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1
Begović, Vitomir. "Sigurnost na izdvojenom mjestu rada." Sigurnost 62, no. 4 (December 28, 2020): 391–401. http://dx.doi.org/10.31306/s.62.4.6.
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Tehnološki i komunikacijski napredak mijenja način života i rada, pa sve više prostora i na razini Europe dobiva mogućnost rada izvan sjedišta poslodavca. Kao primjere rada na izdvojenom mjestu rada mogu se navesti: rad kod kuće (primjerice različiti administrativni poslovi, pisanje i uređivanje tekstova, lektoriranje, i dr.) i rad na izdvojenom radnom mjestu/na putu (primjerice rad trgovačkih putnika, servisera, prodajnih predstavnika kompanija i dr.). U sklopu mjera fizičkog distanciranja koje su uvedene u većini država članica zbog sprečavanja širenja pandemije COVID-19, radnike se potiče ili obvezuje da rade od kuće ako im to dopušta priroda njihova posla. Većina tih radnika prvi put radi na daljinu i njihovo radno okruženje vjerojatno ima mnogo nedostataka u odnosu na njihovo radno mjesto. Sadašnje, a posebno buduće okolnosti upućuju na potrebu usklađivanja odredbi Zakona o radu, kao i propisa iz područja zaštite na radu. Pored navedenog, takav oblik rada trebao bi se precizno ugovoriti kolektivnim ugovorima, internim aktima, odnosno ugovorom između poslodavca i pojedinog radnika, i to prije početka rada, a ovisno o nastalim okolnostima može se sastaviti i aneks ugovora o radu tijekom radnog odnosa.
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Hopkins, S., S. Gertler, and G. Nicholas. "An analysis of adjuvant temozolomide plus radiotherapy vs radiotherapy alone in a single academic institution." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 1575. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.1575.
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1575 Background: The NCIC CE.3/EORTC 22981/26981 was open during the time period of August 2000 to March 2002. When the study closed, there existed a gap in care that did not address the ongoing management of patients (pts) with glioblastoma multiforme (GBM) that had been surgically excised. As a result of this gap, it was decided that the adjuvant use of temozolomide (TMZ) was to become the standard of care at our centre due to its lack of perceived toxicities and early evidence for its activity. Methods: An analysis was performed of all pts with GBM that were seen at the centre from 1998 to the summer of 2005. In total, 240 pts were identified across multiple medical and radiation oncologists. 75 pts were treated with radiotherapy (RAD) alone post surgery, 86 pts were treated with RAD + TMZ post surgery, 18 pts only had surgery and the remaining pts were unresectable. Average age was 59.7 years for pts treated only with RAD, and 54.6 years for those treated with TMZ + RAD (p = 0.028). 59% of pts treated with RAD were male, while 62% treated with RAD + TMZ were male. Median follow-up was 11.3 months for RAD and 15.7 months for TMZ + RAD (p = 0.0001816). Preliminary survival analysis demonstrates a 56% reduction in the risk of death for pts treated with TMZ + RAD when compared to RAD (log rank p = 9.6 × 10−6). Median survival was 12.7 months for pts treated with RAD and 27 months for pts treated with TMZ + RAD (see table ). A further analysis including recursive partitioning analysis (RPA) and duration of therapy post RAD will be attempted to confirm the similarities between the two groups. Conclusion: Adjuvant TMZ + RAD has increased overall survival by 14.3 months in our institution. Further analysis is necessary to determine the impact on duration of therapy of TMZ. [Table: see text] [Table: see text]
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Pan, Jian-ji, Shan-wen Zhang, Chuan-beng Chen, Shao-wen Xiao, Yan Sun, Chang-qin Liu, Xing Su, et al. "Effect of Recombinant Adenovirus-p53 Combined With Radiotherapy on Long-Term Prognosis of Advanced Nasopharyngeal Carcinoma." Journal of Clinical Oncology 27, no. 5 (February 10, 2009): 799–804. http://dx.doi.org/10.1200/jco.2008.18.9670.
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Purpose To centrally assess the safety, efficacy, and 6-year follow-up of recombinant adenovirus-p53 (rAd-p53) combined with radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC). Patients and Methods A randomized controlled clinical study on rAd-p53 combined with RT in 42 patients with NPC was compared with a control group of 40 patients with NPC treated with RT alone. In the group receiving rAd-p53 combined with RT, rAd-p53 was intratumorally injected once a week for 8 weeks. Concurrent RT (70 Gy in 35 fractions) was given to the nasopharyngeal tumor and neck lymph node. Patients and tumors were monitored for adverse events and responses. Results rAd-p53–specific p53 mRNA was detected in postinjection of rAd-p53 biopsies from 16 (94.1%) of 17 patients. Upregulation of p21/WAF1 and Bax and downregulation of vascular endothelial growth factor were observed in postinjection tumor biopsy. Complete response rate in the group receiving rAd-p53 combined with RT was observed at 2.73 times that of the group receiving RT alone (66.7% v 24.4%). Six-year follow-up data showed that rAd-p53 significantly increased the 5-year locoregional tumor control rate by 25.3% for patients with NPC treated with irradiation (P = .002). The 5-year overall survival rate and 5-year disease-free survival rate of the group receiving rAd-p53 combined with RT were 7.5% (P = .34) and 11.7% (P = .21) higher than those of the group receiving RT alone. No dose-limiting toxicity or adverse events appeared, except for transient fever after rAd-p53 administration. Conclusion In patients with NPC, rAd-p53 was safe and biologically active. Our results indicated that rAd-p53 improves radiotherapeutic tumor control and survival rate in patients with NPC.
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Bukowski, Ronald M. "RAD-001: future directions." Medical Oncology 26, S1 (January 2009): 54–57. http://dx.doi.org/10.1007/s12032-008-9149-9.
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Maass, Nicolai, Nadia Harbeck, Christoph Mundhenke, Christian A. Lerchenmuller, Jana Barinoff, Hans-Joachim Lueck, Johannes Ettl, et al. "Everolimus (RAD) as treatment in breast cancer patients with bone metastases only: Results of the phase II RADAR study." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 556. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.556.
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556 Background: RAD001 is an orally bioavailable rapamycin ester analogue, which acts by selectively inhibiting mTOR (mammalian target of rapamycin), a key player in downstream signaling of different pathways. In vitro, RAD stops formation and activity of osteoclasts. Treating progressive bone metastases in breast cancer (bc) with RAD seems reasonable. Methods: We evaluated RAD in a placebo-controlled, phase II, randomized discontinuation study in bc patients (pts) with bone metastases only. Pts were eligible if they had HER2-negative, hormone-receptor (HR)-positive or –negative bc, with a maximum of 2 previous lines of endocrine therapy (ET) and 1 previous line of chemotherapy (CT). All pts received zoledronate and pts with HR-positive bc could receive ET. All pts started with RAD during a run-in phase of 8 weeks. Pts with stable disease were randomized to RAD or placebo; pts with response continued with RAD and pts with progression went off study. Primary outcome was time to progression (TTP) in pts being stable on 8 weeks of RAD. It was assumed that placebo would obtain a median TTP of 8 weeks which would be increased to 16 weeks, thus requiring 76 randomized pts. It was expected that 70% of all pts would have stable disease after the run-in phase. Overall, 110 pts were needed. Due to slow recruitment and dysbalance between randomized and discontinued pts, recruitment stopped in 12/ 2010. Results: From 11/06 until 12/10, 89 pts were enrolled. Median age was 59.5 years. 93% had HR-positive disease. 15% had prior chemotherapy; 58% had prior ET for metastases. 1/3 received concomitant ET. Three pts did not start therapy, 41 discontinued during run-in phase, 32 due to progression. Six continued as responder. 39 pts with SD after run in phase were randomized to RAD or placebo. Twenty-seven stopped due to progression; 9 discontinued due to AE, 4 are still on treatment. 15 pts had 20 serious adverse events; 1 hyperglycemia and one alveolitis. The TTP in patients with RAD was 8.5 months vs. 2.9 months with placebo (HR: 0.559; 95% CI [0.284-1.10] p=0.092. Conclusions: Pts with bone metastases only had a longer TTP on RAD compared to pts on placebo. Overall 7/89 showed a sustained response on RAD + zoledronate ± ET.
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Dondossola, Eleonora, Stefano Casarin, Claudia Paindelli, Elena M. De-Juan-Pardo, Dietmar W. Hutmacher, Christopher J. Logothetis, and Peter Friedl. "Radium 223-Mediated Zonal Cytotoxicity of Prostate Cancer in Bone." JNCI: Journal of the National Cancer Institute 111, no. 10 (January 18, 2019): 1042–50. http://dx.doi.org/10.1093/jnci/djz007.
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Abstract Background Bone-targeting radiotherapy with Radium-223 (Rad-223), a radioisotope emitting genotoxic alpha-radiation with limited tissue penetrance (∼100 µm), prolongs the survival of patients with metastatic prostate cancer (PCa). Confoundingly, the clinical response to Rad-223 is often followed by detrimental relapse and progression, and whether Rad-223 causes tumor-cell directed cytotoxicity in vivo remains unclear. We hypothesized that limited radiation penetrance in situ defines outcome. Methods We tested Rad-223 overall response by PC3 and C4–2B human PCa cell lines in mouse bones (n = 5–18 tibiae per group). Rad-223 efficacy at subcellular resolution was determined by intravital microscopy analysis of dual-color fluorescent PC3 cells (n = 3–4 mice per group) in tissue-engineered bone constructs. In vivo data were fed into an in silico model to predict Rad-223 effectiveness in lesions of different sizes (1–27, 306 initial cells; n = 10–100 simulations) and the predictions validated in vivo by treating PCa tumors of varying sizes in bones (n = 10–14 tibiae per group). Statistical tests were performed by two-sided Student t test or by one-way ANOVA followed by Tukey’s post-hoc test. Results Rad-223 (385 kBq/kg) delayed the growth (means [SD]; comparison with control-treated mice) of PC3 (6.7 × 105[4.2 × 105] vs 2.8 × 106 [2.2 × 106], P = .01) and C4–2B tumors in bone (7.7 × 105 [4.0 × 105] vs 3.5 × 106 [1.3 × 106], P < .001). Cancer cell lethality in response to Rad-223 (385 kBq/kg) was profound but zonally confined along the bone interface compared with the more distant tumor core, which remained unperturbed (day 4; 13.1 [2.3%] apoptotic cells, 0–100 µm distance from bone vs 3.6 [0.2%], >300 µm distance; P = .01).In silico simulations predicted greater efficacy of Rad-223 on single-cell lesions (eradication rate: 88.0%) and minimal effects on larger tumors (no eradication, 16.2% growth reduction in tumors of 27 306 cells), as further confirmed in vivo for PC3 and C4–2B tumors. Conclusions Micro-tumors showed severe growth delay or eradication in response to Rad-223, whereas macro-tumors persisted and expanded. The relative inefficacy in controlling large tumors points to application of Rad-223 in secondary prevention of early bone-metastatic disease and regimens co-targeting the tumor core.
