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Sample records for orthotopic neobladder replacement

  1. Endoscopic Treatment of Studer's Orthotopic Neobladder Lithiasis.

    PubMed

    Gil-Sousa, Diogo; Oliveira-Reis, Daniel; Cavadas, Vitor; Oliveira, Manuel; Soares, José; Fraga, Avelino

    2015-05-01

    Studer's neobladder lithiasis is a rare but important long term complication of this orthotopic bladder substitute technique. We report a case of a 45 year-old male patient, submitted to a radical cystoprostatectomy with a Studer's orthotopic neobladder 4 years before, presenting bad compliance to recommended urinary habits, increased production of mucus and high post voiding residue. CT scan and urethrocystography showed a distended pouch with 2 major sacculations with narrow communication and a stone in each sacculation. A minimally invasive endoscopic technique was successfully used in the treatment of the 2 small calculus. PMID:26793507

  2. Endoscopic Treatment of Studer's Orthotopic Neobladder Lithiasis

    PubMed Central

    Gil-Sousa, Diogo; Oliveira-Reis, Daniel; Cavadas, Vitor; Oliveira, Manuel; Soares, José; Fraga, Avelino

    2015-01-01

    Studer's neobladder lithiasis is a rare but important long term complication of this orthotopic bladder substitute technique. We report a case of a 45 year-old male patient, submitted to a radical cystoprostatectomy with a Studer's orthotopic neobladder 4 years before, presenting bad compliance to recommended urinary habits, increased production of mucus and high post voiding residue. CT scan and urethrocystography showed a distended pouch with 2 major sacculations with narrow communication and a stone in each sacculation. A minimally invasive endoscopic technique was successfully used in the treatment of the 2 small calculus. PMID:26793507

  3. Intravesical OnabotulinumtoxinA Injection for Overactive Orthotopic Ileal Neobladder: Feasibility and Efficacy

    PubMed Central

    2016-01-01

    The efficacy of intravesical onabotulinumtoxinA (BTXA) in the treatment of overactive bladder (OAB) has been well documented. The use of BTXA injection in orthotopic neobladders is yet to be studied. We present 4 cases of patients injected with intravesical BTXA for overactive orthotopic ileal neobladder. We recorded patient demographics, presenting and follow-up symptoms, urodynamic profiles, and Patient Global Impression of Improvement (PGI-I) scores. The 4 patients reported varying degrees of subjective improvements in the symptoms, including urgency, urge incontinence, and pad usage. Mean follow-up duration was 8.3 months (range, 5–14 months). Average PGI-I score was 3 (“a little better”) (range, 2–4). To our knowledge, the current study is the first case series examining BTXA injection for orthotopic neobladder overactivity. BTXA injection yielded varying degrees of objective and subjective improvements, without significant complications. Intravesical BTXA injection is feasible and may be considered as a potential treatment alternative for OAB in orthotopic neobladders, although further study is warranted. PMID:27032562

  4. Comparison Between Ambulatory and Conventional Urodynamics of the Modified Orthotopic Hautmann Neobladder

    PubMed Central

    Georgios, Dimitriadis; Georgios, Gkotsos; Ioannis, Vakalopoulos; Stavros, Ioannidis; Konstantinos, Hatzimoutatidis; Dimitrios, Hatzichristou

    2015-01-01

    Purpose: The aim of the present study was to determine the diagnostic accuracy of conventional and ambulatory urodynamic studies (UDS) in estimating neobladder function. Methods: We evaluated 32 patients who underwent radical cystectomy and orthotopic Hautmann W neobladder with Abol-Enein-Ghoneim uretero-intestinal anastomosis for bladder cancer. The patients were initially examined by using both conventional and ambulatory UDS. Results: Conventional UDS detected a very high mean intravesical pressure at maximum capacity (53.7±17.5 cm H2O). By contrast, the mean intravesical pressure detected by using ambulatory UDS (which reflects the dominant pattern of pressure variation during filling) was significantly lower (34.4±5.2 cm H2O, P<0.001). The comparison between intravesical pressure at half of maximum capacity in conventional UDS and the mean value in ambulatory UDS did not show significant difference (P=0.152). The mean voided volume in conventional UDS was greater than both the mean voided volume (P<0.001) and the mean maximum voided volume in ambulatory UDS (P=0.001). However, this difference did not affect the postvoid residual urine volume measured in both studies (P=0.207). Moreover, incontinence episodes recorded in ambulatory UDS were more frequent but not statistically significantly different from those recorded in conventional UDS (P=0.332). Conclusions: The estimation of neobladder function by means of ambulatory UDS seems to provide interesting research data for the mode of lower urinary tract function in patients with orthotopic substitution after radical cystectomy. The great high value in ambulatory UDS, in cases in which conventional UDS had failed, is due to the exposure of daily and nocturnal incontinence episodes, confirming our patients’ complaints. PMID:26739181

  5. Long-term urodynamic evaluation of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer.

    PubMed

    Wang, Dong; Li, Li-Jun; Liu, Jing; Qiu, Ming-Xing

    2014-09-01

    The long-term urodynamics of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer remain unclear in the clinical setting. The present prospective observational study was conducted between January 2010 and December 2012 to evaluate the 6-month and 12-month follow-up data of urodynamic changes of bladder cancer patients who were initially treated by laparoscopic radical cystectomy with orthotopic ileal neobladder. A total of 53 eligible patients were included, and all patients were followed up for at least 12 months, with a median time of 18 months. During the follow-up period, no patients reported difficulty urinating, and the daily frequency of urination and the urine output were gradually improved with time. Dynamic urodynamic examinations showed that the maximum flow rate (11.4±1.1 vs. 7.3±1.4 ml/sec; P<0.001), residual urine content (22.8±10.5 vs. 40.7±12.7 ml; P<0.001), maximum bladder capacity (373.8±62.2 vs. 229.7±56.3 ml; P<0.001) and maximum bladder pressure during filling (35.8±6.7 vs. 26.4±7.0 cm H2O; P<0.001) at 12 months were all improved significantly compared with that at 6 months after the initial surgical treatment. However, there were no significant differences in maximum bladder pressure during voiding (75.7±24.7 vs. 73.1±24.7 cm H2O; P=0.618) and bladder compliance (26.9±13 vs. 27.4±13.1 cm H2O; P=0.848) at 12 and 6 months after initial surgical treatment. In conclusion, the urodynamics of this orthotopic ileal neobladder gradually improve, and its long-term urine storage and voiding functions are acceptable. PMID:25120652

  6. Preperitoneal placement of an inflatable penile prosthesis reservoir for postoperative erectile dysfunction after radical cystoprostatectomy with orthotopic neobladder

    PubMed Central

    Kim, Jung Kwon; Cho, Min Chul; Ku, Ja Hyeon

    2016-01-01

    Purpose To describe a case of safe placement of an inflatable penile prosthesis reservoir for postoperative erectile dysfunction (ED) with a history of radical cystoprostatectomy with an orthotopic Studer neobladder. Materials and Methods A 55-year-old bladder cancer patient, who underwent radical cystoprostatectomy with orthotopic Studer neobladder 2 years prior, suffered from postoperative ED. A 3-piece inflatable penile prosthesis was implanted via a penoscrotal incision. The alternative reservoir placement began with a longitudinal 4-cm incision, which was 2 finger-breaths to the left and lateral to the umbilicus. Thereafter, the anterior and posterior rectus sheaths were dissected and incised. Then, the transversalis fascia entering into the preperitoneal space was incised, followed by circumferential sweeping using the forefinger, and, finally, placement of a 100 mL 'flat' reservoir. The reservoir was filled with 65 mL saline and then evaluated for back pressure. The reservoir tubing exited through the defect of the rectus sheaths and tunneled through the abdominal fat into the penoscrotal wound. Results Total operative time was 105 minutes, and the estimated blood loss was minimal. The patient was discharged at postoperative day 1 and experienced no perioperative complications. At the 6-month follow-up, there was no abdominal bulging from the preperitoneal reservoir, and the reservoir was not palpable. Conclusions The preperitoneal placement of the flat reservoir at the level of the umbilicus is a safe and acceptable surgical technique for postoperative ED after radical cystoprostatectomy with orthotopic neobladder.

  7. Technical steps of open radical cystectomy and orthotopic neobladder to achieve the goals of “minimally invasive surgery”?

    PubMed Central

    Mandhani, Anil; Dharaskar, Anand; Kapoor, Rakesh

    2010-01-01

    Technical modifications in open approach to radical cystectomy and orthotopic neobladder (ONB), that is, Pfannenstiel incision, single urethral catheter, internal splint, and extraperitonealization of the ONB were done in 36 patients. Median operative time was 300 (240–360) min. Median time to move the bowel and start of oral intake was 4 days (2–8) days. Major complications occurred in 3 (8.33%) patients. Mean postoperative pain score was 2 (1–4). These modifications in open radical cystectomy resulted in better cosmesis, less pain, and more comfort to the patients as they had to carry one urobag for 3 weeks. PMID:21116377

  8. Can we predict the need for clean intermittent catheterization after orthotopic neobladder construction?

    PubMed Central

    Murray, Katie S.; Arther, Andrew R.; Zuk, Keegan P.; Lee, Eugene K.; Lopez-Corona, Ernesto; Holzbeierlein, Jeffrey M.

    2015-01-01

    Introduction: We aimed to identify peri-operative and pathologic characteristics that may predict the need for clean intermittent catheterization (CIC) following radical cystectomy (RC) with orthotopic neobladder (ONB) in order to improve patient counseling on choice of urinary diversion. Materials and Methods: Between July 2004 and February 2013, all patients who underwent RC with ONB were identified. Peri-operative clinical and pathological features were evaluated and correlated with patients reported need for CIC. The independent T-test was performed for continuous variables and Chi-square test was performed for categorical variables. Multivariate forward stepwise logistic regression analysis was used to identify variables that correlated with need for CIC after ONB. Results: During the study period, 114 patients underwent RC with ONB creation. On univariate analysis, patients with higher body mass index, younger age, and non-vaginal or non-nerve-sparing procedures were more likely to require catheterization for complete emptying. Multivariate analysis demonstrates that conservative surgery (nerve sparing in males or vaginal sparing in females) was associated with a significantly lower rate of requiring CIC (Odds Ratio [OR] 0.20, P < 0.01). Surprisingly, older age was also associated with a slightly lower, but statistically significant, rate of requiring CIC (OR 0.92,P < 0.01). Conclusions: When counseling patients regarding the different types of diversions after RC, the potential need for long-term CIC after ONB must be discussed. The clinical factors that appear to increase the need for CIC include non-conservative RC (non-nerve sparing in males and non-vaginal sparing in females) and, to a certain degree, younger age. PMID:26604445

  9. Cystectomy with orthotopic ileal neobladder reconstruction for treatment of bladder contracture after intravesical bacillus Calmette-Guerin therapy

    PubMed Central

    Vetorazzo, José Eduardo; Bahia, Leandro Augusto Costa; Vedovato, Bruno César; Maron, Paulo Eduardo Goulart; Esteves, Paulo Ebert; Fernandes, Roni de Carvalho; Perez, Marjo Deninson Cardenuto

    2014-01-01

    Bladder cancer is an important health problem worldwide due to high prevalence rates and costs related to treatment. A reduction in recurrence rates has been observed since the introduction of adjuvant intravesical immunotherapy with bacillus Calmette-Guerin. There are mild complications that are easily solved by local measures and orientations. Bladder contracture, a rare and severe local complication, in some cases leading to disability, is observed primarily in patients in a maintenance program. In this article we reported the case of a male patient who underwent transurethral resection of the bladder because of a high-grade T1 urothelial carcinoma and developed this complication during treatment with bacillus Calmette-Guerin. For this reason he was submitted to cystoprostatectomy with orthotopic ileal neobladder reconstruction. PMID:25628205

  10. AB054. An improved technique for bladder cancer: pure laparoscopic radical cystectomy with orthotopic U-shape ileal neobladder using titanium staples

    PubMed Central

    Wang, Shuai; Qi, Xiaolong; Liu, Feng; Zheng, Min; Zhang, Dahong

    2015-01-01

    Objective To report our experience with an improved technique of laparoscopic radical cystectomy (LRC) and orthotopic ileal neobladder reconstruction, evaluating the perioperative and pathological outcomes. Methods We retrospectively reviewed the data of 56 cases who underwent radical cystoprostatectomy followed by construction of an orthotopic U-shaped ileal neobladder between August 2010 and December 2014. These data include intraoperative data, early and long-term postoperative complications, neobladder function, urinary continence and oncologic results. Also the key innovative procedure was introduced with details. Results The median time of the overall procedure was 212 min. The median estimated blood loss was 171 mL. The median hospitalization time after the operation was 21 days. Complications included two cases of unilateral ureter-pouch anastomotic strictures, one case of bilateral ureteral stricture, three cases of vesicourethral anastomotic strictures and three cases of vesicourethral leakage. The mean maximum pouch capacity was 446±32 mL, and pouch pressure at capacity was 18.1±2.6 cmH2O. The Qmax was 14±1.2 mL/s, and the mean post-void residual was 25±10 mL. There were nine cases of night-time incontinence at 3 months post-operatively. Negative surgical margins of the bladder specimens were achieved in all patients. During a follow-up period of 3 to 44 months (average 32.6 months), local recurrence was found in two patients and distant metastasis was occurred in another three patients. Conclusions Our preliminary experience showed that pure LRC with non-absorbable titanium staples assisted orthotopic U-shape ileal neobladder reconstruction is feasible based on perioperative data and oncologic features.

  11. Is frozen section analysis of the urethra at the time of radical cystectomy and orthotopic neobladder urinary diversion mandatory?

    PubMed Central

    Sureka, Sanjoy Kumar; Yadav, Abhishek; Arora, Sohrab; Kapoor, Rakesh; Mandhani, Anil

    2015-01-01

    Introduction: This study was aimed at analyzing the need for routine use of frozen section analysis (FSA) before performing orthotopic neobladder (ONB) after radical cystectomy for carcinoma urinary bladder. Materials and Methods: A total of 233 patients underwent radical cystectomy from January 2000 to June 2013. Of these, 151 (65.6%) patients were planned for ONB. In the initial 109 (72%) patients, FSA of urethral margin was performed, but, in the subsequent 42 (28%) patients, frozen section of urethral margin was not sent. Impact of hydroureteronephrosis, tumor size and location of tumor in relation to the bladder neck on the status of the urethral margin was analyzed. Results: Only three of the 109 (2.7%) patients had a positive urethral margin. Two of them had ileal conduit and one, after negative re-resection, had ONB. Although none of the factors was found to be significant, all three patients with a positive urethral margin had growth at the bladder neck and died of cancer at a mean follow up of 29.33 ± 18.3 months, without urethral recurrence. Among the negative FSA (106), two patients had recurrence in the penile urethra. The mean follow-up was 46.3 ± 25.1 months. None of the patients without FSA (42) had urethral recurrence at the mean follow-up of 36 ± 9.3 months. Of the 28 patients who had their growth located at the bladder neck, three had positive FSA, while none with growth away from the bladder neck had positive FSA. Conclusion: Routine FSA of the urethra before performing ONB can be avoided in those patients where the tumor does not reach the bladder neck. PMID:26604448

  12. [A case of metabolic acidosis and tetany after ileal neobladder replacement].

    PubMed

    Nomura, Hironori; Kou, Yohko; Kinjyo, Takanori; Nonomura, Daichi; Yoneda, Suguru; Yamamoto, Yoshiyuki; Tei, Norihide; Takada, Shingo; Matsumiya, Kiyomi

    2013-08-01

    A 64-year-old man visited our hospital with the complaint of macrohematuria and bilateral hydronephrosis. He had undergone total cystectomy and ileal neobladder replacement under the diagnosis of muscle invasive bladder cancer (cT2bN0M0). Tetany due to hyperventilation syndrome appeared on postoperative day 42. Blood gas analysis showed metabolic acidosis (pH 7.260, pO2 148.1 mmHg, pCO2 20.7 mmHg, HCO3 9.1 mmHg, BE -16.0 mmol/l). His condition was immediately improved after a urethral catheter was placed and sodium bicarbonate was administered. After re-removal of the urethral catheter, however, hyperventilation syndrome recurred. He was discharged from the hospital with the urethral catheter placed. PMID:23995533

  13. Tubulovillous Adenoma in a Urethral Neobladder Anastomosis

    PubMed Central

    Morganstern, Bradley A.; Greenblatt, Logan B.; Yaskiv, Oksana; Steckel, Joph

    2015-01-01

    We present a case of a tubulovillous adenoma arising in a neobladder that was managed by cystoscopic resection. A 64 year-old male underwent a cystectomy with creation of an ileocolic neobladder urinary diversion for T2 urothelial carcinoma of the bladder. Nine years following his surgery, the patient noted several episodes of gross hematuria. Cystoscopic evaluation revealed the rare occurrence of a 3 cm tubulovillous adenoma with high-grade dysplasia at the neck of the neobladder. PMID:26793555

  14. Febrile Urinary Tract Infection after Radical Cystectomy and Ileal Neobladder in Patients with Bladder Cancer

    PubMed Central

    2016-01-01

    Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 ± 193.7 vs. 90.5 ± 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction. PMID:27366009

  15. Medial thigh pain: An unusual presentation of giant calculi in sigmoid neobladder

    PubMed Central

    Abrol, Nitin; Gupta, Narmada; Kumar, Rajeev

    2011-01-01

    Calculi in a neobladder usually present with irritative lower urinary tract symptoms, flank pain, and haematuria. We report a case of giant stones in a sigmoid neobladder, who presented with medial thigh pain. PMID:21814323

  16. Robotic radical cystectomy with intracorporeal neobladder: Initial experience and outcomes

    PubMed Central

    Butt, Zulfiqar A.; Forbes, Ellen; Zorn, Jeff; Martin, Blair St

    2015-01-01

    Introduction: Total intra-corporeal robot-assisted radical cystectomy (RARC) with total intracorporeal neobladder formation is relatively new in the treatment of bladder cancer. We present our experience and believe it is the first Canadian reported series with this technique. Methods: This is a case series of 4 patients, who underwent total RARC, pelvic lymphadenectomy and creation of an intra-corporeal ileal neobladder. Surgical technique is described and perioperative variables, pathologic data, and complication rates are reported. Results: The mean patient age was 61.8 and the mean body mass index was 27.01 kg/m2. The mean operative time, estimated blood loss, time to full diet and length of stay were 522.8 minutes (standard deviation [SD] 74.5), 237.5 mL (SD 47.9), 9 days (range: 3–24) and 12.8 days (range: 6–31), respectively. All patients completed postoperative functional evaluation showing a mean neobladder capacity of 575 cc (range: 500–720). Surgical margins and pathological nodal status were negative in all patients with no evidence of disease recurrence or progression on follow-up. Three of the 4 patients suffered a complication within 90 days, with one occurring later in the first year. All early complications were Clavien grade I–II (grade I [n = 1]; grade II [n = 2]) and the later complication was grade IIIa. The mean follow-up was 632 days (range: 562–730). The limitation of our study is its small sample size with highly selected patients to compensate for the learning experience. The follow-up is short; however, the outcomes are comparable to early experiences reported at other institutions. Conclusions: In our initial experience, RARC with total intracorporeal neobladder formation is safe. We expect that with experience the expense of robotic surgery can be compensated with early ambulation and shorter stay. PMID:25844107

  17. Laparoscopic Radical Cystectomy and Ileal Neobladder for Muscle Invasive Bladder Cancer in Combination with One Stage Prophylactic Laparoscopic Sacrospinal Fixation to Avoid Future Pelvic Organ Prolapse

    PubMed Central

    Törzsök, Péter; Bauer, Sophina; Forstner, Rosemarie; Sievert, Karl-Dietrich; Janetschek, Günter

    2016-01-01

    Abstract Background: Women who undergo cystectomy with orthotopic ileal neobladder are more likely to have urinary retention and neocystocele mainly because of anatomical reasons than stress urinary incontinence. The risk is even higher in case of neurologic comorbidities, as in case of our patient. Case Presentation: We present a laparoscopic mesh insertion for sacrospinal colposuspension to prevent a neocystocele and pelvic organ prolapse in combination with laparoscopic radical cystectomy in a female patient suffering from bladder cancer and chronic episodic multiple sclerosis. After a 30-month follow-up, the patient is continent and voids without residual urine. A dynamic MR of the pelvis shows a minimal rectocele without any evidence of a cystocele. Conclusion: Laparoscopic cystectomy combined with sacrospinal mesh fixation is technically feasible and could be an option to prevent neocystocele for female patients.

  18. Ileal Neobladder With Mucous Plugs as a Cause of Obstructive Acute Kidney Injury Requiring Emergent Hemodialysis.

    PubMed

    Singla, Montish; Shikha, Deep; Lee, Sunggeun; Baumstein, Donald; Chaudhari, Ashok; Carbajal, Roger

    2016-01-01

    Ileal neobladder is the preferred technique in the management of urinary diversion postradical cystectomy for bladder malignancy. The common complications associated with this procedure are atrophied kidney, chronic pyelonephritis, decreased renal function, ureteroileal or urethral anastomotic site stricture, urinary tract stones, incontinence, and hyperchloremic metabolic acidosis. Mucous plugs are also seen in 2%-3% patients. We present a rare presentation of a patient who required hemodialysis for severe hyperkalemia and acute kidney injury caused by mucous plugging of ileal neobladder. PMID:25420078

  19. The effect of N-acetyl-L-cysteine on the viscosity of ileal neobladder mucus.

    PubMed

    Schrier, B P; Lichtendonk, W J; Witjes, J A

    2002-05-01

    N-acetyl-L-cysteine (NAC) proved to be an effective mucolytic in pulmonary secretions. Our goal was to investigate the in vitro effect of NAC on viscosity of ileal neobladder mucus. The urine of a patient with an ileal neobladder was collected during the first 7 days postoperatively and stored in a refrigerator. After precipitation, the urine was decanted. The residue was stirred to a homogeneous suspension. To samples of 4.5 ml mucus, 0.5 ml NAC 10% was added. To the control sample, 0.5 ml water was added. The samples were incubated in a water bath at 37 degrees C for 5, 30 and 60 min. Viscosity was measured in the Bohlin VOR Rheometer. The viscosity of the ileal neobladder mucus decreased quickly after incubating with NAC 10%. Viscosity increased slightly after I h of incubation. The viscosity in the control sample was higher than in the other incubated samples. NAC was found to decrease the viscosity of ileal neobladder mucus, supporting the in vivo experience that NAC can be useful in patients with an ileal neobladder to facilitate the evacuation of mucus by decreasing viscosity. PMID:12088194

  20. Risk Factors for Developing Metabolic Acidosis after Radical Cystectomy and Ileal Neobladder

    PubMed Central

    Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Ryu, Dong-Ryeol; Lee, Dong Hyeon

    2016-01-01

    Purpose To investigate the serial changes of metabolic acidosis and identify associated risk factors in patients who underwent radical cystectomy and ileal neobladder. Material and Methods From January 2010 to August 2014, 123 patients who underwent radical cystectomy and ileal neobladder reconstruction for bladder cancer were included in this study. Metabolic acidosis was defined as a serum bicarbonate level less than 22 mEq/L and impaired renal function was defined as a GFR <50ml/min. The presence of metabolic acidosis was evaluated at 1 month, 1 year, and 2 years after surgery. Multivariate logistic regression analysis was conducted to identify risk factors associated with development of metabolic acidosis. Results Metabolic acidosis was observed in 52%, 19.5%, and 7.3% of patients at 1 month, 1 year, and 2 years after surgery, respectively. At 1 month after surgery, impaired renal function was the only independent risk factor associated with metabolic acidosis (OR 3.87, P = 0.046). At 1 year after surgery, diabetes was the only independent risk factor associated with metabolic acidosis (OR 5.68, P = 0.002). At 2 years post-surgery, both age and diabetes were significant risk factors associated with metabolic acidosis. Conclusion Approximately, half of patients experienced metabolic acidosis one month after ileal neobladder reconstruction. Preoperative impaired renal function was the most significant risk factor for developing metabolic acidosis in the early postoperative period. However, the incidence of metabolic acidosis decreased to less than 20% 1 year after surgery, and diabetes was an independent risk factor during this period. PMID:27384686

  1. Orthotopic urinary diversion after radical cystectomy in treatment of muscle invasive bladder cancer.

    PubMed

    Jovan, Hadži-Djokić; Vladan, Andrejević; Tomislav, Pejčić; Miodrag, Aćimović; Uroš, Babić; Miodrag, Stanić; Zoran, Džamić

    2014-01-01

    Surgical treatment of invasive carcinoma of the bladder in males includes total cystectomy removal of the prostate, seminal vesicles, and the distal parts of the urethers and the pelvic lymph node dissection as well. At this moment it is not possible to recommend a particular type of urinary diversion, but today in clinical practice commonly used derivative are ileal orthotopic neobladder as the continent one and ileal conduit as non-continent urinary diversion. Continent urinary diversion after radical cystectomy are the result of the application of technological innovation in surgery, but also knowledge, imagination and skill of well trained urologist. This type of operation significantly improves the quality of life in patients who underwent radical cystectomy, and the proposal is to operate whenever there is a possibility for this type of procedure. Also it is very important, during surgery to respect oncological principles, of complete removal of tumorous tissue and that the functional principle of ensur- ing that the patients have daytime and also nighttime continence later on after the surgery. PMID:25782228

  2. Infections After Orthotopic Liver Transplantation

    PubMed Central

    Pedersen, Mark; Seetharam, Anil

    2014-01-01

    Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. PMID:25755581

  3. Infections Following Orthotopic Liver Transplantation

    PubMed Central

    Arnow, Paul M.

    1991-01-01

    The epidemiology of infections associated with orthotopic liver transplantation is summarized herein, and approaches to prophylaxis are outlined. Infection is a major complication following orthotopic liver transplantation, and more than half of transplant recipients develop at least one infection. The risk of infection is highest in the first month after transplantation, and the most common pathogens are bacteria and cytomegalovirus (CMV). Bacterial infections usually occur in the first month, arise in the abdomen, and are caused by aerobes. The peak incidence of CMV infection is late in the first month and early in the second month after transplantationn. CMV syndromes include fever and neutropenia, hepatitis, pneumonitis, gut ulceration, and disseminated infection. Other significant problems are Candida intraabdominal infection, Herpes simplex mucocutaneous infection or hepatitis, adenovirus hepatitis, and Pneumocystis carinii pneumonia. Prophylaxis of infection in liver transplant recipients has not been well-studied. Several different regimens of parenteral, oral absorbable, and/or oral non-absorbable antibiotics active against bacteria and yeast have been used at various centers, but no randomized controlled trials have been conducted. Selective bowel decontamination appears to be a promising approach to the prevention of bacterial and Candida infections, while oral acyclovir may be a relatively convenient and effective agent for CMV prophylaxis. PMID:1650245

  4. Orthotopic Hind Limb Transplantation in the Mouse.

    PubMed

    Furtmüller, Georg J; Oh, Byoungchol; Grahammer, Johanna; Lin, Cheng-Hung; Sucher, Robert; Fryer, Madeline L; Raimondi, Giorgio; Lee, W P Andrew; Brandacher, Gerald

    2016-01-01

    In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and translational research in the field of transplantation medicine. A vast array of reagents is available exclusively in this setting, including mono- and polyclonal antibodies for both diagnostic and interventional applications. In addition, a vast number of genotyped, inbred, transgenic, and knock out strains allow detailed investigation of the individual contributions of humoral and cellular components to the complex interplay of an immune response and make the mouse the gold standard for immunological research. Vascularized Composite Allotransplantation (VCA) delineates a novel field of transplantation using allografts to replace "like with like" in patients suffering traumatic or congenital tissue loss. This surgical methodological protocol shows the use of a non-suture cuff technique for super-microvascular anastomosis in an orthotopic mouse hind limb transplantation model. The model specifically allows for comparison between established paradigms in solid organ transplantation with a novel form of transplants consisting of various different tissue components. Uniquely, this model allows for the transplantation of a viable vascularized bone marrow compartment and niche that have the potential to exert a beneficial effect on the balance of immune acceptance and rejection. This technique provides a tool to investigate alloantigen recognition and allograft rejection and acceptance, as well as enables the pursuit of functional nerve regeneration studies to further advance this novel field of transplantation. PMID:26967527

  5. Perineal herniation of an ileal neobladder following radical cystectomy and consecutive rectal resection for recurrent bladder carcinoma.

    PubMed

    Neumann, P A; Mehdorn, A S; Puehse, G; Senninger, N; Rijcken, E

    2016-04-01

    Secondary perineal herniation of intraperitoneal contents represents a rare complication following procedures such as abdominoperineal rectal resection or cystectomy. We present a case of a perineal hernia formation with prolapse of an ileum neobladder following radical cystectomy and rectal resection for recurrent bladder cancer. Following consecutive resections in the anterior and posterior compartment of the lesser pelvis, the patient developed problems emptying his neobladder. Clinical examination and computed tomography revealed perineal herniation of his neobladder through the pelvic floor. Through a perineal approach, the hernial sac could be repositioned, and via a combination of absorbable and non-absorbable synthetic mesh grafts, the pelvic floor was stabilised. Follow-up review at one year after hernia fixation showed no signs of recurrence and no symptoms. In cases of extensive surgery in the lesser pelvis with associated weakness of the pelvic compartments, meshes should be considered for closure of the pelvic floor. Development of biological meshes with reduced risk of infection might be an interesting treatment option in these cases. PMID:26985818

  6. Comparison of postoperative acute kidney injury between ileal conduit and neobladder urinary diversions after radical cystectomy: A propensity score matching analysis.

    PubMed

    Joung, Kyoung-Woon; Kong, Yu-Gyeong; Yoon, Syn-Hae; Kim, Yeon Ju; Hwang, Jai-Hyun; Hong, Bumsik; Kim, Young-Kug

    2016-09-01

    Ileal conduit and neobladder urinary diversions are frequently performed after radical cystectomy. However, complications after radical cystectomy may be different according to the type of urinary diversion. Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. This study was performed to compare the incidence of postoperative AKI between ileal conduit and neobladder urinary diversions after radical cystectomy.All consecutive patients who underwent radical cystectomy in 2004 to 2014 in a single tertiary care center were identified. The patients were divided into the ileal conduit and ileal neobladder groups. Preoperative variables, including demographics, cancer-related data and laboratory values, as well as intraoperative data and postoperative outcomes, including AKI, intensive care unit admission rate, and the duration of hospital stay, were evaluated between the groups. Postoperative AKI was defined according to the Kidney Disease: Improving Global Outcome criteria. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences.After performing 1:1 propensity score matching, the ileal conduit and ileal neobladder groups each included 101 patients. The overall incidence of AKI after radical cystectomy was 30.7% (62 out of 202) and the incidences did not significantly differ between the groups (27 [26.7%], ileal conduit group vs 35 [34.7%], ileal neobladder group, P = 0.268). Intraoperative data, intensive care unit admission rate, and the duration of hospital stay were not significantly different between the groups.Postoperative AKI did not significantly differ between ileal conduit and neobladder urinary diversions after radical cystectomy. This finding provides additional information useful for appropriate selection of the urinary diversion type in conjunction with radical cystectomy. PMID:27603401

  7. Orthotopic Injection of Pancreatic Cancer Cells.

    PubMed

    Aiello, Nicole M; Rhim, Andrew D; Stanger, Ben Z

    2016-01-01

    Pancreatic ductal adenocarcinoma is an aggressive disease with a 5-yr survival rate of only 5%. The location of the pancreas in the abdomen, where it is obscured by other organs, makes it a difficult tissue to study and manipulate. This protocol describes in detail how to orthotopically inject cancer cells into the pancreas in mice. This technique is particularly useful when the cells must be manipulated in ways that cannot be modeled genetically. PMID:26729902

  8. Complications of Radical Cystectomy and Orthotopic Reconstruction

    PubMed Central

    Tan, Wei Shen; Lamb, Benjamin W.; Kelly, John D.

    2015-01-01

    Radical cystectomy and orthotopic reconstruction significant morbidity and mortality despite advances in minimal invasive and robotic technology. In this review, we will discuss early and late complications, as well as describe efforts to minimize morbidity and mortality, with a focus on ileal orthotopic bladder substitute (OBS). We summarise efforts to minimize morbidity and mortality including enhanced recovery as well as early and late complications seen after radical cystectomy and OBS. Centralisation of complex cancer services in the UK has led to a fall in mortality and high volume institutions have a significantly lower rate of 30-day mortality compared to low volume institutions. Enhanced recovery pathways have resulted in shorter length of hospital stay and potentially a reduction in morbidity. Early complications of radical cystectomy occur as a direct result of the surgery itself while late complications, which can occur even after 10 years after surgery, are due to urinary diversion. OBS represents the ideal urinary diversion for patients without contraindications. However, all patients with OBS should have regular long term follow-up for oncological surveillance and to identify complications should they arise. PMID:26697063

  9. Surgical techniques of orthotopic rat liver transplantation.

    PubMed

    Spiegel, H U; Palmes, D

    1998-01-01

    Liver transplantation in rats is frequently used as a transplantation model. Although liver transplantation in larger laboratory animals such as dogs and pigs is technically easier, the rat has become the most important subject for experimental liver transplantation because of the availability of genetically defined animals. Numerous surgical techniques have been developed that permit the investigator to carry out studies with high clinical relevance. In this article the principal models of orthotopic rat liver transplantation and their technical modifications of vessel anastomoses, rearterialization, and bile duct reconstruction techniques are reviewed. More than 20 transplantation models are described in detail and demonstrated with clear illustrations. Finally, the advantages and uses of all the surgical procedures (e.g., suture and cuff anastomoses, bile duct anastomoses, and rearterialization techniques), specific problems, and survival criteria are discussed and the experiences of investigators who applied these techniques are analyzed. In conclusion, an overview and critical evaluation of all surgical techniques of orthotopic rat liver transplantation are given, together with instructions for learning these techniques. PMID:9700616

  10. Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney

    PubMed Central

    Song, Jeremy J; Guyette, Jacques; Gilpin, Sarah; Gonzalez, Gabriel; Vacanti, Joseph P; Ott, Harald C

    2013-01-01

    Over 100,000 individuals in the United States currently await kidney transplantation, while 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney’s architecture and function, and permit perfusion, filtration, secretion, absorption, and drainage of urine. We decellularized rat, porcine, and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells, then perfused these cell-seeded constructs in a whole organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused via their intrinsic vascular bed. When transplanted in orthotopic position in rat, the grafts were perfused by the recipient’s circulation, and produced urine via the ureteral conduit in vivo. PMID:23584091

  11. Scedosporium apiosermum infection of the "Native" valve: Fungal endocarditis in an orthotopic heart transplant recipient.

    PubMed

    Clement, Meredith E; Maziarz, Eileen K; Schroder, Jacob N; Patel, Chetan B; Perfect, John R

    2015-09-01

    Scedosporium apiospermum is an increasingly appreciated pathogen in immunosuppressed patients. We present a case of S. apiospermum endocarditis in a 70-year-old male who had undergone orthotopic heart transplant. Echocardiogram demonstrated a 1.4 cm tricuspid valve vegetation. He underwent valve replacement, complicated by fatal massive post-operative haemorrhage. Valve cultures grew S. apiospermum. To our knowledge, our case is the first reported instance of endocarditis caused by S. apiospermum in a recipient of a cardiac transplant. PMID:26288748

  12. Aortic Balloon Valvuloplasty Prior to Orthotopic Liver Transplantation: A Novel Approach to Aortic Stenosis and End-Stage Liver Disease

    PubMed Central

    Coverstone, Edward; Korenblat, Kevin; Crippin, Jeffrey S.; Chapman, William C.; Kates, Andrew M.; Zajarias, Alan

    2014-01-01

    The combination of severe aortic stenosis and end-stage liver disease increases the morbidity and mortality of surgical aortic valve replacement or orthotopic liver transplantation resulting in a prohibitive operative risk. We propose a staged approach of balloon aortic valvuloplasty prior to orthotopic liver transplantation as a bridge to definitive aortic valve replacement. Between 2010 and 2012, four patients with severe aortic stenosis and end-stage liver disease underwent staged balloon aortic valvuloplasty followed by orthotopic liver transplantation. All patients had been deemed to be inappropriate candidates for liver transplantation or aortic valve surgery due to their comorbidity. One patient died of complications from a perivalvular abscess. Three patients went on to successful graft implantation and function and surgical recovery. Two of the three patients proceeded to definitive surgical aortic valve replacement with the remainder currently undergoing evaluation. In this case series, we present a novel approach of balloon aortic valvuloplasty prior to liver transplantation as a potential bridge to definitive treatment of severe aortic stenosis in the end-stage liver patient. PMID:25431682

  13. Cryopreservation and orthotopic transplantation of rat ovaries.

    PubMed

    Dorsch, Martina; Wedekind, Dirk

    2010-01-01

    The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required. PMID:20013242

  14. Intraoperative blood loss in orthotopic liver transplantation: The predictive factors

    PubMed Central

    Pandey, Chandra Kant; Singh, Anshuman; Kajal, Kamal; Dhankhar, Mandeep; Tandon, Manish; Pandey, Vijay Kant; Karna, Sunaina Tejpal

    2015-01-01

    Liver transplantation has been associated with massive blood loss and considerable transfusion requirements. Bleeding in orthotopic liver transplantation is multifactorial. Technical difficulties inherent to this complex surgical procedure and pre operative derangements of the primary and secondary coagulation system are thought to be the principal causes of perioperative hemorrhage. Intraoperative practices such as massive fluid resuscitation and resulting hypothermia and hypocalcemia secondary to citrate toxicity further aggravate the preexisting coagulopathy and worsen the perioperative bleeding. Excessive blood loss and transfusion during orthotopic liver transplant are correlated with diminished graft survival and increased septic episodes and prolonged ICU stay. With improvements in surgical skills, anesthetic technique, graft preservation, use of intraoperative cell savers and overall perioperative management, orthotopic liver transplant is now associated with decreased intra operative blood losses. The purpose of this review is to discuss the risk factors predictive of increased intra operative bleeding in patients undergoing orthotopic liver transplant. PMID:26131330

  15. A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma

    PubMed Central

    Nucera, Carmelo; Nehs, Matthew A.; Mekel, Michal; Zhang, Xuefeng; Hodin, Richard; Lawler, Jack; Nose, Vânia

    2009-01-01

    Background Orthotopic mouse models of human cancer represent an important in vivo tool for drug testing and validation. Most of the human thyroid carcinoma cell lines used in orthotopic or subcutaneous models are likely of melanoma and colon cancer. Here, we report and characterize a novel orthotopic model of human thyroid carcinoma using a unique thyroid cancer cell line. Methods We used the cell line 8505c, originated from a thyroid tumor histologically characterized by anaplastic carcinoma cell features. We injected 8505c cells engineered using a green fluorescent protein–positive lentiviral vector orthotopically into the thyroid of severe combined immunodeficient mice. Results Orthotopic implantation with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck masses, with histopathologic features of a high-grade neoplasm (anaplasia, necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal invasion, lymph node and distant metastases) and immunoprofile of follicular thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8, and for cytokeratins. Conclusions Here we describe a novel orthotopic thyroid carcinoma model using 8505c cells. This model can prove to be a reliable and useful tool to investigate in vivo biological mechanisms determining thyroid cancer aggressiveness, and to test novel therapeutics for the treatment of refractory or advanced thyroid cancers. PMID:19772429

  16. Societal reintegration following cadaveric orthotopic liver transplantation

    PubMed Central

    Kelly, Ryan; Hurton, Scott; Ayloo, Subhashini; Cwinn, Mathew; De Coutere-Bosse, Sarah

    2016-01-01

    Background Studies on patients’ societal reintegration following orthotopic liver transplantation (OLT) are scarce. Methods Between September 2006 and January 2008, all adults who were alive after 3 years post OLT were included in this prospective cohort study. Validated questionnaires were administered to all candidates with the primary aim of investigating the rate of their social re-integration following OLT and potential barriers they might have encountered. Results Among 157 eligible patients 110 (70%) participated. Mean participants’ age was 57 years (SD 11.4) and 43% were females. Prior to OLT, 75% of patients were married and 6% were divorced. Following OLT there was no significant difference in marital status. Employment rate fell from 72% to 30% post-OLT. Patients who had been employed in either low-skill or advanced-skill jobs were less likely to return to work. After OLT, personal income fell an average of 4,363 Canadian dollars (CAN$) (SD 20,733) (P=0.03) but the majority of recipients (80%) reported high levels of satisfaction for their role in society. Conclusions Although patients’ satisfaction post-OLT is high, employment status is likely to be negatively affected for individuals who are not self-employed. Strategies to assist recipients in returning to their pre-OLT jobs should be developed to improve patients’ economical status and societal ability to recoup resources committed for OLT. PMID:27275465

  17. Ankle replacement

    MedlinePlus

    Ankle arthroplasty - total; Total ankle arthroplasty; Endoprosthetic ankle replacement; Ankle surgery ... Ankle replacement surgery is most often done while you are under general anesthesia. This means you will ...

  18. Venous outflow obstruction and portopulmonary hypertension after orthotopic liver transplantation

    PubMed Central

    Aguirre-Avalos, Guadalupe; Covarrubias-Velasco, Marco Antonio; Rojas-Sánchez, Antonio Gerardo

    2013-01-01

    Patient: Female, 54 Final Diagnosis: Suprahepatic inferior vena cava anastomosis stricture Symptoms: Ascites • fatigue • lower limb edema • hepatomegaly Medication: — Clinical Procedure: — Specialty: Transplantology • Critical Care Medicine Objective: Unusual clinical course Background: Suprahepatic inferior vena cava anastomosis stricture is an unusual vascular complication after orthotopic liver transplantation with the “piggyback” technique. Clinical manifestations are dependent upon the severity of the stenosis. Portopulmonary hypertension after orthotopic liver transplantation is a complication that carries high mortality due to cardiopulmonary dysfunction. The pathogenesis of pulmonary vascular disorders after orthotopic liver transplantation remains uncertain. Case Report: We report a case of acute right heart pressure overload after surgical correction of the suprahepatic inferior vena cava anastomotic stricture in a 54-year-old woman who had preexisting pulmonary arterial hypertension associated with portal hypertension after orthotopic liver transplantation. Twenty months posttransplantation, she developed fatigue and progressive ascites. On admission, the patient had hepatomegaly, ascites, and lower limb edema. Symptoms in the patient developed gradually over time. Conclusions: Recurrent portal hypertension by vascular complications is a cause of pulmonary arterial hypertension after orthotopic liver transplantation. Clinical manifestations of suprahepatic inferior vena cava anastomotic stenosis are dependent upon their severity. Sildenafil is an effective drug for treatment of pulmonary arterial hyper-tension after portal hypertension by vascular complications. PMID:24046802

  19. Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

    PubMed Central

    Sjöqvist, Sebastian; Jungebluth, Philipp; Ling Lim, Mei; Haag, Johannes C.; Gustafsson, Ylva; Lemon, Greg; Baiguera, Silvia; Angel Burguillos, Miguel; Del Gaudio, Costantino; Rodríguez, Antonio Beltrán; Sotnichenko, Alexander; Kublickiene, Karolina; Ullman, Henrik; Kielstein, Heike; Damberg, Peter; Bianco, Alessandra; Heuchel, Rainer; Zhao, Ying; Ribatti, Domenico; Ibarra, Cristián; Joseph, Bertrand; Taylor, Doris A.; Macchiarini, Paolo

    2014-01-01

    A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi. PMID:24736316

  20. Scedosporium apiosermum infection of the “Native” valve: Fungal endocarditis in an orthotopic heart transplant recipient

    PubMed Central

    Clement, Meredith E.; Maziarz, Eileen K.; Schroder, Jacob N.; Patel, Chetan B.; Perfect, John R.

    2015-01-01

    Scedosporium apiospermum is an increasingly appreciated pathogen in immunosuppressed patients. We present a case of S. apiospermum endocarditis in a 70-year-old male who had undergone orthotopic heart transplant. Echocardiogram demonstrated a 1.4 cm tricuspid valve vegetation. He underwent valve replacement, complicated by fatal massive post-operative haemorrhage. Valve cultures grew S. apiospermum. To our knowledge, our case is the first reported instance of endocarditis caused by S. apiospermum in a recipient of a cardiac transplant. PMID:26288748

  1. Hip Replacement

    MedlinePlus

    ... replacement is an operation in which a damaged hip joint is removed and replaced with an artificial joint. ... are many medical conditions that can damage the hip joint. (Watch the video to learn about what goes ...

  2. Hip Replacement

    MedlinePlus

    ... surgeon removes damaged cartilage and bone from your hip joint and replaces them with new, man-made parts. A hip replacement can Relieve pain Help your hip joint work better Improve walking and other movements The ...

  3. Shoulder replacement

    MedlinePlus

    ... the opening at the end of the shoulder blade, called the socket. This type of joint allows ... head. The socket part (glenoid) of your shoulder blade will be replaced with a smooth plastic shell ( ...

  4. Knee Replacement

    MedlinePlus

    ... doctor may recommend it if you have knee pain and medicine and other treatments are not helping you anymore. When you have a total knee replacement, the surgeon removes damaged cartilage and bone ...

  5. Outcome of orthotopic liver transplantation in patients with haemophilia

    PubMed Central

    Gordon, F; Mistry, P; Sabin, C; Lee, C

    1998-01-01

    Background—Many patients with haemophilia have developed cirrhosis or hepatocellular carcinoma due to transfusion acquired chronic viral hepatitis. 
Aims—To assess the long term outcome of all haemophilic patients reported to have undergone orthotopic liver transplantation. 
Methods—Transplant centres of patients identified by medical database search were contacted and survival data assessed by Kaplan-Meier analysis. 
Results—Twenty six haemophilic men (median age 46 years, range 5-63 years) underwent orthotopic liver transplantation in 16centres between 1982 and 1996. Indications for transplantation were hepatitis C cirrhosis (69%), hepatitis B with or without C cirrhosis (15%), viral hepatitis related hepatocellular carcinoma (12%), and biliary atresia (4%). Six patients (23%) were infected with human immunodeficiency virus (HIV). Postoperatively, the median time to normal clotting factor levels was 24 hours (range 0-48 hours) and exogenous clotting factors were stopped at a median of 24 hours (range 0-480 hours). Four patients (15%) had bleeding complications. The one and three year survival of HIV positive recipients (67% and 23%) was significantly poorer (p=0.0003) than that of HIV negative recipients (90% and 83%). Coagulopathy was cured in all patients surviving more than 12 days post-transplant. Six of the 20 patients (30%) with hepatitis C cirrhosis pretransplant had evidence of disease recurrence at a mean of nine months post-transplant. 
Conclusions—Hepatitis C cirrhosis is the most common indication for orthotopic liver transplantation in patients with haemophilia. Transplantation results in long term cure of haemophilia but may be complicated by the effects of HIV infection or recurrent viral hepatitis. 

 Keywords: liver transplantation; haemophilia; hepatitis C; cirrhosis; HIV PMID:9659174

  6. Orthotopic non-metastatic and metastatic oral cancer mouse models.

    PubMed

    Bais, Manish V; Kukuruzinska, Maria; Trackman, Philip C

    2015-05-01

    Oral cancer is characterized by high morbidity and mortality with a predisposition to metastasize to different tissues, including lung, liver, and bone. Despite progress in the understanding of mutational profiles and deregulated pathways in oral cancer, patient survival has not significantly improved over the past decades. Therefore, there is a need to establish in vivo models that recapitulate human oral cancer metastasis to evaluate therapeutic potential of novel drugs. Here we report orthotopic tongue cancer nude mouse models to study oral cancer growth and metastasis using human metastatic (UMSCC2) and non-metastatic (CAL27) cell lines, respectively. Transduction of these cell lines with lentivirus expressing red fluorescent protein (DsRed) followed by injection into tongues of immunodeficient mice generated orthotopic tongue tumors that could be monitored for growth and metastasis by fluorescence measurement with an in vivo Imaging System (IVIS 200). The growth rates of CAL27-DsRed induced tumors were higher than UMSCC2-DsRed tumors after day 15, while UMSCC2-DsRed tumors revealed metastasis beginning on day 21. Importantly, UMSCC2 tumors metastasized to a number of tissues including the submandibular gland, lung, kidney, liver, and bone. Further, immunohistochemical analyses of tongue tumors induced by CAL27 and UMSCC2 cells revealed elevated expression of components of protumorigenic pathways deregulated in human cancers, including Cyclin D1, PCNA, Ki-67, LSD1, LOXL2, MT-MMP1, DPAGT1, E-cadherin, OCT4A, and H3K4me1/2. These orthotopic mouse models are likely to be useful tools for gaining insights into the activity and mechanisms of novel oral cancer drug candidates. PMID:25682387

  7. Multimodal Imaging of Orthotopic Mouse Model of Endometrial Carcinoma

    PubMed Central

    Haldorsen, Ingfrid S.; Brekke, Njål; Kopperud, Reidun; Visser, Nicole C.; Rygh, Cecilie B.; Pavlin, Tina; Salvesen, Helga B.; McCormack, Emmet; Krakstad, Camilla

    2015-01-01

    Background Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy. Methods After orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography–computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing 18F-fluorodeoxyglocose (18F-FDG) or 18F- fluorothymidine (18F-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer. Results Increased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUVmean) in 18F-FDG and 18F-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. 18F-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue. Conclusions We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, 18F-FDG and 18F-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models. PMID:26252891

  8. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland.

    PubMed

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID:27413274

  9. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland

    PubMed Central

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID:27413274

  10. Treatment Experience of Severe Abdominal Infection after Orthotopic Liver Transplantation

    PubMed Central

    Wang, Y-G; Wu, J-S; Jiang, B; Wang, J-H; Liu, C-P; Peng, C; Tian, B-Z

    2015-01-01

    ABSTRACT This study aims to investigate the causes and treatment experience of severe abdominal infection after orthotopic liver transplantation. Clinical data were retrospectively analysed in perioperative severe abdominal infection of 186 orthotopic liver transplantation cases from March 2004 to November 2011. Among the 186 patients, 16 cases had severe abdominal infection: five cases had bile duct anastomotic leakage-inducing massive hydrops and infection under liver interstice, 10 cases had extensive bleeding of surgical wound leading to massive haematocele and infection around the liver, and one case had postoperative lower oesophageal fistula leakage causing massive hydrops and infection under the left diaphragm. After definite diagnosis, 12 cases underwent surgery within three days, with no death. Among the four cases that underwent surgery three days after diagnosis, one case died of multiple-organ failure five days after abdominal cavity exploration, which was performed 21 days after liver transplantation. Severe abdominal infections after liver transplantation were the most common causes of death in perioperative liver transplantation. Comprehensive treatment with efficacious antibiotics, multiple-organ support, controlled surgical removal of the lesion, and adequate drainage establishment was the key to the entire treatment. PMID:26426173

  11. A Novel Bioluminescence Orthotopic Mouse Model for Advanced Lung Cancer

    PubMed Central

    Li, Bo; Torossian, Artour; Li, Wenyan; Schleicher, Stephen; Niu, Kathy; Giacalone, Nicholas J.; Kim, Sung June; Chen, Heidi; Gonzalez, Adriana; Moretti, Luigi; Lu, Bo

    2011-01-01

    Lung cancer is the leading cause of cancer-related death in the United States despite recent advances in our understanding of this challenging disease. An animal model for high-throughput screening of therapeutic agents for advanced lung cancer could help promote the development of more successful treatment interventions. To develop our orthotopic lung cancer model, luciferase-expressing A549 cancer cells were injected into the mediastinum of athymic nude mice. To determine whether the model would allow easy monitoring of response to therapeutic interventions, tumors were treated with 30 mg/kg Paclitaxel or were irradiated with 5 fractions of 2 Gy, and tumor burden was monitored using bioluminescence imaging. Evidence of radiation-induced lung injury was assessed using immunohistochemical staining for phospho-Smad2/3 and cleaved caspase-3. We found that tumor implantation recapitulated advanced human lung cancer as evidenced by tumor establishment and proliferation within the mediastinum. The tumor responded to Paclitaxel or radiation as shown by decreased tumor bioluminescence and improved overall survival. Immunohistochemistry revealed increased phospho-Smad2/3 and cleaved caspase-3 in irradiated lungs, consistent with radiation-induced lung injury. This orthotopic lung cancer model may help provide a method to assess therapeutic interventions in a preclinical setting that recapitulates locally advanced lung cancer. PMID:21663394

  12. Multimodality imaging in an orthotopic mammary window chamber model

    NASA Astrophysics Data System (ADS)

    Schafer, Rachel; Leung, Hui Min; Gmitro, Arthur F.

    2013-02-01

    Window chamber models have been utilized for many years to investigate cancer development and the tumor microenvironment. Orthotopic mammary window chamber model have been developed for detailed study of breast cancer. Orthotopic window chamber models, due to the native environment, support more realistic growth and tumor behavior than ectopic models. The work by other groups thus far utilizing mammary window chamber models has focused solely on optical imaging techniques, limited to probing the first millimeter or less of tissue. These techniques do not take full advantage of the unrestricted, three-dimensional tumor growth the model supports. We have developed a custom plastic structure compatible with multimodality imaging. We present in this work the implementation of our custom window chamber in a mouse model and the successful imaging of the window chamber cancer model with MRI, nuclear imaging, and optical techniques. MRI provides a full three-dimensional view of the tumor growth and allows for additional, potentially clinically translatable, approaches to be utilized in investigating the cancer microenvironment. Nuclear imaging is accomplished using the Beta Imager, which is a novel approach to nuclear imaging of window chambers. The Beta Imager detects photons after the interaction of a single positron with a scintillator, instead of the coincidence detection of annihilation gamma ray pairs. We utilized the radioisotope glucose analog, 2-deoxy-2- (18F)fluoro-D-glucose or FDG, with the Beta Imager to obtain information on the glycolytic metabolism of the tumor and surrounding region.

  13. Orthotopic liver transplantation for giant liver haemangioma: A case report

    PubMed Central

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-01-01

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient’s renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient’s lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network “Eurotransplant”. The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  14. Orthotopic liver transplantation for giant liver haemangioma: A case report.

    PubMed

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-12-24

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  15. Development and characterization of a human orthotopic neuroblastoma xenograft

    PubMed Central

    Stewart, Elizabeth; Shelat, Anang; Bradley, Cori; Chen, Xiang; Federico, Sara; Thiagarajan, Suresh; Shirinifard, Abbas; Bahrami, Armita; Pappo, Alberto; Qu, Chunxu; Finkelstein, David; Sablauer, Andras; Dyer, Michael A.

    2016-01-01

    Neuroblastoma is a pediatric cancer of the developing sympathoadrenal lineage. The tumors are known to develop from the adrenal gland or paraspinal ganglia and have molecular and cellular features of sympathetic neurons such as dense core vesicles and catecholamine production. Here we present the detailed molecular, cellular, genetic and epigenetic characterization of an orthotopic xenograft derived from a high-risk stage 4 neuroblastoma patient. Overall, the xenografted tumor retained the high risk features of the primary tumor and showed aggressive growth and metastasis in the mouse. Also, the genome was preserved with no additional copy number variations, structural variations or aneuploidy. There were 13 missense mutations identified in the xenograft that were not present in the patient’s primary tumor and there were no new nonsense mutations. None of the missense mutations acquired in the xenograft were in known cancer genes. We also demonstrate the feasibility of using the orthotopic neuroblastoma xenograft to test standard of care chemotherapy and molecular targeted therapeutics. Finally, we optimized a new approach to produce primary cultures of the neuroblastoma xenografts for high-throughput drug screening which can be used to test new combinations of therapeutic agents for neuroblastoma. PMID:25863122

  16. Shoulder replacement - discharge

    MedlinePlus

    Total shoulder arthroplasty - discharge; Endoprosthetic shoulder replacement - discharge; Partial shoulder replacement - discharge; Partial shoulder arthroplasty - discharge; Replacement - shoulder - discharge; ...

  17. Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

    PubMed Central

    Bermueller, Christian; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

    2013-01-01

    Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair. PMID:23621795

  18. Tissue Engineered Scaffolds for an Effective Healing and Regeneration: Reviewing Orthotopic Studies

    PubMed Central

    2014-01-01

    It is commonly stated that tissue engineering is the most promising approach to treat or replace failing tissues/organs. For this aim, a specific strategy should be planned including proper selection of biomaterials, fabrication techniques, cell lines, and signaling cues. A great effort has been pursued to develop suitable scaffolds for the restoration of a variety of tissues and a huge number of protocols ranging from in vitro to in vivo studies, the latter further differentiating into several procedures depending on the type of implantation (i.e., subcutaneous or orthotopic) and the model adopted (i.e., animal or human), have been developed. All together, the published reports demonstrate that the proposed tissue engineering approaches spread toward multiple directions. The critical review of this scenario might suggest, at the same time, that a limited number of studies gave a real improvement to the field, especially referring to in vivo investigations. In this regard, the present paper aims to review the results of in vivo tissue engineering experimentations, focusing on the role of the scaffold and its specificity with respect to the tissue to be regenerated, in order to verify whether an extracellular matrix-like device, as usually stated, could promote an expected positive outcome. PMID:25250319

  19. Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique.

    PubMed

    Yu, Zhe; Sun, Honghui; Fan, Qingyu; Long, Hua; Yang, Tongtao; Ma, Bao'an

    2009-05-01

    In experimental musculoskeletal oncology, there remains a need for animal models that can be used to assess the efficacy of new and innovative treatment methodologies for bone tumors. Rat plays a very important role in the bone field especially in the evaluation of metabolic bone diseases. The objective of this study was to develop a rat osteosarcoma model for evaluation of new surgical and molecular methods of treatment for extremity sarcoma. One hundred male SD rats weighing 125.45+/-8.19 g were divided into 5 groups and anesthetized intraperitoneally with 10% chloral hydrate. Orthotopic implantation models of rat osteosarcoma were performed by injecting directly into the SD rat femur with a needle for inoculation with SD tumor cells. In the first step of the experiment, 2x10(5) to 1x10(6) UMR106 cells in 50 microl were injected intraosseously into median or distal part of the femoral shaft and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from ultrasound with findings from necropsia and determining time of survival. In the third stage, the orthotopically implanted tumors and lung nodules were resected entirely, sectioned, and then counter stained with hematoxylin and eosin for histopathologic evaluation. The tumor take rate was 100% for implants with 8x10(5) tumor cells or more, which was much less than the amount required for subcutaneous implantation, with a high lung metastasis rate of 93.0%. Ultrasound and necropsia findings matched closely (r=0.942; p<0.01), which demonstrated that Doppler ultrasonography is a convenient and reliable technique for measuring cancer at any stage. Tumor growth curve showed that orthotopically implanted tumors expanded vigorously with time-lapse, especially in the first 3 weeks. The median time of survival was 38 days and surgical mortality was 0%. The UMR106 cell line has strong carcinogenic capability and high lung metastasis frequency. The present rat

  20. Molecular replacement.

    PubMed

    Toth, Eric A

    2007-01-01

    As more protein structures are solved, the likelihood that current structural investigations will involve proteins for which there exists no homologous structure continually decreases. The extraction of phase information from diffraction experiments is one of several great barriers that crystallographers must overcome on the path to structure solution. One means to overcome this obstacle, the technique of molecular replacement, uses the structural similarity between proteins with similar sequences to give a good first estimate of the phases for the diffraction data of the protein of interest. The programs that execute this technique currently come in many flavors, from traditional Patterson-based methods, to stochastic searches in greater than three dimensions, to maximum likelihood-enhanced molecular replacement, each possessing unique advantages that can shake loose a recalcitrant solution. As crystallographers aim to solve larger macromolecular complexes that more faithfully depict the actors in cellular events, having existing phase information for parts of those biological machines will reinforce the technological advancements in data collection and structure solution that have already produced mammoth structures like the ribosome, yielding an ever-clearer picture of the inner workings of biology. PMID:17172763

  1. Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer

    PubMed Central

    Rajput, Ashwani; Agarwal, Ekta; Leiphrakpam, Premila; Brattain, Michael G.

