de l’édition du manuscrit contenant l’anthologie grecque du manuscrit Vaticanus Pal. Gr. 220. Cette anthologie est composée presque intégralement d’une suite d’extraits du texte original, non résumés, dont l’auteur n’est pas Eusèbe et dont la date ne peut pas être reportée avant le V-VIème siècle. Ce...

Cost-utility Analysis: Thiopurines Plus Endoscopy-guided Biological Step-up Therapy is the Optimal Management of Postoperative Crohn's Disease.

Science.gov (United States)

Candia, Roberto; Naimark, David; Sander, Beate; Nguyen, Geoffrey C

2017-11-01

Postoperative recurrence of Crohn's disease is common. This study sought to assess whether the postoperative management should be based on biological therapy alone or combined with thiopurines and whether the therapy should be started immediately after surgery or guided by either endoscopic or clinical recurrence. A Markov model was developed to estimate expected health outcomes in quality-adjusted life years (QALYs) and costs in Canadian dollars (CAD$) accrued by hypothetical patients with high recurrence risk after ileocolic resection. Eight strategies of postoperative management were evaluated. A lifetime time horizon, an annual discount rate of 5%, a societal perspective, and a cost-effectiveness threshold of 50,000 CAD$/QALY were assumed. Deterministic and probabilistic sensitivity analyses were conducted. The model was validated against randomized trials and historical cohorts. Three strategies dominated the others: endoscopy-guided full step-up therapy (14.80 QALYs, CAD$ 462,180), thiopurines immediately post-surgery plus endoscopy-guided biological step-up therapy (14.89 QALYs, CAD$ 464,099) and combination therapy immediately post-surgery (14.94 QALYs, CAD$ 483,685). The second strategy was the most cost-effective, assuming a cost-effectiveness threshold of 50,000 CAD$/QALY. Probabilistic sensitivity analysis showed that the second strategy has the highest probability of being the optimal alternative in all comparisons at cost-effectiveness thresholds from 30,000 to 100,000 CAD$/QALY. The strategies guided only by clinical recurrence and those using biologics alone were dominated. According to this decision analysis, thiopurines immediately after surgery and addition of biologics guided by endoscopic recurrence is the optimal strategy of postoperative management in patients with Crohn's disease with high risk of recurrence (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B654).

Endoscopic ultrasound coil placement of gastric varices: Emerging modality for recurrent bleeding gastric varices

Directory of Open Access Journals (Sweden)

Yogesh Harwani

2014-01-01

Full Text Available Gastric varices are the probable source of bleeding in 10-36% of patients, with acute variceal bleeding and carry high mortality and rebleeding rates. Till date, cyanoacrylate glue injection is considered as the standard of care but has high complication rate. Endoscopic ultrasound (EUS guided coil placement is a new emerging technique of management of gastric varices. In this case report, we detail the EUS guided coil placement for management of gastric varices after failed glue injections.

Characterization and anti-tumor effects of chondroitin sulfate-chitosan nanoparticles delivery system

Science.gov (United States)

Hu, Chieh-Shen; Tang, Sung-Ling; Chiang, Chiao-Hsi; Hosseinkhani, Hossein; Hong, Po-Da; Yeh, Ming-Kung

2014-11-01

We prepared chondroitin sulfate (ChS)-chitosan (CS) nanoparticles (NPs) as a delivery carrier, and doxorubicin (Dox) was used as a model drug. The physicochemical properties and biological activities of the Dox-ChS-CS NPs including the release profile, cell cytotoxicity, cellular internalization, and in vivo anti-tumor effects were evaluated. The ChS-CS NPs and Dox-ChS-CS NPs had a mean size of 262.0 ± 15.0 and 369.4 ± 77.4 nm, and a zeta potential of 30.2 ± 0.9 and 20.6 ± 3.1 mV, respectively. In vitro release tests showed that the 50 % release time for the Dox-ChS-CS NPs was 20 h. Two hepatoma cell models, HepG2 and HuH6, were used for evaluating the cytotoxicity and cell uptake efficiency of the Dox-ChS-CS NPs. A significant difference was observed between doxorubicin solution and the Dox-ChS-CS NPs in the cellular uptake within 60 min ( p < 0.01). For the in vivo human xenograft-nude mouse model, the Dox-ChS-CS NPs were more effective with less body weight loss and anti-tumor growth suppression in comparison with the Dox solution. The prepared Dox-ChS-CS NPs offer a new effective targeting nanoparticle delivery system platform for anti-tumor therapy.

Potential Antitumor Effects of Pomegranates and Its Ingredients.

Science.gov (United States)

Rahmani, Arshad H; Alsahli, Mohammed A; Almatroodi, Saleh A

2017-01-01

The treatment based on plant or plant derivatives is a promising strategy in the killing of cancers cells. Moreover, wide-ranging finding has established that medicinal plant and its ingredient modulate several cells signaling pathways or inhibiting the carcinogenesis process. In this vista, pomegranates fruits, seeds and peels illustrate cancer preventive role seems to be due to rich source of antioxidant and other valuable ingredients. Furthermore, anti-tumour activities of pomegranates have been evidences through the modulation of cell signaling pathways including transcription factor, apoptosis and angiogenesis. In this review article, anti-tumor activity of pomegranates and its components or its different type of extracts are described to understand the mechanism of action of pomegranates in cancer therapy.

Immunological Monitoring to Rationally Guide AAV Gene Therapy

Directory of Open Access Journals (Sweden)

Cedrik Michael Britten

2013-09-01

Full Text Available Recent successes with adeno-associated virus (AAV-based gene therapies fuel the hope for new treatments for hereditary diseases. Pre-existing as well as therapy-induced immune responses against both AAV and the encoded transgenes have been described and may impact on safety and efficacy of gene-therapy approaches. Consequently, monitoring of vector- and transgene-specific immunity is mandated and may rationally guide clinical development. Next to the humoral immune response, the cellular response is central in our understanding of the host reaction in gene therapy. But in contrast to the monitoring of antibodies, which has matured over many decades, sensitive and robust monitoring of T cells is a relatively new development. To make cellular immune assessments fit for purpose, investigators need to know, control and report the critical assay variables that influence the results. In addition, the quality of immune assays needs to be continuously adjusted to allow for exploratory hypothesis generation in early stages and confirmatory hypothesis validation in later stages of clinical development. The concept of immune assay harmonization which includes use of field-wide benchmarks, harmonization guidelines, and external quality control can support the context-specific evolution of immune assays. Multi-center studies pose particular challenges to sample logistics and quality control of sample specimens. Cooperative groups need to define if immune assessments should be performed in one central facility, in peripheral labs or including a combination of both. Finally, engineered reference samples that contain a defined number of antigen-specific T cells may become broadly applicable tools to control assay performance over time or across institutions.

Anti-tumor activity of N-hydroxy-7-(2-naphthylthio) heptanomide, a novel histone deacetylase inhibitor

International Nuclear Information System (INIS)

Kim, Dong Hoon; Lee, Jiyong; Kim, Kyung Noo; Kim, Hye Jin; Jeung, Hei Cheul; Chung, Hyun Cheol; Kwon, Ho Jeong

2007-01-01

Histone deacetylase (HDAC), a key enzyme in gene expression and carcinogenesis, is considered an attractive target molecule for cancer therapy. Here, we report a new synthetic small molecule, N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), as a HDAC inhibitor with anti-tumor activity both in vitro and in vivo. The compound inhibited HDAC enzyme activity as well as proliferation of human fibrosarcoma cells (HT1080) in vitro. Treatment of cells with HNHA elicited histone hyperacetylation leading to an up-regulation of p21 transcription, cell cycle arrest, and an inhibition of HT1080 cell invasion. Moreover, HNHA effectively inhibited the growth of tumor tissue in a mouse xenograph assay in vivo. Together, these data demonstrate that this novel HDAC inhibitor could be developed as a potential anti-tumor agent targeting HDAC

Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

Directory of Open Access Journals (Sweden)

Tania Løve Aaes

2016-04-01

Full Text Available Successful immunogenic apoptosis in experimental cancer therapy depends on the induction of strong host anti-tumor responses. Given that tumors are often resistant to apoptosis, it is important to identify alternative molecular mechanisms that elicit immunogenic cell death. We have developed a genetic model in which direct dimerization of FADD combined with inducible expression of RIPK3 promotes necroptosis. We report that necroptotic cancer cells release damage-associated molecular patterns and promote maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using both FADD-dependent and FADD-independent RIPK3 induction systems, we demonstrate the efficient vaccination potential of immunogenic necroptotic cells. Our study broadens the current concept of immunogenic cell death and opens doors for the development of new strategies in cancer therapy.

Image-guided therapy and minimally invasive surgery in children: a merging future

International Nuclear Information System (INIS)

Shlomovitz, Eran; Amaral, Joao G.; Chait, Peter G.

2006-01-01

Minimally invasive image-guided therapy for children, also known as pediatric interventional radiology (PIR), is a new and exciting field of medicine. Two key elements that helped the rapid evolution and dissemination of this specialty were the creation of devices appropriate for the pediatric population and the development of more cost-effective and minimally invasive techniques. Despite its clear advantages to children, many questions are raised regarding who should be performing these procedures. Unfortunately, this is a gray zone with no clear answer. Surgeons fear that interventional radiologists will take over additional aspects of the surgical/procedural spectrum. Interventional radiologists, on the other hand, struggle to avoid becoming highly specialized technicians rather than physicians who are responsible for complete care of their patients. In this article, we briefly discuss some of the current aspects of minimally invasive image-guided therapy in children and innovations that are expected to be incorporated into clinical practice in the near future. Then, we approach the current interspecialty battles over the control of this field and suggest some solutions to these issues. Finally, we propose the development of a generation of physicians with both surgical and imaging skills. (orig.)

Incidence of bacteremia in cirrhotic patients undergoing upper endoscopic ultrasonography.

Science.gov (United States)

Fernández-Esparrach, Gloria; Sendino, Oriol; Araujo, Isis; Pellisé, Maria; Almela, Manel; González-Suárez, Begoña; López-Cerón, María; Córdova, Henry; Sanabria, Erwin; Uchima, Hugo; Llach, Josep; Ginès, Àngels

2014-01-01

The incidence of bacteremia after endoscopic ultrasonography (EUS) or EUS-guided fine-needle aspiration (EUS-FNA) is between 0% and 4%, but there are no data on this topic in cirrhotic patients. To prospectively assess the incidence of bacteremia in cirrhotic patients undergoing EUS and EUS-FNA. We enrolled 41 cirrhotic patients. Of these, 16 (39%) also underwent EUS-FNA. Blood cultures were obtained before and at 5 and 30 min after the procedure. When EUS-FNA was used, an extra blood culture was obtained after the conclusion of radial EUS and before the introduction of the sectorial echoendoscope. All patients were clinically followed up for 7 days for signs of infection. Blood cultures were positive in 16 patients. In 10 patients, blood cultures grew coagulase-negative Staphylococcus, Corynebacterium species, Propionibacterium species or Acinetobacterium Lwoffii, which were considered contaminants (contamination rate 9.8%, 95% CI: 5.7-16%). The remaining 6 patients had true positive blood cultures and were considered to have had true bacteremia (15%, 95% CI: 4-26%). Blood cultures were positive after diagnostic EUS in five patients but were positive after EUS-FNA in only one patient. Thus, the frequency of bacteremia after EUS and EUS-FNA was 12% and 6%, respectively (95% CI: 2-22% and 0.2-30%, respectively). Only one of the patients who developed bacteremia after EUS had a self-limiting fever with no other signs of infection. Asymptomatic Gram-positive bacteremia developed in cirrhotic patients after EUS and EUS-FNA at a rate higher than in non-cirrhotic patients. However, this finding was not associated with any clinically significant infections. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Role of endoscopic ultrasonography in treatment and prognostic evaluation of esophageal and gastric varices

Directory of Open Access Journals (Sweden)

LI Shuang

2016-12-01

Full Text Available Through a comprehensive evaluation of collateral circulation establishment in portal hypertension, endoscopic ultrasonography (EUS not only helps to predict and evaluate the risks of first bleeding from esophageal and gastric varices and recurrence and rebleeding after treatment, but also guides and participates in the treatment of varices. This article introduces the unique advantages of EUS in the treatment and prognostic evaluation of esophageal and gastric varices and provides an important reference for individualized treatment of patients with liver cirrhosis complicated by esophageal and gastric varices. EUS also helps to improve treatment safety and response rate. EUS for the systematic treatment of portal hypertension has become a hot research topic in recent years.

Endoscopic ultrasound guided injection of iron oxide magnetic nanoparticles for liver and pancreas

DEFF Research Database (Denmark)

Ungureanu, Bogdan Silviu; Pirici, Daniel; Margaritescu, Claudiu

2016-01-01

)-guidance, both systemically and locally in the liver and pancreas in order to study new potential therapies for liver and pancreatic tumors. MATERIAL AND METHODS: Six domestic pigs were used for our study design, and divided into three groups: two were injected in the portal vein, and other four were subjected...... to local exposure of IONs in the liver and pancreas, two each. The pigs were on a 7 days follow-up and necropsy was performed with their organs harvested. A 3T MRI scan was also performed. RESULTS: All animals underwent an endoscopic ultrasound fine needle injection (EUS-FNI) procedure without any...

Antitumor activity and inhibitory effects on cancer stem cell-like properties of Adeno-associated virus (AAV) -mediated Bmi-1 interference driven by Bmi-1 promoter for gastric cancer

Science.gov (United States)

Wang, Xiaofeng; Liu, Xinyang; Huang, Mingzhu; Gan, Lu; Cheng, Yufan; Li, Jin

2016-01-01

Bmi-1 is aberrantly activated in various cancers and plays a vital role in maintaining the self-renewal of stem cells. Our previous research revealed that Bmi-1 was overexpressed in gastric cancer (GC) and it's overexpression was an independent negative prognostic factor, suggesting it can be a therapeutic target. The main purpose of this investigation was to explore the antitumor activity of Bmi-1 interference driven by its own promoter (Ad-Bmi-1i) for GC. In this study, we used adenoviral vector to deliver Bmi-1 shRNA driven by its own promoter to treat GC. Our results revealed that Ad-Bmi-1i could selectively silence Bmi-1 in GC cells which overexpress Bmi-1 and suppress the malignant phenotypes and stem-like properties of GC cells in vitro and in vivo. Moreover, direct injection of Ad-Bmi-1i into xenografts suppressed tumor growth and destroyed cancer cells in vivo. Ad-Bmi-1i inhibited the proliferation of GC cells mainly via inducing senescence in vitro, but it suppressed tumor through inducing senescence and apoptosis, and inhibiting angiogenesis in vivo. Bmi-1 knockdown by Ad-Bmi-1i downregulated VEGF via inhibiting AKT activity. These results suggest that Ad-Bmi-1i not only inhibits tumor growth and stem cell-like phenotype by inducing cellular senescence directly, but also has an indirect anti-tumor activity by anti-angiogenesis effects via regulating PTEN/AKT/VEGF pathway. Transfer of gene interference guided by its own promoter by an adeno-associated virus (AAV) vector might be a potent antitumor approach for cancer therapy. PMID:27009837

Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

Science.gov (United States)

Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

2014-01-01

We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

The novel fusion proteins, GnRH-p53 and GnRHIII-p53, expression and their anti-tumor effect.

Directory of Open Access Journals (Sweden)

Peiyuan Jia

Full Text Available p53, one of the most well studied tumor suppressor factor, is responsible to a variety of damage owing to the induction of apoptosis and cell cycle arrest in the tumor cells. More than 50% of human tumors contain mutation or deletion of p53. Gonadotrophin-releasing hormone (GnRH, as the ligand of Gonadotrophin-releasing hormone receptor (GnRH-R, was used to deliver p53 into tumor cells. The p53 fusion proteins GnRH-p53 and GnRH iii-p53 were expressed and their targeted anti-tumor effects were determined. GnRH mediates its fusion proteins transformation into cancer cells. The intracellular delivery of p53 fusion proteins exerted the inhibition of the growth of H1299 cells in vitro and the reduction of tumor volume in vivo. Their anti-tumor effect was functioned by the apoptosis and cell cycle arrest induced by p53. Hence, the fusion protein could be a novel protein drug for anti-tumor therapy.

Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease.

Science.gov (United States)

Ranaldo, Nunzio; Losurdo, Giuseppe; Iannone, Andrea; Principi, Mariabeatrice; Barone, Michele; De Carne, Massimo; Ierardi, Enzo; Di Leo, Alfredo

2017-09-07

A relevant percentage of non-erosive reflux disease (NERD) is refractory to proton pump inhibitors (PPIs) treatment. Multichannel intraluminal impedance pH (MII-pH) monitoring should give useful pathophysiological information about refractoriness. Therefore, our aim was to assess whether this technique could be useful to guide a 'tailored' therapy in refractory NERD. We retrospectively recruited NERD patients undergoing MII-pH monitoring for unsuccessful treatment. All patients had undergone upper endoscopy, and those with erosive esophagitis were excluded. No patient received PPI during MII-pH monitoring. Subjects were subgrouped into three categories: acid reflux, non-acid reflux and functional heartburn. MII-pH-guided therapy was performed for 4 weeks as follows: patients with acid reflux received PPI at double dose, patients with non-acid reflux PPI at full dose plus alginate four times a day and patients with functional heartburn levosulpiride 75 mg per day. A visual analog scale (VAS) ranging from 0 to 100 mm was administered before and after such tailored therapy to evaluate overall symptoms. Responders were defined by VAS improvement of at least 40%. Sixty-nine patients with refractory NERD were selected (female-male ratio 43 : 26, mean age 47.6±15.2 years). Overall effectiveness of tailored therapy was 84% without statistical difference among subgroups (88.5% acid reflux, 92% non-acid reflux, 66.6% functional heartburn; P=0.06). Univariate analysis showed that therapy failure directly correlated with functional heartburn diagnosis (OR=4.60) and suggested a trend toward a negative correlation with smoking and a positive one with nausea. However, at multivariate analysis, these parameters were not significant. Functional heartburn experienced a lower median percent VAS reduction than acid reflux (52.5% versus 66.6%, Pacid reflux (66.6%). In conclusion, a tailored approach to refractory NERD, guided by MII-pH monitoring, demonstrated to be effective

Clinical outcomes and cost-effectiveness of brief guided parent-delivered cognitive behavioural therapy and solution-focused brief therapy for treatment of childhood anxiety disorders: a randomised controlled trial.

Science.gov (United States)

Creswell, Cathy; Violato, Mara; Fairbanks, Hannah; White, Elizabeth; Parkinson, Monika; Abitabile, Gemma; Leidi, Alessandro; Cooper, Peter J

2017-07-01

Half of all lifetime anxiety disorders emerge before age 12 years; however, access to evidence-based psychological therapies for affected children is poor. We aimed to compare the clinical outcomes and cost-effectiveness of two brief psychological treatments for children with anxiety referred to routine child mental health settings. We hypothesised that brief guided parent-delivered cognitive behavioural therapy (CBT) would be associated with better clinical outcomes than solution-focused brief therapy and would be cost-effective. We did this randomised controlled trial at four National Health Service primary child and mental health services in Oxfordshire, UK. Children aged 5-12 years referred for anxiety difficulties were randomly allocated (1:1), via a secure online minimisation tool, to receive brief guided parent-delivered CBT or solution-focused brief therapy, with minimisation for age, sex, anxiety severity, and level of parental anxiety. The allocation sequence was not accessible to the researcher enrolling participants or to study assessors. Research staff who obtained outcome measurements were masked to group allocation and clinical staff who delivered the intervention did not measure outcomes. The primary outcome was recovery, on the basis of Clinical Global Impressions of Improvement (CGI-I). Parents recorded patient-level resource use. Quality-adjusted life-years (QALYs) for use in cost-utility analysis were derived from the Child Health Utility 9D. Assessments were done at baseline (before randomisation), after treatment (primary endpoint), and 6 months after treatment completion. We did analysis by intention to treat. This trial is registered with the ISCRTN registry, number ISRCTN07627865. Between March 23, 2012, and March 31, 2014, we randomly assigned 136 patients to receive brief guided parent-delivered CBT (n=68) or solution-focused brief therapy (n=68). At the primary endpoint assessment (June, 2012, to September, 2014), 40 (59%) children in

Antitumor effect of combination of the inhibitors of two new oncotargets: proton pumps and reverse transcriptase.