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Machtay, Mitchell. "The Early Rad Catches the Tumor?" Journal of Clinical Oncology 20, no. 14 (July 15, 2002): 3045–47. http://dx.doi.org/10.1200/jco.2002.20.14.3045.
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Kim, Hyo Jung, Eun-Kee Song, Jun Suk Kim, Jin Seok Ahn, Hwan Jung Yun, Yo Han Cho, Keon Uk Park, et al. "A prospective multicenter, single blinded, randomized phase III trial to compare the efficacy of ramosetron, aprepitant and dexamethasone with ondansetron, aprepitant, and dexamethasone for preventing chemotherapy-induced nausea and vomiting: KCSG PC10-21." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 9633. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.9633.
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9633 Background: Combination of aprepitant, 5-HT3 receptor antagonist and steroid improve complete response (CR) of chemotherapy induced nausea and vomiting (CINV). But until now, there was no information whether ramosetron is as effective as other 5-HT3receptor antagonists for the combination regimen. Therefore, we compared a ramosetron, aprepitant and dexamethasone (RAD) with ondansetron, aprepitant and dexamethasone (OAD) to establish the non-inferiority of RAD in controlling highly emetogenic chemotherapy induced nausea and vomiting. Methods: A total of 334 patients with malignant disease who were scheduled to receive highly emetogenic chemotherapy were randomized to RAD or OAD. Aprepitant (125 mg day 1; 80 mg day 2, 3) and dexamethasone (12 mg day 1; 8 mg day 2-4) were administered to both group. Intravenous ramosetron (0.3mg day 1) or ondansetron (16mg day1) was given to RAD or OAD, respectively. Patients recorded vomiting and nausea (VAS score) on the diary. The primary end point was CR (no vomiting or retching and no rescue medication) rate in the acute period (chemotherapy day 1). The non-inferiority margin was defined as -15% differences. Results: 299 patients (RAD 143, OAD 156) were eligible for the efficacy analyses of modified intention-to-treat. Median age and sex were 60 (IQR 52 – 66) and 61 (51.5 – 68, p=0.54), 90 Male/66 Female and 114 Male/29 Female (p<0.0001) in RAD and OAD, respectively. There were no significant differences between two groups on the other baseline characteristics. The CR rates of RAD vs OAD were 84.6% vs 77.6% (95% C.I. -0.4 – 14.5%) at acute period, 69.5% vs 62.6% (-2.1 – 16.0%) at delayed period (days 2-5), and 66.7% vs 58.1% (-0.6 – 17.8%) at overall period. Median nausea score at acute period were 4 (IQR 2 – 5) and 3 (2-5, p=0.14) in RAD and OAD, respectively. There were no grade 3 or 4 toxicities. Conclusions: RAD regimen is as effective and tolerable as OAD antiemetic combination for the prevention of CINV in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered as one of the best partners for aprepitant. Clinical trial information: NCT01536691.
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Kang, Jin Hyoung, Jung Hye Kwon, Yun-Gyoo Lee, Keon Uk Park, Ho Jung An, Joohyuk Sohn, Young Mi Seol, et al. "Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting." Cancer Research and Treatment 52, no. 3 (July 15, 2020): 907–16. http://dx.doi.org/10.4143/crt.2019.713.
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PurposeThe purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting. Materials and MethodsPatients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.ResultsA total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.ConclusionIn all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.
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Kyrdalen, A. E., E. Hernes, S. D. Fossa, and A. A. Dahl. "Chronic fatigue in prostate cancer patients after radical prostatectomy (RP) or high-dose radiotherapy (RAD)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 5164. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.5164.
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5164 Background: Chronic fatigue (CF) is frequent in cancer patients, but has been less studied in prostate cancer patients (PCPs). This study compares CF in PCPs treated with RP or RAD(≥70Gy), who have never received any hormonal therapy. Methods: In 2006 we addressed all Norwegian PCPs who had been diagnosed in 2004 and were alive (N = 2,997). Among the 2,194 PCPs (73%) responding we identified 332 patients with RP and 183 with RAD 12–32 months before our survey. The PCPs returned a mailed questionnaire covering fatigue, quality of life, urinary and bowel bother, sexual function, comorbidity, and lifestyle. Hormonal therapy identified by the national prescription database or self-report, lead to exclusion. Caseness of CF was based on the Fatigue Questionnaire. Results: Caseness of CF was observed in 13.6% of men with RP (95%CI 9.9–17.2%) and in 25.7% after RAD (95%CI 19.4–32.0%) (p = 0.001). The prevalence in the RP group was similar to the norm observed in Norwegian men >60 years. PCPs with RP or RAD had similar prevalence of bother regarding urinary symptoms (13 vs 16%, p = 0.13), while more RAD than RP patients reported bother due to bowel symptoms (24 vs 4%, p < 0.001). Sexual functioning showed a better score in the RAD versus the RP group (p < 0001). In multivariate regression analysis treatment modality did not show any significant association with CF (p = 0.25). In contrast, physical and mental quality of life (both p < 0.001) and bother due to bowel problems (p = 0.005) were associated with CF caseness. No significant associations were found between urinary bother, sexual function and CF caseness. Conclusions: This national study of PCP treated with curative intention showed a much higher prevalence of CF after RAD compared to RP. In multivariate analysis treatment modality was not significantly associated with CF caseness. Bowel bother was more common after RAD, and showed a significant association with CF caseness, however, with a wide confidence interval. No significant financial relationships to disclose.
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Knop, Stefan, Christian Langer, Monika Martha Engelhardt, Johanne Wangemann, Lars Olof Muegge, Florian Bassermann, Kerstin Schaefer-Eckart, et al. "Lenalidomide, doxorubicin hydrochloride and dexamethasone versus bortezomib, lenalidomide, and dexamethasone prior to scheduled stem cell transplant in newly diagnosed myeloma." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 8001. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.8001.
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8001 Background: In younger, medically fit patients (pts) with newly diagnosed (ND) multiple myeloma (MM), autologous stem cell transplant (SCT) remains a standard of care. Prior to SCT, induction triplets with at least one of the newer compounds are recommended. Bortezomib (V), lenalidomide (R) and dexamethasone (D; VRD) ranks amongst the most effective treatments. VRD + SCT proved superior over VRD alone in a randomized, controlled trial (RCT). We found encouraging efficacy and low toxicity with RAD (RD and adriamycin) + SCT and decided to compare RAD versus VRD induction in an RCT. Methods: The DSMM XIV study was set up according to a double 2x2-factorial design to enroll NDMM pts up to 65 years (yrs). Post-induction (PI) CR rate was the efficacy endpoint for the initial study phase. We hypothesized CR rate with RAD would be non-inferior to an estimated 20% CR with VRD. The study was powered to confirm non-inferiority of RAD at a 10% margin with a one-sided α level of .05. Minimal residual disease (MRD) was analyzed by eight-color flow cytometry (EuroFlow standards) on marrow samples. Results: 476 pts were randomized between 05/2012 and 06/2016, 469 of whom (median age 55 (range, 32–65) yrs) received at least one dose of study drug. 18.3% of pts had ISS stage III MM and 17.2%, elevated LDH. 11.3% of pts had del17p; 11.1% had t(4;14); and 4% had t(14;16). 232 pts were randomized to 3 four-week RAD cycles and 237 to 3 three-week VRD cycles, respectively. 89.7% of RAD versus 93.2% of VRD pts completed all induction cycles. PI CR rate was 11.8% (90% CI, 7.9%-16.3%) with RAD versus 13.0% (90% CI, 8.9-18.0) with VRD, (P = .697). 72/317 pts (22.7%) with paired baseline/PI samples achieved negative MRD at a median sensitivity level of 6.73x10-6. 47 (20.3%) RAD versus 35 (14.8%) VRD pts experienced treatment-emergent SAEs (P = .144). Treatment-related induction mortality was 0% in either arm. Conclusions: To the best of our knowledge, this is the first RCT to compare two lenalidomide-based triplets prior to SCT. The endpoint was met with comparable PI CR rates for RAD and VRD, respectively. Tolerability was encouraging in both arms. Follow-up data is needed to analyze time-dependent endpoints. Clinical trial information: NCT01685814.
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Li, Yi, and Longjiang Li. "Intra-arterial infusion of recombinant adenoviral human p53 gene combined chemotherapy for advanced oral cancer: A phase II double-blind randomized clinical trial." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 5507. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.5507.
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5507 Background: The p53 tumor suppressor gene has been shown as having multiple anti-tumor functions and being capable of enhancing the efficacy of chemo-therapy. This study is to investigates clinical outcomes of intra-arterial infusion ofrecombinant adenoviral human p53 gene (rAd-p53) combined with chemotherapy in treatment of advanced oral cancer. Methods: Ninety-nine patients with stage III or IV oral carcinoma, satisfying with the inclusion criteria, were randomly allocated to Group I (G1: n=35; rAd-p53 plus chemotherapy), Group II (G2: n=33; rAd-p53), or Group III (G3: n=31; chemotherapy). Intra-artery infusion of rAd-p53 were given through superficial temporal artery reverse intubation at a dose 1-4 ×1012 viral particles (VP) , once every 3 days for 6 times. Chemotherapy regimen consisted of oxaplatin 200 mg/m2 on day1, bleomycin 8 mg/m2 on day 2, 6, 8 and Methotrexate 30 mg/m2 on day1, 8, for squamous cell carcinoma (SCC), and oxaplatin 200 mg/m2 on day1, 5-Fu 200 mg/m2 on day1,3 and cyclophosphamide 400 mg/m2 on day2, 8 for adenoid cystic carcinoma (ACC). Results: The complete response rate (CR) in G1 (48.5%) was significantly higher than in G2 (16.7%) and G3 (17.2%). The overall response rates (RR) were 88.6%, 54.5%, and 51.6% for G1, G2 and G3, respectively. The 3-year overall survival (OS) of G1 (82.9%) was significantly higher than the patients in G2 (60.6%) and G3 (58.1%). All those patients receiving rAd-p53 had a self-limited fever. Positive Bax immunostaining was detected in all the patients receiving rAd-p53. Conclusions: Intra-arterial infusion of combined rAd-p53 and chemotherapy may represent an alternative to the current standard treatment for the late stage oral carcinoma.
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Zhu, Jingqiang. "A new combination therapy using recombinant human adenovirus p53 injection (rAd-p53) to manage advanced thyroid cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e17585-e17585. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e17585.