    2013-01-01

    Metastases are largely responsible for cancer deaths in solid tumors due to the lack of effective therapies against disseminated disease, and there is an urgent need to fill this gap. This study demonstrates an orthotopic colorectal cancer (CRC) mouse model system to develop spontaneous metastasis in vivo and compare its reproducibility against human CRC. IGF1R-dependent GEO human CRC cells were used to study metastatic colonization using orthotopic transplantation procedures and demonstrated robust liver metastasis. Cell proliferation assays were performed both in the orthotopic primary colon and liver metastatic tumors, and human CRC patient's specimen and similar patterns in H&E and Ki67 staining were observed between the orthotopically generated primary and liver metastatic tumors and human CRC specimens. Microarray analysis was performed to generate gene signatures, compared with deposited human CRC gene expression data sets, analyzed by Oncomine, and revealed similarity in gene signatures with increased aggressive markers expression associated with CRC in orthotopically generated liver metastasis. Thus, we have developed an orthotopic mouse model that reproduces human CRC metastasis. This model system can be effective in developing new therapeutic strategies against disseminated disease and could be implemented for identifying genes that regulate the development and/or maintenance of established metastasis.

  2. Regeneration and orthotopic transplantation of a bioartificial lung.

    PubMed

    Ott, Harald C; Clippinger, Ben; Conrad, Claudius; Schuetz, Christian; Pomerantseva, Irina; Ikonomou, Laertis; Kotton, Darrell; Vacanti, Joseph P

    2010-08-01

    About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient's circulation and ventilated by means of the recipient's airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation. PMID:20628374

  3. A New Rat Model for Orthotopic Abdominal Wall Allotransplantation

    PubMed Central

    Lao, William W.; Wang, Yen-Ling; Ramirez, Alejandro E.; Cheng, Hui-Yun

    2014-01-01

    Background: Abdominal wall, one of the most commonly transplanted composite tissues, is less researched and lacking animal models. Its clinical necessities were emphasized in multiple case series to reconstruct large abdominal defects. Previous animal models have only studied components of the abdominal wall transplant. We describe findings from a new model that more likely reflect clinical transplantation. Methods: Full-thickness hemiabdominal wall flap was procured from Brown Norway (BN) rats and transplanted to an orthotopic defect on Lewis rats. Three groups were studied: group 1: Lewis to Lewis syngeneic; group 2: BN to Lewis control; and group 3: BN to Lewis with postoperative cyclosporine. Vascular imaging and cross vessel section were performed along with full-thickness abdominal wall. Immune cell profiling with flow cytometry at different time points was studied in all groups. Results: Syngeneic group had no rejection. Control group consistently showed rejection around postoperative day 6. With cyclosporine treatment, however, transplant and recipient tissue integration was observed. Flow cytometry revealed that innate immunity is responsible for the initial inflammatory events following abdominal wall engraftment. Adaptive immunity cells, specifically interferon-γ-producing T helper (Th) 1 and interleukin-17-producing Th17 cells, dramatically and positively correlate with rejection progression of abdominal wall transplants. Conclusions: Technical, histological, and immunological aspects of a new rat model are described. These results give clues to what occurs in human abdominal wall transplantation. In addition, Th1, a proinflammatory cell, was found to be a potential biomarker for allograft rejection. PMID:25289329

  4. Hepatitis C Recurrence after Orthotopic Liver Transplantation: Mechanisms and Management

    PubMed Central

    Kakati, Bobby; Seetharam, Anil

    2014-01-01

    Chronic Hepatitis C (HCV) infection is the leading indication for orthotopic liver transplantation and recurrence is nearly universal. Chronic HCV infection is frequently established through evasion of the innate immune system. Priming of adaptive immune responses modulate the severity and rate of fibrosis progression. Those with demonstrable viremia entering the transplant period uniformly suffer recurrence post-transplant. Progression to cirrhosis is accelerated post-transplant secondary to systemic immunosuppression. In addition, a number of factors, including donor, host, and viral characteristics, influence severity and rate of fibrosis progression. Interferon-based therapy, the previous standard of care, in those with advanced cirrhosis or post-transplant has been limited by a number of issues. These include a relative lack of efficacy and poor tolerability with higher incidence of infection and anemia. Recently, approval of direct acting antivirals have ushered in a new era in HCV therapeutics and have applicability in these special populations. Their use immediately prior to or post-transplant is expected to improve both morbidity and mortality. PMID:26355427

  5. Utilization of Murine Colonoscopy for Orthotopic Implantation of Colorectal Cancer

    PubMed Central

    Zigmond, Ehud; Halpern, Zamir; Elinav, Eran; Brazowski, Eli; Jung, Steffen; Varol, Chen

    2011-01-01

    Background Colorectal-cancer (CRC) research has greatly benefited from the availability of small animal tumor models. Spontaneous and chemically-induced CRC models are widely used yet limited in their resemblance to human disease and are often prolonged, not accurately repetitive, and associated with inflammatory side effects. In-situ murine or human tumor implantation in the gastrointestinal tract of mice is extremely challenging, and limited by inter-animal variability and procedure-related complications and mortality. As a result, in frequent studies CRC is implanted in distal sites, most commonly the subcutaneous region, an approach that is greatly limited by the absence of normal gastrointestinal tumor milieu and has substantial effects on tumor development. Aims In this study we aimed to develop a well-tolerated repetitive tool to study CRC in small animals by adapting the murine colonoscopy system to serve as a platform for colonic sub-mucosal orthotopic implantation of human and murine CRC tumor cells. Results We report the establishment of a novel small-animal CRC model that is minimally invasive, rapid, well-tolerated, highly reproducible, and confers precise control of tumor number, location and growth rate. Moreover, we show that this model uniquely allows the side-by-side induction of distinct genetically manipulated tumors, enabling the mechanistic study of tumor interaction and cross-talk within the native intestinal microenvironment. Conclusions Employment of this new approach may represent a major technical advance for the in-vivo study of CRC. PMID:22174916

  6. Inorganic Nanovehicle Targets Tumor in an Orthotopic Breast Cancer Model

    NASA Astrophysics Data System (ADS)

    Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

    2014-03-01

    The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

  7. Inorganic Nanovehicle Targets Tumor in an Orthotopic Breast Cancer Model

    PubMed Central

    Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

    2014-01-01

    The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis. PMID:24651154

  8. Inorganic nanovehicle targets tumor in an orthotopic breast cancer model.

    PubMed

    Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

    2014-01-01

    The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis. PMID:24651154

  9. An Orthotopic Bladder Cancer Model for Gene Delivery Studies

    PubMed Central

    Kasman, Laura; Voelkel-Johnson, Christina

    2013-01-01

    Bladder cancer is the second most common cancer of the urogenital tract and novel therapeutic approaches that can reduce recurrence and progression are needed. The tumor microenvironment can significantly influence tumor development and therapy response. It is therefore often desirable to grow tumor cells in the organ from which they originated. This protocol describes an orthotopic model of bladder cancer, in which MB49 murine bladder carcinoma cells are instilled into the bladder via catheterization. Successful tumor cell implantation in this model requires disruption of the protective glycosaminoglycan layer, which can be accomplished by physical or chemical means. In our protocol the bladder is treated with trypsin prior to cell instillation. Catheterization of the bladder can also be used to deliver therapeutics once the tumors are established. This protocol describes the delivery of an adenoviral construct that expresses a luciferase reporter gene. While our protocol has been optimized for short-term studies and focuses on gene delivery, the methodology of mouse bladder catheterization has broad applications. PMID:24326612

  10. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    PubMed Central

    2013-01-01

    Background Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. Methods We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. Results TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. Conclusions We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies. PMID:23937707

  11. Sequential and simultaneous revascularization in adult orthotopic piggyback liver transplantation.

    PubMed

    Polak, Wojciech G; Miyamoto, Shungo; Nemes, Balazs A; Peeters, Paul M J G; de Jong, Koert P; Porte, Robert J; Slooff, Maarten J H

    2005-08-01

    The aim of the study was to assess whether there is a difference in outcome after sequential or simultaneous revascularization during orthotopic liver transplantation (OLT) in terms of patient and graft survival, mortality, morbidity, and liver function. The study population consisted of 102 adult patients with primary full-size piggyback OLT transplanted between January 1998 and December 2001. In 71 patients (70%) the grafts were sequentially reperfused after completion of the portal vein anastomosis and subsequent arterial reconstruction was performed (sequential reperfusion [SeqR] group). In 31 patients (30%) the graft was reperfused simultaneously via the portal vein and hepatic artery (simultaneous reperfusion [SimR] group). Patient and graft survival at 1, 3, and 6 months and at 1 year did not differ between the SeqR group and the SimR group. The red blood cell (RBC) requirements were significantly higher in the SimR group (5.5 units; range 0-20) in comparison to the SeqR group (2 units; range 0-19) (P = 0.02). Apart from a higher number of biliary anastomotic complications and abdominal bleeding complications in the SimR group in comparison to the SeqR group (13% vs. 2% and 19% vs. 6%, respectively; P = 0.06), morbidity was not different between the groups. No differences between the groups were observed regarding the incidence of primary nonfunction (PNF), intensive care unit stay, and acute rejection. This was also true for the severity of rejections. Postoperative recuperation of liver function was not different between the groups. In conclusion, no advantage of either of the 2 reperfusion protocols could be observed in this analysis, especially with respect to the incidence of ischemic type biliary lesions (ITBL). PMID:16035059

  12. An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis.

    PubMed

    Paschall, Amy V; Liu, Kebin

    2016-01-01

    Metastasis is the primary cause of mortality of breast cancer patients. The mechanism underlying cancer cell metastasis, including breast cancer metastasis, is largely unknown and is a focus in cancer research. Various breast cancer spontaneous metastasis mouse models have been established. Here, we report a simplified procedure to establish orthotopic transplanted breast cancer primary tumor and resultant spontaneous metastasis that mimic human breast cancer metastasis. Combined with the bioluminescence live tumor imaging, this mouse model allows tumor growth and progression kinetics to be monitored and quantified. In this model, a low dose (1 x 10(4) cells) of 4T1-Luc breast cancer cells was injected into BALB/c mouse mammary fat pad using a tuberculin syringe. Mice were injected with luciferin and imaged at various time points using a bioluminescent imaging system. When the primary tumors grew to the size limit as in the IACUC-approved protocol (approximately 30 days), mice were anesthetized under constant flow of 2% isoflurane and oxygen. The tumor area was sterilized with 70% ethanol. The mouse skin around the tumor was excised to expose the tumor which was removed with a pair of sterile scissors. Removal of the primary tumor extends the survival of the 4T-1 tumor-bearing mice for one month. The mice were then repeatedly imaged for metastatic tumor spreading to distant organs. Therapeutic agents can be administered to suppress tumor metastasis at this point. This model is simple and yet sensitive in quantifying breast cancer cell growth in the primary site and progression kinetics to distant organs, and thus is an excellent model for studying breast cancer growth and progression, and for testing anti-metastasis therapeutic and immunotherapeutic agents in vivo. PMID:27584043

  13. Genetically engineered pre-microRNA-34a prodrug suppresses orthotopic osteosarcoma xenograft tumor growth via the induction of apoptosis and cell cycle arrest

    PubMed Central

    Zhao, Yong; Tu, Mei-Juan; Wang, Wei-Peng; Qiu, Jing-Xin; Yu, Ai-Xi; Yu, Ai-Ming

    2016-01-01

    Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of human 143B and MG-63 cells in a dose dependent manner and to much greater degrees than controls, which was attributed to induction of apoptosis and G2 cell cycle arrest. Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6. Furthermore, intravenous administration of in vivo-jetPEI formulated miR-34a prodrug significantly reduced OS tumor growth in orthotopic xenograft mouse models. In addition, mouse blood chemistry profiles indicated that therapeutic doses of bioengineered miR-34a prodrug were well tolerated in these animals. The results demonstrated that bioengineered miR-34a prodrug was effective to control OS tumor growth which involved the induction of apoptosis and cell cycle arrest, supporting the development of bioengineered RNAs as a novel class of large molecule therapeutic agents. PMID:27216562

  14. Current status of auxiliary partial orthotopic liver transplantation for acute liver failure.

    PubMed

    Rela, Mohamed; Kaliamoorthy, Ilankumaran; Reddy, Mettu Srinivas

    2016-09-01

    Auxiliary partial orthotopic liver transplantation (APOLT) is a technique of liver transplantation (LT) where a partial liver graft is implanted in an orthotopic position after leaving behind a part of the native liver. APOLT was previously considered technically challenging with results inferior to orthotopic liver transplantation. Results of this procedure have continued to improve with improving surgical techniques and a better understanding of the natural history of acute liver failure (ALF) and liver regeneration. The procedure is being increasingly accepted as a valid treatment option for ALF-especially in children. This article reviews the historical background to this operation, advances in the technique, and its current place in the management of ALF. Liver Transplantation 22 1265-1274 2016 AASLD. PMID:27357489

  15. Hip joint replacement

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002975.htm Hip joint replacement To use the sharing features on this page, please enable JavaScript. Hip joint replacement is surgery to replace all or part ...

  16. Knee joint replacement

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002974.htm Knee joint replacement To use the sharing features on this page, please enable JavaScript. Knee joint replacement is a surgery to replace a knee ...

  17. Diagnosis of rare association of orthotopic multicystic dysplasia with crossed fused renal ectopia.

    PubMed

    Tang, Linnan; Koshy, June; Spevak, Melissa R; Benson, Jane E; Bosemani, Thangamadhan

    2014-01-01

    Orthotopic multicystic dysplastic kidney with crossed fused ectopia is a rare congenital anomaly. This congenital anomaly may give an appearance of a solitary kidney morphology during the initial imaging evaluation. A solitary kidney should be carefully evaluated for the presence of duplication, horseshoe configuration, or crossed renal ectopy. Vesicoureteral reflux is a common finding associated with a multicystic dysplastic kidney. We present an infant with an orthotopic multicystic dysplastic kidney and an inferiorly placed crossed fused ectopic kidney. The presence of a complex congenital anomaly may warrant further evaluation with cross-sectional imaging to depict the anatomy and structure. PMID:24839577

  18. Diagnosis of Rare Association of Orthotopic Multicystic Dysplasia with Crossed Fused Renal Ectopia

    PubMed Central

    Tang, Linnan; Koshy, June; Spevak, Melissa R.; Benson, Jane E.; Bosemani, Thangamadhan

    2014-01-01

    Orthotopic multicystic dysplastic kidney with crossed fused ectopia is a rare congenital anomaly. This congenital anomaly may give an appearance of a solitary kidney morphology during the initial imaging evaluation. A solitary kidney should be carefully evaluated for the presence of duplication, horseshoe configuration, or crossed renal ectopy. Vesicoureteral reflux is a common finding associated with a multicystic dysplastic kidney. We present an infant with an orthotopic multicystic dysplastic kidney and an inferiorly placed crossed fused ectopic kidney. The presence of a complex congenital anomaly may warrant further evaluation with cross-sectional imaging to depict the anatomy and structure. PMID:24839577

  19. Severe obstruction of the left main coronary artery by mycotic aortic psuedoaneurysm following orthotopic heart transplantation.

    PubMed

    Kamineni, Raghunandan; Lui, Charles Y; Copeland, Jack G

    2004-04-01

    Mycotic aneurysm of the ascending aorta is a rare complication following orthotopic heart transplantation. This article describes a case of mycotic pseudoaneurysm caused by Candida albicans that developed shortly after orthotopic heart transplantation. The pseudoaneurysm compressed the left main coronary artery, which led to the development of congestive heart failure symptoms mimicking sub-acute transplant rejection. The heart failure signs and symptoms resolved completely with resection of the aneurysm. This case reiterates that early diagnosis and complete resection of the aneurysm is associated with good prognosis. PMID:15063413

  20. A case report of a completely vanished liver graft after auxiliary partial orthotopic liver transplantation

    PubMed Central

    Teomete, U; Dandin, O; Tekin, A; Sabuncuoglu, M Z; Chapman, J

    2015-01-01

    Background Auxiliary partial orthotopic liver transplantation is an alternative technique for the treatment of patients with fulminant hepatic failure and metabolic liver disease. It provides temporary support of liver function until sufficient regeneration of the native liver. Pediatric patients have a long life expectancy and are best candidates to benefit from the interruption of antirejection treatment. Description of case A 4-year-old boy underwent auxiliary partial orthotopic liver transplantation for fulminant hepatic failure using a cadaveric left lateral segment of liver. One year after auxiliary partial orthotopic liver transplantation, the patient’s native liver was determined to be completely normal and he was doing well. The patient was then gradually weaned from the immunosuppression over the course of one year. The graft was undetectable on follow-up computerized tomography performed before complete cessation of immunosuppression, leading to the diagnosis of “vanishing graft syndrome”. Conclusion Graft atrophy commonly occurs after auxiliary partial orthotopic liver transplantation due to cessation of antirejection therapy. But to our knowledge, complete graft disappearance is a rare occurrence reported in the English literature. Timing for withdrawal of the immunosuppression is an important decision to be made in this technique. Hippokratia 2015; 19 (3): 274-277.

  1. Endoscopy-guided orthotopic implantation of colorectal cancer cells results in metastatic colorectal cancer in mice.

    PubMed

    Bettenworth, Dominik; Mücke, Marcus M; Schwegmann, Katrin; Faust, Andreas; Poremba, Christopher; Schäfers, Michael; Domagk, Dirk; Lenz, Philipp

    2016-08-01

    Advanced stage colorectal cancer (CRC) is still associated with limited prognosis. For preclinical evaluation of novel therapeutic approaches, murine models with orthotopic tumor growth and distant metastases are required. However, these models usually require surgical procedures possibly influencing tumor immunogenicity and development. The aim of this study was to establish a minimal-invasive endoscopy-based murine orthotopic model of metastatic CRC. During colonoscopy of CD-1 nude and non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, implantation of Caco-2 and HT-29 CRC cells was performed subcutaneously (s.c.) or orthotopic into the colonic submucosa. White light endoscopy (WLE) and fluorescence endoscopy (FE) were applied for tumor detection in vivo. Ex vivo, resected tumors were examined by fluorescence reflectance imaging (FRI), histology, gelatin zymography and immunohistochemistry. In CD-1 nude mice, marked tumor growth was observed within 14 days after subcutaneous implantation while submucosal implantation failed to induce CRC after 17 weeks. In contrast, in NOD/SCID mice submucosal injection of HT-29 cells resulted in pronounced tumor growth 12 days post injectionem. Subsequently, rapid tumor expansion occurred, occupying the entire colonic circumference. Importantly, post mortem histological analyses confirmed liver metastases in 28.6 % and peritoneal metastases in 14.3 % of all mice. FRI and gelatin zymography did not detect a significantly increased matrix metalloproteinases (MMPs) expression in s.c. implanted tumors while MMP-tracer uptake was significantly enhanced in orthotopic implanted tumors. Neither s.c. nor orthotopic Caco-2 cell implantation resulted in tumor development. We successfully established an endoscopy-based model of metastatic CRC in immunodeficient mice. PMID:27146063

  2. Elbow replacement - discharge

    MedlinePlus

    Total elbow arthroplasty - discharge; Endoprosthetic elbow replacement - discharge ... You had surgery to replace your elbow joint with artificial joint parts (prosthetics). The surgeon made a cut (incision) in the back of your upper or lower arm and ...

  3. Partial knee replacement - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100225.htm Partial knee replacement - series To use the sharing features on ... A.M. Editorial team. Related MedlinePlus Health Topics Knee Replacement A.D.A.M., Inc. is accredited ...

  4. Nicotine replacement therapy

    MedlinePlus

    ... If wearing the patch at night causes odd dreams, try sleeping without the patch. People who smoke ... cessation - nicotine replacement; Tobacco - nicotine replacement therapy References American Cancer Society. Guide to quitting smoking. Last revised ...

  5. Partial knee replacement

    MedlinePlus

    Most people recover quickly and have much less pain than they did before surgery. People who have a partial knee replacement recover faster than those who have a total knee replacement. Many people are able to walk ...

  6. Orthotopic mouse liver transplantation to study liver biology and allograft tolerance.

    PubMed

    Yokota, Shinichiro; Ueki, Shinya; Ono, Yoshihiro; Kasahara, Naoya; Pérez-Gutiérrez, Angélica; Kimura, Shoko; Yoshida, Osamu; Murase, Noriko; Yasuda, Yoshikazu; Geller, David A; Thomson, Angus W

    2016-07-01

    Orthotopic liver transplantation in the mouse is a powerful research tool that has led to important mechanistic insights into the regulation of hepatic injury, liver immunopathology, and transplant tolerance. However, it is a technically demanding surgical procedure. Setup of the orthotopic liver transplantation model comprises three main stages: surgery on the donor mouse; back-table preparation of the liver graft; and transplant of the liver into the recipient mouse. In this protocol, we describe our procedure in stepwise detail to allow efficient completion of both the donor and recipient operations. The protocol can result in consistently high technical success rates when performed by personnel experienced in the protocol. The technique can be completed in ∼2-3 h when performed by an individual who is well practiced in performing mouse transplantation in accordance with this protocol. We have achieved a perioperative survival rate close to 100%. PMID:27254462

  7. Multispectral optoacoustic and MRI coregistration for molecular imaging of orthotopic model of human glioblastoma.

    PubMed

    Attia, Amalina Binte Ebrahim; Ho, Chris Jun Hui; Chandrasekharan, Prashant; Balasundaram, Ghayathri; Tay, Hui Chien; Burton, Neal C; Chuang, Kai-Hsiang; Ntziachristos, Vasilis; Olivo, Malini

    2016-07-01

    Multi-modality imaging methods are of great importance in oncologic studies for acquiring complementary information, enhancing the efficacy in tumor detection and characterization. We hereby demonstrate a hybrid non-invasive in vivo imaging approach of utilizing magnetic resonance imaging (MRI) and Multispectral Optoacoustic Tomography (MSOT) for molecular imaging of glucose uptake in an orthotopic glioblastoma in mouse. The molecular and functional information from MSOT can be overlaid on MRI anatomy via image coregistration to provide insights into probe uptake in the brain, which is verified by ex vivo fluorescence imaging and histological validation. In vivo MSOT and MRI imaging of an orthotopic glioma mouse model injected with IRDye800-2DG. Image coregistration between MSOT and MRI enables multifaceted (anatomical, functional, molecular) information from MSOT to be overlaid on MRI anatomy images to derive tumor physiological parameters such as perfusion, haemoglobin and oxygenation. PMID:27091626

  8. Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats.

    PubMed

    Altomonte, Jennifer; Muñoz-Álvarez, Kim A; Shinozaki, Katsunori; Baumgartner, Christine; Kaissis, Georgios; Braren, Rickmer; Ebert, Oliver

    2016-01-01

    Hepatocellular carcinoma (HCC) is a disease with limited treatment options and poor prognosis. In recent years, oncolytic virotherapies have proven themselves to be potentially powerful tools to fight malignancy. Due to the unique dual blood supply in the liver, it is possible to apply therapies locally to orthotopic liver tumors, which are predominantly fed by arterial blood flow. We have previously demonstrated that hepatic arterial delivery of oncolytic viruses results in safe and efficient transduction efficiency of multifocal HCC lesions, resulting in significant prolongation of survival in immune competent rats. This procedure closely mimics the application of transarterial embolization in patients, which is the standard palliative care provided to many HCC patients. The ability to administer tumor therapies through the hepatic artery in rats allows for a highly sophisticated preclinical model for evaluating novel viral vectors under development. Here we describe the detailed protocol for microdissection of the hepatic artery for infusion of oncolytic virus vectors to treat orthotopic HCC. PMID:27167921

  9. Generation of a syngeneic orthotopic transplant model of prostate cancer metastasis.

    PubMed

    Ellis, Leigh; Lehet, Kristin; Ku, ShengYu; Azabdaftari, Gissou; Pili, Roberto

    2014-10-15

    Progression to metastatic disease is the primary cause of mortality in men with prostate cancer (PCa). Mouse models which progress with spontaneous metastasis are limited. Such models would allow for extensive studies of molecular mechanisms of metastasis, and more definite pre- clinical therapy trials. Orthotopic murine models have been described; however a limiting biology of these models is their lack of an intact immune system. Within, we describe the development of an androgen sensitive and castrate resistant tractable orthotopic murine syngeneic (immune competent) model of prostate cancer. Both models develop primary tumors which spontaneously progress to metastatic disease in lymph tissue. These models will allow for more complete mechanistic and therapeutic studies in a short time period. PMID:25485289

  10. Generation of a syngeneic orthotopic transplant model of prostate cancer metastasis

    PubMed Central

    Ellis, Leigh; Lehet, Kristin; Ku, ShengYu; Azabdaftari, Gissou; Pili, Roberto

    2014-01-01

    Progression to metastatic disease is the primary cause of mortality in men with prostate cancer (PCa). Mouse models which progress with spontaneous metastasis are limited. Such models would allow for extensive studies of molecular mechanisms of metastasis, and more definite pre- clinical therapy trials. Orthotopic murine models have been described; however a limiting biology of these models is their lack of an intact immune system. Within, we describe the development of an androgen sensitive and castrate resistant tractable orthotopic murine syngeneic (immune competent) model of prostate cancer. Both models develop primary tumors which spontaneously progress to metastatic disease in lymph tissue. These models will allow for more complete mechanistic and therapeutic studies in a short time period. PMID:25485289

  11. Postoperative imaging findings in children with auxiliary partial orthotopic liver transplant (APOLT).

    PubMed

    Ayyala, Rama S; Martinez, Mercedes; Lobritto, Steven J; Kato, Tomoaki; Ruzal-Shapiro, Carrie

    2016-07-01

    Auxiliary partial orthotopic liver transplant (APOLT) is a treatment technique for people who have acute hepatic failure secondary to fulminant hepatic failure and might ultimately recover normal liver function. This surgical procedure is complicated, involving the placement of a liver graft while maintaining viability of the remaining native portion of the liver. This method allows the native liver to recover hepatic function, therefore eliminating the need for long-term immunosuppression, as is typically needed in post-transplant settings. Postoperative imaging in these cases can be challenging given the complex anatomy, specifically the vascular anastomosis. Therefore it is important for radiologists and clinicians to be aware of the anatomy as well as the variable imaging appearances of the liver. We review the imaging findings in children who have undergone auxiliary partial orthotopic liver transplant (APOLT). PMID:26867605

  12. Role of hepatitis C virus in chronic liver disease occurring after orthotopic liver transplantation.

    PubMed Central

    Pastore, M; Willems, M; Cornu, C; Buts, J P; Reding, R; de Ville de Goyet, J; Rahier, J; Otte, J B; Yap, S H; Sokal, E M

    1995-01-01

    Paediatric orthotopic liver transplant recipients may develop chronic hepatitis after surgery. To investigate the role of hepatitis C virus in this pathology a cohort of 249 paediatric orthotopic liver transplant recipients was studied. Sixteen children (6.4%) were found to have chronic hepatitis C virus hepatitis after orthotopic liver transplantation. All but one of them had serum transaminase values which were persistently raised two to eight times the upper limit of normal. Thirteen were positive for both serology and serum hepatitis C virus RNA. Serum hepatitis C virus RNA detection occurred five to 33 months before hepatitis C virus antibodies. Liver tissue hepatitis C virus RNA and hepatitis C virus core antigen were detected in five. In one patient, tissue hepatitis C virus core antigen was detected when other tests for hepatitis C were negative. Two patients had positive human cytomegalovirus serum antibodies and RNA before transplantation. Although serum hepatitis C virus RNA was not detected after transplantation, serum enzyme immunosorbent assay and tissue core antigen were still detectable in both patients. In another child, serum hepatitis C virus RNA was positive and hepatitis C virus core antigen was found on a liver biopsy specimen but antihepatitis C virus antibodies were negative as well as liver hepatitis C virus RNA. No patient developed severe liver disease or cirrhosis during a follow up of up to 72 months. It is concluded that hepatitis C virus is a significant cause of morbidity after paediatric orthotopic liver transplantation. Diagnosis cannot rely on serological testing only. The patients remained stable on follow up, but longer prospective histological studies remain necessary to establish prognosis. PMID:7618905

  13. Immunotherapy of HPV-associated cancer: DNA/plant-derived vaccines and new orthotopic mouse models.

    PubMed

    Venuti, Aldo; Curzio, Gianfranca; Mariani, Luciano; Paolini, Francesca

    2015-10-01

    Under the optimistic assumption of high-prophylactic HPV vaccine coverage, a significant reduction of cancer incidence can only be expected after decades. Thus, immune therapeutic strategies are needed for persistently infected individuals who do not benefit from the prophylactic vaccines. However, the therapeutic strategies inducing immunity to the E6 and/or E7 oncoprotein of HPV16 are more effective for curing HPV-expressing tumours in animal models than for treating human cancers. New strategies/technologies have been developed to improve these therapeutic vaccines. Our studies focussed on preparing therapeutic vaccines with low-cost technologies by DNA preparation fused to either plant-virus or plant-toxin genes, such as saporin, and by plant-produced antigens. In particular, plant-derived antigens possess an intrinsic adjuvant activity that makes these preparations especially attractive for future development. Additionally, discrepancy in vaccine effectiveness between animals and humans may be due to non-orthotopic localization of animal models. Orthotopic transplantation leads to tumours giving a more accurate representation of the parent tumour. Since HPV can cause cancer in two main localizations, anogenital and oropharynx area, we developed two orthotopic tumour mouse models in these two sites. Both models are bioluminescent in order to follow up the tumour growth by imaging and are induced by cell injection without the need to intervene surgically. These models were utilized for immunotherapies with genetic or plant-derived therapeutic vaccines. In particular, the head/neck orthotopic model appears to be very promising for studies combining chemo-radio-immune therapy that seems to be very effective in patients. PMID:26138695

  14. Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

    PubMed Central

    ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

    2015-01-01

    Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

  15. Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model.

    PubMed

    Weir, Chris J; Hudson, Amanda L; Peters, Lyndsay; Howell, Viive M

    2015-01-01

    The enormous upsurge of interest in immune-based treatments for cancer such as vaccines and immune checkpoint inhibitors, and increased understanding of the role of the tumor microenvironment in treatment response, collectively point to the need for immune-competent orthotopic models for pre-clinical testing of these new therapies. This paper demonstrates how to establish an orthotopic immune-competent rat model of pleural malignant mesothelioma. Monitoring disease progression in orthotopic models is confounded by the internal location of the tumors. To longitudinally monitor disease progression and its effect on circulating immune cells in this and other rat models of cancer, a single tube flow cytometry assay requiring only 25 µl whole blood is described. This provides accurate quantification of seven immune parameters: total lymphocytes, monocytes and neutrophils, as well as the T-cell subsets CD4 and CD8, B-cells and Natural Killer cells. Different subsets of these parameters are useful in different circumstances and models, with the neutrophil to lymphocyte ratio having the greatest utility for monitoring disease progression in the mesothelioma model. Analyzing circulating immune cell levels using this single tube method may also assist in monitoring the response to immune-based treatments and understanding the underlying mechanisms leading to success or failure of treatment. PMID:26485154

  16. Ion replacement electrorefining

    SciTech Connect

    Willit, J.L.; Tomczuk, Z.; Miller, W.E.; Laidler, J.J.

    1994-04-01

    We are developing a two-step electrochemical process for purifying and separating metals called ion replacement electrorefining. In each step, metal cations formed by oxidation at an electrode replace other metal cations that are reduced at another elecmae. Using this approach, we have separated or purified uranium, dysprosium, and lanthanum on a laboratory scale. This paper explains the ion replacement concept and presents results of these demonstration experiments.

  17. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

    PubMed Central

    Lunt, Sarah Jane; Kalliomaki, Tuula MK; Brown, Allison; Yang, Victor X; Milosevic, Michael; Hill, Richard P

    2008-01-01

    Background High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. Methods KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Results Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown

  18. Transcatheter neoaortic valve replacement utilizing the Melody Valve in hypoplastic left heart syndrome.

    PubMed

    Martin, Mary Hunt; Gruber, Peter J; Gray, Robert G

    2015-03-01

    Percutaneous transcatheter pulmonary valve replacement with the Melody Valve is fast becoming an important adjunct in the treatment of older children and adults with failing right ventricular outflow tract conduits. Recently, the Melody Valve has also been successfully implanted in the tricuspid, mitral, and aortic positions, typically within a failing bioprosthetic valve. We present a patient who underwent Fontan palliation for hypoplastic left heart syndrome variant and subsequently developed severe neoaortic regurgitation, which was successfully treated with a transcatheter neoaortic valve replacement. To our knowledge, this is the first successful use of the Melody Valve in the neoaortic position in a patient with single-ventricle physiology. Successful relief of neoaortic valve regurgitation using replacement with a transcatheter valve may allow avoidance of additional surgery, increase functional longevity of single-ventricle palliation, and postpone the need for orthotopic heart transplantation. PMID:24619505

  19. Radiation Source Replacement Workshop

    SciTech Connect

    Griffin, Jeffrey W.; Moran, Traci L.; Bond, Leonard J.

    2010-12-01

    This report summarizes a Radiation Source Replacement Workshop in Houston Texas on October 27-28, 2010, which provided a forum for industry and researchers to exchange information and to discuss the issues relating to replacement of AmBe, and potentially other isotope sources used in well logging.

  20. Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models

    PubMed Central

    Zuo, Bingfeng; Gao, Xianjun; Zhang, Ti; Du, Zhi; Wu, Chenxuan; Yin, HaiFang

    2016-01-01

    Mouse models are commonly used for studying hepatocellular carcinoma (HCC) biology and exploring new therapeutic interventions. Currently three main modalities of HCC mouse models have been extensively employed in pre-clinical studies including chemically induced, transgenic and transplantation models. Among them, transplantation models are preferred for evaluating in vivo drug efficacy in pre-clinical settings given the short latency, uniformity in size and close resemblance to tumors in patients. However methods used for establishing orthotopic HCC transplantation mouse models are diverse and fragmentized without a comprehensive comparison. Here, we systemically evaluate four different approaches commonly used to establish HCC mice in preclinical studies, including intravenous, intrasplenic, intrahepatic inoculation of tumor cells and intrahepatic tissue implantation. Four parameters—the latency period, take rates, pathological features and metastatic rates—were evaluated side-by-side. 100% take rates were achieved in liver with intrahepatic, intrasplenic inoculation of tumor cells and intrahepatic tissue implantation. In contrast, no tumor in liver was observed with intravenous injection of tumor cells. Intrahepatic tissue implantation resulted in the shortest latency with 0.5cm (longitudinal diameter) tumors found in liver two weeks after implantation, compared to 0.1cm for intrahepatic inoculation of tumor cells. Approximately 0.1cm tumors were only visible at 4 weeks after intrasplenic inoculation. Uniform, focal and solitary tumors were formed with intrahepatic tissue implantation whereas multinodular, dispersed and non-uniform tumors produced with intrahepatic and intrasplenic inoculation of tumor cells. Notably, metastasis became visible in liver, peritoneum and mesenterium at 3 weeks post-implantation, and lung metastasis was visible after 7 weeks. T cell infiltration was evident in tumors, resembling the situation in HCC patients. Our study

  1. Metastasis in an Orthotopic Murine Model of Melanoma is Independent of RAS/RAF Mutation

    PubMed Central

    Rozenberg, Gabriela I.; Monahan, Kimberly B.; Torrice, Chad; Bear, James E.; Sharpless, Norman E.

    2010-01-01

    Melanoma is the most lethal skin tumor, in large part because of a propensity for early metastasis. Good models of this most clinically relevant feature of melanoma are lacking. Here we report the development of an in vivo model of metastasis that relies on orthotopic injection of GFP-tagged lines in immunodeficient mice, serial intravital imaging of tumor progression and quantification of distant spread by 2-photon laser scanning microscopy, immunohistochemistry and real-time PCR analysis. Using this system, we report an assessment of the in vivo growth and metastatic properties of 11 well-characterized human melanoma cell lines. A subset of lines demonstrated rapid in vivo growth with invasion of host vasculature and distant seeding of viscera in this system. The ability to form metastasis in vivo did not correlate with 3D collagen invasion in vitro. Surprisingly, similar lines in terms of molecular genetic events differed markedly in their propensity to metastasize to distant organs such as brain and lung. In particular, two lines harboring B-RAF mutation and high levels of phosphorylated ERK and AKT (pERK and pAKT) were reproducibly unable to form tumors after orthotopic injection. Likewise, two previously identified RAS/RAF wild-type “epithelial-like” lines that do not have elevated pERK, pAKT or express TWIST1 mRNA still demonstrated a pronounced ability for orthotopic growth and metastatic spread. All the metastatic cell lines in this model showed increased NEDD9 expression, but NEDD9 lentiviral overexpression did not convey a metastatic phenotype on non-metastatic cells. These data suggest that melanoma metastasis is a molecularly heterogeneous process that may not require epidermal-to-mesenchymal transition or ERK activation, although both may facilitate the process. PMID:20679910

  2. Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models.

    PubMed

    Rao, Quan; You, Abin; Guo, Zhenglong; Zuo, Bingfeng; Gao, Xianjun; Zhang, Ti; Du, Zhi; Wu, Chenxuan; Yin, HaiFang

    2016-01-01

    Mouse models are commonly used for studying hepatocellular carcinoma (HCC) biology and exploring new therapeutic interventions. Currently three main modalities of HCC mouse models have been extensively employed in pre-clinical studies including chemically induced, transgenic and transplantation models. Among them, transplantation models are preferred for evaluating in vivo drug efficacy in pre-clinical settings given the short latency, uniformity in size and close resemblance to tumors in patients. However methods used for establishing orthotopic HCC transplantation mouse models are diverse and fragmentized without a comprehensive comparison. Here, we systemically evaluate four different approaches commonly used to establish HCC mice in preclinical studies, including intravenous, intrasplenic, intrahepatic inoculation of tumor cells and intrahepatic tissue implantation. Four parameters--the latency period, take rates, pathological features and metastatic rates--were evaluated side-by-side. 100% take rates were achieved in liver with intrahepatic, intrasplenic inoculation of tumor cells and intrahepatic tissue implantation. In contrast, no tumor in liver was observed with intravenous injection of tumor cells. Intrahepatic tissue implantation resulted in the shortest latency with 0.5 cm (longitudinal diameter) tumors found in liver two weeks after implantation, compared to 0.1cm for intrahepatic inoculation of tumor cells. Approximately 0.1cm tumors were only visible at 4 weeks after intrasplenic inoculation. Uniform, focal and solitary tumors were formed with intrahepatic tissue implantation whereas multinodular, dispersed and non-uniform tumors produced with intrahepatic and intrasplenic inoculation of tumor cells. Notably, metastasis became visible in liver, peritoneum and mesenterium at 3 weeks post-implantation, and lung metastasis was visible after 7 weeks. T cell infiltration was evident in tumors, resembling the situation in HCC patients. Our study

  3. Establishment of a dual-color fluorescence tracing orthotopic transplantation model of hepatocellular carcinoma.

    PubMed

    Chen, Qian; Wang, Xiaoping; Wu, Hao; Wang, Hui; Zhu, Mingao; Wang, Roushu; Wu, Ying; Zhang, Luyao; Meng, Qiao; Song, Ranran; Zhuang, Zhixiang; Huang, Qiang

    2016-01-01

    Different experimental models of hepatocellular carcinoma (HCC) have been used to investigate the biological mechanisms of hepatocarcinogenesis and its progression. However, previous studies have highlighted the difficulty of distinguishing between the tumor cells and stroma in experimental models of HCC. Therefore the aim of the present study was to establish a red‑green dual‑color fluorescence tracing orthotopic transplantation model of HCC, and investigate its practical values. Stable high red fluorescent protein (RFP)‑expressing HepG2 human hepatoma cells and Hepa1‑6 mice hepatoma cells were injected into the right liver lobe of green fluorescent protein‑expressing nude mice. The growth and metastasis of the tumors were visualized using a whole‑body in vivo fluorescence imaging system in real time. HCC tissues were extracted from tumor‑bearing mice, and cut into 5‑µm serial frozen slices. The organizational structure of the transplanted tumors was observed under a microscope. A dual‑color fluorescence tracing orthotopic transplantation tumor model of HCC was successfully established with a success rate of 100%. The growth and metastasis of the tumors were visualized at each stage of development in the tumor‑bearing mice. Tumor cells with red fluorescence and host cells with green fluorescence were identified to merge in the reconstruction region of tumor tissue. The invasion, migration, and cell fusion between tumor and host cells was observed clearly. The dual‑color fluorescence tracing orthotopic transplantation model of HCC was determined to be a stable and reliable method for tracking tumor progression. Mutual interactions between hepatoma cells and host tissues may be observed directly using this model, further elucidating the development of the tumor microenvironment. PMID:26647736

  4. Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

    SciTech Connect

    Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

    1988-07-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

  5. Orthotopic non-metastatic and metastatic oral cancer mouse models ⋆

    PubMed Central

    Bais, Manish V.; Kukuruzinska, Maria; Trackman, Philip C.

    2015-01-01

    SUMMARY Oral cancer is characterized by high morbidity and mortality with a predisposition to metastasize to different tissues, including lung, liver, and bone. Despite progress in the understanding of mutational profiles and deregulated pathways in oral cancer, patient survival has not significantly improved over the past decades. Therefore, there is a need to establish in vivo models that recapitulate human oral cancer metastasis to evaluate therapeutic potential of novel drugs. Here we report orthotopic tongue cancer nude mouse models to study oral cancer growth and metastasis using human metastatic (UMSCC2) and non-metastatic (CAL27) cell lines, respectively. Transduction of these cell lines with lentivirus expressing red fluorescent protein (DsRed) followed by injection into tongues of immunodeficient mice generated orthotopic tongue tumors that could be monitored for growth and metastasis by fluorescence measurement with an in vivo Imaging System (IVIS 200). The growth rates of CAL27-DsRed induced tumors were higher than UMSCC2-DsRed tumors after day 15, while UMSCC2-DsRed tumors revealed metastasis beginning on day 21. Importantly, UMSCC2 tumors metastasized to a number of tissues including the submandibular gland, lung, kidney, liver, and bone. Further, immunohistochemical analyses of tongue tumors induced by CAL27 and UMSCC2 cells revealed elevated expression of components of protumorigenic pathways deregulated in human cancers, including Cyclin D1, PCNA, Ki-67, LSD1, LOXL2, MT-MMP1, DPAGT1, E-cadherin, OCT4A, and H3K4me1/2. These orthotopic mouse models are likely to be useful tools for gaining insights into the activity and mechanisms of novel oral cancer drug candidates. PMID:25682387

  6. Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer.

    PubMed

    Jones, Lee W; Antonelli, Jodi; Masko, Elizabeth M; Broadwater, Gloria; Lascola, Christopher D; Fels, Diane; Dewhirst, Mark W; Dyck, Jason R B; Nagendran, Jeevan; Flores, Catherine T; Betof, Allison S; Nelson, Erik R; Pollak, Michael; Dash, Rajesh C; Young, Martin E; Freedland, Stephen J

    2012-07-01

    The purpose of this study is to investigate the effects of exercise on cancer progression, metastasis, and underlying mechanisms in an orthotopic model of murine prostate cancer. C57BL/6 male mice (6-8 wk of age) were orthotopically injected with transgenic adenocarcinoma of mouse prostate C-1 cells (5 × 10(5)) and randomly assigned to exercise (n = 28) or a non-intervention control (n = 31) groups. The exercise group was given voluntary access to a wheel 24 h/day for the duration of the study. Four mice per group were serially killed on days 14, 31, and 36; the remaining 38 mice (exercise, n = 18; control, n = 20) were killed on day 53. Before death, MRI was performed to assess tumor blood perfusion. Primary tumor growth rate was comparable between groups, but expression of prometastatic genes was significantly modulated in exercising animals with a shift toward reduced metastasis. Exercise was associated with increased activity of protein kinases within the MEK/MAPK and PI3K/mTOR signaling cascades with subsequent increased intratumoral protein levels of HIF-1α and VEGF. This was associated with improved tumor vascularization. Multiplex ELISAs revealed distinct reductions in plasma concentrations of several angiogenic cytokines in the exercise group, which was associated with increased expression of angiogenic and metabolic genes in the skeletal muscle. Exercise-induced stabilization of HIF-1α and subsequent upregulation of VEGF was associated with "productive" tumor vascularization with a shift toward suppressed metastasis in an orthotopic model of prostate cancer. PMID:22604887

  7. Creation of a murine orthotopic hepatoma model with intra-abdominal metastasis

    PubMed Central

    Harris, Jamie; Kajdacsy-Balla, Andre; Chiu, Bill

    2016-01-01

    Aim: To create an orthotopic hepatoma model with local metastasis monitored with ultrasound could be created as a platform for testing new treatments. Background: Hepatoma accounts for 25% of liver tumors in children with poor overall survival. Intraabdominal metastasis are present in 35% of patients at time of diagnosis. We hypothesized that an orthotopic tumor model with local metastasis could be created as a platform for testing treatment modalities and could be monitored with ultrasound. Patients and methods: One million human hepatoma cells (Hep3B) were injected into the left lobe of the liver of immunocompromised mice. Tumor volume was monitored with high frequency-ultrasound until it reached 1,000mm3. At that time animals were sacrificed and examined for gross metastatic disease. Tumor sections were analyzed with hematoxylin and eosin (H&E) staining. Results: Tumor formed in 8/15 mice. The tumor was detected as small as 19.59mm3 on ultrasound. Of the forming tumors, tumor size was 145±177.93mm3 at 60 days post-injection, 665±650.39mm3 at 67 days, and reached >1000mm3 by 76.6±9.9 days. At necropsy, four mice (50%) had tumor only within the liver, four (50%) had additional tumors in omentum, pelvis and peritoneum. H&E showed tumor within the normal liver parenchyma, with multiple mitotic figures, small areas of necrosis, and hemorrhage within the tumor. Conclusion: We have successfully established an orthotopic hepatoma murine model, with a local metastatic rate of 50%. Non-invasive tumor monitoring is feasible via ultrasound. PMID:27458509

  8. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

    PubMed

    Miller, Amy; Burson, Hannah; Söling, Ariane; Roughan, Johnny

    2016-01-01

    Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of

  9. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice

    PubMed Central

    Miller, Amy; Burson, Hannah; Söling, Ariane

    2016-01-01

    Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of

  10. Mitral valve dysfunction and repair following orthotopic heart transplantation: a case report.

    PubMed

    Wigfield, C H; Lewis, A; Parry, G; Dark, J H

    2008-06-01

    Mitral valve dysfunction after orthotopic heart transplantation may cause symptoms refractory to medical therapy. In this report, we present a patient who underwent mitral annuloplasty for severe symptomatic mitral valve insufficiency 9 years after heart transplantation, and we critically appraise the literature available for mitral valve dysfunction in this setting. Mitral valve repair, when feasible, should be considered for mitral insufficiency after transplantation to improve functional status and reduce the risk of retransplantation--this is particularly prudent in view of chronic donor shortage. PMID:18589200

  11. Auxiliary partial orthotopic liver transplant for Criggler-Najjar Syndrome: Report of 2 cases from Pakistan.

    PubMed

    Dar, Faisal Saud; Bhatti, Abu Bakar Hafeez; Hashmi, Syeda Shaheera; Zia, Haseeb; Malik, Munir Iqbal

    2016-05-01

    Auxiliary partial orthotopic liver transplant (APOLT) is a treatment option for certain liver disorders where liver structure is preserved. It includes Criggler Najjar syndrome (CNS), urea cycle defects and familial hypercholesterolaemia. Liver transplant as a treatment modality has only recently become available in Pakistan. Here we report two paediatric cases of CNS type 1 where auxiliary liver transplant was performed to correct jaundice and prevent inevitable brain damage. Both recipients and their respective living donors had successful surgery and are doing well. PMID:27183949

  12. Hormone Replacement Therapy

    MedlinePlus

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  13. Hip replacement - discharge

    MedlinePlus

    ... a hip replacement and need antibiotics before any dental work. When to Call Your Doctor Call your health care provider if you have: A sudden increase in pain Chest pain or shortness of breath Frequent urination ...

  14. Replacing Arizona's Roofs.

    ERIC Educational Resources Information Center

    Fickes, Michael

    2000-01-01

    Discusses the Arizona statewide mandate to spend $500 million to repair or replace roofs in its public school system. Data from the state's evaluation process are provided, including how the state will fund the project. (GR)

  15. Knee joint replacement

    MedlinePlus

    The results of a total knee replacement are often excellent. The operation relieves pain for most people. Most people do not need help walking after they fully recover. Most artificial knee joints last 10 ...

  16. Hip joint replacement - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100006.htm Hip joint replacement - series—Normal anatomy To use the sharing ... to slide 5 out of 5 Overview The hip joint is made up of two major parts: the ...

  17. Replacing a Missing Tooth

    MedlinePlus

    ... majority of patients with clefts will require full orthodontic treatment, especially if the cleft has passed through ... later replacement of the missing lateral incisor. During orthodontic treatment, an artificial tooth may be attached to ...

  18. Knee joint replacement - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100088.htm Knee joint replacement - series—Normal anatomy To use the sharing ... of 4 Overview The knee is a complex joint. It contains the distal end of the femur ( ...

  19. Kidney Replacement Therapy

    MedlinePlus

    ... their function with either dialysis or a transplant. Dialysis Dialysis, the more common form of kidney-replacement ... the result of diabetes, not of hemodialysis. Peritoneal dialysis Another form of dialysis is called peritoneal dialysis. ...

  20. Artificial Disc Replacement

    MedlinePlus

    ... treat this condition, alternatives to disc replacement include fusion, nonoperative care or no treatment. Typically, surgery is ... operative treatment for disc pain has been spinal fusion. This is a surgical procedure in which disc ...

  1. Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models

    PubMed Central

    Yano, Shuya; Takehara, Kiyoto; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2016-01-01

    Malignant melanoma requires precise resection in order to avoid metastatic recurrence. We report here that the telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401 could label malignant melanoma with GFP in situ in orthotopic mouse models. OBP-401-based fluorescence-guided surgery (FGS) resulted in the complete resection of malignant melanoma in the orthotopic models, where conventional bright-light surgery (BLS) could not. High-dose administration of OBP-401 enabled FGS without residual cancer cells or recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. PMID:26701857

  2. Targeted Regression of Hepatocellular Carcinoma by Cancer-Specific RNA Replacement through MicroRNA Regulation.

    PubMed

    Kim, Juhyun; Won, Ranhui; Ban, Guyee; Ju, Mi Ha; Cho, Kyung Sook; Young Han, Sang; Jeong, Jin-Sook; Lee, Seong-Wook

    2015-01-01

    Hepatocellular carcinoma (HCC) has a high fatality rate and limited therapeutic options with side effects and low efficacy. Here, we proposed a new anti-HCC approach based on cancer-specific post-transcriptional targeting. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically induce therapeutic gene activity through HCC-specific replacement of telomerase reverse transcriptase (TERT) RNA. To circumvent side effects due to TERT expression in regenerating liver tissue, liver-specific microRNA-regulated ribozymes were constructed by incorporating complementary binding sites for the hepatocyte-selective microRNA-122a (miR-122a), which is down-regulated in HCC. The ribozyme activity in vivo was assessed in mouse models orthotopically implanted with HCC. Systemic administration of adenovirus encoding the developed ribozymes caused efficient anti-cancer effect and the least hepatotoxicity with regulation of ribozyme expression by miR-122a in both xenografted and syngeneic orthotopic murine model of multifocal HCC. Of note, the ribozyme induced local and systemic antitumor immunity, thereby completely suppressing secondary tumor challenge in the syngeneic mouse. The cancer specific trans-splicing ribozyme system, which mediates tissue-specific microRNA-regulated RNA replacement, provides a clinically relevant, safe, and efficient strategy for HCC treatment. PMID:26189916

  3. Targeted Regression of Hepatocellular Carcinoma by Cancer-Specific RNA Replacement through MicroRNA Regulation

    PubMed Central

    Kim, Juhyun; Won, Ranhui; Ban, Guyee; Ha Ju, Mi; Sook Cho, Kyung; Young Han, Sang; Jeong, Jin-Sook; Lee, Seong-Wook

    2015-01-01

    Hepatocellular carcinoma (HCC) has a high fatality rate and limited therapeutic options with side effects and low efficacy. Here, we proposed a new anti-HCC approach based on cancer-specific post-transcriptional targeting. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically induce therapeutic gene activity through HCC-specific replacement of telomerase reverse transcriptase (TERT) RNA. To circumvent side effects due to TERT expression in regenerating liver tissue, liver-specific microRNA-regulated ribozymes were constructed by incorporating complementary binding sites for the hepatocyte-selective microRNA-122a (miR-122a), which is down-regulated in HCC. The ribozyme activity in vivo was assessed in mouse models orthotopically implanted with HCC. Systemic administration of adenovirus encoding the developed ribozymes caused efficient anti-cancer effect and the least hepatotoxicity with regulation of ribozyme expression by miR-122a in both xenografted and syngeneic orthotopic murine model of multifocal HCC. Of note, the ribozyme induced local and systemic antitumor immunity, thereby completely suppressing secondary tumor challenge in the syngeneic mouse. The cancer specific trans-splicing ribozyme system, which mediates tissue-specific microRNA-regulated RNA replacement, provides a clinically relevant, safe, and efficient strategy for HCC treatment. PMID:26189916

  4. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus–Seropositive Patients

    PubMed Central

    Kittleson, Michelle M.; Dilibero, Deanna; Hardy, W. David; Kobashigawa, Jon A.; Esmailian, Fardad

    2016-01-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus—accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation. PMID:27047290

  5. An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma.

    PubMed

    Sasaki, Hiromi; Iyer, Swathi V; Sasaki, Ken; Tawfik, Ossama W; Iwakuma, Tomoo

    2015-10-01

    Osteosarcoma, the most common type of primary bone cancer, is the second highest cause of cancer-related death in pediatric patients. To understand the mechanisms behind osteosarcoma progression and to discover novel therapeutic strategies for this disease, a reliable and appropriate mouse model is essential. For this purpose, osteosarcoma cells need to be injected into the bone marrow. Previously, the intratibial and intrafemoral injection methods were reported; however, the major drawback of these methods is the potential leakage of tumor cells from the injection site during or after these procedures. To overcome this, we have established an improved method to minimize leakage in an orthotopic mouse model of osteosarcoma. By taking advantage of the anatomical benefits of the femur with less bowing and larger medullary cavity than those of the tibia, osteosarcoma cells are injected directly into the femoral cavity following reaming of its intramedullary space. To prevent potential leakage of tumor cells during and after the surgery, the injection site is sealed with bone wax. This method requires a minor surgery of approximately 15min under anesthesia. Our established orthotopic osteosarcoma model could serve as a valuable and reliable tool for examining progression of various types of bone tumors. PMID:26142221

  6. The long-term fate of fresh and frozen orthotopic bone allografts in genetically defined rats.

    PubMed

    Bos, G D; Goldberg, V M; Gordon, N H; Dollinger, B M; Zika, J M; Powell, A E; Heiple, K G

    1985-01-01

    Fresh and frozen orthotopic iliac crest bone grafts in rats were studied histologically for determination of the long-term effects of histocompatibility matching and the freezing process on orthotopic bone graft incorporation. Grafts exchanged between groups of inbred rats, syngeneic or differing with respect to major or minor histocompatibility loci, were studied histologically at 20, 30, 40, 50, and 150 days after bone transplantation. A numerical histologic scoring system was developed and used by three observers for evaluation of coded hematoxylin and eosin sections. All frozen graft groups had the same fate regardless of histocompatibility relations between donors and recipients, and all grafts were inferior to fresh syngeneic grafts. Both fresh allograft groups received similar scores and initially at 20 and 30 days had scores similar to those of the fresh syngeneic groups. In the later intervals, however, the fresh allografts were inferior to the fresh syngeneic grafts and similar to the frozen groups. This is consistent with an older model describing two distinct phases of osteogenesis. In the long term, frozen syngeneic and fresh and frozen allografts across major and minor histocompatibility barriers were comparable, but all were significantly inferior to fresh syngeneic bone grafts. PMID:3893828

  7. A New Cone-Shaped Aortic Valve Prosthesis for Orthotopic Position: An Experimental Study in Swine

    SciTech Connect

    Sochman, Jan; Peregrin, Jan H.; Pulda, Zdenek; Pavcnik, Dusan; Uchida, Barry T.; Timmermans, Hans A.; Roesch, Josef

    2010-04-15

    The aim of this experimental study was to evaluate a newly designed cone-shaped aortic valve prosthesis (CAVP) for one-step transcatheter placement in an orthotopic position. The study was conducted in 15 swine using either the transcarotid (11 animals) or the transfemoral (4 animals) artery approach. A 12- or 13-Fr sheath was inserted via arterial cutdown. The CAVP was deployed under fluoroscopic control and its struts, by design, induced significant native valve insufficiency. CAVP function was evaluated by aortography and aortic pressure curve tracing. In 11 of 15 swine the CAVP was properly deployed and functioned well throughout the scheduled period of 2-3 h. In three swine the CAVPs were placed lower than intended, however, they were functional even in the left ventricular outflow tract position. One swine expired due to inadvertent low CAVP placement that caused both aortic regurgitation and immobilization of the anterior mitral valve leaflet by the valve struts. We conclude that this design of CAVP is relatively easy to deploy, works well throughout a short time period (2-3 h), and, moreover, seems to be reliable even in a lower-than-orthotopic position (e.g., infra-annulary space). Longer-term studies are needed for its further evaluation.

  8. Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours.

    PubMed

    Braekeveldt, Noémie; Wigerup, Caroline; Tadeo, Irene; Beckman, Siv; Sandén, Caroline; Jönsson, Jimmie; Erjefält, Jonas S; Berbegall, Ana P; Börjesson, Anna; Backman, Torbjörn; Øra, Ingrid; Navarro, Samuel; Noguera, Rosa; Gisselsson, David; Påhlman, Sven; Bexell, Daniel

    2016-06-01

    Treatment of high-risk childhood neuroblastoma is a clinical challenge which has been hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing. PMID:27000989

  9. Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model

    PubMed Central

    Chen, Xiaoyun; Wang, Jian; Cao, Ziquan; Hosaka, Kayoko; Jensen, Lasse; Yang, Huasheng; Sun, Yuping; Zhuang, Rujie; Liu, Yizhi; Cao, Yihai

    2015-01-01

    Retinoblastoma is a highly invasive malignant tumor that often invades the brain and metastasizes to distal organs through the blood stream. Invasiveness and metastasis of retinoblastoma can occur at the early stage of tumor development. However, an optimal preclinical model to study retinoblastoma invasiveness and metastasis in relation to drug treatment has not been developed. Here, we developed an orthotopic zebrafish model in which retinoblastoma invasion and metastasis can be monitored at a single cell level. We took the advantages of immune privilege and transparent nature of developing zebrafish embryos. Intravitreal implantation of color-coded retinoblastoma cells allowed us to kinetically monitor tumor cell invasion and metastasis. Further, interactions between retinoblastoma cells and surrounding microvasculatures were studied using a transgenic zebrafish that exhibited green fluorescent signals in blood vessels. We discovered that tumor cells invaded neighboring tissues and blood stream when primary tumors were at the microscopic sizes. These findings demonstrate that retinoblastoma metastasis occurs at the early stage and antiangiogenic drugs such as Vegf morpholino and sunitinib could potentially interfere with tumor invasiveness and metastasis. Thus, this orthotopic retinoblastoma model offers a new and unique opportunity to study the early events of tumor invasion, metastasis and drug responses. PMID:26169357

  10. Toxicology of chlorofluorocarbon replacements.

    PubMed Central

    Dekant, W

    1996-01-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements. PMID:8722112

  11. Python import replacement

    Energy Science and Technology Software Center (ESTSC)

    2011-10-01

    SmartImport.py is a Python source-code file that implements a replacement for the standard Python module importer. The code is derived from knee.py, a file in the standard Python diestribution , and adds functionality to improve the performance of Python module imports in massively parallel contexts.

