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Journal articles on the topic 'TROG-2'

Author: Grafiati
Published: 4 June 2021
Last updated: 5 February 2022

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1

Matić, Ana, and Jelena Kuvač Kraljević. "Razumijevanje sintaktičkih struktura u odrasloj dobi – podatci s TROG-2." Logopedija 7, no. 2 (December 28, 2017): 42–48. http://dx.doi.org/10.31299/log.7.2.1.

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Ageing is a complex process characterised by numerous changes like sensory deficits, reduced working memory capacity, slowing of general perceptive and cognitive abilities and changes in language processing. As syntactic processing in adulthood is an understudied field in Croatian language, the main goal of this paper was to examine the comprehension of syntactic structures in adult age. For the purpose of this study TROG-2:HR Test for the reception of grammar (TROG-2:HR; Bishop, Kuvač Kraljević et al., 2014) has been used. The research aimed at inspecting the correlation between age and comprehension of different syntactic structures. Moreover, the goal was to observe the differences between three groups of adult participants, with the assumption that the differences will be manifested for complex structures only, with youngest participants outperforming the rest. There were 69 people in the younger group of participants (aged 18 to 39), 58 in the middle group (aged 40 to 64), and 32 in the older group (aged 65 to 87). The results indicate there is a significant correlation between age and 11 syntactic structures, some of which are also simple, which is contradictory to what was initially expected. This means that not only complex structures are susceptible to change with age. Also, between-group differences were observed in the comprehension of three complex and one simple structure, but only between younger and older and middle and older group. Overall findings are in line with prevailing studies which support the account that the ability of understanding complex syntactic structures declines with age.
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2

Facon, Bruno, and David Magis. "An Item Analysis of the French Version of the Test for Reception of Grammar Among Children and Adolescents With Down Syndrome or Intellectual Disability of Undifferentiated Etiology." Journal of Speech, Language, and Hearing Research 59, no. 5 (October 2016): 1190–97. http://dx.doi.org/10.1044/2016_jslhr-l-15-0179.

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Purpose An item analysis of Bishop's (1983) Test for Reception of Grammar (TROG) in its French version (F-TROG; Lecocq, 1996) was conducted to determine whether the difficulty of items is similar for participants with or without intellectual disability (ID). Method In Study 1, responses to the 92 F-TROG items by 55 participants with Down syndrome (DS), 55 with ID of undifferentiated etiology (UND), and 55 typical children (TYP) matched on their F-TROG total score were compared using the transformed item difficulties method, a statistical approach designed to detect differential item functioning (DIF) between groups. In Study 2, an additional comparison involving 526 TYP participants and 526 participants with UND was conducted to increase the statistical power of the analysis. Results The difficulty of items was highly similar whatever the sample size or clinical status of participants. Fewer than 3.5% of the items were flagged as showing DIF. Conclusions Tests such as the TROG can be used with confidence in clinical practice as well as in research studies comparing participants with or without ID. Methods designed for investigating potential internal test bias—such as done here—should be more regularly employed in the developmental disability field to affirm the absence of DIF.
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3

Hrastinski, Iva, Ljubica Pribanić, and Iva Mrvica. "Razumijevanje rječnika i gramatike učenika s kohlearnim implantatom." Logopedija 9, no. 1 (August 29, 2019): 1–8. http://dx.doi.org/10.31299/log.9.1.1.

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Kohlearnom implantacijom omogućeno je brojnoj djeci pohađanje redovnih obrazovnih programa te razvoj govornog jezika i akademskih vještina. Istraživanja pokazuju značajan pozitivan utjecaj kohlearne implantacije na razvoj govorne i jezične percepcije i ekspresije kod gluhe djece. Međutim, i dalje je značajan broj djece s kohlearnim implantatom, čija se razina receptivnog i ekspresivnog jezika razlikuje od njihovih čujućih vršnjaka. Kako je ova tema nedovoljno istražena u hrvatskom jeziku, glavni je cilj ovog istraživanja ispitivanje receptivnog vokabulara i razumijevanja sintaktičkih struktura kod korisnika kohlearnog implantata, učenika osnovnoškolske dobi od 3. do 8. razreda (N=10). U ovom preliminarnom istraživanju primijenjen je Peabody slikovni test rječnika PPVT-III HR (Dunn i sur., 2010) i Test razumijevanja gramatike TROG-2:HR (Bishop, Kuvač Kraljević i sur., 2014). Većina ispitanika (N=8) postigla je ispodprosječne rezultate na PPVT-III HR u odnosu na populaciju urednoga sluha. Samo dva ispitanika dostigla su rezultat iznad 16. centila. Prosječni broj točno riješenih blokova na TROG-2:HR je 8 (SD=5, min=3, max=19). Rezultati većine ispitanika (N=8) korespondiraju izrazito niskom postignuću (manje ili jednako 1. centilu). Dva ispitanika postigla su visoko prosječni rezultat (55. centil) i visoki rezultat (90. centil) na ovom testu. Usporedbom prosječnih standardiziranih rezultata na testu rječnika i gramatike, s obzirom na kronološku i slušnu dob ispitanika, uočava se da su rezultati ispitanika u odnosu na čujuće vršnjake izrazito lošiji. Međutim, uspoređujući gluhe ispitanike s mlađim čujućim učenicima, izjednačenim po slušnoj dobi, rezultati na PPVT-III HR usporedivi su s rezultatima čujućih. Međutim, prosječni rezultat na TROG-2:HR još je neadekvatan. Ovakvi nalazi mogu ukazivati da morfosintaktičke teškoće perzistiraju u ovoj populaciji i više su otporne na logopedsku intervenciju.
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4

CROOT, KAREN, JOHN R. HODGES, and KARALYN PATTERSON. "Evidence for impaired sentence comprehension in early Alzheimer's disease." Journal of the International Neuropsychological Society 5, no. 5 (July 1999): 393–404. http://dx.doi.org/10.1017/s1355617799555021.

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We investigated sentence comprehension in 46 patients with probable minimal (very mild), mild, or moderate dementia of the Alzheimer type (DAT), comparing their performance on the Test for the Reception of Grammar (TROG), with that of 20 age- and education-matched controls. Performance on the TROG was generally related to dementia severity, independent of lexicosemantic and working memory (digit span) impairments, but related to at least 1 measure of attention. Some patients in the minimal group showed sentence comprehension deficits while others in the moderate group did not, indicating that DAT may impair sentence comprehension at the very earliest stages of disease, but that its effects are heterogeneous. Patients were most impaired on sentences with 2 propositions and noncanonical word order, suggesting difficulties with both interpretative and postinterpretative stages of sentence processing. Further investigation is needed into the relationship between attentional processes, interpretative and postinterpretative stages of syntactic processing in DAT. (JINS, 1999, 5, 393–404.)
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5

Garraffa, Maria, and Esler Megan. "First simple makes last complex. Construct-irrelevant variance effects in the test of grammatical comprehension TROG-2." Aphasiology 32, sup1 (July 26, 2018): 64–66. http://dx.doi.org/10.1080/02687038.2018.1487917.

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6

Matthews, John H. L., Bryan H. Burmeister, Martin Borg, Anne L. Capp, David Joseph, Kerin M. Thompson, Paul I. Thompson, Jennifer A. Harvey, and Nigel A. Spry. "T1-2 anal carcinoma requires elective inguinal radiation treatment – The results of Trans Tasman Radiation Oncology Group study TROG 99.02." Radiotherapy and Oncology 98, no. 1 (January 2011): 93–98. http://dx.doi.org/10.1016/j.radonc.2010.10.005.

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7

Penniment, Michael Gordon, Paolo De Ieso, Rebecca Wong, and Hossein Afzali. "An economic evaluation of palliation of dysphagia in esophageal cancer: Analysis of the TROG 03.01/NCIC ES.2 phase III study in advanced esophageal cancer in patients treated with radiotherapy versus chemoradiotherapy." Journal of Clinical Oncology 38, no. 4_suppl (February 1, 2020): 340. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.340.

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340 Background: In advanced oesophageal cancer (OC), 90% of patients have dysphagia as a principal symptom. The randomised TROG 03.01 trial reported no significant overall survival or dysphagia relief difference between 15 fractions (#) radiotherapy alone (RT) or RT plus chemotherapy (CRT) Future studies may consider RT hypofractionation, different chemotherapy, esophageal stenting, and best supportive care. Comparing costs and outcomes, economic evaluation often informs public funding decisions in countries such as Australia and the UK. The objective of this analysis was to derive baseline cost and outcome for further studies. Methods: Given equal outcomes (non-inferiority) between treatment arms, cost-minimisation analysis (CMA) was used to evaluate cost-effectiveness, cost a deciding factor if no other benefit was predicted. We explored 15 and 10 # courses used in TROG 03.01 and alternatives, 1 or 5 # Study design and uncertainty analyses were provided. Sub-analysis assessed salvage therapy for local and systemic progression. The EQ-5D (and SF-12) was used to determine utility values to estimate Quality-Adjusted Life years (QALYs) for evaluation. Results: From a health system perspective, costs and outcomes of RT were estimated at $4,700 AUD (15 # course). If, compared with RT alone, an alternative option is more costly but more effective, then a cost-utility analysis (CUA) is preferred economic evaluation. Intervention and in/outpatient costs, initial phase and post treatment were considered for stent insertion and alternative chemotherapy regimens. Alternatively, autocontoured CT planning and machine learning were modelled to reduce RT planning cost (est. $650/p). Total cost for 5 # is $3200 could be further reduced through process efficiency savings using CMA approach. Conclusions: The value of palliative approaches in common malignancies is difficult to assess. This study uses economic analysis to guide paying authority decisions. RT can be simplified from the TROG 03.01 approach to lessen cost and simplify treatment. The clinical efficiency of 1 or 5 # should be evaluated.
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8

O'Brien, P. C., D. Roos, K. Liew, G. Pratt, M. Barton, M. Poulsen, I. Olver, and G. Trotter. "2099 A trans-tasman radiation oncology group (TROG) phase 2 study of a simple combined modality regimen using methotrexate and irradiation in primary CNS lymphoma." International Journal of Radiation Oncology*Biology*Physics 45, no. 3 (January 1999): 328. http://dx.doi.org/10.1016/s0360-3016(99)90369-3.