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e17585 Background: Although most thyroid cancers have good clinical outcomes, there still have some advanced and radioiodine-resistant thyroid cancers being lack of effective treatment. In this study, we reported a new combination therapy including recombinant adenovirus-p53 (rAd-p53) to treat advanced thyroid cancers. Methods: Two types of unresectable cancers (one advanced PTC and one ATC) received preoperative intratumoral injection of rAd-p53 combined with radiotherapy to shrink the tumor and surgery to remove the tumor. In the matched controlled clinical trial, 82 advanced PTC patients accorded with the inclusive criteria and exclusion criteria were included and matched into experimental group (EG, n = 41) and control group (CG, n = 41). Compared CG received surgery only, EG received preoperative intratumoral injection of 2×1012rAd-p53 viral particles (VP) per 3 days for 5 times and surgery. Results: In the advanced PTC case, the combination treatments including rAd-p53 gene therapy combined with radiotherapy evidently shrunk the tumor and improved the operative condition. Finally, the patient received a successful surgery to remove the tumor totally. In the ATC case, rAd-p53combined radiotherapy obvious relieved enlargement of the lump in the neck and shrunk the tumor. More importantly, the program of surgery to excise the tumor was deemed suitable for this ATC patient through a series of treatments and severity evaluation. In the matched controlled clinical study, compared the control group (CG), rAd-p53 significantly increased the radically operative rate in experiment group (EG) (92.7% vs73.2 %, P= 0.021, n = 41). The 7 years follow-up data showed rAd-p53 decreased locoregional recurrence rate (19.51% vs 36.59%) and new metastasis rate (7.32% vs 17.07%) and increased the median time to locoregional recurrence (24.5 M vs 23.27 M) and new metastasis (19.0 M vs 9.2 M) and the disease-free survival rate (75.61% vs 46.34%) for patients in EG. Conclusions: The combination therapy improved the prognosis to patients with advanced thyroid cancer, indicating this combination therapy including rAd-p53 has an important implication for managing advanced thyroid cancer.
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Ryan, Charles J., Thian Kheoh, Howard I. Scher, Peter De Porre, Margaret K. Yu, and Michael J. Morris. "Clinical versus radiographic progression and overall survival for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) from COU-AA-302." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 193. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.193.
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193 Background: COU-AA-302 evaluated abiraterone acetate plus prednisone (AA) vs prednisone (P) in chemotherapy-naïve mCRPC pts, with overall survival (OS) and radiographic progression-free survival (rPFS) as co-primary end points. Per study criteria, pts with radiographic progression (RAD) only were allowed to continue treatment, while those with unequivocal clinical progression (UCP) only were not, and were censored for rPFS. We evaluated the clinical significance of survival outcomes for pts with UCP only vs RAD only from the prospective COU-AA-302 trial. Methods: UCP was defined per protocol as ≥ 1 of the following: initiation of chronic opiates, ECOG performance status (PS) decline to ≥ 3, or initiation of chemotherapy, palliative radiation therapy, or surgery. OS was evaluated for each type of progression using Cox proportional hazard models. Results: 500 (92%) pts in the AA arm and 540 (100%) in the P arm discontinued study treatment. Of the 736 pts who discontinued treatment for a protocol-defined reason, 280 (38%) discontinued for UCP only, 332 (45%) for RAD only, and 124 (17%) for both UCP and RAD. Clinical events cited as the reason for discontinuation for UCP (AA vs P arm) included pain requiring opiates (22% vs 25%), ECOG PS ≥ 3 (4% vs 5%), and initiation of chemotherapy (50% vs 53%), radiation therapy (36% vs 27%) and surgery (3% vs 5%). UCP only pts had shorter median OS compared with RAD only pts (Table). Conclusions: UCP is a criterion used as an indicator for a censored event, yet appears to confer inferior survival relative to RAD. The high frequency of UCP implies that it may be an important determinant of clinical outcome. The events that drive UCP should be defined as part of the development of more informative interim trial end points, in line with the PCWG3-proposed “no longer clinically benefitting” outcome measure, which captures pts with UCP. Clinical trial information: NCT00887198. [Table: see text]
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Hartati, Sri. "Penampilan Beberapa Galur Mutan Kacang Hijau Asal Irradiasi Sinar Gamma Cobalt-60 (M3)." Caraka Tani: Journal of Sustainable Agriculture 19, no. 2 (April 19, 2018): 94. http://dx.doi.org/10.20961/carakatani.v19i2.20470.
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<p>Performance of Several Mungbean Lines Resulted from Mutation of Co-60 Gamma Rays Irradiation. Sri Hartati, 23 pages. The objectives of the research were to evaluate the agronomic traits of the fourth generation (M3) of mungbean mutants and to get at least one potential genotype for further selection in order to achieve a new high yielding variety. He research was done in Grumosol of Joho Mojolaban, Sukoharjo.</p><p>The experimental design was completely randomized design with 12 treatments: G1/V1R0: the third generation of ‘Merpati’ with no radiation; G2/V1R1: the third generation of ‘merpati’ radiated at rate of 5 K rad; G3/ViR2: the third generation of ‘Merpati’ radiated at rate of 10 K rad; G4/V1R3: the third generation of ‘Merpati’ radiated at rate of 15 K rad; G5/V2R0: the third generation of ‘Camar’ with no radiation; G6/V2R1: the third generation of ‘Camar’ radiated at rate of 10 K rad; G7/V2R3: the third generation of ‘Camar’ radiated a rate of 15 K rad; G9/V3R0: the third generation of ‘Walet’ no with radiation; G10/V3R1: the third generation of ‘Walet’ radiated at rate of 5 K rad; G11/V3R2: the third generation of ‘Walet’ radiated at rate of 10 K rad; G12/V3R3: the third generation of ‘Walet’ radiated at rate of 15 K rad.</p><p>The research conclude that weight of 1000 seeds and weight of seed per plot from the first to the fourth generation were achieved by ‘Walet’ variety irradiated at the rate of 10 K rad; and thus, this was the potential lines for further selection program.</p>
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Bompani, Barbara. "Religion and development: Tracing the trajectories of an evolving sub-discipline." Progress in Development Studies 19, no. 3 (April 3, 2019): 171–85. http://dx.doi.org/10.1177/1464993419829598.
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Religion and development (RaD) has emerged as a new academic sub-discipline since the turn of the 21st century, following decades of secular assumptions and attitudes dominating development studies, and international development more broadly. In 2019, there was a little doubt that religion has been incorporated into development studies and it is therefore timely to re-appraise RaD. Recent scholarship suggests that RaD increasingly informs, engages with and influences development studies and development practice—providing rich empirical material, broader disciplinary engagement and deeper analytical insight. Drawing on a survey of almost—mainly English language—700 publications, this article traces the emergence and establishment of RaD. The article traces the emergence of the field (2000–10) and then its subsequent more critical engagement with development studies (between 2011 and 2018). The article concludes by identifying five emerging contemporary research themes within RaD and future research opportunities.
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Yangkun, Wang, Hu Yan, and Zhang Tianzhen. "Current status and perspective of RAD-seq in genomic research." Hereditas (Beijing) 36, no. 1 (April 25, 2014): 41–49. http://dx.doi.org/10.3724/sp.j.1005.2014.00041.
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Zhou, Jian, Fumin LIU, and Jie Xiao. "Recombinant adenovirus-p53 combined with chemotherapy in treatment of locally advanced cervical cancer (a phase II study)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 5525. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5525.
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5525 Background: To evaluate the efficacy and safety of recombinant adenovirus-p53 (rAd-p53) combined with chemotherapy in treatment of locally advanced cervical cancer. Methods: Forty patients with stage IIb2 IV locally advanced cervical cancer were randomly divided into 2 groups: 20 patients receiving gene plus chemotherapy (PCG) and 20 receiving sole chemotherapy (CG). The patients in PCG were given one course of PVB (cisplatin + vincristine + pingyangmycin) and 5 times intratumoral injections of rAd-p53 at a dose of 2 x 1012 viral particles once per 3 days. The CG patients received a sole course of PVB. The study patients were followed up for at least one year. The VEGF, p53, Bax, and p21 protein expression in pre- and post-treatment tumor tissues were examined by immunohistochemistry. Results: The response was evaluated at 3 months after treatments. The response rates (CR + PR) were 95% and 75% for the PCG and CG patients, respectively. P53 proteins were strongly expressed in the tumor tissues from both groups. There were no significant changes in expression level of the p53 protein in the tumor tissue from pre- and post-treatment. However, the VEGF, Bax, and p21 protein expressions significantly increased in PCG after treatment. The overall one-year survive rates were 90% and 65%, respectively. A mild to medium grade of fever was found in 90% of the PCG patients. No serious of adverse events relative to rAd-p53 were observed. Conclusions: Combined the rAd-p53 gene with chemotherapy is an effective treatment for the patients with advanced cervical cancer. The rAd-p53 gene therapy is a safe treatment.
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Lilleby, Wolfgang. "Long-term bother profiles in patients with locally advanced prostate cancer treated with radiotherapy compared to men with localized prostate cancer treated with high-dose radiotherapy." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 104. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.104.
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104 Background: We compared the long-term the bother profiles in patients with prostate cancer (T1-3 M0) consecutively referred to the OUS to definitive radiotherapy encompassing the prostate and pelvic lymph nodes (RT+IMRT) (N=90) or radiotherapy to the prostatic gland only (RAD) (N=180), applied with adjuvant androgen deprivation in all patients. Methods: After 36months 206 (76%) of the eligible men (RT+IMRT = 64 and RAD = 142) had completed the UCLA-PCI questionnaire at baseline, 12, 24 and 36 months. The bother scores were adjusted for significant differences in quality of life measured by the SF-12 instrument. Differences in the mean scores between the treatment groups were evaluated by the Mann-Whitney U test for skewed samples. Patients were similar in age and by the distribution of prognostic risk factors in both cohorts. Results: The longitudinal bother mean scores up to 36 months post-treatment for the main domains are reported. Significantly more RAD patients had less urinary bother at baseline compared to RT+IMRT patients. In both groups sexual bother was significantly increased over time. Thus, at 36 months mean scores for urinary, bowel and sexual bother appeared to be stable in both groups. However, despite of increased bowel bother at one year (p= 0.02) in the RT+IMRT group, bowel bother score improved in these patients compared to RAD at last observation (p= 0.25). Conclusions: The long-term bother profiles are similar in the RT+IMRT and RAD groups at 36 months follow-up. Modern radiotherapeutic techniques allow targeting of high-risk patients. Differences in organ function and bother can only be accomplished for by long-term health care assessment.
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Boratyn, Dominik. "Charytatywna działalność gminnych rad młodzieżowych – analiza zagadnienia." UR Journal of Humanities and Social Sciences 16, no. 3 (2020): 141–55. http://dx.doi.org/10.15584/johass.2020.3.8.
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Youth Councils are entities that serve as consultative and advisory bodies to local government units in Poland. The councils, which have been functioning for over 30 years, take part in the activities of local governments and undertake a number of social projects, including those of a charitable nature. The paper presents the results of research that was carried out as part of the project "The importance and role of Youth Councils in the functioning of local governments." The research concerns Youth Councils from 18 voivodeship cities, where local government councils and voivodeship offices are located. The results of the research, presented in the ensuing paper, show the activity of Youth Councils in the field of charitable work.
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Knop, Stefan, Christian Langer, Monika Martha Engelhardt, Florian Bassermann, Martin Schreder, Lars-Olof Muegge, Kerstin Schaefer-Eckart, et al. "Bortezomib, lenalidomide, and dexamethasone (VRD) is superior to lenalidomide, adriamycin, and dexamethasone (RAD) prior to risk-adapted transplant in newly diagnosed myeloma." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 8521. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.8521.