Science.gov (United States)

Lugini, Luana; Sciamanna, Ilaria; Federici, Cristina; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Fais, Stefano

2017-01-17

Tumor therapy needs new approaches in order to improve efficacy and reduce toxicity of the current treatments. The acidic microenvironment and the expression of high levels of endogenous non-telomerase reverse transcriptase (RT) are common features of malignant tumor cells. The anti-acidic proton pump inhibitor Lansoprazole (LAN) and the non-nucleoside RT inhibitor Efavirenz (EFV) have shown independent antitumor efficacy. LAN has shown to counteract drug tumor resistance. We tested the hypothesis that combination of LAN and EFV may improve the overall antitumor effects. We thus pretreated human metastatic melanoma cells with LAN and then with EFV, both in 2D and 3D spheroid models. We evaluated the treatment effect by proliferation and cell death/apoptosis assays in classical and in pulse administration experiments. The action of EFV was negatively affected by the tumor microenvironmental acidity, and LAN pretreatment overcame the problem. LAN potentiated the cytotoxicity of EFV to melanoma cells and, when administered during the drug interruption period, prevented the replacement of tumor cell growth.This study supports the implementation of the current therapies with combination of Proton Pumps and Reverse Transcriptase inhibitors.

Gene therapy of thyroid carcinoma

International Nuclear Information System (INIS)

Zheng Wei; Tan Jian

2007-01-01

Normally, differentiated thyroid carcinoma(DTC) is a disease of good prognosis, but about 30% of the tumors are dedifferentiate, which are inaccessible to standard therapeutic procedures such as 'operation, 131 I therapy and thyroid hormone'. Both internal and abroad experts are researching a new therapy of dedifferentiated thyroid carcinoma--gene therapy. Many of them utilize methods of it, but follow different strategies: (1) transduction of the thyroid sodium/iodide transporter gene to make tissues that do not accumulate iodide treatable by 131 I therapy; (2) strengthening of the anti-tumor immune response; (3) suicide gene therapy; (4) depression the generation of tumor cells; (5) gene therapy of anti- vascularization. (authors)

Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient

International Nuclear Information System (INIS)

Bernal-Estévez, David; Sánchez, Ramiro; Tejada, Rafael E.; Parra-López, Carlos

2016-01-01

Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells. T cells were obtained before and after anti-tumor therapy from peripheral blood of a 63-years old woman diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after 8 months of treatment. Using in vitro cell cultures stimulated with autologous monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we characterize by flow cytometry the phenotype of tumor associated antigens (TAAs) HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes (TILs) were performed in order to correlate both repertoires prior and after therapy. We evidence a functional recovery of T cell responsiveness to polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti-tumor therapy. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and TILs showed that whereas the TCR-Vβ04-02 clonotype is highly expressed in TILs the HER2/neu specific T cells are expressed mainly in blood after therapy, suggesting that this particular TCR was selectively enriched in blood after anti-tumor therapy. Our results show the benefits of anti-tumor therapy in a breast cancer patient with clinical complete response in

In-room CT techniques for image-guided radiation therapy

International Nuclear Information System (INIS)

Ma, C.-M. Charlie; Paskalev, Kamen M.S.

2006-01-01

Accurate patient setup and target localization are essential to advanced radiation therapy treatment. Significant improvement has been made recently with the development of image-guided radiation therapy, in which image guidance facilitates short treatment course and high dose per fraction radiotherapy, aiming at improving tumor control and quality of life. Many imaging modalities are being investigated, including x-ray computed tomography (CT), ultrasound imaging, positron emission tomography, magnetic resonant imaging, magnetic resonant spectroscopic imaging, and kV/MV imaging with flat panel detectors. These developments provide unique imaging techniques and methods for patient setup and target localization. Some of them are different; some are complementary. This paper reviews the currently available kV x-ray CT systems used in the radiation treatment room, with a focus on the CT-on-rails systems, which are diagnostic CT scanners moving on rails installed in the treatment room. We will describe the system hardware including configurations, specifications, operation principles, and functionality. We will review software development for image fusion, structure recognition, deformation correction, target localization, and alignment. Issues related to the clinical implementation of in-room CT techniques in routine procedures are discussed, including acceptance testing and quality assurance. Clinical applications of the in-room CT systems for patient setup, target localization, and adaptive therapy are also reviewed for advanced radiotherapy treatments

Activation of Anti-tumor Immune Response by Ablation of HCC with Nanosecond Pulsed Electric Field.

Science.gov (United States)

Xu, Xiaobo; Chen, Yiling; Zhang, Ruiqing; Miao, Xudong; Chen, Xinhua

2018-03-28

Locoregional therapy is playing an increasingly important role in the non-surgical management of hepatocellular carcinoma (HCC). The novel technique of non-thermal electric ablation by nanosecond pulsed electric field has been recognized as a potential locoregional methodology for indicated HCC. This manuscript explores the most recent studies to indicate its unique anti-tumor immune response. The possible immune mechanism, termed as nano-pulse stimulation, was also analyzed.

Phospholipid micelle-based magneto-plasmonic nanoformulation for magnetic field-directed, imaging-guided photo-induced cancer therapy.

Science.gov (United States)

Ohulchanskyy, Tymish Y; Kopwitthaya, Atcha; Jeon, Mansik; Guo, Moran; Law, Wing-Cheung; Furlani, Edward P; Kim, Chulhong; Prasad, Paras N

2013-11-01

We present a magnetoplasmonic nanoplatform combining gold nanorods (GNR) and iron-oxide nanoparticles within phospholipid-based polymeric nanomicelles (PGRFe). The gold nanorods exhibit plasmon resonance absorbance at near infrared wavelengths to enable photoacoustic imaging and photothermal therapy, while the Fe3O4 nanoparticles enable magnetophoretic control of the nanoformulation. The fabricated nanoformulation can be directed and concentrated by an external magnetic field, which provides enhancement of a photoacoustic signal. Application of an external field also leads to enhanced uptake of the magnetoplasmonic formulation by cancer cells in vitro. Under laser irradiation at the wavelength of the GNR absorption peak, the PGRFe formulation efficiently generates plasmonic nanobubbles within cancer cells, as visualized by confocal microscopy, causing cell destruction. The combined magnetic and plasmonic functionalities of the nanoplatform enable magnetic field-directed, imaging-guided, enhanced photo-induced cancer therapy. In this study, a nano-formulation of gold nanorods and iron oxide nanoparticles is presented using a phospholipid micelle-based delivery system for magnetic field-directed and imaging-guided photo-induced cancer therapy. The gold nanorods enable photoacoustic imaging and photothermal therapy, while the Fe3O4 nanoparticles enable magnetophoretic control of the formulation. This and similar systems could enable more precise and efficient cancer therapy, hopefully in the near future, after additional testing. Copyright © 2013 Elsevier Inc. All rights reserved.

Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: a multicenter study.

Science.gov (United States)

Giovannini, Marc; Thomas, Botelberge; Erwan, Bories; Christian, Pesenti; Fabrice, Caillol; Benjamin, Esterni; Geneviève, Monges; Paolo, Arcidiacono; Pierre, Deprez; Robert, Yeung; Walter, Schimdt; Hanz, Schrader; Carl, Szymanski; Christoph, Dietrich; Pierre, Eisendrath; Jean-Luc, Van Laethem; Jacques, Devière; Peter, Vilmann; Andrian, Saftoiu

2009-04-07

To evaluate the ability of endoscopic ultrasound (EUS) elastography to distinguish benign from malignant pancreatic masses and lymph nodes. A multicenter study was conducted and included 222 patients who underwent EUS examination with assessment of a pancreatic mass (n = 121) or lymph node (n = 101). The classification as benign or malignant, based on the real time elastography pattern, was compared with the classification based on the B-mode EUS images and with the final diagnosis obtained by EUS-guided fine needle aspiration (EUS-FNA) and/or by surgical pathology. An interobserver study was performed. The sensitivity and specificity of EUS elastography to differentiate benign from malignant pancreatic lesions are 92.3% and 80.0%, respectively, compared to 92.3% and 68.9%, respectively, for the conventional B-mode images. The sensitivity and specificity of EUS elastography to differentiate benign from malignant lymph nodes was 91.8% and 82.5%, respectively, compared to 78.6% and 50.0%, respectively, for the B-mode images. The kappa coefficient was 0.785 for the pancreatic masses and 0.657 for the lymph nodes. EUS elastography is superior compared to conventional B-mode imaging and appears to be able to distinguish benign from malignant pancreatic masses and lymph nodes with a high sensitivity, specificity and accuracy. It might be reserved as a second line examination to help characterise pancreatic masses after negative EUS-FNA and might increase the yield of EUS-FNA for lymph nodes.

Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway

Directory of Open Access Journals (Sweden)

Su M

2017-11-01

Full Text Available Meng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by downregulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment. Keywords: Andro, 5-Fu, HCT-116 cells, apoptosis, p-MET

SU-E-J-201: Investigation of MRI Guided Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Li, JS [Fox Chase Cancer Center, Philadelphia, PA (United States)

2015-06-15

Purpose: Image-guided radiation therapy has been employed for cancer treatment to improve the tumor localization accuracy. Radiation therapy with proton beams requires more on this accuracy because the proton beam has larger uncertainty and dramatic dose variation along the beam direction. Among all the image modalities, magnetic-resonance image (MRI) is the best for soft tissue delineation and real time motion monitoring. In this work, we investigated the behavior of the proton beam in magnetic field with Monte Carlo simulations. Methods: A proton Monte Carlo platform, TOPAS, was used for this investigation. Dose calculations were performed with this platform in a 30cmx30cmx30cm water phantom for both pencil and broad proton beams with different energies (120, 150 and 180MeV) in different magnetic fields (0.5T, 1T and 3T). The isodose distributions, dose profiles in lateral and beam direction were evaluated. The shifts of the Bragg peak in different magnetic fields for different proton energies were compared and the magnetic field effects on the characters of the dose distribution were analyzed. Results: Significant effects of magnetic field have been observed on the proton beam dose distributions, especially for magnetic field of 1T and up. The effects are more significant for higher energy proton beam because higher energy protons travel longer distance in the magnetic field. The Bragg peak shift in the lateral direction is about 38mm for 180MeV and 11mm for 120MeV proton beams in 3T magnetic field. The peak positions are retracted back for 6mm and 2mm, respectively. The effect on the beam penumbra and dose falloff at the distal edge of the Bragg peak is negligible. Conclusion: Though significant magnetic effects on dose distribution have been observed for proton beams, MRI guided proton therapy is feasible because the magnetic effects on dose is predictable and can be considered in patient dose calculation.

pH-Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic Photodynamic Therapy/Chemotherapy.

Science.gov (United States)

Tang, Xiang-Long; Jing, Feng; Lin, Ben-Lan; Cui, Sheng; Yu, Ru-Tong; Shen, Xiao-Dong; Wang, Ting-Wei

2018-05-02

By overcoming drug resistance and subsequently enhancing the treatment, the combination therapy of photodynamic therapy (PDT) and chemotherapy has promising potential for cancer treatment. However, the major challenge is how to establish an advanced nanoplatform that can be efficiently guided to tumor sites and can then stably release both chemotherapy drugs and a photosensitizer simultaneously and precisely. In this study, which considered the possibility and targeting efficiency of a magnetic targeting strategy, a novel Fe 3 O 4 @mSiO 2 (DOX)@HSA(Ce6) nanoplatform was successfully built; this platform could be employed as an efficient synergistic antitumor nanoplatform with magnetic guidance for highly specific targeting and retention. Doxorubicin (DOX) molecules were loaded into mesoporous silica with high loading capability, and the mesoporous channels were blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to the outer surface to increase the biocompatibility and blood circulation time, as well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The sustained release of DOX under acidic conditions and the PDT induced by red light exerted a synergistic inhibitory effect on glioma cells. Our experiments demonstrated that the pH-responsive Fe 3 O 4 @mSiO 2 (DOX)@HSA(Ce6) nanoplatform was guided to the tumor region by magnetic targeting and that the nanoplatform suppressed glioma tumor growth efficiently, implying that the system is a highly promising photodynamic therapy/chemotherapy combination nanoplatform with synergistic effects for cancer treatment.

Radiologists' leading position in image-guided therapy.

Science.gov (United States)

Helmberger, Thomas; Martí-Bonmatí, Luis; Pereira, Philippe; Gillams, Alice; Martínez, Jose; Lammer, Johannes; Malagari, Katarina; Gangi, Afshin; de Baere, Thierry; Adam, E Jane; Rasch, Coen; Budach, Volker; Reekers, Jim A

2013-02-01

Image-guided diagnostic and therapeutic procedures are related to, or performed under, some kind of imaging. Such imaging may be direct inspection (as in open surgery) or indirect inspection as in endoscopy or laparoscopy. Common to all these techniques is the transformation of optical and visible information to a monitor or the eye of the operator. Image-guided therapy (IGT) differs by using processed imaging data acquired before, during and after a wide range of different imaging techniques. This means that the planning, performing and monitoring, as well as the control of the therapeutic procedure, are based and dependent on the "virtual reality" provided by imaging investigations. Since most of such imaging involves radiology in the broadest sense, there is a need to characterise IGT in more detail. In this paper, the technical, medico-legal and medico-political issues will be discussed. The focus will be put on state-of-the-art imaging, technical developments, methodological and legal requisites concerning radiation protection and licensing, speciality-specific limitations and crossing specialty borders, definition of technical and quality standards, and finally to the issue of awareness of IGT within the medical and public community. The specialty-specific knowledge should confer radiologists with a significant role in the overall responsibility for the imaging-related processes in various non-radiological specialties. These processes may encompass purchase, servicing, quality management, radiation protection and documentation, also taking responsibility for the definition and compliance with the legal requirements regarding all radiological imaging performed by non-radiologists.

T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor

Directory of Open Access Journals (Sweden)

Kim Tae-Sik

2011-06-01

Full Text Available Abstract Background Although the graft-versus-tumor (GVT effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB transplantation have not been well studied. Methods We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells. Results We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays. Conclusions Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.

Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer.

Science.gov (United States)

Yoshioka, Takahiro; Shien, Kazuhiko; Namba, Kei; Torigoe, Hidejiro; Sato, Hiroki; Tomida, Shuta; Yamamoto, Hiromasa; Asano, Hiroaki; Soh, Junichi; Tsukuda, Kazunori; Nagasaka, Takeshi; Fujiwara, Toshiyoshi; Toyooka, Shinichi

2018-04-01

Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-human epidermal growth factor receptor 2 (HER2) drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. First, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs. In the drug sensitivity analysis, both afatinib and neratinib produced an antitumor effect in most of the HER2-amplified cell lines. However, some cells were not sensitive to the drugs. When the molecular profiles of the cells were compared based on the drug sensitivities, we found that cancer cells with lower mRNA expression levels of IGFBP7, a tumor suppressor gene that inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R), were less sensitive to pan-HER inhibitors. A combination therapy consisting of pan-HER inhibitors and an IGF-1R inhibitor, picropodophyllin, showed a notable synergistic effect. Among 123 clinical samples, we found 19 cases of HER2 amplification and three cases of oncogenic mutations. In conclusion, afatinib and neratinib are promising therapeutic options for the treatment of HER2-amplified gastric cancer. In addition to HER2 amplification, IGFBP7 might be a biomarker of sensitivity to these drugs, and IGF-1R-targeting therapy can overcome drug insensitiveness in HER2-amplified gastric cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Pediatric Anaplastic Embryonal Rhabdomyosarcoma: Targeted Therapy Guided by Genetic Analysis and a Patient-Derived Xenograft Study

Directory of Open Access Journals (Sweden)

Stuart L. Cramer

2018-01-01

Full Text Available Therapy for rhabdomyosarcoma (RMS has generally been limited to combinations of conventional cytotoxic agents similar to regimens originally developed in the late 1960s. Recently, identification of molecular alterations through next-generation sequencing of individual tumor specimens has facilitated the use of more targeted therapeutic approaches for various malignancies. Such targeted therapies have revolutionized treatment for some cancer types. However, malignancies common in children, thus far, have been less amenable to such targeted therapies. This report describes the clinical course of an 8-year-old female with embryonal RMS having anaplastic features. This patient experienced multiple relapses after receiving various established and experimental therapies. Genomic testing of this RMS subtype revealed mutations in BCOR, ARID1A, and SETD2 genes, each of which contributes to epigenetic regulation and interacts with or modifies the activity of histone deacetylases (HDAC. Based on these findings, the patient was treated with the HDAC inhibitor vorinostat as a single agent. The tumor responded transiently followed by subsequent disease progression. We also examined the efficacy of vorinostat in a patient-derived xenograft (PDX model developed using tumor tissue obtained from the patient’s most recent tumor resection. The antitumor activity of vorinostat observed with the PDX model reflected clinical observations in that obvious areas of tumor necrosis were evident following exposure to vorinostat. Histologic sections of tumors harvested from PDX tumor-bearing mice treated with vorinostat demonstrated induction of necrosis by this agent. We propose that the evaluation of clinical efficacy in this type of preclinical model merits further evaluation to determine if PDX models predict tumor sensitivity to specific agents and/or combination therapies.

Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.

Science.gov (United States)

Son, Keum-Joo; Choi, Ki Ryung; Lee, Seog Jae; Lee, Hyunah

2016-02-01

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT(+) CD11c(+) cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

“Two-Step” Raman Imaging Technique To Guide Chemo-Photothermal Cancer Therapy

KAUST Repository

Deng, Lin; Li, Qiujin; Yang, Yang; Omar, Haneen; Tang, Naijun; Zhang, Jianfei; Nie, Zhihong; Khashab, Niveen M.

2015-01-01

Graphene oxide-wrapped gold nanorods (GO@AuNRs) offer efficient drug delivery as well as NIR laser photothermal therapy (PTT) in vitro and in vivo. However, no real-time observation of drug release has been reported to better understand the synergy of chemotherapy and PTT. Herein, surface-enhance Raman spectroscopy (SERS) is employed to guide chemo-photothermal cancer therapy by a two-step mechanism. In the presence of GO as an internal standard, SERS signals of DOX (doxorubicin) loaded onto GO@AuNRs are found to be pH-responsive. Both DOX and GO show strong SERS signals before the DOX@GO@AuNRs are endocytic. However, when the DOX@GO@AuNRs enter acidic microenvironments such as endosomes and/or lysosomes, the DOX signals start decreasing while the GO signals remain the same. This plasmonic antenna could be used to identify the appropriate time to apply the PTT laser during chemo-photothermal therapy.

“Two-Step” Raman Imaging Technique To Guide Chemo-Photothermal Cancer Therapy

KAUST Repository

Deng, Lin

2015-08-13

Graphene oxide-wrapped gold nanorods (GO@AuNRs) offer efficient drug delivery as well as NIR laser photothermal therapy (PTT) in vitro and in vivo. However, no real-time observation of drug release has been reported to better understand the synergy of chemotherapy and PTT. Herein, surface-enhance Raman spectroscopy (SERS) is employed to guide chemo-photothermal cancer therapy by a two-step mechanism. In the presence of GO as an internal standard, SERS signals of DOX (doxorubicin) loaded onto GO@AuNRs are found to be pH-responsive. Both DOX and GO show strong SERS signals before the DOX@GO@AuNRs are endocytic. However, when the DOX@GO@AuNRs enter acidic microenvironments such as endosomes and/or lysosomes, the DOX signals start decreasing while the GO signals remain the same. This plasmonic antenna could be used to identify the appropriate time to apply the PTT laser during chemo-photothermal therapy.

Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Randomized Phase 2 Trial of Neoadjuvant Preoperative Paclitaxel/Cisplatin/Radiation Therapy (RT) or Irinotecan/Cisplatin/RT in Esophageal Adenocarcinoma: Long-Term Outcome and Implications for Trial Design

Energy Technology Data Exchange (ETDEWEB)

Kleinberg, Lawrence R., E-mail: kleinla@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Harvard T.H. Chan School of Public Health, Boston, Massachusetts (United States); Forastiere, Arlene A. [Department of Oncology, Johns Hopkins University, Baltimore, Maryland (United States); Keller, Steven M. [Department of Cardiovascular and Thoracic Surgery, Montefiore Medical Center, Bronx, NY (United States); Mitchel, Edith P. [Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Anne, Pramila Rani [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Benson, Al B. [Department of Medicine-Hematology/Oncology, Lurie Cancer Center, Northwestern University, Chicago, Illinois (United States)

2016-03-15

Purpose: Toxicity, pathologic complete response, and long-term outcomes are reported for the neoadjuvant therapies assessed in a randomized phase 2 Eastern Cooperative Oncology Group and American College of Radiology Imaging Network trial for operable esophageal adenocarcinoma, staged as II-IVa by endoscopy/ultrasonography (EUS). Methods and Materials: A total of 86 eligible patients began treatment. For arm A, preoperative chemotherapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 50 mg/m{sup 2}, on day 1, 8, 22, 29 during 45 Gy radiation therapy (RT), 1.8 Gy per day over 5 weeks. Adjuvant therapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 65 mg/m{sup 2} day 1, 8 every 21 days for 3 cycles. Arm B therapy was cisplatin, 30 mg/m{sup 2}, and paclitaxel, 50 mg/m{sup 2}, day 1, 8, 15, 22, 29 with RT, followed by adjuvant cisplatin, 75 mg/m{sup 2}, and paclitaxel, 175 mg/m{sup 2}, day 1 every 21 days for 3 cycles. Stratification included EUS stage and performance status. Results: In arm A, median overall survival was 35 months, and 5-, 6-, and 7-year survival rates were 46%, 39%, and 35%, respectively, whereas for arm B, they were 21 months and 27%, 27%, and 23%, respectively. Median progression- or recurrence-free survival (PFS) was 39.8 months with a 3-year PFS of 50% for arm A and 12.4 months (P=.046) with 3-year PFS of 28% for arm B. Eighty percent of the observed incidents of progression occurred within 19 months. Survival did not differ significantly by EUS and performance status strata. Conclusions: Long-term survival was similar for both arms and did not appear superior to results achieved with other standard regimens.

Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes simplex virus elicit immune mediated antigliomal effect and antitumor memory

Directory of Open Access Journals (Sweden)

Mohammed G. Ghonime

2018-02-01

Full Text Available Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells. We sought to identify how C134 performed in an immunocompetent tumor model that restricts its replication advantage over first generation viruses. To achieve this we identified tumors that have intact IFN signaling responses that restrict C134 and first generation virus replication similarly. Our results show that both viruses elicit a T cell mediated anti-tumor effect and improved animal survival but that subtle difference exist between the viruses effect on median survival despite equivalent in vivo viral replication. To further investigate this we examined the anti-tumor activity in immunodeficient mice and in syngeneic models with re-challenge. These studies show that the T cell response is integral to C134 replication independent anti-tumor response and that OV therapy elicits a durable and circulating anti-tumor memory. The studies also show that repeated intratumoral administration can extend both OV anti-tumor effects and induce durable anti-tumor memory that is superior to tumor antigen exposure alone.

Application of C-arm CT-guided targeted puncturing technique in performing non-vascular interventional biopsy or interventional therapy

International Nuclear Information System (INIS)

Li Zhen; Han Xinwei; Jiao Dechao; Ren Jianzhuang; Su Yu; Ye Hui

2011-01-01

Objective: to investigate the clinical value of C-arm CT-guided targeted puncturing technique in performing non, vascular interventional biopsy or interventional therapy. Methods: Thirty, one patients, who were encountered in authors' hospital during the period from July 2010 to September 2010, were involved in this study. C-arm CT-guided percutaneous targeted puncturing biopsy or interventional therapy was performed in all 31 patients. All patients had complete clinical data. The complications and positive rate of biopsy were recorded and analyzed. Results: Under C-arm CT-guidance, percutaneous interventional therapy was carried out in 13 patients. The interventional procedures included radiofrequency ablation therapy for hepatic cellular carcinoma (n=2), pelvic abscess draining (n=1), hepatic abscess draining (n=1), ethanol injection for liver cancer (n=4), sclerotic therapy with ethanol injection for renal cyst (n=2), sclerotic therapy with ethanol injection for liver cyst (n=2) and catheter-indwelling drainage for pancreatic pseudocyst (n=1). percutaneous interventional biopsy was performed in the remaining 18 cases, including liver (n=4), lung (n=7), mediastinum (n=2), bone and soft tissue (n=4) and neck mass (n=1). All the procedures were successfully accomplished, no technique, related complications occurred during the operation. For biopsy examination in 18 cases, the positive rate was 94.4% (17/18) and false, negative results was seen in one case with lung lesion. Conclusion: The percutaneous targeted puncturing technique with C, arm CT-guidance combines the advantages of both CT scanning and fluoroscopy. The use of real, time road, mapping function can effectively guide the puncturing and therapeutic management, which can not only optimize the workflow, save the operation time, but also improve the success rate and technical safety. Therefore, it is of great value to popularize this targeted puncturing technique. (authors)

Genetically Guided Statin Therapy

Science.gov (United States)

2017-03-01

number of new statin prescriptions, and (4) patient reported quality of life, physical activity, perceptions regarding statin therapy , and pain as...outcomes known to be prevented by statin therapy , we examined hospitalizations for three diagnoses: acute myocardial infarction (MI), stroke, and...cholesterol. However, the ultimate goal of statin therapy is to decrease incidence of CAD, acute myocardial infarction and perhaps stroke. However, there is a

Fundamental study of photoradiation therapy for cancer

Energy Technology Data Exchange (ETDEWEB)

Kashimura, Hiromasa; Kawakita, Isao; Nakahara, Akira; Sai, Shoki; Mitamura, Keiji; Fukutomi, Hisayuki; Sakita, Takao

1984-12-01

In an attempt to obtain basic data for endoscopical photoactivation therapy for cancer, photoactivation effect of various porphyrins have been studied using a human hepatoceller carcinoma cell line (PLC/PRF/5) and its transplanted tumors. Porphyrins tested were hematoporphyrin derivative (HpD), protoporphyrin disodium (PPNa), hematoporphyrin (Hp), coproporphyrin, and cobalt-protoporphyrin (COPP). To investigate cytocidal effects by laser irradiation with these drugs, the /sup 51/Cr release assay was used. The results indicate that laser irradiation only has no cytocidal effect, while PPNa has more intense cytocidal effect than that of HpD. To investigate anti-tumor effect by PRT further, 2mg of HpD, 2mg of PPNa or 0.9% NaCl were injected into human hepatocellar cartinomas transplanted to the flanks of BALB/c nu nu mice 48 hours before laser irradiation (514.5nm, 0.1 W, 30 min). The results were analized with respect to effects on tumor regression curve and their histology. The results suggest that laser irradiation alone has no antitumor effect, while PRT with PPNa has stronger anti-tumor effect than PRT with HpD. Therefore, PPNa may be used as a new photosensitizer for photoradiation therapy for cancer. (author).

Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

Science.gov (United States)

Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

2011-01-01

The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

The L-arginine/asymmetric dimethylarginine ratio is improved by anti-tumor necrosis factor-α therapy in inflammatory arthropathies. Associations with aortic stiffness.

Science.gov (United States)

Angel, Kristin; Provan, Sella Aarrestad; Mowinckel, Petter; Seljeflot, Ingebjørg; Kvien, Tore Kristian; Atar, Dan

2012-11-01

Anti-Tumor Necrosis Factor (TNF)-α therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The l-arginine/ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-α antagonists on ADMA and l-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies. Forty-eight patients who started with anti-TNF-α therapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months. Anti-TNF-α therapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. -13 [20], P < 0.001) and 12 months (7 [27] vs. -8 [19], P = 0.008), but did not affect ADMA (3 months: 0.00 [0.09] μmol/L vs. 0.02 [0.07] μmol/L, P = 0.42, 12 months: 0.01 [0.08] μmol/L vs. 0.01 [0.09] μmol/L, P = 0.88). Baseline aPWV was associated with ADMA (P = 0.02) and L-arginine/ADMA (P = 0.02) in multiple regression analyses, and the L-arginine/ADMA ratio was continuously associated with aPWV after initiation of anti-TNF-α therapy (P = 0.03). ADMA and L-arginine/ADMA were not correlated with CIMT. Anti-TNF-α therapy improved the L-arginine/ADMA ratio in patients with inflammatory arthropathies. ADMA and the L-arginine/ADMA ratio were associated with aPWV, and might have a mechanistic role in the aortic stiffening observed in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A roadmap for cost-of-goods planning to guide economic production of cell therapy products.

Science.gov (United States)

Lipsitz, Yonatan Y; Milligan, William D; Fitzpatrick, Ian; Stalmeijer, Evelien; Farid, Suzanne S; Tan, Kah Yong; Smith, David; Perry, Robert; Carmen, Jessica; Chen, Allen; Mooney, Charles; Fink, John

2017-12-01

Cell therapy products are frequently developed and produced without incorporating cost considerations into process development, contributing to prohibitively costly products. Herein we contextualize individual process development decisions within a broad framework for cost-efficient therapeutic manufacturing. This roadmap guides the analysis of cost of goods (COG) arising from tissue procurement, material acquisition, facility operation, production, and storage. We present the specific COG considerations related to each of these elements as identified through a 2013 International Society for Cellular Therapy COG survey, highlighting the differences between autologous and allogeneic products. Planning and accounting for COG at each step in the production process could reduce costs, allowing for more affordable market pricing to improve the long-term viability of the cell therapy product and facilitate broader patient access to novel and transformative cell therapies. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Role of endoscopic ultrasonography in the loco-regional staging of patients with rectal cancer

Science.gov (United States)

Marone, Pietro; de Bellis, Mario; D’Angelo, Valentina; Delrio, Paolo; Passananti, Valentina; Di Girolamo, Elena; Rossi, Giovanni Battista; Rega, Daniela; Tracey, Maura Claire; Tempesta, Alfonso Mario

2015-01-01

The prognosis of rectal cancer (RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC (LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy (NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound (EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor (T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery. PMID:26140096

Anti-angiogenesis and anti-tumor activity of recombinant anginex

International Nuclear Information System (INIS)

Brandwijk, Ricardo J.M.G.E.; Dings, Ruud P.M.; Linden, Edith van der; Mayo, Kevin H.; Thijssen, Victor L.J.L.; Griffioen, Arjan W.

2006-01-01

Anginex, a synthetic 33-mer angiostatic peptide, specifically inhibits vascular endothelial cell proliferation and migration along with induction of apoptosis in endothelial cells. Here we report on the in vivo characterization of recombinant anginex and use of the artificial anginex gene for gene therapy approaches. Tumor growth of human MA148 ovarian carcinoma in athymic mice was inhibited by 80% when treated with recombinant anginex. Histological analysis of the tumors showed an approximate 2.5-fold reduction of microvessel density, suggesting that angiogenesis inhibition is the cause of the anti-tumor effect. Furthermore, there was a significant correlation between the gene expression patterns of 16 angiogenesis-related factors after treatment with both recombinant and synthetic anginex. To validate the applicability of the anginex gene for gene therapy, stable transfectants of murine B16F10 melanoma cells expressing recombinant anginex were made. Supernatants of these cells inhibited endothelial cell proliferation in vitro. Furthermore, after subcutaneous injection of these cells in C57BL/6 mice, an extensive delay in tumor growth was observed. These data show that the artificial anginex gene can be used to produce a recombinant protein with similar activity as its synthetic counterpart and that the gene can be applied in gene therapy approaches for cancer treatment

Gastro-pancreaticojejunostomy for treatment of pancreatic ductal obstruction in a post-Whipple procedure patient.

Science.gov (United States)

Rodrigues-Pinto, Eduardo; Grimm, Ian S; Baron, Todd H

2015-01-01

We report a case of a woman with a medical history of classic Whipple surgery who underwent endoscopic ultrasound (EUS)-guided pancreatic drainage due to smouldering acute pancreatitis secondary to an obstructing pancreatic ductal stone. A gastro-pancreaticojejunostomy anastomosis was created anterogradely, with dilation of both the anastomoses in the same procedure, with subsequent decompression of the pancreatic duct. Endoscopic retrograde pancreatography (ERP) is often impossible to perform in patients with post-Whipple procedure anatomy due to inaccessibility to the pancreaticojejunostomy anastomosis. EUS-guided pancreatic drainage may be offered in these patients in whom the pancreatic duct cannot be accessed at ERP. It has been used as a platform for access to and drainage of the pancreatic duct either by rendezvous or transmural drainage. However, only one of four patients achieve successful completion of the rendezvous procedure. There are limited data regarding safety and long-term outcome of this procedure, as well as scant guidelines on the optimal time for leaving stents in place. We believe definitive endoscopic therapy should be attempted, whenever possible, after relief of obstruction. In our case, we expect that stent occlusion is inevitable and that long-term drainage is possible due to drainage occurring between the stent and the stone.

Endoscopic ultrasound guided radiofrequency ablation, for pancreatic cystic neoplasms and neuroendocrine tumors

Science.gov (United States)

Pai, Madhava; Habib, Nagy; Senturk, Hakan; Lakhtakia, Sundeep; Reddy, Nageshwar; Cicinnati, Vito R; Kaba, Iyad; Beckebaum, Susanne; Drymousis, Panagiotis; Kahaleh, Michel; Brugge, William

2015-01-01

AIM: To outline the feasibility, safety, adverse events and early results of endoscopic ultrasound (EUS)-radiofrequency ablation (RFA) in pancreatic neoplasms using a novel probe. METHODS: This is a multi-center, pilot safety feasibility study. The intervention described was radiofrequency ablation (RF) which was applied with an innovative monopolar RF probe (1.2 mm Habib EUS-RFA catheter) placed through a 19 or 22 gauge fine needle aspiration (FNA) needle once FNA was performed in patients with a tumor in the head of the pancreas. The Habib™ EUS-RFA is a 1 Fr wire (0.33 mm, 0.013”) with a working length of 190 cm, which can be inserted through the biopsy channel of an echoendoscope. RF power is applied to the electrode at the end of the wire to coagulate tissue in the liver and pancreas. RESULTS: Eight patients [median age of 65 (range 27-82) years; 7 female and 1 male] were recruited in a prospective multicenter trial. Six had a pancreatic cystic neoplasm (four a mucinous cyst, one had intraductal papillary mucinous neoplasm and one a microcystic adenoma) and two had a neuroendocrine tumors (NET) in the head of pancreas. The mean size of the cystic neoplasm and NET were 36.5 mm (SD ± 17.9 mm) and 27.5 mm (SD ± 17.7 mm) respectively. The EUS-RFA was successfully completed in all cases. Among the 6 patients with a cystic neoplasm, post procedure imaging in 3-6 mo showed complete resolution of the cysts in 2 cases, whilst in three more there was a 48.4% reduction [mean pre RF 38.8 mm (SD ± 21.7 mm) vs mean post RF 20 mm (SD ± 17.1 mm)] in size. In regards to the NET patients, there was a change in vascularity and central necrosis after EUS-RFA. No major complications were observed within 48 h of the procedure. Two patients had mild abdominal pain that resolved within 3 d. CONCLUSION: EUS-RFA of pancreatic neoplasms with a novel monopolar RF probe was well tolerated in all cases. Our preliminary data suggest that the procedure is straightforward and safe. The

Delivery of vincristine sulfate-conjugated gold nanoparticles using liposomes: a light-responsive nanocarrier with enhanced antitumor efficiency

Directory of Open Access Journals (Sweden)

Liu Y

2015-04-01

Full Text Available Ying Liu,1,* Man He,1,* Mengmeng Niu,1 Yiqing Zhao,1 Yuanzhang Zhu,1 Zhenhua Li,2 Nianping Feng1 1Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Cedars-Sinai Medical Center, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Rapid drug release at the specific site of action is still a challenge for antitumor therapy. Development of stimuli-responsive hybrid nanocarriers provides a promising strategy to enhance therapeutic effects by combining the unique features of each component. The present study explored the use of drug–gold nanoparticle conjugates incorporated into liposomes to enhance antitumor efficiency. A model drug, vincristine sulfate, was physically conjugated with gold nanoparticles and verified by UV-visible and fourier transform infrared spectroscopy, and differential scanning calorimetry. The conjugates were incorporated into liposomes by film dispersion to yield nanoparticles (113.4 nm with light-responsive release properties, as shown by in vitro release studies. Intracellular uptake and distribution was studied in HeLa cells using transmission electron microscopy and confocal laser scanning microscopy. This demonstrated liposome internalization and localization in endosomal–lysosomal vesicles. Fluorescence intensity increased in cells exposed to UV light, indicating that this stimulated intracellular drug release; this finding was confirmed by quantitative analyses using flow cytometry. Antitumor efficacy was evaluated in HeLa cells, both in culture and in implants in vivo in nude mice. HeLa cell viability assays showed that light exposure enhanced liposome cytotoxicity and induction of apoptosis. Furthermore, treatment with the prepared liposomes coupled with UV light exposure produced greater antitumor effects in nude mice and reduced side effects, as compared with free vincristine sulfate

A Single Domain–Based Anti-Her2 Antibody Has Potent Antitumor Activities

Directory of Open Access Journals (Sweden)

Xiaoqiong Wu

2018-04-01

Full Text Available Human epidermal growth factor receptor 2 (HER2 is overexpressed in approximately 20% to 30% of breast cancers and various other types of cancers, which plays a vital role in the cancer progression. Monoclonal antibodies targeting Her2 are now used in the clinic to treat Her2 overexpression cancer patients. However, relapse or resistance is frequent with the current therapies. To generate a new treatment avenue against Her2, we immunized and selected a specific anti-Her2 single domain antibody C3 for further studies. The C3-Fc antibody drove antibody-dependent cell-mediated cytotoxicity against Her2-positive tumor cells in vitro and resulted in potent antitumor growth in vivo. These data suggest that the C3-Fc antibody may provide an alternative avenue for Her2-positive cancer therapy.

Reliable and valid assessment of competence in endoscopic ultrasonography and fine-needle aspiration for mediastinal staging of non-small cell lung cancer

DEFF Research Database (Denmark)

Konge, Lars; Vilmann, P; Clementsen, P

2012-01-01

Fine-needle aspiration (FNA) guided by endoscopic ultrasonography (EUS) is important in mediastinal staging of non-small cell lung cancer (NSCLC). Training standards and implementation strategies of this technique are currently under discussion. The aim of this study was to explore the reliabilit...... and validity of a newly developed EUS Assessment Tool (EUSAT) designed to measure competence in EUS - FNA for mediastinal staging of NSCLC....

Smart activatable and traceable dual-prodrug for image-guided combination photodynamic and chemo-therapy.

Science.gov (United States)

Hu, Fang; Yuan, Youyong; Mao, Duo; Wu, Wenbo; Liu, Bin

2017-11-01

Activatable photosensitizers (PSs) and chemo-prodrugs are highly desirable for anti-cancer therapy to reduce systemic toxicity. However, it is difficult to integrate both together into a molecular probe for combination therapy due to the complexity of introducing PS, singlet oxygen quencher, chemo-drug, chemo-drug inhibitor and active linker at the same time. To realize activatable PS and chemo-prodrug combination therapy, we develop a smart therapeutic platform in which the chemo-prodrug serves as the singlet oxygen quencher for the PS. Specifically, the photosensitizing activity and fluorescence of the PS (TPEPY-SH) are blocked by the chemo-prodrug (Mitomycin C, MMC) in the probe. Meanwhile, the cytotoxicity of MMC is also inhibited by the electron-withdrawing acyl at the nitrogen position next to the linker. Upon glutathione activation, TPEPY-S-MMC can simultaneously release active PS and MMC for combination therapy. The restored fluorescence of TPEPY-SH is also used to report the activation for both PS and MMC as well as to guide the photodynamic therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-tumor activity of metformin: from metabolic and epigenetic perspectives

Science.gov (United States)

Zhai, Yansheng; Tong, Chong; Liu, Min; Ma, Lixin; Yu, Xiaolan; Li, Shanshan

2017-01-01

Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications. The effects of metformin on anti-cancer immunity and apoptosis were also described. Understanding these mechanisms will shed lights on application of metformin in clinical trials and development of anti-cancer therapy. PMID:27902459

Fluorescent supramolecular micelles for imaging-guided cancer therapy

Science.gov (United States)

Sun, Mengmeng; Yin, Wenyan; Dong, Xinghua; Yang, Wantai; Zhao, Yuliang; Yin, Meizhen

2016-02-01

A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy.A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth

Image-guided left ventricular lead placement in cardiac resynchronization therapy for patients with heart failure: a meta-analysis.