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9

Macann, A. M. J., T. Fua, C. G. Milross, S. Porceddu, M. G. Penniment, C. Wratten, H. Krawitz, et al. "Influence of Domiciliary Humidification on Symptom Burden and Feeding Tube Use Up to 2 Years Postradiation Therapy for Head and Neck Cancer: Trans-Tasman Radiation Oncology Group (TROG) 07.03 RadioHUM Randomized Phase 2 Trial Secondary Analysis." International Journal of Radiation Oncology*Biology*Physics 96, no. 2 (October 2016): S217—S218. http://dx.doi.org/10.1016/j.ijrobp.2016.06.540.

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Leong, Trevor, Mark Smithers, Michael Michael, Val Gebski, Alex Boussioutas, Danielle Miller, John Raymond Zalcberg, Rebecca Wong, and Karin Haustermans. "TOPGEAR: An international randomized phase III trial of preoperative chemoradiotherapy versus preoperative chemotherapy for resectable gastric cancer (AGITG/TROG/EORTC/NCIC CTG)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): TPS4141. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.tps4141.

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TPS4141 Background: Optimal management of patients with resectable gastric cancer remains unknown. Since the INT0116 and MAGIC trials, there are 2 standards of care for adjuvant therapy: postoperative chemoradiotherapy (CRT) and perioperative ECF chemotherapy. The important question arising from these studies is whether CRT is superior to chemotherapy alone as adjuvant therapy. This randomized phase II/III trial will compare CRT to chemotherapy alone in the preoperative setting. Methods: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either preoperative chemotherapy alone (ECFx3 as per MAGIC regimen) or preoperative CRT (ECFx2 followed by 45Gy of radiation with concurrent 5-FU). Following surgery, both groups will receive 3 further cycles of ECF. The trial is being conducted in two Parts; Part I (phase II component) will recruit 120 patients with the aim of demonstrating sufficient efficacy and safety of preoperative CRT, as well as trial feasibility. Part II (phase III component) will recruit a further 632 patients to provide a total of 752. The primary endpoint for Part I is pathological complete response rate, and for Part 2 it is overall survival. The trial includes formal quality of life and biological sub-studies. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique. Current status: This study is an international, intergroup trial led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. To date, 36 patients have been recruited from 20 sites in Australia and New Zealand; European and Canadian sites will commence recruitment in 2012.
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Mitchell, Paul, Shankar Siva, Peey Sei Kok, Ken O'Byrne, Annie Yeung, Ann Livingstone, Mark Donoghoe, Sonia Yip, and Martin R. Stockler. "NIVORAD: A randomised phase 2 trial of nivolumab and stereotactic ablative body radiotherapy in advanced non-small cell lung cancer, progressing after first or second line chemotherapy." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): TPS9097. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.tps9097.

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TPS9097 Background: Recent data has demonstrated improvements in overall survival in patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab. Radiation may augment the immune response through abscopal effects - evidence of tumour control at sites other than those irradiated. We hypothesize that the addition of stereotactic ablative body radiotherapy (SABR) to immunotherapy with nivolumab will improve progression free survival (PFS) compared with nivolumab alone. Methods: DESIGN: Open label, randomised phase II trial with 25 sites across Australia and New Zealand. ELIGIBILITY: Metastatic NSCLC progressing after 1 or 2 lines of chemotherapy with an extrapulmonary metastasis suitable for SABR. STRATIFICATION: Age, lines of chemotherapy, histology and treating institution. TREATMENT: A single dose of SABR (18-20Gy) plus nivolumab or nivolumab alone (240mg 2-weekly) given until disease progression or prohibitive adverse events. ENDPOINTS: PFS at 6 months (PFS6; primary), objective tumour response rate, adverse events, overall survival, PFS at 1 and 2 years. Tertiary correlative objectives include associations between possible prognostic/ predictive biomarkers and outcomes (including PD-L1 expression). STATISTICS:Total sample size of 120 participants allocated in a ratio of 2:1, 80 to nivolumab + SABR and 40 nivolumab alone to provide 80% power, one-sided type I error rate of 5% for PFS6 of 50% (worthy of pursuit) vs 35% (not worthy of pursuit). BIOSPECIMENS: Tumour tissue and serial bloods (4 time points) will be collected for translational research. CURRENT ENROLLMENT (as of Feb 2017): 2 out of 20 sites are open. NIVORAD is an investigator-initiated, cooperative-group trial led by the ALTG in collaboration with the NHMRC Clinical Trials Centre, University of Sydney and the Trans Tasman Radiation Oncology Group (TROG). Australian New Zealand Clinical Trials Registry: ACTRN12616000352404.
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Ringash, Jolie, Richard Fisher, Lester J. Peters, Brian O'Sullivan, Andy Trotti, Lizbeth M. Kenny, Richard J. Young, and Danny Rischin. "Impact of p16 status on the QOL effects of chemoradiation for locally advanced oropharynx cancer: Results of TROG 02.02." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 5571. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.5571.

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5571 Background: We report the impact of p16 status on quality of life (QOL) for patients with stage III or IV (excluding T1-2N1 and M1) squamous cell carcinoma of the oropharynx (OPC) treated with concurrent chemoradiotherapy in a large international phase III trial (TROG 02.02/HeadSTART). Methods: The 861 patients accrued received definitive radiotherapy (RT) (70 Gy/7 weeks) concurrently with 3 cycles of either cisplatin (100mg/m2) or cisplatin (75 mg/m2) plus tirapazamine (290 mg/m2/day) by random assignment, as previously described. QOL was measured with the FACT-H&N at baseline, 2,6,12, 23 and 38 months. No significant difference in overall or subscale QOL score change from baseline was observed between arms at any subsequent time point; results for the oropharynx subgroup by p16 status are reported for both treatment arms combined. Results: Of 853 eligible participants, 465 had OPC, for whom p16 status could be determined in 206. Of 179 who received adequate RT (≥ 60 Gy, no major deviations) and completed baseline QOL, 104 were p16+ and 79 were p16-. p16+ patients had better baseline ECOG PS, lower T-category, higher N-category, were younger and were less likely to be current smokers. Baseline mean FACT-H&N score was statistically and clinically significantly better in p16+ patients (111 vs. 102, p=0.001). The drop in QOL from baseline to 2 months was more severe in p16+ cases (-20.4 vs -9.1, p=0.001), resulting in an equalization of 2 month scores (p16+: 90.6, p16-: 93.6, p=0.16). At 6 and 12 months post-treatment, no difference in score changes from baseline by p16 status was seen (6 mo, p16+: -6.2, p16 -:-1.2, p=0.22; 12 mo, p16 +: -0.3, p16 -: +2.0, p=0.82). Conclusions: p16 associated oropharyngeal cancer has been shown to be a distinct entity with different demographic features. In our study, such patients exhibited better baseline QOL and a more severe drop immediately after treatment, but did not differ in long-term QOL response to the effects of aggressive concurrent chemoradiation. Given the favorable prognosis of p16-associated oropharyngeal cancer, efforts to reduce the QOL burden of treatment are warranted.
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O'Brien, P. C., D. R. Roos, G. Pratt, K. Liew, M. Barton, M. Poulsen, I. Olver, and G. Trotter. "712 Improved survival at the cost of neurotoxicity in primary CNS lymphoma (PCNSL). Long-term follow-up of a Phase 2 multicentre combined modality study (Trans-Tasman Radiation Oncology Group-TROG)." European Journal of Cancer Supplements 1, no. 5 (September 2003): S214. http://dx.doi.org/10.1016/s1359-6349(03)90743-9.

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14

May-Mederake, Birgit, and Wafaa Shehata-Dieler. "A Case Study Assessing the Auditory and Speech Development of Four Children Implanted with Cochlear Implants by the Chronological Age of 12 Months." Case Reports in Otolaryngology 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/359218.

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Children with severe hearing loss most likely receive the greatest benefit from a cochlear implant (CI) when implanted at less than 2 years of age. Children with a hearing loss may also benefit greater from binaural sensory stimulation. Four children who received their first CI under 12 months of age were included in this study. Effects on auditory development were determined using the German LittlEARS Auditory Questionnaire, closed- and open-set monosyllabic word tests, aided free-field, the Mainzer and Göttinger speech discrimination tests, Monosyllabic-Trochee-Polysyllabic (MTP), and Listening Progress Profile (LiP). Speech production and grammar development were evaluated using a German language speech development test (SETK), reception of grammar test (TROG-D) and active vocabulary test (AWST-R). The data showed that children implanted under 12 months of age reached open-set monosyllabic word discrimination at an age of 24 months. LiP results improved over time, and children recognized 100% of words in the MTP test after 12 months. All children performed as well as or better than their hearing peers in speech production and grammar development. SETK showed that the speech development of these children was in general age appropriate. The data suggests that early hearing loss intervention benefits speech and language development and supports the trend towards early cochlear implantation. Furthermore, the data emphasizes the potential benefits associated with bilateral implantation.
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Ball, J. "Osteopenia (OP) induced by 6 and 18 months androgen deprivation (AD)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 5123. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.5123.

