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Sample records for stages i-iii crc

  1. Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for I-III stage CRC.

    Science.gov (United States)

    Peng, Hong-Xin; Yang, Lin; He, Bang-Shun; Pan, Yu-Qin; Ying, Hou-Qun; Sun, Hui-Ling; Lin, Kang; Hu, Xiu-Xiu; Xu, Tao; Wang, Shu-Kui

    2017-09-01

    Inflammation plays an important role in the development and progression of CRC. The members of inflammatory biomarkers, preoperative NLR and PLR, have been proved by numerous studies to be promising prognostic biomarkers for CRC. However, the diagnostic value of the two biomarkers in CRC remains unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and CEA. Five hundred and fifty-nine patients with I-III stage CRC undergoing surgical resection and 559 gender- and age-matched healthy controls were enrolled in this retrospective study. NLR and PLR were calculated from preoperative peripheral blood cell count detected using white blood cell five classification by Sysmex XT-1800i Automated Hematology System and serum CEA were measured by electrochemiluminescence by ELECSYS 2010. The diagnostic performance of NLR, PLR and CEA for CRC was evaluated by ROC curve. Levels of NLR and PLR in the cases were significantly higher than them in the healthy controls. ROC curves comparison analyses showed that the diagnostic efficacy of NLR (AUC=.755, 95%CI=.728-.780) alone for CRC was significantly higher than PLR (AUC=.723, 95%CI=.696-.749, P=.037) and CEA (AUC=.690, 95%CI=.662-.717, P=.002) alone. In addition, the diagnostic efficacy of the combination of NLR, PLR and CEA(AUC=.831, 95%CI=.807-.852)for CRC was not only significantly higher than NLR alone but also higher than any combinations of the two of these three biomarkers (PCRC diagnostic biomarker, even for early stage CRC, and the combination of NLR, PLR and CEA could significantly improve the diagnostic efficacy. © 2016 Wiley Periodicals, Inc.

  2. Stage I/II endometrial carcinomas: preoperative radiotherapy: results

    International Nuclear Information System (INIS)

    Maingon, P.; Belichard, C.; Horiot, J.C.; Barillot, I.; Fraisse, J.; Collin, F.

    1996-01-01

    The AIM of this retrospective study is to analyse the indications and the results of treatment of endometrial carcinomas by preoperative radiotherapy. MATERIAL: From 1976 to 1995, 183 patients FIGO stage I or II were treated by preoperative radiotherapy consisting in 95 cases of external radiotherapy (XRT) and brachytherapy (BT) followed by surgery (S) and, in 88 cases of BT alone before surgery, XRT was indicated in cases of grade 2 or 3 and/or cervical involvement. METHODS: XRT was delivered with a 4-fields technique to 40 Gy in 20 fractions with a medial shielding at 30 Gy. BT was done with low dose rate Cs137 and Fletcher-Suit-Delclos applicators with two intra-uterine tubes and vaginal ovoieds. Complications were scored using the French-Italian syllabus. RESULTS: Five-year actuarial survival rates per stage are: Ia=91%, Ib=83%, II=71%, and per grade: G1=80%, G2=79%, G3=90%. Failures were pelvic in 5/183 (2.7%), vaginal in 4 cases (2%) and nodal in 2 cases (1%). Twelve patients developed metastases (6.5%). Complications were analysed during the radiotherapy, after the surgery and with unlimited follow-up. After BT/S, 12 grade 1, 1 grade 2 and 1 grade 3 complications were observed. In the group of patients treated by RT/BT/S, 22 grade 1, 11 grade 2, 4 grade 3 occurred. There is no statistical correlation between complications and parameters of treatment (XRT, hwt, HWT, reference dose to the bladder and rectum, dose rate of brachytherapy). SUMMARY: Preoperative irradiation is an effective and safe treatment of high risk stage I/II endometrial carcinomas. Results seem independent of the pathology grade

  3. The relation between lymph node status and survival in Stage I-III colon cancer

    DEFF Research Database (Denmark)

    Lykke, J.; Roikjær, Ole; Jess, P.

    2013-01-01

    Aim: This study involved a large nationwide Danish cohort to evaluate the hypothesis that a high lymph node harvest has a positive effect on survival in curative resected Stage I-III colon cancer and a low lymph node ratio has a positive effect on survival in Stage III colon cancer. Method......: Analysis of overall survival was conducted using a nationwide Danish cohort of patients treated with curative resection of Stage I-III colon cancer. All 8901 patients in Denmark diagnosed with adenocarcinoma of the colon and treated with curative resection in the period 2003-2008 were identified from...... independent prognostic factors in multivariate analysis. Conclusion: High lymph node count was associated with improved overall survival in colon cancer. Lymph node ratio was superior to N-stage in differentiating overall survival in Stage III colon cancer. Stage migration was observed....

  4. Radiotherapy for stage I-II non-small cell lung cancer

    International Nuclear Information System (INIS)

    Okamoto, Yoshiaki; Murakami, Masao; Mizowaki, Takashi; Nakajima, Toshifumi; Kuroda, Yasumasa

    1999-01-01

    Surgery has been regarded as the standard treatment for patients with non-small cell lung cancer in the early stage, while radiotherapy has become an effective alternative for medically inoperable patients and those who refuse surgery. We reviewed the records of 31 patients with stage I-II non-small cell lung cancer treated by radiotherapy between 1980 and 1997. There were 15 patients in stage I and 16 in stage II. The variables analyzed for influence on cause-specific survival and loco-regional control were: age, performance status, clinical stage, tumor size, tumor site, radiation field, radiation dose, and combination with chemotherapy. The overall and cause-specific 1-, 2-, 3-, and 5-years survival rates were 71% and 77%; 63% and 73%; 34% and 48%; and 17% and 32%, respectively. Five-year survival rate for patients with peripheral tumor in the lung was 72%, with 70% loco-regional control, while the 5-year survival rate of patients whose tumor originated in the central region was 20%, with 25% loco-regional control. These differences had marginal significance on univariate analysis (P=0.07), but only tumor site (central vs peripheral) showed marginal significant influence on cause-specific survival (P=0.08) and loco-regional control (P=0.07) on multivariate analysis. There were no fatal complications, including radiation-induced myelopathy. The present series showed satisfactory results with definitive radiotherapy for patients with medically inoperable stage I-II non-small cell lung cancer, with results similar to those in recent reports of radiotherapy. The only significant variable was that patients with peripheral tumors had a better prognosis than patients with central tumors. (author)

  5. Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

    Science.gov (United States)

    Swords, Douglas S; Mulvihill, Sean J; Skarda, David E; Finlayson, Samuel R G; Stoddard, Gregory J; Ott, Mark J; Firpo, Matthew A; Scaife, Courtney L

    2017-07-11

    To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

  6. Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert eMeier

    2015-04-01

    Full Text Available Abstract: Stereotactic body radiotherapy (SBRT is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I dose escalation should yield improved rates of cancer control; (II the unique radiobiology of prostate cancer favors hypofractionation and (III the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity modulated radiotherapy (IMRT. Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife. Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low dose rate (LDR brachytherapy. Patient-reported quality of life (QOL outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After five years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer.

  7. Stage I-II squamous cell carcinoma of the oral cavity treated by iridium-192

    International Nuclear Information System (INIS)

    Piedbois, P.; Mazeron, J.J.; Haddad, E.; Coste, A.; Martin, M.; Levy, C.; Raynal, M.; Pavlovitch, J.M.; Peynegre, R.; Perquin, B.; Bourgeois, J.P. le

    1991-01-01

    This is a retrospective analysis of 233 evaluable patients with stage I-II squamous cell carcinoma of the oral cavity treated by definitive brachytherapy. Minimum follow-up is 3 years. Treatment of the neck was chosen by a multidisciplinary team, according to age, medical status and availability for follow-up. One hundred and ten patients (47 percent) underwent elective neck dissection (END), 28 (25 percent) had positive nodes and received neck irradiation post-operatively. One hundred and twenty-three patients (53 percent) were regularly followed up only, with therapeutic neck dissection (TND) reserved for cases of node relapses. In the END group, there were 19 neck relapses (17 percent): 12/60 (20 percent) in patients with mobile tongue carcinoma and 7/50 (14 percent) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 13-21 (62 percent) cases. Ten-year survival is 37 percent for the END-group and 31 percent for the TND group. Tumour stage and infiltration into underlying tissues increased the probability of neck relapse and death. Furthermore, a multivariate analysis showed that patients treated in the TND group had a higher probability of death than patients treated in the END group (p<0.04). (author). 30 refs.; 2 figs.; 7 tabs

  8. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    Energy Technology Data Exchange (ETDEWEB)

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Rose, Brent S. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Wu, John; Noticewala, Sonal [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T. [Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Department of Family and Preventive Medicine, Biostatistics and Bioinformatics, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  9. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    International Nuclear Information System (INIS)

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D.; Rose, Brent S.; Wu, John; Noticewala, Sonal; McHale, Michael T.; Yashar, Catheryn M.; Vaida, Florin; Mell, Loren K.

    2014-01-01

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification

  10. Breast-conserving therapy (BCT) in stage I-II synchronous bilateral breast cancer (SBBC)

    Energy Technology Data Exchange (ETDEWEB)

    Gollamudi, Smitha V; Gelman, Rebecca S; Peiro, Gloria; Schneider, Lindsey; Connolly, James L; Schnitt, Stuart; Silver, Barbara; Harris, Jay R

    1995-07-01

    PURPOSE: To determine whether patients with early-stage SBBC can be safely and effectively treated with bilateral BCT. MATERIALS and METHODS: We retrospectively reviewed records of 26 patients with clinical Stage I-II SBBC treated between 1968-1989 with bilateral BCT. SBBC was defined as tumors diagnosed no more than one month apart, with both sides demonstrating invasive cancer. Maximum (max) clinical stage was based on the more advanced breast tumor. Median age at diagnosis was 56 years (range, 32-85 years); menopausal status was 6 pre-, 16 post-, 3 peri-, and 1 unknown at diagnosis. Median follow-up for surviving pts is 95 months (range, 68-157). Outcome was compared to 1325 pts with unilateral Stage I or II breast cancer, within the same age range, treated during the same time period. There were no significant differences in median age, median total dose, tumor size, estrogen receptor (ER) status, pathologic nodal status, and use of systemic therapy between the study population and the comparison group. Local recurrence (LR) was evaluated as true recurrence (TR, i.e., in the original tumor bed), marginal miss (MM, at the edge of the boost field), or elsewhere (E). Median total dose to the primary was 6100 cGy (range, 5000-7000). Pathology was available for review in 19 cases. Cytology (nuclear and cytoplasmic features) was similar in (7(19)) evaluable cases, and architecture (growth pattern, ie, papillary, solid) was similar in (5(19)) cases. The presence of either cytologic or architectural similarity was noted in(9(19)) cases. 7 of 19 pts who had axillary lymph node evaluation on at least one side had pathological confirmation of lymph node metastasis. Stage was the same in both breasts in 13 cases (10 Stage I, 3 Stage II); ER status data was complete in 11 pts, and the same in both primaries in 9 cases. Cosmetic results and complications after BCT were scored. Statistical significance was evaluated by use of the Fisher exact test. RESULTS: The 5-yr actuarial

  11. Systems Support Mapping in Guiding Self-Management in Stage I-III Colorectal Cancer Survivors

    Science.gov (United States)

    2018-04-26

    Cancer Survivor; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8

  12. Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer

    Science.gov (United States)

    2018-04-17

    Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage I Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma; Uterine Corpus Sarcoma

  13. Treatment outcome, body image, and sexual functioning after orchiectomy and radiotherapy for Stage I-II testicular seminoma

    International Nuclear Information System (INIS)

    Incrocci, Luca; Hop, Wim C.J.; Wijnmaalen, Arendjan; Slob, A. Koos

    2002-01-01

    Purpose: Orchiectomy followed by infradiaphragmatic irradiation is the standard treatment for Stage I-II testicular seminoma in The Netherlands. Because body image and sexual functioning can be affected by treatment, a retrospective study was carried out to assess treatment outcome, body image, and changes in sexuality after orchiectomy and radiotherapy. Methods and Materials: The medical charts of 166 patients with Stage I-II testicular seminoma were reviewed. A questionnaire on body image and current sexual functioning regarding the frequency and quality of erections, sexual activity, significance of sex, and changes in sexuality was sent to 157 patients (at a mean of 51 months after treatment). Results: Seventy-eight percent (n=123, mean age 42 years) completed the questionnaire. During irradiation, almost half of patients experienced nausea and 19% nausea and vomiting. Only 3 patients had disease relapse. After treatment, about 20% reported less interest and pleasure in sex and less sexual activity. Interest in sex, erectile difficulties, and satisfaction with sexual life did not differ from age-matched healthy controls. At the time of the survey, 17% of patients had erectile difficulties, a figure that was significantly higher than before treatment, but which correlated also with age. Twenty percent expressed concerns about fertility, and 52% found their body had changed after treatment. Cancer treatment had negatively influenced sexual life in 32% of the patients. Conclusions: Orchiectomy with radiotherapy is an effective and well-tolerated treatment for Stage I-II testicular seminoma. Treatment-induced changes in body image and concerns about fertility were detected, but the sexual problems encountered did not seem to differ from those of healthy controls, although baseline data are lacking

  14. Impact of low skeletal muscle mass and density on short and long-term outcome after resection of stage I-III colorectal cancer.

    Science.gov (United States)

    van Vugt, Jeroen L A; Coebergh van den Braak, Robert R J; Lalmahomed, Zarina S; Vrijland, Wietske W; Dekker, Jan W T; Zimmerman, David D E; Vles, Wouter J; Coene, Peter-Paul L O; IJzermans, Jan N M

    2018-06-06

    Preoperative low skeletal muscle mass and density are associated with increased postoperative morbidity in patients undergoing curative colorectal cancer (CRC) surgery. However, the long-term effects of low skeletal muscle mass and density remain uncertain. Patients with stage I-III CRC undergoing surgery, enrolled in a prospective observational cohort study, were included. Skeletal muscle mass and density were measured on CT. Patients with high and low skeletal muscle mass and density were compared regarding postoperative complications, disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). In total, 816 patients (53.9% males, median age 70) were included; 50.4% had low skeletal muscle mass and 64.1% low density. The severe postoperative complication rate was significantly higher in patients with low versus high skeletal muscle and density (20.9% versus 13.6%, p = 0.006; 20.0% versus 11.8%, p = 0.003). Low skeletal muscle mass (OR 1.91, p = 0.018) and density (OR 1.87, p = 0.045) were independently associated with severe postoperative complications. Ninety-day mortality was higher in patients with low skeletal muscle mass and density compared with patients with high skeletal muscle mass and density (3.6% versus 1.7%, p = 0.091; 3.4% versus 1.0%, p = 0.038). No differences in DFS were observed. After adjustment for covariates such as age and comorbidity, univariate differences in OS and CSS diminished. Low skeletal muscle mass and density are associated with short-term, but not long-term, outcome in patients undergoing CRC surgery. These findings recommend putting more emphasis on preoperative management of patients at risk for surgical complications, but do not support benefit for long-term outcome. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  15. Postoperative radiotherapy for stage I/II seminoma: results for 212 patients

    International Nuclear Information System (INIS)

    Bauman, Glenn S.; Venkatesan, Varagur M.; Ago, C. Tetteh; Radwan, John S.; Dar, A. Rashid; Winquist, Eric W.

    1998-01-01

    Purpose: A retrospective review of patients with Stage I and II seminoma treated at a regional cancer center was performed to assess the long term efficacy and toxicity associated with post operative radiotherapy. Methods and Materials: Between 1950 and 1995, 212 patients seen at the London Regional Cancer Centre received adjuvant radiotherapy following orchiectomy for Stage I (169) and II (43) seminoma. Median follow-up for the group was 7.5 years. Results: Progression free, cause specific, and overall survival were 95%, 98%, and 95% at 5 years, and 94%, 98%, and 94% at 10 years respectively. An increased risk of failure was noted among patients with bulky Stage II disease. No other prognostic factors for relapse were identified. Late toxicity was uncommon with only 12/212 (6%) developing any late GI toxicity potentially attributable to radiotherapy. The incidence of second malignancies (excluding second testicular tumors) was 6/212 (actuarial:1%, 1%, 6% at 5,10,15 years respectively). There was a trend toward increased acute complications for patients treated with larger volumes of radiation. No prognostic factors associated with increased risk of late toxicity or second malignancy were identified, likely a consequence of the small number of these events. Conclusion: Survival and toxicity were comparable to that reported in the literature. Post-operative radiotherapy remains a safe and efficacious adjuvant treatment for Stage I and early Stage II seminoma

  16. Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older

    International Nuclear Information System (INIS)

    Furuta, Masaya; Hayakawa, Kazushige; Katano, Susumu

    1996-01-01

    Between 1976 and 1992, 32 patients aged 75 and older with stage I-II non-small cell lung cancer (NSCLC) were given definitive radiation therapy. These patients did not undergo surgery because of old age, poor cardiac/pulmonary condition, or refusal to give consent. The mean age was 79 years, and 11 patients were over 80 years old. The histologic type was squamous cell carcinoma in 25 patients and adenocarcinoma in 7. The clinical T and N stage was T1N0 in 4 patients, T2N0 in 9, and T2N0 in 19. The total dose of radiation therapy given to each patient exceeded 60 Gy using 10-MV X-rays. The treatment was completed in all 32 patients without treatment-related complications. The 2- and 5-year overall actuarial survival rates were 40% and 16%, respectively. Eleven intercurrent deaths occurred, including 7 patients who died of heart disease. The 2- and 5-year cause-specific survival rates were 57% and 36%, respectively. None of the patients developed severe pneumonitis requiring hospitalization. All but three patients received radiation therapy on an inpatient basis. The mean duration of the hospital stay for initial treatment was 56 days, and mean ratio to total survival period (mean 739 days) was 8%. Although many elderly patients have concurrent medical complications such as heart disease and chronic pulmonary disease, the present study showed that elderly patients with clinical stage I-II NSCLC can expert a realistic probability of long-term survival with definitive radiation therapy. (author)

  17. Perioperative and postoperative complications of intracavitary radiation for FIGO stage I-III carcinoma of the cervix

    International Nuclear Information System (INIS)

    Jhingran, Anuja; Eifel, Patricia J.

    2000-01-01

    Purpose: To evaluate perioperative and postoperative complications of low-dose-rate (LDR) intracavitary radiation therapy in patients with FIGO Stage I-III carcinoma of the uterine cervix. Methods and Materials: We retrospectively reviewed the medical and radiotherapy records of all patients treated with radiation between 1960 and 1992 at The University of Texas M. D. Anderson Cancer Center for FIGO I-III carcinomas of the cervix. Patients who had had initial hysterectomy or whose treatment did not include intracavitary irradiation were excluded. The final study included 4043 patients who had undergone 7662 intracavitary procedures. Results: Eleven (0.3%) patients had documented or suspected cases of thromboembolism resulting in 4 deaths. Of these 11 patients, 8 had clinical or radiographic evidence of tumor involving pelvic nodes or fixed pelvic wall. The risk of postoperative thromboembolism did not decrease significantly with the routine use of mini-dose heparin prophylaxis (p = 0.3). Other life-threatening perioperative complications included myocardial infarction (1 death in 5 patients), cerebrovascular accident (2 patients), congestive heart failure or atrial fibrillation (3 patients), and halothane liver toxicity (2 deaths in 2 patients). Intraoperative complications included uterine perforation (2.8%) and vaginal laceration (0.3%), which occurred more frequently in patients ≥ 60 years old (p < 0.01). Fourteen percent of patients had a temperature ≥ 101 deg. F during at least one hospital stay. The only correlation between minor intraoperative complications and disease-specific survival was found in patients who had Stage III disease and uterine perforation; survival was significantly (p = 0.01) decreased in these patients. Conclusions: Fatal or life-threatening complications of intracavitary treatment were very rare. Deep venous thrombosis (DVT) and pulmonary embolism (PE) did not occur in otherwise healthy patients with early disease and were rare even

  18. The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

    Directory of Open Access Journals (Sweden)

    Pruijt Hans FM

    2011-05-01

    Full Text Available Abstract Background The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC. In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0 will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs and/or micrometastases (MMs at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0micro+ patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0micro+ and evaluate the benefits from adjuvant chemotherapy in pN0micro+ CC patients. Methods/design EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an ex vivo sentinel lymph node mapping procedure (SLNM following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0micro+ are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS. Discussion The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 micro+ CC patients by reducing disease recurrence by adjuvant chemotherapy. Trial Registration ClinicalTrials.gov: NCT01097265

  19. Treatment results of radiotherapy for medically inoperable stage I/II non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zhang Li; Wang Lvhua; Zhang Hongxing; Chen Dongfu; Xiao Zefen; Wang Mei; Feng Qinfu; Liang Jun; Zhou Zongmei; Ou Guangfei; Lv Jima; Yin Weibo

    2008-01-01

    Objective: To retrospectively analyze treatment results of radiotherapy for medically inoperable stage I/II non-small cell lung cancer. Methods: Between Jan. 2000 and Dec. 2005, fifty-eight such patients were enrolled into the database analysis, including 37 with clinical stage I and 21 with stage II disease. Fifty patients received radiotherapy alone and eight with radiotherapy and chemotherapy. Forty- three patients were treated with 3-D conformal radiotherapy (3D-CRT) and 15 with conventional radiotherapy. Results: The 1-, 2- and 3-year overall survival rates were 85%, 54% and 30%, and the median survival time was 26.2 months for the whole group. The corresponding figures were 88%, 60%, 36% and 30.8 months for cancer-specific survival; 84%, 64%, 31% and 30.8 months for Stage I disease; 81%, 47%, 28% and 18.8 months for Stage II disease; 95%, 57%, 33% and 30.8 months for 3D-CRT group and 53%, 44%, 24% and 15.3 months for conventional radiotherapy group. By logrank test, tumor volume, pneumonitis of Grade II or higher and weight loss more than 5% showed statistically significant impact on overall survival. Tumor volume was the only independent prognostic factor in Cox multivariable regression. Pneumonitis and esophagitis of Grade II or higher were 16% and 2%, respectively. Age and lung function before treatment had a significant relationship with pneumonitis. Failure included the local recurrence (33%) and distant metastasis (21%). There was no difference between the treatment modalities and failure sites. Conclusions: For medically inoperable early stage non-small cell lung cancer patients, tumor volume is the most important prognostic factor for overall survival. The conformal radiotherapy marginally improves the survival. The age and pulmonary function are related to the incidence of treatment induced pneumonitis. (authors)

  20. Preliminary investigation of stereotactic body radiation therapy for medically inoperable stage I/II non-small cell lung cancer

    International Nuclear Information System (INIS)

    Guo Jindong; Lu Changxing; Wang Jiaming; Liu Jun; Li Hongxuan; Wang Changlu; Gao Lanting; Zhao Lei

    2011-01-01

    Objective: To evaluate the therapeutic efficacy and treatment-related toxicity of stereotactic body radiation therapy (SBRT) in patients with medically inoperable stage I/II non-small cell lung cancer (NSCLC). Methods: SBRT was applied to 30 patients, including clinically staged T 1 , T 2 (≤5 cm) or T 3 (chest wall primary tumors only), N 0 , M 0 ,biopsy-confirmed NSCLC. All patients were precluded from lobotomy because of physical condition or comorbidity. No patients developed tumors of any T-stage in the proximal zone. SBRT was performed with the total dose of 50 Gy to 70 Gy in 10 - 11 fractions during 12 - 15 days. prescription line was set onthe edge of the PTV. Results: The follow-up rate was 100%. The number of patients who completed the 1-, and 2-year follow-up were 15, and 10, respectively. All 30 patients completed therapy as planned. The complete response (CR), partial response (PR) and stable disease (SD) rates were 37%, 53% and 3%, respectively. With a median follow-up of 16 months (range, 4-36 months), Kaplan-Meier local control at 2 years was 94%. The 2-year overall survival was 84% and the 2-year cancer specific survival was 90%. Seven patients(23%) developed Grade 2 pneumonitis, no grade > 2 acute or late lung toxicity was observed. No one developed chest wall pain. Conclusions: It is feasible to deliver 50 Gy to 70 Gy of SBRT in 10 - 11 fractions for medically inoperable patients with stage I / II NSCLC. It was associated with low incidence of toxicities and provided sustained local tumor control.The preliminary investigation indicated the cancer specific survival probability of SBRT was high. It is necessary to perform similar investigation in a larger number of patients with long-term follow-up. (authors)

  1. Macrophage markers in serum and tumor have prognostic impact in American Joint Committee on Cancer stage I/II melanoma

    DEFF Research Database (Denmark)

    Jensen, Trine O.; Schmidt, Henrik; Møller, Holger John

    2009-01-01

    PURPOSE: To evaluate the prognostic role of soluble CD163 (sCD163) in serum and macrophage infiltration in primary melanomas from patients with American Joint Committee on Cancer (AJCC) stage I/II melanoma. The scavenger receptor CD163 is associated with anti-inflammatory macrophages...... melanomas from 190 patients were available for immunohistochemical analyzes of CD163(+) and CD68(+) macrophage infiltration. They were estimated semiquantitatively in three different tumor compartments: tumor nests, tumor stroma, and at the invasive front of the tumor. RESULTS: Serum sCD163 treated......, HR = 1.4; 95% CI, 1.1 to 1.8; P = .003). Melanomas with dense CD163(+) macrophage infiltration in tumor stroma and CD68(+) macrophage infiltration at the invasive front were associated with poor overall survival (CD163, HR = 2.7; 95% CI, 0.8 to 9.3; P = .11; and CD68, HR = 2.8; 95% CI, 1.2 to 6.8; P...

  2. The expression of chemokine receptors CXCR3 and CXCR4 in predicting postoperative tumour progression in stages I-II colon cancer: a retrospective study.

    Science.gov (United States)

    Du, Changzheng; Yao, Yunfeng; Xue, Weicheng; Zhu, Wei-Guo; Peng, Yifan; Gu, Jin

    2014-01-01

    The prognostic significance of chemokine receptors in stage I/II colon cancer is unclear. We assessed the prognostic value of chemokine receptor CXCR3 and CXCR4 in stage I/II colon cancer. 145 patients with stage I/II colon cancer who underwent curative surgery alone from 2000 to 2007 were investigated. Chemokine receptor expression was assessed by immunohistochemistry. The associations between CXCR3, CXCR4 and clinicopathological variables were analysed using the χ2 test, and the relationships between chemokine receptors and a 5-year disease-free survival were analysed by univariate and multivariate analyses. The high-expression rates of CXCR3 and CXCR4 were 17.9% (26/145) and 38.6% (56/145), respectively. There were no significant associations between the expressions of CXCR3, CXCR4 and clinicopathological factors including gender, age, tumour location, histological differentiation, pathological stage, lymphovascular invasion and pretreatment serum carcinoembryonic antigen (CEA). The 5-year disease-free survival was not significantly different between low-expression groups and high-expression groups of CXCR3 and CXCR4. Multivariate analysis revealed that serum CEA and a number of retrieved lymph nodes, rather than chemokine receptors, were independent prognosticators. CXCR3 and CXCR4 are not independent prognosticators for stage I/II colon cancer after curative surgery.

  3. Association of time-to-surgery with outcomes in clinical stage I-II pancreatic adenocarcinoma treated with upfront surgery.

    Science.gov (United States)

    Swords, Douglas S; Zhang, Chong; Presson, Angela P; Firpo, Matthew A; Mulvihill, Sean J; Scaife, Courtney L

    2018-04-01

    Time-to-surgery from cancer diagnosis has increased in the United States. We aimed to determine the association between time-to-surgery and oncologic outcomes in patients with resectable pancreatic ductal adenocarcinoma undergoing upfront surgery. The 2004-2012 National Cancer Database was reviewed for patients undergoing curative-intent surgery without neoadjuvant therapy for clinical stage I-II pancreatic ductal adenocarcinoma. A multivariable Cox model with restricted cubic splines was used to define time-to-surgery as short (1-14 days), medium (15-42), and long (43-120). Overall survival was examined using Cox shared frailty models. Secondary outcomes were examined using mixed-effects logistic regression models. Of 16,763 patients, time-to-surgery was short in 34.4%, medium in 51.6%, and long in 14.0%. More short time-to-surgery patients were young, privately insured, healthy, and treated at low-volume hospitals. Adjusted hazards of mortality were lower for medium (hazard ratio 0.94, 95% confidence interval, .90, 0.97) and long time-to-surgery (hazard ratio 0.91, 95% confidence interval, 0.86, 0.96) than short. There were no differences in adjusted odds of node positivity, clinical to pathologic upstaging, being unresectable or stage IV at exploration, and positive margins. Medium time-to-surgery patients had higher adjusted odds (odds ratio 1.11, 95% confidence interval, 1.03, 1.20) of receiving an adequate lymphadenectomy than short. Ninety-day mortality was lower in medium (odds ratio 0.75, 95% confidence interval, 0.65, 0.85) and long time-to-surgery (odds ratio 0.72, 95% confidence interval, 0.60, 0.88) than short. In this observational analysis, short time-to-surgery was associated with slightly shorter OS and higher perioperative mortality. These results may suggest that delays for medical optimization and referral to high volume surgeons are safe. Published by Elsevier Inc.

  4. Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

    Science.gov (United States)

    2017-11-15

    Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

  5. Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation

    International Nuclear Information System (INIS)

    Fuller, Lillian M.; Krasin, Matthew J.; Velasquez, William S.; Allen, Pamela K.; McLaughlin, Peter; Rodriguez, M. Alma; Hagemeister, Fredrick B.; Swan, Forrest; Cabanillas, Fernando; Palmer, Judy L.; Cox, James D.

    1995-01-01

    Purpose: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). Methods and Materials: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or ≥ 40 Gy and (b) relapse patterns. Results: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of ≥ 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. Conclusion: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients

  6. Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

    Science.gov (United States)

    2018-02-01

    Estrogen Receptor Status; HER2 Positive Breast Carcinoma; Progesterone Receptor Status; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  7. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    Science.gov (United States)

    2017-06-14

    Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  8. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    Science.gov (United States)

    2017-08-07

    Anxiety Disorder; Depression; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  9. Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

    Science.gov (United States)

    2017-07-28

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  10. The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer

    Science.gov (United States)

    2018-03-02

    Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

  11. Acupuncture in Reducing Chemotherapy-Induced Peripheral Neuropathy in Participants With Stage I-III Breast Cancer

    Science.gov (United States)

    2018-05-30

    Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Grade 1 Peripheral Motor Neuropathy, CTCAE; Grade 1 Peripheral Sensory Neuropathy, CTCAE; Grade 2 Peripheral Motor Neuropathy, CTCAE; Grade 2 Peripheral Sensory Neuropathy, CTCAE; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

  12. Demographics and Outcomes of Stage I-II Merkel Cell Carcinoma Treated with Mohs Micrographic Surgery Compared with Wide Local Excision in the National Cancer Data Base.

    Science.gov (United States)

    Singh, Babu; Qureshi, Muhammad M; Truong, Minh Tam; Sahni, Debjani

    2018-02-03

    The optimal surgical approach (wide local excision (WLE) vs. Mohs micrographic surgery (MOHS)) for treating Merkel cell carcinoma (MCC) is yet to be determined. To compare survival outcomes in patients with early stage MCC treated with MOHS versus WLE. A retrospective review of all cases in the National Cancer Data Base (NCDB) of MCC of clinical Stage I-II MCC treated with WLE or MOHS was performed. 1,795 cases of Stage I-II MCC were identified who underwent WLE (N=1,685) or MOHS (N=110). There was no difference in residual tumor on surgical margins between the two treatment groups (p=0.588). On multivariate analysis, there was no difference in overall survival between the treatment modalities (adjusted HR 1.02; 95% CI 0.72-1.45, p=0.897). There was no difference in overall survival between the two groups on propensity score matched analysis. Disease specific survival was not reported as this data in not available in the NCDB. MOHS appears to be as effective as WLE in treating early stage MCC. Copyright © 2018. Published by Elsevier Inc.

  13. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    International Nuclear Information System (INIS)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  14. Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Ruella, Marco [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia (United States); Filippi, Andrea Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Bruna, Riccardo [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Di Russo, Anna [Radiation Oncology, Istituto Nazionale Tumori, Milano (Italy); Magni, Michele [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Caracciolo, Daniele [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Passera, Roberto [Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Matteucci, Paola; Di Nicola, Massimo [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Corradini, Paolo [Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Parvis, Guido [Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino (Italy); Gini, Guido; Olivieri, Attilio [Division of Haematology, Ospedali Riuniti, Ancona (Italy); Ladetto, Marco [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Tarella, Corrado, E-mail: corrado.tarella@gmail.com [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Hemato-Oncology Division, European Institute of Oncology, Milano (Italy); Devizzi, Liliana [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy)

    2016-03-15

    Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m{sup 2}, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

  15. Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

    International Nuclear Information System (INIS)

    Ruella, Marco; Filippi, Andrea Riccardo; Bruna, Riccardo; Di Russo, Anna; Magni, Michele; Caracciolo, Daniele; Passera, Roberto; Matteucci, Paola; Di Nicola, Massimo; Corradini, Paolo; Parvis, Guido; Gini, Guido; Olivieri, Attilio; Ladetto, Marco; Ricardi, Umberto; Tarella, Corrado; Devizzi, Liliana

    2016-01-01

    Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m"2, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

  16. Radiotherapy alone for stage I-III low grade follicular lymphoma: long-term outcome and comparison of extended field and total nodal irradiation

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Alexandrow, Nikolaus; Flentje, Michael

    2012-01-01

    To analyze long-term results of radiotherapy alone for stage I-III low grade follicular lymphoma and to compare outcome after extended field irradiation (EFI) and total nodal irradiation (TNI). Between 1982 and 2007, 107 patients were treated with radiotherapy alone for low grade follicular lymphoma at Ann Arbor stage I (n = 50), II (n = 36) and III (n = 21); 48 and 59 patients were treated with EFI and TNI, respectively. The median total dose in the first treatment series of the diaphragmatic side with larger lymphoma burden was 38 Gy (25 Gy – 50 Gy) and after an interval of median 30 days, a total dose of 28 Gy (12.6 Gy – 45 Gy) was given in the second treatment series completing TNI. After a median follow-up of 14 years for living patients, 10-years and 15-years overall survival (OS) were 64% and 50%, respectively. Survival was not significantly different between stages I, II and III. TNI and EFI resulted in 15-years OS of 65% and 34% but patients treated with TNI were younger, had better performance status and higher stage of disease compared to patients treated with EFI. In multivariate analysis, only age at diagnosis (p < 0.001, relative risk [RR] 1.06) and Karnofsky performance status (p = 0.04, RR = 0.96) were significantly correlated with OS. Freedom from progression (FFP) was 58% and 56% after 10-years and 15-years, respectively. Recurrences outside the irradiated volume were significantly reduced after TNI compared to EFI; however, increased rates of in-field recurrences and extra-nodal out-of-field recurrence counterbalanced this effect resulting in no significant difference in FFP between TNI and EFI. In univariate analysis, FFP was significantly improved in stage I compared to stage II but no differences were observed between stages I/II and stage III. In multivariate analysis no patient or treatment parameter was correlated with FFP. Acute toxicity was significantly increased after TNI compared to EFI with a trend to increased late toxicity as

  17. Intensity-modulated radiation therapy followed by GDP chemotherapy for newly diagnosed stage I/II extranodal natural killer/T cell lymphoma, nasal type.

    Science.gov (United States)

    Huang, Yu; Yang, Jianliang; Liu, Peng; Zhou, Shengyu; Gui, Lin; He, Xiaohui; Qin, Yan; Zhang, Changgong; Yang, Sheng; Xing, Puyuan; Sun, Yan; Shi, Yuankai

    2017-09-01

    Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.

  18. A cohort study of metformin exposure and survival in patients with stage I-III colorectal cancer

    OpenAIRE

    BENNETT, KATHLEEN

    2013-01-01

    PUBLISHED Background: Preclinical evidence suggests a beneficial effect of metformin in colorectal cancer. This study aimed to investigate associations between metformin exposure and colorectal cancer–specific survival using population-level data. Methods: Adult patients with stage I–III colorectal cancer diagnosed from 2001 to 2006 were identified from the National Cancer Registry Ireland. Use of metformin and other antidiabetic medications was determined from a linked national prescr...

  19. Lymphography and computed tomography of abdominal nodes in newly diagnosed patients with Hodgkin's disease in clinical stage I-III

    Energy Technology Data Exchange (ETDEWEB)

    Neumann, C.H.

    1986-10-01

    Between 1978 and 1983, 80 patients with Hodgkin's disease (HD) in clinical Stage I-III had computed tomography (CT) of the abdomen and pelvis and lymphography (LAG) prior to staging laparatomy with multiple lymph node biopsies at Stanford University Medical Center. There were 224 biopsied nodal sites. The sensitivity and specificity for CT to determine the status of biopsied paraortic and iliac nodes was .61 and .91 vs. .94 and .90 for LAG. CT appeared of even lower sensitivity (.13) in evaluating splenic hilar, celiac axis and portal nodes. Including all biopsy proven subdiaphragmatic nodal sites, CT's sensitivity to diagnose the presence of subdiaphragmatic adenopathy was .38 vs. .52 in LAG. Assessment of the final pathological stage was more successful by LAG (.61) than by CT (.49). Positive and negative predictive values of both tests indicate higher reliability of LAG results as regards individual intraabdominal nodes (LAG .71, .98 vs. CT .58, .86), the entire subdiaphragmatic nodal area (LAG .79, .77 vs. CT .61, .71) and prediction of final pathological stage. LAG appeared to be the more useful test during initial staging of newly diagnosed and untreated patients with HD. None of the test for itself or in combination can replace laparatomy when exact information is necessary for further clinical decisions.

  20. Long term results of mantle irradiation(MRT) alone in 261 patients with clinical stage I-II supradiaphragmatic Hodgkin's disease

    International Nuclear Information System (INIS)

    Wirth, A.; Byram, D.; Chao, M.; Corry, J.; Davis, S.; Kiffer, J.; Laidlaw, C.; Quong, G.; Ryan, G.; Liew, K.

    1997-01-01

    Purpose: We report our results using MRT for clinical stage I-II HD and assess the value of published prognostic criteria in our study population. Pts and Methods: Between 1969 and 1994, 261 pts were treated with MRT alone for clinical stage I-II supradiaphragmatic HD. Pt characteristics: median age-30; M-54%/F-46%; stage IA-52%, IB-2%, IIA-37%, IIB-8%; histology LP-21%, NS-51%, MC-23%, other 5%; median ESR 18. CT abdomen and LAG were performed in 61% and 60% respectively. No pt had prior staging laparotomy. No pt received infradiaphragmatic RT. Central axis dose was 32 Gy-36 Gy. Univariate analysis was performed for prognostic factors for progression-free (PFS) and overall survival(OS). Outcome was assessed in favourable subsets as defined by: EORTC (v. favourable: CSIA, LP or NS histology, age < 40, female, no bulk, ESR < 50; favourable: CSI-II, age < 50, < 4 sites, no bulky mediastinal mass, ESR < 50 with no B symptoms or ESR < 30 with B symptoms); Princess Margaret Hospital (PMH) (IA-IIA, LP or NS histology, ESR < 40, age < 50, no large mediastinal mass, no E lesion). Results: 261 pts completed RT, with 5% requiring treatment interruption for toxicity. Significant factors (P<0.05) for PFS were stage, performance status, histology, B symptoms, number of sites, ESR and bulk. Significant factors (P<0.05) for OS were age, performance status, histology and B symptoms. (The results of a multivariate analysis will be presented.) Results in our study population using published prognostic criteria (in %): Thirty-six percent progressed following RT: 8% in-field; 24% out of field only (including 10% in the paraaortic/splenic region alone); 4% marginal; Fifty-seven percent of relapsed pts remain progression free after subsequent salvage treatment. Two cases of acute leukaemia, 8 cases of non-Hodgkin's lymphoma and 14 (non-skin) carcinomas occurred, of which 11 were in-field. Seventy pts have died. The cause was: HD 41%; other malignancy 20%; cardiovascular 17%; other 15

  1. The effects of inpatient exercise therapy on the length of hospital stay in stages I-III colon cancer patients: randomized controlled trial.

    Science.gov (United States)

    Ahn, Ki-Yong; Hur, Hyuk; Kim, Dong-Hyun; Min, Jihee; Jeong, Duck Hyoun; Chu, Sang Hui; Lee, Ji Won; Ligibel, Jennifer A; Meyerhardt, Jeffrey A; Jones, Lee W; Jeon, Justin Y; Kim, Nam Kyu

    2013-05-01

    This study aimed to examine the effects of a postsurgical, inpatient exercise program on postoperative recovery in operable colon cancer patients We conducted the randomized controlled trial with two arms: postoperative exercise vs. usual care. Patients with stages I-III colon cancer who underwent colectomy between January and December 2011 from the Colorectal Cancer Clinic, were recruited for the study. Subjects in the intervention group participated in the postoperative inpatient exercise program consisted of twice daily exercise, including stretching, core, balance, and low-intensity resistance exercises. The usual care group was not prescribed a structured exercise program. The primary endpoint was the length of hospital stay. Secondary endpoints were time to flatus, time to first liquid diet, anthropometric measurements, and physical function measurements. A total of 31 (86.1 %) patients completed the trial, with adherence to exercise interventions at 84.5 %. The mean length of hospital stay was 7.82 ± 1.07 days in the exercise group compared with 9.86 ± 2.66 days in usual care (mean difference, 2.03 days; 95 % confidence interval (CI), -3.47 to -0.60 days; p = 0.005) in per-protocol analysis. The mean time to flatus was 52.18 ± 21.55 h in the exercise group compared with 71.86 ± 29.2 h in the usual care group (mean difference, 19.69 h; 95 % CI, -38.33 to -1.04 h; p = 0.036). Low-to-moderate-intensity postsurgical exercise reduces length of hospital stay and improves bowel motility after colectomy procedure in patients with stages I-III colon cancer.

  2. Role of 10-Gy boost radiation after breast-conserving surgery for stage I-II breast cancer with a 5-mm negative margin

    International Nuclear Information System (INIS)

    Notani, Masafumi; Uchida, Nobue; Kitagaki, Hajime

    2007-01-01

    According to the Guidelines for breast-conserving therapy of the Japanese Breast Cancer Society, the surgical margin is ''negative'' when the minimum distance between the tumor edge and the margin of the resected specimen is more than 5 mm. The value of boost radiation for early breast cancer with a 5-mm negative margin remains unclear. A total of 137 patients with stage I-II breast cancer underwent breast-conserving surgery between July 1987 and August 2002. All of the patients had negative margins according to the Japanese guidelines. Their median age was 50 years and the median follow-up period was 62 months. The entire ipsilateral breast was irradiated to a total dose of 50 Gy (25 fractions). Then an additional 10 Gy (5 fractions) was given to 79 patients, using 6- to 12-MeV electrons (boost group), while 58 patients (no-boost group) received no further radiation. Factors influencing local recurrence were evaluated by univariate and multivariate analyses. For the entire population, the 5-year overall survival, cause-specific survival, disease-free survival, and local recurrence rates were 96.0%, 96.8%, 94.2%, and 1.67%, respectively. Boost radiation reduced local recurrence, but the improvement was not significant (P=0.070). Univariate and multivariate analyses failed to detect any factors that were significantly associated with local control. There were no severe complications in either group and there were no differences between the groups in the cosmetic outcome. Boost radiation can be performed for stage I-II breast cancer with negative margins (Japanese guidelines), and showed a tendency to decrease local recurrence. A large randomized controlled study is necessary to establish final conclusions. (author)

  3. Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Matthew W., E-mail: matthew.jackson@ucdenver.edu [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Rusthoven, Chad G.; Jones, Bernard L. [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Kamdar, Manali [Department of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Rabinovitch, Rachel [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States)

    2016-01-01

    Background: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes. Methods and Materials: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed. Results: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010. Conclusion: This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage

  4. Expression of vascular endothelial factor protein in the tumor tissues of patients with Stages I-II ovarian cancer

    Directory of Open Access Journals (Sweden)

    V. L. Karapetyan

    2010-01-01

    Full Text Available To define tumor markers is presently the most interesting and promising direction for the diagnosis of malignancies. The expression of the major angiogenesis factor vascular endothelial growth factor (VEGF in primary tumor tissue was studied in ovarian cancer (OC patients to define the prognostic value of the marker.The study enrolled 48 patients with OC. The immunohistochemical technique was used to examine VEGF expression in the primary tu- mor tissue. The frequency of VEGF expression, which was associated with lower relapse-free survival rates, was found to be high (85.4% in OC patients (p > 0.05.The tumor expression of the angiogenic factor VEGF was shown to provide prognostic information in early-stage ovarian epithelial cancer.

  5. Macrophage Inhibitory Cytokine-1 (MIC-1 as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuning LIU

    2016-04-01

    Full Text Available Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1, member of transforming growth factor-β (TGF-β superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC. Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001 and benign pulmonary disease patients (P<0.001. A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001, female (P=0.03 and T2 (P=0.022. A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%. Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

  6. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Adam J., E-mail: adam_olszewski@brown.edu; Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  7. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    International Nuclear Information System (INIS)

    Olszewski, Adam J.; Desai, Amrita

    2014-01-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas

  8. Comparative effect of 2 packages of pelvic floor muscle training on the clinical course of stage I-III pelvic organ prolapse.

    Science.gov (United States)

    Kashyap, Rashmi; Jain, Vanita; Singh, Amarjeet

    2013-04-01

    To compare the effect of 2 packages of pelvic floor muscle training (PFMT) on the clinical course of pelvic organ prolapse (POP) among women attending a gynecology outpatient department in Chandigarh, India. A randomized controlled trial was conducted between August 8, 2010, and October 31, 2011. Overall, 140 women with stage I-III POP were allocated to a 24-week behavioral therapy intervention. Group A (n=70) received 1-to-1 PFMT and a self-instruction manual (SIM), whereas Group B (n=70) received SIM alone. Symptoms were assessed using the POP symptom scale (POP-ss), visual analog scale (VAS), and pelvic floor impact questionnaire-7 (PFIQ-7) scores. Marked improvements in mean POP-ss, VAS, PFIQ-7 scores were observed in both groups from baseline to week 24. However, significant between-group changes in mean POP-ss scores were observed from baseline to 6 weeks (P<0.001), 18 weeks (P=0.001), and 24 weeks (P=0.002). Significant between-group changes in mean VAS scores were observed at 18 and 24 weeks (P=0.009 and P=0.005). Significant between-group changes in mean PFIQ-7 scores were observed at 6 (P=0.001), 18 (P<0.001), and 24 weeks (P<0.001). Provision of both 1-to-1 PFMT and SIM led to greater improvements in POP symptoms than provision of SIM alone. ctri.nic.in: CTRI/2010/091/001190. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Development of a nomogram combining clinical staging with 18F-FDG PET/CT image features in non-small-cell lung cancer stage I-III

    International Nuclear Information System (INIS)

    Desseroit, Marie-Charlotte; Visvikis, Dimitris; Majdoub, Mohamed; Hatt, Mathieu; Tixier, Florent; Perdrisot, Remy; Cheze Le Rest, Catherine; Guillevin, Remy

    2016-01-01

    Our goal was to develop a nomogram by exploiting intratumour heterogeneity on CT and PET images from routine 18 F-FDG PET/CT acquisitions to identify patients with the poorest prognosis. This retrospective study included 116 patients with NSCLC stage I, II or III and with staging 18 F-FDG PET/CT imaging. Primary tumour volumes were delineated using the FLAB algorithm and 3D Slicer trademark on PET and CT images, respectively. PET and CT heterogeneities were quantified using texture analysis. The reproducibility of the CT features was assessed on a separate test-retest dataset. The stratification power of the PET/CT features was evaluated using the Kaplan-Meier method and the log-rank test. The best standard metric (functional volume) was combined with the least redundant and most prognostic PET/CT heterogeneity features to build the nomogram. PET entropy and CT zone percentage had the highest complementary values with clinical stage and functional volume. The nomogram improved stratification amongst patients with stage II and III disease, allowing identification of patients with the poorest prognosis (clinical stage III, large tumour volume, high PET heterogeneity and low CT heterogeneity). Intratumour heterogeneity quantified using textural features on both CT and PET images from routine staging 18 F-FDG PET/CT acquisitions can be used to create a nomogram with higher stratification power than staging alone. (orig.)

  10. Conservative surgery and radiotherapy for stage I/II breast cancer using lung density correction: 10-year and 15-year results

    International Nuclear Information System (INIS)

    Pierce, Lori J.; Griffith, Kent A.; Hayman, James A.; Douglas, Kathye R.; Lichter, Allen S.

    2005-01-01

    Purpose: Radiotherapy (RT) planning for breast cancer using lung density correction improves dose homogeneity. Its use obviates the need for a medial wedge, thus reducing scatter to the opposite breast. Although lung density correction is used at many centers in planning for early-stage breast cancer, long-term results of local control and survival have not been reported. Since 1984, we have used lung density correction for dose calculations at the University of Michigan. We now present our 10-year and 15-year results. Methods and Materials: The records of 867 patients with Stage I/II breast cancer treated with breast-conserving surgery and RT with or without systemic therapy were reviewed. Tangential fields delivering 45-50 Gy to the whole breast calculated using lung density correction were used. A boost was added in 96.8% of patients for a total median dose of 61.8 Gy. Results: With a median follow-up of 6.6 years (range, 0.2-18.9 years), 5-, 10-, and 15-year actuarial rates of in-breast tumor recurrence as only first failure were 2.2%, 3.6%, and 5.4%, respectively. With surgical salvage, the 15-year cumulative rate of local control was 99.7%. Factors that significantly predicted for increased rate of local recurrence in multivariate analysis were age ≤ 35 years, hazard ratio 4.8 (95% confidence interval [CI], 1.6-13.9) p = 0.004; negative progesterone receptor status, hazard ratio 6.8 (95% CI, 2.3-20.3) p = < 0.001; negative estrogen receptor status, hazard ratio 4.0 (95% CI, 1.5-11.1) p = 0.007; and lack of adjuvant tamoxifen therapy, hazard ratio 7.7 (95% CI, 1.7-33.3) p = 0.008. Relapse-free survival rates at 5, 10, and 15 years were 84.6%, 70.8%, and 55.9%, respectively; breast cancer-specific survival rates were 94.4%, 90.5%, and 86.9%, respectively; and corresponding estimates for overall survival were 89.7%, 75.7%, and 61.3%. Conclusions: Use of lung density correction was associated with high rates of local control, relapse-free survival, breast

  11. Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy

    Directory of Open Access Journals (Sweden)

    Versmessen Harijati

    2012-10-01

    Full Text Available Abstract Background Health-related quality of life (HRQOL assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR and hypofractionated tomotherapy (TT have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy. Methods A total of 121 stage I–II breast cancer patients who had undergone breast conserving surgery (BCS or mastectomy (MA were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle. Results On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms, nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better

  12. Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy

    International Nuclear Information System (INIS)

    Versmessen, Harijati; Vinh-Hung, Vincent; Van Parijs, Hilde; Miedema, Geertje; Voordeckers, Mia; Adriaenssens, Nele; Storme, Guy; De Ridder, Mark

    2012-01-01

    Health-related quality of life (HRQOL) assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR) and hypofractionated tomotherapy (TT) have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy. A total of 121 stage I–II breast cancer patients who had undergone breast conserving surgery (BCS) or mastectomy (MA) were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error) was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle. On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms), nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better long-term recovery from fatigue than CR patients. ANOVA

  13. Automated quantification of proliferation with automated hot-spot selection in phosphohistone H3/MART1 dual-stained stage I/II melanoma.

    Science.gov (United States)

    Nielsen, Patricia Switten; Riber-Hansen, Rikke; Schmidt, Henrik; Steiniche, Torben

    2016-04-09

    Staging of melanoma includes quantification of a proliferation index, i.e., presumed melanocytic mitoses of H&E stains are counted manually in hot spots. Yet, its reproducibility and prognostic impact increases by immunohistochemical dual staining for phosphohistone H3 (PHH3) and MART1, which also may enable fully automated quantification by image analysis. To ensure manageable workloads and repeatable measurements in modern pathology, the study aimed to present an automated quantification of proliferation with automated hot-spot selection in PHH3/MART1-stained melanomas. Formalin-fixed, paraffin-embedded tissue from 153 consecutive stage I/II melanoma patients was immunohistochemically dual-stained for PHH3 and MART1. Whole slide images were captured, and the number of PHH3/MART1-positive cells was manually and automatically counted in the global tumor area and in a manually and automatically selected hot spot, i.e., a fixed 1-mm(2) square. Bland-Altman plots and hypothesis tests compared manual and automated procedures, and the Cox proportional hazards model established their prognostic impact. The mean difference between manual and automated global counts was 2.9 cells/mm(2) (P = 0.0071) and 0.23 cells per hot spot (P = 0.96) for automated counts in manually and automatically selected hot spots. In 77 % of cases, manual and automated hot spots overlapped. Fully manual hot-spot counts yielded the highest prognostic performance with an adjusted hazard ratio of 5.5 (95 % CI, 1.3-24, P = 0.024) as opposed to 1.3 (95 % CI, 0.61-2.9, P = 0.47) for automated counts with automated hot spots. The automated index and automated hot-spot selection were highly correlated to their manual counterpart, but altogether their prognostic impact was noticeably reduced. Because correct recognition of only one PHH3/MART1-positive cell seems important, extremely high sensitivity and specificity of the algorithm is required for prognostic purposes. Thus, automated

  14. Second cancers after conservative surgery and radiation for stages I-II breast cancer: identifying a subset of women at increased risk

    International Nuclear Information System (INIS)

    Fowble, Barbara; Hanlon, Alexandra; Freedman, Gary; Nicolaou, Nicos; Anderson, Penny

    2001-01-01

    Purpose: To assess the risk and patterns of second malignancy in a group of women treated with conservative surgery and radiation in a relatively contemporary manner for early-stage invasive breast cancer, and to identify a subgroup of these women at increased risk for a second cancer. Methods and Materials: From 1978 to 1994, 1,253 women with unilateral Stage I-II breast cancer underwent wide excision, axillary dissection, and radiation. The median follow-up was 8.9 years, with 446 patients followed for ≥10 years. The median age was 55 years. Sixty-eight percent had T1 tumors and 74% were axillary-node negative. Radiation was directed to the breast only in 78%. Adjuvant therapy consisted of chemotherapy in 19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their association with the cumulative incidence of all second malignancies, contralateral breast cancer, and non-breast cancer malignancy were: age, menopausal status, race, family history, obesity, smoking, tumor size, location, histology, pathologic nodal status, region(s) treated with radiation, and the use and type of adjuvant therapy. Results: One hundred seventy-six women developed a second malignancy (87 contralateral breast cancers at a median interval of 5.8 years, and 98 non-breast cancer malignancies at a median interval of 7.2 years). Nine women had both a contralateral breast cancer and non-breast cancer second malignancy. The 5- and 10-year cumulative incidences of a second malignancy were 5% and 16% for all cancers, 3% and 7% for contralateral breast cancer, 3% and 8%, for all second non-breast cancer malignancies, and 1% and 5%, respectively, for second non-breast cancer malignancies, excluding skin cancers. Patient age was a significant factor for contralateral breast cancer and non-breast cancer second malignancy. Young age was associated with an increased risk of contralateral breast cancer, while older age was associated with an increased the risk of a second non-breast cancer

  15. A comparison of volumetric modulated arc therapy and sliding-window intensity-modulated radiotherapy in the treatment of Stage I-II nasal natural killer/T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xianfeng [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China); Yang, Yong [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Jin, Fu; He, Yanan; Zhong, Mingsong; Luo, Huanli; Qiu, Da; Li, Chao; Yang, Han; He, Guanglei [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China); Wang, Ying, E-mail: zjajf@126.com [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China)

    2016-04-01

    This article is aimed to compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for Stage I-II nasal natural killer/T-cell lymphoma (NNKTL). Ten patients with Stage I-II NNKTL treated with IMRT were replanned with VMAT (2 arcs). The prescribed dose of the planning target volume (PTV) was 50 Gy in 25 fractions. The VMAT plans with the Anisotropic Analytical Algorithm (Version 8.6.15) were based on an Eclipse treatment planning system; the monitor units (MUs) and treatment time (T) were scored to measure the expected treatment efficiency. All the 10 patients under the study were subject to comparisons regarding the quality of target coverage, the efficiency of delivery, and the exposure of normal adjacent organs at risk (OARs). The study shows that VMAT was associated with a better conformal index (CI) and homogeneity index (HI) (both p < 0.05) but slightly higher dose to OARs than IMRT. The MUs with VMAT (650.80 ± 24.59) were fewer than with IMRT (1300.10 ± 57.12) (relative reduction of 49.94%, p = 0.00) when using 2-Gy dose fractions. The treatment time with VMAT (3.20 ± 0.02 minutes) was shorter than with IMRT (7.38 ± 0.18 minutes) (relative reduction of 56.64%, p = 0.00). We found that VMAT and IMRT both provide satisfactory target dosimetric coverage and OARs sparing clinically. Likely to deliver a bit higher dose to OARs, VMAT in comparison with IMRT, is still a better choice for treatment of patients with Stage I-II NNKTL, thanks to better dose distribution, fewer MUs, and shorter delivery time.