Science.gov (United States)

Jin, Yan; Zhang, Qi; Mao, Jia-Liang; He, Ben

2015-05-10

Heart failure (HF) is a debilitating condition that affects millions of people worldwide. One means of treating HF is cardiac resynchronization therapy (CRT). Recently, several studies have examined the use of echocardiography (ECHO) in the optimization of left ventricular (LV) lead placement to increase the response to CRT. The objective of this study was to synthesize the available data on the comparative efficacy of image-guided and standard CRT. We searched the PubMed, Cochrane, Embase, and ISI Web of Knowledge databases through April 2014 with the following combinations of search terms: left ventricular lead placement, cardiac resynchronization therapy, image-guided, and echocardiography-guided. Studies meeting all of the inclusion criteria and none of the exclusion criteria were eligible for inclusion. The primary outcome measures were CRT response rate, change in LV ejection fraction (LVEF), and change in LV end systolic volume (LVESV). Secondary outcomes included the rates of all-cause mortality and HF-related hospitalization. Our search identified 103 articles, 3 of which were included in the analysis. In total, 270 patients were randomized to the image-guided CRT and 241, to the standard CRT. The pooled estimates showed a significant benefit for image-guided CRT (CRT response: OR, 2.098, 95 % CI, 1.432-3.072; LVEF: difference in means, 3.457, 95 % CI, 1.910-5.005; LVESV: difference in means, -20.36, 95 % CI, -27.819 - -12.902). Image-guided CRT produced significantly better clinical outcomes than the standard CRT. Additional trials are warranted to validate the use of imaging in the prospective optimization of CRT.

Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

Science.gov (United States)

Chen, Lili; He, Zhengxiang; Qin, Li; Li, Qinyan; Shi, Xibao; Zhao, Siting; Chen, Ling; Zhong, Nanshan; Chen, Xiaoping

2011-01-01

Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer

Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

Directory of Open Access Journals (Sweden)

Lili Chen

Full Text Available BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL staining and decreased Ki-67 expression in tumors. Through natural killer (NK cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+ T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria

Correlation Theory Applied to the Static and Dynamic Properties of EuO and EuS

DEFF Research Database (Denmark)

Lindgård, Per-Anker

1982-01-01

was used previously in the correlation theory2) primarily to calculate static properties. Self‐consistent dynamic and static calculations have here been performed for EuO, which is an ideal Heisenberg magnet with significant second‐nearest‐neighbor interaction (J2 = J1/5). The two‐pole approximation...... a cutoff of the spectrum at high frequencies, which cannot be seen experimentally, but which significantly influences the frequency moments. It was found that the finite J2 has significant importance for a comparison between theory and experiment. It is concluded that the calculation for a simple cubic n.......n. magnet by Hubbard3) does not describe the EuO data accurately, neither with respect to line shape nor frequency scale. Significant differences are to be expected between EuO and EuS having opposite sign for J2....

Potentiation of antitumor immunity in tumor-bearing mice by a degraded D-manno-D-glucan (DMG), a new antitumor polysaccharide.

Science.gov (United States)

Nakajima, H; Kita, Y; Hashimoto, S; Tsukada, W; Abe, S; Mizuno, D

1983-12-01

DMG, a degraded D-manno-D-glucan from the culture fluid of Microellobosporia grisea, inhibited the growth of murine syngeneic MM46 mammary carcinoma. Mice in which the tumor had completely regressed by DMG treatment showed tumor-specific antitumor resistance. The antitumor action of DMG was studied by examining the influences of DMG on tumor-specific and non-specific immune responses in tumor-bearing hosts. The tumor-specific delayed hypersensitivity reaction appeared transiently on day 7 after tumor inoculation but had decreased by day 15 in untreated tumor-bearing mice. In contrast, the reaction was retained and augmented in DMG-treated tumor-bearing mice. The tumor-neutralizing activity of spleen cells from DMG-treated tumor-bearing mice, tested by a Winn assay, was tumor-specific and significantly higher than that of untreated tumor-bearing mice. The tumor-neutralizing activity of peritoneal cells and the in vitro cytostatic activity of peritoneal macrophages in response to lymphokine supernatants containing macrophage activation factor were also augmented by DMG treatment. In contrast, the level of antitumor antibody in the serum increased with time, irrespective of DMG administration. Thus, DMG potentiated cellular antitumor effector mechanisms.

Endoskopisk ultralydvejledt rendezvous til intern drænage ved galdevejsobstruktion

DEFF Research Database (Denmark)

Knudsen, Marie Høxbro; Vilmann, Peter; Hassan, Hazem

2015-01-01

Endoscopic ultrasound guided rendezvous for biliary drainage Endoscopic retrograde cholangiography (ERCP) is currently standard treatment for biliary drainage. Endoscopic ultrasound guided rendezvous (EUS-RV) is a novel method to overcome an unsuccessful biliary drainage procedure. Under endoscopic...

Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of Rosemary diterpenes in colon and pancreatic cancer.

Directory of Open Access Journals (Sweden)

Margarita González-Vallinas

Full Text Available Colorectal and pancreatic cancers remain important contributors to cancer mortality burden and, therefore, new therapeutic approaches are urgently needed. Rosemary (Rosmarinus officinalis L. extracts and its components have been reported as natural potent antiproliferative agents against cancer cells. However, to potentially apply rosemary as a complementary approach for cancer therapy, additional information regarding the most effective composition, its antitumor effect in vivo and its main molecular mediators is still needed. In this work, five carnosic acid-rich supercritical rosemary extracts with different chemical compositions have been assayed for their antitumor activity both in vivo (in nude mice and in vitro against colon and pancreatic cancer cells. We found that the antitumor effect of carnosic acid together with carnosol was higher than the sum of their effects separately, which supports the use of the rosemary extract as a whole. In addition, gene and microRNA expression analyses have been performed to ascertain its antitumor mechanism, revealing that up-regulation of the metabolic-related gene GCNT3 and down-regulation of its potential epigenetic modulator miR-15b correlate with the antitumor effect of rosemary. Moreover, plasmatic miR-15b down-regulation was detected after in vivo treatment with rosemary. Our results support the use of carnosic acid-rich rosemary extract as a complementary approach in colon and pancreatic cancer and indicate that GCNT3 expression may be involved in its antitumor mechanism and that miR-15b might be used as a non-invasive biomarker to monitor rosemary anticancer effect.

Enhanced antitumor efficacy of doxorubicin-encapsulated halloysite nanotubes

Directory of Open Access Journals (Sweden)

Li K

2017-12-01

Full Text Available Kai Li,1,* Yongxing Zhang,2,* Mengting Chen,1 Yangyang Hu,1 Weiliang Jiang,1 Li Zhou,1 Sisi Li,1 Min Xu,1 Qinghua Zhao,2 Rong Wan1 1Department of Gastroenterology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: To improve the antitumor efficacy of doxorubicin (DOX and provide novel clinical treatment of gastric cancer, halloysite nanotubes (HNTs loaded with DOX were encapsulated by soybean phospholipid (LIP and the formed HNTs/DOX/LIP was systematically characterized via different techniques. The in vitro anticancer activity of HNTs/DOX/LIP was examined using an MTT assay. The antitumor efficacy and biocompatibility were monitored by measuring the tumor volume and assessing the blood routine and serum biochemistry using an ectopic implantation cancer model. The results show that when the concentration of HNTs was 3 mg/mL and the concentration of DOX was 1 mg/mL the optimal DOX loading efficiency was as high as 22.01%±0.43%. In vitro drug release behavior study demonstrated that HNTs/DOX/LIP shows a pH-responsive release property with fast drug release under acidic conditions (pH =5.4. MTT assays and in vivo experimental results revealed that HNTs/DOX/LIP exhibits a significantly higher inhibitory efficacy on the growth of mouse gastric cancer cells than free DOX at the same drug concentration. In addition, the life span of tumor-bearing mice in the HNTs/DOX/LIP-treated group was obviously prolonged compared with the control groups. Moreover, HNTs/DOX/LIP possessed excellent hemocompatibility as shown in the blood and histology studies. These findings indicated that the formed HNTs/DOX/LIP possesses higher antitumor efficacy and may be used as a targeted

Initial Sleep Time Predicts Success in Manual-Guided Cognitive Behavioral Therapy for Insomnia.

Science.gov (United States)

Bothelius, Kristoffer; Kyhle, Kicki; Broman, Jan-Erik; Gordh, Torsten; Fredrikson, Mats

2016-01-01

Cognitive behavioral therapy produces significant and long-lasting improvement for individuals with insomnia, but treatment resources are scarce. A "stepped care" approach has therefore been proposed, but knowledge is limited on how to best allocate patients to different treatment steps. In this study, 66 primary-care patients with insomnia attended a low-end treatment step: manual-guided cognitive behavioral therapy (CBT) for insomnia delivered by ordinary primary-care personnel. Based on clinically significant treatment effects, subjects were grouped into treatment responders or nonresponders. Baseline data were analyzed to identify predictors for treatment success. Long total sleep time at baseline assessment was the only statistically significant predictor for becoming a responder, and sleep time may thus be important to consider before enrolling patients in low-end treatments.

Evaluation of Magnetic Resonance Imaging Responsiveness in Active Psoriatic Arthritis at Multiple Timepoints during the First 12 Weeks of Antitumor Necrosis Factor Therapy.

Science.gov (United States)

Feletar, Marie; Hall, Stephen; Bird, Paul

2016-01-01

To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.

Process-oriented guided-inquiry learning: a natural fit for occupational therapy education.

Science.gov (United States)

Jaffe, Lynn; Gibson, Robert; D'Amico, Mariana

2015-04-01

After a brief review of the major group cooperative learning strategies, this article presents the format and use of Process-Oriented Guided-Inquiry Learning (POGIL) as a recommended teaching strategy for occupational therapy classes. This recommendation is based upon evidence of effectiveness of this strategy for enhancing critical thinking, content retention, and teamwork. Strategies for learning the process and suggestions for its use are based upon literature evidence and the authors' experiences with this strategy over 4 years in a class on evidence-based practice.

Multifunctional antitumor magnetite/chitosan-l-glutamic acid (core/shell) nanocomposites

International Nuclear Information System (INIS)

Santos, Daniela P.; Ruiz, M. Adolfina; Gallardo, Visitación; Zanoni, Maria Valnice B.; Arias, José L.

2011-01-01

The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan-l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.

Multifunctional antitumor magnetite/chitosan- l-glutamic acid (core/shell) nanocomposites

Science.gov (United States)

Santos, Daniela P.; Ruiz, M. Adolfina; Gallardo, Visitación; Zanoni, Maria Valnice B.; Arias, José L.

2011-09-01

The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan- l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.

CT-guided percutaneous acetic acid injection therapy for liver metastasis

International Nuclear Information System (INIS)

Yu Tongfu; Wang Dehang; Zhuang Zhenwu; Li Linxun; Shi Haibin

2002-01-01

Objective: To evaluate the efficacy of CT-guided percutaneous acetic acid injection (PAI) for liver metastasis. Methods: Thirty-five cases (40 lesions) with liver metastasis were treated with PAI. 4-10 ml of 30% acetic acid with 1 ml contrast media was injected into every lesion. PAI was performed twice a week, and repeated for 2 to 3 weeks. Results: The tumors shrunk in 23 lesions, and remained unchanged in 12 lesions. The efficiency was 87.5%. All cases were followed up for 3 months to 3 years. One year survival rates was 62.9% (22 cases), 2 years 40.0% (14 cases), and 3 years 22.9% (8 cases). Conclusion: PAI was an effective therapy for liver metastasis

Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study.

Science.gov (United States)

Napoleon, B; Alvarez-Sanchez, M V; Gincoul, R; Pujol, B; Lefort, C; Lepilliez, V; Labadie, M; Souquet, J C; Queneau, P E; Scoazec, J Y; Chayvialle, J A; Ponchon, T

2010-07-01

Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope. 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months. The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS. CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

Guided Internet-based vs. face-to-face cognitive behaviour therapy for psychiatric and somatic disorders: a systematic review and meta-analysis.

NARCIS (Netherlands)

Andersson, G.; Cuijpers, P.; Carlbring, P.; Riper, H.; Hedman, E.

2014-01-01

Internet-delivered cognitive behavior therapy (ICBT) has been tested in many research trials, but to a lesser extent directly compared to faceto- face delivered cognitive behavior therapy (CBT). We conducted a systematic review and meta-analysis of trials in which guided ICBT was directly compared

Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy.

Science.gov (United States)

Hynynen, Kullervo; Jones, Ryan M

2016-09-07

Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy

Directory of Open Access Journals (Sweden)

Markus Vähä-Koskela

2014-01-01

Full Text Available Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.

Guided parent-delivered cognitive behavioral therapy for childhood anxiety: Predictors of treatment response

OpenAIRE

Thirlwall, Kerstin; Cooper, Peter; Creswell, Cathy

2017-01-01

Background: Guided Parent-delivered Cognitive Behaviour Therapy (GPD-CBT) is a brief, effective treatment for childhood anxiety disorders, however not all children respond favourably. \\ud Aims: To examine predictors of response to GPD-CBT.\\ud Methods: Parents of 125 children (7 – 12 years) with an anxiety disorder received GPD-CBT over 2.6 or 5.3 hours). Recovery was measured post treatment and six months later. \\ud Results: Younger children and those with primary Generalised Anxiety Disorder...

A pH-responsive chitosan-b-poly(p-dioxanone) nanocarrier: formation and efficient antitumor drug delivery

International Nuclear Information System (INIS)

Tang Daolu; Song Fei; Chen Cheng; Wang Xiuli; Wang Yuzhong

2013-01-01

Increasing attention has recently been paid to the fabrication of drug delivery systems with excellent cell internalization and intracellular drug release properties. In this study, an amphiphilic block copolymer of chitosan was synthesized for the first time, which can self-assemble into micelles in a neutral aqueous solution but partially disassemble in an acidic endosomal/lysosomal environment. The antitumor drug, camptothecin (CPT), was encapsulated in the cores of the micelles for tumor cell therapy. In vitro drug release studies demonstrated that the micelles presented a much faster release of CPT at pH 5.0 than at pH 7.4. Blank micelles were found to be nontoxic in preliminary in vitro cytotoxicity assays. Cell experiments showed that the CPT-loaded micelles could be effectively internalized by Hela cells and accomplished a potent antitumor cell efficacy, indicating that the chitosan-based micelles might be an attractive new platform for efficient intracellular drug delivery. (paper)

Role of endoscopic ultrasonography in evaluation of metastatic lesions to the pancreas: a tertiary cancer center experience.

Science.gov (United States)

Atiq, Muslim; Bhutani, Manoop S; Ross, William A; Raju, Gottumukkala S; Gong, Yun; Tamm, Eric P; Javle, Milind; Wang, Xuemei; Lee, Jeffrey H

2013-04-01

Metastatic lesions to the pancreas pose diagnostic challenges with regards to their differentiation from primary pancreatic cancer. Data on the yield of endoscopic ultrasonography (EUS)-guided fine-needle aspiration in detection of these lesions are limited. This is a retrospective review of 23 patients referred to a tertiary referral center for further evaluation of suspected pancreatic metastases. Main outcome measures were diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration in evaluation of metastatic lesions to the pancreas. Of 644 patients, 23 (3.6%) undergoing EUS of the pancreas were diagnosed to have metastatic disease to the pancreas based on clinical, radiological, and cytological results. Mean (SD) age was 64.3 (11.7) years. Of the 23 patients, 18 (78.3%) were asymptomatic. Mean (SD) size of lesion on EUS was 39.1 (19.9) mm. A diagnosis of malignant lesion was made in 21 of 23 cases, with a diagnostic accuracy of 91.3%. Metastatic lesions to the pancreas present as incidental, solitary mass lesions on staging or surveillance imaging. Endoscopic ultrasonography-guided fine-needle aspiration is an important tool in the characterization and further differentiation of metastatic lesions to the pancreas from primary pancreatic cancer.

Treatment of child anxiety disorders via guided parent-delivered cognitive-behavioural therapy: randomised controlled trial.

Science.gov (United States)

Thirlwall, Kerstin; Cooper, Peter J; Karalus, Jessica; Voysey, Merryn; Willetts, Lucy; Creswell, Cathy

2013-12-01

Promising evidence has emerged of clinical gains using guided self-help cognitive-behavioural therapy (CBT) for child anxiety and by involving parents in treatment; however, the efficacy of guided parent-delivered CBT has not been systematically evaluated in UK primary and secondary settings. To evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for children with anxiety disorders. A total of 194 children presenting with a current anxiety disorder, whose primary carer did not meet criteria for a current anxiety disorder, were randomly allocated to full guided parent-delivered CBT (four face-to-face and four telephone sessions) or brief guided parent-delivered CBT (two face-to-face and two telephone sessions), or a wait-list control group (trial registration: ISRCTN92977593). Presence and severity of child primary anxiety disorder (Anxiety Disorders Interview Schedule for DSM-IV, child/parent versions), improvement in child presentation of anxiety (Clinical Global Impression - Improvement scale), and change in child anxiety symptoms (Spence Children's Anxiety Scale, child/parent version and Child Anxiety Impact scale, parent version) were assessed at post-treatment and for those in the two active treatment groups, 6 months post-treatment. Full guided parent-delivered CBT produced superior diagnostic outcomes compared with wait-list at post-treatment, whereas brief guided parent-delivered CBT did not: at post-treatment, 25 (50%) of those in the full guided CBT group had recovered from their primary diagnosis, compared with 16 (25%) of those on the wait-list (relative risk (RR) 1.85, 95% CI 1.14-2.99); and in the brief guided CBT group, 18 participants (39%) had recovered from their primary diagnosis post-treatment (RR = 1.56, 95% CI 0.89-2.74). Level of therapist training and experience was unrelated to child outcome. Full guided parent-delivered CBT is an effective and inexpensive first-line treatment for child anxiety.

Host-Mediated Mechanisms of Resistance to Antitumor Therapies

NARCIS (Netherlands)

Daenen, L.G.M.

2013-01-01

In addition to their direct effects on tumor cells, certain anticancer therapies elicit a prosurvival response in benign tissues in the tumor microenvironment. This host response can be seen as an attempt of the body to diminish chemotherapy-induced damage in tissues crucial for functioning.

Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy.

Directory of Open Access Journals (Sweden)

De-Hua Yu

Full Text Available We identified pyrvinium pamoate, an old anthelminthic medicine, which preferentially inhibits anchorage-independent growth of cancer cells over anchorage-dependent growth (approximately 10 fold. It was also reported by others to have anti-tumor activity in vivo and selective toxicity against cancer cells under glucose starvation in vitro, but with unknown mechanism. Here, we provide evidence that pyrvinium suppresses the transcriptional activation of GRP78 and GRP94 induced by glucose deprivation or 2-deoxyglucose (2DG, a glycolysis inhibitor, but not by tunicamycin or A23187. Other UPR pathways induced by glucose starvation, e.g. XBP-1, ATF4, were also found suppressed by pyrvinium. Constitutive expression of GRP78 via transgene partially protected cells from pyrvinium induced cell death under glucose starvation, suggesting that suppression of the UPR is involved in pyrvinium mediated cytotoxicity under glucose starvation. Xenograft experiments showed rather marginal overall anti-tumor activity for pyrvinium as a monotherapy. However, the combination of pyrvinium and Doxorubicin demonstrated significantly enhanced efficacy in vivo, supporting a mechanistic treatment concept based on tumor hypoglycemia and UPR.