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5123 Background: In a trial evaluating the optimal duration of AD in locally advanced prostate cancer (PC) we sought to determine whether 18 months of zoledronate (Zd) would reverse AD induced OP and reduce bony failure. Methods: In the four arm 2x2 TROG 03.04 (RADAR) trial, men with T2b,c-4 and T2a (Gleason score >6, PSA >10) N0 M0 PC (but without osteoporosis) were randomised to leuprotide (Lp) 22.5 mgs i.m. 3 monthly for 6 months starting 5 months prior to radiotherapy (RT) in Arm A, or the same treatment with Zd mgs i.v.i. 3 months for 18 months commencing on Day 1 (in Arms B and D), or with Lp 22.5 mg i.m. 3 monthly for 12 months after RT (in Arms C and D). Hip and spinal bone mineral densities (BMD) were measured before treatment (bt) and then at 2 and 4 years using DEXA and differences between trial arms were assessed by paired t tests. OP was defined by T- scores <-1. Results: Between October 2003 and January 2006, 930 men were randomized. 124 men with BMD measures bt and at 2 years are evaluable. Mean change (±SD) in BMD between 0 and 2 years was -0.005 ±0.05 (p=0.57) in Arm A, 0.085 ±0.06 (p=<0.001) in Arm B, 0.054 ±0.07 (p=<0.001) in Arm C, and 0.065 ±0.05 (p=<0.001) in Arm D. 98 men had normal BMD bt. Of these 6 of 51 in Arms A, C (no Zd) have developed OP at 2 years while none of 47 in Arms B, D (+Zd) have as yet. Conclusions: At 2 years OP caused by 6 months AD is minimal, but remains significant after 18 months AD. This is reversed by 18 months Zd, but further follow up will determine whether this degree of OP resolves with time or causes fractures. No significant financial relationships to disclose.
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King, Madeleine T., Emma K. Link, Tim J. Whelan, Ivo A. Olivotto, Ian Kunkler, Antonia Helen Westenberg, Guenther Gruber, et al. "Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial." Lancet Oncology 21, no. 5 (May 2020): 685–98. http://dx.doi.org/10.1016/s1470-2045(20)30085-1.

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Krilčić, Paula, Sanja Šimleša, Marina Olujić, and Jelena Kuvač Kraljević. "Povezanost izvršnih funkcija i jezika u odrasloj dobi." Suvremena psihologija 20, no. 1 (June 12, 2017): 53–69. http://dx.doi.org/10.21465/2017-sp-201-04.

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Brojna istraživanja upućuju na povezanost izvršnih funkcija i jezika. Ipak, zbog složenosti izvršnih funkcija, teškoća u njihovu definiranju i ispitivanju, točna priroda te veze još uvijek nije poznata. Većina dosadašnjih istraživanja izvršnih funkcija temelji se na dječjem jezičnom razvoju ili jezičnom razvoju kod specifičnih populacija. S obzirom na to da su i jezik i izvršne funkcije s obzirom na dob osjetljivi konstrukti, za spoznaje o dinamici njihova odnosa nužno je istraživanja proširiti i na odraslu dob. U skladu s time, cilj je ovog istraživanja bio ispitati povezanost pojedinih sastavnica izvršnih funkcija s jezičnim razumijevanjem u odrasloj dobi. Sudionici su bili odrasle osobe (N = 30) u dobi između 21 i 37 godina. Izvršne funkcije prostornog radnog pamćenja, prostornog planiranja, kognitivne fleksibilnosti i kognitivne inhibicije ispitane su CANTAB baterijom testova, a verbalno radno pamćenje ispitano je podljestvicom Pamćenje raspona brojeva WAIS-III testa. Jezične sposobnosti ispitane su Peabody slikovnim testom rječnika (PPVT-III-HR) i Testom razumijevanja gramatike (TROG-2:HR). Rezultati regresijske analize pokazali su doprinos izvršnih funkcija u razumijevanju složenih, ali ne i jednostavnih rečenica, niti riječi. Dobiveni rezultati mogli bi značiti da je potreba za izvršnim funkcijama tijekom jezične obrade u odrasloj dobi ograničena na razumijevanje složenijih sintaktičkih struktura koje predstavljaju veće opterećenje za obradu. Takvi rezultati u skladu su s rezultatima sličnih stranih istraživanja, no za donošenje konačnih zaključaka potrebno je uključiti ispitanike starijih dobnih skupina i varirati veći broj struktura različite razine sintaktičke složenosti. Ključne riječi: izvršne funkcije, jezik, receptivni rječnik, razumijevanje rečenica, odrasla dob
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Sahgal, A., S. D. Myrehaug, S. Siva, L. Masucci, M. C. Foote, M. Brundage, J. Butler, et al. "CCTG SC.24/TROG 17.06: A Randomized Phase II/III Study Comparing 24Gy in 2 Stereotactic Body Radiotherapy (SBRT) Fractions Versus 20Gy in 5 Conventional Palliative Radiotherapy (CRT) Fractions for Patients with Painful Spinal Metastases." International Journal of Radiation Oncology*Biology*Physics 108, no. 5 (December 2020): 1397–98. http://dx.doi.org/10.1016/j.ijrobp.2020.09.019.

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Penniment, Michael Gordon, Jennifer A. Harvey, Rebecca Wong, Sonya Stephens, Heather-Jane Au, Christopher J. O'Callaghan, Andrew Kneebone, et al. "A randomized phase III study in advanced esophageal cancer (OC) to compare the quality of life (QoL) and palliation of dysphagia in patients treated with radiotherapy (RT) or chemoradiotherapy (CRT) TROG 03.01 NCIC CTG ES.2." Journal of Clinical Oncology 32, no. 15_suppl (May 20, 2014): 4009. http://dx.doi.org/10.1200/jco.2014.32.15_suppl.4009.

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Trinh, Bùi Phương, Nguyễn Ngọc Thành, Nguyễn Đình Phương Quyên, Đặng Thanh Hàng, and Lê Anh Tuấn. "Nghiên cứu ảnh hưởng của nhiệt độ dưỡng hộ ban đầu đến cường độ nén của hệ nền xi măng chứa tro bay được hoạt hóa bằng natri sulfat." Tạp chí Khoa học Công nghệ Xây dựng (KHCNXD) - ĐHXD 15, no. 1V (March 23, 2021): 17–28. http://dx.doi.org/10.31814/stce.nuce2021-15(1v)-02.

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Nghiên cứu này tập trung đánh giá ảnh hưởng của nhiệt độ dưỡng hộ ban đầu đến cường độ nén của hệ nền xi măng chứa 0 và 40% tro bay được hoạt hóa bằng natri sulfat (Na2SO4). Hàm lượng Na2SO4 là 0 và 4% theo khối lượng chất kết dính. Sau 24 h, các mẫu được dưỡng hộ ở các nhiệt độ khác nhau (27±2 oC, 60 oC và 100 oC trong lò sấy) trong 6 h. Dưỡng hộ ban đầu ở nhiệt độ cao đã cải thiện cường độ nén ở 3 ngày tuổi của mẫu chứa tro bay được hoạt hóa bằng Na2SO4. Tuy nhiên, cường độ nén ở 7 ngày và 28 ngày tuổi của các mẫu này lại thấp hơn khi so với mẫu được dưỡng hộ ở 27±2 oC. Điều này chứng tỏ rằng dưỡng hộ ban đầu ở nhiệt độ cao đã ảnh hưởng bất lợi đến cường độ nén về sau của hệ nền xi măng chứa tro bay được hoạt hóa bằng Na2SO4. Từ khóa: chất hoạt hóa; cường độ nén; độ linh động; hệ nền xi măng; natri sulfat; nhiệt độ dưỡng hộ ban đầu; thời gian ninh kết; tro bay.
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Perry, James R., Christopher J. O'Callaghan, Keyue Ding, Wilson Roa, Warren P. Mason, J. Gregory Cairncross, Alba Ariela Brandes, et al. "A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): TPS2104. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.tps2104.

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TPS2104 Background: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly diagnosed GBM found improved survival with concomitant and adjuvant temozolomide (TMZ) added to radiotherapy (RT). Study pts were 18-71 (median 56) years; however a sub-group analysis noted a trend of decreasing benefit from the addition of TMZ with increasing age, such that for age 65-71, the hazard ratio of 0.8 did not reach statistical significance (p=0.340). Recent RCTs in elderly GBM found improved survival with RT compared to supportive care alone and detected non-inferiority of 40 Gy/15 vs. a 60 Gy/30 RT regimen. Based upon these results short-course hypofractionated RT is often recommended for elderly pts. However, whether the addition of TMZ to RT confers a survival advantage in elderly pts remains unanswered. Methods: Patients ≥65 yrs of age with histologically confirmed newly diagnosed glioblastoma, ECOG 0-2, are randomized 1:1 to receive 40Gy/15 RT vs. 40Gy/15 RT with 3 weeks of concomitant temozolomide plus monthly adjuvant TMZ until progression or 12 cycles. Stratification is by centre, age (65-70, 71-75, or 76+), ECOG 0,1 vs 2, and biopsy vs resection. For 90% power to detect a 25% reduction in the primary outcome of overall survival (increased MST from 6 to 8 months) between arms, using a two-sided 5% alpha, a minimum of 520 deaths must be observed prior to analysis; total sample size is 560 patients. The trial is open in Canada (NCIC CTG), Europe (EORTC), Australia and New Zealand (TROG), and Japan. As of Jan 25, 2012, 361 (65%) of the target 560 pts were randomized (147 Canada, 144 Europe, 64 Australasia, 6 Japan). Median age of randomized patients is 73 (65-88) years. A planned futility analysis after 120 events by the independent DSMB resulted in a recommendation that the trial continue.Accrual is expected to be complete in 2013. A comprehensive molecular companion analysis, including MGMT promoter methylation, is planned.
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Cicchetti, Alessandro, Tiziana Rancati, Martin Ebert, Claudio Fiorino, Angel Kennedy, David John Joseph, James William Denham, Vittorio Vavassori, Giovanni Fellin, and Riccardo Valdagni. "Modeling severe late rectal bleeding: Results on a large pooled population of prostate cancer patients." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 82. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.82.