  12. Replacing America's Job Bank

    ERIC Educational Resources Information Center

    Vollman, Jim

    2009-01-01

    The Job Central National Labor Exchange (www.jobcentral.com) has become the effective replacement for America's Job Bank with state workforce agencies and, increasingly, with community colleges throughout the country. The American Association of Community Colleges (AACC) has formed a partnership with Job Central to promote its use throughout the…

  13. Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor

    PubMed Central

    2014-01-01

    Background Gastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as the paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance has emerged as a major problem and therefore, the clinical efficacy of other drugs has been investigated. Unfortunately, most clinical trials have failed to identify efficacious drugs despite promising in vitro data and pathological responses in subcutaneous xenografts. We hypothesized that it was feasible to develop orthotopic patient-derived xenografts (PDXs) from resected GIST that could recapitulate the genetic heterogeneity and biology of the human disease. Methods Fresh tumor tissue from three patients with pathologically confirmed GISTs was obtained immediately following tumor resection. Tumor fragments (4.2-mm3) were surgically xenografted into the liver, gastric wall, renal capsule, and pancreas of immunodeficient mice. Tumor growth was serially assessed with ultrasonography (US) every 3-4 weeks. Tumors were also evaluated with positron emission tomography (PET). Animals were sacrificed when they became moribund or their tumors reached a threshold size of 2500-mm3. Tumors were subsequently passaged, as well as immunohistochemically and histologically analyzed. Results Herein, we describe the first model for generating orthotopic GIST PDXs. We have successfully xenografted three unique KIT-mutated tumors into a total of 25 mice with an overall success rate of 84% (21/25). We serially followed tumor growth with US to describe the natural history of PDX growth. Successful PDXs resulted in 12 primary xenografts in NOD-scid gamma or NOD-scid mice while subsequent successful passages resulted in 9 tumors. At a median of 7.9 weeks (range 2.9-33.1 weeks), tumor size averaged 473±695-mm3 (median 199-mm3, range 12.6-2682.5-mm3) by US. Furthermore, tumor size on US within 14 days of death correlated with gross tumor size on necropsy. We also

  14. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours

    PubMed Central

    Braekeveldt, Noémie; Wigerup, Caroline; Gisselsson, David; Mohlin, Sofie; Merselius, My; Beckman, Siv; Jonson, Tord; Börjesson, Anna; Backman, Torbjörn; Tadeo, Irene; Berbegall, Ana P; Öra, Ingrid; Navarro, Samuel; Noguera, Rosa; Påhlman, Sven; Bexell, Daniel

    2015-01-01

    Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose–positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma. What's new? Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease have a poor outcome. Here, the authors established neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high-risk neuroblastoma into immunodeficient mice

  15. Comparison of Survival and Osteogenic Ability of Human Mesenchymal Stem Cells in Orthotopic and Ectopic Sites in Mice.

    PubMed

    Manassero, Mathieu; Paquet, Joseph; Deschepper, Mickael; Viateau, Véronique; Retortillo, Jose; Bensidhoum, Morad; Logeart-Avramoglou, Delphine; Petite, Hervé

    2016-03-01

    Tissue constructs containing mesenchymal stem cells (MSCs) are appealing strategies for repairing large segmental bone defects, but they do not allow consistent bone healing and early cell death was identified as a cause of failure. However, little is known about cell survival in the clinical microenvironment encountered during bone healing process. Osteoconductive coral scaffold with or without luciferase-labeled human MSCs were implanted either in a critical segmental femoral bone defect stabilized by plate or subcutaneously in 44 mice. Cell survival was evaluated by serial bioluminescence imaging (BLI) and osteogenic capabilities by histology and microcomputed tomography. Comparisons between groups were performed with two-way analysis of variance test. Twenty mice were sacrificed 2 weeks after surgery for short-term evaluation and 24 mice at 10 weeks for long-term evaluation. BLI provided evidence of fast and continuous cell death: 85% decrease of the BLI signal over the first 2 weeks in both locations; in fact, less than 2% of the initial cell number was present in all constructs analyzed 4 weeks postimplantation and less than 1% of the initial cell number by 8 weeks postimplantation. By 2 weeks postimplantation, the amount of newly formed bone was self-limited and was similar to ectopic and orthotopic groups. By 10 weeks postimplantation, bone formation was significantly enhanced in the presence of MSCs in orthotopic site and the amount of newly formed bone in cell-containing constructs implanted in orthotopic locations was significantly higher than that observed in the ectopic group. Our results indicated that hMSCs promote bone formation despite early and massive cell death when loaded on coral scaffolds. Interestingly, bone formation was higher in orthotopic than ectopic site despite the same survival pattern. Ectopic implantation of cell-containing constructs is suitable to evaluate cell survival, but assessment of bone formation ability requires

  16. Distribution of Gemcitabine Is Nearly Homogenous in Two Orthotopic Murine Models of Pancreatic Cancer.

    PubMed

    Kramer, Robin M; Russell, James; Humm, John L

    2015-09-01

    Pancreatic cancer is one of the leading causes of cancer-related death in the United States. Gemcitabine is a common treatment, but response rates are low, perhaps due in part to tumor hypoxia. We utilized (14)C-labeled gemcitabine to map distribution of the drug with respect to perfused and hypoxic regions of the tumor microenvironment in two orthotopic xenograft models of pancreatic cancer. There was only a slight reduction in gemcitabine in hypoxic areas, with ∼78% of the drug present in hypoxic compared to perfused areas. In addition, only a 4% reduction in gemcitabine was measured at >100 μm from perfused blood vessels. Thus, despite significant areas of hypoxia in these tumors, gemcitabine distribution is relatively homogenous. Ours is the first study to directly measure gemcitabine distribution within tumor tissue, demonstrating that in these models, tumor tissue does not represent a barrier to gemcitabine penetration. PMID:26203552

  17. Surface coil localization of /sup 31/P NMR signals from orthotopic human kidney and liver

    SciTech Connect

    Jue, T.; Rothman, D.L.; Lohman, J.A.B.; Hughes, E.W.; Hanstock, C.C.; Shulman, R.G.

    1988-02-01

    By incorporating the hyperbolic secant inversion pulses with the image-selected in vivo spectroscopy localization technique and by applying a gradient-echo imaging method, the authors have selected only the /sup 31/P NMR signals from orthotopic human kidney and liver, using a single concentric /sup 1/H//sup 31/P surface coil. Corresponding to the experimental results on animal studies, the phosphocreatine signal is dramatically reduced in the localized spectra. The localization strategy also allows them to shim easily on the well-defined volume of interest and leads to high-resolution spectra that exhibit multiplet structure. The results indicate that they can obtain localized signals from deep small organs and point the way for other human metabolism studies.

  18. Life-Threatening Cardiac Tamponade Secondary to Chylopericardium Following Orthotopic Heart Transplantation-A Case Report.

    PubMed

    Wierzbicki, Karol; Mazur, Piotr; Węgrzyn, Piotr; Kapelak, Bogusław

    2016-08-23

    Chylopericardium is a rare complication in cardiac surgery, and an extremely rare occurrence in patients following orthotopic heart transplantation (OHT), which, however, can lead to cardiac tamponade. Here we present a case of a 59-year-old man who underwent OHT and suffered from chylopericardium resulting in cardiac tamponade late in the postoperative course, despite the initially uneventful early postoperative period (decreasing blood drainage was observed directly after the procedure, and the drains were safely removed). After the diagnosis of chylopericardium was made, the conservative treatment was initiated, which turned out to be insufficient, and eventually invasive approach for the recurrence of tamponade secondary to chylopericardium was required. We discuss the available therapeutic options for chylopericardium and demonstrate the successful invasive therapeutic approach with use of the absorbable fibrin sealant patch. PMID:26548537

  19. Prolonged Intraoperative Cardiac Resuscitation Complicated by Intracardiac Thrombus in a Patient Undergoing Orthotopic Liver Transplantation.

    PubMed

    Kim, Sang; DeMaria, Samuel; Cohen, Edmond; Silvay, George; Zerillo, Jeron

    2016-09-01

    We report the case of successful resuscitation after prolonged cardiac arrest during orthotopic liver transplantation. After reperfusion, the patient developed ventricular tachycardia, complicated by intracardiac clot formation and massive hemorrhage. Transesophageal echocardiography demonstrated stunned and nonfunctioning right and left ventricles, with developing intracardiac clots. Treatment with heparin, massive transfusion and prolonged cardiopulmonary resuscitation ensued for 51 minutes. Serial arterial blood gases demonstrated adequate oxygenation and ventilation during cardiopulmonary resuscitation. Cardiothoracic surgery was consulted for potential use of extracorporeal membrane oxygenation, however, the myocardial function improved and the surgery was completed without further intervention. On postoperative day 6, the patient was extubated without neurologic or cardiac impairment. The patient continues to do well 2 years posttransplant, able to perform independent daily activities of living and his previous job. This case underscores the potential for positive outcomes with profoundly prolonged, effective advanced cardiovascular life support in patients who experience postreperfusion syndrome. PMID:27233818

  20. Orthotopic Heart Transplantation and Mechanical Circulatory Support in Cancer Survivors: Challenges and Outcomes

    PubMed Central

    Ghosh, Nina; Hilton, John

    2015-01-01

    Chemotherapy-induced cardiomyopathy (CCMP) is a significant cause of morbidity and mortality. Compared to cardiomyopathy due to other causes, anthracycline-induced cardiomyopathy is associated with a worse survival. As cancer survival improves, patients with CCMP can be expected to comprise a significant proportion of patients who may require advanced therapies such as inotropic support, cardiac transplantation, or left ventricular assist device (LVAD). Distinct outcomes related to advanced therapies for end-stage heart failure in this patient population may arise due to unique demographic characteristics and comorbidities. We review recent literature regarding the characteristics of patients who have survived cancer undergoing orthotopic heart transplantation and mechanical circulatory support for end-stage heart failure. The challenges and outcomes of advanced therapies for heart failure related specifically to anthracycline-induced cardiomyopathy are emphasized. PMID:26339241

  1. Pharmacologic Strategies to Prevent Blood Loss and Transfusion in Orthotopic Liver Transplantation.

    PubMed

    Tischer, Sarah; Miller, James T

    2016-01-01

    Patients undergoing orthotopic liver transplantation are at risk of both life-threatening blood loss and thrombosis due to preexisting liver dysfunction and major intra- and postoperative coagulopathy. Traditional laboratory markers of hemostasis and coagulopathy are often inadequate to describe the alterations. Whole blood global viscoelastic tests, thromboelastography, and thromboelastometry may provide more complete pictures of the hematologic derangements and allow for more targeted therapy to prevent blood loss and massive transfusion. Antifibrinolytic medications such as aprotinin, tranexamic acid, and [Latin Small Letter Open E]-aminocaproic acid have been used successfully to reduce blood loss and the need for transfusion, although most published data are from small prospective trials or larger retrospective cohorts. Recombinant factor VIIa has not been shown to improve outcomes. Although transfusion needs have been associated with adverse outcomes, no studied medications for prevention of blood loss and transfusion have been associated with improved mortality or graft survival post-liver transplant. PMID:27254642

  2. ARRANGEMENT FOR REPLACING FILTERS

    DOEpatents

    Blomgren, R.A.; Bohlin, N.J.C.

    1957-08-27

    An improved filtered air exhaust system which may be continually operated during the replacement of the filters without the escape of unfiltered air is described. This is accomplished by hermetically sealing the box like filter containers in a rectangular tunnel with neoprene covered sponge rubber sealing rings coated with a silicone impregnated pneumatic grease. The tunnel through which the filters are pushed is normal to the exhaust air duct. A number of unused filters are in line behind the filters in use, and are moved by a hydraulic ram so that a fresh filter is positioned in the air duct. The used filter is pushed into a waiting receptacle and is suitably disposed. This device permits a rapid and safe replacement of a radiation contaminated filter without interruption to the normal flow of exhaust air.

  3. Celotex (Registered) Replacement Study

    SciTech Connect

    Couture, S; Hafner, R

    2002-10-01

    The AL-R8 is the pit storage container in most widespread use at Pantex. The AL-R8 container family consists of standard 20-in.-diameter steel drums, 30 to 60 in. in height, with insulation inserts made of Celotex{reg_sign}--a fiberboard product made from processed sugar cane. Celotex is an acceptable material for inserts in many radioactive material shipping and storage containers. It is a good shock mitigator/insulator, does a fair job in fire protection (when oxygen is excluded), shielding, and criticality, and is inexpensive and easily available. However, the fiberboard absorbs water in humid environments which, when combined with chemical residues in the fiberboard, forms corrosive compounds that can shorten the life of the container and affect container contents. To protect the contents from this potentially damaging environment, the AL-R8 SI was developed to isolate the contents within a sealed stainless steel vessel inside the AL-R8. Although the SI protected the contents, corrosion studies indicated the SI lid bolts might corrode over time and surveillance showed that areas of the outer drum were still subject to corrosion. To address this potential problem, DOE/Albuquerque sponsored bolt and Celotex replacement studies. The bolt replacement study was assigned to Mason and Hanger's Pantex Facility and this Celotex Replacement Study to Lawrence Livermore National Laboratory. The Celotex Replacement Study evaluated options for replacing Celotex with a material that is chemically compatible with the AL-R8 SI container. The evaluation was limited to materials either used previously in nuclear materials shipping and storage containers or materials with known properties in a low-radiation environment. This limitation was set to ensure that the long-term aging effect on the new material is known a priori. Initial material evaluations narrowed the material choices to foam and cork. Although cork performed better than foam in some tests, cork was considered a less

  4. NARC Rayon Replacement Program

    NASA Technical Reports Server (NTRS)

    Wilson, Kenneth P.; McCool, Alex (Technical Monitor)

    2002-01-01

    This viewgraph presentation provides information on the search for a replacement product for the aerospace grade rayon formerly used in the reusable solid rocket motor (RSRM). The rayon used in RSRMs is no longer produced by the North American Rayon Corporation (NARC), though NASA has stockpiled rayon to be used until a suitable replacement is found to be used in the RSRM nozzle carbon cloth phenolic (CCP). The primary considerations are performance, process ability, variability, long term availability, and cost. The preference will be given to commercial off-the-shelf products as opposed to those which are custom made. The candidate materials have been tested in previous phases of this selection process, and Enka Textile Rayon has emerged as a possible fabric, though its availability is still in question.

  5. Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy.

    PubMed Central

    Turner, J. H.; Rose, A. H.; Glancy, R. J.; Penhale, W. J.

    1998-01-01

    Extrapolation to humans from experimental radioimmunotherapy in nude mouse xenograft models is confounded by large relative tumour size and small volume of distribution in mice allowing tumour uptake of radiolabelled antibodies unattainable in patients. Our large animal model of human tumours in cyclosporin-immunosuppressed sheep demonstrated tumour uptake of targeted radiolabelled monoclonal antibodies comparable with uptakes reported in clinical trials. Sheep immunosuppression with daily intravenous cyclosporin augmented by oral ketoconazole maintained trough blood levels of cyclosporin within the range 1000-1500 ng ml(-1). Human tumour cells were transplanted orthotopically by inoculation of 10(7) cells: SKMEL melanoma subcutaneously; LS174T and HT29 colon carcinoma into bowel, peritoneum and liver; and JAM ovarian carcinoma into ovary and peritoneum. Tumour xenografts grew at all sites within 3 weeks of inoculation, preserving characteristic morphology without evidence of necrosis or host rejection. Lymphatic metastasis was demonstrated in regional nodes draining xenografts of melanoma and ovarian carcinoma. Colonic LS1 74T xenografts produced mucin and carcinoembryonic antigen (CEA). The anti-CEA IgG1 monoclonal antibody A5B7 was radiolabelled with iodine-131 and administered intravenously to sheep. Peak uptake at 5 days in orthotopic human tumour transplants in gut was 0.027% DI g(-1) (percentage of injected dose per gram) and 0.034% DI g(-1) in hepatic metastases with tumour to blood ratios of 2-2.5. Non-specific tumour uptake in melanoma was 0.003% DI g(-1). Uptake of radiolabelled monoclonal antibody in human tumours in our large animal model is comparable with that observed in patients and may be more realistic than nude mice xenografts for prediction of clinical efficacy of radioimmunotherapy. Images Figure 1 Figure 2 Figure 3 PMID:9716032

  6. AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models.

    PubMed

    Chang, Edwin; Pohling, Christoph; Natarajan, Arutselvan; Witney, Timothy H; Kaur, Jasdeep; Xu, Lingyun; Gowrishankar, Gayatri; D'Souza, Aloma L; Murty, Surya; Schick, Sophie; Chen, Liyin; Wu, Nicholas; Khaw, Phoo; Mischel, Paul; Abbasi, Taher; Usmani, Shahabuddin; Mallick, Parag; Gambhir, Sanjiv S

    2016-01-01

    Glioblastoma multiforme (GBM) is an aggressive, malignant cancer Johnson and O'Neill (J Neurooncol 107: 359-364, 2012). An extract from the winter cherry plant (Withania somnifera ), AshwaMAX, is concentrated (4.3 %) for Withaferin A; a steroidal lactone that inhibits cancer cells Vanden Berghe et al. (Cancer Epidemiol Biomark Prev 23: 1985-1996, 2014). We hypothesized that AshwaMAX could treat GBM and that bioluminescence imaging (BLI) could track oral therapy in orthotopic murine models of glioblastoma. Human parietal-cortical glioblastoma cells (GBM2, GBM39) were isolated from primary tumors while U87-MG was obtained commercially. GBM2 was transduced with lentiviral vectors that express Green Fluorescent Protein (GFP)/firefly luciferase fusion proteins. Mutational, expression and proliferative status of GBMs were studied. Intracranial xenografts of glioblastomas were grown in the right frontal regions of female, nude mice (n = 3-5 per experiment). Tumor growth was followed through BLI. Neurosphere cultures (U87-MG, GBM2 and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 µM equivalent respectively and by Withaferin A with IC50 of 0.31, 0.28 and 0.25 µM respectively. Oral gavage, every other day, of AshwaMAX (40 mg/kg per day) significantly reduced bioluminescence signal (n = 3 mice, p < 0.02, four parameter non-linear regression analysis) in preclinical models. After 30 days of treatment, bioluminescent signal increased suggesting onset of resistance. BLI signal for control, vehicle-treated mice increased and then plateaued. Bioluminescent imaging revealed diffuse growth of GBM2 xenografts. With AshwaMAX, GBM neurospheres collapsed at nanomolar concentrations. Oral treatment studies on murine models confirmed that AshwaMAX is effective against orthotopic GBM. AshwaMAX is thus a promising candidate for future clinical translation in patients with GBM. PMID:26650066

  7. Sympathetic innervation, norepinephrine content, and norepinephrine turnover in orthotopic and spontaneous models of breast cancer.

    PubMed

    Szpunar, Mercedes J; Belcher, Elizabeth K; Dawes, Ryan P; Madden, Kelley S

    2016-03-01

    Activation of the sympathetic nervous system (SNS) drives breast cancer progression in preclinical breast cancer models, but it has yet to be established if neoplastic and stromal cells residing in the tumor are directly targeted by locally released norepinephrine (NE). In murine orthotopic and spontaneous mammary tumors, tyrosine hydroxylase (TH)+ sympathetic nerves were limited to the periphery of the tumor. No TH+ staining was detected deeper within these tumors, even in regions with a high density of blood vessels. NE concentration was much lower in tumors compared to the more densely innervated spleen, reflecting the relative paucity of tumor TH+ innervation. Tumor and spleen NE concentration decreased with increased tissue mass. In mice treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to selectively destroy sympathetic nerves, tumor NE concentration was reduced approximately 50%, suggesting that the majority of tumor NE is derived from local sympathetic nerves. To evaluate NE utilization, NE turnover in orthotopic 4T1 mammary tumors was compared to spleen under baseline and stress conditions. In non-stressed mice, NE turnover was equivalent between tumor and spleen. In mice exposed to a stressor, tumor NE turnover was increased compared to spleen NE turnover, and compared to non-stressed tumor NE turnover. Together, these results demonstrate that NE in mammary tumors is derived from local sympathetic nerves that synthesize and metabolize NE. However, differences between spleen and tumor NE turnover with stressor exposure suggest that sympathetic NE release is regulated differently within the tumor microenvironment compared to the spleen. Local mammary tumor sympathetic innervation, despite its limited distribution, is responsive to stressor exposure and therefore can contribute to stress-induced tumor progression. PMID:26718447

  8. BDNF signaling contributes to oral cancer pain in a preclinical orthotopic rodent model

    PubMed Central

    Chodroff, Leah; Bendele, Michelle; Valenzuela, Vanessa; Henry, Michael

    2016-01-01

    The majority of patients with oral cancer report intense pain that is only partially managed by current analgesics. Thus, there is a strong need to study mechanisms as well as develop novel analgesics for oral cancer pain. Current study employed an orthotopic tongue cancer model with molecular and non-reflexive behavioral assays to determine possible mechanisms of oral cancer pain. Human oral squamous cell carcinoma cells line, HSC2, was injected into the tongue of male athymic mice and tumor growth was observed by day 6. Immunohistological analyses revealed a well-differentiated tumor with a localized immune response and pronounced sensory and sympathetic innervation and vascularization. The tumor expressed TMPRSS2, a protein previously reported with oral squamous cell carcinoma. ATF3 expression in trigeminal ganglia was not altered by tumor growth. Molecular characterization of the model demonstrated altered expression of several pain-related genes, out of which up-regulation of BDNF was most striking. Moreover, BDNF protein expression in trigeminal ganglia neurons was increased and inhibition of BDNF signaling with a tyrosine kinase B antagonist, ANA-12, reversed pain-like behaviors induced by the oral tumor. Oral squamous cell carcinoma tumor growth was also associated with a reduction in feeding, mechanical hypersensitivity in the face, as well as spontaneous pain behaviors as measured by the conditioned place preference test, all of which were reversed by analgesics. Interestingly, injection of HSC2 into the hindpaw did not reproduce this spectrum of pain behaviors; nor did injection of a colonic cancer cell line into the tongue. Taken together, this orthotopic oral cancer pain model reproduces the spectrum of pain reported by oral cancer patients, including higher order cognitive changes, and demonstrates that BDNF signaling constitutes a novel mechanism by which oral squamous cell carcinoma induces pain. Identification of the key role of tyrosine kinase B

  9. SERPINI1 regulates epithelial-mesenchymal transition in an orthotopic implantation model of colorectal cancer.

    PubMed

    Matsuda, Yasufumi; Miura, Koh; Yamane, Junko; Shima, Hiroshi; Fujibuchi, Wataru; Ishida, Kazuyuki; Fujishima, Fumiyoshi; Ohnuma, Shinobu; Sasaki, Hiroyuki; Nagao, Munenori; Tanaka, Naoki; Satoh, Kennichi; Naitoh, Takeshi; Unno, Michiaki

    2016-05-01

    An increasingly accepted concept is that the progression of colorectal cancer is accompanied by epithelial-mesenchymal transition (EMT). In our study, in order to characterize the properties of EMT in 16 colorectal cancer cell lines, the cells were first orthotopically implanted into nude mice, and the tumors in vivo, as well as cells cultured in vitro, were immunostained for EMT markers. The immunostaining revealed that seven of the cells had an epithelial phenotype with a high expression of E-cadherin, whereas other cells showed opposite patterns, such as a high expression of vimentin (CX-1, COLO205, CloneA, HCT116, and SW48). Among the cells expressing vimentin, some expressed vimentin in the orthotopic tumors but not in the cultured cells (SW480, SW620, and COLO320). We evaluated these findings in combination with microarray analyses, and selected five genes: CHST11, SERPINI1, AGR2, FBP1, and FOXA1. Next, we downregulated the expression of SERPINI1 with siRNA in the cells, the results of which showed reverse-EMT changes at the protein level and in the cellular morphology. Along with immunohistochemical analyses, we confirmed the effect of the intracellular and secreted SERPINI1 protein of SW620 cells, which supported the importance of SERPINI1 in EMT. The development of therapeutic strategies targeting EMT is ongoing, including methods targeting the transforming growth factor-β signaling pathway as well as the Wnt pathway. SERPINI1 is an important regulator of EMT. Our findings help to elucidate the signaling pathways of EMT, hopefully clarifying therapeutic pathways as well. PMID:26892864

  10. Real-time Imaging of Tumor Progression in a Fluorescent Orthotopic Mouse Model of Thyroid Cancer

    PubMed Central

    TRAN CAO, HOP S.; KAUSHAL, SHARMEELA; SNYDER, CYNTHIA S.; ONGKEKO, WEG M.; HOFFMAN, ROBERT M.; BOUVET, MICHAEL

    2015-01-01

    There is a need for a clinically relevant mouse model of thyroid cancer that enables real-time, non-invasive monitoring of tumor growth, progression, and drug response over time. Human thyroid cancer cell lines NPA (papillary) and KAK-1 (anaplastic) were stably transfected to express either red or green fluorescent protein. Cancer cells were injected into the thyroid glands of 8-week-old athymic mice. The animals were imaged with whole-body fluorescence imaging weekly and sacrificed when premorbid. At necropsy, the primary tumor was resected en bloc with the respiratory system for processing and analysis. Histology was performed on fixed tissue specimens for review of morphologic findings. Both anaplastic and papillary thyroid cancer cell lines led to robust development of orthotopic fluorescent tumors in nude mice. Injection of 5×105 cancer cells was sufficient for tumor development. Tumors were visualized for both cell lines via non-invasive imaging as early as 3 weeks post-implantation and were monitored over time. Time to premorbid condition varied between mice and was associated with a primary tumor growth pattern (early local compression of the esophagus vs. late metastatic disease) rather than tumor size. At necropsy, tumor fluorescence demonstrated metastases in the lungs, lymph nodes and vessels that were not visible under white light. Thus an orthotopic mouse model of thyroid cancer has been developed that replicates the major clinical features of thyroid cancer and enables real-time, non-invasive monitoring of tumor progression. This model should permit preclinical evaluation of novel thyroid cancer therapeutics. PMID:21115887

  11. Prognostic Value of Preoperatively Obtained Clinical and Laboratory Data in Predicting Survival Following Orthotopic Liver Transplantation

    PubMed Central

    Cuervas-Mons, Valentin; Millan, Isabel; Gavaler, Judith S.; Starzl, Thomas E.; Van Thiel, David H.

    2010-01-01

    Twenty-seven clinical and laboratory data and the subsequent clinical course of 93 consecutive adult patients who underwent orthotopic liver transplantation for various chronic advanced liver diseases were analyzed retrospectively to assess the risk factors of early major bacterial infection and death after the procedure. Forty-one patients (44%) had early major bacterial infection during hospitalization for orthotopic liver transplantation. The mortality rate was 70.7% in patients with early major bacterial infection and was 7.7% in patients without early major bacterial infection (p < 0.001). Total serum bilirubin, total white blood cell count and polymorphonuclear cell count, IgG (all p < 0.05) and plasma creatinine level (p < 0.001) were higher in patients that developed early major bacterial infection than in those who did not. By step-wise discriminant analysis, the strongest risk factor for early major bacterial infection was the serum creatinine level, which achieved an accuracy of 69% for a creatinine level greater than 1.58 mg per dl. Seven variables (ascites, hepatic encephalopathy, elevated white blood and polymorphonuclear cell count, decreased helper to suppressor T cell ratio and elevated plasma creatinine and bilirubin levels) were associated with a significant increased risk for death. A step-wise discriminant analysis of these seven factors resulted in the demonstration of serum creatinine as the greatest risk factor for mortality. A preoperative serum creatinine either less than or greater than 1.72 mg per dl accurately predicts survival or death, respectively, in 79% of cases. These data suggest that the baseline preoperative serum creatinine level provides the best indication of the short-term prognosis after liver transplantation than does any other preoperatively obtained index of the patient’s status. PMID:3530947

  12. Circulating tumor cells exhibit stem cell characteristics in an orthotopic mouse model of colorectal cancer.

    PubMed

    Schölch, Sebastian; García, Sebastián A; Iwata, Naoki; Niemietz, Thomas; Betzler, Alexander M; Nanduri, Lahiri K; Bork, Ulrich; Kahlert, Christoph; Thepkaysone, May-Linn; Swiersy, Anka; Büchler, Markus W; Reissfelder, Christoph; Weitz, Jürgen; Rahbari, Nuh N

    2016-05-10

    The prognosis of colorectal cancer (CRC) is closely linked to the occurrence of distant metastases, which putatively develop from circulating tumor cells (CTCs) shed into circulation by the tumor. As far more CTCs are shed than eventually metastases develop, only a small subfraction of CTCs harbor full tumorigenic potential. The aim of this study was to further characterize CRC-derived CTCs to eventually identify the clinically relevant subfraction of CTCs.We established an orthotopic mouse model of CRC which reliably develops metastases and CTCs. We were able to culture the resulting CTCs in vitro, and demonstrated their tumor-forming capacity when re-injected into mice. The CTCs were then subjected to qPCR expression profiling, revealing downregulation of epithelial and proliferation markers. Genes associated with cell-cell adhesion (claudin-7, CD166) were significantly downregulated, indicating a more metastatic phenotype of CTCs compared to bulk tumor cells derived from hepatic metastases. The stem cell markers DLG7 and BMI1 were significantly upregulated in CTC, indicating a stem cell-like phenotype and increased capacity of tumor formation and self-renewal. In concert with their in vitro and in vivo tumorigenicity, these findings indicate stem cell properties of mouse-derived CTCs.In conclusion, we developed an orthotopic mouse model of CRC recapitulating the process of CRC dissemination. CTCs derived from this model exhibit stem-cell like characteristics and are able to form colonies in vitro and tumors in vivo. Our results provide new insight into the biology of CRC-derived CTCs and may provide new therapeutic targets in the metastatic cascade of CRC. PMID:27029058

  13. Differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts.

    PubMed Central

    Yashiro, M.; Chung, Y. S.; Kubo, T.; Hato, F.; Sowa, M.

    1996-01-01

    Scirrhous gastric cancer cells proliferate rapidly with fibrosis, when the cancer cells invade into the submucosa of the stomach. To investigate the mechanisms responsible for the rapid proliferation, the growth interaction between gastric cancer cells and fibroblasts was examined. Human gastric cancer cell lines established from scirrhous carcinoma or well-differentiated adenocarcinoma were used. Human fibroblast cell lines were obtained from various organs. The growth interaction between gastric cancer cells and fibroblasts was examined by calculating the number of cancer cells or by measuring [3H]thymidine incorporation of cancer cells. Gastric fibroblasts specifically stimulated the growth of scirrhous gastric cancer cells, but not that of well-differentiated adenocarcinoma cells. The growth factor(s) produced from gastric fibroblasts were then partially purified and characterised. The growth-promoting factor(s) had apparent molecular weights of 10000 dalton and was sensitive both to heat and proteinase treatment. No inhibition for the factor(s) was achieved with defined anti-growth factor antibodies. In this study, differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts were shown. Rapid proliferation of scirrhous gastric carcinoma should be partly controlled by orthotopic fibroblasts. The growth factor(s) from gastric fibroblasts, which was distinct from various defined growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF), transforming growth factor-alpha (TGF-alpha), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and transforming growth factor beta 1 (TGF-beta 1) may play an important role in the progression of scirrhous gastric cancer cells. PMID:8855981

  14. Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model

    NASA Astrophysics Data System (ADS)

    Schwartz, Jon A.; Shetty, Anil M.; Price, Roger E.; Stafford, R. Jason; Wang, James C.; Uthamanthil, Rajesh K.; Pham, Kevin; McNichols, Roger J.; Coleman, Chris L.; Payne, J. Donald

    2009-02-01

    We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8+/-4.1ºC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6+/-1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

  15. Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development

    PubMed Central

    Corson, Timothy W.; Samuels, Brian C.; Wenzel, Andrea A.; Geary, Anna J.; Riley, Amanda A.; McCarthy, Brian P.; Hanenberg, Helmut; Bailey, Barbara J.; Rogers, Pamela I.; Pollok, Karen E.; Rajashekhar, Gangaraju; Territo, Paul R.

    2014-01-01

    Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux () through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed , as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future. PMID:24901248

  16. Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development.

    PubMed

    Corson, Timothy W; Samuels, Brian C; Wenzel, Andrea A; Geary, Anna J; Riley, Amanda A; McCarthy, Brian P; Hanenberg, Helmut; Bailey, Barbara J; Rogers, Pamela I; Pollok, Karen E; Rajashekhar, Gangaraju; Territo, Paul R

    2014-01-01

    Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux ([Formula: see text]) through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed [Formula: see text], as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, [Formula: see text] in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of [Formula: see text] modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future. PMID:24901248

  17. Development of an orthotopic model of invasive pancreatic cancer in an immunocompetent murine host

    PubMed Central

    Tseng, William W.; Winer, Daniel; Kenkel, Justin A.; Choi, Okmi; Shain, Alan H.; Pollack, Jonathan R.; French, Randy; Lowy, Andrew M.; Engleman, Edgar G.

    2010-01-01

    Purpose The most common preclinical models of pancreatic adenocarcinoma utilize human cells or tissues that are xenografted into immunodeficient hosts. Several immunocompetent, genetically engineered mouse models of pancreatic cancer exist; however, tumor latency and disease progression in these models are highly variable. We sought to develop an immunocompetent, orthotopic mouse model of pancreatic cancer with rapid and predictable growth kinetics. Experimental Design Cell lines with epithelial morphology were derived from liver metastases obtained from KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre mice. Tumor cells were implanted in the pancreas of immunocompetent, histocompatible B6/129 mice, and the mice were monitored for disease progression. Relevant tissues were harvested for histological, genomic and immunophenotypic analysis. Results All mice developed pancreatic tumors by 2 weeks. Invasive disease and liver metastases were noted by 6-8 weeks. Histological examination of tumors demonstrated cytokeratin-19-positive adenocarcinoma with regions of desmoplasia. Genomic analysis revealed broad chromosomal changes along with focal gains and losses. Pancreatic tumors were infiltrated with dendritic cells, myeloid-derived suppressor cells, macrophages and T lymphocytes. Survival was decreased in RAG-/- mice, which are deficient in T cells, suggesting that an adaptive immune response alters the course of disease in wild-type mice. Conclusions We have developed a rapid, predictable orthotopic model of pancreatic adenocarcinoma in immunocompetent mice that mimics human pancreatic cancer with regard to genetic mutations, histological appearance and pattern of disease progression. This model highlights both the complexity and relevance of the immune response to invasive pancreatic cancer and may be useful for the preclinical evaluation of new therapeutic agents. PMID:20534740

  18. Renal Replacement Therapy.

    PubMed

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients' clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the "Tower of Babel" of critical care nephrology. PMID:26918174

  19. Renal Replacement Therapy

    PubMed Central

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology. PMID:26918174

  20. Thyroid hormone replacement therapy.

    PubMed

    Wiersinga, W M

    2001-01-01

    Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption phase, associated with palpitations. Liothyronine (T(3)) has the same drawback and requires twice-daily administration in view of its short half-life. Synthetic levothyroxine (L-T(4)) has many advantages: in view of its long half-life, once-daily administration suffices, the occasional missing of a tablet causes no harm, and the extrathyroidal conversion of T(4) into T(3) (normally providing 80% of the daily T(3) production rate) remains fully operative, which may have some protective value during illness. Consequently, L-T(4) is nowadays preferred, and its long-term use is not associated with excess mortality. The mean T(4) dose required to normalize serum thyroid stimulating hormone (TSH) is 1.6 microg/kg per day, giving rise to serum free T(4) (fT(4)) concentrations that are slightly elevated or in the upper half of the normal reference range. The higher fT(4) values are probably due to the need to generate from T(4) the 20% of the daily T(3) production rate that otherwise is derived from the thyroid gland itself. The daily maintenance dose of T(4) varies widely between 75 and 250 microg. Assessment of the appropriate T(4) dose is by assay of TSH and fT(4), preferably in a blood sample taken before ingestion of the subsequent T(4) tablet. Dose adjustments can be necessary in pregnancy and when medications are used that are known to interfere with the absorption or metabolism of T(4). A new equilibrium is reached after approximately 6 weeks, implying that laboratory tests should not be done earlier. With a stable maintenance dose, an annual check-up usually suffices. Accumulated experience with L-T(4) replacement has identified some areas of concern. First, the

  1. Renal Replacement Therapy.

    PubMed

    Villa, Gianluca; Ricci, Zaccaria; Ronco, Claudio

    2015-10-01

    Renal replacement therapy (RRT) is a cornerstone in the clinical management of patients with acute kidney injury. Results from different studies agree that early renal support therapy (aimed to support the residual kidney function during early phases of organ dysfunction) may reduce mortality with respect to late RRT (aimed to substitute the complete loss of function during the advanced kidney insufficiency). Although it seems plausible that a timely initiation of RRT may be associated with improved renal and nonrenal outcomes in these patients, there is scarce evidence in literature to exactly identify the most adequate onset timing for RRT. PMID:26410148

  2. Immediate total tooth replacement.

    PubMed

    Garber, D A; Salama, M A; Salama, H

    2001-03-01

    Successful implant placement at the time of extraction has been documented. Implant placement at the time of extraction was initially performed as a two-stage procedure often with barrier membranes and sophisticated second-stage surgical uncoverings. The authors describe the next generation of this technique, including atraumatic tooth removal with simultaneous root form, implant placement, and temporization at one appointment. This technique of "Immediate Total Tooth Replacement" allows for the maintenance of the bony housing and soft-tissue form that existed before extraction, while at the same time establishing a root form anchor in the bone for an esthetic restoration. PMID:11913258

  3. Real-Time GFP Intravital Imaging of the Differences in Cellular and Angiogenic Behavior of Subcutaneous and Orthotopic Nude-Mouse Models of Human PC-3 Prostate Cancer.

    PubMed

    Zhang, Yong; Toneri, Makoto; Ma, Huaiyu; Yang, Zhijian; Bouvet, Michael; Goto, Yusuke; Seki, Naohiko; Hoffman, Robert M

    2016-11-01

    There are two major types of mouse xenograft models of cancer: subcutaneous implantation and orthotopic implantation. Subcutaneous transplant models are widely used with both cancer cell lines and human-tumor specimens. Recently, subcutaneous models of patient tumors, termed patient-derived xenographs (PDX) have become highly popular and have acquired such names as "Avatar" and "Xenopatients." However, such s.c. models rarely metastasize and are therefore not patient-like. In contrast, orthotopic models have the capability to metastasize. If intact fragments of tumor tissue are implanted by surgical orthotopic implantation (SOI), the metastatic potential can match that of the donor patient. The present study images in real time, using green fluorescent protein (GFP) expression, the very different tumor behavior at the orthotopic and subcutaneous sites of human prostate cancer PC-3 in athymic nude mice. By day-2 after tumor implantation, the orthotopic tumor is already highly vascularized and the cancer cells have begun to migrate out of the tumor. In contrast, the subcutaneous tumor only begins to be vascularized by day-3 and cells do not migrate from the tumor. Angiogenesis is much more extensive in the orthotopic tumor throughout the 2-week observation period. The orthotopic PC-3-GFP tumor progresses very rapidly and distinct metastasis have appeared in lymph nodes by day-3 which rapidly appear in many areas of the abdominal cavity including portal lymph nodes by day-7. At day-14, no invasion or metastasis was observed with the s.c. tumor even when the animal was extensively explored. These results explain why orthotopic tumors mimimc clinical metastatic tumors in nude mice and why subcutaneous tumors do not. J. Cell. Biochem. 117: 2546-2551, 2016. © 2016 Wiley Periodicals, Inc. PMID:27012365

  4. Cadmium plating replacements

    SciTech Connect

    Nelson, M.J.; Groshart, E.C.

    1995-03-01

    The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

  5. Sutureless aortic valve replacement

    PubMed Central

    Phan, Kevin

    2015-01-01

    The increasing incidence of aortic stenosis and greater co-morbidities and risk profiles of the contemporary patient population has driven the development of minimally invasive aortic valve surgery and percutaneous transcatheter aortic valve implantation (TAVI) techniques to reduce surgical trauma. Recent technological developments have led to an alternative minimally invasive option which avoids the placement and tying of sutures, known as “sutureless” or rapid deployment aortic valves. Potential advantages for sutureless aortic prostheses include reducing cross-clamp and cardiopulmonary bypass (CPB) duration, facilitating minimally invasive surgery and complex cardiac interventions, whilst maintaining satisfactory hemodynamic outcomes and low paravalvular leak rates. However, given its recent developments, the majority of evidence regarding sutureless aortic valve replacement (SU-AVR) is limited to observational studies and there is a paucity of adequately-powered randomized studies. Recently, the International Valvular Surgery Study Group (IVSSG) has formulated to conduct the Sutureless Projects, set to be the largest international collaborative group to investigate this technology. This keynote lecture will overview the use, the potential advantages, the caveats, and current evidence of sutureless and rapid deployment aortic valve replacement (AVR). PMID:25870807

  6. Cadmium plating replacements

    NASA Technical Reports Server (NTRS)

    Nelson, Mary J.; Groshart, Earl C.

    1995-01-01

    The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

  7. Power Plant Replacement Study

    SciTech Connect

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University’s aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  8. Power Plant Replacement Study

    SciTech Connect

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University's aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  9. Total disc replacement.

    PubMed

    Vital, J-M; Boissière, L

    2014-02-01

    Total disc replacement (TDR) (partial disc replacement will not be described) has been used in the lumbar spine since the 1980s, and more recently in the cervical spine. Although the biomechanical concepts are the same and both are inserted through an anterior approach, lumbar TDR is conventionally indicated for chronic low back pain, whereas cervical TDR is used for soft discal hernia resulting in cervicobrachial neuralgia. The insertion technique must be rigorous, with precise centering in the disc space, taking account of vascular anatomy, which is more complex in the lumbar region, particularly proximally to L5-S1. All of the numerous studies, including prospective randomized comparative trials, have demonstrated non-inferiority to fusion, or even short-term superiority regarding speed of improvement. The main implant-related complication is bridging heterotopic ossification with resulting loss of range of motion and increased rates of adjacent segment degeneration, although with an incidence lower than after arthrodesis. A sufficiently long follow-up, which has not yet been reached, will be necessary to establish definitively an advantage for TDR, particularly in the cervical spine. PMID:24412045

  10. Power Plant Replacement Study

    SciTech Connect

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self‐funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University’s aging and failing circa 1925 central steam production plant. Twenty‐three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  11. Knee joint replacement prosthesis (image)

    MedlinePlus

    A prosthesis is a device designed to replace a missing part of the body, or to make a part of the body work better. The metal prosthetic device in knee joint replacement surgery replaces cartilage and bone which is damaged from disease or aging.

  12. Successful management of hemolysis in ABO-nonidentical orthotopic liver transplantation by steroid therapy: a case report.

    PubMed

    Auwerda, J J; Bac, D J; van't Veer, M B; de Rave, S; Yzermans, J N

    1996-01-01

    Hemolysis due to donor-derived B lymphocytes has been reported in patients who have undergone ABO-nonidentical orthotopic liver transplantation (OLT). Yet, until now, little was known about the management of this transplantation-induced hemolysis. In this report we describe our experience with hemolysis in a patient after OLT. In addition, based on theoretical assumption, we hypothesize that corticosteroids can be helpful in the management of ABO-nonidentical OLT-induced hemolysis. PMID:8875796

  13. Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial

    PubMed Central

    2013-01-01

    Background In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver transplantation is currently managed by transfusion of red blood cell concentrates, platelet concentrates, fresh frozen plasma, and fibrinogen concentrate. Transfusion of these products may paradoxically result in an increased bleeding tendency due to aggravated portal hypertension. The hemostatic effect of these products may therefore be overshadowed by bleeding complications due to volume overload. In contrast to these transfusion products, prothrombin complex concentrate is a low-volume highly purified concentrate, containing the four vitamin K dependent coagulation factors. Previous studies have suggested that administration of prothrombin complex concentrate is an effective method to normalize a prolonged prothrombin time in patients with liver cirrhosis. We aim to investigate whether the pre-operative administration of prothrombin complex concentrate in patients undergoing liver transplantation for end-stage liver cirrhosis, is a safe and effective method to reduce perioperative blood loss and transfusion requirements. Methods/Design This is a double blind, multicenter, placebo-controlled randomized trial. Cirrhotic patients with a prolonged INR (≥1.5) undergoing liver transplantation will be randomized between placebo or prothrombin complex concentrate administration prior to surgery. Demographic, surgical and transfusion data will be recorded. The primary outcome of this study is RBC transfusion requirements. Discussion Patients with advanced cirrhosis have reduced plasma levels of both pro- and anticoagulant coagulation proteins. Prothrombin complex concentrate is a low-volume plasma product that contains both procoagulant and anticoagulant proteins and

  14. NRL attacks halon replacement

    SciTech Connect

    Baturin, D.

    1994-07-01

    In November 1992, as a result of the International Montreal Protocol Treaty and its addenda, it was announced that worldwide production of halons would halt by January 1994. Research has shown that halons, with the component bromine, would likely be more damaging to the ozone layer than chlorofluorocarbons. Today, while other researchers are looking at ways to limit the use of or to recycle halogenated fire suppressants, the Naval Research Laboratory (NRL) is conducting active programs aimed at developing replacement agents. The program includes laboratory-scale screening of candidate agents, intermediate-scale chamber tests, and full-scale shipboard discharge fire tests. A substantial research effort is underway on the measurement of the effectiveness of alternate, nonhalogen-containing suppressants; the elucidation of the chemical and physical mechanisms by which they suppress fires; and the development of theory and models on the relationship of chemical structures to suppressive behavior.

  15. Aerocoat 7 Replacement Coatings

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Kennedy Space Center has used Aerocoat 7 (AR-7) to protect stainless-steel flex hoses at Launch Complex (LC-39) and hydraulic lines of the Mobile Launcher Platform (MLP) because it provides excellent corrosion protection in low-temperature applications. The Sovereign Company produced AR-7 exclusively for NASA but discontinued production because the coating released high levels of volatile organic compounds (VOCs) and had a significant environmental impact. The purpose of this project was to select and evaluate potential replacement coatings for AR-7 that would be more environmentally sound. The physical and mechanical properties of commercially available coatings were investigated through the Internet. The ideal coating would be fluid enough to penetrate the outer mesh of a stainless-steel flex hose and coat the inner hose, and flexible enough to withstand the movement of the hose, as well as the expansion and contraction of its metal caused by changes in temperature.

  16. Antenna grout replacement system

    NASA Technical Reports Server (NTRS)

    Mcclung, C. E. (Inventor)

    1983-01-01

    An epoxy grout suitable for use in mounting and positioning bearing runner plates used in hydrostatic bearing assemblies for rotatably mounting large radio telescope structures to stationary support pedestals is described. The epoxy grout may be used in original mountings or may be used as part of a replacement system for repairing cavities in existing grout resulting from grout deterioration. The epoxy grout has a relatively short work life and cure time even in the presence of hydraulic oil. The epoxy grout cures without shrinking or sagging to form a grout which is sufficiently strong and durable to provide a grout especially well suited for use under the high pressure loading and close tolerance requirements of large hydrostatic bearing assemblies.

  17. Targeted Non-invasive Imaging of EGFR-expressing Orthotopic Pancreatic Cancer using Multispectral Optoacoustic Tomography (MSOT)

    PubMed Central

    Hudson, Shanice V.; Huang, Justin S.; Yin, Wenyuan; Albeituni, Sabrin; Rush, Jamie; Khanal, Anil; Yan, Jun; Ceresa, Brian P.; Frieboes, Hermann B.; McNally, Lacey R.

    2014-01-01

    Detection of orthotopic xenograft tumors is difficult due to poor spatial resolution and reduced image fidelity with traditional optical imaging modalities. In particular, light scattering and attenuation in tissue at depths beyond subcutaneous implantation hinder adequate visualization. We evaluate the use of multispectral optoacoustic tomography (MSOT) to detect upregulated epidermal growth factor (EGF) receptor in orthotopic pancreatic xenografts using a near-infrared (NIR) EGF-conjugated CF-750 fluorescent probe. MSOT is based on the photoacoustic effect and thus not limited by photon scattering, resulting in high-resolution tomographic images. Pancreatic tumor-bearing mice with luciferase-transduced S2VP10L tumors were intravenously injected with EGF-750 probe prior to MSOT imaging. We characterized probe specificity and bioactivity via immunoblotting, immunocytochemistry, and flow cytometric analysis. In vitro data along with optical bioluminescence/fluorescence imaging were used to validate acquired MSOT in vivo images of probe biodistribution. Indocyanine green dye was used as a non-specific control to define specificity of EGF-probe accumulation. Maximum accumulation occurred at six hours post-injection, demonstrating specific intra-tumoral probe uptake and minimal liver and kidney off-target accumulation. Optical bioluminescence and fluorescence imaging confirmed tumor-specific probe accumulation consistent with MSOT images. These studies demonstrate the utility of MSOT to obtain volumetric images of ligand probe biodistribution in vivo to detect orthotopic pancreatic tumor lesions through active targeting of EGF receptor. PMID:25217521

  18. Disruptive TP53 Mutation is Associated with Aggressive Disease Characteristics in an Orthotopic Murine Model of Oral Tongue Cancer

    PubMed Central

    Sano, Daisuke; Xie, Tong-Xin; Ow, Thomas J.; Zhao, Mei; Pickering, Curtis R.; Zhou, Ge; Sandulache, Vlad C.; Wheeler, David A.; Gibbs, Richard A.; Caulin, Carlos; Myers, Jeffrey N.

    2011-01-01

    Purpose To characterize tumor growth and metastatic potential in head and neck squamous cell carcinoma (HNSCC) cell lines in an orthotopic murine model of oral tongue cancer, and to correlate TP53 mutation status with these findings. Experimental Design Cells from each of 48 HNSCC cell lines were orthotopically injected into the oral tongues of nude mice. Tumor volume, cervical lymph node metastasis, and mouse survival were recorded. Direct sequencing of the TP53 gene and western blot analysis for the p53 protein after induction with 5-fluorouracil was performed. Cell lines were categorized as either mutant TP53 or wild-type TP53, and lines with TP53 mutation were further categorized on the basis of type of mutation (disruptive or non-disruptive), and level of p53 protein expression. The behavior of tumors in these different groups was compared. Results The 48 HNSCC cell lines showed a wide range of behavior from highly aggressive and metastatic to no tumor formation. Mice injected with cells harboring disruptive TP53 mutations had faster tumor growth, greater incidence of cervical lymph node metastasis, and shorter survival than mice injected with cells lacking these mutations. Conclusions HNSCC cell lines display a wide spectrum of behavior in an orthotopic model of oral cancer. Cell lines with disruptive TP53 mutations are more aggressive in this system, corroborating clinical reports that have linked these mutations to poor patient outcome. PMID:21903770

  19. Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours

    PubMed Central

    Steen, Stig; Paskevicius, Audrius; Liao, Qiuming; Sjöberg, Trygve

    2016-01-01

    Abstract Objectives. The aim of this study was to demonstrate safe orthotopic transplantation of porcine donor hearts harvested 24 hours after brain death and preserved for 24 hours before transplantation. Design. Circulatory normalization of brain dead (decapitated) pigs was obtained using a new pharmacological regimen (n = 10). The donor hearts were perfused at 8 °C in cycles of 15 min perfusion followed by 60 min without perfusion. The perfusate consisted of an albumin-containing hyperoncotic cardioplegic nutrition solution with hormones and erythrocytes. Orthotopic transplantation was done in 10 recipient pigs after 24 hours’ preservation. Transplanted pigs were monitored for 24 hours, then an adrenaline stress test was done. Results. All transplanted pigs were stable throughout the 24-hour observation period with mean aortic pressure around 80 mmHg and normal urine production. Mean right and left atrial pressures were in the range of 3–6 and 5–10 mmHg, respectively. Blood gases at 24 hours did not differ from baseline values. The adrenaline test showed a dose dependent response, with aortic pressure increasing from 98/70 to 220/150 mmHg and heart rate from 110 to 185 beats/min. Conclusion. Orthotopic transplantation of porcine hearts harvested 24 hours after brain death and preserved for 24 hours can be done safely. PMID:26882241

  20. Short stem shoulder replacement

    PubMed Central

    Bell, Simon N.; Coghlan, Jennifer A.

    2014-01-01

    Context: It is agreed that it is important to anatomically reproduce the proximal humeral anatomy when performing a prosthetic shoulder replacement. This can be difficult with a long stemmed prosthesis, in particular if there is little relationship of the metaphysis to the humeral shaft. The ‘short stem’ prosthesis can deal with this problem. Aims: A prospective study assessed the results of total shoulder arthroplasty using a short stem humeral prosthesis, a ceramic humeral head, and a pegged cemented polyethylene glenoid. Materials and methods: Patients with primary shoulder osteoarthritis were recruited into this prospective trial and pre-operatively had the ASES, Constant, SPADI, and DASH scores recorded. The patients were clinically reviewed at the two weeks, eight weeks, one year, and two year mark with completion of a data form. Radiological evaluation was at the eight week, one year and two year follow-up. At the one and two year follow-up the satisfaction rating, the range of passive and active motion, Constant, ASES, SPADI, DASH and pain results were recorded and analysed with SPPS 20. Results: During the study period 97 short stem, ceramic head total shoulder replacements were carried out. At the time of follow-up 12 were two years from operation and 38 one year from operation. Active elevation was overall mean 160 degrees. Constant scores were 76 at 1 year, and 86 at 2 years, ASES 88 and 93, and satisfaction 96% and 98% respectively at one and 2 year follow up. There were no problems during insertion of the humeral prosthesis, or any radiolucent lines or movement of the prosthesis on later radiographs. Conclusion: The short stem prosthesis had no complications, and on follow up radiographs good bone fixation. These fairly short term clinical results were overall good. PMID:25258497

  1. TCGA data and patient-derived orthotopic xenografts highlight pancreatic cancer-associated angiogenesis.

    PubMed

    Gore, Jesse; Craven, Kelly E; Wilson, Julie L; Cote, Gregory A; Cheng, Monica; Nguyen, Hai V; Cramer, Harvey M; Sherman, Stuart; Korc, Murray

    2015-04-10

    Pancreatic ductal adenocarcinomas (PDACs) overexpress pro-angiogenic factors but are not viewed as vascular. Using data from The Cancer Genome Atlas we demonstrate that a subset of PDACs exhibits a strong pro-angiogenic signature that includes 37 genes, such as HDAC9, that are overexpressed in PDAC arising in KRC mice, which express mutated Kras and lack RB. Moreover, patient-derived orthotopic xenografts can exhibit tumor angiogenesis, whereas conditioned media (CM) from KRC-derived pancreatic cancer cells (PCCs) enhance endothelial cell (EC) growth and migration, and activate canonical TGF-β signaling and STAT3. Inhibition of the type I TGF-β receptor with SB505124 does not alter endothelial activation in vitro, but decreases pro-angiogenic gene expression and suppresses angiogenesis in vivo. Conversely, STAT3 silencing or JAK1-2 inhibition with ruxolitinib blocks CM-enhanced EC proliferation. STAT3 disruption also suppresses endothelial HDAC9 and blocks CM-induced HDAC9 expression, whereas HDAC9 re-expression restores CM-enhanced endothelial proliferation. Moreover, ruxolitinib blocks mitogenic EC/PCC cross-talk, and suppresses endothelial p-STAT3 and HDAC9, and PDAC progression and angiogenesis in vivo, while markedly prolonging survival of KRC mice. Thus, targeting JAK1-2 with ruxolitinib blocks a final pathway that is common to multiple pro-angiogenic factors, suppresses EC-mediated PCC proliferation, and may be useful in PDACs with a strong pro-angiogenic signature. PMID:25762644

  2. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model.

    PubMed

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-03-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

  3. Effectively Screening for Coronary Artery Disease in Patients Undergoing Orthotopic Liver Transplant Evaluation

    PubMed Central

    Li, Feng; Hanje, Adam J.; Mumtaz, Khalid; Boudoulas, Konstantinos D.; Lilly, Scott M.

    2016-01-01

    Coronary artery disease (CAD) is prevalent in patients with end-stage liver disease and associated with poor outcomes when undergoing orthotopic liver transplantation (OLT); however, noninvasive screening for CAD in this population is less sensitive. In an attempt to identify redundancy, we reviewed our experience among patients undergoing CAD screening as part of their OLT evaluation between May 2009 and February 2014. Demographic, clinical, and procedural characteristics were analyzed. Of the total number of screened patients (n = 132), initial screening was more common via stress testing (n = 100; 75.8%) than coronary angiography (n = 32; 24.2%). Most with initial stress testing underwent angiography (n = 52; 39.4%). Among those undergoing angiography, CAD was common (n = 31; 23.5%). Across the entire cohort the number of traditional risk factors was linearly associated with CAD, and those with two or more risk factors were found to have CAD by angiography 50% of the time (OR 1.92; CI 1.07–3.44, p = 0.026). Our data supports that CAD is prevalent among pre-OLT patients, especially among those with 2 or more risk factors. Moreover, we identified a lack of uniformity in practice and the need for evidence-based and standardized screening protocols. PMID:27418975

  4. Evolving experience with prevention and treatment of splenic artery syndrome after orthotopic liver transplantation.

    PubMed

    Mogl, Martina T; Nüssler, Natascha C; Presser, Sabine J; Podrabsky, Petr; Denecke, Timm; Grieser, Christian; Neuhaus, Peter; Guckelberger, Olaf

    2010-08-01

    Impaired hepatic arterial perfusion after orthotopic liver transplantation (OLT) may lead to ischemic biliary tract lesions and graft-loss. Hampered hepatic arterial blood flow is observed in patients with hypersplenism, often described as arterial steal syndrome (ASS). However, arterial and portal perfusions are directly linked via the hepatic arterial buffer response (HABR). Recently, the term 'splenic artery syndrome' (SAS) was coined to describe the effect of portal hyperperfusion leading to diminished hepatic arterial blood flow. We retrospectively analyzed 650 transplantations in 585 patients. According to preoperative imaging, 78 patients underwent prophylactic intraoperative ligation of the splenic artery. In case of postoperative SAS, coil-embolization of the splenic artery was performed. After exclusion of 14 2nd and 3rd retransplantations and 83 procedures with arterial interposition grafts, SAS was diagnosed in 28 of 553 transplantations (5.1%). Twenty-six patients were treated with coil-embolization, leading to improved liver function, but requiring postinterventional splenectomy in two patients. Additionally, two patients with SAS underwent splenectomy or retransplantation without preceding embolization. Prophylactic ligation could not prevent SAS entirely (n = 2), but resulted in a significantly lower rate of complications than postoperative coil-embolization. We recommend prophylactic ligation of the splenic artery for patients at risk of developing SAS. Post-transplant coil-embolization of the splenic artery corrected hemodynamic changes of SAS, but was associated with a significant morbidity. PMID:20180930

  5. Generation of Noninvasive, Quantifiable, Orthotopic Animal Models for NF2-Associated Schwannoma and Meningioma.

    PubMed

    Burns, Sarah S; Chang, Long-Sheng

    2016-01-01

    Schwannomas and meningiomas are nervous system tumors that can occur sporadically or in patients with neurofibromatosis type 2 (NF2). Mutations of the Neurofibromatosis 2 (NF2) gene are frequently observed in these tumors. Schwannomas and meningiomas cause significant morbidities, and an FDA-approved medical therapy is currently not available. The development of preclinical animal models that accurately capture the clinical characteristics of these tumors will facilitate the evaluation of novel therapeutic agents for the treatment of these tumors, ultimately leading to more productive clinical trials. Here, we describe the generation of luciferase-expressing NF2-deficient schwannoma and meningioma cells and the use of these cells to establish orthotopic tumor models in immunodeficient mice. The growth of these tumors and their response to treatment can be measured effectively by bioluminescence imaging (BLI) and confirmed by small-animal magnetic resonance imaging (MRI). These and other animal models, such as genetically-engineered models, should substantially advance the investigation of promising therapies for schwannomas and meningiomas. PMID:27259921

  6. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts1

    PubMed Central

    Herrmann, Kelsey; Erokwu, Bernadette O.; Johansen, Mette L.; Basilion, James P.; Gulani, Vikas; Griswold, Mark A.; Flask, Chris A.; Brady-Kalnay, Susann M.