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8521 Background: High-dose chemotherapy (HDT) followed by autologous stem cell transplant (SCT) remains a standard of care in patients (pts) with newly diagnosed (ND) multiple myeloma (MM). While lenalidomide (R) maintenance is acknowledged to improve outcomes, intensified consolidation (such as tandem-SCT) has yielded conflicting results. Allogeneic (allo) SCT holds the promise of curative potential at the cost of higher treatment-related mortality (TRM). In a previous phase 2 study, we showed a very low TRM rate (6.1%) and feasibility of 12 months (mos) of R maintenance (maint), with auto/allo SCT after R/adriamycin/dexamethasone (RAD). This prompted us to compare, on a randomized rather than a “biological assignment” basis, a second auto- versus (vs) an allo-SCT in pts with an unfavorable prognosis. Methods: The current protocol (DSMM XIV, NCT01685814) was set up according to a double 2x2-factorial design. Post-induction (PInd) CR rate was the efficacy endpoint for the comparison of RAD vs bortezomib (V)/RD (VRD; 3 cycles each). If pts had achieved >VGPR to HDT, a second randomization (2ndR) compared immediate R maint (arm A2) with a second auto-SCT (B2). In case of < VGPR, pts were randomized between a second auto- (C2) and allo-SCT (D2). Planned R maint. duration was 36 mos, except after allo (12 mos). Results: Between 05/2012-06/2016, 476 pts were randomized and 469 received at least one dose of study drug. Pts’ median age was 55 (range, 32–65) years. 11.3% of pts had FISH del17p; 11.6% had t(4;14); and 4.4% had t(14;16). PInd CR rate was 11.8% (90% CI, 7.9%-16.3%) with RAD and 13.0% (90% CI, 8.9-18.0) with VRD (P = .697). 382 pts underwent R2 with 279 pts. (73%) in >VGPR and 103 (27%) in < VGPR, respectively. Median duration of R maint (N = 298) was 21.2 mos for A2, 23.1 mos for B2, 27.4 mos for C2, and 11.0 mos. for D2. At a median follow-up of 40.2 (0.5-87.0) months, median PFS from first randomization with RAD was 41.7 (95% CI, 35.4-48.5) mos vs. 53.7 (95% CI, 46.2-63.1) mos with VRD (P = .0439). Median PFS from 2ndR was 38.7 (95% CI, 30.3-47.3) mos for the 181 RAD vs. 50.7 (95% CI, 44.4-64.9) mos for the 201 VRD pts (P = .0126). Median overall survival (OS) cannot be estimated. With 47 deceased RAD vs 36 VRD pts, HR was .671 (95% CI, .435-1.037; P = .0703). Conclusions: In this study, median PFS benefit was 12 mos in favor of VRD vs. RAD despite comparable PInd CR. We show for the first time a len-PI to be superior to a len-chemo triplet, confirmed with positive OS trends. 3-year PFS for all consolidation arms will be presented. Clinical trial information: NCT01685814 .
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Kampmann, Eric, Dominique Harnicek, Ana Sofia Cardoso Martins, Berina Eppink, Eike Gallmeier, Lars Lindner, Roland Kanaar, and Rolf D. Issels. "Heat-shock (H-S) and trabectedin efficacy in human soft-tissue sarcoma (STS) cells in vitro." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e13540-e13540. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e13540.
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e13540 Background: Regional hyperthermia improves response and survival when combined with chemotherapy in patients with high-risk STSs (Issels, R.D. Lancet Oncol 2010). Trabectedin is the first marine-derived antineoplastic drug approved in Europe for the treatment of advanced STS after failure of anthracyclines and ifosfamide, or for patients who are unsuited to receive these drugs. Trabectedin’s cytotoxicity is associated with the induction of lethal DNA double-strand breaks (DSB). The rationale to combine trabectedin with H-S is that heat-exposure sensitizes tumor cells by inhibiting the repair of induced DSBs (Krawczyk, P.M. PNAS 2011). Methods: Combinations of trabectedin and H-S at clinically relevant temperatures were examined in 3 different human cell lines: Osteosarcoma (U2Os), liposarcoma (SW872) and synovial sarcoma (SW982). Cells were treated with trabectedin at the dose of 500-4000 pM for 3 hours. H-S was applied in an incubator at 41.8°C and 43°C for 90 or 150 min before, during or after trabectedin incubation. Cytotoxicity was assessed measuring clonogenic survival of cells. Expression of BRCA2, which recruits homologous recombination repair recombinase Rad 51 to DSBs, was measured by Western Blot (WB). Recruitment of Rad 51 and the amount of gH2AX positive DSB-repair-foci were analysed by immunocytochemistry (ICC). Results: All cell lines showed reduced viability after increasing doses of trabectedin at 37°C. Combined treatment with trabectedin and H-S additionally enhanced cytotoxicity of trabectedin with strongest effects observed after simultaneous administration of both. WB-analysis showed strong heat-dependent reduction of BRCA2 expression. ICC revealed that recruitment of Rad 51 to DSBs was reduced after heat exposure at 41.8°C and abolished after exposure at 43°C. Accordingly, combined treatment significantly increased the amount of cells with severe DNA damage (>50 DSBs). Conclusions: Combined treatment with trabectedin and H-S in vitro resulted in significantly enhanced cytotoxicity that was accompanied by elevated DNA-damage in term of DSB-accumulation. The mechanisms of interaction between trabectedin and H-S concerning DNA repair are under investigation.
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Shapiro, E., T. J. Kinsella, R. W. Makuch, B. A. Fraass, E. Glatstein, S. A. Rosenberg, and R. J. Sherins. "Effects of fractionated irradiation of endocrine aspects of testicular function." Journal of Clinical Oncology 3, no. 9 (September 1985): 1232–39. http://dx.doi.org/10.1200/jco.1985.3.9.1232.
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We have examined the hormonal alterations of testicular function in 27 males (14 to 67 years of age) with soft-tissue sarcoma who were treated with surgery and high-dose radiation to the tumor bed. The testicular dose from scatter radiation ranged from 1 to 2,500 rad. There was a dose-dependent increase in the median per patient difference from baseline in serum follicle-stimulating hormone (FSH) values following irradiation, with the maximal difference seen at 6 months. Recovery of serum FSH level was biphasic with a decline in the median difference in values between 6 and 12 months, followed by a gradual descent toward baseline. Only patients receiving less than 50 rad show early complete recovery 12 months after radiation therapy. Radiation injury also induced dose-dependent increases in serum luteinizing hormone (LH) concentration, with the maximal median difference from baseline level occurring at 6 months. Only those patients receiving greater than 200 rad showed statistically significant LH changes from baseline levels at each time interval up to 30 months. No significant changes were observed in total testosterone values. These data provide quantitative guidelines for predicting seminiferous tubule injury and germ cell depletion in men exposed to fractionated radiation. The effects on seminiferous tubule and Leydig cell function, as judged by serum FSH and LH concentrations, suggest that subtle Leydig cell dysfunction, in addition to germ cell depletion, may also occur at exposures greater than 200 rad.
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Nelson, Rebecca, Guy Chadwick, Molly Bruce, Genevieve Young-Southward, and Helen Minnis. "Can reactive attachment disorder persist in nurturing placements? A systematic review and clinical case series." Developmental Child Welfare 2, no. 2 (June 2020): 110–31. http://dx.doi.org/10.1177/2516103220940326.
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Reactive Attachment Disorder (RAD), is characterized by failure to seek and accept comfort in maltreated children. This lack of activation of the attachment system has profound developmental disadvantages yet, in early childhood, usually resolves quickly after placement in nurturing care. Persistence of RAD into middle childhood has been demonstrated in children reared in Romanian Institutions but, in family-reared children older children, there is controversy regarding whether RAD-like behaviors are genuinely attachment-related and stable from early childhood or are, in fact, related to PTSD. We conducted two pieces of research to investigate this: 1. a systematic review to examine persistence/resolution of RAD and 2. a case series of three boys whose RAD symptoms persisted despite living in placements judged by both social and child health services to be of good quality. Our systematic review revealed a paucity of longitudinal data. Except in atypical institutionalized samples, RAD had not been evidenced beyond pre-school. All three boys in the case series met DSM 5 criteria for RAD in late childhood/early adolescence and had stable RAD symptoms since before age 5. Qualitative interviews with their families revealed common themes of family strain, frustration and resentment at the lack of support from services. This paper provides the first opportunity to generate testable hypotheses about environmental circumstances and coexisting symptomatology that may influence RAD trajectories. Persistence of RAD has profoundly negative implications for children and their families. Recognition of RAD symptoms is challenging but crucial in order to improve care of these children and their families.
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Shaffer, D. R., L. E. Abrey, K. Beekman, C. Eicher, M. Morris, S. Slovin, J. Feldstein, S. Larson, N. Rosen, and H. I. Scher. "A phase I/II trial of RAD 001 with gefitinib in patients with castrate metastatic prostate cancer and glioblastoma multiforme." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14520. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14520.
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14520 Background: Inactivation of the Pten tumor suppressor gene, leading to constitutive activation of the PI3K/AKT/mTOR pathway, is correlated with resistance to EGFR-targeted therapies. This trial tested the concept that inhibition of mTOR by RAD 001 (NOVARTIS) will restore sensitivity to EGFR inhibition by gefitinib (ASTRA ZENECA), in patients with progressive PC and GBM. Methods: Phase I was designed to determine a safe and tolerable dose and the pharmacokinetics (PK) of RAD (30/ 50/ 70 mg po weekly) with a fixed dose of gefitinib (250 mg po qd) in patients with PC and GBM. Phase II evaluated the proportion of PC patients with no change or a decline in PSA at 12 weeks, without clinical or radiographic progression. FDG PET imaging and immunohistochemistry were included as correlative studies. Results: 12 patients (2 GBM, 10 PC) were treated in Phase I, and 22 of 27 PC patients have been treated in Phase II. (The GBM Phase II results are reported separately). 20/32 (63%) of PC patients had received prior chemotherapy. No dose limiting toxicities were observed in Phase I, and 70 mg of RAD 001 weekly with gefitinib 250 mg qd was studied as the Phase II dose. PK parameters estimated during a 3 week single agent lead-in phase and during subsequent combined therapy suggested no clinically relevant PK interactions between RAD and gefitinib. The most common drug-related grade 3/4 toxicities were lymphopenia (28%) and elevated ALT (7%). Serial FDG PET scans showed > 25% decline in SUV uptake in 9/23 evaluable patients during the first week of treatment; of these, 3 patients showed no progression at 12 weeks. Overall, 5/29 PC patients showed no progression at 12 weeks, 3 (60%) of whom had received prior chemotherapy. Conclusions: Combination therapy with RAD 70 mg weekly and gefitinib 250 mg daily appears to be safe and is associated with modest activity in metastatic prostate cancer. Support: Novartis Pharmaceuticals, Astra Zeneca Pharmaceuticals. [Table: see text]
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Hu, Yi. "Recombinant adenoviral human p53 gene intracavity infusion in treatment of malignant pleural effusions and peritoneal effusions." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e13521-e13521. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e13521.