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82 Background: To develop a model for grade 3 (G3) late rectal bleeding (LRB) after radical radiotherapy (RT) for prostate cancer, in a pooled population from 2 large prospective trials: Airopros0102 (Fellin RO2014) and TROG 03.04 RADAR (Ebert IJROBP2015). Methods: Both trials included patients (pts) treated with 3DCRT at 66-80Gy, conventional fractionation. Planning data were available for all pts, G3 LRB was prospectively scored using the SOMA/LENT, with a minimum follow-up of 3 years. Rectal dose-volume histograms were reduced to Equivalent Uniform Dose (EUD) calculated with volume parameter n derived by 3 studies: n=0.06 (Rancati RO2004), n=0.05 (Rancati RO2011) and n=0.018 (Defraene IJROBP2011). EUD was inserted into multivariable logistic regression (MVL) together with clinical and treatment features. Irradiation of seminal vesicles (SV), irradiation of pelvic nodes, hormonal therapy, hypertension, previous abdominal surgery (SURG), use of anticoagulants, diabetes, cardiovascular diseases and presence of acute toxicity were considered as potential dose-modifying factors. Goodness of fit was evaluated with Hosmer Lemeshow test (HL), calibration through calibration slope and AUC was used for discrimination power. Results: 1,337 pts were available: 708 RADAR and 669 Airopros. G3 LRB was scored in 95 pts (7.1%): 62 RADAR and 33 Airopros. EUD calculated with n=0.05 was the best dosimetric predictor for G3 LRB. A 4-variable MVL model was fitted including EUD (OR=1.07 p=0.16), SV (OR=4.75 p<0.001), SURG (OR=2.30 p=0.02) and cardiovascular disease (OR=1.42 p=0.18). AUC=0.63, calibration slope=0.99 (R^2=0.89), p for HL=0.43. Inclusion of acute toxicity (OR=2.34 p<0.001) slightly improved AUC (0.65), confirming a possible role of consequential injury. Conclusions: EUD with n=0.05 was predictive of G3 LRB in this pooled population, confirming the importance of sparing the rectum from high doses. Irradiation of seminal vesicles together with the presence of cardiovascular disease and previous abdominal surgery were relevant dose-modifying factors highly impacting the incidence of G3 LRB. The study was funded by: AIRC IG16087, Fondazione Monzino, NHMRC (300705, 455521, 1006447)
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Chính, Nguyễn Văn, and Phạm Công Tuấn Trung. "Nghiên cứu thực nghiệm khả năng chống xâm thực axit của bê tông sử dụng xỉ lò cao và tro bay." Tạp chí Khoa học Công nghệ Xây dựng (KHCNXD) - ĐHXD 15, no. 3V (July 17, 2021): 79–92. http://dx.doi.org/10.31814/stce.nuce2021-15(3v)-07.

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Bài báo trình bày kết quả nghiên cứu thực nghiệm ảnh hưởng của xỉ lò cao S95 và tro bay loại F từ nhà máy nhiệt điện Vũng Áng đến khả năng chống xâm thực axit của bê tông. Tỉ lệ các thành phần cấp phối là chất kết dính : cát : đá : nước = 1 : 2 : 3 : 0,6. Xi măng portland được thay thế bởi xỉ lò cao S95 và tro bay loại F với tổng tỉ lệ thay thế theo khối lượng là 20%, trong khi chất kết dính được định nghĩa bằng tổng của xi măng, xỉ lò cao và tro bay. Thí nghiệm về khả năng chống xâm thực axit sunfuric được thực hiện trên mẫu lập phương kích thước 100 × 100 × 100 mm sau khi ngâm 28, 56 và 90 ngày. Kết quả thí nghiệm cho thấy rằng nằm trong giới hạn nghiên cứu, xỉ lò cao và tro bay đều góp phần nâng cao độ linh động của vữa bê tông. Xỉ lò cao và tro bay đều nâng cao khả năng chống xâm thực axit của bê tông thông qua việc giảm sự hư hại bề mặt, giảm sự hao hụt khối lượng và sự suy giảm cường độ chịu nén. Ngoài ra, khả năng chống xâm thực axit sunfuric của tro bay lớn hơn so với xỉ lò cao.
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Tabatabai, Ghazaleh, and Michael Weller. "Bevacizumab plus radiotherapy for elderly patients with glioblastoma (ARTE)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): TPS2105. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.tps2105.

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TPS2105 Background: The standard of care for patients with newly diagnosed glioblastomas after surgical resection is radiotherapy with concomitant and adjuvant temozolomide chemotherapy. Yet, inclusion into the pivotal trial was limited to patients up to the age of 70, and subgroup analyses suggested that older patients did not gain benefit from combined modality treatment. Further, the efficacy of radiotherapy has been confirmed in a randomized trial comparing best supportive care versus radiotherapy alone. Of note, hypofractionated radiotherapy is equieffective in patients aged 65-70 years and more. Two randomized trials in elderly patients (NOA-08, Nordic Trial) indicated smilar efficacy of primary temozolomide chemotherapy alone compared with radiotherapy alone. Combined radiochemotherapy is compared with radiotherapy alone in an ongoing NCIC-CTG EORTC TROG Japanese group trial 26062-22061. Thus, radiotherapy alone is the standard of care for newly diagnosed glioblastoma of elderly patients. These clinical data justify the exploration of new, temozolomide-free first-line treatment strategies in elderly patients. Methods: The ARTE trial will therefore investigate bevacizumab when added to a short course of radiotherapy and bevacizumab maintenance therapy until progression. The translational research program shall include blood and urine biomarker analysis and FET-PET in addition to MRI for monitoring the course of the disease. This trial is an explorative randomized, non-comparative phase II trial aiming at recruiting 60 patients in Switzerland. Elderly patients (> 65) will be randomized 2:1 either to the experimental arm (bevacizumab plus radiotherapy) or the standard arm (radiotherapy). The primary endpoint is median overall survival. Secondary endpoints include overall survival at 6 months, overall survival at 12 months, median progression-free survival, progression-free survival at 6 months, median time to treatment failure.
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Nguyễn Tấn, Khoa, and Sang Nguyễn Thanh. "Tính chất cơ học và độ bền của bê tông cát xỉ lò cao và khả năng ứng dụng trong công trình biển." Transport and Communications Science Journal 71, no. 5 (June 28, 2020): 568–82. http://dx.doi.org/10.25073/tcsj.71.5.9.

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Tro bay và xỉ lò cao là các loại vật liệu đã cho thấy được sự cải thiện các tính chất cường độ và độ bền khi được sử dụng trong bê tông cát. Sự kết hợp đồng thời của 2 loại vật liệu này với nhau có thể sẽ nâng cao hơn nữa hiệu quả sử dụng so với việc dùng riêng từng loại. Bài báo trình bày một nghiên cứu thực nghiệm về tính chất cơ học và độ bền của bê tông cát (BTC) khi sử dụng kết hợp đồng thời TB và XLC. Các loại bê tông cát được chế tạo với lượng cố định 150 kg/m3 tro bay trong khi XLC thay thế chất kết dính (CKD) với các tỷ lệ khác nhau để xem xét sự ảnh hưởng của tỷ lệ sử dụng XLC đến tính chất của BTC đóng rắn. Một cấp phối bê tông thường (BTT) sử dụng lượng xi măng tương đương tổng lượng CKD trong BTC được chế tạo với mục đích so sánh. Kết quả nghiên cứu cho thấy tính chất cường độ chịu nén, cường độ ép chẻ, độ mài mòn trong nước của bê tông cát tối ưu với tỷ lệ XLC thay thế 20%. Độ thấm clorua của BTC thấp nhất với tỷ lệ XLC thay thế 30%. Tỷ lệ XLC thay thế càng lớn, độ giãn nở của BTC trong dung dịch sunfat càng thấp sau 6 tháng. Ba loại BTC ứng với tỷ lệ XLC thay thế 10%, 20%, 30% có tính chất cường độ và độ bền đáp ứng được yêu cầu của bê tông làm việc trong môi trường biển theo TCVN 12041: 2017 và CSA A23.1: 2004.
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Rischin, Danny, Madeleine T. King, Lizbeth M. Kenny, Sandro Porceddu, Christopher Wratten, Andrew Macann, James E. Jackson, et al. "Randomized trial of radiotherapy with weekly cisplatin or cetuximab in low risk HPV associated oropharyngeal cancer (TROG 12.01): A Trans-Tasman Radiation Oncology Group study." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 6012. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.6012.