  16. Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

    International Nuclear Information System (INIS)

    Hata, Masaharu; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-01-01

    Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade ≥3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC

  17. Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.

    Science.gov (United States)

    Zhang, Lu; Yu, Qingzhao; Wu, Xiao-Cheng; Hsieh, Mei-Chin; Loch, Michelle; Chen, Vivien W; Fontham, Elizabeth; Ferguson, Tekeda

    2018-05-01

    To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations. Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score. Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51). Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.

  18. Adjuvant whole abdominal intensity modulated radiotherapy (IMRT) for high risk stage FIGO III patients with ovarian cancer (OVAR-IMRT-01) – Pilot trial of a phase I/II study: study protocol

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Jensen, Alexandra D; Sterzing, Florian; Munter, Marc W; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2007-01-01

    The prognosis for patients with advanced epithelial ovarian cancer remains poor despite aggressive surgical resection and platinum-based chemotherapy. More than 60% of patients will develop recurrent disease, principally intraperitoneal, and die within 5 years. The use of whole abdominal irradiation (WAI) as consolidation therapy would appear to be a logical strategy given its ability to sterilize small tumour volumes. Despite the clinically proven efficacy of whole abdominal irradiation, the use of radiotherapy in ovarian cancer has profoundly decreased mainly due to high treatment-related toxicity. Modern intensity-modulated radiation therapy (IMRT) could allow to spare kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. The OVAR-IMRT-01 study is a single center pilot trial of a phase I/II study. Patients with advanced ovarian cancer stage FIGO III (R1 or R2< 1 cm) after surgical resection and platinum-based chemotherapy will be treated with whole abdomen irradiation as consolidation therapy using intensity modulated radiation therapy (IMRT) to a total dose of 30 Gy in 1.5 Gy fractions. A total of 8 patients will be included in this trial. For treatment planning bone marrow, kidneys, liver, spinal cord, vertebral bodies and pelvic bones are defined as organs at risk. The planning target volume includes the entire peritoneal cavity plus pelvic and para-aortic node regions. The primary endpoint of the study is the evaluation of the feasibility of intensity-modulated WAI and the evaluation of the study protocol. Secondary endpoint is evaluation of the toxicity of intensity modulated WAI before continuing with the phase I/II study. The aim is to explore the potential of IMRT as a new method for WAI to decrease the dose to kidneys, liver, bone marrow while covering the peritoneal cavity with a homogenous dose, and to implement whole abdominal intensity-modulated radiotherapy into the adjuvant multimodal

  19. A phase I/II study of neoadjuvant chemotherapy followed by radiation with boost chemotherapy for advanced T-stage nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Johnson, Faye M.; Garden, Adam S.; Palmer, J. Lynn; Shin, Dong M.; Morrison, William; Papadimitrakopoulou, Vassiliki; Khuri, Fadlo; Clayman, Gary; Goepfert, Helmuth; Ang, K. Kian; Hong, Waun K.; Glisson, Bonnie S.

    2005-01-01

    Purpose: Local recurrence is the most common site of failure for locally advanced nasopharyngeal carcinoma (NPC) treated with neoadjuvant cisplatin/5-fluorouracil (PF) and definitive radiation at our center. Based on this, we studied the addition of chemotherapy during the boost phase of radiation after neoadjuvant PF for advanced T-stage (T3-T4) NPC. This strategy was based on theoretical radiosensitization with chemotherapy during accelerated repopulation of the tumor with relatively radioresistant clonogens. Methods and Materials: Three cycles of neoadjuvant PF was followed by conventionally fractionated radiation with additional PF during the boost portion of the radiation course. An initial Phase I study was done to establish the maximum tolerated dose of concurrent PF. Results: Forty-four patients were enrolled. Six patients in Phase I defined the MTD for concurrent PF as: cisplatin 10 mg/m 2 /day and PF 320 mg/m 2 /day, on Days 1-5 during Weeks 6 and 7 of radiation therapy based on dose-limiting toxicities of mucositis, neutropenia, and thrombocytopenia. Forty-one patients were treated with concurrent therapy per protocol: complete, partial, and minor responses were seen in 23, 16, and 2 patients, respectively. Progression-free and overall survival rates at 5 years were 55% (95% CI, 41-75%) and 66% (95% CI, 52-85%), respectively. Seven of 11 tumor-related deaths were due to local recurrence. Nine of 10 patients with local recurrence had T4-stage disease at presentation. Local control of T4 disease was achieved in 74% of patients overall, and in 25% (1/4) with World Health Organization (WHO) type 1, 76% (16/21) with WHO type 2, and 90% (9/10) with WHO type 3 histology. Common toxicities included mucositis, dermatitis, fatigue, vomiting, and weight loss. Conclusions: This regimen was feasible and associated with promising overall survival. Local recurrence remains the major reason for treatment failure in advanced T-stage NPC, especially WHO types 1 and 2

  20. PECULIARITIES OF THE CLINICAL COURSE OF NON-ALCOHOLIC STEATOHEPATITIS AGAINST THE BACKGROUND OF THE CHRONIC KIDNEY DISEASE OF THE I-III STAGE WITH SECONDARY ARTERIAL HYPERTENSION.

    Science.gov (United States)

    Hukhlina, O; Antoniv, A; Dudka, I; Dudka, T; Mandryk, O

    2017-09-01

    The article addresses the theoretical generalization of the clinical study of non-alcoholic steatohepatitis peculiarities in comorbidity with obesity and chronic kidney disease of the І-ІІІ stage, characterized by higher frequency and intensity of clinical and biochemical syndromes, the manifestation of which is likely to increase the occurrence of secondary arterial hypertension (portal hypertension syndromes, cholestasis, mesenchymal inflammation). Comorbid course of non-alcoholic steatohepatitis with chronic kidney disease is characterized by higher degree of liver steatosis compared to the patients with only non-alcoholic steatohepatitis (p<0.05), and a higher diagnostic threshold of the hepatorenal index values, which correlates with the Steato-test index (p<0.001) with strong interdependence.

  1. Relationship between vitamin D and lung function, physical performance and balance on patients with stage I-III chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tuncay Yumrutepe

    2015-04-01

    Full Text Available Summary Objectives: vitamin D is important for muscle function and it affects different aspects of muscle metabolism. This study aim to determine whether serum 25(OH D levels are related to lung functions, physical performance and balance in patients with chronic obstructive pulmonary disease (COPD. Methods: in 90 patients with COPD and 57 healthy controls lung function tests, physical performance tests (time up and go, gait velocity test, sit-to-stand test, isometric strength, isokinetic strength, static (functional reach test and dynamic (time up and go balance tests and the association of 25(OHD levels with lung functions, physical performance and balance were evaluated. Results: the COPD patients had significantly more deficit in physical function and balance parameters, and in dynamic balance test (p<0.005. Isokinetic knee muscle strength (flexor and extensor in COPD patients was significantly lower than in the controls (p<0.05; FEV1 (p=0.008, FVC (p=0.02, FEV1/FVC (p=0.04, TLC (p=0.01 were lower in COPD patients with vitamin D deficiency [25(OH D less than 15ng/mL] than in COPD patients without vitamin D deficiency. Hand grip test (p=0.000 and isokinetic knee muscle strength (flexor and extensor (p<0.05 were also lower in COPD patients with vitamin D deficiency. Vitamin D deficiency was more pronounced in patients with stage III COPD (p<0.05. Conclusion: patients with COPD had worst physical functioning, poor balance and less muscle strength. Severe disturbed lung and peripheral muscle functions are more pronounced in COPD patients with vitamin D deficiency.

  2. Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial

    Science.gov (United States)

    2012-01-01

    Background TomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities. Methods The trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test. Results By May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05). Conclusions There were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need confirmation with longer

  3. HLA-G 3'UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment.

    Science.gov (United States)

    Garziera, Marica; Bidoli, Ettore; Cecchin, Erika; Mini, Enrico; Nobili, Stefania; Lonardi, Sara; Buonadonna, Angela; Errante, Domenico; Pella, Nicoletta; D'Andrea, Mario; De Marchi, Francesco; De Paoli, Antonino; Zanusso, Chiara; De Mattia, Elena; Tassi, Renato; Toffoli, Giuseppe

    2015-01-01

    An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host's immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3'UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3'UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3'UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3'UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3'UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38-0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26-0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19-5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16-6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3'UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G.

  4. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix; Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd; Porsch, Peter; Studnicka, Michael

    2015-01-01

    While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [de

  5. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Paracelsus Medizinische Privatuniversitaet, Institute for Research and Development of Advanced Radiation Technologies (radART), Salzburg (Austria); Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Porsch, Peter; Studnicka, Michael [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Pneumologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria)

    2014-09-23

    While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for < 2.5 cm, 79.2 Gy for 2.5-4.5 cm, 84.6 Gy for 4.5-6 cm, 90 Gy for > 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [German] Die Standardbehandlung fuer nichtkleinzellige Bronchialkarzinome (NSCLC) im Stadium I/II ist die Operation, wobei Radiotherapie fuer Patienten, die nicht operabel sind oder die Operation ablehnen, als Alternative

  6. Evolving concepts in staging and treatment of colorectal cancer

    NARCIS (Netherlands)

    Sloothaak, D.A.M.

    2015-01-01

    For localized colorectal cancer (CRC), lymph node metastases are the most powerful prognostic factor for disease specific and overall survival. In the first part of the thesis, we explore the prognostic role of lymph nodes in patients with stage I/II colon cancer. In these patients, nodal metastases

  7. Serial Determination of bcl-2 Major Breakpoint Region (MBR) Rearrangement, t(14;18) (q32;q21), in the Bone Marrow and Peripheral Blood for Stages I - III Follicular Lymphoma after Central Lymphatic Irradiation (CLI) - A Preliminary Report

    International Nuclear Information System (INIS)

    Ha, C.S.; Cabanillas, F.; Lee, M.; Besa, P.C.; McLaughlin, P.W.; Cox, J.D.

    1995-01-01

    Purpose/Objective: About (2(3)) of all cases of follicular lymphoma have rearrangement of bcl-2 MBR through t(14;18) (q32;q21). This arrangement could serve as a sensitive marker for follicular lymphoma cells. The objectives of this study are two fold: 1) To assess complete molecular response rate of stages I-III follicular lymphoma to CLI by detection of PCR amplifiable bcl-2 MBR rearrangement in the bone marrow and peripheral blood before and after CLI. 2) To assess the significance of the molecular response as a prognostic indicator. Materials and Methods: 13 patients with stages I-III follicular lymphoma were treated with CLI as a part of a prospective randomized protocol comparing CLI with chemotherapy. Bone marrow and peripheral blood samples were obtained from the patients before initiation of CLI. By using the PCR technique, the DNA sequences from the bone marrow and peripheral blood samples that flank the bcl-2 MBR involved in t(14;18) (q32;q21) were amplified. For the patients who had positive PCR result, bone marrow and blood samples were followed at regular intervals during and after CLI. The patients with negative PCR result prior to CLI did not have follow-up PCR analysis. The results of the PCR amplification were correlated with clinical findings. Results: All 13 patients achieved clinical complete response after CLI. No patient has relapsed with a median follow-up period of 11 months (range 5 to 24 months). Pretreatment PCR results are available in 13 patients for peripheral blood and in 9 patients for bone marrow. (7(13)) blood and (5(9)) bone marrow samples were PCR-positive for bcl-2 MBR rearrangement. All 5 patients with positive pretreatment bone marrow also had positive pretreatment peripheral blood. (6(7)) patients with positive pretreatment blood PCR converted to negative within 2,3,5,6,6, and 10 months from the 1st day of CLI. The 7th patient has no follow-up PCR available yet. Follow-up PCR results from the pretreatment bone

  8. Advances in CRC prevention: screening and surveillance

    NARCIS (Netherlands)

    Dekker, Evelien; Rex, Douglas K.

    2018-01-01

    Colorectal cancer (CRC) is amongst the most commonly diagnosed cancers and causes of death from cancer across the world. CRC can, however, be detected in asymptomatic patients at a curable stage, and several studies have shown lower mortality among patients who undergo screening compared to those

  9. Slender CRC Columns

    DEFF Research Database (Denmark)

    Aarup, Bendt; Jensen, Lars Rom; Ellegaard, Peter

    2005-01-01

    CRC is a high-performance steel fibre reinforced concrete with a typical compressive strength of 150 MPa. Design methods for a number of structural elements have been developed since CRC was invented in 1986, but the current project set out to further investigate the range of columns for which...

  10. Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for Stage IIIA and Stage IIIB non-small cell lung cancer: results of a Phase I-II study by the GOTHA group

    Energy Technology Data Exchange (ETDEWEB)

    Alberto, P.; Mermillod, B. [Hopital Cantonal Geneve, Geneva (Switzerland); Mirimanoff, R.O.; Leyvraz, S.; Nagy-Mignotte, H.; Bolla, M.; Wellmann, D.; Moro, D.; Brambilla, E. [Hopital Cantonal Universitaire, Lausanne (Switzerland)

    1995-08-01

    The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy. (author).

  11. Main: CRC101 [AT Atlas

    Lifescience Database Archive (English)

    Full Text Available CRC101 CRC1 Establishment of Chemical Library and Development of Protein Regulation... Technology Chemical library Tetsuo Nagano Graduate School of Pharmaceutical Sciences, The University CRC101.csml ...

  12. Survivin -31 G/C polymorphism might contribute to colorectal cancer (CRC) risk: a meta-analysis.

    Science.gov (United States)

    Yao, Linhua; Hu, Yi; Deng, Zhongmin; Li, Jingjing

    2015-01-01

    Published data has shown inconsistent findings about the association of survivin -31 G/C polymorphism with the risk of colorectal cancer (CRC). This meta-analysis quantitatively assesses the results from published studies to provide a more precise estimate of the association between survivin -31 G/C polymorphism as a possible predictor of the risk of CRC. We conducted a literature search in the PubMed, Web of Science, and Cochrane Library databases. Stata 12 software was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) based on the available data from each article. Six studies including 1840 cases with CRC and 1804 controls were included in this study. Survivin -31 G/C polymorphism was associated with a significantly increased risk of CRC (OR = 1.78; 95% CI, 1.53-2.07; I(2) = 0%). In the race subgroup analysis, both Asians (OR = 1.72; 95% CI, 1.44-2.05; I(2) = 0%) and Caucasians (OR = 1.93; 95% CI, 1.46-2.55; I(2) = 0%) with survivin -31 G/C polymorphism had increased CRC risk. In the subgroup analysis according to site of CRC, survivin -31 G/C polymorphism was not associated with colon cancer risk (OR = 2.02; 95% CI, 0.79-5.22; I(2) = 82%). However, this polymorphism was significantly associated with rectum cancer risk (OR = 1.98; 95% CI, 1.42-2.74; I(2) = 0%). In the subgroup analysis by clinical stage, both early stage (I+II) and advanced stage (III+IV) were associated with survivin -31 G/C polymorphism (OR = 1.61; 95% CI, 1.20-2.16; I(2) = 0% and OR = 2.30; 95% CI, 1.70-3.13; I(2) = 0%, respectively). In the subgroup analysis by smoke status, both smokers and non-smokers with survivin -31 G/C polymorphism showed increased CRC risk (OR = 1.47; 95% CI, 1.01-2.13; I(2) = 60% and OR = 1.71; 95% CI, 1.28-2.30; I(2) = 0%, respectively). In the subgroup analysis by drink status, both drinkers and non-drinkers with survivin -31 G/C polymorphism showed increased CRC risk (OR = 1.58; 95% CI, 1.06-2.37; I(2) = 8% and OR = 1.61; 95% CI, 1

  13. Advances in CRC Prevention: Screening and Surveillance.

    Science.gov (United States)

    Dekker, Evelien; Rex, Douglas K

    2018-05-01

    Colorectal cancer (CRC) is among the most commonly diagnosed cancers and causes of death from cancer across the world. CRC can, however, be detected in asymptomatic patients at a curable stage, and several studies have shown lower mortality among patients who undergo screening compared with those who do not. Using colonoscopy in CRC screening also results in the detection of precancerous polyps that can be directly removed during the procedure, thereby reducing the incidence of cancer. In the past decade, convincing evidence has appeared that the effectiveness of colonoscopy as CRC prevention tool is associated with the quality of the procedure. This review aims to provide an up-to-date overview of recent efforts to improve colonoscopy effectiveness by enhancing detection and improving the completeness and safety of resection of colorectal lesions. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. The Impact of Colorectal Cancer (CRC) in Mississippi, and the need for Mississippi to Eliminate its CRC Burden.

    Science.gov (United States)

    Duhé, Roy J

    2016-03-01

    Colorectal cancer (CRC), while highly preventable and highly treatable, is a major public health problem in Mississippi. This article reviews solutions to this problem, beginning with the relationship between modifiable behavioral risk factors and CRC incidence. It then describes the impact of CRC screening on national downward trends in CRC incidence and mortality and summarizes recent data on the burden of CRC in Mississippi. While other states have created Comprehensive Colorectal Cancer Control Programs in an organized effort to manage this public health problem, Mississippi has not. Responding to Mississippi's situation, the 70x2020 Colorectal Cancer Screening Initiative arose as an unconventional approach to increase CRC screening rates throughout the state. This article concludes by considering the current limits of CRC treatment success and proposes that improved clinical outcomes should result from research to translate recently-identified colorectal cancer subtype information into novel clinical paradigms for the treatment of early-stage colorectal cancer.

  15. Prognostic value of pretreatment serum carcinoembryonic antigen and squamous cell carcinoma antigen levels for patients with stage I-III non-small cell lung cancer treated with radiation therapy alone

    International Nuclear Information System (INIS)

    Saito, Yoshihiro; Mitsuhashi, Norio; Hayakawa, Kazushige

    1998-01-01

    Serum carcinoembryonic antigen (CEA) and serum squamous cell carcinoma antigen (SCC Ag) levels have been reported to be useful as prognostic factors, indicators of clinical response, and predictors for recurrence in patients with lung cancer treated by surgery or chemotherapy. We investigated whether pretreatment serum CEA and SCC Ag levels were useful as independent prognostic factors in patients with stage I to III non-small cell lung cancer who were treated with radiation therapy alone. The serum CEA and SCC Ag levels were measured in 158 and 47 patients, respectively, before radiation therapy. Serum CEA and SCC Ag levels were measured by sandwich radioimmunoassay using the CEA-RIA (radioimmunoassay) kit and the SCC-RIA kit. Serum CEA and SCC Ag levels were above reference values in 19% and 30% of the patients, respectively. The 5-year survival rates were significantly better for patients with a negative SCC Ag result than for those with positive SCC Ag levels (p=0.0001), though no significant difference in survival rates was seen by CEA positivity (p=0.25). SCC Ag positivity (p=0.0006) and stage (p=0.04) were the important prognostic factors, as determined by multivariate analyses. Pretreatment serum SCC Ag level may be useful as an independent prognostic factor in patients with stage I to III non-small cell lung cancer who are treated with radiation therapy alone. (author)

  16. High Rab27A expression indicates favorable prognosis in CRC.

    Science.gov (United States)

    Shi, Chuanbing; Yang, Xiaojun; Ni, Yijiang; Hou, Ning; Xu, Li; Zhan, Feng; Zhu, Huijun; Xiong, Lin; Chen, Pingsheng

    2015-06-13

    Rab27A is a peculiar member in Rab family and has been suggested to play essential roles in the development of human cancers. However, the association between Rab27A expression and clinicopathological characteristics of colorectal cancer (CRC) has not been elucidated yet. One-step quantitative real-time polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 112 CRC cases were executed to evaluate the relationship between Rab27A expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for 112 CRC patients. The results specified that the expression levels of Rab27A mRNA and protein were significantly higher in CRC tissues than that in matched non-cancerous tissues, in both qPCR test (p = 0.029) and IHC analysis (p = 0.020). The IHC data indicated that the Rab27A protein expression in CRC was statistically correlated with lymph node metastasis (p = 0.022) and TNM stage (p = 0.026). Cox multi-factor analysis and Kaplan-Meier method suggested Rab27A protein expression (p = 0.012) and tumor differentiation (p = 0.004) were significantly associated with the overall survival of CRC patients. The data indicated the differentiate expression of Rab27A in CRC tissues and matched non-cancerous tissues. Rab27A may be used as a valuable prognostic biomarker for CRC patients.

  17. Long-term follow-up of a phase I/II trial of dose escalating three-dimensional conformal thoracic radiation therapy with induction and concurrent carboplatin and paclitaxel in unresectable stage IIIA/B non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Lee, Carrie B; Moore, Dominic T; Rivera, M Patricia; Halle, Jan; Limentani, Steven; Rosenman, Julian G; Socinski, Mark A

    2008-11-01

    We conducted a modified phase I/II trial investigating the incorporation of three-dimensional conformal thoracic radiation therapy (TCRT) into the treatment paradigm of induction and concurrent carboplatin and paclitaxel in patients with unresectable stage IIIA/B non-small cell lung cancer. Patients received 2 cycles of induction carboplatin (area under the curve of 6) and paclitaxel (225 mg/m) on days 1, and 22. On day 43 concurrent TCRT and weekly x6 of carboplatin (area under the curve = 2) and paclitaxel (45 mg/m) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy), and the 74 Gy cohort was expanded into a phase II trial. Sixty-two patients were enrolled; the median age 57 years (range, 36-82), 39 were male (63%), 61 (98%) had a performance status of 0 or 1, 28 (45%) had stage IIIA disease, 21 (34%) had >5% weight loss, and the median forced expiratory volume 1 = 2.10 liters (range, 1.02-3.75). With a median follow-up for survivors of approximately 9 years (range, 7-11 years) the median progression-free survival, time to tumor progression, and overall survival (OS) (with 95% confidence intervals) were 10 (8.5-17), 15 (9-50), and 25 months (18-37), respectively. The 5-year progression-free survival and OS rates were 21% (12-32%) and 27% (17-39%), respectively. The 10-year OS rate was 14% (7-25%). The long term survival rate compares favorably to other treatment approaches for stage III non-small cell lung cancer.

  18. Tape Storage and CRC Protection

    CERN Document Server

    Ha, Karel

    2014-01-01

    Over 100 Petabytes of data is stored on several kind of physical support, namely disks and tapes. Data on any physical support or traveling on a data link (network, fibre channel...) can be subject to silent data corruption. A possible improvement is introducing end-to-end data integrity from the filesystem down to the tape layer. For the tape back-end it can be done by using Logical Block Protection, which computes and compares CRC checksum of every single block of data. During my work, I improved on-the-fly CRC calculation for the tape storage system, which was achieved by introducing a multithreaded implementation - a technique applicable to arbitrary CRC algorithm. Finally, I per...

  19. Performance Analysis of CRC Codes for Systematic and Nonsystematic Polar Codes with List Decoding

    Directory of Open Access Journals (Sweden)

    Takumi Murata

    2018-01-01

    Full Text Available Successive cancellation list (SCL decoding of polar codes is an effective approach that can significantly outperform the original successive cancellation (SC decoding, provided that proper cyclic redundancy-check (CRC codes are employed at the stage of candidate selection. Previous studies on CRC-assisted polar codes mostly focus on improvement of the decoding algorithms as well as their implementation, and little attention has been paid to the CRC code structure itself. For the CRC-concatenated polar codes with CRC code as their outer code, the use of longer CRC code leads to reduction of information rate, whereas the use of shorter CRC code may reduce the error detection probability, thus degrading the frame error rate (FER performance. Therefore, CRC codes of proper length should be employed in order to optimize the FER performance for a given signal-to-noise ratio (SNR per information bit. In this paper, we investigate the effect of CRC codes on the FER performance of polar codes with list decoding in terms of the CRC code length as well as its generator polynomials. Both the original nonsystematic and systematic polar codes are considered, and we also demonstrate that different behaviors of CRC codes should be observed depending on whether the inner polar code is systematic or not.

  20. CRC concise encyclopedia of mathematics

    CERN Document Server

    Weisstein, Eric W

    2003-01-01

    Upon publication, the first edition of the CRC Concise Encyclopedia of Mathematics received overwhelming accolades for its unparalleled scope, readability, and utility. It soon took its place among the top selling books in the history of Chapman & Hall/CRC, and its popularity continues unabated. Yet also unabated has been the dedication of author Eric Weisstein to collecting, cataloging, and referencing mathematical facts, formulas, and definitions. He has now updated most of the original entries and expanded the Encyclopedia to include 1000 additional pages of illustrated entries. The accessibility of the Encyclopedia along with its broad coverage and economical price make it attractive to the widest possible range of readers and certainly a must for libraries, from the secondary to the professional and research levels. For mathematical definitions, formulas, figures, tabulations, and references, this is simply the most impressive compendium available.

  1. Report: Cultural Research Centre (CRC)

    OpenAIRE

    Cross-Cultural Foundation of Uganda

    2010-01-01

    This report arises from research carried out in Iganga and Namutumba districts in late 2006/early 2007 by the Cultural Research Centre (CRC), based in Jinja. Our research focus was to gauge the impact of using Lusoga as a medium of instruction (since 2005 in "pilot" lower primary classes) within and outside the classroom. This initiative was in response to a new set of circumstances in the education sector in Uganda, especially the introduction by Government of teaching in local languages in ...

  2. The influence of marital status on stage at diagnosis and survival of patients with colorectal cancer.

    Science.gov (United States)

    Li, Qingguo; Gan, Lu; Liang, Lei; Li, Xinxiang; Cai, Sanjun

    2015-03-30

    Marital status was found to be an independent prognostic factor for survival in various cancer types, but it hasn't been fully studied in colorectal cancer (CRC). The Surveillance, Epidemiology and End Results database was used to compare survival outcomes with marital status in each stage. In total, 112, 776 eligible patients were identified. Patients in the widowed group were more frequently elderly women, more common of colon cancer, and more stage I/II in tumor stage (P married group (94.72% VS 94.10%). Married CRC patients had better 5year cause-specific survival (CSS) than those unmarried (P married patients at stage I (94.8% vs 89.8%, P vs 76.5%, P vs 53.9%, P VS 8.2%, P unmarried patients were at greater risk of cancer specific mortality. Despite favorable clinicpathological characteristics, widowed patients were at highest risk of death compared with other groups.

  3. Two small RNAs, CrcY and CrcZ, act in concert to sequester the Crc global regulator in Pseudomonas putida, modulating catabolite repression.

    Science.gov (United States)

    Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

    2012-01-01

    The Crc protein is a translational repressor that recognizes a specific target at some mRNAs, controlling catabolite repression and co-ordinating carbon metabolism in pseudomonads. In Pseudomonas aeruginosa, the levels of free Crc protein are controlled by CrcZ, a sRNA that sequesters Crc, acting as an antagonist. We show that, in Pseudomonas putida, the levels of free Crc are controlled by CrcZ and by a novel 368 nt sRNA named CrcY. CrcZ and CrcY, which contain six potential targets for Crc, were able to bind Crc specifically in vitro. The levels of CrcZ and CrcY were low under conditions generating a strong catabolite repression, and increased strongly when catabolite repression was absent. Deletion of either crcZ or crcY had no effect on catabolite repression, but the simultaneous absence of both sRNAs led to constitutive catabolite repression that compromised growth on some carbon sources. Overproduction of CrcZ or CrcY significantly reduced repression. We propose that CrcZ and CrcY act in concert, sequestering and modulating the levels of free Crc according to metabolic conditions. The CbrA/CbrB two-component system activated crcZ transcription, but had little effect on crcY. CrcY was detected in P. putida, Pseudomonas fluorescens and Pseudomonas syringae, but not in P. aeruginosa. © 2011 Blackwell Publishing Ltd.

  4. CRC handbook of modern telecommunications

    CERN Document Server

    Morreale, Patricia A

    2001-01-01

    This authoritative handbook, contributed to by a team of international experts, covers the most dynamic areas in the changing telecommunications landscape. Written for telecommunications specialists who implement the new technologies, The CRC Handbook of Modern Telecommunications is an excellent companion volume to the authors' The Telecommunications Handbook, but stands well on its own, as it extends the range of topics to include voice over Internet, traffic management, quality of service, and other dominant future trends. It is an indispensable reference for all professionals working in the

  5. The requirement for freshly isolated human colorectal cancer (CRC) cells in isolating CRC stem cells.

    Science.gov (United States)

    Fan, F; Bellister, S; Lu, J; Ye, X; Boulbes, D R; Tozzi, F; Sceusi, E; Kopetz, S; Tian, F; Xia, L; Zhou, Y; Bhattacharya, R; Ellis, L M

    2015-02-03

    Isolation of colorectal cancer (CRC) cell populations enriched for cancer stem cells (CSCs) may facilitate target identification. There is no consensus regarding the best methods for isolating CRC stem cells (CRC-SCs). We determined the suitability of various cellular models and various stem cell markers for the isolation of CRC-SCs. Established human CRC cell lines, established CRC cell lines passaged through mice, patient-derived xenograft (PDX)-derived cells, early passage/newly established cell lines, and cells directly from clinical specimens were studied. Cells were FAC-sorted for the CRC-SC markers CD44, CD133, and aldehyde dehydrogenase (ALDH). Sphere formation and in vivo tumorigenicity studies were used to validate CRC-SC enrichment. None of the markers studied in established cell lines, grown either in vitro or in vivo, consistently enriched for CRC-SCs. In the three other cellular models, CD44 and CD133 did not reliably enrich for stemness. In contrast, freshly isolated PDX-derived cells or early passage/newly established CRC cell lines with high ALDH activity formed spheres in vitro and enhanced tumorigenicity in vivo, whereas cells with low ALDH activity did not. PDX-derived cells, early passages/newly established CRC cell lines and cells from clinical specimen with high ALDH activity can be used to identify CRC-SC-enriched populations. Established CRC cell lines should not be used to isolate CSCs.

  6. Type I-II laryngeal cleft: clinical course and outcome.

    Science.gov (United States)

    Slonimsky, Guy; Carmel, Eldar; Drendel, Michael; Lipschitz, Noga; Wolf, Michael

    2015-04-01

    Laryngeal cleft (LC) is a rare congenital anomaly manifesting in a variety of symptoms, including swallowing disorders and aspirations, dyspnea, stridor and hoarseness. The mild forms (types I-II) may be underdiagnosed, leading to protracted symptomatology and morbidity. To evaluate the diagnostic process, clinical course, management and outcome in children with type I-II laryngeal clefts. We conducted a retrospective case analysis for the years 2005-2012 in a tertiary referral center. Seven children were reviewed: five boys and two girls ranging in age from birth to 5 years. The most common presenting symptoms were cough, aspirations and pneumonia. Evaluation procedures included fiber-optic laryngoscopy (FOL), direct laryngoscopy (DL) and videofluoroscopy. Other pathologies were seen in three children. Six children underwent successful endoscopic surgery and one child was treated conservatively. The postoperative clinical course was uneventful in most of the cases. Types I-II LC should be considered in the differential diagnosis of children presenting with protracted cough and aspirations. DL is crucial for establishing the diagnosis. Endoscopic surgery is safe and should be applied promptly when conservative measures fail.

  7. Attitudes towards colorectal cancer (CRC) and CRC screening tests among elderly Malay patients.

    Science.gov (United States)

    Al-Naggar, Redhwan A; Al-Kubaisy, Waqar; Yap, Bee W; Bobryshev, Yuri V; Osman, Muhamed T

    2015-01-01

    Colorectal cancer (CRC) is the third most common malignancy in Malaysia, where data are limited regarding knowledge and barriers in regard to CRC and screening tests. The aim of the study was to assess these parameters among Malaysians. The questionnaires were distributed in the Umra Private Hospital in Selangor. The questionnaire had four parts and covered social-demographic questions, respondent knowledge about CRC and colorectal tests, attitude towards CRC and respondentaction regarding CRC. More than half of Malay participants (total n=187) were female (57.2%) and 36.9% of them were working as professionals. The majority of the participants (93.6%) never had a CRC screening test. The study found that only 10.2% of the study participants did not consider that their chances of getting CRC were high. A high percentage of the participants (43.3%) believed that they would have good chance of survival if the cancer would be found early. About one third of the respondents did not want to do screening because of fear of cancer, and concerns of embarrassment during the procedure adversely affected attitude to CRC screening as well. Age, gender, income, family history of CRC, vegetable intake and physical activity were found to be significant determinants of knowledge on CRC. The major barriers identified towards CRC screening identified in our study were fear of pain and embarrassment. The findings have implications for understanding of similarities and differences in attitude to CRC amongst elderly patients in other cultural/ geographic regions.

  8. Expressions of IGF-1, ERK, GLUT4, IRS-1 in metabolic syndrome complicated with colorectal cancer and their associations with the clinical characteristics of CRC.

    Science.gov (United States)

    Hu, Jianxia; Liu, Xiaoyi; Chi, Jingwei; Che, Kui; Feng, Yan; Zhao, Shihua; Wang, Zhongchao; Wang, Yangang

    2018-01-01

    Epidemiological data have revealed that colorectal cancer (CRC) risk is increased in patients with Metabolic syndrome. To explore the expressions of IGF-1, ERK, GLUT4, IRS-1 in MS patients with CRC and their associations with the clinical characteristics of CRC. We investigated the expressions of IGF-1, ERK, GLUT4 and IRS-1 in greater omental adipose tissues of 168 MS patients with/without CRC, 85 CRC patients without MS and 98 healthy controls by RT-PCR, and analyzed the relationships between their expressions and clinical characteristics of CRC. The expression levels of IGF-1 and ERK in MS patients with/without CRC were higher while the expression levels of GLUT4 were lower compared with CRC patients without MS and healthy controls (PCRC were higher while expression levels of GLUT4 were lower compared to MS patients without CRC (PCRC, including tumor size, distant metastasis and advanced stages (III/IV) (PCRC.

  9. Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives.

    Science.gov (United States)

    Kahouli, Imen; Tomaro-Duchesneau, Catherine; Prakash, Satya

    2013-08-01

    Colorectal cancer (CRC) is the third most common form of cancer. Diverse therapies such as chemotherapy, immunotherapy and radiation have shown beneficial effects, but are limited because of their safety and toxicity. Probiotic formulations have shown great promise in CRC as preventive and early stage therapeutics. This review highlights the importance of a balanced intestinal microbiota and summarizes the recent developments in probiotics for treating CRC. Specifically, this report describes evidence of the role of probiotics in modulating the microbiota, in improving the physico-chemical conditions of the gut and in reducing oxidative stress. It also discusses the mechanisms of probiotics in inhibiting tumour progression, in producing anticancer compounds and in modulating the host immune response. Even though some of these effects were observed in several clinical trials, when probiotic formulations were used as a supplement to CRC therapies, the application of probiotics as biotherapeutics against CRC still needs further investigation.

  10. Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance.

    Science.gov (United States)

    Krzystek-Korpacka, Malgorzata; Diakowska, Dorota; Kapturkiewicz, Bartosz; Bębenek, Marek; Gamian, Andrzej

    2013-08-28

    Alternate colorectal cancer (CRC) screening and surveillance strategies are needed to pre-select candidates for invasive methods. We compared systemic inflammatory profiles in CRC (n=99), health (n=98), high CRC-risk conditions (n=48) and overt inflammation (n=69) by multiplexed analysis of IL-1β, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-B and CEA. Cytokines corresponded with CRC advancement. FGF2, GM-CSF, IL-1β, IL-6, MIP-1α, PDGF-BB, TNF-α, and VEGF-A were higher than in controls already in stage I CRC with FGF2, IL1-β, and MIP-1α higher than in high CRC-risk individuals as well. Cytokine panels devised to differentiate early CRC from controls, adenomas, or inflammatory bowel disease patients (IBD) had good accuracy but only IBD panel had promising specificity at 95% sensitivity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. CRC-cards for Product Modelling

    DEFF Research Database (Denmark)

    Hvam, Lars; Riis, Jesper; Hansen, Benjamin Loer

    2003-01-01

    , transportation, service and decommissioning. A main challenge when building product models is to collect and document the product related data, information and knowledge in a structured way. CRC cards are index cards (or computerized versions of these) which are used to record proposed classes, the behavior......This paper describes the CRC (class, responsibility, collaboration) modelling process for building product models. A product model is normally represented in an IT system which contains data, information and knowledge on industrial products and their life cycle properties e.g. manufacturing...... of the classes, their responsibilities, and their relationship to other classes (collaboration). CRC modelling gives an effective, low-tech method for domain-experts, programmers and users to work closely together to identify, structure, understand and document a product model. CRC cards were originally...

  12. Deletions at SLC18A1 increased the risk of CRC and lower SLC18A1 expression associated with poor CRC outcome.

    Science.gov (United States)

    Zhang, Dandan; Li, Zhenli; Xu, Xiaohong; Zhou, Dan; Tang, Shunli; Yin, Xiaoyang; Xu, Fangying; Li, Hui; Zhou, Yuan; Zhu, Tao; Deng, Hong; Zhang, Shuai; Huang, Qiong; Wang, Jing; Yin, Wei; Zhu, Yimin; Lai, Maode

    2017-10-26

    Copy number variations (CNVs) contribute to the development of colorectal cancer (CRC). We conducted a two-stage association study to identify CNV risk loci for CRC. We performed a gene-based rare CNV study on 694 sporadic CRC and 1641 controls using Illumina Human-OmniExpress-12v1.0 BeadChips, and further replicated in 934 CRC cases and 2680 controls for risk CNVs by using TaqMan Copy Number Assay. Tumor buddings, cancer cells in the center of primary tumor and normal intestinal epithelial cells were captured using laser capture microdissection (LCM) and were assayed using AffymetrixGeneChip® Human Genome U133 Plus 2.0 Array. In addition, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus data were assessed for the effects of risk CNVs. We found that germline deletions affecting the last six exons of SLC18A1 significantly associated with CRC with a combined P value of 6.4 × 10-5 by a two-stage analysis. Both in TCGA CRC RNA seq dataset and GDS4382, SLC18A1 was significantly down regulated in CRC tissues than in paired normal tissues (N = 32 and 17 pairs, P = 0.004 and 0.009, respectively). In LCM samples, similar observations were obtained that the expression levels of SLC18A1 in the tumor buddings, cancer cells in the center of primary tumor, and stroma of both tumor budding and cancer cells were lower than normal intestinal epithelial and stromal cells (fold change = 0.17-0.62, 0.12-0.57 and 0.37-0.68, respectively). In summary, the germline deletions at SLC18A1 contributed to the development of CRC. The role of SLC18A1 required further exploration. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Manda d'hajje I-II : [luuletused] / Uku Masing

    Index Scriptorium Estoniae

    Masing, Uku, 1909-1985

    2001-01-01

    Tekst eesti ja inglise k. U. Masingu lühibiograafia eesti ja inglise k. lk. 75. Sisu: Manda d'hajje I-II ; "Lennata mõtles kord muinasmaa liblikas..." = "Once a fairyland butterfly thought it would fly..." ; "Sa oled mägi, mida kardavad me karjed..." = "You are the mountain that our herds fear..." ; "Ammu tõusnud koopast, sygavalt ja kaugelt..." = "Long since risen from a cave, deep and far away..." ; "Imelik, et Sinu silmad mind ei karda..." ; "Strange that Your eyes do not fear me..." ; "Ööl järveks laiud. Ja siis äkki tõusvad üles..." = "At night You grow into a lake. From its bed..." ; "Sinu keha tõuseb minu käsivartelt..." = "Your body rises from my arms to meet me..."

  14. Pseudomonas putida growing at low temperature shows increased levels of CrcZ and CrcY sRNAs, leading to reduced Crc-dependent catabolite repression.

    Science.gov (United States)

    Fonseca, Pilar; Moreno, Renata; Rojo, Fernando

    2013-01-01

    The Crc protein of Pseudomonas inhibits the expression of genes involved in the transport and assimilation of a number of non-preferred carbon sources when preferred substrates are available, thus coordinating carbon metabolism. Crc acts by binding to target mRNAs, inhibiting their translation. In Pseudomonas putida, the amount of free Crc available is controlled by two sRNAs, CrcY and CrcZ, which bind to and sequester Crc. The levels of these sRNAs vary according to metabolic conditions. Pseudomonas putida grows optimally at 30°C, but can also thrive at 10°C. The present work shows that when cells grow exponentially at 10°C, the repressive effect of Crc on many genes is significantly reduced compared with that seen at 30°C. Total Crc levels were similar at both temperatures, but those of CrcZ and CrcY were significantly higher at 10°C. Therefore, Crc-mediated repression may, at least in part, be reduced at 10°C because the fraction of Crc protein sequestered by CrcZ and CrcY is larger, reducing the amount of free Crc available to bind its targets. This may help P. putida to face cold stress. The results reported might help understanding the behaviour of this bacterium in bioremediation or rhizoremediation strategies at low temperatures. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  15. SPIRIT: A seamless phase I/II randomized design for immunotherapy trials.

    Science.gov (United States)

    Guo, Beibei; Li, Daniel; Yuan, Ying

    2018-06-07

    Immunotherapy-treatments that enlist the immune system to battle tumors-has received widespread attention in cancer research. Due to its unique features and mechanisms for treating cancer, immunotherapy requires novel clinical trial designs. We propose a Bayesian seamless phase I/II randomized design for immunotherapy trials (SPIRIT) to find the optimal biological dose (OBD) defined in terms of the restricted mean survival time. We jointly model progression-free survival and the immune response. Progression-free survival is used as the primary endpoint to determine the OBD, and the immune response is used as an ancillary endpoint to quickly screen out futile doses. Toxicity is monitored throughout the trial. The design consists of two seamlessly connected stages. The first stage identifies a set of safe doses. The second stage adaptively randomizes patients to the safe doses identified and uses their progression-free survival and immune response to find the OBD. The simulation study shows that the SPIRIT has desirable operating characteristics and outperforms the conventional design. Copyright © 2018 John Wiley & Sons, Ltd.

  16. The Crc/CrcZ-CrcY global regulatory system helps the integration of gluconeogenic and glycolytic metabolism in Pseudomonas putida.

    Science.gov (United States)

    La Rosa, Ruggero; Nogales, Juan; Rojo, Fernando

    2015-09-01

    In metabolically versatile bacteria, carbon catabolite repression (CCR) facilitates the preferential assimilation of the most efficient carbon sources, improving growth rates and fitness. In Pseudomonas putida, the Crc and Hfq proteins and the CrcZ and CrcY small RNAs, which are believed to antagonize Crc/Hfq, are key players in CCR. Unlike that seen in other bacterial species, succinate and glucose elicit weak CCR in this bacterium. In the present work, metabolic, transcriptomic and constraint-based metabolic flux analyses were combined to clarify whether P. putida prefers succinate or glucose, and to identify the role of the Crc protein in the metabolism of these compounds. When provided simultaneously, succinate was consumed faster than glucose, although both compounds were metabolized. CrcZ and CrcY levels were lower when both substrates were present than when only one was provided, suggesting a role for Crc in coordinating metabolism of these compounds. Flux distribution analysis suggested that, when both substrates are present, Crc works to organize a metabolism in which carbon compounds flow in opposite directions: from glucose to pyruvate, and from succinate to pyruvate. Thus, our results support that Crc not only favours the assimilation of preferred compounds, but balances carbon fluxes, optimizing metabolism and growth. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. Radiotherapeutic aspects of the treatment of adult patients with supradiaphragmatic Hodgkin's disease CS I/II. Pt. 1; Regarding the indications of primary and adjuvant radiotherapy. Fragen und Aspekte zur Radiotherapie bei erwachsenen Patienten mit lokalisierten supradiaphragmalen Stadien (CS I/II) eines Morbus Hodgkin. T. 1; Fragen und Aspekte zu den Indikationen einer primaeren und einer adjuvanten Radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Glanzmann, C. (Universitaetsspital, Klinik fuer Radio-Onkologie, Zurich (Switzerland)); Luetolf, U.M. (Universitaetsspital, Klinik fuer Radio-Onkologie, Zurich (Switzerland))

    1993-08-01

    Randomized studies of chemo- vs radiotherapy in patients with PS I/II A and some PS III A have shown conflicting results. Patients with supra-diaphragmatic Hodkin's disease and CS I/II can be subdivided according to radiotherapy as: 1. Patients with a very low or a low recurrence risk of approximately 10 to 20%: Patients less than 40 years old and CS I/II A NS/LP with less than three involved regions and no bulky mediastinal mass and an ESR below 30 mm. In the other patients, primary irradiation of an extended mantle field without a staging laparotomy is an acceptable primary treatment, achieving a recurrence-free survival rate of approximately 80%. Another option is a staging laparotomy with splenectomy and a mantle radiotherapy for PS I/II. Few groups prefer primary chemotherapy alone or some type of a reduced chemotherapy with lesser toxicity combined with localized radiotherapy and long-term observations of a larger group of patients after the last type of treatment have to confirm the excellent early results. 2. Patients with an intermediate recurrence risk of approximately 20 to 40%: Patients, who do not belong to group one or group 3. Patients less than 50 years old with CS I/II and an ESR less than 50 mm and without bulky mediastinal involvement and with one of the following signs: Three involved regions or MC or one B symptom. A patient with more than one of these signs or with two or three B symptoms should be classified in group 3. For these patients, we recommend staging laparotomy and radiotherapy if PS I/II or primary chemotherapy with or without radiotherapy of the involved regions. 3. Patients with a high recurrence risk (40% or higher): (Abstract Truncated)

  18. Assessment of Jordanian Patient's Colorectal Cancer Awareness and Preferences towards CRC Screening: Are Jordanians Ready to Embrace CRC Screening?

    Science.gov (United States)

    Omran, Suha; Barakat, Husam; Muliira, Joshua Kanaabi; Bashaireh, Ibrahim; Batiha, Abdul-Moni'm

    2015-01-01

    Colorectal cancer (CRC is increasingly becoming a major cause of cancer morbidity and mortality in Jordan. However the population's level of awareness about CRC, CRC screening test preferences and willingness to embrace screening are not known. The aim of this study was to assess the level of CRC awareness and screening preferences among Jordanian patients. A survey assessing the CRC knowledge levels was distributed among patients attending outpatient gastroenterology clinics in public hospitals throughout Jordan. A total of 800 surveys were distributed and of these 713 (89.1%) were returned. Only 22% of the participants correctly judged CRC among the choices provided as the commonest cause of cancer related deaths. The majority of participants (68.3%) underestimated their risk for CRC. Only 26.8% correctly judged their life time risk while 5% overestimated their risk. Two thirds of participants (66%) were willing to pay 500 Jordanian Dinars (equivalent to 706 US$) in order to get a prompt colonoscopy if recommended by their physician, while 25.5% reported that they would rather wait for 6 months in order to get a free colonoscopy. Although the participants tended to underestimate their risk for CRC, they were mostly aware of CRC as a major cause of mortality and were willing to embrace the concept of CRC screening and bear the related financial costs. These findings about CRC awareness and propensity for screening provide a good foundation as the Jordanian health system moves forward with initiatives to promote CRC screening and prevention.

  19. More comprehensive discussion of CRC screening associated with higher screening.

    Science.gov (United States)

    Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

    2013-04-01

    Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

  20. Method for making graded I-III-VI.sub.2 semiconductors and solar cell obtained thereby

    Science.gov (United States)

    Devaney, Walter E.

    1987-08-04

    Improved cell photovoltaic conversion efficiencies are obtained by the simultaneous elemental reactive evaporation process of Mickelsen and Chen for making semiconductors by closer control of the evaporation rates and substrate temperature during formation of the near contact, bulk, and near junction regions of a graded I-III-VI.sub.2, thin film, semiconductor, such as CuInSe.sub.2 /(Zn,Cd)S or another I-III-VI.sub.2 /II-VI heterojunction.

  1. Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey.

    Science.gov (United States)

    Longhurst, H J; Zanichelli, A; Caballero, T; Bouillet, L; Aberer, W; Maurer, M; Fain, O; Fabien, V; Andresen, I

    2017-04-01

    Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P types I/II, respectively. © 2016 British Society for Immunology.

  2. Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

    Science.gov (United States)

    Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

    2017-03-14

    BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 - and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation.

  3. Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin.

    Science.gov (United States)

    Overman, Michael J; Morris, Van; Moinova, Helen; Manyam, Ganiraju; Ensor, Joe; Lee, Michael S; Eng, Cathy; Kee, Bryan; Fogelman, David; Shroff, Rachna T; LaFramboise, Thomas; Mazard, Thibault; Feng, Tian; Hamilton, Stanley; Broom, Bradley; Lutterbaugh, James; Issa, Jean-Pierre; Markowitz, Sanford D; Kopetz, Scott

    2016-10-11

    Hypermethylation of promoter CpG islands (CIMP) has been strongly implicated in chemotherapy resistance and is implicated in the pathogenesis of a subset of colorectal cancers (CRCs) termed CIMP-high. This phase I/II study in CRC (phase II portion restricted to CIMP-high CRC), treated fluoropyrimidine/oxaliplatin refractory patients with azacitidine (75 mg/m2/day subcutaneously D1-5) and CAPOX (capecitibine and oxaliplatin) every three weeks. Twenty-six patients (pts) were enrolled in this study: 15 pts (12 treated at MTD) in phase I and 11 pts in phase II. No dose limiting toxicities were observed. A total of 14 pts were CIMP-high. No responses were seen. CIMP-high status did not correlate with efficacy endpoints [stable disease (SD) or progression-free survival (PFS)] or baseline vimentin methylation level. Changes in vimentin methylation over time did not correlate with efficacy outcomes. Baseline methylated vimentin correlated with tumor volume (PCIMP-high pts, but no objective responses. Serum methylated vimentin may be associated with benefit from a regimen including a hypomethylation agent, although this study is not able to separate a potential prognostic or predictive role for the biomarker.

  4. Hereditary Colorectal Cancer (CRC Program in Latvia

    Directory of Open Access Journals (Sweden)

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  5. Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis.

    Science.gov (United States)

    Sethi, Manveen K; Thaysen-Andersen, Morten; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S; Packer, Nicolle H; Paik, Young-Ki; Hancock, William S; Fanayan, Susan

    2015-08-03

    Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR(+) CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR(-) tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

    Science.gov (United States)

    Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

    2015-01-01

    Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

  7. Status of the Olympus experiment at CRC

    Science.gov (United States)

    Rogers, David V.

    1992-01-01

    The status of the Olympus Propagation Experiment of the Communications Research Centre in Ottawa, Canada, is briefly summarized. Path attenuation measurements at multiple frequencies correlated with concurrent dual polarized radar data provide a unique method to investigate propagation effects. An experiment of this type is being implemented by the Communications Research Centre (CRC) on the grounds of the National Research Council of Canada in Ottawa. Beacon receivers monitor signals from the Olympus satellite at 12.5, 19.77, and 29.66 GHz at a path elevation angle of 14.2 deg. Sky noise radiometers operating near the same frequencies and pointed along the same path provide additional propagation information. A colocated dual-polarized 9.6-GHz radar probes the precipitation state on the path, permitting identification of precipitation regimes that cause the observed impairments. The Olympus experiment configuration is displayed pictorially. Information on path propagation phenomena can be deduced by correlating the radar, beacon, and sky noise data. Melting layer effects and propagation losses for higher time percentages are prime interests. Data collected by Diversitel Communications during equipment verification tests are presented.

  8. Pesan Sosial dalam Foto Jurnalistik (Analisis Semiotika dalam Buku ‘Jakarta Estetika Banal’, Bab I, III, V, dan VII

    Directory of Open Access Journals (Sweden)

    Jaka Priyo Nuswantara

    2014-01-01

    Full Text Available This study aims to determine the meaning of denotation and connotation, and social message in the book 'Aesthetics Jakarta Banal', Chapter I, III, V, and VII. The author uses the theory Semiotics of Roland Barthes. Where Semiotics of Roland Barthes uses two stages of analysis denotation and connotation. The research method used is a Roland Barthes semiotic analysis method on the basis that this study analyzes the messages conveyed in the book 'Aesthetics Jakarta Banal', which gives an explanation and overview of issues related to the formulation. Inferred outline text analysis results indicate that the social life of silence in the city with the concept of light to be seen. Of all the images examined, the object edges and political society into something dominant to be something that should be understood by the reader.

  9. A Novel Least Significant Bit First Processing Parallel CRC Circuit

    Directory of Open Access Journals (Sweden)

    Xiujie Qu

    2013-01-01

    Full Text Available In HDLC serial communication protocol, CRC calculation can first process the most or least significant bit of data. Nowadays most CRC calculation is based on the most significant bit (MSB first processing. An algorithm of the least significant bit (LSB first processing parallel CRC is proposed in this paper. Based on the general expression of the least significant bit first processing serial CRC, using state equation method of linear system, we derive a recursive formula by the mathematical deduction. The recursive formula is applicable to any number of bits processed in parallel and any series of generator polynomial. According to the formula, we present the parallel circuit of CRC calculation and implement it with VHDL on FPGA. The results verify the accuracy and effectiveness of this method.

  10. Mucin Expression in Colorectal Cancer (CRC): Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Niv, Yaron; Rokkas, Theodore

    2018-05-18

    A body of evidence has suggested that mucins play an important role in adhesion, invasion, and cancer metastasis. However, this evidence is scarce and sometimes confusing. We performed a systematic review and meta-analysis of available studies to better define the role of mucins in the behavior of colorectal cancer (CRC). Medical literature was searched through November 30, 2017, using suitable keywords. Pooled estimates, that is, odd ratios (ORs), were obtained using fixed or random-effects models, as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test and I values, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test and by the Egger regression test. A total of 2234 CRC patients were included in 12 studies, eligible for meta-analysis. There was a significant difference concerning total mucin expression between CRC patients and controls [pooled ORs (95% confidence interval)=8.156 (2.624-25.354), test for overall effect Z=3.627, PCRC, that is advanced stage versus localized disease [ORs (95% confidence interval)=2.724 (1.211-6.127), Z= 2.423, P=0.015], as opposed to MUC2 and MUC4. MUC1 is overexpressed in CRC tissue comparing with healthy mucosa, and may have a role in the neoplastic transformation and metastatic process. MUC2 has probably no role in carcinogenesis.

  11. How does the serrated polyp pathway alter CRC screening and surveillance?

    Science.gov (United States)

    Kahi, Charles J

    2015-03-01

    Screening and surveillance for colorectal cancer (CRC) reduces mortality through the detection of early-stage adenocarcinoma, and more importantly the detection and removal of premalignant polyps. While adenomas have historically been considered the most common and screening-relevant precursor lesions, there is accumulating evidence showing that the serrated pathway is an important contributor to CRC, and a disproportionate contributor to interval or postcolonoscopy CRC, particularly in the proximal colon. The serrated pathway is characterized by mutations in the BRAF gene, high levels of methylation of promoter CpG islands (CIMP-high), and the sessile serrated adenoma/polyp (SSA/P) is the most important precursor lesion. The study of serrated polyps has been complicated by evolving nomenclature, substantial variation among pathologists in the identification of SSA/Ps, high variability in endoscopic detection rates, and uncertainty regarding the relation to synchronous and metachronous colonic neoplasia. This paper presents an overview of the serrated polyp pathway and discusses its clinical implications including its impact on CRC screening.

  12. Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial

    International Nuclear Information System (INIS)

    Allal, Abdelkarim S.; Bieri, Sabine; Bruendler, Marie-Anne; Soravia, Claudio; Gertsch, Philippe; Bernier, Jacques; Morel, Philippe; Roth, Arnaud D.

    2002-01-01

    Purpose: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. Methods and Materials: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. Results: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located ≤6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). Conclusion: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a

  13. Upregulated STAT3 and RhoA signaling in colorectal cancer (CRC) regulate the invasion and migration of CRC cells.

    Science.gov (United States)

    Zhang, G-Y; Yang, W-H; Chen, Z

    2016-05-01

    We aimed to reveal the expression and activation of signal transducers and activators of transcription 3 (STAT3) and RhoA/Rho-associated coiled-coil forming kinase 1 (ROCK1) signaling in CRC tissues, and to investigate the regulatory role of STAT3 and RhoA signaling in the invasion and migration of colorectal cancer cells. We examined the expression of STAT3, RhoA and ROCK1 in CRC tissues with real-time PCR and Western blotting methods. And then we examined the interaction between STAT3 and RhoA/ROCK1 signaling in CRC HT-29 cells with gain-of-function and loss-of-function strategies. In addition, we determined the regulation by STAT3 and RhoA/ROCK1 on the invasion and migration of CRC HT-29 cells. Our study demonstrated a significant upregulation of RhoA and ROCK1 expression and STAT3-Y705 phosphorylation in 32 CRC specimens, compared to the 17 normal CRC tissues. Further study demonstrated there was a coordination between STAT3 and RhoA/Rock signaling in the HT-29 cells. Moreover, STAT3 knockdown or RhoA knockdown significantly repressed the migration and invasion in HT-29 cells and vice versa. STAT3 and RhoA signaling regulate the invasion and migration of CRC cells, implying the orchestrated and oncogenic roles of STAT3 and RhoA/ROCK1 signaling in CRC.