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e13521 Background: Malignant pleural or peritoneal effusion adversely affects patients' quality of life. Once the effusions formed it is difficult to control. This report showed intra-cavity infusion of recombinant adenoviral human p53 gene (rAd-p53) was very effective for controlling malignant pleural or peritoneal effusion. Methods: Twenty-seven patients, 15 males and 12 females with a median age of 59 years old , were included this study. The malignant pleural effusions, consisting of 13 patients, were caused by primary lung cancers (12 cases) and breast cancer (1 case), and 14 cases of peritoneal effusions were caused by gastric cancer (5 cases), ovarian cancers (3 cases), primary live cancer (2 cases), pancreatic cancer (2 cases), esophageal cancer (1 case) and bile duct cancer (1 case). The rAd-p53 intra-cavity infusion was given after removing most of fluids. For intra-chest cavity infusion 2×1012 viral particles (VP) of rAd-p53 diluted into 200 ml of saline solution, and for intra-abdominal cavity infusion 4×1012 VP of rAd-p53 diluted into 500 ml of saline solution, were given weekly for 3 weeks. Results: A total of 3 cases, 2 with pleural effusion and 1 with peritoneal effusion achieved a complete response (CR), and 10 cases (7 pleural effusions and 3 peritoneal effusions) had a partial response (PR). The overall response rate is 48.1%. The CR was defined as the complete disappearance of pleural or peritoneal fluid and negative cytologic findings for >4 weeks, and the PR is defined as a decrease over 50% of the fluid without the need of drainage and negative cytologic findings for >4 weeks. The fluids in 8 cases with peritoneal effusions decreased by over 30% but less than 50%. The associated symptoms relieved in 23 patients (85.2%). There were no serious side effects observed except for self-limited fever found in all the cases. Conclusions: For some patients with malignant pleural or peritoneal effusions, Intra-cavity infusion of rAd-p53 is effective and safe controlling treatment.
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Shore, Neal D., Stephen A. Boorjian, Daniel J. Canter, Kenneth Ogan, Lawrence I. Karsh, Tracy M. Downs, Leonard G. Gomella, et al. "Intravesical rAd–IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin–Refractory or Relapsed Non–Muscle-Invasive Bladder Cancer: A Phase II Randomized Study." Journal of Clinical Oncology 35, no. 30 (October 20, 2017): 3410–16. http://dx.doi.org/10.1200/jco.2017.72.3064.
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Purpose Many patients with high-risk non–muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd–IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd–IFNα/Syn3 (randomly assigned 1:1 to 1 × 1011 viral particles (vp)/mL or 3 × 1011 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd–IFNα/Syn3 (1 × 1011 vp/mL, n = 21; 3 × 1011 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd–IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd—IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.
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Sakate, Makoto, Luigi Vercesi, Maria Aparecida Coelho Arruda Henry, and Pedro Héllo Lucchiari. "Polarography of Walker Tumor Submitted to Radiotherapy." Tumori Journal 73, no. 6 (December 1987): 555–58. http://dx.doi.org/10.1177/030089168707300603.
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A Polarographic study of oxigen was done in 57 rats inoculated with Walker 256 tumor and platinum electrode implanted in muscle and in tumor. The goal of the research was the study of oxygen in tumor before and after irradiation. Tumor growth caused a decrease in tumoral oxygen. Oxygen was always lower in the tumor than in the muscle. Radiotherapy with 2000 rad (but not with 1000 rad) increased oxygen in the tumor.
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Boorjian, Stephen A., Neal D. Shore, Daniel Canter, Kenneth Ogan, Lawrence Ivan Karsh, Tracy Downs, Leonard G. Gomella, et al. "Intravesical rad-IFNα/Syn3 for patients with high-grade, bacillus Calmette-Guérin (BCG) refractory or relapsed non-muscle invasive bladder cancer: A phase II randomized study." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 279. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.279.
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279 Background: While bacillus Calmette-Guérin (BCG) is the most effective intravesical treatment for reducing recurrence and progression for high-risk non-muscle invasive bladder cancer (NMIBC), many patients are either refractory to treatment or relapse. We assessed the efficacy and safety of rAd-IFNα/Syn 3 (Instiladrin, FKD Finland), a replication deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG refractory or relapsed NMIBC. Methods: In this open-label, US multicenter (n=13), parallel-arm Phase II study (NCT01687244), 43 patients with HG BCG refractory or relapsed NMIBC were randomized 1:1 to receive intravesical rAd-IFNα/Syn3 at 1x1011 or 3x1011viral particles/mL. Patients responding at months 3, 6, and 9 were re-treated at months 4, 7, and 10. Most patients (n=21) had a primary tumor classification of carcinoma in situ (CIS); 9 had both CIS and Ta/T1 disease and 10 had Ta/T1 disease alone. The primary endpoint was 12-month HG recurrence-free survival (RFS). All patients receiving at least one dose were included in efficacy and safety analyses. Results: Forty patients received rAd-IFNα/Syn3 (1 x 1011 vp/mL: n=21; 3 x 1011vp/mL: n=19) between November 2012 and April 2015. Fourteen patients (35.0%; 90% CI 22.6%, 49.2%) remained free of HG tumor recurrence 12 months after initial treatment. Comparable 12 month HG RFS was noted between dosage arms, as well as between patients with refractory and relapsed NMIBC. Interestingly, the 12 month HG recurrence-free survival for patients with Ta/T1-only disease was 50% (5/10). rAd-IFNα/Syn3 was well-tolerated, with no Grade 5 adverse events (AEs), one Grade 4 AE (COPD; unrelated to treatment), and no patient discontinuing treatment due to an adverse event. The most frequently reported AEs were micturition urgency (n=16), dysuria and pollakiuria (n=13 each), fatigue (n=9), and nocturia (n=10). Conclusions: rAd-IFNα/Syn3 was well tolerated and demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who are unable or unwilling to undergo radical cystectomy. A phase III trial utilizing this novel agent is ongoing. Clinical trial information: 01687244.
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Winter, Jane N., David J. Inwards, Stewart Spies, Gregory Wiseman, David Patton, William Erwin, Alfred W. Rademaker, et al. "Yttrium-90 Ibritumomab Tiuxetan Doses Calculated to Deliver up to 15 Gy to Critical Organs May Be Safely Combined With High-Dose BEAM and Autologous Transplantation in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma." Journal of Clinical Oncology 27, no. 10 (April 1, 2009): 1653–59. http://dx.doi.org/10.1200/jco.2008.19.2245.
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Purpose To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 (90Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation. Patients and Methods Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized 90Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of 90Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation. Results Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively. Conclusion Dose-escalated 90Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.
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Chun, Asaph Young, Steven G. Heeringa, and Barry Schouten. "Responsive and Adaptive Design for Survey Optimization." Journal of Official Statistics 34, no. 3 (September 1, 2018): 581–97. http://dx.doi.org/10.2478/jos-2018-0028.
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Abstract We discuss an evidence-based approach to guiding real-time design decisions during the course of survey data collection. We call it responsive and adaptive design (RAD), a scientific framework driven by cost-quality tradeoff analysis and optimization that enables the most efficient production of high-quality data. The notion of RAD is not new; nor is it a silver bullet to resolve all the difficulties of complex survey design and challenges. RAD embraces precedents and variants of responsive design and adaptive design that survey designers and researchers have practiced over decades. In this paper, we present the four pillars of RAD: survey process data and auxiliary information, design features and interventions, explicit quality and cost metrics, and a quality-cost optimization tailored to survey strata. We discuss how these building blocks of RAD are addressed by articles published in the 2017 JOS special issue and this special section. It is a tale of the three perspectives filling in each other. We carry over each of these three perspectives to articulate the remaining challenges and opportunities for the advancement of RAD. We recommend several RAD ideas for future research, including survey-assisted population modeling, rigorous optimization strategies, and total survey cost modeling.
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Palačić, Darko, Željka Lalić, Ljubomir Pintarić, and Danijel Kurbanjev. "Analiza modela procesa upravljanja zaštitom na radu u Republici Hrvatskoj." Sigurnost 62, no. 2 (July 8, 2020): 139–50. http://dx.doi.org/10.31306/s.62.2.4.
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SAŽETAK: Rad prikazuje analizu modela procesa upravljanja zaštitom na radu u Republici Hrvatskoj. Model procesa proizlazi iz nacionalnih zakonskih odredaba kojima se uređuje ovo područje. U prvom dijelu rada težište se daje na teoretske postavke upravljanja procesima, procesnog pristupa i zaštite na radu. Razumijevanje teoretskih postavki neophodno je zbog provedbe sustavne analize modela procesa upravljanja zaštitom na radu. U drugom dijelu rada prikazuje se analiza modela procesa upravljanja zaštitom na radu. Pri tome se analiziraju ključne dužnosti i obveze sudionika procesa upravljanja zaštitom na radu u Republici Hrvatskoj. Na temelju provedene analize u raspravi i zaključku navode se mogućnosti za poboljšanje upravljanja procesom zaštite na radu u Republici Hrvatskoj.
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Lee, Sung-Eun, Soo Young Choi, Jae-Yong Kwak, Hawk Kim, Jeong-A. Kim, Young Rok Do, Hyeoung Joon Kim, et al. "Predictive Value of 3-Month Early Molecular Response in New Chronic Phase Chronic Myeloid Leukemia Patients Treated with Radotinib." Blood 126, no. 23 (December 3, 2015): 4053. http://dx.doi.org/10.1182/blood.v126.23.4053.4053.