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6012 Background: The excellent prognosis of patients with low risk HPV associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiotherapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an EGFR targeting antibody, when combined with radiotherapy would result in a decrease in symptom burden and toxicity with similar efficacy when compared to weekly cisplatin. Methods: TROG 12.01, a randomised, multicentre trial involving 15 sites in Australia and New Zealand enrolled patients with HPV associated oropharyngeal squamous cell carcinoma, AJCC 7th edition Stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomised (1:1) to receive radiotherapy (70Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40mg/m2 or cetuximab, loading dose of 400mg/m2 followed by 7 weekly doses of 250 mg/m2. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks post completion of radiotherapy using the area under the time-severity curve (AUC). Sample size was 170 evaluable patients to provide at least 90% power to detect an effect size of 0.5, using a 2-sided test at 0.05 level of significance. Trial was registered on ClinicalTrials.gov: NCT01855451. Results: Between 17th June 2013 and 7th June 2018, 189 patients were enrolled and 182 were evaluable, with 92 on cisplatin arm and 90 on cetuximab included in the main analysis. The median follow-up was 4.1 years (0.4 - 5.3). Analyses were performed in all eligible randomised patients that commenced treatment (modified intention-to-treat population). There was no difference in the primary endpoint of symptom severity; difference in AUC cetuximab – cisplatin was 0.05 (95%CI: -0.19, 0.30), p= 0.66. The T-score (mean number of > grade 3 acute adverse events) was 4.35 (SD 2.48) in the cisplatin arm and 3.82 (SD 1.8) in the cetuximab arm, p= 0.108. The 3 -year failure-free survival rates were 93% (95% CI: 86-97%) in the cisplatin arm and 80% (95% CI: 70-87%) in the cetuximab arm (hazard ratio = 3.0 (95% CI: 1.2-7.7); p=0.015. The increase in failures in the cetuximab arm was evenly split between distant and locoregional failures. Conclusions: For patients with low risk HPV associated oropharyngeal cancer, radiotherapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared to radiotherapy and weekly cisplatin. Radiotherapy and cisplatin remains the standard of care. Clinical trial information: NCT01855451.
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Pearse, Maria, Andrew Kneebone, Gillian M. Duchesne, Richard Fisher, Carol Fraser-Browne, Mark Frydenberg, Annette Haworth, et al. "What is optimal timing of post prostatectomy radiotherapy? Is adjuvant radiotherapy equivalent to early salvage radiotherapy? The “RAVES” phase III randomized clinical trial." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): TPS4690. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.tps4690.

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TPS4690 Background: Three randomised trials have demonstrated a significant benefit of adjuvant post prostatectomy radiotherapy in patients with positive margins, extra capsular extension or seminal vesicle involvement, and it should be regarded as current standard of care. However, adopting this approach will expose nearly half of such patients to unnecessary radiotherapy and potential treatment morbidity. Salvage radiotherapy, if given early, is recognised to be effective. The RAVES trial is designed to compare these two approaches, and was developed in collaboration with the Trans Tasman Radiation Oncology Group (TROG), Australian and New Zealand Urogenital and Prostate Trials Group (ANZUP) and the Urological Society of Australia and New Zealand (USANZ). It aims to test the hypothesis that active surveillance with early salvage radiotherapy is non-inferior to adjuvant radiotherapy with respect to risk of biochemical failure (defined as PSA level ≥ 0.40 ng/mL and rising). Methods: Patients must have at least one of the following risk factors: positive margins, extracapsular extension or seminal vesicle involvement. They must start radiotherapy within 4 months of radical prostatectomy (RP) and have an undetectable PSA (≤ 0.10 ng/ml) prior to randomisation. Patients receiving androgen deprivation or who have an artificial hip are excluded. Eligible patients are randomised to either: Arm 1: Adjuvant RT (64Gy in 32#) commenced within 4 months of RP, or Arm 2: Active surveillance with 3 monthly PSA tests and commencement of early salvage RT (64Gy in 32#) if PSA rises ≥ 0.20 ng/ml. Stratification is by seminal vesicle invasion, Gleason Score, pre-operative PSA, margin positivity (no/yes) and radiotherapy institution. A sample size of 470 patients is required to detect a 10% non-inferiority margin in the 5-year biochemical failure-free rate between the adjuvant and active surveillance arms. As of 31 Jan 2012, 186 patients have been recruited across 26 centres in Australia and New Zealand. A meta analysis with the MRC RADICALS and GETUG-17 trials will be prospectively designed to detect a survival difference between the two approaches.
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El Kharras, A., S. Semlali, A. Darbi, S. Akjouj, J. El Fenni, A. Hanine, M. Benameur, and D. Bassou. "TROP-WS-2 Hydatidose musculaire primitive." Journal de Radiologie 89, no. 10 (October 2008): 1615. http://dx.doi.org/10.1016/s0221-0363(08)77060-4.

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29

Raji, Rhoda, Federica Guzzo, Luisa Carrara, Joyce Varughese, Emiliano Cocco, Stefania Bellone, Marta Betti, et al. "Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody." Journal of Experimental & Clinical Cancer Research 30, no. 1 (2011): 106. http://dx.doi.org/10.1186/1756-9966-30-106.

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30

Wick, W., C. Engel, S. E. Combs, G. Nikkhah, J. Steinbach, R. Kortmann, M. Simon, C. Wille, G. Reifenberger, and M. Weller. "NOA-08 randomized phase III trial of 1-week-on/1-week-off temozolomide versus involved-field radiotherapy in elderly (older than age 65) patients with newly diagnosed anaplastic astrocytoma or glioblastoma (Methusalem)." Journal of Clinical Oncology 28, no. 18_suppl (June 20, 2010): LBA2001. http://dx.doi.org/10.1200/jco.2010.28.18_suppl.lba2001.

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LBA2001 Background: The median survival time for elderly patients (pts) with malignant gliomas is in the range of a few months. Radiotherapy (RT) is the standard treatment and superior to best supportive care both with respect to progression-free and overall survival. The benefit derived from surgery and RT is modest, and both treatments are less well tolerated in elderly pts than in the young. The availability of a potentially effective pharmacological agent, temozolomide (TMZ), for malignant glioma, which exhibits a favorable safety profile, necessitated a reconsideration of the widespread therapeutic nihilism with malignant glioma in the elderly. Methods: The NOA-08 trial of the Neurooncology Working Group (NOA) of the German Cancer Society compared standard postsurgical involved-field RT to a dose of 54-60 Gy, in pts with anaplastic astrocytoma or glioblastoma > 65 ys with a Karnofsky performance score ≥ 60, to TMZ in an one week on/one week off schedule at 100 mg/m2 with dose modification in 25 mg steps in both directions. The primary endpoint was the median survival time (OS) during the follow-up in the 12 months after date of operation. The trial sought to demonstrate the non-inferiority of TMZ compared with RT. Regarding a maximal difference of 25% between both treatment arms in OS as being equivalent, 2 x 206 pts were randomized between May 15, 2005 and Nov 2, 2009 in 22 German and one Suisse sites to provide 80% power to achieve significance at a one-sided level of 0.05. Thirty-nine patients were excluded from the intention-to-treat (ITT) population because no therapy was applied (n=22) or withdrawal of informed consent (n=17). Results: All histological diagnoses were centrally confirmed. Pts characteristics were balanced between arms in the ITT population (n=373) except for more resections and more anaplastic astrocytomas in the RT arm. The non-inferiority of TMZ was not shown. In contrast, pts in the TMZ arm had an increased risk of death (HR=1.24 [95% CI: 0.94-1.63]) compared to pts in the RT arm. The rate of adverse and serious adverse events was higher in the TMZ arm. Conclusions: This trial fails to show the non-inferiority of dose-intensified TMZ alone compared with RT alone in the primary treatment of older pts with malignant glioma. Unlike anaplastic glioma in the younger patient population, RT cannot be safely deferred in the treatment of elderly patients with anaplastic astrocytoma or glioblastoma. Whether RT plus TMZ is superior to RT alone, is addressed in the ongoing companion trial conducted by NCIC, EORTC and TROG. [Table: see text] [Table: see text]
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Simms, Anthony, Reuben P. Jacob, Cynthia Cohen, and Momin T. Siddiqui. "TROP-2 expression in papillary thyroid carcinoma." Diagnostic Cytopathology 44, no. 1 (October 19, 2015): 26–31. http://dx.doi.org/10.1002/dc.23382.

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32

Goldenberg, David M., and Robert M. Sharkey. "Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: A case study of anti-TROP-2 sacituzumab govitecan." mAbs 11, no. 6 (July 18, 2019): 987–95. http://dx.doi.org/10.1080/19420862.2019.1632115.

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33

Bhave, Prachi, Angela M. Hong, Rebecca Johnson, Alexander M. Menzies, Georgina V. Long, Joanna Mangana, Douglas Buckner Johnson, et al. "Efficacy of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9578. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9578.