    2016-01-01

    Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI) techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents. PMID:27084431

  7. Prolonged Delirium With Catatonia Following Orthotopic Liver Transplant Responsive to Memantine.

    PubMed

    Brown, Gregory D; Muzyk, Andrew J; Preud'homme, Xavier A

    2016-03-01

    A 59-year-old man with nonalcoholic steatohepatitis cirrhosis underwent an orthotopic liver transplant and experienced a complicated postoperative course, including a prolonged delirium. After discharge to rehabilitation, he had 2 subsequent admissions for delirium. On the first readmission, the transplant team started the patient on risperidone and resumed treatment with sertraline. On his second readmission, neurology and psychiatry were consulted. On evaluation, the patient demonstrated signs of catatonia. On the basis of recommendations from psychiatry, the risperidone and sertraline were stopped, and the patient was started on mirtazapine. He failed to demonstrate improvement within the next 48 hours. Extensive work-up demonstrated a multifactorial etiology for his delirium, including calcineurin-related neuropsychiatric toxicity from tacrolimus leading to possible posterior reversible encephalopathy syndrome. However, after the initiation of memantine on hospital day 3-before the cessation of tacrolimus-the patient demonstrated marked improvement in mental status and motor symptoms. His magnetic resonance imaging, in addition to findings that raised concerns about posterior reversible encephalopathy syndrome, had demonstrated bilateral basal ganglia abnormalities on T1 imaging of uncertain origin. It is postulated that these findings served as predisposing factors for the patient's catatonic symptoms. Although it has been described in case reports following liver transplant, catatonia remains an underrecognized neuropsychiatric complication following liver transplant. This case demonstrates the effectiveness of memantine, an N-methyl-D-aspartic acid antagonist that decreases glutamine excitotoxicity, as a potential treatment for catatonia in postliver transplant patients. PMID:27138082

  8. Dexmedetomidine Pretreatment Attenuates Kidney Injury and Oxidative Stress during Orthotopic Autologous Liver Transplantation in Rats

    PubMed Central

    Wu, Shan; Jin, Yi; Wang, Yiheng; Cai, Jun

    2016-01-01

    This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecific α2 receptor blocker) + high dose Dex (group B1), ARC239 (a specific α2B/c receptor blocker) + high dose Dex (group B2), and BRL-44408 (a specific α2A receptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (all P < 0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 through α2A receptor, increases the antioxidant levels, and attenuates renal injury during OALT. PMID:26682005

  9. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

    PubMed Central

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-01-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

  10. TCGA data and patient-derived orthotopic xenografts highlight pancreatic cancer-associated angiogenesis

    PubMed Central

    Gore, Jesse; Craven, Kelly E.; Wilson, Julie L.; Cote, Gregory A.; Cheng, Monica; Nguyen, Hai V.; Cramer, Harvey M.; Sherman, Stuart; Korc, Murray

    2015-01-01

    Pancreatic ductal adenocarcinomas (PDACs) overexpress pro-angiogenic factors but are not viewed as vascular. Using data from The Cancer Genome Atlas we demonstrate that a subset of PDACs exhibits a strong pro-angiogenic signature that includes 37 genes, such as HDAC9, that are overexpressed in PDAC arising in KRC mice, which express mutated Kras and lack RB. Moreover, patient-derived orthotopic xenografts can exhibit tumor angiogenesis, whereas conditioned media (CM) from KRC-derived pancreatic cancer cells (PCCs) enhance endothelial cell (EC) growth and migration, and activate canonical TGF-β signaling and STAT3. Inhibition of the type I TGF-β receptor with SB505124 does not alter endothelial activation in vitro, but decreases pro-angiogenic gene expression and suppresses angiogenesis in vivo. Conversely, STAT3 silencing or JAK1–2 inhibition with ruxolitinib blocks CM-enhanced EC proliferation. STAT3 disruption also suppresses endothelial HDAC9 and blocks CM-induced HDAC9 expression, whereas HDAC9 re-expression restores CM-enhanced endothelial proliferation. Moreover, ruxolitinib blocks mitogenic EC/PCC cross-talk, and suppresses endothelial p-STAT3 and HDAC9, and PDAC progression and angiogenesis in vivo, while markedly prolonging survival of KRC mice. Thus, targeting JAK1–2 with ruxolitinib blocks a final pathway that is common to multiple pro-angiogenic factors, suppresses EC-mediated PCC proliferation, and may be useful in PDACs with a strong pro-angiogenic signature. PMID:25762644

  11. Temozolomide/PLGA microparticles plus vatalanib inhibits tumor growth and angiogenesis in an orthotopic glioma model.

    PubMed

    Zhang, Yu-Hui; Yue, Zhi-Jian; Zhang, He; Tang, Gu-Sheng; Wang, Yang; Liu, Jian-Min

    2010-11-01

    Temozolomide (TM) has anti-tumor activity in patients with malignant glioma. Implantable poly (D,L-lactide-co-glycolide) (PLGA) microparticles of TM (TM-MS) have been developed, enhancing the cytotoxicity of TM to Glioma C6 cells. Vatalanib, as anti-angiogenic agent, has also shown anti-tumor activity with malignant gliomas. We examined the combined effects of TM-MS and vatalanib in a rat orthotopic glioma model and found TM-MS offered a greater tumor inhibition than TM, and combination treatment with both of them improved the survival time versus single agent therapy. The combination treatment also demonstrated an inhibition to rat glioma tumors, a significant decrease in cell proliferation, an increase in apoptosis, and a lower microvessel density within the glioma tumors. The results suggest that TM-MS can more effectively inhibit tumor than TM, and combination treatment with TM-MS and vatalanib inhibits tumor growth and angiogenesis and may prove to be a promising therapy for malignant gliomas. PMID:20816959

  12. Incidence of and risk factors for ischemic-type biliary lesions following orthotopic liver transplantation.

    PubMed

    Heidenhain, Christoph; Pratschke, Johann; Puhl, Gero; Neumann, Ulf; Pascher, Andreas; Veltzke-Schlieker, Winfried; Neuhaus, Peter

    2010-01-01

    Ischemic-type biliary lesions (ITBL) account for a major part of patients' morbidity and mortality after orthotopic liver transplantation (OLT). The exact origin of this type of biliary complication remains unknown. This study retrospectively evaluated 1843 patients. Patients with primary sclerosing cholangitis were excluded from this study. The diagnosis of ITBL was established only when all other causes of destruction of the biliary tree were ruled out. Donor age (P = 0.028) and cold ischemic time (CIT) (P = 0.002) were found to be significant risk factors for the development of ITBL. Organs that were perfused with University of Wisconsin (UW) solution developed ITBL significantly more often than Histidine-Tryptophan-Ketoglutarate (HTK)-perfused organs (P = 0.036). The same applied to organs harvested externally and shipped to our center versus those that were procured locally by our harvest teams (P < 0.001). Pressure perfusion via the hepatic artery significantly reduced the risk of ITBL (P = 0.001). The only recipient factor that showed a significant influence was Child-Pugh score status C (P = 0.021). Immunologic factors had no significant impact on ITBL. The clinical consequences of this study for our institution have been the strict limitation of CIT to <10 h and the exclusive use of HTK solution. We further advocate that all organ procurement teams perform pressure perfusion on harvested organs. PMID:19691661

  13. Role of Interventional Radiology in the Treatment of Biliary Strictures Following Orthotopic Liver Transplantation

    SciTech Connect

    Righi, Dorico; Cesarani, Federico; Muraro, Emanuele; Gazzera, Carlo; Salizzoni, Mauro; Gandini, Giovanni

    2002-01-15

    Purpose: To evaluate the efficacy and safety of percutaneous treatment of biliary strictures complicating orthotopic liver transplantation (OLT). Methods: Between October 1990 and May 2000, 619 patients underwent 678 liver transplants. Seventy of the 619 (11%) patients were found to be affected by biliary strictures by July 2000. Bilioplasty was performed in 51 of these 70 (73%) patients. A cohort of 33 of 51 (65%) patients were clinically followed for more than 12 months after the last percutaneous treatment and included in the survey results. Results: After one to three treatments 24 of 33 (73%)patients were stricture-free on ultrasound and MR cholangiography follow-up. A delayed stricture recurrence required a fourth percutaneous bilioplasty in two of 33 (6%) patients. A surgical bilioenteric anastomosis was performed in six of 33 (18%) patients.Retransplantation was performed due to ischemic damage in one of 33(3%) patients. Conclusion: Interventional radiology is an effective therapeutic alternative for the treatment of most biliary strictures complicating OLT. It has a high success rate and should be considered before surgical interventions. Elective surgery may be necessary in a few failed cases or those with more severe and extensive biliary strictures.

  14. Transcatheter Splenic Artery Occlusion for Treatment of Splenic Artery Steal Syndrome After Orthotopic Liver Transplantation

    SciTech Connect

    Uflacker, Renan; Selby, J. Bayne; Chavin, Kenneth; Rogers, Jeffrey; Baliga, Prabhakar

    2002-08-15

    Purpose: To review some aspects of the problem of splenic artery steal syndrome as cause of ischemia in transplanted livers and treatment by selective splenic artery occlusion. Materials and Methods: Eleven liver transplant patients from a group of 350 patients, nine men and two women,ranging in age from 40 years to 61 years (mean 52 years), presented with biochemical evidences of liver ischemia and failure, ranging from one to 60 days following orthotopic liver transplantation. Diagnosis of splenic artery steal syndrome was suspected by elevated enzymes, Doppler ultrasound and confirmed by celiac angiogram. Patients with confirmed hepatic artery thrombosis before angiography were excluded from the study. Embolization with Gianturco coils was performed. Results: All patients were treated by splenic artery embolization with Gianturco coils. The 11 patients improved clinically within 24 hours of the procedure with significant change in the biochemical and clinical parameters. Followup ranged from one month to two years. One of the 11 patient initially improved, but developed hepatic artery thrombosis within 24 hours of the embolic treatment,requiring surgical repair. Conclusion: Splenicartery steal syndrome following liver transplantation surgery can be diagnosed by celiac angiography, and effectively treated by splenic artery embolization with coils. Embolization is one of the treatments available, it is minimally invasive, and leads to immediate clinical improvement. Hepatic artery thrombosis is a possible complication of the procedure.

  15. Use of multiphoton microscopy to diagnose liver cancer and lung metastasis in an orthotopic rat model.

    PubMed

    Yan, Jun; Zhuo, Shuangmu; Chen, Gang; Tan, Changjun; Zhu, Weifeng; Lu, Jianping; Fan, Jia; Chen, Jianxin; Zhou, Jian

    2012-01-01

    Liver or lung biopsy for suspicious lesions has several disadvantages such as bleeding, bile leak or pneumothorax, needle track seeding, and time-consuming histopathological procedure. The ability to directly observe cellular and subcellular details and then perform "optical biopsy" is a major goal in the development of new interventional techniques. Multiphoton microscopy (MPM) enables real-time noninvasive visualization of tissue architecture and cell morphology in live tissue. We performed a study to evaluate whether MPMcan make real-time optical diagnosis for liver cancer and lung metastasis using an orthotopic rat model with Morris hepatoma. We found that real-time high-resolution MPMimaging could clearly show tissue architecture and cell morphology. In the normal liver tissue, MPMimaging clearly revealed the blood-filled sinusoids and cords of hepatocytes. In the cancerous tissue, MPMimaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. MPMimages were comparable to golden standard hematoxylin-eosin staining images. Moreover, MPMimaging had deep penetration with the capability of optical sectioning. In short, MPMcan make real-time optical diagnosis for liver cancer and lung metastasis. This study provides the groundwork for further using multiphoton endoscopy to perform real-time noninvasive "optical biopsy" for liver cancer and lung metastasis in the near future. PMID:22331704

  16. An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis.

    PubMed

    Reiberger, Thomas; Chen, Yunching; Ramjiawan, Rakesh R; Hato, Tai; Fan, Christopher; Samuel, Rekha; Roberge, Sylvie; Huang, Peigen; Lauwers, Gregory Y; Zhu, Andrew X; Bardeesy, Nabeel; Jain, Rakesh K; Duda, Dan G

    2015-08-01

    Subcutaneous xenografts have been used for decades to study hepatocellular carcinoma (HCC). These models do not reproduce the specific pathophysiological features of HCCs, which occur in cirrhotic livers that show pronounced necroinflammation, abnormal angiogenesis and extensive fibrosis. As these features are crucial for studying the role of the pathologic host microenvironment in tumor initiation, progression and treatment response, alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC model in immunocompetent mice with liver cirrhosis induced by carbon tetrachloride (CCl4) that recapitulates key features of human HCC. Induction of substantial hepatic fibrosis requires 12 weeks of CCl4 administration. Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse. Tumor growth varies by tumor cell line and mouse strain used. Alternatively, tumors can be induced in a genetically engineered mouse model. In this setting, CCl4 is administered for 12 weeks after tail-vein injection of Cre-expressing adenovirus (adeno-Cre) in Stk4(-/-)Stk3(F/-) (also known as Mst1(-/-)Mst2(F/-); F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis. PMID:26203823

  17. Establishment of an Orthotopic Xenograft Mice Model of Retinoblastoma Suitable for Preclinical Testing.

    PubMed

    Cassoux, Nathalie; Thuleau, Aurélie; Assayag, Franck; Aerts, Isabelle; Decaudin, Didier

    2015-04-01

    Retinoblastoma is a rare cancer that occurs during childhood. The goal of current and future therapeutic strategies is to conserve the eye and visual function without using external beam radiotherapy, which is known to increase the risk of secondary cancers in genetically predisposed patients. Multimodality therapy (usually intravenous but also intra-arterial and intravitreal chemotherapy, transpupillary thermotherapy, cryotherapy, or brachytherapy) has recently improved the eye salvage rate in retinoblastoma and has led to a decreased need for external beam radiotherapy. However, the treatment of advanced intraocular retinoblastoma remains a real challenge, especially in cases of vitreous and subretinal seeding. There is a need for alternative and less toxic therapies as well as for better ways to administer the drugs. Animal models are an integral part of preclinical research in the field of oncology. This paper describes the different xenograft rodent models published in the literature so far. We will also describe a new orthotopic xenografted retinoblastoma model in immunodeficient mice, which is suitable for preclinical assays. The xenograft model was established from tumor tissue obtained directly from surgical samples and closely mimics human retinoblastoma. PMID:27171982

  18. A novel mucosal orthotopic murine model of human papillomavirus-associated genital cancers.

    PubMed

    Decrausaz, Loane; Gonçalves, Ana-Rita; Domingos-Pereira, Sonia; Pythoud, Christelle; Stehle, Jean-Christophe; Schiller, John; Jichlinski, Patrice; Nardelli-Haefliger, Denise

    2011-05-01

    Cervical cancer results from infection with high-risk type human papillomaviruses (HPV). Therapeutic vaccines aiming at controlling existing genital HPV infections and associated lesions are usually tested in mice with HPV-expressing tumor cells subcutaneously implanted into their flank. However, effective vaccine-induced regression of these ectopic tumors strongly contrasts with the poor clinical results of these vaccines produced in patients with HPV-associated genital neoplasia. To assess HPV therapeutic vaccines in a more relevant setting, we have, here, established an orthotopic mouse model where tumors in the genital mucosa (GM) develop after an intravaginal instillation of HPV16 E6/E7-expressing tumor cells transduced with a luciferase-encoding lentiviral vector for in vivo imaging of tumor growth. Tumor take was 80-90% after nonoxynol-9 induced damage of the epithelium. Tumors remained localized in the genital tract, and histological analysis showed that most tumors grew within the squamous epithelium of the vaginal wall. Those tumors induced (i) E7-specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non-regressing HPV lesions. This novel genital HPV-tumor model by requiring GM homing of vaccine-induced immune responses able to overcome local immuno-suppression may be more representative of the situation occurring in patients upon therapeutic vaccination. PMID:20635385

  19. N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation.

    PubMed

    Taut, F J; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E

    2001-05-01

    In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P < or = 0.02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213

  20. N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

    PubMed Central

    Taut, F J H; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E

    2001-01-01

    In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P ≤ 0·02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213

  1. Technique of Porcine Liver Procurement and Orthotopic Transplantation using an Active Porto-Caval Shunt

    PubMed Central

    Spetzler, Vinzent N.; Goldaracena, Nicolas; Knaak, Jan M.; Louis, Kristine S.; Selzner, Nazia; Selzner, Markus

    2015-01-01

    The success of liver transplantation has resulted in a dramatic organ shortage. Each year, a considerable number of patients on the liver transplantation waiting list die without receiving an organ transplant or are delisted due to disease progression. Even after a successful transplantation, rejection and side effects of immunosuppression remain major concerns for graft survival and patient morbidity. Experimental animal research has been essential to the success of liver transplantation and still plays a pivotal role in the development of clinical transplantation practice. In particular, the porcine orthotopic liver transplantation model (OLTx) is optimal for clinically oriented research for its close resemblance to human size, anatomy, and physiology. Decompression of intestinal congestion during the anhepatic phase of porcine OLTx is important to guarantee reliable animal survival. The use of an active porto-caval-jugular shunt achieves excellent intestinal decompression. The system can be used for short-term as well as long-term survival experiments. The following protocol contains all technical information for a stable and reproducible liver transplantation model in pigs including post-operative animal care. PMID:25992583

  2. Postoperative left ventricular apical ballooning: Transient Takotsubo cardiomyopathy following orthotopic liver transplantation

    PubMed Central

    Bedanova, Helena; Orban, Marek; Nemec, Petr

    2013-01-01

    Patient: Female, 51 Final Diagnosis: Takotsubo cardiomyopathy Symptoms: — Medication: — Clinical Procedure: — Specialty: Cardiology • Transplantology Objective: Rare disease Background: Left ventricular apical ballooning syndrome (LVAB), also known as Takotsubo cardiomyopathy, is a cardiac syndrome characterized by transient left ventricular dysfunction in the absence of obstructive atherosclerotic coronary artery disease. An episode of emotional stress, typically in female patients, is believed to precede and trigger the development of this syndrome. Case Report: We report a case of Takotsubo cardiomyopathy that developed after orthotopic liver transplantation in a 51-year-old woman. On D2 (day 2) the patient had severe hemodynamic compromise. Echocardiography showed systolic dysfunction of the left ventricle (LV), with ejection fraction (EF) of 20% and anteroapical akinesis and ballooning of the apical 2/3 of the LV. Troponin T was elevated but other markers of myocardial necrosis were negative, as was coronary angiography. From D7 onward, there was an improvement in the hemodynamics in conjunction with a gradual increase of LV EF. The patient was dismissed from the hospital on D30 with signs of normal cardiac function and LV motion and EF of 50%. Liver function was also excellent. Conclusions: Every major operation, including liver transplantation, is associated with emotional stress for the patient. Therefore, it is necessary to consider Takotsubo cardiomyopathy in the differential diagnosis of heart failure developing early after LT, and clinicians should subsequently use adequate diagnostic and therapeutic measures. PMID:24298303

  3. Orthotopic transplantation of LH receptor knockout and wild-type ovaries.

    PubMed

    Chudgar, Daksha; Lei, Zhenmin; Rao, Ch V

    2005-10-01

    Luteinizing hormone (LH) receptor knockout animals have an ovarian failure due to an arrest in folliculogenesis at the antral stage. As a result, the animals have an infertility phenotype. The present study was undertaken to determine whether this phenotype could be reversed by orthotopic transplantation of wild-type ovaries. The results revealed that transplanting wild-type ovaries into null animals did not result in resumption of estrus cycles. Although the number of different types of follicles increased, none progressed to ovulation. The serum hormone profiles improved, reflecting the ovarian changes. The wild-type animals with null ovaries also failed to cycle and their ovaries and serum hormone levels were more like null animals with their own ovaries. Although the lack of rescue of null ovaries placed into wild-type animals was predicted, the failure of wild-type ovaries placed in null animals was not, which could be due to chronic exposure of transplanted tissue to high circulating LH levels and also possibly due to altered internal milieu in null animals. These findings may have implications for potential future considerations of grafting normal donor ovaries into women who have an ovarian failure resulting from inactivating LH receptor mutations. PMID:15964032

  4. An improved syngeneic orthotopic murine model of human breast cancer progression.

    PubMed

    Rashid, Omar M; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine; Schaum, Julia; Yamada, Akimitsu; Terracina, Krista P; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2014-10-01

    Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous (OP) injection in the area of the nipple, or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. ODV produced less variable-sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development . PMID:25200444

  5. Establishment of an Orthotopic Xenograft Mice Model of Retinoblastoma Suitable for Preclinical Testing

    PubMed Central

    Cassoux, Nathalie; Thuleau, Aurélie; Assayag, Franck; Aerts, Isabelle; Decaudin, Didier

    2015-01-01

    Retinoblastoma is a rare cancer that occurs during childhood. The goal of current and future therapeutic strategies is to conserve the eye and visual function without using external beam radiotherapy, which is known to increase the risk of secondary cancers in genetically predisposed patients. Multimodality therapy (usually intravenous but also intra-arterial and intravitreal chemotherapy, transpupillary thermotherapy, cryotherapy, or brachytherapy) has recently improved the eye salvage rate in retinoblastoma and has led to a decreased need for external beam radiotherapy. However, the treatment of advanced intraocular retinoblastoma remains a real challenge, especially in cases of vitreous and subretinal seeding. There is a need for alternative and less toxic therapies as well as for better ways to administer the drugs. Animal models are an integral part of preclinical research in the field of oncology. This paper describes the different xenograft rodent models published in the literature so far. We will also describe a new orthotopic xenografted retinoblastoma model in immunodeficient mice, which is suitable for preclinical assays. The xenograft model was established from tumor tissue obtained directly from surgical samples and closely mimics human retinoblastoma. PMID:27171982

  6. Real Time Metastatic Route Tracking of Orthotopic PC-3-GFP Human Prostate Cancer Using Intravital Imaging.

    PubMed

    Zhang, Yong; Wang, Xiaoen; Hoffman, Robert M; Seki, Naohiko

    2016-04-01

    The cellular basis of metastasis is poorly understood. An important step to understanding this process is to be able to visualize the routes by which cancer cells migrate from the primary tumor to various distant sites to eventually form metastasis. Our laboratory previously developed single-cell in vivo imaging using fluorescent proteins to label cancer cells. In the present study, using PC-3 human prostate cancer cells labeled with green fluorescent protein (GFP) and orthotopic tumor transplantation, we have imaged in live mice various highly diverse routes by which PC-3 cells metastasize superiorly and inferiorly to distant sites, including in the portal area, stomach area, and urogenital system. Imaging began at day 9, at which time distant metastasis had already occurred, and increased at each imaging point at days 10, 13, 14, and 16. Metastatic cells were observed migrating superiorly and inferiorly from the primary tumor as well as in lymphatic channels and trafficking in various organ systems demonstrating that PC-3 has multiple metastatic routes similar to hormone-independent advanced-stage prostate cancer in the clinic. PMID:26515240

  7. An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis

    PubMed Central

    Reiberger, Thomas; Chen, Yunching; Ramjiawan, Rakesh R; Hato, Tai; Fan, Christopher; Samuel, Rekha; Roberge, Sylvie; Huang, Peigen; Lauwers, Gregory Y; Zhu, Andrew X; Bardeesy, Nabeel; Jain, Rakesh K; Duda, Dan G

    2016-01-01

    Subcutaneous xenografts have been used for decades to study hepatocellular carcinoma (HCC). These models do not reproduce the specific pathophysiological features of HCCs, which occur in cirrhotic livers that show pronounced necroinflammation, abnormal angiogenesis and extensive fibrosis. As these features are crucial for studying the role of the pathologic host microenvironment in tumor initiation, progression and treatment response, alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC model in immunocompetent mice with liver cirrhosis induced by carbon tetrachloride (CCl4) that recapitulates key features of human HCC. Induction of substantial hepatic fibrosis requires 12 weeks of CCl4 administration. Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse. Tumor growth varies by tumor cell line and mouse strain used. Alternatively, tumors can be induced in a genetically engineered mouse model. In this setting, CCl4 is administered for 12 weeks after tail-vein injection of Cre-expressing adenovirus (adeno-Cre) in Stk4−/−Stk3F/− (also known as Mst1−/−Mst2F/−; F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis. PMID:26203823

  8. A pseudo-outbreak of disseminated cryptococcal disease after orthotopic heart transplantation.

    PubMed

    Kennedy, E; Vanichanan, J; Rajapreyar, I; Gonzalez, B; Nathan, S; Gregoric, I; Kar, B; Loyalka, P; Weeks, P; Chavez, V; Wanger, A; Ostrosky Zeichner, L

    2016-02-01

    Cryptococcal infection is the third most common invasive fungal infection (IFI) among solid-organ transplant (SOT) recipients and is considered an important opportunistic infection due to its significant morbidity and mortality. To determine whether a cluster of cryptococcosis in heart transplant patients was of nosocomial nature, three cases of orthotopic heart transplant recipients with postoperative disseminated cryptococcal infection were investigated and paired with an environmental survey in a tertiary care hospital. The infection prevention department conducted a multidisciplinary investigation, which did not demonstrate any evidence of health care-associated environmental exposure. Moreover, multilocus sequence typing showed that one isolate was unique and the two others, although identical, were not temporally related and belong to the most common type seen in the Southern US. Additionally, all three patients had preexisting abnormalities of the CT chest scan and various degrees of acute and chronic rejection. Reactivation was suggested in all three patients. Screening methods may be useful to identify at risk patients and trigger a prophylactic or preemptive approach. However, more data is needed. PMID:26627342

  9. Uptake of verteporfin by orthotopic xenograft pancreas models with different levels of aggression

    NASA Astrophysics Data System (ADS)

    O'Hara, Julia; Samkoe, Kimberley S.; Chen, Alina; Hoopes, P. Jack; Rizvi, Imran; Hasan, Tayyaba; Pogue, Brian W.

    2009-06-01

    Pancreatic cancer is an aggressive disease with a poor prognosis, usually treated with chemoradiation therapy. Interstitial photodynamic therapy is a potentially effective adjuvant treatment that is under development. In the current study, two orthotopic pancreatic cancer models (AsPC-1 and Panc-1), have been characterized with respect to growth rates, morphology and liposomal drug (Verteporfin) uptake and distribution in SCID mice. Fluorescence of Verteporfin was measured in liver and tumor in vivo using a PDT fluorescence dosimeter with measurements taken before and up to one hour after tail vein injection. Fluorescence reached a plateau by about 15 minutes and did not decrease over the first hour. At time points from 15 minutes to 24 hrs, the internal organs (kidney, spleen, pancreas, tumor, muscle, lung, liver, and skin were excised and scanned on a Typhoon imager. The ratio of fluorescence in tumor versus normal tissues was analyzed with image processing, calculated at each time point and compared to in vivo results. Tissue distribution of Verteporfin in relation to functional vasculature marked by DiOc7 was carried out on frozen sections. Final analysis will result in determination of the ideal time point to administer light to achieve maximum tumor destruction while preserving normal tissue.

  10. Graft complications following orthotopic liver transplantation: Role of non-invasive cross-sectional imaging techniques.

    PubMed

    Boraschi, Piero; Della Pina, Maria Clotilde; Donati, Francescamaria

    2016-07-01

    Orthotopic liver transplantation is the treatment of choice in adult patients with endstage liver disease. Survival of both graft and patient has progressively improved over time due to improvements in surgical and medical treatment. However, post-transplant complications still have a significant impact on morbidity and mortality associated with transplant surgery. The most common adverse events of the graft include vascular (arterial and venous stenosis and thrombosis), biliary (leakage, strictures, stones) and parenchymal complications (hepatitis virus C infection, HCC recurrence, liver abscesses). The diagnosis of these adverse events is often challenging because of the low specificity of clinical and biologic findings. Different diagnostic algorithms have been proposed for the detection of graft complications and, in this setting, radiological evaluation plays a key role in differential diagnosis of graft complications and the exclusion of other adverse events. Ultrasound examination is established the first-line method of identifying adverse events in liver transplant recipients but a normal or a technically unsatisfactory study cannot exclude the presence of biliary, vascular and/or parenchymal complications. In these circumstances, before planning any treatment, multi-detector CT and/or MR imaging and MR cholangiography should be performed for the evaluation of vascular structures, biliary system, liver parenchyma and fluid collections. The aim of this review is to illustrate the role and state-of-the-art of non-invasive cross-sectional imaging techniques in the diagnosis and management of complications which primarily affect the graft in patients after liver transplantation. PMID:27235874

  11. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    SciTech Connect

    Pennock, J.L.; Reitz, B.A.; Beiber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-12-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either Cy A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

  12. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    SciTech Connect

    Pennock, J.L.; Reitz, B.A.; Bieber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-12-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either CY A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI plus Cy A when compared with using Cy A alone. TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

  13. Replacement, reduction and refinement.

    PubMed

    Flecknell, Paul

    2002-01-01

    In 1959, William Russell and Rex Burch published "The Principles of Humane Experimental Technique". They proposed that if animals were to be used in experiments, every effort should be made to Replace them with non-sentient alternatives, to Reduce to a minimum the number of animals used, and to Refine experiments which used animals so that they caused the minimum pain and distress. These guiding principles, the "3 Rs" of animal research, were initially given little attention. Gradually, however, they have become established as essential considerations when animals are used in research. They have influenced new legislation aimed at controlling the use of experimental animals, and in the United Kingdom they have become formally incorporated into the Animal (Scientific) Procedures Act. The three principles, of Replacement, Reduction and Refinement, have also proven to be an area of common ground for research workers who use animals, and those who oppose their use. Scientists, who accept the need to use animals in some experiments, would also agree that it would be preferable not to use animals. If animals were to be used, as few as possible should be used and they should experience a minimum of pain or distress. Many of those who oppose animal experimentation, would also agree that until animal experimentation is stopped, Russell and Burch's 3Rs provide a means to improve animal welfare. It has also been recognised that adoption of the 3Rs can improve the quality of science. Appropriately designed experiments that minimise variation, provide standardised optimum conditions of animals care and minimise unnecessary stress or pain, often yield better more reliable data. Despite the progress made as a result of attention to these principles, several major problems have been identified. When replacing animals with alternative methods, it has often proven difficult to formally validate the alternative. This has proven a particular problem in regulatory toxicology

  14. Reuse, replace, recycle

    PubMed Central

    McMurray, Michael A.; Thorner, Jeremy W.

    2015-01-01

    Septins are guanine nucleotide-binding proteins that form hetero-oligomeric complexes, which assemble into filaments and higher-order structures at sites of cell division and morphogenesis in eukaryotes. Dynamic changes in the organization of septin-containing structures occur concomitantly with progression through the mitotic cell cycle and during cell differentiation. Septins also undergo stage-specific post-translational modifications, which have been implicated in regulating their dynamics, in some cases via purported effects on septin turnover. In our recent study, the fate of two of the five septins expressed in mitotic cells of budding yeast (Saccharomyces cerevisiae) was tracked using two complementary fluorescence-based methods for pulse-chase analysis. During mitotic growth, previously-made molecules of both septins (Cdc10 and Cdc12) persisted through multiple successive divisions and were incorporated equivalently with newly synthesized molecules into hetero-oligomers and higher-order structures. Similarly, in cells undergoing meiosis and the developmental program of sporulation, pre-existing copies of Cdc10 were incorporated into new structures. In marked contrast, Cdc12 was irreversibly excluded from septin complexes and replaced by another septin, Spr3. Here, we discuss the broader implications of these results and related findings with regard to how septin dynamics is coordinated with the mitotic cell cycle and in the yeast life cycle, and how these observations may relate to control of the dynamics of other complex multi-subunit assemblies. PMID:19164941

  15. Assessment of the Early Effects of 5,6-Dimethylxanthenone-4-Acetic Acid Using Macromolecular Contrast Media-Enhanced Magnetic Resonance Imaging: Ectopic Versus Orthotopic Tumors

    SciTech Connect

    Seshadri, Mukund Bellnier, David A.; Cheney, Richard T.

    2008-11-15

    Purpose: To investigate the early effects of a vascular disrupting agent (VDA) in ectopic and orthotopic tumors by using macromolecular contrast media (MMCM)-enhanced magnetic resonance imaging (MMCM-MRI). Methods and Materials: The MMCM-MRI of ectopic and orthotopic MCA205 murine fibrosarcomas was performed using the intravascular contrast agent albumin-(gadopentetate dimeglumine){sub 35}. Change in longitudinal relaxation rate ({delta}R1) was measured 24 hours after treatment with 5,6-dimethylxanthenone-4-acetic acid (DMXAA; 30 mg/kg) and used to compute tumor vascular volume and permeability. Correlative histologic and immunohistochemical evaluation was carried out, along with measurement of tumor necrosis factor {alpha} and vascular endothelial growth factor levels in whole tumor extracts using the enzyme-linked immunosorbent assay. Results: Orthotopic tumors showed higher vascular volume (p < 0.05) than ectopic tumors before treatment. Twenty-four hours after DMXAA treatment, a significant (p < 0.0001), but differential, decrease in {delta}R1 (70% in ectopic and 50% in orthotopic tumors) was observed compared with baseline estimates. Consistent with this observation, greater levels of tumor necrosis factor {alpha}, an important mediator of the antivascular activity of DMXAA, were measured in ectopic tumors 3 hours posttreatment compared with orthotopic tumors (p < 0.05). Immunohistochemical (CD31) and histologic (hematoxylin and eosin) sections of ectopic and orthotopic tumors showed highly tumor-selective vascular damage after treatment with the presence of viable surrounding normal tissue. Conclusions: The MMCM-MRI provided early quantitative estimates of change in tumor perfusion after VDA treatment that showed good correlation with cytokine induction. Differences in the response of ectopic and orthotopic tumors highlight the influence of the host microenvironment in modulating the activity of VDAs.

  16. Antenna Controller Replacement Software

    NASA Technical Reports Server (NTRS)

    Chao, Roger Y.; Morgan, Scott C.; Strain, Martha M.; Rockwell, Stephen T.; Shimizu, Kenneth J.; Tehrani, Barzia J.; Kwok, Jaclyn H.; Tuazon-Wong, Michelle; Valtier, Henry; Nalbandi, Reza; Wert, Michael; Leung, Patrick

    2010-01-01

    The Antenna Controller Replacement (ACR) software accurately points and monitors the Deep Space Network (DSN) 70-m and 34-m high-efficiency (HEF) ground-based antennas that are used to track primarily spacecraft and, periodically, celestial targets. To track a spacecraft, or other targets, the antenna must be accurately pointed at the spacecraft, which can be very far away with very weak signals. ACR s conical scanning capability collects the signal in a circular pattern around the target, calculates the location of the strongest signal, and adjusts the antenna pointing to point directly at the spacecraft. A real-time, closed-loop servo control algorithm performed every 0.02 second allows accurate positioning of the antenna in order to track these distant spacecraft. Additionally, this advanced servo control algorithm provides better antenna pointing performance in windy conditions. The ACR software provides high-level commands that provide a very easy user interface for the DSN operator. The operator only needs to enter two commands to start the antenna and subreflector, and Master Equatorial tracking. The most accurate antenna pointing is accomplished by aligning the antenna to the Master Equatorial, which because of its small size and sheltered location, has the most stable pointing. The antenna has hundreds of digital and analog monitor points. The ACR software provides compact displays to summarize the status of the antenna, subreflector, and the Master Equatorial. The ACR software has two major functions. First, it performs all of the steps required to accurately point the antenna (and subreflector and Master Equatorial) at the spacecraft (or celestial target). This involves controlling the antenna/ subreflector/Master-Equatorial hardware, initiating and monitoring the correct sequence of operations, calculating the position of the spacecraft relative to the antenna, executing the real-time servo control algorithm to maintain the correct position, and

  17. Leukocyte populations and IL-6 in the tumor microenvironment of an orthotopic colorectal cancer model.

    PubMed

    Miller, Sarah; Senior, Paul V; Prakash, Monica; Apostolopoulos, Vasso; Sakkal, Samy; Nurgali, Kulmira

    2016-04-01

    Colorectal cancer (CRC) is a major health problem worldwide. It is often diagnosed late due to its asymptomatic nature. As with all cancers, an immune reaction is involved; however, in CRC, it is unknown if this immune response is favorable or unfavorable for disease progression. In this study, the immune response in mesenteric lymph nodes (MLNs) and Peyer's patches was investigated during development of CRC in an orthotopic mouse model. CRC was induced by injecting CT26 cells into the cecum wall of BALB/c mice. Flow cytometry was used to analyze leukocyte populations involved in tumor immunity in MLNs and Peyer's patches. Cryostat sections for immunohistochemistry were prepared from the caecum and colon from CRC-induced and sham-operated animals. Cytokines produced by mouse CT26 cell line were measuredin vitroandin vivo Significant increases in the number of CD8(+)/TCR(+)and CD49b(+)/TCR(-)(natural killer) cells were found in MLNs and Peyer's patches in the CRC group. In addition, γδT cells were present in the lamina propria of the colon tissues from sham-operated mice, but absent in the colon tissues from mice with CRC. Immunohistochemical analysis of tumorous tissues showed eosinophil, CD69(+)T cell, and CD11b(+)cell infiltration. Bothin vitroandin vivoCT26 tumor cells were interleukin (IL)-6 positive. In addition, tumor-infiltrating CD45(+)cells were also IL-6 positive. In summary, the kinetics of the immune response to CRC and the key effector lymphocytes that are implicated in tumor immunity are demonstrated. Furthermore, IL-6 is a key cytokine present within the tumor microenvironment. PMID:26893144

  18. A protective effect after clearance of orthotopic rat hepatocellular carcinoma by nanosecond pulsed electric fields.

    PubMed

    Chen, Ru; Sain, Nova M; Harlow, K Tyler; Chen, Yeong-Jer; Shires, Peter K; Heller, Richard; Beebe, Stephen J

    2014-10-01

    Strategies for treating liver cancer using radiation, chemotherapy combinations and tyrosine kinase inhibitors targeting specific mutations have provided longer survival times, yet multiple treatments are often needed and recurrences with new malignant phenotypes are not uncommon. New and innovative treatments are undoubtedly needed to successfully treat liver cancer. Over the last decade, nanosecond pulsed electric fields (nsPEFs) have shown promise in pre-clinical studies; however, these have been limited to treatment of skin cancers or xenographs in mice. In the present report, an orthotopic hepatocellular carcinoma (HCC) model is established in rats using N1-S1 HCC cells. Data demonstrate a response rate of 80-90% when 1000 pulses are delivered with 100ns durations, electric field strengths of 50kV/cm and repetition rates of 1Hz. N1-S1 tumours treated with nsPEFs expressed significant number of cells with active caspase-3 and caspase-9, but not caspase-8, indicating an intrinsic apoptosis mechanism(s) as well as caspase-independent mechanisms. Most remarkably, rats with successfully ablated tumours failed to re-grow tumours when challenged with a second injection of N1-S1 cells when implanted in the same or different liver lobe that harboured the original tumour. Given this protective effect, infiltration of immune cells and the presence of granzyme B expressing cells within days of treatment suggest the possibility of an anti-tumour adaptive immune response. In conclusion, NsPEFs not only eliminate N1-S1 HCC tumours, but also may induce an immuno-protective effect that defends animals against recurrences of the same cancer. PMID:25081978

  19. Endoscopic retrograde cholangiopancreatography in patients with biliary complications after orthotopic liver transplantation: outcomes and complications.

    PubMed

    Sanna, C; Saracco, G M; Reggio, D; Moro, F; Ricchiuti, A; Strignano, P; Mirabella, S; Ciccone, G; Salizzoni, M

    2009-05-01

    Biliary complications after orthotopic liver transplantation (OLT) still remain a major cause of morbidity and mortality. The most frequent complications are strictures and leakages in OLT cases with duct-to-duct biliary reconstruction (D-D), which can be treated with dilatation or stent placement during endoscopic retrograde cholangiopancreatography (ERCP), although this procedure is burdened with potentially severe complications, such as retroperitoneal perforation, acute pancreatitis, septic cholangitis, bleeding, recurrence of stones, strictures due to healing process. The aim of the study was to analyze the outcome of this treatment and the complications related to the procedure. Among 1634 adult OLTs, we compared postprocedural complications and mortality rates with a group of 5852 nontransplanted patients (n-OLTs) who underwent ERCP. Of 472 (28,8%) post-OLT biliary complications, 319 (67.6%) occurred in D-D biliary anstomosis cases and 94 (29.5%) patients underwent 150 ERCP sessions. Among 49/80 patients (61.2%) who completed the procedure, ERCP treatment was successful. Overall complication rate was 10.7% in OLT and 12.8% in n-OLT (P = NS). Compared with the n-OLT group, post-ERCP bleeding was more frequent in OLT (5.3% vs 1.3%, P = .0001), while the incidence of pancreatitis was lower (4.7% vs 9.6%, P = .04). Procedure-related mortality rate was 0% in OLT and 0.1% in n-OLT (P = NS). ERCP is a safe procedure for post-OLT biliary complications in the presence of a D-D anastomosis. Morbidity and mortality related with this procedure are acceptable and similar to those among nontransplanted population. PMID:19460551

  20. Regression of Established Hepatocellular Carcinoma Is Induced by Chemo-immunotherapy in an Orthotopic Murine Model

    PubMed Central

    Avella, Diego M.; Li, Guangfu; Schell, Todd D.; Liu, Dai; Zhang, Samuel Shao-Min; Lou, Xi; Berg, Arthur; Kimchi, Eric T.; Tagaram, Hephzibah Rani S.; Yang, Qing; Shereef, Serene; Garcia, Luis S.; Kester, Mark; Isom, Harriet C.; Rountree, C. Bart; Staveley-O’Carroll, Kevin F.

    2011-01-01

    The high rate of mortality and frequent incidence of recurrence associated with hepatocellular carcinoma (HCC) reveal the need for new therapeutic approaches. In this report, we evaluated the efficacy of a novel chemo-immunotherapeutic strategy to control HCC and investigated the underlying mechanism that increased the antitumor immune response. We developed a novel orthotopic mouse model of HCC through seeding of tumorigenic hepatocytes from SV40 T antigen (Tag) transgenic MTD2 mice into the livers of syngeneic C57BL/6 mice. These MTD2-derived hepatocytes form Tag expressing HCC tumors specifically within the liver. This approach provides a platform to test therapeutic strategies and antigen specific immune-directed therapy in an immunocompetent murine model. Using this model, we tested the efficacy of a combination of oral sunitinib, a small molecule multi-targeted receptor tyrosine kinase (RTK) inhibitor, and adoptive transfer of tumor antigen-specific CD8+ T cells to eliminate HCC. Sunitinib treatment alone promoted a transient reduction in tumor size. Sunitinib treatment combined with adoptive transfer of tumor antigen-specific CD8+ T cells led to elimination of established tumors without recurrence. In vitro studies revealed that HCC growth was inhibited through suppression of STAT3 signaling. In addition, sunitinib treatment of tumor-bearing mice was associated with suppression of STAT3 and a block in T cell tolerance. Conclusion These findings indicate that sunitinib inhibits HCC tumor growth directly through the STAT3 pathway and prevents tumor antigen-specific CD8+ T cell tolerance, thus defining a synergistic chemo-immunotherapeutic approach for HCC. PMID:21898502

  1. Aerosol Azacytidine Inhibits Orthotopic Lung Cancers in Mice through Its DNA Demethylation and Gene Reactivation Effects

    PubMed Central

    Qiu, Xuan; Liang, Yuanxin; Sellers, Rani S.; Perez-Soler, Roman; Zou, Yiyu

    2014-01-01

    We devised an aerosol based demethylation therapy to achieve therapeutic efficacy in premalignant or in situ lesions of lung cancer, without systemic toxicity. Optimum regimens of aerosolized azacytidine (Aza) were designed and used in orthotopic human non-small cell lung cancer xenograft models. The therapeutic efficacy and toxicity of aerosol Aza were compared with intravenously administered Aza. We observed that 80% of the droplets of the aerosol Aza measured ∼0.1–5 microns, which resulted in deposition in the lower bronchial airways. An animal model that phenocopies field carcinogeneisis in humans was developed by intratracheal inoculation of the human lung cancer cells in mice, thus resulting in their distribution throughout the entire airway space. Aerosolized Aza significantly prolonged the survival of mice bearing endo-bronchial lung tumors. The aerosol treatment did not cause any detectable lung toxicity or systemic toxicity. A pre-pharmacokinetic study in mice demonstrated that lung deposition of aerosolized Aza was significantly higher than the intravenous route. Lung tumors were resected after aerosol treatment and the methylation levels of 24 promoters of tumor-suppresser genes related to lung cancer were analyzed. Aerosol Aza significantly reduced the methylation level in 9 of these promoters and reexpressed several genes tested. In conclusion, aerosol Aza at non-cytotoxic doses appears to be effective and results in DNA demethylation and tumor suppressor gene re-expression. The therapeutic index of aerosol Aza is >100-fold higher than that of intravenous Aza. These results provide a preclinical rationale for a phase I clinical trial of aerosol Aza to be initiated at our Institution. PMID:25347303

  2. Standardized orthotopic xenografts in zebrafish reveal glioma cell-line-specific characteristics and tumor cell heterogeneity

    PubMed Central

    Welker, Alessandra M.; Jaros, Brian D.; Puduvalli, Vinay K.; Imitola, Jaime; Kaur, Balveen; Beattie, Christine E.

    2016-01-01

    ABSTRACT Glioblastoma (GBM) is a deadly brain cancer, for which few effective drug treatments are available. Several studies have used zebrafish models to study GBM, but a standardized approach to modeling GBM in zebrafish was lacking to date, preventing comparison of data across studies. Here, we describe a new, standardized orthotopic xenotransplant model of GBM in zebrafish. Dose-response survival assays were used to define the optimal number of cells for tumor formation. Techniques to measure tumor burden and cell spread within the brain over real time were optimized using mouse neural stem cells as control transplants. Applying this standardized approach, we transplanted two patient-derived GBM cell lines, serum-grown adherent cells and neurospheres, into the midbrain region of embryonic zebrafish and analyzed transplanted larvae over time. Progressive brain tumor growth and premature larval death were observed using both cell lines; however, fewer transplanted neurosphere cells were needed for tumor growth and lethality. Tumors were heterogeneous, containing both cells expressing stem cell markers and cells expressing markers of differentiation. A small proportion of transplanted neurosphere cells expressed glial fibrillary acidic protein (GFAP) or vimentin, markers of more differentiated cells, but this number increased significantly during tumor growth, indicating that these cells undergo differentiation in vivo. By contrast, most serum-grown adherent cells expressed GFAP and vimentin at the earliest times examined post-transplant. Both cell types produced brain tumors that contained Sox2+ cells, indicative of tumor stem cells. Transplanted larvae were treated with currently used GBM therapeutics, temozolomide or bortezomib, and this resulted in a reduction in tumor volume in vivo and an increase in survival. The standardized model reported here facilitates robust and reproducible analysis of glioblastoma tumor cells in real time and provides a platform for

  3. Orthotopic Human Choroidal Melanoma Xenografts in Nude Rats with Aggressive and Nonaggressive PAS Staining Patterns

    PubMed Central

    Braun, Rod D.; Abbas, Asad

    2007-01-01

    PURPOSE Choroidal melanoma is the most common primary ocular cancer among the adult population. Patient survival has been linked to the periodic acid-Schiff base (PAS)–positive vascular patterns in the tumors. The presence of PAS-positive loops or cross-linking parallel channels is a marker of an aggressive tumor. The purpose of this study was to develop new xenograft models of human choroidal melanoma that predictably demonstrate the PAS staining patterns associated with nonaggressive and aggressive tumors in humans. METHODS Three human choroidal melanoma cell lines (C918, M619, and OCM-1) were used. C918 and M619 are considered aggressive, based on their ability to form PAS-positive channels in vitro. The nonaggressive OCM-1 cells do not form these channels. C918, M619, and OCM-1 spheroids were grown and implanted in the suprachoroidal space of 20, 17, and 16 WAG/RijHs-rnu nude rats, respectively. Tumors were grown for 1 to >4 weeks, and histology was performed to evaluate tumor growth and determine PAS labeling patterns. RESULTS Growth of C918, M619, and OCM-1 xenografts were histologically verified in 20/20, 15/17, and 16/16 rats, respectively. PAS staining revealed loops and cross-linking parallel channels, typical of aggressive tumors in patients, in 90% of C918 and 100% of M619 xenografts. Only 4 of 16 OCM-1 xenografts showed PAS-positive loops. The rest showed no PAS staining or only perivascular staining, indicative of nonaggressive tumors. CONCLUSIONS It is possible to grow human choroidal melanoma orthotopic xenografts in nude rats that reproduce the PAS staining patterns associated with aggressive and nonaggressive choroidal melanomas in patients. PMID:16384938

  4. Intraductal Delivery of Adenoviruses Targets Pancreatic Tumors in Transgenic Ela-myc Mice and Orthotopic Xenografts

    PubMed Central

    José, Anabel; Sobrevals, Luciano; Camacho-Sánchez, Juan Miguel; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p<0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors. PMID:23328228

  5. Splenic Artery Syndrome After Orthotopic Liver Transplantation: Treatment With the Amplatzer Vascular Plug

    SciTech Connect

    Maurer, M. H.; Mogl, M. T.; Podrabsky, P.; Denecke, T.; Grieser, C.; Froeling, V.; Scheurig-Muenkler, C.; Guckelberger, O.; Kroencke, T. J.

    2011-12-15

    Purpose: To evaluate the safety and efficacy of the Amplatzer vascular plug (AVP) for embolization of the splenic artery in patients with hepatic hypoperfusion after orthotopic liver transplantation (OLT). Materials and Methods: Thirteen patients (9 men and 4 women) with a mean age of 56 years (range 22-70) who developed splenic artery syndrome after OLT with decreased liver perfusion and clinically relevant impairment of liver function (increased transaminase or serum bilirubin levels, thrombocytopenia, and/or therapy-refractory ascites) were treated by embolization of the proximal third of the splenic artery using the AVP. The plugs ranged in diameter from 6 to 16 mm, and they were introduced through femoral (n = 9), axillary (n = 3), or brachial (n = 1) access using a 5F or 8F guiding catheter. Results: The plugs were successfully placed, and complete occlusion of the splenic artery was achieved in all patients. Placement of two plugs was necessary for complete occlusion in 3 of the 13 patients. Occlusion took on average 10 min (range 4-35). There was no nontarget embolization or plug migration into more distal segments of the splenic artery. All patients showed improved arterial perfusion, including the liver periphery, on postinterventional angiogram. After embolization, liver function parameters (transaminase and bilirubin levels) improved with normalization of concomitant thrombocytopenia and a decrease in ascites volume. Conclusion: Our initial experience in a small patient population with SAS suggests that the AVP enables precise embolization of the proximal splenic artery, thus providing safe and effective treatment for poor liver perfusion after OLT due to SAS.

  6. Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model.

    PubMed

    Reardon, David A; Gokhale, Prafulla C; Klein, Sarah R; Ligon, Keith L; Rodig, Scott J; Ramkissoon, Shakti H; Jones, Kristen L; Conway, Amy Saur; Liao, Xiaoyun; Zhou, Jun; Wen, Patrick Y; Van Den Abbeele, Annick D; Hodi, F Stephen; Qin, Lei; Kohl, Nancy E; Sharpe, Arlene H; Dranoff, Glenn; Freeman, Gordon J

    2016-02-01

    Inhibition of immune checkpoints, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and its ligand PD-L1, has demonstrated exciting and durable remissions across a spectrum of malignancies. Combinatorial regimens blocking complementary immune checkpoints further enhance the therapeutic benefit. The activity of these agents for patients with glioblastoma, a generally lethal primary brain tumor associated with significant systemic and microenvironmental immunosuppression, is not known. We therefore systematically evaluated the antitumor efficacy of murine antibodies targeting a broad panel of immune checkpoint molecules, including CTLA-4, PD-1, PD-L1, and PD-L2 when administered as single-agent therapy and in combinatorial regimens against an orthotopic, immunocompetent murine glioblastoma model. In these experiments, we observed long-term tumor-free survival following single-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy in 50%, 20%, and 15% of treated animals, respectively. Combination therapy of anti-CTLA-4 plus anti-PD-1 cured 75% of the animals, even against advanced, later-stage tumors. In long-term survivors, tumor growth was not seen upon intracranial tumor rechallenge, suggesting that tumor-specific immune memory responses were generated. Inhibitory immune checkpoint blockade quantitatively increased activated CD8(+) and natural killer cells and decreased suppressive immune cells in the tumor microenvironment and draining cervical lymph nodes. Our results support prioritizing the clinical evaluation of PD-1, PD-L1, and CTLA-4 single-agent targeted therapy as well as combination therapy of CTLA-4 plus PD-1 blockade for patients with glioblastoma. PMID:26546453

  7. Histologic differences between orthotopic xenograft pancreas models affect Verteporfin uptake measured by fluorescence microscopy and spectroscopy

    NASA Astrophysics Data System (ADS)

    O'Hara, Julia A.; Samkoe, Kimberley S.; Chen, Alina; Isabelle, Martin; Hoopes, P. J.; Hasan, Tayyaba; Pogue, Brian W.

    2012-02-01

    Photodynamic therapy (PDT) that uses the second generation photosensitizer, verteporfin (VP), is a developing therapy for pancreatic cancer. The optimal timing of light delivery related to VP uptake and distribution in pancreatic tumors will be important information to obtain to improve treatment for this intractable disease. In this work we examined uptake and distribution of VP in two orthotopic pancreatic tumors with different histological structure. ASPC-1 (fast-growing) and Panc-1 (slower growing) tumors were implanted in SCID mice and studied when tumors were approximately 100mm3. In a pilot study, these tumors had been shown to differ in uptake of VP using lightinduced fluorescence spectroscopy (LIFS) in vivo and fluorescence imaging ex vivo and that work is extended here. In vivo fluorescence mean readings of tumor and liver increased rapidly up to 15 minutes after photosensitizer injection for both tumor types, and then continued to increase up to 60 minutes post injection to a higher level in ASPC-1 than in Panc-1. There was variability among animals with the same tumor type, in both liver and tumor uptake and no selectivity of tumor over liver. In this work we further examined VP uptake at multiple time points in relation to microvascular density and perfusion, using DiOC7 (to mark blood vessels) and VP fluorescence in the same tissue slices. Analysis of DiOC7 fluorescence indicates that AsPC-1 and Panc-1 have different vascular densities but AsPC-1 vasculature is more perfusive. Analysis of colocalized DiOC7 and VP fluorescence showed ASPC-1 with higher accumulation of VP 3 hrs after injection and more VP at a distance from blood vessels compared to Panc-1. This work shows the need for techniques to analyze photosensitizer distribution in order to optimize photodynamic therapy as an effective treatment for pancreatic tumors.

  8. Using your shoulder after replacement surgery

    MedlinePlus

    Joint replacement surgery - using your shoulder; Shoulder replacement surgery - after ... You have had shoulder replacement surgery to replace the bones of your shoulder joint with artificial parts. The parts include a stem made ...

  9. On total disc replacement.

    PubMed

    Berg, Svante

    2011-02-01

    Low back pain consumes a large part of the community's resources dedicated to health care and sick leave. Back disorders also negatively affect the individual leading to pain suffering, decreased quality-of-life and disability. Chronic low back pain (CLBP) due to degenerative disc disease (DDD) is today often treated with fusion when conservative treatment has failed and symptoms are severe. This treatment is as successful as arthroplasty is for hip arthritis in restoring the patient's quality of life and reducing disability. Even so, there are some problems with this treatment, one of these being recurrent CLBP from an adjacent segment (ASD) after primarily successful surgery. This has led to the development of alternative surgical treatments and devices that maintain or restore mobility, in order to reduce the risk for ASD. Of these new devices, the most frequently used are the disc prostheses used in Total Disc Replacement (TDR). This thesis is based on four studies comparing total disc replacement with posterior fusion. The studies are all based on a material of 152 patients with DDD in one or two segments, aged 20-55 years that were randomly treated with either posterior fusion or TDR. The first study concerned clinical outcome and complications. Follow-up was 100% at both one and two years. It revealed that both treatment groups had a clear benefit from treatment and that patients with TDR were better in almost all outcome scores at one-year follow-up. Fusion patients continued to improve during the second year. At two-year follow-up there was a remaining difference in favour of TDR for back pain. 73% in the TDR group and 63% in the fusion group were much better or totally pain-free (n.s.), while twice as many patients in the TDR group were totally pain free (30%) compared to the fusion group (15%). Time of surgery and total time in hospital were shorter in the TDR group. There was no difference in complications and reoperations, except that seventeen of the

  10. Replacement Cost of Domestic Crude

    Energy Science and Technology Software Center (ESTSC)

    1994-12-01

    The DEEPWATER model forecasts the replacement cost of domestic crude oil for 13 offshore regions in the lower 48 states. The replacement cost of domestic crude oil is the constant or levelized selling price that will recover the full expense of exploration, development, and productions with a reasonable return on capital.

  11. Biomaterials in total joint replacement.

    PubMed

    Katti, Kalpana S

    2004-12-10

    The current state of materials systems used in total hip replacement is presented in this paper. An overview of the various material systems used in total hip replacement reported in literature is presented in this paper. Metals, polymers, ceramics and composites are used in the design of the different components of hip replacement implants. The merits and demerits of these material systems are evaluated in the context of mechanical properties most suitable for total joint replacement such as a hip implant. Current research on advanced polymeric nanocomposites and biomimetic composites as novel materials systems for bone replacement is also discussed. This paper examines the current research in the materials science and the critical issues and challenges in these materials systems that require further research before application in biomedical industry. PMID:15556342

  12. Porphyrin lipid nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model

    NASA Astrophysics Data System (ADS)

    MacLaughlin, Christina M.; Ding, Lili; Jin, Cheng; Cao, Pingjiang; Siddiqui, Iram; Hwang, David M.; Chen, Juan; Wilson, Brian C.; Zheng, Gang; Hedley, David W.

    2016-03-01

    Local disease control is a major problem in the treatment of pancreatic cancer, because curative-intent surgery is only possible in a minority of patients, and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for ablation of pancreatic tumors, this approach remains under investigated. Using photothermal sensitizers in combination with laser light for PTT can result in more efficient conversion of light energy to heat, and confinement of thermal destruction to the tumor, thus sparing adjacent organs and vasculature. Porphyrins have been previously employed as photosensitizers for PDT and PTT, however their incorporation in to "porphysomes", lipid-based nanoparticles each containing ~80,000 porphyrins through conjugation of pyropheophorbide to phospholipids, carries two distinct advantages: 1) high-density porphyrin packing imparts the nanoparticles with enhanced photonic properties for imaging and phototherapy; 2) the enhanced permeability and retention effect may be exploited for optimal delivery of porphysomes to the tumor region thus high payload porphyrin delivery. The feasibility of porphysome-enhanced PTT for pancreatic cancer treatment was investigated using a patient-derived orthotopic pancreas xenograft tumor model. Uptake of porphysomes at the orthotopic tumor site was validated using ex vivo fluorescence imaging of intact organs of interest. The accumulation of porphysomes in orthotopic tumor microstructure was also confirmed by fluorescence imaging of excised tissue slices. PTT progress was monitored as changes in tumor surface temperature using IR optical imaging. Histological analyses were conducted to examine microstructure changes in tissue morphology, and the viability of remaining tumor tissues following exposure to heat. These studies may also provide insight as to the contribution of heat sink in application of thermal therapies to highly vascularized pancreatic tumors.

  13. The HDACi Panobinostat Shows Growth Inhibition Both In Vitro and in a Bioluminescent Orthotopic Surgical Xenograft Model of Ovarian Cancer

    PubMed Central

    Helland, Øystein; Popa, Mihaela; Bischof, Katharina; Gjertsen, Bjørn Tore; McCormack, Emmet; Bjørge, Line

    2016-01-01

    Background In most epithelial ovarian carcinomas (EOC), epigenetic changes are evident, and overexpression of histone deacetylases (HDACs) represents an important manifestation. In this study, we wanted to evaluate the effects of the novel HDAC inhibitor (HDACi) panobinostat, both alone and in combination with carboplatin, on ovarian cancer cell lines and in a murine bioluminescent orthotopic surgical xenograft model for EOC. Methods The effects of panobinostat, both alone and in combination with carboplatin, on proliferation and apoptosis in ovarian cancer cell lines, were evaluated using colony and WST-1 assays, Hoechst staining and flow cytometry analysis. In addition, mechanisms were characterised by western blotting and phosphoflow analysis. Immuno-deficient mice were engrafted orthotopically with SKOV-3luc+ cells and serial bioluminescence imaging monitored the effects of treatment with panobinostat and/or carboplatin and/or surgery. Survival parameters were also measured. Results Panobinostat treatment reduced cell growth and diminished cell viability, as shown by the induced cell cycle arrest and apoptosis in vitro. We observed increased levels of cleaved PARP and caspase-3, downregulation of cdc2 protein kinase, acetylation of H2B and higher pH2AX expression. The combined administration of carboplatin and panobinostat synergistically increased the anti-tumour effects compared to panobinostat or carboplatin treatment alone. In our novel ovarian cancer model, the mice showed significantly higher rates of survival when treated with panobinostat, carboplatin or a combination of both, compared to the controls. Panobinostat was as efficient as carboplatin regarding prolongation of survival. No significant additional effect on survival was observed when surgery was combined with carboplatin/panobinostat treatment. Conclusions Panobinostat demonstrates effective in vitro growth inhibition in ovarian cancer cells. The efficacy of panobinostat and carboplatin was

  14. Enhanced bone morphogenetic protein-2-induced ectopic and orthotopic bone formation by intermittent parathyroid hormone (1-34) administration.