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Abstract Background: Recent studies have demonstrated that early molecular milestones were able to identify high-risk chronic myeloid leukemia patients treated with frontline imatinib (IM) and second generation tyrosine kinase inhibitors (2G TKIs) such as nilotinib and dasatinib. However, whether a single measurement of BCR-ABL1 transcripts level after 3 months of treatment is sufficient to define failure necessitating a change of treatment is not confirmed. Radotinib (RAD) is a 2G TKI for BCR-ABL1 tyrosine kinase, which was approved by the Korea FDA for the second-line therapy, and the phase 3 study comparing the efficacy and safety of RAD 300 and 400 mg twice daily and IM 400 mg once daily in patients with newly diagnosed CP CML was performed. The aim of this study was to identify the predictive value of 3-month molecular milestone for an achievement of major molecular response (MMR) by 12 months to RAD therapy. Additionally, in the same population, predictive factors for achieving MMR by 12 months were analyzed. Methods: Among 241 patients who were enrolled in the randomized, open-label, phase 3 study of RAD, 236 patients with available 3-month qRT-PCR on study therapy [RAD 300 mg twice (n = 79), RAD 400 mg twice (n = 79), IM 400 mg once (n = 78)] were evaluated. Molecular responses were monitored using a qRT-PCR assay in 3-month intervals by 12 months. All qRT-PCR were tested with at least 4.5-log sensitivity in the central laboratory (Cancer Research Institute, The Catholic University of Korea, Seoul, Korea) and MMR was defined as a BCR-ABL1 transcript level of 0.1% or lower on the international scale (IS). Results: 236 patients (including 149 men and 87 women) with available 3-month qRT-PCR on study therapy were evaluated. With a median age of 45 years (range, 18-84 years), the distribution of low, intermediate and high Sokal risk scores were 27%, 47% and 26%, respectively. At 3 months, BCR-ABL1 ≤10% [RAD 300 mg twice (n = 68), RAD 400 mg twice (n = 69), IM 400 mg once (n = 55)] and >10% [RAD 300 mg twice (n = 11), RAD 400 mg twice (n = 10), IM 400 mg once (n = 23)] were observed. In the IM 400 mg once group, patients with BCR-ABL1 ≤10% at 3 months showed a significant higher rate of MMR by 12 months compared with that of patients with BCR-ABL1 >10% (38.2% vs 13.0%, P = 0.028). In the RAD 300 and 400 mg twice group, an achievement of 3-month EMR was associated with a higher rate of MMR by 12 months [57.4% vs 18.2%, P = 0.016 (RAD 300 mg twice) and 50.7% vs 10.0%, P = 0.018 (RAD 400 mg twice)]. After adjusting for factors affecting achievement of MMR by 12 months on univariate analyses, multivariate analyses showed that b2a2 transcript type (RR of 0.46, P = 0.023), large spleen size (RR of 0.91, P = 0.001), and no achievement of 3-month EMR (RR of 0.24, P = 0.004) were predictor for not achieving MMR by 12 months. Significance of 3-month EMR for achieving MMR by 12 months was observed in the separated treatment groups: RR of 0.24, P = 0.037 in the IM 400 mg once group, RR of 0.17 P = 0.028 in the RAD 300 mg twice group, and RR of 0.11, P = 0.040 in the RAD 400 mg twice group. Conclusions: Our results suggest that 3-month EMR can play key roles for 12-month MMR achievement in CP CML patients treated with IM and RAD. In addition, some factors for achieving 12-month MMR were detected. To evaluate the long-term prognostic value of 3-month EMR, further clinical investigations in a larger patient population with longer follow-up are needed. Disclosures Kim: IL-YANG Pharm.Co.Ltd: Research Funding. Chung:Alexion Pharmaceuticals: Research Funding.
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Fatimah, Dini Destiani Siti, Asep Deddy Supriatna, and Rina Kurniawati. "Design of personnel information systems using rapid application development method." MATEC Web of Conferences 197 (2018): 03016. http://dx.doi.org/10.1051/matecconf/201819703016.
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Information system is a system that is interconnected and integrated with each other and aims to provide personnel information to support operations, management and decision-making functions within an organization. The purpose of this research is to build personnel information system with Rapid Application Development (RAD) method. The methodology used in this design is the RAD method which consists of identifying the objectives and information requirements, designing the system, building the system, and introducing the new system. This study is limited to the design stage only. The design result is a more effective and efficient employee information system design. The conclusion of this research is that the information system built with RAD method takes shorter time, but required good coordination between system designer with user.
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Zhang, Zhong-guo. "Recombinant adeno-viral human p53 gene combined with FOLFOX4 in the treatment of advanced colorectal cancer." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e14036-e14036. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14036.
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e14036 Background: Metastatic or recurrent colorectal cancers generally become unresectable and will not respond to radio- or chemo-therapy. Studies showed that p53 has a synergic effect with radio- or chemotherapy. This study is to determine the efficacy and safety of recombinant adenoviral human p53 gene (rAd-p53) combined with standard FOLFOX4 regimen in treatment of advanced colorectal cancer. Methods: From July 2008 to Dec. 2011, 56 patients with an advanced colorectal cancer or local recurrent disease were treated with rAd-p53 and standard FOLFOX4 regimen. For local tumor, 1-4×1012 viral particles (VP) of rAd-p53 diluted into 5 ml of saline solution was injected into tumor at multiple directions, once a week for 6 weeks. If tumor spreading into abdominal cavity, 4×1012 VPs diluted in 500 ml of saline solution were injected inraperitoneally, twice in 2 weeks. If having lung or liver metastasis, 2×1012 VPs diluted into 100 ml of saline solution were given intravenously twice in 2 weeks. Three days after the first gene therapy, the standard FOLFOX4 regimen was given for six cycles. Results: The follow-up time was 3~38 months with a median of 19.5 months. Among these patients, 8 (14.3%) patients were assessed as complete response, 31 (55.4%) as partial response and 11 (19.6%) as stable disease. After the combined treatment, a radical resection was successfully performed in 18 cases with local recurrent disease. All these patients were still alive at the last follow-up. Common adverse events were 38.4~40.5 oC self-limited fever, occurring in 86% patients. No serious adverse events were observed. Conclusions: rAd-p53 combined with FOLFOX4 is a safe and effective treatment for advanced colorectal cancer or local recurrent disease.
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Stübig, Thomas, Christian Langer, Monika Engelhardt, Lars-Olof Mügge, Florian Bassermann, Martin Schreder, Kerstin Schäfer-Eckart, et al. "Lenalidomide, Adriamycin and Dexamethasone (RAD) Versus Bortezomib, Lenalidomide and Dexamethasone (VRD) in Newly Diagnosed Multiple Myeloma (MM) - Post-Induction Response and MRD Results By Flow Cytometry and NGS from a Phase 3 Randomized Controlled Clinical Trial (RCT)." Blood 132, Supplement 1 (November 29, 2018): 1979. http://dx.doi.org/10.1182/blood-2018-99-116067.
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Abstract Introduction High-dose chemotherapy and stem cell transplant (SCT) remains a standard of care in medically fit patients (pts) with newly diagnosed (ND) MM. Induction triplets with at least one of the newer compounds are recommended. Bortezomib (V), lenalidomide (R) and dexamethasone (D; VRD) ranks among the most effective regimens and VRD/SCT was superior to VRD alone in an RCT. In a phase 2 study, we demonstrated RAD induction (lenalidomide 25 mg d1-21; Adriamycin 9 mg/m2 iv d1-4; dexamethasone 40 mg d 1-4 and 17-20 every 4 weeks) followed by SCT to be safe and effective (Knop et al., Leukemia 2017). Therefore, we decided to compare RAD versus (vs) VRD (lenalidomide 25 mg, d1-14; subcutaneous bortezomib 1.3 mg/m2 d 1, 4, 8, 11; dexamethasone 20 mg d 1+2, 4+5, 8+9, 11+12 every 3 weeks) induction (3 cycles each) in an RCT. MethodsThe current study was set up according to a double 2x2-factorial design to enrol transplant-eligible pts up to 65 years. The post-induction (PI) complete response (CR) rate as per IMWG criteria was the efficacy co-primary endpoint. We hypothesized the CR rate following RAD to be non-inferior to VRD which was estimated to be 20%. The study was powered to confirm non-inferiority of RAD at a margin of 10% with a one-sided alpha level of .05. Cytogenetic characterization was performed by fluorescence in situ hybridization (FISH) from CD138-enriched plasma cells. Minimal residual disease (MRD) was assessed by second-generation eight-color flow cytometry (FC; EuroFlow protocol). Bone marrow (BM) samples from baseline and defined restaging time points were analyzed for an acquisition of ⩾107cells/sample. In a subgroup of 103 pts, we evaluated the applicability of comprehensive immunoglobulin (Ig) amplicon next generation sequencing (NGS) to detect molecular MRD markers and to compare the results with FC. NGS-based marker screening was performed in baseline BM. Sequencing libraries were prepared using 2-step PCR employing multiplex primer sets for IGH V-D-J (FR1, FR2 and FR3), IGH D-J and IGK loci (V-J and KDe). For MRD detection, we used 1-step library preparation with the same primer sets. Results476 pts with a median age of 55 (range, 32-65) years were randomized between 05/2012 and 06/2016 and 469 received at least one dose of study drug. High-risk (HR) FISH abnormalities comprised del17p (11.3% of pts); t(4;14) (11.7%); and t(14;16) (4.5%). 232 pts were randomized to receive RAD, and 237 to VRD, respectively. 90.5% of RAD vs 93.7% of VRD pts completed all 3 cycles. PI CR rate was 13.5% (95% CI, 9.4%-18.7%) with RAD vs 13.4% (95% CI, 9.3-18.5) with VRD, (P=.971). Rates of ≥VGPR were 40.6% (50% CI, 34.2%-47.3%) with RAD vs 48.9% (95% CI, 42.3-55.6%) with VRD (P=.076). In pts with HR cytogenetics, rates of ≥VGPR were 43.3% (RAD) vs. 59.3% (VRD; P=.096). From 317 pts with paired samples, 33/151 (21.9%) of RAD vs 45/166 (27.1%) of VRD pts were FC MRD negative (P=.169) following induction at a median sensitivity level of 6.73x10-6. 197/239 positive pts (82.4%%) had MRD levels above 0.01%, and 42 (17.6%), between 0.0001 and 0.01%. Flow MRD negativity as per IMWG MRD criteria (Kumar et al, Lancet Oncol 2016) was seen in 8/151 (5.2%) pts with RAD vs 6/166 (3.6%) with VRD (P=.27). The remainder of pts did not (yet) fulfil IMWG CR for various reasons. NGS marker screening identified at least 1 Ig marker in 98/103 evaluable patients. To date, 47/98 pts were analyzed for NGS MRD following induction. Four out of 47 (8.5%) subjects were sequencing negative (3/4 post-VRD) with all of them also being IMWG FC MRD negative. One VRD patient died during induction for a mortality rate of 0.2 %. 62.1% of RAD vs 55.3% of VRD pts experienced at least one serious adverse event (SAE; p=.16). SAEs with relationship to study drugs of at least °3 severity occurred in 26.3% (RAD) vs 23.6% (VRD) pts (p=.523). ConclusionsTo the best of our knowledge, this is the first RCT to compare two R-based triplets in SCT-eligible pts. The co-primary efficacy endpoint was met with identical PI CR rates of around 13% for RAD and VRD, respectively. However, a trend emerges to favor VRD over RAD in terms of at least VGPR including HR FISH subjects. Analysis of MRD by multicolor FC showed 5% of pts to be already IMWG flow MRD-negative. Results for all 98 pts evaluable for NGS MRD will be presented. As of yet, too few progression events have occurred to estimate the second co-primary endpoint, 3-year progression-free survival. Longitudinal response and MRD analysis are ongoing. Disclosures Langer: Celgene: Consultancy. Mügge:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Amgen: Honoraria. Blau:Amgen: Other: Advisory board; BMS: Other: Advisory board; Novartis: Other: Advisory boards; Takeda: Other: Advisory board; Janssen: Other: Advisory board, Research Funding; Celgene: Other: Advisory board, Research Funding. Rollig:Janssen: Research Funding; Bayer: Research Funding. Dechow:AMGEN: Consultancy; Celgene: Honoraria. Gramatzki:Affimed: Research Funding. Brümmendorf:Merck: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Schmidt:Gilead: Honoraria, Other: Travel Grants; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Celgene: Honoraria. Knop:Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.