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9578 Background: Adjuvant (adj) radiotherapy (RT) halves the risk of locoregional (LR) recurrence in patients (pts) with high risk stage III melanoma after lymphadenectomy (CLND), however its role in the adj immunotherapy (IO) era without CLND is unknown. Methods: Pts with resected stage III melanoma who received adj IO and recurred with resectable LR only disease were studied. After resection of this 1st recurrence, adj RT may or may not have been administered. Disease characteristics, treatment at relapse and outcomes were examined. Results: 71 pts from 9 centres were included. Prior to adj IO, median age was 60y, 59% male, 56% BRAF mutant, 61% stage IIIC (AJCC V8), 52% underwent CLND and 17% had in-transit (IT) only disease. Adj IO included: 90% single agent anti-PD1, 8% ipilimumab-nivolumab (IN) and 1% nivolumab or IN (blinded on trial). Median duration of adj IO was 5 months. 21(30%) pts had high risk stage III disease at diagnosis, per previously established TROG criteria; 3 (4%) received upfront adj RT prior to recurrence. Median time to 1st recurrence was 7 months. 49 (69%) pts recurred during and 22 (31%) after cessation of adj IO. At 1st recurrence, 9 (13%) pts had stage IIIB disease, 55 (77%) IIIC, 7 (10%) IIID and 8 (11%) continued prior adj IO, 31 (44%) commenced therapy and 32 (45%) had no systemic therapy. 24 (34%) pts received adj RT after resection of 1st recurrence and 47 (66%) did not (Table). Adj RT was associated with a reduced risk of any 2nd recurrence (7/24, 29% vs 26/47, 55%, p=0.03) and LR 2nd recurrence (2/24, 8% vs 17/47, 36%, p=0.012). Whilst pts who received adj RT at 1st recurrence were more likely to have LN only disease, extra nodal extension and involved surgical margins, these factors did not significantly affect overall risk of 2nd recurrence on multivariate analysis. Of note, 70% of pts who did not receive adj RT at 1st recurrence had IT only disease, and though this did not significantly affect rate of 2nd recurrence (p=0.19), this likely reflects an inherent selection bias in this study. RT toxicity occurred in 16 (67%) pts, 10 with dermatitis only, and all grade 1 or 2. Median follow up was 22 months. Median recurrence free survival to 2nd recurrence was 23 months for all pts, not reached for those who had adj RT at 1st recurrence and 19 months for those who did not have adj RT (p=0.047). Median overall survival was not reached. Conclusions: Whilst adj RT appears to reduce 2nd recurrences, this may have been influenced by an unavoidable selection bias in the data, particularly an imbalance in the percentage of pts with IT disease. Prospective data with larger cohorts is needed to validate our results.[Table: see text]
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Zaman, Saif, Hassan Jadid, Aaron C. Denson, and Jhanelle E. Gray. "Targeting Trop-2 in solid tumors: future prospects." OncoTargets and Therapy Volume 12 (March 2019): 1781–90. http://dx.doi.org/10.2147/ott.s162447.

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35

Guerra, E., M. Trerotola, A. L. Aloisi, R. Tripaldi, G. Vacca, R. La Sorda, R. Lattanzio, M. Piantelli, and S. Alberti. "The Trop-2 signalling network in cancer growth." Oncogene 32, no. 12 (May 7, 2012): 1594–600. http://dx.doi.org/10.1038/onc.2012.151.

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36

Lee, Edmund WJ, Mesfin Awoke Bekalu, Rachel McCloud, Donna Vallone, Monisha Arya, Nathaniel Osgood, Xiaoyan Li, Sara Minsky, and Kasisomayajula Viswanath. "The Potential of Smartphone Apps in Informing Protobacco and Antitobacco Messaging Efforts Among Underserved Communities: Longitudinal Observational Study." Journal of Medical Internet Research 22, no. 7 (July 7, 2020): e17451. http://dx.doi.org/10.2196/17451.

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Background People from underserved communities such as those from lower socioeconomic positions or racial and ethnic minority groups are often disproportionately targeted by the tobacco industry, through the relatively high levels of tobacco retail outlets (TROs) located in their neighborhood or protobacco marketing and promotional strategies. It is difficult to capture the smoking behaviors of individuals in actual locations as well as the extent of exposure to tobacco promotional efforts. With the high ownership of smartphones in the United States—when used alongside data sources on TRO locations—apps could potentially improve tobacco control efforts. Health apps could be used to assess individual-level exposure to tobacco marketing, particularly in relation to the locations of TROs as well as locations where they were most likely to smoke. To date, it remains unclear how health apps could be used practically by health promotion organizations to better reach underserved communities in their tobacco control efforts. Objective This study aimed to demonstrate how smartphone apps could augment existing data on locations of TROs within underserved communities in Massachusetts and Texas to help inform tobacco control efforts. Methods Data for this study were collected from 2 sources: (1) geolocations of TROs from the North American Industry Classification System 2016 and (2) 95 participants (aged 18 to 34 years) from underserved communities who resided in Massachusetts and Texas and took part in an 8-week study using location tracking on their smartphones. We analyzed the data using spatial autocorrelation, optimized hot spot analysis, and fitted power-law distribution to identify the TROs that attracted the most human traffic using mobility data. Results Participants reported encountering protobacco messages mostly from store signs and displays and antitobacco messages predominantly through television. In Massachusetts, clusters of TROs (Dorchester Center and Jamaica Plain) and reported smoking behaviors (Dorchester Center, Roxbury Crossing, Lawrence) were found in economically disadvantaged neighborhoods. Despite the widespread distribution of TROs throughout the communities, participants overwhelmingly visited a relatively small number of TROs in Roxbury and Methuen. In Texas, clusters of TROs (Spring, Jersey Village, Bunker Hill Village, Sugar Land, and Missouri City) were found primarily in Houston, whereas clusters of reported smoking behaviors were concentrated in West University Place, Aldine, Jersey Village, Spring, and Baytown. Conclusions Smartphone apps could be used to pair geolocation data with self-reported smoking behavior in order to gain a better understanding of how tobacco product marketing and promotion influence smoking behavior within vulnerable communities. Public health officials could take advantage of smartphone data collection capabilities to implement targeted tobacco control efforts in these strategic locations to reach underserved communities in their built environment.
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Stahlfeld, Charlotte, Jamie Sperger, Susan F. Slovin, Scott T. Tagawa, Christos Kyriakopoulos, Manish Kohli, Liguo Wang, Liewei Wang, Scott Dehm, and Joshua Michael Lang. "TROP-2 co-expression with androgen receptor splice variants as a new therapeutic target in prostate cancer." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 5060. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.5060.

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5060 Background: Tumor-associated calcium signal transducer 2 (TROP-2, TACSTD2) is a transmembrane glycoprotein that is highly expressed in many epithelial cancers. Overexpression of TROP-2 is postulated to mediate cancer cell growth, invasion, and is associated with more aggressive disease. TROP-2 has emerged as a therapeutic target for antibody-drug conjugates in clinical trials including sacituzumab govitecan and DS-1062. Here, we evaluated the expression of TROP-2 in tumor biopsies and circulating tumor cells (CTCs) in men with metastatic castration resistant prostate cancer (mCRPC) to evaluate TROP-2 as a clinically relevant target. Methods: RNA-seq data from the SU2C-PCF database and PROMOTE clinical trial (NCT#01953640) was assessed for TACSTD2 and androgen receptor (AR) splice variant ( AR_V7/AR_V9) expression. Prostate cancer ChIP-seq data was analyzed to identify binding of the AR to the TROP-2 promoter. EpCAM and TROP-2 captured CTCs were isolated from patients with mCRPC using the VERSA (Versatile Exclusion-based Rare Sample Analysis) platform and assessed for splice variant, neuroendocrine (NE), and AR-regulated gene signatures, in addition to CTC enumeration and TROP-2 protein expression. Results: TROP-2 expression was detectable in 90% of patients, in both bone and visceral metastatic biopsies (SUC2-PCF). Although TROP-2 low biopsies were infrequent (10%), 58% of these samples showed high levels of NE markers, as compared with 5% in all other patients. In the PROMOTE study, elevated TROP-2 gene expression was significantly higher in biopsies with high AR_V7 expression than in those with low (p = 0.04) or negative (p <.01) AR_V7 expression. ChIP-seq data demonstrated binding of AR at the TROP-2 promoter as well as at a potential enhancer site upstream, suggesting that TROP-2 expression can be regulated by AR activity. Splice variants and NE gene signatures were expressed in CTCs captured with both EpCAM and TROP-2, although markedly different gene expression profiles between EpCAM and TROP-2 CTCs were observed in a subset of patients with neuroendocrine prostate cancer. Detection of AR_V7 from TROP-2 CTCs corresponded to shorter overall survival in 20 patients with mCRPC. TROP-2 protein expression was identified on EpCAM captured CTCs, although patients exhibited a wide degree of both intra- and inter-patient heterogeneity. Conclusions: Our findings demonstrate that TROP-2 is highly expressed in mCRPC, and is reduced in a subset of patient tumors expressing neuroendocrine markers. In the PROMOTE clinical trial with abiraterone acetate, TROP-2 AR variant expression correlated with increased TROP-2 expression. Binding of the AR to the TROP-2 promoter and potential enhancer was observed in prostate cancer cell lines and biopsies. These results indicate TROP-2 is a high value a biomarker and therapeutic target mCRPC.
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Izci, Hava, Kevin Punie, Lise Waumans, Annouschka Laenen, Hans Wildiers, Freija Verdoodt, Christine Desmedt, et al. "Correlation of Trop-2 expression with clinicopathological characteristics, sTILs, AR expression and outcome in primary TNBC." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e12558-e12558. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e12558.