    PubMed

    Kempen, Diederik H R; Lu, Lichun; Hefferan, Theresa E; Creemers, Laura B; Heijink, Andras; Maran, Avudaiappan; Dhert, Wouter J A; Yaszemski, Michael J

    2010-12-01

    Bone morphogenetic proteins (BMPs) play a central role in local bone regeneration strategies, whereas the anabolic features of parathyroid hormone (PTH) are particularly appealing for the systemic treatment of generalized bone loss. The aim of the current study was to investigate whether local BMP-2-induced bone regeneration could be enhanced by systemic administration of PTH (1-34). Empty or BMP-2-loaded poly(lactic-co glycolic acid)/poly(propylene fumarate)/gelatin composites were implanted subcutaneously and in femoral defects in rats (n = 9). For the orthotopic site, empty defects were also tested. Each of the conditions was investigated in combination with daily administered subcutaneous PTH (1-34) injections in the neck. After 8 weeks of implantation, bone mineral density (BMD) and bone volume were analyzed using microcomputed tomography and histology. Ectopic bone formation and almost complete healing of the femoral defect were only seen in rats that received BMP-2-loaded composites. Additional treatment of the rats with PTH (1-34) resulted in significantly (p < 0.05) enhanced BMD and bone volume in the BMP-2 composites at both implantation sites. Despite its effect on BMD in the humerus and vertebra, PTH (1-34) treatment had no significant effect on BMD and bone volume in the empty femoral defects and the ectopically or orthotopically implanted empty composites. Histological analysis showed that the newly formed bone had a normal woven and trabecular appearance. Overall, this study suggests that intermittent administration of a low PTH dose alone has limited potential to enhance local bone regeneration in a critical-sized defect in rats. However, when combined with local BMP-2-releasing scaffolds, PTH administration significantly enhanced osteogenesis in both ectopic and orthotopic sites. PMID:20666615

  15. Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique12

    PubMed Central

    Ni, Jie; Cozzi, Paul; Hung, Tzong-Tyng; Hao, Jingli; Graham, Peter; Li, Yong

    2016-01-01

    Prostate cancer (CaP) is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D) ultrasound system equipped with photoacoustic (PA) imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8). Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r2 = 0.948, 0.955, and 0.953, respectively) and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P < .001). The application of 3D ultrasound imaging proved to be a useful imaging modality in monitoring tumor growth in an orthotopic mouse model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research. PMID:26947880

  16. Percutaneous Valve Replacement: Significance of Different Delivery Systems In Vitro and In Vivo

    SciTech Connect

    Attmann, Tim; Lutter, Georg Quaden, Rene; Jahnke, Thomas; Rumberg, Kristin; Cremer, Jochen; Muller-Hulsbeck, Stefan

    2006-06-15

    Background and purpose. Percutaneous heart valve replacement is an exciting growing field in cardiovascular medicine yet still with some major problems. Only sophisticated improvement of the instruments could make it a real alternative to conventional surgery. Therefore, the aim of this study was to evaluate different delivery devices for percutaneous heart valve replacement in vitro and in vivo. Methods. A catheter prototype designed by our group, and two commercially available devices for the delivery of esophageal stents and aortic endoprostheses, were tested. After in vitro experiments, an ovine animal model of transfemoral pulmonary valve implantation was established using biological valved self-expanding stents. Only the delivery device for aortic endografts (Medtronic, Talent, Santa Rosa, CA, USA) allowed fast in vitro procedures without material fatigue. This device was chosen for the in vivo tests. Results. Technical success was achieved in 9 of 10 animals (90%). One animal died after perforation of the ventricular wall. Orthotopic pulmonary placement was performed in 6 animals and intentional supravalvular valved stent placement in 3 animals. Conclusions. An adequate in vitro model for this evolving field of interventional heart valve replacement is presented. Furthermore, the present study pinpoints the key characteristics that are mandatory for a delivery system in percutaneous pulmonary valve implantation. With regard to the delivery device's ductility observed during this 'venous' study, an approach to transfemoral aortic valve implantation seems feasible.

  17. Imaging the microenvironment of pancreatic cancer patient-derived orthotopic xenografts (PDOX) growing in transgenic nude mice expressing GFP, RFP, or CFP.

    PubMed

    Hoffman, Robert M; Bouvet, Michael

    2016-09-28

    We have developed a multi-color, imageable, orthotopic mouse model for individual patients with pancreatic cancer. The tumors are labeled by first passaging them orthotopically through transgenic nude mice expressing green fluorescent protein (GFP), red fluorescent protein (RFP), or cyan fluorescent protein (CFP). Passage of the tumors in these colored transgenic mice labels the stromal cells of the tumor. The cancer cells in the PDOX are labeled in situ with GFP by telomerase-dependent adenovirus OBP-401. The models are termed imageable patient-derived orthotopic xenografts (iPDOX). The tumors acquired brightly-fluorescent stromal cells from the transgenic host mice, which were stably associated with the tumors through multiple passages. The colored fluorescent protein-expressing stromal cells included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). This model enables powerful color-coded imaging of the interaction of cancer and stromal cells during tumor progression and treatment. PMID:26742463

  18. [Detubularized U-shaped enterocystoplasty after cystoprostatectomy].

    PubMed

    el Mrini, M; Aboutaieb, R; el Fatimi, A; Sarf, I; Joual, A; Bennani, S; Elmoussaoui, A; Benjelloun, S

    1996-01-01

    We reviewed the charts of 58 patients who underwent orthotopic bladder replacement after total cystoprostatectomy for muscle invasive bladder cancer. Mean age was 56 years. As described by Camey, 60 centimetres of small bowel, are isolated, detubularised then folded upon itself to form a U shaped reservoir, which is anastomosed to the urethra. Death occurred in 5%. Urologic complications observed were: urinary leakage (15%), ureteral reflux (6.8%), ureteral stenosis (8.6%) and stones of the neobladder (5.1%). 64.2% of the patients were immediately continent during the day. Nocturnal continence was obtained for 50% immediately and for 80% three months postoperatively. Detubularised and U shaped cystoplasty achieve a low pressure reservoir, with protection of the upper urinary tract, and a diurnal continence. Nocturnal continence is achieved later. PMID:8767813

  19. Establishment of a Non-Invasive Semi-Quantitative Bioluminescent Imaging Method for Monitoring of an Orthotopic Esophageal Cancer Mouse Model

    PubMed Central

    Kuroda, Shinji; Kubota, Tetsushi; Aoyama, Katsuyuki; Kikuchi, Satoru; Tazawa, Hiroshi; Nishizaki, Masahiko; Kagawa, Shunsuke; Fujiwara, Toshiyoshi

    2014-01-01

    Orthotopic models of various types of tumors are widely used in anti-tumor therapeutic experiments in preclinical studies. However, there are few ways to appropriately monitor therapeutic effect in orthotopic tumor models, especially for tumors invisible from the outside. In this study we aimed to establish a non-invasive semi-quantitative bioluminescent imaging method of monitoring an orthotopic esophageal cancer mouse model. We confirmed that the TE8 esophageal cancer cell line implanted orthotopically into the abdominal esophagus of nu/nu mice (n = 5) developed not only a main tumor at the implanted site, but also local lymph node metastases and peritoneal disseminations within 6 weeks after inoculation. We established a TE8 cell line that stably expressed the firefly luciferase gene (TE8-Luc). We showed that TE8-Luc cells implanted subcutaneously into nu/nu mice (n = 5) grew over time until 5 weeks after inoculation. Tumor volume was strongly correlated with luminescent intensity emitted from the tumor, which was quantified using the IVIS imaging system. We then showed that TE8-Luc cells implanted orthotopically into the mouse abdominal esophagus (n = 8) also formed a tumor and that the luminescent intensity of such a tumor, as detected by IVIS, increased over time until 7 weeks after inoculation and was therefore likely to reflect tumor progression. We therefore propose that this orthotopic esophageal cancer model, monitored using the non-invasive semi-quantitative IVIS imaging system, will be useful for in vivo therapeutic experiments against esophageal cancer. This experimental setting is expected to contribute to the development of novel therapeutic technologies for esophageal cancer in preclinical studies. PMID:25493557

  20. Detection of Phosphatidylcholine-Coated Gold Nanoparticles in Orthotopic Pancreatic Adenocarcinoma using Hyperspectral Imaging.

    PubMed

    England, Christopher G; Huang, Justin S; James, Kurtis T; Zhang, Guandong; Gobin, André M; Frieboes, Hermann B

    2015-01-01

    Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure and dense extracellular matrix may hinder local penetration. Extravascular diffusivity depends upon nanoparticle size, surface modifications, and tissue vascularization. Gold nanoparticles functionalized with biologically-compatible layers may achieve improved uptake and distribution while enabling cytotoxicity through synergistic combination of chemotherapy and thermal ablation. Evaluation of nanoparticle uptake in vivo remains difficult, as detection methods are limited. We employ hyperspectral imaging of histology sections to analyze uptake and distribution of phosphatidylcholine-coated citrate gold nanoparticles (CGN) and silica-gold nanoshells (SGN) after tail-vein injection in mice bearing orthotopic pancreatic adenocarcinoma. For CGN, the liver and tumor showed 26.5 ± 8.2 and 23.3 ± 4.1 particles/100 μm2 within 10 μm from the nearest source and few nanoparticles beyond 50 μm, respectively. The spleen had 35.5 ± 9.3 particles/100 μm2 within 10 μm with penetration also limited to 50 μm. For SGN, the liver showed 31.1 ± 4.1 particles/100 μm2 within 10 μm of the nearest source with penetration hindered beyond 30 μm. The spleen and tumor showed uptake of 22.1 ± 6.2 and 15.8 ± 6.1 particles/100 μm2 within 10 μm, respectively, with penetration similarly hindered. CGH average concentration (nanoparticles/μm2) was 1.09 ± 0.14 in the liver, 0.74 ± 0.12 in the spleen, and 0.43 ± 0.07 in the tumor. SGN average concentration (nanoparticles/μm2) was 0.43 ± 0.07 in the liver, 0.30 ± 0.06 in the spleen, and 0.20 ± 0.04 in the tumor. Hyperspectral imaging of histology sections enables analysis of phosphatidylcholine-coated gold-based nanoparticles in

  1. Role of interleukin-17A in early graft rejection after orthotopic lung transplantation in mice

    PubMed Central

    Chen, Qi-Rui; Wang, Li-Feng; Xia, Si-Si; Zhang, Ya-Mei; Xu, Jiang-Nan

    2016-01-01

    Background The cellular and molecular mechanisms underlying lung allograft rejection remain poorly understood. We investigated the potential role of interleukin (IL)-17A in lung transplant rejection in a mouse model, because previous studies in clinical and rodent models have implicated IL-17A in both acute and chronic rejection. Methods To generate an orthotopic lung transplantation model, lungs from C57BL/6 or BALB/c mice were transplanted into C57BL/6 mice (isograft and allograft models, respectively). The effects of anti-IL-17A treatment in allograft recipients were investigated. The histological features and rejection status of isografts and allografts were assessed at 3, 7, and 28 days after transplantation, and differences in graft infiltrating cells and mRNA expression of relevant cytokines were quantified at 3 and 7 days after transplantation. Results As expected, isografts showed no obvious signs of rejection, whereas allografts exhibited minimal-to-mild rejection (grade A1–A2) by day 3 and moderate-to-severe rejection (grade A3–A4) by day 7, without evidence of obliterative bronchiolitis (OB). However, by 28 days, evidence of OB was observed in 67% (2/3) of allografts and severe rejection (grade A4) was observed in all. IL-17 mRNA expression in allografts was increased with rejection, and interferon (IFN)-γ and IL-6 mRNA expression levels followed a similar pattern. In contrast, IL-22 expression in allografts was only slightly increased. Antibody (Ab) neutralization of IL-17A diminished the signs of acute rejection at 7 days after transplantation in allografts, and this early protection was accompanied by a decrease in cellular stress according to histological evaluation, suggesting the involvement of IL-17A in the development of early post-transplantation lesions. Conclusions Our data indicate that IL-17A is important in the pathophysiology of allograft rejection, and neutralization of IL-17A is a potential therapeutic strategy to preventing lung

  2. Detection of Phosphatidylcholine-Coated Gold Nanoparticles in Orthotopic Pancreatic Adenocarcinoma using Hyperspectral Imaging

    PubMed Central

    England, Christopher G.; Huang, Justin S.; James, Kurtis T.; Zhang, Guandong; Gobin, André M.; Frieboes, Hermann B.

    2015-01-01

    Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure and dense extracellular matrix may hinder local penetration. Extravascular diffusivity depends upon nanoparticle size, surface modifications, and tissue vascularization. Gold nanoparticles functionalized with biologically-compatible layers may achieve improved uptake and distribution while enabling cytotoxicity through synergistic combination of chemotherapy and thermal ablation. Evaluation of nanoparticle uptake in vivo remains difficult, as detection methods are limited. We employ hyperspectral imaging of histology sections to analyze uptake and distribution of phosphatidylcholine-coated citrate gold nanoparticles (CGN) and silica-gold nanoshells (SGN) after tail-vein injection in mice bearing orthotopic pancreatic adenocarcinoma. For CGN, the liver and tumor showed 26.5±8.2 and 23.3±4.1 particles/100μm2 within 10μm from the nearest source and few nanoparticles beyond 50μm, respectively. The spleen had 35.5±9.3 particles/100μm2 within 10μm with penetration also limited to 50μm. For SGN, the liver showed 31.1±4.1 particles/100μm2 within 10μm of the nearest source with penetration hindered beyond 30μm. The spleen and tumor showed uptake of 22.1±6.2 and 15.8±6.1 particles/100μm2 within 10μm, respectively, with penetration similarly hindered. CGH average concentration (nanoparticles/μm2) was 1.09±0.14 in the liver, 0.74±0.12 in the spleen, and 0.43±0.07 in the tumor. SGN average concentration (nanoparticles/μm2) was 0.43±0.07 in the liver, 0.30±0.06 in the spleen, and 0.20±0.04 in the tumor. Hyperspectral imaging of histology sections enables analysis of phosphatidylcholine-coated gold-based nanoparticles in pancreatic tumors with the goal to improve

  3. Fracture After Total Hip Replacement

    MedlinePlus

    ... er Total Hip Replacement cont. • Dislocation • Limb length inequality • Poor fracture healing • Repeat fracture • Lack of in- ... Surgeons (AAOS). To learn more about your orthopaedic health, please visit orthoinfo.org. Page ( 5 ) AAOS does ...

  4. When to Replace a Prosthesis

    MedlinePlus

    Donate Fundraise Connect Contact Us Materiales en español Amputee Coalition Navigation HOME WHO WE ARE About Us ... Advisory Committee Connect With Us! STORE CALENDAR SEARCH Amputee Coalition > Limb Loss Resource Center > When to Replace ...

  5. High Resolution Ultrasound and Photoacoustic Imaging of Orthotopic Lung Cancer in Mice: New Perspectives for Onco-Pharmacology

    PubMed Central

    Sobilo, Julien; Le Mée, Marilyne; Rétif, Stéphanie; Natkunarajah, Sharuja; Lerondel, Stéphanie; Le Pape, Alain

    2016-01-01

    Objectives We have developed a relevant preclinical model associated with a specific imaging protocol dedicated to onco-pharmacology studies in mice. Materials and Methods We optimized both the animal model and an ultrasound imaging procedure to follow up longitudinally the lung tumor growth in mice. Moreover we proposed to measure by photoacoustic imaging the intratumoral hypoxia, which is a crucial parameter responsible for resistance to therapies. Finally, we compared ultrasound data to x-ray micro computed tomography and volumetric measurements to validate the relevance of this approach on the NCI-H460 human orthotopic lung tumor. Results This study demonstrates the ability of ultrasound imaging to detect and monitor the in vivo orthotopic lung tumor growth by high resolution ultrasound imaging. This approach enabled us to characterize key biological parameters such as oxygenation, perfusion status and vascularization of tumors. Conclusion Such an experimental approach has never been reported previously and it would provide a nonradiative tool for assessment of anticancer therapeutic efficacy in mice. Considering the absence of ultrasound propagation through the lung parenchyma, this strategy requires the implantation of tumors strictly located in the superficial posterior part of the lung. PMID:27070548

  6. Targeting Hypoxia-Inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment.

    PubMed

    Nigim, Fares; Cavanaugh, Jill; Patel, Anoop P; Curry, William T; Esaki, Shin-ichi; Kasper, Ekkehard M; Chi, Andrew S; Louis, David N; Martuza, Robert L; Rabkin, Samuel D; Wakimoto, Hiroaki

    2015-07-01

    Tissue hypoxia and necrosis represent pathophysiologic and histologic hallmarks of glioblastoma (GBM). Although hypoxia inducible factor 1α (HIF-1α) plays crucial roles in the malignant phenotypes of GBM, developing HIF-1α-targeted agents has been hampered by the lack of a suitable preclinical model that recapitulates the complex biology of clinical GBM. We present a new GBM model, MGG123, which was established from a recurrent human GBM. Orthotopic xenografting of stem-like MGG123 cells reproducibly generated lethal tumors that were characterized by foci of palisading necrosis, hypervascularity, and robust stem cell marker expression. Perinecrotic neoplastic cells distinctively express HIF-1α and are proliferative in both xenografts and the patient tissue. The xenografts contain scattered hypoxic foci that were consistently greater than 50 μm distant from blood vessels, indicating intratumoral heterogeneity of oxygenation. Hypoxia enhanced HIF-1α expression in cultured MGG123 cells, which was abrogated by the HIF-1α inhibitors digoxin or ouabain. In vivo, treatment of orthotopic MGG123 xenografts with digoxin decreased HIF-1α expression, vascular endothelial growth factor mRNA levels, and CD34-positive vasculature within the tumors, and extended survival of mice bearing the aggressive MGG123 GBM. This preclinical tumor model faithfully recapitulates the GBM-relevant hypoxic microenvironment and stemness and is a suitable platform for studying disease biology and developing hypoxia-targeted agents. PMID:26083570

  7. Orthotopic genital sparing radical cystectomy in pre-menopausal women with muscle-invasive bladder carcinoma: A prospective study

    PubMed Central

    Moursy, Essam ElDin S.; Eldahshoursy, Mohammed Z.; Gamal, Wael M.; Badawy, Abdelbasset A.

    2016-01-01

    Introduction: Invasive cancer bladder is a life-threatening disease that is best treated with radical cystectomy and a suitable urinary diversion. The aim of this study was to evaluate the oncological outcome, voiding and sexual functions after genital sparing radical cystectomy with orthotopic bladder reconstruction in pre-menopausal women with bladder cancer. Materials and Methods: 18 pre-menopausal women who underwent radical cystectomy and orthotopic urinary diversion with preservation of genital organs were included for this study. The patients were followed-up clinically and radiologically to assess their oncological outcome in addition to their voiding and sexual function. Results: Mean age of the patients was 37.8 years, and the median follow-up after surgery was 70 months. One patient was lost to follow-up at 12 months post-operatively. The surgery was completed as planned in all patients, with a mean operative time of 290 min and an average blood loss of 750 mL. 14 patients were able to void satisfactorily, being continent day and night, while four patients needed clean intermittent catheterization. Sexual life remained unchanged in 15 cases, while three patients reported dysparunea. Till the last follow-up, there was no local recurrence while distant metastases were detected in three cases, two of whom died. Conclusions: Genital sparing cystectomy is a valid option for managing carefully selected women with muscle-invasive bladder cancer with good functional and sexual outcomes. PMID:26941498

  8. Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3

    PubMed Central

    Subramaniam, Aruljothi; Shanmugam, Muthu K; Ong, Tina H; Li, Feng; Perumal, Ekambaram; Chen, Luxi; Vali, Shireen; Abbasi, Taher; Kapoor, Shweta; Ahn, Kwang Seok; Kumar, Alan Prem; Hui, Kam M; Sethi, Gautam

    2013-01-01

    BACKGROUND AND PURPOSE Aberrant activation of STAT3 is frequently encountered and promotes proliferation, survival, metastasis and angiogenesis in hepatocellular carcinoma (HCC). Here, we have investigated whether emodin mediates its effect through interference with the STAT3 activation pathway in HCC. EXPERIMENTAL APPROACH The effect of emodin on STAT3 activation, associated protein kinases and apoptosis was investigated using various HCC cell lines. Additionally, we also used a predictive tumour technology to analyse the effects of emodin. The in vivo effects of emodin were assessed in an orthotopic mouse model of HCC. KEY RESULTS Emodin suppressed STAT3 activation in a dose- and time-dependent manner in HCC cells, mediated by the modulation of activation of upstream kinases c-Src, JAK1 and JAK2. Vanadate treatment reversed emodin-induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase and emodin induced the expression of the tyrosine phosphatase SHP-1 that correlated with the down-regulation of constitutive STAT3 activation. Interestingly, silencing of the SHP-1 gene by siRNA abolished the ability of emodin to inhibit STAT3 activation. Finally, when administered i.p., emodin inhibited the growth of human HCC orthotopic tumours in male athymic nu/nu mice and STAT3 activation in tumour tissues. CONCLUSIONS AND IMPLICATIONS Emodin mediated its effects predominantly through inhibition of the STAT3 signalling cascade and thus has a particular potential for the treatment of cancers expressing constitutively activated STAT3. PMID:23848338

  9. Zyflamend Suppresses Growth and Sensitizes Human Pancreatic Tumors to Gemcitabine in an Orthotopic Mouse Model Through Modulation of Multiple Targets

    PubMed Central

    Kunnumakkara, Ajaikumar B.; Sung, Bokyung; Ravindran, Jayaraj; Diagaradjane, Parmeswaran; Deorukhkar, Amit; Dey, Sanjit; Koca, Cemile; Tong, Zhimin; Gelovani, Juri G.; Guha, Sushovan; Krishnan, Sunil; Aggarwal, Bharat B.

    2011-01-01

    Agents that can potentiate the efficacy of standard chemotherapy against pancreatic cancer are of great interest. Because of their low cost and safety, patients commonly use a variety of dietary supplements, although evidence of their efficacy is often lacking. One such commonly used food supplement, Zyflamend, is a polyherbal preparation with potent anti-inflammatory activities, and preclinical efficacy against prostate and oral cancer. Whether Zyflamend has any efficacy against human pancreatic cancer alone or in combination with gemcitibine, a commonly used agent, was examined in cell cultures and in an orthotopic mouse model. In vitro, Zyflamend inhibited the proliferation of pancreatic cancer cell lines regardless of p53 status and also enhanced gemcitabine-induced apoptosis. This finding correlated with inhibition of NF-κB activation by Zyflamend and suppression of cyclin D1, c-myc, COX-2, Bcl-2, IAP, survivin, VEGF, ICAM-1, and CXCR4. In nude mice, oral administration of Zyflamend alone significantly inhibited the growth of orthotopically transplanted human pancreatic tumors, and when combined with gemcitabine, further enhanced the antitumor effects. Immunohistochemical and Western blot analyses of tumor tissue showed that the suppression of pancreatic cancer growth correlated with inhibition of proliferation index marker (Ki-67), COX-2, MMP-9, NF-κB, and VEGF. Overall, these results suggest that the concentrated multiherb product Zyflamend alone can inhibit the growth of human pancreatic tumors and, in addition, can sensitize pancreatic cancers to gemcitabine through the suppression of multiple targets linked to tumorigenesis. PMID:21935918

  10. Models of Human Metastatic Colon Cancer in Nude Mice Orthotopically Constructed by Using Histologically Intact Patient Specimens

    NASA Astrophysics Data System (ADS)

    Fu, Xinyu; Besterman, Jeffrey M.; Monosov, Ann; Hoffman, Robert M.

    1991-10-01

    There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients.

  11. Targeting Hypoxia-inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment

    PubMed Central

    Nigim, Fares; Cavanaugh, Jill; Patel, Anoop P.; Curry, William T.; Esaki, Shin-ichi; Kasper, Ekkehard M.; Chi, Andrew S.; Louis, David N.; Martuza, Robert L.; Rabkin, Samuel D.; Wakimoto, Hiroaki

    2015-01-01

    Tissue hypoxia and necrosis represent pathophysiological and histological hallmarks of glioblastoma (GBM). Although hypoxia inducible factor 1α (HIF-1α) plays crucial roles in the malignant phenotypes of GBM, developing HIF-1α-targeted agents has been hampered by the lack of a suitable preclinical model that recapitulates the complex biology of clinical GBM. We present a new GBM model, MGG123, which was established from a recurrent human GBM. Orthotopic xenografting of stem-like MGG123 cells reproducibly generated lethal tumors that were characterized by foci of palisading necrosis, hypervascularity, and robust stem cell marker expression. Perinecrotic neoplastic cells distinctively express HIF-1α and are proliferative in both xenografts and the patient tissue. The xenografts contain scattered hypoxic foci that were consistently >50 μm distant from blood vessels, indicating intratumoral heterogeneity of oxygenation. Hypoxia enhanced HIF-1α expression in cultured MGG123 cells, which was abrogated by the HIF-1α inhibitors digoxin or ouabain. In vivo, treatment of orthotopic MGG123 xenografts with digoxin decreased HIF-1α expression, vascular endothelial growth factor mRNA levels and CD34-positive vasculature within the tumors, and extended survival of mice bearing the aggressive MGG123 GBM. This preclinical tumor model faithfully recapitulates the GBM-relevant hypoxic microenvironment and stemness, and is a suitable platform for studying disease biology and developing hypoxia-targeted agents. PMID:26083570

  12. Orthotopic human melanoma xenograft model systems for studies of tumour angiogenesis, pathophysiology, treatment sensitivity and metastatic pattern.

    PubMed Central

    Rofstad, E. K.

    1994-01-01

    Adequate tumour models are a prerequisite in experimental cancer research. The purpose of the present work was to establish and assess the validity of four new orthotopic human melanoma xenograft model systems (A-07, D-12, R-18, U-25). Permanent cell lines were established in monolayer culture from subcutaneous metastases of four different melanoma patients by using an in vivo-in vitro procedure, and cells from these lines were inoculated intradermally in Balb/c nu/nu mice to form tumours. Individual xenografted tumours of the same line differed substantially in growth and pathophysiological parameters, probably as a consequence of differences between inoculation sites in host factors which influence tumour angiogenesis. Nevertheless, xenografted tumours of different lines showed distinctly different biological characteristics. Several biological characteristics of the donor patients' tumours were retained in the xenografted tumours, including angiogenic potential; growth, histopathological and pathophysiological parameters; and sensitivity to radiation, heat and dacarbazine treatment. Moreover, the organ-specific metastatic pattern of the xenografted tumours reflected the pattern of distant metastases in the donor patients. The organs of preference for distant metastases were lungs (A-07, D-12), lymph nodes (R-18) and brain (U-25). R-18 lymph node metastases and U-25 brain metastases developed in the absence of lung involvement. The four orthotopic human melanoma xenograft model systems show great promise for future studies of tumour angiogenesis, pathophysiology, treatment sensitivity and metastatic pattern. Images Figure 1 Figure 4 Figure 5 Figure 7 PMID:7947084

  13. Percutaneous Transluminal Angioplasty of Hepatic Artery Stenosis in Patients After Orthotopic Liver Transplantation: Mid-term Results

    SciTech Connect

    Jarmila, Lastovickova Jan, Peregrin

    2011-12-15

    Purpose: This study was designed to present our experience with percutaneous treatment of hepatic artery stenosis in orthotopic liver transplant patients and to evaluate the efficacy, technical outcomes, and mid-term clinical results of the procedure. Methods: Twenty-two percutaneous transluminal angioplasties (PTAs) were performed in 19 liver transplant recipients at our institution between 1998 and 2010. Stents were placed into the hepatic/celiac artery in 16 PTAs, but balloon dilatation alone was performed in 6 because of the anatomical condition of the vessel. PTA/stenting was indicated in 17 patients because of elevated liver enzymes; 2 patients were asymptomatic. The objective of treating stenosis was prevention of long-term complications, including thrombosis. Results: Technical success was achieved in all patients. There was only one complication: dissection of the treated artery without any subsequent adverse effects. In all patients, elevated liver enzyme levels improved after treatment. No restenosis was observed in any patient during a mean follow-up of 2.6 years (1 month to 5.5 years). Conclusions: Percutaneous angioplasty/stent placement is a safe method for the treatment of hepatic artery stenosis after orthotopic liver transplantation, with a high technical success rate and promising mid-term results.

  14. Lentivirus IL-10 gene therapy down-regulates IL-17 and attenuates mouse orthotopic lung allograft rejection.

    PubMed

    Hirayama, S; Sato, M; Loisel-Meyer, S; Matsuda, Y; Oishi, H; Guan, Z; Saito, T; Yeung, J; Cypel, M; Hwang, D M; Medin, J A; Liu, M; Keshavjee, S

    2013-06-01

    The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-γt without affecting levels of IL-12 and interferon-γ (IFN-γ). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation. PMID:23601206

  15. Prioritization Methodology for Chemical Replacement

    NASA Technical Reports Server (NTRS)

    Cruit, W.; Schutzenhofer, S.; Goldberg, B.; Everhart, K.

    1993-01-01

    This project serves to define an appropriate methodology for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semiquantitative approach derived from quality function deployment techniques (QFD Matrix). This methodology aims to weigh the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives. The results are being implemented as a guideline for consideration for current NASA propulsion systems.

  16. Wafer Replacement Cluster Tool (Presentation);

    SciTech Connect

    Branz, H. M.

    2008-04-01

    This presentation on wafer replacement cluster tool discusses: (1) Platform for advanced R and D toward SAI 2015 cost goal--crystal silicon PV at area costs closer to amorphous Si PV, it's 15% efficiency, inexpensive substrate, and moderate temperature processing (<800 C); (2) Why silicon?--industrial and knowledge base, abundant and environmentally benign, market acceptance, and good efficiency; and (3) Why replace wafers?--expensive, high embedded energy content, and uses 50-100 times more silicon than needed.

  17. Chimney renovation versus chimney replacement

    SciTech Connect

    Porthouse, R.A.

    1999-11-01

    Chimneys are an integral part of a fossil fueled generating station and perhaps one of the most commonly neglected and misunderstood structures at the plant. Structural damage caused by wind, earthquake, corrosive operating conditions, inadequate design, ever changing operating conditions, or years of neglect can render the structure unsafe and result in the need to perform major renovations or replace the entire chimney. The decision to renovate or replace an existing chimney is complex and should consider the following factors: (1) Age and condition of shell; (2) Type and condition of lining; (3) New operating conditions; (4) Cost of renovation vs replacement; (5) Unit outage time required; and (6) Cost for replacement power during outage. Information needed to make an informed decision regarding renovation or replacement, which most often involves several million dollars, can be best obtained from experienced chimney contractors and engineering specialists. This paper addresses four projects that utilized unique renovation techniques in lieu of partial or complete replacement of the structure.

  18. Prioritization methodology for chemical replacement

    NASA Technical Reports Server (NTRS)

    Cruit, Wendy; Goldberg, Ben; Schutzenhofer, Scott

    1995-01-01

    Since United States of America federal legislation has required ozone depleting chemicals (class 1 & 2) to be banned from production, The National Aeronautics and Space Administration (NASA) and industry have been required to find other chemicals and methods to replace these target chemicals. This project was initiated as a development of a prioritization methodology suitable for assessing and ranking existing processes for replacement 'urgency.' The methodology was produced in the form of a workbook (NASA Technical Paper 3421). The final workbook contains two tools, one for evaluation and one for prioritization. The two tools are interconnected in that they were developed from one central theme - chemical replacement due to imposed laws and regulations. This workbook provides matrices, detailed explanations of how to use them, and a detailed methodology for prioritization of replacement technology. The main objective is to provide a GUIDELINE to help direct the research for replacement technology. The approach for prioritization called for a system which would result in a numerical rating for the chemicals and processes being assessed. A Quality Function Deployment (QFD) technique was used in order to determine numerical values which would correspond to the concerns raised and their respective importance to the process. This workbook defines the approach and the application of the QFD matrix. This technique: (1) provides a standard database for technology that can be easily reviewed, and (2) provides a standard format for information when requesting resources for further research for chemical replacement technology. Originally, this workbook was to be used for Class 1 and Class 2 chemicals, but it was specifically designed to be flexible enough to be used for any chemical used in a process (if the chemical and/or process needs to be replaced). The methodology consists of comparison matrices (and the smaller comparison components) which allow replacement technology

  19. Homologous gene replacement in Physarum

    SciTech Connect

    Burland, T.G.; Pallotta, D.

    1995-01-01

    The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1 in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.

  20. Optimization of station battery replacement

    NASA Astrophysics Data System (ADS)

    Jancauskas, J. R.; Shook, D. A.

    1994-08-01

    During a loss of ac power at a nuclear generating station (including diesel generators), batteries provide the source of power which is required to operate safety-related components. Because traditional lead-acid batteries have a qualified life of 20 years, the batteries must be replaced a minimum of once during a station's lifetime, twice if license extension is pursued, and more often depending on actual in-service dates and the results of surveillance tests. Replacement of batteries often occurs prior to 20 years as a result of systems changes caused by factors such as Station Blackout Regulations, control system upgrades, incremental load growth, and changes in the operating times of existing equipment. Many of these replacement decisions are based on the predictive capabilities of manual design basis calculations. The inherent conservatism of manual calculations may result in battery replacements occurring before actually required. Computerized analysis of batteries can aid in optimizing the timing of replacements as well as in interpreting service test data. Computerized analysis also provides large benefits in maintaining the as-configured load profile and corresponding design margins, while also providing the capability to quickly analyze proposed modifications and respond to internal and external audits.

  1. Cobra Probes Containing Replaceable Thermocouples

    NASA Technical Reports Server (NTRS)

    Jones, John; Redding, Adam

    2007-01-01

    A modification of the basic design of cobra probes provides for relatively easy replacement of broken thermocouples. Cobra probes are standard tube-type pressure probes that may also contain thermocouples and that are routinely used in wind tunnels and aeronautical hardware. They are so named because in side views, they resemble a cobra poised to attack. Heretofore, there has been no easy way to replace a broken thermocouple in a cobra probe: instead, it has been necessary to break the probe apart and then rebuild it, typically at a cost between $2,000 and $4,000 (2004 prices). The modified design makes it possible to replace the thermocouple, in minimal time and at relatively low cost, by inserting new thermocouple wire in a tube.

  2. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the emory experience

    PubMed Central

    Landry, Jerome C.

    2016-01-01

    Background Cholangiocarcinoma (CCA) is a bile duct tumor with a grim prognosis. The median survival after radiotherapy of unresectable disease is 9-12 months. The following is a review of our experience with neoadjuvant (NEO) chemoradiation followed by orthotopic liver transplantation (OLT) for CCA. Methods Ten patients with CCAs were selected as candidates for NEO-OLT between 2008-2011. Patients with unresectable CCA above the cystic duct without intra or extrahepatic metastases were eligible. Primary sclerosing cholangitis (PSC) patients were included due to their poor resection response. Patients initially received external-beam radiation [via conventional fields or volumetric-modulated arc therapy (VMAT)] plus capecitabine (XEL) or 5-fluorouracil (5-FU), followed by either Iridium192 (Ir192) brachytherapy high dose rate (HDR) or external boost. 5-FU or XEL was administered until OLT. Patients underwent periodic surveillance computed tomography (CT)/MRIs after OLT. Primary endpoints included actuarial rates (AR)/crude rates (CR) of overall survival (OS), and local control (LC) at 6, 12, and 24 months. Results Five males and five females were identified. Mean age was 58.3 years (range, 38-71 years). Mean composite radiation dose delivered was 59.0 Gy (range, 54-71.4 Gy). Forty percent of patients had an HDR boost. Fifty percent of patients received XEL during NEO. Two patients were excluded from the analysis as they did not go on to OLT due to metastases (n=1) and death due to GI bleed (n=1). Thirty-eight percent of the OLT patients had a pathological complete response (pCR) after NEO, while 25% required a Whipple due to positive margins. Median follow-up for the OLT group was 23 months (range, 6.5-37 months). Six, twelve, and twenty-four months LC AR was 100%. LC CR was 100% at longest interval (30 months). Six, twelve, and twenty-four months OS AR was 100%, 87.5%, and 87.5%, respectively. Mean OS AR was 30.2 months (95% CI: 22.8-37.7). OS CR was 75% at longest

  3. (68)Ga-labeled 3PRGD2 for dual PET and Cerenkov luminescence imaging of orthotopic human glioblastoma.

    PubMed

    Fan, Di; Zhang, Xin; Zhong, Lijun; Liu, Xujie; Sun, Yi; Zhao, Huiyun; Jia, Bing; Liu, Zhaofei; Zhu, Zhaohui; Shi, Jiyun; Wang, Fan

    2015-06-17

    β-Emitters can produce Cerenkov radiation that is detectable by Cerenkov luminescence imaging (CLI), allowing the combination of PET and CLI with one radiotracer for both tumor diagnosis and visual guidance during surgery. Recently, the clinical feasibility of CLI with the established therapeutic reagent Na(131)I and the PET tracer (18)F-FDG was demonstrated. (68)Ga possesses a higher Cerenkov light output than (18)F and (131)I, which would result in higher sensitivity for CLI and improve the outcome of CLI in clinical applications. However, the research on (68)Ga-based tumor-specific tracers for CLI is limited. In this study, we examined the use of (68)Ga-radiolabeled DOTA-3PRGD2 ((68)Ga-3PRGD2) for dual PET and CLI of orthotopic U87MG human glioblastoma. For this purpose, the Cerenkov efficiencies of (68)Ga and (18)F were measured with the IVIS Spectrum system (PerkinElmer, USA). The CLI signal intensity of (68)Ga was 15 times stronger than that of (18)F. PET and CLI of (68)Ga-3PRGD2 were performed in U87MG human glioblastoma xenografts. Both PET and CLI revealed a remarkable accumulation of (68)Ga-3PRGD2 in the U87MG human glioblastoma xenografts at 1 h p.i. with an extremely low background in the brain when compared with (18)F-FDG. Furthermore, (68)Ga-3PRGD2 was used for dual PET and CLI of orthotopic human glioblastoma. The orthotopic human glioblastoma was clearly visualized by both imaging modalities. In addition, the biodistribution of (68)Ga-3PRGD2 was assessed in normal mice to estimate the radiation dosimetry. The whole-body effective dose is 20.1 ± 3.3 μSv/MBq, which is equal to 3.7 mSv per whole-body PET scan with a 5 mCi injection dose. Thus, (68)Ga-3PRGD2 involves less radiation exposure in patients when compared with (18)F-FDG (7.0 mSv). The use of (68)Ga-3PRGD2 in dual PET and CLI shows great promise for tumor diagnosis and image-guided surgery. PMID:25853280

  4. Molecular replacement: tricks and treats

    SciTech Connect

    Abergel, Chantal

    2013-11-01

    To be successful, molecular replacement relies on the quality of the model and of the crystallographic data. Some tricks that could be applied to the models or to the crystal to increase the success rate of MR are discussed here. Molecular replacement is the method of choice for X-ray crystallographic structure determination provided that suitable structural homologues are available in the PDB. Presently, there are ∼80 000 structures in the PDB (8074 were deposited in the year 2012 alone), of which ∼70% have been solved by molecular replacement. For successful molecular replacement the model must cover at least 50% of the total structure and the C{sub α} r.m.s.d. between the core model and the structure to be solved must be less than 2 Å. Here, an approach originally implemented in the CaspR server (http://www.igs.cnrs-mrs.fr/Caspr2/index.cgi) based on homology modelling to search for a molecular-replacement solution is discussed. How the use of as much information as possible from different sources can improve the model(s) is briefly described. The combination of structural information with distantly related sequences is crucial to optimize the multiple alignment that will define the boundaries of the core domains. PDB clusters (sequences with ≥30% identical residues) can also provide information on the eventual changes in conformation and will help to explore the relative orientations assumed by protein subdomains. Normal-mode analysis can also help in generating series of conformational models in the search for a molecular-replacement solution. Of course, finding a correct solution is only the first step and the accuracy of the identified solution is as important as the data quality to proceed through refinement. Here, some possible reasons for failure are discussed and solutions are proposed using a set of successful examples.

  5. HST Replacement Battery Initial Performance

    NASA Technical Reports Server (NTRS)

    Krol, Stan; Waldo, Greg; Hollandsworth, Roger

    2009-01-01

    The Hubble Space Telescope (HST) original Nickel-Hydrogen (NiH2) batteries were replaced during the Servicing Mission 4 (SM4) after 19 years and one month on orbit.The purpose of this presentation is to highlight the findings from the assessment of the initial sm4 replacement battery performance. The batteries are described, the 0 C capacity is reviewed, descriptions, charts and tables reviewing the State Of Charge (SOC) Performance, the Battery Voltage Performance, the battery impedance, the minimum voltage performance, the thermal performance, the battery current, and the battery system recharge ratio,

  6. Prioritization methodology for chemical replacement

    NASA Technical Reports Server (NTRS)

    Goldberg, Ben; Cruit, Wendy; Schutzenhofer, Scott

    1995-01-01

    This methodology serves to define a system for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semi quantitative approach derived from quality function deployment techniques (QFD Matrix). QFD is a conceptual map that provides a method of transforming customer wants and needs into quantitative engineering terms. This methodology aims to weight the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives.

  7. Circulating tumor cells are correlated with disease progression and treatment response in an orthotopic hepatocellular carcinoma model.

    PubMed

    Yan, Jun; Fan, Zhichao; Wu, Xiufeng; Xu, Min; Jiang, Jiahao; Tan, Changjun; Wu, Weizhong; Wei, Xunbin; Zhou, Jian

    2015-11-01

    Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by rapid progression, poor prognosis, and frequent hematogenous metastasis. A minimally invasive diagnostic biomarker that can predict disease progression and treatment response would be of extraordinary benefit. Therefore, we have investigated whether the number of circulating tumor cells (CTCs) is correlated with disease progression and treatment response in HCC. Here we report that the number of CTCs, monitored by in vivo flow cytometry (IVFC), is strongly correlated with disease progression and treatment response in a highly metastatic orthotopic nude mouse model of green fluorescent protein (GFP)-labeled HCC. Sorafenib treatment reduces the number of CTCs significantly. The decreased number of CTCs is consistent with low lung metastasis. This study has demonstrated a considerable clinical value of CTCs as a biomarker in predicting disease progression and monitoring therapeutic efficacy in patients with HCC. PMID:26355643

  8. Longitudinal stent fracture and migration of a stent fragment complicating treatment of hepatic vein stenosis after orthotopic liver transplantation.

    PubMed

    Goelitz, Brian W; Darcy, Michael

    2007-09-01

    We report a case of inferior vena cava (IVC) stent placement complicated by longitudinal stent fracture and migration of a stent fragment to the right pulmonary artery 2 years after initial placement. During attempted stenting of a hepatic venous anastomotic stenosis following orthotopic liver transplantation, a Palmaz P308 stent (Cordis International, Miami, FL) migrated and was redeployed into the IVC. Two years later, the patient had recurrent ascites and liver failure. Chest radiograph showed the Palmaz P308 stent had fractured longitudinally with a fragment in the right interlobular pulmonary artery. Half of the stent remained in the IVC. Mild stenosis was noted in the IVC where the stent was deployed. Overdilation of stents may be associated with stent fracture and should be performed with caution. PMID:21326480

  9. Asparagus polysaccharide and gum with hepatic artery embolization induces tumor growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model.

    PubMed

    Weng, Ling-Ling; Xiang, Jian-Feng; Lin, Jin-Bo; Yi, Shang-Hui; Yang, Li-Tao; Li, Yi-Sheng; Zeng, Hao-Tao; Lin, Sheng-Ming; Xin, Dong-Wei; Zhao, Hai-Liang; Qiu, Shu-Qi; Chen, Tao; Zhang, Min-Guang

    2014-01-01

    Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy. PMID:25605207

  10. Replaceable Sleeve Protects Welder Coil

    NASA Technical Reports Server (NTRS)

    Baker, W. L.; Simpson, C., E.

    1983-01-01

    New replaceable carbon insert for deflection coil in electron-beam welder promises to decrease maintenance costs. Inserts made from materials other than carbon (not yet tried) are less expensive, thus reducing costs even further. With carbon insert, deflection coils last longer and are easier to maintain.

  11. Developing High Quality Replacement Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Traditional approaches for postweaning development of replacement heifers used during the last several decades have primarily focused on feeding heifers to achieve or exceed an appropriate target weight, and thereby maximize heifer pregnancy rates. However, substantial changes in cattle genetics and...

  12. Will peanut hulls replace oil

    SciTech Connect

    Not Available

    1980-12-01

    A low-cost, fast-curing wood adhesive has been recently developed by the University of Georgia, in which up to 80% of the petroleum ingredients can be replaced with a substance extracted from peanut hulls. An outline of the process is given.

  13. Dehydroepiandrosterone replacement in addison's disease.

    PubMed

    Kim, S S; Brody, K H

    2001-07-01

    Addison's disease is a rare endocrine disorder which can be life-threatening. It can also interfere with the normal development of adrenarche, resulting in the absence of pubic and axillary hair growth. We report a case of satisfactory restoration of adrenarche through DHEA administered in conjunction with the standard glucocortisone and fluorocortisone replacement. PMID:11435018

  14. Testing of Replacement Bag Material

    SciTech Connect

    Laurinat, J.E.

    1998-11-03

    Recently, the FB-Line bagout material was changed to simplify the processing of sand, slag, and crucible.The results of the strength tests and the outgassing measurements and calculations demonstrate that the proposed replacement nylon bag materials (HRMP and orange anti-static material) are acceptable substitutes for LDPE and the original nylon with respect to mechanical properties.

  15. The therapeutic efficacy of I131-PSCA-mAb in orthotopic mouse models of prostate cancer

    PubMed Central

    2013-01-01

    Background Prostate stem cell antigen (PSCA) is upregulated in prostate cancer tissues. Here we aimed to study the therapeutic efficacy of a monoclonal antibody of PSCA-labeled I131 (I131-PSCA-mAb) in orthotopic mouse models of prostate cancer. Methods The proliferation, apoptosis and invasion abilities of PC-3 and LNCaP cells treated with I131-PSCA-mAb were measured by methyl thiazolyl tetrazolium assay, flow cytometry and transwell culture, respectively. The human prostate cancer models were established by orthotopic implantation of PC-3 and LNCaP cells in nude mice. I131-PSCA-mAb distribution and tumor cell apoptosis in the tumor-bearing nude mice were measured. Results The inhibitory and apoptosis rates of PC-3 and LNCaP cells treated with I131-PSCA-mAb reached a maximum of 84%, 80% and 50%, 46%, respectively, which were obviously higher than in the cells treated with I131-IgG or PSCA-mAb. The invaded number of PC-3 and LNCaP cells treated with I131-PSCA-mAbe was significantly reduced (P < 0.01) compared with the control group. The ratios of I131-PSCA-mAb in tumor to intramuscular I131-PSCA-mAb (T/NT) in tumor-bearing nude mice were increased with time and reached the highest level after 8 h. T/NT stayed above 3.0 after 12 h, and the tumor could still be developed after 24 h. The number of apoptotic cells in tumor tissue of nude mice treated with I131-PSCA-mAb was larger than that in the control group. Conclusion I131-PSCA-mAb has the potential to become a new targeted therapy drug for the treatment of prostate cancer. PMID:24330823

  16. Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

    PubMed Central

    Gatesman Ammer, Amanda; Hayes, Karen E.; Martin, Karen H.; Zhang, Lingqing; Spirou, George A.; Weed, Scott A.

    2011-01-01

    Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1nu/nu mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting. PMID:21808230

  17. MR Molecular Imaging of Prostate Cancer with a Peptide Targeted Contrast Agent in a Mouse Orthotopic Prostate Cancer Model

    PubMed Central

    Tan, Mingqian; Burden-Gulley, Susan M.; Li, Wen; Wu, Xueming; Lindner, Daniel; Brady-Kalnay, Susann M.; Gulani, Vikas; Lu, Zheng-Rong

    2014-01-01

    Purpose To study the effectiveness of a peptide targeted nanoglobular Gd-DOTA complexes for MR molecular imaging of prostate cancer in a mouse orthotopic PC-3 prostate cancer model. Methods A CLT1 (CGLIIQKNEC) peptide targeted generation 2 nanoglobular Gd-DOTA monoamide conjugate [CLT1-G2-(Gd-DOTA)] was used for imaging fibrin-fibronectin complexes in prostate tumor using a non-specific peptide KAREC modified conjugate, KAREC-G2-(Gd-DOTA) as a control. Cy5 conjugates of CLT1 and KAREC were synthesized for binding studies. Orthotopic PC-3 prostate tumors were established in the prostate of athymic male nude mice. MRI study was performed on a Bruker 7T animal scanner. Results CLT1 peptide showed specific binding in the prostate tumor with no binding in normal tissues. The control peptide had little binding in both normal and tumor tissues. CLT1-G2-(Gd-DOTA) resulted in stronger contrast enhancement in the tumor tissue than the KAREC-G2-(Gd-DOTA). CLT1-G2-(Gd-DOTA) generated approximately 100% increase in contrast-to-noise ratio (CNR) in the tumor as compared to precontrast CNR at 1 minute post-injection, while the control agent KAREC-G2-(Gd-DOTA) only resulted in 8% CNR increase. Conclusion CLT1-G2-(Gd-DOTA) is a promising molecular MRI contrast agent for fibrin-fibronectin complexes in the tumor stroma. It has a potential for the diagnosis and assessing prognosis of malignant tumors with MRI. PMID:22139536

  18. Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft.

    PubMed

    Inamoto, Teruo; Taniguchi, Kohei; Takahara, Kiyoshi; Iwatsuki, Ayako; Takai, Tomoaki; Komura, Kazumasa; Yoshikawa, Yuki; Uchimoto, Taizo; Saito, Kenkichi; Tanda, Naoki; Kouno, Junko; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Akao, Yukihiro; Azuma, Haruhito

    2015-08-28

    We previously reported that the level of microRNA (miR)-145 is attenuated in human bladder cancer cells. In this current study, we investigated whether intravesical administration of miR-145 could be a potential therapeutic strategy for controlling bladder cancer by using an orthotopic human bladder cancer xenograft model. Following transfection of 253J B-V cells with miR-145, the effects of the ectopic expression of miR-145 were examined by performing MTT, Western blotting analysis, Hoechst33342 staining, and wound healing assay in vitro. Also, a mouse orthotopic human bladder cancer model was established by inoculating 253J B-V cells into the bladder wall of mice. The anti-cancer effects of intravesical injections of miR-145 into these mice were then assessed. Transfection of 253J B-V cells with miR-145 induced apoptosis and suppression of cell migration in vitro. Western blotting showed that the levels of c-Myc, socs7, FSCN1, E-cadherin, β-catenin, and catenin δ-1 were decreased and that the PI3K/Akt and Erk1/2 signaling pathways were increased in compensatory fashion. In vivo, mice treated with miR-145 showed 76% inhibition of tumor growth, with a significant prolongation of animal survival (p = 0.0183 vs. control). Western blotting showed that both apoptosis and cell motility-related genes were significantly decreased as seen in vitro. Furthermore, PI3k/Akt and Erk1/2 signaling pathways, which were activated in a compensatory manner in vitro, were decreased in vivo. Intravesical administration of exogenous miR-145 was thus concluded to be a valid therapy for bladder cancer in this human bladder cancer xenograft model. PMID:26036261

  19. Intratracheally Administered 5-Azacytidine Is Effective Against Orthotopic Human Lung Cancer Xenograft Models and Devoid of Important Systemic Toxicity

    PubMed Central

    Mahesh, Sameer; Saxena, Ashish; Qiu, Xuan; Perez-Soler, Roman; Zou, Yiyu

    2014-01-01

    Introduction Hypermethylation of key tumor suppressor genes plays an important role in lung carcinogenesis. The purpose of this study is to explore the therapeutic potential of regional administration (via the airways) of the demethylating agent 5-azacytidine (5-Aza) for the treatment of early lung cancer. Patients and Methods We administered 5-Aza solution directly into the trachea in imprinting control region (ICR) mice (to study its toxicity) and in nude mice bearing orthotopic human lung cancer xenografts (to assess its antitumor activity). Results In vitro, 5-Aza inhibited the growth of human lung cancer cell lines H226, H358, and H460 in a dose-dependent manner. The concentrations to inhibit cell growth by 50% (IC50) were about 0.6-4.9 μg/mL. 5-Azacytidine reversed hypermethylation in the promoter of tumor suppressor gene RASSF1a in the H226 cells at a 6000-fold lower concentration than its IC50. In animal studies, intratracheal (I.T.) administration of 90 mg/kg 5-Aza (the maximum tolerated dose of 5-Aza intravenous injection [I.V.]) resulted in moderate pulmonary toxicity and 5-fold reduced myelosuppression compared with the same dose of I.V. 5-Aza. Using an optimized multiple dose schedule, I.T. 5-Aza was about 3-fold more effective than I.V. 5-Aza in prolonging the survival of mice bearing orthotopic H460 and H358 xenografts, and did not cause any detectable toxicity. Conclusion 5-Azacytidine can reverse the hypermethylation in the human lung cancer cell lines at a nontoxic dose. Regional administration to the airways enhances the therapeutic index of 5-Aza by 75-fold. The potential of regional administration of 5-Aza (including by aerosolization) for the treatment of advanced bronchial premalignancy deserves further investigation. PMID:21062731

  20. Imaging Hypoxia in Orthotopic Rat Liver Tumors with Iodine 124–labeled Iodoazomycin Galactopyranoside PET1

    PubMed Central

    Riedl, Christopher C.; Brader, Peter; Zanzonico, Pat B.; Chun, Yun Shin; Woo, Yanghee; Singh, Paramjeet; Carlin, Sean; Wen, Bixiu; Ling, C. Clifton; Hricak, Hedvig; Fong, Yuman

    2008-01-01

    Purpose: To evaluate iodine 124 (124I)-labeled iodoazomycin galactopyranoside (IAZGP) positron emission tomography (PET) in the detection of hypoxia in an orthotopic rat liver tumor model by comparing regions of high 124I-IAZGP uptake with independent measures of hypoxia and to determine the optimal time after injection to depict hypoxia. Materials and Methods: The institutional animal care and use committee approved this study. Morris hepatoma tumors were established in the livers of 15 rats. Tumor oxygenation was measured in two rats with a fluorescence fiberoptic oxygen probe. 124I-IAZGP was coadministered with the established hypoxia markers pimonidazole and EF5 in nine rats; 12-hour PET data acquisition was performed 24 hours later. Tumor cryosections were analyzed with immunofluorescence and autoradiography. In the four remaining rats, serial 20- and 60-minute PET data acquisition was peformed up to 48 hours after tracer administration. Results: Oxygen probe measurements showed severe hypoxia (<1 mm Hg) distributed evenly throughout tumor tissue. Analysis of cryosections showed diffuse homogeneous uptake of 124I-IAZGP throughout all tumors. The 124I-IAZGP distribution correlated positively with pimonidazole (r = 0.78) and EF5 (r = 0.76) distribution. Tracer uptake in tumors was detectable with PET after 24 hours in seven of nine rats. In rats that underwent serial PET, tumor-to-liver contrast was sufficient to enable detection of hypoxia between 6 and 48 hours after tracer administration. The optimal ratio between signal intensity and tumor-to-liver contrast occurred 6 hours after tracer administration. Conclusion: Regions of high 124I-IAZGP uptake in orthotopic rat liver tumors are consistent with independent measures of hypoxia; visualization of hypoxia with 124I-IAZGP PET is optimal 6 hours after injection. © RSNA, 2008 PMID:18641253

  1. Use of Panitumumab-IRDye800 to Image Microscopic Head and Neck Cancer in an Orthotopic Surgical Model

    PubMed Central

    Heath, C. Hope; Deep, Nicholas L.; Sweeny, Larissa; Zinn, Kurt R; Rosenthal, Eben L.

    2013-01-01

    Background Fluorescence imaging hardware (SPY) has recently been developed for intraoperative assessment of blood flow via detection of probes emitting in the near-infrared (NIR) spectrum. This study sought to determine if this imaging system was capable of detecting micrometastatic head and neck squamous cell carcinoma (HNSCC) in preclinical models. Methods A NIR fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody targeting EGFR (panitumumab) or non-specific IgG. HNSCC flank (SCC-1) and orthotopic (FADU and OSC19) xenografts were imaged 48-96hrs following systemic injection of labeled panitumumab or IgG. The primary tumor and regional lymph nodes were dissected using fluorescence guidance with the SPY system and grossly assessed with a charge-coupled NIR system (Pearl). Histologic slides were also imaged with a NIR charged-coupled device (Odyssey) and fluorescence intensity was correlated with pathologic confirmation of disease. Results Orthotopic tongue tumors were clearly delineated from normal tissue with tumor-to-background ratios of 2.9(Pearl) and 2.3(SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (P<0.05). Tissue biopsies (average size=3.7mm) positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (n=25/25). Biopsies of non-fluorescent tissue were proven to be negative for malignancy (n=28/28). The SPY was able to detect regional lymph node metastasis (<1.0mm) and microscopic areas of disease. Standard histological assessment in both frozen and paraffin-embedded histologic specimens was augmented using the Odyssey. Conclusions Panitumumab-IRDye800 may have clinical utility in detection and removal of microscopic HNSCC using existing intraoperative optical imaging hardware and may augment analysis of frozen and permanent pathology. PMID:22669455

  2. Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

    PubMed

    Ota, Shinichi; Geschwind, Jean-Francois H; Buijs, Manon; Wijlemans, Joost W; Kwak, Byung Kook; Ganapathy-Kanniappan, Shanmugasundaram

    2013-06-01

    Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer. PMID:23529644

  3. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE... Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means a dwelling selected by the head of a household as a replacement dwelling that meets the criteria of...

  4. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE... Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means a dwelling selected by the head of a household as a replacement dwelling that meets the criteria of...

  5. [MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT].

    PubMed

    Tabata, Minoru

    2016-03-01

    Minimally invasive aortic valve replacement (MIAVR) is defined as aortic valve replacement avoiding full sternotomy. Common approaches include a partial sternotomy right thoracotomy, and a parasternal approach. MIAVR has been shown to have advantages over conventional AVR such as shorter length of stay and smaller amount of blood transfusion and better cosmesis. However, it is also known to have disadvantages such as longer cardiopulmonary bypass and aortic cross-clamp times and potential complications related to peripheral cannulation. Appropriate patient selection is very important. Since the procedure is more complex than conventional AVR, more intensive teamwork in the operating room is essential. Additionally, a team approach during postoperative management is critical to maximize the benefits of MIAVR. PMID:27295772

  6. Indications for ulnar head replacement.

    PubMed

    Berger, Richard A

    2008-08-01

    Implanting an endoprosthesis is a clinically proven means of reestablishing mechanical contact between the distal radius and ulna, thus providing the foundation for stability of the entire forearm. The indications for, contraindications to, and outcomes of ulnar head replacement are discussed, together with the underlying mechanics, pathomechanics of ulnar head excision, the theoretical basis for implant arthroplasty, and the designs that have been employed. PMID:18836608

  7. Synthetic meniscus replacement: a review.

    PubMed

    Vrancken, Anne Christiane Theodora; Buma, Pieter; van Tienen, Tony George

    2013-02-01

    The number of meniscus-related operations continues to rise due to the ageing and more active population. Irreparable meniscal lesions generally require (partial) meniscectomy. Although a majority of the patients benefit from pain relief and functional improvement post-meniscectomy, some remain symptomatic. As an alternative to a meniscal allograft, which is only indicated for the severely damaged meniscus, most patients can nowadays be treated by implantation of a synthetic meniscal substitute. Currently three of these implants, two partial and one total replacement, are clinically available and several others are in the stage of preclinical testing. Grossly, two types of meniscal substitutes can be distinguished: porous, resorbable implants that stimulate tissue regeneration and solid, non-resorbable implants that permanently replace the whole meniscus. Although the implantation of a porous meniscus replacement generally seems promising and improves clinical outcome measures to some degree, their superiority to partial meniscectomy still needs to be proven. The evaluation of new prostheses being developed requires a wider focus than has been adopted so far. Upon selection of the appropriate materials, preclinical evaluation of such implants should comprise a combination of (in vitro) biomechanical and (in vivo) biological tests, while up to now the focus has mainly been on biological aspects. Obviously, well-defined randomised controlled trials are necessary to support clinical performance of new implants. Since the use of a meniscus replacement requires an additional costly implant and surgery compared to meniscectomy only, the clinical outcome of new products should be proven to surpass the results of the conventional therapies available. PMID:23100123

  8. Mitral valve repair versus replacement

    PubMed Central

    Keshavamurthy, Suresh; Gillinov, A. Marc

    2015-01-01

    Degenerative, ischemic, rheumatic and infectious (endocarditis) processes are responsible for mitral valve disease in adults. Mitral valve repair has been widely regarded as the optimal surgical procedure to treat mitral valve dysfunction of all etiologies. The supporting evidence for repair over replacement is strongest in degenerative mitral regurgitation. The aim of the present review is to summarize the data in each category of mitral insufficiency and to provide recommendations based upon this data. PMID:26309824

  9. Nicotine Replacement Therapy: An Overview

    PubMed Central

    Wadgave, Umesh; Nagesh, L

    2016-01-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  10. Nicotine Replacement Therapy: An Overview.