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Bontkes, Hetty J., Janneke J. Ruizendaal, Marco W. J. Schreurs, Duco Kramer, Chris J. L. M. Meijer, and Erik Hooijberg. "Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors." Analytical Cellular Pathology 27, no. 3 (January 1, 2005): 175–82. http://dx.doi.org/10.1155/2005/753549.
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Recombinant adenoviruses (RAd) and recombinant vaccinia viruses (RVV) expressing tumour-associated antigens (TAA) are used as anti-tumour vaccines. It is important that these vaccines deliver the TAA to dendritic cells (DC) for the induction of a strong immune response. Infection of myeloid DC (MDC) with RAd alone is relatively inefficient but CD40 retargeting significantly increases transduction efficiency and DC maturation. Infection with RVV is efficient without DC maturation. Plasmacytoid dendritic cells (PDC) play a role in the innate immune response to viral infections through the secretion of IFNα but may also play a role in specific T-cell induction. The aim of our study was to investigate whether PDC are better targets for RAd and RVV based vaccines. RAd alone hardly infected PDC (2%) while CD40 retargeting did not improve transduction efficiency, but it did increase PDC maturation (25% CD83 positive cells). Accordingly, specific CTL activation by RAd infected PDC was limited (the number of IFNγ producing CTL was reduced by 75% compared to stimulation with peptide loaded PDC). RVV infected PDC specifically stimulated CTL but PDC were not activated. These Results indicate that PDC are not ideal targets for RAd and RVV based vaccines. However, PDC induced specific CTL activation after pulsing with recombinant protein, indicating that PDC can also cross-present antigens released from surrounding infected cells.
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Perry, M. C., J. E. Herndon, W. L. Eaton, and M. R. Green. "Thoracic radiation therapy added to chemotherapy for small-cell lung cancer: an update of Cancer and Leukemia Group B Study 8083." Journal of Clinical Oncology 16, no. 7 (July 1998): 2466–67. http://dx.doi.org/10.1200/jco.1998.16.7.2466.
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PURPOSE To provide a 10-year update of the experience of the Cancer and Leukemia Group B (CALGB) in the addition of thoracic radiation therapy to chemotherapy in limited-stage small-cell lung cancer. PATIENTS AND METHODS Three hundred ninety-nine patients with limited-stage small-cell lung cancer were randomized to receive thoracic radiation therapy that started on day 1 (arm I) or day 64 of chemotherapy treatment (arm II), or chemotherapy alone with cyclophosphamide, vincristine, and etoposide (later, doxorubicin). Thoracic radiation therapy consisted of 4,000 rad to the tumor and mediastinum with a 1,000-rad boost. All patients received prophylactic cranial radiation to a dose of 3,000 rad. RESULTS Arm I patients had a median survival of 13.04 months, arm II patients 14.54 months, and arm III patients 13.58 months (log-rank test, P = .0072). Median time to clinical failure was 11 months in arm I, 11.21 months in arm II, and 8.7 months in arm III (log-rank test, P = .0004). CONCLUSION With 10 years of follow-up, the two arms that included thoracic radiation therapy remain superior to chemotherapy alone. The addition of thoracic radiation therapy to combination chemotherapy improved both complete response rates and survival, with increased but acceptable toxicity.
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Pritchett, Rachel, Jennifer Pritchett, Emma Marshall, Claire Davidson, and Helen Minnis. "Reactive Attachment Disorder in the General Population: A Hidden ESSENCE Disorder." Scientific World Journal 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/818157.
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Reactive attachment disorder (RAD) is a severe disorder of social functioning. Previous research has shown that children with RAD may have poor cognitive and language abilities; however, findings mainly come from biased, institutionalised samples. This paper describes the characteristics of all children who were given a suspected or likely diagnosis of reactive attachment disorder in an epidemiological study of approximately 1,600 children investigating the prevalence of RAD in the general population. We found that children with RAD are more likely to have multiple comorbidities with other disorders, lower IQs than population norms, more disorganised attachment, more problem behaviours, and poorer social skills than would be found in the general population and therefore have a complex presentation than can be described as ESSENCE. We discuss the clinical and educational implications.
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Kelly, William Kevin, Benjamin Leiby, David Johnson Einstein, Russell Zelig Szmulewitz, A. Oliver Sartor, Eddy Shih-Hsin Yang, and Guru Sonpavde. "Radium-223 (Rad) and niraparib (Nira) treatment (tx) in castrate-resistant prostate cancer (CRPC) patients (pts) with and without prior chemotherapy (chemo)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 5540. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.5540.
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5540 Background: Despite multimodality txs such as surgery, radiotherapy, hormonal tx and chemo, metastatic CRPC (mCRPC) prognosis remains poor. Research suggests PARP-1 is a key regulator of androgen receptor (AR) signaling and transition to lethal CRPC. Nira is a safe, potent and selective PARP-1/2 inhibitor that has shown single agent clinical activity in CRPC, and Rad is an alpha particle emitter. Addition of PARP inhibition may further enhance the clinical benefit of Rad. Nira has a favorable safety profile however, data on safety, tolerability and efficacy of Nira plus radiotherapy is limited. We hypothesize that targeting the PARP-1/AR axis in combination with radiation is safe and will improve mCRPC management. Methods: This is a phase (ph) Ib dose finding study (NCT03076203) of pts with progressive mCRPC using Time-to-Event Continual Reassessment Method (TITE-CRM). The primary objective is to determine the optimum ph II dose of Nira plus Rad (55 kBq/kg of body weight) in pts with and without prior chemo. Secondary endpoints include PSA reduction at 12 weeks (wks) and radiographic progression-free survival at 6 months. Pts enrolled to one of three dose levels of Nira (100, 200, and 300 mg PO daily). After completing 6 cycles of Rad, pts continued on Nira alone until objective progression, tx intolerance or pt decision. TITE-CRM identifies the maximum tolerated dose (MTD) based on toxicities observed over 12 wks of tx. Results: Between Oct 2017 and Jan 2020, 30 pts were enrolled (15 per stratum). Median age was 70 years; ECOG performance status was 0. The MTD of Nira was 100 mg in the chemo-exposed arm and 200 mg in the chemo-naïve arm. 19 Grade ≥ 3 adverse events were possibly related to tx: lymphocyte count decrease (n = 4, 13%), neutrophil count decrease (n = 3, 10%), anemia (n = 3, 10%), hypertension (n = 3, 10%), platelet count decrease (n = 2, 7%), creatinine increase (n = 1, 3%), hydronephrosis (n = 1, 3%), nausea (n = 1, 3%), white blood cell count decrease (n = 1, 3%). Tx duration and PSA response are shown in the table. Conclusions: Nira plus Rad was determined to be safe and tolerable. The MTD of Nira was identified and is pending ph II investigation. Managed by: Prostate Cancer Clinical Trials Consortium; Funded by: Janssen Scientific Affairs and Bayer Healthcare Pharmaceuticals, Inc Clinical trial information: NCT03076203 . [Table: see text]
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Haramina, Hrvoje, Marin Širol, Davor Sumpor, and Josip Petrlić. "Modeliranje dispečerskog sustava za podršku u upravljanju željezničkim prometom u kolodvorskom području temeljenog na neizrazitoj logici (fuzzy logic)." Sigurnost 62, no. 3 (October 2, 2020): 259–64. http://dx.doi.org/10.31306/s.62.3.4.
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SAŽETAK: Suvremeni pristup upravljanju željezničkim prometom na glavnim koridorima podrazumijeva centralizirano upravljanje željezničkim prometom. U tom je pristupu glavna uloga u upravljanju prometom povjerena dispečeru. Imajući za cilj smanjenje radnog opterećenja dispečera i istovremeno povećanje razine performanse i efikasnosti njegova rada, te veću učinkovitost upravljanja prometom, razvijaju se prikladni sustavi potpore u odlučivanju. Članak prikazuje model sustava podrške u upravljanju željezničkim prometom temeljen na umjetnoj inteligenciji. Predloženi model sustava temeljenog na neizrazitoj logici trebao bi u određenoj mjeri smanjiti negativan učinak različitih distraktora i nepovoljnih okolnosti u radnom i prometnom okruženju na rad dispečera.
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Steyvers, Kristof. "Doing Comparative Research on Local Politics." Hrvatska i komparativna javna uprava 19, no. 1 (March 28, 2019): 53–78. http://dx.doi.org/10.31297/hkju.19.1.3.
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Zagovara se potreba strožeg i sustavnijeg pristupa komparativnim istraživanjima lokalne politike, tj. istraživanjima koja se bave akterima, instrumentima, institucijama i procesima u lokalnom sustavu upravljanja. Navode se prednosti takvog pristupa (prisutne kad se metodologija istraživanja bavi deskriptivnim, eksplanativnim i pragmatičkim pitanjima) kao i njegovi nedostaci (mnogobrojne teorije srednjeg dometa i kompromisi nužno prisutni u metodologiji komparativnih istraživanja).Rad nudi pregled komparativnih istraživanja lokalne politike te specificira tri razvojne faze. Prve dvije faze se bave izazovom klasifikacije (gdje postoje deskriptivnija i eksplanativnija varijanta, a obje imaju temelje u starom institucionalizmu), dok se treća faza bavi teorijskim razvojem (i opis i objašnjenje imaju temelj u novom institucionalizmu). Za svaku se fazu navodi jedan ili više reprezentativnih slučajeva kako bi se predočila složenost i dostignuća svake faze. Što se tiče klasifikacije, u radu se nastoji prikazati kako klasični kategorijski pristup usmjeren na zapadne zemlje polako postaje raznovrsniji i uključuje slučajeve iz ostalih dijelova Europe. Istodobno postupno jača prisutnost unutarupravne perspektive, ponekad u kombinaciji s njenim ranijim ekvivalentom u integriranijim oblicima lokalne demokracije. Što se tiče teorijskog razvoja, dolazi do prijelaza s koncepta vladanja (governing) i njegovih varijanti na governance koncept te se suvremene analize sve se više bave posljedicama empirijski dokazanog udaljavanja od koncepta vladanja. Rad također nudi nekoliko prijedloga za poboljšanje istraživanja, posebno u pogledu tumačenja (primjerice višerazinsko s fokusom na lokalno upravljanje), teorija (predlaže se razvoj i provjera empirijskih implikacija ili prijedloga koji će biti održivi na više razina i unutar razina), oblikovanja (predlaže se iskoristiti dodanu vrijednost brojnosti i blizine predmeta istraživanja) i mjerenja (bavljenje pitanjima ekvivalencije).
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Zu, Maoheng, Qingqiao Zang, Ning Wei, and Wei Xu Xu. "Bronchial artery infusion of recombinant adenovirus-p53 and chemotherapeutic agents in treatment of bronchogenic carcinoma in advanced stage and failed to response to standard treatments." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e13004-e13004. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e13004.