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e12558 Background: Trophoblast cell-surface antigen-2 (Trop-2) is a transmembrane calcium signal transducer highly expressed in multiple tumor types including breast cancer. Trop-2 overexpression is associated with poor survival. Given the approval of sacituzumab govitecan in advanced triple-negative breast cancer (TNBC), Trop-2 emerges as an important target for antibody-drug conjugates. Limited data exist about correlations of Trop-2 expression with clinicopathological characteristics and outcome in early TNBC. Methods: We included 127 patients with early TNBC, treated with primary surgery at UZLeuven from 2005-2017. Trop-2 expression was determined with IHC (ab227689, Abcam) on whole slide tumor sections from resection specimens and assessed as continuous (H-score 0-300) and categorical (high 201-300, medium 100-200 and low < 100) variables. Stromal tumor infiltrating lymphocytes (sTIL; low, intermediate and high), mitotic score and androgen receptor (AR) expression (1% or 10%-cutoff) were scored. We assessed associations between Trop-2 expression and age, BMI, BRCA status, tumor grade and size, lymphovascular invasion (LVI), DCIS, nodal status, sTILs, AR, mitotic index and outcome (Invasive disease free survival and breast cancer specific survival). Results: The median age at diagnosis was 51y (range 26-80y) and the median follow-up 8.5y. Low, medium and high Trop-2 expression was seen in 50%, 37% and 13% of cases. AR was positive in 32% of cases (10%-cutoff). Higher Trop-2 expression was correlated with age (ρ = 0.192, p = 0.03) and inversely correlated with mitosis/mm² (ρ = -0.2, p = 0.02). Patients with high Trop-2-expression were older compared to patients with low Trop-2-expression (median 58 vs 47 years, p = 0.02). LVI was more frequent in Trop-2-high (65%) compared to TROP-2-medium (15%) or -low (16%) (p < 0.001). Median mitosis/mm² was higher in Trop-2-low (14) compared to Trop-2-medium (10) and -high (8) (p = 0.004). Patients in Trop-2-high subgroup had more nodal involvement (53%) compared to Trop-2-medium (23%) and -low (21%) (p = 0.03). There was no correlation between Trop-2 expression and sTILs, AR or outcome. Conclusions: In this patient cohort with TNBC treated with upfront surgery, higher Trop-2 expression was correlated with older age, with more LVI and nodal involvement, while mitosis/mm² were higher in tumors with low Trop-2 expression. Trop-2 expression was not correlated with sTILs, AR or outcome. Limited numbers of events warrant caution in interpretation.
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Bignotti, Eliana, Antonella Ravaggi, Chiara Romani, Marcella Falchetti, Silvia Lonardi, Fabio Facchetti, Sergio Pecorelli, et al. "Trop-2 Overexpression in Poorly Differentiated Endometrial Endometrioid Carcinoma: Implications for Immunotherapy With hRS7, a Humanized Anti–Trop-2 Monoclonal Antibody." International Journal of Gynecologic Cancer 21, no. 9 (November 2011): 1613–21. http://dx.doi.org/10.1097/igc.0b013e318228f6da.

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ObjectiveWe evaluated the expression of human trophoblast cell surface marker (Trop-2) in endometrial endometrioid carcinoma (EEC) and the potential application of hRS7, a humanized monoclonal anti–Trop-2 antibody, as a therapeutic agent against poorly differentiated EEC.MethodsTrop-2 expression was evaluated by immunohistochemistry in 131 EEC with different degrees of differentiation and 32 normal endometrial controls (NEC). Trop-2 expression was also evaluated by quantitative real-time polymerase chain reaction and flow cytometry in 3 primary EEC cell lines derived from patients harboring poorly differentiated EEC. Finally, the sensitivity of grade 3 EEC cell lines to hRS7 antibody-dependent cellular cytotoxicity was tested in standard 5-hour51Cr release assays.ResultsTrop-2 expression was detected in 126 (96.2%) of 131 EEC samples. Tumor tissues showed markedly increased Trop-2 positivity compared with NEC (P= 0.001). Trop-2 expression was significantly higher in all grades of EEC versus NEC. Grade 3 tumors displayed significantly stronger Trop-2 immunostaining compared with grade 1 EEC (P= 0.01). High Trop-2 expression by quantitative real-time polymerase chain reaction and flow cytometry was found in 1 grade 3 EEC primary cell line (EEC-ARK-1). Unlike Trop-2–negative EEC cell lines, EEC-ARK-1 was found highly sensitive to hRS7-mediated antibody-dependent cellular cytotoxicity in vitro (range of killing, 33.9%–50.6%;P= 0.004). Human serum did not significantly inhibit hRS7-mediated cytotoxicity against EEC-ARK-1 (P= 0.773).ConclusionsTrop-2 is highly expressed in EEC, and its expression is significantly higher in poorly differentiated EEC when compared with well-differentiated EEC. Primary grade 3 EECs overexpressing Trop-2 are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for the treatment of high-grade EEC refractory to standard treatment modalities.
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Penniment, M. G., J. A. Harvey, R. Wong, S. Stephens, H. Au, C. J. O'Callaghan, A. B. Kneebone, et al. "Best Practice in Advanced Esophageal Cancer: A Report on Trans-Tasman Radiation Oncology Group TROG 03.01 and NCIC CTG ES.2 Multinational Phase 3 Study in Advanced Esophageal Cancer (OC) Comparing Quality of Life (QOL) and Palliation of Dysphagia in Patients Treated With Radiation Therapy (RT) or Chemoradiation Therapy (CRT)." International Journal of Radiation Oncology*Biology*Physics 90, no. 1 (September 2014): S3. http://dx.doi.org/10.1016/j.ijrobp.2014.06.021.

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41

Nguyen, Trung Thanh, Hong Nhat Nguyen, Thi Quynh Anh Nguyen, Phuoc Toan Phan, and Nhat Huy Nguyen. "Emission and management for rice husk ash in An Giang Province, Viet Nam." Journal of Vietnamese Environment 11, no. 1 (June 30, 2019): 21–26. http://dx.doi.org/10.13141/jve.vol11.no1.pp21-26.

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An Giang province is one of the largest rice producer regions in Vietnam with 600,000 hectares of paddy field and 4 million tons of rice production every year. The rice milling industry generates a huge amount of rice husk (~23% of paddy rice). The rice husk is currently used as fuel around the province generating rice husk ash (RHA) which causes environmental and health issues. This study focuses on surveying and analyzing the current situation for utilization, management, treatment, and awareness of enterprises and community about generated RHA via a household investigation method. The results showed that, in average, a factory generates 862.4 tons of RHA per year, whereas half of them are reused or are sold for re-utilization in other factories, 56.3% are disposed in the private landfill of the factory, and 1.6 to 6.3 % are directly disposed to nearby rivers or in soil. Most of the interviewed citizens reported that they were aware of the RHA impact on the environment nevertheless, only 2% knew that RHA can be re-utilized for other purposes. Therefore, it is necessary to raise public awareness about the reuse and utilization of RHA to reduce the environmental impact and contribute to the sustainable development of the rice production. Tỉnh An Giang là một trong những vựa lúa lớn nhất Việt Nam, với diện tích khoảng 600.000 ha và sản lượng gần 4 triệu tấn/năm. Cùng với lúa, lượng trấu phát sinh từ quá trình xay xát đang được tái sử dụng làm nhiên liệu đốt cho các quá trình sản xuất khác ở địa phương. Tuy nhiên lượng tro sau quá trình đốt nhiên liệu trấu cũng đang tạo nên một áp lực lên chất lượng môi trường. Do vậy, nghiên cứu này tập trung vào việc khảo sát và phân tích hiện trạng sử dụng, quản lý, xử lý và nhận thức của cơ sở sản xuất hay cộng đồng đối với vấn đề phát thải tro trấu thông qua phương pháp điều tra thực tế. Kết quả cho thấy trung bình mỗi cơ sở phát sinh 862,4 tấn tro trấu/năm với khoảng phân nửa trong số đó được tái sử dụng, 56,3% xử lý bằng cách chôn lấp; 1,6% đến 6,3% xử lý bằng cách đổ bỏ. Hầu hết những người được phỏng vấn biết việc phát thải tro trấu có ảnh hưởng đến chất lượng môi trường, tuy nhiên chỉ có 2% hộ nhận thức được tro trấu có thể tái sử dụng cho các mục đích khác. Điều này cho thấy cần có biện pháp nâng cao nhận thức của cộng đồng đối với việc tái sử dụng tro trấu, nhằm góp phần giảm áp lực của phát thải lên môi trường và đóng góp vào sự phát triển của ngành sản xuất lúa gạo theo định hướng bền vững.
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42

Cook, O., A. Moore, R. Kaderka, K. Moore, P. Keall, and J. Martin. "PO-1111 Knowledge-Based Planning as a Real Time Review QA Feedback Tool in the TROG 1501 SPARK trial." Radiotherapy and Oncology 133 (April 2019): S617—S618. http://dx.doi.org/10.1016/s0167-8140(19)31531-2.

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43

Khoury, Katia, Rebecca Feldman, Paula Raffin Pohlmann, Arielle Lutterman Heeke, Zoran Gatalica, Yvonne Veloso, Gregory A. Vidal, et al. "Molecular characterization of trophoblast cell surface antigen 2 (Trop-2) positive triple negative breast cancer (TNBC)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14651-e14651. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14651.