Systematic measurements of whole-body imaging dose distributions in image-guided radiation therapy

International Nuclear Information System (INIS)

Hälg, Roger A.; Besserer, Jürgen; Schneider, Uwe

2012-01-01

Purpose: The full benefit of the increased precision of contemporary treatment techniques can only be exploited if the accuracy of the patient positioning is guaranteed. Therefore, more and more imaging modalities are used in the process of the patient setup in clinical routine of radiation therapy. The improved accuracy in patient positioning, however, results in additional dose contributions to the integral patient dose. To quantify this, absorbed dose measurements from typical imaging procedures involved in an image-guided radiation therapy treatment were measured in an anthropomorphic phantom for a complete course of treatment. The experimental setup, including the measurement positions in the phantom, was exactly the same as in a preceding study of radiotherapy stray dose measurements. This allows a direct combination of imaging dose distributions with the therapy dose distribution. Methods: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The dose distributions from imaging devices used with treatment machines from the manufacturers Accuray, Elekta, Siemens, and Varian and from computed tomography scanners from GE Healthcare were determined and the resulting effective dose was calculated. The list of investigated imaging techniques consisted of cone beam computed tomography (kilo- and megavoltage), megavoltage fan beam computed tomography, kilo- and megavoltage planar imaging, planning computed tomography with and without gating methods and planar scout views. Results: A conventional 3D planning CT resulted in an effective dose additional to the treatment stray dose of less than 1 mSv outside of the treated volume, whereas a 4D planning CT resulted in a 10 times larger dose. For a daily setup of the patient with two planar kilovoltage images or with a fan beam CT at the TomoTherapy unit, an additional effective dose outside of the treated volume of less than 0.4 mSv and 1

Functional image-guided stereotactic body radiation therapy planning for patients with hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Tsegmed, Uranchimeg [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nakashima, Takeo [Division of Radiation Therapy, Hiroshima University Hospital, Hiroshima (Japan); Nakamura, Yuko; Higaki, Toru [Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Imano, Nobuki; Doi, Yoshiko; Kenjo, Masahiro; Ozawa, Shuichi; Murakami, Yuji [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Awai, Kazuo [Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nagata, Yasushi [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan)

2017-07-01

The aim of the current planning study is to evaluate the ability of gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI)–guided stereotactic body radiation therapy (SBRT) planning by using intensity-modulated radiation therapy (IMRT) techniques in sparing the functional liver tissues during SBRT for hepatocellular carcinoma. In this study, 20 patients with hepatocellular carcinoma were enrolled. Functional liver tissues were defined according to quantitative liver-spleen contrast ratios ≥ 1.5 on a hepatobiliary phase scan. Functional images were fused with the planning computed tomography (CT) images; the following 2 SBRT plans were designed using a “step-and-shoot” static IMRT technique for each patient: (1) an anatomical SBRT plan optimization based on the total liver; and (2) a functional SBRT plan based on the functional liver. The total prescribed dose was 48 gray (Gy) in 4 fractions. Dosimetric parameters, including dose to 95% of the planning target volume (PTV D{sub 95%}), percentages of total and functional liver volumes, which received doses from 5 to 30 Gy (V5 to V30 and fV5 to fV30), and mean doses to total and functional liver (MLD and fMLD, respectively) of the 2 plans were compared. Compared with anatomical plans, functional image-guided SBRT plans reduced MLD (mean: plan A, 5.5 Gy; and plan F, 5.1 Gy; p < 0.0001) and fMLD (mean: plan A, 5.4 Gy; and plan F, 4.9 Gy; p < 0.0001), as well as V5 to V30 and fV5 to fV30. No differences were noted in PTV coverage and nonhepatic organs at risk (OARs) doses. In conclusion, EOB-MRI–guided SBRT planning using the IMRT technique may preserve functional liver tissues in patients with hepatocellular carcinoma (HCC).

Predictive Biomarkers for Bevacizumab in Anti-tumor Therapy

Directory of Open Access Journals (Sweden)

Qingqing PAN

2011-07-01

Full Text Available Bevacizumab, the monoclonal antibody of vascular endothelial growth factor (VEGF has been applied to the therapy of several neoplasms, but an appropriate biomarker to predict the efficacy has not been found. Those markers can originate from peripheral circulation, tumor tissue and genes. Some researches have found that low level of vascular cell adhesion molecule-1 (VCAM-1, E-selectin, angiopoietin 2 (Ang-2 in circulation or carbonic anhydrase 9 (CA9, CD31-microvessel density (CD31-MVD in tumor tissue can predict better activity of bevacizumab. Moreover, high level of soluble VEGFR2 (sVEGFR2 in circulation or the ratio of phosphorylated-VEGFR2 (p-VEGFR2 and VEGFR2 in tumor tissue increasing has the same predictive function. As to the gene, VEGF-634 CC, VEGF-1498 TT and VEGFR2 H472Q are only related to the side effct. Thus more clinical tirals and basic researches should be performed to find out effective biomarkers in bevacizumab’s therapy.

Utility of dysphagia grade in predicting endoscopic ultrasound T-stage of non-metastatic esophageal cancer.

Science.gov (United States)

Fang, T C; Oh, Y S; Szabo, A; Khan, A; Dua, K S

2016-08-01

Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively. Overall, there was a significant positive correlation between dysphagia grade and the EUS T-stage of esophageal cancer. All patients with dysphagia grade ≥3 had T3 lesions. This may have clinical implications for patients who can only swallow liquids or have complete dysphagia by allowing for prompt initiation of neoadjuvant therapy, especially in countries/centers where EUS service is difficult to access in a timely manner or not available. © 2015 International Society for Diseases of the Esophagus.

Early Outcomes From Three Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Mendenhall, Nancy P.; Li Zuofeng; Hoppe, Bradford S.; Marcus, Robert B.; Mendenhall, William M.; Nichols, R. Charles; Morris, Christopher G.; Williams, Christopher R.; Costa, Joseph; Henderson, Randal

2012-01-01

Purpose: To report early outcomes with image-guided proton therapy for prostate cancer. Methods and Materials: We accrued 211 prostate cancer patients on prospective Institutional Review Board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low–risk disease, dose escalation from 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel followed by androgen deprivation for high-risk disease. Minimum follow-up was 2 years. Results: One intermediate-risk patient and 2 high-risk patients had disease progression. Pretreatment genitourinary (GU) symptom management was required in 38% of patients. A cumulative 88 (42%) patients required posttreatment GU symptom management. Four transient Grade 3 GU toxicities occurred, all among patients requiring pretreatment GU symptom management. Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1 Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months, with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy. Univariate and multivariate analyses showed significant correlation between Grade 2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum) receiving doses ranging from 40 CGE (10 CGE) to 80 CGE. Conclusions: Early outcomes with image-guided proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.

Early Outcomes From Three Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Mendenhall, Nancy P., E-mail: menden@shands.ufl.edu [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Li Zuofeng; Hoppe, Bradford S.; Marcus, Robert B.; Mendenhall, William M.; Nichols, R. Charles; Morris, Christopher G. [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Williams, Christopher R.; Costa, Joseph [Division of Urology, College of Medicine, University of Florida, Jacksonville, FL (United States); Henderson, Randal [University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

2012-01-01

Purpose: To report early outcomes with image-guided proton therapy for prostate cancer. Methods and Materials: We accrued 211 prostate cancer patients on prospective Institutional Review Board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, dose escalation from 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel followed by androgen deprivation for high-risk disease. Minimum follow-up was 2 years. Results: One intermediate-risk patient and 2 high-risk patients had disease progression. Pretreatment genitourinary (GU) symptom management was required in 38% of patients. A cumulative 88 (42%) patients required posttreatment GU symptom management. Four transient Grade 3 GU toxicities occurred, all among patients requiring pretreatment GU symptom management. Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1 Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months, with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy. Univariate and multivariate analyses showed significant correlation between Grade 2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum) receiving doses ranging from 40 CGE (10 CGE) to 80 CGE. Conclusions: Early outcomes with image-guided proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.

Five-Year Outcomes from 3 Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Mendenhall, Nancy P., E-mail: menden@shands.ufl.edu [University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Hoppe, Bradford S.; Nichols, Romaine C.; Mendenhall, William M.; Morris, Christopher G.; Li, Zuofeng; Su, Zhong [University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Williams, Christopher R.; Costa, Joseph [Division of Urology, College of Medicine, University of Florida, Jacksonville, Florida (United States); Henderson, Randal H. [University of Florida Proton Therapy Institute, Jacksonville, Florida (United States)

2014-03-01

Purpose: To report 5-year clinical outcomes of 3 prospective trials of image-guided proton therapy for prostate cancer. Methods and Materials: A total of 211 prostate cancer patients (89 low-risk, 82 intermediate-risk, and 40 high-risk) were treated in institutional review board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel therapy followed by androgen deprivation therapy for high-risk disease. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Median follow-up was 5.2 years. Results: Five-year rates of biochemical and clinical freedom from disease progression were 99%, 99%, and 76% in low-, intermediate-, and high-risk patients, respectively. Actuarial 5-year rates of late CTCAE, version 3.0 (or version 4.0) grade 3 gastrointestinal and urologic toxicity were 1.0% (0.5%) and 5.4% (1.0%), respectively. Median pretreatment scores and International Prostate Symptom Scores at >4 years posttreatment were 8 and 7, 6 and 6, and 9 and 8, respectively, among the low-, intermediate-, and high-risk patients. There were no significant changes between median pretreatment summary scores and Expanded Prostate Cancer Index Composite scores at >4 years for bowel, urinary irritative and/or obstructive, and urinary continence. Conclusions: Five-year clinical outcomes with image-guided proton therapy included extremely high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes. Further follow-up and a larger patient experience are necessary to confirm these favorable outcomes.

Five-Year Outcomes from 3 Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Mendenhall, Nancy P.; Hoppe, Bradford S.; Nichols, Romaine C.; Mendenhall, William M.; Morris, Christopher G.; Li, Zuofeng; Su, Zhong; Williams, Christopher R.; Costa, Joseph; Henderson, Randal H.

2014-01-01

Purpose: To report 5-year clinical outcomes of 3 prospective trials of image-guided proton therapy for prostate cancer. Methods and Materials: A total of 211 prostate cancer patients (89 low-risk, 82 intermediate-risk, and 40 high-risk) were treated in institutional review board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel therapy followed by androgen deprivation therapy for high-risk disease. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Median follow-up was 5.2 years. Results: Five-year rates of biochemical and clinical freedom from disease progression were 99%, 99%, and 76% in low-, intermediate-, and high-risk patients, respectively. Actuarial 5-year rates of late CTCAE, version 3.0 (or version 4.0) grade 3 gastrointestinal and urologic toxicity were 1.0% (0.5%) and 5.4% (1.0%), respectively. Median pretreatment scores and International Prostate Symptom Scores at >4 years posttreatment were 8 and 7, 6 and 6, and 9 and 8, respectively, among the low-, intermediate-, and high-risk patients. There were no significant changes between median pretreatment summary scores and Expanded Prostate Cancer Index Composite scores at >4 years for bowel, urinary irritative and/or obstructive, and urinary continence. Conclusions: Five-year clinical outcomes with image-guided proton therapy included extremely high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes. Further follow-up and a larger patient experience are necessary to confirm these favorable outcomes

Potential benefits of combining cytosine deaminase/5-fluorocytosine gene therapy and irradiation for prostate cancer. Experimental study

Energy Technology Data Exchange (ETDEWEB)

Kato, Hiroaki; Koshida, Kiyoshi; Yokoyama, Kunihiko; Mizokami, Atsushi; Namiki, Mikio [Kanazawa Univ. (Japan). School of Medicine

2002-10-01

The purpose of this study was to investigate the potential of combining cytosine deaminase/5-fluorocytosine (CD/5-FC) gene therapy and radiation therapy (either external beam radiation or radioimmunotherapy [RIT]), for the treatment of prostate cancer. Tumor xenografts of CD-transduced LNCaP cells grown in the testes of severe combined immunodeficiency (SCID) mice were used to evaluate antitumor effect. The mice were injected intraperitoneally with 500 mg/kg of 5-FC, or with 5, 15 or 30 mg/kg of 5-fluorouracil (5-FU), for 9 days. The tumors were treated with fractionated radiation at a dose of 1 or 3 Gy/day for 3 days, or I-131 labelled anti-prostate specific antigen (anti-PSA) monoclonal antibody (mAb) administration at a subtherapeutic dose of 20 or 80 {mu}Ci. Intratumoral and serum concentrations of 5-FU were measured using high performance liquid chromatography. Mice treated with CD/5-FC gene therapy presented a significant tumor growth inhibition comparable to that obtained with 15 mg/kg, 5-FU systemic administration without marked weight loss. Treatment with CD/5-FC gene therapy resulted in higher tumor but lower serum concentrations of 5-FU than treatment with systemic 5-FU chemotherapy. An additive antitumor effect was obtained when CD/5-FC therapy was combined with 1 Gy irradiation, which by itself did not produce a significant antitumor effect. However, the efficacy of CD/5-FC therapy was not enhanced when combined with RIT, probably due to poor accumulation of the mAb as the tumor/blood ratio never exceeded 1. These findings indicate that CD/5-FC gene therapy for prostate cancer may function with enhanced antitumor effect when combined with external beam radiation. However, combining CD/5-FC gene therapy and RIT using an anti-PSA mAb may not be effective because of insufficient accumulation of the mAb at the target tumors. (author)

Potential benefits of combining cytosine deaminase/5-fluorocytosine gene therapy and irradiation for prostate cancer. Experimental study

International Nuclear Information System (INIS)

Kato, Hiroaki; Koshida, Kiyoshi; Yokoyama, Kunihiko; Mizokami, Atsushi; Namiki, Mikio

2002-01-01

The purpose of this study was to investigate the potential of combining cytosine deaminase/5-fluorocytosine (CD/5-FC) gene therapy and radiation therapy (either external beam radiation or radioimmunotherapy [RIT]), for the treatment of prostate cancer. Tumor xenografts of CD-transduced LNCaP cells grown in the testes of severe combined immunodeficiency (SCID) mice were used to evaluate antitumor effect. The mice were injected intraperitoneally with 500 mg/kg of 5-FC, or with 5, 15 or 30 mg/kg of 5-fluorouracil (5-FU), for 9 days. The tumors were treated with fractionated radiation at a dose of 1 or 3 Gy/day for 3 days, or I-131 labelled anti-prostate specific antigen (anti-PSA) monoclonal antibody (mAb) administration at a subtherapeutic dose of 20 or 80 μCi. Intratumoral and serum concentrations of 5-FU were measured using high performance liquid chromatography. Mice treated with CD/5-FC gene therapy presented a significant tumor growth inhibition comparable to that obtained with 15 mg/kg, 5-FU systemic administration without marked weight loss. Treatment with CD/5-FC gene therapy resulted in higher tumor but lower serum concentrations of 5-FU than treatment with systemic 5-FU chemotherapy. An additive antitumor effect was obtained when CD/5-FC therapy was combined with 1 Gy irradiation, which by itself did not produce a significant antitumor effect. However, the efficacy of CD/5-FC therapy was not enhanced when combined with RIT, probably due to poor accumulation of the mAb as the tumor/blood ratio never exceeded 1. These findings indicate that CD/5-FC gene therapy for prostate cancer may function with enhanced antitumor effect when combined with external beam radiation. However, combining CD/5-FC gene therapy and RIT using an anti-PSA mAb may not be effective because of insufficient accumulation of the mAb at the target tumors. (author)

Delivering Acceptance and Commitment Therapy for Weight Self-Stigma through Guided Self-Help: Results from an Open Pilot Trial

OpenAIRE

Levin, Michael E.; Potts, Sarah; Haeger, Jack; Lillis, Jason

2017-01-01

Weight self-stigma is a promising target for innovative interventions seeking to improve outcomes among overweight/obese individuals. Preliminary research suggests acceptance and commitment therapy (ACT) may be an effective approach for reducing weight self-stigma, but a guided self-help version of this intervention may improve broad dissemination. This pilot open trial sought to evaluate the potential acceptability and efficacy of a guided self-help ACT intervention, included coaching and a ...

Melatonin enhances the anti-tumor effect of fisetin by inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways.

Directory of Open Access Journals (Sweden)

Canhui Yi

Full Text Available Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells. The combinational treatment of fisetin with melatonin increased the cleavage of PARP proteins, triggered more release of cytochrome-c from the mitochondrial inter-membrane, enhanced the inhibition of COX-2 and iNOS expression, repressed the nuclear localization of p300 and NF-κB proteins, and abrogated the binding of NF-κB on COX-2 promoter. Thus, these results demonstrated that melatonin potentiated the anti-tumor effect of fisetin in melanoma cells by activating cytochrome-c-dependent apoptotic pathway and inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways, and our study suggests the potential of such a combinational treatment of natural products in melanoma therapy.

Melatonin Enhances the Anti-Tumor Effect of Fisetin by Inhibiting COX-2/iNOS and NF-κB/p300 Signaling Pathways

Science.gov (United States)

Yu, Zhenlong; Xiao, Yao; Wang, Jingshu; Qiu, Huijuan; Yu, Wendan; Tang, Ranran; Yuan, Yuhui; Guo, Wei; Deng, Wuguo

2014-01-01

Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells. The combinational treatment of fisetin with melatonin increased the cleavage of PARP proteins, triggered more release of cytochrome-c from the mitochondrial inter-membrane, enhanced the inhibition of COX-2 and iNOS expression, repressed the nuclear localization of p300 and NF-κB proteins, and abrogated the binding of NF-κB on COX-2 promoter. Thus, these results demonstrated that melatonin potentiated the anti-tumor effect of fisetin in melanoma cells by activating cytochrome-c-dependent apoptotic pathway and inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways, and our study suggests the potential of such a combinational treatment of natural products in melanoma therapy. PMID:25000190

Anti-tumor effect of polysaccharides from rhizome of Curculigo ...

African Journals Online (AJOL)

The anti-tumor effect of PDC on cervical cancer was investigated in vivo in mice injected with Hela cells. The parameters measured were tumor volume and weight. In vitro anti-tumor effects of PDC were assessed by measuring expressions of caspase-3, caspase-9 and P53 proteins in Hela cells via ELISA assay. Thymus ...

MRI-guided and CT-guided cervical nerve root infiltration therapy. A cost comparison

Energy Technology Data Exchange (ETDEWEB)

Maurer, M.H.; Froeling, V.; Roettgen, R.; Bucourt, M. de; Hamm, B.; Streitparth, F. [Charite University Medicine Berlin (Germany). Dept. of Diagnostic and Interventional Radiology; Bretschneider, T. [Magdeburg Univ. (Germany). Dept. of Radiology and Nuclear Medicine; Hartwig, T.; Disch, A.C. [Charite University Medicine Berlin (Germany). Center for Musculoskeletal Surgery

2014-06-15

Purpose: To evaluate and compare the costs of MRI-guided and CT-guided cervical nerve root infiltration for the minimally invasive treatment of radicular neck pain. Materials and Methods: Between September 2009 and April 2012, 22 patients (9 men, 13 women; mean age: 48.2 years) underwent MRI-guided (1.0 Tesla, Panorama HFO, Philips) single-site periradicular cervical nerve root infiltration with 40 mg triamcinolone acetonide. A further 64 patients (34 men, 30 women; mean age: 50.3 years) were treated under CT fluoroscopic guidance (Somatom Definition 64, Siemens). The mean overall costs were calculated as the sum of the prorated costs of equipment use (purchase, depreciation, maintenance, and energy costs), personnel costs and expenditure for disposables that were identified for MRI- and CT-guided procedures. Additionally, the cost of ultrasound guidance was calculated. Results: The mean intervention time was 24.9 min. (range: 12-36 min.) for MRI-guided infiltration and 19.7 min. (range: 5-54 min.) for CT-guided infiltration. The average total costs per patient were EUR 240 for MRI-guided interventions and EUR 124 for CT-guided interventions. These were (MRI/CT guidance) EUR 150/60 for equipment use, EUR 46/40 for personnel, and EUR 44/25 for disposables. The mean overall cost of ultrasound guidance was EUR 76. Conclusion: Cervical nerve root infiltration using MRI guidance is still about twice as expensive as infiltration using CT guidance. However, since it does not involve radiation exposure for patients and personnel, MRI-guided nerve root infiltration may become a promising alternative to the CT-guided procedure, especially since a further price decrease is expected for MRI devices and MR-compatible disposables. In contrast, ultrasound remains the less expensive method for nerve root infiltration guidance. (orig.)