  14. Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

    Science.gov (United States)

    Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

    2011-04-01

    Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

  15. Seroprevalence of HTLV -I/II amongst Blood Donors in Osogbo ...

    African Journals Online (AJOL)

    Background: HTLV type I/II is a blood borne infection that can be transmitted via blood transfusion. Objective: To determine the seroprevalence of human T – lymphotropic virus among blood donors in Osogbo, Nigeria. Methods: Diagnosis of Human T. Lymphotropic virus antigen was carried out on 372 serum samples ...

  16. Interaction forces between salivary proteins and Streptococcus mutans with and without antigen I/II

    NARCIS (Netherlands)

    Xu, C.P.; Belt-Gritter, van de B.; Dijkstra, R.J.B.; Norde, W.; Mei, van der H.C.; Busscher, H.J.

    2007-01-01

    The antigen I/II family of surface proteins is expressed by oral streptococci, including Streptococcus mutans, and mediates specific binding to, among others, salivary films. The aim of this study was to investigate the interaction forces between salivary proteins and S. mutans with (LT11) and

  17. System applications CRC -Biomass + Coal; Aplicaciones Sistema CRC-Biomasa+Carbon

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    Main object of Phase I of the project is to analyse the technical-economic feasibility of the combined use of biomass and coal for power generation in the Spanish region of Andalusia, by means of new medium-size independent power plants or using biomass as supplementary fuel in existing large coal power plants, including: -Analysis and classification of biomass and coal resources in the region -Technical-economic study of conventional alternatives using the steam cycle -Analysis of efficiency improvement provided by advanced Rankine-cycle technologies, like the SMR cycle -Analysis of alternatives based on parallel combined cycles using gas turbines, including advanced solutions, like the EAPI and CRC-EAPI systems. -Description and evaluation of different biomass drying systems. -Description and evaluation of the three main biomass gasification systems currently under development: atmospheric direct, atmospheric indirect and pressurized. Main objects of Phase II of the project are to analyse a specific application of the EAPI system to a real cogeneration plant project and to analyse the application of the CRC2 system to a commercial supercritical power plant, including technical-economic study of both applications. (Author)

  18. Observations on Polar Coding with CRC-Aided List Decoding

    Science.gov (United States)

    2016-09-01

    TECHNICAL REPORT 3041 September 2016 Observations on Polar Coding with CRC-Aided List Decoding David Wasserman Approved for public release. SSC...described in [2, 3]. In FY15 and FY16 we used cyclic redundancy check (CRC)-aided polar list decoding [4]. Section 2 describes the basics of polar coding ...and gives details of the encoders and decoders we used. In the course of our research, we performed simulations of polar codes in hundreds of cases

  19. Polar Coding with CRC-Aided List Decoding

    Science.gov (United States)

    2015-08-01

    TECHNICAL REPORT 2087 August 2015 Polar Coding with CRC-Aided List Decoding David Wasserman Approved...list decoding . RESULTS Our simulation results show that polar coding can produce results very similar to the FEC used in the Digital Video...standard. RECOMMENDATIONS In any application for which the DVB-S2 FEC is considered, polar coding with CRC-aided list decod - ing with N = 65536

  20. Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers

    NARCIS (Netherlands)

    de Cuba, E. M. V.; Snaebjornsson, P.; Heideman, D. A. M.; van Grieken, N. C. T.; Bosch, L. J. W.; Fijneman, R. J. A.; Belt, E.; Bril, H.; Stockmann, H. B. A. C.; Hooijberg, E.; Punt, C. J. A.; Koopman, M.; Nagtegaal, I. D.; Coupé, V. H. M.; Carvalho, B.; Meijer, G. A.

    2016-01-01

    Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear

  1. Calorimetric comparison of the interactions between salivary proteins and Streptococcus mutans with and without antigen I/II

    NARCIS (Netherlands)

    Xu, C.P.; Belt-Gritter, van de B.; Busscher, H.J.; Mei, van der H.C.; Norde, W.

    2007-01-01

    Antigen I/II can be found on streptococcal cell surfaces and is involved in their interaction with salivary proteins. In this paper, we determine the adsorption enthalpies of salivary proteins to Streptococcus mutans LT11 and S. mutans IB03987 with and without antigen I/II, respectively, using

  2. Calorimetric comparison of the interactions between salivary proteins and Streptococcus mutans with and without antigen I/II

    NARCIS (Netherlands)

    Xu, Chun-Ping; Belt-Gritter, van de Betsy; Busscher, Henk J.; van der Mei, Henny C.; Norde, Willem

    2007-01-01

    Antigen I/II can be found on streptococcal cell surfaces and is involved in their interaction with salivary proteins. In this paper, we determine the adsorption enthalpies of salivary proteins to Streptococcus mutans LT 11 and S. mutans IB03987 with and without antigen I/II, respectively, using

  3. Effect of Crc and Hfq proteins on the transcription, processing, and stability of the Pseudomonas putida CrcZ sRNA.

    Science.gov (United States)

    Hernández-Arranz, Sofía; Sánchez-Hevia, Dione; Rojo, Fernando; Moreno, Renata

    2016-12-01

    In Pseudomonas putida, the Hfq and Crc proteins regulate the expression of many genes in response to nutritional and environmental cues, by binding to mRNAs that bear specific target motifs and inhibiting their translation. The effect of these two proteins is antagonized by the CrcZ and CrcY small RNAs (sRNAs), the levels of which vary greatly according to growth conditions. The crcZ and crcY genes are transcribed from promoters PcrcZ and PcrcY, respectively, a process that relies on the CbrB transcriptional activator and the RpoN σ factor. Here we show that crcZ can also be transcribed from the promoter of the immediate upstream gene, cbrB, a weak constitutive promoter. The cbrB-crcZ transcript was processed to render a sRNA very similar in size to the CrcZ produced from promoter PcrcZ The processed sRNA, termed CrcZ*, was able to antagonize Hfq/Crc because, when provided in trans, it relieved the deregulated Hfq/Crc-dependent hyperrepressing phenotype of a ΔcrcZΔcrcY strain. CrcZ* may help in attaining basal levels of CrcZ/CrcZ* that are sufficient to protect the cell from an excessive Hfq/Crc-dependent repression. Since a functional sRNA can be produced from PcrcZ, an inducible strong promoter, or by cleavage of the cbrB-crcZ mRNA, crcZ can be considered a 3'-untranslated region of the cbrB-crcZ mRNA. In the absence of Hfq, the processed form of CrcZ was not observed. In addition, we show that Crc and Hfq increase CrcZ stability, which supports the idea that these proteins can form a complex with CrcZ and protect it from degradation by RNases. © 2016 Hernández-Arranz et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  4. A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Suenaga M

    2015-03-01

    Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Keisho Chin,1 Toshiharu Yamaguchi2 1Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan Background: Triweekly capecitabine plus irinotecan (XELIRI is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI in metastatic colorectal cancer (mCRC because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV as second-line chemotherapy for mCRC.Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin and BV and had a UGT1A1 genotype of wild-type or heterozygous for UGT1A1*6 or *28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5 mg/kg on day 1 every 2 weeks. The phase I study consisted of two steps (irinotecan 150 and 180 mg/m2, and dose-limiting toxicity was assessed during the first treatment cycle. The primary endpoint of the phase II study was progression-free survival (PFS.  Results: The recommended dose of irinotecan was determined to be 180 mg/m2 in the phase I study. Between November 2010 and August 2013, 44 patients were enrolled in phase II. The patients’ characteristics were as follows (N=44: median age, 60 years (range 32–80; male/female, 21/23; and UGT1A1 wild-type/heterozygous, 29/15. The median PFS was 6.8 months (95% confidence interval, 5.3–8.2 months, and the primary endpoint was met. Median overall survival was 18.3 months. The response rate was 22.7%. There was no significant difference in PFS or overall survival according to UGT1A1 status. Grade 3 or higher adverse events were mainly neutropenia in six

  5. Fault isolation through no-overhead link level CRC

    Science.gov (United States)

    Chen, Dong; Coteus, Paul W.; Gara, Alan G.

    2007-04-24

    A fault isolation technique for checking the accuracy of data packets transmitted between nodes of a parallel processor. An independent crc is kept of all data sent from one processor to another, and received from one processor to another. At the end of each checkpoint, the crcs are compared. If they do not match, there was an error. The crcs may be cleared and restarted at each checkpoint. In the preferred embodiment, the basic functionality is to calculate a CRC of all packet data that has been successfully transmitted across a given link. This CRC is done on both ends of the link, thereby allowing an independent check on all data believed to have been correctly transmitted. Preferably, all links have this CRC coverage, and the CRC used in this link level check is different from that used in the packet transfer protocol. This independent check, if successfully passed, virtually eliminates the possibility that any data errors were missed during the previous transfer period.

  6. Colorectal cancer diagnosis in 2012: A new focus for CRC prevention--more serration, less inflammation

    NARCIS (Netherlands)

    East, James E.; Dekker, Evelien

    2013-01-01

    Knowledge of colorectal cancer (CRC) risks has been rebalanced in 2012. The 'serrated pathway' to CRC, exemplified by serrated polyposis syndrome, emphasizes the importance of serrated lesions. The dogma that patients with IBD are at high risk of CRC, however, might be overstated; optimizing CRC

  7. Dynamic fracture initiation in brittle materials under combined mode I/II loading

    International Nuclear Information System (INIS)

    Nakano, M.; Kishida, K.; Yamauchi, Y.; Sogabe, Y.

    1994-01-01

    A new test method has been developed to measure the resistance of dynamic fracture initiation in brittle materials under combined mode I/II loadings. The Brazilian disks with center-cracks have been fractured under oblique impact loadings in diametral-compression. The dynamic stress intensity factors of mode I and II are evaluated from the superposition integrals of the step response functions for the cracked disk. The experimental results are presented to elucidate the influence of loading rate on the combined mode fracture toughness for ceramics and glasses. (orig.)

  8. MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in colorectal cancer (CRC).

    Science.gov (United States)

    Tong, Feng; Ying, Youhua; Pan, Haihua; Zhao, Wei; Li, Hongchen; Zhan, Xiaoli

    2018-01-17

    MicroRNAs (miRNAs) have an important role in the regulation of tumor development and metastasis. In this study, we investigated the clinical and prognostic value as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR-466 expression was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). mRNA and protein levels of cyclin D1, apoptosis regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT-PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466 mimics or negative control miRNA. Effects of miR-466 on SW-620 cell proliferation, cell cycle and apoptosis, and invasion were investigated using CCK-8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was significantly downregulated in tumor tissues compared to matched adjacent non-tumor tissues. Low expression of miR-466 was significantly correlated with the tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant metastasis. The overall survival of CRC patients with low miR-466 expression was significantly shorter compared to high-miR-466 expression group (log-rank test: p = 0.0103). Multivariate analysis revealed that low miR-466 expression was associated with poor prognosis in CRC patients. The ectopic expression of miR-466 suppressed cell proliferation and migration/invasion, as well as induced G0/G1 arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466 decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as a suppressor miRNA in CRC and may be used as a prognostic factor in these patients.

  9. Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H).

    Science.gov (United States)

    Goldstein, J; Tran, B; Ensor, J; Gibbs, P; Wong, H L; Wong, S F; Vilar, E; Tie, J; Broaddus, R; Kopetz, S; Desai, J; Overman, M J

    2014-05-01

    The microsatellite instability-high (MSI-H) phenotype, present in 15% of early colorectal cancer (CRC), confers good prognosis. MSI-H metastatic CRC is rare and its impact on outcomes is unknown. We describe survival outcomes and the impact of chemotherapy, metastatectomy, and BRAF V600E mutation status in the largest reported cohort of MSI-H metastatic colorectal cancer (CRC). A retrospective review of 55 MSI-H metastatic CRC patients from two institutions, Royal Melbourne Hospital (Australia) and The University of Texas MD Anderson Cancer Center (United States), was conducted. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Median age was 67 years (20-90), 58% had poor differentiation, and 45% had stage IV disease at presentation. Median overall survival (OS) from metastatic disease was 15.4 months. Thirteen patients underwent R0/R1 metastatectomies, with median OS from metastatectomy 33.8 months. Thirty-one patients received first-line systemic chemotherapy for metastatic disease with median OS from the start of chemotherapy 11.5 months. No statistically significant difference in progression-free survival or OS was seen between fluoropyrimidine, oxaliplatin, or irinotecan based chemotherapy. BRAF V600E mutation was present in 14 of 47 patients (30%). BRAF V600E patients demonstrated significantly worse median OS; 10.1 versus 17.3 months, P = 0.03. In multivariate analyses, BRAF V600E mutants had worse OS (HR 4.04; P = 0.005), while patients undergoing metastatectomy (HR 0.11; P = CRC do not appear to have improved outcomes. BRAF V600E mutation is a poor prognostic factor in MSI-H metastatic CRC.

  10. Rock Fracture Toughness Study Under Mixed Mode I/III Loading

    Science.gov (United States)

    Aliha, M. R. M.; Bahmani, A.

    2017-07-01

    Fracture growth in underground rock structures occurs under complex stress states, which typically include the in- and out-of-plane sliding deformation of jointed rock masses before catastrophic failure. However, the lack of a comprehensive theoretical and experimental fracture toughness study for rocks under contributions of out-of plane deformations (i.e. mode III) is one of the shortcomings of this field. Therefore, in this research the mixed mode I/III fracture toughness of a typical rock material is investigated experimentally by means of a novel cracked disc specimen subjected to bend loading. It was shown that the specimen can provide full combinations of modes I and III and consequently a complete set of mixed mode I/III fracture toughness data were determined for the tested marble rock. By moving from pure mode I towards pure mode III, fracture load was increased; however, the corresponding fracture toughness value became smaller. The obtained experimental fracture toughness results were finally predicted using theoretical and empirical fracture models.

  11. The "Interval Walking in Colorectal Cancer" (I-WALK-CRC) study: Design, methods and recruitment results of a randomized controlled feasibility trial.

    Science.gov (United States)

    Banck-Petersen, Anna; Olsen, Cecilie K; Djurhuus, Sissal S; Herrstedt, Anita; Thorsen-Streit, Sarah; Ried-Larsen, Mathias; Østerlind, Kell; Osterkamp, Jens; Krarup, Peter-Martin; Vistisen, Kirsten; Mosgaard, Camilla S; Pedersen, Bente K; Højman, Pernille; Christensen, Jesper F

    2018-03-01

    Low physical activity level is associated with poor prognosis in patients with colorectal cancer (CRC). To increase physical activity, technology-based platforms are emerging and provide intriguing opportunities to prescribe and monitor active lifestyle interventions. The "Interval Walking in Colorectal Cancer"(I-WALK-CRC) study explores the feasibility and efficacy a home-based interval-walking intervention delivered by a smart-phone application in order to improve cardio-metabolic health profile among CRC survivors. The aim of the present report is to describe the design, methods and recruitment results of the I-WALK-CRC study.Methods/Results: The I-WALK-CRC study is a randomized controlled trial designed to evaluate the feasibility and efficacy of a home-based interval walking intervention compared to a waiting-list control group for physiological and patient-reported outcomes. Patients who had completed surgery for local stage disease and patients who had completed surgery and any adjuvant chemotherapy for locally advanced stage disease were eligible for inclusion. Between October 1st , 2015, and February 1st , 2017, 136 inquiries were recorded; 83 patients were eligible for enrollment, and 42 patients accepted participation. Age and employment status were associated with participation, as participants were significantly younger (60.5 vs 70.8 years, P CRC survivors was feasible but we aim to better the recruitment rate in future studies. Further, the study clearly favored younger participants. The I-WALK-CRC study will provide important information regarding feasibility and efficacy of a home-based walking exercise program in CRC survivors.

  12. CRC Credential Attainment by State Vocational Rehabilitation Counselors

    Science.gov (United States)

    Harpster, Anna M.; Byers, Katherine L.; Harris, LaKeisha L.

    2011-01-01

    This study examines 137 state vocational rehabilitation (VR) counselors' perceptions of the value of having the Certified Rehabilitation Counselor (CRC) credential. While almost 53% of this sample included persons who were certified, the majority who were not indicated that the two major reasons for not currently having this designation were: (a)…

  13. Phase I/II trial of concurrent use of S-1 and radiation therapy for T2 glottic cancer

    International Nuclear Information System (INIS)

    Nakayama, Meijin; Hayakawa, Kazushige; Okamoto, Makito; Niibe, Yuzuru; Ishiyama, Hiromichi; Kotani, Shouko

    2010-01-01

    A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events. In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m 2 , for a total daily dose of 80 mg/m 2 . The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation. Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2). The use of S-1 at 80 mg/m 2 per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life. (author)

  14. Genetic diagnosis of high-penetrance susceptibility for colorectal cancer (CRC) is achievable for a high proportion of familial CRC by exome sequencing.

    Science.gov (United States)

    Chubb, Daniel; Broderick, Peter; Frampton, Matthew; Kinnersley, Ben; Sherborne, Amy; Penegar, Steven; Lloyd, Amy; Ma, Yussanne P; Dobbins, Sara E; Houlston, Richard S

    2015-02-10

    Knowledge of the contribution of high-penetrance susceptibility to familial colorectal cancer (CRC) is relevant to the counseling, treatment, and surveillance of CRC patients and families. To quantify the impact of germline mutation to familial CRC, we sequenced the mismatch repair genes (MMR) APC, MUTYH, and SMAD4/BMPR1A in 626 early-onset familial CRC cases ascertained through a population-based United Kingdom national registry. In addition, we evaluated the contribution of mutations in the exonuclease domain (exodom) of POLE and POLD1 genes that have recently been reported to confer CRC risk. Overall mutations (pathogenic, likely pathogenic) in MMR genes make the highest contribution to familial CRC (10.9%). Mutations in the other established CRC genes account for 3.3% of cases. POLE/POLD1 exodom mutations were identified in three patients with family histories consistent with dominant transmission of CRC. Collectively, mutations in the known genes account for 14.2% of familial CRC (89 of 626 cases; 95% CI = 11.5, 17.2). A genetic diagnosis is feasible in a high proportion of familial CRC. Mainstreaming such analysis in clinical practice should enable the medical management of patients and their families to be optimized. Findings suggest CRC screening of POLE and POLD1 mutation carriers should be comparable to that afforded to those at risk of HNPCC. Although the risk of CRC associated with unexplained familial CRC is in general moderate, in some families the risk is substantive and likely to be the consequence of unidentified genes, as exemplified by POLE and POLD1. Our findings have utility in the design of genetic analyses to identify such novel CRC risk genes. © 2015 by American Society of Clinical Oncology.

  15. The Phase I/II BNCT Trials at the Brookhaven medical research reactor: Critical considerations

    International Nuclear Information System (INIS)

    Diaz, A.Z.

    2001-01-01

    A phase I/II clinical trial of boronophenylalanine-fructose (BPA-F) mediated boron neutron capture therapy (BNCT) for Glioblastoma Multiforme (GBM) was initiated at Brookhaven National Laboratory (BNL) in 1994. Many critical issues were considered during the design of the first of many sequential dose escalation protocols. These critical issues included patient selection criteria, boron delivery agent, dose limits to the normal brain, dose escalation schemes for both neutron exposure and boron dose, and fractionation. As the clinical protocols progressed and evaluation of the tolerance of the central nervous system (CNS) to BPA-mediated BNCT at the BMRR continued new specifications were adopted. Clinical data reflecting the progression of the protocols will be presented to illustrate the steps taken and the reasons behind their adoption. (author)

  16. Hypoactivation of reward motivational system in patients with newly diagnosed hypertension grade I-II.

    Science.gov (United States)

    Aftanas, L I; Brak, I V; Gilinskaya, O M; Korenek, V V; Pavlov, S V; Reva, N V

    2014-08-01

    In patients with newly diagnosed untreated grade I-II hypertension, EEG oscillations were recorded under conditions activation of the two basic motivational systems, defensive motivational system and positive reinforcement system, evoked by recall of personally meaningful emotional events. The 64-channel EEG and cardiovascular reactivity (beat-by-beat technology) were simultaneously recorded. At rest, hypertensive patients had significantly reduced platelet serotonin concentrations in comparison with healthy individuals. The patients experiencing emotional activation were characterized by significantly lower intensity of positive emotions associated with more pronounced suppression of EEG activity in the delta (2-4 Hz) and theta (ranges of frequency 4-6 and 6-8 Hz) oscillators in the parieto-occipital cortex (zones P and PO) in both hemispheres of the brain. The findings attest to insufficient function of the brain serotonin system and hypoactivation of the reward/reinforcement system in patients with primary hypertension.

  17. Clinical effects of Angelica dahurica dressing on patients with I-II phase pressure sores.

    Science.gov (United States)

    Gong, Fen; Niu, Junzhi; Pei, Xing

    2016-11-02

    Angelica dahurica is a well-known traditional Chinese Medicine (TCM), while little information is available about its effects on pressure sores. We aimed to investigate the clinical effect of Angelica dahurica on patients with I-II phase pressure sores, as well as the underlying mechanism. Patients (n = 98) with phase I and phase II pressure sores were enrolled and randomly assigned to control and treated groups. In addition to holistic nursing, patients in the control group received compound clotrimazole cream, while patients in the treated group received continuous 4 weeks of external application of Angelica dahurica dressing. Therapeutic effect was recorded, along with the levels of interleukin-8 (IL-8), epidermal growth factor (EGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF). Besides, HaCaT cells were cultured with different concentrations of Angelica dahurica, and then cell viability, clone formation numbers, cell cycle, and levels of cyclin D1 and cyclin-dependent kinase (CDK) 2 were determined. The total effective rate in the treated group was significantly higher than in the control group. Levels of IL-8, EGF, TGF-β, and VEGF were statistically increased by Angelica dahurica. In addition, the cell viability and clone formation numbers were significantly upregulated by Angelica dahurica in a dose-dependent manner. Also, the percentage of cells in G0/G1 phase, and levels of cyclin D1 and CDK2 were significantly elevated. Our results suggest that Angelica dahurica may provide an effective clinical treatment for I-II phase pressure sores.

  18. Preliminary results of a phase I/II study of HDR brachytherapy alone for T1/T2 breast cancer

    International Nuclear Information System (INIS)

    Wazer, David E.; Berle, Lisa; Graham, Roger; Chung, Maureen; Rothschild, Janice; Graves, Theresa; Cady, Blake; Ulin, Kenneth; Ruthazer, Robin; DiPetrillo, Thomas A.

    2002-01-01

    Purpose: To investigate the feasibility, toxicity, cosmetic outcome, and local control of high-dose-rate (HDR) brachytherapy alone without whole breast external beam irradiation for early-stage breast carcinoma. Methods and Materials: Between June 1997 and August 1999, 32 women diagnosed with a total of 33 AJCC Stage I/II breast carcinomas underwent surgical breast excision and postoperative irradiation using HDR brachytherapy interstitial implantation as part of a multi-institutional clinical Phase I/II protocol. Eligible patients included those with T1, T2, N0, N1 (≤3 nodes positive), and M0 tumors of nonlobular histologic features with negative surgical margins, no extracapsular lymph node extension, and a negative postexcision mammogram. Brachytherapy catheters were placed at the initial excision, reexcision, or either sentinel or full-axillary sampling. Direct visualization, surgical clips, and ultrasound and/or CT scan assisted in the delineation of the target volume, defined as the excision cavity plus a 2-cm margin. High-activity 192 Ir (3-10 Ci) was used to deliver 340 cGy/fraction, 2 fractions/d, for 5 consecutive days, to a total dose of 34 Gy to the target volume. Source position and dwell times were calculated using standard volume optimization techniques. Results: The median follow-up of all patients was 33 months, and the mean patient age was 63 years. The mean tumor size was 1.3 cm, and 55% had an extensive intraductal component. Three patients had positive axillary nodes. Two patients experienced moderate perioperative pain that required narcotic analgesics. No peri- or postoperative infections occurred. No wound healing problems and no significant skin reactions related to the implant developed. The Radiation Therapy Oncology Group late radiation morbidity scoring scheme was applied to the entire 33-case cohort. In the assessment of the skin, 30 cases were Grade 0-1 and 3 cases were Grade 2. Subcutaneous toxicity was scored as 11 patients with

  19. Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab.

    Science.gov (United States)

    Weber, Jeffrey; Gibney, Geoffrey; Kudchadkar, Ragini; Yu, Bin; Cheng, Pingyan; Martinez, Alberto J; Kroeger, Jodie; Richards, Allison; McCormick, Lori; Moberg, Valerie; Cronin, Heather; Zhao, Xiuhua; Schell, Michael; Chen, Yian Ann

    2016-04-01

    The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3-4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%-41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naïve and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3-4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%-82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3-4 immune-related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab. ©2016 American Association for Cancer Research.

  20. Phase I/II trial of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Fujii, Masato; Tsukuda, Mamoru; Kubota, Akira; Kida, Akinori; Okami, Kenji

    2003-01-01

    Docetaxel (DOC) is one of the most promising drugs for head and neck cancer (HNSCC). A phase I/II trial of concurrent DOC and radiation for HNSCC was conducted to estimate the recommended dose schedule of DOC, and then to evaluate the therapeutic benefit based on the response and toxicity of the recommended dose schedule. Patients with squamous cell carcinomas of the head and neck were entered. All the patients received radiation with 2.0 Gy single daily fractions up to 60 Gy. DOC was administered weekly for 6 consecutive weeks during radiotherapy. Dose-limiting toxicities, grade 3/4 mucositis and grade 3 pain, manifested in four patients in level 2, and that dose of DOC, 15 mg/m 2 , was considered the maximum tolerated dose (MTD). The recommended dose was decided as 10 mg/m 2 . The phase II study was conducted using DOC at 10 mg/m 2 . Thirty-nine patients with stage II, III or IV were registered, and 35 patients were eligible, 32 patients were evaluable for the response and 34 patients for the toxicity. The overall response rate was 96.9%. The prognoses of the complete response (CR) patients were statistically better than for the partial response (PR) patients. Grade 3 or 4 adverse events consisted of lymphopenia in 64.7%, mucositis in 41.2% and anorexia in 20.6% of the patients. Thirty-two of the 35 eligible patients showed high compliance of over 90%, and their toxicities were manageable. Even low-dose DOC shows a strong effect on HNSCC in combination with radiation, with high survival rates in CR patients. The effect on survival will be assessed by further follow-up. (author)

  1. A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

    Science.gov (United States)

    Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

    2016-08-17

    This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

  2. 29 CFR 37.84 - What happens if CRC does not have jurisdiction over a complaint?

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true What happens if CRC does not have jurisdiction over a complaint? 37.84 Section 37.84 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE... Procedures § 37.84 What happens if CRC does not have jurisdiction over a complaint? If CRC does not have...

  3. 12 CFR 617.7310 - What is the review process of the CRC?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is the review process of the CRC? 617.7310... on Applications; Review of Credit Decisions § 617.7310 What is the review process of the CRC? (a) How will an applicant or borrower know when the CRC will consider the review request? The qualified lender...

  4. 29 CFR 37.38 - What information must grant applicants and recipients provide to CRC?

    Science.gov (United States)

    2010-07-01

    ... provide to CRC? 37.38 Section 37.38 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE... information must grant applicants and recipients provide to CRC? In addition to the information which must be collected, maintained, and, upon request, submitted to CRC under § 37.37: (a) Each grant applicant and...

  5. 29 CFR 37.88 - Who may contact CRC about a complaint?

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Who may contact CRC about a complaint? 37.88 Section 37.88... PROVISIONS OF THE WORKFORCE INVESTMENT ACT OF 1998 (WIA) Compliance Procedures § 37.88 Who may contact CRC... contact CRC for information about the complaint. The Director will determine what information, if any...

  6. Treatment of large stage I-II lung tumors using stereotactic body radiotherapy (SBRT): Planning considerations and early toxicity

    International Nuclear Information System (INIS)

    Ong, Chin Loon; Palma, David; Verbakel, Wilko F.A.R.; Slotman, Ben J.; Senan, Suresh

    2010-01-01

    Purpose: To study the dosimetric predictors of early clinical toxicity following SBRT in patients with lung tumors and planning target volumes (PTV) exceeding 80 cm 3 . Methods: Eighteen consecutive patients who were treated using volumetric modulated arc therapy (RapidArc TM ) were assessed. All were either unfit or refused to undergo surgery or chemoradiotherapy. PTV planning objectives were as used in the ROSEL study protocol. Clinical toxicity was scored using Common Toxicity Criteria AE4.0. Lung volumes receiving 5, 10, 15, and 20 Gy (V 5 , V 10 , V 15 and V 20 ) and mean lung dose were assessed and correlated to symptomatic radiation pneumonitis (RP). Results: Median age, age-adjusted Charlson-comorbidity score and PTV size were 74, 7.5 and 137 cm 3 , respectively. At a median follow-up of 12.8 months, 8 deaths were recorded: 5 arising from comorbidity, 2 were potentially treatment-related and 1 had local recurrence. RP was reported in 5 patients (grade 2 in 3 and grade 3 in 2). All RP occurred in plans without a high priority optimization objective on contralateral lung. Acute RP was best predicted by contralateral lung V 5 (p 80 cm 3 , the contralateral lung V 5 best predicts RP. Limiting contralateral lung V 5 to <26% may reduce acute toxicity.

  7. Quality of Sleep and Related Factors During Chemotherapy in Patients with Stage I/II Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hsiao-Hsuan Kuo

    2006-01-01

    Conclusion: The study showed poor sleep quality and daytime sleepiness in patients with breast cancer during the active phase of chemotherapy. Chemotherapy may bring symptom distress to patients and adversely influence sleep quality.

  8. Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer

    Science.gov (United States)

    2013-01-31

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  9. Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.

    Science.gov (United States)

    Thomas, A L; Cox, G; Sharma, R A; Steward, W P; Shields, F; Jeyapalan, K; Muller, S; O'Byrne, K J

    2000-12-01

    The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.

  10. Mixed-mode I/III fracture toughness of a ferritic/martensitic stainless steel

    International Nuclear Information System (INIS)

    Li, Huaxin; Jones, R.H.; Gelles, D.S.; Hirth, J.P.

    1993-10-01

    The critical J-integrals of mode I (J IC ), mixed-mode I/III (J MC ), and mode III (J IIIC ) were examined for a ferritic stainless steel (F-82H) at ambient temperature. A determination of J MC was made using modified compact-tension specimens. Different ratios of tension/shear stress were achieved by varying the principal axis of the crack plane between 0 and 55 degrees from the load line. Results showed that J MC and tearing modulus (T M ) values varied with the crack angles and were lower than their mode I and mode III counterparts. Both the minimum J MC and T M values occurred at a crack angle between 40 and 50 degrees, where the load ratio of σ i /σ iii was 1.2 to 0.84. The J min was 240 Kj/M 2 , and ratios of J IC /J min and J IIIC /J min were 2.1 and 1.9, respectively. The morphology of fracture surfaces was consistent with the change of J MC and T M values. While the upper shelf-fracture toughness of F-82H depends on loading mode, the J min remains very high. Other important considerations include the effect of mixed-mode loading on the DBT temperature, and effects of hydrogen and irradiation on J min

  11. Concurrent chemoradiotherapy in locally advanced carcinoma of the uterine cervix: a phase I/II prospective study

    International Nuclear Information System (INIS)

    Kang, One Chul; Choi, Eun Kyung; Chung, Weon Kuu; Kim, Jong Hoon; Chang, Hye Sook; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun; Mok, Jung Eun; Lee, Moo Song

    1998-01-01

    Prospective, single arm. Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. From May 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The international Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4, 140-5, 040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/m 2 /day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/m 2 /dy intravenous bolus for 3 days, day 1-3, 29-31) administered starting on day 1 of 1 of RT. The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52% and 64%, respectively. The 5-year actuarial survival for stage IIB and II+IVA patients were 58% and 36%, respectively. The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71% and 46%, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9% (19/68): local failure in 5.9% (4/68), distant metastasis in 10.3% (7/68) and both in 11.8% (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment, the complete response rate was 78% (50/64). Concurrent chemoradiation appear to be a

  12. Revision of Primary I-III Science Curriculum in Somalia. African Studies in Curriculum Development & Evaluation No. 83.

    Science.gov (United States)

    Abdi, Ahmed Ali

    This study was designed to evaluate: (1) the content of the primary I-III science curriculum in Somalia; (2) the instructional materials that back up the content and methodologies; and (3) the professional competence of the teachers in charge of teaching this subject. Data were collected by means of a questionnaire, observations, and unstructured…

  13. Identification of sodium channel isoforms that mediate action potential firing in lamina I/II spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Smith Paula L

    2011-09-01

    Full Text Available Abstract Background Voltage-gated sodium channels play key roles in acute and chronic pain processing. The molecular, biophysical, and pharmacological properties of sodium channel currents have been extensively studied for peripheral nociceptors while the properties of sodium channel currents in dorsal horn spinal cord neurons remain incompletely understood. Thus far, investigations into the roles of sodium channel function in nociceptive signaling have primarily focused on recombinant channels or peripheral nociceptors. Here, we utilize recordings from lamina I/II neurons withdrawn from the surface of spinal cord slices to systematically determine the functional properties of sodium channels expressed within the superficial dorsal horn. Results Sodium channel currents within lamina I/II neurons exhibited relatively hyperpolarized voltage-dependent properties and fast kinetics of both inactivation and recovery from inactivation, enabling small changes in neuronal membrane potentials to have large effects on intrinsic excitability. By combining biophysical and pharmacological channel properties with quantitative real-time PCR results, we demonstrate that functional sodium channel currents within lamina I/II neurons are predominantly composed of the NaV1.2 and NaV1.3 isoforms. Conclusions Overall, lamina I/II neurons express a unique combination of functional sodium channels that are highly divergent from the sodium channel isoforms found within peripheral nociceptors, creating potentially complementary or distinct ion channel targets for future pain therapeutics.

  14. Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs.

    Science.gov (United States)

    Sun, Xiangwei; Hu, Yingying; Zhang, Liang; Hu, Changyuan; Guo, Gangqiang; Mao, Chenchen; Xu, Jianfeng; Ye, Sisi; Huang, Guanli; Xue, Xiangyang; Guo, Aizhen; Shen, Xian

    2016-01-01

    Colorectal cancer (CRC) is one of the deadliest tumours, but its pathogenesis remains unclear. The involvement of differentially expressed long non-coding RNAs (lncRNAs) in CRC tumorigenesis makes them suitable tumour biomarkers. Here, we screened 150 cases of CRC and 85 cases of paracancerous tissues in the GEO database for differentially expressed lncRNAs. The levels of lncRNA candidates in 84 CRC and paracancerous tissue samples were validated by qRT-PCR and their clinical significance was analyzed. We identified 15 lncRNAs with differential expression in CRC tumours; among them, AK098081 was significantly up-regulated, whereas AK025209, BC040303, BC037331, AK026659, and CR749831 were down-regulated in CRC. In a receiver operating characteristic curve analysis, the area under the curve for the six lncRNAs was 0.914. High expression of AK098081 and low expression of BC040303, CR749831, and BC037331 indicated poor CRC differentiation. CRC patients with lymph node metastasis had lower expression of BC037331. In addition, the group with high AK098081 expression presented significantly lower overall survival and disease-free survival rates than the low-expression group, confirming AK098081 as an independent risk factor for CRC patients. In conclusion, we have identified multiple CRC-associated lncRNAs from microarray expression profiles that can serve as novel biomarkers for the diagnosis and prognosis of CRC.

  15. A significant increase in the pepsinogen I/II ratio is a reliable biomarker for successful Helicobacter pylori eradication.

    Directory of Open Access Journals (Sweden)

    Hiroki Osumi

    Full Text Available Helicobacter pylori (H. pylori eradication is usually assessed using the 13C-urea breath test (UBT, anti-H. pylori antibody and the H. pylori stool antigen test. However, a few reports have used pepsinogen (PG, in particular, the percentage change in the PG I/II ratio. Here, we evaluated the usefulness of the percentage changes in serum PG I/II ratios for determining the success of eradication therapy for H. pylori.In total, 650 patients received eradication therapy from October 2008 to March 2013 in our Cancer Institute Hospital. We evaluated the relationship between H. pylori eradication and percentage changes in serum PG I/II ratios before and 3 months after treatment with CLEIA® (FUJIREBIO Inc, Tokyo, Japan. The gold standard of H. pylori eradication was defined as negative by the UBT performed 3 months after completion of eradication treatment. Cut-off values for percentage changes in serum PG I/II ratios were set as +40, +25 and +10% when the serum PG I/II ratio before treatment was below 3.0, above 3.0 but below 5.0 and 5.0 or above, respectively.Serum PG I and PG II levels were measured in 562 patients with H. pylori infection before and after eradication therapy. Eradication of H. pylori was achieved in 433 patients studied (77.0%. The ratios of first, second, third-line and penicillin allergy eradication treatment were 73.8% (317/429, 88.3% (99/112, 75% (12/16 and 100% (5/5, respectively. An increasing percentage in the serum levels of the PG I/II ratios after treatment compared with the values before treatment clearly distinguished success from failure of eradication (108.2±57.2 vs. 6.8±30.7, p<0.05. Using the above cut-off values, the sensitivity, specificity and validity for determination of H. pylori were 93.1, 93.8 and 93.2%, respectively.In conclusion, the percentage changes in serum PG I/II ratios are useful as evaluation criteria for assessing the success of eradication therapy for H. pylori.

  16. Radiation therapy for ocular choroidal neovascularization (phase I/II study): preliminary report

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Ogura, Yuichiro; Ngata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

    1997-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angioid streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well-demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the sub retinal neovascular membranes in CNV. We conducted a Phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Methods and Materials: Between April, 1994 and July, 1995, 36 patients with choroidal neovascularization (34 with ARMD and 2 with angioid streaks) were treated with radiation therapy. Treatment planning was performed using a CT simulator that enables real-time treatment planning from multiple CT slices. The clinical target volume that included the macula and optic disc received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions/2 weeks (last 18 eyes). All eyes were irradiated with a single lateral 6 MV photon beam, angled 10 degrees posteriorly to exclude the ipsilateral lens and the contralateral eye from the radiation field. The ipsilateral lens was irradiated with less than 10% of the total reference dose. The field size averaged 3.0 x 2.5 cm. Records of the 17 eyes with CNV referred to our hospital in 1993, which satisfied the eligibility criteria for this study, were retrospectively analyzed for comparison. Results: There was no significant acute morbidity. All patients were followed regularly by both ophthalmologists and radiation oncologists. Cataract formation after 1 year of the treatment was observed in one patient who had received a dose of 20 Gy. One patient who had received 20 Gy complained of transient dry-eye sensation 2 months after treatment, but this had disappeared spontaneously by the fourth month. The subjective symptoms, visual acuity, and size of the neovascular membrane were evaluated at 6 and 12 months after treatment in each patient. In the group of patients irradiated with 10 Gy and with 20 Gy, respectively, subjective symptoms improved in five and seven eyes, did not change in seven and four eyes, and deteriorated in six and six eyes at 12 months. Although visual acuity was significantly decreased in the control group, the patients in both irradiated groups did not show such a decrease in visual acuity. The size of the neovascular membrane in the control group progressed significantly. However, the patients in the 20 Gy group showed significant regression of the membrane, although those in the 10 Gy group showed no significant change in size. Conclusion: This Phase I/II study including a dose escalation study showed that radiation therapy seems to be useful for CNV. The dose of 20 Gy in 10 fractions was more useful in treating neovascular membranes than the dose of 10 Gy in five fractions. These results have encouraged us to start a multicenter randomized prospective study of the treatment of CNV with radiation therapy

  17. Uncertainty and sensitivity studies supporting the interpretation of the results of TVO I/II PRA

    International Nuclear Information System (INIS)

    Holmberg, J.

    1992-01-01

    A comprehensive Level 1 probabilistic risk assessment (PRA) has been performed for the TVO I/II nuclear power units. As a part of the PRA project, uncertainties of risk models and methods were systematically studied in order to describe them and to demonstrate their impact by way of results. The uncertainty study was divided into two phases: a qualitative and a quantitative study. The qualitative study contained identification of uncertainties and qualitative assessments of their importance. The PRA was introduced, and identified assumptions and uncertainties behind the models were documented. The most significant uncertainties were selected by importance measures or other judgements for further quantitative studies. The quantitative study included sensitivity studies and propagation of uncertainty ranges. In the sensitivity studies uncertain assumptions or parameters were varied in order to illustrate the sensitivity of the models. The propagation of the uncertainty ranges demonstrated the impact of the statistical uncertainties of the parameter values. The Monte Carlo method was used as a propagation method. The most significant uncertainties were those involved in modelling human interactions, dependences and common cause failures (CCFs), loss of coolant accident (LOCA) frequencies and pressure suppression. The qualitative mapping out of the uncertainty factors turned out to be useful in planning quantitative studies. It also served as internal review of the assumptions made in the PRA. The sensitivity studies were perhaps the most advantageous part of the quantitative study because they allowed individual analyses of the significance of uncertainty sources identified. The uncertainty study was found reasonable in systematically and critically assessing uncertainties in a risk analysis. The usefulness of this study depends on the decision maker (power company) since uncertainty studies are primarily carried out to support decision making when uncertainties are present. (author). 13 refs, 6 figs

  18. CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer.

    Science.gov (United States)

    Nguyen, Minh Nam; Choi, Tae Gyu; Nguyen, Dinh Truong; Kim, Jin-Hwan; Jo, Yong Hwa; Shahid, Muhammad; Akter, Salima; Aryal, Saurav Nath; Yoo, Ji Youn; Ahn, Yong-Joo; Cho, Kyoung Min; Lee, Ju-Seog; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Sung Soo

    2015-10-13

    Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies.

  19. Radiation therapy for ocular choroidal neovascularization (phase I/II study)

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Hiraoka, Masahiro

    1996-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angio-streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the subretinal neovascular membranes in CNV. We conducted a phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Materials and Methods: Between April 1994 and July 1995, 36 patients with choroidal neovascularization (34 with ARMD; 2 with angiostreaks) were treated with radiation therapy. Eligibility criteria for this study were as follows: the eyes had subretinal neovascular membranes in the avascular area of the fovea; the neovascular membranes had grown in size in the last 6 months; the best pretreatment corrected visual acuity was worse than (20(25)); there were no large subretinal hemorrhages causing decrease in visual acuity; patients were 50 years or older and had not received laser photocoagulation nor other treatment for this condition. Written informed consent was obtained from all patients. The patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Fluorescein angiography, measurement of the best corrected visual acuity, ophthalmoscopic and biomicroscopic examinations were performed at 1, 3, 6, and 12 months after treatment. Treatment planning was performed using a CT simulator which enables real-time treatment planning from multiple CT slices. The clinical target volume included the macula and optic disc, which received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions/2 weeks (last 18 eyes). All eyes were irradiated with a single lateral 6 MV photon beam, angled 10 degree posteriorly to exclude the ipsilateral lens and the contralateral eye from the radiation field. The ipsilateral lens was irradiated with less than 10% of the total reference dose. The field size averaged 3.0 x 2.5 cm. Records of the 17 eyes with CNV referred to our hospital in 1993, which satisfied the eligibility criteria for this study, were retrospectively analyzed for comparison. Results: There was no significant acute morbidity. All patients were followed regularly by both ophthalmologists and radiation oncologists. One patient treated with a dose of 20 Gy died due to intercurrent disease 2 months after irradiation. Median follow up periods for the group of patients receiving 10 Gy and for the group of patients receiving 20 Gy were 18 months, and 9 months, respectively. One patient who received 20 Gy complained of transient dry-eye sensation 2 months after treatment, but this disappeared spontaneously at the 4th month. Subjective symptoms, visual acuity and size of the neovascular membrane were evaluated 6 months after treatment in each group. In the group of patients irradiated with 10 Gy, subjective symptoms improved in 3 eyes, did not change in 10, and deteriorated in 5. In the 20 Gy group, 8 improved, 5 did not change, and 4 deteriorated. Although visual acuity was significantly decreased in the control group, patients of both irradiated groups did not show such a decrease in visual acuity. The size of the neovascular membrane in the control group progressed significantly. However, patients in the 20 Gy group showed significant regression of the membrane, although the 10 Gy group showed no significant change in size. Conclusions: This phase I/II study including a dose escalation study showed that radiation therapy seems to be useful for CNV. The dose of 20 Gy in 10 fractions was more useful in treating neovascular membranes than the dose of 10 Gy in 5 fractions. These results have encouraged us to start a multi-center randomized prospective study of the treatment of CNV with radiation therapy

  20. Organic Iodine(I, III, and V Chemistry: 10 Years of Development at the Medical University of Warsaw, Poland

    Directory of Open Access Journals (Sweden)

    Lech Skulski

    2000-12-01

    Full Text Available This review reports some novel (or considerably improved methods for the synthesis of aromatic iodides, (dichloroiodoarenes, (diacetoxyiodoarenes, iodylarenes and diaryliodonium salts, as well as some facile, oxidative anion metatheses in crude diaryliodonium halides and, for comparison, potassium halides. All these new results were obtained in our laboratory over the past decade (1990-2000. A full list of our papers dealing with the organic iodine(I, III and V chemistry, covering exlusively the aromatic derivatives, is also provided.

  1. 12 CFR 617.7305 - What is a CRC and who are the members?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is a CRC and who are the members? 617.7305... on Applications; Review of Credit Decisions § 617.7305 What is a CRC and who are the members? The... decisions made by a qualified lender. The CRC may only review adverse credit decisions at the request of the...

  2. The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development.

    Science.gov (United States)

    Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

    2014-11-01

    CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far generally accepted. © The Author 2014. Published by

  3. The Pseudomonas aeruginosa catabolite repression control protein Crc is devoid of RNA binding activity.

    Science.gov (United States)

    Milojevic, Tetyana; Grishkovskaya, Irina; Sonnleitner, Elisabeth; Djinovic-Carugo, Kristina; Bläsi, Udo

    2013-01-01

    The Crc protein has been shown to mediate catabolite repression control in Pseudomonas, leading to a preferential assimilation of carbon sources. It has been suggested that Crc acts as a translational repressor of mRNAs, encoding functions involved in uptake and breakdown of different carbon sources. Moreover, the regulatory RNA CrcZ, the level of which is increased in the presence of less preferred carbon sources, was suggested to bind to and sequester Crc, resulting in a relief of catabolite repression. Here, we determined the crystal structure of Pseudomonas aeruginosa Crc, a member of apurinic/apyrimidinic (AP) endonuclease family, at 1.8 Å. Although Crc displays high sequence similarity with its orthologs, there are amino acid alterations in the area corresponding to the active site in AP proteins. Unlike typical AP endonuclease family proteins, Crc has a reduced overall positive charge and the conserved positively charged amino-acid residues of the DNA-binding surface of AP proteins are partially substituted by negatively charged, polar and hydrophobic residues. Crc protein purified to homogeneity from P. aeruginosa did neither display DNase activity, nor did it bind to previously identified RNA substrates. Rather, the RNA chaperone Hfq was identified as a contaminant in His-tagged Crc preparations purified by one step Ni-affinity chromatography from Escherichia coli, and was shown to account for the RNA binding activity observed with the His-Crc preparations. Taken together, these data challenge a role of Crc as a direct translational repressor in carbon catabolite repression in P. aeruginosa.

  4. Detection of colorectal cancer (CRC) by urinary volatile organic compound analysis.

    Science.gov (United States)

    Arasaradnam, Ramesh P; McFarlane, Michael J; Ryan-Fisher, Courtenay; Westenbrink, Erik; Hodges, Phoebe; Hodges, Paula; Thomas, Matthew G; Chambers, Samantha; O'Connell, Nicola; Bailey, Catherine; Harmston, Christopher; Nwokolo, Chuka U; Bardhan, Karna D; Covington, James A

    2014-01-01

    Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

  5. Do recent epidemiologic observations impact who and how we should screen for CRC?

    Science.gov (United States)

    Bortniker, Ethan; Anderson, Joseph C

    2015-03-01

    Colorectal cancer (CRC) screening is recommended to begin at age 50 for those patients with no significant family history of CRC. However, even within this group of average-risk patients, there is data to suggest that there may be variation in CRC risk. These observations suggest that perhaps CRC screening should be tailored to target those patients at higher risk for earlier or more invasive screening as compared to those individuals at lower risk. The strategy of how to identify those higher-risk patients may not be straightforward. One method might be to use single risk factors such as smoking or elevated BMI as has been suggested in the recent American College of Gastroenterology CRC screening guidelines. Another paradigm involves the use of models which incorporate several risk factors to stratify patients by risk. This article will highlight recent large studies that examine recognized CRC risk factors as well as review recently developed CRC risk models. There will also be a discussion of the application of these factors and models in an effort to make CRC screening more efficient.

  6. Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Watanabe Masahiko

    2011-05-01

    Full Text Available Abstract Background Inhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY, neuronal nitric oxide synthase (nNOS or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III. Results Galanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted ~7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in ~6% of GABAergic boutons in laminae I-IIo, and ~1% of those in laminae IIi-III. Conclusions These results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina II.

  7. Novel Easy Preparations of Some Aromatic Iodine(I, III, and V Reagents, Widely Applied in Modern Organic Synthesis

    Directory of Open Access Journals (Sweden)

    Lech Skulski

    2003-01-01

    Full Text Available We report our novel (or considerably improved methods for the synthesis of aromatic iodides, (dichloroiodoarenes, (diacetoxyiodoarenes, [bis(trifluoroacetoxy-iodo]arenes, iodylarenes and diaryliodonium salts, as well as some facile, oxidative anion metatheses in crude diaryliodonium or tetraalkylammonium halides and, for comparison, potassium halides. All our formerly published papers were discussed and explained in our review “Organic Iodine(I, III, and V Chemistry: 10 Years of Development at the Medical University of Warsaw, Poland” (1990-2000 [1]. Our newest results are discussed below.

  8. Colorectal cancer stages transcriptome analysis.

    Directory of Open Access Journals (Sweden)

    Tianyao Huo

    Full Text Available Colorectal cancer (CRC is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA. Gene expression differences were evaluated across CRC stages using linear regression. Genes with p≤0.001 in expression differences were evaluated further in principal component analysis and genes with p≤0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6. Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3 had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.

  9. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

    Science.gov (United States)

    Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

    2016-04-01

    Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

  10. Phase I-II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints.

    Science.gov (United States)

    Winqvist, Maria; Mozaffari, Fariba; Palma, Marzia; Eketorp Sylvan, Sandra; Hansson, Lotta; Mellstedt, Håkan; Österborg, Anders; Lundin, Jeanette

    2017-01-01

    This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3-4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67 + ) CD8 + T cells was increased at week 4, with further increase in both the CD4 + and CD8 + subsets (p cells increased at week 4 as the frequency of effector memory cells increased in the CD8 + subset (p cells decreased in both the CD8 + and CD4 + subsets (p regulatory T cells was reduced (p T cells decreased, and effector memory T cells increased (p T cells increased at 30-week follow-up (p T cells, including increased proliferative activity and cytotoxic potential.

  11. Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population.

    Science.gov (United States)

    Sun, Rui; Liu, Jian-Ping; Gao, Chang; Xiong, Ying-Ying; Li, Min; Wang, Ya-Ping; Su, Yan-Wei; Lin, Mei; Jiang, An-Li; Xiong, Ling-Fan; Xie, Yan; Feng, Jue-Ping

    2016-05-17

    Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ2 test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (pCRC was observed in TC or TC/CC than CC individuals (pCRC risk was observed in AG, GG, and AG/GG than AA individuals (pCRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation.

  12. Effectiveness of Colorectal Cancer Screening in Detecting Earlier-stage Disease - a Nationwide Cohort Study in Denmark

    DEFF Research Database (Denmark)

    Larsen, Mette Bach; Njor, Sisse; Ingeholm, Peter

    2018-01-01

    program (March 1, 2014 through June 30, 2015). A total of 402,826 residents of Denmark (50-72 years old) were randomly invited to undergo CRC screening within the study period and 956,514 were invited thereafter. We obtained information on CRC diagnosis, date, and stage at diagnosis from the Danish.......6/100,000 not yet invited individuals. CRC incidence increased with age among invited and not yet invited individuals. For invited women compared to not yet invited women, the RR of being diagnosed with stage I CRC was 3.39 (95% CI, 2.61-4.39); with stage II CRC was 2.16 (95% CI, 1.71-2.72); with stage III CRC...

  13. Changes in histoanatomical distribution of types I, III and V collagen promote adaptative remodeling in posterior tibial tendon rupture

    Directory of Open Access Journals (Sweden)

    Érika Satomi

    2008-01-01

    Full Text Available INTRODUCTION: Posterior tibial tendon dysfunction is a common cause of adult flat foot deformity, and its etiology is unknown. PURPOSE: In this study, we characterized the morphologic pattern and distribution of types I, III and V collagen in posterior tibial tendon dysfunction. METHOD: Tendon samples from patients with and without posterior tibial tendon dysfunction were stained by immunofluorescence using antibodies against types I, III and V collagen. RESULTS: Control samples showed that type V deposited near the vessels only, while surgically obtained specimens displayed type V collagen surrounding other types of collagen fibers in thicker adventitial layers. Type III collagen levels were also increased in pathological specimens. On the other hand, amounts of collagen type I, which represents 95% of the total collagen amount in normal tendon, were decreased in pathological specimens. CONCLUSION: Fibrillogenesis in posterior tibial tendon dysfunction is altered due to higher expression of types III and V collagen and a decreased amount of collagen type I, which renders the originating fibrils structurally less resistant to mechanical forces.

  14. Effects of solid acellular type-I/III collagen biomaterials on in vitro and in vivo chondrogenesis of mesenchymal stem cells.

    Science.gov (United States)

    Gao, Liang; Orth, Patrick; Cucchiarini, Magali; Madry, Henning

    2017-09-01

    Type-I/III collagen membranes are advocated for clinical use in articular cartilage repair as being able of inducing chondrogenesis, a technique termed autologous matrix-induced chondrogenesis (AMIC). Area covered: The current in vitro and translational in vivo evidence for chondrogenic effects of solid acellular type-I/III collagen biomaterials. Expert commentary: In vitro, mesenchymal stem cells (MSCs) adhere to the fibers of the type-I/III collagen membrane. No in vitro study provides evidence that a type-I/III collagen matrix alone may induce chondrogenesis. Few in vitro studies compare the effects of type-I and type-II collagen scaffolds on chondrogenesis. Recent investigations suggest better chondrogenesis with type-II collagen scaffolds. A systematic review of the translational in vivo data identified one long-term study showing that covering of cartilage defects treated by microfracture with a type-I/III collagen membrane significantly enhanced the repair tissue volume compared with microfracture alone. Other in vivo evidence is lacking to suggest either improved histological structure or biomechanical function of the repair tissue. Taken together, there is a paucity of in vitro and preclinical in vivo evidence supporting the concept that solid acellular type-I/III collagen scaffolds may be superior to classical approaches to induce in vitro or in vivo chondrogenesis of MSCs.

  15. A Phase I/II Protocol Using 252Cf for the Treatment of Cervical Carcinoma

    International Nuclear Information System (INIS)

    Anita Mahajan; Mark J. Rivard; Evelyn R. Nunez; David E. Wazer

    2000-01-01

    For this clinical study, external photon beam irradiation will be given in a standard fashion with intravenous cisplatinum (CDDP) every week as a radiosensitizing agent. We will incorporate 252 Cf as the brachytherapy source replacing 192 Ir, theoretically improving patient outcomes with its lack of cell cycle and oxygen dependence, and a therapeutic ratio possibly greater than unity. Local tumor control and control of systemic disease are potentially feasible using 252 Cf to initially debulk and destroy local bulky tumor with CDDP and X rays to enhance treatment efficacy and treat minimal microscopic and distant micrometastases. The initial 22 Cf dose will be 1 Gy per weekly fraction with 0.25-Gy increments toward a 2.5-Gy limit. Patients will be stratified according to their stage, toxicities and outcomes will be monitored closely, and the study will be halted if undo morbidities are noted

  16. Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

    Science.gov (United States)

    Piao, Mei-Yu; Cao, Hai-Long; He, Na-Na; Xu, Meng-Que; Dong, Wen-Xiao; Wang, Wei-Qiang; Wang, Bang-Mao; Zhou, Bing

    2016-01-01

    Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

  17. CRC-cards to support development and maintenance of product configuration systems

    DEFF Research Database (Denmark)

    Haug, Anders; Hvam, Lars

    2009-01-01

    This article presents a new definition of special Class, Responsibility and Collaboration (CRC) cards to be used for the development and maintenance of Product Configuration Systems (PCSs). CRC cards were introduced as an informal and user-friendly technique for teaching object-oriented modelling...... and maintenance of PCSs. This procedure has since been applied in several configuration projects and further developed at the Centre for Product Modelling (CPM) at the Technical University of Denmark. However, the investigations of two companies that applies CRC cards to document the knowledge base of their PCSs...

  18. Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate.