    PubMed

    Wadgave, Umesh; Nagesh, L

    2016-07-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  11. Mediastinitis and Mycotic Aneurysm of the Aorta after Orthotopic Heart Transplantation

    PubMed Central

    Anthuber, Matthias; Kemkes, Bernhard M.; Kreuzer, Ekkehard; Gokel, Michael; Schuetz, Albert; Kugler, Christian; Sudhoff, Frank

    1991-01-01

    After cardiac transplantation, bacterial mediastinitis is a rare but dangerous early complication. Of the 113 patients who underwent heart or heart-lung transplantation at our hospital from August 1981 to April 1989, 8 developed purulent mediastinitis. Treatment involved surgical débridment, local irrigation, drainage, and high-dose systemic antibiotics. No patient died of an acute mediastinal infection. In 2 cases, however, chronic mediastinitis led to the formation of a huge mycotic aneurysm of the ascending aorta. Eleven days after surgical intervention for rupture, 1 patient died of aneurysmal rerupture; the 2nd patient remains well 16 months after prosthetic replacement of the ascending aorta and reconstruction of the necrotic proximal portion of the left coronary artery with a saphenous vein patch. (Texas Heart Institute Journal 1991;18:186-93) Images PMID:15227478

  12. Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models.

    PubMed

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-10-13

    Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis. PMID:26375054

  13. Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models

    PubMed Central

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M.

    2015-01-01

    Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis. PMID:26375054

  14. Targeted Therapy Against VEGFR and EGFR With ZD6474 Enhances the Therapeutic Efficacy of Irradiation in an Orthotopic Model of Human Non-Small-Cell Lung Cancer

    SciTech Connect

    Shibuya, Keiko; Komaki, Ritsuko; Shintani, Tomoaki; Itasaka, Satoshi; Ryan, Anderson; Juergensmeier, Juliane M.; Milas, Luka; Ang, Kian; Herbst, Roy S.; O'Reilly, Michael S.

    2007-12-01

    Purpose: Conventional therapies for patients with lung cancer have reached a therapeutic plateau. We therefore evaluated the feasibility of combined vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and epidermal growth factor (EGF) receptor (EGFR) targeting with radiation therapy in an orthotopic model that closely recapitulates the clinical presentation of human lung cancer. Methods and Materials: Effects of irradiation and/or ZD6474, a small-molecule inhibitor of VEGFR2 and EGFR tyrosine kinases, were studied in vitro for human lung adenocarcinoma cells by using proliferation and clonogenic assays. The feasibility of combining ZD6474 with radiation therapy was then evaluated in an orthotopic model of human lung adenocarcinoma. Lung tumor burden and spread within the thorax were assessed, and tumor and adjacent tissues were analyzed by means of immunohistochemical staining for multiple parameters, including CD31, VEGF, VEGFR2, EGF, EGFR, matrix metalloproteinase-2 and -9, and basic fibroblast growth factor. Results: ZD6474 enhanced the radioresponse of NCI-H441 human lung adenocarcinoma cells by a factor of 1.37 and markedly inhibited sublethal damage repair. In vivo, the combined blockade of VEGFR2 and EGFR by ZD6474 blocked pleural effusion formation and angiogenesis and enhanced the antivascular and antitumor effects of radiation therapy in the orthotopic human lung cancer model and was superior to chemoradiotherapy. Conclusions: When radiation therapy is combined with VEGFR2 and EGFR blockade, significant enhancement of antiangiogenic, antivascular, and antitumor effects are seen in an orthotopic model of lung cancer. These data provide support for clinical trials of biologically targeted and conventional therapies for human lung cancer.

  15. Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.

    PubMed

    Westwood, Jennifer A; Potdevin Hunnam, Titaina C U; Pegram, Hollie J; Hicks, Rodney J; Darcy, Phillip K; Kershaw, Michael H

    2014-01-01

    We have found previously that the tumor cell lines, Renca (a renal cancer) and MC38 (a colon tumor) which had been injected subcutaneously in mice, could be successfully treated with a combination therapy of an oligodeoxynucleotide (CpG1826) (injected intratumorally) and anti-CD137 antibody (injected intraperitoneally). Thus the combination treatment was expected to initiate a "danger" signal via TLR9 on immune cells, and the anti-CD137 was expected to further activate T cells. In the present study, we found that several other tumor types injected subcutaneously could also be successfully treated with this combination therapy. In addition, we wished to determine if the treatment could work as effectively in an orthotopic metastatic model, which is more physiologically relevant to cancer in humans. Renca was selected as we were familiar with injecting this orthotopically into the outer cortex of the kidney in mice, and it spontaneously metastasizes to lung and abdominal sites. We tested various routes of delivery of CpG combined with intraperitoneal delivery of anti-CD137. Orthotopic tumors were injected with CpG intratumorally, using ultrasound-guided delivery on multiple occasions, combined with anti-CD137 intraperitoneally. A reduction in primary tumor size was observed following intratumoral injection of CpG compared to other treatments. We found that there was a statistically significant increase in survival of mice with orthotopic Renca tumor following intratumoral injection of CpG. However, we determined that the most effective route of delivery of CpG was intravenous, which led to further significantly enhanced survival of mice when combined with anti-CD137 intraperitoneally, likely due to inhibition of metastatic disease. Our data supports future development of this combination therapy for cancer. PMID:24788789

  16. Fluorescent-Antibody Targeting of Insulin-Like Growth Factor-1 Receptor Visualizes Metastatic Human Colon Cancer in Orthotopic Mouse Models

    PubMed Central

    Park, Jeong Youp; Murakami, Takashi; Lee, Jin Young; Zhang, Yong; Hoffman, Robert M.; Bouvet, Michael

    2016-01-01

    Fluorescent-antibody targeting of metastatic cancer has been demonstrated by our laboratory to enable tumor visualization and effective fluorescence-guided surgery. The goal of the present study was to determine whether insulin-like growth factor-1 receptor (IGF-1R) antibodies, conjugated with bright fluorophores, could enable visualization of metastatic colon cancer in orthotopic nude mouse models. IGF-1R antibody (clone 24–31) was conjugated with 550 nm, 650 nm or PEGylated 650 nm fluorophores. Subcutaneous, orthotopic, and liver metastasis models of colon cancer in nude mice were targeted with the fluorescent IGF-1R antibodies. Western blotting confirmed the expression of IGF-1R in HT-29 and HCT 116 human colon cancer cell lines, both expressing green fluorescent protein (GFP). Labeling with fluorophore-conjugated IGF-1R antibody demonstrated fluorescent foci on the membrane of colon cancer cells. Subcutaneously- and orthotopically-transplanted HT-29-GFP and HCT 116-GFP tumors brightly fluoresced at the longer wavelengths after intravenous administration of fluorescent IGF-1R antibodies. Orthotopically-transplanted HCT 116-GFP tumors were brightly labeled by fluorescent IGF-1R antibodies such that they could be imaged non-invasively at the longer wavelengths. In an experimental liver metastasis model, IGF-1R antibodies conjugated with PEGylated 650 nm fluorophores selectively highlighted the liver metastases, which could then be non-invasively imaged. The IGF-1R fluorescent-antibody labeled liver metastases were very bright compared to the normal liver and the fluorescent-antibody label co-located with green fluorescent protein (GFP) expression of the colon cancer cells. The present study thus demonstrates that fluorophore-conjugated IGF-1R antibodies selectively visualize metastatic colon cancer and have clinical potential for improved diagnosis and fluorescence-guided surgery. PMID:26731105

  17. Closure in Knee Replacement Surgery

    PubMed Central

    Kharat, Kiran

    2012-01-01

    Total Knee replacement (TKR) is one of the commonest arthroplasty surgeries performed. Various techniques of closures in TKR are described. This technical note describes an useful technique of achieving water tight closure in TKR. An optimal tension watertight closure also reduces the chances of dead space hematomas and infection. The author has described his technique where the soft tissues are never unduly compromised. In his experience the patient can be mobilized freely in bed and even allowed to sleep prone after first wound check.

  18. Senate committee recommends replacing FEMA

    NASA Astrophysics Data System (ADS)

    Zielinski, Sarah

    2006-05-01

    Flaws in the U.S. Federal Emergency Management Agency (FEMA) that were exposed after Hurricane Katrina struck the U.S. Gulf Coast in August 2005 are too substantial to be fixed, and the agency should be replaced with a more capable structure, recommends a 27 April report released by the Senate Committee on Homeland Security and Government Affairs. ``FEMA is discredited, demoralized, and dysfunctional. It is beyond repair. Just tweaking the organizational chart will not solve the problem,'' said Committee Chair Sen. Susan Collins (R-Maine).

  19. [Hemophilia B replacement therapy drugs].

    PubMed

    Yan, Hong; Zeng, Fanyi

    2016-02-01

    Hemophilia B is an X chromosome linked hereditary hemorrhagic disease, which is caused by the lose function mutation of factor IX (FIX), and significantly affects the patients' lifespan and life quality. The severity of hemophilia B depends on the FIX level in the plasma. By referring to the relevant literatures, we reviewed and summarized hemophilia B replacement therapies. Specifically, we focus on recombinant factor IX products on the market and those in the pipeline, especially on the long-acting factor IX drugs, to provide the basis for researches of new hemophilia B drugs. PMID:27382766

  20. Solvent replacement for green processing.

    PubMed Central

    Sherman, J; Chin, B; Huibers, P D; Garcia-Valls, R; Hatton, T A

    1998-01-01

    The implementation of the Montreal Protocol, the Clean Air Act, and the Pollution Prevention Act of 1990 has resulted in increased awareness of organic solvent use in chemical processing. The advances made in the search to find "green" replacements for traditional solvents are reviewed, with reference to solvent alternatives for cleaning, coatings, and chemical reaction and separation processes. The development of solvent databases and computational methods that aid in the selection and/or design of feasible or optimal environmentally benign solvent alternatives for specific applications is also discussed. Images Figure 2 Figure 3 PMID:9539018

  1. Replacing London's cast iron mains

    SciTech Connect

    Thorne, A. ); Mathews, P. )

    1992-07-01

    This paper discusses the cast iron gas distribution systems that exist in many cities and contains considerable amounts of pipe that vary in age from 20 to 150 years. In many ways, cast iron is an excellent material. It is inherently corrosion resistant, easy to install and cheap. However, it is also brittle and smaller diameter cast iron pipe has a relatively low beam strength. This can lead, under some circumstances, to failure without external warning, with typically a full-circumferential failure. In congested areas this can lead to serious consequences. As a result, cast iron replacement programs are a common feature in such urban gas distribution systems.

  2. Metallofullerene-based Nanoplatform for Brain Tumor Brachytherapy and Longitudinal Imaging in a Murine Orthotopic Xenograft Model

    PubMed Central

    Shultz, Michael D.; Wilson, John D.; Fuller, Christine E.; Zhang, Jianyuan; Dorn, Harry C.

    2011-01-01

    Purpose: To demonstrate in an orthotopic xenograft brain tumor model that a functionalized metallofullerene (f-Gd3N@C80) can enable longitudinal tumor imaging and, when radiolabeled with lutetium 177 (177Lu) and tetraazacyclododecane tetraacetic acid (DOTA) (177Lu-DOTA-f-Gd3N@C80), provide an anchor to deliver effective brachytherapy. Materials and Methods: All experiments involving the use of mice were carried out in accordance with protocols approved by the institutional animal care and use committee. Human glioblastoma U87MG cells were implanted by using stereotactic procedures into the brains of 37 female athymic nude-Foxn1nu mice and allowed to develop into a tumor for 8 days. T1- and T2-weighted magnetic resonance (MR) imaging was performed in five mice. Biodistribution studies were performed in 12 mice at four time points over 7 days to evaluate gadolinium content. Survival studies involved 20 mice that received infusion of a nanoplatform by means of convection-enhanced delivery (CED) 8 days after tumor implantation. Mice in survival studies were divided into two groups: one comprised untreated mice that received f-Gd3N@C80 alone and the other comprised mice treated with brachytherapy that received 1.11 MBq of 177Lu-DOTA-f-Gd3N@C80. Survival data were evaluated by using Kaplan-Meier statistical methods. Results: MR imaging showed extended tumor retention (25.6% ± 1.2 of the infused dose at 52 days, confirmed with biodistribution studies) of the f-Gd3N@C80 nanoplatform, which enabled longitudinal imaging. Successful coupling of 177Lu to the f-Gd3N@C80 surface was achieved by using a bifunctional macrocyclic chelator. The extended tumor retention allowed for effective brachytherapy, as indicated by extended survival time (>2.5 times that of the untreated group) and histologic signs of radiation-induced tumor damage. Conclusion: The authors have developed a multimodal nanoplatform and have demonstrated longitudinal tumor imaging, prolonged intratumoral probe

  3. A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model.

    PubMed

    Fu, Yilong; Ong, Lai-Chun; Ranganath, Sudhir H; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K H; Wang, Chi-Hwa

    2016-01-01

    Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID:26844770

  4. A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

    PubMed Central

    Ranganath, Sudhir H.; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K. H.; Wang, Chi-Hwa

    2016-01-01

    Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID:26844770

  5. A deimmunized bispecific ligand directed toxin that shows an impressive anti-pancreatic cancer effect in a systemic nude mouse orthotopic model

    PubMed Central

    Oh, Seunguk; Todhunter, Deborah A.; Panoskaltsis-Mortari, Angela; Buchsbaum, Donald J.; Toma, Shoko; Vallera, Daniel A.

    2011-01-01

    Objective The objective was to test a bispecific ligand directed toxin (BLT), with reduced immunogenicity for enhanced efficacy in targeting orthotopic pancreatic cancer in vivo. Method A new BLT was created in which both human EGF and IL-4 cytokines were cloned onto the same single chain molecule with deimmunized pseudomonas exotoxin (dEGF4KDEL). Key amino acids dictating B cell generation of neutralizing anti-toxin antibodies were mutated. Bioassays were used to determine whether mutation reduced potency, and ELISA studies were performed to determine whether anti-toxin antibodies were reduced. A genetically altered luciferase MIA PaCa-2 xenograft model was used to image in real time and determine affects on systemic malignant human cancer. BLTs targeting B cells were used as specificity controls. Results dEGF4KDEL was significantly effective following systemic injection against established orthotopic MIA PaCa-2 pancreatic cancer and selectively prevented metastasis. Mutagenesis significantly reduced anti-toxin levels in vivo with no apparent activity loss in vitro. The drug was effective against three human pancreatic cancer lines in vitro, MIA PaCa-2, SW1990, and S2VP10. Conclusions Despite the metastatic nature of the MIA PaCa-2 orthotopic tumor xenografted in nude mice, high percentages of tumors responded to extended dEGFKDEL treatment resulting in significant anti-cancer effects and disease-free survivors. PMID:22258068

  6. Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

    NASA Astrophysics Data System (ADS)

    Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

    2013-12-01

    The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755). After 24 h, the Olympus OV100 small-animal imaging system was used for noninvasive and intravital fluorescence imaging of mice. Dyes were compared with respect to depth of imaging, resolution, tumor-to-background ratio (TBR), photobleaching, and hemoglobin quenching. The longer wavelength dyes had increased depth of penetration and ability to detect the smallest tumor deposits and provided the highest TBRs, resistance to hemoglobin quenching, and specificity. The shorter wavelength dyes were more photostable. This study showed unique advantages of each dye for specific cancer imaging in a clinically relevant orthotopic model.

  7. The future of nicotine replacement.

    PubMed

    Russell, M A

    1991-05-01

    Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether. PMID:1859935

  8. Total hip replacement in dancers.

    PubMed

    Buyls, Inge R A E; Rietveld, A B M Boni; Ourila, Tiia; Emerton, Mark E; Bird, H A

    2013-04-01

    A case report of a professional contemporary dancer who successfully returned to the stage after bilateral total hip replacements (THR) for osteoarthritis is presented, together with her own commentary and a retrospective cohort study of total hip replacements in dancers. In the presented cohort, there were no post-operative dislocations or infections, the original pain had been relieved, rehabilitation was objectively normal and all resumed their dance (teaching) activities. Nevertheless, they were disappointed about the prolonged rehabilitation. Due to their high demands as professional dancers, post-operative expectations were too optimistic in view of the usual quick and favourable results of THR in the older and less physically active, general population. In all dancers with unilateral osteoarthritis, the left hip was involved, which may reflect the tendency to use the left leg as standing leg and be suggestive that strenuous physical activity may lead to osteoarthritis. Better rehabilitation guidelines are needed for dancer patients undergoing THR, especially drawing their attention to realistic post-operative expectations. PMID:23588878

  9. Deciding to have knee or hip replacement

    MedlinePlus

    ... patientinstructions/000368.htm Deciding to have knee or hip replacement To use the sharing features on this page, ... make a decision. Who Benefits From Knee or hip Replacement Surgery? The most common reason to have a ...

  10. Risks of hip and knee replacement

    MedlinePlus

    ... is normal to lose blood during and after hip or knee replacement surgery. Some people need a blood transfusion during ... clot form are higher during and soon after hip or knee replacement surgery. Sitting or lying down for long periods ...

  11. B Plant process piping replacement feasibility study

    SciTech Connect

    Howden, G.F.

    1996-02-07

    Reports on the feasibility of replacing existing embedded process piping with new more corrosion resistant piping between cells and between cells and a hot pipe trench of a Hanford Site style canyon facility. Provides concepts for replacement piping installation, and use of robotics to replace the use of the canyon crane as the primary means of performing/supporting facility modifications (eg, cell lining, pipe replacement, equipment reinstallation) and operational maintenenace.

  12. Knee Replacement - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Knee Replacement (Arabic) العربية Bilingual PDF Health Information Translations Bosnian (Bosanski) Total Knee Replacement Potpuna zamjena koljena - Bosanski (Bosnian) Bilingual PDF Health Information Translations Chinese - Simplified (简体中文) Total Knee Replacement 全膝关节置换 - 简体中文 ( ...

  13. 48 CFR 8.715 - Replacement commodities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Replacement commodities. 8... Are Blind or Severely Disabled 8.715 Replacement commodities. When a commodity on the Procurement List is replaced by another commodity which has not been previously acquired, and a qualified...

  14. Perfusion CT estimates photosensitizer uptake and biodistribution in a rabbit orthotopic pancreas cancer model: a pilot study

    PubMed Central

    Elliott, Jonathan T.; Samkoe, Kimberley S.; Gunn, Jason R.; Stewart, Errol E.; Gardner, Timothy B.; Tichauer, Kenneth M.; Lee, Ting-Yim; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

    2015-01-01

    Objectives It was hypothesized that perfusion computed tomography (CT) blood flow (BF), blood volume (BV) and vascular permeability surface-area (PS) product parameters would be predictive of therapeutic anti-cancer agent uptake in pancreatic cancer, facilitating image-guided interpretation of human treatments. The hypothesis was tested in an orthotopic rabbit model of pancreatic cancer, by establishing the model, imaging with endoscopic ultrasound and contrast CT, and spatially comparing the perfusion maps to the ex vivo uptake values of injected photosensitizer, vertepofin. Materials and Methods Nine New Zealand White rabbits underwent direct pancreas implantation of VX2 tumors and CT perfusion or endoscopic ultrasound was performed 10 days post-implantation. Verteporfin was injected during CT imaging and tissue was removed 1 h post-injection for frozen tissue fluorescence scanning. Region-of-interest comparisons of CT data with ex vivo fluorescence and histopathological staining were performed. Results DCE-CT showed enhanced BF, BV, and PS in the tumor rim, and decreased BF, BV and PS in the tumor core. Significant correlations were found between ex vivo verteporfin concentration and each of BF, BV, and PS. Conclusions The efficacy of verteporfin delivery in tumors is estimated by perfusion CT, providing a non-invasive method of mapping photosensitizer dose. PMID:25683500

  15. Vγ9Vδ2 T cells and zoledronate mediate antitumor activity in an orthotopic mouse model of human chondrosarcoma.

    PubMed

    Sun, L; Li, Y; Jiang, Z; Zhang, J; Li, H; Li, B; Ye, Z

    2016-06-01

    Chondrosarcoma (CS) is a cartilaginous malignant neoplasm characterized by resistance to conventional adjuvant therapy. The prognosis of unresectable or metastatic CS is poor. Therefore, it is imperative to explore novel therapeutic approaches to improve the treatment efficacy for those CS patients. Emerging data has implicated the synergistic antitumor activity of zoledronate (ZOL) and Vγ9Vδ2 T cells. However, whether ZOL-stimulated Vγ9Vδ2 T cells could infiltrate bone sarcoma and inhibit tumor growth has not been thoroughly answered yet. In this study, Vγ9Vδ2 T cells from healthy donors and CS patients were expanded in the presence of ZOL (1 μM) and IL-2 (400 IU/ml). The antitumor activity of Vγ9Vδ2 T cells to ZOL-pretreated human CS was examined both in vitro and in vivo. ZOL pretreatment substantially enhanced the cytotoxicity of Vγ9Vδ2 T cells to SW1353 and primary CS cells. ZOL potentiated the migration and cytotoxicity of Vγ9Vδ2 T cells to SW1353 in dose- and time-dependent manner. Moreover, weekly intravenous ZOL followed by Vγ9Vδ2 T cells inhibited subcutaneous xenograft growth. Thus, Vγ9Vδ2 T cells were able to infiltrate bone tumor and significantly suppressed the development of orthotopic SW1353 xenografts. Altogether, the study raises the possibility of combining ZOL with Vγ9Vδ2 T cells for CS treatment. PMID:26676633

  16. Efficient lung orthotopic tumor-growth suppression of oncolytic adenovirus complexed with RGD-targeted bioreducible polymer.

    PubMed

    Kim, J; Nam, H Y; Choi, J W; Yun, C-O; Kim, S W

    2014-05-01

    Oncolytic adenoviruses (Ad) have been developed for the eradication of tumors. Although they hold much promise as a cancer therapy, they have a short blood circulation time and high liver toxicity. An effective strategy to overcome these problems has been complexing Ad with shielding materials. However, the therapeutic efficacy of the Ad complexes has also been an issue because passive accumulation does not allow for sufficient delivery of Ad to the cancer cells. To enhance the therapeutic efficacy of the polymer-coated Ads, the attachment of a targeting moiety to polymer-coated Ad vectors is inescapable. Our lab has previously reported the potential use of Arg-Gly-Asp (RGD)-targeted bioreducible polymers with a polyethylene glycol (PEG) linker for delivering oncolytic Ads. We have shown the enhanced in vitro transduction efficiency and increased cancer-killing effect with producing progeny oncolytic Ad particles. In addition, we have shown significant tumor-growth inhibition of the polymer-shielded Ad in an in vivo lung orthotopic tumor model. The shielding effect of the Ad surface with the polymers allowed evasion of host immune responses and reduction of liver toxicity. This data demonstrates that the RGD-conjugated bioreducible polymer for delivering the oncolytic Ad vectors could be utilized for cancer therapy via systemic administration. PMID:24598892

  17. An iTEP-salinomycin nanoparticle that specifically and effectively inhibits metastases of 4T1 orthotopic breast tumors.

    PubMed

    Zhao, Peng; Xia, Guiquan; Dong, Shuyun; Jiang, Zhaong-Xing; Chen, Mingnan

    2016-07-01

    Cancer stem cell (CSC) inhibitors are a new category of investigational drugs to treat metastasis. Salinomycin (Sali) is one of most studied CSC inhibitors and has reached clinical tests. Several drug carriers have been developed to improve efficacy of Sali. However, Sali has not been shown to inhibit metastasis from orthotopic tumors, the gold standard for metastasis. To fill this gap, we developed an immune-tolerant, elastin-like polypeptide (iTEP)-based nanoparticle (iTEP-Sali-ABA NP) that released 4-(aminomethyl)benzaldehyde-modified Sali (Sali-ABA) under acidic conditions. We found that the NP increased the area under the curve (AUC) of Sali-ABA by 30-fold and the tumor accumulation by 3.4-fold. Furthermore, no metastasis was detected in any of the mice given the NP. However, all the mice died of primary tumor burdens. To overcome primary tumor growth and improve the overall survival, we applied a combination therapy consisting of the iTEP-Sali-ABA NP and iTEP NP-delivered paclitaxel. This therapy effectively retarded primary tumor growth, and most importantly, improved the overall survival. In conclusion, delivery of Sali-ABA by the NP, alone or in combination with paclitaxel, was more effective than free Sali-ABA in decreasing metastasis and increasing survival. This iTEP-Sali-ABA NP represents a novel and clinically promising therapy to combat metastasis. PMID:27060212

  18. Detection and Quantitation of Circulating Tumor Cell Dynamics by Bioluminescence Imaging in an Orthotopic Mammary Carcinoma Model

    PubMed Central

    Sasportas, Laura Sarah; Hori, Sharon Seiko; Pratx, Guillem; Gambhir, Sanjiv Sam

    2014-01-01

    Circulating tumor cells (CTCs) have been detected in the bloodstream of both early-stage and advanced cancer patients. However, very little is know about the dynamics of CTCs during cancer progression and the clinical relevance of longitudinal CTC enumeration. To address this, we developed a simple bioluminescence imaging assay to detect CTCs in mouse models of metastasis. In a 4T1 orthotopic metastatic mammary carcinoma mouse model, we demonstrated that this quantitative method offers sensitivity down to 2 CTCs in 0.1–1mL blood samples and high specificity for CTCs originating from the primary tumor, independently of their epithelial status. In this model, we simultaneously monitored blood CTC dynamics, primary tumor growth, and lung metastasis progression over the course of 24 days. Early in tumor development, we observed low numbers of CTCs in blood samples (10–15 cells/100 µL) and demonstrated that CTC dynamics correlate with viable primary tumor growth. To our knowledge, these data represent the first reported use of bioluminescence imaging to detect CTCs and quantify their dynamics in any cancer mouse model. This new assay is opening the door to the study of CTC dynamics in a variety of animal models. These studies may inform clinical decision on the appropriate timing of blood sampling and value of longitudinal CTC enumeration in cancer patients. PMID:25188396

  19. Percutaneous Treatment of Biliary Cast Syndrome After Orthotopic Liver Transplantation: Comparison of Mechanical Versus Hydraulic Rheolytic Cast Extraction

    SciTech Connect

    Lopez-Benitez, R. Wielpuetz, M. O. Bryant, M. G. H.; Ganten, Tom; Richter, G. M.; Flach, N. Hallscheidt, P. J.

    2011-10-15

    Purpose: Biliary cast syndrome (BCS) is the presence of casts within the intrahepatic or extrahepatic biliary system after orthotopic liver transplantation. Our work compares two percutaneous methods for BCS treatment: the mechanical cast-extraction technique (MCE) versus the hydraulic cast-extraction (HCE) technique using a rheolytic system. Materials and Methods: A total of 24 patients were included in the study. Six patients were referred for HCE, and 18 patients were treated with MCE. A statistically significant larger number of sessions was required in the MCE group (21.0, range 11 to 72 sessions) (p = 0.033). Results: Median therapy duration was shorter in the HCE group at 2.4 months (range 2 to 5) compared with 6.7 months (range 3 to 39) in the MCE group (p < 0.001). Both patient acceptance was better and costs for total therapy were 40% less in the HCE group. No significant differences where found concerning clinical and biochemical improvement or graft and patient survival. Conclusion: The use of the hydraulic rheolytic system decreased total therapy time, thereby decreasing the induced inflammation time of the biliary tree. A significant benefit of HCE has been observed in our patients when we compare our results with those of MCE.

  20. Sodium orthovanadate inhibits growth of human hepatocellular carcinoma cells in vitro and in an orthotopic model in vivo.

    PubMed

    Wu, Yaohua; Ma, Yong; Xu, Zhilin; Wang, Dawei; Zhao, Baolei; Pan, Huayang; Wang, Jizhou; Xu, Dongsheng; Zhao, Xiaoyang; Pan, Shangha; Liu, Lianxin; Dai, Wenjie; Jiang, Hongchi

    2014-08-28

    The transition metal vanadium is widely distributed in the environment and exhibits various biological and physiological effects in the human body. As a well known vanadium compound, sodium orthovanadate (SOV) has shown promising antineoplastic activity in several human cancers. However, the effects of SOV on liver cancer are still unknown. In this study, for the first time, we showed that SOV could effectively suppress proliferation, induce G2/M cell cycle arrest and apoptosis, and diminish the mitochondrial membrane potential (MMP) of HCC cells in vitro. In addition, our in vitro results were recapitulated in vivo, showing that SOV exhibited a dose-dependent inhibition of growth of human HCC in an orthotopic model, evidenced by the reduction in tumor size, proliferation index and microvessel density, and increase in cell apoptosis. Most important, we found that SOV could inhibit autophagy in HCC cells in vitro and in vivo, which plays a prodeath role. Thus, our findings suggest that SOV could effectively suppress the growth of human HCC through the regulations of proliferation, cell cycle, apoptosis and autophagy, and thus may act as a potential therapeutic agent in HCC treatment. PMID:24858025

  1. The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC.

    PubMed

    Herz, Corinna; Hertrampf, Anke; Zimmermann, Stefan; Stetter, Nadine; Wagner, Meike; Kleinhans, Claudia; Erlacher, Miriam; Schüler, Julia; Platz, Stefanie; Rohn, Sascha; Mersch-Sundermann, Volker; Lamy, Evelyn

    2014-12-01

    In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level. PMID:25256442

  2. Iron-Oxide-Based Nanovector for Tumor Targeted siRNA Delivery in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model.

    PubMed

    Wang, Kui; Kievit, Forrest M; Sham, Jonathan G; Jeon, Mike; Stephen, Zachary R; Bakthavatsalam, Arvind; Park, James O; Zhang, Miqin

    2016-01-27

    Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Small interfering RNA (siRNA) holds promise as a new class of therapeutics for HCC, as it can achieve sequence-specific gene knockdown with low cytotoxicity. However, the main challenge in the clinical application of siRNA lies in the lack of effective delivery approaches that need to be highly specific and thus incur low or no systemic toxicity. Here, a nonviral nanoparticle-based gene carrier is presented that can specifically deliver siRNA to HCC. The nanovector (NP-siRNA-GPC3 Ab) is made of an iron oxide core coated with chitosan-polyethylene glycol (PEG) grafted polyethyleneimine copolymer, which is further functionalized with siRNA and conjugated with a monoclonal antibody (Ab) against human glypican-3 (GPC3) receptor highly expressed in HCC. A rat RH7777 HCC cell line that coexpresses human GPC3 and firefly luciferase (Luc) is established to evaluate the nanovector. The nanoparticle-mediated delivery of siRNA against Luc effectively suppresses Luc expression in vitro without notable cytotoxicity. Significantly, NP-siLuc-GPC3 Ab administered intravenously in an orthotopic model of HCC is able to specifically bound to tumor and induce remarkable inhibition of Luc expression. The findings demonstrate the potential of using this nanovector for targeted delivery of therapeutic siRNA to HCC. PMID:26641029

  3. Duct-to-duct biliary reconstruction in orthotopic liver transplantation for primary sclerosing cholangitis: a viable and safe alternative.

    PubMed

    Damrah, Osama; Sharma, Dinesh; Burroughs, Andrew; Rolando, Nancy; Fernando, Bimbi; Davidson, Brian; Rolles, Keith

    2012-01-01

    Roux-en-Y loop is considered the reconstruction method of choice in Orthotopic Liver Transplantation (OLT) for Primary Sclerosing Cholangitis (PSC). We have adopted an approach of duct-to-duct (D-D) reconstruction when recipient common bile duct is free of gross disease. Patients were divided into two groups: patients who underwent a Roux-en-Y choledochojejunostomy and patients who had a D-D anastomosis. Morbidity, mortality, disease recurrence and graft and patient survival were compared between the two groups and analyzed. Ninety-one patients had OLT for PSC. Sixty-three patients underwent a D-D biliary reconstruction, whereas 28 patients had a Roux-en-Y loop. Biliary leak complicated 8% from the D-D group, and 14% from the Roux-en-Y group (P = 0.08), whereas biliary strictures were identified in 10% vs. 7% patients from the D-D and Roux-en-Y group, respectively (P = 0.9). Actuarial 1, 3 and 10 year survival for D-D and Roux-en-Y group was (87%, 80% and 62%) and (82%, 73% and 73%), respectively (P = 0.7). The corresponding 1, 3 and 10 year graft survival was (72%, 58% and 42%) and (67%, 58% and 53%), respectively (P = 0.6). No difference was seen in disease recurrence rates. D-D biliary reconstruction in OLT for selected PSC patients remains our first option of reconstruction. PMID:22017643

  4. A“Proteoglycan Targeting Strategy” for the Scintigraphic Imaging and Monitoring of the Swarm Rat Chondrosarcoma Orthotopic Model

    PubMed Central

    Peyrode, Caroline; Gouin, François; Vidal, Aurélien; Auzeloux, Philippe; Besse, Sophie; Dauplat, Marie-Mélanie; Askienazy, Serge; Heymann, Dominique; Chezal, Jean-Michel; Redini, Françoise; Miot-Noirault, Elisabeth

    2011-01-01

    Our lab developed 99mTc-NTP 15-5 radiotracer as targeting proteoglycans (PGs) for the scintigraphic imaging of joint. This paper reports preclinical results of 99mTc-NTP 15-5 imaging of an orthotopic model of Swarm rat chondrosarcoma (SRC). 99mTc-NTP 15-5 imaging of SRC-bearing and sham-operated animals was performed and quantified at regular intervals after surgery and compared to bone scintigraphy and tumoural volume. Tumours were characterized by histology and PG assay. SRC exhibited a significant 99mTc-NTP 15-5 uptake at very early stage after implant (with tumour/muscle ratio of 1.61 ± 0.14), whereas no measurable tumour was evidenced. As tumour grew, mean tumour/muscle ratio was increased by 2.4, between the early and late stage of pathology. Bone scintigraphy failed to image chondrosarcoma, even at the later stage of study. 99mTc-NTP 15-5 imaging provided a suitable set of quantitative criteria for the in vivo characterization of chondrosarcoma behaviour in bone environment, useful for achieving a greater understanding of the pathology. PMID:21331335

  5. Cannulation Selection of Portal Venous and Splenic Venous Catheterization in Venovenous Bypass of Swine Orthotopic Liver Transplantation.

    PubMed

    Wang, Meng-Yuan; Wang, Meng-Hao; Peng, Yong; You, Hai-Bo; Chen, Xian-Feng; Zhao, Lei; Gan, Lin; Li, Min; Li, Jin-Zheng; Gong, Jian-Ping; Li, Xu-Hong

    2016-01-01

    BACKGROUND The aim of this study was to compare the hemodynamic changes in 2 different cannulations in portal system (portal venous catheterization and splenic venous catheterization) during venovenous bypass (VVB) of swine orthotopic liver transplantation (OLT) MATERIAL AND METHODS Thirty pairs (a total of 60) of healthy Duroc pigs were selected for OLT. According to the difference of cannulation in portal venous system during VVB, these pigs were divided into 2 groups: the PVC group (pigs with portal venous catheterization, n=15) and the SVC group (pigs with splenic venous catheterization, n=15). Intraoperative hemodynamic parameters were monitored continuously. RESULTS Two recipients in the PVC group died: 1 died of unsmooth bypass during the operation and 1 died of disseminated intravascular coagulation (DIC). There was only 1 death in the SVC group, due to hemorrhagic shock. The duration of anhepatic phase (AP) in the SVC group was significantly shorter than in the PVC group (P<0.05). Moreover, hemodynamic parameters in phase III (5 min after start of portal vein suturing) and phase IV (5 min after graft reperfusion) were remarkably different between the SVC group and the PVC group (P<0.05). CONCLUSIONS Our results show that VVB via splenic venous catheterization in swine OLT: 1) shortens the AP time; 2) keeps the hemodynamics stable; and 3) reduces the occurrence of postoperative complications. Thus, SVC appears to be superior to PVC. PMID:27251849

  6. The application of surgical navigation system using optical molecular imaging technology in orthotopic breast cancer and metastasis studies

    NASA Astrophysics Data System (ADS)

    Chi, Chongwei; Zhang, Qian; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Du, Yang; Tian, Jie

    2014-02-01

    Currently, it has been an international focus on intraoperative precise positioning and accurate resection of tumor and metastases. The methods such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role in preoperative accurate diagnosis. However, most of them are inapplicable for intraoperative surgery. We have proposed a surgical navigation system based on optical molecular imaging technology for intraoperative detection of tumors and metastasis. This system collects images from two CCD cameras for real-time fluorescent and color imaging. For image processing, the template matching algorithm is used for multispectral image fusion. For the application of tumor detection, the mouse breast cancer cell line 4T1-luc, which shows highly metastasis, was used for tumor model establishment and a model of matrix metalloproteinase (MMP) expressing breast cancer. The tumor-bearing nude mice were given tail vein injection of MMP 750FAST (PerkinElmer, Inc. USA) probe and imaged with both bioluminescence and fluorescence to assess in vivo binding of the probe to the tumor and metastases sites. Hematoxylin and eosin (H&E) staining was performed to confirm the presence of tumor and metastasis. As a result, one tumor can be observed visually in vivo. However liver metastasis has been detected under surgical navigation system and all were confirmed by histology. This approach helps surgeons to find orthotopic tumors and metastasis during intraoperative resection and visualize tumor borders for precise positioning. Further investigation is needed for future application in clinics.

  7. The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC

    PubMed Central

    Herz, Corinna; Hertrampf, Anke; Zimmermann, Stefan; Stetter, Nadine; Wagner, Meike; Kleinhans, Claudia; Erlacher, Miriam; Schüler, Julia; Platz, Stefanie; Rohn, Sascha; Mersch-Sundermann, Volker; Lamy, Evelyn

    2014-01-01

    In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level. PMID:25256442

  8. Mitochondrial Replacement: Ethics and Identity.

    PubMed

    Wrigley, Anthony; Wilkinson, Stephen; Appleby, John B

    2015-11-01

    Mitochondrial replacement techniques (MRTs) have the potential to allow prospective parents who are at risk of passing on debilitating or even life-threatening mitochondrial disorders to have healthy children to whom they are genetically related. Ethical concerns have however been raised about these techniques. This article focuses on one aspect of the ethical debate, the question of whether there is any moral difference between the two types of MRT proposed: Pronuclear Transfer (PNT) and Maternal Spindle Transfer (MST). It examines how questions of identity impact on the ethical evaluation of each technique and argues that there is an important difference between the two. PNT, it is argued, is a form of therapy based on embryo modification while MST is, instead, an instance of selective reproduction. The article's main ethical conclusion is that, in some circumstances, there is a stronger obligation to use PNT than MST. PMID:26481204

  9. Optimal randomized scheduling by replacement

    SciTech Connect

    Saias, I.

    1996-05-01

    In the replacement scheduling problem, a system is composed of n processors drawn from a pool of p. The processors can become faulty while in operation and faulty processors never recover. A report is issued whenever a fault occurs. This report states only the existence of a fault but does not indicate its location. Based on this report, the scheduler can reconfigure the system and choose another set of n processors. The system operates satisfactorily as long as, upon report of a fault, the scheduler chooses n non-faulty processors. We provide a randomized protocol maximizing the expected number of faults the system can sustain before the occurrence of a crash. The optimality of the protocol is established by considering a closely related dual optimization problem. The game-theoretic technical difficulties that we solve in this paper are very general and encountered whenever proving the optimality of a randomized algorithm in parallel and distributed computation.

  10. Mitochondrial Replacement: Ethics and Identity

    PubMed Central

    Wilkinson, Stephen; Appleby, John B.

    2015-01-01

    Abstract Mitochondrial replacement techniques (MRTs) have the potential to allow prospective parents who are at risk of passing on debilitating or even life‐threatening mitochondrial disorders to have healthy children to whom they are genetically related. Ethical concerns have however been raised about these techniques. This article focuses on one aspect of the ethical debate, the question of whether there is any moral difference between the two types of MRT proposed: Pronuclear Transfer (PNT) and Maternal Spindle Transfer (MST). It examines how questions of identity impact on the ethical evaluation of each technique and argues that there is an important difference between the two. PNT, it is argued, is a form of therapy based on embryo modification while MST is, instead, an instance of selective reproduction. The article's main ethical conclusion is that, in some circumstances, there is a stronger obligation to use PNT than MST. PMID:26481204

  11. The Attenborough total knee replacement.

    PubMed

    Attenborough, C G

    1978-08-01

    The stabilised gliding knee prosthesis is a compromise between hinged joints and condylar prostheses. It is a two-piece implant designed to allow normal gliding movements of flexion and extension and which, stabilised by a connecting rod between the femoral and tibial components, allows a designed laxity of rotation and lateral movements. A modification of the original femoral component is described. Two hundred and forty-five knee replacement operations have been done between January 1973 and September 1977 and the results are reported. The results using this prosthesis are at least equal to those using hinged or condylar prostheses. So far there has been no case of spontaneous loosening of the components and the implant can be used in patients who, because of severe deformities and instability, are unsuitable for condylar prostheses. PMID:681407

  12. Replacement Sequence of Events Generator

    NASA Technical Reports Server (NTRS)

    Fisher, Forest; Gladden, Daniel Wenkert Roy; Khanampompan, Teerpat

    2008-01-01

    The soeWINDOW program automates the generation of an ITAR (International Traffic in Arms Regulations)-compliant sub-RSOE (Replacement Sequence of Events) by extracting a specified temporal window from an RSOE while maintaining page header information. RSOEs contain a significant amount of information that is not ITAR-compliant, yet that foreign partners need to see for command details to their instrument, as well as the surrounding commands that provide context for validation. soeWINDOW can serve as an example of how command support products can be made ITAR-compliant for future missions. This software is a Perl script intended for use in the mission operations UNIX environment. It is designed for use to support the MRO (Mars Reconnaissance Orbiter) instrument team. The tool also provides automated DOM (Distributed Object Manager) storage into the special ITAR-okay DOM collection, and can be used for creating focused RSOEs for product review by any of the MRO teams.

  13. Dental ontogeny and replacement in Pliosauridae

    PubMed Central

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-01-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or ‘movement paths’, of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context. PMID:26715998

  14. Dental ontogeny and replacement in Pliosauridae.

    PubMed

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-11-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or 'movement paths', of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context. PMID:26715998

  15. Visual Image Sensor Organ Replacement

    NASA Technical Reports Server (NTRS)

    Maluf, David A.

    2014-01-01

    This innovation is a system that augments human vision through a technique called "Sensing Super-position" using a Visual Instrument Sensory Organ Replacement (VISOR) device. The VISOR device translates visual and other sensors (i.e., thermal) into sounds to enable very difficult sensing tasks. Three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. Because the human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns, the translation of images into sounds reduces the risk of accidentally filtering out important clues. The VISOR device was developed to augment the current state-of-the-art head-mounted (helmet) display systems. It provides the ability to sense beyond the human visible light range, to increase human sensing resolution, to use wider angle visual perception, and to improve the ability to sense distances. It also allows compensation for movement by the human or changes in the scene being viewed.

  16. Engineering Alloplastic Temporomandibular Joint Replacements

    PubMed Central

    Sinno, Hani; Tahiri, Youssef; Gilardino, Mirko; Bobyn, Dennis

    2011-01-01

    Temporomandibular disorders (TMD) are part of a heterogeneous group of pathologies that manifest with a constellation of signs and symptoms. They are the most frequent cause of chronic orofacial pain and are prevalent in 12% of the general population. Despite the debilitating nature of these disorders, there is no standardization for treatment of the diseased temporomandibular joint (TMJ). In this review, we present an overview of the functional anatomy of the TMJ and the engineering concepts that must be understood to better understand the indications for surgical management, the types of available treatments and the requirements for reconstruction. A comparison is made of the clinical outcomes with autogenous versus alloplastic reconstruction, including a history of alloplastic materials and the design features of currently available implants. Emphasis is made on material selection, modulus, stiffness, notch sensitivity and modularity. For the treatment of TMD, engineered TMJ alloplastic replacements have had considerable promise with additional room for improvement using new materials and recent design concepts. PMID:22363183

  17. Recurrence of hepatitis C virus genotype-4 infection following orthotopic liver transplantation: Natural history and predictors of outcome

    PubMed Central

    Mudawi, Hatim; Helmy, Ahmed; Kamel, Yasser; Al Saghier, Mohammed; Al Sofayan, Mohammed; Al Sebayel, Mohammed; Khalaf, Hatem; Al Bahili, Hamad; Al Shiek, Yasser; Alawi, Khalil; AlJedai, Ahmed; Mohamed, Hazem; Al Hamoudi, Waleed; Abdo, Ayman

    2009-01-01

    BACKGROUND AND OBJECTIVES: There are few reports on hepatitis C virus genotype 4 (HCV-4) recurrences after orthotopic liver transplantation (OLT). Therefore, we undertook a study to determine the epidemiological, clinical and virological characteristics of patients with biopsy-proven recurrent HCV infection and analyzed the factors that influence recurrent disease severity. We also compared disease recurrence and outcomes between HCV-4 and other genotypes. PATIENTS AND METHODS: All patients who underwent OLT (locally or abroad) for HCV related hepatic cirrhosis from 1991 to 2006 and had recurrent HCV infection were identified. Clinical, laboratory and pathological data before and after OLT were collected and analyzed. RESULTS: Of 116 patients who underwent OLT for hepatitis C, 46 (39.7%) patients satisfied the criteria of recurrent hepatitis C. Twenty-nine (63%) patients were infected with HCV genotype 4. Mean (SD) for age was 54.9 (10.9) years. Nineteen of the HCV genotype 4 patients (65.5%) were males, 21 (72.4%) received deceased donor grafts, and 7 (24.1%) developed ≥1 acute rejection episodes. Pathologically, 7 (24.1%) and 4 (13.8%) patients had inflammation grade 3-4 and fibrosis stage 3-4, respectively. Follow-up biopsy in 9 (31%) HCV genotype 4 patients showed stable, worse and improved fibrosis stage in 5, 2 and 2 patients, respectively. Of the 7 patients in the recurrent HCV group who died, 6 were infected with genotype 4 and 4 of them died of HCV-related disease. CONCLUSION: This analysis suggests that HCV recurrence following OLT in HCV-4 patients is not significantly different from its recurrence for other genotypes. PMID:19318754

  18. Vasculature-specific MRI reveals differential anti-angiogenic effects of a biomimetic peptide in an orthotopic breast cancer model.

    PubMed

    Kim, Eugene; Lee, Esak; Plummer, Charlesa; Gil, Stacy; Popel, Aleksander S; Pathak, Arvind P

    2015-04-01

    Translational vasculature-specific MRI biomarkers were used to measure the effects of a novel anti-angiogenic biomimetic peptide in an orthotopic MDA-MB-231 human triple-negative breast cancer model at an early growth stage. In vivo diffusion-weighted and steady-state susceptibility contrast (SSC) MRI was performed pre-treatment and 2 weeks post-treatment in tumor volume-matched treatment and control groups (n = 5/group). Treatment response was measured by changes in tumor volume; baseline transverse relaxation time (T2); apparent diffusion coefficient (ADC); and SSC-MRI metrics of blood volume, vessel size, and vessel density. These vasculature-specific SSC-MRI biomarkers were compared to the more conventional, non-vascular biomarkers (tumor growth, ADC, and T2) in terms of their sensitivity to anti-angiogenic treatment response. After 2 weeks of peptide treatment, tumor growth inhibition was evident but not yet significant, and the changes in ADC or T2 were not significantly different between treated and control groups. In contrast, the vascular MRI biomarkers revealed a significant anti-angiogenic response to the peptide after 2 weeks—blood volume and vessel size decreased, and vessel density increased in treated tumors; the opposite was seen in control tumors. The MRI results were validated with histology—H&E staining showed no difference in tumor viability between groups, while peptide-treated tumors exhibited decreased vascularity. These results indicate that translational SSC-MRI biomarkers are able to detect the differential effects of anti-angiogenic therapy on the tumor vasculature before significant tumor growth inhibition or changes in tumor viability. PMID:25408417

  19. Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

    PubMed Central

    Coutinho de Souza, Patricia; Mallory, Samantha; Smith, Nataliya; Saunders, Debra; Li, Xiao-Nan; McNall-Knapp, Rene Y.; Fung, Kar-Ming; Towner, Rheal A.

    2015-01-01

    Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients. PMID:26248280

  20. Inflammatory responses in a new mouse model of prolonged hepatic cold ischemia followed by arterialized orthotopic liver transplantation.

    PubMed

    Shen, Xiu-Da; Gao, Feng; Ke, Bibo; Zhai, Yuan; Lassman, Charles R; Tsuchihashi, Sei-Ichiro; Farmer, Douglas G; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W

    2005-10-01

    The current models of liver ischemia/reperfusion injury (IRI) in mice are largely limited to a warm ischemic component. To investigate the mechanism of hepatic "cold" IRI, we developed and validated a new mouse model of prolonged cold preservation followed by syngeneic orthotopic liver transplantation (OLT). Two hundred and forty-three OLTs with or without rearterialization and preservation in University of Wisconsin solution at 4 degrees C were performed in Balb/c mice. The 14-day survivals in the nonarterialized OLT groups were 92% (11/12), 82% (9/11), and 8% (1/12) after 1-hour, 6-hour and 24-hour preservation, respectively. In contrast, hepatic artery reconstruction after 1-hour, 6-hour, and 24-hour preservation improved the outcome as evidenced by 2-week survival of 100% (12/12), 100% (10/10), and 33% (4/12), respectively, and diminished hepatocellular damage (serum alanine aminotransferase /histology). Moreover, 24-hour (but not 1-h) cold preservation of rearterialized OLTs increased hepatic CD4+ T-cell infiltration and proinflammatory cytokine (tumor necrosis factor-alpha, interleukin 2, interferon-gamma) production, as well as enhanced local apoptosis, and Toll-like receptor 4/caspase 3 expression. These cardinal features of hepatic IRI validate the model. In conclusion, we have developed and validated a new mouse model of IRI in which hepatic artery reconstruction was mandatory for long-term animal survival after prolonged (24-h) OLT preservation. With the availability of genetically manipulated mouse strains, this model should provide important insights into the mechanism of antigen-independent hepatic IRI and help design much needed refined therapeutic means to combat hepatic IRI in the clinics. PMID:16184555

  1. Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer.

    PubMed

    Poczobutt, Joanna M; De, Subhajyoti; Yadav, Vinod K; Nguyen, Teresa T; Li, Howard; Sippel, Trisha R; Weiser-Evans, Mary C M; Nemenoff, Raphael A

    2016-03-15

    Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and they alter their phenotype in response to local environmental cues. Whereas the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes has not been well studied, particularly in lung cancer. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multimarker flow cytometry, we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and expresses multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor and selectively expresses a panel of chemokine genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict outcomes in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and they suggest that distinct populations play specific roles in tumor progression. PMID:26873985

  2. Surgery combined with controlled-release doxorubicin silk films as a treatment strategy in an orthotopic neuroblastoma mouse model

    PubMed Central

    Chiu, B; Coburn, J; Pilichowska, M; Holcroft, C; Seib, F P; Charest, A; Kaplan, D L

    2014-01-01

    Background: Neuroblastoma tumour resection goal is maximal tumour removal. We hypothesise that combining surgery with sustained, local doxorubicin application can control tumour growth. Methods: We injected human neuroblastoma cells into immunocompromised mouse adrenal gland. When KELLY cell-induced tumour volume was >300 mm3, 80–90% of tumour was resected and treated as follows: instantaneous-release silk film with 100 μg doxorubicin (100IR), controlled-release film with 200 μg (200CR) over residual tumour bed; and 100 and 200 μg intravenous doxorubicin (100IV and 200IV). Tumour volume was measured and histology analysed. Results: Orthotopic tumours formed with KELLY, SK-N-AS, IMR-32, SH-SY5Y cells. Tumours reached 1800±180 mm3 after 28 days, 2200±290 mm3 after 35 days, 1280±260 mm3 after 63 days, and 1700±360 mm3 after 84 days, respectively. At 3 days post KELLY tumour resection, tumour volumes were similar across all groups (P=0.6210). Tumour growth rate was similar in untreated vs control film, 100IV vs 100IR, and 100IV vs 200IV. There was significant difference in 100IR vs 200CR (P=0.0004) and 200IV vs 200CR (P=0.0003). Tumour growth with all doxorubicin groups was slower than that of control (P: <0.0001–0.0069). At the interface of the 200CR film and tumour, there was cellular necrosis, surrounded by apoptotic cells before reaching viable tumour cells. Conclusions: Combining surgical resection and sustained local doxorubicin treatment is effective in tumour control. Administering doxorubicin in a local, controlled manner is superior to giving an equivalent intravenous dose in tumour control. PMID:24921912

  3. iTEP Nanoparticle-Delivered Salinomycin Displays an Enhanced Toxicity to Cancer Stem Cells in Orthotopic Breast Tumors

    PubMed Central

    2015-01-01

    Salinomycin (Sali) has selective toxicity to cancer stem cells (CSCs), a subpopulation of cancer cells that have been recently linked with tumor multidrug resistance (MDR). To utilize its selective toxicity for cancer therapy, we sought to devise a nanoparticle (NP) carrier to deliver Sali to solid tumors through the enhanced permeability and retention effect and, hence, to increase its exposure to CSCs. First, hydrophobic Sali was conjugated to a hydrophilic, immune-tolerant, elastin-like polypeptide (iTEP); the amphiphilic iTEP–Sali conjugates self-assemble into NPs. Next, free Sali was encapsulated into the NPs alone or with two additives, N,N-dimethylhexylamine (DMHA) and α-tocopherol. The coencapsulation significantly improved the loading efficiency and release profile of Sali. The resulting NPs of the coencapsulation, termed as iTEP–Sali NP3s, have an in vitro release half-life of 4.1 h, four times longer than iTEP–Sali NP2s, the NPs that have encapsulated Sali only. Further, the NP3 formulation increases the plasma area under curve and the tumor accumulation of Sali by 10 and 2.4 times, respectively. Lastly, these improved pharmacokinetic and tumor accumulation profiles are consistent with a boost of CSC-elimination effect of Sali in vivo. In NP3-treated 4T1 orthotopic tumors, the mean CSC frequency is 55.62%, a significant reduction from the mean frequencies of untreated tumors, 75.00%, or free Sali-treated tumors, 64.32%. The CSC-elimination effect of the NP3 can further translate to a delay of tumor growth. Given the role of CSCs in driving tumor MDR and recurrence, it could be a promising strategy to add the NP3 to conventional cancer chemotherapies to prevent or reverse the MDR. PMID:24960465

  4. Integrated self-assembling drug delivery system possessing dual responsive and active targeting for orthotopic ovarian cancer theranostics.

    PubMed

    Lin, Chun-Jui; Kuan, Chen-Hsiang; Wang, Li-Wen; Wu, Hsi-Chin; Chen, Yunching; Chang, Chien-Wen; Huang, Rih-Yang; Wang, Tzu-Wei

    2016-06-01

    Ovarian cancers are the leading cause for mortality among gynecologic malignancies with five-year survival rate less than 30%. The purpose of this study is to develop a redox and pH-sensitive self-assembling hyaluronic acid nanoparticle with active targeting peptide for anticancer drug delivery. Anti-cancer drug is grafted onto hyaluronic acid (HA) via cis-aconityl linkage and disulfide bond to possess pH sensitivity and redox property, respectively. This conjugate is amphiphilic and can self-assemble into nanoparticle (NP) in aqueous solution. The results show that the nanoconjugate is successfully developed and the grafting ratio of cystamine (cys) is 17.8% with drug loading amount about 6.2% calculated by (1)H NMR spectra. The particle size is approximately 229.0 nm using dynamic light scatting measurement, and the morphology of nanoparticles is observed as spherical shape by transmission electron microscope. The pH and redox sensitivities are evaluated by changing either pH value or concentration of dithiothreitol in the medium. It is proved that the drug carrier is capable of achieving sustained controlled release of anti-cancer drug to 95% within 150 h. The intracellular uptake is observed by fluorescent microscope and the images show that conjugating luteinizing hormone-releasing hormone (LHRH) peptide can enhance specific uptake of nanoparticles by OVCAR-3 cancer cells; thus, resulting in inhibitory cell growth to less than 20% in 72 h in vitro. Orthotopic ovarian tumor model is also established to evaluate the therapeutic and diagnostic efficacy using non-invasive in vivo imaging system. The representative results demonstrate that LHRH-conjugated NPs possess a preferable tumor imaging capability and an excellent antitumor ability to almost 30% of original size in 20 days. PMID:26974704

  5. Pulsed Versus Conventional Radiation Therapy in Combination With Temozolomide in a Murine Orthotopic Model of Glioblastoma Multiforme

    SciTech Connect

    Lee, David Y.; Chunta, John L.; Park, Sean S.; Huang, Jiayi; Martinez, Alvaro A.; Grills, Inga S.; Krueger, Sarah A.; Wilson, George D.; Marples, Brian

    2013-08-01

    Purpose: To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model. Methods and Materials: Orthotopic U87MG hGBM tumors were established in Nu-Foxn1{sup nu} mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as a single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry. Results: Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ. Conclusions: PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM.

  6. Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

    NASA Astrophysics Data System (ADS)

    Kawamura, Wataru; Miura, Yutaka; Kokuryo, Daisuke; Toh, Kazuko; Yamada, Naoki; Nomoto, Takahiro; Matsumoto, Yu; Sueyoshi, Daiki; Liu, Xueying; Aoki, Ichio; Kano, Mitsunobu R.; Nishiyama, Nobuhiro; Saga, Tsuneo; Kishimura, Akihiro; Kataoka, Kazunori

    2015-06-01

    Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by αVβ3 and αvβ5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress αVβ3 integrins.

  7. Chronic Rejection Pathology after Orthotopic Lung Transplantation in Mice: The Development of a Murine BOS Model and Its Drawbacks

    PubMed Central

    De Vleeschauwer, Stéphanie; Jungraithmayr, Wolfgang; Wauters, Shana; Willems, Stijn; Rinaldi, Manuela; Vaneylen, Annemie; Verleden, Stijn; Willems-Widyastuti, Anna; Bracke, Ken; Brusselle, Guy; Verbeken, Erik; Van Raemdonck, Dirk; Verleden, Geert; Vanaudenaerde, Bart

    2012-01-01

    Almost all animal models for chronic rejection (CR) after lung transplantation (LTx) fail to resemble the human situation. It was our attempt to develop a representative model of CR in mice. Orthotopic LTx was performed in allografts receiving daily immunosuppression with steroids and cyclosporine. Controls included isografts and mice only undergoing thoracotomy (SHAM). Allografts were sacrificed 2, 4, 6, 8, 10 or 12 weeks after LTx. Pulmonary function was measured repeatedly in the 12w allografts, isografts and SHAM mice. Histologically, all allografts demonstrated acute rejection (AR) around the blood vessels and airways two weeks after LTx. This decreased to 50–75% up to 10 weeks and was absent after 12 weeks. Obliterative bronchiolitis (OB) lesions were observed in 25–50% of the mice from 4–12 weeks. Isografts and lungs of SHAM mice were normal after 12 weeks. Pulmonary function measurements showed a decline in FEV0.1, TLC and compliance in the allografts postoperatively (2 weeks) with a slow recovery over time. After this initial decline, lung function of allografts increased more than in isografts and SHAM mice indicating that pulmonary function measurement is not a good tool to diagnose CR in a mouse. We conclude that a true model for CR, with clear OB lesions in about one third of the animals, but without a decline in lung function, is possible. This model is an important step forward in the development of an ideal model for CR which will open new perspectives in unraveling CR pathogenesis and exploring new treatment options. PMID:22238655

  8. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model.