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e14651 Background: Trop-2 is a glycoprotein found in various carcinomas, known to play a role in tumor development and progression. A humanized antibody drug conjugate (ADC) targeting Trop-2 for delivery of the topoisomerase-I (TOPO1) inhibitor SN-38 (payload) is currently in clinical development for TNBC. Clinical response in a previously reported phase I/II study was associated with Trop-2 immunohistochemistry (IHC) staining intensity (Bardia A et al. J Clin Oncol 2017). Herein we investigated the prevalence of Trop-2 expression in an unselected cohort of TNBC tumors, and the association with other markers of interest that could suggest novel drug combinations. Methods: A cohort of 68 TNBC specimens with available archival tumor submitted to Caris Life Sciences were tested via protein expression (IHC) for Trop-2 with dichotomous categorization for results. Positivity required at least 10% of tumor cells to be stained, with an intensity of 1+ (weak), 2+ (moderate) and 3+ (strong), with same cutoff used in ongoing clinical trials of Trop-2 ADC. Comprehensive molecular profiles were performed using 592-gene next generation sequencing (average read depth 500X). Chi-square tests were used for statistics. Results: The median age in this cohort was 54 (range: 28-90). 38 (56%) tumors were positive for Trop-2. There was no difference in age distribution between Trop-2 positive and negative tumors. Trop-2 expression was present in 48.6% (17/35) and 63.6% (21/33) of primary and metastatic sites, respectively. TOPO1 by IHC was negative in 11 (29%) of Trop-2 positive tumors. Trop-2 expression was inversely associated with PIK3CA and RB1 mutations (p = 0.012 and 0.011, respectively). There was no difference in PDL1 expression by IHC, tumor mutational burden (TMB), BRCA1/2 or other homologous recombination deficiency gene mutations between Trop-2 positive and negative tumors. Conclusions: In a cohort that used the same cutoffs in ongoing trials with Trop-2 ADC, we found a lower prevalence of Trop-2 positivity in TNBC than what has been previously reported. One third of Trop-2 positive tumors were TOPO1 negative which may have treatment implications given the pharmacology of ADC currently in development.
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44

Ku, Kimberly Peihsi, Joshua Michael Lang, Jamie Sperger, Scott Dehm, Manish Kohli, Liguo Wang, Liewei Wang, Scott T. Tagawa, and Howard I. Scher. "Trop-2 expression on treatment resistant cancer cells in castrate-resistant prostate cancer (CRPC) as a predictive biomarker for targeted therapy." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 5045. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.5045.

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5045 Background: Trophoblastic cell-surface antigen (Trop-2) is a transmembrane glycoprotein that is highly expressed in many solid tumors. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate of an anti-Trop-2 humanized antibody with SN-38. Early clinical trials have shown high response rates in a broad range of diseases including triple negative breast and urothelial cancers. We evaluated Trop-2 expression in tumor biopsies and circulating tumor cells (CTCs) from men with mCRPC (metastatic castrate-resistant prostate cancer). Methods: Trop-2 expression was evaluated from mCRPC biopsies from patients (Pts) treated with abiraterone acetate (AA) on the PROMOTE clinical trial, CTCs from a separate cohort treated with either enzalutamide or AA. Trop-2 CTCs were compared with EpCAM captured CTCs using a microscale technology termed the VERSA (Vertical Exclusion-based Rare Sample Analysis) platform to compare protein and gene expression signatures of resistance to these agents. Results: RNA sequencing identified Trop-2 gene expression in > 70% of metastatic biopsies. The AR splice variant V7 was found in 48 biopsies that also expressed Trop-2. Trop-2 expression was not altered by treatment with AA at 12 weeks. The number of CTCs captured from 25 pts with Trop-2 or EpCAM were closely correlated (R2= 0.84). Gene expression analysis showed similar patterns of expression for the TROP-2 and EPCAM captured cells. AR splice variant expression (AR-V7, AR-V9) in Trop-2 and EpCAM CTCs was detected in 33% of patients. Expression of neuroendocrine markers was identified in 40% of Trop-2 CTCs. Conclusions: Trop-2 is frequently expressed in mCRPC and co-expressed in tumors that express AR splice variants. Trop-2 CTCs are detected in CRPC pts previously treated with AA or Enzalutamide that also express multiple AR splice variants and neuroendocrine markers. The results support Trop-2 expression as predictive biomarker of sensitivity to targeted therapies tumors resistant to AA or Enzalutamide. Men with mCRPC are being enrolled on a Phase I trial with IMMU-132, and multi-site Phase II clinical trial in men who have progressed on AA or Enzalutamide is being finalized.
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45

Ngo, L. L., E. Delhom, T. H. Mai, T. D. Lé, and F. M. Lopez. "TROP-WP-2 Imagerie en coupes de l’ascaridiose hepatobiliaire." Journal de Radiologie 90, no. 10 (October 2009): 1591. http://dx.doi.org/10.1016/s0221-0363(09)76249-3.

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46

Ambrogi, Federico, Marco Fornili, Patrizia Boracchi, Marco Trerotola, Valeria Relli, Pasquale Simeone, Rossana La Sorda, et al. "Trop-2 Is a Determinant of Breast Cancer Survival." PLoS ONE 9, no. 5 (May 13, 2014): e96993. http://dx.doi.org/10.1371/journal.pone.0096993.

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47

Trerotola, M., P. Cantanelli, E. Guerra, R. Tripaldi, A. L. Aloisi, V. Bonasera, R. Lattanzio, et al. "Upregulation of Trop-2 quantitatively stimulates human cancer growth." Oncogene 32, no. 2 (February 20, 2012): 222–33. http://dx.doi.org/10.1038/onc.2012.36.

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48

Dalmat, Yann-Mickael. "Sars-CoV-2, Trod, PCR : un peu de pédagogie." Option/Bio 32, no. 629-630 (March 2021): 9. http://dx.doi.org/10.1016/s0992-5945(21)00037-4.

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49

Alberti, Saverio, Marco Trerotola, Valeria Relli, Chiara Pedicone, Antonella D' Amore, Francesca Dini, Silvia Fratarcangeli, and Emanuela Guerra. "Novel domain-targeted anti-Trop-2 monoclonal antibodies to elicit therapeutic synergy against multiple human cancers." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e14002-e14002. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14002.

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e14002 Background: Trop-2 is a calcium signal transducer that drives tumor cell growth. Trop-2 is overexpressed in the majority of carcinomas, where it associates with worse prognosis. The Trop-2 extracellular domain contains a N-terminal cysteine-rich globular domain followed by a stem-like cysteine-less region that connects to the transmembrane domain. Trop-2 engages in homophylic interactions between adjacent cells and interacts with tight-junction proteins, which may severely affect accessibility by therapeutic monoclonal antibodies (mAb). Available anti-Trop-2 mAb mostly recognize a single immunodominant epitope between the globular and stem regions, and have limited or no therapeutic efficacy. In order to untap the potential of anti-Trop-2 immunotherapy we generated novel anti-Trop-2 mAb with tailored specificity towards the globular versus stem regions. Methods: Balb-C mice were immunized with soluble human Trop-2 produced in human 293 and murine L cell lines and in baculovirus expression system. Domain-targeted anti-Trop-2 mAb were selected by flow cytometry using live 293 transfectants.Therapeutic potential was assessed in human cancer xenografts in murine models. mAb mode of action was investigated by Western blot, live-cell imaging and in vitro ADCC and cancer cell growth inhibition assays. Results: mAb were identified that were differentially directed against the Trop-2 stem versus globular regions. These mAb efficiently bound Trop-2 expressing cancer cells and inhibited cell growth in vitro. In vivo, naked anti-globular OX-G64 and anti-stem OX-S55 mAb were most effective in inhibiting the growth of colon, ovary, breast and prostate cancers as xenografts in nude mice. NSG mice and in vitro mechanism profiling indicated efficient ADCC, together with efficient internalization for ADC development. Differential efficacy for established tumors versus isolated-cell models of metastatic dissemination was shown. Most remarkably, OX-G64/OX-S55 co-administration demonstrated sinergic growth inhibition in vivo. Conclusions: The OX-G64 and OX-S55 anti-Trop-2 mAb are novel domain-targeted, sinergic therapeutic mAb for game-changing anti-cancer immunotherapy.
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50

Alberti, S., M. Trerotola, G. Vacca, R. Zappacosta, C. Rossi, E. Guerra, V. Bonasera, R. Lasorda, R. Lattanzio, and M. Piantelli. "TROP2 is a major determinant of growth and metastatic spreading of human cancer." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 10510. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.10510.

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10510 Background: The TROP2 gene encodes a transmembrane calcium signal transducer, involved in the regulation of cell- cell adhesion. Methods: To identify the role of Trop-2 in transformed cells, we studied its expression pattern and function by DNA array and SAGE analysis, Northern and Western blotting, flow cytometry, confocal microscopy and IHC in experimental systems and in man. Overexpression or down-regulation of Trop-2 and directed mutagenesis were used to identify its role in tumor growth and metastasis in vivo. Results: DNA microarray, EST, SAGE, RT-PCR and Northern blot analysis of human tumors revealed expression of the TROP2 gene in most cancers. IHC analysis of human tumors (1755 cases) revealed a corresponding overexpression of Trop-2 protein. Trop-2 potently stimulated the growth of tumor cells, whereas TROP2 siRNA inhibited it. Deletion of the cytoplasmic region of Trop-2 abolished the growth stimulatory capacity, as did mutagenesis of the S303 PKC phosphorylation site. Proteomic analysis showed that multiple PKC isoforms partecipate to the Trop-2 signaling network. In vivo imaging showed dynamic colocalization of PKCs and Trop-2 in vivo in membrane ruffles and podosomes. DN PKCs and siRNA abolished Trop-2-induced growth. Strikingly, comparative global gene expression analysis revealed that TROP2 was the only gene up-regulated across different metastatic models, tumor types and animal species. IHC analysis revealed a dramatic up-regulation in metastases from colon, stomach, breast and ovary tumors in man. To assess if Trop-2 may play a causal role in metastatic spreading, TROP2-transfected KM12SM colon cancer cells were orthotopically injected in nude mice. TROP2-overexpressing transfectants demonstrated increased metastatic potential to the liver. Deletion of the HIKE domain of Trop-2 severely diminished, whereas that of the whole cytoplasmic region vastly increased metastatic diffusion, indicating the existence of both metastatic enhancers and silencers in the Trop-2 cytoplasmic tail. Conclusions: Our findings demonstrate that Trop-2 is a novel, widespread, stimulator of human cancer growth and a unique marker and causal factor of metastatic cancer, and candidate Trop-2 as a target of novel diagnostic and therapeutic procedures. No significant financial relationships to disclose.
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