MRI-guided and CT-guided cervical nerve root infiltration therapy. A cost comparison

International Nuclear Information System (INIS)

Maurer, M.H.; Froeling, V.; Roettgen, R.; Bucourt, M. de; Hamm, B.; Streitparth, F.; Bretschneider, T.; Hartwig, T.; Disch, A.C.

2014-01-01

Purpose: To evaluate and compare the costs of MRI-guided and CT-guided cervical nerve root infiltration for the minimally invasive treatment of radicular neck pain. Materials and Methods: Between September 2009 and April 2012, 22 patients (9 men, 13 women; mean age: 48.2 years) underwent MRI-guided (1.0 Tesla, Panorama HFO, Philips) single-site periradicular cervical nerve root infiltration with 40 mg triamcinolone acetonide. A further 64 patients (34 men, 30 women; mean age: 50.3 years) were treated under CT fluoroscopic guidance (Somatom Definition 64, Siemens). The mean overall costs were calculated as the sum of the prorated costs of equipment use (purchase, depreciation, maintenance, and energy costs), personnel costs and expenditure for disposables that were identified for MRI- and CT-guided procedures. Additionally, the cost of ultrasound guidance was calculated. Results: The mean intervention time was 24.9 min. (range: 12-36 min.) for MRI-guided infiltration and 19.7 min. (range: 5-54 min.) for CT-guided infiltration. The average total costs per patient were EUR 240 for MRI-guided interventions and EUR 124 for CT-guided interventions. These were (MRI/CT guidance) EUR 150/60 for equipment use, EUR 46/40 for personnel, and EUR 44/25 for disposables. The mean overall cost of ultrasound guidance was EUR 76. Conclusion: Cervical nerve root infiltration using MRI guidance is still about twice as expensive as infiltration using CT guidance. However, since it does not involve radiation exposure for patients and personnel, MRI-guided nerve root infiltration may become a promising alternative to the CT-guided procedure, especially since a further price decrease is expected for MRI devices and MR-compatible disposables. In contrast, ultrasound remains the less expensive method for nerve root infiltration guidance. (orig.)

The hTERT promoter enhances the antitumor activity of an oncolytic adenovirus under a hypoxic microenvironment.

Directory of Open Access Journals (Sweden)

Yuuri Hashimoto

Full Text Available Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin, in which the human telomerase reverse transcriptase (hTERT promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5. In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen or a hypoxic (1% oxygen condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1α and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells.

Multimodal OCT for complex assessment of tumors response to therapy

Science.gov (United States)

Sirotkina, Marina A.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Zaitsev, Vladimir Yu.; Matveyev, Alexander L.; Shirmanova, Marina V.; Sovetsky, Alexander A.; Moiseev, Alexander A.; Zagaynova, Elena V.; Vitkin, Alex; Gladkova, Natalia D.

2017-07-01

Multimodal OCT is a promising tool for monitoring of individual tumor response to antitumor therapies. The changes of tumor cells, connective tissue, microcirculation and stiffness can be estimated simultaneously in real time with high resolution.

Antitumor function and mechanism of phycoerythrin from Porphyra haitanensis

Directory of Open Access Journals (Sweden)

Qunwen Pan

2013-01-01

Full Text Available The anti-tumor effect of R-Phycoerythrin (R-PE from Porphyra haitanensis was studied using cell line HeLa as an in vitro model and Sarcoma-180 (S180 tumor-bearing mice as an in vivo model. The results showed that the combination treatment of R-PE and photodynamic therapy PDT significantly inhibited the growth of HeLa cells up to 81.5%, with a fair dose-effect relationship, but did not inhibit endothelial cells. The annexin v-fitc/PI fluorescence staining experiments demonstrated that at doses between 0~60µg/mL, apoptosis cells and later stage apoptosis cells or necrosis cells increased significantly as the R-PE dosage increased. DNA electrophoresis showed that after R-PE+PDT treatment of HeLa cells for 24 hours, a light "smear" band between 100~400bp appeared to indicate the degradation of genomic DNA. The QRT-PCR results showed that R-PE+PDT treatment increased caspase-3 and caspase-10 gene expression and decreased the Bcl-2 gene expression level significantly as the R-PE dose increased, implying that R-PE promoted HeLa cell apoptosis. Compared with untreated S180 tumor-bearing mice, R-PE injection significantly inhibited the growth of S180 in tumor-bearing mice up to 41.3% at a dose of 300mg-kg-1. Simultaneously, the significant increase of superoxide dismutase (SOD activity in serum (p < 0.01 and the decrease of the malondialdehyde (MDA level in liver suggests that R-PE improved the anti-oxidant ability of the S180 tumor-bearing mice, which may related to its antitumor effect. In addition, the R-PE caused a significant increase (p < 0.05 in the spleen index and thymus index, and a significant increase (p < 0.01 in lymphocyte proliferation, NK cell kill activity and the TNF-α level in the serum of S180 tumor-bearing mice. These results strongly suggest that the antitumor effect of R-PE from Porphyra haitanensis functioned by increasing the immunity and antioxidant ability of S180 tumor-bearing mice, promoting apoptosis by increasing protease

Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with {sup 131}I-MIP-1095

Energy Technology Data Exchange (ETDEWEB)

Afshar-Oromieh, Ali; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Zechmann, Christian; Mier, Walter; Spohn, Fabian; Debus, Nils; Kratochwil, Clemens [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Armor, Thomas [Progenics Pharmaceuticals, Inc., New York, NY (United States); Holland-Letz, Tim [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Babich, John [Weill Cornell Medicine, Division of Radiopharmaceutical Sciences, Department of Radiology, New York, NY (United States); Weill Cornell Medicine, Citigroup Biomedical Imaging Center, New York, NY (United States); Weill Cornell Medicine, Meyer Cancer Center, New York, NY (United States)

2017-06-15

Prostate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies. Thirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with {sup 131}I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy. The applied doses were separated in three groups: <3.5, 3.5-5.0 and >5.0 GBq. Antitumor and side-effects were analyzed by blood samples and other clinical data. Follow-up was conducted for up to 5 years. The best therapeutic effect was achieved by the first therapy. A PSA decline of ≥50% was achieved in 70.6% of the patients. The second and third therapies were significantly less effective. There was neither an association between the applied activity and PSA response or the time-to-progression. Hematologic toxicities were less prevalent but presented in a higher percentage of patients with increasing number of therapies. After hematologic toxicities, xerostomia was the second most frequent side effect and presented more often and with higher intensity after the second or third therapy. The first dose of RLT with {sup 131}I-MIP-1095 presented with low side effects and could significantly reduce the tumor burden in a majority of patients. The second and third therapies were less effective and presented with more frequent and more intense side effects, especially hematologic toxicities and xerostomia. (orig.)

Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

DEFF Research Database (Denmark)

Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

2014-01-01

and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

Antitumor Activities of Kushen: Literature Review

Directory of Open Access Journals (Sweden)

Mingyu Sun

2012-01-01

Full Text Available To discover and develop novel natural compounds with therapeutic selectivity or that can preferentially kill cancer cells without significant toxicity to normal cells is an important area in cancer chemotherapy. Kushen, the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As and kushen flavonoids (KS-Fs are well-characterized components in kushen. KS-As containing oxymatrine, matrine, and total alkaloids have been developed in China as anticancer drugs. More potent antitumor activities were identified in KS-Fs than in KS-As in vitro and in vivo. KS-Fs may be developed as novel antitumor agents.

Chimeric antigen receptor T cells: a novel therapy for solid tumors

Directory of Open Access Journals (Sweden)

Shengnan Yu

2017-03-01

Full Text Available Abstract The chimeric antigen receptor T (CAR-T cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2, and mesothelin (MSLN, as well as the challenges for CAR-T cell therapy.

Antitumor effects of radioiodinated antisense oligonucleotide mediated by VIP receptor

International Nuclear Information System (INIS)

Ou Xiaohong; Tan Tianzhi; Li Yunchun; Kuang Anren

2004-01-01

Purpose: we had constructed a targeting delivery system based on intestinal peptide (VIP) for antisense oligonucleotide (ASON) transfer into VIP receptor-positive cells in previous study. The aims of present studies are to observe the antitumor effect of VIP-131I-ASON in HT29 human colon adenocarcinoma xenografts. Methods: A 15-met phosphorothioate ASON, which was complementary to the translation start region of the C-myc oncogene mRNA, was labeled with 131I and the labelled compound was linked to the VIP bound covalently 'to a polylysine chain so as to deliver oligonucleotide into tumor cells. Distribution experiments for evaluating the radiolabeled antisense complexe uptake in tumor tissue were performed in BALB/c nude mice bearing with HT29 tumor xenografts. Nude mice beating HT29 tumor xenografts were adminstered VIP-131I-ASON (3.7,7.4 MBq) or 131I-ASON (3.7 MBq), 131I labeled control sense and nosense DNA (3.7 MBq), or saline. Antitumor effects were assessed using endpoints of tumor growth delay. C-myc-encoded protein expression of tumor was measured by immunocytohistochemical staining. Results: Distribution experiment performed with athymic mice bearing human colon tumor xenografts revealed maximal accumulation of conjugated ASON in the tumor tissue 2 h after administration and significantly higher than that in nude mice injected unconjngated ASON [(5.89±1.03)%ID/g and(1.56±0.31)%ID/g, respectively; t=7.7954 P<0.001]. The radioratio of tumor to muscle was peaked 4h after administration. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing their growth rate 7-fold compare with that in saline-treated mice(tumor growth delay, 25.4±0.89 day). The antitumor effects of unconjugated 131I-ASON were much less profound than VIP-131I-ASON (tumor growth delay, 3.2±1.3 and 25.4±0.89 day, respectively; q=51.4126 P<0.01). Sense, nosense control ON with VIP carder caused no therapeutic effect. There was no progressive weight loss or

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Science.gov (United States)

Felker, G Michael; Anstrom, Kevin J; Adams, Kirkwood F; Ezekowitz, Justin A; Fiuzat, Mona; Houston-Miller, Nancy; Januzzi, James L; Mark, Daniel B; Piña, Ileana L; Passmore, Gayle; Whellan, David J; Yang, Hongqiu; Cooper, Lawton S; Leifer, Eric S; Desvigne-Nickens, Patrice; O'Connor, Christopher M

2017-08-22

The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results. To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with

Developing Quality Assurance Processes for Image-Guided Adaptive Radiation Therapy

International Nuclear Information System (INIS)

Yan Di

2008-01-01

Quality assurance has long been implemented in radiation treatment as systematic actions necessary to provide adequate confidence that the radiation oncology service will satisfy the given requirements for quality care. The existing reports from the American Association of Physicists in Medicine Task Groups 40 and 53 have provided highly detailed QA guidelines for conventional radiotherapy and treatment planning. However, advanced treatment processes recently developed with emerging high technology have introduced new QA requirements that have not been addressed previously in the conventional QA program. Therefore, it is necessary to expand the existing QA guidelines to also include new considerations. Image-guided adaptive radiation therapy (IGART) is a closed-loop treatment process that is designed to include the individual treatment information, such as patient-specific anatomic variation and delivered dose assessed during the therapy course in treatment evaluation and planning optimization. Clinical implementation of IGART requires high levels of automation in image acquisition, registration, segmentation, treatment dose construction, and adaptive planning optimization, which brings new challenges to the conventional QA program. In this article, clinical QA procedures for IGART are outlined. The discussion focuses on the dynamic or four-dimensional aspects of the IGART process, avoiding overlap with conventional QA guidelines

Studies on photodynamic mechanism of a novel chlorine derivative (TDPC and its antitumor effect for photodynamic therapy in vitro and in vivo

Directory of Open Access Journals (Sweden)

Ying Ye

2015-01-01

Full Text Available Photodynamic therapy (PDT represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer (PS play key roles in the treatment efficacy. In this study, a novel PS, 5,10,15,20-tetrakis((5-dipropylaminopentyl-chlorin (TDPC which displayed a characteristic long wavelength absorption peak at 650 nm were synthesized. It also shows a singlet oxygen generation rate of 4.257 min-1. Generally, TDPC is localized in mitochondria and nucleus of cell. After light irradiation with 650 nm laser, it can kill many types of cell, in addition, TDPC–PDT can destroy ECA-109 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following TDPC–PDT. The results showed that it either increased or decreased, among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. In general, TDPC is an effective antitumor PS in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new PSs.

Predictors of Malignancy and Recommended Follow-Up for Patients with Negative Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Suspected Pancreatic Lesions

Directory of Open Access Journals (Sweden)

Bret J Spier

2009-01-01

Full Text Available BACKGROUND: Endoscopic ultrasound (EUS with fine-needle aspiration (FNA can characterize and diagnose pancreatic lesions as malignant, but cannot definitively rule out the presence of malignancy. Outcome data regarding the length of follow-up in patients with negative or nondiagnostic EUS-FNA of pancreatic lesions are not well-established.

Guided parent-delivered cognitive behavioral therapy for childhood anxiety: Predictors of treatment response.

Science.gov (United States)

Thirlwall, Kerstin; Cooper, Peter; Creswell, Cathy

2017-01-01

Guided Parent-delivered Cognitive Behaviour Therapy (GPD-CBT) is a brief, effective treatment for childhood anxiety disorders, however not all children respond favourably. To examine predictors of response to GPD-CBT. Parents of 125 children (7-12 years) with an anxiety disorder received GPD-CBT over 2.6 or 5.3h. Recovery was measured post treatment and six months later. Younger children and those with primary Generalised Anxiety Disorder (GAD) improved more post treatment, but older children and those without primary GAD had better outcomes at six month follow up. Fewer children allocated to 2.6h had recovered post treatment compared to those allocated to the 5.2h intervention, but did not differ significantly six months later. The identification of predictors of short and longer-term treatment outcomes can guide treatment decisions following this low-intensity approach. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The anti-tumor effect and biological activities of the extract JMM6 from the stem-barks of the Chinese Juglans mandshurica Maxim on human hepatoma cell line BEL-7402.

Science.gov (United States)

Zhang, Yongli; Cui, Yuqiang; Zhu, Jiayong; Li, Hongzhi; Mao, Jianwen; Jin, Xiaobao; Wang, Xiangsheng; Du, Yifan; Lu, Jiazheng

2013-01-01

Juglans mandshurica Maxim is a traditional herbal medicines in China, and its anti-tumor bioactivities are of research interest. Bioassay-guided fractionation method was employed to isolate anti-tumor compounds from the stem barks of the Juglans mandshurica Maxim. The anti-tumor effect and biological activities of the extracted compound JMM6 were studied in BEL-7402 cells by MTT, Cell cycle analysis, Hoechst 33342 staining, Annexin V-FITC/PI assay and Detection of mitochondrial membrane potential (ΔΨm). After treatment with the JMM6, the growth of BEL-7402 cells was inhibited and cells displayed typical morphological apoptotic characteristics. Further investigations revealed that treatment with JMM6 mainly caused G2/M cell cycle arrest and induced apoptosis in BEL-7402 cells. To evaluate the alteration of mitochondria in JMM6 induced apoptosis. The data showed that JMM6 decreased significantly the ΔΨm, causing the depolarization of the mitochondrial membrane. Our results show that the JMM6 will have a potential advantage of anti-tumor, less harmful to normal cells. This paper not only summarized the JMM6 pick-up technology from Juglans mandshurica Maxim and biological characteristic, but also may provide further evidence to exploit the potential medicine compounds from the stem-barks of the Chinese Juglans mandshurica Maxim.

Bifidobacterial recombinant thymidine kinase-ganciclovir gene therapy system induces FasL and TNFR2 mediated antitumor apoptosis in solid tumors

International Nuclear Information System (INIS)

Wang, Changdong; Ma, Yongping; Hu, Qiongwen; Xie, Tingting; Wu, Jiayan; Zeng, Fan; Song, Fangzhou

2016-01-01

Directly targeting therapeutic suicide gene to a solid tumor is a hopeful approach for cancer gene therapy. Treatment of a solid tumor by an effective vector for a suicide gene remains a challenge. Given the lack of effective treatments, we constructed a bifidobacterial recombinant thymidine kinase (BF-rTK) -ganciclovir (GCV) targeting system (BKV) to meet this requirement and to explore antitumor mechanisms. Bifidobacterium (BF) or BF-rTK was injected intratumorally with or without ganciclovir in a human colo320 intestinal xenograft tumor model. The tumor tissues were analyzed using apoptosis antibody arrays, real time PCR and western blot. The colo320 cell was analyzed by the gene silencing method. Autophagy and necroptosis were also detected in colo320 cell. Meanwhile, three human digestive system xenograft tumor models (colorectal cancer colo320, gastric cancer MKN-45 and liver cancer SSMC-7721) and a breast cancer (MDA-MB-231) model were employed to validate the universality of BF-rTK + GCV in solid tumor gene therapy. The survival rate was evaluated in three human cancer models after the BF-rTK + GCV intratumor treatment. The analysis of inflammatory markers (TNF-α) in tumor indicated that BF-rTK + GCV significantly inhibited TNF-α expression. The results suggested that BF-rTK + GCV induced tumor apoptosis without autophagy and necroptosis occurrence. The apoptosis was transduced by multiple signaling pathways mediated by FasL and TNFR2 and mainly activated the mitochondrial control of apoptosis via Bid and Bim, which was rescued by silencing Bid or/and Bim. However, BF + GCV only induced apoptosis via Fas/FasL signal pathway accompanied with increased P53 expression. We further found that BF-rTK + GCV inhibited the expression of the inflammatory maker of TNF-α. However, BF-rTK + GCV did not result in necroptosis and autophagy. BF-rTK + GCV induced tumor apoptosis mediated by FasL and TNFR2 through the mitochondrial control of apoptosis via Bid and Bim

Synthesis of multifunctional gold nanoparticles for image guided therapy

International Nuclear Information System (INIS)

Laurent, Gautier

2014-01-01

The original properties of nanoparticles make them extremely attractive in the field of oncology. In fast, gold nanoparticles coated by macrocyclic ligands allow imaging and therapy with only one object. Therefore, multifunctional platforms are very promising for image-guided therapy, winch constitutes an important step towards personalization of treatment. This consists of stimulating the therapeutic activity of the nanoparticles when their accumulation is high within the tumor zone and low in healthy tissues. A higher selectivity of the treatment is therefore expected. Biodistribution study by SPECT/CT has shown free circulation, renal elimination and a moderate retention by the liver of the nanoparticles. However, this retention is not due to the opsonisation processes. The MRI study of rats' brain carrying a gliosarcoma has shown an accumulation of nanoparticles Au-at-FADOTAGA-Gd in the tumor. Moreover, the co-labeling of these nanoparticles by Ge and 64Cts2+ was successfully performed. As a result, PET/MRI images, a much researched combination but rarely achieved, were acquired on the same animal alter intravenous injection of the co-labeled nanoparticles. The radiosensitizing character of nanoparticles Au-at-TADOTAGA was confirmed by the follow up of tumor growth alter a treatment by MRT (microbeam irradiation) 15 minutes after intratumoral injection of nanoparticles. The therapeutic gain of this treatment has been validated by MRT 24 hours after intravenous injection of nanoparticles to rats carrying gliosarcoma (radioresistant tumor in radiosensitive organ). (author)

Ultrasound-Guided Application of Percutaneous Electrolysis as an Adjunct to Exercise and Manual Therapy for Subacromial Pain Syndrome: a Randomized Clinical Trial.