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e13004 Background: Patients with advanced bronchogenic carcinoma (BC), who failed common standard treatments, poses a big challenge for clinicians. Here we report success cases of using bronchial artery infusion of recombinant adenovirus-p53 (rAd-p53) and chemotherapeutic agents in treatment of advanced BC failed to response to standard treatments. Methods: Sixteen patients with advanced unresectable BC, who failed standard chemo- and radio-therapy, were included in this study. There were 11 males and 5 Females with an average age of 59.4 years old. They received bronchial artery infusion of 2×1012 rAd-p53 viral particles (VP), 40 mg of cisplatin (PPD), 20 mg of pirarubicin (THP), 0.5 g of 5-Fu, and 30 mg of endostatin. The infusion was given daily for 3 days. Response rate and overall survival were evaluated. Results: At 3 months follow-up after the last infusion, the partial response rate was 68.8% (11/16). Symptoms like cough and short of breath were significantly relieved in those patients responding to the treatment. Overall survival rate of one year was 81.3% and median survival time was 11.6 months. No significant adverse events were found in those patients. Conclusions: Bronchial artery infusion of rAd-p53 combined with chemotherapeutic agents is effective and safe treatment for patients with advanced BC, who failed common standard treatments.
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Chen, Fei, and Feng Wang. "Recombinant adenoviral human p53 gene combined radio- and chemotherapy after a tumorectomy in treatment of laryngeal carcinoma in advanced stage." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 6050. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.6050.
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6050 Background: To investigate the benefits of post-surgery using recombinant adenoviral human p53 gene (rAd-p53) combined with radio- and chemo-therapy in treatment of laryngeal carcinoma in advanced stage. Methods: A total of 61 patients with a stage III or IV laryngeal cancer, 51 males and 10 females with an average age of 63.2, were randomly divided into three groups: G1, G2 and G3. The 18 G1 patients received no treatment after surgery. The patients in G2 (21 patients) and G3 (22 patients) received rAd-p53 followed by radio-and chemo-therapy, and only radio- and chemo-therapy, respectively. The rAd-p53 was injected into the surgery wound bed at a dose of 2 x 1012 viral particles (VP) once per 3 days for 5 times. Radiotherapy was given at a total dose of 63-67 Gy in 7 weeks. The chemo-regimen included 5- Fu 500 mg/ m2 from day 1 to day 5 and DDP 30 mg / m2 from day 1 to day 3 in a treatment course of 21days for two courses. Results: All the study patients were followed up for at least 3 years. One patient in G2 lost to follow up. The local control rates (no recurrence) at 3 years were 38.9% (7/18), 75.0% (15/20), and 54.5% (12/22) for G1, G2, and G3, respectively. The 3-years progress free survivals (PSF) were 38.9%, 50.0%, and 45.0% for G1, G2, and G3, respectively. The 3-years overall survivals (OS) were 38.9%, 65.0%, and 45.0% for G1, G2, and G3, respectively. The three efficacy endpoints of G2 were significantly better than both G1 and G3. These efficacy measures of G3 were significantly higher than G1. Conclusions: Post-surgery chemo- and radiotherapy is necessary to increase the local control rate, prolong both PRF and OS. The rAd-p53 gene therapy can farther increase the efficacy measures.
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Rao, R. D., J. B. Allred, H. E. Windschitl, W. J. Maples, R. R. McWilliams, E. T. Creagan, J. S. Kaur, et al. "N0377: Results of NCCTG phase II trial of the mTOR inhibitor RAD-001 in metastatic melanoma." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 8530. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.8530.
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8530 Background: RAD-001 (Everolimus) is an oral inhibitor of mammalian target of rapamycin (mTOR). Interim analysis results from a phase II study of RAD-001 in patients with metastatic melanoma (MM) were presented at ASCO 2005. This study was re-opened using a higher dose based on an improvement in the 16 week progression free survival (PFS) rate and good tolerability. Methods: A two- stage, phase II multi-institutional trial was conducted in patients with MM to assess that 16 weeks PFS rate was at least 50%. Inclusion criteria: measurable disease, ECOG performance score of 0–2. Exclusion criteria: presence of intracranial metastases, concurrent use of inducers of cytochrome 3A4 and abnormal organ function. The dose of RAD-001 in the second cohort was increased to 10 mg daily (increased from 30 mg weekly) based on evidence of safety of the higher dose. Results: Twenty-nine patients were enrolled; baseline information is available on 27. Median age was 63 yrs; 15 (56%) had >2 sites of metastatic disease. Most (48%) had stage M1c disease. PS was 0, 1 and 2 in 58%, 38% and 4%. All but 4 (15%) had received prior therapy. Grade 3 adverse events included stomatitis and fatigue (2 each), leukopenia, neutropenia, diarrhea, anorexia, dehydration, dyspnea, hyperglycemia, and hypersensitivity (1 each). Planned interim analysis was done after 20 patients were enrolled. 14 (70%) had progressed 16 weeks, failing to meet the decision rule needed (PFS >30%) to restart accrual. The median PFS for all 29 patients was 56 days. The median overall survival (OS) has not been reached. For the entire cohort of 53 pts treated on this study (at both dose levels), the median PFS, median OS were 59 and 286 days respectively. Conclusion: Interim analysis after enrollment of 20 patients at a higher dose of RAD-001 demonstrated significantly more toxicity and no added clinical efficacy. The 16 week PFS rate target was not reached, and accrual was suspended. No significant financial relationships to disclose.
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Wenger, Christa, Sara Lyn Crump, Jessica LaFollette, and Megan Kurtz. "Explorations of Family-school Relationships Regarding Children with RAD and/or EBD: A Review of Relevant Literature from 1995-2016." Open Family Studies Journal 9, no. 1 (October 10, 2017): 111–21. http://dx.doi.org/10.2174/1874922401709010111.
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Background: School and family interactions that include a focus on students from all backgrounds and ability levels are crucial for promoting students’ social, academic, and behavioral success. Specifically, it is important that educators and other stakeholders focus on developing effective interactions with the families of students who have Emotional and Behavioral Disorders (EBD) or Reactive Attachment Disorder (RAD). Objective: The aim of this study is to gain an understanding of the relationships between schools and the families of students with EBD or RAD as represented in published research. Another goal of this study is to understand whether these relationships have changed over time (1995-present). Method: This investigation sought to find empirical studies concerning relationships between schools and the families of students with EBD or RAD. The researchers divided the 1995-2016 time period into five- to-six-year increments and then searched for qualitative articles using agreed upon search terms. The authors used mainly the ERIC database from which to conduct their initial search. Results: There were 11 qualitative studies reviewed for this article. The articles were summarized and discussed according to two categories: “Families of Children with RAD” and “Families of Children with EBD.” Among these studies, three themes emerged in response to the research question: “The Importance of Caregivers,” “Family and School Communication,” and “Support Systems and Interventions.” These themes revealed critical ideologies regarding persons diagnosed with RAD or EBD and their family-school partnerships. Further, this review of literature indicates qualitative studies involving students with RAD or EBD in connection with family-school ties are limited, although a significant amount of literature exists regarding school-family ties. Conclusion: More qualitative studies are needed involving students with RAD and/or EBD and the connection to family-school relationships. The reviewed articles indicated that family-school partnerships depend on the landscape of the school system. Communication from the families to the schools and vice versa is important for persons with RAD or EBD diagnoses, as well as interventions and support systems. While this review does help to better understand these family–school partnerships, educators would benefit from additional studies during this time of the Common Core State Standards, increased accountability, inclusion, and high–stakes testing.
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Laleta, Sandra, and Darja Senčur Peček. "Atipični rad - izazovi zaštite od psihosocijalnih rizika i stresa na radu i u vezi s radom." Sigurnost 59, no. 4 (December 20, 2017): 315–30. http://dx.doi.org/10.31306/s.59.4.1.
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SUMMARY: Analysed in the paper are the atypical forms of employment and work organisation, with special accent on the work conditions and the protection of workers from psycho-social risks and work related stress, all in the light of the obligations of the EU member states and European social partners in this field of safety and health at work. The authors provide a comparative legal analysis and submit propositions de lege ferenda.
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Bachmann, Friederike, Martin Schreder, Monika Engelhardt, Christian Langer, Denise Wolleschak, Lars Olof Mügge, Heinz Dürk, et al. "Kinetics of Renal Function during Induction in Newly Diagnosed Multiple Myeloma: Results of Two Prospective Studies by the German Myeloma Study Group DSMM." Cancers 13, no. 6 (March 16, 2021): 1322. http://dx.doi.org/10.3390/cancers13061322.
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Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.
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Krivokuca, A., M. Cavic, E. Malisic, D. Kolarevic Ivankovic, R. Jankovic, and M. Brankovic-Magic. "456 RAD, TP53 and XRCC1 polymorphisms in triple-negative breast cancer." European Journal of Cancer 51 (September 2015): S97. http://dx.doi.org/10.1016/s0959-8049(16)30290-8.
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Hu, Kaiweng. "Recombinant adenoviral human p53 gene infusion in treatment of malignant pleural effusions and malignant ascites." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 3027. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3027.
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3027 Background: Malignant pleural or peritoneal effusions are frequently developed in the late-stage malignant tumors in chest or abdominal cavity. Various drainage methods and intra-cavity chemotherapy have transient and limited benefits. Here we evaluated the role of recombinant adenoviral human p53 gene (rAd-p53) infusion for patients with malignant pleural or peritoneal effusions. Methods: Thirty-two patients with historically diagnosed malignant pleural (18 cases) or peritoneal (14 cases) effusions, 19 males and 13 females with an average age of 61 years old (37–80 years), were included this study. The malignant pleural effusions were caused by primary lung cancers (8 cases), lung metastatic tumors (4 cases), breast cancers (3 cases), pleural mesothelioma (2 cases), lymphoma (1 cases), and the peritoneal effusions were caused by ovarian cancers (5 cases), primary liver cancers (4 cases), liver metastatic tumors (2 cases), colon cancer (1 case), gastric cancer (1 case), and prostate cancer (1 case). After draining most of the fluids, 4×1012 viral particles (VP) of rAd-p53 diluted into 1,000 ml of saline solution for intra-abdominal cavity infusion and 2×1012VP of rAd-p53 diluted into 500 ml of saline solution for intra-chest cavity infusion, were given weekly for 4 weeks. The response rate was evaluated. The complete response is defined as the complete disappearance of pleural or peritoneal fluid and negative cytologic findings for >4 weeks, and the partial response is defined as a decrease over 50% of the fluid without the need of drainage and negative cytologic findings for >4 weeks. Results: The pleural effusion showed a complete response in 6 patients (33.3%) and a partial response in 6 patients (33.3%). The peritoneal effusion had a complete response in 3 patients (21.4%) and a partial response in 7 patients (50.0%). The overall response rate was 68.8% (22/32). The symptoms associated with the malignant effusion relieved in 27 patients (84.4%). There were no serious side effects observed except for self-limited fever found in all the cases. Conclusions: Intra-abdominal or chest cavity infusion of rAd-p53 is a safe and effective treatment for some malignant pleural or peritoneal effusions.