    Science.gov (United States)

    Myers, Michael A; Hagan, Michael P; Todor, Dorin; Gilbert, Lynn; Mukhopadhyay, Nitai; Randolf, Jessica; Heimiller, Jeffrey; Anscher, Mitchell S

    2012-01-01

    A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant. From 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128Gy (α/β=3). Patients whose pretreatment PSA was ≥10ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation. Median followup was 53 months (9-68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities. Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  19. Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

    Science.gov (United States)

    Papagiorgis, Petros Christakis

    2016-05-01

    Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

  20. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study

    Energy Technology Data Exchange (ETDEWEB)

    Trip, Anouk K. [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Poppema, Boelo J. [Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Berge Henegouwen, Mark I. van [Department of Surgical Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Siemerink, Ester [Department of Internal Medicine, Ziekenhuisgroep Twente, Hengelo (Netherlands); Beukema, Jannet C. [Department of Radiation Oncology, University Medical Centre Groningen (Netherlands); Verheij, Marcel [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Plukker, John T.M. [Department of Surgical Oncology, University Medical Centre Groningen (Netherlands); Richel, Dick J. [Department of Medical Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Hulshof, Maarten C.C.M. [Department of Radiation Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Sandick, Johanna W. van [Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Cats, Annemieke [Department of Gastroenterology and Hepatology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Jansen, Edwin P.M. [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Hospers, Geke A.P., E-mail: g.a.p.hospers@umcg.nl [Department of Medical Oncology, University Medical Centre Groningen (Netherlands)

    2014-08-15

    Objectives: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods: In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results: Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions: In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates.

  1. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study

    International Nuclear Information System (INIS)

    Trip, Anouk K.; Poppema, Boelo J.; Berge Henegouwen, Mark I. van; Siemerink, Ester; Beukema, Jannet C.; Verheij, Marcel; Plukker, John T.M.; Richel, Dick J.; Hulshof, Maarten C.C.M.; Sandick, Johanna W. van; Cats, Annemieke; Jansen, Edwin P.M.; Hospers, Geke A.P.

    2014-01-01

    Objectives: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods: In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results: Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions: In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates

  2. 12 CFR 617.7315 - What records must the qualified lender maintain on behalf of the CRC?

    Science.gov (United States)

    2010-01-01

    ... on behalf of the CRC? 617.7315 Section 617.7315 Banks and Banking FARM CREDIT ADMINISTRATION FARM... must the qualified lender maintain on behalf of the CRC? A qualified lender must maintain a complete file of all requests for CRC reviews, including participation in state mediation programs, the minutes...

  3. Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting

    Directory of Open Access Journals (Sweden)

    van der Meijde Jolanda

    2007-08-01

    Full Text Available Abstract Background Fasting has dramatic effects on small intestinal transport function. However, little is known on expression of intestinal transport and phase I/II metabolism genes during fasting and the role the fatty acid-activated transcription factor PPARα may play herein. We therefore investigated the effects of fasting on expression of these genes using Affymetrix GeneChip MOE430A arrays and quantitative RT-PCR. Results After 24 hours of fasting, expression levels of 33 of the 253 analyzed transporter and phase I/II metabolism genes were changed. Upregulated genes were involved in transport of energy-yielding molecules in processes such as glycogenolysis (G6pt1 and mitochondrial and peroxisomal oxidation of fatty acids (Cact, Mrs3/4, Fatp2, Cyp4a10, Cyp4b1. Other induced genes were responsible for the inactivation of the neurotransmitter serotonin (Sert, Sult1d1, Dtd, Papst2, formation of eicosanoids (Cyp2j6, Cyp4a10, Cyp4b1, or for secretion of cholesterol (Abca1 and Abcg8. Cyp3a11, typically known because of its drug metabolizing capacity, was also increased. Fasting had no pronounced effect on expression of phase II metabolic enzymes, except for glutathione S-transferases which were down-regulated. Time course studies revealed that some genes were acutely regulated, whereas expression of other genes was only affected after prolonged fasting. Finally, we identified 8 genes that were PPARα-dependently upregulated upon fasting. Conclusion We have characterized the response to fasting on expression of transporters and phase I/II metabolic enzymes in murine small intestine. Differentially expressed genes are involved in a variety of processes, which functionally can be summarized as a increased oxidation of fat and xenobiotics, b increased cholesterol secretion, c increased susceptibility to electrophilic stressors, and d reduced intestinal motility. This knowledge increases our understanding of gut physiology, and may be of relevance for e.g. pre-surgery regimen of patients.

  4. Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment.

    Science.gov (United States)

    Wu, Kaiming; Zhao, Zhenxian; Liu, Kuanzhi; Zhang, Jian; Li, Guanghua; Wang, Liang

    2017-07-03

    Long non-coding RNAs (LncRNAs) have been recently regarded as systemic regulators in multiple biologic processes including tumorigenesis. In this study, we observed the expression of lncRNA lnc-sox5 was significantly increased in colorectal cancer (CRC). Despite the CRC cell growth, cell cycle and cell apoptosis was not affected by lnc-sox5 knock-down, lnc-sox5 knock-down suppressed CRC cell migration and invasion. In addition, xenograft animal model suggested that lnc-sox5 knock-down significantly suppressed the CRC tumorigenesis. Our results also showed that the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was significantly reduced by lnc-sox5 knock-down and therefore modulated the infiltration and cytotoxicity of CD3 + CD8 + T cells. Taken together, these results suggested that lnc-sox5 unbalances tumor microenvironment to regulate colorectal cancer progression.

  5. High-pressure single-crystal elasticity study of CO{sub 2} across phase I-III transition

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jin S., E-mail: zhang72@illinois.edu; Bass, Jay D. [Department of Geology, University of Illinois, Urbana-Champaign, Illinois 61801 (United States); Shieh, Sean R. [Departments of Earth Sciences and Physics and Astronomy, University of Western Ontario, London, Ontario N6A 5B7 (Canada); Dera, Przemyslaw [Hawaii Institute of Geophysics and Planetology, University of Hawaii at Manoa, Honolulu, Hawaii 96822 (United States); Prakapenka, Vitali [Center for Advanced Radiation Sources, University of Chicago, Chicago, Illinois 60637 (United States)

    2014-04-07

    Sound velocities and elastic moduli of solid single-crystal CO{sub 2} were measured at pressures up to 11.7(3) GPa by Brillouin spectroscopy. The aggregate adiabatic bulk modulus (K{sub S}), shear modulus (G), and their pressure derivatives for CO{sub 2} Phase I are K{sub S0} = 3.4(6) GPa, G{sub 0} = 1.8(2) GPa, (dK{sub S}/dP){sub 0} = 7.8(3), (dG/dP){sub 0} = 2.5(1), (d{sup 2}K{sub S}/dP{sup 2}){sub 0} = −0.23(3) GPa{sup −1}, and (d{sup 2}G/dP{sup 2}){sub 0} = −0.10(1) GPa{sup −1}. A small increase of elastic properties was observed between 9.8(1) and 10.5(3) GPa, in agreement with the CO{sub 2} I-III transition pressure determined from previous x-ray diffraction experiments. Above the transition pressure P{sub T}, we observed a mixture dominated by CO{sub 2}-I, with minor CO{sub 2}-III. The CO{sub 2}-I + III mixture shows slightly increased sound velocities compared to pure CO{sub 2}-I. Elastic anisotropy calculated from the single-crystal elasticity tensor exhibits a decrease with pressure beginning at 7.9(1) GPa, which is lower than P{sub T}. Our results coincide with recent X-ray Raman observations, suggesting that a pressure-induced electronic transition is related to local structural and optical changes.

  6. A Mixed-Mode (I-II) Fracture Criterion for AS4/8552 Carbon/Epoxy Composite Laminate

    Science.gov (United States)

    Karnati, Sidharth Reddy

    A majority of aerospace structures are subjected to bending and stretching loads that introduce peel and shear stresses between the plies of a composite laminate. These two stress components cause a combination of mode I and II fracture modes in the matrix layer of the composite laminate. The most common failure mode in laminated composites is delamination that affects the structural integrity of composite structures. Damage tolerant designs of structures require two types of materials data: mixed-mode (I-II) delamination fracture toughness that predicts failure and delamination growth rate that predicts the life of the structural component. This research focuses determining mixed-mode (I-II) fracture toughness under a combination of mode I and mode II stress states and then a fracture criterion for AS4/8552 composite laminate, which is widely used in general aviation. The AS4/8552 prepreg was supplied by Hexcel Corporation and autoclave fabricated into a 20-ply unidirectional laminate with an artificial delamination by a Fluorinated Ethylene Propylene (FEP) film at the mid-plane. Standard split beam specimens were prepared and tested in double cantilever beam (DCB) and end notched flexure modes to determine mode I (GIC) and II (GIIC) fracture toughnesses, respectively. The DCB specimens were also tested in a modified mixed-mode bending apparatus at GIIm /GT ratios of 0.18, 0.37, 0.57 and 0.78, where GT is total and GIIm is the mode II component of energy release rates. The measured fracture toughness, GC, was found to follow the locus a power law equation. The equation was validated for the present and literature experimental data.

  7. A Novel Procedure for Prediction of Mixed Mode I/II in Fracture Toughness of Laminate Composites

    Directory of Open Access Journals (Sweden)

    M. Mahmood Shokrieh

    2014-06-01

    Full Text Available Delamination is one of the important modes of failure in laminated composite materials. In this respect, the mixed mode I/II fracture is the most major mode of delamination incidence in laminated composite. In the present research, a relation between the fracture toughness of double cantilever beam (DCB and asymmetric double cantilever beam (ADCB specimens is presented. The DCB and ADCB samples are used for measuring the mode I and mixed mode I/II fracture toughness (G of laminated composite materials, respectively. By considering the diversity of the stacking sequence of lay-ups, the test performance on all different types of lay-ups in order to measure the fracture toughness of laminated composites is a tedious, costly and time consuming task. The purpose of deriving this relation is to estimate the value of the strain energy release rate of laminated composite ADCB specimens by testing a unidirectional DCB. To develop this relationship, the geometry of DCB and ADCB specimens are considered to obtain fracture toughness of multi-directional laminate composites of ADCB samples with arbitrary ply sequence which may be used for design purposes. The procedure presented here reduces the calculation costs of the finite element modeling and its corresponding test significantly. The results obtained by this method are compared with those of experimental and numerical methods. It is shown that the fracture toughness of multi-directional lay-ups can be predicted by measuring the unidirectional ply with an error less than 10% demonstrating the accuracy of the procedure developed in the present research.

  8. Detection of colorectal cancer (CRC by urinary volatile organic compound analysis.

    Directory of Open Access Journals (Sweden)

    Ramesh P Arasaradnam

    Full Text Available Colorectal cancer (CRC is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB testing has largely been superseded by Faecal Immunochemical testing (FIT, but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs signature(s for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer. FAIMS is able to identify Inflammatory Bowel disease (IBD patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK. Data was processed using Fisher Discriminant Analysis (FDA after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS with potential as a novel screening tool.

  9. Structure analysis of the global metabolic regulator Crc from Pseudomonas aeruginosa.

    Science.gov (United States)

    Wei, Yong; Zhang, Heng; Gao, Zeng-Qiang; Xu, Jian-Hua; Liu, Quan-Sheng; Dong, Yu-Hui

    2013-01-01

    The global metabolic regulator catabolite repression control (Crc) has recently been found to modulate the susceptibility to antibiotics and virulence in the opportunistic pathogen Pseudomonas aeruginosa and been suggested as a nonlethal target for novel antimicrobials. In P. aeruginosa, Crc couples with the CA motifs from the small RNA CrcZ to form a post-transcriptional regulator system and is removed from the 5'-end of the target mRNAs. In this study, we first reported the crystal structure of Crc from P. aeruginosa refined to 2.20 Å. The structure showed that it consists of two halves with similar overall topology and there are 11 β strands surrounded by 13 helices, forming a four-layered α/β-sandwich. The circular dichroism spectroscopy revealed that it is thermostable in solution and shares similar characteristics to that in crystal. Comprehensive structural analysis and comparison with the homologies of Crc showed high similarity with several known nucleases and consequently may be classified into a member exodeoxyribonuclease III. However, it shows distinct substrate specificity (RNA as the preferred substrate) compared to these DNA endonucleases. Structural comparisons also revealed potential RNA recognition and binding region mainly consisting of five flexible loops. Our structure study provided the basis for the future application of Crc as a target to develop new antibiotics. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  10. A Risk Prediction Model for Sporadic CRC Based on Routine Lab Results.

    Science.gov (United States)

    Boursi, Ben; Mamtani, Ronac; Hwang, Wei-Ting; Haynes, Kevin; Yang, Yu-Xiao

    2016-07-01

    Current risk scores for colorectal cancer (CRC) are based on demographic and behavioral factors and have limited predictive values. To develop a novel risk prediction model for sporadic CRC using clinical and laboratory data in electronic medical records. We conducted a nested case-control study in a UK primary care database. Cases included those with a diagnostic code of CRC, aged 50-85. Each case was matched with four controls using incidence density sampling. CRC predictors were examined using univariate conditional logistic regression. Variables with p value CRC prediction models which included age, sex, height, obesity, ever smoking, alcohol dependence, and previous screening colonoscopy had an AUC of 0.58 (0.57-0.59) with poor goodness of fit. A laboratory-based model including hematocrit, MCV, lymphocytes, and neutrophil-lymphocyte ratio (NLR) had an AUC of 0.76 (0.76-0.77) and a McFadden's R2 of 0.21 with a NRI of 47.6 %. A combined model including sex, hemoglobin, MCV, white blood cells, platelets, NLR, and oral hypoglycemic use had an AUC of 0.80 (0.79-0.81) with a McFadden's R2 of 0.27 and a NRI of 60.7 %. Similar results were shown in an internal validation set. A laboratory-based risk model had good predictive power for sporadic CRC risk.

  11. KRAS polymorphisms are associated with survival of CRC in Chinese population.

    Science.gov (United States)

    Dai, Qiong; Wei, Hui Lian; Huang, Juan; Zhou, Tie Jun; Chai, Li; Yang, Zhi-Hui

    2016-04-01

    rs12245, rs12587, rs9266, rs1137282, rs61764370, and rs712 of KRAS oncogene are characterized in the 3'UTR. The study highlights the important role of these polymorphisms playing in the susceptibility, oxaliplatin-based chemotherapy sensitivity, progression, and prognosis of CRC. Improved multiplex ligation detection reaction (iMLDR) technique is used for genotyping. An unconditional logistic regression model was used to estimate the association of certain polymorphism and CRC risk. The Kaplan-Meier method, log-rank test, and Cox regression model were used to evaluate the effects of polymorphisms on survival analysis. Results demonstrated that TT genotype and T allele of rs712 were associated with the increased risk of CRC; the patients with GG genotype and G allele of rs61764370 had a shorter survival and a higher risk of relapse or metastasis of CRC. Our studies supported the conclusions that rs61764370 and rs712 polymorphisms of the KRAS are functional and it may play an important role in the development of CRC and oxaliplatin-based chemotherapy efficiency and prognosis of CRC.

  12. Cross-regulation by CrcZ RNA controls anoxic biofilm formation in Pseudomonas aeruginosa

    Science.gov (United States)

    Pusic, Petra; Tata, Muralidhar; Wolfinger, Michael T.; Sonnleitner, Elisabeth; Häussler, Susanne; Bläsi, Udo

    2016-12-01

    Pseudomonas aeruginosa (PA) can thrive in anaerobic biofilms in the lungs of cystic fibrosis (CF) patients. Here, we show that CrcZ is the most abundant PA14 RNA bound to the global regulator Hfq in anoxic biofilms grown in cystic fibrosis sputum medium. Hfq was crucial for anoxic biofilm formation. This observation complied with an RNAseq based transcriptome analysis and follow up studies that implicated Hfq in regulation of a central step preceding denitrification. CrcZ is known to act as a decoy that sequesters Hfq during relief of carbon catabolite repression, which in turn alleviates Hfq-mediated translational repression of catabolic genes. We therefore inferred that CrcZ indirectly impacts on biofilm formation by competing for Hfq. This hypothesis was supported by the findings that over-production of CrcZ mirrored the biofilm phenotype of the hfq deletion mutant, and that deletion of the crcZ gene augmented biofilm formation. To our knowledge, this is the first example where competition for Hfq by CrcZ cross-regulates an Hfq-dependent physiological process unrelated to carbon metabolism.

  13. Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

    Science.gov (United States)

    Sobhani, I; Itti, E; Luciani, A; Baumgaertner, I; Layese, R; André, T; Ducreux, M; Gornet, J-M; Goujon, G; Aparicio, T; Taieb, J; Bachet, J-B; Hemery, F; Retbi, A; Mons, M; Flicoteaux, R; Rhein, B; Baron, S; Cherrak, I; Rufat, P; Le Corvoisier, P; de'Angelis, N; Natella, P-A; Maoulida, H; Tournigand, C; Durand Zaleski, I; Bastuji-Garin, S

    2018-04-01

    [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13  €, P CRC. The control group had very close follow

  14. MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals.

    Science.gov (United States)

    Ying, Hou-Qun; Peng, Hong-Xin; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Sun, Hui-Ling; Liu, Xian; Chen, Jie; Lin, Kang; Wang, Shu-Kui

    2016-11-15

    Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.

  15. Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure

    DEFF Research Database (Denmark)

    St John Sutton, Martin; Ghio, Stefano; Plappert, Ted

    2009-01-01

    BACKGROUND: Cardiac resynchronization therapy (CRT) improves LV structure, function, and clinical outcomes in New York Heart Association class III/IV heart failure with prolonged QRS. It is not known whether patients with New York Heart Association class I/II systolic heart failure exhibit left...... ventricular (LV) reverse remodeling with CRT or whether reverse remodeling is modified by the cause of heart failure. METHODS AND RESULTS: Six hundred ten patients with New York Heart Association class I/II heart failure, QRS duration > or =120 ms, LV end-diastolic dimension > or =55 mm, and LV ejection...... reduction in LV end-diastolic and end-systolic volume indexes and a 3-fold greater increase in LV ejection fraction in patients with nonischemic causes of heart failure. CONCLUSIONS: CRT in patients with New York Heart Association I/II resulted in major structural and functional reverse remodeling at 1 year...

  16. ZEB1 Mediates Drug Resistance and EMT in p300-Deficient CRC.

    Science.gov (United States)

    Lazarova, Darina; Bordonaro, Michael

    2017-01-01

    We discuss the hypothesis that ZEB1-Wnt-p300 signaling integrates epithelial to mesenchymal transition (EMT) and resistance to histone deacetylase inhibitors (HDACis) in colorectal cancer (CRC) cells. The HDACi butyrate, derived from dietary fiber, has been linked to CRC prevention, and other HDACis have been proposed as therapeutic agents against CRC. We have previously discussed that resistance to butyrate likely contributes to colonic carcinogenesis, and we have demonstrated that butyrate resistance leads to cross-resistance to cancer therapeutic HDACis. Deregulated Wnt signaling is the major initiating event in most CRC cases. One mechanism whereby butyrate and other HDACis exert their anti-CRC effects is via Wnt signaling hyperactivation, which promotes CRC cell apoptosis. The histone acetylases (HATs) CBP and p300 are mediators of Wnt transcriptional activity, and play divergent roles in the downstream consequences of Wnt signaling. CBP-mediated Wnt signaling is associated with cell proliferation and stem cell maintenance; whereas, p300-mediated Wnt activity is associated with differentiation. We have found that CBP and p300 differentially affect the ability of butyrate to influence Wnt signaling, apoptosis, and proliferation. ZEB 1 is a Wnt signaling-targeted gene, whose product is a transcription factor expressed at the invasive front of carcinomas where it promotes malignant progression and EMT. ZEB1 is typically a transcriptional repressor; however, when associated with p300, ZEB1 enhances transcription. These changes in ZEB1 activity likely affect the cancer cell phenotype. ZEB1 has been shown to promote resistance to chemotherapeutic agents, and expression of ZEB1 is upregulated in butyrate-resistant CRC cells that lack p300 expression. Since the expression of ZEB1 correlates with poor outcomes in cancer, ZEB represents a relevant therapeutic target. Here we propose that targeting the signaling network established by ZEB1, Wnt signaling, and p300

  17. The CRC 20 years: An overview of some of the major achievements and remaining challenges.

    Science.gov (United States)

    Doek, Jaap E

    2009-11-01

    On 20 November 1989, the General Assembly of the United Nations adopted the Convention on the Rights of the Child (CRC). It entered into force on 2 September 1990 and has by now been ratified by 193 States, making the most universally ratified human rights treaty. This overview will present and discuss the impact of this treaty both at the international and the national level, an overview which necessarily has to be limited to some of the developments as a result of the implementation of the CRC. The first part of this paper will be devoted to the impact the CRC had and still has on the setting and development of the international agenda for the promotion and protection of the rights and welfare of children. Special attention will given to developments, achievements, and remaining challenges at the international level with regard to protection of children in armed conflict; prevention and the protection of children from sexual exploitation; and from all forms of violence. This will include some information on the impact of these international developments and actions at the national level, for example, in the area of legislation. The second part will focus on the impact at the national level. Given the wide scope of the CRC this part will be limited to some of the General Measures of Implementation (law reform, national programmes, and independent monitoring) and the General Principles (non-discrimination, best interest, right to be heard) of the CRC. This will be based on reports of States on the implementation of the CRC submitted to the CRC Committee and the Concluding Observations of this Committee and on a number of studies. The conclusion will provide remarks on poverty as one of the major remaining challenges for the implementation of children's rights.

  18. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    International Nuclear Information System (INIS)

    Huijts, Charlotte M; Santegoets, Saskia J; Eertwegh, Alfons J van den; Pijpers, Laura S; Haanen, John B; Gruijl, Tanja D de; Verheul, Henk M; Vliet, Hans J van der

    2011-01-01

    For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell carcinoma and increase the antitumor efficacy of everolimus. ClinicalTrials.gov Identifier http://www.clinicaltrials.gov/ct2/show/NCT01462214, EudraCT number 2010-024515-13, Netherlands Trial Register number http://www.trialregister.nl/trialreg/admin/rctview.asp?TC

  19. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    Directory of Open Access Journals (Sweden)

    Huijts Charlotte M

    2011-11-01

    Full Text Available Abstract Background For patients with metastatic renal cell cancer (mRCC who progressed on vascular endothelial growth factor (VEGF receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. Methods/design This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part. In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. Discussion This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell carcinoma and increase the antitumor efficacy of everolimus. Trial Registration ClinicalTrials.gov Identifier NCT01462214, EudraCT number 2010-024515-13, Netherlands Trial Register number NTR3085.

  20. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

    Science.gov (United States)

    Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

    2010-07-01

    Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

  1. Genetic variants in IL-6/JAK/STAT3 pathway and the risk of CRC.

    Science.gov (United States)

    Wang, Shuwei; Zhang, Weidong

    2016-05-01

    Interleukin (IL)-6 and the downstream Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway have previously been reported to be important in the development of colorectal cancer (CRC), and several studies have shown the relationship between the polymorphisms of related genes in this pathway with the risk of CRC. However, the findings of these related studies are inconsistent. Moreover, there has no systematic review and meta-analysis to evaluate the relationship between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility. Hence, we conducted a meta-analysis to explore the relationship between polymorphisms in IL-6/JAK/STAT3 pathway genes and CRC risk. Eighteen eligible studies with a total of 13,795 CRC cases and 18,043 controls were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library databases for the period up to September 15, 2015. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were used to calculate the strength of the association. Our results indicated that IL-6 genetic variants in allele additive model (OR = 1.05, 95 % CI = 1.00, 1.09) and JAK2 genetic variants (OR = 1.40, 95 % CI = 1.15, 1.65) in genotype recessive model were significantly associated with CRC risk. Moreover, the pooled data revealed that IL-6 rs1800795 polymorphism significantly increased the risk of CRC in allele additive model in Europe (OR = 1.07, 95 % CI = 1.01, 1.14). In conclusion, the present findings indicate that IL-6 and JAK2 genetic variants are associated with the increased risk of CRC while STAT3 genetic variants not. We need more well-designed clinical studies covering more countries and population to definitively establish the association between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility.

  2. Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.

    Science.gov (United States)

    Han, Xinxin; Yin, Linlin; Xue, Hongwei

    2012-07-01

    Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.

  3. Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence.

    Science.gov (United States)

    Troiani, Teresa; Napolitano, Stefania; Della Corte, Carminia Maria; Martini, Giulia; Martinelli, Erika; Morgillo, Floriana; Ciardiello, Fortunato

    2016-01-01

    Epidermal growth factor receptor (EGFR) plays a key role in tumour evolution, proliferation and immune evasion, and is one of the most important targets for biological therapy, especially for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). In the past 15 years, several EGFR antagonists have been approved for the treatment of NSCLC and metastatic CRC (mCRC). To optimise the use of anti-EGFR agents in clinical practice, various clinical and molecular biomarkers have been investigated, thus moving their indication from unselected to selected populations. Nowadays, anti-EGFR drugs represent a gold-standard therapy for metastatic NSCLC harbouring EGFR activating mutation and for RAS wild-type mCRC. Their clinical efficacy is limited by the presence of intrinsic resistance or the onset of acquired resistance. In this review, we provide an overview of the antitumour activity of EGFR inhibitors in NSCLC and CRC and of mechanisms of resistance, focusing on the development of a personalised approach through 15 years of preclinical and clinical research.

  4. Diverse Reactions of Thiophenes, Selenophenes, and Tellurophenes with Strongly Oxidizing I(III) PhI(L)2 Reagents.

    Science.gov (United States)

    Egalahewa, Sathsara; Albayer, Mohammad; Aprile, Antonino; Dutton, Jason L

    2017-02-06

    We report the outcomes of the reactions of aromatic group 16 thiophene, selenophene, and tellurophene rings with the I(III) oxidants PhI(OAc)(OTf) and [PhI(Pyr) 2 ][OTf] 2 (Pyr = pyridine). In all reactions, oxidative processes take place, with generation of PhI as the reduction product. However, with the exception of tellurophene with PhI(OAc)(OTf), +4 oxidation state complexes are not observed, but rather a variety of other processes occur. In general, where a C-H unit is available on the 5-membered ring, an electrophilic aromatic substitution reaction of either -IPh or pyridine onto the ring occurs. When all positions are blocked, reactions with PhI(OAc)(OTf) give acetic and triflic anhydride as the identifiable oxidative byproducts, while [PhI(Pyr) 2 ][OTf] 2 gives pyridine electrophilic aromatic substitution onto the peripheral rings. Qualitative mechanistic studies indicate that the presence of the oxidizable heteroatom is required for pyridine to act as an electrophile in a substantial manner.

  5. Deterministic Role of CEA and MSI Status in Predicting Outcome of CRC Patients: a Perspective Study Amongst Hospital Attending Eastern Indian Populations.

    Science.gov (United States)

    Koyel, Banerjee; Priyabrata, Das; Rittwika, Bhattacharya; Swati, Dasgupta; Soma, Mukhopadhyay; Jayasri, Basak; Ashis, Mukhopadhyay

    2017-12-01

    Carcinoembryonic antigen (CEA) is an important deterministic factor in predicting colorectal carcinoma (CRC) progression. It is also evident that microsatellite instability (MSI) which results in a hypermutable phenotype of genomic DNA is common in CRC. Owing to the scarcity of reports from India, our aim of this study was to understand the clinicopathological correlations of CEA status with surgery and chemotherapy, correlate the same with socio-demographic status of the patients, determine the MSI status amongst them and understand the prognostic implications of CEA and MSI as CRC progression marker amongst patients. The serum CEA level was estimated by chemiluminescence assay (CLIA). Serum liver enzyme assay was carried out following the manufacturer's instructions using auto-analysers (E. Merck and Sera mol. Health Care, India). MSI analysis was carried out by PCR-SSCP. From our study, most frequently detected colorectal cancer was in 40-49 years age group (25.26%) with 61.05% male and 38.95% females. CEA showed a significant association with higher TNM staging, tumour size, smoking habit and MSI status ( p   0.05). After surgery and chemotherapy, CEA and WBCs were decreased significantly ( p   0.05). Overall, microsatellite instability was observed in approximately 40% of the populations. From our study, it was also evident that for both, MSI and abnormal CEA level predicted poor prognosis for the patient (by using Kaplan-Meier survival analysis; p  = 0.04). Thus, CEA and initial MSI status can be used as prognostic markers of CRC.

  6. Effects of recombinant human granulocyte colony-stimulating factor on leucopenia in zidovudine-treated patients with AIDS and AIDS related complex, a phase I/II study

    NARCIS (Netherlands)

    van der Wouw, P. A.; van Leeuwen, R.; van Oers, R. H.; Lange, J. M.; Danner, S. A.

    1991-01-01

    Twelve male patients, eight with the acquired immunodeficiency syndrome (AIDS) and four with AIDS related complex (ARC), who had zidovudine associated neutropenia (less than 1 x 10(9) neutrophils/l) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) in a phase I/II

  7. IRRIGATION PRACTICES IN LONG-TERM SURVIVORS OF COLORECTAL CANCER (CRC) WITH COLOSTOMIES

    OpenAIRE

    Grant, Marcia; McMullen, Carmit K.; Altschuler, Andrea; Hornbrook, Mark C.; Herrinton, Lisa J.; Wendel, Christopher S.; Baldwin, Carol M.; Krouse, Robert S.

    2012-01-01

    Creation of a colostomy in colorectal (CRC) cancer patients results in a loss of control over bowel evacuation. The only way to re-establish some control is through irrigation, a procedure that involves instilling fluid into the bowel to allow for gas and fecal output. This article reports on irrigation practices of participants in a large, multi-site, multi-investigator study of health-related quality of life (HR-QOL) in long term CRC survivors. Questions about irrigation practices were iden...

  8. Mode I and mixed I/III crack initiation and propagation behavior of V-4Cr-4Ti alloy at 25{degrees}C

    Energy Technology Data Exchange (ETDEWEB)

    Li, H.X.; Kurtz, R.J.; Jones, R.H. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-04-01

    The mode I and mixed-mode I/III fracture behavior of the production-scale heat (No. 832665) of V-4Cr-4Ti has been investigated at 25{degrees}C using compact tension (CT) specimens for a mode I crack and modified CT specimens for a mixed-mode I/III crack. The mode III to mode I load ratio was 0.47. Test specimens were vacuum annealed at 1000{degrees}C for 1 h after final machining. Both mode I and mixed-mode I/III specimens were fatigue cracked prior to J-integral testing. It was noticed that the mixed-mode I/III crack angle decreased from an initial 25 degrees to approximately 23 degrees due to crack plane rotation during fatigue cracking. No crack plane rotation occurred in the mode I specimen. The crack initiation and propagation behavior was evaluated by generating J-R curves. Due to the high ductility of this alloy and the limited specimen thickness (6.35 mm), plane strain requirements were not met so valid critical J-integral values were not obtained. However, it was found that the crack initiation and propagation behavior was significantly different between the mode I and the mixed-mode I/III specimens. In the mode I specimen crack initiation did not occur, only extensive crack tip blunting due to plastic deformation. During J-integral testing the mixed-mode crack rotated to an increased crack angle (in contrast to fatigue precracking) by crack blunting. When the crack initiated, the crack angle was about 30 degrees. After crack initiation the crack plane remained at 30 degrees until the test was completed. Mixed-mode crack initiation was difficult, but propagation was easy. The fracture surface of the mixed-mode specimen was characterized by microvoid coalescence.

  9. Influence of the Hfq and Crc global regulators on the control of iron homeostasis in Pseudomonas putida.

    Science.gov (United States)

    Sánchez-Hevia, Dione L; Yuste, Luis; Moreno, Renata; Rojo, Fernando

    2018-04-30

    Metabolically versatile bacteria use catabolite repression control to select their preferred carbon sources, thus optimizing carbon metabolism. In pseudomonads, this occurs through the combined action of the proteins Hfq and Crc, which form stable tripartite complexes at target mRNAs, inhibiting their translation. The activity of Hfq/Crc is antagonised by small RNAs of the CrcZ family, the amounts of which vary according to carbon availability. The present work examines the role of Pseudomonas putida Hfq protein under conditions of low-level catabolite repression, in which Crc protein would have a minor role since it is sequestered by CrcZ/CrcY. The results suggest that, under these conditions, Hfq remains operative and plays an important role in iron homeostasis. In this scenario, Crc appears to participate indirectly by helping CrcZ/CrcY to control the amount of free Hfq in the cell. Iron homeostasis in pseudomonads relies on regulatory elements such as the Fur protein, the PrrF1-F2 sRNAs, and several extracytoplasmic sigma factors. Our results show that the absence of Hfq is paralleled by a reduction in PrrF1-F2 small RNAs. Hfq thus provides a regulatory link between iron and carbon metabolism, coordinating the iron supply to meet the needs of the enzymes operational under particular nutritional regimes. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

  10. Interplay between the catabolite repression control protein Crc, Hfq and RNA in Hfq-dependent translational regulation in Pseudomonas aeruginosa.

    Science.gov (United States)

    Sonnleitner, Elisabeth; Wulf, Alexander; Campagne, Sébastien; Pei, Xue-Yuan; Wolfinger, Michael T; Forlani, Giada; Prindl, Konstantin; Abdou, Laetitia; Resch, Armin; Allain, Frederic H-T; Luisi, Ben F; Urlaub, Henning; Bläsi, Udo

    2018-02-16

    In Pseudomonas aeruginosa the RNA chaperone Hfq and the catabolite repression control protein (Crc) act as post-transcriptional regulators during carbon catabolite repression (CCR). In this regard Crc is required for full-fledged Hfq-mediated translational repression of catabolic genes. RNAseq based transcriptome analyses revealed a significant overlap between the Crc and Hfq regulons, which in conjunction with genetic data supported a concerted action of both proteins. Biochemical and biophysical approaches further suggest that Crc and Hfq form an assembly in the presence of RNAs containing A-rich motifs, and that Crc interacts with both, Hfq and RNA. Through these interactions, Crc enhances the stability of Hfq/Crc/RNA complexes, which can explain its facilitating role in Hfq-mediated translational repression. Hence, these studies revealed for the first time insights into how an interacting protein can modulate Hfq function. Moreover, Crc is shown to interfere with binding of a regulatory RNA to Hfq, which bears implications for riboregulation. These results are discussed in terms of a working model, wherein Crc prioritizes the function of Hfq toward utilization of favored carbon sources.

  11. Tolerance and Acceptance Results of a Palladium-103 Permanent Breast Seed Implant Phase I/II Study

    International Nuclear Information System (INIS)

    Pignol, Jean-Philippe; Rakovitch, Eileen; Keller, Brian M.; Sankreacha, Raxa; Chartier, Carole

    2009-01-01

    Purpose: To test, in a prospective Phase I/II trial, a partial breast irradiation technique using a 103 Pd permanent breast seed implant (PBSI) realized in a single 1-h procedure under sedation and local freezing. Methods and Materials: Eligible patients had infiltrating ductal carcinoma ≤3 cm in diameter, surgical margin ≥2 mm, no extensive intraductal component, no lymphovascular invasion, and negative lymph nodes. Patients received a permanent seed implant, and a minimal peripheral dose of 90 Gy was prescribed to the clinical target volume, with a margin of 1.5 cm. Results: From May 2004 to April 2007, 67 patients received the PBSI treatment. The procedure was well tolerated, with 17% of patients having significant pain after the procedure. Only 1 patient (1.5%) had an acute skin reaction (Grade 3 according to the National Cancer Institute Common Toxicity Criteria). The rates of acute moist desquamation, erythema, and indurations were 10.4%, 42%, and 27%, respectively. At 1 year the rate of Grade 1 telangiectasia was 14%. The rate of skin reaction decreased from 65% to 28% when skin received less than the 85% isodose. According to a Radiation Therapy Oncology Group questionnaire, 80-90% of patients were very satisfied with their treatment, and the remainder were satisfied. One patient (1.5%) developed an abscess, which resolved after the use of antibiotics. There was no recurrence after a median follow-up of 32 months (range, 11-49 months). Conclusions: The feasibility, safety, and tolerability of PBSI compares favorably with that of external beam and other partial breast irradiation techniques.

  12. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    Energy Technology Data Exchange (ETDEWEB)

    Mimura, Hidefumi, E-mail: mimura@marianna-u.ac.jp [St. Marianna University School of Medicine, Department of Radiology (Japan); Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp [Mie University School of Medicine, Department of Interventional Radiology (Japan); Sone, Miyuki, E-mail: msone@me.com; Takeuchi, Yoshito, E-mail: yotake62@qg8.so-net.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Miki, Tsuneharu, E-mail: tmiki@koto.kpu-m.ac.jp [Kyoto Prefectural University of Medicine, Department of Urology (Japan); Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan); Sakuhara, Yusuke, E-mail: yusaku@med.hokudai.ac.jp [Hokkaido University School of Medicine, Department of Diagnostic and Interventional Radiology (Japan); Yamamoto, Takanobu, E-mail: tyamamot@tcc.pref.tochigi.lg.jp [Tochigi Cancer Center, Department of Radiology (Japan); Sato, Yozo, E-mail: ysato@aichi-cc.jp [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kanazawa, Susumu, E-mail: susumu@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan)

    2016-05-15

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  13. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    International Nuclear Information System (INIS)

    Mimura, Hidefumi; Arai, Yasuaki; Yamakado, Koichiro; Sone, Miyuki; Takeuchi, Yoshito; Miki, Tsuneharu; Gobara, Hideo; Sakuhara, Yusuke; Yamamoto, Takanobu; Sato, Yozo; Kanazawa, Susumu

    2016-01-01

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  14. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials

    International Nuclear Information System (INIS)

    Chen Zhinan; Mi Li; Xu Jing

    2006-01-01

    Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p 131 I) metuximab injection is safe and active for HCC patients

  15. A phase I/II study of Docetaxel/TS-1 with radiation for esophageal cancer patients. Step 1

    International Nuclear Information System (INIS)

    Matsumoto, Hideo; Hirai, Toshihiro; Hirabayashi, Youko

    2006-01-01

    The therapy 5-fluorouracil (FU) and cisplatin (CDDP) with radiation is thought to be the standard therapy for esophageal cancer patients by now. However, the therapy is associated with a comparatively high incidence of gastrointestinal disorders and requires hospitalization. We have proposed a new regimen of Docetaxel and TS-1 with radiation for maintaining of QOL and improving outcome. Step 1 of the clinical phase I/II study was conducted for 10 cases from May 2004 to March 2006. Treatment could be accomplished in all cases, and no treatment-related deaths or adverse events of grade 4 were observed in any case. As for hematotoxicity, one case had leucopenia of grade 3 and neutropenia of grade 2. As for non-hematotoxic adverse events, anorexia of grade 3 was recognized in one case of level 3. The response rate evaluated by RECIST was 66% (CR in 2 cases, PR in 4 cases,) and the rate based on the Guide Lines for the Clinical and Pathologic Studies on Carcinoma of Esophagus by the Japanese Society for Esophageal Cancer was 70% (CR in 3 cases, PR in 4 cases). We assumed that the recommended dosage of TXT was 30 mg/m 2 and that of TS-1 was 60 mg/m 2 with radiotherapy of 60 Gy. This combination therapy may be recommended because of fewer adverse events and a higher responsive rate than the standard therapies. We intend to continue this study to step 2 and 3, and to reveal the response rate and adverse events for more esophageal cancer patients. (author)

  16. A Multicenter Phase I/II Study of the BCNU Implant (Gliadel ® Wafer) for Japanese Patients with Malignant Gliomas

    Science.gov (United States)

    AOKI, Tomokazu; NISHIKAWA, Ryo; SUGIYAMA, Kazuhiko; NONOGUCHI, Naosuke; KAWABATA, Noriyuki; MISHIMA, Kazuhiko; ADACHI, Jun-ichi; KURISU, Kaoru; YAMASAKI, Fumiyuki; TOMINAGA, Teiji; KUMABE, Toshihiro; UEKI, Keisuke; HIGUCHI, Fumi; YAMAMOTO, Tetsuya; ISHIKAWA, Eiichi; TAKESHIMA, Hideo; YAMASHITA, Shinji; ARITA, Kazunori; HIRANO, Hirofumi; YAMADA, Shinobu; MATSUTANI, Masao

    2014-01-01

    Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe. PMID:24739422

  17. Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

    Science.gov (United States)

    Paris, K J; Spanos, W J; Lindberg, R D; Jose, B; Albrink, F

    1993-03-15

    To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

  18. Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study.

    Science.gov (United States)

    Cukras, Catherine A; Petrou, Philip; Chew, Emily Y; Meyerle, Catherine B; Wong, Wai T

    2012-06-22

    Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME. A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA). Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors. In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.).

  19. Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.

    Science.gov (United States)

    Petrou, Philip A; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y; Wong, Wai T

    2014-12-18

    To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  20. Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer--A preliminary report

    International Nuclear Information System (INIS)

    Teh, Bin S.; Aguilar-Cordova, Estuardo; Kernen, Kenneth; Chou, C.-C.; Shalev, Moshe; Vlachaki, Maria T.; Miles, Brian; Kadmon, Dov; Mai, W.-Y.; Caillouet, James; Davis, Maria; Ayala, Gustavo; Wheeler, Thomas; Brady, Jett; Carpenter, L. Steve; Lu, Hsin H.; Chiu, J. Kam; Woo, Shiao Y.; Thompson, Timothy; Butler, E. Brian

    2001-01-01

    Purpose: To report the preliminary results of a Phase I/II study combining radiotherapy and in situ gene therapy (adenovirus/herpes simplex virus thymidine kinase gene/valacyclovir) with or without hormonal therapy in the treatment of prostate cancer. Methods and Materials: Arm A: low-risk patients (T1-T2a, Gleason score <7, pretreatment PSA <10) were treated with combined radio-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated radiotherapy. Arm B: high-risk patients (T2b-T3, Gleason score ≥7, pretreatment PSA ≥10) were treated with combined radio-gene therapy and hormonal therapy. Hormonal therapy was comprised of a 4-month leuprolide injection and 2-week use of flutamide. Arm C: Stage D1 (positive pelvic lymph node) patients received the same regimen as Arm B, with the additional 45 Gy to the pelvic lymphatics. Treatment-related toxicity was assessed using Cancer Therapy Evaluation Program common toxicity score and Radiation Therapy Oncology Group (RTOG) toxicity score. Results: Thirty patients (13 in Arm A, 14 in Arm B, and 3 in Arm C) completed the trial. Median follow-up was 5.5 months. Eleven patients (37%) developed flu-like symptoms (Cancer Therapy Evaluation Program Grade 1) of fatigue and chills/rigors after gene therapy injection but recovered within 24 h. Four patients (13%) and 2 patients (7%) developed Grade 1 and 2 fever, respectively. There was no patient with weight loss. One patient in Arm B developed Grade 3 elevation in liver enzyme, whereas 11 and 2 patients developed Grade 1 and 2 abnormal liver function tests. There was no Grade 2 or above hematologic toxicity. Three patients had transient rise in creatinine. There was no RTOG Grade 3 or above lower gastrointestinal toxicity. Toxicity levels were as follows: 4 patients (13%), Grade 2; 6 patients (20%), Grade 1; and 20 patients (67%), no toxicity. There was 1 patient with RTOG Grade 3 genitourinary toxicity, 12 patients (40%) with Grade 2, 8 patients

  1. A phase I/II study of hypofractionated whole abdominal radiation therapy in patients with chemoresistant ovarian carcinoma: Karnofsky score determines treatment outcome

    International Nuclear Information System (INIS)

    Faul, Clare; Gerszten, Kristina; Edwards, Robert; Land, Stephanie; D'Angelo, Gina M.S.; Kelley, Joseph; Price, Fredric

    2000-01-01

    life in patients with Karnofsky score <90 despite symptomatic response. Median survival was 3 months from the date of treatment. Conclusion: Hypofractionated radiation therapy is an effective palliative treatment for end-stage ovarian cancer patients. Karnofsky score can help determine the duration of response and survival for this high-risk population

  2. Finite element analysis and experimental verification of Polymer reinforced CRC improved for close-in detonation

    DEFF Research Database (Denmark)

    Riisgaard, Benjamin; Georgakis, Christos; Stang, Henrik

    2007-01-01

    Compact Reinforced Composite, CRC, is a high-strength cement-based composite that holds an enormous flexural and energy-absorbing capacity due to the close-spaced high strength steel reinforcement and a high-strength cement-based fiber DSP matrix. The material has been used in various constructions...

  3. Structural stability, electronic, mechanical and superconducting properties of CrC and MoC

    Energy Technology Data Exchange (ETDEWEB)

    Kavitha, M.; Sudha Priyanga, G. [Department of Physics, N.M.S.S.V.N College, Madurai 625019, Tamilnadu (India); Rajeswarapalanichamy, R., E-mail: rrpalanichamy@gmail.com [Department of Physics, N.M.S.S.V.N College, Madurai 625019, Tamilnadu (India); Iyakutti, K. [Department of Physics and Nanotechnology, SRM University, Chennai 603203, Tamilnadu (India)

    2016-02-01

    The structural, electronic, mechanical and superconducting properties of chromium carbide (CrC) and molybdenum carbide (MoC) are investigated using first principles calculations based on density functional theory (DFT). The computed ground state properties like equilibrium lattice constants and cell volume are in good agreement with available theoretical and experimental data. A pressure induced structural phase transition from tungsten carbide phase (WC) to zinc blende phase (ZB) and then zinc blende phase (ZB) to nickel arsenide phase (NiAs) are observed in both chromium and molybdenum carbides. Electronic structure reveals that these carbides are metallic at ambient condition. All the calculated elastic constants obey the Born–Huang stability criteria, suggesting that they are mechanically stable at normal and high pressure. The super conducting transition temperatures for CrC and MoC in WC phase are found to be 31.12 K and 17.14 K respectively at normal pressure. - Highlights: • Electronic and mechanical properties of CrC and MoC are investigated. • Pressure induced structural phase transition is predicted at high pressure. • Electronic structure reveals that these materials exhibit metallic behaviour. • Debye temperature values are computed for CrC and MoC. • Superconducting transition temperature values are computed.

  4. Aberrant methylation of GCNT2 is tightly related to lymph node metastasis of primary CRC.

    Science.gov (United States)

    Nakamura, Kazunori; Yamashita, Keishi; Sawaki, Hiromichi; Waraya, Mina; Katoh, Hiroshi; Nakayama, Nobukazu; Kawamata, Hiroshi; Nishimiya, Hiroshi; Ema, Akira; Narimatsu, Hisashi; Watanabe, Masahiko

    2015-03-01

    Glycoprotein expression profile is dramatically altered in human cancers; however, specific glycogenes have not been fully identified. A comprehensive real-time polymerase chain reaction (PCR) system for glycogenes (CRPS-G) identified several outstanding glycogenes. GCNT2 was of particular interest after GCNT2 expression and epigenetics were rigorously investigated in primary colorectal cancer (CRC). The highlights of this work can be summarized as follows: (i) Expression of GCNT2 was remarkably suppressed. (ii) Silenced expression of GCNT2 was reactivated by combined demethylating agents. (iii) Promoter DNA methylation of GCNT2 was silenced in CRC cell lines and tissues. Hypomethylation of GCNT2 variant 2 is tightly associated with lymph node metastasis in primary CRC. (iv) GCNT2 methylation level in the normal tissues also showed a close association with that in the tumor tissues and reflected lymph node metastasis. We identified aberrant expression of GCNT2, which can be explained by promoter DNA hypermethylation. Hypomethylation of the GCNT2 variant 2 reflected lymph node metastasis of CRC in the tumor and normal tissues. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Barriers to CRC Screening among Latino Adults in Pennsylvania: ACCN Results

    Science.gov (United States)

    Garcia-Dominic, Oralia; Lengerich, Eugene J.; Wray, Linda A.; Parrott, Roxanne; Aumiller, Betsy; Kluhsman, Brenda; Renderos, Carlos; Dignan, Mark

    2012-01-01

    Objectives: To describe knowledge of and barriers to colorectal cancer (CRC) screening by sex and geography among Latino adults in Pennsylvania. Methods: Eighty-two Latinos greater than 50 years old engaged in one of 8 focus groups. Focus groups consisted of 4 components. Focus group data were audiotaped, transcribed, and grouped into thematic…

  6. Self Reported Awareness of Child Maltreatment among School Professionals in Saudi Arabia: Impact of CRC Ratification

    Science.gov (United States)

    AlBuhairan, Fadia S.; Inam, Sarah S.; AlEissa, Majid A.; Noor, Ismail K.; Almuneef, Maha A.

    2011-01-01

    Objectives: The Convention on the Rights of the Child (CRC) was ratified by Saudi Arabia 15 years ago; yet addressing the issue of child maltreatment only began in more recent years. School professionals play a significant role in children's lives, as they spend a great deal of time with them and are hence essential to protecting and identifying…

  7. The CRC 20 Years: An Overview of Some of the Major Achievements and Remaining Challenges

    Science.gov (United States)

    Doek, Jaap E.

    2009-01-01

    On 20 November 1989, the General Assembly of the United Nations adopted the Convention on the Rights of the Child (CRC). It entered into force on 2 September 1990 and has by now been ratified by 193 States, making the most universally ratified human rights treaty. This overview will present and discuss the impact of this treaty both at the…

  8. Performance of continuously reinforced concrete pavements volume 5 : maintenance and repair of CRC pavements.

    Science.gov (United States)

    1998-10-01

    This report is one of a series of reports prepared as part of a recent study sponsored by the Federal Highway Administration (FHWA) aimed at updating the state-of-the-art of the design, construction, maintenance, and rehabiilitation of CRC pavements....

  9. Phase I/II Study Evaluating Early Tolerance in Breast Cancer Patients Undergoing Accelerated Partial Breast Irradiation Treated With the MammoSite Balloon Breast Brachytherapy Catheter Using a 2-Day Dose Schedule

    International Nuclear Information System (INIS)

    Wallace, Michelle; Martinez, Alvaro; Mitchell, Christina; Chen, Peter Y.; Ghilezan, Mihai; Benitez, Pamela; Brown, Eric; Vicini, Frank

    2010-01-01

    Purpose: Initial Phase I/II results using balloon brachytherapy to deliver accelerated partial breast irradiation (APBI) in 2 days in patients with early-stage breast cancer are presented. Materials and Methods: Between March 2004 and August 2007, 45 patients received adjuvant radiation therapy after lumpectomy with balloon brachytherapy in a Phase I/II trial delivering 2800 cGy in four fractions of 700 cGy. Toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria for Adverse Events v3.0 scale and cosmesis was documented at ≥6 months. Results: The median age was 66 years (range, 48-83) and median skin spacing was 12 mm (range, 8-24). The median follow-up was 11.4 months (5.4-48 months) with 21 patients (47%) followed ≥1 year, 11 (24%) ≥2 years, and 7 (16%) ≥3 years. At <6 months (n = 45), Grade II toxicity rates were 9% radiation dermatitis, 13% breast pain, 2% edema, and 2% hyperpigmentation. Grade III breast pain was reported in 13% (n = 6). At ≥6 months (n = 43), Grade II toxicity rates were: 2% radiation dermatitis, 2% induration, and 2% hypopigmentation. Grade III breast pain was reported in 2%. Infection was 13% (n = 6) at <6 months and 5% (n = 2) at ≥6 months. Persistent seroma ≥6 months was 30% (n = 13). Fat necrosis developed in 4 cases (2 symptomatic). Rib fractures were seen in 4% (n = 2). Cosmesis was good/excellent in 96% of cases. Conclusions: Treatment with balloon brachytherapy using a 2-day dose schedule resulted acceptable rates of Grade II/III chronic toxicity rates and similar cosmetic results observed with a standard 5-day accelerated partial breast irradiation schedule.

  10. Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

    Science.gov (United States)

    Jansen, Anne M L; Geilenkirchen, Marije A; van Wezel, Tom; Jagmohan-Changur, Shantie C; Ruano, Dina; van der Klift, Heleen M; van den Akker, Brendy E W M; Laros, Jeroen F J; van Galen, Michiel; Wagner, Anja; Letteboer, Tom G W; Gómez-García, Encarna B; Tops, Carli M J; Vasen, Hans F; Devilee, Peter; Hes, Frederik J; Morreau, Hans; Wijnen, Juul T

    2016-01-01

    Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

  11. Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

    Directory of Open Access Journals (Sweden)

    Visser Otto

    2010-06-01

    Full Text Available Abstract Background Diagnosing colorectal cancer (CRC at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear. Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC. Methods Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B and late stage (Dukes C or D cancer. Patients were followed up for 3.5 years after diagnosis. Results In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE was 31 (1.5 weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (p = 0.27. In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank p = 0.93. In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank p = 0.01. In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median versus short delay (≤median was 1.8 (95% confidence interval (CI 1.1 to 3.0; p = 0.01. Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors. Conclusion In symptomatic CRC patients, a longer diagnostic and

  12. An overview of the MIZ-1 borehole investigations during phase I/II. MIZ-1 progress report 03-01

    International Nuclear Information System (INIS)

    Ota, Kunio; Takeuchi, Shinji; Ikeda, Koki

    2004-05-01

    Surface-based investigations have now been carried out, in a step-by-step fashion, with the main aims of the development of conceptual models of the geological environment and the enhancement of the understanding of the undisturbed deep geological environment before excavation of the shafts and experimental drifts. The MIZ-1 borehole investigation programme was launched in December 2002, as a step of the field investigations at the MIU Construction Site. The overall goals of the MIZ-1 borehole investigations are to characterise the geological environment from the surface to over 1,000 m depth in the crystalline basement, to establish baseline conditions before excavation of the shafts and experimental drifts, and to provide a deep borehole for observing hydraulic responses during the shaft and drift excavation and experiments in the drifts during the Construction and the Operation Phases. The borehole is planned to be drilled in an overall south-westerly direction from the north-eastern area of the MIU Site. The planned inclination varies from vertical at shallower depths to 12deg from vertical at greater depths down to 1,350 m along the borehole length, which will be achieved by controlled directional drilling. In MIZ-1 Phase I/II (from March to May 2003), the borehole was drilled vertically, through the entire sedimentary formations, down to 123.00 m in the uppermost part of the Toki granite at the MIU Construction Site. The new method of wireline core drilling with a downhole motor was introduced for the drilling. Planned geological, geophysical and hydrochemical investigations and complementary hydraulic and hydrochemical monitoring were performed. In addition, as a complete loss of drilling fluid was encountered at 115.85 m along the borehole length, modified work procedures resulted in the execution of hydraulic tests with groundwater sampling, from necessity, in that section and of further drilling work. The local QC system was applied to all the investigations. Quality-controlled data on geology, hydrogeology and hydrochemistry of the sedimentary formations and the Toki granite were acquired, thereby advancing the understanding of the shallow geological environment at the MIU Construction Site. Specifically, a very highly transmissive WCF and Na-Cl-HCO 3 type groundwater in the uppermost part of the Toki granite were identified. However, the difficulty in modelling heterogeneous geological structures was highlighted. In addition, throughout the investigation programme, from technical and QC viewpoints, a range of successes and set-backs was produced and lessons and feedback from the achievements were obtained. (author)

  13. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE: the IEO phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M.; Baio, Silvia M.; Lombardo, Dario; Chinol, Marco; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta; Ferrari, Mahila E. [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Fazio, Nicola [European Institute of Oncology, Division of Medical Oncology, Milan (Italy); Iodice, Simona [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Bartolomei, Mirco [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); M. Bufalini Hospital, Division of Nuclear Medicine, Cesena, FC (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Unit of Radiometabolic Medicine, Meldola, FC (Italy)

    2011-12-15

    Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst{sub 2}), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of {sup 177}Lu-DOTATATE in multiple cycles. Fifty-one consecutive patients with unresectable/metastatic sst{sub 2}-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of {sup 177}Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. {sup 177}Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. (orig.)

  14. Motivations to participate in a Phase I/II HIV vaccine trial: A descriptive study from Dar es Salaam, Tanzania

    Directory of Open Access Journals (Sweden)

    E. A. M. Tarimo

    2016-02-01

    Full Text Available Abstract Background The search for an efficacious HIV vaccine is a global priority. To date only one HIV vaccine trial (RV144 has shown modest efficacy in a phase III trial. With existing different HIV-1 subtypes and frequent mutations, multiple trials are needed from different geographical sites particularly in sub-Saharan Africa where most HIV infections occur. Thus, motivations to participate in HIV vaccine trials among Tanzanians need to be assessed. This paper describes the motives of Police Officers who showed great interest to volunteer in HIVIS-03 in Dar es Salaam, Tanzania. Methods A descriptive cross-sectional study was conducted among Police Officers who showed interest to participate in the HIVIS-03, a phase I/II HIV vaccine trial in Dar es Salaam. Prior to detailed training sessions about HIV vaccine trials, the potential participants narrated their individual motives to participate in the trial on a piece of paper. Descriptive analysis using content approach and frequency distributions were performed. Results Of the 265 respondents, 242 (91.3 % provided their socio-demographic characteristics as well as reasons that would make them take part in the proposed trial. Majority, (39.7 %, cited altruism as the main motive. Women were more likely to volunteer due to altruism compared to men (P < 0.01. Researchers’ explanations about HIV/AIDS vaccine studies motivated 15.3 %. More men (19.6 % than women (1.7 % were motivated to volunteer due to researchers’ explanations (P < 0.001. Also, compared to other groups, those unmarried and educated up to secondary level of education were motivated to volunteer due to researchers’ explanation (P < 0.05. Other reasons were: desire to become a role model (18.6 %; to get knowledge for educating others (14.0 %; to cooperate with researchers in developing an HIV vaccine (9.5 %; to get protection against HIV infection (7.0 %, and severity of the disease within families (6.2 %. These results were supported by testimonies from both men and women. Conclusions Participation in an HIV vaccine trial in a Tanzanian context is likely to be influenced by altruism and comprehensive education about the trial. Gender differences, marital status and education level need to be considered to enhance participation in future HIV vaccine trials.