    PubMed

    Scott, Katherine A; Dalgleish, Angus G; Liu, Wai M

    2014-12-01

    High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis. In an attempt to improve treatment outcome, we have investigated the effect of Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261). Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS). Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS. Median effect analysis revealed all combinations to be hyperadditive [T98G 48-hour combination index (CI) at FU50, 0.77-1.09]. Similarly, pretreating cells with THC-P and CBD-P together for 4 hours before irradiation increased their radiosensitivity when compared with pretreating with either of the cannabinoids individually. The increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis. These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation (day 21: 5.5 ± 2.2 mm(3) vs. 48.7 ± 24.9 mm(3) in the control group; P < 0.01). Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities. PMID:25398831

  9. Spatial and temporal mapping of heterogeneity in liposome uptake and microvascular distribution in an orthotopic tumor xenograft model.

    PubMed

    Ekdawi, Sandra N; Stewart, James M P; Dunne, Michael; Stapleton, Shawn; Mitsakakis, Nicholas; Dou, Yannan N; Jaffray, David A; Allen, Christine

    2015-06-10

    Existing paradigms in nano-based drug delivery are currently being challenged. Assessment of bulk tumor accumulation has been routinely considered an indicative measure of nanomedicine potency. However, it is now recognized that the intratumoral distribution of nanomedicines also impacts their therapeutic effect. At this time, our understanding of the relationship between the bulk (i.e., macro-) tumor accumulation of nanocarriers and their intratumoral (i.e., micro-) distribution remains limited. Liposome-based drug formulations, in particular, suffer from diminished efficacy in vivo as a result of transport-limiting properties, combined with the heterogeneous nature of the tumor microenvironment. In this report, we perform a quantitative image-based assessment of macro- and microdistribution of liposomes. Multi-scalar assessment of liposome distribution was enabled by a stable formulation which co-encapsulates an iodinated contrast agent and a near-infrared fluorescence probe, for computed tomography (CT) and optical microscopy, respectively. Spatio-temporal quantification of tumor uptake in orthotopic xenografts was performed using CT at the bulk tissue level, and within defined sub-volumes of the tumor (i.e., rim, periphery and core). Tumor penetration and relative distribution of liposomes were assessed by fluorescence microscopy of whole tumor sections. Microdistribution analysis of whole tumor images exposed a heterogeneous distribution of both liposomes and tumor vasculature. Highest levels of liposome uptake were achieved and maintained in the well-vascularized tumor rim over the study period, corresponding to a positive correlation between liposome and microvascular density. Tumor penetration of liposomes was found to be time-dependent in all regions of the tumor however independent of location in the tumor. Importantly, a multi-scalar comparison of liposome distribution reveals that macro-accumulation in tissues (e.g., blood, whole tumor) may not reflect

  10. Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts.

    PubMed

    Coutinho de Souza, Patricia; Mallory, Samantha; Smith, Nataliya; Saunders, Debra; Li, Xiao-Nan; McNall-Knapp, Rene Y; Fung, Kar-Ming; Towner, Rheal A

    2015-01-01

    Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients. PMID:26248280

  11. PTEN Loss Does Not Predict for Response to RAD001 (Everolimus) in a Glioblastoma Orthotopic Xenograft Test Panel

    PubMed Central

    Yang, Lin; Clarke, Michelle J.; Carlson, Brett L.; Mladek, Ann C.; Schroeder, Mark A.; Decker, Paul; Wu, Wenting; Kitange, Gaspar J.; Grogan, Patrick T.; Goble, Jennie M.; Uhm, Joon; Galanis, Evanthia; Giannini, Caterina; Lane, Heidi A.; James, C. David; Sarkaria, Jann N.

    2014-01-01

    Purpose Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus). Experimental Design To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN. Results Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy. Conclusion These data suggest that loss of PTEN function is insufficient to adequately predict responsiveness to mTOR inhibitors in glioblastoma multiforme. PMID:18559622

  12. MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma

    PubMed Central

    Sachdeva, Mohit; Whitley, Melody J.; Mito, Jeffrey K.; Ma, Yan; Lev, Dina C.; Cardona, Diana M.; Kirsch, David G.

    2015-01-01

    ABSTRACT MicroRNAs (miRNAs) can regulate tumor cell invasion and metastasis in a tumor-specific manner. We recently demonstrated that global downregulation of miRNAs after deleting dicer can promote development of distant metastases in a mouse model of primary soft tissue sarcoma (STS). In this study, we identified miRNAs that are differentially downregulated in metastatic STS in both human and mouse, and investigated the role of these miRNAs in metastasis. miRNA- TaqMan PCR arrays showed a global downregulation of miRNAs in metastatic human sarcomas. Similar analysis in mouse metastatic sarcomas revealed overlap for several downregulated miRNAs including miR-16, miR-103, miR-146a, miR-223, miR-342 and miR-511. Restoration of these downregulated miRNAs in mouse primary sarcoma cell lines showed that miR-16, but not other downregulated miRNAs, was able to significantly suppress both migration and invasion in vitro, without altering cell proliferation. In addition, orthotopic transplantation of a sarcoma cell line stably expressing miR-16 into the muscle of immunocompromised mice revealed that restoration of miR-16 can significantly decrease lung metastasis in vivo. However, no change in the rate of lung metastasis was observed when miR-16 was deleted in mouse primary sarcomas at sarcoma initiation. Taken together, these results indicate that miR-16 can have metastasis-suppressing properties both in vitro and in vivo. However, the loss-of-function experiments in autochthonous tumors indicate that loss of miR-16 is not sufficient to promote metastasis in vivo. PMID:26044957

  13. Modulation of HCV reinfection after orthotopic liver transplantation by fibroblast growth factor-2 and other non-interferon mediators

    PubMed Central

    Van, Nguyen Dinh; Falk, Christine S; Sandmann, Lisa; Vondran, Florian W R; Helfritz, Fabian; Wedemeyer, Heiner; Manns, Michael P; Ciesek, Sandra; von Hahn, Thomas

    2016-01-01

    Objective In HCV infected individuals graft infection occurs shortly after orthotopic liver transplantation (OLT). We aimed to describe the composition of the inflammatory response at this time, how it affects the HCV replication cycle and identify novel proviral and antiviral factors. Design We used a Luminex assay to quantify 50 inflammatory mediators in sera before and shortly after OLT. In vitro grown HCV based on the JFH-1 isolate were used to characterise the effects of patient sera and individual mediators on HCV. Results Although the mediator composition is highly variable between individuals, sera drawn immediately post-OLT significantly enhance HCV infectivity compared with control sera from before OLT in about half of the cases. Among 27 non-interferon inflammatory mediators fibroblast growth factor (FGF)-2 stood out as it enhanced HCV RNA replication and release of infectious particles. The effect was concentration-dependent and detectable in dividing and non-dividing cells. Moreover, pharmacological inhibition of FGF-2 receptor signalling abrogated the enhancing effect of FGF-2 and inhibited HCV replication in the absence of serum FGF-2 suggesting that HCV replication is dependent on basal activation of the FGF-2 triggered signalling pathway. Finally, in individuals with chronic HCV infection with high viral load, serum FGF-2 was significantly higher compared with those with low viral load. Conclusions Although no single mediator may account for this effect, serum shortly post-OLT enhances HCV infection. FGF-2 is a novel endogenous driver of HCV replication and a potential therapeutic target. PMID:25800783

  14. How to overcome difficulties with reserves replacement

    SciTech Connect

    Brashear, J.P.; Becker, A.B.; Godec, M.L.; Crawford, P.M.

    1997-03-10

    The first part of this article discussed the challenge of replacing reserves while maintaining high levels of profitability. An examination of the 82 largest US-based, publicly traded exploration and production (E and P) companies, grouped by size, suggested a potential conflict between reserves replacement and profitability--a ``devil`s dilemma`` between long term viability and financial performance. The 10 largest companies failed to replace their production in the US or worldwide (although they did in non-US operations). They were, however, the most profitable on a per-barrel-equivalent basis. In general, the smaller the company, the higher its reserves-replacement ratio, reflecting greater relative effort but lower unit profitability. This article examines the difficulties that companies face in reserves replacement planning, the accommodations they make to these difficulties, and the problems caused by these accommodations. It then suggests an analytical structure for reserves replacement planning that contributes to overcoming the difficulties.

  15. Biology of tooth replacement in amniotes

    PubMed Central

    Whitlock, John A; Richman, Joy M

    2013-01-01

    Tooth replacement is a common trait to most vertebrates, including mammals. Mammals, however, have lost the capacity for continuous tooth renewal seen in most other vertebrates, and typically have only 1–2 generations of teeth. Here, we review the mechanisms of tooth replacement in reptiles and mammals, and discuss in detail the current and historical theories on control of timing and pattern of tooth replacement and development. PMID:23788284

  16. Reoperations Following Cervical Disc Replacement

    PubMed Central

    Skovrlj, Branko; Lee, Dong-Ho; Caridi, John Michael

    2015-01-01

    Cervical disc replacement (CDR) has emerged as an alternative surgical option to cervical arthrodesis. With increasing numbers of patients and longer follow-ups, complications related to the device and/or aging spine are growing, leaving us with a new challenge in the management and surgical revision of CDR. The purpose of this study is to review the current literature regarding reoperations following CDR and to discuss about the approaches and solutions for the current and future potential complications associated with CDR. The published rates of reoperation (mean, 1.0%; range, 0%-3.1%), revision (mean, 0.2%; range, 0%-0.5%), and removal (mean, 1.2%; range, 0%-1.9%) following CDR are low and comparable to the published rates of reoperation (mean, 1.7%; range; 0%-3.4%), revision (mean, 1.5%; range, 0%-4.7%), and removal (mean, 2.0%; range, 0%-3.4%) following cervical arthrodesis. The surgical interventions following CDR range from the repositioning to explantation followed by fusion or the reimplantation to posterior foraminotomy or fusion. Strict patient selection, careful preoperative radiographic review and surgical planning, as well as surgical technique may reduce adverse events and the need for future intervention. Minimal literature and no guidelines exist for the approaches and techniques in revision and for the removal of implants following CDR. Adherence to strict indications and precise surgical technique may reduce the number of reoperations, revisions, and removals following CDR. Long-term follow-up studies are needed, assessing the implant survivorship and its effect on the revision and removal rates. PMID:26097667

  17. Peach bottom recirculation piping replacement ALARA program

    SciTech Connect

    Englesson, G.A.; Hilsmeier, A.E.; Mann, B.J.

    1986-01-01

    In late 1983, Philadelphia Electric Company (PECo) began detailed planning to replace the recirculation, residual heat removal, and part of the reactor water cleanup piping of the Peach Bottom Unit 2 reactor. Included in this work was an estimate of the collective exposure expected during piping replacement. That initial estimate, 1945 man-rem, is compared with the actual collective dose incurred during the piping replacement program. Also included are the exposures incurred during two additional tasks (safe end replacement and recirculation pump disassembly and decontamination) not considered in the initial estimate.

  18. Opportunistic replacement of fusion power system parts

    SciTech Connect

    Day, J.A.; George, L.L.

    1981-10-26

    This paper describes a maintenance problem in a fusion power plant. The problem is to specify which life limited parts should be replaced when there is an opportunity. The objective is to minimize the cost rate of replacement parts and of maintenance actions while satisfying a power plant availability constraint. The maintenance policy is to look ahead and replace all parts that will reach their life limits within a time called a screen. Longer screens yield greater system availabilities because more parts are replaced prior to their life limits.

  19. Total quality management approach improves medication replacement.

    PubMed

    Anderson, L K

    1994-07-01

    Total quality management (TQM) is based on understanding customer needs, improving key processes that affect customer satisfaction, and creating cross-functional teams to resolve process problems. This article describes application of TQM principles and problem-solving processes to improve one OR's medication exchange system. The problem was excessive monthly pharmacy medication replacement costs. The goal was to reduce the monthly medication replacement costs by 50%. Within four months, monthly medication replacement charges decreased from $656 to $302, and by one year, monthly charges decreased to $160. The new process had fewer steps, fewer staff members involved, and fewer delays in medication replacement. PMID:8085806

  20. In vitro and in vivo evaluation of intravesical docetaxel loaded hydrophobically derivatized hyperbranched polyglycerols in an orthotopic model of bladder cancer.

    PubMed

    Mugabe, Clement; Matsui, Yoshiyuki; So, Alan I; Gleave, Martin E; Heller, Markus; Zeisser-Labouèbe, Magali; Heller, Lindsay; Chafeeva, Irina; Brooks, Donald E; Burt, Helen M

    2011-04-11

    The objective of this study was to evaluate the tolerability, to establish a dosing regimen, and to evaluate the efficacy of intravesical docetaxel (DTX) formulations in a mouse model of bladder cancer. DTX in commercial formulation (Taxotere, DTX in Tween 80) or loaded in hyperbranched polyglycerols (HPGs) was evaluated. The synthesis and characterization of HPGs with hydrophobic cores and derivatized with methoxy poly(ethylene glycol) in the shell and further functionalized with amine groups (HPG-C(8/10)-MePEG and HPG-C(8/10)-MePEG-NH(2)) is described. Intravesical DTX in either commercial or HPGs formulations (up to 1.0 mg/mL) was instilled in mice with orthotopic bladder cancer xenografts and was well tolerated with no apparent signs of local or systemic toxicities. Furthermore, a single dose of intravesical DTX (0.5 mg/mL) loaded in HPGs was significantly more effective in reducing the tumor growth in an orthotopic model of bladder cancer than the commercial formulation of Taxotere. In addition, DTX-loaded HPG-C(8/10)-MePEG-NH(2) was found to be more effective at lower instillation dose than DTX (0.2 mg/mL)-loaded HPG-C(8/10)-MePEG. Overall, our data show promising antitumor efficacy and safety in a recently validated orthotopic model of bladder cancer. Further research is warranted to evaluate its safety and efficacy in early phase clinical trials in patients refractory to standard intravesical therapy. PMID:21355626

  1. Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

    PubMed

    Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

    2016-07-01

    Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. PMID:27125846

  2. The Value of SPECT/CT in Monitoring Prefabricated Tissue-Engineered Bone and Orthotopic rhBMP-2 Implants for Mandibular Reconstruction.

    PubMed

    Zhou, Miao; Peng, Xin; Mao, Chi; Tian, Jia-he; Zhang, Shu-wen; Xu, Fang; Tu, Jing-jing; Liu, Sheng; Hu, Min; Yu, Guang-yan

    2015-01-01

    Bone tissue engineering shows good prospects for mandibular reconstruction. In recent studies, prefabricated tissue-engineered bone (PTEB) by recombinant human bone morphogenetic proteins (rhBMPs) applied in vivo has found to be an effective alternative for autologous bone grafts. However, the optimal time to transfer PTEB for mandibular reconstruction is still not elucidated. Thus, here in an animal experiment of rhesus monkey, the suitable transferring time for PTEB to reconstruct mandibular defects was evaluated by 99mTc-MDP SPECT/CT, and its value in monitoring orthotopic rhBMP-2 implants for mandibular reconstruction was also evaluated. The result of SPECT/CT showed higher 99mTc-MDP uptake, indicating osteoinductivity, in rhBMP-2 incorporated demineralized freeze-dried bone allograft (DFDBA) and coralline hydroxyapatite (CHA) implants than those without BMP stimulation. 99mTc-MDP uptake of rhBMP-2 implant peaked at 8 weeks following implantation while CT showed the density of these implants increased after 13 weeks' prefabrication. Histology confirmed that mandibular defects were repaired successfully with PTEB or orthotopically rhBMP-2 incorporated CHA implants, in accordance with SPECT/CT findings. Collectively, data shows 99mTc-MDP SPECT/CT is a sensitive and noninvasive tool to monitor osteoinductivity and bone regeneration of PTEB and orthotopic implants. The PTEB achieved peak osteoinductivity and bone density at 8 to 13 weeks following ectopic implantation, which would serve as a recommendable time frame for its transfer to mandibular reconstruction. PMID:26340447

  3. The Value of SPECT/CT in Monitoring Prefabricated Tissue-Engineered Bone and Orthotopic rhBMP-2 Implants for Mandibular Reconstruction

    PubMed Central

    Zhou, Miao; Peng, Xin; Mao, Chi; Tian, Jia-he; Zhang, Shu-wen; Xu, Fang; Tu, Jing-jing; Liu, Sheng; Hu, Min; Yu, Guang-yan

    2015-01-01

    Bone tissue engineering shows good prospects for mandibular reconstruction. In recent studies, prefabricated tissue-engineered bone (PTEB) by recombinant human bone morphogenetic proteins (rhBMPs) applied in vivo has found to be an effective alternative for autologous bone grafts. However, the optimal time to transfer PTEB for mandibular reconstruction is still not elucidated. Thus, here in an animal experiment of rhesus monkey, the suitable transferring time for PTEB to reconstruct mandibular defects was evaluated by 99mTc-MDP SPECT/CT, and its value in monitoring orthotopic rhBMP-2 implants for mandibular reconstruction was also evaluated. The result of SPECT/CT showed higher 99mTc-MDP uptake, indicating osteoinductivity, in rhBMP-2 incorporated demineralized freeze-dried bone allograft (DFDBA) and coralline hydroxyapatite (CHA) implants than those without BMP stimulation. 99mTc-MDP uptake of rhBMP-2 implant peaked at 8 weeks following implantation while CT showed the density of these implants increased after 13 weeks’ prefabrication. Histology confirmed that mandibular defects were repaired successfully with PTEB or orthotopically rhBMP-2 incorporated CHA implants, in accordance with SPECT/CT findings. Collectively, data shows 99mTc-MDP SPECT/CT is a sensitive and noninvasive tool to monitor osteoinductivity and bone regeneration of PTEB and orthotopic implants. The PTEB achieved peak osteoinductivity and bone density at 8 to 13 weeks following ectopic implantation, which would serve as a recommendable time frame for its transfer to mandibular reconstruction. PMID:26340447

  4. Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging

    PubMed Central

    Batey, Michael A.; Almeida, Gilberto S.; Wilson, Ian; Dildey, Petra; Sharma, Abhishek; Blair, Helen; Hide, I. Geoff; Heidenreich, Olaf; Vormoor, Josef; Maxwell, Ross J.; Bacon, Chris M.

    2014-01-01

    Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2−/−/γc−/− mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which

  5. Efficacy of Tumor-Targeting Salmonella A1-R on a Melanoma Patient-Derived Orthotopic Xenograft (PDOX) Nude-Mouse Model

    PubMed Central

    Yamamoto, Mako; Zhao, Ming; Hiroshima, Yukihiko; Zhang, Yong; Shurell, Elizabeth; Eilber, Fritz C.; Bouvet, Michael; Noda, Makoto; Hoffman, Robert M.

    2016-01-01

    Tumor-targeting Salmonella enterica serovar Typhimurium A1-R (Salmonella A1-R) had strong efficacy on a melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse model. GFP-expressing Salmonella A1-R highly and selectively colonized the PDOX melanoma and significantly suppressed tumor growth (p = 0.021). The combination of Salmonella A1-R and cisplatinum (CDDP), both at low-dose, also significantly suppressed the growth of the melanoma PDOX (P = 0.001). Salmonella A1-R has future clinical potential for combination chemotherapy with CDDP of melanoma, a highly-recalcitrant cancer. PMID:27500926

  6. Isolation and (111)In-Oxine Labeling of Murine NK Cells for Assessment of Cell Trafficking in Orthotopic Lung Tumor Model.

    PubMed

    Malviya, Gaurav; Nayak, Tapan; Gerdes, Christian; Dierckx, Rudi A J O; Signore, Alberto; de Vries, Erik F J

    2016-04-01

    A noninvasive in vivo imaging method for NK cell trafficking is essential to gain further understanding of the pathogenesis of NK cell mediated immune response to the novel cancer treatment strategies, and to discover the homing sites and physiological distribution of NK cells. Although human NK cells can be labeled for in vivo imaging, little is known about the murine NK cell labeling and its application in animal models. This study describes the isolation and ex vivo radiolabeling of murine NK cells for the evaluation of cell trafficking in an orthotopic model of human lung cancer in mice. Scid-Tg(FCGR3A)Blt transgenic SCID mice were used to isolate NK cells from mouse splenocytes using the CD49b (DX5) MicroBeads positive selection method. The purity and viability of the isolated NK cells were confirmed by FACS analysis. Different labeling buffers and incubation times were evaluated to optimize (111)In-oxine labeling conditions. Functionality of the radiolabeled NK cell was assessed by (51)Cr-release assay. We evaluated physiological distribution of (111)In-oxine labeled murine NK cells in normal SCID mice and biodistribution in irradiated and nonirradiated SCID mice with orthotopic A549 human lung tumor lesions. Imaging findings were confirmed by histology. Results showed that incubation with 0.011 MBq of (111)In-oxine per million murine NK cells in PBS (pH 7.4) for 20 min is the best condition that provides optimum labeling efficiency without affecting cell viability and functionality. Physiological distribution in normal SCID mice demonstrated NK cells homing mainly in the spleen, while (111)In released from NK cells was excreted via kidneys into urine. Biodistribution studies demonstrated a higher lung uptake in orthotopic lung tumor-bearing mice than control mice. In irradiated mice, lung tumor uptake of radiolabeled murine NK cells decreased between 24 h and 72 h postinjection (p.i.), which was accompanied by tumor regression, while in nonirradiated mice

  7. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as...

  8. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as...

  9. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as...

  10. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as...

  11. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as...

  12. Mercury Thermometer Replacements in Chemistry Laboratories

    ERIC Educational Resources Information Center

    Foster, Barbara L.

    2005-01-01

    The consequences of broken mercury-in-glass thermometers in academic laboratories results in various health and environmental hazards, which needs to be replaced, by long-stem digital thermometers and non-mercury glass thermometers. The factors that should be considered during the mercury replacement process are types of applications in the…

  13. 47 CFR 13.17 - Replacement license.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Replacement license. 13.17 Section 13.17 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL RADIO OPERATORS General § 13.17 Replacement license. (a) Each licensee or permittee whose original document is lost, mutilated, or destroyed...

  14. Condylar hyperplasia following unilateral temporomandibular joint replacement.

    PubMed

    Machon, V; Levorova, J; Hirjak, D; Foltan, R

    2015-06-01

    Total joint replacement of the temporomandibular joint (TJR) can be associated with intraoperative and postoperative complications. We report herein the occurrence of a postoperative open bite malocclusion, the result of condylar hyperplasia affecting the non-operated joint at 1 year after unilateral total joint replacement. PMID:25662429

  15. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than...

  16. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than...

  17. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than...

  18. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than...

  19. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than...

  20. Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model.

    PubMed

    McCullough, Danielle J; Nguyen, Linda M-D; Siemann, Dietmar W; Behnke, Bradley J

    2013-12-01

    Regular physical exercise is considered to be an integral component of cancer care strategies. However, the effect of exercise training on tumor microvascular oxygenation, hypoxia, and vascular function, all of which can affect the tumor microenvironment, remains unknown. Using an orthotopic preclinical model of prostate cancer, we tested the hypotheses that, after exercise training, in the tumor, there would be an enhanced microvascular Po2, increased number of patent vessels, and reduced hypoxia. We also investigated tumor resistance artery contractile properties. Dunning R-3327 AT-1 tumor cells (10(4)) were injected into the ventral prostate of 4-5-mo-old male Copenhagen or Nude rats, which were randomly assigned to tumor-bearing exercise trained (TB-Ex trained; n = 15; treadmill exercise for 5-7 wk) or sedentary groups (TB-Sedentary; n = 12). Phosphorescence quenching was used to measure tumor microvascular Po2, and Hoechst-33342 and EF-5 were used to measure patent vessels and tumor hypoxia, respectively. Tumor resistance artery function was assessed in vitro using the isolated microvessel technique. Compared with sedentary counterparts, tumor microvascular Po2 increased ∼100% after exercise training (TB-Sedentary, 6.0 ± 0.3 vs. TB-Ex Trained, 12.2 ± 1.0 mmHg, P < 0.05). Exercise training did not affect the number of patent vessels but did significantly reduce tumor hypoxia in the conscious, resting condition from 39 ± 12% of the tumor area in TB-Sedentary to 4 ± 1% in TB-Ex Trained. Exercise training did not affect vessel contractile function. These results demonstrate that after exercise training, there is a large increase in the driving force of O2 from the tumor microcirculation, which likely contributes to the considerable reduction in tumor hypoxia. These results suggest that exercise training can modulate the microenvironment of the tumor, such that a sustained reduction in tumor hypoxia occurs, which may lead to a less aggressive phenotype and

  1. Pien Tze Huang inhibits liver metastasis by targeting TGF-β signaling in an orthotopic model of colorectal cancer.

    PubMed

    Lin, Wei; Zhuang, Qunchuan; Zheng, Liangpu; Cao, Zhiyun; Shen, Aling; Li, Qiongyu; Fu, Caixuan; Feng, Jianyu; Peng, Jun

    2015-04-01

    Metastasis is the leading cause of cancer-related mortality in almost all types of cancers, including colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) is a critical process during the metastatic cascade. This process may be a potential target for the diagnosis and treatment of CRC. Pien Tze Huang (PZH), a well-known traditional Chinese formula, has been demonstrated to be clinically effective in treating various types of human malignancies, including CRC. Our published data suggest that PZH can induce apoptosis, as well as inhibit cell proliferation and tumor angiogenesis, thus suppressing CRC growth in vitro and in vivo. We evaluated the therapeutic efficacy of PZH against CRC metastasis using a CRC liver metastasis mouse model to further explore the mechanisms underlying the antitumor action of PZH. MTT, migration, and Matrigel invasion assays were used to assess the effect of PZH on cell viability, migration and invasion. We then established an orthotopic liver metastasis model of colon cancer using microsurgical techniques. Mice were intragastrically administered 234 mg/kg/day dose of either PZH or saline for 14 days. The body and tumor weights of the mice were measured after they were sacrificed. Moreover, we examined the effect of PZH inhibition on liver metastasis. Finally, EMT-related proteins and the TGF-β signaling pathway were assessed using immunohistochemical staining (IHS). The present data revealed that PZH significantly inhibited the migration and invasion of CT-26 cells in a dose-dependent manner, which affirmed the inhibitory effect of PZH on CRC cell metastasis. No significant change was observed between the in vivo primary tumor growth and body weight. However, the control group had five cases of liver metastasis (5/6), whereas one case was found in the PZH group (1/6). Thus, PZH exhibited therapeutic efficacy against CRC metastasis without apparent toxicity. The inhibitory effect of PZH on EMT resulted in an increase in

  2. Evaluation of miR-122-regulated suicide gene therapy for hepatocellular carcinoma in an orthotopic mouse model

    PubMed Central

    Wang, Gang; Dong, Xiaoyan; Tian, Wenhong; Lu, Yue; Hu, Jianyan; Liu, Yunfan; Yuchi, Jie

    2013-01-01

    Objective Intratumoral administration of adenoviral vector encoding herpes simplex virus (HSV) thymidine kinase (TK) gene (Ad-TK) followed by systemic ganciclovir (GCV) is an effective approach in treating experimental hepatocellular carcinoma (HCC). However, hepatotoxicity due to unwanted vector spread and suicide gene expression limited the application of this therapy. miR-122 is an abundant, liver-specific microRNA whose expression is decreased in human primary HCC and HCC-derived cell lines. These different expression profiles provide an opportunity to induce tumor-specific gene expression by miR-122 regulation. Methods By inserting miR-122 target sequences (miR-122T) in the 3' untranslated region (UTR) of TK gene, we constructed adenovirus (Ad) vectors expressing miR-122-regulated TK (Ad-TK-122T) and report genes. After intratumoral administration of Ad vectors into an orthotopic miR-122-deficient HCC mouse model, we observed the miR-122-regulated transgene expression and assessed the antitumor activity and safety of Ad-TK-122T. Results Insertion of miR-122T specifically down-regulated transgene expression in vitro and selectively protected the miR-122-positive cells from killing by TK/GCV treatment. Insertion of miR-122T led to significant reduction of tansgene expression in the liver without inhibition of its expression in tumors in vivo, resulting in an 11-fold improvement of tumor-specific transgene expression. Intratumoral injection of Ad vectors mediated TK/GCV system led to a vector dosage-dependent regression of tumor. The insertion of miR-122T does not influence the antitumor effects of suicide gene therapy. Whereas mice administrated with Ad-TK showed severe lethal hepatotoxicity at the effective therapeutic dose, no liver damage was found in Ad-TK-122T group. Conclusions miR-122-regulated TK expression achieved effective anti-tumor effects and increased the safety of intratumoral delivery of adenovirus-mediated TK/GCV gene therapy for miR-122

  3. Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model

    PubMed Central

    Murakami, Takashi; DeLong, Jonathan; Eilber, Fritz C.; Zhao, Ming; Zhang, Yong; Zhang, Nan; Singh, Arun; Russell, Tara; Deng, Samantha; Reynoso, Jose; Quan, Cuong; Hiroshima, Yukihiko; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Chawla, Sant; Endo, Itaru; Hoffman, Robert M.

    2016-01-01

    A patient with high grade undifferentiated pleomorphic soft-tissue sarcoma from a striated muscle was grown orthotopically in the right biceps femoris muscle of mice to establish a patient-derived orthotopic xenograft (PDOX) model. Twenty PDOX mice were divided into 4 groups: G1, control without treatment; G2, Salmonella typhimurium (S. typhimurium)A1-R administered by intratumoral (i.t.) injection once a week for 4 weeks; G3, doxorubicin (DOX) administered by intraperitoneal (i.p.) injection once a week for 4 weeks; G4, S. typhimurium A1-R (i.t.) administered once a week for 2 weeks followed by i.p. doxorubicin once a week for 2 weeks. On day 25 from the initiation of treatment, tumor volume in G2, G3, and G4 was significantly lower than G1. Mice found without gross tumor included one mouse (20%) in G2; one mouse (20%) in G3; and 3 mice (60%) in G4. Body weight loss did not significantly differ between the 3 treated groups or from the untreated control. Histological examination revealed eradication of tumor only in G4 where mice were treated with S. typhimurium A1-R followed by DOX. Our present study indicates future clinical potential of combining S. typhimurium A1-R with chemotherapy such as DOX for soft tissue sarcoma patients. PMID:26859573

  4. Effectiveness of Combined Modality Radiotherapy of Orthotopic Human Squamous Cell Carcinomas in Nu/Nu Mice Using Cetuximab, Tirapazamine and MnSOD-Plasmid Liposome Gene Therapy

    PubMed Central

    EPPERLY, MICHAEL W.; LAI, STEPHEN Y.; KANAI, ANTHONY J.; MASON, NEAL; LOPRESI, BRIAN; DIXON, TRACEY; FRANICOLA, DARCY; NIU, YUNYUN; WILSON, WILLIAM R.; GREENBERGER, JOEL S.

    2010-01-01

    Hypoxic regions limit the radiocontrollability of head and neck carcinomas. Whether or not combinations of plasmid/liposome mediated overexpression of normal tissue protective manganese superoxide dismutase (MnSOD), cetuximab (C225), and the hypoxic cytotoxin tirapazamine (TPZ) enhanced radiotherapeutic effects was tested in a CAL-33 orthotopic mouse cheek tumor model. The tumor volume continued to increase in the control (untreated) mice, with a ninefold increase by 10 days when the tumors exceeded 2 cm3. The mice receiving 14 Gy only showed reduced tumor growth to 3.1±0.1 fold at day 10. The mice receiving MnSOD-PL, C225, TPZ plus 14 Gy had the best outcome with 0.7±0.1 fold increase in tumor volume by 10 days (p=0.015) compared to irradiation only. The addition of MnSOD-PL, TPZ, and C225 to irradiation optimized the therapeutic ratio for the local control of hypoxic region-containing CAL-33 orthotopic tumors. PMID:20133969

  5. Evaluation of the Antitumor Efficacy of RNAi-Mediated Inhibition of CDC20 and Heparanase in an Orthotopic Liver Tumor Model.

    PubMed

    Liu, Meizhou; Zhang, Yangde; Liao, Yunjun; Chen, Yixing; Pan, Yifeng; Tian, Hu; Zhan, Yongqiang; Liu, Dongjing

    2015-08-01

    Over 90% of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. This study investigated the antitumor efficacy of the inhibition of cell division cycle protein 20 (CDC20) and heparanase (HPSE) expression in Hepa1-6 mouse hepatoma cells. Cell viability was measured by the MTT assay. Cell cycle was analyzed by cytometry. The invasion assay was performed using the Transwell chamber. The orthotopic liver tumor model was established by inoculating the livers of immunocompetent Kunming mice with Hepa1-6 cells. The MTT assay showed that 50 and 100 nM CDC20 siRNA-1 and HPSE siRNA-2 significantly reduced Hepa1-6 cell viability with the combination of CDC20 and HPSE siRNA being the most effective. Silencing of CDC20 or both CDC20 and HPSE expression significantly induced G2/M phase cell cycle arrest in Hepa1-6 HCC cells. Silencing HPSE expression significantly inhibited the invasion ability of Hepa1-6 cells with the combination of CDC20 and HPSE silencing being more effective than HPSE alone. Silencing CDC20 and HPSE expression significantly inhibited HCC tumor growth in the orthotopic liver tumor model, but the combination was most effective. Silencing CDC20 and HPSE expression activated cell apoptosis and autophagy. In conclusion, targeting inhibition of both CDC20 and HPSE expression is an ideal strategy for HCC therapy. PMID:26132704

  6. Oncolytic virotherapy with an armed vaccinia virus in an orthotopic model of renal carcinoma is associated with modification of the tumor microenvironment

    PubMed Central

    Fend, Laetitia; Remy-Ziller, Christelle; Foloppe, Johann; Kempf, Juliette; Cochin, Sandrine; Barraud, Luc; Accart, Nathalie; Erbs, Philippe; Fournel, Sylvie; Préville, Xavier

    2016-01-01

    ABSTRACT Oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. We have constructed a vaccinia virus (WR strain) deleted for thymidine kinase (TK) and ribonucleotide reductase (RR) genes that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. We evaluated this construct (VV-FCU1) in the orthotopic model of renal carcinoma (RenCa). Systemic administration of VV-FCU1 resulted in orthotopic tumor growth inhibition, despite temporary expression of viral proteins. VV-FCU1 treatment was associated with an infiltration of tumors by CD8+ T lymphocytes and a decrease in the proportion of infiltrating Tregs, thus modifying the ratio of CD8+/CD4+ Treg in favor of CD8+cytotoxic T cells. We demonstrated that VV-FCU1 treatment prolonged survival of animals implanted with RenCa cells in kidney. Depletion of CD8+ T cells abolished the therapeutic effect of VV-FCU1 while depletion of CD4+ T cells enhanced its protective activity. Administration of the prodrug 5-fluorocytosine (5-FC) resulted in a sustained control of tumor growth but did not extend survival. This study shows the importance of CD4+ and CD8+ T cells in vaccinia virus-mediated oncolytic virotherapy and suggests that this approach may be evaluated for the treatment of human renal cell carcinoma. PMID:27057460

  7. Effectiveness of combined modality radiotherapy of orthotopic human squamous cell carcinomas in Nu/Nu mice using cetuximab, tirapazamine and MnSOD-plasmid liposome gene therapy.

    PubMed

    Epperly, Michael W; Lai, Stephen Y; Kanai, Anthony J; Mason, Neal; Lopresi, Brian; Dixon, Tracey; Franicola, Darcy; Niu, Yunyun; Wilson, William R; Greenberger, Joel S

    2010-01-01

    Hypoxic regions limit the radiocontrollability of head and neck carcinomas. Whether or not combinations of plasmid/liposome mediated overexpression of normal tissue protective manganese superoxide dismutase (MnSOD), cetuximab (C225), and the hypoxic cytotoxin tirapazamine (TPZ) enhanced radiotherapeutic effects was tested in a CAL-33 orthotopic mouse cheek tumor model. The tumor volume continued to increase in the control (untreated) mice, with a ninefold increase by 10 days when the tumors exceeded 2 cm(3). The mice receiving 14 Gy only showed reduced tumor growth to 3.1+/-0.1 fold at day 10. The mice receiving MnSOD-PL, C225, TPZ plus 14 Gy had the best outcome with 0.7+/-0.1 fold increase in tumor volume by 10 days (p=0.015) compared to irradiation only. The addition of MnSOD-PL, TPZ, and C225 to irradiation optimized the therapeutic ratio for the local control of hypoxic region-containing CAL-33 orthotopic tumors. PMID:20133969

  8. Targeting the insulin growth factor-1 receptor with fluorescent antibodies enables high resolution imaging of human pancreatic cancer in orthotopic mouse models

    PubMed Central

    Park, Jeong Youp; Lee, Jin Young; Zhang, Yong; Hoffman, Robert M.; Bouvet, Michael

    2016-01-01

    The goal of the present study was to determine whether insulin-like growth factor-1 receptor (IGF-1R) antibodies, conjugated with bright fluorophores, could enable visualization of pancreatic cancer in orthotopic nude mouse models. IGF-1R antibody (clone 24-31) was conjugated with 550 nm or 650 nm fluorophores. Western blotting confirmed the expression of IGF-1R in Panc-1, BxPC3, and MIAPaCa-2 human pancreatic cancer cell lines. Labeling with fluorophore-conjugated IGF-1R antibody demonstrated fluorescent foci on the membrane of the pancreatic cancer cells. Subcutaneous Panc-1, BxPC-3, and MIA PaCa-2 tumors became fluorescent after intravenous administration of fluorescent IGF-1R antibodies. Orthotopically-transplanted BxPC-3 tumors became fluorescent with the conjugated IGF-1R antibodies, and were easily visible with intravital imaging. Gross and microscopic ex vivo imaging of resected pancreatic tumor and normal pancreas confirmed that fluorescence indeed came from the membrane of cancer cells, and it was stronger from the tumor than the normal tissue. The present study demonstrates that fluorophore-conjugated IGF-1R antibodies can visualize pancreatic cancer and it can be used with various imaging devices such as endoscopy and laparoscopy for diagnosis and fluorescence-guided surgery. PMID:26919100

  9. 3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

    PubMed

    Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

    2016-03-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT. PMID:26708213

  10. 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth

    PubMed Central

    WANG, TING-AN; ZHANG, XIAO-DONG; GUO, XING-YU; XIAN, SHU-LIN; LU, YUN-FEI

    2016-01-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT. PMID:26708213

  11. 2′-(2-bromohexadecanoyl)-paclitaxel conjugate nanoparticles for the treatment of non-small cell lung cancer in an orthotopic xenograft mouse model

    PubMed Central

    Peng, Lei; Schorzman, Allison N; Ma, Ping; Madden, Andrew J; Zamboni, William C; Benhabbour, Soumya Rahima; Mumper, Russell J

    2014-01-01

    A nanoparticle (NP) formulation with 2′-(2-bromohexadecanoyl)-paclitaxel (Br-16-PX) conjugate was developed in these studies for the treatment of non-small cell lung cancer (NSCLC). The lipophilic paclitaxel conjugate Br-C16-PX was synthesized and incorporated into lipid NPs where the 16-carbon chain enhanced drug entrapment in the drug delivery system and improved in vivo pharmacokinetics. The electron-withdrawing bromine group was used to facilitate the conversion of Br-C16-PX to paclitaxel at the tumor site. The developed system was evaluated in luciferase-expressing A549 cells in vitro and in an orthotopic NSCLC mouse model. The results demonstrated that the Br-C16-PX NPs had a higher maximum tolerated dose (75 mg/kg) than Taxol® (19 mg/kg) and provided significantly longer median survival (88 days versus 70 days, P<0.05) in the orthotopic NSCLC model. An improved pharmacokinetic profile was observed for the Br-C16-PX NPs at 75 mg/kg compared to Taxol at 19 mg/kg. The area under the concentration versus time curve (AUC)0–96 h of Br-C16-PX from the NPs was 91.7-fold and 49.6-fold greater than Taxol in plasma and tumor-bearing lungs, respectively, which provided sustained drug exposure and higher antitumor efficacy in the NP-treated group. PMID:25114529

  12. Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model

    PubMed Central

    Mullins, Stefanie; Sulikowski, Michal G.; Martin, Philip; Brown, Lee; Lewis, Arthur; Davies, Gareth; Morrow, Michelle; Wilkinson, Robert W.

    2016-01-01

    Despite the availability of recently developed chemotherapy regimens, survival times for pancreatic cancer patients remain poor. These patients also respond poorly to immune checkpoint blockade therapies (anti-CTLA-4, anti-PD-L1, anti-PD-1), which suggests the presence of additional immunosuppressive mechanisms in the pancreatic tumour microenvironment (TME). CD40 agonist antibodies (αCD40) promote antigen presenting cell (APC) maturation and enhance macrophage tumouricidal activity, and may therefore alter the pancreatic TME to increase sensitivity to immune checkpoint blockade. Here, we test whether αCD40 transforms the TME in a mouse syngeneic orthotopic model of pancreatic cancer, to increase sensitivity to PD-L1 blockade. We found that whilst mice bearing orthotopic Pan02 tumours responded poorly to PD-L1 blockade, αCD40 improved overall survival. αCD40 transformed the TME, upregulating Th1 chemokines, increasing cytotoxic T cell infiltration and promoting formation of an immune cell-rich capsule separating the tumour from the normal pancreas. Furthermore, αCD40 drove systemic APC maturation, memory T cell expansion, and upregulated tumour and systemic PD-L1 expression. Combining αCD40 with PD-L1 blockade enhanced anti-tumour immunity and improved overall survival versus either monotherapy. These data provide further support for the potential of combining αCD40 with immune checkpoint blockade to promote anti-tumour immunity in pancreatic cancer. PMID:26918344

  13. Newly Designed Y-configured Single-Catheter Stenting for the Treatment of Hilar-Type Nonanastomotic Biliary Strictures After Orthotopic Liver Transplantation

    SciTech Connect

    Wang Changming; Li Xuan; Song Shibing; Lv Xianjun; Luan Jingyuan; Dong Guoxiang

    2012-02-15

    Purpose: This study was designed to introduce our novel technique of percutaneous single catheter placement into the hilar bile ducts strictures while fulfilling the purpose of bilateral biliary drainage and stenting. We investigated the efficacy and safety of the technique for the treatment of hilar nonanastomotic biliary strictures. Methods: Ten patients who were post-orthotopic liver transplantation between July 2000 and July 2010 were enrolled in this study. Percutaneous Y-configured single-catheter stenting for bilateral bile ducts combined with balloon dilation was designed as the main treatment approach. Technical success rate, clinical indicators, complications, and recurrent rate were analyzed. Results: Technical success rate was 100%. Nine of the ten patients had biochemical normalization, cholangiographic improvement, and clinical symptoms relief. None of them experienced recurrence in a median follow-up of 26 months after completion of therapy and removal of all catheters. Complications were minor and limited to two patients. The one treatment failure underwent a second liver transplantation but died of multiple system organ failure. Conclusions: Percutaneous transhepatic Y-configured single-catheter stenting into the hilar bile ducts is technically feasible. The preliminary trial of this technique combined with traditional PTCD or choledochoscopy for the treatment of hilar biliary strictures after orthotopic liver transplantation appeared to be effective and safe. Yet, further investigation is needed.

  14. Optimal composition of fluid-replacement beverages.

    PubMed

    Baker, Lindsay B; Jeukendrup, Asker E

    2014-04-01

    The objective of this article is to provide a review of the fundamental aspects of body fluid balance and the physiological consequences of water imbalances, as well as discuss considerations for the optimal composition of a fluid replacement beverage across a broad range of applications. Early pioneering research involving fluid replacement in persons suffering from diarrheal disease and in military, occupational, and athlete populations incurring exercise- and/or heat-induced sweat losses has provided much of the insight regarding basic principles on beverage palatability, voluntary fluid intake, fluid absorption, and fluid retention. We review this work and also discuss more recent advances in the understanding of fluid replacement as it applies to various populations (military, athletes, occupational, men, women, children, and older adults) and situations (pathophysiological factors, spaceflight, bed rest, long plane flights, heat stress, altitude/cold exposure, and recreational exercise). We discuss how beverage carbohydrate and electrolytes impact fluid replacement. We also discuss nutrients and compounds that are often included in fluid-replacement beverages to augment physiological functions unrelated to hydration, such as the provision of energy. The optimal composition of a fluid-replacement beverage depends upon the source of the fluid loss, whether from sweat, urine, respiration, or diarrhea/vomiting. It is also apparent that the optimal fluid-replacement beverage is one that is customized according to specific physiological needs, environmental conditions, desired benefits, and individual characteristics and taste preferences. PMID:24715561

  15. Replacement solvents for use in chemical synthesis

    DOEpatents

    Molnar, Linda K.; Hatton, T. Alan; Buchwald, Stephen L.

    2001-05-15

    Replacement solvents for use in chemical synthesis include polymer-immobilized solvents having a flexible polymer backbone and a plurality of pendant groups attached onto the polymer backbone, the pendant groups comprising a flexible linking unit bound to the polymer backbone and to a terminal solvating moiety. The polymer-immobilized solvent may be dissolved in a benign medium. Replacement solvents for chemical reactions for which tetrahydrofuran or diethyl may be a solvent include substituted tetrahydrofurfuryl ethers and substituted tetrahydro-3-furan ethers. The replacement solvents may be readily recovered from the reaction train using conventional methods.

  16. Conceptual Design Plan SM-43 Replacement Project

    SciTech Connect

    University of California, Los Alamos National Laboratory, SCC Project Office

    2000-11-01

    The Los Alamos National Laboratory Conceptual Design Plan for the SM-43 Replacement Project outlines plans for replacing the SM-43 Administration Building. Topics include the reasons that replacement is considered a necessity; the roles of the various project sponsors; and descriptions of the proposed site and facilities. Also covered in this proposal is preliminary information on the project schedule, cost estimates, acquisition strategy, risk assessment, NEPA strategy, safety strategy, and safeguards and security. Spreadsheets provide further detail on space requirements, project schedules, and cost estimates.

  17. Minimally Invasive Transcatheter Aortic Valve Replacement (TAVR)

    MedlinePlus Videos and Cool Tools

    Watch a Broward Health surgeon perform a minimally invasive Transcatheter Aortic Valve Replacement (TAVR) Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2016 BroadcastMed, Inc. All rights reserved.

  18. Mitochondrial DNA replacement versus nuclear DNA persistence

    NASA Astrophysics Data System (ADS)

    Serva, Maurizio

    2006-10-01

    In this paper we consider two populations whose generations are not overlapping and whose size is large. The number of males and females in both populations is constant. Any generation is replaced by a new one and any individual has two parents concerning nuclear DNA and a single one (the mother) concerning mtDNA. Moreover, at any generation some individuals migrate from the first population to the second. In a finite random time T, the mtDNA of the second population is completely replaced by the mtDNA of the first. In the same time, the nuclear DNA is not completely replaced and a fraction F of the ancient nuclear DNA persists. We compute both T and F. Since this study shows that complete replacement of mtDNA in a population is compatible with the persistence of a large fraction of nuclear DNA, it may have some relevance for the 'out of Africa'/multiregional debate in palaeoanthropology.

  19. Older Person's Guide to Joint Replacement

    MedlinePlus

    ... he or she will refer you to an orthopedic surgeon who does hip and knee replacement surgery. ... The Arthritis Foundation Web The American Academy of Orthopedic Surgeons ' The American Association of Knee and Hip ...

  20. Replacement Saltwell Pumping System Document Bibliography

    SciTech Connect

    BELLOMY, J.R.

    2000-12-07

    This document bibliography is prepared to identify engineering documentation developed during the design of the Replacement Saltwell Pumping System. The bibliography includes all engineering supporting documents and correspondence prepared prior to the deployment of the system in the field. All documents referenced are available electronically through the Records Management Information System (RMIS). Major components of the Replacement Saltwell Pumping System include the Sundyne Canned Motor Pump, the Water Filter Skid, the Injection Water Skid and the Backflow Preventer Assembly. Drawing H-14-104498 provides an index of drawings (fabrication details, P&IDs, etc.) prepared to support development of the Replacement Saltwell Pumping System. Specific information pertaining to new equipment can be found in Certified Vendor Information (CVI) File 50124. This CVI file has been established specifically for new equipment associated with the Replacement Saltwell Pumping System.

  1. [Graft Replacement for Adult Aortic Coarctation].

    PubMed

    Fuke, Megumi; Nishimura, Kazunori; Kehara, Hiromu; Terasaki, Takamitsu; Sakaguchi, Masayuki; Takano, Tamaki

    2015-07-01

    Case 1:a 47-year-old woman who complained of sweating, finger tremor, and chest pain was diagnosed with coarctation of the aorta and hyperthyroidism. She had been diagnosed with hypertension at 25 years of age but had not undergone further examination. Graft replacement was performed without cardiopulmonary or temporary bypass. Case 2:a 30-year-old woman was diagnosed with coarctation during infertility treatment. Although health screening had revealed hypertension 8 years previously, no further assessment took place. She underwent graft replacement with partial cardiopulmonary bypass. In both cases, we conducted a clamp test to decide whether cardiopulmonary or partial bypass was necessary for graft replacement. Blood pressure discrepancy between upper and lower extremities disappeared immediately after surgery, and no ischemic complications were observed. Hypertension in young adults should prompt further scrutiny for anatomical disorders such as coarctation. A clamp test is considered helpful regarding the surgical approach to graft replacement for coarctation. PMID:26197824

  2. Gyrator-type circuits replace ungrounded inductors

    NASA Technical Reports Server (NTRS)

    Deboo, G. J.

    1968-01-01

    Gyrator circuits using only transistors, capacitors, and resistors which can replace both grounded and ungrounded inductors have been developed to permit complete microminiaturization of circuitry by integration of the components.

  3. Aortic valve replacement in rheumatoid aortic incompetence.

    PubMed Central

    Devlin, A B; Goldstraw, P; Caves, P K

    1978-01-01

    Rheumatoid aortic valve disease is uncommon. and there are few reports of valve replacement in this condition. Aortic valve replacement and partial pericardiectomy was performed in a patient with acute rheumatoid aortitis and aortic incompetence. Previous reports suggest that any patient with rheumatoid arthritis who develops cardiac symptoms should be carefully assessed for surgically treatable involvement of the pericardium or heart valves. Images PMID:725829

  4. Activ C cervical disc replacement for myelopathy

    PubMed Central

    McGonagle, L.; Cadman, S.; Chitgopkar, S. D.; Canavan, L.; O’Malley, M.; Shackleford, I. M.

    2011-01-01

    Background: Cervical disc replacement is becoming an increasingly popular treatment option for cervical myelopathy. It retains motion at the affected segment, unlike anterior cervical discectomy and fusion. The aim of this study is to assess the outcomes of a series of patients who underwent Activ C disc replacement for cervical myelopathy. Materials and Methods: A series of patients at the above Trust with clinical and radiological evidence of cervical myelopathy who were suitable for cervical disc replacement from 2007 to 2009 were included. Implants were inserted by one of two consultant surgeons {IMS, MO’M}. Patients were assessed preoperatively and at six, 12 and 24 months, postoperatively, with a visual analogue score (VAS) for neck and arm pain severity and frequency, the Neck Disability Index questionnaire (NDI) and the Centre for Epidemiologic Studies Depression questionnaire (CES-D). Results: Ten patients underwent surgery between May 2007 and July 2009, 6 women, and 4 men. Average age was 54 years (40-64). Disc levels replaced were: four at C4-5; eight at C5-6; seven at C6-7. Three patients had one disc replaced, five patients had two discs replaced, and two patients had three discs replaced. The VAS for neck pain improved from 5.9 pre-operatively to 1.4-24 months postoperatively and the VAS arm pain improved from 5.4 to 2.6. The NDI improved from 51% preoperatively to 26.8% at 24 months postoperatively. The CES-D showed a slight increase from 19.5 preoperatively to 21.7 at 24 months, postoperatively. Conclusion: Cervical decompression and disc replacement improves pain and function in patients with cervical myelopathy. This benefit is maintained at 24 months post op, with no cases requiring revision. PMID:23125494

  5. [Osteoporosis in men and androgen replacement therapy].

    PubMed

    Tsujimura, Akira; Okuyama, Akihiko

    2003-11-01

    Androgen plays an important role in bone maturation and maintenance of bone mass. Androgen deficiency associated with aging causes osteoporosis for men. With respect to this disease, androgen replacement treatment has been performed for aging male. However, available preparations of androgen are limited in Japan and each of them has both merit and demerit. Establishment of guideline for androgen replacement treatment including criteria of serum testosterone concentration is the problem, which now confronts us. PMID:15775234

  6. A replaceable reflective film for solar concentrators

    SciTech Connect

    Not Available

    1991-09-01

    The 3M Company manufactures a silvered acrylic film called ECP-305 that is regarded as the preferred reflective film for use on stretched-membrane heliostats. However, ECP-305 will degrade in time, due to both corrosion of the silver layer and delamination at the film's silver-to-acrylic interface, and will eventually need to be replaced. 3M uses a very aggressive adhesive on this film, and once it is laminated, replacement is very difficult. The purpose of this investigation was the development of a replaceable reflector, a reflective film that can be easily removed and replaced. A replaceable reflector was successfully configured by laminating ECP-305 to the top surface of a smooth, dimensionally stable polymer film, with a removable adhesive applied to the underside of the polymer film. Several stages of screening and testing led to the selection of a 0.010-inch thick polycarbonate (GE 8030) as the best polymer film and a medium tack tape (3M Y-9425) was selected as the best removable adhesive. To demonstrate the feasibility of the replaceable reflector concept and to provide a real-time field test, the chosen construction was successfully applied to the 50-m{sup 2} SKI heliostat at the Central Receiver Test Facility at Sandia National Laboratories in Albuquerque. 4 refs., 13 figs., 7 tabs.

  7. Deprivation and outcome of total knee replacement.

    PubMed

    Murray, James R D; Birdsall, Paul D; Sher, J Lester; Deehan, David J

    2006-03-01

    Deprivation correlates with poor health and psychosocial variables can affect the symptoms of knee arthritis. Our aim was to determine the effect of deprivation on the level of knee function and health-related quality of life at the time of arthroplasty and 12 months after total knee replacement. From our database of over 2500 knee replacements, we analysed both clinical and quality of life outcome measures. We analysed the relationship between deprivation (by Townsend score), knee function (Knee Society Score) and health-related quality of life (Nottingham Health Profile) before total knee replacement (TKR) and at 12 months post-operation. There was no significant correlation between Townsend score, Knee Society Score and Nottingham Health Profile preoperatively or at 12 months after knee replacement, thus showing that there was no association between deprivation and the severity of knee arthritis at the time of joint replacement nor was there a relationship between deprivation and the short-term outcome from total knee replacement. PMID:16469499

  8. Annual report for Ion Replacement Program

    SciTech Connect

    Tomczuk, Z.; Willit, J.L.; Fischer, A.K.

    1993-07-01

    Ion replacement electrorefining is an innovative electrochemical approach to purifying and separating metals. This approach overcomes the shortcomings of conventional electrorefining and has the potential for processing a wider range of metals and metal halide salts. Salt waste is also minimized with this approach. The key element of ion replacement electrorefining is the ion replacement electrode. This electrode allows a decoupling of the electrotransport process into two separate steps, anodic dissolution and cathodic deposition. Three key accomplishments described in this report that demonstrate the feasibility of ion replacement electrorefining are: (1) we have identified a suitable sodium/{beta}{double_prime}-alumina/molten salt electrolyte system that functions reproducibly at 723 K, (2) we have oxidized and deposited dysprosium, lanthanum, uranium, and titanium by using a sodium ion replacement electrode. In several experiments, an actual separation of dysprosium and lanthanum was observed, and (3) we have identified a metal alloy, Li{sub x}Sb, as an alternative ion replacement electrode. The next stage in the program is the design, construction, and testing of a laboratory-scale electrorefiner. Follow-on development with funding from industrial and federal sponsors is being pursued.

  9. Ileal nutritional function after one-stage orthotopic ileum transplantation in the growing pig: reversal of lethal short bowel syndrome.

    PubMed

    Pakarinen, M; Kuusanmäki, P; Halttunen, J

    1996-05-01

    Intestinal isolation is associated with hypoplasia of defunctioned mucosa and reduction in the segmental absorption, whereas the presence of luminal nutrition is essential for the expression of the ileal adaptive response after proximal small bowel resection. On the other hand, intensive postoperative graft monitoring is obligatory because of the disastrous consequences of small bowel graft rejection. Thus, the authors sought to develop an experimental ileum transplantation model that provided immediate graft placement in bowel continuity, together with readily available graft monitoring connection through a proximal Roux-en-Y enterostomy. Four groups of pigs were prepared: RESTX (n = 9), proximal 50% small bowel resection with simultaneous orthotopic ileum autotransplantation; RES (n = 7), proximal 50% small bowel resection; NONRES (n = 6), transection; and SB (n = 5), short bowel. Early (1 to 4 weeks) and long-term (5 to 12 weeks) studies of animal growth, nutritional status, disaccharide absorption, water and electrolyte balances, and liver function were performed after ileum autotransplantation (IAT) in relation to small intestine of variable length with undivided mesentery (intact neural and lymphatic connections). The perioperative transplantation mortality rate remained at about 10%. Reasons not related to the transplantation procedure accounted for the late complication rate of 38%. In the ileum autotransplantation (RESTX) group, weight gain was recovered 2 to 3 weeks after transplantation, and the mean weight reached the preoperative level at 5 weeks. The SB pigs underwent progressive weight loss. The transection (NONRES) and proximal resection (RES) animals gained weight at similar rates. IAT had no effect on the plasma protein concentrations. Proximal resection, with or without IAT, was associated with depressed plasma cholesterol contents in the early period. Plasma cholesterol levels amended long-term, after both IAT and proximal resection. IAT

  10. Utility and Applications of Orthotopic Models of Human Non-Small Cell Lung Cancer (NSCLC) for the Evaluation of Novel and Emerging Cancer Therapeutics

    PubMed Central

    Justilien, Verline; Fields, Alan P.

    2014-01-01

    Lung cancer is a leading cause of cancer deaths worldwide. Despite advances in chemotherapy, radiation therapy, and surgery, lung cancer continues to have a low 5-year survival rate. Thus, there is a need to better understand the molecular signaling mechanisms that drive lung tumor formation, maintenance, and progression, and to translate this knowledge into better therapeutic intervention strategies. Mouse models that recapitulate the clinical features of advanced human lung cancer are critical for testing novel therapeutic approaches. This unit describes a highly reproducible, easy-to-establish orthotopic murine model of lung cancer, provides methods for in vivo imaging and monitoring of tumor growth, and discusses the usefulness of this model for translational lung cancer research and the development of therapeutic strategies. PMID:24510718

  11. Integrated Proteomics Identified Up-Regulated Focal Adhesion-Mediated Proteins in Human Squamous Cell Carcinoma in an Orthotopic Murine Model

    PubMed Central

    Granato, Daniela C.; Zanetti, Mariana R.; Kawahara, Rebeca; Yokoo, Sami; Domingues, Romênia R.; Aragão, Annelize Z.; Agostini, Michelle; Carazzolle, Marcelo F.; Vidal, Ramon O.; Flores, Isadora L.; Korvala, Johanna; Cervigne, Nilva K.; Silva, Alan R. S.; Coletta, Ricardo D.; Graner, Edgard; Sherman, Nicholas E.; Leme, Adriana F. Paes

    2014-01-01

    Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules. PMID:24858105

  12. Kittiwakes strategically reduce investment in replacement clutches

    USGS Publications Warehouse

    Gasparini, J.; Roulin, A.; Gill, V.A.; Hatch, Shyla A.; Boulinier, T.