Science.gov (United States)

de-Miguel-Valtierra, Lorena; Salom-Moreno, Jaime; Fernández-de-Las-Peñas, César; Cleland, Joshua A; Arias-Buría, José L

2018-05-16

This randomized clinical trial compared the effects of adding US-guided percutaneous electrolysis into a program consisting of manual therapy and exercise on pain, related-disability, function and pressure sensitivity in subacromial pain syndrome. Fifty patients with subacromial pain syndrome were randomized into manual therapy and exercise or percutaneous electrolysis group. All patients received the same manual therapy and exercise program, one session per week for 5 consecutive weeks. Patients assigned to the electrolysis group also received the application of percutaneous electrolysis at each session. The primary outcome was Disabilities of the Arm, Shoulder and Hand (DASH). Secondary outcomes included pain, function (Shoulder Pain and Disability Index-SPADI) pressure pain thresholds (PPTs) and Global Rating of Change (GROC). They were assessed at baseline, post-treatment, and 3, and 6 months after treatment. Both groups showed similar improvements in the primary outcome (DASH) at all follow-ups (P=0.051). Subjects receiving manual therapy, exercise, and percutaneous electrolysis showed significantly greater changes in shoulder pain (P0.91) for shoulder pain and function at 3 and 6 months in favour of the percutaneous electrolysis group. No between-groups differences in PPT were found. The current clinical trial found that the inclusion of US-guided percutaneous electrolysis in combination with manual therapy and exercise resulted in no significant differences for related-disability (DASH) than the application of manual therapy and exercise alone in patients with subacromial pain syndrome. Nevertheless, differences were reported for some secondary outcomes such as shoulder pain and function (SPADI). Whether or not these effects are reliable should be addressed in future studies Perspective This study found that the inclusion of US-guided percutaneous electrolysis into a manual therapy and exercise program resulted in no significant differences for disability

Endoscopic ultrasound in gastroenterology: from diagnosis to therapeutic implications.

Science.gov (United States)

Mekky, Mohamed A; Abbas, Wael A

2014-06-28

Since its advent in 1980, the scope of endoscopic ultrasound (EUS) has grown to include a wide range of indications, and it is now being incorporated as an integral part of everyday practice in the field of gastroenterology. Its use is extending from an adjuvant imaging aid to utilization as a therapeutic tool for various gastrointestinal disorders. EUS was first used to visualize remote organs, such as the pancreas and abdominal lymph nodes. When fine needle aspiration was introduced, the indications for EUS expanded to include tissue sampling for diagnostic purposes. At the same time, the needle can be used to convey a potential therapy to the internal organs, allowing access to remote sites. In this review, we aim to highlight the expanding spectrum of EUS indications and uses in the field of gastroenterology.

Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

Science.gov (United States)

Canitano, Andrea; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Federici, Cristina; Fais, Stefano

2016-07-01

Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A case of cardiac cancer diagnosed after 30 Gy radiation therapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma without helicobacter pylori (H. pylori) infection

International Nuclear Information System (INIS)

Ito, Kazuhiro; Akamatsu, Taiji; Shinji, Akihiro

2005-01-01

An 80-year-old man was referred to Shinshu University Hospital in April 2001 for treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. He had received anti-biotic therapy in spite of no evidence of H. pylori infection in the former hospital 3 years ago, but no remarkable improvement was recognized and endoscopic findings were progressive. An esophagogastroduodenoscopy (EGD) revealed mucosal redness on the greater curvature and the anterior wall of the body. Biopsy specimens taken from the lesions showed remarkable infiltration of atypical small lymphocytes, and this lesions were diagnosed MALT lymphoma by an immunophenotypic studies. Endoscopic ultrasonography (EUS) showed that MALT lymphoma was limited within the mucosa and submucosa. Staging work up revealed stage I. After written informed consent, he was treated by 30 Gy radiation therapy for gastric MALT lymphoma. Response assessment was performed by EGD, EUS, and biopsy specimens, and a complete remission was confirmed. After that, he was followed up with regular intervals, and EGD was performed every 6 months. He was diagnosed to have O I type cardiac cancer at 21 months after radiation therapy. He underwent proximal partial gastrectomy, and histopathological findings showed as follows: O I type, 17 x 12 mm, tub 2, SM, ly 1, v 1, n 0, PM (-), DM (-), INFγ, stage I A. No residual lesion of gastric MALT lymphoma and no dysplasia of gastric mucosa was recognized. Causal relationship between radiation therapy and carcinogenesis in this case is unclear. However, it might be suggested by the facts that cancer occurred in the radiation field where MALT lymphoma had been presented and gastric cancer was rare in the stomach without H. pylori infection. (author)

Available clinical markers of treatment outcome integrated in mathematical models to guide therapy in HIV infection.

Science.gov (United States)

Vergu, Elisabeta; Mallet, Alain; Golmard, Jean-Louis

2004-02-01

Because treatment failure in many HIV-infected persons may be due to multiple causes, including resistance to antiretroviral agents, it is important to better tailor drug therapy to individual patients. This improvement requires the prediction of treatment outcome from baseline immunological or virological factors, and from results of resistance tests. Here, we review briefly the available clinical factors that have an impact on therapy outcome, and discuss the role of a predictive modelling approach integrating these factors proposed in a previous work. Mathematical and statistical models could become essential tools to address questions that are difficult to study clinically and experimentally, thereby guiding decisions in the choice of individualized drug regimens.

Noncirrhotic portal fibrosis after Wilms' tumor therapy

International Nuclear Information System (INIS)

Barnard, J.A.; Marshall, G.S.; Neblett, W.W.; Gray, G.; Ghishan, F.K.

1986-01-01

A 9-yr-old girl developed massive hemorrhage from esophageal varices 2 yr after combined modality therapy for Wilms' tumor. Evaluation showed a patent extrahepatic portal venous system and an elevated splenic pulp pressure. In contrast to previous reports of hepatopathy after irradiation injury, histologic sections of the liver did not demonstrate occlusion of the central veins, but rather a diffuse obliteration of intrahepatic portal venous radicles. This pattern of noncirrhotic portal fibrosis has not been described following antitumor therapy

Ultrasound-guided stellate ganglion blocks combined with pharmacological and occupational therapy in Complex Regional Pain Syndrome (CRPS): a pilot case series ad interim.

Science.gov (United States)

Wei, Karin; Feldmann, Robert E; Brascher, Anne-Kathrin; Benrath, Justus

2014-12-01

This preliminary and retrospective pilot case series examines a treatment concept consisting of ultrasound-guided stellate ganglion blocks (SGBs) combined with pharmacological and occupational therapy in patients with complex regional pain syndrome (CRPS) of the hand. Efficacy of combined treatment concepts and safety of ultrasound-guided SGB have not been sufficiently investigated yet. A total number of 156 blocks were evaluated in 16 patients with CRPS in a retrospective analysis. All patients received pharmacotherapy and a standard regimen of occupational therapy offered simultaneously to the SGBs. Changes in both spontaneous and evoked pain levels were assessed by numerical pain rating score before and after the last blockade of a series. Side effects were documented. The overall mean pain reduction was 63.2% regarding spontaneous and 45.3% regarding evoked pain. Mild complications, such as hoarseness or dysphagia, occurred in 13.5% of the blocks (21 SGBs). Serious complications, such as plexus paresis or accidental puncture of vessels or other structures, did not occur. Time between symptom onset and start of treatment did not affect the extent of pain reduction. The combination of ultrasound-guided SGB and simultaneous pharmacological and occupational therapy showed encouraging treatment results under conditions of this pilot case series. Assessment of efficacy of this combined treatment concept and safety of ultrasound-guided SGB require further prospective clinical studies with larger number of participants. Wiley Periodicals, Inc.

Nasal methicillin-resistant Staphylococcus aureus polymerase chain reaction: a potential use in guiding antibiotic therapy for pneumonia.

Science.gov (United States)

Johnson, Jennifer A; Wright, Michael E; Sheperd, Lyndsay A; Musher, Daniel M; Dang, Bich N

2015-01-01

The role at admission of nasal polymerase chain reaction (PCR) for patients with methicillin-resistant Staphylococcus aureus (MRSA) in guiding antibiotic therapy for lower respiratory tract infection is unknown. To determine whether nasal MRSA PCR at admission can predict the absence of MRSA in lower respiratory tract secretions. We performed a retrospective study of adult patients admitted to a large urban hospital. Patients had a nasal MRSA PCR test and a lower respiratory tract culture obtained within 48 hours of admission and the culture yielded S aureus. Sensitivity, specificity, and positive and negative predictive values. Our results showed high sensitivity (93.3%) and negative predictive value (95.2%) of nasal PCR for MRSA in the lower respiratory tract. With its high sensitivity and negative predictive value, a nasal MRSA PCR test performed within 48 hours of hospital admission could help guide the discontinuation of MRSA-directed empiric antibiotic therapy in patients who are unlikely to be infected with this organism. A prospective study is needed to confirm these findings.

Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice

International Nuclear Information System (INIS)

Itasaka, Satoshi; Komaki, Ritsuko; Herbst, Roy S.; Shibuya, Keiko; Shintani, Tomoaki D.D.S.; Hunter, Nancy R. M.S.; Onn, Amir; Bucana, Corazon D.; Milas, Luka; Ang, K. Kian; O'Reilly, Michael S.

2007-01-01

Purpose: Clinical trials of antiangiogenic agents used alone for advanced malignancy have been disappointing but preclinical studies suggest that the addition of radiation therapy could improve antitumor efficacy. To test the hypothesis that antiangiogenic therapy combined with radiation therapy can overcome the limitations of antiangiogenic monotherapy, we studied the effects of endostatin combined with radiation on the growth and vascularization of A431 human epidermoid carcinomas growing intramuscularly in the legs of mice. Methods and Materials: Mice with established A431 human epidermoid leg tumors were treated with radiation, endostatin, both radiation and endostatin, or vehicle control. The experiment was repeated and mice from each group were killed at 2, 7, and 10 days after irradiation so that tumor tissue could be obtained to further analyze the kinetics of the antitumor, antivascular, and antiangiogenic response to therapy. Results: Endostatin enhanced the antitumor effects of radiation, and prolonged disease-free survival was observed in the combined treatment group. Endothelial cell proliferation was increased in tumors after irradiation but was blocked by the concurrent administration of endostatin, and the combination of endostatin with radiation enhanced endothelial cell apoptosis within 48 h after irradiation. Expression of vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 were increased in tumors after irradiation, and this increase was blocked by concurrent administration of endostatin. Conclusion: These data indicate that endostatin can block tumor revascularization after radiation therapy and thereby augment radioresponse

Synergistic combination therapy of antitumor agents, membrane modification agents and irradiation

International Nuclear Information System (INIS)

Watarai, Jiro; Itagaki, Takatomo; Akutsu, Thoru; Yamaguchi, Kouichi; Kato, Isao

1983-01-01

Larygeal cancer were treated with synergistic combination therapy of Futraful in suppository, vitamin A, cepharanthin and irradiation from April 1981 to June 1982. This combination therapy resulted in high percentage of the tumor regression in the case of the invading laryngeal cancer and negligible complication. (author)

Oridonin Loaded Solid Lipid Nanoparticles Enhanced Antitumor Activity in MCF-7 Cells

Directory of Open Access Journals (Sweden)

Lu Wang

2014-01-01

Full Text Available Oridonin (ORI, a famous diterpenoid from Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis and autophagy-inducing activity in human cancer therapy, while clinical application of ORI is limited by its strong hydrophobicity and rapid plasma clearance. The purpose of this study was to evaluate whether the antitumor activity of ORI could be enhanced by loading into solid lipid nanoparticles (SLNs. ORI-loaded SLNs were prepared by hot high pressure homogenization with narrow size distribution and good entrapment efficacy. MTT assay indicated that ORI-loaded SLNs enhanced the inhibition of proliferation against several human cancer cell lines including breast cancer MCF-7 cells, hepatocellular carcinoma HepG 2 cells, and lung carcinoma A549 cells compared with free ORI, while no significant enhancement of toxicity to human mammary epithelial MCF-10A cells was shown. Meanwhile, flow cytometric analysis demonstrated that ORI-SLNs induced more significant cell cycle arrest at S and decreased cell cycle arrest at G1/G0 phase in MCF-7 cells than bulk ORI solution. Hoechst 33342 staining and Annexin V/PI assay indicated that apoptotic rates of cells treated with ORI-loaded SLNs were higher compared with free ORI. In summary, our data indicated that SLNs may be a potential carrier for enhancing the antitumor effect of hydrophobic drug ORI.

Research progress of PARP-1 inhibitors in antitumor drugs and radionuclide markers

International Nuclear Information System (INIS)

Zhao Lingzhou; Zhang Huabei

2011-01-01

Poly(ADP-ribose)polymerase (PARP) is a new target in the cancer treatment nowadays. PARP not only can repair DNA damage, regulate and control transcription, maintain the stability of intracellular environment and genome, regulate the process of cell survival and death, but also is the main transcription factor in the development of inflammation and the process of cancer. To inhibit PARP activity can reduce the DNA repair function in tumor cells, and increase the sensibility to DNA damage agents, so as to improve the efficacy of radiation therapy and chemotherapy for tumor. A number of studies have suggested that, whether used alone or combination with other chemotherapy drugs, PARP inhibitors show the potential in the anti-tumor therapeutic areas. In this paper, PARP-1 inhibitors were reviewed in antitumor research progress. According to the stage of development , PARP-1 inhibitors are classified. Several representative PARP-1 inhibitors, in clinical trials, with potential clinical value were introduced. Positron emission tomography (PET), uses the main short half-life elementary in human body as tracer, and at the molecular level, achieve the no wound, quantitative and dynamic observation about the different changes of metabolites or drugs in the body. PET is the most advanced contemporary video diagnostic technology, and this paper simply introduce the research progress of PARP-1 inhibitors labeled with radioactive nuclides. (authors)

Homeostatic T Cell Expansion to Induce Anti-Tumor Autoimmunity in Breast Cancer

National Research Council Canada - National Science Library

Baccala, Roberto

2007-01-01

... that (a) homeostatic T-cell proliferation consistently elicits anti-tumor responses; (b) irradiation is more effective than Tcell depletion by antibodies in inducing anti-tumor responses mediated by homeostatic T-cell proliferation...

Antitumor effect of degalactosylated gc-globulin on orthotopic grafted lung cancer in mice.

Science.gov (United States)

Hirota, Keiji; Nakagawa, Yoshinori; Takeuchi, Ryota; Uto, Yoshihiro; Hori, Hitoshi; Onizuka, Shinya; Terada, Hiroshi

2013-07-01

Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. DG3 proved to be promising as an antitumor agent, similarly to GcMAF.

Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy

Directory of Open Access Journals (Sweden)

Dapeng Zhou

2018-05-01

Full Text Available Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three O-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five O-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed.

Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

Energy Technology Data Exchange (ETDEWEB)

Ohta, Kengo, E-mail: yesterday.is.yesterday@gmail.com; Shimohira, Masashi, E-mail: mshimohira@gmail.com [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan); Sasaki, Shigeru, E-mail: ssasaki916@yahoo.co.jp; Iwata, Hiromitsu, E-mail: h-iwa-ncu@nifty.com; Nishikawa, Hiroko, E-mail: piroko1018@gmail.com; Ogino, Hiroyuki, E-mail: oginogio@gmail.com; Hara, Masaki, E-mail: mhara@med.nagoya-cu.ac.jp [Nagoya City West Medical Center, Department of Radiation Oncology, Nagoya Proton Therapy Center (Japan); Hashizume, Takuya, E-mail: tky300@gmail.com; Shibamoto, Yuta, E-mail: yshiba@med.nagoya-cu.ac.jp [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan)

2015-10-15

PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.

Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

International Nuclear Information System (INIS)

Ohta, Kengo; Shimohira, Masashi; Sasaki, Shigeru; Iwata, Hiromitsu; Nishikawa, Hiroko; Ogino, Hiroyuki; Hara, Masaki; Hashizume, Takuya; Shibamoto, Yuta

2015-01-01

PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors

CT-guided percutaneous ethanol nerve block therapy of celiac plexus embedded in metastatic lymph nodes for the treatment of intractable carcinomatous abdominal pain

International Nuclear Information System (INIS)

Xi Qian; Wang Peijun; Shang Mingyi; Ma Jun; Lu Ying; Huang Zongliang; Tang Junjun; Gao Xiaolong

2010-01-01

Objective: To evaluate CT-guided percutaneous ethanol nerve block therapy of celiac plexus embedded in metastatic lymph nodes in treating intractable carcinomatous abdominal pain. Methods: A total of 104 patients with late stage cancers were enrolled in this study. All patients suffered from serious carcinomatous pain at upper abdomen and their retroperitoneal lymph nodes were extensively enlarged and fused, together with the involved celiac plexus, into a hard crumb. As the patients failed to respond to narcotic analgesics CT-guided ethanol nerve block therapy of celiac plexus was carried out by pushing the puncture needle through the fused lymphatic mass to celiac plexus site. The analgesic effects and complications were observed and the therapeutic results were evaluated. Results: The analgesic effective rate of ethanol nerve block therapy immediately after the procedure was 100%, and at 2 weeks, 1, 2, 3 and 4 months after the treatment it was 100%, 100%, 98.0%, 96.9% and 92.6%, respectively. No serious complications occurred during perioperative period. The living quality was markedly improved in all patients. Conclusion: For the treatment of intractable carcinomatous abdominal pain in patients with their celiac plexus being embedded in mass-like metastatic retroperitoneal lymph nodes CT-guided percutaneous ethanol nerve block therapy by pushing the puncture needle through the fused lymphatic mass to celiac plexus site is of great clinical value in relieving carcinomatous abdominal pain. (authors)

Hydroxyurea derivatives of irofulven with improved antitumor efficacy.

Science.gov (United States)

Staake, Michael D; Kashinatham, Alisala; McMorris, Trevor C; Estes, Leita A; Kelner, Michael J

2016-04-01

Irofulven is a semi-synthetic derivative of Illudin S, a toxic sesquiterpene isolated from the mushroom Omphalotus illudens. Irofulven has displayed significant antitumor activity in various clinical trials but displayed a limited therapeutic index. A new derivative of irofulven was prepared by reacting hydroxyurea with irofulven under acidic conditions. Acetylation of this new compound with acetic anhydride produced a second derivative. Both of these new derivatives displayed significant antitumor activity in vitro and in vivo comparable to or exceeding that of irofulven. Copyright © 2016 Elsevier Ltd. All rights reserved.

pH/Ultrasound Dual-Responsive Gas Generator for Ultrasound Imaging-Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy.

Science.gov (United States)

Feng, Qianhua; Zhang, Wanxia; Yang, Xuemei; Li, Yuzhen; Hao, Yongwei; Zhang, Hongling; Hou, Lin; Zhang, Zhenzhong

2018-03-01

Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO 2 generation and HMME release with spatial/temporal resolution. Afterward, the CO 2 bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO 2 make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The vitamin-like dietary supplement para-aminobenzoic acid enhances the antitumor activity of ionizing radiation

International Nuclear Information System (INIS)

Xavier, Sandhya; MacDonald, Shannon; Roth, Jennifer; Caunt, Maresa; Akalu, Abebe; Morais, Danielle; Buckley, Michael T.; Liebes, Leonard; Formenti, Silvia C.; Brooks, Peter C.