  15. Evaluation of a Hanging-Breast PET System for Primary Tumor Visualization in Patients With Stage I-III Breast Cancer: Comparison With Standard PET/CT.

    Science.gov (United States)

    Teixeira, Suzana C; Rebolleda, José Ferrér; Koolen, Bas B; Wesseling, Jelle; Jurado, Raúl Sánchez; Stokkel, Marcel P M; Del Puig Cózar Santiago, María; van der Noort, Vincent; Rutgers, Emiel J Th; Valdés Olmos, Renato A

    2016-06-01

    The purposes of this study were to evaluate the performance of a mammography with molecular imaging PET (MAMMI-PET) system for breast imaging in the hanging-breast position for the visualization of primary breast cancer lesions and to compare this method with whole-body PET/CT. Between March 2011 and March 2014, a prospective evaluation included women with one or more histologically confirmed primary breast cancer lesions (index lesions). After injection of 180-240 MBq of (18)F-FDG, whole-body PET/CT and MAMMI-PET acquisitions were performed, index lesions were scored 0, 1, or 2 for FDG uptake relative to background. Detection and FDG uptake were compared by breast length, maximal tumor diameter, affected breast quadrants, tumor grade, and histologic and immunologic sub-types. Finally, the two PET modalities were compared for detection of index lesions. For 234 index lesions (diameter, 5-170 mm), the overall sensitivity was 88.9% for MAMMI-PET and 91% for PET/CT (p = 0.61). Twenty-three (9.8%) index lesions located too close to the pectoral muscle were missed with MAMMI-PET, and 20 index lesions were missed with PET/CT. Lesion visibility on MAMMI-PET images was influenced by tumor grade (p = 0.034) but not by cancer subtype (p = 0.65). Although in an overall evaluation MAMMI-PET was not superior to PET/CT, MAMMI-PET does have higher sensitivity for primary breast cancer lesions within the scanning range of the device. Optimization of the positioning device may increase visualization of the most dorsal lesions.

  16. Superior outcome of women with stage I/II cutaneous melanoma: Pooled analysis of four European organisation for research and treatment of cancer phase III trials

    NARCIS (Netherlands)

    A. Joosse (Arjen); S. Collette (Sandra); S. Suciu (Stefan); T.E.C. Nijsten (Tamar); F.J. Lejeune (Ferdy); U.R. Kleeberg (Ulrich); J.W.W. Coebergh (Jan Willem); A.M.M. Eggermont (Alexander); E.G.E. de Vries (Elisabeth)

    2012-01-01

    textabstractPurpose: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for

  17. Virulence of Pseudomonas syringae pv. tomato DC3000 Is Influenced by the Catabolite Repression Control Protein Crc.

    Science.gov (United States)

    Chakravarthy, Suma; Butcher, Bronwyn G; Liu, Yingyu; D'Amico, Katherine; Coster, Matthew; Filiatrault, Melanie J

    2017-04-01

    Pseudomonas syringae infects diverse plant species and is widely used as a model system in the study of effector function and the molecular basis of plant diseases. Although the relationship between bacterial metabolism, nutrient acquisition, and virulence has attracted increasing attention in bacterial pathology, it is largely unexplored in P. syringae. The Crc (catabolite repression control) protein is a putative RNA-binding protein that regulates carbon metabolism as well as a number of other factors in the pseudomonads. Here, we show that deletion of crc increased bacterial swarming motility and biofilm formation. The crc mutant showed reduced growth and symptoms in Arabidopsis and tomato when compared with the wild-type strain. We have evidence that the crc mutant shows delayed hypersensitive response (HR) when infiltrated into Nicotiana benthamiana and tobacco. Interestingly, the crc mutant was more susceptible to hydrogen peroxide, suggesting that, in planta, the mutant may be sensitive to reactive oxygen species generated during pathogen-associated molecular pattern-triggered immunity (PTI). Indeed, HR was further delayed when PTI-induced tissues were challenged with the crc mutant. The crc mutant did not elicit an altered PTI response in plants compared with the wild-type strain. We conclude that Crc plays an important role in growth and survival during infection.

  18. Many unexpected abdominal findings on staging computed tomography in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Holmsted, Kim; Nørring, Keld; Laustrup, Lene Collatz

    2011-01-01

    ; an issue that was previously studied in relation to CT colonography, but not in relation to staging CT with intravenous contrast in CRC patients. The aim of the present study was to evaluate the number and significance of such unexpected findings on staging CTs in CRC patients.......Computed tomography (CT) was proven to be superior to preoperative abdominal ultrasound in the preoperative setting for detection of hepatic metastases from colorectal cancer (CRC). The higher sensitivity of CT has resulted in a number of unexpected abdominal findings of varying importance...

  19. CCF analysis of BWR reactor shutdown systems based on the operating experience at the TVO I/II in 1981-1993

    International Nuclear Information System (INIS)

    Mankamo, T.

    1996-04-01

    The work constitutes a part of the project conducted within the research program of the Swedish Nuclear Power Inspectorate SKI, aimed to develop the methods and data base for the Common Cause Failure (CCF) analysis of highly redundant reactor scram systems. The data analysis for the TVO I/II plant is focused on the hydraulic scram system, and control rods and drives. It covers operating experiences from 1981 through 1993. (9 refs., 9 figs., 7 tabs.)

  20. [Processes of ventricles I-III. Review of the patient population of the Neurosurgery Clinic of the Karl Marx University 1953-1983].

    Science.gov (United States)

    Niebeling, H G; Goldhahn, W E

    1985-01-01

    Within three decades 254 patients with processes of the brain ventricles I-III have been treated at the Leipzig Neurosurgical Clinic. The article subdivides the patients in general and according to the histology, localisation, lateral differences, dignity, operability as well as the postoperative lethality. The evaluation gives many clues with respect to the diagnostics and therapy of these ventricular processes. Today, the improvements obtained by computer tomography and by microsurgery are well the to fore.

  1. Self reported awareness of child maltreatment among school professionals in Saudi Arabia: impact of CRC ratification.

    Science.gov (United States)

    AlBuhairan, Fadia S; Inam, Sarah S; AlEissa, Majid A; Noor, Ismail K; Almuneef, Maha A

    2011-12-01

    The Convention on the Rights of the Child (CRC) was ratified by Saudi Arabia 15 years ago; yet addressing the issue of child maltreatment only began in more recent years. School professionals play a significant role in children's lives, as they spend a great deal of time with them and are hence essential to protecting and identifying those in danger or at risk. The objective of this study is to identify school professional's awareness of child maltreatment and the existing national policies and procedures to examine the extent of efforts made in Saudi Arabia and to activate the roles of schools and school professionals in protecting children from violence and implementation of Article 19 of the CRC. This was a cross-sectional study, where school professionals from randomly selected schools throughout the country were invited to participate in a self-administered questionnaire. A total of 3,777 school professionals participated in the study. Fifty-five percent of professionals had at least 10 years of work experience. A low-level of awareness of child maltreatment was found in about 1/3 of school professionals. Only 1.9% of school professionals had ever attended any sort of specific training on child maltreatment, though 69.3% of those who had not, were willing to attend future training. With regards to awareness of CRC Article 19 or policies and procedures addressing child maltreatment, only 22% reported being aware of it. The majority of school professionals in Saudi Arabia have a low-intermediate level of awareness of child maltreatment, ratification of CRC, and related national policies and procedures, yet most are willing to attend training programs on this subject matter. Efforts need to be made in the country to fill this gap. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

    Science.gov (United States)

    Mohapatra, Shyam S; Batra, Surinder K; Bharadwaj, Srinivas; Bouvet, Michael; Cosman, Bard; Goel, Ajay; Jogunoori, Wilma; Kelley, Michael J; Mishra, Lopa; Mishra, Bibhuti; Mohapatra, Subhra; Patel, Bhaumik; Pisegna, Joseph R; Raufman, Jean-Pierre; Rao, Shuyun; Roy, Hemant; Scheuner, Maren; Singh, Satish; Vidyarthi, Gitanjali; White, Jon

    2018-05-01

    Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.

  3. Influence of the Crc regulator on the hierarchical use of carbon sources from a complete medium in Pseudomonas.

    Science.gov (United States)

    La Rosa, Ruggero; Behrends, Volker; Williams, Huw D; Bundy, Jacob G; Rojo, Fernando

    2016-03-01

    The Crc protein, together with the Hfq protein, participates in catabolite repression in pseudomonads, helping to coordinate metabolism. Little is known about how Crc affects the hierarchy of metabolite assimilation from complex mixtures. Using proton Nuclear Magnetic Resonance (NMR) spectroscopy, we carried out comprehensive metabolite profiling of culture supernatants (metabolic footprinting) over the course of growth of both Pseudomonas putida and P. aeruginosa, and compared the wild-type strains with deletion mutants for crc. A complex metabolite consumption hierarchy was observed, which was broadly similar between the two species, although with some important differences, for example in sugar utilization. The order of metabolite utilization changed upon inactivation of the crc gene, but even in the Crc-null strains some compounds were completely consumed before late metabolites were taken up. This suggests the presence of additional regulatory elements that determine the time and order of consumption of compounds. Unexpectedly, the loss of Crc led both species to excrete acetate and pyruvate as a result of unbalanced growth during exponential phase, compounds that were later consumed in stationary phase. This loss of carbon during growth helps to explain the contribution of the Crc/Hfq regulatory system to evolutionary fitness of pseudomonads. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. Low Complexity List Decoding for Polar Codes with Multiple CRC Codes

    Directory of Open Access Journals (Sweden)

    Jong-Hwan Kim

    2017-04-01

    Full Text Available Polar codes are the first family of error correcting codes that provably achieve the capacity of symmetric binary-input discrete memoryless channels with low complexity. Since the development of polar codes, there have been many studies to improve their finite-length performance. As a result, polar codes are now adopted as a channel code for the control channel of 5G new radio of the 3rd generation partnership project. However, the decoder implementation is one of the big practical problems and low complexity decoding has been studied. This paper addresses a low complexity successive cancellation list decoding for polar codes utilizing multiple cyclic redundancy check (CRC codes. While some research uses multiple CRC codes to reduce memory and time complexity, we consider the operational complexity of decoding, and reduce it by optimizing CRC positions in combination with a modified decoding operation. Resultingly, the proposed scheme obtains not only complexity reduction from early stopping of decoding, but also additional reduction from the reduced number of decoding paths.

  5. Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC)

    DEFF Research Database (Denmark)

    Winther, Stine Braendegaard; Zubcevic, Kanita; Qvortrup, Camilla

    2016-01-01

    BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate...... of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx......) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44...

  6. Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review).

    Science.gov (United States)

    Nikolouzakis, Taxiarchis Konstantinos; Vassilopoulou, Loukia; Fragkiadaki, Persefoni; Mariolis Sapsakos, Theodoros; Papadakis, Georgios Z; Spandidos, Demetrios A; Tsatsakis, Aristides M; Tsiaoussis, John

    2018-06-01

    Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer‑related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).

  7. Assessing Religious Orientations: Replication and Validation of the Commitment-Reflectivity Circumplex (CRC Model

    Directory of Open Access Journals (Sweden)

    Steven L. Isaak

    2017-09-01

    Full Text Available The Commitment-Reflectivity Circumplex (CRC model is a structural model of religious orientation that was designed to help organize and clarify measurement of foundational aspect of religiousness. The current study successfully replicated the CRC model using multidimensional scaling, and further evaluated the reliability, structure, and validity of their measures in both a university student sample (Study 1 and a nationally representative sample (Study 2. All 10 subscales of the Circumplex Religious Orientation Inventory (CROI demonstrated good reliability across both samples. A two-week test-retest of the CROI showed that the subscales are stable over time. A confirmatory factor analysis of the CROI in the representative adult sample demonstrated good model fit. Finally, the CROI’s validity was examined in relation to the Intrinsic, Extrinsic and Quest measures. Overall, the CROI appears to clarify much of the ambiguity inherent in the established scales by breaking down what were very broad orientations into very specific suborientations. The results suggest that the CRC model is applicable for diverse populations of adults. In addition, the CROI appears to be construct valid with good structural and psychometric properties across all 10 subscales.

  8. Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Sonnleitner, Elisabeth; Valentini, Martina; Wenner, Nicolas; Haichar, Feth el Zahar; Haas, Dieter; Lapouge, Karine

    2012-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is able to utilize a wide range of carbon and nitrogen compounds, allowing it to grow in vastly different environments. The uptake and catabolism of growth substrates are organized hierarchically by a mechanism termed catabolite repression control (Crc) whereby the Crc protein establishes translational repression of target mRNAs at CA (catabolite activity) motifs present in target mRNAs near ribosome binding sites. Poor carbon sources lead to activation of the CbrAB two-component system, which induces transcription of the small RNA (sRNA) CrcZ. This sRNA relieves Crc-mediated repression of target mRNAs. In this study, we have identified novel targets of the CbrAB/Crc system in P. aeruginosa using transcriptome analysis in combination with a search for CA motifs. We characterized four target genes involved in the uptake and utilization of less preferred carbon sources: estA (secreted esterase), acsA (acetyl-CoA synthetase), bkdR (regulator of branched-chain amino acid catabolism) and aroP2 (aromatic amino acid uptake protein). Evidence for regulation by CbrAB, CrcZ and Crc was obtained in vivo using appropriate reporter fusions, in which mutation of the CA motif resulted in loss of catabolite repression. CbrB and CrcZ were important for growth of P. aeruginosa in cystic fibrosis (CF) sputum medium, suggesting that the CbrAB/Crc system may act as an important regulator during chronic infection of the CF lung.

  9. Association between hMLH1 hypermethylation and JC virus (JCV) infection in human colorectal cancer (CRC).

    Science.gov (United States)

    Vilkin, Alex; Niv, Yaron

    2011-04-01

    Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA. Chromosomal instability (CIN) was established as the key mechanism in cancer development. Later, it was found that CRC results not only from the progressive accumulation of genetic alterations but also from epigenetic changes. JC virus (JCV) is a candidate etiologic factor in sporadic CRC. It may act by stabilizing β-catenin, facilitating its entrance to the cell nucleus, initialing proliferation and cancer development. Diploid CRC cell lines transfected with JCV-containing plasmids developed CIN. This result provides direct experimental evidence for the ability of JCV T-Ag to induce CIN in the genome of colonic epithelial cells. The association of CRC hMLH1 methylation and tumor positivity for JCV was recently documented. JC virus T-Ag DNA sequences were found in 77% of CRCs and are associated with promoter methylation of multiple genes. hMLH1 was methylated in 25 out of 80 CRC patients positive for T-Ag (31%) in comparison with only one out of 11 T-Ag negative cases (9%). Thus, JCV can mediate both CIN and aberrant methylation in CRC. Like other viruses, chronic infection with JCV may induce CRC by different mechanisms which should be further investigated. Thus, gene promoter methylation induced by JCV may be an important process in CRC and the polyp-carcinoma sequence.

  10. Geographic Variations of Colorectal and Breast Cancer Late-Stage Diagnosis and the Effects of Neighborhood-Level Factors.

    Science.gov (United States)

    Lin, Yan; Wimberly, Michael C

    2017-04-01

    The purpose of this study was to examine the geographic variations of late-stage diagnosis in colorectal cancer (CRC) and breast cancer as well as to investigate the effects of 3 neighborhood-level factors-socioeconomic deprivation, urban/rural residence, and spatial accessibility to health care-on the late-stage risks. This study used population-based South Dakota cancer registry data from 2001 to 2012. A total of 4,878 CRC cases and 6,418 breast cancer cases were included in the analyses. Two-level logistic regression models were used to analyze the risk of late-stage CRC and breast cancer. For CRC, there was a small geographic variation across census tracts in late-stage diagnosis, and residing in isolated small rural areas was significantly associated with late-stage risk. However, this association became nonsignificant after adjusting for census-tract level socioeconomic deprivation. Socioeconomic deprivation was an independent predictor of CRC late-stage risk, and it explained the elevated risk among American Indians. No relationship was found between spatial accessibility and CRC late-stage risk. For breast cancer, no geographic variation in the late-stage diagnosis was observed across census tracts, and none of the 3 neighborhood-level factors was significantly associated with late-stage risk. Results suggested that socioeconomic deprivation, rather than spatial accessibility, contributed to CRC late-stage risks in South Dakota as a rural state. CRC intervention programs could be developed to target isolated small rural areas, socioeconomically disadvantaged areas, as well as American Indians residing in these areas. © 2016 National Rural Health Association.

  11. The New UN CRC General Comment 13: "The Right of the Child to Freedom from All Forms of Violence"--Changing How the World Conceptualizes Child Protection

    Science.gov (United States)

    Svevo-Cianci, Kimberly A.; Herczog, Maria; Krappmann, Lothar; Cook, Philip

    2011-01-01

    The UN Committee on the Rights of the Child established CRC General Comment 13 (April 2011) to address today's unabating high rates of violence against children globally despite CRC advances. GC13 provides clear interpretations and stronger detail to supplement the legal language of CRC Article 19, intended to establish protection of children from…

  12. Evaluating adhesion reduction efficacy of type I/III collagen membrane and collagen-GAG resorbable matrix in primary flexor tendon repair in a chicken model.

    Science.gov (United States)

    Turner, John B; Corazzini, Rubina L; Butler, Timothy J; Garlick, David S; Rinker, Brian D

    2015-09-01

    Reduction of peritendinous adhesions after injury and repair has been the subject of extensive prior investigation. The application of a circumferential barrier at the repair site may limit the quantity of peritendinous adhesions while preserving the tendon's innate ability to heal. The authors compare the effectiveness of a type I/III collagen membrane and a collagen-glycosaminoglycan (GAG) resorbable matrix in reducing tendon adhesions in an experimental chicken model of a "zone II" tendon laceration and repair. In Leghorn chickens, flexor tendons were sharply divided using a scalpel and underwent repair in a standard fashion (54 total repairs). The sites were treated with a type I/III collagen membrane, collagen-GAG resorbable matrix, or saline in a randomized fashion. After 3 weeks, qualitative and semiquantitative histological analysis was performed to evaluate the "extent of peritendinous adhesions" and "nature of tendon healing." The data was evaluated with chi-square analysis and unpaired Student's t test. For both collagen materials, there was a statistically significant improvement in the degree of both extent of peritendinous adhesions and nature of tendon healing relative to the control group. There was no significant difference seen between the two materials. There was one tendon rupture observed in each treatment group. Surgical handling characteristics were subjectively favored for type I/III collagen membrane over the collagen-GAG resorbable matrix. The ideal method of reducing clinically significant tendon adhesions after injury remains elusive. Both materials in this study demonstrate promise in reducing tendon adhesions after flexor tendon repair without impeding tendon healing in this model.

  13. Epigenetic Metabolite Acetate Inhibits Class I/II Histone Deacetylases, Promotes Histone Acetylation, and Increases HIV-1 Integration in CD4+ T Cells.

    Science.gov (United States)

    Bolduc, Jean-François; Hany, Laurent; Barat, Corinne; Ouellet, Michel; Tremblay, Michel J

    2017-08-15

    In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4 + T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4 + T cells upon acetate treatment. This enhancing effect correlates with increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration into the genome of CD4 + T cells. Thus, we propose that upon antigen presentation, acetate influences class I/II HDAC activity that transforms condensed chromatin into a more relaxed structure. This event leads to a higher level of viral integration and enhanced HIV-1 production. In line with previous studies showing reactivation of latent HIV-1 by SCFAs, we provide evidence that acetate can also increase the susceptibility of primary human CD4 + T cells to productive HIV-1 infection. IMPORTANCE Alterations in the fecal microbiota and intestinal epithelial damage involved in the gastrointestinal disorder associated with HIV-1 infection result in microbial translocation that leads to disease progression and virus-related comorbidities. Indeed, notably via production of short-chain fatty acids, bacteria migrating from the lumen to the intestinal mucosa could influence HIV-1 replication by epigenetic regulatory mechanisms, such as histone acetylation. We demonstrate that acetate enhances virus production in primary human CD4 + T cells. Moreover, we report that acetate impairs class I/II histone deacetylase activity and increases integration of HIV-1 DNA into the host genome. Therefore, it can be postulated that bacterial metabolites such as acetate modulate HIV-1-mediated disease progression. Copyright © 2017 American Society for Microbiology.

  14. Stages of endometriosis: Does it affect in vitro fertilization outcome

    Directory of Open Access Journals (Sweden)

    Sonja Pop-Trajkovic

    2014-06-01

    Conclusion: The American Society for Reproductive Medicine classification of endometriosis is useful in predicting IVF outcome. Advanced endometriosis means a worse prognosis for IVF treatment compared to milder stages or tubal factor infertility. The decreased fertilization rate in Stage I/II endometriosis might be a cause of subfertility in these women, as a result of a hostile environment caused by the disease.

  15. Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial.

    Science.gov (United States)

    Lubis, Andri M T; Siagian, Carles; Wonggokusuma, Erick; Marsetyo, Aldo F; Setyohadi, Bambang

    2017-04-01

    Glucosamine, chondroitinsulfate are frequently used to prevent further joint degeneration in osteoarthritis (OA). Methylsulfonylmethane (MSM) is a supplement containing organic sulphur and also reported to slow anatomical joint progressivity in the knee OA. The MSM is often combined with glucosamine and chondroitin sulfate. However, there are controversies whether glucosamine-chondroitin sulfate or their combination with methylsulfonylmethane could effectively reduce pain in OA. This study is aimed to compare clinical outcome of glucosamine-chondroitin sulfate (GC), glucosamine-chondroitin sulfate-methylsulfonylmethane (GCM), and placeboin patients with knee osteoarthritis (OA) Kellgren-Lawrence grade I-II. a double blind, randomized controlled clinical trial was conducted on 147 patients with knee OA Kellgren-Lawrence grade I-II. Patients were allocated by permuted block randomization into three groups: GC (n=49), GCM (n=50), or placebo (n=48) groups. GC group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of saccharumlactis; GCM group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of MSM; while placebo group received three matching capsules of saccharumlactis. The drugs were administered once daily for 3 consecutive months VAS and WOMAC scores were measured before treatment, then at 4th, 8th and 12th week after treatment. on statistical analysis it was found that at the 12th week, there are significant difference between three treatment groups on the WOMAC score (p=0.03) and on the VAS score (p=0.004). When analyzed between weeks, GCM treatment group was found statistically significant on WOMAC score (p=0.01) and VAS score (p<0.001). Comparing the score difference between weeks, WOMAC score analysis showed significant difference between GC, GCM, and placebo in week 4 (p=0.049) and week 12 (p=0.01). In addition, VAS score also showed significant difference between groups in week 8 (p=0.006) and week 12 (p<0.001). combination of glucosamine-chondroitinsulfate-methylsulfonylmethane showed clinical benefit for patients with knee OAK ellgren-Lawrence grade I-II compared with GC and placebo. GC did not make clinical improvement in overall groups of patients with knee OA Kellgren Lawrence grade I-II.

  16. Binding Properties of Streptococcus gordonii SspA and SspB (Antigen I/II Family) Polypeptides Expressed on the Cell Surface of Lactococcus lactis MG1363

    OpenAIRE

    Holmes, Ann R.; Gilbert, Christophe; Wells, Jeremy M.; Jenkinson, Howard F.

    1998-01-01

    The oral bacterium Streptococcus gordonii expresses two cell wall-associated polypeptides, designated SspA (1,542 amino acid residues) and SspB (1,462 amino acid residues), that have 70% sequence identity. These polypeptides are members of the antigen I/II family of oral streptococcal adhesins and mediate the binding of streptococci to salivary glycoproteins, collagen, and other oral microorganisms such as Actinomyces naeslundii. To determine if SspA and SspB have differential binding propert...

  17. G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of Plk1.

    Science.gov (United States)

    Zhang, Jie; Wang, Yafang; Shen, Yanyan; He, Pengxing; Ding, Jian; Chen, Yi

    2018-01-01

    Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a. Detailed molecular mechanisms underlying the effect of G9a on Plk1 expression were determined by performing point mutation analysis, chromatin immunoprecipitation analysis, and luciferase reporter assay. Correlation between G9a and Plk1 expression was determined by analyzing clinical samples of patients with CRC by performing immunohistochemistry. Results: Our study is the first to report a significant positive correlation between G9a and Plk1 levels in 89 clinical samples of patients with CRC. Moreover, G9a depletion decreased Plk1 expression and suppressed CRC cell growth both in vitro and in vivo , thus confirming the significant correlation between G9a and Plk1 levels. Further, we observed that G9a-induced Plk1 regulation depended on p53 inhibition. G9a dimethylated p53 at lysine 373, which in turn increased Plk1 expression and promoted CRC cell growth. Conclusions: These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.

  18. The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells.

    Science.gov (United States)

    Jumpertz, Sandra; Hennes, Thomas; Asare, Yaw; Vervoorts, Jörg; Bernhagen, Jürgen; Schütz, Anke K

    2014-09-01

    COP9 signalosome subunit 5 (CSN5) plays a decisive role in cellular processes such as cell cycle regulation and apoptosis via promoting protein degradation, gene transcription, and nuclear export. CSN5 regulates cullin-RING-E3 ligase (CRL) activity through its deNEDDylase function. It is overexpressed in several tumor entities, but its role in colorectal cancer (CRC) is poorly understood. Wnt/β-catenin signaling is aberrant in most CRC cells, resulting in increased levels of oncogenic β-catenin and thus tumor progression. Under physiological conditions, β-catenin levels are tightly regulated by continuous proteasomal degradation. We recently showed that knockdown of CSN5 in model and CRC cells results in decreased (phospho)-β-catenin levels. Reduced β-catenin levels were associated with an attenuated proliferation rate of different CRC cell types after CSN5 knockdown. The canonical Wnt pathway involves degradation of β-catenin by a β-TrCP1-containing E3 ligase, but is mostly non-functional in CRC cells. We thus hypothesized that alternative β-catenin degradation mediated by SIAH-1 (seven in absentia homolog-1), is responsible for the effect of CSN5 on β-catenin signaling in CRC cells. We found that SIAH-1 plays an essential role in β-catenin degradation in HCT116 CRC cells and that CSN5 affects β-catenin target gene expression in these cells. Of note, CSN5 affected SIAH-1 mRNA and SIAH-1 protein levels. Moreover, β-catenin and SIAH-1 form protein complexes with CSN5 in HCT116 cells. Lastly, we demonstrate that CSN5 promotes SIAH-1 degradation in HCT116 and SW480 cells and that this is associated with its deNEDDylase activity. In conclusion, we have identified a CSN5/β-catenin/SIAH-1 interaction network that might control β-catenin degradation in CRC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Diagnostic value of fecal tumor M2-pyruvate kinase for CRC screening: a systematic review and meta-analysis.

    Science.gov (United States)

    Li, Rui; Liu, Jianjun; Xue, Huiping; Huang, Gang

    2012-10-15

    The measurement of fecal tumor M2-pyruvate kinase (PKM2), overexpressed in tumor cells, has been proposed as a novel tool for detecting colorectal cancer (CRC). However, the sensitivity and specificity of this test varied among studies. The aim of this meta-analysis was to determine the diagnostic accuracy of fecal PKM2 for CRC and to evaluate its utility in the CRC screening. It was compared to guaiac fecal occult blood test (gFOBT) or immunological fecal occult blood test (iFOBT). Through comprehensive literature search, 10 studies met the inclusion criteria and were included. Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The hierarchical summary receiver operating characteristic curve was also undertaken. The overall sensitivity and specificity of fecal PKM2 for detecting CRC were 79% (95% CI = 75-83%) and 81% (95% CI = 73-87%), respectively. The summary positive predictive value and negative predictive value were 74% (95% CI = 56-87%) and 86% (95% CI = 79-91%), respectively. The pooled diagnostic odds ratio was 16 (95% CI = 10-26). In head-to-head comparison, the diagnostic odds ratio of PKM2 and gFOBT for CRC were 10.167 (95% CI = 5.992-17.250) and 6.557 (95% CI = 3.467-12.403), respectively. The diagnostic odds ratio of PKM2 and iFOBT for CRC were 9.542 (95% CI = 5.893-15.452) and 67.248 (95% CI = 16.194-279.26), respectively. The fecal PKM2 test was a diagnostic tool with moderate sensitivity and specificity for detecting CRC. Its diagnostic efficiency was similar to that of gFOBT. Because of its relatively low specificity and positive predict value, fecal PKM2 was not recommended used alone as a screening tool for CRC. Copyright © 2012 UICC.

  20. MEG3 is a prognostic factor for CRC and promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis.

    Science.gov (United States)

    Li, Lixia; Shang, Jian; Zhang, Yupeng; Liu, Shi; Peng, Yanan; Zhou, Zhou; Pan, Huaqing; Wang, Xiaobing; Chen, Lipng; Zhao, Qiu

    2017-09-01

    A major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to oxaliplatin-based chemotherapy. Recently, studies have shown that long non-coding RNAs (lncRNAs) play an important role in drug resistance. Using HiSeq sequencing methods, we identified that lncRNAs show differential expression levels in oxaliplatin-resistant (OxR) and non-resistant CRC patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MEG3 was verified to be downregulated in non-responding patients and to have considerable discriminating potential to identify responding patients from non-responding patients. Moreover, decreased serum MEG3 expression was associated with poor chemoresponse and low survival rate in CRC patients receiving oxaliplatin treatment. Subsequently, OxR cell lines were established, and MEG3 was significantly downregulated in HT29 OxR and SW480 OxR cells. In addition, overexpression of MEG3 with pMEG3 reversed oxaliplatin resistance in both CRC cell lines. Flow cytometric apoptosis analysis indicated that MEG3 promoted CRC cell apoptosis. More importantly, MEG3 enhanced oxaliplatin‑induced cell cytotoxicity in CRC. In conclusion, our integrated approach demonstrated that decreased expression of lncRNA MEG3 in CRC confers potent poor therapeutic efficacy, and that MEG3 promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis. Thus, overexpression of MEG3 may be a future direction by which to develop a novel therapeutic strategy to overcome oxaliplatin resistance of CRC patients.

  1. DEAD-box helicase 27 promotes colorectal cancer growth and metastasis and predicts poor survival in CRC patients.

    Science.gov (United States)

    Tang, Jieting; Chen, Huarong; Wong, Chi-Chun; Liu, Dabin; Li, Tong; Wang, Xiaohong; Ji, Jiafu; Sung, Joseph Jy; Fang, Jing-Yuan; Yu, Jun

    2018-03-14

    Copy number alterations (CNAs) are crucial for colorectal cancer (CRC) development. In this study, DEAD box polypeptide 27 (DDX27) was identified to be highly amplified in both TCGA CRC (474/615) and primary CRC (47/103), which was positively correlated with its mRNA overexpression. High DDX27 mRNA (N = 199) and protein expression (N = 260) predicted poor survival in CRC patients. Ectopic expression of DDX27 increased CRC cells proliferation, migration and invasion, but suppressed apoptosis. Conversely, silencing of DDX27 exerted opposite effects in vitro and significantly inhibited murine xenograft tumor growth and lung metastasis in vivo. Up-regulation of DDX27 enhanced and prolonged TNF-α-mediated NF-κB signaling. Nucleophosmin (NPM1) was identified as a binding partner of DDX27. DDX27 increased nuclear NPM1 and NF-κB-p65 interaction to enhance DNA binding activity of NF-κB. Silencing NPM1 abrogated DDX27-activating NF-κB signaling and its tumor-promoting function. Together, DDX27 is overexpressed and plays a pivotal oncogenic role in CRC.

  2. RGC32 induces epithelial-mesenchymal transition by activating the Smad/Sip1 signaling pathway in CRC.

    Science.gov (United States)

    Wang, Xiao-Yan; Li, Sheng-Nan; Zhu, Hui-Fang; Hu, Zhi-Yan; Zhong, Yan; Gu, Chuan-Sha; Chen, Shi-You; Liu, Teng-Fei; Li, Zu-Guo

    2017-05-04

    Response gene to complement 32 (RGC32) is a transcription factor that regulates the expression of multiple genes involved in cell growth, viability and tissue-specific differentiation. However, the role of RGC32 in tumorigenesis and tumor progression in colorectal cancer (CRC) has not been fully elucidated. Here, we showed that the expression of RGC32 was significantly up-regulated in human CRC tissues versus adjacent normal tissues. RGC32 expression was significantly correlated with invasive and aggressive characteristics of tumor cells, as well as poor survival of CRC patients. We also demonstrated that RGC32 overexpression promoted proliferation, migration and tumorigenic growth of human CRC cells in vitro and in vivo. Functionally, RGC32 facilitated epithelial-mesenchymal transition (EMT) in CRC via the Smad/Sip1 signaling pathway, as shown by decreasing E-cadherin expression and increasing vimentin expression. In conclusion, our findings suggested that overexpression of RGC32 facilitates EMT of CRC cells by activating Smad/Sip1 signaling.

  3. Increased risk for CRC in diabetic patients with the nonrisk allele of SNPs at 8q24.

    Science.gov (United States)

    Ishimaru, Shinya; Mimori, Koshi; Yamamoto, Ken; Inoue, Hiroshi; Imoto, Seiya; Kawano, Shuichi; Yamaguchi, Rui; Sato, Tetsuya; Toh, Hiroyuki; Iinuma, Hisae; Maeda, Toyoki; Ishii, Hideshi; Suzuki, Sadao; Tokudome, Shinkan; Watanabe, Masahiko; Tanaka, Jun-ichi; Kudo, Shin-ei; Sugihara, Ken-ichi; Hase, Kazuo; Mochizuki, Hidetaka; Kusunoki, Masato; Yamada, Kazutaka; Shimada, Yasuhiro; Moriya, Yoshihiro; Barnard, Graham F; Miyano, Satoru; Mori, Masaki

    2012-09-01

    Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.

  4. The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa.

    Science.gov (United States)

    Dong, Yi-Hu; Zhang, Xi-Fen; Zhang, Lian-Hui

    2013-02-01

    The opportunistic pathogen Pseudomonas aeruginosa utilizes type III secretion system (T3SS) to translocate effector proteins into eukaryotic host cells that subvert normal host cell functions to the benefit of the pathogen, and results in serious infections. T3SS in P. aeruginosa is controlled by a complex system of regulatory mechanisms and signaling pathways. In this study, we described that Crc, an RNA-binding protein, exerts a positive impact on T3SS in P. aeruginosa, as evidenced by promoter activity assays of several key T3SS genes, transcriptomics, RT-PCR, and immunoblotting in crc mutant. We further demonstrated that the regulatory function of Crc on the T3SS was mediated through the T3SS master regulator ExsA and linked to the Cbr/Crc signaling system. Expression profiling of the crc mutant revealed a downregulation of flagship T3SS genes as well as 16 other genes known to regulate T3SS gene expression in P. aeruginosa. On the basis of these data, we proposed that Crc may exert multifaceted control on the T3SS through various pathways, which may serve to fine-tune this virulence mechanism in response to environmental changes and nutrient sources. © 2012 The Authors. Published by Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  5. Evaluating the impact of an educational intervention to increase CRC screening rates in the African American community: a preliminary study.

    Science.gov (United States)

    Philip, Errol J; DuHamel, Katherine; Jandorf, Lina

    2010-10-01

    Despite the acknowledged importance of colorectal cancer (CRC) screening and its proven prognostic benefit, African American men and women simultaneously possess the highest rates of CRC-related incidence and mortality (Swan et al. in Cancer 97(6):1528-1540, 2003) and lowest screening rates in the United States (Polite et al. in Med Clin N Am 89(4):771-793, 2005). Effective, targeted interventions that promote CRC screening for this community are therefore critical. The current study evaluated the impact of a print-based educational intervention on screening behavior and associated patient-based factors, including cancer-related knowledge, fatalism, worry, and decisional balance (pros-cons). One hundred and eighteen individuals (mean age = 56.08, SD = 5.58) who had not undergone screening were recruited from two health clinics in New York City. Each participant received educational print materials regarding the need for screening, the process of undergoing screening, and the benefits of regular CRC screening. One in four individuals had undergone post-intervention screening at a three-month follow-up. Whereas all participants reported a decrease in cancer-related worry (p benefits and barriers of screening may be critical in the decision to undergo CRC screening. Future interventions to increase CRC-screening rates for this community may be improved by focusing on these patient-based factors.

  6. B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jiali Li

    2018-01-01

    Full Text Available Background/Aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Results: Fifty out of 136 CRC patients (37% expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031 and lymph node metastasis (P=0.012. Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289. β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227. Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT.

  7. The safety and efficacy of microwave ablation for the treatment of CRC pulmonary metastases.

    Science.gov (United States)

    Cheng, Gui; Shi, Liangrong; Qiang, Weiguang; Wu, Jun; Ji, Mei; Lu, Qicheng; Li, Xiaodong; Xu, Bin; Jiang, Jingting; Wu, Changping

    2017-11-16

    Microwave ablation (MWA) is a recently developed thermal ablation technique that has been used for the treatment of different types of tumours. In the present study, we retrospectively evaluated the safety and efficacy of CT-guided percutaneous MWA for the treatment of colorectal cancer (CRC) pulmonary metastases. From June 2010 to June 2015, 48 unresectable lesions in 32 patients with CRC pulmonary metastases were subjected to CT-guided MWA. Imaging follow-up was with contrast-enhanced CT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Oncologic imaging showed that 42 (87.5%) of the 48 lesions in the 32 patients were completely ablated. Needle track metastatic seeding was not found, and no patient deaths occurred within 30 d after ablation. The mean hospital stay was 3 d (range, 2-7 d). Pneumothorax was the most frequent complication and occurred in 6 (12.5%) of the 48 lesions. The median survival time was 31 months (95% CI: 15.4-46.6). The 1-, 2- and 3-year survival rates were 79.5%, 63.1% and 44.4%, respectively. Univariate Cox regression analysis showed that tumour size, disease-free interval (DFI) and number of tumours were significantly related to the overall survival time (p = .007, p = .022 and p = .030, respectively). Multivariate analysis showed that tumour size was an independent prognostic factor for survival (p = .017). CT-guided percutaneous MWA is a safe and effective minimally invasive method for treating CRC pulmonary metastases.

  8. Enhancement MRI evaluation of neuroblastoma staging in children

    International Nuclear Information System (INIS)

    Li Xin; Wang Chunxiang; Zhao Bin; Liu Peifang

    2002-01-01

    Objective: To evaluate the value and limitation of Gd-DTPA enhanced MRI for neuroblastoma staging in children. Methods: Twelve cases of neuroblastoma proved by operation or bone marrow aspiration were examined by gadolinium-enhanced MRI. The age ranged from seven months to five years, mean 3.7 years. Eight tumors originated from adrenal, and four from posterior mediastinum. Conventional sequences, double dose gadolinium-enhanced MRI, and 3D CEMRA were used in all patients. Six cases were examined by CT in same time. Imaging staging on surgic-histopathological-based International Neuroblastoma Staging System (INSS) was performed. Results: Six patients were staged by CT, including stage I-II in 2 cases, stage III in 4 cases, and stage IV in none. Twelve patients were staged by conventional MRI, including stage I-II in 2 cases, stage III in 9 cases, and stage IV in 1 case. Twelve patients were staged by double dose gadolinium-enhanced MRI, including stage I-II in 1 case, stage III in 1 case, and stage IV in 10 cases. Conclusion: Gadolinium-enhanced MRI was a single best imaging modality for neuroblastoma, most useful for distal to diaphragm metastasis, dumbbell tumor intraspinal extension, and bone marrow metastasis that was not detected by aspirate examination. Enhancement MRI was important in evaluating the therapy and was also helpful in assessing the therapeutic efficacy and relapse. 3D CEMRA helps demonstrate large vascular encasement and tumor erosion into important organs, and it is useful in assessing the respectability. Long examination time and lack in showing the characteristic calcium were the limitations

  9. From Large-Scale Synthesis to Lighting Device Applications of Ternary I-III-VI Semiconductor Nanocrystals: Inspiring Greener Material Emitters.

    Science.gov (United States)

    Chen, Bingkun; Pradhan, Narayan; Zhong, Haizheng

    2018-01-18

    Quantum dots with fabulous size-dependent and color-tunable emissions remained as one of the most exciting inventories in nanomaterials for the last 3 decades. Even though a large number of such dot nanocrystals were developed, CdSe still remained as unbeatable and highly trusted lighting nanocrystals. Beyond these, the ternary I-III-VI family of nanocrystals emerged as the most widely accepted greener materials with efficient emissions tunable in visible as well as NIR spectral windows. These bring the high possibility of their implementation as lighting materials acceptable to the community and also to the environment. Keeping these in mind, in this Perspective, the latest developments of ternary I-III-VI nanocrystals from their large-scale synthesis to device applications are presented. Incorporating ZnS, tuning the composition, mixing with other nanocrystals, and doping with Mn ions, light-emitting devices of single color as well as for generating white light emissions are also discussed. In addition, the future prospects of these materials in lighting applications are also proposed.

  10. Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?

    International Nuclear Information System (INIS)

    Aloysius, Mark M; Zaitoun, Abed M; Bates, Timothy E; Ilyas, Mohammad; Constantin-Teodosiu, Dumitru; Rowlands, Brian J; Lobo, Dileep N

    2010-01-01

    Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis. This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. MMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours. Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets

  11. Effect of Compressive Mode I on the Mixed Mode I/II Fatigue Crack Growth Rate of 42CrMo4

    Science.gov (United States)

    Heirani, Hasan; Farhangdoost, Khalil

    2018-01-01

    Subsurface cracks in mechanical contact loading components are subjected to mixed mode I/II, so it is necessary to evaluate the fatigue behavior of materials under mixed mode loading. For this purpose, fatigue crack propagation tests are performed with compact tension shear specimens for several stress intensity factor (SIF) ratios of mode I and mode II. The effect of compressive mode I loading on mixed mode I/II crack growth rate and fracture surface is investigated. Tests are carried out for the pure mode I, pure mode II, and two different mixed mode loading angles. On the basis of the experimental results, mixed mode crack growth rate parameters are proposed according to Tanaka and Richard with Paris' law. Results show neither Richard's nor Tanaka's equivalent SIFs are very useful because these SIFs depend strongly on the loading angle, but Richard's equivalent SIF formula is more suitable than Tanaka's formula. The compressive mode I causes the crack closure, and the friction force between the crack surfaces resists against the crack growth. In compressive loading with 45° angle, d a/d N increases as K eq decreases.

  12. Surgical Strategies in the Treatment of Gynecomastia Grade I-II: The Combination of Liposuction and Subcutaneous Mastectomy Provides Excellent Patient Outcome and Satisfaction.

    Science.gov (United States)

    Schröder, Lars; Rudlowski, Christian; Walgenbach-Brünagel, Gisela; Leutner, Claudia; Kuhn, Walther; Walgenbach, Klaus-Jürgen

    2015-07-01

    Gynecomastia (GM) is a benign condition with glandular tissue enlargement of the male breast. GM is classified into 4 grades of increasing severity. We describe a series of GM grade I-II, diagnosed, treated surgically and analyzed regarding feasibility, complication rate, and satisfaction. From 2005 to 2012, a chart review was performed for 53 patients. Preoperative examination included endocrine and urological examination and exclusion of other pathological conditions. The surgical technique consisted of liposuction through an inframammarian-fold incision and excision of the glandular tissue by a minimal periareolar approach. A total number of 53 male patients with 104 breasts were available for analysis. By liposuction, a median of 300 ml (range: 10-1000 ml) was aspirated from each breast and 25.1 g (range: 3-233 g) gland tissue was resected. Surgery lasted between 25 and 164 min per patient (median: 72 min). 2 postoperative hemorrhages occurred (n = 2, 3.8%). 2 patients underwent re-operation due to cosmetic reasons (n = 2, 3.8%). This analysis demonstrates that treatment of GM grade I-II can easily be performed by liposuction combined with subcutaneous resection of the glandular tissue as a minimally invasive and low-impact surgical treatment with a low rate of complications and excellent patient satisfaction. Preoperative workup is important to rule out specific diseases or malignancy causing the GM.

  13. IRRIGATION PRACTICES IN LONG-TERM SURVIVORS OF COLORECTAL CANCER (CRC) WITH COLOSTOMIES

    Science.gov (United States)

    Grant, Marcia; McMullen, Carmit K.; Altschuler, Andrea; Hornbrook, Mark C.; Herrinton, Lisa J.; Wendel, Christopher S.; Baldwin, Carol M.; Krouse, Robert S.

    2014-01-01

    Creation of a colostomy in colorectal (CRC) cancer patients results in a loss of control over bowel evacuation. The only way to re-establish some control is through irrigation, a procedure that involves instilling fluid into the bowel to allow for gas and fecal output. This article reports on irrigation practices of participants in a large, multi-site, multi-investigator study of health-related quality of life (HR-QOL) in long term CRC survivors. Questions about irrigation practices were identified in open-ended questions within a large HR-QOL survey and in focus groups of men and women with high and low HR-QOL. Descriptive data on survivors were combined with content analysis of irrigation knowledge and practices. Patient education and use of irrigation in the United States has decreased over the years, with no clear identification of why this change in practice has occurred. Those respondents who used irrigation had their surgery longer ago, and spent more time in colostomy care than those that did not irrigate. Reasons for the decrease in colostomy irrigation are unreported and present priorities for needed research. PMID:23022935

  14. Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Bazarbashi, Shouki; Aljubran, Ali; Alzahrani, Ahmad; Mohieldin, Ahmed; Soudy, Hussein; Shoukri, Mohammed

    2015-01-01

    Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m 2 . Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity

  15. The translational repressor Crc controls the Pseudomonas putida benzoate and alkane catabolic pathways using a multi-tier regulation strategy.

    Science.gov (United States)

    Hernández-Arranz, Sofía; Moreno, Renata; Rojo, Fernando

    2013-01-01

    Metabolically versatile bacteria usually perceive aromatic compounds and hydrocarbons as non-preferred carbon sources, and their assimilation is inhibited if more preferable substrates are available. This is achieved via catabolite repression. In Pseudomonas putida, the expression of the genes allowing the assimilation of benzoate and n-alkanes is strongly inhibited by catabolite repression, a process controlled by the translational repressor Crc. Crc binds to and inhibits the translation of benR and alkS mRNAs, which encode the transcriptional activators that induce the expression of the benzoate and alkane degradation genes respectively. However, sequences similar to those recognized by Crc in benR and alkS mRNAs exist as well in the translation initiation regions of the mRNA of several structural genes of the benzoate and alkane pathways, which suggests that Crc may also regulate their translation. The present results show that some of these sites are functional, and that Crc inhibits the induction of both pathways by limiting not only the translation of their transcriptional activators, but also that of genes coding for the first enzyme in each pathway. Crc may also inhibit the translation of a gene involved in benzoate uptake. This multi-tier approach probably ensures the rapid regulation of pathway genes, minimizing the assimilation of non-preferred substrates when better options are available. A survey of possible Crc sites in the mRNAs of genes associated with other catabolic pathways suggested that targeting substrate uptake, pathway induction and/or pathway enzymes may be a common strategy to control the assimilation of non-preferred compounds. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  16. NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.

    Science.gov (United States)

    Narayan, Satya; Jaiswal, Aruna S; Sharma, Ritika; Nawab, Akbar; Duckworth, Lizette Vila; Law, Brian K; Zajac-Kaye, Maria; George, Thomas J; Sharma, Jay; Sharma, Arun K; Hromas, Robert A

    2017-08-22

    The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. In the present study, we have identified a novel orphan molecule NSC30049 (NSC49L) that is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. It also inhibits the sphere forming activity of CRC stem cells, and decreases the expression levels of mRNAs of CRC stem cell marker genes. Results showed that NSC49L induces 5-FU-mediated S-phase cell cycle arrest due to increased load of DNA damage and increased γ-H2AX staining as a mechanism of cytotoxicity. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life. The drug is highly tolerated by animals with no pathological aberrations. Furthermore, NSC49L showed very potent activity in a HDTX model of CRC stem cell tumors either alone or in combination with 5-FU. Thus, NSC49L as a single agent or combined with 5-FU can be developed as a therapeutic agent by targeting the Chk1 pathway in 5-FU-resistant CRC heterogeneous bulk and CRC stem cell populations.

  17. Overexpression of the S100A2 protein as a prognostic marker for patients with stage II and III colorectal cancer

    Science.gov (United States)

    MASUDA, TAIKI; ISHIKAWA, TOSHIAKI; MOGUSHI, KAORU; OKAZAKI, SATOSHI; ISHIGURO, MEGUMI; IIDA, SATORU; MIZUSHIMA, HIROSHI; TANAKA, HIROSHI; UETAKE, HIROYUKI; SUGIHARA, KENICHI

    2016-01-01

    We aimed to identify a novel prognostic biomarker related to recurrence in stage II and III colorectal cancer (CRC) patients. Stage II and III CRC tissue mRNA expression was profiled using an Affymetrix Gene Chip, and copy number profiles of 125 patients were generated using an Affymetrix 250K Sty array. Genes showing both upregulated expression and copy number gains in cases involving recurrence were extracted as candidate biomarkers. The protein expression of the candidate gene was assessed using immunohistochemical staining of tissue from 161 patients. The relationship between protein expression and clinicopathological features was also examined. We identified 9 candidate genes related to recurrence of stage II and III CRC, whose mRNA expression was significantly higher in CRC than in normal tissue. Of these proteins, the S100 calcium-binding protein A2 (S100A2) has been observed in several human cancers. S100A2 protein overexpression in CRC cells was associated with significantly worse overall survival and relapse-free survival, indicating that S100A2 is an independent risk factor for stage II and III CRC recurrence. S100A2 overexpression in cancer cells could be a biomarker of poor prognosis in stage II and III CRC recurrence and a target for treatment of this disease. PMID:26783118

  18. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse

    Directory of Open Access Journals (Sweden)

    Rabeah A. Al-Temaimi

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT. Resultant genes were classified based on gene ontology (GO, which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.

  19. Toxoplasma Chinese 1 Strain of WH3Δrop16I/III/gra15II Genetic Background Contributes to Abnormal Pregnant Outcomes in Murine Model

    Directory of Open Access Journals (Sweden)

    Cong Wang

    2018-06-01

    Full Text Available Toxoplasma gondii infection evokes a strong Th1-type response with interleukin (IL-12 and interferon (IFN-γ secretion. Recent studies suggest that the infection of pregnant mice with T. gondii may lead to adverse pregnancy results caused by subversion of physiological immune tolerance at maternofetal interface rather than direct invasion of the parasite. Genotype-associated dense granule protein GRA15II tends to induce classically activated macrophage (M1 differentiation and subsequently activating NK, Th1, and Th17 cells whereas rhoptry protein ROP16I/III drives macrophages to alternatively activated macrophage (M2 polarization and elicits Th2 immune response. Unlike the archetypal strains of types I, II, and III, type Chinese 1 strains possess both GRA15II and ROP16I/III, suggesting a distinct pathogenesis of Toxoplasma-involved adverse pregnancies. We constructed T. gondii type Chinese 1 strain of WH3Δrop16 based on CRISPR/Cas9 technology to explore the ROP16I/III-deficient/GRA15II-dominant parasites in induction of trophoblast apoptosis in vitro and abnormal pregnant outcomes of mice in vivo. Our study showed that Toxoplasma WH3Δrop16 remarkably induced apoptosis of trophoblasts. C57BL/6 pregnant mice injected with the tachyzoites of WH3Δrop16 presented increased absorptivity of fetuses in comparison with the mice infected with WH3 wild type (WH3 WT parasites although no remarkable difference of virulence to mice was seen between the two strains. Additionally, the mice inoculated with WH3Δrop16 tachyzoites exhibited a notable expression of both IL-17A and IFN-γ, while the percentage of CD4+CD25+FoxP3 [T regulatory cells (Tregs] were diminished in splenocytes and placenta tissues compared to those infected with WH3 WT parasites. Accordingly, expressions of IL-4, IL-10, and transforming growth factor beta 1, the pivotal cytokines of Th2 and Tregs response, were significantly dampened whereas IFN-γ and IL-12 expressions were

  20. Identification and Construction of Combinatory Cancer Hallmark-Based Gene Signature Sets to Predict Recurrence and Chemotherapy Benefit in Stage II Colorectal Cancer.

    Science.gov (United States)

    Gao, Shanwu; Tibiche, Chabane; Zou, Jinfeng; Zaman, Naif; Trifiro, Mark; O'Connor-McCourt, Maureen; Wang, Edwin

    2016-01-01

    Decisions regarding adjuvant therapy in patients with stage II colorectal cancer (CRC) have been among the most challenging and controversial in oncology over the past 20 years. To develop robust combinatory cancer hallmark-based gene signature sets (CSS sets) that more accurately predict prognosis and identify a subset of patients with stage II CRC who could gain survival benefits from adjuvant chemotherapy. Thirteen retrospective studies of patients with stage II CRC who had clinical follow-up and adjuvant chemotherapy were analyzed. Respective totals of 162 and 843 patients from 2 and 11 independent cohorts were used as the discovery and validation cohorts, respectively. A total of 1005 patients with stage II CRC were included in the 13 cohorts. Among them, 84 of 416 patients in 3 independent cohorts received fluorouracil-based adjuvant chemotherapy. Identification of CSS sets to predict relapse-free survival and identify a subset of patients with stage II CRC who could gain substantial survival benefits from fluorouracil-based adjuvant chemotherapy. Eight cancer hallmark-based gene signatures (30 genes each) were identified and used to construct CSS sets for determining prognosis. The CSS sets were validated in 11 independent cohorts of 767 patients with stage II CRC who did not receive adjuvant chemotherapy. The CSS sets accurately stratified patients into low-, intermediate-, and high-risk groups. Five-year relapse-free survival rates were 94%, 78%, and 45%, respectively, representing 60%, 28%, and 12% of patients with stage II disease. The 416 patients with CSS set-defined high-risk stage II CRC who received fluorouracil-based adjuvant chemotherapy showed a substantial gain in survival benefits from the treatment (ie, recurrence reduced by 30%-40% in 5 years). The CSS sets substantially outperformed other prognostic predictors of stage 2 CRC. They are more accurate and robust for prognostic predictions and facilitate the identification of patients with stage

  1. A Quality Improvement Initiative to Increase Colorectal Cancer (CRC) Screening: Collaboration between a Primary Care Clinic and Research Team.

    Science.gov (United States)

    Green, Beverly B; Fuller, Sharon; Anderson, Melissa L; Mahoney, Christine; Mendy, Peter; Powell, Susan L

    2017-01-01

    Multiple randomized controlled trials have demonstrated that mailed fecal testing programs are effective in increasing colorectal cancer screening participation. However, few healthcare organization in the US have Implemented such programs. Stakeholders from one clinic in an integrated healthcare system in Washington State initiated collaboration with researchers with expertise in CRC screening, aiming to increase screening rates at their clinic. Age-eligible individuals who were overdue for CRC screening and had previously completed a fecal test were randomized to receive mailed fecal immunochemical test kits (FIT) at the start of the project (Early) or 6 months later (Late). Outcomes included comparing FIT completion at 6 months by randomization group, and overall CRC screening rates at 12 months. We also assessed implementation facilitators and challenges. Overall 2,421 FIT tests were mailed at a cost of $10,739. At 6 months, FIT completion was significantly higher among the Early compared to the Late group (62% vs.47%, p CRC screening rate was 75.1% at baseline and 78.0% 12 months later. Key constructs associated with successful program implementation included strong stakeholder involvement, use of evidence-based strategies, simplicity, and low cost. Challenges included lack of a plan for maintaining the program. Collaboration between clinic stakeholders and researchers led to a successful project that rapidly increased CRC screening rates. However, institutional normalization of the program would be required to maintain it.

  2. The Crc protein inhibits the production of polyhydroxyalkanoates in Pseudomonas putida under balanced carbon/nitrogen growth conditions.

    Science.gov (United States)

    La Rosa, Ruggero; de la Peña, Fernando; Prieto, María Axiliadora; Rojo, Fernando

    2014-01-01

    Pseudomonas putida synthesizes polyhydroxyalkanoates (PHAs) as storage compounds. PHA synthesis is more active when the carbon source is in excess and the nitrogen source is limiting, but can also occur at a lower rate under balanced carbon/nitrogen ratios. This work shows that PHA synthesis is controlled by the Crc global regulator, a protein that optimizes carbon metabolism by inhibiting the expression of genes involved in the use of non-preferred carbon sources. Crc acts post-transcriptionally. The mRNAs of target genes contain characteristic catabolite activity (CA) motifs near the ribosome binding site. Sequences resembling CA motifs can be predicted for the phaC1 gene, which codes for a PHA polymerase, and for phaI and phaF, which encode proteins associated to PHA granules. Our results show that Crc inhibits the translation of phaC1 mRNA, but not that of phaI or phaF, reducing the amount of PHA accumulated in the cell. Crc inhibited PHA synthesis during exponential growth in media containing a balanced carbon/nitrogen ratio. No inhibition was seen when the carbon/nitrogen ratio was imbalanced. This extends the role of Crc beyond that of controlling the hierarchical utilization of carbon sources and provides a link between PHA synthesis and the global regulatory networks controlling carbon flow. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. I-III-VI.sub.2 based solar cell utilizing the structure CuInGaSe.sub.2 CdZnS/ZnO

    Science.gov (United States)

    Chen, Wen S.; Stewart, John M.