    2006-01-01

    Many life-history traits are expressed interactively in life, but to a varying extent on different occasions. Changes in trait expression can be accounted for by differences in the quality of the environment ('environmental constraint' hypothesis) or by strategic adjustments, if the relative contribution of the trait to fitness varies with time ('strategic allocation' hypothesis). In birds, egg production is lower in replacement clutches than in first clutches, but it is unknown whether this reduction results from an environmental constraint (e.g. food being less available at the time when the replacement clutch is produced) or from a strategic allocation of resources between the two breeding attempts. To distinguish between these two hypotheses, we performed an experiment with black-legged kittiwakes (Rissa tridactyla). Pairs were either food-supplemented or not before the first clutch was laid onwards and we induced them to produce a replacement clutch by removing eggs once when the first clutch was complete. As predicted by the 'strategic allocation' hypothesis, egg production of food-supplemented and non-food-supplemented birds decreased between first and replacement clutches. This suggests that kittiwakes strategically reduce investment in egg production for their replacement clutches compared to first clutches. ?? 2006 The Royal Society.

  13. Managing the replacement cycle of laser inventory.

    PubMed

    Davis, C E

    1992-01-01

    Medical lasers are quickly moving into the replacement phase of technology management. Barnes Hospital (St. Louis, MO) is using its laser team to define a process of planned laser replacement using the experience gained from traditional medical equipment replacement cycles, quality improvement principles and tools, and other formalized interdisciplinary teams. The process described in this paper has six basic steps: (1) A decision is made to request a replacement laser. (2) An appropriation request form is completed and submitted with the clinical and/or technical justifications. (3) Those requests initiated outside of the Clinical Engineering Department are reviewed by the Clinical Engineer/Medical Laser Safety Officer (CE/MLSO). (4) The CE/MLSO presents the requests to the hospital Laser Committee, and (5) then to the Laser Users' Group. (6) Finally, an Expenditure Authorization Committee reviews all capital expense requests, including those for replacement lasers, and allocates funds for the next fiscal year. This paper illustrates and evaluates the process, using an example from the review process for 1993 equipment purchases at Barnes Hospital. PMID:10124683

  14. Dexmedetomidine Inhibits TLR4/NF-κB Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats.

    PubMed

    Yao, Hui; Chi, Xinjin; Jin, Yi; Wang, Yiheng; Huang, Pinjie; Wu, Shan; Xia, Zhengyuan; Cai, Jun

    2015-01-01

    Patients who undergo orthotopic liver transplantation often sustain acute kidney injury(AKI). The toll-like receptor 4(TLR4)/Nuclear factor-кB(NF-кB) pathway plays a role in AKI. Dexmedetomidine(Dex) has been shown to attenuate AKI. The current study aimed to determine whether liver transplantation-induced AKI is associated with inflammatory response, and to assess the effects of dexmedetomidine pretreatment on kidneys in rats following orthotopic autologous liver transplantation(OALT). Seventy-seven adult male rats were randomized into 11 groups. Kidney tissue histopathology and levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were evaluated. Levels of TLR4, NF-κB, tumor necrosis factor-α, and interleukin-1β levels were measured in kidney tissues. OALT resulted in significant kidney functional impairment and tissue injury. Pre-treatment with dexmedetomidine decreased BUN and SCr levels and reduced kidney pathological injury, TLR4 expression, translocation of NF-κB, and cytokine production. The effects of dexmedetomidine were reversed by pre-treatment with atipamezole and BRL44408, but not ARC239. These results were confirmed by using α2A-adrenergic receptor siRNA which reversed the protective effect of dexmedetomidine on attenuating NRK-52E cells injury induced by hypoxia reoxygenation. In conclusion, Dexmedetomidine-pretreatment attenuates OALT-induced AKI in rats which may be contributable to its inhibition of TLR4/MyD88/NF-κB pathway activation. The renoprotective effects are related to α2A-adrenergic receptor subtypes. PMID:26585410

  15. Combretastatin A-4 inhibits cell growth and metastasis in bladder cancer cells and retards tumour growth in a murine orthotopic bladder tumour model

    PubMed Central

    Shen, Cheng-Huang; Shee, Jia-Jen; Wu, Jin-Yi; Lin, Yi-Wen; Wu, Jiann-Der; Liu, Yi-Wen

    2010-01-01

    BACKGROUND AND PURPOSE Bladder cancer is a highly recurrent cancer after intravesical therapy, so new drugs are needed to treat this cancer. Hence, we investigated the anti-cancer activity of combretastatin A-4 (CA-4), an anti-tubulin agent, in human bladder cancer cells and in a murine orthotopic bladder tumour model. EXPERIMENTAL APPROACH Cytotoxicity of CA-4 was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, propidium iodide (PI) staining assay and clonogenic survival assay. In vivo microtubule assembly assay, cell cycle analyses, Western blot and cell migration assay were used to study the mechanism of CA-4. The effect of intravesical CA-4 therapy on the development of tumours was studied in the murine orthotopic bladder tumour model. KEY RESULTS CA-4 inhibited microtubule polymerization in vivo. Cytotoxic IC50 values of CA-4 in human bladder cancer cells were below 4 nM. Analyses of cell-cycle distribution showed CA-4 obviously induced G2-M phase arrest with sub-G1 formation. The analyses of apoptosis showed that CA-4 induced caspase-3 activation and decreased BubR1 and Bub3 in cancer cells. In addition to apoptosis, CA-4 was also found to induce the formation of multinucleated cells. CA-4 had a significantly reduced cell migration in vitro. Importantly, the in vivo study revealed that intravesical CA-4 therapy retarded the development of murine bladder tumours. CONCLUSIONS AND IMPLICATIONS These data demonstrate that CA-4 kills bladder cancer cells by inducing apoptosis and mitotic catastrophe. It inhibited cell migration in vitro and tumour growth in vivo. Hence, CA-4 intravesical therapy could provide another strategy for treating superficial bladder cancers. PMID:20649598

  16. Dexmedetomidine Inhibits TLR4/NF-κB Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats

    PubMed Central

    Yao, Hui; Chi, Xinjin; Jin, Yi; Wang, Yiheng; Huang, Pinjie; Wu, Shan; Xia, Zhengyuan; Cai, Jun

    2015-01-01

    Patients who undergo orthotopic liver transplantation often sustain acute kidney injury(AKI). The toll-like receptor 4(TLR4)/Nuclear factor-кB(NF-кB) pathway plays a role in AKI. Dexmedetomidine(Dex) has been shown to attenuate AKI. The current study aimed to determine whether liver transplantation-induced AKI is associated with inflammatory response, and to assess the effects of dexmedetomidine pretreatment on kidneys in rats following orthotopic autologous liver transplantation(OALT). Seventy-seven adult male rats were randomized into 11 groups. Kidney tissue histopathology and levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were evaluated. Levels of TLR4, NF-κB, tumor necrosis factor-α, and interleukin-1β levels were measured in kidney tissues. OALT resulted in significant kidney functional impairment and tissue injury. Pre-treatment with dexmedetomidine decreased BUN and SCr levels and reduced kidney pathological injury, TLR4 expression, translocation of NF-κB, and cytokine production. The effects of dexmedetomidine were reversed by pre-treatment with atipamezole and BRL44408, but not ARC239. These results were confirmed by using α2A-adrenergic receptor siRNA which reversed the protective effect of dexmedetomidine on attenuating NRK-52E cells injury induced by hypoxia reoxygenation. In conclusion, Dexmedetomidine-pretreatment attenuates OALT-induced AKI in rats which may be contributable to its inhibition of TLR4/MyD88/NF-κB pathway activation. The renoprotective effects are related to α2A-adrenergic receptor subtypes. PMID:26585410

  17. MicroPET/CT Imaging of an Orthotopic Model of Human Glioblastoma Multiforme and Evaluation of Pulsed Low-Dose Irradiation

    SciTech Connect

    Park, Sean S.; Chunta, John L.; Robertson, John M.; Martinez, Alvaro A.; Oliver Wong, Ching-Yee; Amin, Mitual; Wilson, George D.; Marples, Brian

    2011-07-01

    Purpose: Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. Methods: Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CT (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. Results: Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 x 10{sup 6} cells produced a 50- to 70-mm{sup 3} tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). Conclusion: This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage.

  18. Effects of Dexmedetomidine on Postoperative Cognitive Dysfunction and Serum Levels of b-Amyloid and Neuronal Microtubule-Associated Protein in Orthotopic Liver Transplantation Patients.

    PubMed

    Xu, Guang; Li, Lan-Lan; Sun, Zhen-Tao; Zhang, Wei; Han, Xue-Ping

    2016-01-01

    BACKGROUND Because of the restricted data available on patients with postoperative cognitive dysfunction (POCD) in orthotopic liver transplantation (OLT), the goal of our study was to determine the outcome of dexmedetomidine (DEX) on POCD and the mechanism operating in OLT patients. MATERIAL AND METHODS Our study included 80 patients randomly divided into 2 equal groups: the DEX group and the control group. In the DEX group, our patients received an initial dose of DEX at 1 µg/kg for 10 min followed by a continuous infusion at 0.3 µg/kg/h until the end of surgery. The control group received a saline treatment, and neurological tests were performed to assess the status of POCD. Serum level of b-amyloid protein (Aβ) and neuronal microtubule-associated protein (Tau) were measured at designated time points: at pre-operation (T1), 0.5 h after the anhepatic phase (T2), 2 h after the reperfusion of the new liver (T3), at the completion of operation (T4), at day 1 (T5), and at day 7 (T6) after the operation. RESULTS The incidence of POCD was significantly reduced in the DEX group (P=0.017). The score from the neurological tests was significantly decreased in the control group after the operation, but no statistical difference was observed in the DEX group. The DEX groups demonstrated a lower level of β-amyloid and Tau protein than those at the corresponding time points (T4~T6) in the control group (P<0.01). CONCLUSIONS Dexmedetomidine reduced the incidence of postoperative cognitive dysfunction in orthotopic liver transplantation patients. The decreased levels of b-amyloid and Tau protein may have contributed to this favorable outcome. PMID:27527391

  19. Orthotopic transplantation of cryopreserved mouse ovaries and gonadotrophin releasing hormone analogues in the restoration of function following chemotherapy-induced ovarian damage.

    PubMed

    Li, Qing; Szatmary, Peter; Liu, Yanyang; Ding, Zhenyu; Zhou, Jin; Sun, Yi; Luo, Feng; Wang, Yan; Zhu, Jiang

    2015-01-01

    Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients' quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I); cyclophosphamide only (group II); cyclophosphamide plus GnRHa (group III); cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV). Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide. PMID:25811681

  20. Treatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice

    PubMed Central

    Jacoby, Jörg J.; Erez, Baruch; Korshunova, Maria V.; Williams, Ryan R.; Furutani, Kazuhisa; Takahashi, Osamu; Kirkpatrick, Lynn; Lippman, Scott M.; Powis, Garth; O’Reilly, Michael S.; Herbst, Roy S.

    2011-01-01

    Introduction PX-478 is a potent small-molecule inhibitor of HIF-1α. In preclinical studies, it had antitumor activity against various solid tumors in subcutaneous xenografts but had no measurable activity against a non-small cell lung cancer (NSCLC) xenograft. To determine the effectiveness of PX-478 against lung tumors, we investigated HIF-1α expression in several lung cancer cell lines, both in vitro and in vivo, and treated orthotopic mouse models of human lung cancer with PX-478. Methods Cells from two human lung adenocarcinoma cell models (PC14-PE6 and NCI-H441) or two human small cell lung cancer (SCLC) models (NCI-H187 and NCI-N417) were injected into the left lungs of nude mice and were randomized 16 to 18 days after injection with daily oral treatment with PX-478 or vehicle for 5 days. Results In the PC14-PE6 NSCLC model, treatment with 20 mg/kg PX-478 significantly reduced the median primary lung tumor volume by 87% (p = 0.005) compared with the vehicle-treated group. PX-478 treatment also markedly reduced mediastinal metastasis and prolonged survival. Similar results were obtained in a second NSCLC model. In SCLC models, PX-478 was even more effective. In the NCI-H187 model, the median primary lung tumor volume was reduced by 99% (p = 0.0001). The median survival duration was increased by 132%. In the NCI-N417 model, the median primary lung tumor volume was reduced by 97% (p = 0.008). Conclusions We demonstrated that the PX-478, HIF-1α inhibitor, had significant antitumor activity against two orthotopic models of lung adenocarcinomas and two models of SCLC. These results suggest the inclusion of lung cancer patients in phase I clinical trials of PX-478. PMID:20512076

  1. Oral inoculation of probiotics Lactobacillus acidophilus NCFM suppresses tumour growth both in segmental orthotopic colon cancer and extra-intestinal tissue.

    PubMed

    Chen, Chien-Chang; Lin, Wei-Chuan; Kong, Man-Shan; Shi, Hai Ning; Walker, W Allan; Lin, Chun-Yen; Huang, Ching-Tai; Lin, Yung-Chang; Jung, Shih-Ming; Lin, Tzou-Yien

    2012-06-01

    Modulation of the cellular response by the administration of probiotic bacteria may be an effective strategy for preventing or inhibiting tumour growth. We orally pre-inoculated mice with probiotics Lactobacillus acidophilus NCFM (La) for 14 d. Subcutaneous dorsal-flank tumours and segmental orthotopic colon cancers were implanted into mice using CT-26 murine colon adenocarcinoma cells. On day 28 after tumour initiation, the lamina propria of the colon, mesenteric lymph nodes (MLN) and spleen were harvested and purified for flow cytometry and mRNA analyses. We demonstrated that La pre-inoculation reduced tumour volume growth by 50·3 %, compared with untreated mice at 28 d after tumour implants (2465·5 (SEM 1290·4) v. 4950·9 (SEM 1689·3) mm³, P<0·001). Inoculation with La reduced the severity of colonic carcinogenesis caused by CT-26 cells, such as level of colonic involvement and structural abnormality of epithelial/crypt damage. Moreover, La enhanced apoptosis of CT-26 cells both in dorsal-flank tumour and segmental orthotopic colon cancer, and the mean counts of apoptotic body were higher in mice pre-inoculated with La (P<0·05) compared with untreated mice. La pre-inoculation down-regulated the CXCR4 mRNA expressions in the colon, MLN and extra-intestinal tissue, compared with untreated mice (P<0·05). In addition, La pre-inoculation reduced the mean fluorescence index of MHC class I (H-2Dd, -Kd and -Ld) in flow cytometry analysis. Taken together, these findings suggest that probiotics La may play a role in attenuating tumour growth during CT-26 cell carcinogenesis. The down-regulated expression of CXCR4 mRNA and MHC class I, as well as increasing apoptosis in tumour tissue, indicated that La may be associated with modulating the cellular response triggered by colon carcinogenesis. PMID:21992995

  2. FLT3 and CDK4/6 inhibitors: signaling mechanisms and tumor burden in subcutaneous and orthotopic mouse models of acute myeloid leukemia.

    PubMed

    Zhang, Yaping; Hsu, Cheng-Pang; Lu, Jian-Feng; Kuchimanchi, Mita; Sun, Yu-Nien; Ma, Ji; Xu, Guifen; Zhang, Yilong; Xu, Yang; Weidner, Margaret; Huard, Justin; D'Argenio, David Z

    2014-12-01

    FLT3(ITD) subtype acute myeloid leukemia (AML) has a poor prognosis with currently available therapies. A number of small molecule inhibitors of FLT3 and/or CDK4/6 are currently under development. A more complete and quantitative understanding of the mechanisms of action of FLT3 and CDK4/6 inhibitors may better inform the development of current and future compounds that act on one or both of the molecular targets, and thus may lead to improved treatments for AML. In this study, we investigated in both subcutaneous and orthotopic AML mouse models, the mechanisms of action of three FLT3 and/or CDK4/6 inhibitors: AMG925 (Amgen), sorafenib (Bayer and Onyx), and quizartinib (Ambit Biosciences). A composite model was developed to integrate the plasma pharmacokinetics of these three compounds on their respective molecular targets, the coupling between the target pathways, as well as the resulting effects on tumor burden reduction in the subcutaneous xenograft model. A sequential modeling approach was used, wherein model structures and estimated parameters from upstream processes (e.g. PK, cellular signaling) were fixed for modeling subsequent downstream processes (cellular signaling, tumor burden). Pooled data analysis was employed for the plasma PK and cellular signaling modeling, while population modeling was applied to the tumor burden modeling. The resulting model allows the decomposition of the relative contributions of FLT3(ITD) and CDK4/6 inhibition on downstream signaling and tumor burden. In addition, the action of AMG925 on cellular signaling and tumor burden was further studied in an orthotopic tumor mouse model more closely representing the physiologically relevant environment for AML. PMID:25326874

  3. Soy phytochemicals prevent orthotopic growth and metastasis of bladder cancer in mice by alterations of cancer cell proliferation and apoptosis and tumor angiogenesis.

    PubMed

    Singh, Ajita V; Franke, Adrian A; Blackburn, George L; Zhou, Jin-Rong

    2006-02-01

    A role of dietary bioactive components in bladder cancer prevention is biologically plausible because most substances or metabolites are excreted through the urinary tract and are consequently in direct contact with the mucosa of the bladder. We first determined antigrowth activity of genistein against poorly differentiated 253J B-V human bladder cancer cells in vitro. Genistein inhibited the cell growth in a time- and dose-dependent manner via G(2)-M arrest, down-regulation of nuclear factor kappaB (NF-kappaB), and induction of apoptosis. We also evaluated both genistin, which is a natural form of genistein, and the isoflavone-rich soy phytochemical concentrate (SPC) on the growth and metastasis of 253J B-V tumors in an orthotopic tumor model. Mice treated with genistin and SPC had reduced final tumor weights by 56% (P < 0.05) and 52% (P < 0.05), respectively, associated with induction of tumor cell apoptosis and inhibition of tumor angiogenesis in vivo. In addition, SPC treatment, but not genistin treatment, significantly inhibited lung metastases by 95% (P < 0.01) associated with significant down-regulation of NF-kappaB expression in tumor tissues and reduction of circulating insulin-like growth factor-I levels, suggesting that SPC may contain other bioactive ingredients that have antimetastatic activity. The results from our studies suggest that further clinical investigation should be warranted to apply soy phytochemicals, such as SPC, as a potent prevention regimen for bladder cancer progression. This orthotopic human bladder tumor model also provides a clinically relevant experimental tool for assessing potential preventive activity of other dietary components against bladder tumor growth and metastasis. PMID:16452247

  4. Hip or knee replacement - in the hospital after

    MedlinePlus

    Hip replacement surgery - after - self-care; Knee replacement surgery - after - self-care ... occupational therapist will teach people who have had hip replacement how to safely perform daily activities . All of ...

  5. Hip or knee replacement - after - what to ask your doctor

    MedlinePlus

    ... Below are some questions you may want to ask your health care provider to help you take ... What to ask your doctor after hip or knee replacement; Hip replacement - after - what to ask your doctor; Knee replacement - after - ...

  6. Hip or knee replacement - after - what to ask your doctor

    MedlinePlus

    ... PA: Elsevier Mosby; 2012:chap 7. Read More Hip joint replacement Hip pain Knee joint replacement Knee pain ... joint replacement - discharge Taking care of your new hip joint Update Date 3/5/2015 Updated by: C. ...

  7. Hip or knee replacement - before - what to ask your doctor

    MedlinePlus

    ... PA: Elsevier Mosby; 2012:chap 7. Read More Hip joint replacement Hip pain Knee joint replacement Knee pain ... joint replacement - discharge Taking care of your new hip joint Update Date 3/5/2015 Updated by: C. ...

  8. Dead pixel replacement in LWIR microgrid polarimeters.

    PubMed

    Ratliff, Bradley M; Tyo, J Scott; Boger, James K; Black, Wiley T; Bowers, David L; Fetrow, Matthew P

    2007-06-11

    LWIR imaging arrays are often affected by nonresponsive pixels, or "dead pixels." These dead pixels can severely degrade the quality of imagery and often have to be replaced before subsequent image processing and display of the imagery data. For LWIR arrays that are integrated with arrays of micropolarizers, the problem of dead pixels is amplified. Conventional dead pixel replacement (DPR) strategies cannot be employed since neighboring pixels are of different polarizations. In this paper we present two DPR schemes. The first is a modified nearest-neighbor replacement method. The second is a method based on redundancy in the polarization measurements.We find that the redundancy-based DPR scheme provides an order-of-magnitude better performance for typical LWIR polarimetric data. PMID:19547086

  9. [Update in continuous renal replacement techniques].

    PubMed

    Romero-García, M; de la Cueva-Ariza, L; Delgado-Hito, P

    2013-01-01

    Acute renal failure affects 25% of patients hospitalized in intensive care units. Despite technological advances, the mortality of these patients is still high due to its associated complications. Continuous renal replacement techniques are one of the treatments for acute renal failure because they make it possible to treat the complications and decrease mortality. The nurse's knowledge and skills regarding these techniques will be decisive for the success of the therapy. Consequently, the nurse's experience and training are key components. The objective of this article is to update the knowledge on continuous renal replacement techniques. Keeping this in mind, a review has been made of the physical and chemical principles such as diffusion and convection, among others. A description of the different continuous renal replacement techniques, a presentation of the main vascular access, and a description of the nursing cares and complications related to techniques used have also been provided. PMID:23498371

  10. Immunoglobulin Replacement Therapy in Secondary Hypogammaglobulinemia

    PubMed Central

    Compagno, Nicolò; Malipiero, Giacomo; Cinetto, Francesco; Agostini, Carlo

    2014-01-01

    Immunoglobulin (Ig) replacement therapy dramatically changed the clinical course of primary hypogammaglobulinemias, significantly reducing the incidence of infectious events. Over the last two decades its use has been extended to secondary antibody deficiencies, particularly those related to hematological disorders as lymphoproliferative diseases (LPDs) and multiple myeloma. In these malignancies, hypogammaglobulinemia can be an intrinsic aspect of the disease or follow chemo-immunotherapy regimens, including anti-CD20 treatment. Other than in LPDs the broadening use of immunotherapy (e.g., rituximab) and immune-suppressive therapy (steroids, sulfasalazine, and mycophenolate mofetil) has extended the occurrence of iatrogenic hypogammaglobulinemia. In particular, in both autoimmune diseases and solid organ transplantation Ig replacement therapy has been shown to reduce the rate of infectious events. Here, we review the existing literature about Ig replacement therapy in secondary hypogammaglobulinemia, with special regard for subcutaneous administration route, a safe, effective, and well-tolerated treatment approach, currently well established in primary immunodeficiencies and secondary hypogammaglobulinemias. PMID:25538710

  11. Dead pixel replacement in LWIR microgrid polarimeters

    NASA Astrophysics Data System (ADS)

    Ratliff, Bradley M.; Tyo, J. Scott; Boger, James K.; Black, Wiley T.; Bowers, David L.; Fetrow, Matthew P.

    2007-06-01

    LWIR imaging arrays are often affected by nonresponsive pixels, or “dead pixels.” These dead pixels can severely degrade the quality of imagery and often have to be replaced before subsequent image processing and display of the imagery data. For LWIR arrays that are integrated with arrays of micropolarizers, the problem of dead pixels is amplified. Conventional dead pixel replacement (DPR) strategies cannot be employed since neighboring pixels are of different polarizations. In this paper we present two DPR schemes. The first is a modified nearest-neighbor replacement method. The second is a method based on redundancy in the polarization measurements.We find that the redundancy-based DPR scheme provides an order-of-magnitude better performance for typical LWIR polarimetric data.

  12. Nashville Gas treads carefully to replace pipe

    SciTech Connect

    1997-06-01

    The private gas utility, Nashville Gas, was responsible for replacing damaged or inadequate 2- and 4-inch steel gas lines beneath Music City, USA. The line replacements required either size for size or upsizing. The first choice was directional drilling, which was quickly determined to be unpractical because of rocky soil conditions. The second option was open trenching. Undoubtedly, trenching would mean having to contend with angry residents and tourists, since gas lines ran beneath yards, mature trees, sidewalks, roadways, and railways. In addition to the negative social factors, trenching would require additional funds for substantial landscaping and pavement replacement. It at all possible, a no-dig alternative was desired. Nashville Gas found Grundomat piercing tools which create a bore, then pushes pipe back through it. These same tools can simultaneously pull in pipe. These tools were customized for the Nashville project.

  13. Replacement of charcoal sorbent in the VOST

    SciTech Connect

    Johnson, L.D.; Fuerst, R.G.; Foster, A.L.; Bursey, J.T.

    1993-01-01

    EPA Method 0030, the Volatile Organic Sampling Train (VOST), for sampling volatile organics from stationary sources, specifies the use of petroleum-base charcoal in the second sorbent tube. Charcoal has proven to be a marginal performer as a sampling sorbent, partly due to inconsistency in analyte recovery. In addition, commercial availability of petroleum charcoal for VOST tubes has been variable. Lack of data on comparability and variability of charcoals for VOST application has created uncertainty when other charcoals are substituted. Five potential sorbent replacements for charcoal in Method 0030 were evaluated along with a reference charcoal. Two of the sorbents tested, Ambersorb XE-340 and Tenax GR, did not perform well enough to qualify as replacements. Three candidates, Anasorb 747, Carbosieve S-III and Kureha Beaded Activated Charcoal, performed adequately, and produced statistically equivalent results. Anasorb 747 appears to be an acceptable replacement for petroleum charcoal, based on a combination of performance, availability, and cost.

  14. Rapid prototyping of ossicular replacement prostheses

    NASA Astrophysics Data System (ADS)

    Ovsianikov, A.; Chichkov, B.; Adunka, O.; Pillsbury, H.; Doraiswamy, A.; Narayan, R. J.

    2007-05-01

    Materials used in ossicular replacement prostheses must demonstrate appropriate biological compatibility, acoustic transmission, stability, and stiffness properties. Prostheses prepared using Teflon ®, titanium, Ceravital and other conventional materials have demonstrated several problems, including migration, perforation of the tympanic membrane, difficulty in shaping the prostheses, and reactivity with the surrounding tissues. We have used two-photon polymerization for rapid prototyping of Ormocer ® middle-ear bone replacement prostheses. Ormocer ® surfaces fabricated using two-photon polymerization exhibited acceptable cell viability and cell growth profiles. The Ormocer ® prosthesis was able to be inserted and removed from the site of use in the frozen human head without fracture. Our results demonstrate that two-photon polymerization is able to create ossicular replacement prostheses and other medical devices with a larger range of sizes, shapes and materials than other microfabrication techniques.

  15. Nonoperative replacement of a jejunostomy feeding catheter.

    PubMed

    Stogdill, B J; Page, C P; Pestana, C

    1984-02-01

    Nonoperative replacement of lost or occluded jejunal feeding catheters proved successful in 8 of 11 patients. This technique is recommended as a nonoperative means of replacing a needle catheter jejunostomy when it is accidentally lost or becomes occluded. Adherence to sterile technique and gentle advancement of the guide wire to avoid injury to the bowel are important. Since the technique depends on an established tract between the skin and the bowel, catheter replacement should not be attempted when the feeding catheter is lost or becomes occluded in the immediate postoperative period. In addition, confirmation of catheter patency and intraluminal position with sterile water-soluble contrast medium is critical to the safe use of this technique. PMID:6421183

  16. Method and apparatus for replacing bearing

    SciTech Connect

    Bryan, L. E.; Grove, R. W.; Primus, W. F.

    1985-07-02

    A method and apparatus are provided for replacing the bearing between the sampson post and the walking beam of an oil well pump. The walking beam and the pitman arms are securely fastened together to prevent relative movement therebetween. The head portion is adjustably restrained against the force of the counter-weight. The walking beam is allowed to pivot on the connection between the walking beam and the pitman arms so that the walking beam moves away from the sampson post so that the bearing may be replaced.

  17. Valve assembly having remotely replaceable bearings

    DOEpatents

    Johnson, Evan R.; Tanner, David E.

    1980-01-01

    A valve assembly having remotely replaceable bearings is disclosed wherein a valve disc is supported within a flow duct for rotation about a pair of axially aligned bearings, one of which is carried by a spindle received within a diametral bore in the valve disc, and the other of which is carried by a bearing support block releasably mounted on the duct circumferentially of an annular collar on the valve disc coaxial with its diametrical bore. The spindle and bearing support block are adapted for remote removal to facilitate servicing or replacement of the valve disc support bearings.

  18. The immunologic barriers to replacing damaged organs

    PubMed Central

    Cascalho, Marilia; Platt, Jeffrey L.

    2005-01-01

    The recent years have brought breathtaking advances in the biomedical sciences and biomedical engineering. These advances offer the promise that diseases responsible for most disability and early death may soon be addressed by replacing damaged organs with bio-engineered substitutes. Application of these technologies, however, is impeded by the immune response directed against foreign cells and tissues. Here we consider the potentiality and the limitations of these new technologies and how the technologies might be combined to generate novel approaches to organ replacement that overcome immunological barriers to success. PMID:12934939

  19. WEIGHT LOSS WITH MEAL REPLACEMENT AND MEAL REPLACEMENT PLUS SNACKS: A RANDOMIZED TRIAL

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To evaluate whether snacking would improve weight loss and weight maintenance in overweight individuals within the context of a structured meal replacement (MR) weight loss program. A prospective 24 week, 2 (snacking vs nonsnacking) x 2 (MR vs meal replacement augmented with snacks (MRPS)...

  20. 24 CFR 891.745 - Replacement reserve.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Replacement reserve. 891.745 Section 891.745 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT (CONTINUED) OFFICE OF THE ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (SECTION 8...

  1. 24 CFR 891.745 - Replacement reserve.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 891.745 Section 891.745 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF THE ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (SECTION 8...

  2. Hip Replacement - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Hip Replacement - Multiple Languages To use the sharing features on this page, please enable JavaScript. Arabic (العربية) Bosnian (Bosanski) Chinese - Simplified (简体中文) Chinese - Traditional ( ...

  3. Fluid and electrolyte replacement in soccer.

    PubMed

    Kirkendall, D T

    1998-10-01

    Soccer can be played under a wide range of environmental conditions. Traditionally, fluid replacement is limited during the game, but in reality, there are numerous opportunities for fluid ingestion during a match. Many of the recommendations on fluid replenishment have been directed at continuous exercise, and application of those suggestions can be applied to an intermittent sport like soccer. PMID:9922897

  4. Do Formal Supports Replace Informal Supports?

    ERIC Educational Resources Information Center

    Barer, Barbara M.; And Others

    Health policy researchers have long been interested in the extent to which the provision of formal supports replaces or undermines the informal support system. This study examined the linkages between the formal and informal support system as they are mediated by a health care setting which readily provides patients with access to social services.…

  5. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... HPG funds; (3) Must meet all applicable requirements of 7 CFR 3550.57; and (4) May not be sold within... 7 Agriculture 13 2014-01-01 2013-01-01 true Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL...

  6. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... HPG funds; (3) Must meet all applicable requirements of 7 CFR 3550.57; and (4) May not be sold within... 7 Agriculture 13 2010-01-01 2009-01-01 true Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL...

  7. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... HPG funds; (3) Must meet all applicable requirements of 7 CFR 3550.57; and (4) May not be sold within... 7 Agriculture 13 2011-01-01 2009-01-01 true Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL...

  8. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 13 2013-01-01 2013-01-01 false Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED)...

  9. 7 CFR 1944.659 - Replacement housing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... HPG funds; (3) Must meet all applicable requirements of 7 CFR 3550.57; and (4) May not be sold within... 7 Agriculture 13 2012-01-01 2012-01-01 false Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL...

  10. 24 CFR 891.405 - Replacement reserve.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 891.405 Section 891.405 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF THE ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (SECTION 8...

  11. 24 CFR 970.31 - Replacement units.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... must comply with 24 CFR part 905, Public Housing Capital Fund Program, as well as 24 CFR part 941. ...) OFFICE OF ASSISTANT SECRETARY FOR PUBLIC AND INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING PROGRAM-DEMOLITION OR DISPOSITION OF PUBLIC HOUSING PROJECTS § 970.31 Replacement...

  12. 24 CFR 970.31 - Replacement units.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... must comply with 24 CFR part 905, Public Housing Capital Fund Program, as well as 24 CFR part 941. ...) OFFICE OF ASSISTANT SECRETARY FOR PUBLIC AND INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING PROGRAM-DEMOLITION OR DISPOSITION OF PUBLIC HOUSING PROJECTS § 970.31 Replacement...

  13. 24 CFR 970.31 - Replacement units.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... must comply with 24 CFR part 905, Public Housing Capital Fund Program, as well as 24 CFR part 941. ...) OFFICE OF ASSISTANT SECRETARY FOR PUBLIC AND INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING PROGRAM-DEMOLITION OR DISPOSITION OF PUBLIC HOUSING PROJECTS § 970.31 Replacement...

  14. 24 CFR 970.31 - Replacement units.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... must comply with 24 CFR part 905, Public Housing Capital Fund Program, as well as 24 CFR part 941. ...) OFFICE OF ASSISTANT SECRETARY FOR PUBLIC AND INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING PROGRAM-DEMOLITION OR DISPOSITION OF PUBLIC HOUSING PROJECTS § 970.31 Replacement...

  15. School-Based Aggression Replacement Training

    ERIC Educational Resources Information Center

    Roth, Becky Sue; Striepling-Goldstein, Susan

    2003-01-01

    Aggression Replacement Training (ART) is a potent K-12 intervention that responds to many of the developmental and natural needs of aggressive and antisocial students. Woven into the curriculum preventatively or as a stand-alone course in response to an antisocial school climate, ART facilitates the learning necessary to reach and provide lasting…

  16. REPLACING SOLVENT CLEANING WITH AQUEOUS CLEANING

    EPA Science Inventory

    The report documents actions taken by Robert Bosch Corp., Charleston, SC, in replacing the cleaning solvents 1, 1, 2- trichloro-1, 2, 2-trifluoroethane (CFC-113) and trichloroethylene (TCE) with aqueous solutions. Bosch has succeeded in eliminating all their CFC-113 use and so f...

  17. REPLACING SOLVENT CLEANING WITH AQUEOUS CLEANING

    EPA Science Inventory

    The report documents actions taken by Robert Bosch Corp., Charleston, SC, in replacing the cleaning solvents 1, 1, 2- trichloro-1, 2, 2-trifluoroethane (CFC-113) and trichloroethylene (TCE) with aqueous solutions. osch has succeeded in eliminating all their CFC-113 use and so far...

  18. A Helix Replacement Mechanism Directs Metavinculin Functions

    SciTech Connect

    Rangarajan, Erumbi S.; Lee, Jun Hyuck; Yogesha, S.D.; Izard, Tina

    2010-10-11

    Cells require distinct adhesion complexes to form contacts with their neighbors or the extracellular matrix, and vinculin links these complexes to the actin cytoskeleton. Metavinculin, an isoform of vinculin that harbors a unique 68-residue insert in its tail domain, has distinct actin bundling and oligomerization properties and plays essential roles in muscle development and homeostasis. Moreover, patients with sporadic or familial mutations in the metavinculin-specific insert invariably develop fatal cardiomyopathies. Here we report the high resolution crystal structure of the metavinculin tail domain, as well as the crystal structures of full-length human native metavinculin (1,134 residues) and of the full-length cardiomyopathy-associated {Delta}Leu954 metavinculin deletion mutant. These structures reveal that an {alpha}-helix (H1{prime}) and extended coil of the metavinculin insert replace {alpha}-helix H1 and its preceding extended coil found in the N-terminal region of the vinculin tail domain to form a new five-helix bundle tail domain. Further, biochemical analyses demonstrate that this helix replacement directs the distinct actin bundling and oligomerization properties of metavinculin. Finally, the cardiomyopathy associated {Delta}Leu954 and Arg975Trp metavinculin mutants reside on the replaced extended coil and the H1{prime} {alpha}-helix, respectively. Thus, a helix replacement mechanism directs metavinculin's unique functions.

  19. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General..., mutual self-help housing or other federally assisted housing programs. (c) Is in an area not subjected to... person if, after he receives a replacement housing payment and any available housing assistance...

  20. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General..., mutual self-help housing or other federally assisted housing programs. (c) Is in an area not subjected to... person if, after he receives a replacement housing payment and any available housing assistance...

  1. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General..., mutual self-help housing or other federally assisted housing programs. (c) Is in an area not subjected to... person if, after he receives a replacement housing payment and any available housing assistance...

  2. [Exoprosthetic Replacement of the Upper Extremity].

    PubMed

    Salminger, S; Mayer, J A; Sturma, A; Riedl, O; Bergmeister, K D; Aszmann, O C

    2016-08-01

    During the last years, the prosthetic replacement in upper limb amputees has undergone different developments. The use of new nerve surgical concepts improved the control strategies tremendously, especially for high-level amputees. Technological innovation in the field of pattern recognition enables the control of multifunctional myoelectric hand prostheses in a natural and intuitive manner. However, the different levels of amputation pose different challenges for the therapeutic team which concern not only the prosthetic attachment; also the expected functional outcome of prosthetic limb replacement differs greatly between the individual levels of amputation. Therefore, especially in partial hand amputations the indication for prosthetic fitting has to be evaluated critically, as these patients may benefit more from biologic reconstructive concepts. The value of the upper extremity, in particular of the hand, is undisputable and, as such represents the driving force for the technological and surgical developments within the exoprosthetic replacement. This article discusses the possibilities and limitations of exoprosthetic limb replacement on the different amputation levels and explores new developments. PMID:27547980

  3. 24 CFR 891.405 - Replacement reserve.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Replacement reserve. 891.405 Section 891.405 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT (CONTINUED) OFFICE OF THE ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (SECTION 8...

  4. Measure Guideline: Window Repair, Rehabilitation, and Replacement

    SciTech Connect

    Baker, P.

    2012-12-01

    This measure guideline provides information and guidance on rehabilitating, retrofitting, and replacing existing window assemblies in residential construction. The intent is to provide information regarding means and methods to improve the energy and comfort performance of existing wood window assemblies in a way that takes into consideration component durability, in-service operation, and long term performance of the strategies.

  5. Mitochondrial Replacement Techniques: Divergence in Global Policy.

    PubMed

    Schandera, Johanna; Mackey, Tim K

    2016-07-01

    In 2015, the UK became the first country permitting the clinical application of mitochondrial replacement techniques (MRT). Here, we explore how MRT have led to diverging international policy. In response, we recommend focused regulatory efforts coupled with United Nations (UN) leadership to build international consensus on the future of MRT. PMID:27206380

  6. Recent Advances in Hydrocortisone Replacement Treatment.

    PubMed

    Mallappa, Ashwini; Debono, Miguel

    2016-01-01

    Since the first use of cortisone in patients around 65 years ago, the use of synthetic glucocorticoids has made a crucial impact on the treatment of several diseases in medicine. Although significant reductions in morbidity and mortality have occurred in patients suffering from cortisol deficiency, conventional hydrocortisone replacement treatment is still inadequate. A major limitation is that it fails to replace cortisol in a physiological manner. Cortisol has a distinct circadian rhythm and acts as a secondary messenger synchronizing the central to peripheral clocks, hence playing a key role in biological processes and the circadian timing system. Circadian misalignment has been associated with ill-health and so nonphysiological glucocorticoid treatment could explain the increased mortality rate, poor quality of life and metabolic complications in patients suffering from adrenal insufficiency. Attempts at replacing cortisol in a physiological manner have shown significant progress in the past decade with the development of modified-release formulations of hydrocortisone (Chronocort® and Plenadren®) and continuous subcutaneous hydrocortisone infusions. Initial studies investigating the use of these replacement regimens are promising, demonstrating both clinical and biochemical improvement. Larger studies are needed to determine whether this novel approach enhances long-term outcomes in both children and adults with cortisol deficiency. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel. PMID:26683495

  7. Reaction induced fracturing during replacement processes

    NASA Astrophysics Data System (ADS)

    Jamtveit, Bjørn; Putnis, Christine V.; Malthe-Sørenssen, Anders

    2009-01-01

    Replacement processes are common transformation mechanisms in minerals and rocks at a variety of conditions and scales. The underlying mechanisms are, in general, poorly understood, but both mechanical and chemical processes are thought to be important. Replacement of leucite (KAlSi2O6) by analcime (NaAlSi2O6 .H2O) is common in silica-poor igneous rocks. A 10% increase in volume is associated with the replacement process, and this generates stresses that eventually cause fracturing of the reacting leucite. Experimentally reacted leucite samples display characteristic fracturing patterns that include both spalling of concentric ‘onion-skin’-like layers near the reacting interface and the formation of cross-cutting, often hierarchically arranged, sets of fractures that divide the remaining leucite into progressively smaller domains. These structures may explain the ‘patchy’ alteration patterns observed in natural leucite samples and similar, so-called, mesh-textures associated with the serpentinization of olivine grains during hydration of mafic or ultramafic rocks. They are also strikingly similar to larger scale patterns formed during spheroidal weathering processes. A simple discrete element model illustrates the mechanics that control the formation of such systems, and shows how these replacement processes may be accelerated due to the generation of new reactive surface area by hierarchical fracturing processes.

  8. 48 CFR 8.715 - Replacement commodities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Replacement commodities. 8.715 Section 8.715 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition From Nonprofit Agencies Employing People...

  9. Aggression Replacement Training and Childhood Trauma

    ERIC Educational Resources Information Center

    Amendola, A. Mark; Oliver, Robert W.

    2013-01-01

    Aggression Replacement Training (ART) was developed by the late Arnold Goldstein of Syracuse University to teach positive alternatives to children and youth with emotional and behavioral problems (Glick & Gibbs, 2011; Goldstein, Glick, & Gibbs, 1998). ART provides cognitive, affective, and behavioral interventions to build competence in…

  10. Probability Issues in without Replacement Sampling

    ERIC Educational Resources Information Center

    Joarder, A. H.; Al-Sabah, W. S.

    2007-01-01

    Sampling without replacement is an important aspect in teaching conditional probabilities in elementary statistics courses. Different methods proposed in different texts for calculating probabilities of events in this context are reviewed and their relative merits and limitations in applications are pinpointed. An alternative representation of…

  11. SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

    EPA Science Inventory

    The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.

    Didecyldimethylammonium chloride [DDAC] was...

  12. Mineral replacement front propagation in deformed rocks

    NASA Astrophysics Data System (ADS)

    Beaudoin, Nicolas; Koehn, Daniel; Kelka, Ulrich

    2015-04-01

    Fluid migrations are a major agent of contaminant transport leading to mineral replacement in rocks, impacting their properties as porosity, permeability, and rheology. Understanding the physical and chemical mechanisms that govern mineralogical replacement during and after deformation is required to better understand complex interplays between fluid and rocks that are involved in faulting, seismic cycle, and resource distribution in the upper crust. Dolomitization process related to hydrothermal fluid flow is one of the most studied and debated replacement processes in earth sciences. Dolomitization of limestone is of economic importance as well, as it stands as unconventional oil reservoirs and is systematically observed in Mississippian-Valley Type ore deposit. Despite recent breakthrough about dolomitization processes at large-scale, the small-scale propagation of the reaction front remains unclear. It is poorly documented in the occurrence of stylolites and fractures in the medium while pressure-solution and fracture network development are the most efficient deformation accomodation mechanism in limestone from early compaction to layer-parallel shortening. Thus, the impact of such network on geometry of replaced bodies and on replacement front propagation deserves specific attention. This contribution illustrates the role of fracture and stylolites on the propagation of a reaction front. In a 2 dimensional numerical model we simulate the dolomitization front propagation in a heterogeneous porous medium. The propagation of the reaction front is governed by the competition between advection and diffusion processes, and takes into account reaction rates, disorder in the location of the potential replacement seeds, and permeability heterogeneities. We add stylolites and fractures that can act as barriers or drains to fluid flow according to their orientation and mineralogical content, which can or cannot react with the contaminant. The patterns produced from

  13. Coronary Ostial Stenosis after Aortic Valve Replacement

    PubMed Central

    Ziakas, Antonios G.; Economou, Fotios I.; Charokopos, Nicholas A.; Pitsis, Antonios A.; Parharidou, Despina G.; Papadopoulos, Thomas I.; Parharidis, Georgios E.

    2010-01-01

    Coronary ostial stenosis is a rare but potentially serious sequela after aortic valve replacement. It occurs in the left main or right coronary artery after 1% to 5% of aortic valve replacement procedures. The clinical symptoms are usually severe and may appear from 1 to 6 months postoperatively. Although the typical treatment is coronary artery bypass grafting, patients have been successfully treated by means of percutaneous coronary intervention. Herein, we present the cases of 2 patients in whom coronary ostial stenosis developed after aortic valve replacement. In the 1st case, a 72-year-old man underwent aortic valve replacement and bypass grafting of the saphenous vein to the left anterior descending coronary artery. Six months later, he experienced a non-ST-segment-elevation myocardial infarction. Coronary angiography revealed a critical stenosis of the right coronary artery ostium. In the 2nd case, a 78-year-old woman underwent aortic valve replacement and grafting of the saphenous vein to an occluded right coronary artery. Four months later, she experienced unstable angina. Coronary angiography showed a critical left main coronary artery ostial stenosis and occlusion of the right coronary artery venous graft. In each patient, we performed percutaneous coronary intervention and deployed a drug-eluting stent. Both patients were asymptomatic on 6-to 12-month follow-up. We attribute the coronary ostial stenosis to the selective ostial administration of cardioplegic solution during surgery. We conclude that retrograde administration of cardioplegic solution through the coronary sinus may reduce the incidence of postoperative coronary ostial stenosis, and that stenting may be an efficient treatment option. PMID:20844624

  14. Influence of Total Knee Arthroplasty on Gait Mechanics of the Replaced and Non-Replaced Limb During Stair Negotiation.

    PubMed

    Standifird, Tyler W; Saxton, Arnold M; Coe, Dawn P; Cates, Harold E; Reinbolt, Jeffrey A; Zhang, Songning

    2016-01-01

    This study compared biomechanics during stair ascent in replaced and non-replaced limbs of total knee arthroplasty (TKA) patients with control limbs of healthy participants. Thirteen TKA patients and fifteen controls performed stair ascent. Replaced and non-replaced knees of TKA patients were less flexed at contact compared to controls. The loading response peak knee extension moment was greater in control and non-replaced knees compared with replaced. The push-off peak knee abduction moment was elevated in replaced limbs compared to controls. Loading and push-off peak hip abduction moments were greater in replaced limbs compared to controls. The push-off peak hip abduction moment was greater in non-replaced limbs compared to controls. Future rehabilitation protocols should consider the replaced knee and also the non-replaced knee and surrounding joints. PMID:26231075

  15. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in FPMR 41 CFR 101-38.9 and DOE-PMR 41 CFR 109-38.9. (b) The... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Replacement of...

  16. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in 41 CFR 102-34.270 and 109-38.402. (b) The Heads of Contracting... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Replacement of...

  17. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in FPMR 41 CFR 101-38.9 and DOE-PMR 41 CFR 109-38.9. (b) The... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Replacement of...

  18. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in FPMR 41 CFR 101-38.9 and DOE-PMR 41 CFR 109-38.9. (b) The... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Replacement of...

  19. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with the replacement standards prescribed in 41 CFR 102-34.270 and 109-38.402. (b) The Heads of Contracting... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Replacement of...

  20. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement...

  1. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement...

  2. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement...

  3. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement...

  4. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement...

  5. Two-level total lumbar disc replacement

    PubMed Central

    Bakaloudis, Georgios; Lolli, Francesco; Vommaro, Francesco; Parisini, Patrizio

    2009-01-01

    Total lumbar disc replacement (TDR) has been widely used as a treatment option for 2-level symptomatic degenerative disc disease. However, recent studies have presented conflicting results and some authors concluded that outcome deteriorated when disc replacement was performed bisegmentally, with an increase of complications for bisegmental replacements in comparison with monosegmental disc arthroplasty. The goal of the present retrospective study is to investigate results in a group of patients who have received bisegmental TDR with SB Charitè III artificial disc for degenerative disc disease with a minimum follow-up of 3 years, and to compare the results of 2-level disc replacement versus 1-level patients treated with the same prosthesis. A total of 32 patients had at least 3-years follow-up and were reviewed. The average age of the patients was 38.5 years. There were 11 males and 21 females. About 16 patients received 2-level TDR (SB Charitè III) and 16 received 1-level TDR (SB Charitè III). Both radiographic and functional outcome analysis, including patient’s satisfaction, was performed. There were no signs of degenerative changes of the adjacent segments in any case of the 2- or 1-level TDR. There was no statistically significant difference between 2- and 1-level TDR both at 12 months and at 3-years follow-up on functional outcome scores. There was a statistically insignificant difference concerning the patients satisfaction between 1- and 2-level surgeries at the last follow-up (P = 0.46). In the 2-level TDR patients, there were 5 minor complications (31.25%), whereas major complications occurred in 4 more patients (25%) and required a new surgery in 2 cases (12.5%). In the 1-level cases there were 2 minor complications (12.5%) and 2 major complications (12.5%) and a new revision surgery was required in 1 patient (6.25%). In conclusion, the use of 2-level disc replacement at last follow-up presented a higher incidence of complications than in cases

  6. Successful Bridge to Orthotopic Cardiac Transplantation with Implantation of a HeartWare HVAD in Management of Systemic Right Ventricular Failure in a Patient with Transposition of the Great Arteries and Previous Atrial Switch Procedure.

    PubMed

    Stokes, Michael B; Saxena, Pankaj; McGiffin, David C; Marasco, Silvana; Leet, Angeline S; Bergin, Peter

    2016-05-01

    A clinical case is described of a patient with a history of dextro-transposition of the great arteries (d-TGA) and prior atrial switch procedure who developed significant pulmonary hypertension whilst awaiting orthotopic cardiac transplantation. The increase in his pulmonary pressures necessitated de-listing for cardiac transplantation. A strategy of ventricular assist device (VAD) placement was then employed which provided improvement in his systemic cardiac output with left atrial off-loading to provide pulmonary vascular remodelling and consequently reduction in pulmonary vascular resistance (PVR). He was supported for a period of 408 days prior to successful orthotopic cardiac transplantation. A small number of cases with this abnormality undergoing VAD implantation have been described. Mechanical circulatory support has an important role in some patients with congenital heart disease. PMID:26712611

  7. Replacements For Ozone-Depleting Foaming Agents

    NASA Technical Reports Server (NTRS)

    Blevins, Elana; Sharpe, Jon B.

    1995-01-01

    Fluorinated ethers used in place of chlorofluorocarbons and hydrochlorofluorocarbons. Replacement necessary because CFC's and HCFC's found to contribute to depletion of ozone from upper atmosphere, and manufacture and use of them by law phased out in near future. Two fluorinated ethers do not have ozone-depletion potential and used in existing foam-producing equipment, designed to handle liquid blowing agents soluble in chemical ingredients that mixed to make foam. Any polyurethane-based foams and several cellular plastics blown with these fluorinated ethers used in processes as diverse as small batch pours, large sprays, or double-band lamination to make insulation for private homes, commercial buildings, shipping containers, and storage tanks. Fluorinated ethers proved useful as replacements for CFC refrigerants and solvents.

  8. Mitochondrial replacement therapy in reproductive medicine.

    PubMed

    Wolf, Don P; Mitalipov, Nargiz; Mitalipov, Shoukhrat

    2015-02-01

    Mitochondrial dysfunction is implicated in disease and age-related infertility. Mitochondrial replacement therapies (MRT) in oocytes or zygotes, such as pronuclear (PNT), spindle (ST), or polar body (PBT) transfer, could prevent second-generation transmission of mitochondrial DNA (mtDNA) defects. PNT, associated with high levels of mtDNA carryover in mice but low levels in human embryos, carries ethical issues secondary to donor embryo destruction. ST, developed in primates, supports normal development to adults and low mtDNA carryover. PBT in mice, coupled with PN or ST, may increase the yield of reconstructed embryos with low mtDNA carryover. MRT also offers replacement of the deficient cytoplasm in oocytes from older patients, with the expectation of high pregnancy rates following in vitro fertilization. PMID:25573721

  9. Enzyme replacement in Tay-Sachs disease.

    PubMed

    von Specht, B U; Geiger, B; Arnon, R; Passwell, J; Keren, G; Goldman, B; Padeh, B

    1979-06-01

    Enzyme replacement therapy was attempted with two Tay-Sachs-diseased individuals--a 14-month-old child and a 7-week-old infant. Treatment consisted of repeated weekly intrathecal injections of pure hexosaminidase A. Injection of this enzyme resulted in almost complete disappearance of GM2 from the serum, but did not bring about dissolution of the GM2 membranous cytoplasmic bodies in the brain, as detected by electronmicroscopy. Both patients tolerated the treatment without apparent clinical complications, but no clear-cut improvement was noted as a result of prolonged injections of hexosaminidase A. Since this treatment was initiated in both an advanced stage and a very early stage of the disease, we conclude that enzyme replacement treatment by this route is not beneficial for patients with Tay-Sachs disease. PMID:572006

  10. Parameters for novel incus replacement prostheses.

    PubMed

    Kaftan, Holger; Böhme, Andrea; Martin, Heiner

    2016-09-01

    Prostheses replacing the incus in its normal position and equipped with two joints might transfer sound as effectively as the intact ossicular chain and allow adjustment to quasi-static pressure changes. A prerequisite for prostheses development is the access to dimensions and distances of the ossicular chain which are necessary to conceptualize shape and size. Fifteen cadaveric human temporal bone specimens were investigated by means of micro-CT followed by 3D analysis. Each specimen was scanned three times: after removal of incus, after additional removal of the malleus head, and after approaching the umbo to the promontory. Artificial umbo medialization as a surrogate for quasi-static pressure changes leads to relevant variations in the distance between the upper part of the malleus and the stapes. Prostheses replacing the incus in its normal position should be equipped with a sliding ball joint or similar construction to allow adjustment to quasi-static pressure changes. PMID:26538426

  11. Technical evaluation process for specifying replacement items

    SciTech Connect

    Craig, W.E. ); Mulford, T.J. )

    1989-01-01

    As nuclear power plants continue in the transition to a strictly operating and maintenance mode, the engineering involvement required to specify and procure replacement parts and components continues to increase. The evaluation process for a replacement item has one simple goal: to specify an effective set of technical and quality requirements that will result in the procurement of an item meeting the plant design basis. The evaluation process is depicted in a simplified block diagram showing the elements of engineering evaluation from a functional perspective. These elements are the following: (1) need for a technical evaluation; (2) components and part classification; (3) failure mode and effect analysis (FMEA); (4) critical characteristics for design determination; (5) like-for-like or alternate item evaluation; and (6) technical and quality requirements determination.

  12. Hip replacement by a minimal anterior approach.

    PubMed

    Paillard, P

    2007-08-01

    The mini-incision anterior approach in total hip replacement is not new, but uses a shorter incision than the traditional Hueter approach, typically only 6-8 cm in length. Despite its size, the single anterior incision allows good exposure. It is very atraumatic, preserves muscles and tendons, and allows the patient early mobilisation and fast postoperative recovery. Although, a special table (e.g., a Judet table) and specific tools (e.g., a curved reamer) are needed to perform hip replacement via the mini-anterior approach, any kind of hip prosthesis (cemented or uncemented) can be implanted. As there is a significant learning curve in mastering the mini-incision anterior approach, surgeons are advised to start with a longer incision and then to decrease its length with increasing experience. PMID:17657491

  13. Hormone replacement therapy for the adolescent patient.

    PubMed

    DiVasta, Amy D; Gordon, Catherine M

    2008-01-01

    Pubertal induction and hormone replacement therapy (HRT) during adolescence are conducted with the aim of closely mirroring the pubertal changes that occur in children with a normal hypothalamic-pituitary-ovarian axis. The challenge for the clinician is to determine the most appropriate form, dosing, and duration of replacement therapy to achieve that goal in an individual patient. While the optimal regimen remains unclear and data in adolescents are limited, this review presents the evidence available to clinicians as they care for adolescent girls and young women. Both the goals and phases of HRT are reviewed, and commonly used medication regimens are presented. Both the benefits and risks associated with various methods of HRT are also discussed, as are special issues of concern regarding adolescent HRT, including eating disorders and bone health. PMID:18574226

  14. Tissue engineering: an option for esophageal replacement?

    PubMed

    Zani, Augusto; Pierro, Agostino; Elvassore, Nicola; De Coppi, Paolo

    2009-02-01

    Esophageal replacement is required in several pediatric surgical conditions, like long-gap esophageal atresia. Although several techniques have been described to bridge the gap, all of them could be followed by postoperative complications. Esophageal tissue engineering could represent a valid alternative thanks to the recent advances in biomaterial science and cellular biology. Numerous attempts to shape a new esophagus in vitro have been described in the last decade. Herein, we review the main studies on the experimental use of nonabsorbable and absorbable materials as well as the development of cellularized patches. Furthermore, we describe the future perspectives of esophageal tissue engineering characterized by the use of stem cells seeded on new biopolymers. This opens to the construction of a functional allograft that could allow an anatomical replacement that grows with the children and does not severely impair their anatomy. PMID:19103424

  15. The Anterior Approach for Total Hip Replacement.

    PubMed

    Hochfelder, Jason P; Davidovitch, Roy I

    2016-03-01

    The anterior approach for total hip replacements has recently gained popularity. Some authors report faster recoveries and decreased dislocation rated with no increased risk of complications. However others claim no difference in outcomes when compared to other approaches yet an increase in complication rates. This paper provides a brief history of the approach, discusses various indications and contraindications, preoperative considerations, surgical techniques, and postoperative protocols. PMID:26977549

  16. Biosurfactants: a sustainable replacement for chemical surfactants?

    PubMed

    Marchant, Roger; Banat, Ibrahim M

    2012-09-01

    Glycolipid biosurfactants produced by bacteria and yeasts provide significant opportunities to replace chemical surfactants with sustainable biologically produced alternatives in bulk commercial products such as laundry detergents and surface cleaners. Sophorolipids are already available in sufficient yield to make their use feasible while rhamnolipids and mannosylerythritol lipids require further development. The ability to tailor the biosurfactant produced to the specific needs of the product formulation will be an important future step. PMID:22618240

  17. Hip Replacement - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Portuguese (português) Russian (Русский) Somali (af Soomaali) Spanish (español) Tagalog ( ... 한국어 (Korean) Bilingual PDF Health Information Translations Portuguese (português) Total Hip Replacement Substituição total de quadril - português ( ...

  18. Knee Replacement - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Portuguese (português) Russian (Русский) Somali (af Soomaali) Spanish (español) Tagalog ( ... 한국어 (Korean) Bilingual PDF Health Information Translations Portuguese (português) Total Knee Replacement Substituição total do joelho - português ( ...

  19. Total Hip Joint Replacement Biotelemetry System

    NASA Technical Reports Server (NTRS)

    Boreham, J. F.; Postal, R. B.; Luntz, R. A.

    1981-01-01

    The development of a biotelemetry system that is hermetically sealed within a total hip replacement implant is reported. The telemetry system transmits six channels of stress data to reconstruct the major forces acting on the neck of the prosthesis and uses an induction power coupling technique to eliminate the need for internal batteries. The activities associated with the telemetry microminiaturization, data recovery console, hardware fabrications, power induction systems, electrical and mechanical testing and hermetic sealing test results are discussed.

  20. Early results of the Acclaim elbow replacement.

    PubMed

    Bassi, R S; Simmons, D; Ali, F; Nuttall, D; Birch, A; Trail, I A; Stanley, J K

    2007-04-01

    The Acclaim total elbow replacement is a modular system which allows implantation in both unlinked and linked modes. The results of the use of this implant in primary total elbow replacement in 36 patients, operated on between July 2000 and August 2002, are presented at a mean follow-up of 36 months (24 to 49). Only one patient did not have good relief of pain, but all had improved movement and function. No implant showed clinical or radiological loosening, although one had a lucent area in three of seven humeral zones. The short-term results of the Acclaim total elbow replacement are encouraging. However, 11 patients (30.5%) suffered an intra-operative fracture of the humeral condyle. This did not affect the outcome, or the requirement for further surgery, except in one case where the fracture failed to unite. This problem has hopefully been addressed by redesigning the humeral resection guide. Other complications included three cases of ulnar neuropathy (8.3%) and one of deep infection (2.8%). PMID:17463117