2006-01-01

Purpose: To determine whether para-aminobenzoic acid (PABA) alters the sensitivity of tumor cells to ionizing radiation in vitro and in vivo. Methods and Materials: Cellular proliferation was assessed by WST-1 assays. The effects of PABA and radiation on tumor growth were examined with chick embryo and murine models. Real-time reverse transcriptase-polymerase chain reaction and Western blotting were used to quantify p21 CIP1 and CDC25A levels. Results: Para-aminobenzoic acid enhanced (by 50%) the growth inhibitory activity of radiation on B16F10 cells, whereas it had no effect on melanocytes. Para-aminobenzoic acid enhanced (50-80%) the antitumor activity of radiation on B16F10 and 4T1 tumors in vivo. The combination of PABA and radiation therapy increased tumor apoptosis. Treatment of tumor cells with PABA increased expression of CDC25A and decreased levels of p21 CIP1 . Conclusions: Our findings suggest that PABA might represent a compound capable of enhancing the antitumor activity of ionizing radiation by a mechanism involving altered expression of proteins known to regulate cell cycle arrest

Continuous therapy with certolizumab pegol maintains remission of patients with Crohn's disease for up to 18 months

DEFF Research Database (Denmark)

Lichtenstein, Gary R; Thomsen, Ole Ø; Schreiber, Stefan

2010-01-01

BACKGROUND & AIMS: The safety and efficacy of maintenance therapy with the anti-tumor necrosis factor certolizumab pegol has not been reported beyond 6 months. We assessed the long-term efficacy, safety, and immunogenicity of continuous versus interrupted maintenance therapy with subcutaneous cer...

Is self-guided internet-based cognitive behavioural therapy (iCBT) harmful? An individual participant data meta-analysis.

Science.gov (United States)

Karyotaki, Eirini; Kemmeren, Lise; Riper, Heleen; Twisk, Jos; Hoogendoorn, Adriaan; Kleiboer, Annet; Mira, Adriana; Mackinnon, Andrew; Meyer, Björn; Botella, Cristina; Littlewood, Elizabeth; Andersson, Gerhard; Christensen, Helen; Klein, Jan P; Schröder, Johanna; Bretón-López, Juana; Scheider, Justine; Griffiths, Kathy; Farrer, Louise; Huibers, Marcus J H; Phillips, Rachel; Gilbody, Simon; Moritz, Steffen; Berger, Thomas; Pop, Victor; Spek, Viola; Cuijpers, Pim

2018-03-15

Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration. Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates. Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.

Guided Internet-based cognitive behavioral therapy for mild and moderate depression: A benchmarking study

Directory of Open Access Journals (Sweden)

Hanne Jakobsen

2017-03-01

Full Text Available Major depression is among the most common and debilitating disorders worldwide, associated with large societal and individual costs. Effective treatments exist, but accessibility is scarce. Guided Internet-Based Cognitive Behavioral Therapy (guided iCBT is a promising approach to reach more people in need of help. In the present pilot study, we investigated the outcome of a guided iCBT program for mild and moderate depression when disseminated from Sweden to Norway. The guided iCBT intervention was implemented within a university-based outpatient clinic by six student therapists under supervision. Twenty-two participants with mild and moderate depression were included in the study. Large treatment effects were found for depressive symptoms, whereas small to medium effects were observed for anxiety symptoms. More than half (55% of the participants were classified as recovered at post-treatment and more than a third (41% at follow-up. No participants had a significant deterioration from pre- to post-treatment, but two reported a significant deterioration from post-treatment to 6-month follow-up. Benchmarking the present results against those reported in the four original Swedish studies, we found that the treatment effect in the Norwegian study was slightly higher at post-treatment and slightly lower at 6-month follow-up compared to the outcome in the Swedish studies. The results should be interpreted with caution, as our sample was small and had no control group.

Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity.

Science.gov (United States)

Ichikawa, Kosuke; Kagamu, Hiroshi; Koyama, Kenichi; Miyabayashi, Takao; Koshio, Jun; Miura, Satoru; Watanabe, Satoshi; Yoshizawa, Hirohisa; Narita, Ichiei

2012-09-21

MHC class I-restricted peptide-based vaccination therapies have been conducted to treat cancer patients, because CD8⁺ CTL can efficiently induce apoptosis of tumor cells in an MHC class I-restricted epitope-specific manner. Interestingly, clinical responders are known to demonstrate reactivity to epitopes other than those used for vaccination; however, the mechanism underlying how antitumor T cells with diverse specificity are induced is unclear. In this study, we demonstrated that dendritic cells (DCs) that engulfed apoptotic tumor cells in the presence of non-tumor MHC class II-restricted epitope peptides, OVA(323-339), efficiently presented tumor-associated antigens upon effector-dominant CD4⁺ T cell balance against regulatory T cells (Treg) for the OVA(323-339) epitope. Th1 and Th17 induced tumor-associated antigens presentation of DC, while Th2 ameliorated tumor-antigen presentation for CD8⁺ T cells. Blocking experiments with anti-IL-23p19 antibody and anti-IL-23 receptor indicated that an autocrine mechanism of IL-23 likely mediated the diverted tumor-associated antigens presentation of DC. Tumor-associated antigens presentation of DC induced by OVA(323-339) epitope-specific CD4⁺ T cells resulted in facilitated antitumor immunity in both priming and effector phase in vivo. Notably, this immunotherapy did not require pretreatment to reduce Treg induced by tumor. This strategy may have clinical implications for designing effective antitumor immunotherapies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cytomorphological monitoring in multimodality therapy of endometral cancer patients

International Nuclear Information System (INIS)

Galil-Ogly, G.A.; Titova, V.A.; Yarovaya, N.Yu.; Ingberman, Ya.Kh.; Bershchanskaya, A.M.; Pukhlikov, A.V.

1990-01-01

The paper is devoted to analysis of clinicomorphological data on the status of a primary endometrial tumor in 209 endometrial cancer patients, treated by radical and palliative radiation therapy (112 patients) and the combined method (88 patients) including preoperative intensive concentrated intracavitary irradiation and hormonotherapy. Dynamic cytological monitoring was performed during radiation therapy and in a period up to 12 mos. after the discontinuation of antitumor therapy. Dynamic cytomorphological monitoring is an important stage in patients who cannot be operated upon as a result of tumor spreading or somatic contraindications

Role of endoscopic ultrasound in diagnosis and management of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Koduru P

2015-10-01

Full Text Available Pramoda Koduru,1 Rei Suzuki,2 Sundeep Lakhtakia,3 Mohan Ramchandani,3 Dadang Makmun,4 Manoop S Bhutani,1 1Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Gastroenterology and Rheumatology, Fukushima University School of Medicine, Fukushima, Japan; 3Asian Institute of Gastroenterology, Hyderabad, India; 4University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia Abstract: Hepatocellular carcinoma (HCC is an aggressive tumor and a leading cause of cancer-related deaths globally. The mortality rate remains high despite many advances in treatment. HCC is frequently diagnosed late in its course due to lack of classical symptoms at earlier stages. Endoscopic ultrasound (EUS has emerged as an important diagnostic tool for the diagnostic evaluation, staging, and treatment of gastrointestinal tract disorders. EUS-guided fine needle aspiration has been a valuable addition to EUS by being able to obtain tissue under direct visualization. Here, we review the potential role of EUS in the diagnosis and management of HCC. EUS seems to be a safe and reliable alternative method for obtaining tissue for diagnosis of liver cancer, especially for lesions that are inaccessible by traditional methods. EUS could play an important role in the diagnosis and management of HCC. Keywords: endoscopic ultrasound, fine needle aspiration, hepatocellular carcinoma, hepatoma

Piezoelectrically Actuated Robotic System for MRI-Guided Prostate Percutaneous Therapy

Science.gov (United States)

Su, Hao; Shang, Weijian; Cole, Gregory; Li, Gang; Harrington, Kevin; Camilo, Alexander; Tokuda, Junichi; Tempany, Clare M.; Hata, Nobuhiko; Fischer, Gregory S.

2014-01-01

This paper presents a fully-actuated robotic system for percutaneous prostate therapy under continuously acquired live magnetic resonance imaging (MRI) guidance. The system is composed of modular hardware and software to support the surgical workflow of intra-operative MRI-guided surgical procedures. We present the development of a 6-degree-of-freedom (DOF) needle placement robot for transperineal prostate interventions. The robot consists of a 3-DOF needle driver module and a 3-DOF Cartesian motion module. The needle driver provides needle cannula translation and rotation (2-DOF) and stylet translation (1-DOF). A custom robot controller consisting of multiple piezoelectric motor drivers provides precision closed-loop control of piezoelectric motors and enables simultaneous robot motion and MR imaging. The developed modular robot control interface software performs image-based registration, kinematics calculation, and exchanges robot commands and coordinates between the navigation software and the robot controller with a new implementation of the open network communication protocol OpenIGTLink. Comprehensive compatibility of the robot is evaluated inside a 3-Tesla MRI scanner using standard imaging sequences and the signal-to-noise ratio (SNR) loss is limited to 15%. The image deterioration due to the present and motion of robot demonstrates unobservable image interference. Twenty-five targeted needle placements inside gelatin phantoms utilizing an 18-gauge ceramic needle demonstrated 0.87 mm root mean square (RMS) error in 3D Euclidean distance based on MRI volume segmentation of the image-guided robotic needle placement procedure. PMID:26412962

Dose Recalculation and the Dose-Guided Radiation Therapy (DGRT) Process Using Megavoltage Cone-Beam CT

International Nuclear Information System (INIS)

Cheung, Joey; Aubry, Jean-Francois; Yom, Sue S.; Gottschalk, Alexander R.; Celi, Juan Carlos; Pouliot, Jean

2009-01-01

Purpose: At University of California San Francisco, daily or weekly three-dimensional images of patients in treatment position are acquired for image-guided radiation therapy. These images can be used for calculating the actual dose delivered to the patient during treatment. In this article, we present the process of performing dose recalculation on megavoltage cone-beam computed tomography images and discuss possible strategies for dose-guided radiation therapy (DGRT). Materials and Methods: A dedicated workstation has been developed to incorporate the necessary elements of DGRT. Patient image correction (cupping, missing data artifacts), calibration, completion, recontouring, and dose recalculation are all implemented in the workstation. Tools for dose comparison are also included. Examples of image correction and dose analysis using 6 head-and-neck and 2 prostate patient datasets are presented to show possible tracking of interfraction dosimetric endpoint variation over the course of treatment. Results: Analysis of the head-and-neck datasets shows that interfraction treatment doses vary compared with the planning dose for the organs at risk, with the mean parotid dose and spinal cord D 1 increasing by as much as 52% and 10%, respectively. Variation of the coverage to the target volumes was small, with an average D 5 dose difference of 1%. The prostate patient datasets revealed accurate dose coverage to the targeted prostate and varying interfraction dose distributions to the organs at risk. Conclusions: An effective workflow for the clinical implementation of DGRT has been established. With these techniques in place, future clinical developments in adaptive radiation therapy through daily or weekly dosimetric measurements of treatment day images are possible.

Strategies for combinational cancer therapies

International Nuclear Information System (INIS)

Khleif, Samir

2014-01-01

The countless pre-clinical studies and many clinical trials that have applied tumor antigen-based therapies for the cancer treatment, and although the necessary tumor-specific immune response may be elicited in tumor-bearing hosts, this was not sufficient for the positive therapeutic outcome since there are multiple mechanisms that tumors develop to escape immune surveillance. The tumor-mediated inhibitory mechanisms involve co-inhibitory receptor-ligand interactions, such as PD-1/ PD-L1, secretion of inhibitory molecules, such as TGFb, and recruitment of suppressive cells, such as regulatory T cells (Treg), myeloid derived suppressor cells (MDSC), etc. Therefore, we hypothesized that successful cancer immunotherapy requires not only induction and enhancement of effector immune response but also simultaneous targeting of suppressor arm of immune system, thus in addition to enhancing antigen-specific immunity using vaccines or radiation therapy, one should also target tumor-mediated immune suppression to improve the overall efficacy of therapy. We developed multiple strategies to target various tumor-mediated immune inhibitory mechanisms that can enhance anti-tumor immunity and restructure tumor microenvironment to allow effector cells generated due to vaccination or radiation therapy to function potently. We evaluated the immune and therapeutic efficacy of multiple combinational therapies, including blocking and agonist antibodies to co-inhibitory/co-stimulatory molecules, such as PD-1, PD-L1, OX40, CTLA-4, GITR, inhibitors and neutralizing antibodies to inhibitory cytokines/molecules, such as IL-10, TGFb, IDO, and small molecules for selective inhibition of Tregs. In addition to evaluation of anti-tumor efficacy we are also investigated cellular and molecular mechanisms of action for these agents when combined with vaccine or radiation therapy and exploring the interactions between compounds within combinational therapies in animal tumor models. We are

Dll4 blockade potentiates the anti-tumor effects of VEGF inhibition in renal cell carcinoma patient-derived xenografts.

Directory of Open Access Journals (Sweden)

Kiersten Marie Miles

Full Text Available The Notch ligand Delta-like 4 (Dll4 is highly expressed in vascular endothelium and has been shown to play a pivotal role in regulating tumor angiogenesis. Blockade of the Dll4-Notch pathway in preclinical cancer models has been associated with non-productive angiogenesis and reduced tumor growth. Given the cross-talk between the vascular endothelial growth factor (VEGF and Delta-Notch pathways in tumor angiogenesis, we examined the activity of a function-blocking Dll4 antibody, REGN1035, alone and in combination with anti-VEGF therapy in renal cell carcinoma (RCC.Severe combined immunodeficiency (SCID mice bearing patient-derived clear cell RCC xenografts were treated with REGN1035 and in combination with the multi-targeted tyrosine kinase inhibitor sunitinib or the VEGF blocker ziv-aflibercept. Immunohistochemical and immunofluorescent analyses were carried out, as well as magnetic resonance imaging (MRI examinations pre and 24 hours and 2 weeks post treatment. Single agent treatment with REGN1035 resulted in significant tumor growth inhibition (36-62% that was equivalent to or exceeded the single agent anti-tumor activity of the VEGF pathway inhibitors sunitinib (38-54% and ziv-aflibercept (46%. Importantly, combination treatments with REGN1035 plus VEGF inhibitors resulted in enhanced anti-tumor effects (72-80% growth inhibition, including some tumor regression. Magnetic resonance imaging showed a marked decrease in tumor perfusion in all treatment groups. Interestingly, anti-tumor efficacy of the combination of REGN1035 and ziv-aflibercept was also observed in a sunitinib resistant ccRCC model.Overall, these findings demonstrate the potent anti-tumor activity of Dll4 blockade in RCC patient-derived tumors and a combination benefit for the simultaneous targeting of the Dll4 and VEGF signaling pathways, highlighting the therapeutic potential of this treatment modality in RCC.

Intratumoral IL-12 and TNF-alpha-loaded microspheres lead to regression of breast cancer and systemic antitumor immunity.

Science.gov (United States)

Sabel, Michael S; Skitzki, Joseph; Stoolman, Lloyd; Egilmez, Nejat K; Mathiowitz, Edith; Bailey, Nicola; Chang, Wen-Jian; Chang, Alfred E

2004-02-01

Local, sustained delivery of cytokines at a tumor can enhance induction of antitumor immunity and may be a feasible neoadjuvant immunotherapy for breast cancer. We evaluated the ability of intratumoral poly-lactic-acid-encapsulated microspheres (PLAM) containing interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) in a murine model of breast cancer to generate a specific antitumor response. BALB/c mice with established MT-901 tumors underwent resection or treatment with a single intratumoral injection of PLAM containing IL-12, TNF-alpha, or GM-CSF, alone or in combination. Two weeks later, lymph nodes and spleens were harvested, activated with anti-CD3 monoclonal antibodies (mAb) and rhIL-2, and assessed for antitumor reactivity by an interferon gamma (IFNgamma) release assay. Tumor-infiltrating lymphocyte (TIL) analysis was performed on days 2 and 5 after treatment by mechanically processing the tumors to create a single cell suspension, followed by three-color fluorescence-activated cell sorter (FACS) analysis. Intratumoral injection of cytokine-loaded PLAM significantly suppressed tumor growth, with the combination of IL-12 and TNF-alpha leading to increased infiltration by polymorphonuclear cells and CD8+ T-cells in comparison with controls. The induction of tumor-specific reactive T-cells in the nodes and spleens, as measured by IFN-gamma production, was highest with IL-12 and TNF-alpha. This treatment resulted in resistance to tumor rechallenge. A single intratumoral injection of IL-12 and TNF-alpha-loaded PLAM into a breast tumor leads to infiltration by polymorphonuclear cells and CD8+ T-cells with subsequent tumor regression. In addition, this local therapy induces specific antitumor T-cells in the lymph nodes and spleens, resulting in memory immune response.

Preparation, Characterization, and In Vitro and Vivo Antitumor Activity of Oridonin-Conjugated Multiwalled Carbon Nanotubes Functionalized with Carboxylic Group

Directory of Open Access Journals (Sweden)

Chuanjin Wang

2016-01-01

Full Text Available Carbon nanotubes have shown great potential in tumor therapy. Oridonin (ORI is a poorly water-soluble diterpenoid compound (C20H28O6 used in the treatment of esophageal and hepatic carcinoma for decades. For the purpose of enhancing the antitumor potency and reducing cytotoxicity of ORI, multiwalled carbon nanotubes functionalized with carboxylic group (MWCNTs-COOH were used as ORI carrier. ORI was noncovalently encapsulated into (or onto the functionalized carbon nanotubes (MWCNTs-ORI. The obtained MWCNTs-ORI has been characterized. The ORI loading efficiency in MWCNTs-COOH carrier was studied to be about 82.6% (w/w. In vitro cytotoxicity assay on MWCNTs-ORI gave IC50 of 7.29±0.5 μg/mL and ORI-F gave IC50 of 14.5±1.4 μg/mL. The antitumor effect studies in vivo showed that MWCNTs-ORI improved antitumor activity of ORI in comparison with ORI-F. The tumor inhibition ratio for MWCNTs-ORI (1.68×10-2 g·Kg−1·d−1 was 86.4%, higher than that of ORI-F (1.68×10-2 g·Kg−1·d−1 which was 39.2%. This can greatly improve the pharmaceutical efficiency and reduce potential side effects.

Antitumor Activity of Kielmeyera Coriacea Leaf Constituents in Experimental Melanoma, Tested in Vitro and in Vivo in Syngeneic Mice

Directory of Open Access Journals (Sweden)

Carlos Rogério Figueiredo

2014-10-01

Full Text Available Purpose: The antitumor activity of Kielmeyera coriacea (Clusiaceae, a medicinal plant used in the treatment of parasitic, as well as fungal and bacterial infections by the Brazilian Cerrado population, was investigated. Methods: A chloroform extract (CE of K. coriacea was tested in the murine melanoma cell line (B16F10-Nex2 and a panel of human tumor cell lines. Tumor cell migration was determined by the wound-healing assay and the in vivo antitumor activity of CE was investigated in a melanoma cell metastatic model. 1H NMR and GC/MS were used to determine CE chemical composition. Results: We found that CE exhibited strong cytotoxic activity against murine melanoma cells and a panel of human tumor cell lines in vitro. CE also inhibited growth of B16F10-Nex2 cells at sub lethal concentrations, inducing cell cycle arrest at S phase, and inhibition of tumor cell migration. Most importantly, administration of CE significantly reduced the number of melanoma metastatic nodules in vivo. Chemical analysis of CE indicated the presence of the long chain fatty compounds, 1-eicosanol, 1-docosanol, and 2-nonadecanone as main constituents. Conclusion: These results indicate that K. coriacea is a promising medicinal plant in cancer therapy exhibiting antitumor activity both in vitro and in vivo against different tumor cell lines.

Early Tissue Effects of Stereotactic Body Radiation Therapy for Spinal Metastases

NARCIS (Netherlands)

Steverink, Jasper G.; Willems, Stefan M.; Philippens, Marielle E.P.; Kasperts, Nicolien; Eppinga, Wietse S.C.; Versteeg, Anne L.; van der Velden, Joanne M.; Faruqi, Salman; Sahgal, Arjun; Verlaan, Jorrit Jan

2018-01-01

Purpose: Stereotactic body radiation therapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent data have suggested radiobiologic effects of SBRT that expand beyond the traditional concept of DNA damage. Antitumor immunity, vascular damage leading

Minimally invasive neuronavigator-guided microsurgery and photodynamic therapy for gliomas.