    1992-01-07

    A thin film I-III-VI.sub.2 based solar cell having a first layer of copper indium gallium selenide, a second layer of cadmium zinc sulfide, a double layer of zinc oxide, and a metallization structure comprised of a layer of nickel covered by a layer of aluminum. An optional antireflective coating may be placed on said metallization structure. The cadmium zinc sulfide layer is deposited by means of an aqueous solution growth deposition process and may actually consist of two layers: a low zinc content layer and a high zinc content layer. Photovoltaic efficiencies of 12.5% at Air Mass 1.5 illumination conditions and 10.4% under AMO illumination can be achieved.

  4. The PACOVAR-trial: A phase I/II study of pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant recurrent, pre-treated ovarian cancer

    International Nuclear Information System (INIS)

    Eichbaum, Michael; Fersis, Nikos; Schmidt, Marcus; Wallwiener, Markus; Schneeweiss, Andreas; Sohn, Christof; Mayer, Christine; Eickhoff, Regina; Bischofs, Esther; Gebauer, Gerhard; Fehm, Tanja; Lenz, Florian; Fricke, Hans-Christian; Solomayer, Erich

    2011-01-01

    The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC) is poor. There is no standard treatment available. Emerging evidence suggests a major role for antiangiogenic treatment modalities in EOC, in particular in combination with the metronomic application of low dose chemotherapy. The novel, investigational oral antiangiogenic agent pazopanib targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit is currently being studied in different tumour types and is already used as first line therapy in recurrent renal cell carcinoma. A combined therapy consisting of pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, pretreated EOC. This study is designed as a multicenter phase I/II trial evaluating the optimal dose for pazopanib (phase I) as well as activity and tolerability of a combination regimen consisting of pazopanib and metronomic cyclophosphamide in the palliative treatment of patients with recurrent, platinum-resistant, pre-treated ovarian cancer (phase II). The patient population includes patients with histologically or cytologically confirmed diagnosis of EOC, cancer of the fallopian tube or peritoneal cancer which is platinumresistant or -refractory. Patients must have measurable disease according to RECIST criteria and must have failed available standard chemotherapy. Primary objectives are determination of the optimal doses for pazopanib (phase I) and the overall response rate according to RECIST criteria (phase II). Secondary objectives are time to progression, overall survival, safety and tolerability. The treatment duration is until disease progression or intolerability of study drug regimen (with a maximum of 13 cycles up to 52 weeks per subject). The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01238770

  5. The liquid-liquid extraction of chloro-(trichlorostannato)-rhodium(I/III) and -ruthenium (II) complexes from dilute hydrochloric acid into 4-methylpentan-2-one

    International Nuclear Information System (INIS)

    Wyrley-Birch, J.M.

    1984-10-01

    The effect of stannous chloride on the liquid-liquid extraction of rhodium and ruthenium from hydrochloric acid solutions into 4-methyl-pentan-2-one (MIBK)/hexane mixtures was studied in detail. Stannous chloride concentrations were found to considerably increase the efficiency of the extraction of rhodium and ruthenium into the organic phase. Chloro-(trichlorostannato)-rhodium (I/III) complexes were formed at room temperature. The rate of chloro-(trichlorostannato)-ruthenium (II) complex formation was extremely slow at room temperature, but increased on heating of the aqueous solutions. The amount of rhodium and ruthenium extracted into the organic phase depend on the Sn(II):M molar ratio, the HCl, H sup(+) and Cl sup(-) concentrations, as well as the equilibration time. A 119 Sn NMR study of the MIBK extracts, showed that the stoichiometry of the chloro-(trichlorostannato)-rhodium (I/III) complexes extracted into the organic phase was dependent on the Sn(II):Rh(III) molar ratio as well as the HCl, H sup(+) and Cl sup(-) concentrations in the aqueous phase. The predominant species observed in the organic phase from HCl solutions containing Sn(II):Rh(III) ratios >= 5:1, was shown to be an hydrido complex having the form [RhH(SnCl 3 ) 4 Cl] 3 sup(-) or [RhH(SnCl 3 ) 4 ]2 sup(-). An essentially quantitative separation of rhodium and ruthenium was achieved utilising the variation in the rates of rhodium-tin and ruthenium-tin complex formation

  6. Backbone and stereospecific (13)C methyl Ile (δ1), Leu and Val side-chain chemical shift assignments of Crc.

    Science.gov (United States)

    Sharma, Rakhi; Sahu, Bhubanananda; Ray, Malay K; Deshmukh, Mandar V

    2015-04-01

    Carbon catabolite repression (CCR) allows bacteria to selectively assimilate a preferred compound among a mixture of several potential carbon sources, thus boosting growth and economizing the cost of adaptability to variable nutrients in the environment. The RNA-binding catabolite repression control (Crc) protein acts as a global post-transcriptional regulator of CCR in Pseudomonas species. Crc triggers repression by inhibiting the expression of genes involved in transport and catabolism of non-preferred substrates, thus indirectly favoring assimilation of preferred one. We report here a nearly complete backbone and stereospecific (13)C methyl side-chain chemical shift assignments of Ile (δ1), Leu and Val of Crc (~ 31 kDa) from Pseudomonas syringae Lz4W.

  7. Instantaneous Kinematics Analysis via Screw-Theory of a Novel 3-CRC Parallel Mechanism

    Directory of Open Access Journals (Sweden)

    Hussein de la Torre

    2016-06-01

    Full Text Available This paper presents the mobility and kinematics analysis of a novel parallel mechanism that is composed by one base, one platform and three identical limbs with CRC joints. The paper obtains closed-form solutions to the direct and inverse kinematics problems, and determines the mobility of the mechanism and instantaneous kinematics by applying screw theory. The obtained results show that this parallel robot is part of the family 2R1T, since the platform shows 3 DOF, i.e.: one translation perpendicular to the base and two rotations about skew axes. In order to calculate the direct instantaneous kinematics, this paper introduces the vector mh, which is part of the joint velocity vector that multiplies the overall inverse Jacobian matrix. This paper compares the results between simulations and numerical examples using Mathematica and SolidWorks in order to prove the accuracy of the analytical results.

  8. Polarization Property Measurement of the Long Undulator Radiation Using Cr/C Multilayer Polarization Elements

    International Nuclear Information System (INIS)

    Niibe, Masahito; Mukai, Mikihito; Shoji, Yoshihiko; Kimura, Hiroaki

    2004-01-01

    A rotating analyzer ellipsometry (RAE) system was developed with Cr/C multilayers that function as polarization elements for photon energy range of 110 - 280 eV. Polarization properties of a planar undulator change axisymmetrically in off-axial manner, and the second harmonic is more remarkable for the change. By using the RAE system, the polarization property of the second harmonic radiation from the NewSUBARU long undulator at the energy of 180 eV was examined. The degree of linear polarization of the on-axis radiation was over 0.996. The spatial distribution of the polarization azimuth was measured and was in fair agreement with the theoretical calculation. A peculiar behavior of the polarization property near the radiation peak of the second harmonic was observed by changing the height of the undulator gap

  9. Is Travel Time to Colonoscopy Associated With Late-Stage Colorectal Cancer Among Medicare Beneficiaries in Iowa?

    Science.gov (United States)

    Charlton, Mary E; Matthews, Kevin A; Gaglioti, Anne; Bay, Camden; McDowell, Bradley D; Ward, Marcia M; Levy, Barcey T

    2016-09-01

    Colorectal cancer (CRC) screening has been shown to decrease the incidence of late-stage colorectal cancer, yet a substantial proportion of Americans do not receive screening. Those in rural areas may face barriers to colonoscopy services based on travel time, and previous studies have demonstrated lower screening among rural residents. Our purpose was to assess factors associated with late-stage CRC, and specifically to determine if longer travel time to colonoscopy was associated with late-stage CRC among an insured population in Iowa. SEER-Medicare data were used to identify individuals ages 65 to 84 years old diagnosed with CRC in Iowa from 2002 to 2009. The distance between the centroid of the ZIP code of residence and the ZIP code of colonoscopy was computed for each individual who had continuous Medicare fee-for-service coverage for a 3- to 4-month period prior to diagnosis, and a professional claim for colonoscopy within that time frame. Demographic characteristics and travel times were compared between those diagnosed with early- versus late-stage CRC. Also, demographic differences between those who had colonoscopy claims identified within 3-4 months prior to diagnosis (81%) were compared to patients with no colonoscopy claims identified (19%). A total of 5,792 subjects met inclusion criteria; 31% were diagnosed with early-stage versus 69% with late-stage CRC. Those divorced or widowed (vs married) were more likely to be diagnosed with late-stage CRC (OR: 1.20, 95% CI: 1.06-1.37). Travel time was not associated with diagnosis of late-stage CRC. Among a Medicare-insured population, there was no relationship between travel time to colonoscopy and disease stage at diagnosis. It is likely that factors other than distance to colonoscopy present more pertinent barriers to screening in this insured population. Additional research should be done to determine reasons for nonadherence to screening among those with access to CRC screening services, given that over

  10. Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.

    Science.gov (United States)

    Deevi, Ravi Kiran; Javadi, Arman; McClements, Jane; Vohhodina, Jekaterina; Savage, Kienan; Loughrey, Maurice Bernard; Evergren, Emma; Campbell, Frederick Charles

    2018-04-01

    Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi-lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low-grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high-grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high-grade morphology in formalin-fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of

  11. Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

    Science.gov (United States)

    Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

    2016-03-01

    BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

  12. Family history assessment for colorectal cancer (CRC) risk analysis - comparison of diagram- and questionnaire-based web interfaces.

    Science.gov (United States)

    Schultz, Michael; Seo, Steven Bohwan; Holt, Alec; Regenbrecht, Holger

    2015-11-18

    Colorectal cancer (CRC) has a high incidence, especially in New Zealand. The reasons for this are unknown. While most cancers develop sporadically, a positive family history, determined by the number and age at diagnosis of affected first and second degree relatives with CRC is one of the major factors, which may increase an individual's lifetime risk. Before a patient can be enrolled in a surveillance program a detailed assessment and documentation of the family history is important but time consuming and often inaccurate. The documentation is usually paper-based. Our aim was therefore to develop and validate the usability and efficacy of a web-based family history assessment tool for CRC suitable for the general population. The tool was also to calculate the risk and make a recommendation for surveillance. Two versions of an electronic assessment tool, diagram-based and questionnaire-based, were developed with the risk analysis and recommendations for surveillance based on the New Zealand Guidelines Group recommendations. Accuracy of our tool was tested prior to the study by comparing risk calculations based on family history by experienced gastroenterologists with the electronic assessment. The general public, visiting a local science fair were asked to use and comment on the usability of the two interfaces. Ninety people assessed and commented on the two interfaces. Both interfaces were effective in assessing the risk to develop CRC through their familial history for CRC. However, the questionnaire-based interface performed with significantly better satisfaction (p = 0.001) than the diagram-based interface. There was no difference in efficacy though. We conclude that a web-based questionnaire tool can assist in the accurate documentation and analysis of the family history relevant to determine the individual risk of CRC based on local guidelines. The calculator is now implemented and assessable through the web-page of a local charity for colorectal cancer

  13. Disease severity does not affect the interval between IBD diagnosis and the development of CRC: results from two large, Dutch case series.

    Science.gov (United States)

    Mooiweer, Erik; Baars, Judith E; Lutgens, Maurice W M D; Vleggaar, Frank; van Oijen, Martijn; Siersema, Peter D; Kuipers, Ernst J; van der Woude, C Janneke; Oldenburg, Bas

    2012-05-01

    The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (pCRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  14. The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

    Science.gov (United States)

    Henriksen, Hege Berg; Ræder, Hanna; Bøhn, Siv Kjølsrud; Paur, Ingvild; Kværner, Ane Sørlie; Billington, Siv Åshild; Eriksen, Morten Tandberg; Wiedsvang, Gro; Erlund, Iris; Færden, Arne; Veierød, Marit Bragelien; Zucknick, Manuela; Smeland, Sigbjørn; Blomhoff, Rune

    2017-01-30

    Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for

  15. The Crc and Hfq proteins of Pseudomonas putida cooperate in catabolite repression and formation of ribonucleic acid complexes with specific target motifs.

    Science.gov (United States)

    Moreno, Renata; Hernández-Arranz, Sofía; La Rosa, Ruggero; Yuste, Luis; Madhushani, Anjana; Shingler, Victoria; Rojo, Fernando

    2015-01-01

    The Crc protein is a global regulator that has a key role in catabolite repression and optimization of metabolism in Pseudomonads. Crc inhibits gene expression post-transcriptionally, preventing translation of mRNAs bearing an AAnAAnAA motif [the catabolite activity (CA) motif] close to the translation start site. Although Crc was initially believed to bind RNA by itself, this idea was recently challenged by results suggesting that a protein co-purifying with Crc, presumably the Hfq protein, could account for the detected RNA-binding activity. Hfq is an abundant protein that has a central role in post-transcriptional gene regulation. Herein, we show that the Pseudomonas putida Hfq protein can recognize the CA motifs of RNAs through its distal face and that Crc facilitates formation of a more stable complex at these targets. Crc was unable to bind RNA in the absence of Hfq. However, pull-down assays showed that Crc and Hfq can form a co-complex with RNA containing a CA motif in vitro. Inactivation of the hfq or the crc gene impaired catabolite repression to a similar extent. We propose that Crc and Hfq cooperate in catabolite repression, probably through forming a stable co-complex with RNAs containing CA motifs to result in inhibition of translation initiation. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  16. DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC.

    Science.gov (United States)

    Liu, Yan-Ping; Zhu, Hui-Fang; Liu, Ding-Li; Hu, Zhi-Yan; Li, Sheng-Nan; Kan, He-Ping; Wang, Xiao-Yan; Li, Zu-Guo

    2016-11-22

    Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.

  17. A phase I/II study on stereotactic body radiotherapy with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm for lung tumors.

    Science.gov (United States)

    Iwata, Hiromitsu; Ishikura, Satoshi; Murai, Taro; Iwabuchi, Michio; Inoue, Mitsuhiro; Tatewaki, Koshi; Ohta, Seiji; Yokota, Naoki; Shibamoto, Yuta

    2017-08-01

    In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade ≥3 radiation pneumonitis (RP) within 180 days of the start of SBRT. The secondary endpoint was local control and overall survival rates. Five patients were initially enrolled at level 1 [50 Gy/4 fractions (Fr)]; during the observation period, level 0 (45 Gy/4 Fr) was opened. The dose was escalated to the next level when grade ≥3 RP was observed in 0 out of 5 or 1 out of 10 patients. Virtual quality assurance planning was performed for 60 Gy/4 Fr; however, dose constraints for the organs at risk did not appear to be within acceptable ranges. Therefore, level 2 (55 Gy/4 Fr) was regarded as the upper limit. After the recommended dose (RD) was established, 15 additional patients were enrolled at the RD. The prescribed dose was normalized at the 95% volume border of the planning target volume based on the Monte Carlo algorithm. Between September 2011 and September 2015, 40 patients (primary 30; metastasis 10) were enrolled. Five patients were enrolled at level 0, 15 at level 1, and 20 at level 2. Only one grade 3 RP was observed at level 1. Two-year local control and overall survival rates were 98 and 81%, respectively. The RD was 55 Gy/4 Fr. SBRT with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm was tolerated well and appeared to be effective for solitary lung tumors.

  18. EFECTO DE LA ADICIÓN DE CARRAGENINA KAPPA I.II Y GOMA TARA SOBRE CARACTERÍSTICAS DE CALIDAD DEL JAMÓN DE CERDO PICADO Y COCIDO EFFECT OF THE ADDITION OF KAPPA I.II CARRAGEENAN AND TARA GUM ON QUALITY CHARACTERISTICS OF COOKED AND CHOPPED PORK HAMS

    OpenAIRE

    Diego Alonso Restrepo Molina; Fabio Alexander Molina Cote; Kenneth Roy Cabrera Torres

    2010-01-01

    Se evaluaron sinéresis, color y dureza instrumental y, sensorialmente las características de olor, sabor, color y dureza en jamones inyectados, cocidos y picados de cerdo, los cuales se habían elaborado aplicando en la salmuera de inyección una mezcla de hidrocoloides compuesta por carragenina kappa I.II y goma tara en una proporción de 79:21, en niveles del 1% y 1,2%, usando tres repeticiones para el estudio. Los jamones así elaborados se compararon contra un jamón testigo, elaborado sin el ...

  19. The role of RCAS1 as a biomarker in diagnosing CRC and monitoring tumor recurrence and metastasis.

    Science.gov (United States)

    Han, Su-xia; Wang, Jing; Wang, Li-juan; Jin, Gui-hua; Ying, Xia; He, Chen-chen; Guo, Xi-jing; Zhang, Jian-ying; Zhang, Ying; Zhu, Qing

    2014-06-01

    Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) plays an important role in tumor progression by helping tumor cell to escape from host immunological surveillance or modifying the characteristics of connective tissue around. RCAS1 may appropriately reflect the development and prognosis of tumor. In the study, we sought to identify the clinical significance of RCAS1 in colorectal cancer (CRC) diagnosis and tumor recurrence monitoring. Immunohistochemistry (IHC) with tissue array slides was preformed to analyze RCAS1 protein expression in CRC, colorectal polyps, and normal colon tissues. RCAS1 levels in colorectal cancer were significantly higher than those in colorectal polyps and normal colon tissues (PCRC are significantly higher than in healthy controls and polyps (PCRC was 82.1 %, which was higher than carcinoembryonic antigen (CEA). Especially in CEA-negative cases, the sensitivity of RCAS1 was 88.2 %. Finally, CRC patients who were followed up showed a serum RCAS1 level which significantly decreased after surgery (PCRC diagnosis but also useful for monitoring tumor recurrence. RCAS1 might be a supplementary serological marker for CRC.

  20. Protecting Children from Violence and Maltreatment: A Qualitative Comparative Analysis Assessing the Implementation of U.N. CRC Article 19

    Science.gov (United States)

    Svevo-Cianci, Kimberly A.; Hart, Stuart N.; Rubinson, Claude

    2010-01-01

    Objectives: (1) To identify which United Nations Convention on the Rights of the Child (CRC) recommended child protection (CP) measures, such as policy, reporting systems, and services for child abuse and neglect (CAN) victims, individually or in combination, were most important in establishing a basic level of child protection in 42 countries;…

  1. CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

    International Nuclear Information System (INIS)

    Seidel, Claudia; Dietrich, Antje; Wondrak, Marit; Kunz-Schughart, Leoni A.; Grade, Marian; Ried, Thomas

    2009-01-01

    The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133 + ) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133 + subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133 + cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133 + / CD133 - subpopulations

  2. Comprehensive analysis of published phase I/II clinical trials between 1990-2010 in osteosarcoma and Ewing sarcoma confirms limited outcomes and need for translational investment

    Directory of Open Access Journals (Sweden)

    van Maldegem Annemiek M

    2012-01-01

    Full Text Available Abstract Background High grade primary bone sarcomas are rare cancers that affect mostly children and young adults. Osteosarcoma and Ewing sarcoma are the most common histological subtypes in this age group, with current multimodality treatment strategies achieving 55-70% overall survival. As there remains an urgent need to develop new therapeutic interventions, we have reviewed published phase I/II trials that have been reported for osteosarcoma and Ewing sarcoma in the last twenty years. Results We conducted a literature search for clinical trials between 1990 and 2010, either for trials enrolling bone sarcoma patients as part of a general sarcoma indication or trials specifically in osteosarcoma and Ewing sarcoma. We identified 42 clinical trials that fulfilled our search criteria for general sarcoma that enrolled these patient groups, and eight and twenty specific trials for Ewing and osteosarcoma patients, respectively. For the phase I trials which enrolled different tumour types our results were incomplete, because the sarcoma patients were not mentioned in the PubMed abstract. A total of 3,736 sarcoma patients were included in these trials over this period, 1,114 for osteosarcoma and 1,263 for Ewing sarcoma. As a proportion of the worldwide disease burden over this period, these numbers reflect a very small percentage of the potential patient recruitment, approximately 0.6% for Ewing sarcoma and 0.2% for osteosarcoma. However, these data show an increase in recent activity overall and suggest there is still much room for improvement in the current trial development structures. Conclusion Lack of resources and commercial investment will inevitably limit opportunity to develop sufficiently rapid improvements in clinical outcomes. International collaboration exists in many well founded co-operative groups for phase III trials, but progress may be more effective if there were also more investment of molecular and translational research into disease focused phase I/II clinical trials. Examples of new models for early translational and early phase trial collaboration include the European based EuroBoNeT network, the Sarcoma Alliance for Research through Collaboration network (SARC and the new European collaborative translational trial network, EuroSarc.

  3. Recruiting community health centers into pragmatic research: Findings from STOP CRC.

    Science.gov (United States)

    Coronado, Gloria D; Retecki, Sally; Schneider, Jennifer; Taplin, Stephen H; Burdick, Tim; Green, Beverly B

    2016-04-01

    Challenges of recruiting participants into pragmatic trials, particularly at the level of the health system, remain largely unexplored. As part of Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC), we recruited eight separate community health centers (consisting of 26 individual safety net clinics) into a large comparative effectiveness pragmatic study to evaluate methods of raising the rates of colorectal cancer screening. In partnership with STOP CRC's advisory board, we defined criteria to identify eligible health centers and applied these criteria to a list of health centers in Washington, Oregon, and California affiliated with Oregon Community Health Information Network, a 16-state practice-based research network of federally sponsored health centers. Project staff contacted centers that met eligibility criteria and arranged in-person meetings of key study investigators with health center leadership teams. We used the Consolidated Framework for Implementation Research to thematically analyze the content of discussions during these meetings to identify major facilitators of and barriers to health center participation. From an initial list of 41 health centers, 11 met the initial inclusion criteria. Of these, leaders at three centers declined and at eight centers (26 clinic sites) agreed to participate (73%). Participating and nonparticipating health centers were similar with respect to clinic size, percent Hispanic patients, and percent uninsured patients. Participating health centers had higher proportions of Medicaid patients and higher baseline colorectal cancer screening rates. Common facilitators of participation were perception by center leadership that the project was an opportunity to increase colorectal cancer screening rates and to use electronic health record tools for population management. Barriers to participation were concerns of center leaders about ability to provide fecal testing to and assure follow-up of

  4. Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk.

    Science.gov (United States)

    Wang, Wei; Shao, Yan; Tang, Shenhua; Cheng, Xianyong; Lian, Haifeng; Qin, Chengyong

    2015-01-01

    The association between the peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk was inconclusive. We conducted a meta-analysis to evaluate the association between PPARγ Pro12Ala polymorphism and CRC risk. We searched Pubmed, EMBASE, and China National Knowledge Infrastructure databases. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 17 case-control studies with 12635 and 15803 controls were included in this meta-analysis. Overall, PPARγ Pro12Ala polymorphism was associated with CRC risk (OR = 0.84, 95% CI 0.75-0.94, P = 0.003, I(2) = 35%). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR = 0.85, 95% CI 0.75-0.96, P = 0.007, I(2) = 38%) but not among Asians (OR = 0.76, 95% CI 0.51-1.12, P = 0.17, I(2) = 28%). In the subgroup analysis by CRC site, a significant association was found among colon cancer (OR = 0.81, 95% CI 0.66-0.98, P = 0.03, I(2) = 16%) but not among rectal cancer (OR = 0.83, 95% CI 0.57-1.21, P = 0.34, I(2) = 63%). The sensitivity analysis did not influence the result by omitting low-quality studies (OR = 0.76, 95% CI 0.63-0.93, P = 0.006, I(2) = 51%). In conclusion, this meta-analysis suggested that PPARγ Pro12Ala polymorphism was significant associated with CRC risk.

  5. Randomized controlled dissemination study of community-to-clinic navigation to promote CRC screening: Study design and implications.

    Science.gov (United States)

    Larkey, Linda; Szalacha, Laura; Herman, Patricia; Gonzalez, Julie; Menon, Usha

    2017-02-01

    Regular screening facilitates early diagnosis of colorectal cancer (CRC) and reduction of CRC morbidity and mortality. Screening rates for minorities and low-income populations remain suboptimal. Provider referral for CRC screening is one of the strongest predictors of adherence, but referrals are unlikely among those who have no clinic home (common among poor and minority populations). This group randomized controlled study will test the effectiveness of an evidence based tailored messaging intervention in a community-to-clinic navigation context compared to no navigation. Multicultural, underinsured individuals from community sites will be randomized (by site) to receive CRC screening education only, or education plus navigation. In Phase I, those randomized to education plus navigation will be guided to make a clinic appointment to receive a provider referral for CRC screening. Patients attending clinic appointments will continue to receive navigation until screened (Phase II) regardless of initial arm assignment. We hypothesize that those receiving education plus navigation will be more likely to attend clinic appointments (H1) and show higher rates of screening (H2) compared to those receiving education only. Phase I group assignment will be used as a control variable in analysis of screening follow-through in Phase II. Costs per screening achieved will be evaluated for each condition and the RE-AIM framework will be used to examine dissemination results. The novelty of our study design is the translational dissemination model that will allow us to assess the real-world application of an efficacious intervention previously tested in a randomized controlled trial. Copyright © 2016. Published by Elsevier Inc.

  6. Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients.

    Science.gov (United States)

    Tsoi, H; Lam, K C; Dong, Y; Zhang, X; Lee, C K; Zhang, J; Ng, S C; Ng, S S M; Zheng, S; Chen, Y; Fang, J; Yu, J

    2017-11-02

    One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression level of pre-45s rRNA is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients.

  7. Single-particle spectroscopy of I-III-VI semiconductor nanocrystals: spectral diffusion and suppression of blinking by two-color excitation.

    Science.gov (United States)

    Sharma, Dharmendar Kumar; Hirata, Shuzo; Bujak, Lukasz; Biju, Vasudevanpillai; Kameyama, Tatsuya; Kishi, Marino; Torimoto, Tsukasa; Vacha, Martin

    2016-07-14

    Ternary I-III-VI semiconductor nanocrystals have been explored as non-toxic alternatives to II-VI semiconductors for optoelectronic and sensing applications, but large photoluminescence spectral width and moderate brightness restrict their practical use. Here, using single-particle photoluminescence spectroscopy on nanocrystals of (AgIn)xZn2(1-x)S2 we show that the photoluminescence band is inhomogeneously broadened and that size distribution is the dominant factor in the broadening. The residual homogeneous linewidth of individual nanocrystals reaches up to 75% of the ensemble spectral width. Single nanocrystals undergo spectral diffusion which also contributes to the inhomogeneous band. Excitation with two lasers with energies above and below the bandgap reveals coexistence of two emitting donor states within one particle. Spectral diffusion in such particles is due to temporal activation and deactivation of one such state. Filling of a trap state with a lower-energy laser enables optical modulation of photoluminescence intermittency (blinking) and leads to an almost two-fold increase in brightness.

  8. Predicting the mixed-mode I/II spatial damage propagation along 3D-printed soft interfacial layer via a hyperelastic softening model

    Science.gov (United States)

    Liu, Lei; Li, Yaning

    2018-07-01

    A methodology was developed to use a hyperelastic softening model to predict the constitutive behavior and the spatial damage propagation of nonlinear materials with damage-induced softening under mixed-mode loading. A user subroutine (ABAQUS/VUMAT) was developed for numerical implementation of the model. 3D-printed wavy soft rubbery interfacial layer was used as a material system to verify and validate the methodology. The Arruda - Boyce hyperelastic model is incorporated with the softening model to capture the nonlinear pre-and post- damage behavior of the interfacial layer under mixed Mode I/II loads. To characterize model parameters of the 3D-printed rubbery interfacial layer, a series of scarf-joint specimens were designed, which enabled systematic variation of stress triaxiality via a single geometric parameter, the slant angle. It was found that the important model parameter m is exponentially related to the stress triaxiality. Compact tension specimens of the sinusoidal wavy interfacial layer with different waviness were designed and fabricated via multi-material 3D printing. Finite element (FE) simulations were conducted to predict the spatial damage propagation of the material within the wavy interfacial layer. Compact tension experiments were performed to verify the model prediction. The results show that the model developed is able to accurately predict the damage propagation of the 3D-printed rubbery interfacial layer under complicated stress-state without pre-defined failure criteria.

  9. Hypoxia Is a Critical Parameter for Chondrogenic Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells in Type I/III Collagen Sponges

    Directory of Open Access Journals (Sweden)

    Tangni Gómez-Leduc

    2017-09-01

    Full Text Available Umbilical cord blood (UCB is an attractive alternative to bone marrow for isolation of mesenchymal stem cells (MSCs to treat articular cartilage defects. Here, we set out to determine the growth factors (bone morphogenetic protein 2 (BMP-2 and transforming growth factor-β (TGF-β1 and oxygen tension effects during chondrogenesis of human UCB-MSCs for cartilage engineering. Chondrogenic differentiation was induced using 3D cultures in type I/III collagen sponges with chondrogenic factors in normoxia (21% O2 or hypoxia (<5% O2 for 7, 14 and 21 days. Our results show that UCB-MSCs can be committed to chondrogenesis in the presence of BMP-2+TGF-β1. Normoxia induced the highest levels of chondrocyte-specific markers. However, hypoxia exerted more benefit by decreasing collagen X and matrix metalloproteinase-13 (MMP13 expression, two chondrocyte hypertrophy markers. However, a better chondrogenesis was obtained by switching oxygen conditions, with seven days in normoxia followed by 14 days in hypoxia, since these conditions avoid hypertrophy of hUCB-MSC-derived chondrocytes while maintaining the expression of chondrocyte-specific markers observed in normoxia. Our study demonstrates that oxygen tension is a key factor for chondrogenesis and suggests that UBC-MSCs 3D-culture should begin in normoxia to obtain a more efficient chondrocyte differentiation before placing them in hypoxia for chondrocyte phenotype stabilization. UCB-MSCs are therefore a reliable source for cartilage engineering.

  10. Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition

    Directory of Open Access Journals (Sweden)

    Schlichter Rémy

    2008-05-01

    Full Text Available Abstract Background Recent evidence suggests that oxytocin (OT, secreted in the superficial spinal cord dorsal horn by descending axons of paraventricular hypothalamic nucleus (PVN neurons, produces antinociception and analgesia. The spinal mechanism of OT is, however, still unclear and requires further investigation. We have used patch clamp recording of lamina II neurons in spinal cord slices and immunocytochemistry in order to identify PVN-activated neurons in the superficial layers of the spinal cord and attempted to determine how this neuronal population may lead to OT-mediated antinociception. Results We show that OT released during PVN stimulation specifically activates a subpopulation of lamina II glutamatergic interneurons which are localized in the most superficial layers of the dorsal horn of the spinal cord (lamina I-II. This OT-specific stimulation of glutamatergic neurons allows the recruitment of all GABAergic interneurons in lamina II which produces a generalized elevation of local inhibition, a phenomenon which might explain the reduction of incoming Aδ and C primary afferent-mediated sensory messages. Conclusion Our results obtained in lamina II of the spinal cord provide the first clear evidence of a specific local neuronal network that is activated by OT release to induce antinociception. This OT-specific pathway might represent a novel and interesting therapeutic target for the management of neuropathic and inflammatory pain.

  11. Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study

    Directory of Open Access Journals (Sweden)

    Freihorst Joachim

    2007-08-01

    Full Text Available Abstract Background Vaccination against Pseudomonas aeruginosa is a desirable albeit challenging strategy for prevention of airway infection in patients with cystic fibrosis. We assessed the immunogenicity of a nasal vaccine based on the outer membrane proteins F and I from Pseudomonas aeruginosa in the lower airways in a phase I/II clinical trial. Methods N = 12 healthy volunteers received 2 nasal vaccinations with an OprF-OprI gel as a primary and a systemic (n = 6 or a nasal booster vaccination (n = 6. Antibodies were assessed in induced sputum (IS, bronchoalveolar lavage (BAL, and in serum. Results OprF-OprI-specific IgG and IgA antibodies were found in both BAL and IS at comparable rates, but differed in the predominant isotype. IgA antibodies in IS did not correlate to the respective serum levels. Pulmonary antibodies were detectable in all vaccinees even 1 year after the vaccination. The systemic booster group had higher IgG levels in serum. However, the nasal booster group had the better long-term response with bronchial antibodies of both isotypes. Conclusion The nasal OprF-OprI-vaccine induces a lasting antibody response at both, systemic and airway mucosal site. IS is a feasible method to non-invasively assess bronchial antibodies. A further optimization of the vaccination schedule is warranted.

  12. Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis

    Directory of Open Access Journals (Sweden)

    Shunsuke Baba

    2016-01-01

    Full Text Available Regenerative medicine is emerging as a promising option, but the potential of autologous stem cells has not been investigated well in clinical settings of periodontal treatment. In this clinical study, we evaluated the safety and efficacy of a new regenerative therapy based on the surgical implantation of autologous mesenchymal stem cells (MSCs with a biodegradable three-dimensional (3D woven-fabric composite scaffold and platelet-rich plasma (PRP. Ten patients with periodontitis, who required a surgical procedure for intrabony defects, were enrolled in phase I/II trial. Once MSCs were implanted in each periodontal intrabony defect, the patients were monitored during 36 months for a medical exam including laboratory tests of blood and urine samples, changes in clinical attachment level, pocket depth, and linear bone growth (LBG. All three parameters improved significantly during the entire follow-up period (p<0.0001, leading to an average LBG of 4.7 mm after 36 months. Clinical mobility measured by Periotest showed a decreasing trend after the surgery. No clinical safety problems attributable to the investigational MSCs were identified. This clinical trial suggests that the stem cell therapy using MSCs-PRP/3D woven-fabric composite scaffold may constitute a novel safe and effective regenerative treatment option for periodontitis.

  13. 29 CFR 37.64 - What procedures must the Director follow when CRC has completed a post-approval compliance review?

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true What procedures must the Director follow when CRC has completed a post-approval compliance review? 37.64 Section 37.64 Labor Office of the Secretary of Labor... (WIA) Compliance Procedures § 37.64 What procedures must the Director follow when CRC has completed a...

  14. Quantitative proteomics unravels that the post-transcriptional regulator Crc modulates the generation of vesicles and secreted virulence determinants of Pseudomonas aeruginosa.

    Science.gov (United States)

    Reales-Calderón, Jose Antonio; Corona, Fernando; Monteoliva, Lucía; Gil, Concha; Martínez, Jose Luis

    2015-09-08

    Recent research indicates that the post-transcriptional regulator Crc modulates susceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Several P. aeruginosa virulence factors are secreted or engulfed in vesicles. To decipher the Crc modulation of P. aeruginosa virulence, we constructed a crc deficient mutant and measure the proteome associated extracellular vesicles and the vesicle-free secretome using iTRAQ. Fifty vesicle-associated proteins were more abundant and 14 less abundant in the crc-defective strain, whereas 37 were more abundant and 17 less abundant in the vesicle-free secretome. Among them, virulence determinants, such as ToxA, protease IV, azurin, chitin-binding protein, PlcB and Hcp1, were less abundant in the crc-defective mutant. Transcriptomic analysis revealed that some of the observed changes were post-transcriptional and, thus, could be attributed to a direct Crc regulatory role; whereas, for other differentially secreted proteins, the regulatory role was likely indirect. We also observed that the crc mutant presented an impaired vesicle-associated secretion of quorum sensing signal molecules and less cytotoxicity than its wild-type strain. Our results offer new insights into the mechanisms by which Crc regulates P. aeruginosa virulence, through the modulation of vesicle formation and secretion of both virulence determinants and quorum sensing signals. This article is part of a Special Issue entitled: HUPO 2014. Published by Elsevier B.V.

  15. Modeling how substitution of sedentary behavior with standing or physical activity is associated with health-related quality of life in colorectal cancer survivors

    OpenAIRE

    van Roekel, Eline H.; Bours, Martijn J. L.; Breedveld-Peters, Jos? J. L.; Willems, Paul J. B.; Meijer, Kenneth; Kant, IJmert; van den Brandt, Piet A.; Beets, Geerard L.; Sanduleanu, Silvia; Weijenberg, Matty P.

    2016-01-01

    Purpose Previous research indicates that sedentary behavior is unfavorably associated with health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. Using isotemporal substitution modeling, we studied how substituting sedentary behavior with standing or physical activity was associated with HRQoL in CRC survivors, 2?10?years post-diagnosis. Methods A cross-sectional study was conducted in stage I?III CRC survivors (n?=?145) diagnosed at Maastricht University Medical Center+...

  16. Anti-VEGF agents in metastatic colorectal cancer (mCRC: are they all alike?

    Directory of Open Access Journals (Sweden)

    Saif MW

    2013-06-01

    Full Text Available Muhammad Wasif Saif GI Oncology Program, Tufts University School of Medicine, Boston, MA, USA Abstract: Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States, VEGF receptors (eg, ramucirumab, and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors. The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012, using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking. Keywords: aflibercept, antiangiogenesis, metastatic colorectal cancer (mCRC, tyrosine kinase inhibitor (TKI, vascular endothelial growth factor (VEGF

  17. Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

    Directory of Open Access Journals (Sweden)

    O'Gara Fergal

    2010-11-01

    Full Text Available Abstract Background Catabolite repression control (CRC is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas

  18. Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria.

    Science.gov (United States)

    Browne, Patrick; Barret, Matthieu; O'Gara, Fergal; Morrissey, John P

    2010-11-25

    Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate nutritional status cues with the regulation

  19. Conditionally reprogrammed cells (CRC) methodology does not allow the in vitro expansion of patient-derived primary and metastatic lung cancer cells.

    Science.gov (United States)

    Sette, Giovanni; Salvati, Valentina; Giordani, Ilenia; Pilozzi, Emanuela; Quacquarini, Denise; Duranti, Enrico; De Nicola, Francesca; Pallocca, Matteo; Fanciulli, Maurizio; Falchi, Mario; Pallini, Roberto; De Maria, Ruggero; Eramo, Adriana

    2018-07-01

    Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for non-small cell lung cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC cultures were obtained from both tumor and non-malignant tissues with extraordinary high efficiency. Tumor cells were tracked in vitro through tumorigenicity assay, monitoring of tumor-specific genetic alterations and marker expression. Cultures were composed of EpCAM+ lung epithelial cells lacking tumorigenic potential. NSCLC biopsies-derived cultures rapidly lost patient-specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC cultures examined displayed epithelial lung stem cell phenotype and function. In contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures. In conclusion, patient-derived primary and metastatic lung cancer cells were negatively selected under CRC conditions, limiting the expansion to non-malignant lung epithelial stem cells from either tumor or non-tumor tissue sources. Thus, CRC approach cannot be applied for direct therapeutic testing of patient lung tumor cells, as the tumor-derived CRC cultures are composed of (non-tumoral) airway basal cells. © 2018 UICC.

  20. Expression of the MAP kinase phosphatase DUSP4 is associated with microsatellite instability in colorectal cancer (CRC) and causes increased cell proliferation.

    Science.gov (United States)

    Gröschl, Benedikt; Bettstetter, Marcus; Giedl, Christian; Woenckhaus, Matthias; Edmonston, Tina; Hofstädter, Ferdinand; Dietmaier, Wolfgang

    2013-04-01

    DUSP4 (MKP-2), a member of the mitogen-activated protein kinase phosphatase (MKP) family and potential tumor suppressor, negatively regulates the MAPKs (mitogen-activated protein kinases) ERK, p38 and JNK. MAPKs play a crucial role in cancer development and progression. Previously, using microarray analyses we found a conspicuously frequent overexpression of DUSP4 in colorectal cancer (CRC) with high frequent microsatellite instability (MSI-H) compared to microsatellite stable (MSS) CRC. Here we studied DUSP4 expression on mRNA level in 38 CRC (19 MSI-H and 19 MSS) compared to matched normal tissue as well as in CRC cell lines by RT-qPCR. DUSP4 was overexpressed in all 19 MSI-H tumors and in 14 MSS tumors. Median expression levels in MSI-H tumors were significantly higher than in MSS-tumors (p CRC cell lines showed 6.8-fold higher DUSP4 mRNA levels than MSS cell lines. DUSP4 expression was not regulated by promoter methylation since no methylation was found by quantitative methylation analysis of DUSP4 promoter in CRC cell lines neither in tumor samples. Furthermore, no DUSP4 mutation was found on genomic DNA level in four CRC cell lines. DUSP4 overexpression in CRC cell lines through DUSP4 transfection caused upregulated expression of MAPK targets CDC25A, CCND1, EGR1, FOS, MYC and CDKN1A in HCT116 as well as downregulation of mismatch repair gene MSH2 in SW480. Furthermore, DUSP4 overexpression led to increased proliferation in CRC cell lines. Our findings suggest that DUSP4 acts as an important regulator of cell growth within the MAPK pathway and causes enhanced cell growth in MSI-H CRC. Copyright © 2012 UICC.

  1. NR2F2 inhibits Smad7 expression and promotes TGF-β-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21.

    Science.gov (United States)

    Wang, Hao; Nie, Lei; Wu, Lei; Liu, Qiufang; Guo, Xueyan

    2017-03-25

    Metastasis is one of the most decisive factors influencing CRC patient prognosis and current studies suggest that a molecular mechanism known as EMT broadly regulates cancer metastasis. NR2F2 is a key molecule in the development of CRC, but the roles and underlying mechanisms of NR2F2 in TGF-β induced EMT in CRC remain largely unknown. In the current study, we were interested to examine the role of NR2F2 in the TGF-β-induced EMT in CRC. Here, we found NR2F2 was upregulated in CRC cells and promotes TGF-β-induced EMT in CRC. Using comparative miRNA profiling TGF-β pre-treated CRC cells in which NR2F2 had been knocked down with that of control cells, we identified miR-21 as a commonly downregulated miRNA in HT29 cells treated with TGF-β and NR2F2 siRNA, and its downregulation inhibiting migration and invasion of CRC cells. Moreover, we found NR2F2 could transcriptional activated miR-21 expression by binding to miR-21 promoter in HT29 by ChIP and luciferase assay. In the last, our data demonstrated that Smad7 was the direct target of miR-21 in CRC cells. Thus, NR2F2 could promote TGF-β-induced EMT and inhibit Smad7 expression via transactivation of miR-21, and NR2F2 may be a new common therapeutic target for CRC. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

    LENUS (Irish Health Repository)

    Browne, Patrick

    2010-11-25

    Abstract Background Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5\\' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate

  3. Erectile insufficiency as first symptom of HTLV-I/II associated myelopathy: case report Insuficiência erétil como primeiro sintoma da mielopatia associada ao HTLV I/II: relato de caso

    Directory of Open Access Journals (Sweden)

    JOSÉ TEOTONIO OLIVEIRA

    1998-03-01

    Full Text Available A case of HTLV-I/II myelopathy in which the initial complaint was erectile insufficiency (EI is reported. The only abnormalities found on the neurological exam were discrete weakness of the psoas and increased knee jerk reflexes. Diagnosis was made by demonstrating antibodies anti-HTLV I/II in the serum and cerebrospinal fluid (with the techniques of ELISA and Western blot, with confirmation by the polymerase chain reaction (PCR. EI can thus be the first symptom of HTLV-I/II infection and patients with EI of unknown etiology should be tested for HTLV-I/II in endemic areas.É relatado um caso de mielopatia associada ao HTLV I/II cuja primeira manifestação foi insuficiência erétil (IE. O exame neurológico do paciente apresentava somente discreta fraqueza dos psoas e aumento dos reflexos patelares. O diagnóstico foi feito pelo achado de anticorpos anti-HTLV I/II no soro e no líquor (com as técnicas de ELISA e Western blot e confirmado pela reação em cadeia da polimerase (PCR. Insuficiência erétil pode ser a primeira manifestação clínica de infecção pelo HTLV I/II e pacientes com IE de etiologia desconhecida devem ser testados para HTLV-I/II em áreas endêmicas.

  4. A structural investigation of complex I and I+III2 supercomplex from Zea mays at 11-13 angstrom resolution : Assignment of the carbonic anhydrase domain and evidence for structural heterogeneity within complex I

    NARCIS (Netherlands)

    Peters, Katrin; Dudkina, Natalya V.; Jaensch, Lothar; Braun, Hans-Peter; Boekema, Egbert J.; Jänsch, Lothar

    The projection structures of complex I and the I+III2 supercomplex from the C-4 plant Zea mays were determined by electron microscopy and single particle image analysis to a resolution of up to 11 angstrom. Maize complex I has a typical L-shape. Additionally, it has a large hydrophilic, extra-domain

  5. Tolko poetom hotel bõt : Rastrogannost; Dozhdlivõi den; Jaanov ogon; Setumaa I-II; Tolko poetom. Haralskije zhizneopissanija : Aire Valgus; Aare Valgus; Peeter Petrov; Vaike Metsleht; Valdur Laiapea; Hillar Aruda, ekonomist; Pärja Lumendi; Valjo Z

    Index Scriptorium Estoniae

    Traat, Mats, 1936-

    1996-01-01

    Orig.: Heldimus; Sajupäev; Jaanituli; Setumaa I-II; Ainult poeet. Harala elulood: Aire Valgus; Aare Valgus; Peeter Petrov; Vaike Metsleht; Valdur Laiapea; Hillar Aruda, ökonomist; Pärja Lumendi; Valjo Zeiger; Pavlo Moskalenko; Johannes Iva; Viljar Laanemägi; Olga Kaljusaar; Aimi Vaimets; Einard Kalm (1923-1984); Sonetid vaikimisest I; Kui

  6. Quality control of the NPL-CRC secondary standard system used for activimeters calibration at IPEN, Sao Paulo, Brazil;Ccontrole de qualidade do sistema padrao secundario NPL-CRC utilizado na calibracao de ativimetros no IPEN

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Elaine W.; Potiens, Maria da P.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    The objective of this study was to establish a quality control program to be applied at the NPL-CRC activimeter secondary standard system, used as reference to comparison in tests made with the work tertiary standard activimeter, Capintec basic CRC{sup R}-15BT, both belonging to the Calibration Laboratory of IPEN. The repeatability, reproducibility and the precision tests were performed using a sealed check source of {sup 133}Ba, from Amersham. It was made 70 series of 10 measurements to each activimeter, totaling 1400 measurements. Considering the variation limit of 5% to precision and reproducibility tests in the nuclear medicine services, recommended by the Brazilian standard CNEN-NN-3.05, the results observed in the behavior of the IPEN activimeter were satisfactory. (author)

  7. Concurrent radiation, mitomycin C and 5-fluorouracil in poor prognosis carcinoma of cervix: preliminary results of a Phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, G.; Dembo, A.; Beale, F.; Bean, H.; Bush, R.; Herman, J.; Pringle, J.; Rawlings, G.; Sturgeon, J.; Fine, S.

    1984-09-01

    Between July 1981 and June 1983, 27 patients with advanced primary squamous cell carcinoma (SCC) of cervix and 8 with recurrent disease were treated using a pilot regimen of combination chemotherapy (CT): Mitomycin C (MIT), 5 Fluorouracil (5 FU), and radiation therapy (RT). CT and RT doses on this Phase I-II Study were escalated to the current regimen. A split course of RT was used, either pelvic RT alone or the same pelvic RT plus para-aortic RT. CT was given by continuous IV infusion days 1 through 4 of each half-course of RT. This was followed by one application of intrauterine /sup 137/Cs when possible. Three of the 8 patients with recurrence in the pelvis or para-aortic nodes had a complete response (CR) to CT-RT and are alive without disease at 19, 19 and 22 months after treatment, respectively. Twenty of the 27 (74%) primary patients had a CR. With a median duration of follow-up of 6 months 4/20 have relapsed, 1 in RT field, 2 at distant sites, and 1 in both. The acute toxicity of this regimen was tolerable: 2/35 developed transient leukopenia with one febrile episode, 9/35 developed transient thrombocytopenia without bleeding. Symptomatic sigmoid strictures developed in two patients, one requiring surgical intervention. Typically, near complete regression of tumor is noted on completion of the external RT, reproducing the dramatic responses that have been observed in SCC of the anal canal, esophagus and head and neck, with this CT-RT regimen.

  8. Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study

    International Nuclear Information System (INIS)

    Spanos, W.J. Jr.; Wasserman, T.; Meoz, R.; Sala, J.; Kong, J.; Stetz, J.

    1987-01-01

    Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses

  9. A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment

    International Nuclear Information System (INIS)

    Herrera, Fernanda G.; Chan, Philip; Doll, Corinne; Milosevic, Michael; Oza, Amit; Syed, Amy; Pintilie, Melania; Levin, Wilfred; Manchul, Lee; Fyles, Anthony

    2007-01-01

    Purpose: To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer. Methods and Materials: Thirty-one patients were accrued to a phase I-II trial of celecoxib 400 mg by mouth twice per day for 2 weeks before and during CRT. Tumor oxygenation (HP 5 ) and interstitial fluid pressure (IFP) were measured before and 2 weeks after celecoxib administration alone. The median follow-up time was 2.7 years (range, 1.1-4.4 years). Results: The most common acute G3/4 toxicities were hematologic (4/31, 12.9%) and gastrointestinal (5/31, 16.1%) largely attributed to chemotherapy. Late G3/4 toxicity was seen in 4 of 31 patients (13.7% actuarial risk at 2 yr), including fistulas in 3 patients (9.7%). Within the first year of follow-up, 25 of 31 patients (81%) achieved complete response (CR), of whom 20 remained in CR at last follow-up. After 2 weeks of celecoxib administration before CRT, the median IFP decreased slightly (median absolute, -4.6 mm Hg; p = 0.09; relative, -21%; p = 0.07), whereas HP 5 did not change significantly (absolute increase, 3.6%; p = 0.51; median relative increase, 11%; p = 0.27). No significant associations were seen between changes in HP 5 or IFP and response to treatment (p = 0.2, relative HP 5 change and p = 0.14, relative IFP change). Conclusions: Celecoxib in combination with definitive CRT is associated with acceptable acute toxicity, but higher than expected late complications. Celecoxib is associated with a modest reduction in the angiogenic biomarker IFP, but this does not correspond with tumor response

  10. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Directory of Open Access Journals (Sweden)

    L John Hoffer

    Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials.ClinicalTrials.gov NCT01050621.

  11. The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

    International Nuclear Information System (INIS)

    Vuong, Te; Waschke, Kevin; Niazi, Tamim; Richard, Carole; Parent, Josee; Liberman, Sender; Mayrand, Serge; Loungnarath, Rasmy; Stein, Barry; Devic, Slobodan

    2011-01-01

    Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

  12. Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: A phase I-II study

    International Nuclear Information System (INIS)

    Amichetti, M.; Graiff, C.; Fellin, G.; Pani, G.; Bolner, A.; Maluta, S.; Valdagni, R.

    1993-01-01

    Hyperthermia is now being widely used to treat clinical malignancies, especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplantin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m 2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5 degrees C for 30 min). Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systematic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, they observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change. The study confirms the feasibility of the combination of cisplantin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors. 43 refs., 3 figs., 4 tabs

  13. A-Part Gel, an adhesion prophylaxis for abdominal surgery: a randomized controlled phase I-II safety study [NCT00646412].

    Science.gov (United States)

    Lang, Reinhold; Baumann, Petra; Schmoor, Claudia; Odermatt, Erich K; Wente, Moritz N; Jauch, Karl-Walter

    2015-01-01

    Intra-abdominal surgical intervention can cause the development of intra-peritoneal adhesions. To reduce this problem, different agents have been tested to minimize abdominal adhesions; however, the optimal adhesion prophylaxis has not been found so far. Therefore, the A-Part(®) Gel was developed as a barrier to diminish postsurgical adhesions; the aim of this randomized controlled study was a first evaluation of its safety and efficacy. In this prospective, controlled, randomized, patient-blinded, monocenter phase I-II study, 62 patients received either the hydrogel A-Part-Gel(®) as an anti-adhesive barrier or were untreated after primary elective median laparotomy. Primary endpoint was the occurrence of peritonitis and/or wound healing impairment 28 ± 10 days postoperatively. As secondary endpoints anastomotic leakage until 28 days after surgery, adverse events and adhesions were assessed until 3 months postoperatively. A lower rate of wound healing impairment and/or peritonitis was observed in the A-Part Gel(®) group compared to the control group: (6.5 vs. 13.8 %). The difference between the two groups was -7.3%, 90 % confidence interval [-20.1, 5.4 %]. Both treatment groups showed similar frequency of anastomotic leakage but incidence of adverse events and serious adverse events were slightly lower in the A-Part Gel(®) group compared to the control. Adhesion rates were comparable in both groups. A-Part Gel(®) is safe as an adhesion prophylaxis after abdominal wall surgery but no reduction of postoperative peritoneal adhesion could be found in comparison to the control group. This may at least in part be due to the small sample size as well as to the incomplete coverage of the incision due to the used application. NCT00646412.

  14. A phase I/II exploratory clinical trial for intracordal injection of recombinant hepatocyte growth factor for vocal fold scar and sulcus.

    Science.gov (United States)

    Hirano, Shigeru; Kawamoto, Atsuhiko; Tateya, Ichiro; Mizuta, Masanobu; Kishimoto, Yo; Hiwatashi, Nao; Kawai, Yoshitaka; Tsuji, Takuya; Suzuki, Ryo; Kaneko, Mami; Naito, Yasushi; Kagimura, Tatsuo; Nakamura, Tatsuo; Kanemaru, Shin-Ichi

    2018-04-01

    Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 μg of HGF per vocal fold; Step II received 3 μg of HGF; and Step III received 10 μg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

    Science.gov (United States)

    Lorusso, V; Leone, B; Di Vagno, G; Manzione, L; Palmeri, S; Vallejo, C; Machiavelli, M; Nacci, G; Bilancia, D; Leonardi, V; Catino, A; Gargano, G; Loverro, G; Selvaggi, L; De Lena, M

    1998-02-01

    Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

  16. Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

    International Nuclear Information System (INIS)

    Menkarios, Cathy; Fortin, Bernard; Lambert, Carole; Vigneault, Éric; Brochet, Nicolas; Nguyen, David HA; Bahary, Jean-Paul; Jolicoeur, Marjory; Beauchemin, Marie-Claude; Villeneuve, Hugo; Van Nguyen, Thu

    2011-01-01

    Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival. Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%. Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed

  17. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Science.gov (United States)

    Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

    2015-01-01

    Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials. ClinicalTrials.gov NCT01050621.

  18. Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Han, Ji-Youn; Lee, Soo Hyun; Lee, Geon Kook; Yun, Tak; Lee, Young Joo; Hwang, Kum Hui; Kim, Jin Young; Kim, Heung Tae

    2015-03-01

    Vorinostat has been shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated non-small cell lung cancer (NSCLC). A 3 + 3 dose-escalation design was used to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Three dose levels were tested: 250 mg/day gefitinib on days 1-28 and 200, 300 or 400 mg/day vorinostat on days 1-7, and 15-21 out of every 28 days. The primary endpoint was median progression-free survival (PFS). Fifty-two patients were enrolled and treated (43 in phase II). The median age was 59 years, 28 patients were male, 44 had adenocarcinoma, 29 had never smoked, and 36 had undergone one prior treatment. Twenty-two patients exhibited sensitive EGFR mutations. Planned dose escalation was completed without reaching the MTD. The RP2D was 250 mg gefitinib and 400 mg vorinostat. In 43 assessable patients in phase II, the median PFS was 3.2 months; the overall survival (OS) was 19.0 months. There were 16 partial responses and six cases of stable disease. In EGFR-mutant NSCLC, response rate was 77 %, median PFS was 9.1 months, and median OS was 24.1 months. The most common adverse events were anorexia and diarrhea. Treatment with 250 mg gefitinib daily with biweekly 400 mg/day vorinostat was feasible and well tolerated. In an unselected patient population, this combination dose did not improve PFS. However, this combination showed a potential for improving efficacy of gefitinib in EGFR-mutant NSCLC (NCT01027676).

  19. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 4 AND 5 OF CRYSTAL RIVER UNIT 3

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth D. Wright

    1997-07-30

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 4 and 5 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies.

  20. CRC DEPLETION CALCULATIONS FOR THE RODDED ASSEMBLIES IN BATCHES 1, 2, 3, AND 1X OF CRYSTAL RIVER UNIT 3

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth D. Wright

    1997-09-03

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain rodded fuel assemblies from batches 1, 2, 3, and 1X of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A rodded assembly is one that contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) for some period of time during its irradiation history. The objective of this analysis is to provide SAS2H calculated isotopic compositions of depleted fuel and depleted burnable poison for each fuel assembly to be used in subsequent CRC reactivity calculations containing the fuel assemblies.

  1. CRC DEPLETION CALCULATIONS FOR THE RODDED ASSEMBLIES IN BATCHES 1, 2, 3, AND 1X OF CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wright, Kenneth D.

    1997-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain rodded fuel assemblies from batches 1, 2, 3, and 1X of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A rodded assembly is one that contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) for some period of time during its irradiation history. The objective of this analysis is to provide SAS2H calculated isotopic compositions of depleted fuel and depleted burnable poison for each fuel assembly to be used in subsequent CRC reactivity calculations containing the fuel assemblies

  2. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 8 AND 9 CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wilson, Michael L.

    2001-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 8 and 9 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

  3. Quality control of the NPL-CRC secondary standard system used for activimeters calibration at IPEN, Sao Paulo, Brazil

    International Nuclear Information System (INIS)

    Martins, Elaine W.; Potiens, Maria da P.A.

    2009-01-01

    The objective of this study was to establish a quality control program to be applied at the NPL-CRC activimeter secondary standard system, used as reference to comparison in tests made with the work tertiary standard activimeter, Capintec basic CRC R -15BT, both belonging to the Calibration Laboratory of IPEN. The repeatability, reproducibility and the precision tests were performed using a sealed check source of 133 Ba, from Amersham. It was made 70 series of 10 measurements to each activimeter, totaling 1400 measurements. Considering the variation limit of 5% to precision and reproducibility tests in the nuclear medicine services, recommended by the Brazilian standard CNEN-NN-3.05, the results observed in the behavior of the IPEN activimeter were satisfactory. (author)

  4. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 4 AND 5 OF CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wright, Kenneth D.

    1997-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 4 and 5 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

  5. CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 1, 2, AND 3 OF CRYSTAL RIVER UNIT 3

    International Nuclear Information System (INIS)

    Wright, Kenneth D.

    1997-01-01

    The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 1, 2, and 3 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

  6. High reflectance Cr/C multilayer at 250 eV for soft X-ray polarimetry

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Mingwu; Jiang, Li; Zhang, Zhong; Huang, Qiushi [MOE Key Laboratory of Advanced Micro-Structured Materials, Institute of Precision Optical Engineering (IPOE), School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Wang, Zhanshan, E-mail: wangzs@tongji.edu.cn [MOE Key Laboratory of Advanced Micro-Structured Materials, Institute of Precision Optical Engineering (IPOE), School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); She, Rui; Feng, Hua [Department of Engineering Physics, Tsinghua University, Beijing (China); Wang, Hongchang [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2015-10-01

    X-ray reflection near 45° via multilayer mirrors can be used for astronomical polarization measurements. A Cr/C multilayer mirror (designed for X-ray polarimetry at 250 eV), with a period thickness of 3.86 nm and a bi-layer number of 100, was fabricated using direct current magnetron sputtering. Grazing incidence X-ray reflectometry at 8 keV and transmission electron microscopy were used to investigate the multilayer structure. Different models were introduced to fit the hard X-ray reflectivity curve, which indicates that the layer thickness of two materials slightly drifts from the bottom to the top of the stack. Both the chromium and carbon layers are amorphous with asymmetric interfaces, while the Cr-on-C interface is slightly wider. Based on the good quality of the multilayer structure, a high reflectivity of 21.8% for the s-polarized light was obtained at 250 eV at a grazing incidence angle of 40.7°. The fabricated Cr/C multilayer mirror exhibits high reflectivity and polarization levels in the energy region of 240 eV–260 eV. - Highlights: • We fabricated Cr/C multilayer with 3.8 nm d-spacing. • X-ray reflectometry was used to determine the exact structure of Cr/C multilayer. • A high reflectivity of 21.8% for the s-polarized light was obtained at 250 eV. • Both Cr and C were found to be amorphous with slightly asymmetric interfaces. • A 4-layer model was used to fit and explain the results.

  7. A shift from distal to proximal neoplasia in the colon: a decade of polyps and CRC in Italy

    Directory of Open Access Journals (Sweden)

    Panzone Sergio

    2010-11-01

    Full Text Available Abstract Background In the last years a trend towards proximalization of colorectal carcinomas (CRC has been reported. This study aims to evaluate the distribution of CRC and adenomatous polyps (ADP to establish the presence of proximalization and to assess the potential predictors. Methods We retrieved histology reports of colonic specimens excised during colonoscopy, considering the exams performed between 1997 and 2006 at Cuneo Hospital, Italy. We compared the proportion of proximal lesions in the period 1997-2001 and in the period 2002-2006. Results Neoplastic lesions were detected in 3087 people. Proximal CRC moved from 25.9% (1997-2001 to 30.0% (2002-2006. Adjusting for sex and age, the difference was not significant (OR 1.23; 95% CI: 0,95-1,58. The proximal ADP proportion increased from 19.2% (1997-2001 to 26.0% (2002-2006 (OR: 1.43; 95% CI: 1.17-1.89. The corresponding figures for advanced proximal ADP were 6.6% and 9.5% (OR: 1.48; 95% CI: 1.02-2.17. Adjusting for gender, age, diagnostic period, symptoms and number of polyps the prevalence of proximal advanced ADP was increased among people ≥ 70 years compared to those aged 55-69 years (OR 1.49; 95% CI: 1.032.16. The main predictor of proximal advanced neoplasia was the number of polyps detected per exam (> 1 polyp versus 1 polyp: considering all ADP: OR 2.16; 95% CI: 1.59-2.93; considering advanced ADP OR 1.63; 95% CI: 1.08-2.46. Adjusting for these factors, the difference between the two periods was no longer significant. Conclusions CRC do not proximalize while a trend towards a proximal shift in adenomas was observed among people ≥ 70 years.

  8. A hhase I/II trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for Stage I/II breast carcinoma: Initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) Study 0319

    International Nuclear Information System (INIS)

    Vicini, Frank; Winter, Kathryn M.S.; Straube, William; Wong, John; Pass, Helen; Rabinovitch, Rachel; Chafe, Susan; Arthur, Douglas; Petersen, Ivy; McCormick, Beryl

    2005-01-01

    Background: This prospective study (Radiation Therapy Oncology Group Study 0319) examines the use of three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Reproducibility, as measured by technical feasibility, was the primary end point with the goal of demonstrating whether the technique is widely applicable in a multicenter setting before a Phase III trial is undertaken. Methods and Materials: This study was designed such that if fewer than 5 cases out of the first 42 patients evaluable were scored as unacceptable, the treatment would be considered reproducible. Patients received 38.5 Gy in 3.85 Gy/fraction delivered twice daily. The clinical target volume included the lumpectomy cavity plus a 10-15-mm margin bounded by 5 mm within the skin surface and the lung-chest wall interface. The planning target volume (PTV) included the clinical target volume plus a 10-mm margin. Treatment plans were judged as follows: (1) No variations (total coverage), 95% isodose surface covers 100% of the PTV and all specified critical normal tissue dose-volume histogram (DVH) limits met. (2) Minor variation (marginal coverage), 95% isodose surface covers between ≥95% and <100% of the PTV. No portion of PTV receives <93% of prescription (isocenter) dose. All specified critical normal tissue DVH limits fall within 5% of the guidelines. (3) Major variation (miss), 95% isodose surface covers <95% of the PTV. Portion of PTV receives <93% of prescription isocenter dose. Any critical normal tissue DVH limit exceeds 5% of the specified value. Results: A total of 58 patients were enrolled on this study between 8/15/03 and 4/30/04, 5 of whom were ineligible or did not receive protocol treatment. Two additional patients were excluded, one because the on-study form was not submitted, and the other because no treatment planning material was submitted. This primary end point analysis is based on the first 42 (out of 51) evaluable patients, which were accrued from 17 different institutions (31 centers were credentialed for case enrollment, but because of rapid accrual, not all centers were able to submit cases before trial closure). These 42 patients had the following characteristics: median age was 61 years; 48% had a maximum tumor dimension of <1 cm; 86% had invasive ductal carcinoma; 64% were postmenopausal; the location of tumor was upper outer for 40% and upper central for 21%; 79% had no chemotherapy, and 64% had no hormonal therapy. There were 4 cases with major variations (all 4 related to normal tissue DVHs exceeding 5% of the specified limit). A total of 32 cases with minor variations in treatment plans were detected (16 related to normal tissue DVHs exceeding the specified limits [by ≤5%], 6 related to suboptimal coverage of the PTV, and 10 related to both). There were 6 cases with no variations. Of the 51 total evaluable patients, 1 additional major variation was noted (PTV receiving <93% of the prescription dose). An additional 5 cases with minor variations in treatment plans were detected (3 related to normal tissue DVHs exceeding the specified limits [by ≤5%], 1 related to suboptimal coverage of the PTV, and 1 related to both). There were 3 more cases with no variations. Conclusion: Accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy was shown in this preliminary analysis of the first 42 evaluable patients to be technically feasible and reproducible in a multi-institutional trial using exceptionally strict dosimetric criteria

  9. The Crc protein participates in down-regulation of the Lon gene to promote rhamnolipid production and rhl quorum sensing in Pseudomonas aeruginosa.

    Science.gov (United States)

    Yang, Nana; Ding, Shuting; Chen, Feifei; Zhang, Xue; Xia, Yongjie; Di, Hongxia; Cao, Qiao; Deng, Xin; Wu, Min; Wong, Catherine C L; Tian, Xiao-Xu; Yang, Cai-Guang; Zhao, Jing; Lan, Lefu

    2015-05-01

    Rhamnolipid acts as a virulence factor during Pseudomonas aeruginosa infection. Here, we show that deletion of the catabolite repression control (crc) gene in P. aeruginosa leads to a rhamnolipid-negative phenotype. This effect is mediated by the down-regulation of rhl quorum sensing (QS). We discover that a disruption of the gene encoding the Lon protease entirely offsets the effect of crc deletion on the production of both rhamnolipid and rhl QS signal C4-HSL. Crc is unable to bind lon mRNA in vitro in the absence of the RNA chaperon Hfq, while Crc contributes to Hfq-mediated repression of the lon gene expression at a posttranscriptional level. Deletion of crc, which results in up-regulation of lon, significantly reduces the in vivo stability and abundance of the RhlI protein that synthesizes C4-HSL, causing the attenuation of rhl QS. Lon is also capable of degrading the RhlI protein in vitro. In addition, constitutive expression of rhlI suppresses the defects of the crc deletion mutant in rhamnolipid, C4-HSL and virulence on lettuce leaves. This study therefore uncovers a novel posttranscriptional regulatory cascade, Crc-Hfq/Lon/RhlI, for the regulation of rhamnolipid production and rhl QS in P. aeruginosa. © 2015 John Wiley & Sons Ltd.

  10. Identification of miRNAs associated with recurrence of stage II colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Tobiasen, Heidi; Schepeler, Troels

    2011-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer deaths. Twenty-five percent of the patients radically treated for a stage II CRC (no lymph node or distant metastasis) later develop recurrence and dies from the disease. MicroRNAs (miRNAs) are aberrantly expressed or mutated in human...... target prediction and transcript profiling. Initially, miRNA over-expression in HCT116 cells was followed by transcriptional profiling of transfected cells using GeneChip Human Exon 1.0 ST Arrays. Three in silico predicted miRNA targets showing differential mRNA expression upon miRNA up-regulation were...... cancers, and function either as tumour suppressors or oncogenes. Additionally, they also appear to have both diagnostic and prognostic significance. The aim of the present study was to identify miRNAs associated with recurrence of stage II CRC, followed up by an investigation of how these potential...

  11. Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

    OpenAIRE

    Murphy, Caitlin C.; Sanoff, Hanna K.; Stitzenberg, Karyn B.; Baron, John A.; Lund, Jennifer L.; Sandler, Robert S.

    2017-01-01

    Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n = 6, 862). Tumor characteristics...

  12. Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.

    Science.gov (United States)

    Niess, Hanno; von Einem, Jobst C; Thomas, Michael N; Michl, Marlies; Angele, Martin K; Huss, Ralf; Günther, Christine; Nelson, Peter J; Bruns, Christiane J; Heinemann, Volker

    2015-04-08

    Adenocarcinoma originating from the digestive system is a major contributor to cancer-related deaths worldwide. Tumor recurrence, advanced local growth and metastasis are key factors that frequently prevent these tumors from curative surgical treatment. Preclinical research has demonstrated that the dependency of these tumors on supporting mesenchymal stroma results in susceptibility to cell-based therapies targeting this stroma. TREAT-ME1 is a prospective, uncontrolled, single-arm phase I/II study assessing the safety and efficacy of genetically modified autologous mesenchymal stromal cells (MSC) as delivery vehicles for a cell-based gene therapy for advanced, recurrent or metastatic gastrointestinal or hepatopancreatobiliary adenocarcinoma. Autologous bone marrow will be drawn from each eligible patient after consent for bone marrow donation has been obtained (under a separate EC-approved protocol). In the following ~10 weeks the investigational medicinal product (IMP) is developed for each patient. To this end, the patient's MSCs are stably transfected with a gamma-retroviral, replication-incompetent and self-inactivating (SIN) vector system containing a therapeutic promoter - gene construct that allows for tumor-specific expression of the therapeutic gene. After release of the IMP the patients are enrolled after given informed consent for participation in the TREAT-ME 1 trial. In the phase I part of the study, the safety of the IMP is tested in six patients by three treatment cycles consisting of re-transfusion of MSCs at different concentrations followed by administration of the prodrug Ganciclovir. In the phase II part of the study, sixteen patients will be enrolled receiving IMP treatment. A subgroup of patients that qualifies for surgery will be treated preoperatively with the IMP to verify homing of the MSCs to tumors as to be confirmed in the surgical specimen. The TREAT-ME1 clinical study involves a highly innovative therapeutic strategy combining cell and gene therapy and is conducted at a high level of pharmaceutical quality ensuring patient safety. This patient-tailored approach represents the first clinical study worldwide utilizing genetically engineered MSCs in humans. EU Clinical Trials Register/European Union Drug Regulating Authorities Clinical Trials Database number: 2012-003741-15.

  13. Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma.

    Science.gov (United States)

    Huang, Yan; Liang, Wenhua; Yang, Yunpeng; Zhao, Liping; Zhao, Hongyun; Wu, Xuan; Zhao, Yuanyuan; Zhang, Yang; Zhang, Li

    2016-07-13

    This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab (®)-paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m(2) on day 1; 2) IV nab-paclitaxel 140 mg/m(2) on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m(2) on day 1. Treatment continued for 4-6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6-12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. ClinicalTrials.gov ID: NCT01735409 . The trial was registered on November 20th, 2012.

  14. Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Huang, Yan; Liang, Wenhua; Yang, Yunpeng; Zhao, Liping; Zhao, Hongyun; Wu, Xuan; Zhao, Yuanyuan; Zhang, Yang; Zhang, Li

    2016-01-01

    This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab ® -paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m 2 on day 1; 2) IV nab-paclitaxel 140 mg/m 2 on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m 2 on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m 2 on day 1. Treatment continued for 4–6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6–12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. ClinicalTrials.gov ID: NCT01735409. The trial was registered on November 20th, 2012. The online version of this article (doi:10.1186/s12885-016-2517-5) contains supplementary material, which is available to authorized users

  15. Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

    Energy Technology Data Exchange (ETDEWEB)

    Kankaanranta, Leena [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Seppaelae, Tiina; Koivunoro, Hanna [Department of Physics, University of Helsinki, Helsinki (Finland); Boneca Corporation, Helsinki (Finland); Saarilahti, Kauko [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Atula, Timo [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Collan, Juhani [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Salli, Eero; Kortesniemi, Mika [Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Uusi-Simola, Jouni [Department of Physics, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Vaelimaeki, Petteri [Department of Physics, University of Helsinki, Helsinki (Finland); Boneca Corporation, Helsinki (Finland); Maekitie, Antti [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Seppaenen, Marko [Turku PET Centre, Turku University Hospital, Turku (Finland); Minn, Heikki [Department of Oncology, Turku University Central Hospital, Turku (Finland); Revitzer, Hannu [Aalto University School of Science and Technology, Esopo (Finland); Kouri, Mauri [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro [VTT Technical Research Centre of Finland, Espoo (Finland); Savolainen, Sauli [Department of Physics, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Joensuu, Heikki, E-mail: heikki.joensuu@hus.fi [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland)

    2012-01-01

    Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by use of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was acceptable. Further research on novel modifications of the method is warranted.

  16. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer.

    Science.gov (United States)

    Podrazil, Michal; Horvath, Rudolf; Becht, Etienne; Rozkova, Daniela; Bilkova, Pavla; Sochorova, Klara; Hromadkova, Hana; Kayserova, Jana; Vavrova, Katerina; Lastovicka, Jan; Vrabcova, Petra; Kubackova, Katerina; Gasova, Zdenka; Jarolim, Ladislav; Babjuk, Marek; Spisek, Radek; Bartunkova, Jirina; Fucikova, Jitka

    2015-07-20

    We conducted an open-label, single-arm Phase I/II clinical trial in metastatic CRPC (mCRPC) patients eligible for docetaxel combined with treatment with autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa). The primary and secondary endpoints were safety and immune responses, respectively. Overall survival (OS), followed as a part of the safety evaluation, was compared to the predicted OS according to the Halabi and MSKCC nomograms. Twenty-five patients with progressive mCRPC were enrolled. Treatment comprised of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 107 dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis. No serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13-0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17-0.63) predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS. In patients with mCRPC, the combined chemoimmunotherapy with DCVAC/PCa and docetaxel was safe and resulted in longer than expected survival. Concomitant chemotherapy did not preclude the induction of specific anti-tumor cytotoxic T cells.

  17. Allogeneic marrow transplantation following cyclophosphamide and escalating doses of hyperfractionated total body irradiation in patients with advanced lymphoid malignancies: a phase I/II trial

    International Nuclear Information System (INIS)

    Demirer, Taner; Petersen, Finn B.; Appelbaum, Frederick R.; Barnett, Todd A.; Sanders, Jean; Deeg, H. Joachim; Storb, Rainer; Doney, Kristine; Bensinger, William I.; Shannon-Dorcy, Kathleen; Buckner, C. Dean

    1995-01-01

    Purpose: To define the maximum tolerated dose (MTD) of unshielded total body irradiation (TBI) delivered from dual 60 C sources at an exposure rate of 0.08 Gy/min and given in thrice daily fractions of 1.2 Gy in patients with advanced lymphoid malignancies. Methods and Materials: Forty-four patients with a median age of 28 (range 6-48) years were entered into a Phase I/II study. All patients received cyclophosphamide (CY), 120 mg/kg administered over 2 days before TBI. Marrow from human leukocyte antigen (HLA) identical siblings was infused following the last dose of TBI. An escalation-deescalation schema designed to not exceed an incidence of 25% of Grade 3-4 regimen-related toxicities (RRTs) was used. The first dose level tested was 13.2 Gy followed by 14.4 Gy. Results: None of the four patients at the dose level of 13.2 Gy developed Grade 3-4 RRT. Two of the first eight patients receiving 14.4 Gy developed Grade 3-4 RRT, establishing this as the MTD. An additional 32 patients were evaluated at the 14.4 Gy level to confirm these initial observations. Of 40 patients receiving 14.4 Gy, 13 (32.5%) developed Grade 3-4 RRTs; 46% in adults and 12% in children. The primary dose limiting toxicity was Grade 3-4 hepatic toxicity, which occurred in 12.5% of patients. Noninfectious Grade 3-4 interstitial pneumonia syndrome occurred in 5% of patients. The actuarial probabilities of event-free survival, relapse, and nonrelapse mortality at 2 years were 0.10, 0.81, and 0.47, respectively, for patients who received 14.4 Gy of TBI. Conclusions: The outcome for patients receiving 14.4 Gy of TBI was not different from previous studies of other CY and TBI regimens in patients with advanced lymphoid malignancies. These data showed that the incidence of Grade 3-4 RRTs in adults was greater than the 25% maximum set as the goal of this study, suggesting that 13.2 Gy is a more appropriate dose of TBI for adults, while 14.4 Gy is an appropriate dose for children

  18. miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

    Science.gov (United States)

    Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

    2017-08-08

    Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

  19. INFUSION OF THIRD-PARTY MESENCHYMAL STEM CELLS (MSC) AFTER KIDNEY AND LIVER TRANSPLANTATION: A PHASE I-II, OPEN-LABEL, CLINICAL STUDY (EudraCT 2011-001822-81 & NCT01429038)

    OpenAIRE

    DETRY, Olivier; DELBOUILLE, Marie-Hélène; LECHANTEUR, Chantal; SOMJA, Joan; DE ROOVER, Arnaud; WEEKERS, Laurent; SQUIFFLET, Jean-Paul; Honoré, Pierre; DELVENNE, Philippe; MEURISSE, Michel; BAUDOUX, Etienne; BEGUIN, Yves

    2013-01-01

    MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing...

  20. The Crc global regulator inhibits the Pseudomonas putida pWW0 toluene/xylene assimilation pathway by repressing the translation of regulatory and structural genes.

    Science.gov (United States)

    Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

    2010-08-06

    In Pseudomonas putida, the expression of the pWW0 plasmid genes for the toluene/xylene assimilation pathway (the TOL pathway) is subject to complex regulation in response to environmental and physiological signals. This includes strong inhibition via catabolite repression, elicited by the carbon sources that the cells prefer to hydrocarbons. The Crc protein, a global regulator that controls carbon flow in pseudomonads, has an important role in this inhibition. Crc is a translational repressor that regulates the TOL genes, but how it does this has remained unknown. This study reports that Crc binds to sites located at the translation initiation regions of the mRNAs coding for XylR and XylS, two specific transcription activators of the TOL genes. Unexpectedly, eight additional Crc binding sites were found overlapping the translation initiation sites of genes coding for several enzymes of the pathway, all encoded within two polycistronic mRNAs. Evidence is provided supporting the idea that these sites are functional. This implies that Crc can differentially modulate the expression of particular genes within polycistronic mRNAs. It is proposed that Crc controls TOL genes in two ways. First, Crc inhibits the translation of the XylR and XylS regulators, thereby reducing the transcription of all TOL pathway genes. Second, Crc inhibits the translation of specific structural genes of the pathway, acting mainly on proteins involved in the first steps of toluene assimilation. This ensures a rapid inhibitory response that reduces the expression of the toluene/xylene degradation proteins when preferred carbon sources become available.

  1. ESTUDIO PRELIMINAR SOBRE LA INFLUENCIA DE LA CARRAGENINA KAPPA, KAPPA I.II Y GOMA TARA EN LA VISCOSIDAD Y TIXOTROPÍA DE LAS SALMUERAS DE INYECCIÓN PARA JAMONES COCIDOS PICADOS DE CERDO PRELIMINARY STUDY ON THE INFLUENCE OF KAPPA, KAPPA I.II CARRAGEENAN AND TARA GUM IN THE VISCOSITY AND THIXOTROPY OF INJECTION BRINES FOR COOKED CHOPPED HAMS OF PORK

    Directory of Open Access Journals (Sweden)

    Fabio Alexander Molina Cote

    2010-12-01

    Full Text Available El presente estudio determinó el efecto que sobre la viscosidad y la tixotropía de una salmuera de masajeo para jamones picados cocidos de cerdo, tiene la adición de carragenina kappa, carragenina kappa I.II y goma tara, cuando son usadas a un nivel del 1% en la salmuera. Para tal efecto se incorporaron seis mezclas distintas de hidrocoloides provenientes de la carragenina kappa, kappa I.II y goma tara (individualmente, en mezclas binarias y mezclas terciarias, en una salmuera de inyección y masajeo para jamones; a las cuales se les determinó su comportamiento viscoso y tixotrópico a 4 ºC. Los datos obtenidos de índice de tixotropía (máximos, se analizaron mediante un modelo cuadrático derivado de un arreglo de mezclas. Los resultados mostraron que todas las salmueras se comportaron tixotrópicamente, presentando mayor área de histéresis, las mezclas que contenían goma tara. El modelo usado para el índice de tixotropía arrojó, con un nivel de significancia de 0,05, que la relación óptima, es la que contiene la mezcla de carragenina kappa I.II-goma tara (79% y 21%. Adicionalmente, las salmueras que contenían carragenina kappa, carragenina kappa I.II y carragenina kappa-carragenina kappa I.II presentaron menor viscosidad que las mezclas que contenían goma tara.The aim of this study was to determine the thixotropy´s effect of a massage brine in cooked chopped pork hams with addition of kappa, kappa I.II carrageenan, tara gum and their mixtures, when were used at 1% injection level of brine to meat. Six mixtures were evaluated. A protocol for thixotropy measurement adjusted to the conditions of brines used taking in account salinity, pH, temperature and shear stress. Data obtained from thixotropy index (maximum were analyzed with quadratic model derived from blends array. Results showed thixotropic measurement to brines presented a very small area, showing structural changes, but with very fast recovery. It was observed thixotropic behavior in kappa, kappa I.II, tara gum and their mixtures evaluated. Brines containing kappa, kappa I.II and kappa-kappa I.II showed lower viscosity values than blends with tara gum which produced more viscosity in cold conditions than kappas. In the quadratic arrangement of mixtures, it was observed in terms of maximum thixotropic index the more optimal region was for mixture containing kappa I.II-tara gum (79% and 21%, correspondly with a significant level of 0.05.

  2. Associations of Census-Tract Poverty with Subsite-Specific Colorectal Cancer Incidence Rates and Stage of Disease at Diagnosis in the United States

    Directory of Open Access Journals (Sweden)

    Kevin A. Henry

    2014-01-01

    Full Text Available Background. It remains unclear whether neighborhood poverty contributes to differences in subsite-specific colorectal cancer (CRC incidence. We examined associations between census-tract poverty and CRC incidence and stage by anatomic subsite and race/ethnicity. Methods. CRC cases diagnosed between 2005 and 2009 from 15 states and Los Angeles County (N=278,097 were assigned to 1 of 4 groups based on census-tract poverty. Age-adjusted and stage-specific CRC incidence rates (IRs and incidence rate ratios (IRRs were calculated. Analyses were stratified by subsite (proximal, distal, and rectum, sex, race/ethnicity, and poverty. Results. Compared to the lowest poverty areas, CRC IRs were significantly higher in the most impoverished areas for men (IRR = 1.14 95% CI 1.12–1.17 and women (IRR = 1.06 95% CI 1.05–1.08. Rate differences between high and low poverty were strongest for distal colon (male IRR = 1.24 95% CI 1.20–1.28; female IRR = 1.14 95% CI 1.10–1.18 and weakest for proximal colon. These rate differences were significant for non-Hispanic whites and blacks and for Asian/Pacific Islander men. Inverse associations between poverty and IRs of all CRC and proximal colon were found for Hispanics. Late-to-early stage CRC IRRs increased monotonically with increasing poverty for all race/ethnicity groups. Conclusion. There are differences in subsite-specific CRC incidence by poverty, but associations were moderated by race/ethnicity.

  3. Associations of Census-Tract Poverty with Sub site-Specific Colorectal Cancer Incidence Rates and Stage of Disease at Diagnosis in the United States

    International Nuclear Information System (INIS)

    Henry, K. A.; Stroup, A. M.; Sherman, R. L.

    2014-01-01

    It remains unclear whether neighborhood poverty contributes to differences in subsite-specific colorectal cancer (CRC) incidence. We examined associations between census-tract poverty and CRC incidence and stage by anatomic sub site and race/ethnicity. Methods. CRC cases diagnosed between 2005 and 2009 from 15 states and Los Angeles County (N = 278,097) were assigned to 1 of 4 groups based on census-tract poverty. Age-adjusted and stage-specific CRC incidence rates (IRs) and incidence rate ratios (IRRs) were calculated. Analyses were stratified by sub site (proximal, distal, and rectum), sex, race/ethnicity, and poverty. Results. Compared to the lowest poverty areas, CRC IRs were significantly higher in the most impoverished areas for men (IRR = 1.14 95% CI 1.12-1.17) and women (IRR = 1.06 95% CI 1.05-1.08). Rate differences between high and low poverty were strongest for distal colon (male IRR = 1.24 95% CI 1.20-1.28; female IRR = 1.14 95% CI 1.10-1.18) and weakest for proximal colon. These rate differences were significant for non-Hispanic whites and blacks and for Asian/Pacific Islander men. Inverse associations between poverty and IRs of all CRC and proximal colon were found for Hispanics. Late-to-early stage CRC IRRs increased monotonically with increasing poverty for all race/ethnicity groups. Conclusion. There are differences in sub site-specific CRC incidence by poverty, but associations were moderated by race/ethnicity.

  4. MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma: a phase I/II study.

    Science.gov (United States)

    Albarran Y Carvajal, Antonio; de la Garza, Alfonso; Cruz Quiroz, Benitez Jose Cecilio; Vazquez Zea, Eduardo; Díaz Estrada, Ismael; Mendez Fuentez, Ernesto; López Contreras, Mario; Andrade-Manzano, Alejandro; Padilla, Santiago; Varela, Axel Ramírez; Rosales, Ricardo

    2007-01-01

    Human papillomavirus (HPV) is the etiologic agent for warts and cervical cancer. In Mexico, the death rate from cervical cancer is extremely high, and statistical data show that since 1990 the number of deaths is increasing. Condylomas and cancer of the penis are the most common lesions presented in men; bladder and prostate cancer in men are also associated with the presence of HPV. Since HPV is transmitted by sexual intercourse, treating both partners is necessary in order to eliminate the virus in the population. Approaches to this include preventative vaccines such as Gardasil, and therapeutic vaccines to treat established infections in both men and women. This will be the only way to decrease the numbers of deaths due to this malignancy. We conducted a phase I/II clinical trial to evaluate the potential use of the recombinant vaccinia viral vaccine MVA E2 (composed of modified vaccinia virus Ankara [MVA] expressing the E2 gene of bovine papillomavirus) to treat flat condyloma lesions associated with oncogenic HPV in men. Fifty male patients with flat condyloma lesions were treated with either MVA E2 therapeutic vaccine or fluorouracil (5-fluorouracil). Thirty men received the therapeutic vaccine, at a total of 10(6) virus particles per dose, administered directly into the urethra once every week over a 4-week period. Twenty control patients were treated with 5% fluorouracil 1mL twice weekly over a 4-week period directly into the urethra. Reduction of lesions or absence of papillomavirus infection was monitored by colposcopy and histologic analysis. The immune response after MVA E2 treatment was determined by measuring the antibodies against the MVA E2 virus and by analyzing the lymphocyte cytotoxic activity against cancer cells bearing oncogenic papillomavirus. Presence of papillomavirus was determined by the Hybrid Capture method. Twenty-eight of 30 patients showed no lesion or presence of papillomavirus as diagnosed by colposcopy and brush histologic examination after 4 weeks of MVA E2 treatment. These patients showed complete elimination of flat condyloma in the urethra and no acetowhite spots were detected over the prepuce. In two other patients the acetowhite spots and flat condyloma did not diminish. All patients developed antibodies against the MVA E2 vaccine and E2 protein, and generated a specific cytotoxic response against papilloma-transformed cells. Viral DNA was not detected in MVA E2-treated patients. In the control group, 13 of 20 patients were free of lesions. Three of these patients had recurrence of lesions after 3 months of treatment and none of the patients developed specific antibodies against cancer cells. In contrast, patients treated with MVA E2 did not show any recurrence of lesions after 1 year of treatment. In addition, none of the patients had local or systemic adverse effects according to the WHO classification 1-4. Therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of flat condyloma lesions in men.

  5. Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

    Directory of Open Access Journals (Sweden)

    Nativ Ofer

    2012-11-01

    Full Text Available Abstract Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10, and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC-controlled Phase I/II study (N = 7 in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10: All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7: Hemostatic success at 10 min (primary endpoint was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. Conclusions The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Trial registration Phase I/II trial, NCT00598130

  6. Changes in soluble CEA and TIMP-1 levels during adjuvant chemotherapy for stage III colon cancer

    DEFF Research Database (Denmark)

    Aldulaymi, Bahir; Christensen, Ib Jarle; Sölétormos, György

    2010-01-01

    Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antige...... (CEA) levels in patients with stage III colon cancer.......Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antigen...

  7. Stage design

    International Nuclear Information System (INIS)

    Shacter, J.

    1975-01-01

    A method is described of cycling gases through a plurality of diffusion stages comprising the steps of admitting the diffused gases from a first diffusion stage into an axial compressor, simultaneously admitting the undiffused gases from a second diffusion stage into an intermediate pressure zone of said compressor corresponding in pressure to the pressure of said undiffused gases, and then admitting the resulting compressed mixture of diffused and undiffused gases into a third diffusion stage

  8. Staging Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    and lived as people are “staging themselves” (from below). Staging mobilities is a dynamic process between “being staged” (for example, being stopped at traffic lights) and the “mobile staging” of interacting individuals (negotiating a passage on the pavement). Staging Mobilities is about the fact...

  9. Clinical outcomes of a phase I/II study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame

    International Nuclear Information System (INIS)

    Nagata, Yasushi; Takayama, Kenji; Matsuo, Yukinori; Norihisa, Yoshiki; Mizowaki, Takashi; Sakamoto, Takashi; Sakamoto, Masato; Mitsumori, Michihide; Shibuya, Keiko; Araki, Norio; Yano, Shinsuke; Hiraoka, Masahiro

    2005-01-01

    Purpose: To evaluate the clinical outcomes of 48 Gy of three-dimensional stereotactic radiotherapy in four fractions for treating Stage I lung cancer using a stereotactic body frame. Methods and Materials: Forty-five patients who were treated between September 1998 and February 2004 were included in this study. Thirty-two patients had Stage IA lung cancer, and the other 13 had Stage IB lung cancer where tumor size was less than 4 cm in diameter. Three-dimensional treatment planning using 6-10 noncoplanar beams was performed to maintain the target dose homogeneity and to decrease the irradiated lung volume >20 Gy. All patients were irradiated using a stereotactic body frame and received four single 12 Gy high doses of radiation at the isocenter over 5-13 (median = 12) days. Results: Seven tumors (16%) completely disappeared after treatment (CR) and 38 tumors (84%) decreased in size by 30% or more (PR). Therefore, all tumors showed local response. During the follow-up of 6-71 (median = 30) months, no pulmonary complications greater than an National Cancer Institute-Common Toxicity Criteria of Grade 3 were noted. No other vascular, cardiac, esophageal, or neurologic toxicities were encountered. Forty-four (98%) of 45 tumors were locally controlled during the follow-up period. However, regional recurrences and distant metastases occurred in 3 and 5 of T1 patients and zero and 4 of T2 patients, respectively. For Stage IA lung cancer, the disease-free survival and overall survival rates after 1 and 3 years were 80% and 72%, and 92% and 83%, respectively, whereas for Stage IB lung cancer, the disease-free survival and overall survival rates were 92% and 71%, and 82% and 72%, respectively. Conclusion: Forty-eight Gy of 3D stereotactic radiotherapy in 4 fractions using a stereotactic body frame is useful for the treatment of Stage I lung tumors

  10. Pickled meat consumption and colorectal cancer (CRC): a case-control study in Newfoundland and Labrador, Canada.

    Science.gov (United States)

    Squires, Josh; Roebothan, Barbara; Buehler, Sharon; Sun, Zhuoyu; Cotterchio, Michelle; Younghusband, Ban; Dicks, Elizabeth; Mclaughlin, John R; Parfrey, Patrick S; Wang, Peizhong Peter

    2010-09-01

    Although a large body of epidemiological research suggests that red meat intake increases the risk of colorectal cancer, little is known regarding how such an association varies across populations and types of red meat. The objective of this study was to assess whether an association exists between the intakes of total red meat and pickled red meat and the risk of colorectal cancer in study subjects residing in Newfoundland and Labrador. This case-control study of 1,204 residents of Newfoundland and Labrador was part of a larger study on colorectal cancer. Personal history food frequency questionnaires were used to collect retrospective data from 518 individuals diagnosed with colorectal cancer and 686 controls. Intakes were ranked and divided into tertiles. Logistic regression was used to examine the possible association between meat intakes and colorectal cancer diagnosis while controlling for possible confounding factors. A positive, but non-statistically significant, association between total red meat intake and CRC was observed in this study. Pickled red meat consumption was found to be significantly associated with an increased risk of CRC (men, OR = 2.07, 95% CI 1.37-3.15; women, OR = 2.51, 95% CI 1.45-4.32), the odds ratios increasing with each tertile of consumption, suggesting a dose-response effect. Intake of pickled red meat appears to increase the risk of colorectal cancer in Newfoundland and Labrador.

  11. The KRAS Strip Assay for detection of KRAS mutation in Egyptian patients with colorectal cancer (CRC): A pilot study

    International Nuclear Information System (INIS)

    Abd El Kader, Y.; Safwat, E.; Kassem, H.A.; Kassem, N.M.; Emera, G.

    2013-01-01

    Background: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefltinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. Purpose: Detection of KRAS mutation in Egyptian colorectal cancer (CRC) patients by the KRAS Strip Assay. Methods: Examination of 20 colorectal cancer (CRC) patients is done to detect KRAS mutations by KRAS Strip Assay. For the Strip Assay, a mutant-enriched PCR was followed by hybridization to KRAS-specific probes bound to a nitrocellulose strip. Results: Among 20 patients, KRAS mutations were identified in 80% of patients by the KRAS Strip Assay. Conclusions: Our preliminary results suggest that KRAS Strip Assay is an alternative to protocols currently in use for KRAS mutation detection

  12. Millimeter-wave spectroscopy of CrC (X(3)Σ(-)) and CrCCH (X̃ (6)Σ(+)): Examining the chromium-carbon bond.

    Science.gov (United States)

    Min, J; Ziurys, L M

    2016-05-14

    Pure rotational spectroscopy of the CrC (X(3)Σ(-)) and CrCCH (X̃ (6)Σ(+)) radicals has been conducted using millimeter/sub-millimeter direct absorption methods in the frequency range 225-585 GHz. These species were created in an AC discharge of Cr(CO)6 and either methane or acetylene, diluted in argon. Spectra of the CrCCD were also recorded for the first time using deuterated acetylene as the carbon precursor. Seven rotational transitions of CrC were measured, each consisting of three widely spaced, fine structure components, arising from spin-spin and spin-rotation interactions. Eleven rotational transitions were recorded for CrCCH and five for CrCCD; each transition in these cases was composed of a distinct fine structure sextet. These measurements confirm the respective (3)Σ(-) and (6)Σ(+) ground electronic states of these radicals, as indicated from optical studies. The data were analyzed using a Hund's case (b) Hamiltonian, and rotational, spin-spin, and spin-rotation constants have been accurately determined for all three species. The spectroscopic parameters for CrC were significantly revised from previous optical work, while those for CrCCH are in excellent agreement; completely new constants were established for CrCCD. The chromium-carbon bond length for CrC was calculated to be 1.631 Å, while that in CrCCH was found to be rCr-C = 1.993 Å - significantly longer. This result suggests that a single Cr-C bond is present in CrCCH, preserving the acetylenic structure of the ligand, while a triple bond exists in CrC. Analysis of the spin constants suggests that CrC has a nearby excited (1)Σ(+) state lying ∼16 900 cm(-1) higher in energy, and CrCCH has a (6)Π excited state with E ∼ 4800 cm(-1).

  13. Why Wait Until Our Community Gets Cancer?: Exploring CRC Screening Barriers and Facilitators in the Spanish-Speaking Community in North Carolina.

    Science.gov (United States)

    Martens, Christa E; Crutchfield, Trisha M; Laping, Jane L; Perreras, Lexie; Reuland, Daniel S; Cubillos, Laura; Pignone, Michael P; Wheeler, Stephanie B

    2016-12-01

    Colorectal cancer (CRC) is a leading cause of death among Hispanics in the United States. Despite the benefits of CRC screening, many Hispanics are not being screened. Using a combined methodology of focus groups and discrete choice experiment (DCE) surveys, the objectives for this research were as follows: (1) to improve understanding of preferences regarding potential CRC screening program characteristics, and (2) to improve understanding of the barriers and facilitators around CRC screening with the Hispanic, immigrant community in North Carolina. Four gender-stratified focus groups were conducted and DCE surveys were administered to 38 Spanish-speaking individuals across four counties in North Carolina. In-depth content analysis was used to examine the focus group data; descriptive analyses and mean attribute importance scores for cost of screening and follow-up care, travel time, and test options were calculated from DCE data. Data analyses showed that this population has a strong interest in CRC screening but experience barriers such as lack of access to resources, cost uncertainty, and stigma. Some of these barriers are unique to their cultural experiences in the United States, such as an expressed lack of tailored CRC information. Based on the DCE, cost variables were more important than testing options or travel time. This study suggests that Hispanics may have a general awareness of and interest in CRC screening, but multiple barriers prevent them from getting screened. Special attention should be given to designing culturally and linguistically appropriate programs to improve access to healthcare resources, insurance, and associated costs among Hispanics.

  14. New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case-control study in UK general practice.

    Science.gov (United States)

    García Rodríguez, Luis A; Soriano-Gabarró, Montse; Bromley, Susan; Lanas, Angel; Cea Soriano, Lucía

    2017-09-07

    Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up. Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19). Patients starting low-dose aspirin therapy have a reduced

  15. EFECTO DE LA ADICIÓN DE CARRAGENINA KAPPA I.II Y GOMA TARA SOBRE CARACTERÍSTICAS DE CALIDAD DEL JAMÓN DE CERDO PICADO Y COCIDO EFFECT OF THE ADDITION OF KAPPA I.II CARRAGEENAN AND TARA GUM ON QUALITY CHARACTERISTICS OF COOKED AND CHOPPED PORK HAMS

    Directory of Open Access Journals (Sweden)

    Diego Alonso Restrepo Molina

    2010-12-01

    Full Text Available Se evaluaron sinéresis, color y dureza instrumental y, sensorialmente las características de olor, sabor, color y dureza en jamones inyectados, cocidos y picados de cerdo, los cuales se habían elaborado aplicando en la salmuera de inyección una mezcla de hidrocoloides compuesta por carragenina kappa I.II y goma tara en una proporción de 79:21, en niveles del 1% y 1,2%, usando tres repeticiones para el estudio. Los jamones así elaborados se compararon contra un jamón testigo, elaborado sin el uso de estos hidrocoloides. Los valores obtenidos para los atributos, se analizaron mediante un diseño de una sola vía, con 5 repeticiones en el tiempo (0, 10, 20, 28 y 34 días, dando un arreglo factorial. Los resultados muestran que el tratamiento 2 (1,2% presentó la menor liberación de agua y la mayor dureza. No se registró diferencia entre los tratamientos y el testigo para la característica elasticidad. El testigo mostró las mejores características de color, olor y sabor sensoriales. La edad influyó en las características dureza y sinéresis en forma determinante, señalando el período desde el día 15 hasta el día 28 como aquel en que más se agudiza la sinéresis, siendo ésta más notable en el testigo que no contenía hidrocoloide.Characteristics of quality, color, texture and sineresis (instrumental and, odor, flavor, color and hardness (sensory of injected, cooked and chopped pork hams were assessed, which were manufactured using a mix of hydrocolloids in the brine of injection comprised by kappa I.II carrageenan and tara gum in a 79:21 ratio, at levels of 1% and 1.2%, using three replicates for the study; the finished hams were compared with a control ham, manufactured without the use of these hydrocolloids. The values obtained for the attributes, were analyzed through a one way design, with 5 repetitions in time (0, 10, 20, 28 and 34 days, providing a factorial arrangement. The results showed that the treatment 2 (1.2% presented the lower water release and the higher hardness. It showed no significant difference between the treatments and the control for the characteristic of elasticity. The control showed the best sensory characteristics of color, odor, and taste. The age strongly influenced in the characteristics of hardness and sineresys, defining the time from the day 15 to the 28, as the period with the highest sneresys, most noticeable in the control with no hydrocolloid addtion.

  16. Prognostic implications of occult nodal tumour cells in stage I and II colon cancer: The correlation between micrometastasis and disease recurrence

    NARCIS (Netherlands)

    Sloothaak, D. A. M.; van der Linden, R. L. A.; van de Velde, C. J. H.; Bemelman, W. A.; Lips, D. J.; van der Linden, J. C.; Doornewaard, H.; Tanis, P. J.; Bosscha, K.; van der Zaag, E. S.; Buskens, C. J.

    2017-01-01

    Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer. The objective of this retrospective multicenter study

  17. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer

    DEFF Research Database (Denmark)

    Yu, Jun; Feng, Qiang; Wong, Sunny Hei

    2017-01-01

    known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4...... in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I-II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC. CONCLUSIONS: We present the first metagenomic profiling study of CRC faecal microbiomes...

  18. The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis.

    Science.gov (United States)

    Song, Lele; Jia, Jia; Peng, Xiumei; Xiao, Wenhua; Li, Yuemin

    2017-06-08

    The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.

  19. ColoFinder: a prognostic 9-gene signature improves prognosis for 871 stage II and III colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Mingguang Shi

    2016-03-01

    Full Text Available Colorectal cancer (CRC is a heterogeneous disease with a high mortality rate and is still lacking an effective treatment. Our goal is to develop a robust prognosis model for predicting the prognosis in CRC patients. In this study, 871 stage II and III CRC samples were collected from six gene expression profilings. ColoFinder was developed using a 9-gene signature based Random Survival Forest (RSF prognosis model. The 9-gene signature recurrence score was derived with a 5-fold cross validation to test the association with relapse-free survival, and the value of AUC was gained with 0.87 in GSE39582(95% CI [0.83–0.91]. The low-risk group had a significantly better relapse-free survival (HR, 14.8; 95% CI [8.17–26.8]; P < 0.001 than the high-risk group. We also found that the 9-gene signature recurrence score contributed more information about recurrence than standard clinical and pathological variables in univariate and multivariate Cox analyses when applied to GSE17536(p = 0.03 and p = 0.01 respectively. Furthermore, ColoFinder improved the predictive ability and better stratified the risk subgroups when applied to CRC gene expression datasets GSE14333, GSE17537, GSE12945and GSE24551. In summary, ColoFinder significantly improves the risk assessment in stage II and III CRC patients. The 9-gene prognostic classifier informs patient prognosis and treatment response.

  20. Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients.

    Science.gov (United States)

    De Monte, Ariella; Brunetti, Davide; Cattin, Luigi; Lavanda, Francesca; Naibo, Erica; Malagoli, Maria; Stanta, Giorgio; Bonin, Serena

    2018-03-01

    Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival. The present population-based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health information system. CRC-specific and relative survival probabilities were computed for each group of patients defined by CRC stage, presence or absence of DM2 treated with metformin, and presence or absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study. At the time of CRC diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA daily. The five-year relative survival for stage III CRC was 101% [95% confidence interval (CI)=76-126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2 treated with metformin, however not with ASA. The findings support the hypothesis of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized controlled trials are required to verify this hypothesis.

  1. Viability study for application of combined reheater cycle (CRC) to fluidized bed combustion plants; Estudio de Viabilidad para la Aplicacion del Ciclo de Recalentamiento Combinado (CRC) a Plantas de Combustion de Lecho Fuido Atmosferico

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    Basically, the project try to analyze the application viability of a first reheating in steam cycles of little power plants, useful mainly for biomass and wastes, in our case with coal blends; and a second reheating of the steam in conventional and fluidized bed combustion plants. Using in both cases the thermic energy of the exhaust gases from one gas turbine. The advantages of the CRC cycle are: (1) Reduction of the moisture in the turbine, increasing the energy efficiency and blade protection. (2) To take advantage of the waste gas energy from the gas turbine in optimum way. (3) Great operation flexibility under good efficiency results. In general, the system can use the synergy between gas, coal and waste energies with the highest global efficiency. (Author)

  2. Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

    Science.gov (United States)

    Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

    2017-07-01

    Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A Longitudinal Comparison of Arm Morbidity in Stage I-II Breast Cancer Patients Treated with Sentinel Lymph Node Biopsy, Sentinel Lymph Node Biopsy Followed by Completion Lymph Node Dissection, or Axillary Lymph Node Dissection

    NARCIS (Netherlands)

    Kootstra, Jan J.; Hoekstra-Weebers, Josette E. H. M.; Rietman, Johan S.; de Vries, Jakob; Baas, Peter C.; Geertzen, Jan H. B.; Hoekstra, Harald J.

    Background. Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and

  4. A longitudinal comparison of arm morbidity in stage I-II breast cancer patients treated with sentinel lymph node biopsy, sentinel lymph node biopsy followed by completion lymph node dissection, or axillary lymph node dissection

    NARCIS (Netherlands)

    Kootstra, Jan J.; Hoekstra-Weebers, Josette E.; Rietman, Johan Swanik; de Vries, Jakob; Baas, Peter C.; Geertzen, Jan H.B.; Hoekstra, Harald J.

    2010-01-01

    Background: Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and

  5. Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems

    Directory of Open Access Journals (Sweden)

    Rowe Krista L

    2008-11-01

    Full Text Available Abstract Background Stage at diagnosis plays a significant role in colorectal cancer (CRC survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. Methods Two distinct healthcare populations in the United States (US were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA hospitals from 2003–2007. We assessed metastatic CRC patients treated from 2003–2006 at 10 non-VA, fee-for-service (FFS practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic. Race was dichotomized (white, non-white. Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. Results 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77% reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD age 67 (11, Charlson index 2.0 (1.0, and were 63% white. FFS patients were mean age 61 (13, Charlson index 1.6 (1.0, and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR 0.76, 95% confidence interval (CI 0.58–1.00; p = 0.045; no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82–1.44; p = 0.57. In both cohorts, no association was found between stage at diagnosis and either age or race. Conclusion Higher comorbidity may lead to

  6. Efecto de la adición de carragenina kappa i.ii y goma tara sobre características de calidad del jamón de cerdo picado y cocido.

    OpenAIRE

    Restrepo Molina, Diego Alonso; Molina Cote, Fabio Alexander; Cabrera Torres, Kenneth Roy

    2011-01-01

    Se evaluaron sinéresis, color y dureza instrumental y, sensorialmente las características de olor, sabor, color y dureza en jamones inyectados, cocidos y picados de cerdo, los cuales se habían elaborado aplicando en la salmuera de inyección una mezcla de hidrocoloides compuesta por carragenina kappa I.II y goma tara en una proporción de 79:21, en niveles del 1% y 1,2%, usando tres repeticiones para el estudio. Los jamones así elaborados se compararon contra un jamón testigo, elaborado sin el ...

  7. Trading stages

    DEFF Research Database (Denmark)

    Steiner, Uli; Tuljapurkar, Shripad; Coulson, Tim

    2012-01-01

    Interest in stage-and age structured models has recently increased because they can describe quantitative traits such as size that are left out of age-only demography. Available methods for the analysis of effects of vital rates on lifespan in stage-structured models have not been widely applied ...... examples. Much of our approach relies on trading of time and mortality risk in one stage for time and risk in others. Our approach contributes to the new framework of the study of age- and stage-structured biodemography....

  8. Imposition of Antidumping Duty (BAMD Towards China’s Cold Rolled Coil/Sheet (CRC/S Products

    Directory of Open Access Journals (Sweden)

    Lila Pratiwi

    2013-05-01

    Full Text Available Steel industry is a strategic sector in the economy of a country. Steel industry in Indonesia has not been able to fulfill their domestic demand that is still necessary to import steel product. However, many of these imported products are sold at dumping prices, especially those from china giving rise to unfair trade. One of trade remedy measures as a result of unfair trade remedies can recover trough the imposition of antidumping duty. In 2013, Indonesia imposes antidumping duty for Cold Rolled Coil/Sheet (CRC/S from China and other countries. Imposition of antidumping duty will be analyzed descriptively with the antidumping agreement conformity. While, it cannot be denied that political factors also determine imposition of antidumping duty. It is need to use analytical theory of justice in order to enforce fair-trade

  9. DECOVALEX - Mathematical models of coupled T-H-M processes for nuclear waste repositories. Executive summary for Phases I,II and III

    International Nuclear Information System (INIS)

    Jing, L.; Stephansson, O.; Tsang, C.F.; Kautsky, F.

    1996-06-01

    This executive summary presents the motivation, structure, objectives, methodologies and results of the first stage of the international DECOVALEX project - DECOVALEX I (1992-1995). The acronym stands for Development of Coupled Models and their Validation against Experiment in Nuclear Waste Isolation, and the project is an international effort to develop mathematical models, numerical methods and computer codes for coupled thermo-hydro-mechanical processes in fractured rocks and buffer materials for geological isolation of spent nuclear fuel and other radioactive wastes, and validate them against laboratory and field experiments. 24 refs

  10. Assessment of the cardiac safety between cetuximab and panitumumab as single therapy in Chinese chemotherapy-refractory mCRC.

    Science.gov (United States)

    Tang, Xue-Miao; Chen, Hao; Li, Qing; Song, Yiling; Zhang, Shuping; Xu, Xiao-Shuan; Xu, Yiwei; Chen, Shulin

    2018-01-01

    The cardiac safety of cetuximab and panitumumab, particularly as single agents, has not been investigated extensively. This trial was designed to specifically evaluate the cardiac safety of cetuximab and panitumumab as single therapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients. Sixty-one patients received cetuximab at an initial dose of 400 mg/m 2 intravenously over 120 minutes on day 1 (week 1), followed by a maintenance dose of 250 mg/m 2 intravenously over 60 minutes on day 1 of each 7-day cycle. Forty-three patients received panitumumab at a dose of 6 mg/kg intravenously every 14 days. Routine laboratory tests and electrocardiogram (ECG) were performed at baseline, during therapy and after the treatment (4th and 10th months). The incidence of elevation of troponin I ultra (TNI Ultra), abnormal ECGs, cardiac events and noncardiac adverse events (AEs) were recorded and analyzed. The incidence of elevation of TNI Ultra between the two groups had no significance ( p =0.681), and TNI Ultra+ was observed more frequently in patients with metastases to more than three organs and they received fourth or above lines of chemotherapy. The most frequent abnormal ECG manifestations were nonspecific ST changes and QTc prolongation in the two groups. At 10 months after treatment, most of the abnormal ECG manifestations were reversed. The most common cardiac AEs of cetuximab and panitumumab included palpitations, dyspnea, chest pain and arrhythmias requiring treatment. Most of the events were mild and transient. The incidence of cardiac AEs had no significant difference between the two groups. Rash was still the most common noncardiac AE in both groups. Cetuximab and panitumumab showed favorable cardiac safety as single agents for Chinese chemotherapy-refractory mCRC patients. But monitoring for cardiac AEs is still necessary throughout the entire treatment process.

  11. Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC).

    Science.gov (United States)

    Zhang, Tiening; Cai, Xun; Li, Qi; Xue, Peng; Chen, Zhixiao; Dong, Xiao; Xue, Ying

    2016-07-05

    Hsa-miRNA-875-5p (miR-875-5p) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-875-5p on colorectal carcinoma (CRC) is still ambiguous. In this study, we investigated the role of miR-875-5p on the development of CRC. The results indicated that miR-875-5p was significantly down-regulated in primary tumor tissues and very low levels were found in CRC cell lines. Ectopic expression of miR-875-5p in CRC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-875-5p induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-875-5p inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene EGFR was revealed to be a putative target of miR-875-5p, which was inversely correlated with miR-875-5p expression in CRC. Taken together, our results demonstrated that miR-875-5p played a pivotal role on CRC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic EGFR.

  12. 'Mälestus päikesest - kuhu küll jäi see...'; Tsarskoje Selos I, III; 'Talveingel talvepäeval...'; 'Sadu kordi olen neednud...'; Loti naine; Miikal; Itk; 'Oli taevas nii põhjatu, kõrge ja sinise laega...' : [luuletused] / Anna Ahmatova ; vene k

    Index Scriptorium Estoniae

    Ahmatova, Anna, pseud., 1889-1966

    1997-01-01

    Orig.: "Pamjat o solntse v serdtse slabejet..." ; V Tsarskom Sele I-III ; "Bozhi Angel, zimnim utrom..." ; "Stolko raz ja proklinala..." ; Lotova zhena ; Melhola ; Pritshitanije ; "Nebõvalaja ossen postroila kupol võssoki..."

  13. Genetic and cytokine changes associated with symptomatic stages of CLL.

    Science.gov (United States)

    Agarwal, Amit; Cooke, Lawrence; Riley, Christopher; Qi, Wenqing; Mount, David; Mahadevan, Daruka

    2014-09-01

    The pathogenesis and drug resistance of symptomatic CLL patients involves genetic changes associated with the CLL clone as well as changes within the microenvironment. To further understand these processes, we compared early stage CLL to symptomatic late stage using gene expression and serum cytokine profiling to gain insight of the genetic and microenvironment changes associated with the most severe form of the disease. Patients were classified into low stage (Rai stage 0/I/II) and high stage (Rai stage III/IV). Gene expression profiles were obtained on pretreatment samples using the HG-U133A 2.0 Affymetrix platform. A comparison of low versus high stage CLL revealed a set of 21 genes differentially expressed genes. 15 genes were up regulated in the high stage compared to low stage while 6 genes were down regulated. Analysis of GO molecular function revealed 9 of 21 genes were involved in transcription factor activity. Serum cytokine profiles showed six cytokines to be significantly different in high stage patients. Two chemokines, SDF-1/CXCL12 and uPAR known to be involved in stem cell mobilization and homing were increased in serum of high stage patients. This study has identified therapeutic targets for symptomatic CLL patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Interpretation of electrocardiographic, echocardiographic and biochemical findings during different stages of Canine Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Ural K

    2017-09-01

    Full Text Available Objective. The purpose of the present study was to test the hypothesis that cardiac alterations participate within different stages of CVL. Materials and methods. Twenty-eight dogs were diagnosed with CVL, were classified [based on clinical signs, rapid ELISA/IFAT, hematological and serum biochemical tests, urinary protein/creatinine ratio, ECG and ECHO]. as follows; group I (mild disease, group II (moderate disease, group III (severe disease, group IV (very severe disease and group V included healthy controls. Results. Ig G antibodies against leishmaniasis as tested by IFAT, were deemed 1/64 to 1/16000 among infected groups. There were statistical significance regarding mean values for WBC [among healthy control group (V. and other groups (p=0.049], RBC [among stage III-stage IV and other groups (p=0.001], Hb [between stage I and stage III-stage IV (p=0.008, HCT [between stage I and other groups (p = 0.001] MCHC [between stage I and stage II- stage IV (p=0.046], serum creatinine [(p=0.008 stage IV and stage I-II within group V], serum protein [(p=0.002 among stage IV and stage I-III- healthy control groups] and serum albumine [(p=0.004 among stage IV and stage I-II]. There was no alteration in CTnI concentrations,among groups. UPC analysis revealed statistical difference among control group and stage II to IV dogs (p=0.000. Moderate or severe ECG abnormalities were detected in 6/28 of diseased dogs. Regarding ECHO examination LA/ Ao value presented significant difference (p=0.003 among stage IV and other groups. Conclusions. It may be suggested that establishing Leishvet Working Group to those of dogs classified into stage I to IV, ECG [left atrial/ventricular enlargement, myocardial hypoxia] and ECHO [left atrial dilation, decrased/increased LVIDs, decrased/increased LVIDd, shortened FS and EF (systolic dysfunction] alterations must be taken into account along with hematological and serum biochemical analysis.

  15. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    Science.gov (United States)

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

  16. Preoperative Radiotherapy of Advanced Rectal Cancer With Capecitabine and Oxaliplatin With or Without Cetuximab: A Pooled Analysis of Three Prospective Phase I-II Trials

    International Nuclear Information System (INIS)

    Weiss, Christian; Arnold, Dirk; Dellas, Kathrin; Liersch, Torsten; Hipp, Matthias; Fietkau, Rainer; Sauer, Rolf; Hinke, Axel; Roedel, Claus

    2010-01-01

    Purpose: A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades. Methods and Materials: Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recorded for all patients. Results: Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab. Conclusions: Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.

  17. Staging atmospheres

    DEFF Research Database (Denmark)

    Bille, Mikkel; Bjerregaard, Peter; Sørensen, Tim Flohr

    2015-01-01

    The article introduces the special issue on staging atmospheres by surveying the philosophical, political and anthropological literature on atmosphere, and explores the relationship between atmosphere, material culture, subjectivity and affect. Atmosphere seems to occupy one of the classic...

  18. Mutations in TGFbeta-RII and BAX mediate tumor progression in the later stages of colorectal cancer with microsatellite instability

    International Nuclear Information System (INIS)

    Yashiro, Masakazu; Hirakawa, Kosei; Boland, C Richard

    2010-01-01

    Microsatellite instability (MSI) occurs in 15% of colorectal cancers (CRC). The genetic targets for mutation in the MSI phenotype include somatic mutations in the transforming growth factor beta receptor typeII (TGFbetaRII), BAX, hMSH3 and hMSH6. It is not clear how mutations of these genes mediate tumor progression in the MSI pathway, and the temporal sequence of these mutations remains uncertain. In this study, early stage CRCs were examined for frameshift mutations in these target genes, and compared with late stage tumors and CRC cell lines. We investigated 6 CRC cell lines and 71 sporadic CRCs, including 61 early stage cancers and 10 late stage cancers. Mutations of repetitive mononucleotide tracts in the coding regions of TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR and Fas antigen were identified by direct sequencing. Thirteen (18.3%) of 71 CRC, including 9/61 (14.7%) early stage cancers and 4/10 (40%) late stage cancers, were identified as MSI and analyzed for frameshift mutations. No mutation in the target genes was observed in any of the 9 early stage MSI CRCs. In contrast, frameshift mutations of TGFbetaRII, BAX, hMSH3 and hMSH6 were present in 3/4 late stage MSI tumors. There is a statistical association (p = 0.014) between mutation in any one gene and tumor stage. TGFbetaRII, BAX, hMSH3 and hMSH6 mutations are relatively late events in the genesis of MSI CRCs. The frameshift mutations in these target genes might mediate progression from early to late stage cancer, rather than mediating the adenoma to carcinoma transition

  19. A prospective phase I/II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix - acute toxicity and biomarker response analysis

    International Nuclear Information System (INIS)

    Chan, P.; Doll, C.; Oza, A.; Pintilie, M.; Levin, W.; Manchul, L.; Fyles, A.; Milosevic, M.

    2003-01-01

    To evaluate the toxicity and biomarker response of celecoxib (C) as a biologic modifier in combination with definitive chemoradiotherapy (CRT) in women with cervix cancer. Fifteen cervix patients were entered into the first phase of this prospective study between March 2001 and January 2002. FIGO stages included IB(2), IIB(8), IIIB(4), and IVA(1), and median age was 51 years (range 26-62). Celecoxib 400mg orally was given b.i.d. 2 weeks prior to, and during the CRT. Toxicity assessments were performed weekly up to 12 weeks following treatment prior to further accrual using the NCIC-CTC. Hypoxia (HP5) and interstitial fluid pressure (IFP) assays were performed at day 0 and 14. Eleven patients completed the prescribed therapy. Only 2 of 4 patients discontinued C due to GI toxicity. In total there were 6 (40%) with grade 3/4 acute toxicity. Four were related to GI, one to skin reaction while the other was haematological. Although it was difficult to distinguish CRT toxicity from C, the proportion of patients with severe acute toxicity was similar to what we previously reported with CRT alone (8/24 (33%), Rodrigues, IJROBP 2001:Vol 51:(3): (Supp 1): 334). GI toxicity was more common in this study whereas haematologic effects were more frequent in the previous study. Evaluating the most recent measurable data set, 6 of 16 patients showed a decrease in HP5, (3.8 - 89.7%) while 10 of 14 patients had a reduction in IFP, (1.3 - 16.2mmHg). Two grade 4 late GI toxicity developed. Celecoxib is tolerated by patients receiving CRT for cervix cancer. Response of microenvironmental biomarkers to C was seen in the majority, suggesting a role as early markers of treatment outcome. Further follow-up is needed to assess the risk of late toxicity. The trial has been re-opened with C reduced to 300 mg b.i.d

  20. Outcome of Children With Metastatic Medulloblastoma Treated With Carboplatin During Craniospinal Radiotherapy: A Children's Oncology Group Phase I/II Study

    Science.gov (United States)

    Jakacki, Regina I.; Burger, Peter C.; Zhou, Tianni; Holmes, Emiko J.; Kocak, Mehmet; Onar, Arzu; Goldwein, Joel; Mehta, Minesh; Packer, Roger J.; Tarbell, Nancy; Fitz, Charles; Vezina, Gilbert; Hilden, Joanne; Pollack, Ian F.

    2012-01-01

    Purpose We evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (M+) MB. Patients and Methods After surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m2/dose), along with vincristine (VCR) once per week for 6 weeks. Patients on regimen A received 6 months of maintenance chemotherapy (MC) with cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of carboplatin was determined, cisplatin was added to the MC (regimen B). Results In all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years) were enrolled. Myelosuppression was dose limiting and 35 mg/m2/dose × 30 was determined to be the RP2D of carboplatin. Twenty-nine (36%) of 81 patients with M+ MB had diffuse anaplasia. Four patients were taken off study within 11 months of completing radiotherapy for presumed metastatic progression and are long-term survivors following palliative chemotherapy. Excluding these four patients, 5-year overall survival ± SE and progression-free survival ± SE for M+ patients treated at the RP2D on regimen A was 82% ± 9% and 71% ± 11% versus 68% ± 10% and 59% ± 10% on regimen B (P = .36). There was no difference in survival by M stage. Anaplasia was a negative predictor of outcome. Conclusion The use of carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB. Early progression should be confirmed by biopsy. PMID:22665539

  1. A phase I-II study of the histone deacetylase inhibitor vorinostat plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced breast cancer.

    Science.gov (United States)

    Tu, Yifan; Hershman, Dawn L; Bhalla, Kapil; Fiskus, Warren; Pellegrino, Christine M; Andreopoulou, Eleni; Makower, Della; Kalinsky, Kevin; Fehn, Karen; Fineberg, Susan; Negassa, Abdissa; Montgomery, Leslie L; Wiechmann, Lisa S; Alpaugh, R Katherine; Huang, Min; Sparano, Joseph A

    2014-07-01

    Histone deacetylases (HDACs) are a family of enzymes that regulate chromatin remodeling and gene transcription. Vorinostat is a panHDAC inhibitor that sensitizes breast cancer cells to taxanes and trastuzumab by suppressing HDAC6 and Hsp90 client proteins. Fifty-five patients with clinical stage IIA-IIIC breast cancer received 12 weekly doses of paclitaxel (80 mg/m(2)) plus vorinostat (200-300 mg PO BID) on days 1-3 of each paclitaxel dose plus trastuzumab (for Her2/neu positive disease only), followed by doxorubicin/cyclophosphamide (60/600 mg/m(2) every 2 weeks plus pegfilgrastim). The primary study endpoint was pathologic complete response (pCR). pCR occurred in 13 of 24 evaluable patients with Her2-positive disease (54, 95 % confidence intervals [CI] 35-72 %), which met the prespecified study endpoint. pCR occurred in 4 of 15 patients with triple negative disease (27, 95 % CI 11-52 %) and none of 12 patients with ER-positive, Her2/neu negative disease (0, 95 % CI 0-24 %), which did not meet the prespecified endpoint. ER-positive tumors exhibited lower Ki67 and higher Hsp70 expression, and HDAC6, Hsp70, p21, and p27 expression were not predictive of response. Vorinostat increased acetylation of Hsp90 and alpha tubulin, and reduced expression of Hsp90 client proteins and HDAC6 in the primary tumor. Combination of vorinostat with weekly paclitaxel plus trastuzumab followed by doxorubicin-cyclophosphamide is associated with a high pCR rate in locally advanced Her2/neu positive breast cancer. Consistent with cell line and xenograft data, vorinostat increased acetylation of Hsp90 and alpha tubulin, and decreased Hsp90 client protein and HDAC6 expression in human breast cancers in vivo.

  2. STUDY OF THE INFLUENCE OF COMPLEX TREATMENT USING IMMUNOMODULATORS ON THE STATE OF LOCAL IMMUNITY IN PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS I-II SEVERITY ON ENTEROBIASIS

    Directory of Open Access Journals (Sweden)

    Savel’eva NN

    2016-12-01

    Full Text Available Introduction. Due to the high prevalence of chronic generalized periodontitis there is a need for a broader analysis of the causes and development of diseases, as well as the search for effective treatments for etiopathogenetical. The aim of this work was to study the effect of newly developed therapy on local immunity in patients CGP I and II severity with enterobiasis. Material & methods. The main group consisted of 32 people with СGP I degree and 60 people with СGP II severity who were treated according to our scheme. The control group consisted of 30 people with СGP I degree and 58 people with СGP II severity, treated with conventional treatment. The control group consisted of 30 people without periodontal disease and chronic diseases of other systems. All patients were studied the main group and the comparison group conducted a basic local therapeutic treatment of periodontal disease, including professional oral hygiene, temporary splinting of teeth, selective prishlifovyvanie teeth. For medical treatment of periodontal tissues using 0.05% - 0.2% solution of chlorhexidine bigluconate. Further treatment of patients of the main group carried out in 2 stages. At the first stage the main group received: irrigation and instillation of periodontal tissue in periodontal pockets antiseptic preparation "Dekasan" application keratoplastic drug "Katomas". Systemically administered drug tonic "Sage oil" probiotic "Kvertulin" immunomodulator "Erbisol". In the second phase, patients received: applications on the gums periodontal gel "Lizomukoid" systemically complex preparation "Оil extract from pumpkin seeds." All patients of the main group used toothpaste "Lacalut flora" and rinse "grapefruit". In the comparison group, patients received applications in periodontal pockets (drug Dalatsin C application to the gums (keratoplastic drug Aekol system - a probiotic Linex, immunomodulator "Echinacea compositum С". All patients with the comparison group

  3. Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC).

    Science.gov (United States)

    Hammoudi, Abeer; Song, Fei; Reed, Karen R; Jenkins, Rosalind E; Meniel, Valerie S; Watson, Alastair J M; Pritchard, D Mark; Clarke, Alan R; Jenkins, John R

    2013-10-25

    Colorectal cancer (CRC) is the fourth most common cause of cancer-related death worldwide. Accurate non-invasive screening for CRC would greatly enhance a population's health. Adenomatous polyposis coli (Apc) gene mutations commonly occur in human colorectal adenomas and carcinomas, leading to Wnt signalling pathway activation. Acute conditional transgenic deletion of Apc in murine intestinal epithelium (AhCre(+)Apc(fl)(/)(fl)) causes phenotypic changes similar to those found during colorectal tumourigenesis. This study comprised a proteomic analysis of murine small intestinal epithelial cells following acute Apc deletion to identify proteins that show altered expression during human colorectal carcinogenesis, thus identifying proteins that may prove clinically useful as blood/serum biomarkers of colorectal neoplasia. Eighty-one proteins showed significantly increased expression following iTRAQ analysis, and validation of nine of these by Ingenuity Pathaway Analysis showed they could be detected in blood or serum. Expression was assessed in AhCre(+)Apc(fl)(/)(fl) small intestinal epithelium by immunohistochemistry, western blot and quantitative real-time PCR; increased nucelolin concentrations were also detected in the serum of AhCre(+)Apc(fl)(/)(fl) and Apc(Min)(/)(+) mice by ELISA. Six proteins; heat shock 60kDa protein 1, Nucleolin, Prohibitin, Cytokeratin 18, Ribosomal protein L6 and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5,were selected for further investigation. Increased expression of 4 of these was confirmed in human CRC by qPCR. In conclusion, several novel candidate biomarkers have been identified from analysis of transgenic mice in which the Apc gene was deleted in the intestinal epithelium that also showed increased expression in human CRC. Some of these warrant further investigation as potential serum-based biomarkers of human CRC. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations.

    Science.gov (United States)

    ElSharawy, Abdou; Röder, Christian; Becker, Thomas; Habermann, Jens K; Schreiber, Stefan; Rosenstiel, Philip; Kalthoff, Holger

    2016-11-15

    The emerging potential of miRNAs as biomarkers for cancer detection demands parallel evaluation of strategies for reliable identification of disease-related signatures from easily accessible and pertinent body compartments. Here, we addressed whether efficient concentration of circulating miRNA-carrying particles is a rationale for miRNA biomarker discovery. We systematically compared miRNA signatures in 93 RNA preparations from three serum entities (whole serum, particle-concentrated, and particle-depleted fractions) and corresponding tissue samples from patients with colorectal cancer (CRC) as a model disease. Significant differences between whole sera and particle-concentrated serum fractions of CRC patients emerged for 45 of 742 tested miRNAs. Twenty-eight of these 45 miRNAs were differentially expressed between particle-concentrated serum fractions of metastatic CRC- and healthy individuals. Over half of these candidates (15 of 28) showed deregulations only in concentrated serum fractions, but not in whole sera, compared to the respective controls.Our results also provided evidence of a consistent downregulation of miR-486 and miR-92a, and further showed a possible "strand-specific" deregulation of extracellular miRNAs in CRC. More importantly, most of the identified miRNAs in the enriched sera reflected the patterns of the corresponding tumor tissues and showed links to cancer-related inflammation. Further investigation of seven serum pools revealed a subset of potential extracellular miRNA candidates to be implicated in both neoplastic and inflammatory bowel disease.Our findings demonstrate that enrichment and sensitive detection of miRNA carriers is a promising approach to detect CRC-related pathological changes in liquid biopsies, and has potential for clinical diagnostics.

  5. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

    Directory of Open Access Journals (Sweden)

    Spugnini Enrico P

    2011-12-01

    the quality of life in pets with down staged cancer and in the majority of the treated animals PPI were well tolerated. Further studies are warranted to assess the efficacy of this strategy in patients with advanced cancers in companion animals as well as in humans.

  6. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors.

    Science.gov (United States)

    Spugnini, Enrico P; Baldi, Alfonso; Buglioni, Sabrina; Carocci, Francesca; de Bazzichini, Giulia Milesi; Betti, Gianluca; Pantaleo, Ilaria; Menicagli, Francesco; Citro, Gennaro; Fais, Stefano

    2011-12-28

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI) increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Thirty-four companion animals (27 dogs and 7 cats) were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats) whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6%) the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17%) experienced short lived partial responses (1-3 months duration) while all the others died of progressive disease within two months. high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of the quality of life in pets with down staged cancer and in

  7. Ultrasound-guided high dose rate conformal brachytherapy boost in prostate cancer: treatment description and preliminary results of a phase I/II clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Stromberg, Jannifer; Martinez, Alvaro; Gonzalez, Jose; Edmundson, Gregory; Ohanian, Neshan; Vicini, Frank; Hollander, Jay; Gustafson, Gary; Spencer, William; Di, Yan; Brabbins, Donald

    1995-08-30

    Purpose: To improve results for locally advanced prostate cancer, a prospective clinical trial of concurrent external beam irradiation and fractionated iridium-192 (Ir-192) high dose rate (HDR) conformal boost brachytherapy was initiated. Methods and Materials: Between November 1991 and February 1994, 99 implants were performed on 33 patients with prostatic adenocarcinoma at William Beaumont Hospital. Using AJCC staging criteria, 9 patients had T2b tumors, 17 patients had T2c tumors, and 7 patients had T3 disease. Patients were treated with (a) 45.6 Gy whole pelvis external irradiation and (b) three HDR fractions of 5.5 Gy each (18 patients) or 6 Gy each (15 patients) to the prostate. Transperineal needle implants using real-time ultrasound guidance with interactive on-line isodose distributions were performed on an outpatient basis during weeks 1, 2, and 3 of external irradiation. Acute toxicity was scored using the Radiation Therapy Oncology Group (RTOG) morbidity grading system. Results: This technique of concurrent external pelvic irradiation and conformal HDR brachytherapy was well tolerated. No significant intraoperative or perioperative complications occurred. Three patients (9%) experienced Grade 3 acute toxicity (two dysuria and one diarrhea). All toxicities were otherwise Grades 1 or 2 and were primarily as expected from pelvic external irradiation. Persistent implant-related toxicities included Grades 1-2 perineal pain (12%) and hematospermia (15%). Median follow-up time was 13 months. Serum prostatic-specific antigen (PSA) levels normalized in 91% of patients (29 out of 32) within 1-14 months (median 2.8 months) after irradiation. PSA levels were progressively decreasing in the other three patients at last measurement. Prospectively planned prostatic rebiopsies done at 18 months in the first 10 patients were negative in 9 out of 10 (90%). Conclusions: Acute toxicity has been acceptable with this unique approach using conformal high dose rate Ir-192

  8. Valor diagnóstico del pepsinógeno i/ii como biomarcador de lesiones pre-malignas y malignas gástricas: revisión sistemática

    OpenAIRE

    Hidalgo Mora, Viviana Marcela; Whang, Joon Kyung

    2016-01-01

    Antecedentes: El cáncer gástrico se diagnostica tardíamente. Sólo en países como Corea y Japón existen políticas de tamizaje, que se justificarían en cualquier país con alta prevalencia de cáncer gástrico como Colombia o Chile. El análisis del pepsinógeno sérico se ha propuesto para el diagnóstico de lesiones premalignas y malignas gástricas, por lo cual se pretende revisar sistemáticamente en la literatura el valor diagnóstico del cociente pepsinógeno I/II como marcador de lesiones premalign...

  9. Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression.

    Science.gov (United States)

    Reguart, Noemi; Rosell, Rafael; Cardenal, Felipe; Cardona, Andres F; Isla, Dolores; Palmero, Ramon; Moran, Teresa; Rolfo, Christian; Pallarès, M Cinta; Insa, Amelia; Carcereny, Enric; Majem, Margarita; De Castro, Javier; Queralt, Cristina; Molina, Miguel A; Taron, Miquel

    2014-05-01

    Vorinostat or suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with demonstrated antiproliferative effects due to drug-induced accumulation of acetylated proteins, including the heat shock protein 90. We prospectively studied the activity of vorinostat plus erlotinib in EGFR-mutated NSCLC patients with progression to tyrosine kinase inhibitors. We conducted this prospective, non-randomized, multicenter, phase I/II trial to evaluate the maximum tolerated dose, toxicity profile and efficacy of erlotinib and vorinostat. Patients with advanced NSCLC harboring EGFR mutations and progressive disease after a minimum of 12 weeks on erlotinib were included. The maximum tolerated dose of vorinostat plus erlotinib was used as recommended dose for the phase II (RDP2) to assess the efficacy of the combination. The primary end point was progression-free-survival rate at 12 weeks (PFSR12w). Pre-treatment plasma samples were required to assess T790M resistant mutation. A total of 33 patients were enrolled in the phase I-II trial. The maximum tolerated dose was erlotinib 150 mg p.o., QD, and 400mg p.o., QD, on days 1-7 and 15-21 in a 28-day cycle. Among the 25 patients treated at the RDP2, the most common toxicities included anemia, fatigue and diarrhea. No responses were observed. PFSR12w was 28% (IC 95%: 18.0-37.2); median progression-free survival (PFS) was 8 weeks (IC 95%: 7.43-8.45) and overall survival (OS) 10.3 months (95% CI: 2.4-18.1). Full dose of continuous erlotinib with vorinostat 400mg p.o., QD on alternative weeks can be safely administered. Still, the combination has no meaningful activity in EGFR-mutated NSCLC patients after TKI progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Clinicopathological predictors of benefit from adjuvant chemotherapy for stage C colorectal cancer: Microsatellite unstable cases benefit.

    Science.gov (United States)

    Thomas, Michelle L; Hewett, Peter J; Ruszkiewicz, Andrew R; Moore, James W E

    2015-12-01

    In colorectal cancer (CRC), adjuvant therapy is offered on the basis of stage and attempts to identify factors to better target treatment have not been successful. Recent work suggested that mismatch repair deficient CRCs may not benefit from 5FU adjuvant chemotherapy but studies remain conflicting. We aimed to determine if gender, tumor site, tumor pathological characteristics and microsatellite instability (MSI) predict survival benefit from adjuvant chemotherapy in stage C CRC. Data were collated on ACPS (Australian Clinico-pathological Staging System) stage C CRC cases that underwent curative resection over a 23-year period. Pathology was reevaluated, DNA was extracted from the formalin-fixed paraffin specimen, and MSI status was established by BAT26 instability. Multivariate analysis was performed using Cox proportional hazard model and effects modification interaction testing. In total 814 unselected cases were included, of whom 37% received chemotherapy. Seventy-seven cases exhibited MSI. Overall, adjuvant chemotherapy produced a cancer-specific survival benefit (HR 0.52, 95% CI 0.39-0.70; P benefit. Chemotherapy was beneficial in both the MSI (HR 0.08, 95% CI 0.02-0.27; P = benefit from 5FU adjuvant chemotherapy for stage C CRC does not vary according to gender, site of tumor, pathological characteristics or MSI status. This study suggests that it would be unwise to exclude patients from being offered adjuvant chemotherapy on the basis of MSI. © 2015 The Authors. Asia-Pacific Journal of Clinical Oncology Published by Wiley Publishing Asia Pty Ltd.

  11. Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I-II trial

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnt, T.; Pigorsch, S.; Pelz, T.; Haensgen, G.; Dunst, J. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Becker, A. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Dept. of Radiotherapy, Municipial Hospital, Dessau (Germany); Bloching, M.; Passmann, M. [Dept. of Head and Neck Surgery, Martin Luther Univ., Halle (Germany); Lotterer, E. [Dept. of Internal Medicine I, Martin Luther Univ., Halle (Germany)

    2003-10-01

    We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m{sup 2} on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m{sup 2} twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 {+-} 61 cm{sup 3}. The mean follow-up was 30 months (range 4-39 months). Results: One early death (peritonitis and sepsis a t day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m{sup 2} paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m{sup 2} twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30

  12. Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I-II trial

    International Nuclear Information System (INIS)

    Kuhnt, T.; Pigorsch, S.; Pelz, T.; Haensgen, G.; Dunst, J.; Becker, A.; Bloching, M.; Passmann, M.; Lotterer, E.

    2003-01-01

    We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m 2 on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m 2 twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 ± 61 cm 3 . The mean follow-up was 30 months (range 4-39 months). Results: One early death (peritonitis and sepsis a t day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m 2 paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m 2 twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30 of neutropenic infection

  13. Early stage cervical cancer of the uterine

    International Nuclear Information System (INIS)

    Kaneyasu, Yuuko; Fujiwara, Hisaya

    2011-01-01

    This paper describes the present state of radiotherapy (RT) of early stage cervical cancer involving the history, outcomes of clinical trials, procedure for each stage, irradiation methods, concurrent chemo-RT (CCRT), late adverse events, and QOL after RT. It has a history of >100 years from the brachytherapy with radium, but is not yet completely established even now. There are many RT trials hitherto. Retrospectively, no significant difference is seen in outcomes of radical RT and surgery: 80-90% efficacy for stage I and 60-80% for II in the former, respectively, and 80-96% and 65-80%, in the latter. Between RT and surgery, there is a report of randomized comparative study in Italy. In Japan, reported are comparative outcomes based on patients' choice for therapy, retrospective studies including authors' one, prospective multi-institutional cooperative trials by Japanese Radiation Oncology Study Group, and Treatment Guidelines for Cervical Cancer (2007). RT procedure depends on the stage defined by FIGO (International Federation of Gynecology and Obstetrics) and at stages I-II, intracavitary RT is major with optimal dose 29 Gy/5 fractions for I, and 23/4 Gy with external total pelvic radiation 50 Gy for II. In external radiation, the planning target volume includes the whole pelvic field with 1.8-2 Gy/5 weeks and optionally, the extended field when metastasis suspicious. Intracavitary RT with application device in the uterine is of significance for the cancer as 50% complete cure even in stage III is reported. CCRT brings about good prognosis, which is shown in a Japanese trial to compare postoperative RT alone and CCRT with CDDP and 5-FU. The late adverse events are seen mainly in the large bowel and studies of QOL, an important factor for choice of treatment, are now in progress. (T.T.)

  14. CRC handbook of radiobiology

    International Nuclear Information System (INIS)

    Prasad, K.N.

    1984-01-01

    The author presents Development of Radiobiology. A Review. Basic Cell Biology. Physics of Radiation Biology. Cellular Radiation Damage. Modifications of Cellular Radiation Damage. Repair of Radiation Damage. Molecular Radiation Biology. Radiation Syndromes and their Modifications. Radiation Damage of Skin and Mucous Membrane. Radiation Damage of Nervous Tissue. Radiation Damage of Reproductive Organs. Radiation Damage of Other Organ Systems. Radiation Immunology. Background, Medical and Commercial Sources. Radiation Injuries to Human Fetuses. Radiation-Induced Genetic Damage. Radiation Carcinogenesis: Tissue Culture Model. Radiation Carcinogenesis: Animal Model. Radiation Carcinogenesis: Human Model. Radiation Carcinogenesis: Secondary Neoplasms. After Therapy of Tumors. Other Late Effects: Aging, Cataract, Aplastic Anemia. Maximum Permissible Dose (MPD). Radiation Response of Human Tumor. Radioisotopes in Biology and Medicine

  15. Destan Geleneğinden Tarihi Romana: Tölögön Kasımbek ve Kırılan Kılıç I,II From Legend Tradition to Historical Novels: Tölögön Kasımbek and Broken Sword I,II

    Directory of Open Access Journals (Sweden)

    Canan OLPAK KOÇ

    2012-09-01

    Full Text Available Being a social entity, humanity has been searching the ways of transferring their feelings, thoughts, imaginations and impressions to next generations all the time. Before written expressions became widespread, they used to try to accomplish this aim with the help of verbal folk literature. In this sense, epic had become the most significant tool to transfer experiences not only for individuals but also for communities. After written expressions became widespread, epic gave its place to written literature genres like novel and story. However, those narrative genres have been written by individual authors and they have reflected cultures which they had grown in to their works. Kyrgyz have a considerably old past. Interaction between Turkish Literature and Kyrgyz Literature had developed pretty limited because of several reasons. Especially in period when there was no relation with Kyrgyzstan, there had been very few publications about the Kyrgyz Literature. With increasing relations after the year of 1990, Kyrgyz Literature began known. Bringing Kırılan Kılıç I (Broken Sword I and Kırılan Kılıç II (Broken Sword II novels, which are belong to Tölögön Kasımbek, in to Turkish Literature is the product of increasing interest in this period. It is important that how the man understand the story of existance and how he/she tell the existence of the public. Tölögön Kasımbek, in his novels Kırılan Kılıç I ,II (Broken Sword I,II has told the adventure of kyrgyz people and how they’d been destroyed by being defeated by the Russians. The book can be accepted as a legendary historical novel within this aspects. We, in this study, will see how close are the epic motifs of the Tölögön who wrote the history of Kyrgyz, to the reali ty which the historical novels never leaves. Toplumsal bir varlık olarak insan duygularını, düşüncelerini, hayallerini, izlenimlerini her zaman bir sonraki nesle aktarmanın yolunu aramıştır. Yazılı kültür yaygınlaşmadan önce bunu sözlü halk edebiyatı türleri ile yapmaya çalışmıştır. Bu anlamda destanlar sadece bireyin değil milletlerin deneyimlerini aktarmada en önemli araç olmuştur. Yazılı kültürün yaygınlaşması ile birlikte destanların yerini roman, hikâye gibi edebi türler almıştır. Ancak bu anlatı türleri tek bir kişi tarafından yazılmıştır. Fakat yazar içinde yetiştiği toplumun kültürünü yazdığı esere aktarmaktadır. Kırgızların oldukça eskiye dayanan bir geçmişleri vardır. Türk yazınının Kırgız Edebiyatıyla ilişkisi, çeşitli etmenlere dayalı olarak oldukça sınırlı gelişmiştir. Özellikle Kırgızistan ile ilişkilerin olmadığı dönemde Kırgız edebiyatıyla ilgili neşriyat da çok az olmuştur. 1990 yılı sonrasında artan ilişkilerle beraber Kırgız edebiyatı tanınmaya başlar. Tölögön Kasımbek’e ait Kırılan Kılıç I- Kırılan Kılıç II romanlarının Türkiye Türkçesine kazandırılması da bu dönemde artan ilginin bir ürünüdür. İnsanın var oluş öyküsünü nasıl anladığı ve toplumun varlığını nasıl anlattığı önemlidir. Bu çerçeve de Tölögön Kasımbek, destansı özellikler çerçevesinde ve tarihi roman bağlamında değerlendirilecek olan Kırılan Kılıç I ve II romanında Kırgız halkının var oluş serüvenini ve Ruslar karşısında nasıl yenilgiye uğrayıp yıkıldığını anlatmıştır. Tarihi roman henüz kesin olarak tanımı yapılamasa da tarihsel bir bilginin edebi duyarlılıklar eşliğinde romana dönüştürülmesidir diyebiliriz. Biz bu çalışmamızda Kırgızlarının tarihini yazıya döken Tölögön’ün destana ait motifleri tarihi romanın elden bırakmadığı gerçekliğe ne kadar yaklaştırdığını göreceğiz.

  16. The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Min, Byung-Hoon; Kim, Kyoung-Mee; Kang, Gyeong Hoon; Bae, Jeong Mo; Lee, Eui Jin; Yu, Hong Suk; Kim, Young-Ho; Chang, Dong Kyung; Kim, Hee Cheol; Park, Cheol Keun; Lee, Suk-Hee

    2011-01-01

    Colorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear. A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status. CIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022). Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results

  17. The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Park Cheol

    2011-08-01

    Full Text Available Abstract Background Colorectal carcinoma (CRC with CpG island methylator phenotype (CIMP is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear. Methods A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status. Results CIMP-high CRCs were identified in 34 cases (13.9%, and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100% showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4% (P = 0.022. Conclusions Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results.

  18. The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

    Science.gov (United States)

    2011-01-01

    Background Colorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear. Methods A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status. Results CIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022). Conclusions Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results. PMID:21827707

  19. Mechanisms of topoisomerase I (TOP1) gene copy number increase in a stage III colorectal cancer patient cohort

    DEFF Research Database (Denmark)

    Smith, David Hersi; Christensen, Ib Jarle; Jensen, Niels Frank

    2013-01-01

    Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III C...

  20. Predictive value of pretreatment lymphocyte count in stage II colorectal cancer and in high-risk patients treated with adjuvant chemotherapy.

    Science.gov (United States)

    Liang, Lei; Zhu, Ji; Jia, Huixun; Huang, Liyong; Li, Dawei; Li, Qingguo; Li, Xinxiang

    2016-01-05

    Pretreatment lymphocyte count (LC) has been associated with prognosis and chemotherapy response in several cancers. The predictive value of LC for stage II colorectal cancer (CRC) and for high-risk patients treated with adjuvant chemotherapy (AC) has not been determined. A retrospective review of prospectively collected data from 1332 consecutive stage II CRC patients who underwent curative tumor resection was conducted. A pretreatment LC value risk, 459 (62.2%) of whom received AC. Patients with low LCs had significantly worse 5-year OS (74.6% vs. 90.2%, p risk patients with low LCs had the poorest DFS (p value or combined with high-risk status were both independent prognostic factors(p risk, AC-treated patients with high LCs had significantly longer DFS than untreated patients (HR, 0.594; 95% CI, 0.364-0.970; p = 0.035). There was no difference or trend for DFS or OS in patients with low LCs, regardless of the use of AC (DFS, p = 0.692; OS, p = 0.522). Low LC was also independently associated with poorer DFS in high-risk, AC-treated patients (HR, 1.885; 95% CI, 1.112-3.196; p = 0.019). Pretreatment LC is an independent prognostic factor for survival in stage II CRC. Furthermore, pretreatment LC reliably predicts chemotherapeutic efficacy in high-risk patients with stage II CRC.

  1. Predicting Outcome and Therapy Response in mCRC Patients Using an Indirect Method for CTCs Detection by a Multigene Expression Panel: A Multicentric Prospective Validation Study

    Directory of Open Access Journals (Sweden)

    Yolanda Vidal Insua

    2017-06-01

    Full Text Available Colorectal cancer (CRC is one of the major causes of cancer-related deaths. Early detection of tumor relapse is crucial for determining the most appropriate therapeutic management. In clinical practice, computed tomography (CT is routinely used, but small tumor changes are difficult to visualize, and reliable blood-based prognostic and monitoring biomarkers are urgently needed. The aim of this study was to prospectively validate a gene expression panel (composed of GAPDH, VIL1, CLU, TIMP1, TLN1, LOXL3 and ZEB2 for detecting circulating tumor cells (CTCs as prognostic and predictive tool in blood samples from 94 metastatic CRC (mCRC patients. Patients with higher gene panel expression before treatment had a reduced progression-free survival (PFS and overall-survival (OS rates compared with patients with low expression (p = 0.003 and p ≤ 0.001, respectively. Patients with increased expression of CTCs markers during treatment presented PFS and OS times of 8.95 and 11.74 months, respectively, compared with 14.41 and 24.7 for patients presenting decreased expression (PFS; p = 0.020; OS; p ≤ 0.001. Patients classified as non-responders by CTCs with treatment, but classified as responders by CT scan, showed significantly shorter survival times (PFS: 8.53 vs. 11.70; OS: 10.37 vs. 24.13; months. In conclusion, our CTCs detection panel demonstrated efficacy for early treatment response assessment in mCRC patients, and with increased reliability compared to CT scan.

  2. The catabolite repression control protein Crc plays a role in the development of antimicrobial-tolerant subpopulations in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Zhang, Lianbo; Chiang, Wen-Chi; Gao, Qingguo

    2012-01-01

    Bacteria form complex surface-attached biofilm communities in nature. Biofilm cells differentiate into subpopulations which display tolerance towards antimicrobial agents. However, the signal transduction pathways regulating subpopulation differentiation in biofilms are largely unelucidated. In t....... In the present study, we show that the catabolite repression control protein Crc regulates the metabolic state of Pseudomonas aeruginosa cells in biofilms, and plays an important role in the development of antimicrobial-tolerant subpopulations in P. aeruginosa biofilms....

  3. Effect of CRC::etr1-1 transgene expression on ethylene production, sex expression, fruit set and fruit ripening in transgenic melon (Cucumis melo L.).

    Science.gov (United States)

    Switzenberg, Jessica A; Beaudry, Randy M; Grumet, Rebecca

    2015-06-01

    Ethylene is a key factor regulating sex expression in cucurbits. Commercial melons (Cucumis melo L.) are typically andromonoecious, producing male and bisexual flowers. Our prior greenhouse studies of transgenic melon plants expressing the dominant negative ethylene perception mutant gene, etr1-1, under control of the carpel- and nectary-primordia targeted CRAB'S CLAW (CRC) promoter showed increased number and earlier appearance of carpel-bearing flowers. To further investigate this phenomenon which could be potentially useful for earlier fruit production, we observed CRC::etr1-1 plants in the field for sex expression, fruit set, fruit development, and ripening. CRC::etr1-1 melon plants showed increased number of carpel-bearing open flowers on the main stem and earlier onset by 7-10 nodes. Additional phenotypes observed in the greenhouse and field were conversion of approximately 50% of bisexual buds to female, and elongated ovaries and fruits. Earlier and greater fruit set occurred on the transgenic plants. However, CRC::etr1-1 plants had greater abscission of young fruit, and smaller fruit, so that final yield (kg/plot) was equivalent to wild type. Earlier fruit set in line M5 was accompanied by earlier appearance of ripe fruit. Fruit from line M15 frequently did not exhibit external ripening processes of rind color change and abscission, but when cut open, the majority showed a ripe or overripe interior accompanied by elevated internal ethylene. The non-ripening external phenotype in M15 fruit corresponded with elevated etr1-1 transgene expression in the exocarp. These results provide insight into the role of ethylene perception in carpel-bearing flower production, fruit set, and ripening.

  4. Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer.

    Science.gov (United States)

    Mohan, H M; Ryan, E; Balasubramanian, I; Kennelly, R; Geraghty, R; Sclafani, F; Fennelly, D; McDermott, R; Ryan, E J; O'Donoghue, D; Hyland, J M P; Martin, S T; O'Connell, P R; Gibbons, D; Winter, Des; Sheahan, K

    2016-11-01

    Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes. Copyright © 2016. Published by Elsevier Ltd.

  5. Colorectal cancer staging: comparison of whole-body PET/CT and PET/MR.

    Science.gov (United States)

    Catalano, Onofrio A; Coutinho, Artur M; Sahani, Dushyant V; Vangel, Mark G; Gee, Michael S; Hahn, Peter F; Witzel, Thomas; Soricelli, Andrea; Salvatore, Marco; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce R; Gervais, Debra

    2017-04-01

    Correct staging is imperative for colorectal cancer (CRC) since it influences both prognosis and management. Several imaging methods are used for this purpose, with variable performance. Positron emission tomography-magnetic resonance (PET/MR) is an innovative imaging technique recently employed for clinical application. The present study was undertaken to compare the staging accuracy of whole-body positron emission tomography-computed tomography (PET/CT) with whole-body PET/MR in patients with both newly diagnosed and treated colorectal cancer. Twenty-six patients, who underwent same day whole-body (WB) PET/CT and WB-PET/MR, were evaluated. PET/CT and PET/MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Correct staging was compared between methods using McNemar's Chi square test. The two methods were in agreement and correct for 18/26 (69%) patients, and in agreement and incorrect for one patient (3.8%). PET/MR and PET/CT stages for the remaining 7/26 patients (27%) were discordant, with PET/MR staging being correct in all seven cases. PET/MR significantly outperformed PET/CT overall for accurate staging (P = 0.02). PET/MR outperformed PET/CT in CRC staging. PET/MR might allow accurate local and distant staging of CRC patients during both at the time of diagnosis and during follow-up.

  6. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

    International Nuclear Information System (INIS)

    Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

    2015-01-01

    Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with administration of multiples of the human dose in healthy Balb/c mice but no histopathological abnormalities were noted in any tissues. There were no significant differences in body mass between mice injected with 111 In-BzDTPA-pertuzumab or control mice. Conclusion: Preclinical studies predicted that 111 In-BzDTPA-pertuzumab is safe to administer to humans at a dose of 111 MBq (5 mg). The radiopharmaceutical exhibited preclinical pharmacokinetic, biodistribution and radiation dosimetry properties suitable for advancement to a first-in-humans clinical trial. Advances in knowledge and implications for patient care: The results of these studies supported the regulatory approval by Health Canada of 111 In-BzDTPA-pertuzumab for a Phase I/II clinical trial of for imaging the response of patients with metastatic BC to treatment with trastuzumab combined with chemotherapy (PETRA trial; ClinicalTrials.gov identifier: NCT01805908)

  7. Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG Study

    Directory of Open Access Journals (Sweden)

    Arie Figer, Aviram Nissan, Adi Shani, Riva Borovick, Mariana Stiener, Mario Baras, Herbert R. Freund, Aaron Sulkes, Alexander Stojadinovic, Tamar Peretz

    2011-01-01

    Full Text Available Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC. This study evaluates long-term (10-year outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV or 5-FU/Levamisole (5FU+LEV.Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months.Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02 and gastrointestinal toxicity with 5FU+LV (p=0.03. Female patients treated with 5FU+LEV had improved overall survival.Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

  8. Multiple Hfq-Crc target sites are required to impose catabolite repression on (methyl)phenol metabolism in Pseudomonas putida CF600.

    Science.gov (United States)

    Wirebrand, Lisa; Madhushani, Anjana W K; Irie, Yasuhiko; Shingler, Victoria

    2018-01-01

    The dmp-system encoded on the IncP-2 pVI150 plasmid of Pseudomonas putida CF600 confers the ability to assimilate (methyl)phenols. Regulation of the dmp-genes is subject to sophisticated control, which includes global regulatory input to subvert expression of the pathway in the presence of preferred carbon sources. Previously we have shown that in P. putida, translational inhibition exerted by the carbon repression control protein Crc operates hand-in-hand with the RNA chaperon protein Hfq to reduce translation of the DmpR regulator of the Dmp-pathway. Here, we show that Crc and Hfq co-target four additional sites to form riboprotein complexes within the proximity of the translational initiation sites of genes encoding the first two steps of the Dmp-pathway to mediate two-layered control in the face of selection of preferred substrates. Furthermore, we present evidence that Crc plays a hitherto unsuspected role in maintaining the pVI150 plasmid within a bacterial population, which has implications for (methyl)phenol degradation and a wide variety of other physiological processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  9. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer

    International Nuclear Information System (INIS)

    Cheruvu, Praveena; Metcalfe, Su K; Metcalfe, Justin; Chen, Yuhchyau; Okunieff, Paul; Milano, Michael T

    2011-01-01

    Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC. We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions. Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%). Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed

  10. IIIST1\\NTI-i\\III.

    African Journals Online (AJOL)

    guests in September 1914. (1) Major-General Sir Lothian Nicholson. KCB, CMG, and Major H 1. MacMullen, MC, History of the East Lancashire Regiment in the Great. War 1914-1918, Littlebury. Bros, Ltd. Liverpool,. 1936. p 114. Ti\\.~TI(~S-1\\ IIIST ••III. ~SI Til VI~V. I..•f :01 i\\. f~•• 10III.SOIl ~IIII~ 1~lt. The study of military tactics ...

  11. Reactor oscillator - I - III, Part I

    International Nuclear Information System (INIS)

    Lolic, B.

    1961-12-01

    Project 'Reactor oscillator' covers the following activities: designing reactor oscillators for reactors RA and RB with detailed engineering drawings; constructing and mounting of the oscillator; designing and constructing the appropriate electronic equipment for the oscillator; measurements at the RA and RB reactors needed for completing the oscillator construction

  12. IIIST1\\NTI-i\\III.

    African Journals Online (AJOL)

    The similarity of these reports to the UFO reports of our own times is striking. But it is suggested that this piece of the jigsaw puzzle does fit. It certainly would explain why itwas necessary to develop the anti-aircraft guns and to demon- strate one of them in public in the presence of such distinguished guests in September ...

  13. Revised Editor's Note pp.i-iii

    African Journals Online (AJOL)

    Jimmy Gitonga

    Second, the ethical implications of our individual and corporate decisions ... philosophy, and especially positivism which is closely associated with rational choice ... implications for framing social science research and development policy in.

  14. Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study.

    Science.gov (United States)

    Tsuruta, Atsushi; Yamashita, Kazuki; Tanioka, Hiroaki; Tsuji, Akihito; Inukai, Michio; Yamakawa, Toshiki; Yamatsuji, Tomoki; Yoshimitsu, Masanori; Toyota, Kazuhiro; Yamano, Taketoshi; Nagasaka, Takeshi; Okajima, Masazumi

    2016-01-01

    Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m 2 on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.

  15. A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT and intraoperative radiation therapy (IORT in patients with retroperitoneal soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Roeder Falk

    2012-07-01

    Full Text Available Abstract Background Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT are considered. Methods/design The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy followed by surgery and IORT (10–12 Gy in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. Discussion The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. Trial registration NCT01566123

  16. Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: Findings from a prospective, multi-institutional, phase I/II dose-escalation study

    International Nuclear Information System (INIS)

    Roach, Mack; Winter, Kathryn; Michalski, Jeffrey M.; Cox, James D.; Purdy, James A.; Bosch, Walter; Lin Xiao; Shipley, William S.

    2004-01-01

    Purpose: To assess the relationship between the dose to the bulb of the penis and the risk of impotence in men treated on Radiation Therapy Oncology Group (RTOG) 9406. Methods and materials: Men enrolled on a Phase I/II dose-escalation study, RTOG 9406, who were reported to be potent at entry and evaluable (n = 158) were selected for inclusion. Follow-up evaluations were scheduled every 3, 4, and 6 months for the first, second, and the third through fifth years, then annually. At each follow-up visit an assessment of potency status was made. Penile structures were defined by a single observer blinded to the potency status, using Web-based, on-line software. The dosimetry for penile structures was calculated at the Quality Assurance Center at Washington University and provided to RTOG Statistical Headquarters to determine whether there was a relationship between dose and impotence. Results: Patients whose median penile dose was ≥52.5 Gy had a greater risk of impotence compared with those receiving <52.5 Gy (p = 0.039). In a multivariate analysis neither age, the dose to the prostate, nor the use of hormonal therapy correlated with the risk of impotence. Conclusions: Dose to the bulb of the penis seems to be associated with the risk of radiation-induced impotence

  17. Clinical phase I/II trial to investigate neoadjuvant intensity-modulated short term radiation therapy (5 × 5 gy) and intraoperative radiation therapy (15 gy) in patients with primarily resectable pancreatic cancer - NEOPANC

    International Nuclear Information System (INIS)

    Roeder, Falk; Debus, Juergen; Huber, Peter E; Werner, Jens; Timke, Carmen; Saleh-Ebrahimi, Ladan; Schneider, Lutz; Hackert, Thilo; Hartwig, Werner; Kopp-Schneider, Annette; Hensley, Frank W; Buechler, Markus W

    2012-01-01

    The current standard treatment, at least in Europe, for patients with primarily resectable tumors, consists of surgery followed by adjuvant chemotherapy. But even in this prognostic favourable group, long term survival is disappointing because of high local and distant failure rates. Postoperative chemoradiation has shown improved local control and overalls survival compared to surgery alone but the value of additional radiation has been questioned in case of adjuvant chemotherapy. However, there remains a strong rationale for the addition of radiation therapy considering the high rates of microscopically incomplete resections after surgery. As postoperative administration of radiation therapy has some general disadvantages, neoadjuvant and intraoperative approaches theoretically offer benefits in terms of dose escalation, reduction of toxicity and patients comfort especially if hypofractionated regimens with highly conformal techniques like intensity-modulated radiation therapy are considered. The NEOPANC trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant short course intensity-modulated radiation therapy (5 × 5 Gy) in combination with surgery and intraoperative radiation therapy (15 Gy), followed by adjuvant chemotherapy according to the german treatment guidelines, in patients with primarily resectable pancreatic cancer. The aim of accrual is 46 patients. The primary objectives of the NEOPANC trial are to evaluate the general feasibility of this approach and the local recurrence rate after one year. Secondary endpoints are progression-free survival, overall survival, acute and late toxicity, postoperative morbidity and mortality and quality of life. http://www.clinicaltrials.gov/ct2/show/NCT01372735

  18. A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma

    International Nuclear Information System (INIS)

    Roeder, Falk; Hensley, Frank W; Buechler, Markus W; Debus, Juergen; Koch, Moritz; Weitz, Juergen; Bischof, Marc; Schulz-Ertner, Daniela; Nikoghosyan, Anna V; Huber, Peter E; Edler, Lutz; Habl, Gregor; Krempien, Robert; Oertel, Susanne; Saleh-Ebrahimi, Ladan

    2012-01-01

    Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT) are considered. The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy) followed by surgery and IORT (10–12 Gy) in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. NCT01566123

  19. MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy

    International Nuclear Information System (INIS)

    Bos, Willemien van den; Bruin, D.M. de; Randen, A. van; Engelbrecht, M.R.W.; Postema, A.W.; Muller, B.G.; Zondervan, P.J.; Laguna Pes, M.P.; Reijke, T.M. de; Rosette, J.J.M.C.H. de la; Varkarakis, I.M.; Skolarikos, A.; Savci-Heijink, C.D.; Jurhill, R.R.; Wijkstra, H.

    2016-01-01

    Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H and E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. (orig.)

  20. Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer.

    Science.gov (United States)

    Fucikova, Jitka; Podrazil, Michal; Jarolim, Ladislav; Bilkova, Pavla; Hensler, Michal; Becht, Etienne; Gasova, Zdenka; Klouckova, Jana; Kayserova, Jana; Horvath, Rudolf; Fialova, Anna; Vavrova, Katerina; Sochorova, Klara; Rozkova, Daniela; Spisek, Radek; Bartunkova, Jirina

    2018-01-01

    Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population. The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively. No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment. Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

  1. A randomized Phase I/II Trial of HQK-1001, an oral fetal globin gene inducer, in β–thalassaemia intermedia and HbE/β–thalassaemia

    Science.gov (United States)

    Fucharoen, Suthat; Inati, Adlette; Siritanaratku, Noppadol; Thein, Swee Lay; Wargin, William C.; Koussa, Suzanne; Taher, Ali; Chaneim, Nattawara; Boosalis, Michael; Berenson, Ronald; Perrine, Susan P.

    2014-01-01

    β–thalassemia intermedia syndromes (BTI) cause hemolytic anemia, ineffective erythropoiesis, and widespread complications. Higher fetal globin expression within genotypes reduces globin imbalance and ameliorates anemia. Sodium 2,2 dimethylbutyrate (HQK-1001), an orally bioavailable short-chain fatty acid derivative, induces γ-globin expression experimentally and is well-tolerated in normal subjects. Accordingly, a randomized, blinded, placebo-controlled, Phase I/II trial was performed in 21 adult BTI patients (14 with HbE/β0 thalassemia and 7 with β+/β0 thalassemia intermedia, to determine effective doses for fetal globin induction, safety, and tolerability. HQK-1001 or placebo were administered once daily for 8 weeks at four dose levels (10, 20, 30, or 40 mg/kg/day), and subjects were monitored for laboratory and clinical events. Pharmacokinetic profiles demonstrated a t1/2 of 10–12 hours. Adverse events with HQK-1001 treatment were not significantly different from placebo treatment. Median HbF increased with the 20 mg/kg treatment doses above baseline levels by 6.6% and 0.44 g/dL (p <0.01) in 8/9 subjects; total hemoglobin (Hgb) increased by a mean of 1.1 gm/dL in 4/9 subjects. These findings identify a safe oral therapeutic which induces fetal globin in BTI. Further investigation of HQK-1001 with longer dosing to definitively evaluate its hematologic potential appears warranted. PMID:23530969

  2. Expression Analysis of Previously Verified Fecal and Plasma Dow-regulated MicroRNAs (miR-4478, 1295-3p, 142-3p and 26a-5p), in FFPE Tissue Samples of CRC Patients.

    Science.gov (United States)

    Ghanbari, Reza; Rezasoltani, Sama; Hashemi, Javad; Mohamadkhani, Ashraf; Tahmasebifar, Arash; Arefian, Ehsan; Mobarra, Naser; Asadi, Jahanbakhsh; Nazemalhosseini Mojarad, Ehsan; Yazdani, Yaghoub; Knuutila, Sakari; Malekzadeh, Reza

    2017-02-01

    Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality worldwide. Early diagnosis of this neoplasm is critical and may reduce patients' mortality. MicroRNAs are small non-coding RNA molecules whose expression pattern can be altered in various diseases such as CRC. In this study, we evaluated the expression levels of miR-142-3p, miR-26a-5p (their reduced expression in plasma samples of CRC patients was previously confirmed), miR-4478 and miR-1295-3p (their reduced expression in stool samples of CRC patients was previously confirmed) in tissue samples of CRC patients in comparison to healthy subjects. To achieve this purpose, total RNA including small RNA was extracted from 53 CRC and 35 normal subjects' Formalin-fixed, Paraffin-embedded (FFPE) tissue samples using the miRNeasy FFPE Mini Kit. The expression levels of these four selected miRNAs were measured using quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). We found that the expression levels of miR-4478 and miR-1295b-3p (two previously down-regulated fecal miRNAs) were significantly decreased in FFPE samples of CRC patients compared to healthy controls. On the other hand, no significant differences were seen in expression levels of miR-142-3p and miR-26a-5p (two previously down-regulated circulating miRNAs) in FFPE samples between these two groups. Regarding current findings, it may be concluded that to diagnose CRC patients based on the miRNAs approach, stool samples are more likely preferable to plasma samples; nevertheless, additional studies with more samples are needed to confirm the results.

  3. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand up 2 cancer study.

    Science.gov (United States)

    Azad, Nilofer S; El-Khoueiry, Anthony; Yin, Jun; Oberg, Ann L; Flynn, Patrick; Adkins, Douglas; Sharma, Anup; Weisenberger, Daniel J; Brown, Thomas; Medvari, Prakriti; Jones, Peter A; Easwaran, Hariharan; Kamel, Ihab; Bahary, Nathan; Kim, George; Picus, Joel; Pitot, Henry C; Erlichman, Charles; Donehower, Ross; Shen, Hui; Laird, Peter W; Piekarz, Richard; Baylin, Stephen; Ahuja, Nita

    2017-05-23

    Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy. Forty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median. In this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS.

  4. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand Up 2 cancer study

    Science.gov (United States)

    Azad, Nilofer S.; el-Khoueiry, Anthony; Yin, Jun; Oberg, Ann L.; Flynn, Patrick; Adkins, Douglas; Sharma, Anup; Weisenberger, Daniel J.; Brown, Thomas; Medvari, Prakriti; Jones, Peter A.; Easwaran, Hariharan; Kamel, Ihab; Bahary, Nathan; Kim, George; Picus, Joel; Pitot, Henry C.; Erlichman, Charles; Donehower, Ross; Shen, Hui; Laird, Peter W.; Piekarz, Richard; Baylin, Stephen; Ahuja, Nita

    2017-01-01

    Purpose Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. Experimental Design We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy. Results Forty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median. Conclusion In this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS. PMID:28186961

  5. BRAFV600E mutation analysis in patients with metastatic colorectal cancer (mCRC in daily clinical practice: correlations with clinical characteristics, and its impact on patients' outcome.

    Directory of Open Access Journals (Sweden)

    Zacharenia Saridaki

    Full Text Available To prospectively evaluate the usefulness of the BRAFV600E mutation detection in daily clinical practice in patients with metastatic Colorectal Cancer (mCRC.504 mCRC patients treated with systemic chemotherapy ± biologics were analyzed.A statistically significant higher incidence of the BRAF mutation was observed in patients with ECOG-PS 2 (p=0.001, multiple metastatic sites (p=0.002,> 65 years old (p=0.004, primary tumors located in the colon (p<0.001, high-grade tumors (p=0.001 and in those with mucinous features (p=0.037. Patients with BRAFV600E mutated tumors had a statistically significantly reduced progression-free survival (PFS compared to wild-type (wt ones (4.1 and 11.6 months, respectively; p<0.001 and overall survival (OS (14.0 vs. 34.6 months, respectively; p<0.001. In the multivariate analysis the BRAFV600E mutation emerged as an independent factor associated with reduced PFS (HR: 4.1, 95% CI 2.7-6.2; p<0.001 and OS (HR: 5.9, 95% CI 3.7-9.5; p<0.001. Among the 273 patients treated with salvage cetuximab or panitumumab, the BRAFV600E mutation was correlated with reduced PFS (2.2 vs. 6.0 months; p<0.0001 and OS (4.3 vs. 17.4 months; p<0.0001.The presence of BRAFV600E-mutation in mCRC characterizes a subgroup of patients with distinct biologic, clinical and pathological features and is associated with very poor patients' prognosis.